HEW Publication No. 77—3056

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Commissioner
Decision

DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE
Food and Drug Administration

 

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Table of Contents

Preface by Donald Kennedy, Commissioner, Food and Drug Page

Administration ........................................... ui
Statement by Julius Richmond, Assistant Secretary for Health. . . . VI
Summary .................................................. X
Laetrile; Commissioner’s Decision ............................. l

 

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Preface
BY

DONALD KENNEDY
Commissioner, Food and Drug Administration

Every decade or so, an unproven cancer remedy is promoted in the United
States so effectively that it becomes nationally known and used by thousands
of cancer victims. Some of these patients have natural remissions, or feel
better, as a consequence of abandoning often painful conventional therapy.
They—and their relatives and loved ones—often attribute the “Cure” to the
remedy, and become its most vigorous proponents.

The unproven cancer remedy of the 1970’s is Laetrile, also known as
amygdalin or vitamin B—17. It is made from apricot kernels or the seeds
of other related fruits. It was ﬁrst broadly promoted for cancer treatment
in the early 1950’s, and rose to national prominence in the 1970’s when a
group called “The Committee for Freedom of Choice in Cancer Therapy”
organized in 1972 to defend a physician accused of using Laetrile. The
leaders of this group not only promote Laetrile, but also proﬁt ﬁnancially
from its sale.

The ascent to popular attention, and the subsequent decline, of quack
cancer remedies is a fascinating phenomenon. Years from now, after
Laetrile has long been forgotten, historians will wonder how so many cancer
victims and their families could spend so much money on a remedy that is
considered ineffective by virtually all medical experts.

But we are not yet at a point from which we can look back. Laetrile is a
genuine public health menace in the United States today. Many cancer vic-
tims—made fearful by tales of the harsh side effects of proven remedies, and
persuaded that Laetrile may work—turn to Laetrile, and then ﬁnd out too
late that it does not work. With cancer, early treatment is essential, for can-
cer is progressive. Another substantial group of patients is avoiding eFfective
therapy altogether while using Laetrile. The question for -these patients is
one of life and death.

Those of us in biomedical research wish we could claim that all patients
who turn to conventional therapy for cancer will be cured. Unfortunately,
while we are making progress against cancer every year, we are still not at
the point where we can cure most forms of the disease. Cancer has turned
out to be a complex disease of multiple origin. But there are effective treat-
ments that can prolong life, and in some cases cure. Patients who avoid these
therapies and turn instead to Laetrile are taking grave risks.

Cancer victims turn to such remedies for a complex set of reasons. Cancer
is the most frightening of diseases. It can strike someone at any time. It can
kill slowly and painfully. Like no other disease, it frustrates and agonizes
the families of sufferers. Thus cancer has come to have a special place in our
perception of illness; it is the disease Americans fear more than they fear
war.

The purveyors of false remedies take advantage of these fears. They offer
a simple explanation, a painless cure, and a false hope.

Laetrile is perhaps unique among the cancer remedies in that it has be-
come as much a political issue as a medical one. The Laetrile proponents
maintain that even if the drug does not work, people still have the right to
take it because they deserve “freedom of choice.” On this basis, several
State legislatures have passed laws legalizing’Laetrile. But the sellers of
Laetrile do not offer a free choice—they are persuading cancer victims,
desperate and dying and the most vulnerable members of our society, to buy
a drug that does not work, on the basis of false hope and false information.
0?in informed choices are free; when a cancer sufferer is offered Laetrile
by a doctor with the assertion that it works, the patient is hardly free to
choose.

The Food and Drug Administration is concerned about the sale and
promotion of drugs like Laetrile. It is our responsibility as a Federal regula-
tory agency to protect people from fraud and from deception in the market-
place, and to assure that the drugs we use are safe and effective. Over the
years, FDA has looked carefully at all the evidence on Laetrile. We have
looked at the five animal studies conducted by the National Cancer Insti-
tute, at the extensive animal study conducted by the Sloan Kettering Me-
morial Cancer Center, and at dozens of other animal studies. We have
never found any evidence that Laetrile works. Further, we have looked at
patient records to see whether patients who claim to have improved on
Laetrile actually did. Again, we found no evidence that Laetrile works.

This report is the most comprehensive analysis ever done on the Laetrile
question. It was compiled in response to a directive from the U.S. District
Court for the Western District of Oklahoma. We solicited material from
Laetrile proponents and opponents and looked at the material objectively
and carefully. I personally reviewed a large part of the 5,500 pages of writ-
ten material on the two-day hearing record. ,

This review has affirmed my conviction that Laetrile is a major health
fraud in the United States today, that there is no evidence of its safety and
effectiveness, and that we are on the right track in protecting cancer victims
by barring its shipment in interstate commerce.

Further, this review has persuaded me that our present law—which pro-
tects all Americans from fraudulent drugs and from unsafe and ineffective
products—is more necessary than ever before. A handful of promoters has
succeeded in persuading large numbers of cancer victims to spend millions
of dollars on a worthless remedy. Our drug laws protect us from such fraud

and from the health hazards associated with the sale of unsafe and ineffective
medicines.

The report is long and detailed. We felt that we had to address all the
issues—legal as well as scientific—raised by the Laetrile phenomenon, as
well as the social and psychological reasons that cancer victims turn to
ineffective medicines.

After this report was presented to Judge Bohanon, additional information
came to light on the toxicity and composition of Laetrile. On August 9, 1977,
Julius Richmond, M.D., Assistant Secretary for Health of the Department
of Health, Education, and Welfare, addressed himself in some detail to these
issues at a press conference in Washington, DC. Although Laetrile pro-
ponents have been maintaining that Laetrile is a harmless substance, we
are learning that it is not. The text of Dr. Richmond’s remarks are reprinted
here to bring up to date the public record on Laetrile. Following Dr. Rich-
mond’s statement are a summary of the report itself, including its history
and major conclusions, and the text of the report, as printed in the FED-
ERAL REGISTER of August 5, 1977.

Statement
By

JULIUS RICIHMOND, M.D.
Assistant Secretary for Health
Department of Health, Education, and Welfare
August 9, 1977

We in the Public Health Service are concerned about the increasing
use of Laetrile by cancer patients in this country.

Laetrile is a cyanide-containing substance derived from apricot and
other fruit kernels. Its proponents say that it is effective in the prevention,
cure or control of cancer.

No evidence to support these claims has ever been submitted to the Food
and Drug Administration. The National Cancer Institute has conducted
ﬁve tests on Laetrile and concluded that it is ineffective in animal systems.
There have been many other tests of Laetrile in animals, and FDA and NCI
have even looked at the records of patients who have used Laetrile to see
whether there is any evidence at all that it works.

We have found none. And in fact there is considerable evidence that it
does not work.

The Commissioner of FDA has just concluded a new and exhaustive
review of all information on Laetrile. His conclusion, published last Friday,
is that there not only is no evidence that Laetrile is safe and effective, but
further that it poses a genuine public health problem in the United States
today. I concur in his conclusions.

Today I would like to focus on some disturbing new information about
the safety and content of this drug.

This new information is particularly important because some terminally
ill cancer victims are now legally obtaining Laetrile under a court order
issued by the U.S. District Court for the Western District of Oklahoma.

The ﬁrst problem is Laetrile toxicity?»

The Laetrile promoters say it is harmless, and that patients should have
the right to take any substance that at least does no harm even if it is not
effective.

As our experiences with Laetrile grow, we are ﬁnding that it is not harm-
less. Quite to the contrary, we are ﬁnding that Laetrile is a potentially dan-
gerous substance, especially in its oral form. Enzymes present in the human
digestive tract can break down the drug to release deadly cyanide.

vi

On July 12, 1977, before a Congressional hearing, Dr. Joseph F. Ross,
professor of medicine at the UCLA School of Medicine in Los Angeles, doc-
umented 37 cases of poisoning and 17 deaths from Laetrile and cyanide-con-
taining fruit kernels. The cases were collected from the United States and
at least six other countries.

In one case, an 11-month old girl in Attica, New York, died after ingest-
ing up to ﬁve of her father’s 500 milligram Laetrile tablets. Her death was
listed by the Medical Examiner as “due to amygdalin ingestion.”

Dr. Ross testiﬁed that Laetrile, in addition to possibly causing acute toxic
effects, may also result in chronic poisoning, such as neurological degen-
erative disease.

Dr. Ross concluded: “There is ample scientiﬁc evidence that Laetrile is a
toxic material which is potentially lethal when ingested and may produce
adverse symptoms when injected.”

. Dr. Jerry P. Lewis, Professor of Medicine at the University of California
School of Medicine, reports these plus other adverse reactions. In an article
in the July 1977 issue of the Western Journal of Medicine, he cited a number
of cases of documented Laetrile toxicity with manifestations ranging from
itching, dizziness and headaches to vomiting, diarrhea and high fevers. He,
too, noted that in some cases, ingestion of amygdalin is fatal.

The most recent report of adverse reactions to Laetrile was reported in
July of this year by four doctors at Georgetown University. In this report
one cancer patient who resorted to Laetrile developed fever, skin rash, and
abdominal pain, while a second developed difﬁculty in eye movement and
weakness in the arm and legs.

When Laetrile was discontinued, the symptoms disappeared in both pa-
tients. In one patient the Laetrile was resumed and the symptoms returned.
The other patient did not resume Laetrile.

I believe the information we are now starting to see on Laetrile toxicity
may be just the tip of the iceberg. It demonstrates once again how critical
are our laws that require that drugs be adequately tested before they are
sold.

The second issue I would like to address here today is the quality of the
Laetrile now being sold to cancer victims.

Laetrile is produced in factories that are not registered with the U.S. Gov-
ernment and that are not inspected by the Food and Drug Administration.
There is therefore no way the Government or a prescribing physician can
assure the quality and purity of the product being imported under the
current court order or being imported illegally.

Tests conducted by FDA, the Stanford Research Laboratory and other
laboratories show that the Laetrile now being bought in the United States,
whether imported from Mexico or made elsewhere, varies widely in its in-
gredients, quality and purity. These tests have revealed serious problems of
adulteration, decomposition and misbranding as well as inconsistency in the

vii

kinds of ingredients being used. And we are now receiving early reports of
serious microbial contamination of Laetrile.

—We have found tablets of Laetrile seldom meeting their declared
strength. Tablets have been found to vary in content from 42 to 450
milligrams.

——Actual content of amygdalin in the injectable form has been found to
vary from 14 to 87 percent. No injectable product has been found to contain
100 percent of its declared potency. And on closer examination, these vials
were found to contain two different isomers of the drug, which are likely
to vary widely in their effect on the body.

——We have found impurities in some samples. Some producers of inject-
able Laetrile are using isopropyl alcohol instead of ethyl alcohol in the pro-
duction process. Isopropyl alcohol may cause a more painful injection and,
if high levels are used, may be a hazard in itself.

—Even more frightening, a very recent analysis of ampules of amygdalin
from Mexico revealed evidence of microbial contamination visible to the
naked eye. Microbial contamination could lead to serious illness and death
if the substance is injected into the blood-stream.

—Recent analyses of these samples from Mexico revealed serious prob-
lems with the seals on the ampules so that leakage could occur. This permits
microbial contamination.

So, on the basis of all the information available, I have concluded that
Laetrile not only is an ineffective cancer drug, but that cancer victims who
buy it are not even getting what they are paying for, and in fact may be
buying a dangerous and contaminated drug.

These ﬁndings are very troublesome to me. Cancer victims have enough to
worry about without being subjected to an outright health hazard.

The major hazard of Laetrile still must be considered the diversion of
patients from conventional, proven therapy. \Ve are increasingly receiving
reports from physicians of patients with early, curable cancer who have
turned to Laetrile and then ﬁnd out too late that it does not work. The new
information we are discussing today compounds that hazard.

I understand well why cancer victims turn to unproven remedies like
Laetrile. Laetrile is not the ﬁrst unproven cancer drug to come to national
prominence, and until we develop better treatments for cancer, it will not
be the last.

But I urge cancer victims who are now taking Laetrile, whether legally
or illegally, and those who may consider it, to be fully alert to these new
hazards we are just now starting to identify.

Further, I would urge all cancer patients, their relatives, and their friends
to avoid the use of this dangerous, fraudulent drug and to seek effective treat-
ment through their family doctors and the specialists they recommend. Those
who persist in the use of Laetrile should limit the amount taken by mouth and
should under no circumstances drink the injectable form because of its higher
concentration. They should be prepared to seek prompt medical attention

viii

in case of any unexpected effects of Laetrile and should be aware of the
possibility of chronic cyanide poisoning as well as acute toxicity which can
result in sudden death.

In conclusion, let me reassure cancer victims that the National Cancer
Institute is doing all that it can to develop new and effective treatments
for this bafﬂing range of diseases called cancer. And let me further reassure
the public that the Food and Drug Administration will not stand in the
way of swift approval of any signiﬁcant new treatments that will be de-
veloped in the future. We in the Public Health Service are committed to
increasing our knowledge of all diseases and to developing new methods of
curing, treating and preventing them and seeing that these methods are made
available to the public as rapidly as possible. I reject any implication by the
proponents of Laetrile that the Federal Government is blocking the use of
new therapies against cancer.

In the case of Laetrile, we have documented our search for evidence for
the public to see. We have found none. In the process we have discovered
that the drug can be hazardous. In the meantime, thousands of cancer vic-
tims with false hopes are spending enormous sums of money on a substance
that does not cure or prevent cancer, or prolong the life of the cancer victim,
but which instead may cause serious harm. These are the reasons I have
issued this statement today.

246-920 0 - 78 - 2

Summary

Laetrile is a substance derived from apricot kernels and other fruit kernels.
It has been promoted for about ‘25 years as a cancer treatment. Historically,
FDA has taken the position that Laetrile, also known as amygdalin or vita-
min B—17, has not been demonstrated by well-controlled studies to be a safe
and effective cancer treatment. Under Federal law, it is the responsibility of
the sponsor of a drug to demonstrate safety and effectiveness; no such evi-
dence ever has been submitted to FDA, and the studies reviewed by the
Agency indicated that Laetrile was not safe and effective. Therefore, FDA
has always prohibited the shipment in interstate commerce of this drug.

In February 1977, at the direction of a court, FDA began a formal and
exhaustive medical and legal review of Laetrile. It was undertaken on the
order of the Court of Appeals for the Tenth Circuit in the case of Rutherford
v. United States, in which a Kansas resident sought judicial permission to
obtain Laetrile legally. The District Court had ruled in favor of Mr. Ruther-
ford, but the C0urt of Appeals, in reviewing that decision, said there was an
insuﬂicient administrative record supporting FDA’s position. Accordingly,
it remanded the case to the District Court for the development of such a
record, and the District Court, in an order issued January 4, 1977, ordered
FDA to develop it.

FDA acted to comply by commencing a rule making proceeding that
began as of February 18, 1977. In accord with the court’s order, it was
directed at two issues:

1. Is Laetrile a “new drug” in that it is not generally recognized among
qualiﬁed experts as safe and effective for use in the cure, mitigation, treat—
ment or prevention of cancer, and, therefore, is subject to the premarket
approval requirements of the Federal Food, Drug, and Cosmetic Act?

2. If Laetrile is a “new drug,” is it exempt from the premarket approval
requirements of the law by the “grandfather” provisions of the Act?

During the court-ordered review, FDA received more than 4-0 submissions
totaling more than 5,500 pages. These submissions, representing the views
of both proponents and opponents of Laetrile, came from cancer patients,
consumers, experts in drug testing and cancer therapy, physicians, state gov-
ernments, university hospitals and interested organizations. In addition,
FDA held a public hearing in Kansas City, Missouri, May 2 and 3 to re-
ceive additional testimony. Forty-seven people made presentations.

The Commissioner of Food and Drugs has now completed his evaluation
of the entire record and has concluded that: (1) Laetrile is a “new drug”

X

under the law because it is not generally recognized by qualiﬁed experts as
a safe and effective cancer drug, and (2) Laetrile is not exempt from the
premarket approval requirements for “new drugs” by virtue of the “grand-
father” provisions of the law.

The Commissioner concluded that distribution of Laetrile in interstate
commerce remains illegal and subject to regulatory activity by FDA.

In addition to the legal issues, the Commissioner also addressed the larger
public health issues involved with the use of Laetrile. Following is a sum-
mary of his conclusions:

—The use of Laetrile in the United States has become a genuine public
health problem. Increasingly, doctors dealing with cancer patients are ﬁnd-
ing that patients are coming to proven, effective therapy too late, having
delayed while trying Laetrile. Another substantial group of cancer victims
is avoiding effective therapy altogether and using Laetrile instead. The ques-
tion has become one of life and death for these patients and for others who
may be convinced in the future to use Laetrile.

—There is considerable confusion, even among its proponents, about
what Laetrile is. Different people use the term “Laetrile” to mean different
substances.

—Just as the identity for Laetrile is unclear, so are the claims. The
claims appear to vary in relation to the sophistication of the intended audi-
ence. Over the years, proponents have claimed that Laetrile is a cure for
cancer, that it is palliative, that it prevents cancer, that it is a pain killer,
or that it facilitates other cancer treatments. Then have even been claims
that Laetrile raises the red count in blood, is of value in treating sickle cell
anemia, can be used to treat parasitic diseases, helps regulate intestinal ﬂora,
causes a lowering of blood pressure in cancer victims and provides relief
from arthritis.

—~The theories about how Laetrile works against cancer also have changed
over the years. The theories advanced for Laetrile’s supposed action are
based on false or questionable assumptions.

—FDA reviewed all case histories submitted by Laetrile proponents and
found no evidence that the drug works. For example, the Commissioner con-
cluded that case histories cited in a recent book by Dr. John Richardson, a
Laetrile proponent, not only do not provide the kinds of adequate and well-
controlled studies needed to show the effectiveness of a drug, “it is not even
on its face a particularly credible recounting of medical. case histories.”

—Many of the testimonials offered in favor of Laetrile may be accounted

for by explanations other than the claimed effectiveness of the drug. The
“placebo effect” accounts for some of the reports, particularly those claiming
decrease in pain and increased sense of well-being. Most of the cancer
patients reporting cure by Laetrile appear also to have had the beneﬁt of
other, proven therapies, but choose without adequate evidence to give
Laetrile sole credit. Some of those who believe themselves cured never had
cancer at all. Others may not be cured, despite their belief.

xi

—FDA reviewed all studies submitted by the Laetrile proponents in de-
tail. FDA found that claims of success in animal studies are untrue. The
failure of Laetrile to work in animal tests is important because, according
to the National Cancer Institute, “of the 30 or 4-0 drugs that are regularly
available and known to have effe(t In certain forms of human cancer all
of these drugs have demonstrated activity, signiﬁcant activity, in one or
more of these animal tumor systems.”

—There is no evidence that Laetrile is safe, and there is evidence that
when apricot kernels are ingested, they are harmful. There are documented
cases of cyanide poisoning, some fatal, due to the consumption of apricot
pits or kernels.

—The current Laetrile movement resembles earlier movements for other
unproven cancer remedies. Each decade seems to have an unproven cancer
remedy that is promoted so effectively it attracts a large following. In the
1940’s and 1950’s, for example, the Koch Antitoxins were heavily promoted
as a cancer cure. Cancer victims paid as much as $300 for this worthless
remedy. In the 1950’s, Harry Hoxsey promoted a cancer cure; a permanent

injunction stopped the use of this remedy in 1960. The “cancer cure” of
the 1960’s was Krebiozen.

All these movements have similar characteristics:

The proponents don the mantle of science while at the same time tra—
ducing the reputable scientists of their day;

They claim that prejudice of organized medicine hinders their efforts;

They cite examples of physicians and scientists of the past who were
forced to ﬁght the rigid dogma of their day;

They rely heavily on testimonials and anecdotes as evidence that their
remedy is a safe and effective cancer drug;

They do not use regular channels of communications, such as journals,
for reporting scientiﬁc information, but rely instead on the mass media
and word of mouth;

Their chief supporters are not people trained or experienced in treating
cancer or in scientiﬁc methodology;

They offer a simplistic theory for causation of the disease;

Their remedy 15 easy and pleasant, compared with the frightening thera-
pies wielded by orthodox physicians ,

And they claim the mode of administration of the drug and the method
of treatment can be learned only from them.

——The reason that cancer victims throughout history have turned to
unproven remedies is complex. Cancer engenders fear, and the hope offered
by proven remedies often is modest. Cancer victims’ families feel both sym—
pathy and guilt at being unable to relieve the victim’s suffering. These

elings are exploited skillfully by the purveyors of false cures. Cancer vic—
tims and their families are extremely vulnerable to the kind of persuasion
so skillfully used by Laetrile’s promoters. This promotion may take the form
of highly polished and convincing ﬁlms and books or of personal visits. In

xii

addition, Laetrile promoters are diligent in searching out persons with
reported cancer, actively trying to persuade them to use the drug. Pro-
moters play upon the victim’s frustration with a medical establishment that
cannot offer the certainty of a cure, and build upon the cancer patient’s
fear of legitimate cancer therapies.

—The choice to use Laetrile seldom is a free one. Cancer victims are beset
by immense stresses—physical, psychological, emotional and societal. The
Laetrile proponents do not set forth a rational argument for use of their drug.
The information that the proponents provide is false, and few patients make
an effort to hear the arguments against Laetrile therapy. Thus, the idea
that a reasoned free choice is involved in the selection of Laetrile is an
illusion.

Furthermore, the very act of forming a government necessarily involves
the yielding of some freedoms in order to obtain others. In passing the re-
quirement that drugs must be proved effective before they can be sold,
Congress indicated its conclusion that the absolute freedom to choose an
ineffective drug was properly surrendered in exchange for the freedom from
the danger to each person’s health and well-being from the sale and use of
worthless drugs.

—There is no international recognition of Laetrile. The State Depart-
ment and the United States Mission of the World Health Organization in-
quired of all countries and found none in which Laetrile is accepted therapy.
Among the countries indicating that Laetrile is unknown or is not approved
for use in treating cancer were Japan, the United Kingdom, Belgium, Italy,
South Africa, the Republic of Germany, France, Korea, Taiwan, Israel,
and India. In Madagascar Laetrile is known as amygdalin and is considered
poison by health authorities.

—While some Laetrile proponents claim the substance is a vitamin, ex-
perts in the vitamin area have concluded that it is not.

HClaims that populations which consume large amounts of Laetrile-like
substances are free from cancer are not true. This includes the Kingdom of
Hunza in the Himalayan Mountains and the Eskimos.

On the basis of all available evidence, the Commissioner has concluded
that there is no basis in law or in fact for the use of Laetrile or related
substances in the prevention or treatment of cancer.

xiii

i/V/

DEPARTMENT OF HEALTH,
EDUCATION, AND WELFARE

Food and Drug Administration
[Docket No. 77N—0048]

LAETRILE
Commissioner's Decision

AGENCY: Food and Drug Administra-
tion.

ACTION: Notice.

SUMMARY: The Commissioner of Food
and Drugs announces that he has com-
piled a comprehensive administrative
record containing information about the
drug Laetrile in general and, speciﬁcally,
about two issues concerning Laetrile’s
“new drug” status: (1) Whether Laetrile
is generally recognized by qualiﬁed ex-
perts as a safe and effective cancer drug,
and (2) whether Laetrile is exempt from
the premarket approval requirements for
new drugs by virtue of the “grandfather"
provisions of the Federal Food, Drug,
and Cosmetic Act. The Commissioner
concludes, after careful review of this
administrative record, including oral
argument presented at a public hearing,
that: (1) Laetrile is not generally
recognized by qualiﬁed experts as a safe
and eﬁective cancer drug and (2) La:
trile is not exempt from the premarket
approval requirements for new drugs by
virtue of the “grandfather” provisions
of the act. Distribution of Laetrile in
interstate commerce is thus illegal and
subject to regulatory activity by the Food
and Drug Administration. Conclusions
, on other issues related to the controversy

Lgoncerning Laetrile are also set out.

EFFECTIVE DATE: August 5, 1977.

ADDRESSES: The transcript of oral
argument presented at the public hear-
ing, affidavits, written testimony, and all
other submissions compiled as the ad-
ministrative record for this proceeding
may be seen in the ofﬁce of the Hearing
Clerk. (HFC—20) , Food and Drug Admin-
istration, Rm. 4—65, 5600 Fishers Lane,
Rockville, MD 20857, between 9 am. and
4 p.m., Monday through Friday. In addi-
tion. one copy of the administrative
record (except two videotapes of inter-
views with cancer patients who had been
treated with Laetrile) is available for

Laetrile

public examination at the following Food
and Drug Administration ofﬁces during
regular business hours: 850 Third Ave.,
Brooklyn. NY 11232; 880 W. Peachtree
St.. Altanta, GA 30309; 433 W. Van
Buren St., Chicago, IL 60607; 1009 Cherry

St., Kansas City, MO 64106; 1521 W.
Pico Blvd., Los Angeles, CA 90015; 909
First Ave., Seattle, WA 98104.

FOR FURTHER INFORMATION CON-
TACT:

Tenny P. Neprud, Compliance Reg-
ulations Policy Staff (HFC—lﬂ), Food
and Drug Administration, Department
of Health, Education, and Welfare,
5600 Fishers Lane, Rockille, MD 20857,
301—443—3480.

SUPPLEMENTARY INFORMATION:
In a notice published in the FEDERAL

REGISTER of February 18, 1977 (42 FR
10066), the Commissioner announced
that he was initiating a rule making
proceeding to comply with the opinion of
the Court of Appeals in Rutherford v.
United States, 542 F.2d 1137 (10th Cir.
1976) , and the order of the District Court
in Rutherford v. United States, 424 F.
Supp. 105 (W. D. Okla. 1977). In those
proceedings, the Food and Drug Ad-
ministration (FDA) was ordered to
develop an administrative record con-
cerning the following two issues:

1. Whether the product Laetrile (also
known as vitamin B—17 and amygdalin)
is a “new drug” within the meaning of
section 201 (p) of the Federal Food, Drug,
and Cosmetic Act (21 U.S.C. 321(p))
in that it is not generally recognized,
among experts qualiﬁed by scientiﬁc
training and experience to evaluate the
safety and effectiveness of drugs, as safe
and effective for use in the cure, mitiga-
tion, treatment, or prevention of cancer
in man (“the new drug issue”) .

2. Whether, if Laetrile is a “new drug”
within the meaning of the act, it is ex-
empt from the premarket approval re-
quirements of section 505 of the act (21
U.S.C. 355) in that:

(a) At any time before June 25, 1938,
it was subject to the Food and Drugs
Act of 1906, as amended, and at such
time its labeling contained the same rep-
resentations concerning the conditions
of its use as its present labeling (“the

Commissioner’s Decision

1938 grandfather issue,” 21 U.S.C. 321
(p) (1) ) ; or

(b) It meets each of the following
conditions: (1) On October 9, 1962, it
was commercially used or sold in the
United States; (2) On October 9, 1962,
it was generally recognized, among ex-
perts qualiﬁed by scientiﬁc training and
experience to evaluate the safety of
drugs, as safe for use in the cure, miti-
gation, treatment, or prevention of can-
cer in man; (3) On October 9, 1962, it
was not covered by an effective new drug
application (NDA) under section 505 of
the act (21 U.S.C. 355); (4) It is cur-
rently intended solely for use under con-
ditions prescribed, recommended, or sug-
gested in its labeling on October 9, 1962
(“the 1962 grandfather issue,” Pub. L.
87—781, section 107(c)(4)).

The February 18, 1977 notice included
detailed information regarding the sub-
mission of testimony. In response to the
notice, over 400 submissions totaling
more than 5,500 pages were received.
These submissions, representing the
views of both proponents and opponents
of Laetrile. came from cancer patients,
consumers, experts in drug testing and
cancer therapy, physicians, State gov-
ernments, universities, hospitals, and in-
terested organizations.

The District Court, in directing FDA
to develop an administrative record, sug-
gested that the agency invite the follow-
ing individuals to participate in the ad-
ministrative proceeding: Dr. Dean Burk,
Ernst Krebs, Jr., Mike Culbert, Edward
Grifﬁn, and Mike Spencer, Rutherford v.
United States, supra, 424 F. Supp. at
108. The three individuals whose address—
es could be obtained were speciﬁcally in-
vited to give their views (R 3, 4, 5).l
(Kenneth Coe, attorney for plaintiff
Glen Rutherford, who had proposed that
FDA be required to invite the five named
individuals, could not provide the ad-
dresses for Griffin and Spencer and
agreed that invitations to the three
individuals whose addresses he could
supply would sufﬁce.) Mr. Grifﬁn did re-
ceive notice of the proceeding and he
participated (see R 404). Written sub-
missions were received from Dr. Burk
(R 302) and Mr. Grifﬁn (Tr. Ex. 1) and
from plaintiff Glen Rutherford (R 258).

The Bureau of Drugs, FDA, presented
evidence probative of the new drug and
grandfather status of Laetrile. For the
purposes of the administrative proceed-
ing, separation of functions requirements
were observed between the Commissioner

and persons advising him and the Bureau
of Drugs and persons advising it (see
21 CFR 10.55).

The February 18, 1977 notice stated
that oral argument would be held in
Kansas City on May 2. A subsequent no-
tice published in the FEDERAL REGISTER
of March 25, 1977 (42 FR 16191) set
forth the exact time and place: begin-
ning at 9 am. on May 2 at the Radisson
Muehlebach Hotel, Kansas City, MO. Dr.
John Jennings, Associate Commissioner
for Medical Affairs, presided over the
oral argument. Approximately 40 persons
ﬁled written requests to make oral pres-
entations; others took advantage of the
opportunity to speak without the ﬁling
of such a request as time allowed. Every
person who wished to participate in, and
who was present at, the oral argument
was given an opportunity to express his
or her views. In all, 47 persons made pres-
entations. The transcript of the oral ar-
gument has been made a part of the
record of the administrative proceeding.

Individuals named by the District
Court were again notiﬁed of the exact
time and place of the argument (R 253—
55, see also R 247). Oral presentations
were made by Edward Grifﬁn (Tr. at
11), Michael L. Culbert (Tr. at 35) , Ernst
T. Krebs, Jr. (Tr. at 228) and Dr. Dean
Burk (Tr. at 401). In addition, plaintiff
Glen L. Rutherford and his attorney,
Kenneth Coe, Eso., spoke at oral argu-
ment (Tr. at 297, 442).

Written submissions presented at the
time of oral argument were made part
of the record and considered despite the
fact that they were received at a date
later than the one set forth in the
February 18, 1977 notice. The record
of this proceeding was, however, closed
at the conclusion of the oral argument.
Submissions received thereafter have
been docketed with the FDA Hearing
Clerk but have not been considered as
part of the record. The Commissioner's
opinion is based entirely upon the ad-
ministrative record and does not reflect

 

1 Submissions to the record are referred to
by the number assigned to them upon ﬁling
by the Hearing Clerk. When exhibits or at-
tachments accompany a submission, they
follow the record number of that submis-
sion, e.g., “R 12, Ex. A". References to the
transcript of the oral argument are cited as
”.Tr at" with the applicable page number
supplied. Written submissions presented to
the energy at the time of oral argument are
referred to as transcript exhibits, e.g., Tr,
Ex. 1.

information brought to FDA’s attention
subsequent to the closing of that record.

No legal memoranda were solicited by
the Commissioner in this proceeding.
One such memorandum was submitted
by the American Cancer Society and has
been made a part of this docket in the

____Hearing Clerk’s ofﬁce.

In the Commissioner’s opinion, the use
of Laetrile in the United States has be-

come a genuine public hea_l_t_h problem»...

Increasinmma‘l’ﬁig wi can-
cer patients are ﬁnding that the patients
are coming to legitimate therapy too late,
having delayed while trying Laetrile. It
seems clear that another substantial
group of persons afﬂicted with cancer is
avoiding effective therapy altogether and
using Laetrile instead. The question has
become one of life and death for these
patients and for others who may be con-
vinced to use Laetrile in the future. For
this reason the Commissioner has con-
sidered not only the evidence in the rec-
ord addressed to the speciﬁc legal issues
remanded to FDA by the courts, but also
the great amount of evidence submitted
by both proponents and opponents of
Laetrile regarding other issues of im-
portance to the controversy over the use
of the drug. Since the Commissioner’s
discussion of these issues is necessarily
detailed, he is setting forth, for the read-
er’s convenience, an outline of that dis-
cussion as follows:
I. LAETRILE
A. DEFINITION OF CANCER

. COMPOSITION AND IDENTITY OF "LAETRILE"

. Glossary.

. What is Amygdalin?

. What is Laetrile (with a capital L)?
. What is laetrile (with a small 1)?

. What is Sarcarcinase?

Una-COMM hi

i C. CLAIMS FOR LAETRILE

. Treatment (Cure or Mitigation of Cancer.

. Analgesic (Pain Killer).

. Prevention of Cancer.

. Facilitation of Other Cancer Therapy.

Hemoglobin Index.

Reduction of Odor Associated with Malig-
nancy.

. Sickle Cell Anemia.

. Parasitic Diseases.

. Regulating Intestinal Flora.

. Hypotensive Effect.

owmq gapnhceuw

H

D. 'rmzoaras or LAE’I‘BILE’S ACTION
II. THE “NEW DRUG" ISSUE

A. GENERAL RECOGNITION OF EFFECTIVENESS

* 1. Objective Evidence of Eﬂ'ectiveness.

246-920 0 - '18 - 3

Laetrile

HBWNH

(a) What are the Required Studies?
(b) The Need for Controlled Studies.
(0) The ”Evidence" of Laetrile’s Effec-
tiveness.
(1) Case Reports.
(ii) Animal Testing of Laetrile.

. Testimony of Experts.

(a) Experts Opposed to Laetrile.
(b) Supporters of Laetrile.

B. GENERAL RECOGNITION OF SAFETY

. Lack of Adequate Testing.
. Testimony of Experts.

III. THE "GBANDFATHER" ISSUE
A. THE 1938 GRANDFATHER CLAUSE

B. THE 1962 GRANDFATHER CLAUSE

. Composition.

. Investigational Use.

. Conditions of Use in Labeling.

. Lack of General Recognition of Safety in

1962.
(a) The Prerequisites.

(1) Lack of General Knowledge

of Use.

(11) Lack of General Knowledge
of Formulation.

(iii) Lack of General Knowledge
of Conditions of Use Sug-
gested.

(iv) Lack of Safety Data in
Scientific Literature.

(v) Lack of Showing of Safety by
Adequate Testing.

(b) Statements by Experts.
(0) Lack of General Recognition of E1-
fectiveness in 1962.

IV. THE POPULARITY OF LAE'I'RILE
A. LAE'raILE AND OTHER UNPROVEN REMEDIES

. The History of Cancer Quackery in the

United States.

. Similarities Between Laetriie Promotion

and That of Other Recent “Unproven”
Cancer Remedies.
(a) Mantle of Science.
(b) Attacks on the “Establishment."
(c) Claimed Parallel with Scientiﬁc
Pioneers.
(d) Reliance on Testimonials.
(e) Lack of Scientific Publication.
(f) Nonexpert Supporters.
(g) Simplistic Theories of Causation
and Reliance on Diet.
(h) A Painless Cure.
(1) Only Proponents can Eﬂectively Use
the Drug.

B. WHY DO PEOPLE USE LAETRILE?

. The Emotional Reaction to Discovery of

Cancer.

. The Role of Loved Ones.
. Methods of Promotion of Laetrile.
. The Sampson Survey.

C. THE LAE'I'BILE TESTIMONIALS

V. OTHER ISSUES REGARDING LAETRILE

. USE OF LAETRILE OUTSIDE THE UNITED STATES

Commissioner's Decision

B. CLAIMS THAT LAETRILE IS A VITAMIN OR FOOD

, A Vitamin or Food May Be a Drug As Well.
2. Is Laetrlle a Vitamin?

(a) Proponents’ Claims.

(b) Vitamin Experts’ Position.
3. Dangers of Ingestion of “Vitamin B—17."

H

C. FREEDOM OF CHOICE

l. Balancing Freedoms.
2. The Choice Is Not Free.

D. ALLEGATIONS OF“ BIAS
E. LIMITING USE TO TERMINAL PATIENTS

1. Who Is Terminal.
2. Effects on other Patients.

F. USE CONCURRENTLY WITH OTHER THERAPY
VI. CONCLUSIONS
I. LAETRILE
A. DEFINITION OF CANCER

Laetrile has been, over the years. rec-
ommended for use in the treatment of

cancer. An understanding of the issues
concerning the drug requires that the
term “cancer” be deﬁned. Cancer has
been stated to include “* ‘ * all malig-

nant neoplasms regardless of the tissue
of origin including malignant lymphoma,
Hodgkins disease, and leukemia” (R
173, Att., “Laws and Regulations Relat-
ing to the Diagnosis and Treatment of
Cancer,” State of California, Division 2,
Chapter 7, Section 1705). For an almost
identical deﬁnition by the American
Cancer Society, Inc., see R 173, Att.,
“American Cancer Society, Inc., Medical
Affairs Department, (State) Cancer
Remedy Act." A neoplasm is a new and
abnormal growth such as a tumor. Ma-
lignant neoplasms are “neoplasms that
are characterized by unregulated, un-
controlled, and unrestrained growth and
proliferation” (R 190 at ‘J 14; R 194 at 3;
R 195 at i] 11). It has been said that the
“distinguishing feature of cancer is its
ability to invade, erode and to metasta-
size to more or less distant parts” (R
183, Att. '7 at 15). Metastasis, in relation
to cancer, means the transfer or spread
of the cancer from one site to another,
usually through the blood stream or the
lymphatic system. In this process, cells
may travel throughout the body; when
they ﬁnally lodge they begin to grow as a
new cancer.

There are more than 100 different en-
tities involved in the disease known as
“cancer." These many forms of clinical
cancer differ materially in terms of the
factors which cause them as well as in
terms of populations they affect, their

prognosis, and the ease with which they
may be treated (Tr. at 144; cf. R 190 at
'i 14; R 186 at ii 7—9). The cause of can-
cer is not a question addressed in this
proceeding. It should be noted, however,
that the record includes indications that
various cancers are associated with
chronic irritation (e.g., a high frequency
of cancer of the groin in textile workers
whose jobs required straddling a metal
shaft) (R 318 at 3'7), with cancer-caus-
ing chemical substances called carcino—
gens (e.g., a high frequency of lung can-
cer in chimney sweepers and coal miners
probably caused by inhaling dust par-
ticles) (id.), with irradiation (id. at 38).
with virus (Tr. at 223; R 318 at 38),
and with hereditary effects (R 318 at 38).

Two novel theories, neither of which
has gained acceptance by the scientiﬁc
community, have been at various times

plain how cancer is caused. The ﬁrst of
these theories is said to have been ﬁrst
developed by Professor John Beard of
Scotland. In 1902, Professor Beard an-
nounced his “ﬁndings” that the cancer
cell and the “trophoblast" cell were one
and the same (R 318 at 60). Trophoblast
cells are present during pregnancy and
they prepare a niche in the uterine wall
where the fertilized egg can nestle (R 318
at 56). According to Beard, they share
several characteristics with cancer cells:
Both are invasive, erosive, corrosive and
can be carried through the blood stream
to other parts of the body (R 318 at 57).
Beard believed that trophoblast cells
could be expected to develop at various
places in the body from precursor cells
distributed throughout the body during
the embryonic stage. If the pancreas
gland were functioning properly it
would, in his theory, produce enzymes
which would destroy these trophoblast
cells. If such enzymes were not produced,

\/spoused by Laetrile’s proponents to ex-

(1 cancer would occur (R 318 at 58—59).

The proponents of Laetrile have more
recently taken the position that cancer
is a metabolic deﬁciency or dietary dis-
ease (cf. R 302, Ex. H at 76—77). It is
claimed that cancer is a “* ‘ * system-
ic, chronic, metabolic deﬁciency dis-
ease" (Tr. at 348) or “" * * a chronic
or metabolic disease that is not caused by
some mysterious virus” (Tr. at 234) . The
“nutritional deﬁciency" theory is re-
futed by at least one expert (Tr. at 223).

B. COMPOSITION AND IDENTITY or
“LAETRILE”

Several terms, such as “Laetrile,” “lae-

Laetrile

trile(s)," “amygdalin,” “nitriloside(s) ,”
“vitamin B—17,” and “Sarcarcinase” have
in many instances been used inter-
changeably by both proponents and op-
ponents of Laetrile. There are, however,
distinctions among these terms, which
must be understood in order to deal with
the issues in this proceeding. The Com-
‘missioner will discuss in detail what the
record indicates about the meaning of
the terms “amygdalin,” “Laetrile," “lae-
trile” and “Sarcarcinase.”

1. Glossary

The following glossary provides a deﬁ—
nition or description of the above terms
and others that will be used in this
opinion:

Amygdalin: A speciﬁc chemical entity
having the chemical formula:

o—caz

cHzoa CN
I
“ o 8 0 0—011
H
0" OH H
H0 H H H
" 0“ H OH

D-ulndelonitriIe-beta—D-g lucosido—G-beta-D-glucos ide

(Merck Index, 9th Ed. at 81).

beta-Cyanogenic glucosides; beta-cyano-
phoric glucosides; beta-cyanogenetic
glucosides: Terms used interchange-
ably in the record. In general, they are
used in the record to include com—
pounds which can break down to yield
cyanide and glucose. The terms are
used to refer to amygdalin, a glucoside
present in kernels or seeds of prac-
tically all fruits (see, e.g., R 302, Ex.
H at 75; R 173, Att., California Admin-
istrative Code, Section 10400.1 at 16;
Tr. at 272). beta-Cyanogenic gluco-
sides belong to the large class of chem-
icals known as beta-cyanogenic glyco-
sides. (See deﬁnition of glucosides and
glycosides below.)

beta-Glucosidase: An enzyme present in
plants that participates in the metabo-
lism of glucosides. The enzyme has
been identiﬁed in apricot and peach
kernels and catalyzes the breakdown
of amygdalin to free two molecules of
glucose and a molecule of mandelo-
nitrile. The enzyme is found only in
trace amounts in animal tissues (R

173, Att., “The Vitamin Fraud in Can-
cer Quackery” (hereinafter “Vitamin
Fraud”) at 345) .

beta-Glucuronidase: An enzyme present
in animal tissues that participates in
the metabolism of glucuronic acid
derivatives (also called glucurono-
sides). The enzyme reportedly cata-
lyzes the breakdown of “Laetrile” (1-
mandelonitrile-beta-glucuronic acid)
to free glucuronic acid and mandel-
onitrile.

Enzymes: Chemical compounds (all of
them proteins) produced by living or-
ganisms that serve as catalysts in
metabolic reactions. The sufﬁx “-ase”
is given to most enzymes.

Glucoside: A term applied to any glyco-
side having glucose as its sugar con-
stituent.

Glucuronide; glucuronoside: Terms used
in the record to refer to chemical de-
rivatives of glucuronic acid. As an
example, Laetrile is identiﬁed as l-
mandelonitrile-beta-glucuronic acid”
in the Merck Index 9th Ed., at 702
and as “laevo-mandelonitrile—beta-
glucuronoside" in the book Control for
Cancer (R 318 at 73).

Glycosides: A broad term which encom-
passes glucosides. Not all glycosides
are glucosides (cf. The Condensed
Chemical Dictionary, 7th Ed. at 455).

Laetrile: A speciﬁc chemical entity hav-
ing the chemical formula:

COOH

H 0 on
H I
43—01
"0 on H
H OH

I
.ku. _

" l-mandelanitrile-betI-glucuroni: acid (Merck Index, 9th

Ed. at 702). The name "Laetrile" vu purportedly assigned

to this compound by Ernst T. Krebl, Jr. (R 318 at 73).

laetrile: A term used interchangeably
with “Laetrile,” “amygdalin,” “nitrilo-
side," and “vitamin B-17” (R 302, Ex.
A; R 183, Att. 100). The term is also
used to include a number of com-
pounds, in which case it may appear
as “laetriles.”

Mandelom‘trile: A speciﬁc chemical en-
tity having the chemical formula:

Commissioner’s Decision

CN

HO—CH

(Merck Index, 9th Ed. at 743).

Nitriloside: A term proposed by Ernst T.
Krebs, Jr.. for all cyanophorioglyco-
sides of dietary signiﬁcance (R 302, Ex.
H at 75).

Prunasin: A speciﬁc chemical entity
having the chemical formula:

 

Handelonitrile Glucoaide (Merck Index, 9th Ed. It 743).

Sarcarcinase.‘ The name given to an en-
zyme preparation developed by Dr. E.
T. Krebs, Sr., and described by him in
a 1933 patent application as a mixture
of the following enzymes—amygdalase,
prunase, oxynitrilase, catalase, peroxy-
dase, and a proteolytic enzyme. He also
suggested the presence of isomaltase
and a lipase and perhaps other en-
zymes (R 424).

Vitamin B—17: Described as a group of
compounds which include water-solu-
ble, essentially nontoxic, sugary com-
pounds found in over “800 plants" (R
302, Ex. H at 75) used interchangeably
with “nitriloside,” “Laetrile,” “amyg-
dalin.” “beta-cyanogenic glucosides”
and “cyanophoric glucosides” (e.g., R
302, Ex. H at 75; R 302, Ex. A).

2. What is Amygdalin?

Amygdalin was reportedly ﬁrst isolated
from bitter almonds by the French
chemists Robiquet and Burton-Charland
in 1830 (R 1'73, Att., “Vitamin Fraud”
at 345). The name “amygdalin” was de-
rived from the word “amygdala”, Greek
for almond (R 302, Ex. L at 1; 9). Amyg-
dalin is a. chemical mound composed
of_two glucose. molecules and one mole-
cule of mandelonitrile. Mandelonitrile is
a chemical in which cyanide is combined
with benzaldehyde (cf. R 173, Att.,
“Vitamin Fraud” at 345). The German
chemists Liebig and Wohler observed
that an enzyme preparation (later called
emulsin) from bitter almonds was cap—
able of hydrolyzing amygdalin, i.e.,
breaking it down into the two glucose
molecules, the benzaldehyde molecule
and a hydrogen cyanide molecule (id.).
It was later shown that this hydrolysis
occurs through the action of two en-
zymes (beta-D-glucosidase and beta-
oxynitrilase) which are present in emul-
sin (id.). The beta-D-glucosidase hydro-
lyzes the beta-D—glucoside bond and thus
frees the two glucose molecules from the
mandelonitrile. beta-Oxynitrilase is the
catalyst for the breakdown of mandelo—
nitrile into benzaldehyde and hydrogen
cyanide (id.).

Amygdalin may be extracted from
apricot kernels (id.), and is present in
seeds of other members of the rose fam-
ily (R 416 at Tl 31A). The Commissioner
concludes that amygdalin, a cyanogenic
glucoside, is a chemical having the chem-
ical name D-mandelonitrile-beta-D-glu-
cosido-6-beta-D-glucoside (Merck Index,
9th Ed. at 81, compound 630; R 183, Att.
10b). The chemical structure of amyg—
dalin is:

o—Cﬂ2

cuzos CIN
1* O H 0 o-CH
H
0“ on n
no u H H
ﬂ 0" u on

3. What is Laetril (With a Capital L)?

The term “Laetrile” has been used in-
terchangeably with “amygdalin,” ”lae-
trile," “vitamin B—17,” “nitrilosldes,” and
“beta-cyanogenetic glucosides" (R 173,
Att., Laws and Regulations Relating to
the Diagnosis and Treatment of Cancer
10400.1 at 16; R 302, Ex. A; Tr. at 405,
272, 465). It appears, however, that the
term “Laetrile” (with a capital L) has

Laetrile

been used by the drug’s proponents to
refer to a particular substance. There are
essentially two versions of what that sub-
stance is:

(a) The term has been used to refer
to a speciﬁc..chemica1.compound which
was prepared in 1952 by Ernst T. Krebs,
Jr., who is said to have derived the name
“Laetrile” from the compound’s chemi-
cal name: laevo-mandelonitrile-beta-
glucuronoside (R 318 at 73; see also R
262; R 183, Att. 16 at 1 and 2). This
chemical is related to, but is distinctly
different from, amygdalin. It is claimed
that the laevo-mandelonitrile-beta-glu—
curonoside was derived by Ernst T.
Krebs, Jr., while working with the apri-
cot extract his father had prepared and
studied some 20 years earlier (R 318 at
70—73). The chemical structure of this
material is depicted in several places (R
318 at 154, 157, 162) and is in agreement
with the chemical name. The chemical
structure of this version of Laetrile is:

COOH
H 0 CN
H 0—— cu
HO OH H
H OH

(b) In a 1965 affidavit, however, Dr.
Krebs, Sr., stated that the name “Lae-
trile” was devised in 1949 by his son,
Ernst T. Krebs. Jr., for a form of amyg-
dalin which Dr. Krebs, Sr., was produc-
ing at that time (R 183, Att. 13). As can
be seen from the diagrams set out in this
opinion, the chemical structure of amyg-
dalin is different from that of Laetrile
as described by Mr. Krebs, Jr.

In the second version of the identity
of Laetrile, the source of the name is
stated as follows: “Because this apricot
preparation was ‘Laevorotatory’ (left-
handed) to polarized light, and because
Amygdalin was chemically a ‘mandeloni—
trile,’ Krebs, Jr., united the ﬁrst and the
last syllables to invent a name for the
new cancericidal drug—LAETRILE”
(R 183, Att. 7 at 24).

The confusion about the meaning of
the term “Laetrile” is long-standing and
may in part be the result of a desire on
the part of promoters to continue to use
drugs containing amygdalin while justi-
fying the use of the drugs by theories as-
sociated with the Laetrile of Krebs. Jr.

For example, in a February 17, 1953 let-
ter to Dr. Ian Macdonald, the Chairman
of the Cancer Commission of the Cali-
fornia Medical Association, Ernst T.
Krebs, Jr., advised that he was forward-
ing “* * * samples of the biosynthet-
ically degraded amygdalin in which one
dextrose was removed by prunasin and
the resulting compound, in the presence
of platinum black, was oxidized to the
corresponding glucuronoside" (R 183,
Att. 14). (Note: the compound thus ob-
tained should have been l-mandeloni-
trile-beta-glucuronoside or “Laetrile" as
described by E. T. Krebs, Jr., R 318 at
73.) The Cancer Commission of the Cal-
ifornia Medical Association, in its 1953
report, stated: “Chemical analyses done
independently for the Commission have
identified in the product distributed as
Laetrile only the presence of a natural
laetrile termed amygdalin” (R 378, Att.
15 at 326).

The question of the identity of the ma-
terial distributed as “Laetrile” arose
again in the early 1960’s when the Can-
cer Advisory Council of the State of Cal-
ifornia was gathering information on
Laetrile in order to enforce the 1959 Cal-
ifornia law dealing with cancer quack-
ery. In 1963 the Council reported that
the California State Department of Pub-
li-c Health had examined different va-
rieties of Laetrile and found that the
products were markedly different in
composition but did contain varying per-
centages of amygdalin (R 183, Att. 16,
App. 7 and 8). A Canadian Medical As-
sociation report published in 1965 found
that the United States and Canadian
versions of the drug were different—a
larger percentage of the Canadian ver-
sion than of the United States version
was found to be made up of amygdalin
(R 189; see also R 378, Att.. “Supplemen-
tary Report by the Cancer Advisory
Council" at 1—2).

The record reveals a number of refer-
ences by Laetrile proponents which use
the terms “Laetrile” and “amygdalin”
interchangeably (see, e.g., Tr. at 238 and
246, and the book Control for Cancer
(R 318) ). Even some labels for the drug
use the terms synonymously: one identi-
ﬁes the product as “Laetrile (Amygda-
lin) 400 mg capsules” (R 183, Att. 10a;
see also R 183, Att. 10d). The National
Cancer Institute, in its October 1975
“Background Statement on Laetrile”
notes the fact that supporters of the drug
have used the names “Laetrile" and
“amygdalin” interchangeably. The re-

Commissioner’s Decision

port then correctly identiﬁes amygdalin
as mandelonitrile - beta - gentiobioside
(this chemical name for amygdalin is
listed in the Merck Index, 9th Ed. at 81,

compound No. 630) and states that the
compound actually tested in 1957, 1960,

1969, 1973, and 1975 by the National Can-
cer Institute was amygdalin (R 173, Att.,
“NCI Testing of Laetrile (Amygdalin) ") .

Yet it is not possible simply to conclude
that the many references to Laetrile as
a speciﬁc substance are a hoax on the
part of Mr. Krebs, Jr., and that Laetrile
as used is simply amygdalin. A number
of reports by Dr. Manuel Navarro of
the Philippines stated that the Laetrile
of Ernst T. Krebs, Jr., was in use (R 318
at 155, 161)), as did a report by Dr. John
A. Morrone of New Jersey (R 318 at 205).

Additional confusion is added to the
record by an article “Nitrilosides (Lae-
triles) Their Rationale and Clinical
Utilization in Human Cancer (December
1962),” by Ernst T. Krebs, Jr., and Dr.
N. R. Bouziane, in which the authors re-
port on their use of “non-toxic nitrilo-
sides (Laetrile) , to which the trophoblast
is susceptible, on terminal cancer cases
for two years in Canada * * *” (R 318 at
187). While the article refers to “cyano-
phoric glucosides and cyanophoric glu-
curonosides” (id. at 189), the authors do
not identify the “Laetrile” they had been
using and about which they were report-
ing. The authors cite a chemical com-
pound in their discussion (id. at 190)
that is not amygdalin nor is it “Laetrile”
as described and named by Ernst T.
Krebs, Jr. (id. at 73).

While the prevailing confusion over
the true identity of material called “Lae-
trile" would be a severe drawback to
anyone seeking to show through testing
that Laetrile was safe and effective, this
lack of uniformity has been adopted by
Laetrile proponents as a means of dis-
counting data showing the drug to be in-
effective and thus unsafe. An example is
found in the statement by Ernst T.
Krebs, Jr., that “The * * * single nega-
tive report on Laetrile, which is based
upon the observations of unidentiﬁed in-
vestigators in unidentiﬁed institutions
administering a purported Laetrile not
obtained from the only source of the ma-
terial, is to be found in California M edi-
cine, 78:320 (1953) " (emphasis added)
(R 318 at 251) . It should be recalled that
at least some of the material supplied to
the California Cancer Commission was
sent by Ernst T. Krebs, Jr., himself (R
183, Att. 14). In May of 1971, Mr. Mc-

Naughton of the pro-Laetrile McNaugh-
ton Foundation, in a meeting with FDA’s
Ad Hoc Committee of Oncology Experts.
stated that data obtained prior to 1968
are frequently not valid because of the
variability of Laetrile formulations (R
173, Att. “Report of the Ad Hoc Commit-
tee of Oncology Consultants” at 1). See
also statement of Robert Bradford, Pres-
ident of the Committee for Freedom of
Choice in Cancer Therapy, Inc.: “As an
aside, an important aspect of animal
tests, and indeed, of human tests has
been from time to time the availability
of amygdalin which did not meet the
speciﬁed identiﬁcation criteria, that is,
for its use. Tests with defective mate-
rials, as Sloan-Kettering found out, will
not be efﬁcacious. Defective material
likewise will not be effective in humans”
(Bradford, Tr. at 350).

In its 1971 report to FDA, the Ad Hoc
Committee of Oncology Consultants
agreed that uncertainty about the iden-
tity of the drug tested makes the test
results obtained questionable. The
Committee stated that because of the
variability in composition of early prep-
arations, doubt was cast on the bulk of
the 1970 McNaughton Foundation Notice
of Claimed Investigational Exemption
for a New Drug (IND) for Laetrile, which
was based almost exclusively on such
early material (R 173, “Report of the
Ad Hoc Committee of Oncology Con-
sultants” at 1). The Committee further
suggested that any protocol for study
contain a full description of the drug
(formulation, stability etc.) (id. at 4).

There is, quite simply, no one answer
to the question “What is Laetrile?”. In
the glossary to this opinion, the chemical
composition of Laetrile is considered to
be that described by Ernst T. Krebs, Jr.
Yet if some other substance is being used
to treat cancer patients, testing of that
“Laetrile" would be of no relevance.

Because different persons have used
the terms “Laetrile" and “amygdalin” to
mean different substances, uniformity of
deﬁnition will not be possible in discuss-
ing the evidence in the record. For this
reason, the Commissioner will not, in
quoting or citing parts of the adminis—
trative record, attempt to deﬁne or to
determine the identity of the material
under discussion but will simply use the
term as it appears in that portion of the
record. Attempts to identify the mate-
rial referred to will be made only when
necessary for a rational resolution of an
issue, e.g., a reference to Sarcarcinase as

Laetrile

amygdalin or as Laetrile will not be ac-
cepted blindly.

4. What is laetrile (With a Small 1) ?

As noted in the glossary, the term
“laetrile” (with a small 1) has been used
interchangeably with or synonymously
for: nitriloside. Laetrile, vitamin B~17,
and amygdalin (e.g., R 302, Ex. A; R. 183,
Att. 100; R 378, Att. 6). The term has,
however, also been used to describe a
class or group of compounds. For exam-
ple, amygdalin and prunasin are de-
scribed as “two common Laetriles" (R
173, Att., “Vitamin Fraud” at 345). It
has been stated that: “The term LAE-
TRILE is used to designate the laevo-
rotatory containing glucosides in general
and the corresponding glucuronoside in
particular. The former are found in
plants whereas the latter are synthetic”
(italics in original) (R 318 at 155). (See
also, R 318, at 240 if 9 which deﬁnes nat-
ural laetriles as beta-cyanogenetic glu-
cosides and glucuron0sides.) The Com-
missioner concludes that the term “lae-
trile” is an imprecise term and that it
does not imply a speciﬁc chemical com-
pound. The term is, rather, a broad or
generic term for a group of compounds
of unknown number.

5. What is Sarcarcinase?

Dr. Ernst T. Krebs, Sr., claims to have
developed a product called “Sarcarcin-
ase” in 1926 (R 183, Att. 13). “Sarcar-
cinase” is stated to be a registered trade-
mark in the United States and 10 other
countries (with registrations dating from
March 1933 to January 1934) (see R 260:
R 259). The process for preparing the
product is stated to be patented in 15
countries including the United States
(see R. 260). It is also reported that
Sarcarcinase was used in Japan in 1934
and in Czechoslovakia in 1935 (R 259).
Other references in the same timespan
refer to an “enzyme preparation” or
“enzyme injection” used within the
United States as well as several foreign
countries (id.).

Ernst T. Krebs, Jr., stated at oral
argument that as early as 1932 his
father “* * * observed the use of amyg-
dalin, or laetrile; made it available
across the country and abroad under the
term ‘Sarcarcinase’ to physicians, to re-
searchers” (Tr. at 238). He also stated,
““ * ‘ the first amygdalin was used—
1932—it was labeled as ‘Sarcarcinase’ ”
(Tr. at 246) . Sarcarcinase was not, how-
ever, amygdalin nor did it contain amyg-

dalin in any quantity. Rather, in the
words of Dr. Krebs, Sr.’s 1933 patent ap-
plication, Sarcarcinase was “an enzyme
for treatment of malignant growths.”
The patent application actually describes
the product as “an enzyme complex"
containing “amygdalase, prunase, oxy-
nitrilase, catalase, peroxydase and pro-
teolytic enzyme” plus a suggestion of
“isomaltase and a lipase with possibly
others” (Patent application attached to
R 424 and to R 259).

Amygdalin is not an enzyme. As will
be discussed in more detail below, en-
zymes are chemicals which catalyze the
breakdown of other chemicals and which
are often named by attaching the ending
“-ase” to the chemical which they at-
tack. Thus, “amygdalase,” stated by Dr.
Krebs, Sr., to be part of his enzyme
complex, may have been meant to de-
scribe an enzyme which would break
down amygdalin.

It has been argued that Sarcarcinase
contained some quantity of amygdalin
(R 183, Att. 13, and Att. 7 at 23). An
expert chemist has stated, however. that
much or all of the small amounts of
amygdalin in the apricot kernels used in
making Sarcarcinase would be destroyed
by enzyme action when the kernels are
ground up and that only a small frac-
tion of any that remained would survive
the rest of the process (R 424). It should
be noted that, even if there were any
amygdalin in Sarcarcinase, that would
not make that drug equivalent to a drug
made up of amygdalin either totally or
in greater proportions either in a scien-
tiﬁc sense or in a legal sense.

There is some indication that Dr.
Krebs, Sr., had abandoned Sarcarcinase
even at the time when the patent ap-
plications were being obtained. One sub-
mission by a Laetrile proponent states
that Dr. Krebs, Sr., “* * * resigned
himself to the fact that there was no
sense continuing this particular research
to identify the toxic element or elements
in the apricot extract he prepared
(sometime after 1926) until he acquired
the additional knowledge necessary to
understand the mysteries that were oc-
curring in his test tubes. He put his ex-
tract aside and returned his books”
(R 318 at 42). Krebs himself states that
in 1936 he developed a new product.
whose “active principle” was amygdalin
of 66 percent purity (R 183, Att. 13).
(The inactive ingredients of this prep-
aration are not identiﬁed.) It is not clear
whether it is Sarcarcinase or this new

\/

Commissioner’s Decision

product about which Krebs, Sr., speaks
when he states that his “apricot ex-
tract” was “so toxic that he and col-
leagues who were experimenting with
him were reluctant to continue its use,
except in dire circumstances” (R 183,
Att. 7 at 23). It was apparently these
toxicity problems that led Krebs, Jr.,
to seek to improve his father’s work
(id.). Since “Laetrile” was not developed
until 1952 by Krebs, Jr., any statement
that “Laetrile” was sold as Sarcarcinase
in the 1930’s is patently erroneous.

C. CLAIMS FOR LAETRILE

Laetrile (or amygdalin) has been rec-
ommended over the years primarily for
use in the treatment and, more recently,
“control” of cancer. The claims appear
to vary in relation to the sophistication
of the intended audience. Thus in the
1962 new drug application (NDA) for
Laetrile submitted by Ernst T. Krebs,
Jr., to FDA, the drug was claimed to be
a palliative (i.e., a drug that mitigates
the symptoms of a disease without cur-
ing it) to be used with other recognized
therapies (R 201, Ex. B at 102). By con-
trast, in a pamphlet in use in 1965, ap-
parently addressed in part to prospective
patients, it is stated that “Laetrile does
not palliate, it acts chemically to kill
the cancer cell selectively * * *,” and
use of other cancer therapies concur-
rently is discouraged (R 201. Ex. 0.,
# III). The following claims have been
made for Laetrile (amygdalin) :

\/1. Treatment (Care or Mitigation) of

Cancer

The pamphlet discussed above and
others obtained from Dr. Krebs, Sr., by
FDA investigators at the same time rec-
ommended Laetrile for treatment of
cancer (see, generally, R 201, Ex. C).
Dr. Krebs, Sr., in a pamphlet entitled
“The Treatment of Breast Cancer with
Laetrile by Iontophoresis" promotes the
drug for treatment of a number of can-
cers (R 183, Att. 7 at 26—27 and 30).

A label for 400 mg capsules of “Laetrile
(Amygdalin) " claims that the “non-
toxic cyanide glucoside is used for speciﬁc
treatment of cancer by physicians or un-
der directions of a physician" (R 173, Att.
102). Amygdalin has been promoted (as
an ingredient of “Bitter Food Tablets”)
for the cure, mitigation, and treatment
of cancer in man (R 173, Att., United
States v. Spectro Foods, Civ. No. 76—101
(D,N.J., Jan. 28, 1976) Findings 16
through 23).

As noted above, some claims are limited
to palliation. (See, e.g., R 216 at 348; R
318 at 175; Tr. at 238.) Recently, Laetrile
has been touted as a “control” for cancer.
Proponents of Laetrile making this claim
assert that no “cure” for cancer exists
(see Tr. at 303). Control for Cancer is
also the title of a paperback book on
Laetrile (R 318). It is not entirely clear
from the record whether “control”
means palliation. Laetrile therapy is said
to be responsible for increased appetite
and weight gain and an increased “sense
of well-being” among treated cancer pa-
tients (R 318 at 158 and 165).

\/ 2. Analgesic (Pain Killer)

13 An information booklet for physicians
about amygdalin makes the claim that
the product is a nontoxic analgesic that
is highly effective in relieving the pain of
terminal cancer (R 183, Att. 10b). The
booklet claims that the oral route is the
most convenient route of administration
for both patient and physician.

Nora: The Commissioner points out
that both proponents and opponents
have warned against oral use of amyg-
dalin or Laetrile.

See R 318 at 167: “' * * it [Laetrile]
should never be given by mouth because
the HCl [of the stomach] is capable of
hydrolyzing the Laetrile”; see also R 318
at 158. Compare R 173, Att., Interview
with Robert C. Eyerly, American Cancer
Society: “Taken orally, it [Amygdalin]
is decomposed in the intestinal tract by
beta-glucosidase into highly lethal hy-
drogen cyanide.” “Orally it [Laetrile] is
extremely toxic due to the release of
hydrogen cyanide on contact with the
hydrochloric acid of the gastric juice
(R 318 at 205).

A label for “The Original Laetrile”
claims that the product “relieves pain
due to malignancy” (R 183, Att. 9). For
another claim that Laetrile reduces can-
oer-connected pain, see Tr. at 44. It has
also been asserted that the hydrogen
cyanide and benzaldehyde liberated by
hydrolysis of Laetrile are potent anal-
gesics (R 318 at 164).

/ 3. Prevention of Cancer
/;«, With the advent of their theory that

cancer is a deficiency disease and that
that deficiency can be overcome by their
product, either characterized as a pro-
vitamin for vitamin B—12 (R 201, Ex. C,
No. IV), or as new vitamin B—17 (see R
183, Att. 10c), proponents of Laetrile

10

Laetrile

have promoted it as a preventative for
cancer (see the above references and R
198, Ex. 2 (transcript of the ﬁlm World
Without Cancer); cf. Tr. at 465). (See
also R 173. Att.. United States v. Spectra
Foods, supra, Findings 16 through 23.)
While proving that Laetrile (or amyg-
dalin) did not prevent cancer would be
extremely difficult, the record does con-
tain evidence that at least one person
taking it as a preventative did contract
cancer (Tr. at 120).

4. Facilitation of Other Cancer Therapy

7 While, as noted above, some labeling

recommends against use of other cancer
therapies with Laetrile, it has been stated
that “" * ‘ if you combine toxic chemo-
therapy with Laetrile, you can give very
high doses' of toxic chemotherapy with
no side effects, physical and no effects
on the blood. That is, you don’t get neu-
cophenia [leukopenia?] and you don’t
get chromositophenia [chromocytom-
penia?]” (Tr. at 480).

\/ 5 . Hemoglobin Index

One set of labeling for “Laetrile
(Amygdalin),” which appears at two
points in the record, recommends the
product “for raising hemoglobin index

.Land red count * " "’ (R 183, Att. 9; R

‘ 201,Ex.C.No.I).

6. Reduction of Odor Associated with
Malignancy

It is also claimed that topical applica-
tion of Laetrile relieves fetor (odor) re-
sulting from the secondary infection of
ulcerated carcinoma and that parenteral
administration takes care of fetor as-
sociated with internal cancers. This ac-
tion is ascribed to the “antiseptic” prop-
erties of HCN and benzaldehyde, which
is converted by the cells to benzoic acid
(R 318 at 158 and 165).

7. Sickle Cell Anemia

It is theorized that nitriloside (Lae-
trile) might be of value in the treatment
of sickle cell anemia because of the re—
lease of cyanide and the subsequent
formation of thiocyanates (R 217, article
by R. G. Houston). (See also Tr. at 465.)
This claim is reportedly refuted by ex-
perts in sickle cell hemoglobin (R 416
at 23) .

t 8. Parasitic Diseases

The Houston article also references a
report by Navarro and others of the
clinical control of schistosomiasis (a

246-920 0 - 7B - 4

snail-borne infection) with nitriloside
(Laetrile) (R 217, Houston article at 58).
The possibility of using Laetrile to treat
parasitic diseases such as schistosomiasis
or malaria is discussed in the book Con-
trol for Cancer but there are no reports
of actual use in the book (R 318 at
111—12).

‘/ 9. Regulating Intestinal Flora

11

It has also been suggested that amyg-
dalin has some utility in regulating in-
testinal ﬂora (Tr. at 476).

V 10. Hypotensive Eﬁ‘ect

It has also been claimed that use of
Laetrile causes a hypotensive effect (i.e.,
it reduces blood pressure), at least in
cancer patients (R 318 at 165; cf. Tr.
at 465).

In addition to these claims by Laetrile
proponents (developers, distributors, and
promoters), numerous comments from
interested citizens contained references
to or claims for its therapeutic effects as
a cancer cure or as a preventative. There
are also references to relief, attributed
to Laetrile, from other ailments un-
related to cancer, e.g., arthritis (R 391).

D. THEORIES OF LAETRILE’S ACTION

A thorough understanding of the man-
ner in which a compound achieves its
therapeutic or beneﬁcial effects is highly
desirable. A cancer drug which had been
shown to be safe and effective would
not, however, be denied marketing ap-
proval simply because its action could
not be explained. Experience has shown
that a good theory to explain or predict
the action of a chemical in the body
does not assure success; neither does a
weak theory, or even what turns out
to be a totally incorrect theory, mean
certain failure.

I/ Some cancer patients may be turn-
ing to Laetrile in the mistaken belief
that its use is supported by a respectable
—even if not widely accepted—scientific
theory. (Unproven remedies throughout
the years have beneﬁted from the use of
the type of “scientiﬁc” theories asso-
ciated with Laetrile (see, generally, R
413).) The Commissioner ﬁnds from the
ecord that the theories advanced for
Laetrile’s supposed action are based on
false or questionable assumptions. An
‘understanding of these theories, further—
more, points up important differences be-
tween the “Laetrile” whose use is “justi-
ﬁed” by the theories of Krebs, Jr., and

Commissioner's Decision

the amygdalin-containing products ac-
tually being used.

Since a large part of the Laetrile
theory of action deals with enzymes, the
Commissioner believes that a few brief
introductory comments about enzymes
would be useful. Enzymes are protein
molecules manufactured in the cells of
the body which help the cells perform
chemical reactions involving other com-
pounds. As an example, trypsin, a com~
mon enzyme, aids in the metabolism of
proteins in food by breaking these large
molecules into smaller, easier—to-handle
pieces. Enzymes generally are very spe-
ciﬁc in the types of chemicals they will
attack. Frequently, the name of an en-
zyme is derived from the compounds that
enzyme will break down. The ending
“-ase” is often used to indicate an
enzyme.

The chemical “beta—glucosidase” ap-
pears frequently in the Laetrile record.
The name of this chemical indicates that
it is an enzyme (-ase) and, furthermore,
the name indicates that it attacks
glucose—containing compounds (gluco-
sides) from which it will liberate glucose
molecules. As an example, beta-glucosi-
dase liberates two molecules of glucose
from amygdalin. If the chemical com-
pound does not contain glucose mole-
cules, beta-glucosidase will not attack it.
In a similar vein, beta-glucuronidase will
attack chemical compounds that contain
glucuronic acid. (These chemical com-
pounds are called “glucuronides” or
“glucuronosides” or “glucuronic acid
derivatives”)

The original theory of Ernst T. Krebs,
Jr., for Laetrile’s action involved two
enzymes, rhodanese and beta-glucosi-
dase (R 318 at 72). Krebs claimed that
normal cells produced these two enzymes,
while cancer cells were deﬁcient in
rhodanese. In cancerous areas, the
theory continues, the beta-glucosidase
accumulates in great quantities (R 318 at
72).

According to the theory, when Laetrile
comes into contact with the cancerous
areas it is hydrolyzed by the enzyme
beta-glucosidase to liberate cyanide and
benzaldehyde. In normal cells, the en-
zyme rhodanese converts the liberated
cyanide to the less toxic thiocyanate.
Cancer cells, lacking rhodanese, are said
to be killed by the liberated cyanide
when it reacts with cellular components.
Rhodanese from normal cells cannot
protect cancer cells because, it is claimed,
cancer cells produce chorionic gonado-

12

tropic hormone that effectively blocks
the action of rhodanese (R 318 at 153).
In later versions of the theory, the benz-
aldehyde is also considered to be respon-
sible for killing the cancer cells, either
alone or in concert with the cyanide.
According to this theory, benzaldehyde is
normally converted by a cell to benzoic
acid by oxidation. Cancer cells are said to
oxidize the benezaldehyde at a slower
rate than normal cells, making it toxic to
cancer cells and nontoxic to normal cells.
(See Krebs, Jr., “The Nitrilosides (Vita-
min B—17)—Their Nature, Occurrence
and Metabolic Signiﬁcance (Antineo-
plastic Vitamin B—17)" (R 183, Att. 10c
at 80) .) 3

In fantithasbeen reported that only
traces of beta-glucosidases have been
found in animal tissues and even less in
experimental tumors than in such organs
as liverand spleemiR 173, Att., “Vitamin
Fraud” at 345). Apparently for this rea-
son, Krebs, Jr., at one time modiﬁed his
theory. In the modiﬁed version it is beta—
glucuronidase rather, than beta-gluco-
sidase which is abundant in cancerous
areas. This change is reflected in a 1955
pamphlet co-authored by Dr. Krebs, Sr.,
and Dr. Arthur T. Harris, in which it is
stated: “As soon as the Laetrile beta-
glucuronidase, which bathed the cancer
cell, because of its afﬁnity for sugar split
the glucoside (or sugar radical) from the
Laetrile molecule” (R 183, Att. 7 at 24).
(See also R 318 at 151—53.)

The change in theory is important.
beta—Glucuronidase hydrolyzes (breaks
down) beta—glucuronosides (or “beta-
glucuronic acids" or “beta-glucuron-
ides”) but does not hydrolyze beta—glu-
oosides (R 318, Att. 16 at 24). Thus,
beta-glucuronidase will hydrolyze “Lae-
trile” of the formulation devised by

2In his 1933 patent application for Sar-
carclnase, Dr. Ernst T. Krebs, Sr., discussed
his own theory of cancer, apparently now
abandoned by Laetrile proponents. He per-
ceived a malignant protein (“* ‘ ‘ a so-called
abnormal glucosido-protein " ‘ "’) in cancer
cells and explained why his enzyme extract,
prepared from apricot kernels, should be ef-
fective against those cells (R 424). He be-
lieved that the enzyme would break up the
abnormal gluco-protein and thus be an
effective treatment against cancer (R 318 at
40—41). While it is claimed that some positive
effects were observed in cancers in mice, the
extract proved to be toxic and Dr. Krebs, Sr.,
discontinued working on the extract (id. at
42).

Laetrile

Krebs, Jr. (i.e., laevo-mandelonitrile-
beta-glucuronoside), but it will not by-
drolyze amygdalin (D-mandelonitrile-
beta- D-glucosido-G-beta-D- glucoside)
or other “nitrolosides” found in nature.
What this means is that amygdalin,
which has been sold as “Laetrile,” would
not be hydrolyzed by the body to liber-
ate cyanide (R 183, Att. 16 at 41).
Recognition of this fact apparently
led Krebs, Jr., to formulate his version
of Laetrile in the ﬁrst place. He is re-
ported to have stated in a manuscript
that “the natural laetriles have been

abandoned for the more specific syn-
thetic laetrile tailored as speciﬁc glucu-
ronsidic substrates for the tumor beta-
glucuronidase” (R 183, Att. 16 at 14).

The speciﬁcity of beta-glucuronidase
for glucuronides (or glucuronosides) and
its lack of activity against glucosides
(such as amygdalin) is rigorously ad-
dressed in the record:

Numerous glucuronides are hydrolyzed by
beta-glucuronidase. * * * Mentyl-alpha-D-
glucuronide and alpha-and beta-methyl-D-
glucosides are not split by the enzyme.

Further checking of this important point
is consistent with the idea that the enzyme
in question (beta-glucuronidase) not hydro-
lyze the beta-glucosides, which are the only
Laetriles actually utilized by the Krebs’ for
human treatment (R 183, Att. 16 at 24).

(It should be remembered that the Can-
cer Commission of the California Medi-
_ cal Association had determined that the
material labeled “Laetrile” was in fact
amygdalin—a glucoside and not a glucu-
ronoside (R 378, Att. 15 at 326) .)

The conclusion seems justiﬁed that the
presence of the terminal carboxyi group on
position 6 appears to be the important fac-
tor in determining a speciﬁcity which is
markedly diﬁ‘erent from that of B. Gluco-
sidase " " ' (R 183,Att.16 at 25).

(The Commissioner points out that
amygdalin has two glucose molecules but
does not have a carboxyl group. Laetrile,
as reportedly prepared, described, and
named by Ernst T. Krebs, Jr., in the late
1940’s or early 1950’s (R 318 at 73) does
have a carboxyl group on position 6 (the
glucuronic acid portion of the mole-
cule) .)

Dr. Krebs, Sr., in his 1955 pamphlet
on Laetrile appears to recognize that
“animal beta—glucuronidase” and beta-
glucosidase are different substances.
(He characterizes the latter as a “pre-
pared enzyme.”) He does claim that the
two enzymes react with Laetrile in the
same manner (R 183, Att. 7 at 24).

13

There is some indication that Ernst
Krebs, Jr., in later years abandoned his
attempt to develop a Laetrile that could
be broken down by beta-glucuronidase
and began treating beta-glucuronidase
and beta-glucosidase as equivalent. In
a 1962 letter, Krebs, Jr., seems to refer
to the former as an example of the lat-
ter: “beta glucosidases (e.g., beta glu-
curonidase)” (R 183, Att. 16, App. 12 at
2) and seeks, in describing an experi-
ment with water ﬂeas he had designed,
to extrapolate results obtained with
beta-glucosidase to results with the beta-
glucuronidase he feels is found in malig-
nant lesions (id. at 4). (See also Krebs’
1970 article “The Nitrilosides (Vitamin
B—17)—Their Nature, Occurrence and
Metabolic Signiﬁcance (Antineoplastic
Vitamin B—17)” in which he again
equates beta-glucosidase with beta-glu-
curonidase (R 183, Att. 10c at 82).)

Three other problems with this theory
are quickly identiﬁable: (1) there is evi-
dence that beta-glucuronidase is not par- .
ticularly abundant in malignant tissues.
The record shows that “* * * beta-glu-
curonidase is found in all tissues of the

animal body and in particularly high

concentrations in spleen, liver, and en-
docrine organs, as well as in plasma and
in tumors arising from estrogen-inﬂu—
enced tissues. Per gram of tissue, the
spleen and liver have a higher concen-
tration of beta-glucuronidase than do
most tumors,” (R 183, Att. 16 at 15 and
App. 14). It is further stated, “Such a
statement as ‘* * * the malignant cell
* * * is virtually an island surrounded
by a sea of beta-glucuronidase’ is sheer
nonsense” (R 183, Att. 16 at 15 and App.
14).

(2) There is no evidence that cancer
cells are deﬁcient in the enzyme rhoda—
nese. In reviewing the record, the Com-
missioner has not found any support for
the bald assertion by the Krebs and other
Laetrile proponents that cancer cells are
deﬁcient in the production of a hydro-
gen cyanide-inactivating enzyme called
rhodanese. If there is any scientiﬁc sup-
port for that assertion, it is indeed
strange that it has never been cited by
the Krebs’ or otherwise brought to the
attention of the scientiﬁc community.
The record shows, in fact, that: “There
is no evidence of pronounced differential
between the rhodanese content of com—
parable normal and cancerous tissue” (R
378, Att. 9 at 346).

(3) The complete breakdown of Lae-
trile into cyanide may require an en—

Commissioner's Decision

zyme not-found mammal tissues. Hy-
drolysis of Laetrile by beta-glucuroni-
dase (and hydrolysis of amygdalin by
beta-glucosidase) only represents the
ﬁrst step in breaking down the molecules
to release hydrogen cyanide and benzal-
dehyde (which are supposed to kill the
cancer cell). The ﬁrst reaction in each
case would yield mandelonitrile plus (for
Laetrile) glucuronic acid or (for amyg-
dalin) glucose. Mandelonitrile must then
be hydrolyzed or broken down to yield
hydrogen cyanide and benzaldehyde (R
416 at ii 8) .

Enzymes present in apricot kernels
(speciﬁcally oxynitrilase) will hydrolyze
mandelonitrile to cyanide and benzalde-
hyde, but this enzyme is not reported to
exist in animal tissues (R 399 at 11 7B).
Nor does the record show that any other
enzyme capable of breaking down the
mandelonitrile exists in animal tissues
(or in malignant lesions). Thus, if Lae-
trile were injected into the blood stream
and did go tothe malignant lesion, even
if it were broken down into mandeloni-
trile and glucuronic acid, it might never
be further broken down to yield hydrogen
cyanide and the supposed action of that
substance in killing the cancer cell would
never take place.

At one time, Ernst T. Krebs, Jr., ap-
parently attempted to deal with some of
these problems .by separating out the
elements of the apricot extract his father
had prepared. The fact that both beta-
glucosidase and oxynitrilase are present
in apricot pits and thus in the extract
provides the potential for the whole
breakdown process to occur in the apricot
extract itself at the time when it is pre-
pared. Krebs, Jr., sought to prevent this
from happening (and perhaps sought to
reduce toxicity) by separating amygda-
lin from “emulsin” by purifying the apri-
cot extract. Emulsin contains, among
other things, beta-glucosidase and beta-
oxynitrilase (R 173, Att., “Vitamin
Fraud” at 345).

Ernst T. Krebs, Jr., reportedly sepa-
rated amygdalin from emulsin in 1952
and “ * * * advised their administration
separately in order to avoid the prema-
ture trigger-off of HCN (hydrogen cya-
nide) from the chemical breakdown in
the somatic (or normal) tissue ' * * ”
(R 183, Att. 7 at 23). It is further stated
that by injecting the cyanogenetic gluco-
side (amygdalin) followed 15 minutes
later by the enzyme beta—glucosidase
a “high degree of safety” as well as can-
cerolytic eﬁect was obtained (id. at

14

23—24) .

If the beta-glucosidase preparation
reached the same area of the body
that the amygdalin had reached, its
presence would lead to the breakdown of
amygdalin to release mandelonitrile (see
R 416 at ‘H 18; R 183, Att. 7 at 31). While
Ernst T. Krebs, Jr., apparently recom—
mended that the second injection be of
emulsin (R 183, Att. 7 at 23), Dr. Krebs,
Sr., states that his second injection would
consist only of the enzyme beta-glucosi-
dase (id. at 24). If the second injection
did contain emulsin, the presence of the
oxynitrilase in that complex might in
fact lead. assuming the emulsin caught
up with the amygdalin in the body, to
breakdown of the mandelonitrile to re-
lease hydrogen cyanide (and benzalde-
hyde). However, there is little reason to
believe that this release of cyanide would
occur only in or near tumor cells. (In
the same article in which Ernst T. Krebs,
Sr., explained the process of injecting the
beta-glucosidase, he stated his under-
standing that it was the beta-glucuroni-
dase “which bathed the cancer cell" that
acted to break down the amygdalin (id.
at 25).) It should be noted that, since
the time o: the 1955 pamphlet, no evi-
dence has appeared, at least in this rec-
ord, that two injections, one containing
beta-glucosidase, are being used in Lae-
trile therapy.

In light of the above, one must be con-
cerned that products are being used that
contain not only amygdalin but emulsin.
As the Krebs themselves recognized, un-
less emulsin is separated from amygdalin
(both of which exist in the apricot ex-
tract), there may occur the premature
trigger—off of HCN [hydrogen cyanide]
from the chemical breakdown in the so-
matic (or normal) tissue (R 183, Att. 7
at 23) . It is this type of cyanide poisoning
which has occurred from ingestion of
Laetrile and from eating apricot kernels.
(See R 378, California Morbidity, Nov.
14, 1975, No. 45.)

It is thus clear that the theory pro-
pounded by the promoters of Laetrile is
based on faulty and unproven assump-
tions. The invention of Laetrile as de-
scribed by Krebs, Jr., and his suggestion
that an injection of amygdalin be fol-
lowed by an injection of emulsin were
two different ways to deal with the fact
that enzyme beta-glucosidase does not
exist in human tissues. What is perhaps
most important about the proffered theo—
retical justiﬁcation for Laetrile’s action

Laetrile

is that, even if they were accepted, they
would not justify the administration of
amygd lin alone.

M Tm: “NEW DRUG" ISSUE

The ommissioner will now address the
ﬁrst of the two issues remanded to the
agency: Whether Laetrile is a “new
drug” within the meaning of the Federal
Food, Drug, and Cosmetic Act, 21 U.S.C.
301 et seq. (hereinafter the act). Based
upon a careful review of the administra-
tive record, as detailed below, the Com—
missioner ﬁnds that Laetrile is not gen-
erally recognized by qualiﬁed experts
as a. safe and effective cancer drug. Ac-
cordingly, the Commissioner concludes
as a matter of law that Laetrile is a new
drug and thus subject to the premarket
approval requirements of the act.

‘ “ The term “new drug” is deﬁned by sec-
tion 201(p) (1) of the act (21 U.S.C. 321
(p) (1)) as follows:

Any drug ‘ ' ' the composition of which
is such that such drug is not generally
recognized, among experts qualiﬁed by
scientiﬁc training and experience to evaluate
the safety and effectiveness of drugs, as safe
and effective for use under the conditions
prescribed. recommended, or suggested in the
labeling thereof " ' '.

Although the act deﬁnes “new drug", it
does not contain a deﬁnition of “generally
recognized as safe and effective."
1111973, the Supreme Court, in a series
of four cases [Weinberger v. Hynson,
Westcott & Dunning, Inc, 412 U.S. 609
(1973); Ciba Corp. v. Weinberger, 412
U.S. 640 (1973); Weinberger v. Bentex
Pharmaceuticals, Inc., 412 U.S. 645
(1973); USV Pharmaceutical Corp. v.
Weinberger, 412 U.S. 655 (1973)] involv-

ing the procedures adopted and utilized 4

by FDA to regulate new drugs pursuant
to the Drug Amendments of 1962 '76
Stat. 780) , established the legal principles
that are applicable and controlling here.
In Hynson, the Court discussed “general
recognition” as it pertains to the effec-
tiveness of a drug as follows:

The thrust of § 201(p) is both qualitative
and quantitative. The Act, however, nowhere
deﬁnes what constitutes “general recogni-
tion" among experts. ' r r We agree with
FDA, however, that the statutory scheme and
overriding purpose of the 1962 amendments
compel the conclusion that the hurdle of
"general recognition" of effectiveness re-
quires at least "substantial evidence” of
effectiveness for approval of an NBA. In the
absence of any evidence of adequate and well-
controlled investigation supporting the em-
cacy of [a drug]. a fortiori [that drug] would

15

be a “new drug" subject to the provisions of
the Act. 412 U.S. at 629—30.

‘ O D t t

We accordingly have concluded that a drug
can be “generally recognized" by experts as
effective for intended use within the mean-
ing of the Act only when that expert con-
sensus is founded upon “substantial evi-
dence” as deﬁned in §505(d). 412 U.S. at
632.

The term “substantial evidence" is de-
ﬁned in the last sentence of section 505
(d), 21 U.S.C. 355(d), as:

evidence consisting of adequate and well-
controlled investigations, including clinical
investigations, by experts qualiﬁed by scien-
tiﬁc training and experience to evaluate the
effectiveness of the drug involved, on the
basis of which it could fairly and respon-
sibly be concluded by such experts that the
drug will have the effect it purports or is rep-
resented to have under the conditions of use
prescribed, recommended, or suggested in

the labeling or proposed labeling thereof.

In Bentex, based upon its discussion

of the term “general recognition” in
Hynson, the Court concluded:
Whether a particular drug is a “new drug"
depends in part on the expert knowledge
and experience of scientists based on con-
trolled clinical experimentation and backed
by substantial support in scientiﬁc litera-
ture. 412 U.S. at 652.

It accordingly held that “the reach of
scientiﬁc inquiry under both section 505
(d) and under section 201(p) is precisely
the same” (id.).S

The requirements that a drug have not
only controlled clinical investigations
but also publication of the studies con-
cerning it in the scientific literature are
designed to assure that the community
of qualiﬁed experts in general is aware
of the data concerning the drug. Thus,
one could not obtain general recognition
just by doing the required studies with-
out publishing them in the scientiﬁc
literature, making them available to
other scientists. (Studies submitted to
scientific publications must undergo peer
review before they are published. A study

 

3Section 505(d) of the act (21 U.S.C. 355
(d)) sets forth the standards applicable to
obtain marketing approval of a new drug.
With respect to reports of investigations
which are required to be submitted concern-
ing the safety of a drug, the act provides
that such reports must include “adequate
tests by all methods reasonably applicable
to show whether or not such drug is safe for
use under the conditions prescribed, recom-
mended. or suggested in the proposed label-
ing thereof”.

Commissioner's Decision

published in a scientiﬁc journal is thus
more likely to form a basis for expert
recognition than is one published by the
lay press.) A practical effect of the
statutory system, as the Supreme Court
acknowledged in Hynson, supra, is that
drugs will have accumulated for them-
selves sufﬁcient scientiﬁc evidence to
justify approval of an NDA “long before
they are in a position to drop out of ac-
tive regulation by ceasing to be a ‘new
drug’ ” (412 US. at 631).

Under the Supreme Court’s authorita-
tive interpretation of the act, therefore,
general recognition of the safety and ef-
fectiveness of Laetrile depends upon two
criteria: (1) Controlled clinical investi-
gations conducted by qualiﬁed experts
establishing the safety and effectiveness
of the drug and published in the scien-
tiﬁc literature, and (2) expert consensus,
based upon that evidence, that the drug
is safe and effective. Both requirements
must be met in order for Laetrile to es-
cape the need for premarket approval
under the act; however, a ﬁnding of a
failure to meet either set of require-
ments is sufﬁcient to classify the drug as
a new drug.

With respect to the ﬁrst criterion, the
safety of Laetrile must be established by
adequate tests by all methods reasonably
applicable (see 21 U.S.C. 355(d) ; 21 CFR
314.111(a) (1) ). In addition, the effec-
tiveness of Laetrile must be established
by “substantial evidence,” which the
statute (21 U.S.C. 355(d)) deﬁnes as
evidence consisting of adequate and well-
controlled clinical investigations. (Clini-
cal investigations are studies involving
human beings as test subjects.) The re-
quirements for an adequate and well-
controlled clinical investigation are set
forth in 21 CFR 314.111(a) (5) (see dis-
cussion below). Both types of testing
must be available to the community of
experts in the evaluation of drug safety
and effectiveness by means of publica—
tion in the scientiﬁc literature.

For satisfaction of the second criterion,
a showing must be made of recognition
among the qualiﬁed experts which is
“general.” It has been held that a
genuine difference of opinion among ex-
perts on the question of general recogni-
tion is sufﬁcient to show that such recog-
nition of a drug’s safety does not exist
[see United States v. An Article of Drug,
Etc.. 294 F. Supp. 1307, 1311 (ND. Ga.
1968) aﬁ'd 415 F. 2d 390 (5th Cir. 1969);
United States v. 354 Bulk Cartons, Etc.,
178 F. Supp. 847, 853 (D.N.J. 1959);

Merritt Corp. v. Folsom. 165 F. Supp.
418, 421 (D.D.C. 1958) ]. This interpreta-
tion of “general recognition” has been
criticized as requiring “unanimous”
recognition (see United States v. 7 Car-
tons, More or Less, Etc., 293 F. Supp.
660. 662—63 (SD. Ill. 1968) aﬂ’d 424 F.
2d 1364 (7th Cir. 1970). For purposes of
completeness, the Commissioner in his
opinion will consider “general recogni-
tion” to require, as the 7 Cartons Court
suggested, recognition “extensively,
though not universally; most frequently,
but not without exception” (id.).

A. GENERAL RECOGNITION or EFFECTIVENESS
1. Objective Evidence of Effectiveness

The Courts thus have determined that,
as a matter of law, no “general recogni-
tion” of a drug’s effectiveness can exist
absent adequate and well-controlled
clinical investigations and substantial
support in the scientiﬁc literature. There
are no clinical investigations of Laetrile’s
effectiveness, published or otherwise,
which are even arguably adequate and
well-controlled. (See, e.g., R 185 at i] 19;
R 186 at 1112; R 390 at 11 19). For this
reason, Laetrile cannot escape “new
drug” status as “generally recognized” as
safe and effective. It is thus a new drug
without an approved new drug applica-
tion whose sale or distribution, where
interstate commerce is involved, is illegal.

There is, however, an apparent public
lack of understanding of what the re-
quired studies consist of and why they are
required. The Commissioner will thus
include in this opinion a discussion of
what adequate and well-controlled
studies are and why they are needed. He
will then discuss the deﬁcient “evidence”
of effectiveness submitted by Laetrile’s
proponents.

.. (a). What Are the Required Studies.

“(A) dequate and well-controlled clinical

investigations,” as those terms are used
in the act (21 U.S.C. 355(d)) are deﬁned
in detail by regulation (21 CFR 314.111
(a) (5) (ii) ). These regulations, discussed
with approval by the Supreme Court in
Weinberger v. Hynson, Westcott & Dun-
ning, Ina, supra, 412 US. at 617—19,
were upheld in Upjohn v. Finch, 422 F.2d
944 (6th Cir. 1970) and Pharmaceutical
Manufacturers Ass’n v. Richardson, 318
F. Supp. 301 (D. Del. 1970). Simply
stated, such investigations are designed
to determine whether an improvement
noted after administration of a drug is in
response to the drug or whether it is

(.

Laetrile

caused by some other factor. To do this,
patients as nearly identical in their
disease state as possible are divided into
groups and treated, insofar as possible,
exactly the same in all respects except
one: One group receives the test drug;
the other receives a placebo (a substance
that looks just like the test drug but is
not a drug). Since a patient might feel
better through knowledge of receiving
the test drug, and since the investigator
might subconsciously record better re-
sults because of the knowledge that he
or she were administering the test drug,
the experiment is “double-blind”:
Neither the patient nor the investigator
knows until after the experiment which
patient is getting the test drug and which
the placebo. If, at the end of the investi-
gation, the patients receiving the drug
did better than those not receiving it, one
can be fairly certain that it was the drug
and not some other factor that caused

, the improvement.

(b) The Need for Controlled Studies.
In 1962, the Congress of the United
States, after extensive hearings,‘ con-
cluded that testimonial evidence of a
drug’s effectiveness—even including tes-
timonials and illustrative “case histories"
by physicians—was simply not reliable. It
passed the law requiring that effective-
ness be shown by “adequate and well-
controlled clinical investigations” which
is discussed elsewhere in this opinion.

The Supreme Court examined this
issue closely in 1973 and determined that
Congress’ decision and FDA’s enforce-
ment of that decision were supported by
the evidence elicited at the congressional
hearings:

[The FDA’s] strict and demanding stand-
ards, barring anectodal evidence indicating
that doctors “believe” in the efﬁcacy of a
drug, are amply justiﬁed by the legislative
history. The hearings underlying the 1962
Act show a marked concern that impressions
or beliefs of physicians, no matter how fer-
vently held, are treacherous. (emphasis
added).

Weinberger v. Hynson, Westcott & Dun-
ning, Inc., supra, 412 U.S. at 619. It
noted:

*See, e.g., Hearings on S. 1552 before the
Subcommittee on Antitrust and Monopoly
of the Senate Committee on the Judiciary,
87th Cong., lst Sess., pt. 1, at 195, 282, 411—
12. For a detailed discussion of the Con-
gressional decision in 1962 to require ade-
quate testing of drugs' effectiveness, see
Pharmaceutical Manufacturers Ass'n v. Rich-
ardson, supra, 318 F. Supp. at 306 et seq.

the conclusion of Congress, based upon hear-
ings, that clinical impressions of practicing
physicians and poorly controlled experiments
do not constitute an adequate basis for es—
tablishing efﬁcacy.

(id., 412 U.S. at 630). '

Since both the Congress and the Su-
preme Court have spoken on this ques-
tion, no further discussion by the Com-
missioner of the need for adequate and
well—controlled studies," rather than re-
liance on testimonial evidence, to show
a drug’s effectiveness is legally necessary.
However, there is a continued public
belief in testimonial or anecdotal evi-
dence, fostered even by the lawyer of one
of Laetrile’s supporters. (See oral argu-
ment of Kenneth Coe, in which he con-
tends that the safety and effectiveness of
Laetrile has been shown by ”anecdotes
of people who have been diagnosd as
terminal with cancer, anecdotes of peo-
ple who have been cured of cancer, anec-
dotes of people who are walking around
today, that are here today-nwell" (Tr.
at 453).) For this reason, the Commis—
sioner will discuss the evidence in the
record illustrating the need for scientiﬁc
studies to show a drug’s effectivness.

In his afﬁdavit (R 175, Ex. A at ﬂ 3),
Dr. William Beaver, an expert in drug
testing, notes that critics of well-con-
trolled studies “often point out the un-
disputed fact that great strides have
been made in therapy in the past without
the beneﬁt of this experimental device,
but simply on the basis of the uncon-
trolled observations of astute clinicians
* * *. [However], these critics often fail
to mention the thousands of drugs which,
on the basis of ‘clinical experience,’ were
once accorded an ‘indispensable place’
in therapy, and which are now known
to be useless.” Dr. Beaver states (id, at
1M): “The function of the controlled
clinical trial is not the ‘discovery' of a
new drug or therapy. Discoveries are
made in the animal laboratory, by chance
observation, or at the bedside by an as-
tute clinician. The function of the formal
controlled clinical trial is to separate the
relative handful of discoveries which
prove to be true advances in therapy
from a legion of false leads and unveri-
ﬁable clinical impressions, and to delin-
eate in a scientific way the extent of

'-'>It should be noted that other types of
testing are required to show a drug’s safety,
some of which must be completed before
clinical investigations to show effectiveness
can begin. (See 21 U.S.C. 355(d) .)

Commissioner's Decision

and the limitations which attend the ef-
fectiveness of drugs.” See also afﬁdavit of
Bryant L. Jones (R 431 at 118): “Most
medical mistakes of past centuries were
a direct result of beliefs that were pred—
icated on conviction rather than evi-
dence. Most medical advances in modern
times can be traced directly to the scien-
tists insistence on valid scientiﬁc evidence
to support use of today’s drugs.”

Because of the insidious nature of can-
cer. it is all the more important that the
effectiveness of a drug purported to be
useful in the treatment of cancer be
demonstrated by well—controlled clinical
studies and not solely by testimonials or
anecdotes. Cancers in humans vary
greatly in their behavior, i.e., their rate
of growth, pattern of spread, effects on
the normal organs of the person, and the
types of clinical symptoms or signs they
produce. There is wide variability in the
pattern of spread and the outcome for
an individual. The effects of cancer on
an individual have an element of rand-
omness, that is, an element of chance.
Physicians are therefore simply unable
to predict the outcome of any cancer at
any stage of development with great ac-
curacy. Patients with terrible and widely
spread cancer will occasionally have
miraculous or unexpected remissions of
the disease. Untrained clinical investiga-
tors who administer any remedy to a
large enough group of patients with can-
cer will ultimately observe a miraculous
outcome. This apparently miraculous
outcome may well mislead the untrained
investigator into belief that the remedy
was responsible for the result (R 390 at

it 14—15).

It has been noted above that, in an
adequate and well-controlled study, nei-
ther the patient nor the investigator is
told that the test drug is being adminis-
tered because, if they knew, they might
report results based merely on high ex-
pectations. This problem of assigning im-
provement to a drug when the improve-
ment was simply a result of high expec-
tations is known as the problem of the
“placebo effect.” The placebo effect
is particularly common in cancer pa-
tients. A study of the placebo effect
among 288 cancer patients undergoing
controlled trials of oral analgesics
showed that 112 patients received 50 per-
cent or greater relief from placebo (i.e..
nondrug) formulations (R 186 at ‘H 13)

In his afﬁdavit (R 185 at ‘H 20f) Dr.
Daniel S. Martin states: “Humans are
very susceptible, particularly when ill

18

and desperate with hope, to the power of
positive suggestion—namely, when given
a ‘drug’ by an authority ﬁgure (e.g., a
physician) with the ﬁrm statement and
promise they will now begin to feel better,
to have pain relief, to eat better, and to
get well, these hopeful patients fre-
quently do just what they have been told
to expect.” This, Dr. Martin states “is
termed the placebo effect.” Dr. Martin
also explains that “Cancer is a chronic
disease which some patients can live with
for years before dying of the disease.
During this slow death there are periods
of ‘ups’ as well as ‘downs,’ and it is not
surprising to have a Laetrile patient
ascribe the ‘up’ to Laetrile, when it was
merely coincidental timing” (id.). Simi-
larly, Dr. Carl M. Leventhal states (R
184 at i 7): “(P)sychogenic responses,
popularly known as the placebo effect,
are well documented and have been
shown to occur from 30 to 70 percent
of patients who are treated for pain.”

The need for controlled testing as op-
posed to testimonial or ancedotal evi-
dence of effectiveness is well-recognized
by experts in the evaluation and use of
drugs. As Dr. Bayard H. Morrison states:
“The problem is the anecdote doesn’t
permit you to know what happened yes-
terday. It doesn‘t permit you to know
what is really going on today and cer-
tainly it doesn’t give you any insight at
all in what will happen to a given pa-
tient tomorrow, next week, or next year.
To really know what a drug, any treat-
ment, does to a patient you have to be
able to evaluate him in the context of a
large group whose disease you can follow
carefully over a considerable period of
time” (Tr. at 150).

(c) The "Evidence” of Laetrile’s Ef-
fectiveness. (i) Case Reports—The pro-
ponents of Laetrile (or amygdalin) have
not submitted anything to the record
that could be characterized as an ade—
quate and well-controlled clinical study
of Laetrile. In the regulation which de-
ﬁnes adequate and well-controlled clin-
ical investigations, it is clearly stated
that: “Isolated case reports, random
experience, and reports lacking the de—
tails which permit scientiﬁc evaluation
will not be considered,” even as corrobo-
rative evidence for adequate and well-
controlled studies (21 CFR 314.111(a)
(5)(ii) (0)). Yet that kind of report is
the only “evidence” of Laetrile‘s ef-
fectiveness which has been submitted.

Because of the possible public belief in
this kind of report, the Commissioner

Laetrile

will discuss those submitted to this rec-
ord. In addition, evaluations, submitted
to the record. of earlier “case histories”
or testimonials relating to use of Lae-
trile will be discussed.

' ’01) Reports Submitted to This Record
(1) Dr. Binzel

Phillip E. Binzel, Jr., M.D., Scientiﬁc
Advisor to the Committee for Freedom
of Choice, and in private practice as a
family physician since 1955, appeared at
the hearing to make an oral presentation
(Tr. at 360-364) and to submit written
testimony (Tr. Ex. 13). Dr. Binzel’s sub-
mission at the hearing (id.) was a re-
port of a study he conducted on more
than 200 cancer patients to whom he
administered a nutritional program, in-
cluding Laetrile. Dr. Binzel stated that
he had excluded from his report the
following patients: “1: Those who were
alive but who had been under treatment
for less than 4 months. 2: Those who
had died within the ﬁrst 3 months of
treatment. These are the patients whose
disease was already too far advanced
for any form of treatment to be benefi-
cial ‘ ‘ ‘. 3: Those on whom there is
not sufficiently adequate follow-up in-
formation to know for certain what their
present condition is” (id.) .

After the above exclusions, there re-
mained 107 patients in Dr. Binzel’s study
who had been treated between 4 months
and 21/2 years and who, according to
Dr. Binzel, “are spread pretty equally
throughout those time periods” (id.). He
reported that 57 patients had primary
carcinoma, and 50 patients had proven
metastatic carcinoma at the time they
started “nutritional therapy” ( id.) .

Dr. Binzel’s exclusion from his study
of patients for whom adequate followup
information could not be obtained can
be expected to exclude those patients
who were dissatisfied with Laetrile treat-
ment and left his care. That exclusion,
together with the exclusion from con-
sideration of patients who died within
3 months of the ﬁrst treatment, would
be expected to bias the study in favor
of effectiveness.

Dr. Binzel states that he “did not at—
tempt to differentiate between those pa-
tients who have had surgery and/or
cobalt and/or chemotherapy and those
who had none of these ‘conventional’
treatments” (Tr. Ex. 13, “Nutrition and
the Cancer Patient” at 2). This, as Dr.
Binzel notes, presents a “very valid ques-
tion.” Without knowing whether the pa-

246-920 0 - 7B - 5

19

tients in whom he saw improvement had
had other, recognized effective, treat-
ments, his conclusions cannot be eval-
uated (cf. 21 CFR 314.111(a) (5) (ii)
(a) (2)(iii)).

Dr. Binzel’s three-page “study,” which
was submitted without supporting doc-
umentation, simply lacks the details
necessary to permit scientiﬁc evalua-
tion and would not, for that reason, be
considered by experts in drug evaluation
even as corroborative of adequate and
well-controlled studies if such studies
existed (21 CFR 314.111(a)(5)(ii)(c)).

(2) Dr. Richardson

Edward Grifﬁn, at the oral argument
in this proceeding, submitted page proofs
of a book entitled Laetrile Case Histories,
The Richardson Cancer Clinic Experi-
ence by John A. Richardson and Patricia
Grifﬁn (Tr, Ex. 1.) Grifﬁn stated: “Pre-
viously the opponents of Laetrile have
said that there is no evidence that Lae-
trile works. There has been evidence of
course, known to those of us who have
been close to the subject, But admittedly,
there has not been a great deal of medi-
cally documented evidence open to the
public. And I believe that with the pub-
lication of this book at least we will be
able to put an end once and for all to this
claim of there not being any evidence"
(Tr. at 15—16). Dr. Richardson does not
claim to have conducted a research pro-
gram, and his case histories in no way

even approximate an adequate and well-~

controlled clinical investigation.

Dr. Richardson’s license for the prac—
tice of medicine has been revoked by the
State of California (R 183 at 13) because
he was found to have discouraged pa-
tients from seeking conventional therapy
and to have practiced a type of treat-
ment of cancer patients characterized as
“an extreme departure from the stand-
ard practice of medicine” (R 179, Ex. B
at 5). The California State Board of
Medical Quality Assurance stated that
these two ﬁndings established “gross
negligence” on the part of Dr. Richard-
son (id. at 10). Dr. Richardson did not
choose to appear in the administrative
proceeding in which his license was
ordered revoked (id. at 1—2).

A number of obvious questions are
raised by Dr. Richardson’s book: (1)
There is no indication in this book—nor
is there in the other reports in this sec-
tion—of the chemical composition of the
“Laetrile” which was used. Since there
are variations in the composition of the

[l/

Commissioner's Decision

drugs called by the name “Laetrile,” this
fact leaves the reader with no certainty
as to what substance is claimed to be
effective.

(2) The technique for selecting pa-
tients for reporting is hardly scientiﬁc.
The book states: “Out of [a group of
approximately 4,000 cancer patients], we
selected a cross-section of about 500 for
our study. We were able to establish con-
tact and a working relationship with
only about 250 of these. The cases with
the weakest medical histories were dis-
carded, as were those which were overly
repetitious. The remainder [62] are con—
tained in the study; but by no means do
they represent our entire files” (Tr. Ex. 1
at 118—19).

It is absolutely incredible that anyone
would expect to show the effectiveness of
Wat—describing 62 out of over 4,000
patients “with a selection process of the
type Richardson describes. The Commis-
sioner has no means of knowing what
happened to the other 3,938 or more pa-
tients. No details are given to show how
the 500 patients representing a “crOss—
section” of the 4,000 were chosen. The
failure “to establish contact and a work—
ing relationship” with half of the pa-
tients that were chosen illustrates a seri—
ous lack of followup. Logic suggests that
th0se patients who were not beneﬁted by
Laetrile would be less likely to be willing
to develop a “working relationship” with
Dr. Richardson’s ofﬁce. Clearly patients
who had died would not be available for
such a relationship. The discarding of
weak medical histories has never been
an accepted practice in the study of any
drug. What constitutes the weakness of
a medical history is not explained.

(3) There is some question whether
what Richardson claimed to be positive
effects were in fact positive. The authors
admit that one of the weaknesses of the
study is the shortage of cases involving
5-year survival or longer (Tr. Ex. 1 at
120).

Indeed, the case histories section of the
book (Tr. Ex. 1 at 126—276) list for each
of the 13 different groupings of cancer
the expected death rate for those cancers
in terms of percentage survival over a set
number of years, usually 5 years. Many
of the patients simply had not survived
long enough at the time of the book’s
writing to constitute successes.

For example, six cases of female breast
cancer are reported (Tr. Ex. 1 at 126—
137). According to Dr. Richardson, these
women have received metabolic therapy,

20

including Laetrile. for periods varying
from 13 to 32 months with an average of
less than 21 months. Since Dr. Richard—
son states (Tr. Ex. 1 at 126) : “Two out of
every 3 patients with cancer of the breast
who do not use Leatrile but choose in-
stead to submit to orthodox therapies
will be dead within five years,” the fact
that he has six patients who have sur-
vived 13 to 32 months with a mean of
less than 21 months does not provide any
evidence of the effectiveness of Dr.
Richardson’s treatment.

Dr. Richardson recognizes that some of
the patients whom he has selected may
not have had cancer. See, e.g., Tr. Ex. 1
at 148, patient B1381 where Dr. Richard-
son, in discussing the chest x-rays of a
patient, states that the period of May 73
to January 77 represented: “A three:
and-one-half—year remission of. probable
cancer of the lung.” (emphasis added).
For several other patients, Dr. Richard-
son does not quote from the pathology
report but merely reports that such a re-
port was positive for cancer (see, e.g.,
patient P1318 (Tr. Ex. 1 at 167)).

(4) Dr. Richardson relies in many in-
stances upon what patients have toldhim
about their medical histories, either
orally or in writing. Some patient reports
upon which he relies are hardly credible.
(See, e.g., patient ClOGMA (Tr. Ex. 1 at
146) : “The patient states the local doc-
tors strongly recommended removal of
both lungs and the permanent hospitali-
zation of the patient, who then would be
forever dependent on machines to do her
breathing")

(5) Some patient reports are so
sketchy as to provide no basis for any
conclusion. See, e.g., patient B144J (Tr.
Ex. 1 at 202—203: There is no information
regarding how the diagnosis of cancer
was made. There is no indication that
Dr. Richardson ever characterized the
size of the tumor or whether he relied
on the patient’s description. There is no
indication whether the patient had re-
ceived any Laetrile since January 1970.
There is no indication that there has
been any contact with the patient since
February 1976.

(6) As noted above, for each of the
13 groups of cancer which Dr. Richard-
son has used in his book he cites the
anticipated fatality rates for patients re-
ceiving only orthodox treatment. As dis-
cussed elsewhere in this opinion, cancers
are very different in their behavior, i.e.,
their rate of growth, their pattern of
spread, their effects on the normal

organs of the person and the types of
clinical symptoms or signs that they pro-
duce (R 390 at 1! 14). Experts in the test-
ing of cancer drugs stress that the effects
of cancer on a person have an element
of randomness and that the ability to
predict the outcome of any cancer at any
stage of development varies (id). In
light of the regularity with which cancer
patients’ diseases vary from their ex-
pected courses, it would have been sur-
prising if Dr. Richardson were unable to
report that 62 out of 4,000 (c. 11/2 per-
cent) of patients he saw had remissions
for periods of up to, but often much
shorter than, 5 years.

Thus, the Richardson book is not only
not the kind of adequate and well-
controlled clinical investigation neces-
sary to show the effectiveness of a drug.
it is not even on its face a particularly
credible recounting of medical case his-
tories.

(3) Dr. McDonald

Lawrence Patton McDonald, M.D., a
urologist, and a member of the United
States House of Representatives, sub-
mitted a statement in which he reported
the following observations after treating
almost 200 cancer patients (R 509 at 3) 2

“(1) Most patients had proven cancer
and had had surgery and radiation
and/ or chemotherapy. Most cases would
have been hopeless by routine medical
standards.

“(2) Perhaps 30-35% received mini-
mal to no beneﬁt from the program.

“(3) Approximately 40—45% received
notable beneﬁts from the program such
as improved appetite, improved interest
in life, weight gain, lessening or cessa-
tion of pain. This category ultimately
died but were individually pleased with
their improvements.

“(4) About 20% were in the category
of marked improvement. In some cases
this has been miraculous with these
same patients doing very well today.”

Dr. McDonald provided no details what-
soever other than those quoted above.
Dr. McDonald’s report was not, nor does
it appear to have been submitted as, an
adequate and well-controlled clinical
investigation.

(4) Dr. Soto

Although Dr. Mario H. Soto appeared
and testiﬁed (Tr. at 478—481) at the oral
argument and was given an opportunity
(Tr. at 481) to submit for the record
data from his treatment of cancer pa-

Laetrile

21

tients with Laetrile. no data have been
received from him.

(b) Case Reports Evaluated Previously

Much of the evaluation of case reports
has been done in California, where Lae-
trile originated and was, along with a
number of other “unproven” remedies.
responsible for the 1959 passage of a
State law aimed at cancer quackery. In
1952, the Cancer Commission of the Cali-
fornia Medical Association collected in-
formation on 44 patients treated with
Laetrile, all of whom either had active
disease or were dead of their disease.
with 1 exception. In some instances, the
members of the Cancer Commission had
the opportunity of seeing the patients
thus treated. The conclusions of the
Cancer Commission were that, of those
alive with disease at the time of the
study, no patient had been found with
objective evidence of control of cancer
under treatment with Laetrile. Nine pa-
tients who died from cancer after treat—
ment with Laetrile were autopsied. His-
tological studies done for the Commis-
sion by ﬁve different pathologists showed
no evidence of any chemotherapeutic
effect (R 378, Att. 15 at 320—326; R 183,
Att. 16 at 2—19 and App. 2—3).

In June 1962, the Cancer Advisory
Council of the State of California De-
partment of Public Health examined a
total of 35 case histories of cancer pa-
tients treated with Laetrile. The Council
unanimously judged these cases inade-
quate for any critical evaluation of Lae-
trile. “Many of the cases had received
orthodox treatment; objective evidence
of beneﬁt was absent or insufficient,
most of the documentation (dealt) with
subjective improvement; some contained
no pathological proof of malignancy;
many were 1961 cases without followup;
the duration of treatment was frequently
unknown because the data reported the
period of hospitalization only and often
discharge dates were not shown" (R 183.
Att. 16 at 30—31).

Thirty-six clinical records translated
into English from the French were evalu-
ated by the Cancer Advisory Council in
December 1962. The Council reached the
following conclusions:

1. The records failed to indicate that the
patients treated with Laetrile secured either
palliation or regression of their cancerous
ailliction as a result of the therapy.

2. In several instances, there was absolutely
no evidence presented as to the response of
the patient to the therapy.

3. In other instances, objective evidence

Commissioner’s Decision

documenting the statement of beneﬁts, was
not provided.

4. In one group of 17 of these cases, sufﬁ-
cient followup was absent. The longest period
of followup was 14 months, 12 days and 23
days of hospitalization. The next longest was
381 days and the last was 127.

5. Results which were reported as “im-
proved" were without meaning since no
criteria. subjective or objective, were pro-
vided.

6. The evidence presented lends no cre-
dence to the alleged efﬁcacy of Laetrile and
Vitamin B15 in the treatment. durative or
palliative, of advanced cancer (R 183, Att.
16 at 34—35).

In preparing its 1963 report, the Can-
cer Advisory Council also reviewed about
16 pounds of documentary material de-
livered by Laetrile proponents. The ma-
terial contained a total of 63 case his-
tories. 15 of which were submitted by
two doctors in the United States (Dr.
Ray Evers, Allusia, Ala... and Dr. John
R. Morrone, Jersey City, N.J.) .

The opinion [of the Cancer Advisory Coun-
cil] on review of these cases is that they give
no credence to the claimed curative effects
of Laetrile in human cancer nor in those
animal cancers where it had been investi-
gated. The evidence of palliative response,
both subjective and objective, is tenuous and
poorly documented. Except in the cases in
which death intervened and one or two
others in which there was questionable diag-
nosis of cancer, no followup has been re-
corded, with the result that the ﬁnal out-
come of the cases is not recorded (R 183,
Att. 16 at 35—88).

In January 1963, the McNaughton
Foundation and the North End Medical
Center, both in Montreal, Canada, sub-
mitted to the Cancer Advisory Council
of the California State Department of
Public Health a total of 14 clinical rec-
ords on patients treated with Laetrile.
These were not complete records but
were abstracts furnished by various hos-
pitals in Canada to the McNaughton
Foundation. The Cancer Advisory Coun-
cil appointed a committee of three physi-
cians highly qualiﬁed and actively en-
gaged in the treatment of cancer to re-
view and evaluate these records. Each
igjhysician made an independent evalua-

on.

The committee reported: “These 14
records provided by the McNaughton
Foundation were examined and fail to in-
dicate that the patient treated with Lae-
trile secured either palliation or regres-
sion of their cancerous aﬂiliction as a.
consequence of the therapy. In several in-
tances, there is absolutely no evidence

22

presented as to the response of the pa-
tient to the therapy and in other in-
stances objective evidence which docu-
ments claims of beneﬁt is not provided.
It is concluded from careful review of
these records that they are inadequate as
reports of therapeutic use of Laetrile, and
they do not indicate that therapeutic
beneﬁt resulted from treatment with
Laetrile, and do not indicate that this
agent is of value in the treatment, cure,
or palliation of cancer. In only one in-
stance is there a statement by the ex-
amining physician indicating that a
deﬁnite beneﬁcial effect from Laetrile
might have occurred” (emphasis in orig-
inal) (R 378, Att. 14 at 26).

In 1971—72, the FDA, together with the
National Cancer Institute, investigated
and evaluated 12 clinical histories sub-
mitted by Dr. Ernesto Contreras of Mex-
ico covering his experience with Laetrile
in the treatment of cancer (see R 184, Ex.
3). FDA was able to obtain documenta-
tion covering the full course of the disease
in 7 of the 12 case reports. All seven pa-
tients whose records were reviewed had
received treatment other than Laetrile,
including surgery, chemotherapy, or ra-
diotherapy, or more than one of these
approaches, either before, after, or con-
currently with Laetrile therapy (R 184,
Ex. 3: R 198 at 9-10).

Most of the alleged improvements
stated, in the 7 case reports which could
be evaluated, to be associated with Lae-
trile treatment have been found to be as-
sociated with one or more of the follow-
ing events in the patient's disease (see
R 183. Att. 16 at 10—11):

a. Subjective improvement was interpreted
as being evidence of the agent's affecting the
neoplasm, rather than being due to the gen-
eral effect on the host, whether by metabolic
or psychologic reasons.

b. Phases in the natural history of malig-
nant neoplasm not infrequently observed in
patients who are receiving no treatment
whatever were interpreted as being due to the
therapy employed (emphasis in original).
‘ " * lFor example,] occasional patients
with widespread peritoneal carcinomatosis
will exhibit regression of their disease follow-
ing simple exploratory procedures.

c. Patients reported as showing regression
of cancer with Laetrile were either receiving
concurrent treatment by other methods, or
had in their recent past been treated by some
[orthodox therapy] and were exhibiting a
degree of control of their disease entirely at-
tributable to the previous treatment (em-
phasis in original). " r ‘

d. A few of the patients treated did not
have proof of the presence of cancer in the
form of histological diagnoses, the evidence

Laetrile

being more or less inferential, as radio-
graphic observation of lesions in the lung,
or a surgeon’s diagnosis of a lesion as can-
cerous on observations of gross pathology
at operation, without conﬁrmation with
biopsy.

e. Very few of the clinical records to which
the Cancer Commission had access contained
any sort of satisfactory evidence as to ob-
jective, accurate evaluation of the progress
of the primary neoplasm or its metastases
while under treatment.

(ii) Animal Testing of Laetrile—As
indicated elsewhere in this opinion, gen-
eral recognition of Laetrile’s effective-
ness among experts in the evaluation of
drug effectiveness could only be based
upon adequate and well-controlled clin-
ical (i.e., human) investigations. Thus,
even if Laetrile had been shown to be
eﬁective in animal_tes_t systems, and the
Commissioner concludes it has not, that
fact would not remove Laetrile from the
category of “new drug.”

Nevertheless, in the interest of pro-
viding the public with all the informa-
tion available in the record concerning
this drug, the Commissioner will discuss
the animal tests done with amygdalin
about which there is controversy. Amyg-
dalin has been extensively tested in an-
imal systems. From the tests done, Dr.
Dean Burk, president of the Dean Burk
Foundation, Inc., has selected three tests
done in the United States as showing a
positive effect (R 302) . In each case the
laboratories which ran the tests found
them to be negative. Dr. Burk also cites
two foreign reports, one of which was
not published (id.) . His contentions, and
the evidence relating to each in the
record, will be discussed point by point
and other animal testing done with the
drug will be noted.

(a) Tests Claimed to Show a Positive
Eﬂect

( 1) Sloan-Kettering

Dr. Burk includes the following in his
list of animal studies showing a positive
effect for amygdalin:

Sloan-Kettering Cancer Center (New
York), with CD51”l mice bearing spontaneous
mammary carcinomas: Inhibition of forma-
tion of lung metastases, inhibition of growth
of primary tumors, and greater health and
appearance of animal hosts, upon treatment
with 1—2 gm crystalline amygdalin/kg body
weight/day (Report of K. Sugiura, June 13,
1973) (R 302, Ex. A at 15).

Regarding the studies conducted at
Sloan-Kettering, C. Chester Stock, Ph.
D., Vice President and Associate Director

23

for Administrative and Academic Affairs,
Sloan-Kettering Institute for Cancer Re-
search, stated in his afﬁdavit (R 195)
that:

We have tested amygdaiin at high doses.
1000 mg/k/day, in over a dozen transplant-
able tumor systems and one induced tumor
system without seeing any action against
the tumors. The chemotherapeutic agents ef-
fective in clinical cancer have had or would
have had their activities detected in one or
more of those systems.

In spite of demonstrated utility of trans-
planted experimental animal tumor systems,
some individuals believe that use of spon-
taneous animal tumors is more appropriate
for seeking drugs for use in man. It was
considered that this would be true of the
advocates of the use of Laetrile who believe
it needs to be used for relatively long pe-
riods of time.

Consequently, Dr. K. Sugiura in my labora-
tory looked for the effects of amygdamn on
the growth of spontaneous mammary tumors
in CDXFI, mice and also on metastatic spread
to lungs of the hosts. Early observations of
Sugiura featured an apparent inhibition of
the appearance of metastases in the lungs of
mice given daily (except Sunday) doses of
2000 mg/k of amygdalin in his 3 initial ex-
periments. The treated mice showed lung
metastases in 20% while 80% of the controls
had metastases. The mice had been injected
until death or until the primary tumors were
over 2.5 cm in diameter. The data from these
experiments were leaked to the press un-
fortunately before they could be checked
adequately. Subsequent experiments, in some
of which Dr. Sugiura participated, some con-
ducted with Dr. Daniel Martin of the Catho-
lic Medical Center of Brooklyn and Queens
and some which were independent by other
investigators in our Institute, showed that
the initial results were not consistently ob-
servable. In some experiments there were
more metastatic mice in the treated than
in the control mice. In the latest experiment
in which Dr. Sugiura read the lungs of the
mice without knowing what treatment they
had received, there was essentially no dif-
ference found between the'tmted and con-
trol groups (R 195 at TI 10) .

In his afﬁdavit (R 185), Daniel S.
Martin, M.D., states that: “My labora-
tory's tests with Laetrile demonstrated
Laetrile to be without effect (on spon-
taneous tumors in experimental ani-
mals). Further, these negative tests on
these animal tumors were conﬁrmed by
three other investigators at Memorial
Sloan-Kettering Cancer Center in New
York. One of the latter investigators (Dr.
K. Sugiura) reported his initial experi-
ments to demonstrate Laetrile to have
anti-cancer activity, but his subsequent
results were negative. A degree of vari-
ability in resul‘.s is common in biological

Commissioner's Decision
A .

research, and the ﬁnal opinion is based
on whatever the majority of the ﬁndings
are. Inethisdnstancepthe totality of the
data clearly and unequivocally reveals
Laetrile to be without anti-cancer acti-
vity” (R 185 at 11 21 (c—d) ).

(2) Southern Research Institute

Dr. Burk’s citations continue:

Southern Research Institute (Birmingham,
Alabama) for the National Cancer Institute,
in a majority of 280 BDF'1 mice bearing
Lewis lung cancers, treated with up to 400
mg crystalline amygdalin per kg body weight.
with respect to increased life span (Report,
December 3, 1974) (R 302, Ex. A at 15).

The results of two studies conducted
by Southern Research Institute for the
National Cancer Institute were published
in the scientiﬁc literature in 1975. One
of the studies-involved an experiment
“in which four transplantable rodent tu-
mors (L1210 lymphoid leukemia. P388
lymphocytic leukemia, Bis melanoma,
and Walker 256 carcinosarcoma) were
used to investigate the antitumor activity
of amygdalin MF ‘ ' " alone and in com-
bination with beta-glucosidase" (R 184,
Ex. 3b at 939) . Neantitumor activity was
obsewed. iii-any oi thefour tumor sys-
tems tested with amygdalin alone or in
combination with beta-glucoeidase (id.;
see also R 173, Att, Memorandum,
March 12, 1973) .

The second study, in which amygdalin
MF (i.e., amygdalin provided by the
McNaughton Foundation) was evaluated
alone or in combination with beta-glu-
cosidase against three transplantable ro-
dent tumors (Ridgeway osteogenic sar-
coma, Lewis lung carcinoma, and P388
leukemia), showed that amygdalin alone
or in combination with beta-glucosidase
did not demonstrate antitumor activity
against any of these three tumor systems
(R 184, Ex. 30 at 952—53).

At the oral argument, Bayard H. Mor-
rison, M.D., Assistant Director at the
National Cancer Institute stated that the
Institute:

has sponsored—other organizations have
conducted—tests of Laetrile at various dos-
age levels in a variety of animal tumor sys-
tems, probably exceeding 15 or more, prob-
ably cioser to 20.

This indeed really is about the most exten-

, sive that NCI and other laboratories in the

' mas, sarcomas,

aggregate have tested of essentially a non-
active substance. For in all of these tests
which include tumors ranging from carcino-
lymphomas, any kind of

' tumor which parallels to a large degree the

human type 01' tumor. the results have been

24

/ essentially negative. There have been occa-
r sional, marginal evidences of activity which
\have not been reproducible.

So, in balance, Laetrile has failed the test
of demonstrating activity in the preclinical
animal tumor systems that we know now
predict for activity in human cancer.

And I should add that of the 30 or 40 drugs
that are now regularly available and known
to have eil'ect in certain forms of human
cancer, all of these drugs have demonstrated
activity, signiﬁcant activity, in one or more
01' these animal tumor systems (Tr. at 146A—
4'7).

The proponents of Laetrile question the
statistical controls and experimental de-
sign employed in the studies conducted
by Southern Research Institute (see R
302, Ex. E). They suggest the utilization
of methods of statistical analysis devel-
oped for use in judging results obtained
with physical, rather than biological, sys-
tems. One of the research scientists at
the National Cancer Institute responsi-
ble for the studies conducted by South-
ern Research Institute points out that
“[t]he variation in all biological sys-
tems is far greater than that involving
physical phenomena” (R 438 at 1). He
suggests that it is, for that reason, not
possible to use the internal statistical
analyses suggested by the proponents of
Laetrile (id.).

(3) Scind Laboratories

Dr. Burk’s third reference is:

Scind Laboratories, University of San Fran-
cisco, 400 rats bearing Walker 256 carcinoma
(200 treated with amygdalin, 200 controls),
with 80 percent increase in life span at opti-
mum dosages (500 mg amygdalin/kg body
weight) (October 10, 1968). Cf. FDA—IND ap-
plication No. 6734, pp. 247—8, 00080—00093
(R 302, Ex. A at 15).

The Scind Laboratory data were sub-
mitted to FDA in support of the Mc-
Naughton Foundation’s IND for amyg-
dalin in 1970. An ad hoc committee of
cancer experts evaluated these data dur-
ing its review of the IND. In its report,
the Committee stated: “We are particu-
larly cognizant of: the lack of adequate
evidence of in vivo antineoplastic char—
acteristics. The Scind Laboratory data
in the initial submission of IND 6734,
April 6, 1970, concerning two experiments
with a Walker 256 system are considered
unacceptable because of inadequate doc-
umentation of status of animals, per-
centage of tumor take, rate of growth,
and accounting for acute deaths[,] and
the other substantial lack is a statistical
analysis. Scind Laboratory, in'a letter

dated October 18, 1968, filed with [an]
October 31, 1970, amendment, states
‘Laetrile, when administered without
Beta glucosidase has little or no eﬁect
upon transplanted rodent tumor systems
tested.’ (emphasis theirs [i.e., Scind
Laboratory’sl)" (R 184. Ex. 2 at 1).

(4) Pasteur Institute

Dr. Burk's fourth reference is:

Pasteur Institute (Paris), with human can-
cer strain maintained in mice treated at
optimal dosage of 500 mg Amygdalin Mar-
san/kg body weight/day: increased life span
and delayed tumor growth up to 100 percent
(Dec. 6, 1971 report by M. Metianu) (R 302,
Ex. A at 16) .

In a sworn aﬂidavit (R 422), a medi-
cal oﬁicer in the Bureau of Drugs, who is
trained in medicine and experienced in
scientiﬁc research and who is ﬂuent in
both French and German, commented
on the cited studies conducted at the
Pasteur Institute in Paris and the Insti-
tute von Ardenne in Dresden (see discus-
sion below) .

The medical ofﬁcer, through the Amer-
ican Embassy in Paris, learned that the
report entitled, “Anti-Tumor Toxicity
and Activity” was written on the letter-
head of the Institute Pasteur and was
an internal report of the Institute that
has never been published in any scien-
tiﬁc journal. In the affidavit, the medi-
cal oﬂ‘icer states that the fact that the
report “represents preliminary work only
and has not been published in any sci-
entiﬁc journal since it was prepared six
years ago raises my suspicions that the
preliminary results obtained could not
be reproduced" (R 422 at 1] 6).

(5) Institut von Ardenne

The fifth reference cited by Dr. Burk
is:
Institut von Ardenne (Dresden, Germany),
H strain mice bearing Ehrlich ascites carci-
noma treated with bitter almond amygdalin
ad libitum in addition to the regular chow
diet: increased life span and decreased rate
of cancer growth. treatment beginning 15
days before cancer inoculation (Arch.
Geschwulstforsch 42, 135—7. 1973) (R 302.
Ex. A at 15).

After reviewing the article published
in the Arch. Geschwulstforsch, the Eu-
reau of Drugs medical ofﬁcer made the
following comments:

The author's terms (in the summary sec-
tion) “feeding with bitter almonds." "pro-
longation of survival" (due to feeding with
bitter almonds), and "inhibition of tumor

Laetrile

25

growth" are not adequately deﬁned in the
subsequent text or by the content of the
text and thus are uninterpretabie.

The description of the methodology is
deﬁcient for a number of reasons. It falls
to provide information whether the mice
were kept singly or caged in groups. It falls
to provide information on the techniques
for demonstrating whether and how much
of the bitter almonds had been eaten by
each experimental mouse. It falls to inform
on the origin, quality, and composition of the
bitter almonds with respect to the latter al-
leged role of “amygdaline” and HCN. Due to
these failings it is not possible to draw con-
clusions from any differences of events be-
tween experimental and control animals—
if such differences could be demonstrated
at all. The author also fails to give the age
of the mice and the body weight of each
individual mouse of each group and at
each weighing date. The use of sole mean
values in this paper is potentially mislead-
ing. (The scientiﬁc evaluation of data re-
quires implementation of variabilities of
the individual measurements.)

The author makes statements on “tu-

mor growth” which are based on implica-
tions, indirect deductions, and on arbi—
trary assumptions.
The term “tumor growth" is potentially mis-
leading for the Ehrlich ascites cancer which
consists of a cancer cell suspension in the
peritoneal ﬂuid. The study fails to use precise
methods of measuring the number of cancer
cells present in each mouse.
It

III III

t it

In my opinion, this article fails to provide
any evidence that bitter almonds are effective
in inhibiting the growth of tumors (R 422 at
ii 7).

(b) Other Tests

As noted above, the two tests done by
the Southern Research Institute and the
Sloan-Kettering studies now . completed
have demonstrated conclusively, in the
view of most experts, that amygdalin,
either alone or in conjunction with the
enzyme beta-glucosidase, exhibits no an-
titumor effect. These results are in ac-
cord with the negative ﬁndings of three
earlier animal studies commissioned by
the National Cancer Institute. Those
tests are summarized in the record as
follows:

1957: Amygdalin was tested with three
transplanted mouse tumor systems used at
the time by the NCI Cancer Chemotherapy
National Service Center (CCNSC) to screen
compounds for anti-cancer activity. Amyg-
dalin produced no signiﬁcant inhibition or
growth of the carcinoma 775 or sarcoma 180
tumors, and produced no signiﬁcant increase

Commissioner’s Decision

in the lifespan of mice with leukemia L1210
tumors.

1960: Material from a different source was
tested against the same three mouse tumors.
The compound failed to show antitumor ac-
tivity.

1969: Amygdalin was tested alone and in
combination with beta-glucosidase against
leukemia. L1210 in mice. Amygdalin was in-
active against the tumor, alone and in com-
bination with the enzyme. Toxic side effects
increased when the drug and enzyme were
given together (R 173, Att., “NCI Testing of
Laetrile (Amygdalin) ”) :

A study, entitled “Failure of Amygdalin
to Arrest BIG Melanoma and BW5147
AKR Leukemia.” Hill et al.. Cancer Re-
search, 36:2102—07, June 1976, appears as
Exhibit 3 to R 170. The December 9, 1976
report of yet another animal test of
amygdalin is Exhibit 3D to R 184. The
drug was found not to be active against
human breast and colon tumor xeno-
grafts in athymic mice.

The failure of Laetrile (or amygdalin)
teshow-any effect in animal systems is
important because those systems have
shaman-ability to predict eﬂectiveness
in humans. See the statement of Dr.
James F. Holland (R 396) : “No drughas
been proved active in human cancer
which does not show anti-cancer ac-
tivity in experimental animals. Human
cells are not so diiTerent from other
mammalian cancer cells that an active
drug does not act on at least one other
mammalian system * ‘ ‘. Laetrile is
completely inactive against animal can-
cers. It has been repeatedly tested in
reputable laboratories against a broad
spectrum of rodent neoplasms. Inasmuch
as no drug has been found active against
cancer which isn’t active in the screen-
ing tumors, there is no basis to consider
Laetrile a candidate chemotherapeutic
compound against human cancer ‘ ‘ ‘.
No scientiﬁcally accepted data whatever
have been presented indicating evidence
of beneﬁt from Laetrile.”

See also the statement of Dr. Bayard
H. Morrison. Assistant Director of the
National Cancer Institute: “[Olf the 30
or 40 drugs that are [now] regularly
available and known to have eﬂect in
certain forms of human cancer all of
these drugs have demonstrated activity,
signiﬁcant activity, in one or more of
these animal tumor systems.” (Tr. at
147).

One comment theorized that the rea-
son why animal tests do not show
Laetrile to have any anticancer activity

26

is because the laboratory animals are
bred to have defective immune rejection
systems (R 235 at '7). This theory as-
sumes that Laetrile is hydrolyzed by an
enzyme that is in greater concentration
at the cancer site than at other locations
in the body. The comment explains that:
“If, because of a defective immune sys-
tem, laboratory animals produce no hy—
drolyzing enzyme at the cancer, (sic)
site, that fact alone would explain why
Laetrile doesn't work on laboratory
animals. It can't work on any organism
that has a defective immune system.”’
(See R 235 at 7—8.) No evidence has been
submitted to support the comment’s
theory.

The Commissioner concludes that the
animal studies conducted to date fail to
show that Laetrile (or amygdalin)
has anticancer activity in laboratory
animals. As has been noted previously,
even if these tests showed that the drug
had anticancer activity in laboratory
animals, such ﬁndings would not be
relevant to the question whether it is
generally recognized by qualiﬁed ex-
perts as a safe and effective anticancer
drug, since general recognition must be
based upon testing in human beings.
The lack of positive effect in test
animals is of some importance, since a
clear showing of success in animals
might suggest the propriety of clinical
testing in humans. The failure of amyg-
dalin to produce an anticancer eiTect in
animals is added reason for skepticism
concerning the claims that it is effective
in humans.

2. Testimony of Experts

(a) Experts Opposed to Laetrile. The
evidence that experts in the evaluation of
drug safety and effectiveness do not
“generally” recognize Laetrile as effective
for any therapeutic use is overwhelming.
(It should be remembered that for recog-
nition to be general it must be shown
that most qualiﬁed experts recognize the
drug’s safety and effectiveness. The fact
that a few persons claiming expertise
believe the drug safe and eﬁective is thus
not sufﬁcient.) The record contains
statements that Laetrile is not consid-
ered as an effective cancer therapy from
several organizations with members who
are experts in cancer drug evaluation—
e.g., the American Cancer Society, the
American Medical Association, the Com-
mittee on Neoplastic Diseases of the
American Academy of Pediatrics—and
from a large number of the Nation’s

most eminent and well-qualiﬁed experts
in the area of cancer drug evaluation. It
is difficult to conceive of a clearer show-
ing of a lack of “general" recognition of a
drug’s effectiveness than the expression
of the views of these many experts.
The Commissioner will describe the
qualiﬁcations of some of these experts
and either quote from or summarize the
views which they have expressed. Each
of the submissions referred to contains a
great deal of information concerning
Laetrile and the consensus of expert
opinion about it, and the following ex-
cerpts are meant only to be illustrative
of the views each expert expressed:
Arthur I. Holleb, M.D., Senior Vice
President for Medical Aﬂ’airs, American
Cancer Society, Inc., submitted an aili-
davit (R173). His curriculum vitae lists
his membership in and leadership of
several professional societies, which in-
clude the James Ewing Society and the
American Radium Society. He also serves
on the Cancer Commissions of the Amer-
ican College of Surgeons and the Amer-
ican College of Radiology and is editor-
in-chief of CA, a cancer journal pub-
lished by the American Cancer Society.
Dr. Holleb stated (R 173 at 113) that
he had reviewed three basic documents
attached as exhibits to his afﬁdavit and
supporting documents for these basic
documents and that the information con-
tained therein was true and correct. Sub-
mitted as an attachment to Dr. Holleb‘s
affidavit is a “Statement Concerning Lae-
trile” by Frank J. Rauscher, Jr., Ph. D.,
Former Director, National Cancer Pro-
gram, National Cancer Institute. Dr.
Rauscher states, “There is no evidence
that Laetrile works. Over the last decade,
or more. N01 has repeatedly conducted
tests of Laetrile in a variety of animal
tumor systems. Most have been com-
pletely negative. The others have shown
only marginal levels of activity which
could not be reproduced. The animal sys-
tems used are these which have detected
the active properties of the scores of
drugs which, unlike Laetrile, have proven
to be of demonstrable value in patients
with many forms of cancer. The thera-
peutic beneﬁts as well as the attending
side effects of these materials have been
clearly and amply documented in clinical
literature based on carefully conceived,
meticulously conducted and monitored
clinical trials. The same cannot be said
for Laetrile where clinical reports are
largely anecdotal and unsubstantiated.
Thus, there is no laboratory or clinical

Laetrile

evidence of the effectiveness of Laetrile"
(id. at 2).

See also testimony of R. Lee Clark,
M.D., President, American Cancer So-
ciety, in which he states: “The American
Cancer Society views Laetrile as having
no proven value in the treatment of hu-
man cancers. The Society has made a
continuing review of all the literature
and other information available and
ﬁnds no eviden:e that treatment with
Laetrile results in ob1ective beneﬁts to
patients with cancer. Since 1956, the
National Cancer Institute, in conjunc-
tion with the cancer research centers of
America, has reviewed over 300,000
drugs, chemicals, antibiotics, and other
agents including Laetrile to evaluate
them in regard to their usefulness in
cancer treatment. From this research,
more than forty spe:iﬂc agents have
been found to have an effect against
cancer in animal and in man. Although
several trials have been made with Lae-
trile, it has never been proved effective
i1; (liancer in any way whatsoever” (R 307
a ).

Frederick N. Silverman, M.D., Chair-
man, Committee on Neoplastic Diseases,
American Academy of Pediatrics, sub-
mitted testimony (R 233 and 317) which
included the following comments from
his committee: “Laetrile has never been
shown to exhibit any emcacy in the
treatment of neoplastic disease in chil-
dren. It cannot be regarded as safe if it
is used in lieu of drugs currently em-
ployed either as accepted treatment or
in carefully designed investigative treat-
ment protocols.”

William R. Barclay, M.D., testiﬁed
(Tr. 269—281) for the American Medical
Association (AMA). The AMA supports
the “FDA’s contention that laetrile is a
new drug and is neither generally rec-
ognized by experts. as safe and effective
for its purported use nor should (it) be
distributed in interstate commerce until
such time as its safety and efficacy for
the treatment of cancer have been es-
tablished through controlled preclinical
and clinical studies” (Tr. at 272).

Dr. Barclay discussed (Tr. at 274) a
May 1965 report in the Canadian Medi-
cal Association Journal which “con-
cluded that laetrile could not be con-
sidered as a palliative in cancer therapy
on the basis of the biological rationale
advanced by the manufacturer.” He fur-
ther states that: "the American Cancer
So:iety has long pointed out through

27

Commissioner's Decision

its continuous reviews of the scientiﬁc
literature that laetrile is not a proven
or generally recognized treatment for
cancer. The American Medical Associa-
tion likewise views laetrile as ineffective
in the treatment of cancer” (Tr. at 275—
276) . At its 1976 Clinical Convention, the
AMA adopted the following resolution
pertaining to the profession's view of
Laetrile: “Resolved: That the American
Medical Association continue to inform
the public of the danger of delay in the
diagnosis and treatment of malignanties
by methods not generally recognized by
the medical profession as beneﬁcial and
effective; and be it further Resolved
That the American Medical Association
inform the public that the safety and
efﬁcacy of amygdalin for the treatment
or palliation of malignancies is unproven
and that the use of amygdalin in such
cases exploits the victims of malignan-
cies and their families by preying upon
the emotions of the hopelessly ill, in some
cases for the proﬁt of the unscrupulous.”
Dr. Barclay (Tr. at 276) states: “We be-
lieve that experts qualiﬁed by s:ientiﬁc
training and experience to evaluate the
safety and effectiveness of drugs are vir-
tually unanimous in their recognition of
the ineffectiveness of laetrile for the
treatment of cancer.” The AMA testi-
mony concludes (Tr. 280): ”It is clear
that laetrile is not generally recognized
by experts qualiﬁed to evaluate the
safety and effectiveness of drugs as safe
and effective.”

W. Sherwood Lawrence, M.D., a
Medical Officer of the State of California
Department of Health. Public Health
Division, Food and Drug Section, serves
as the Executive Secretary of the State
of California Cancer Advisory Council.
He is the custodian of the records of the
Council and is knowledgeable of the work
of the Council and the study that the
Council has conducted (R 183 at 1). Dr.
Lawrence states (R 183 at 1'7): “The
evaluation by the Council of all the clin-
ical data available here and in Canada
has failed to establish any evidence of
clinical efﬁcacy. The proponents have
never published competent well-designed
controlled clinical studies demonstrat-
ing the slightest efﬁcacy of Laetrile in
the cure, amelioration or control of
cancer. Laetrile (amygdalin) is not
generally recognized by qualiﬁed experts
as either safe or effective in cancer
therapy.”

Jonathan E. Rhoads, M.D., is National
Chairman of the National Cancer Ad-

,

28

visory Board, a surgeon, former Presi-
dent of the American Cancer Society and
a member of a number of organizations
focusing on research, including the
American Association for Cancer Re-
search and the American Institute on
Nutrition. He made a presentation at
the oral argument (Tr. at 109—115), on
behalf of himself, as a citizen, and the
American Cancer Society. Dr. Rhoads
stated (Tr. at 114) : “The position of the
American Cancer Society is that Laetrile
can be toxic in some doses and some
modes of administration. But that more
importantly, it is unsafe because its ef-
fectiveness has not been demonstrated
scientiﬁcally so that reliance on it may
lead patients to forego better treatment.
Laetrile certainly has not been proven
effective as a cancer treatment or cure
and is not generally recognized by quali-
ﬁed experts as safe and effective for
cancer."

Jesse L. Steinfeld, M.D., is Dean of the
School of Medicine, Medical College of
Virginia, Richmond, VA; he was
formerly Deputy Director of the National
Cancer Institute; United States Surgeon
General; Deputy Assistant Secretary for
Health and Scientiﬁc Affairs, Depart-
ment of Health, Education, and Welfare;
and Chairman of the Department of On-
cology and Director of the Comprehen-
sive Cancer Center at the Mayo Clinic.
His professional experience includes
over 20 years of involvement in cancer
research, particularly with respect to the
metabolic effects in cancer patients that
occur as cancers grow and metastasize
(R 194). Dr. Steinfeld was recognized as
an expert in the evaluation of the safety
and effectiveness of cancer drugs by the
Court in Durom‘c v. Richardson, 479 F.
2d 242, 248 (7th Cir), cert. denied 414
US. 944 (1973). He states that neither
amygdalin nor any other cyanogenic
glycoside is generally recognized by him-
self or by experts generally, to be safe
and effective for any medical purpose
(id. at 5). Dr. Steinfeld also states: “I
have reviewed the clinical records of a
number of patients who have received
laetrile as treatment for cancer, while I
was in California. In that review, there
was no evidence to support the view that
laetrile was of value to cancer patients.
I have reviewed the volumes of material
submitted to the FDA in 1970, requesting
an Investigational New Drug Application
(IND) for laetrile. The application was
not approved because of serious ﬁaws or
deﬁciences in both the animal and hu-

man trials” (id. at 8).

Richard H. Lange, M.D., is Chief, Sec—
tion of Nuclear Medicine, Ellis Hospital,
Schenectady, N.Y. He submitted veriﬁed
testimony (R 385) in which he cited his
experience in the ﬁeld of internal medi-
cine, nuclear medicine, and his particular
interests in the problem of cancer. Dr.
Lange states: “When one reviews the ex-
tensive information presently available
from leading experts on cancer, there is
no evidence to suggest that Laetrile is in
any way an effective cancer drug. * * ‘
The theory that Laetrile is effective be—
cause it destroys cancer cells by produc-
ing a release of cyanide has never had
any scientiﬁc support, nor has the newer
claim in the prior approach that cancer
is caused by a vitamin B—17 deﬁciency
and that Laetrile is vitamin B—17. No
scientiﬁc group has recognized Laetrile
as a vitamin. * * * Evidence of an anti-
tumor effect in animals must be sug-
gested or proven before a drug can be
used in human clinical trials. Without
such proof of effectiveness, the concept of
scientiﬁc investigation would be altered;
the gates would be open to all sorts of
quacks and utter confusion would result.
Placebo effects and personal testimonials
must be separated from competent ob-
jective scientiﬁc investigation which is
free from bias, personal prejudice or
emotional involvement” (R 385 at 1—2).

Michael B. Shimkin, M.D., is Professor
of Community Medicine and Oncology,
School of Medicine, University of Cali-
fornia, San Diego, and has had 40 years
of experience in cancer research, teach-
ing, and clinical treatment of patients.
He has authored or co-authored over 280
publications on clinical and laboratory
cancer research (R 192). Dr. Shimkin
states: “My knowledge about amygdalin
(‘Laetrile’) spans some 30 years. At no
time, nor now, has there been evidence
that this material is useful in the preven-
tion or treatment of cancer in man or in
experimental animals. I know of no ex-
pert of cancer in chemotherapy who has
evidence of usefulness of amygdalin in
the treatment of cancer, nor of any rec-
ognized journals or textbooks in medi-
cine that indicate such usefulness. I
know of no laboratory or clinical studies
of amygdalin that demonstrate scientif-
icallv any signiﬁcant, repeatable beneﬁt
in animals or in man" (id. at Ti 12).

Bernard C. Korbitz, M.D., is Chief of
the Chemotherapy Section, Department
of Oncology at the Radiologic Center,

Inc., Nebraska Medical Hospital, Omaha,

Laetrile

29

Nebraska. He has been involved in var-
ious aspects of cancer research and can-
cer therapy since approximately 1954.
His professional training and experience
includes the authorship or co-authorship
of approximately 40 articles relating to
cancer hematology and internal medi-
cine (R 181). Dr. Korbitz states: “To
date, there has been no bona ﬁde or sub-
stantiated evidence that Laetrile has any
signiﬁcant anti-tumor effect in any of
the rodent animal systems evaluated. I
have reviewed reports by Dr. Navarro in
the Philippine Medical Journal who pur-
ported to have produced good results in
cancer patients using larger doses. In
reviewing his studies there is no objec—
tive evidence to support these claims that
Laetrile is effective in any dose range
against cancer” (id. at 3). Dr. Korbitz
also states, “There is no objective evi-
dence of any sort from pre-clinical or
sketchy clinical reports to indicate that
Laetrile has any beneﬁt in the treatment
of cancer patients” (id. at 4).

Susan J. Mellette, M.D., is Associate
Professor of Medical Oncology, Medical
College of Virginia and has had over 20
years experience in a private practice
essentially limited to patients with meta-
static malignant diseases. In 1975 she
was President of the American Associa-
tion for Cancer Education, an organiza-
tion of medical and dental school faculty
interested in cancer teaching in profes-
sional schools (R 420). Dr. Mellette
states, “My views on the substance Lae-
trile are based on reports of the ineffec-
tiveness of amygdalin which have been
published in the standard scientiﬁc lit-
erature and also on two books and other
printed materials put out by proponents
of Laetrile which I have read. In the lat—
ter, I have found only unsubstantiated
testimonials and hearsay in the patient
reports and so-called scientiﬁc argu-
ments which reach unwarranted conclu-
sions without appropriate experimental
methodology” (R 420 at 1).

Daniel S. Martin, M.D., has been in-
volved in general cancer research since
1946. Since 1950, he has worked in can-
cer chemotherapy, and since 1958 in can-
cer immunology as well. His professional
bibliography includes over 100 publica-
tions, the vast majority of which re-
sulted from research in cancer immuno-
logy and chemotherapy (R 185). Dr.
Martin states, “The proponents of
Laetrile claim that their clinical studies
in cancer patients demonstrated that
Laetrile often reduced the size of a

Commissioner's Decision

malignant tumor and caused some
tumors to completely regress. Evi-
dence—none; i.e., no objective evidence
to support such a claim. No ‘hard’
patient data, no tumor measurements of
the progress of the disease state, no bio-
chemical data, no survival data, etc. The
pro-Laetrilists do not present any com-
petent scientiﬁc evidence that Laetrile
is effective for the treatment of can-
cer. Only testirnonials—‘anecdotal’ evi-
dence—are presented that the Laetrile-
cancer patients and their doctors ‘be-
lieve’ in its efficacy. Belief, however, is
not adequate for reliance of drug eﬂi-
cacy. Only strict scientiﬁc standards
should be employed; namely, adequately
documented scientiﬁc, well-controlled,
evidence of objective antineoplastic ef-
fects in humans. The fact that a great
many cancer patients have received
Laetrile and attest to its benefits is not
evidence. Mere clinical experience per
se is not a substitute for lack of appro-
priate objective documentation of clini-
cal efﬁcacy” (emphasis in original) (id.
at 11 20c).

Harold James Wallace, Jr., M.D., is
Director of Cancer Control and Rehabil-
itation at Roswell Park Memorial Insti-
tute, Buffalo, NY. He has had extensive
training in the clinical pharmacology of
cancer drugs and has participated di-
rectly in the clinical testing of a number
of new anti—cancer drugs. He has, over
the past 20 years, conducted and pub-
lished the results of controlled clinical
trials of drugs, radiation therapy, and
other treatments of cancer (R 199). He
is a cured cancer patient (Tr. at 170).
Dr. Wallace states: “There is no evidence
in either animal models or in the large
numbers of patients who have received
amygdalin that it is effective in any way
in preventing cancer, causing a regres-
sion or remission of cancer, or improv-
ing the life expectancy of the cancer
patient. Neither has there been any evi-
dence that it decreases the symptoms
of pain, weakness, or depression from
cancer in any direct way. It is not anal-
gesic or antiemetic in character. The
anecdotal evidence claimed by amyg-
dalin proponents has not been presented
to me or to any scientiﬁc forum for cri-
tical review and these claims have not
been substantiated by documentation in
medical records available for review” (R
199 at m4).

John T. P. Cudmore, M.D., is a Board-
certiﬁed surgeon whose professional ex-
perience includes the practice at oncol-

30

ogy for the past 20 years. Dr. Cudmore
stated that his work requires him to be
acquainted with the literature related to
drugs used in the treatment of cancer
published in professional journals, and
that he regularly attends meetings of ex-
perts at which drugs used in the treat-
ment of cancer are discussed and eval-
uated (R 178). Dr. Cudmore states (id.
at illO): “In my practice of oncology
in San Diego since 1956, I have examined
numerous patients after their treat-
ments with amygdalin or Laetrile in
nearby Tijuana, Mexico. I have never
seen any evidence of cure or palliation
with Laetrile. I can conclude from my
personal experience that Laetrile or
amygdalin is ineffective in the treat-
ment and prevention of cancer.” In sup-
port of these statements, Dr. Cudmore
discusses in his aﬁidavit the case his-
tories of nine patients who have received
Laetrile, all of whom in his opinion re-
ceived no beneﬁts therefrom. Dr. Cud-
more states (id. at 1] 8) : “The composi-
tion of amygdalin is such that I do not
recognize it, nor is it generally recog-
nized by experts qualified through scien-
tiﬁc training and experience to evaluate
the safety and effectiveness of drugs, as
safe and effective for the use in treat-
ment or prevention of cancer.”

Sidney Weinhouse, Professor of Bio-
chemistry at Temple University School
of Medicine, is a researcher in the ﬁeld
of cancer for the past 30 years, editor
of the journal, Cancer Research, and a
member of the Board of Directors of the
American Cancer Society (R 384). He
made the following statement regarding
Laetrile: “Although widely touted for
its curative effects on cancer for many
years, there is no shred of evidence from
any reputable cancer researcher that
this substance has any therapeutic
value. I know of no reputable scientist
who has published evidence for the ef-
fectiveness of Laetrile” (id. at 1).

Bryant L. Jones, M.D., is a Medical Di-
rector in the Commissioned Corps of the
United States Public Health Service (R
431). Since 1960, ﬁrst in the pharma-
ceutical research industry and then in
government, he has worked with the de-
sign and evaluation 01' clinical investiga-
tions, the purpose of which were to de-
termine the safety and effectiveness of
drugs (id. at 11 2). Dr. Jones states, “I am
presently responsible for the review and
evaluation of protocols and reports con-
cerning the use of drugs subject to New
Drug Applications (NDA’s) and Notices

Laetrile

of Claimed Investigational Exemption
for New Drugs (IND’s). I review such
protocols and reports for the purpose of
determining whether or not they provide
scientiﬁcally acceptable standards of
safety and effectiveness. I would estimate
that I have reviewed several thousands
such reports, most of which were and
are directly related to and involve drugs
intended for use in the ﬁeld of oncology,
which is the management of cancer” (id.
at 11 3). Dr. Jones states, “I have made a
careful review of the statements which
are part of the record in this proceeding
identified as:

1. Comments: 00001 through C0247.

2. Testimony: TS 01 through 14.

3. Letters: Let # 1 through 49.

4. Oral arguments: OR 01 through 11.
(When submissions were received by the
Hearing Clerk, they were assigned both
a number-letter code (used here by Dr.
Jones) and an R number, utilized for
purposes of citation in this opinion.) I
have evaluated each statement and re-
port which purports to show that Lae-
trile, amygdalin, or any of the cyanoge-
netic glycosides are safe or effective in
the treatment of cancer, as a palliative,
as an analgesic, or for any medical pur-
pose. None of the statements or reports
are adequate, well-controlled scientiﬁc
studies. The reports I have examined fail
to measure up to the principles applicable
to adequate, well-controlled s:ientiﬁc
studies in every particular. The studies
not only fail to measure up to minimum
standards applicable to adequate, well-
controlled scientiﬁc studies, but also fail
to present any scientiﬁcally acceptable,
objectively documented clinical evidence
of safety and effectiveness for amygda-
lin, Laetrile, or any cyanogenic glyco-
side” (id. at 11 6).

George J. Hill, II., M.D., is Professor
and Chairman of the Department of
Surgery and Associate Dean for Clinical
Affairs of the Marshall University School

of Medicine, Huntington, West Virginia
(R 170). His professional duties involve
the medical management of cancer and
require that he be familiar with drugs
that are generally recognized as safe and
effective in treating cancer. He keeps
abreast of the consensus of informed
opinion by reading medical literature
concerning cancer and its management,
by attending meetings of experts where
methods of treatment that are recog-
nized as safe and effective are described
and discussed, and through teaching,

31

conducting research, and exchanging
vieWS with his colleagues who are ex-
perts in the ﬁeld (id. at 1112). He has
himself conducted studies on amygdalin,
the reports of which have been published
and are attached as Exhibits 2 and 3 to
his afﬁdavit. He states, “In the course of
my investigation of amygdalin’s poten-
tial as an antitumor agent, an extensive
review of both popular and scientiﬁc
literature relating to it and Laetrile was
conducted. Most reports in the scientiﬁc
literature supporting Laetrile have ap-
peared in foreign medical journals. Only
one preliminary report purporting to
support use of Laetrile was found in an
American journal. The favorable reports
concerning clinical use of Laetrile or
amygdalin were testimonials based on
individual case reports. There were no
adequate, well-controlled clinical studies
which demonstrated or purported to
demonstrate that amygdalin or Laetrile
were safe and effective for use in the
medical management of cancer. Neither
were there any favorable clinical reports
in which an attempt was made to meas-
ure any objective parameters for ade-
quate periods of followup to determine
any possible drug-induced effect. The
literature also contains reports concern-
ing a limited number of carefully moni-
tored clinical cases in which use of
amygdalin failed to result in any objec-
tive beneﬁt in the management of can-
cer" (id. at T! 9—10). Dr. Hill also states,
“The composition of amygdalin is such
that I do not recognize it, nor is it gen-
erally recognized among experts quali-
ﬁed through scientiﬁc training and ex-
perience to evaluate the safety and ef-
fectiveness of drugs, as safe and effective
for use in cancer management, or for
any other known medical use. I know of
no medical school where use of amygda-
lin for treatment or prevention of can-
cer is taught. I know of no medical ex-
pert qualiﬁed through scientiﬁc training
and experience in the control of cancer
who advocates use of amygdalin” (id. at
11 13).

Vincent T. DeVita, Jr., M.D., is Pro-
fessor of Medicine at the George Wash-
ington University School of Medicine,
Washington, DC, and is a diplomate of
the American Board of Internal Medi-
cine, with subspeciality certiﬁcation in
Hematology and Medical Oncology (R
169) . Dr. DeVita has been Director of the
Division of Cancer Treatment, National
Cancer Institute, since 1974. His job re-
quires that he regularly attend meetings

Commissioner's Decision

of experts at which drugs used in the
treatment of cancer are discussed and
evaluated and that he be acquainted with

the literature published in professional
journals relating to drugs used in the
treatment of cancer (R 169 at 111—16).
Dr. DeVita states (id. at 11 18—19), “The
composition of amygdalin is such that
I do not recognize it, nor is it generally
recognized by experts qualiﬁed through
scientiﬁc training and experience to
evaluate the safety and effectiveness of
drugs, as safe and effective for use in the
treatment or prevention of cancer. I
know of no adequate, well-controlled
clinical study which shows it to be safe
and effective for use in the treatment or
prevention of cancer in humans. I know
of no medical school where use of amyg-
dalin is taught, and of no recognized
medical text which prescribes, recom-
mends, or suggests its use. Neither do I
know of any expert in cancer chemo-
therapy who is of the opinion that it is
useful in the treatment or prevention of
cancer, or that there is evidence that it
is useful in the medical management of
cancer.”

R. L. Meckelnburg, M.D., is Director,
Department of Nuclear Medicine, Wil-
mington Medical Center, Wilmington,
Delaware, and a physician concerned
with the care and treatment of cancer
patients by means of chemotherapy (R
154). He described his limited experience
with treating patients with Laetrile in
the years 1963—1967. Although Dr. Meck-
elnburg states (and the Commissioner
agrees) that the study was not a clini-
cally controlled series, he reports that
“the results of these treatments were
uniformly unsuccessful.” Dr. Meckeln-
burg noted, “The individuals who were
most interested in promoting the use of
Laetrile failed to administer the drug in
a manner consistent with good clinical
investigative methodologies, particularly
the use of the double blind control and
crossover models of study.” He con-
cluded, “The promulgation of the drug as
a preventive for cancer in the light of
today’s knowledge is totally absurd”
(id.).

Robert C. Eyerly, M.D., is a physician
and surgeon on the staff of the Geisinger
Clinic in Danville, Pennsylvania. and a
diplomate of the American Board of
Surgery (R 167). He currently serves as
Chairman of th Committee on Unproven
Methods of Cancer Management, Ameri-
can Cancer Society. This Committee’s
chief concern is, “With methods that are

32

promoted as having established value in
diagnosis, prevention, treatment, or con-
trol of cancer, despite a lack of compe-
tent scientiﬁc evidence to support claims
made for them. The Committee reviews
material assembled by its staff, mostly
from published sources, to ﬁnd out what
kind of claims are made, and they eval-
uate scientiﬁc literature to see if it con-
tains evidence to support such claims”
(id. at TI5—7). Dr. Eyerly states, “The
composition of amygdalin is such that
I do not recognize it, nor is it generally
recognized by experts qualiﬁed through
scientiﬁc training and experience to
evaluate the safety and effectiveness of
drugs as safe and effective for adminis-
tration to humans for the treatment or
prevention of cancer, or for any other
purpose" (id. at 11 10).

Several experts qualiﬁed by scientiﬁc
training and experience in the ﬁeld of
cancer research and cancer treatment
submitted similar statements attesting
that they knew of no cyanogenic gly-
coside that is generally recognized as safe
and effective for the treatment, preven-
tion, or cure of can:er, for the relief of
pain associated with cancer, or for any
medical purpose. They also stated that
the composition of these cyanogenic gly-
cosides, in general, and of amygdalin, in
particular, is such that they do not rec-
ognize them, and the cyanogenic glyco-
sides are not generally recognized among
experts qualiﬁed through scientiﬁc train-
ing and experien:e to evaluate drugs, as
safe and effective for the treatment of
cancer, for prophylaxis against cancer,
for relief of pain associated with cancer,
or for any medical use. These experts
further stated that the scientiﬁc litera-
ture contains no reports of adequate,
well-controlled, scientiﬁc studies or other
evidence upon which recognition of
safety and effectiveness may be pred-
icated. They did not know of any rec-
ognized medical text in which the use of
amygdalin or any other cyanogenic gly-
coside is recommended for the treatment
of cancer. They did not know of any
medical school where use of these sub-
stances for such purpose is taught.
They did not know of any expert in
cancer chemotherapy who is of the view
that there is evidence that these sub-
stances have any useful effect in treat-
ing cancer. They did not know of any re-
port in the scientiﬁc literature describ-
ing an adequate, well-controlled study
which demonstrates that amygdalin or

Laetrile

any other cyanogenic glycoside is safe
and effective (Dr. Daniel S. Martin, R
185; Dr. Joseph F. Ross, R 190; Dr.
Charles G. Moertel, R 186; Dr. Jesse L.
Steinfeld, R 194; Dr. C. Chester Stock,
R 195; Dr. Harold James Wallace, R
199; Dr. Peter H. Wiernik, R 200; Dr.
Emil J. Freireich, R 390; Dr. David T.
Carr, R 1'76). The qualiﬁcations of the
individuals not previously discussed are
set forth in the following paragraphS‘

Joseph F. Ross, M.D., is Professor
of Medicine at the University of Cali—
fornia School of Medicine at Los Angeles,
California, and Director of the United
States Publi: Health Service-funded Re—
search Training Program in Hematology
and Hematologic Oncology at UCLA. He
submitted an afﬁdavit (R 190) in which
he described his educational background
and experience in teaching medical stu-
dents and physicians. He is actively in-
volved in the medical care of cancer
patients. Dr. Ross listed his membership
in several societies and councils whi:h
deal with cancer treatment and his
membership on the editorial boards of
several scientiﬁc publications.

Charles G. Moertel, M.D., is Chairman
of the Department of Oncology at the
Mayo Clinic, Director of the Mayo Com-
prehensive Cancer Center, and Professor
of Medicine at the Mayo Medical School.
Rochester, Minnesota. He described his
educational background and experience
which have included serving as Editor of
Cancer Yearbook, Associate Editor of
Cancer Medicine, serving on the editorial
board of Cancer, serving on a number of
cancer committees, being involved in
clinical research in pharmacology con-
cerning cancer chemotherapy and clin-
ical oncology, and publishing as author
or co-author over 200 articles, abstracts,
and editorials in recognized medical and
scientiﬁc journals (R 186).

C. Chester Stock, Ph.D., is Vice Presi-
dent and Associate Director for Admin-
istrative and Academic Affairs of the
Sloan-Kettering Institute for Cancer
Research, New York, New York, and Pro-
fessor Emeritus in Biochemistry at Cor-
nell University. He described his educa-
tional background and experience as in-
cluding serving as a member of several
boards and societies concerned with can-
cer research and serving as Chief of the
Division of Experimental Chemotherapy
at Sloan-Kettering, where for many
years he has had a major responsibility
in the development of new drugs for the
treatment of cancer (R 195).

33

Peter H. Wiernik, M.D., is Professor of
Medicine, University of Maryland School
of Medicine and Chief, Clinical Oncol-
ogy Branch, National Cancer Institute,
Baltimore Cancer Research Center. His
educational background and experiences
include duties as a reviewer for 9 medi-
cal-scientiﬁc journals, co-editor of 2
journals and the author or co-author
of over 140 articles, editorials, and ab-
stracts which have appeared in medical-
scientiﬁc literature most of which deal
directly with cancer (R 200).

Emil J. Freireich, M.D., is Head of the
Department of Developmental Thera-
peutics and Professor of Medicine, and
Chief, Division of Oncology at the Uni-
versity of Texas Medical School at Hous—
ton, Texas. His educational background
and experience includes membership in
several societies and committees con-
cerned directly with cancer treatment.
In addition, Dr. Freireich serves as a
member of editorial boards of medical
and scientiﬁc journals concerned with
cancer research and, as such, reviews
and evaluates scientiﬁc papers relating
to the causes, treatments and control of
cancer. He has published in internation-
ally recognized journals over 250 articles,
the majority of which have been con-
cerned with cancer (R 390).

David T. Carr, M.D., is Professor of
Medicine at the Mayo Medical School,
Associate Director for Cancer Control
and Community Relations of the Mayo
Comprehensive Cancer Center, and a
member of several professional societies
and committees concerned with the
treatment of cancer. His professional ed-
ucation and experience include the re-
sponsibility for a program of public edu—
cation about cancer. His special interests
are internal medicine and medical on—
cology, and he is regularly engaged in
the medical management of cancer (R
176 (see also Tr. at 180—89) ) .

Several other experts submitted testi-
mony in which they stated that, in their
experience, Laetrile was not effective in
the treatment of cancer. Their qualiﬁ-

cations are set out in the following para-
graphs:

James F. Holland, M.D., Professor and
Chairman, Department of Neoplastic
Diseases; Chief, Division of Medical On—
cology; and Director, the Cancer Center,
Mount Sinai School of Medicine, is a
physician who has worked exclusively in
cancer medication for over 26 years, spe-
cializing in cancer chemotherapy. He

Commissioner's Decision

states, in his veriﬁed testimony, that he
is thoroughly familiar with the action
of drugs on cancer (R 396) .

Carl M. Leventhal, M.D., is Deputy Di-
rector of the Bureau of Drugs, Food and
Drug Administration. He holds the rank
of Medical Director in the Commissioned
Corps of the Public Health Service and
is Assistant Professor of Neurology and
Pathology at Georgetown University. As
Deputy Director of the Bureau of Drugs,
he participates in meetings in which the
status of Laetrile is discussed and
evaluated (R 184).

William A. Nolen, M.D., is Chief of
Surgery at the Meeker County Hospital,
Litchﬂeld, Minnesota. He has served on
the board of editors of the Minnesota
State Medical Journal and has written a
number of articles, editorials, and books
on subjects of public health interest, in-
cluding a book entitled Healing: A Doc-
tor in Search of a Miracle, in which he
describes his personal experience with a
patient who lost her life because she
chose Laetrile for treatment of an early
cancer, thereby delaying conventional
medical treatment (R 188) .

Thomas H. Jukes, Ph.D., is Professor
of Medical Physics and Research Bio-
chemist at the University of California,
Berkeley, California. He is a member of
several professional societies, serves on
the editorial boards of several scientiﬁc
publications, has written three books
and over 250 articles in scientiﬁc jour-
nals and has conducted research in the
vitamin and cancer ﬁelds (R 416 (see
also R 41)).

Robert S. K. Young, M.D., Ph.D., is a
physician and has a doctorate in phar-
macology. He serves as adjunct Assist-
ant Professor of Pharamacology at
Georgetown University School of Medi-
cine and Dentistry and is group leader
for the Oncologic Drug Class, Bureau of
Drugs, Food and Drug Administration
(R 201 (see also R 430)).

(b) Supporters of Laetrile—In con-
trast to the great amount of evidence
that experts in drug evaluation do not
generally recognize Laetrile (or amyg-
dalin) as effective, the evidence in the
record to the contrary is meager. The
Commissioner will outline qualiﬁcations
of those persons who claim any modicum
of training or experience in the area of
drug evaluation whose support for the
use of Laetrile appears in the record.
The submissions of the following three
physicians are discussed under II.A.1.c.
above, “The ‘Evidence’ of Laetrile’s Ef-

34

fectiveness”:

John A. Richardson, M.D., stated in
testimony (Tr. at 462—463) that he had
been in general practice for 25 years
and since 1971 had been engaged in nu-
tritional medicine using Laetrile, amyg-
dalin, or vitamin B—1'7 and that he had
treated, over the past 6 years, between
4,000 and 5,000 cancer patients. Dr. Rich-
ardson made no claim to special training
or board certiﬁcation in the area of on-
cology or of training or experience in the
evaluation of the safety and eiTective-
ness of drugs. Dr. Richardson’s license
to practice medicine has been revoked
(R 183 at 13).

Philip E. Binzel, Jr., M.D., stated that
he has been a family physician since
1955 and currently serves as scientiﬁc
advisor to the Committee for Freedom
of Choice (Tr. Ex. 13). He stated that he
has treated over 400 patients in the last
3 years with a “metabolic therapy” for
cancer (Tr. at 360—361). No special
training in oncology or in the evaluation
of drug safety or effectivenes is claimed.

Lawrence (Larry) Patton McDonald,
M.D., who stated that he has been a
urologist since 1963, is a former member
of the State of Georgia Medical Educa-
tion Board, and is currently a member
of the US. House of Representatives. He
stated that he was a member of several
societies and associations, including the
American Society of Clinical Urologists,
the Southeastern Section of the Ameri-
can Urological Association, and the
American Association of Physicians and
Surgeons (R 509). No showing has been
made that Dr. McDonald has a specific
expertise in cancer treatment or in the
evaluation of the safety and effectiveness
of drugs.

Dr. Edward M. Arana, who spoke at
the oral argument in this proceeding,
identiﬁed himself only as a practicing
dentist in Carmel, California (Tr. 472—
A).

Ernst T. Krebs, Jr., spoke at oral argu-
ment in this proceeding (Tr. at 228-248).
While he is referred to as Doctor, he did
not complete his medical training and is
a doctor only by virtue of an honorary
degree. No special training in the area
of cancer therapy or in the evaluation
of safety and effectiveness of drugs has
been shown for Mr. Krebs, Jr.

Paul Hart, M.D., spoke at oral argu-
ment. He described himself as having
been employed at a pathology laboratory
that dealt with the effects of radiation
from atomic bombing in Japan and that

was associated with Deaconess Hospital
in Boston (Tr. at 457—58), and as being a
diplomate of the National Board of Medi-
cal Examiners (Tr. at 457). He stated
that he has an interest in “the Carl 0.
Simonton, M.D., psychotherapeutic ap-
proach to cancer therapy ‘ ‘ "” (Tr. at
458). While he indicated a personal re-
spect for various Laetrile proponents, he
did not give an opinion as to whether or
not Laetrile is generally recognized by
experts qualiﬁed to evaluate the safety
and effectiveness of drugs as safe and
effective for use in cancer therapy.

Dr. Mario A. Soto spoke at oral argu-
ment. He described himself as being
former head of the chemotherapy de-
partments of two different Mexican hos-
pitals. He stated that he is an independ-
ent investigator for the National Cancer
Institute and a conventional oncologist
and chemotherapist. He is medical direc-
tor of a Laetrile clinic in Tijuana, Mex-
ico (Tr. at 478—479) .

Dean Burk, Ph. D., who spoke at oral
argument and provided a written sub-
mission (R 302), is a biochemist and is
president of the Dean Burk Foundation,
Inc. He stated at oral argument that he
had spent 50 years in research on cancer
and vitamins, 35 of which were with the
National Cancer Institute (Tr. at 402).
His position is that Laetrile is not a drug
but a vitamin.

An afﬁdavit of Chauncey D. Leake,
Ph. D., prepared for another proceeding,
was submitted to this record (R 302, Ex.
K). The aﬂidavit indicates that he is
Senior Lecturer in Pharmacology at the
University of California School of Medi-
cine, San Francisco. His curriculum vitae
shows that he has a history of teaching,
participation in organizations dealing
with medicine and pharmacology, editing
of journals, and authorship of books and
articles.

An afﬁdavit of Charles Gurchot, also
apparently prepared for another pro—
ceeding, was submitted as Exhibit L to R
302. His degree is in chemistry and physi-
ology. Now semiretired, he has taught
pharmacology, biochemistry and chem-
istry at several schools of medicine and
is a member of a number of scientiﬁc
societies.

James Cason, Ph. D., submitted a state-
ment in which he states that he has been
a chemistry professor for some 35 years,
has published over 100 research papers
in scholarly journals and has served on
the editorial boards of Organic Syn-

theses, and the Journal of Organic

Laetrile

35

Che‘r'nistry (R 217) . He is currently a pro-
fessor of chemistry at the University of
California, Berkely (id.). While he states
his opinion that a diet high in nitrilo-
sides leads to a low incidence of cancer,
he gives no opinion as to whether or not
Laetrile (or Amygdalin) is generally
recognized by qualiﬁed experts to be a
safe and effective cancer drug.

The statute requires that “general
recognition" be among experts qualiﬁed
by scientiﬁc training and experience to
evaluate the safety and effectiveness of
drugs (21 U.S.C. 321 (p) (1) ) . Few of the
proponents of Laetrile who have made
submissions to this record possess the
necessary training and experience to
qualify them as such experts. The Com-
missioner has, however, for purposes of
completeness, considered as coming
within the category of “experts” for this
purpose, persons, including those listed
above, who have exhibited even a small
modicum of scientiﬁc experience or ex-
perience in the area in which they have
offered submissions. The weight to be
given the testimony of such persons, of
course, must correspond to their exper-
tise, cf. United States v. 1,048,000 Cap-
sules, More or Less, Etc, 347 F. Supp.
768, 771 (SD. Tex. 1972), aff'd 494 F.2d
1158 (5th Cir. 1974).

The Commissioner concludes that. the
lack of adequate and well-controlled
clinical investigations published in the
scientiﬁc literature aside, the record
clearly demonstrates that the over-
whelming majority of experts in the
evaluation of the safety and effective-
ness of drugs do not recognize Laetrile
as effective. Even the proponents of Lae-
trile, while they may argue that the ma-
jority is wrong, could hardly be heard to
argue this point. Laetrile is thus a new
drug within the meaning of the act.

B. GENERAL RECOGNITION OF SAFETY

As noted above, for a drug to be ex-
empt from new drug status under 21
U.S.C. 321(p) (1) it must be recognized
by “experts qualiﬁed by scientiﬁc train-
ing and experience to evaluate the safe-
ty and effectiveness of drugs” to be both
safe and effective under the conditions
of its intended use. While lack of such
recognition of Laetrile’s effectiveness
has already been shown, the Commis-
sioner will discuss in addition the evi-
dence on the question of general recog-
nition of the drug’s safety. He ﬁnds that
such recognition does not exist.

1. Lack of Adequate Testing

Commissioner’s Decision

As has been discussed above, for a
drug to be generally recognized as safe
it must have accumulated at least the
amount of evidence of safety that would
be required for approval of a new drug
application and that evidence must be
generally available to the community of
experts through publication in the scien-
tiﬁc literature. In order for a new drug
application for a drug to be approved,
there must exist as to that drug “ade-
quate tests by all methods reasonably
applicable” that show the drug’s safety
(21 U.S.C. 355(d); cf. 21 CFR 314.111
(a) (1)).

An attempt to show that Laetrile had
been proven by adequate testing to be
safe for use in man was made in 1970
when the McNaughton Foundation sub-
mitted to FDA arnotice of claimed in-
vestigational exemption for a new drug
(IND) for Laetrile. The FDA terminated
that exemption because of a lack of evi-
dence of safety. Subsequent to the ter-
mination, the IND was referred to an
Ad Hoc Committee of Oncology Con-
sultants. The report of this committee is
submitted with R 184 as Exhibit 2. This
report states, “The Committee concurs
with the action of the Commissioner in
termination of IND 6734.” Addressing
the toxicity question, the Committee
concluded (id. at 2), “Although it is
often stated in the IND that amygdalin
is non-toxic, data to demonstrate this
lack of toxicity are absent, particularly
with respect to the oral route."

The animal studies done to show Lae-
trile’s safety did not justify use of the
dosage suggested in the IND. “[T]he
sponsor wishes to begin oral studies in
patients at 2.95 mg/kg (oral); this is
to be compared with a documented safe
oral dose in dogs of 7.5 mg/kg daily for
6 months * * ‘. On the basis of docu-
mented data, if substantiated. then a
proper starting dose that might be con-
sidered in man, would be 1/10 of 7.5
mg/kg or 0.75 mg/kg (oral). The pro-
posed starting dose of 2.95 mg/kg is
1/ 100 of the oral acute LDsn in mice. It
is considered to be dangerous to base
the starting dose for a chronic (6 +
weeks) study in man on a single dose
study in mice. It is also dangerous to
initiate human studies while the nature
of the toxicity has not been elucidated
in large animal species. No documented
data are presented in the IND to permit
a higher starting dose" (id. at 3—4) .

Dr. W. Sherwood Lawrence, Executive
Secretary for the State of California

36

Cancer Advisory Council states (R 183
at 17), “An extensive review of the
world’s scientiﬁc literature has been
made by the Council. The evidence avail-
able for the determination of the recog-
nition of safety of the compound is
characterized by the lack of a body of
scientiﬁcally sound information such
that experts qualified by experience and
training to make such determinations
are unable to do so. In the absence of
such a determination by qualiﬁed ex-
perts Laetrile (amygdalin) cannot be
considered to be generally recognized
as safe.”

There is thus an absence of scientiﬁ-
cally sound data upon which experts
qualiﬁed by training and experience to
evaluate the safety and effectiveness of
drugs could base an opinion that Lae-
trile is safe for use in man. In the ab-
sence of such data the Commissioner
must conclude that the safety of use of
Laetrile in man has never been, and is
not now, “generally recognized" by ex-
perts qualiﬁed by scientiﬁc training and
experience to evaluate the safety and
effectiveness of drugs.

2. Testimony of Experts

The Commissioner’s conclusion of lack
of general recognition among experts of
Laetrile’s safety is supported by testi-
mony of such experts in the administra-
tive record. (The qualiﬁcations of the
experts whose statements are quoted
have been discussed above.)

As one expert notes, while the toxicity
of injected Laetrile has not been studied,
there is evidence that amvgdalin when
ingested (eaten) is harmful to humans.
evidence that has led to cautions on the
part of Laetrile promoters themselves:
In discussing the use of Laetriles, Dr. W.
Sherwood Lawrence states (R 183 at 16),
“There has never been a formal evalua-
tion of the safety of these compounds
to determine their safety. Although the
proponents claim Laetriles are non-toxic,
there are bonaﬂde reports of clinical
toxicity on oral intake (California Mor-
bidity Reports, Ankara), and even fa-
tality (Bitter Almond Poisoning, Zmedi-
zinfrul). Furthermore the proponents
themselves are aware of this toxicity as
evidence by the proposed labeling sub-
mitted in an application for an exemp-
tion for an Investigational New Drug
which warned: ‘CAUTION: Laetrile is
not to be taken orally. It is extremely
toxic by this route of administration
‘ ‘ ‘.’ There are no studies adequately
showing the distribution, activity and

Laetrile

metabolic fate of the parenterally ad-
ministered compound. Chronic effects
are not studied and reported in depth.
There is cause for the concern as other
similar beta-cyanogenetic compounds
cause serious toxic effects when ingested
on a chronic basis, e.g., Tropical Atataxic
Neuropathy in Nigeria (Attachment 20).
Effects of industrial poisoning from
chronic low concentration exposure are
well-known.” (See also, for discussion
of toxicity of Laetrile, section V.B.3. be-
low, “Dangers of Ingestion of ‘Vitamin
B—1‘7’ ”.)

Dr. Robert C. Eyerly reports, “One of
the unproven remedies for cancer man-
agement which the committee (on Un—
proven Methods of Cancer Management)
investigated is the drug Laetrile. Other
names for Laetrile include amygdalin
and prunasin. These compounds are
classiﬁed as cyanogenic glycosides. Cya-
nogenic glycosides, including amygdalin,
are generally regarded as toxic sub-
stances, rather than as foods, because
when they break down they liberate hy—
drogen cyanide, one of the most toxic
substances known” (R 167 at if 8).

Dr. Robert S. K. Young states (R 430
at 111i 4, 5, and 7), “The FDA does not
have authenticated or validated data on
the toxicity of amygdalin in humans. It
does not have scientiﬁc studies or the
data upon which scientiﬁc studies might
be constructed, in humans receiving
amygdalin which would allow it to de-
ﬁne the toxic effects of this drug. There
are no such reports in the medical litera—
ture. Nevertheless, Dr. Nepier from Ger-
many has reported that amygdalin causes
hypotension and hemoglobinurea in
humans. There have been reported cases
of cyanide poisoning in humans who ate
apricot kernels. The symptomatology in-
cludes dyspnea, cyanosis, vomiting, pros-
tration, convulsions, stupor, and paral-
ysis. Since these toxic effects are caused
by the cyanide, which is a constituent
part of amygdalin, amygdalin could cause
the same toxic effects. Although it is
possible that amygdalin can be given to
humans in doses which are non-toxic in
man, the drug is unsafe for use in
humans. There is no scientiﬁc evidence
that the drug can cure or is effective as a
treatment for any human cancer.” Dr.
Young also states (id. at W 2—3) , “There
is a difference between a drug’s toxicity
and a drug’s safety. The toxic effects of
a drug are those effects which are not
beneﬁcial to the person taking the drug,
but are deleterious. The safety of a drug

37

is deﬁned by the context of its use and
includes consideration of issues such as a
disease for which the drug is intended,
the alternative remedies which are avail-
able and their efficacy and safety, and
the possible abuse of the drug by those
who do not have the disease for which
the drug is intended. Acute toxicity tests
of amygdalin have been carried out in
animals. It appears that relatively large
quantities of amygdalin can be given
parenterally. When given by the oral
route, however, the toxicity of amygdalin
is greatly increased (by a factor of ap-
proximately twenty-ﬁve times) .”

James F. Holland, M.D., indicated that
he does not accept the theory of propo-
nents of Laetrile that patients should be
allowed to take Laetrile since, even if it
is ineffective, it cannot hurt. He states
(R 396 at 1), “It can hurt by interfering
with patients’ acceptance of indicated
therapy in the mistaken and false hope of
potential beneﬁt from Laetrile. Delayed
operation, refused radiotherapy, skipped
chemotherapy all risk an increasing
cancer morbidity and mortality because
of the premise that Laetrile is active.
This is a very dangerous side effect,
indeed.”

In addressing whether or not Laetrile
is safe, Dr. Carl M. Leventhal states (R
184 at 1119), “The question of whether
Laetrile is now, or ever was, generally
recognized as safe goes beyond the ab-
sence of any evidence indicating the lack
of toxicity of the drug. The safety of a
drug for human use depends, in large
measure, on the therapeutic effectiveness
of the particular drug. When patients
forego effective forms of therapy and
turn instead to worthless potions and
nostrums, their disease may progress
while effective therapies are foresaken.
In the case of cancer, treatment with an
ineffective drug will inevitably and in-
exorably lead to the patient’s death.
Seen in this light, an ineffective cancer
drug is inherently unsafe and even lethal,
because of the patient deaths which will
necessarily ensue.”

Dr. Harold J. Wallace, Jr., states (Tr.
at 174) that: “The safety of the various
forms of amygdalin has not been tested
by the usual scientific methods of clini-
cal pharmacology. There is evidence that
the crude oral form can and has caused
toxicity in humans and may cause death.
There has been no documentation of the
usual parameters that we require of drugs
when used in a clinical situation. We
don’t have blood levels achieved, activa-

 

Commissioner’s Decision

tion, clearance, metabolism, distribution
or excretion of amygdalin compounds in
man, as is usually required in the pre-
clinical and clinical evaluation testing
of chemotherapeutic compounds or other
drugs.”

Dr. Frank Rauscher, a former Direc-
tor of the National Cancer Institute
(NCI), and currently associated with the
American Cancer Society, said in his
statement concerning Laetrile, while he
was Director, NCI: “Assertions of the
non—toxic nature of Laetrile have not
been demonstrated in vigorous clinical
studies. Even if this claim is true, there
is no basis whatsoever for recommending
the clinical use of any non-toxic agent
if it cannot be expected to produce ob-
jective clinical beneﬁts" (R 173, Att.
“Statement Concerning Laetrile” at 2—
3).

Dr. Thomas H. Jukes states (R 41 at
l) : “Laetrile is not generally recognized
by experts as safe. In the presence of the
enzyme beta-glucosidase, Laetrile is hy—
drolized to glucose and mandelonitrile.
Mandelonitrile readily decomposes with
the liberation of hydrocyanic acid, which
is extremely poisonous at low levels. The
enzyme beta-glucosidase is widely dis-
tributed in materials of plant- origin. The
potential danger that laetrile may be de-
composed with liberation of hydrocyanic
acid makes it unsafe.”

Dr. George J. Hill, II, after noting that
ineifective remedies for cancer can lead
to delay in treatment and “needless and
untimely death,” states: “In the absence
of scientiﬁc evidence of effectiveness, no
drug intended for use in treating cancer
can be regarded as safe” (R 170 at i
11).

Dr. Joseph F. Ross noted that that de-
lay in cancer therapy because of use of
Laetrile “results in loss of life, tragic
suffering, and shortened life span” (R
190 at 8) and that use of the drug is
“hazardous to the health of cancer pa-
tients” (id. at 7). He states: ”Addition-
ally, the use of ‘Laetrile,’ Vitamin B—17,
‘Aprikern’ and other such amygdalin
containing materials when ingested pre-
sents a deﬁnite health hazard. The ac-
tion of gastrointestinal ﬂuids and en-
zymes releases the C=N (cyanide) radi-
cal from the compound and this may
produce acute cyanide poisoning” (id.
at 8).

Several additional experts submitted
afﬁdavits in which they state that
neither amygdalin nor any other cyano-
genic glycoside has ever been generally

38

recognized as safe (Dr. Charles G. Moer-
tel, R 186 at i 12; Dr. Jesse L. Steinfeld.
R 194 at 5—6; Dr. Peter G. Wiernik, R
200 at 'n 16; Dr. Emil J. Freireich, R 390
at 1T 19; and others).

III. THE “GRANDFAIHER” ISSUE

Because Laetrile is not generally rec-
ognized by qualiﬁed experts as safe and
effective (see discussion above) ,it is sub-
ject to the Act as a “new drug” unless it
is exempted from the statute’s provisions
under either of the two “grandfather
clauses.” These two exceptions, described
in more detail below, limit the protec-
tion provided to the public with respect
to certain drugs that fulﬁll a number of
carefully deﬁned conditions. According-
ly, the courts have recognized the nar-
rowness of these exceptions. United
States v. Allan Drug Corp, 357 F. 2d 713,
718 (10th Cir. 1966) cert. denied 385 US.
899 (1966): “Since we are dealing with
a Grandfather Clause exception, we must
construe it strictly against one who in-
vokes it.”; Durovic v. Richardson, supra,
479 F. 2d at 250 n. 6; United States v.
An Article of Drug * * * "Bentex Ul-
cerine” * * *, 469 F. 2d 875, 878 (5th
Cir. 1972), cert. denied 412 US. 938
(1973); United States v. 1,048,000 Cap-
sules, More or Less, Etc., supra, 347 F.
Supp. at 770.

The Court in Bentex Ulcerine held,
469 F. 2d at 878, that any party seeking
to show that a drug comes within the
grandfather exemptions “must prove ev-
ery essential fact necessary for invoca-
tion of the exemption.” Accordingly, the
Commission concludes that Laetrile will
not qualify for grandfather clause ex-
emption unless each of the essential facts
has been proved by evidence submitted in
the record.

In the February 18, 1977 FEDERAL
REGISTER notice initiating this proceed-
ing, proponents of Laetrile were in-
formed of their obligation to bring forth
evidence that would support their claim
that Laetrile qualiﬁes for this exception.
The notice set forth the provisions of a
regulation (21 CFR 314.200(e) (2)) that
detailed the format to which submissions
directed to the grandfather clause ex-
ceptions should conform (42 FR 10069).
Failure to submit formulas, labeling and
evidence of marketing in that format
was stated to constitute a waiver of any
contention that Laetrile was exempt
from new drug provisions of the act.
Failure to submit evidence in the format
has resulted in such a waiver.

‘4

Laetrile

Despite the waiver, the Commissioner,
in order to fully address the issue re-
manded by the courts, has culled the
entire record for evidence that might
arguably be relevant to the grandfather
status of Laetrile. He has considered this
evidence in determining whether the es-
sential facts necessary to invoke the
grandfather clause exemptions have
been proved. Moreover, against. the
chance that it should later be held that
those contending that Laetrile‘s use is
illegal must prove the nonexistence of
the essential facts necessary for the in-
vocation of the grandfather clause ex-
ceptions, the Commissioner has consid-
ered the evidence in the record in light
of this possibility.

The essential facts necessary to invoke
the two exemptions are discussed, to-
gether with the evidence relevant to
each, below. The Commissioner’s conclu-
sions on these issues may be summarized
as follows:

(1) Contentions that Laetrile qualiﬁes
for either grandfather clause exception
are waived.

(2) Evidence presented does not prove
the existence of each essential fact nec-
essary to the invocation of either grand-
father clause.

(3) While it is of course not possible
to prove a negative with regard to the
existence of each of the essential facts
involved, the record assembled contains
substantial evidence, constituting a clear
preponderance of the evidence submitted,
that these essential facts do not exist.

A. THE 1938 GRANDFATHER CLAUSE

To qualify for exemption from the
deﬁnition of a new drug under the 1938
grandfather clause, it must be shown
that the drug “at any time prior to the
enactment of this chapter [1938] ‘ * *
was subject to the Food and Drugs Act
otJune 30, 1906, as amended, and * " ‘
at such time its labeling contained the
same representations concerning the
conditions of its use; ‘ " "’ 21 U.S.C.
321(p) (1).

Thus, to qualify for this exemption, it
must be proved that (1) the identical
drug (2) bearing labeling containing the
identical representations concerning the
conditions of its use (3) was introduced
into interstate commerce in the United
States (or was manufactured in a Fed-
eral territory or the District of Colum-
bia) after June 30, 1906 and prior to the
enactment of the act in 1938. The ex-

39

emption applies onbi to drugs whose
labeling with respect to representations
as to conditions of use has undergone no
changes whatsoever from the labeling
utilized prior to the passage of the 1938
act, and whose composition is completely
identical to its composition prior to this
passage. If any change in representa-
tions for conditions of use in labeling or
any change in composition has occurred
since the enactment of the 1938 act, such
change precludes the applicability of the
1938 exemption. The proof required
would necessarily involve the production
of quantitative formulas, labeling, and
evidence of marketing both for the pre-
1938 use and for the present use. While
submissions to the administrative record
contained a number of references to use
of Laetrile or its predecessors before
1938, no proof was submitted to show
that what was termed “Laetrile" or
“amygdalin” as used before 1938 was the
same drug which is now being marketed.
Nor is there any indication whatever
that the labeling of the various drugs
claimed to have been marketed before
1938 contained representations concern-
ing conditions of use which are identical
to the representations associated with
the presently marketed drug. It should
be noted that the term “labeling” is
deﬁned in the act to include not only
“all labels” but also, “other written,
printed, or graphic matter (1) upon any
article or any of its containers or wrap-
pers, or (2) accompanying such article,"
21 U.S.C. 321(m). This deﬁnition has
been given a broad interpretation, see,
e.g., Kordel v. United States, 335 US.
345, 347—50 (1948): United States v.
Urbuteit, 335 US. 355, 357 (1948).

A number of submissions in the record
referred to use of substances claimed to
be related to Laetrile or amygdalin in
ancient times. While each of these state-
ments was hearsay unsupported by any
sort of corroborating evidence and thus
cannot be considered trustworthy, it is
apparent that even if accepted at face
value these claims would not justify
invocation of the 1938 grandfather
clause. Examples of such claims in the
record include those found in a Mc-
Naughton Foundation article entitled
“Information for Physicians: Amyg-
dalin, The Non-Toxic Analgesic” which
cites use by the Chinese 3,500 years ago
as well as use by the Greeks and the
Romans (R 183, Att. 106 at 1] 1). See
also Hanson v. United States, 417 F.
Supp. 30, 36 (D. Minn.) aﬂE’d 540 F.2d

Commissioner’s Decision

947 (8th Cir. 1976) (copy of opinion
attached to R 173) , noting that plaintiffs
in that court action had introduced
hearsay concerning the use of amyg-
dalin by ancient Egyptians, evidence
upon which the court did not rely; affi-
davit of Chauncey Leake, Ph.D.—rec-
ommendation of almonds for various
purposes (not to cure cancer) by a ﬁrst
century Greek surgeon (R 302, Ex. K);
statement by John J. O’Conner, Jr., in
support of a Maryland State bill on
Laetrile—bitter almond used by Chinese
for the treatment of tumors 3.500 years
ago; use by Greeks and by Romans (Tr.
Ex. 4, Att. at 22).

Other submissions mentioned that
amygdalin was prepared by two French-
men in 1830 and analyzed by two Ger-
mans shortly thereafter. (See R 183, Att.
10b at 11 1; R 302, Ex, K; R 168, Att. at
345; R 80, Att.) No claims were made
that these 19th century experimenters
used amygdalin to treat cancer. There
is a claim, however, that a Russian phy-
sician used amygdalin for that purpose
in 1845. The reference is to a report in
the Gazette Medicale De Paris. Tome
XIII, Samedi, Le 13 Septembre 1845, by
Dr. Inosemtzeﬂ’. This article is referred
to in a number of submissions. (See, e.g.,
R 259, Att. at 1.) It was not, however,
itself submitted and in thus not part of
the record available for analysis by the
Commissioner. According to the descrip-
tion in the “Listing of Documents Rela-
tive to ‘ ‘ “ Laetrile” attached to R 259,
a submission by Mr. Wynn Earl West-
over, the author of the 1845 article was a
professor of surgery at the Imperial Uni-
versity of Moscow, and his article de-
scribed two cases of cancer apparently
successfully controlled for 11 years and 3
years, respectively, by the use of
amygdalin (for other references to this
article, see R 260, Att. at 1: R 302, Ex.
L at ‘H 5) .

As is obvious, this “evidence” relating
to ancient and 19th century use is irrel-
evant to the 1938 grandfather clause
issue for the following reasons: (1) It
does not indicate that the drug was used
in the United States after June 30, 1906
and before 1938. (2) It gives no indica-
tion that the drug used was the same as
Laetrile. Most of the references in fact
indicate that the substances used were
either some extract of almonds, or, as in
the case of the alleged Russian physi-
cian, simple amygdalin. (3) No sugges-
tion that any drug was to be used in ac-
cordance with the indications now asso—

40

ciated with treatment with Laetrile may
be found in these references. Again,
where the submissions go into detail con-
cerning the historical uses of almonds or
amygdalin, it is apparent that different
conditions of use are involved.

A number of claims purporting to be
relevant to the 1938 grandfather issue
dealt with the appearance of almond ex-
tract in various Pharmacopeia. (See, e.g.,
Tr. at 250; R 302, Ex. K and Ex. L, '7 9—12
'I‘r. Ex. 9.) The opinion in Hanson v.
United States, supra, indicates that
plaintiffs in that case relied upon a list-
ing of amygdalin in the Merck Index of
1896. The references in the Pharmaco-
peia involve in each case some sort of
almond extract. There is no indication
that that extract was to be used as an
injection to cure, control, or prevent
cancer. The references to the Pharmaco-
peia. as is the case with other general,
unsupported references indicating use in
cancer patients in previous centuries
(see, e.g., R 509 at 2) are for the reasons
detailed simply not probative of grand-
father status.

Of more direct relevance to possible
grandfather status is the information in
the record regarding the work done with
what was apparently Laetrile’s prede-
cessor by Dr. Ernst Krebs. Sr. A great
deal of conﬂicting information regarding
the dates of Dr. Krebs’ work was sub-
mitted to the record. There are numerous
instances in the record of statements
that Dr. Krebs developed a drug related
in some way to modern day Laetrile
either in 1920 or shortly thereafter, while
a new and allegedly nontoxic form of Lae-
trile was developed by Ernst T. Kerbs. J r..
in 1952 or in the early 1950’s. See, e.g., the
American Cancer Society Committee on
Unproven Methods of Cancer Manage-
ment’s article on Laetrile (R 167, Ex. 2) ;
A Report on the Treatment of Cancer
with Beta—Cyanogenetic Glucosides
(“Laetriles”) by the Cancer Advisory
Council, State of California (1963) at 2
(R 183, Att. 16). The latter report may
be the genesis of the 1920 date, though
the former indicates that it is reporting
the date “According to" Dr. Krebs. At
any rate, the 1920 date appears in or is
alluded to in a number of submissions
(see R 173, Att., “Questions Most Fre-
quently Asked,” and Att., “Laetrile: The
Making of a Myth,” FDA Consumer (Dec.
1976—Jan. 1977) at 6; R 184 at 11 6; Tr. at
272; Tr. at 41; R 250 at 2—3; R 170, Ex. 3
at 2104; R 258, Ex. 16; R 386; Tr. Ex. 10;
R 183, Ex. 3 at 33.) There may have been

Laetrile

some basis for the original statement
that Dr. Krebs had begun to work or had
achieved results on a substance contain-
ing amygdalin in 1920 or in the early
1920’s. but nothing has been submitted
to indicate what that basis is. The ap-
parent manner in which one submission
has relied upon another on this question
illustrates the undersirability of relying
on hearsay accounts to prove a fact of
this kind. None of these statements indi-
cate, in any case, that the materials with
which Dr. Krebs was experimenting were
identical to, and were used under con-
ditions indicated in labeling which were
identical to, the composition and indica-
tions for present day Laetrile.

Michael L. Culbert, representing the
Committee for Freedom of Choice in
Cancer Therapy at the oral hearing,
stated: “Dr. Krebs, Sr., both publicly
and privately and in numerous diﬂ'erent
ways, has published not only results but
some labels of material that goes back
to the 1920’s when Dr. Stohl in Switzer-
land and a number of Japanese scien-
tists and Dr. Krebs, Sr., and others were
working with the original extract” (Tr.
at 41). If Mr. Culbert or his group have
in their possession such publications,
they have not submitted them.

A document submitted which would
seem, questions of credibility aside, to be
the most reliable on the question of the
dates of Dr. Krebs’ work and that of his
son is an afﬁdavit signed and sworn to by
Dr. Krebs on April 28, 1965. This aﬂi-
davit, taken by an FDA employee, ap-
pears as Exhibit 6 to R 184 and as at-
tachment 13 to R 183. Since this afﬁdavit
is under oath and is by the person most
likely to know of the dates in question,
the Commissioner concludes that where
the dates in the afﬁdavit are difierent
from those appearing elsewhere, chief
reliance should be placed on the afﬁ-
davit. In the relevant paragraphs, Dr.
Krebs says:

i t t t a

2. In 1926, I made an extract from apricot
kernels which I called Sarcarcinase. This
extract contained Amygdaiin and 1-g1uco—
sidase. When I injected this product into
rats it was toxic and killed some of them.

3. In 1936, I changed the composition of
the preparation resulting from the extract
of apricot kernels so that the only active
principle which remained was Amygdalin.

4. During the period between 1936 and
1960, I perfected the puriﬁcation process so
that the purity of the Amygdalin rose from
66 percent in 1936 to 99.8 percent by 1960.

5. In 1955, I began to lyophilize the Amyg-
dalin and I have been lyophilizing it in its

41

ﬁnal form ever since when I produce it in my
laboratories.

6. In 1949, my son, Ernst T. Krebs, Jr..
gave the name Laetrile to the Amygdalin I
was producing and I have used the name of
Laetrile ever since that time for the ﬁnal
form of the Amygdalin which I produce.

7. As early as 1926 and up through 1962, I
ﬁrst began to ship and have done so continu-
ously thereafter the Sarcarcinase extract (cf
2), then the amygdalin (cf 3), then the puri-
ﬁed amygdalin (cf 4), then the puriﬁed and
lyophilized amygdalin (5), and then since
1949 (cf 6) the latter under the name of
Laetrile to persons in other States outside
of the State of California and in many other
countries. Many of these persons have re—
ported their studies in scientific and medical
Journals and in private communications over
several decades. The above shipments were
for investigational use only.

As the dates cited by Dr. Krebs illustrate,
the substance with which he experi-
mented in the 1920’s and 1930’s was not
the same substance as that which he was
using in 1962. The pre-1938 use is, for
that reason alone, not sufﬁcient to
qualify Laetrile for exemption from cov—
erage of the act under the 1938 grand—
father clause.

In another document upon which the
Commissioner would ordinarily place re-
liance, a December 15, 1962 report by
FDA inspectors describing their conver-
sations with Dr. Krebs, Sr. (R 184, Ex.
5), Dr. Krebs is reported to have stated
that “he began experimenting some 10
months ago with the extraction of Cyan-
ogentic Glucoside from a mixture con-
taining apricot pits. The puriﬁcation of
this glucoside was effected in the labor-
atories of Dr. Krebs and used in the
treatment of his patients with, according
to him, satisfactory results. This mate-
rial assertedly liquiﬁes malignant
growths by the release of cyanide in the
area. Injections are made around the
area and the case of lung cancer injec-
tions are made in the apex of the tra-
pezei.” It may be that Dr. Krebs in his
statement to the inspectors was speaking
of his eiIorts to purify Amygdalin, re-
ferred to in paragraph 4 of his afﬁdavit.
On the second page of the inspectors’
report, they indicate that “E. T. Krebs,
Jr., stated that Dr. Harry Pincus Jacob-
son, M.D., was the ﬁrst to use ‘Laetrile’
on humans and that this was in June
1952. Up to the present time [December
1952] he has used the product on ap-
proximately 14 cases.”

This last quotation from the inspection
report comports with statements else-
where indicating that in 1952 Mr. Krebs,

Commissioner's Decision

Jr., developed a new product, related to
the products with which his father had
been working, which he called Laetrile.
While the failure of the afﬁdavit of Dr.
Krebs, Sr., to mention this “improve-
ment" by Mr. Krebs, Jr., might lead one
to question whether such an improve-
ment had taken place, an article by the
senior Krebs and Dr. Arthur Harris,
copyright 1955, entitled, “The Treat-
ment of Breast Cancer with Laetrile by
Iontophoresis” (R 183, Att. 7) at 23—24,
states as follows:

In 1952 the senior author's biochemist son,
Ernst T. Krebs, Jr., became interested in the
preparation his father had used on cancer for
so many years In his laboratory—the John
Beard Memorial Foundation—he tore the
drug apart and came to the conclusion that
it was not only the glucoside but more par-
ticularly the cyanogenetic glucosxde that had
beneﬁted cancer patients. He succeeded in
separating the enzyme Emulsin from the
cyanogenetic gluccside and advised their ad-
ministration separateiy, in order to avoid the
premature trigger-off of HCN from the chem-
ical breakdown in the somatic (or normal)
tissue, for this gas—HCN—was the active
agent in destroying the cancer cell.

Again the senior author tried each puriﬁed
preparation—the cyanogenetic glucoside and
the enzyme Beta-g1ucosidase—separately. He
administered the cyanogenetic glucoside
parenterally (by injection) and followed it
in ﬁfteen minutes or so with an injection
of the enzyme Beta-glucosidase. The cancer
victims so treated tolerated both the drug
and the enzyme excellently—and were im-
measurably improved. Using the chemical
and the enzyme separately, therefore, gave
a high degree of safety as well as enhancing
its cancerolytic effect.

t n t It t

Because this apricot kernel preparation
was “Laevorotatory” (left-handed) to polar-
ized light, and because Amygdalin was chem-
ically a "mandelonitrile," Krebs, Jr., united
the first and last syllables to invent a name

for the new cancericidal drug-LAETRILE.

Krebs Jr. uncovered the vital link that
united Laetrile with the Unitarian or
Trophoblastic Thesis of Cancer. In the pre-
vious chapter we emphasized the known
fact that most malignant lesions are focally
characterized by high concentrations of the
enzyme Beta-giucuronidase—one of the main
attributes common to both the trophoblast
cell and the cancer cell. The Beta-
glucuronidase of the animal kingdom is the
equivalent of Emulsin in the vegetable king-
dom, and Emulsin is the very enzyme that
Krebs, Jr. separated from Amygdalin to make
the empirical apricot formula safe for par-
enteral (injection) administration to
humans! 7

42

This was an epochal milestone. Krebs, Jr.,
worked and experimented feverishly now:
he was on the brink of cataclysmic discov-
eries, discoveries which, if substantiated,
could mean victory over invincible Cancer!

He found that when he added Emulsin to
Laetrile and incubated the mixture, hydro-
cyanic acid gas (HCN), one of the deadliest
of gaseous poisons, was given off. He found
that when he added animal Beta-
glucuronidase (or prepared enzyme Beta-
giucosidase) to Laetrile and incubated the
mixture, HCN was again given off. This, he
knew then, was the reaction that took place
within the body—IN THE CANCER CELL!

The need for Krebs, Jr.’s improvement
was related to the lack of safety of his
father’s original preparation. As this ar-
ticle co-authored by the senior Krebs
states, the original “preparation proved
so toxic that he and his colleagues who
were experimenting with him were re-
luctant to continue its use, except in dire
circumstances” (id. at 23; cf R 167, Ex.
2; R 170, Ex. 3 at 2014; R 386, Att. at
2-3) . Again, it is apparent that the im-
provement in the substance used by the
Krebs (father and son) after 1938 made

the drug different in composition, and
also in indications for use, from the drug
which was used before 1938. The 1952
date appears at several points in the
record. (See, e.g., R 167, Ex. 2; R 173,
Att. “Laetrile: The Making of A Myth”
supra; R 173, Att. 3; R 184 at H 6; R 189;
Tr. at 272; R 250 at 2—3; Tr. Ex. 10 at 3 ‘

In the submission of Mr. Wynn Earl
Westover (R 259) (see also R 260), in a
document entitled “Listing of Documents
Relative to the Krebs Enzyme Extracts
Later Known as Laetrile,” at 13, there is
a list of registrations of trademarks and
issuances of letters patents allegedly
granted for Sarcarcinase during the
years 1930 through 1935. These docu-
ments have not all been submitted. Ap-
parently submitted as representative of
the patents is a patent speciﬁcation from
the Government of Ireland. As the above
discussion indicates, the material covered
in these patents is different from the
material now known as Laetrile. A sub-
mission by Eric E. Conn, Professor of
Biochemistry at. the University of Cali-
fornia, Davis (R 424) discusses this pat-
ent application and states that if the
procedure set out in the patent is fol—
lowed, “much or all of the amygdalin in
the intact kernels may be destroyed by
enzymes set in action by the grinding”
of the kernels to produce the extract.
Most of the amygdalin remaining would
be lost in processing. The extract pro-

Laetrile

duced “would be a mixture of glycerides,
esters, certain pigments and other fat—
soluable compounds that might or might
not also contain a small amount (less
than 5 percent) of the amygdalin re-
maining in the ﬁnely ground kernels.”
Compare the claims by Robert W. Brad-
ford, President of the Committee for
Freedom of Choice in Cancer Therapy,
Inc., at the oral argument, that “Laetrile
was ﬁrst offered for sale in a trademark
assigned in 1934, that it was sold at that
time in three different forms: tablets,
capsules, and injectables, [and that it]
pharmaceutically was the same sub-
stance used today in cancer therapy.
There can be no disagreement on this
point” (Tr. at 346). Mr. Bradford sub-
mitted nothing to support his claim,
which is at odds with the factual infor-
mation submitted in the record and dis-
cussed above.

The Westover submission (R 259) also
includes copies of a number of letters by
various doctors who indicate that they
have used the senior Krebs’ formula-
tion in the treatment of tumors or can-
cer. The letters bear dates in the 1930’s.
Mr. Westover’s submission claims that
there are a large number of other letters,
not submitted, which are of generally the
same type. Ernst T. Krebs, J r., appearing
at the oral argument, testified that amyg-
dalin had been used as early as 1932. He
indicated that the product then in use
was labeled Sarcareinase. (See Tr. at 232,
238, 246.) Sarcarcinase is the name of
the product which was, according to Mr.
Westover, granted a United States trade-
mark in 1934. (See also Tr. at 446-48.)
Two afﬁdavits, apparently prepared for
some court action, by Charles Gurchot,
Ph.D., and Chauncey Leake, Ph.D., indi-
cate that the aﬂiants were involved in the
treatment of patients with Krebs, Sr.’s
product in the 1930‘s (R 302, Ex. K and
L).

The Commissioner has carefully sur-
veyed the entire administrative record
brought together for this proceeding.
While it appears that Dr. Krebs, Sr., was
utilizing some substance, which appar-
ently had the trademark name of Sar—
carcinase, before 1938, there is no evi-
dence that that substance is identical in
its formulation, or in its indications for
use, to present day Laetrile (of R 416 at
1! 27(1) (7) (pg. 23) ) . In fact, as discussed
above, the record is clear that the sub-
stance with which Dr. Krebs, Sr., experi-
mented in the 1930’s is different from the
drug now being used by Laetrile propo-

43

nents. The evidence suggests that the
substance used by Dr. Krebs, Sr., in the
1930's was too toxic for general use. This
toxicity appears to have been the reason
for the work of Mr. Krebs, Jr., which,
apparently, culminated in a substantial
change in the formulation around 1952.

The Commissioner thus concludes that
(1) no proof has been offered which
shows that Laetrile was used and labeled
before 1938 in a manner identical to its
present use and labeling, and that (2)
the evidence in the record demonstrates
that present day Laetrile was not devel-
oped until after 1938. Thus, regardless
of where the burden of proof lies in an
administrative proceeding of this type,
the Commissioner must conclude that
Laetrile is not eligible for exemption
from the protection to the public pro-
vided by the new drug provisions of the
act h cause of use prior to 1938 involving
identical labeling as to conditions of use.

D. THE 1962 GRANDFATHER CLAUSE

The provision that has been character-
ized as the “1962 grandfather clause” is
set forth at section 107(c) (4) of Pub. L.
87—781 [note following 21 U.S.C. 321]:

(4) In the case of any drug which, on [Oc-
tober 9, 1962] the day immediately preceding
the enactment date, (A) was commercially
used or sold in the United States, (B) was
not a new drug as deﬁned by section 201(p)
of the basic Act as then in force. and (C)
was not covered by an effective application
under section 505 of the Act, the amend-
ments to section 201(p) made by this Act
shall not apply to such drug when intended
solely for use under conditions prescribed,
recommended, or suggested in labeling with
respect to such drug on that day.

The “basic Act as then in force” read
in relevant part as follows:

Sec. 201. For the purposes of this Act-

* t t l- n:
(p) The term “new drug" means—

(1) Any drug the composition of which is
such that such drug is not generally recog-
nized, among experts qualiﬁed by scientiﬁc
training and experience to evaluate the safety
of drugs, as safe for use under the conditions
prescribed. recommended, or suggested in the
labeling thereof, except that such a drug not
so recognized shall not be deemed to be a
"new drag’ if at any time prior to the enact-
ment of this Act it was subject to the Food
9 d Drugs Act of June 30, 1906, as amended,
and ' ‘ at such time its labeling contained the
same representations concerning the condi-
tions of its use; or

(2) Any drug the composition of which is
such that such drug, as a result of investi-
gations to determine its safety for use under

Commissioner's Decision

such conditions, has become so recognized,
but which has not, otherwise than in such
investigations, been used to a material ex-
tent or for a material time under such
conditions.

The Commissioner has previously ad-
mitted that one of the conditions for
1962 grandfather status does exist— Lae-
trile (or amygdalin) was not covered by
an effective NDA on October 9, 1962. (See
42 FR 10069.) The Commissioner con-
cludes on the basis of the information
in the administrative record that Laetrile
(or amygdalin) fails to meet all of the
other requirements for qualifying for the
1962 grandfather clause exemption: (1)
No showing has been made that a drug
was used or sold on October 9, 1962 which
has the same composition as a drug used
or sold, or sought to be used or sold, to-
day. (2) The record is clear that any use
of drugs called “Laetrile” or “amygda-
lin" in cancer therapy in 1962 was for
investigational use. Investigational use
can not provide the basis for exemption
from new drug status on October 9, 1962
(see section 201(p) (2) of the act as then
in force, set forth above) and of course
does not constitute commercial use or
sale. (3) No showing has been made that
conditions of use recommended in label-
ing of a drug used or sold on October 9,
1962 are the same as those now recom-
mended in labeling for the same drug.
In fact, neither present labeling nor 1a-
beling in use on October 9, 1962 has been
submitted to the record. Review of la-
beling available for “Laetrile” before and
after October 9, 1962 reveals substantial
changes in the prescribed conditions of
use. (4) Laetrile (or amygdalin) was not
generally recognized, by experts qualiﬁed
by scientiﬁc training and experience to
evaluate drug safety, as safe for use in
cancer therapy on October 9, 1962.

As has been noted above, the Commis—
sioner has concluded that the proponents
of the proposition that Laetrile is exempt
from the act because of “grandfather”
status must bear the burden of proving
that it is exempt. As has also been pre-
viously noted, however, the Commis-
sioner has made a determination based
on the alternative theory that the Gov-
ernment must prove that at least one
of the essential facts leading to exemp-
tion does not exist. Proof of a negative
is obviously more feasible in some in-
stances than in others. The record leaves
no doubt that use of Laetrile (or amyg-
dalin) on October 9, 1962 was for in-
vestigational purposes and that use of

44

the drug in cancer therapy was not “gen-
erally recognized” by qualiﬁed experts
to be safe on that date. Since neither the
present composition nor the present 1a-
beling of the drug appears in the record,
it may not be conclusively determined
that that composition and the conditions
of use suggested in that labeling are not
the same as the composition and sug-
gested conditions of use of some drug in
1962. Nonetheless, the Commissioner is
able to conclude, based upon substantial
evidence which constitutes the prepon-
derance of the evidence in the record,
that neither of those essential facts (i.e.,
identical formulation and identical con-
ditions of use) do exist as to Laetrile
(or amygdalin) .

1. Composition

Clearly, for the 1962 grandfather
clause to apply, the identical drug must
have been used or sold in 1962 as is pres-
ently used or sold. The fact that a drug
with the identical name (or names) was
being used is irrelevant. Similarly, the
fact that a drug in commercial use on
October 9, 1962 has ingredients (such as
amygdalin) in common with drugs in
use today would not be sufﬁcient under
the grandfather clause if any of the in-
gredients of the drug, or the proportions
in which those ingredients appeared in
the drug, had changed (see generally 21
CFR 310.3(h) ). Even a change in an in-
active ingredient wiil make a drug a “new
drug,” (see 21 CFR 310.3(h) (1); United
States v. Article of Drug "Entrol-C Med-
icated,” 513 F.2d 1127, 1130 n. 7 (9th Cir.
1975) ).

The discussion earlier in this opinion
of the identity of drugs characterized at
different times as “amygdalin” or as
“Laetrile” illustrates the wide variation
in composition of these drugs. There is
no evidence in the record of the present
formulation of Laetrile or of amygdalin
medication. Neither is there evidence of
the composition of such a drug on Oc-
tober 9, 1962. The Commissioner thus
concludes that there has been no show-
ing that Laetrile or amygdalin as pres-
ently constituted was in use on October
9, 1962. The Commissioner also con-
cludes, based upon the evidence of wide
variation in the drugs’ composition, both
before and after 1962 (discussed below),
that the 1962 versions and the versions
of the drugs currently in use are not
identical.

It should be noted that the Commis-
sioner’s decision on this point is in ac-

Laetrile

cord with a statement by Andrew Mc-
Naughton of the pro-Laetrile McNaugh-
ton Foundation, discussed earlier, that
data on Laetrile obtained prior to 1968
are frequently not reliable because of
the variability in composition of early
preparations (R 173, Att., “Report of
Ad Hoc Committee of Oncology Con-
sultants”). Other evidence on the ques—
tion of composition of the drugs consists
of (1) analyses done of Laetrile products
and (2) representations made as to the
products’ composition. (The discussion
of the 1938 grandfather issue sufﬁciently
catalogues and disposes of claims that
drugs similar to Laetrile or amygdalin
were marketed prior to 1938, and this
section will thus discuss evidence post-
dating 1938.)

Analyses. As discussed previously, the
results of analyses of drugs called “Lae-
trile” have often been at variance with
their labeled composition. Analyses by
Canadian investigators, reported in 1965,
found that two versions of the drug, one
manufactured in the United States and
one manufactured in Canada, had dif-
ferent compositions. The American ver-
sion contained 9812 percent amygda-
lin plus .5 percent phenol. The Canadian
version contained 87:2 percent amygda-
lin, 5 percent di-isopropylammonium
iodide, and 8:2 percent sucrose (R 189,
Att., “Laetrile: A Study of its Physio-
chemical and Biochemical Properties” at
1059).

Analyses done in 1961 and 1962 for the
California Cancer Advisory Council of
samples of Laetrile from various differ-
ent sources—samples obtained in 1951
and 1953, samples obtained from Hale
Laboratories, and samples obtained from
Dr. Krebs, Sr.—also showed a variation
in composition among the drugs (R 183.
Att. 16 at 27) . Similarities to commercial
amygdalin were revealed in some tests.
(See, e.g., R 183, Att. 16 at 28 and App.
8.) “The old Laetrile [1951 and 1953]
was similar but not identical to amygda-
lin in the [infra-red examination], while
the new Laetrile exhibited certain simi-
larities and certain dissimilarities to
both the old Laetrile and to amygdalin”
(R 183, Att. 16, App. 8 at 1). Some
samples were found to contain inorganic
iodine; others did not contain that sub-
stance. (See, generally, R 183, Att. 16,
App. 7 and 8.)

Claims. A new drug application sub-
mitted to FDA by Ernst T. Krebs, Jr., on
October 3, 1962, lists the composition of
Laetrile as:

45

L-mandelonitrite-diglucoside

dalin] 1,000 mg.

N, N-diisopropylammonium iodide 50

mg.

Inactive saccharides, principally su-

crose 176-250 mg.
The drug was to be reconstituted with a
sterile isotonic solution (R 201, Ex. B at
101—102).

Dr. Krebs, Sr., in his 1965 afﬁdavit,
stated that his preparation contained
amygdalin as its only active principle
and that that amygdalin, by 1960 at
least, was lyophilized and 99.8 percent
pure. (See R 183, Att. 13.) It is not clear
whether other, inactive, ingredients were
a part of the drug he prepared.

A 1953 letter from Ernst T. Krebs, Jr.,
to California medical authorities states
that he was forwarding to Dr. Mac-
donald “samples of biosynthetically de-
graded amygdalin in which one dextrose
was removed by prunasin and the result-
ing compound, in the presence of plati-
num black, was oxidized to the corre-
sponding glucuronoside” (R 183, Att.
14).

In 1965, FDA investigators obtained
examples of labeling utilized by the
senior Krebs’ laboratory. The labeling
indicates that Laetrile is “cyanide gluco-
side type amygdalin.” Additional label—
ing, a pamphlet entitled “Laetrile: Direc-
tions for the Administration of Laetrile,”
states that the drug is to be reconsti-
tuted with water, a non-isotonic solution
(see R 201 at 11 10a and Ex. C).

Mr. Krebs, Jr., in a 1970 article in the
Journal of Applied Nutrition (R 183, Att.
10c) in which he explained his theory
that Laetrile and similar substances
make up Vitamin B—l'l, suggested the
drug use of a substance clearly different
from all other Laetrile drugs previously
in use. While what had been used pre-
viously had apparently been a manufac-
tured drug containing either the “Lae-
trile” of his own formulation or amyg-
dalin in a more or less puriﬁed form, in
this article he advised that “one gram
of defatted apricot seed or kernel car-
ries about 30 milligrams of nitriloside.
Six or seven teaspoonsful will supply
what our clinical investigators consider
an adequate oral dose—one gram. It is
best that the [beta] -g1ucosidase enzyme
be completely heat inactivated in such
material" (id. at 84). As discussed pre-
viously, this advocacy of the use of apri-
cot kernels rather than a manufactured
drug represents a change in the formu-
lation of the product which is of particu-

[amyg-

Commissioner's Decision

lar importance because of the danger of
toxicity associated with oral ingestion of
apricot kernels.

The Commissioner concludes that
drugs called variously Laetrile and
amygdalin have no set composition,
their makeup varies depending upon the
manufacturer and the time of manufac-
ture. It thus appears that any drug in
use on October 9, 1962 was different in
composition from Laetrile as used. or
proposed to be used, today.

2. I nvestigational Use

The record is clear that use of Laetrile
(amygdalin) on October 9, 1962 was for
investigational, not commercial, pur-
poses. This fact is borne out by legal
documents concerned with each of the
two major ﬁgures in its development—
Dr. Ernst T. Krebs, Sr., and his son,
Ernst T. Krebs, Jr.—and by other in-
formation in the record. Much of the
evidence relating to the 1962 grand-
father issue, like that relating to the
1938 grandfather issue, is not of the type
which would be considered reliable evi-
dence in a court of law. In many cases
the “evidence” consists of hearsay which
is not substantiated by any documenta-
tion. The record does contain, however,
a sworn afﬁdavit of Ernst T. Krebs, Sr.
In this aﬂidavit (R 183, Att. 13 at 11 7)
Dr. Krebs describes his shipment in in—
terstate commerce of various versions of
his cancer cure, including amygdalin
which he stated to have been sold after
1949 under the name of Laetrile, “up
through 1962.” Dr. Krebs states, “The
above shipments were for investigation—
al use only.”

Ernst T. Krebs, Jr., and the John
Beard Memorial Foundation were con-
victed in 1962, upon pleas of guilty, of
charges of introducing and delivering for
introduction in interstate commerce a
new drug without an approved new
drug application (R 183, Att. 16, App.
17) . The drug involved there was another
unproved remedy, called by Mr. Krebs
“pangamic acid” or “Vitamin B—15.”
Sentence of imprisonment on those
charges was suspended and the defend-
ants placed on probation for 3 years
on the condition that they not manu-
facture, sell, offer for sale, hold for sale,
or deliver or give away any “new drug.”
Mr. Krebs, Jr., obtained a special order
which allowed him to ship 400 vials of
Laetrile to the McNaughton Foundation
in Canada, “for investigational use” pro-

vided the Canadian Food and Drug D1-

46

rectorate acquiesced in that shipment.
In a supplemental order of June 28,
1962, Ernst T. Krebs, Jr., was permitted,
under certain detailed conditions, to
deliver Laetrile to experts qualiﬁed by
scientiﬁc training and experience to in-
vestigate the safety of drugs. The drug
was not to be administered to any
patient except one with extensive mal-
ignancy who was receiving Laetrile un-
der Kreb’s direction as of June 15, 1962.
Thus, if Laetrile were in commercial use
on October 9, 1962, and if the Laetrile
involved were supplied by Mr. Krebs, J r.,
he was in violation of this court order.
Copies of the court papers involved in
this criminal prosecution are found at
appendix 17 to attachment 16 to R 183.

Use of a drug is investigational, as
contrasted with commercial, when that
use is for the purpose of determining
whether, or demonstrating that, the
drug in question is safe and effective.
The record contains no evidence to sug-
gest that, contrary to the aﬂidavit of
Dr. Krebs, Sr., or to the court order bind-
ing Ernst T. Krebs, Jr., Laetrile (or
amygdalin) was being used on October 9,
1962 for other than investigational uses.

“In 1953 the Cancer Commission of
the California Medical Association in-
vestigated the claims made for the use
of Laetrile in cancer treatment and con-
demned its use” (R 168, Att. “Vitamin
Fraud”). The activities that led to the
Medical Association action were ap-
parently based upon Dr. Krebs’ use of
Laetrile. As shown by labeling collected
during a 1952 FDA inspection, the Lae-
trile then in use was labeled, “Caution:
New Drug limited by Federal Law to
investigational use.” (See R 184, Ex. 5.)

A submission to the record which con-
tains much information about the use
of Laetrile at about the crucial date of
October 9, 1962 is the 1963 report of the
California State Cancer Advisory Coun-
cil entitled “Treatment of Cancer with
Beta-cyanogcnetic Glucosides (‘Lae-
triles’) ” (R 183, Att. 16). While the
Council concluded that use of Laetrile
was not warranted in any context, its re-
port does not contradict Krebs’ claims
that use was investigational at that
time.

Other references to the use of Laetrile
prior to 1962 do not specify whether or
not the use mentioned was investigation-
al, see R 183, Atts. 5, 6; R 307 at 1; R 64;
R 174. Ex. 2; Tr. at 81—82.

A pamphlet entitled Information for
Physicians, Amygdalin The Non-Toxic
Analgesic provides information about

Laetrile

what it states to be the experience of
various doctors around the world in ad-
ministering amygdalin to patients.
Some of the statements indicate use by
doctors before 1962—that use appears to
be investigational and was not, with the
exception of 10 cases reported by a New
Jersey doctor, in the United States (R
183, Att. 10 (b) ).

The article by Levi et al., “Laetrile: A
study of its Physiochemical and Bio-
chemical Properties,” discussed above,
refers to Laetrile as “a drug manufac-
tured and distributed until recently for

clinical trial in Canada and the United
States to determine its value as a pallia—
tive in cancer therapy" (R 189, Att. at
1057).

In 1970 the McNaughton Foundation
submitted an IND for Laetrile, which
was disapproved by FDA (R 184 at 11 9).
An IND is a notice, filed by persons in-
terested in the development of a drug
product, which seeks permission to dis-
tribute an unapproved new drug for the
purpose of conducting clinical investiga-
tions of it in humans. Such clinical in-
vestigations must be completed to form.
the basis for an NDA for the drug. The
fact that Laetrile’s proponents were still
seeking to investigate its use in 1970 is
additional evidence that any use of the
drug on October 9, 1962 was investiga-
tional.

3. Conditions of Use in Labeling

In order to qualify for the 1962 grand-
father clause, Laetrile (or amygdalin)
would need to “be intended solely for use
under conditions prescribed, recom-
mended, or suggested in labeling with
respect to such drug on” October 9, 1962
(section 107(c)(4) of Pub. L. 87481).
Conditions of use include, among other
things, what the drug is recommended
for, how it is to be administered, and in
what quantities it is to be administered.
Under the statute, any change in those
conditions from October 9, 1962 to the
present disqualiﬂes the drug from ex-
emption. (See United States 1). Allan
Drug Corp. supra.) Here, no submission
contains either labeling now in use or
proposed for use, or labeling used on Oc-
tober 9, 1962.

Since no labeling in use on October 9,
1962 has been submitted, the indications
found in labeling in use in years prior
to that time will be discussed as illustra-
tive of the variation in proposed condi-
tions of use apparent in the record. The

47

Commissioner will then review labeling
from dates after October 9, 1962. As the
following discussion demonstrates, not
only do the proposed conditions for use
of Laetrile (amygdalin) vary from before
October 9, 1962 to after that date, no
two sets of labeling propose the same
conditions.

Before October 9, 1962

A new drug application (NDA) sub-
mitted to FDA by the John Beard Me-
morial Foundation and Ernst T. Krebs,
Jr., on October 3, 1962 indicates that
Laetrile was a lyophilized water-soluble
powder for use in the palliation of human
cancer. Excerpts from the NDA, attached
as Exhibit B to R 201, provide informa-
tion concerning its intended uses: It was
to be administered by injections of 1
gram each, which were to be either every
day or every second day and either intra-
venously or intramuscularly. Intravenous
administration was stated to be prefer-
red. The average administration was
stated to be every other day for a total of
10 injections. Apparently, a total of 20
grams of Laetrile were expected to be ad-
ministered. Dosages, frequency, and route
of administration are described as vary-
ing widely with each individual case. The
application indicated that Laetrile often
produces a temporary hypotensive reac—
tion shortly after injection, especially in
hypertensive patients. Laetrile is not in-
dicated for use to the exclusion of surg-
ery, radiation, or other chemotherapeu-
tic substances where those ﬂnd any in-
dication.

The proposed labeling in the NDA is,
of course, not an example of labeling in
commercial use at the time of the NDA’s
submission. The NDA does, however,
state the indications which Mr. Krebs,
Jr., thought to be most appropriate for
the use of Laetrile at that time. Thus, if
Laetrile had been commercially used at
that time, it is reasonable to believe that
the indications proposed in the NDA
would be the ones proposed in any label-
ing used for such a commercial product.

An article by Dr. Krebs, Sr., and Dr.
Arthur T. Harris, entitled “The Treat-
ment of Breast Cancer With Laetrile By
Iontophoresis” (copyright 1955 by the
John Beard Memorial Foundation) (R
183, Att. 7) proposes three different
methods of utilizing Laetrile. At page 30,
the “three main methods of administer-
ing Laetrile and its auxiliary Beta-glu-
cosidase" are described as: (1) Paren-
teral administration (injection into the

Commissioner’s Decision

muscle), (2) iontophoresis, discussed be-
low, and(3) tamponade.

Perhaps the most bizarre of the pro-

posed methods of administration for Lae-
trile is “Iontophoresis”. This new pro-
cedure developed by the senior Krebs for
treatment of cancers “especially in the
breast” is described as “infinitely more
effective and thorough." The procedure is
described as follows:
It is to force by galvanic current the Laetrile
through the skin and into as well as between
the individual cancer cells. The apparatus we
use is a simple galvanic instrument (or, pref-
erably, one of the modern instruments with
resistors instead of tubes). The positive pole
lead goes to the tumor site—the breast—the
negative to the back. The solution of Laetrile
is soaked in gauze and covered by a block tin
electrode, then positioned ﬂrmly over the
tumor. The negative pad, well moistened, is
positioned on the back, and the current
turned on. Slowly the amperage is raised to
10 milliamperes then 15, never more than 20
except in a very thick chest wall. In ﬁfteen
to thirty minutes, depending on the size of
the growth, the pad has become almost dry:
the Laetrile has been driven into—not
around—the cancer cells (id. at 26—27).

The action of iontophoresis is described
in more detail on pages 30—31. Appar-
ently it is expected that the iontophore-
sis therapy will liquify the tumor mass,
and a physician will thus be able to draw
out, with an aspirating needle, the “can-
cer-jute” before administering the next
iontophoresis treatment (id. at 32) . Ion-
tophorosis therapy involves administra-
tion every 2 to 5 days (id. at 31).

This article, which has been quoted
and referred to previously, explains some
of the history and theories of Laetrile’s
use. The article promotes the “Howard
Beard Anthrone Test” for the diagnosis
of cancer (id. at 34). This test involves
analysis of the urine of the patients (see
id. at 16—19). The authors recommend
against biopsies to determine whether
tumors are malignant (id. at 27—28) . The
authors state their opposition to surgery
prior to “control” of the cancer by Lae-
trile (id. at 35).

Laetrile (amygdalin) is apparently
currently in use as an oral medication.
Nothing in the record, other than con-
clusory statements of the most general
kind, indicates that any version of the
drug was in use as an oral medication on
October 9, 1962. The only statement that
such a drug was ever used orally before
that date whi:h purports to be based on
ﬁrst-hand knowledge is the statement of
Charles Gurchot, PhD. (R 302, Ex. L at
11 8), that between 1933 and 1934 a Dr.

48

Lewis administered amygdalin orally as
well as intramuscularly and intrave-
nously. Dr. Gurchot states that use in
California, in which he participated be-
tween 1934 and 1945, involved adminis-
tration intramuscularly and intrave-
nously (id. at ‘n 14). As discussed above
in the section on the 1938 grandfather
clause, the “amygdalin” Dr. Gurchot
states he was involved in using is differ-
ent from that used at later dates.

After October 9, 1962

Variations in the conditions for use of
Laetrile (or amygdalin) proposed in its
labeling continued after the critical Oc-
tober 9, 1962 date. In 1965, an FDA in-
spection of Krebs’ Laboratories pro-
duced labeling for Laetrile which sug-
gested a new set of conditions for its use
(see, generally, R 201, Ex. 0.). The labels
on the packages of the drug stated “For
raising hemoglobin index and red
count[;l relieves pain due to malig—
nancy.” (Similar labels were obtained
by California State health ofﬁcials in
1971 (R 183, Att. 9) .)

In a pamphlet published by Krebs'
Laboratories, obtained in the 1965 in-
spection, injections at various sites were
indicated for various types of cancer—
brachial vein for cancer of lungs; bra-
chial vein and innominate artery for
breast cancer; external carotid or one
of its branches for cancer of the neck.
thyroid, face, and temple area; brachial
vein for cancer of liver, gastro-intestinal
tract and the spleen; the vault of the
vagina, the abdominal aorta, or the in-
ternal iliac arteries for cancer of the
uterus and ovaries; the scrotal sac for
cancer of the prostate and testicle (R
201,Ex. C, II).

Two pamphlets obtained in the 1965
inspection are in fact inconsistent with
each other in some instan:es, though the
similarities in printing style indicate
that they were printed at about the same
time. One states the dose of Laetrile to
be administered to be “[glenerally
speaking 10 mgs. per pound of patient’s
weight, with “occasionally” 15 mgs. per
pound and “very rarely” 20 mgs. per
pound (id.). The second states that:
“The usual daily dose of Laetrile now is
20 mgs. of the glucoside Amygdalin for
every pound of the patient’s weight, or
even twice this, particularly in bone can-
cer.” Three gms. are recommended for
a ISO-pound person and 4 gms. for a 175-
pound patient, i.e., over 20 mgs. per
pound (id. at Ex. C, III). (While no la-

beling indicating such conditions was
submitted, it should be noted that Dr.
Binzel, at oral argument, talked of in—
jections of from 9 to 15 grams of amyg-
dalin at one time (Tr. at 363). The page
proofs of Dr. Richardson’s book indicate
that he uses intravenous injections of
“6—9 gms. or more" of Laetrile during
the ﬁrst month of treatment with intra-
venous or intramuscular injestions of 3
grams thereafter (Tr. Ex. 1 at 124).)

More important, however, are the dif-
ferences between the conditions recom-
mended in the labeling collected in 1965
and those in that submitted with the 1962
NDA. In the 1962 NDA, Laetrile was to
palliate, not to cure; in the 1965 labeling
it is stated: “Laetrile does not palliate, it
acts chemically to kill the cancer cells se-
lectively without injury to the normal tis-
sues of the body" (R 201, Ex. C). While
the 1962 NBA stated that Laetrile was
not indicated to the exclusion of other
recognized cancer therapies, the labeling
collected in 1965 states: ”The less drugs
and medicines given, during the Laetrile
treatment the better. What should be es-
pecially avoided is sulphur and sulphur
drugs and other cancer therapies, * ‘ ‘ ”
(emphasis added) (id.). Even more
frightening to those who are concerned
that utilization of therapies of proven ef-
fectiveness will be delayed until too late
because of use of Laetrile is the statement
in the pamphlet in use in 1965 that:
“Being harmless * * * Laetrile should
be used ﬁrst instead of last as generally
has been done when everything else has
been tried and hope is gone” (id.). An
afﬁdavit submitted by Dr. Robert S. K.
Young describes the medical importance
of the numerous variations between the
1962 labeling and that of 1965 (see 11 11
of R 201) .

The labeling discussed, which bears the
name of Krebs Laboratories and of Dr.
Krebs, Sr., appears as Ex. C to R 201. It
should be noted that there is no copyright
or other date on the labeling that was
found in Dr. Krebs‘ establishment in
1965. One of the pamphlets, that which
contains some of the statements quoted
above, is described as a “pre-1963 pam-
phlet” in the affidavit of Dr. Sherwood
Lawrence (R 183 at 4). It appears as at-
tachment 8 to that afﬁdavit.

A pamphlet published by the Me-
Naughton Foundation suggests intra-
venous dosages of amygdalin of from 3
to 6 grams a day administered over a 24-
hour period (R 183, Ex. 10b at 5). That
pamphlet, which cites references dated

Laetrile

49

May 11, 1970 and thus must have been
published thereafter, described the use
of amygdalin as an analygesic, yet also
indicates that the drug inhibits the
growth of malignancies (id. at 1).

The record contains labeling for Lae-
trile (or amygdalin), which was in use
after October 9, 1962, which clearly rec—
ommends oral administration of the
drug. See R 183, Att. 10a—capsules, 400
mg; R 183, Att. 4c—capsules, 400 and 500
mg.; R 183, Att. 10b—amygdalin tablets
which may be broken up and added to
drinking water or food (1/2 to 2 grams per
day recommended); R 183, Att. 10d—
“Magydalin” capsules with 500 mgs. of
“pure crystalline LAETRILE (amyg-
dalin)”.

While in 1962 Laetrile was proposed in
the NDA as a palliative, the labeling in
the record makes clear that it has been
touted since that time as a treatment for
cancer (see R 183, Att. 10a.; see also R
201, Ex. C, discussed above). Mr. Krebs,
Jr., claims Vitamin B—17, which may be
or may contain Laetrile, to be “antineo-
plastic” and to be instrumental in
“therapy” for cancer (Journal of Applied
Nutrition, Vol. 22, “The Nitrilosides
(Vitamin B—17)—Their Nature, Occur-
rence and Metabolic Signiﬁcance (Anti-
neoplastic Vitamin B-17),” at 75, 81 (R
183, Att. 10c).

In a transcript dated November 18,
1974, prepared by FDA, of a ﬁlm entitled
“World Without Cancer”, produced by
the proponents of the use of Laetrile, the
claim is made that 15 percent of persons
with advanced metastasized cancer will
be saved by “vitamin therapy,” which
from the context inxludes vitamin B—17
(Laetrile) . The ﬁlm claims that, of those
with cancer diagnosed early, at least 80
percent will be saved by vitamin therapy.
Of those who are healthy with no clini-
cal evidence of cancer, the ﬁlm‘s narrator
states that close to 100 percent can ex-
pect to be free from cancer as long as
they utilize vitamin B—17. The use of the
term “vitamin B—17” indicates that the
ﬁlm was made after 1962, since Laetrile
was not claimed to be a “vitamin” until
after that time (see, generally, exhibit 2
to R 198).

As discussed above, to qualify for ex-
emption from the "new drug” deﬁnition
of 21 U.S.C. 321 (p) pursuant to the
“1962 grandfather clause,” the propon-
ents of Laetrile (or amygdalin) would
need to show among other things that
the drug in question is now “intended
solely for use under conditions pre-

Commissioner’s Decision

scribed, recommended, or suggested in
labeling with respect to such drug on"
October 9, 1962. No evidence in the rec-
ord shows either that the drug was used
or that any conditions of use were rec-
ommended for it on that date. Evidence
in the record indicates that conditions of
use recommended prior to the critical
date not only conﬂict with each other,
but also conﬂict with recommendations
after that date, which themselves conﬂict
with each other. The Commissioner con-
cludes, on the basis of the evidence in the
record, that Laetrile as now known is not
intended solely for use under conditions
recommended in labeling on October 9,
1962.

4. Lack of General Recognition of Safety
in 1962

As discussed above, a drug could not
escape new drug status under the “1962
grandfather clause" if it were a “new
drug” on October 9, 1962. To have been
exempted from new drug status on that
date, Laetrile (or amygdalin) would have
to have been “generally recognized
among experts qualiﬁed by scientiﬁc
training and experience to evaluate the
safety of drugs, as safe for use under the
conditions prescribed, recommended, or
suggested in the labeling thereof” (21
U.S.C. 321(p) (1) (1962)), and that gen-
eral recognition would have to be based
upon use other than investigational use
(21 U.S.C. 321 (p) (2) (1962)).The Com-
missioner has elsewhere discussed the ev-
idence that demonstrates that Laetrile
and amygdalin (to the extent that they
are different) are not now generally rec-
ognized by qualiﬁed experts as safe for
use under the conditions prescribed, rec-
ommended or suggested in their label-
ing. While the present lack of general
recognition of the substances would not
necessarily demonstrate that they were
not so generally recognized in 1962, that
fact does provide evidence of the earlier
lack of recognition.

The evidence in the record provides a
number of independent grounds upon
“hich the Commissioner concludes that
Laetrile (or amygdalin) was not gen-
erally recognized by experts in drug
safety evaluation as safe on October 9,
1962. That conclusion is supported ( 1)
by the proven lack of a number of pre-
requisites to such general recognition:
lack of knowledge among such experts
generally of Laetrile’s use, of Laetrile’s
formulation, and of the proposed condi-
tions of Laetrile’s use; lack of data pub-
lished in the scientiﬁc literature support-

50

ing Laetrile’s safety as a cancer drug;
and lack of scientiﬁc testing sufﬁcient to
show safety; (2) by statements in the
record by experts in the evaluation of the
drug safety that Laetrile was not gen-
erally recognized as safe as a cancer
drug by themselves and their peers on
October 9, 1962; and (3) by abundant
evidence that Laetrile was not generally
recognized by appropriately qualiﬁed ex-
perts to be effective in cancer therapy on
October 9, 1962. The Commissioner con-
cludes that the showing in the record on
each of these points is itself sufﬁcient to
demonstrate that Laetrile (or amygda-
lin) was a new drug in 1962.

(a) The Prerequisites. (i) Lack of
General Knowledge of Use—A number of
submissions to the administrative record
indicated that the use, and the details of
the use, of Laetrile or amygdalin were
simply not generally known to the com-
munity of experts in the safety evalua-
tion of drugs on October 9, 1962. Thus.
there could not be any sort of “general"
recognition of the substances’ safety in
1962. (See, e.g., the oral testimony of Dr.
Rhoads, the national chairman of the
National Cancer Advisory Board (Tr. at
110—111; Tr. Ex. 5) ; oral testimony of Dr.
Carr, professor in medicine at the Mayo
Medical School (Tr. at 181) .)

(ii) Lack of General Knowledge of
formulation—The variability in, and
uncertainty about, the composition of
the drug in use at that date (discussed in
detail above) means that “general recog-
nition” of the drug’s safety by experts in
drug safety evaluation would be impos-
sible. The fact was recognized in Durom‘c
v. Richardson, supra, 479 F. 2d at 251, in
which another unproven cancer remedy
was ruled not to be exempted from regu-
lation by the 1962 grandfather clause.

(iii) Lack of General Knowledge of
Conditions of Use Suggested—Equally
important, the variation in and uncer-
tainty about the conditions of use sug-
gested in the labeling of Laetrile (or
amygdalin) on October 9, 1962, also dis-
cussed in detail above, means that such
general recognition could not have ex-
isted. The law as of that date is clear that
general recognition must be of safety
“for use under the conditions prescribed,
recommended. or suggested in the label-
ing" of the drug (21 U.S.C. 321(p) (1)
(1962) ). If experts throughout the coun-
try could not have known of those condi-
tions of use, recognition of safety by them
could not have existed.

(iv) Lack of Safety Data in Scientiﬁc

Literature.—The existence of published
data available in the scientiﬁc literature
on the safety of a drug is a prerequisite to
general recognition by experts of that
drug’s safety within the meaning of 21
U.S.C. 321(p). Weinberger v. Bentex
Pharmaceuticals, Inc., supra, 412 US. at
652; see United States v. 41 Cases, More
or Less, 420 F. 2d 1126, 1130 (5th Cir.
1970); United States v. 1,048,000 Cap-
sules, More or Less, supra, 347 F. Supp. at
771. The record lacks any reference to
any such published data available to ex-
perts on October 9, 1962.

In fact, the record demonstrates that,
while data showing the lack of Laetrile’s
effectiveness have been published in the
scientiﬁc literature, data upon which an
expert in the evaluation of drug safety
could make a judgment that Laetrile was
safe for use in cancer therapy do not exist
in the scientiﬁc literature available to ex-
perts generally even today.

(v) Lack of Showing of Safety by Ade-
quate Testing.—As noted in the sections
of this opinion dealing with the new drug
issue, the Supreme Court has held in
Weinberger v. Bentex Pharmaceuticals,
Inc., supra that “general recognition,” as
those terms are used in 21 U.S.C. 321(p),
requires the same type of showing of
safety and efﬁcacy necessary for approval
of an NDA pursuant to 21 U.S.C. 355(d).
For approval of an NDA prior to October
9, 1962, the application was required to
contain “adequate tests by all methods
reasonably applicable to show whether or
not such drug is safe” for its intended
uses, and those tests were required to in
fact show that the drug was safe (21
U.S.C. 355(d) (1962)). It appears from
the record that no such tests existed for
Laetrile (or amygdalin) on October 9.
1962. Were there a question about the
lack of such studies, that question could
be resolved by the fact that, at approxi-
mately the time in question, NDA’s for
Laetrile and for a combination of Lae-
trile and iodomine were submitted to the
FDA. Both applications were declared to
be incomplete because of the lack of re-
quired data to show safety and effective-
ness. (See, generally, the letter from
John L. Harvey, FDA Deputy Commis-
sioner, to K. F. Ernst, M.D., April 30, 1963
(R 183. Att. 16, App. 18) .)

(b) Statements by Experts. Even set-
ting aside the above important prerequi-
sites to general recognition, the evidence
in the record that Laetrile was not gen-
erally recognized as safe by experts in
the evaluation of drug safety on October

Laetrile

51

9, 1962 is extremely strong.

The plethora of statements of experts
in drug evaluation that Laetrile (or
amygdalin) is not now generally recog-
nized as safe is discussed elsewhere.
Some of the experts focused upon the
October 9, 1962 date. (See afﬁdavit of Dr.
Emil J. Freireich: “Neither amygdalin
nor any other cyanogenic glycoside was
generally recognized as safe for any [use
in the treatment of cancer or prophylaxis
against cancer or relief of pain associated
with cancer, or for any medical use] on
October 10, 1962” (R 390 at ‘U 19) ; accord
afﬁdavit of Dr. Daniel T. Carr, (R 1'76
at 11 15) .) For a similar statement that
Laetrile was not generally recognized as
safe by appropriately qualiﬁed experts in
1962, see afﬁdavit of Dr. Carl M. Leveri-
thal (R 184 at H 13).

Even more compelling evidence on this
question can be gleaned from statements
of experts in drug safety evaluation made
near the October 9, 1962 date. Fortun-
ately, at just about that date the State of
California Cancer Advisory Counsel was
polling just that type of expert concern-
ing Laetrile (R 183, Att. 16 at 37—38).
(Since the Krebs Laboratory was located
in California, it would seem that experts
in the California area would be most
likely to be aware of recognition of Lae-
trile or amygdalin’s safe use as cancer
therapy.) The experts polled, represent-
ing each of the medical schools in the
California university system, were asked
about the drug’s eﬂicacy rather than
their views on the question of the safety
of Laetrile’s use in cancer therapy. Clay-
ton G. Loosli, M.D., Dean of the Univer-
sity of Southern California School of
Medicine, speaking for the members of
the school’s faculty, indicated that Lae-
trile, while extensively investigated, was
in the unanimous opinion of the faculty
without value in the treatment of human
cancer. He stated that “further, we con-
sider its use not only not valuable even
as a placebo but harmful in that use of
Laetrile prevents patients from receiving
what otherwise might be an effective
modality of treatment” (id., App. 10).
J. B. deC. M. Saunders, M.D., Dean of the
University of California School of Medi-
cine at San Francisco, speaking for the
clinical staff of his medical school, gave
their opinion that the use of Laetrile was
of no value in the treatment of cancer.
He said “[ilt may not only delay or in-
terfere with conventional therapy (sur-
ery and radiation) but indeed could seri-
ously jeopardize whatever chances the
patient may have for cure. The unscru-

Commissioner's Decision

pulous use of unproven cancer ‘remedies‘
such as Laetrile tragically increases the
human suffering already associated with
cancer” (id.).

The only evidence submitted by pro-
ponents of Laetrile that experts quali-
ﬁed to evaluate the safety of drugs gen-
erally recognized the drug as safe when
used in cancer therapy were two affi-
davits by Charles Gurchot, Ph.D., and
Chauncey D. Leake, Ph.D., (R 302, Exs.
K and L). The Gurchot affidavit states
in paragraph 14 that amygdalin in
liquid and solid form was used prior
to 1962 (between 1934 and 1945) by
Gurchot, under the supervision of ﬁve
named medical doctors at the University
of California Medical School at San
Francisco (R 302, Ex. L) . This amygdalin
was, according to his statement, ad-
ministered “on patients intramuscularly
and intravenously” (id.). At the same
time, the amygdalin preparation he
used, he states, was used by “about a
dozen physicians throughout California
through the University of California
Medical Schools and as recommended by
members of the Hospital Staff of the
University of California Medical School
at San Francisco” (id.). Gurchot states
that these physicians were qualiﬁed by
medical and scientific training and pro-
fessional experience to evaluate the
safety of substances such as amygdalin
and that they recognized it as safe (id.).
The Gurchot affidavit should be com-
pared, in the ﬁrst instance, to the 1962
statement, already discussed, of the Dean
of the University of California Medical
School at San Francisco, which states,
“Laetrile is not, nor has it been, in
clinical use or in experimental trials in
this institution ‘ " "’ (emphasis added)
(R 183, Att. 16, App. 10 at 8).

Even were the Commissioner to credit
Dr. Gurchot’s statement, he would have
to conclude that, whatever had happened
in the years 1934—1945, that experience
did not form a basis for general recogni-
tion by qualified experts of safety in
1962, since even the faculty of the med-
ical school in which Gurchot claimed
the experiments had taken place had
no knowledge of them. It should also
be noted that, as discussed in the sec-
tion on the 1938 grandfather clause,
the “amygdalin” Gurchot could have
been using would not have been the same
substance in use today. His evidence, in
addition, speaks only of investigational,
as opposed to commercial, use of the

52

drug—an improper basis for “general
recognition” (see discussion above). In
light of these facts, and of the other
information in the record on this is—
sue, Gurchot’s statement in paragraph
16 of his afﬁdavit indicating his belief
that the general recognition of safety
requirement for exemption from new
drug status did exist for amygdalin on
or prior to October 10, 1962 must be
questioned.

The affidavit of Chauncey D. Leake,
Ph.D., indicates that he is familiar with
Dr. Gurchot’s use of amygdalin in the
mid—1930’s and 1940’s at the University
of California Medical School Hospital
in San Francisco. He states that at
that time, i.e., in the 1930’s, “it was
generally held by physicians and other
scientists familiar with it, that amyg-
dalin was safe when used in the treat-
ment of cancer as well as in its use
as an expectorant or cough suppressant”
(R 302, Ex. K at 116). This conclusion
does not, however, indicate recognition
by anybody in 1962; it does not, as
demonstrated elsewhere, deal with the
drug presently being used (see affidavit
of Dr. Krebs, Sr., (R 183, Att. 13)); it
refers only to physicians and scientists
“familiar with it”, thus not addressing
the question of whether recognition was
general.

(c) Lack of General Recognition of
Eﬂ‘ectiveness in 1962.——Experts in the
evaluation of the safety of a drug do
not conclude that a drug is safe, if that
drug is intended for the treatment of a
life-threatening disease, if it has not
been shown to be effective. The record
illustrates a broad consensus of cancer
researchers and physicians that Laetrile
presents a grave danger to patients who
might be helped by orthodox therapy.
The concern is that such patients may
be induced to turn instead to this in-
effective drug, their disease may progress
while effective therapies are foresaken,
and the use of the ineffective cancer
drug will inevitably and inexorably lead
to the patient’s death. (See, e.g., R 396
at 1; R 384; R 170 at 1111; R 183 at 18;
R 266, Ex. 3 at 865; R 192 at 1114; R 193
at 1; and R 195 at 1] 13.) Thus, even if it
were shown, as it has not been, that ex-
perts in 1962 generally were aware of
the drug, its formulation, its conditions
of use, and of toxicity data concerning it
published in the scientiﬁc literature, the
alleged nontoxicity of Laetrile (or amyg—
dalin) would not form a sufficient basis

for general recognition of safety in 1962.

At the time of the 1962 amendments
to the act, it was made clear that, where
drugs utilized for life-threatening dis-
eases are involved, evidence of effective-
ness is essential to proof of safety. The
Senate report on the amendments
stated:

The Food and Drug Administration now
requires, in determining whether a “new
drug” is safe, a showing as to the drug’s
effectiveness where the drug is offered for
use in the treatment of a life-threatening
disease, or where it appears that the “new
drug” will occasionally produce serious toxic
or even lethal effects so that only its useful-
ness would justify the risks involved in its
use.

(S. Rep. No. 1744, 8'7 Cong. 2d. Sess., 1962
US. Code Cong. Ad. News 2884, 2891.)
The report made it clear that the amend-
ments were “in no way intended to affect
any existing authority of the [FDA] to
consider and evaluate the eﬂ'ectiveness
of a new drug in the context of passing
upon its safety” (emphasis added) (id.
at 2892).

As the Court held, when dealing with
a similar unproven cancer remedy, in
Durovic v. Richardson, supra, lack of
general recognition of the effectiveness
of a drug intended for treatment of a
life-threatening disease on October 9.
1962 means that general recognition of
its safety could not have existed:
[A] drug offered for use in the treatment of
cancer is now, and was before the amend-
ments, a new drug unless it has achieved
general recognition among the experts as
safe and effective for such use (479 F. 2d at
250).

The evidence in the record overwhelm-
ingly demonstrates that, among experts
in the evaluation of the safety and effec-
tiveness of drugs, Laetrile (or amyg-
dalin) is not recognized as effective (see
discussion above). It is a fair inference,
absent any indication to the contrary,
that a drug not recognized as effective
now was not so recognized on October 9,
1962.

Again, however, the record supplies
evidence of opinions of such experts
given at almost exactly the time in ques-
tion. As noted above, the medical schools
in California were asked their opinions
of Laetrile’s effectiveness. Each of the
medical schools contacted stated that
Laetrile was never used in their institu-
tions and that they concluded that it was

Laetrile

not effective and had not been shown by
testing to be effective. (See, in addition
to the letters discussed above, letters
from Dean David B. Hinshaw, M.D.,
Dean of Loma Linda University Medical
School, Dr. M. H. Simmers, Coordinator,
Cancer Training, California College of
Medicine, Sherman M. Mellinkoff, Dean,
University of California, Los Angeles
Medical School.) These letters are
printed as appendix 10 to R 183, Att. 165
see also R 183, Att. 16 at 38. The report
states that Robert H. Alway, M.D., Dean
of Stanford University School of Medi-
cine, also indicated that Laetrile was of
no value in cancer treatment and was
not part of the treatment program at his
medical school (R 183, Att. 16 at 38).
The report also states that two other
professors involved with cancer therapy
and research concurred in this evalua-
tion (id.). The report of the California
Cancer Advisory Counsel itself consti-
tutes convincing evidence that at about
the time of the crucial date, October 9,
1962, experts did not generally recognize
Laetrile as safe for the treatment of
cancer, in particular because it was con-
sidered to be a worthless treatment for
a life-threatening disease. As has been
pointed out elsewhere, no adequate and
well-controlled clinical investigations,
the prerequisite for general recognition
by experts of a drug‘s effectiveness
(Weinberger v. Hynson, Wescott and
Dunning, I nc., supra) exist as to Laetrile.
Thus, even were the testimony in the
record on this question less conclusive
than it is, it would be necessary to find
that there was no general recognition
by experts that Laetrile was safe for use
for any purpose on October 9, 1962.

The Commissioner thus concludes that
Laetrile (or amygdalin) does not qualify
for exemption from the new drug provi-
sion of the act by virtue of compliance
with the 1962 grandfather clause.

IV. THE POPULARITY or LAETRILE
A. LAETRILE AND OTHER UNPROVEN REMEDIES

Laetrile, as far as is known, has
nothing in common scientiﬁcally with
any of the other “unproven” cancer rem-
edies of the past.“ Yet the method of

“Dr. Ernst Krebs, Sr., though he thought
people should be allowed to use his Laetrile,
and a number of other remedies since for-
gotten by the public, is on record as stating
that he could see no rationale for Krebiozen,
the last of the highly publicized "unproven"
cancer remedies (R 183, Att. 14 at 2).

Commissioner's Decision

promotion of the drug and the argu-
ments advanced for its use are markedly
similar to those of past cancer frauds.

1. The History of Cancer Quackery in
the United States

Through the ages there have been lit-
erally thousands of supposed remedies
for cancer, generally so outlandish that
it seems incredible that people once be-
lieved in them. One historian of health
quackery pointed out that the promotion
of “unproven" cancer cures has a long
history in this country:

Cancer quackery appeared in America dur—
ing colonial times, one example being the
alleged ”Chinese Stones" vended by a pur-
ported Frenchman, Francis Torres, who
hawked his cures from town to town. During
the nineteenth century, an alert physician.
Caleb 'I‘ichnor, bemoaned the breed of can-
cer quack, (each of whom oﬂers) his “secret
speciﬁc" to the panicked citizenry who, "like
a drowning person grasping at straws seize
upon the frail hope that is offered by the
hand of ignorant charlatanryi” “Dr. John-
son’s Mild Combination Treatment for Can—
cer” oﬂered the first serious legal challenge
to the 1906 Pure Food and Drug Act, requir-
ing the CongreSS to enact the Sherley Amend-
ment of 1912. At this same time, Dr. Arthur
J. Cramp of the American Medical Associa-
tion devoted fifty pages in his ﬁrst Nostrums
and Quackery volume to a detailed account
of ten major cancer 'cures' deceiving the
American people. Compiling a third volume
in 1936, Dr. Cramp pointed to twenty-nine
purported cancer cures, stating that ”hardly
a week has passed when the Bureau of In-
vestigation of the American Medical Asso-
ciation has not received one or more letters
in which the writers stated that they had
discovered, or had in their possession, a ‘sure
cure‘ for cancer."

Nor has cancer quackery diminished as the
twentieth century has progressed. Indeed,
with the decline of contagious diseases, due
mainly to the chemotherapeutic revolution,
and the consequent rise or cancer into sec-
ond place as a cause of death, cancer quack-
ery has expanded. The 1971 edition of Un-
proven Methods 0/ Cancer Management, pub-
lished by the American Cancer Society, de-
scribed fifty-four promotions offering hope
to cancer sufferers but deemed devoid of
value by A03. The 1976 edition of Unproven
Methods of Cancer Management cites in its
appendix seventy-one such methods (R 400
at 1—2; see also R 400, Ex. 2).

Evaluation of approximately 60 of these
methods may be found as attachments to
R 400, Ex. 2.

Each decade seems to have an un-
proven cancer remedy that is promoted
so effectively that it attracts a large fol-
lowing and becomes a cause celebre. In
the 1940's and early 1950’s, the Koch

Antitoxins were heavily promoted as a
speciﬁc cure for cancer. The Koch Anti-
toxins thesis, promoted by William F.
Koch, M.D., advanced “the theory that
cancer is caused by a microorganism re-
sembling the spirochete of syphilis,
which could be destroyed by a differen-
tial poison of his invention” (R 183, Att.
3 at 43). “The Koch medications, known
collectively as Koch’s Synthetic Anti-
toxins or oxidation catalysts, were indi-
vidually packaged in 2 ml ampules. Mal-
onide and glyoxylide [were] claimed to
be present in a concentration of one part
in a trillion parts of water, and para-
benzoquinone one part in a million parts
of water” (id). “Glyoxylic acid, of which
glyoxylide is the anhydride (the result-
ing element after water is removed), is a
normal constituent of the human body.
About two grams are formed daily—at
any given time there are about ﬁve milli-
grams in the human body, whether
healthy or diseased. It would take a tril-
lion 2 ml ampules of Koch’s glyoxylide
to equal the amount produced daily by
the body, and two and one half billion
ampules to equal the amount present in
the body at any one time” (id. at 44).
Even so, cancer patients paid as much as
$300 per injection for this worthless rem-
edy (R 400, Ex. 2, ACS “Koch Anti-
toxins").

Another unproven cancer remedy
whose promotion reached substantial
proportions in the 1950’s was the medi-
cations of Harry Hoxsey. Two liquid mix-
tures played the central role in the Hox-
sey remedy. The “brownish black liquid”
contained potassium iodide and “some of
all of the following inorganic substances
as the individual case may demand: Lico-
rice, red clover, burdock root, stillingia
root, berberis root, poke rot, cascara,
Aromatic USP 14 prickly ash bark, [and]
buckthorn bark (R 400, Ex. 2, ACS “Hox-
sey Method”). The “pink liquid” was
composed of lactate of pepsin and other
ingredients (R 416. Ex. 6 at 368).

Hoxsey and his spokesmen were frank
to confess that they did not completely
know why his colored mixtures cured
cancer. They asserted that they had been
kept too busy treating cancer patients
and ﬁghting court battles to keep their
clinic open “to spare the time, personnel,
and facilities for objective study” (id. at
369). Hoxsey’s hypothesis “held that a
major chemical imbalance in the body
caused normal cells to mutate into a
cancerous form, and his medicines re-
stored the original chemical environ-

Laetrile

ment, checking and killing the cancer-
ous cells” (id. at 369). The proponents
of the Hoxsey remedy, like the Laetrile
proponents of today, condemned the
only treatments then recognized as hav-
ing value in cancer therapy. The Hoxsey
proponents held that “X—ray and radium
[had] no place in the treatment of can-
cer * ‘ ‘. They further upset basic cell
metabolism rather than do anything to
correct it" (id. at 369) .

Harry Hoxsey promoted his unproven
cancer remedy for more than 30 years
until 1960, when after years of numerous
local, State, and federal court actions,
the sale of the Hoxsey medicines was
stopped in the United States. At the time
of the 1960 permanent injunction ban-
ning the sale of Hoxsey remedy at the
Taylor Clinic, more than 10,000 patients
were receiving the remedy. (See, gen-
erally, R 400, Ex. 2, ACS “Hoxsey
Method”; R 416, Ex. 6.)

In 1964 a California State government
report stated that, at that time, “Pos-
sibly no other unproven treatment for
cancer has received so much public at-
tention or approbation as Krebiozen. This
agent has been the subject of intense
scrutiny by scientists and government
ofﬁcials, and loudly discussed by the press
and by the general public. The events
surrounding the introduction of Krebio—
zen as a potential cancer cure and the
subsequent trials to test its capabilities
produced an air of notoriety seldom seen
in the medical world" (R 183, Att. 3 at
59).

Unlike Harry Hoxsey’s backwoods herb
remedy. Krebiozen. the most heavily pro-
moted unproven cancer remedy of the
1960‘s, had an aura of high scientific
prestige. The drug’s principal proponent
in the United States was Dr. Andrew C.
Ivy, then Vice-President in charge of the
Chicago Professional Colleges, Distin-
guished Professor of Physiology and Head
of the Department of Clinical Science,
University of Illinois (id.) Krebiozen was
reportedly produced originally in Argen-
tina by Stevan Durovic, M.D., a Yugo-
slavian physician, and brought to the
United States in 1949 (R 400, Ex. 2, ACS
“Krebiozen and Carcalon”). “According
to Dr. Durovic, the original 2 grams of
powder, from which he said 200,000 doses
were prepared, was obtained as an extract
of the blood of 2,000 Argentinian horses
which had previously been injected with
a sterile extract of Actinomyces bovis, a
microorganism which causes a disease
called ‘lumpy jaw’ in cattle” (id.) . “Food

55

and Drug Administration analyses of
Krebiozen ampules (showed) that those
sold before 1960 (were) different from
those sold in 1963, and that neither con-
tainled] any of the powder identiﬁed in
July 1963 by Dr. Stevan Durovic as Kre-
biozen, and found to be creatine mono-
hydrate, which will not dissolve in min-
eral oil. ‘ ‘ “ analyses of Krebiozen am-
pules shipped before 1960 showed they
contained nothing but mineral oil, while
ampules shipped since then contained
mineral oil plus minute amounts of amyl
alcohol and l-methylhydantoin, a de-
rivative of creatine which will dissolve
in mineral oil” (id.).

In 1963. a committee of 24 cancer ex-
perts was appointed by the Director of
the National Cancer Institute to review
clinical records on 504 patients treated
with Krebiozen. and to recommend
whether the Institute should sponsor
clinical trials of Krebiozen. The com-
mittee unanimously concluded that
Krebiozen was an ineffective cancer drug
and strongly urged that no clinical trial
be undertaken (id.).

In November 1964, Drs. Ivy and Duro-
vic and other proponents of Krebiozen
were indicted on 49 counts for violations
of the Federal Food, Drug, and Cosmetic
Act, mail fraud, mislabeling, making
false statements to the government, and
conspiracy. All of the defendants were
acquitted in January 1966, after a 9-
month jury trial (id.). Although the ac-
quittal meant that the government did
not prove its case beyond a reasonable
doubt, it did not have any bearing on the
question of whether Krebiozen was a
safe and effective cancer drug. As an un-
approved new drug, its distribution in
interstate commerce remained illegal. In
spite of the acquittal, the Krebiozen
boom collapsed shortly thereafter.

2. Similarities Between Laetrile Promo-
tion and That of Other Recent "Un-
proven” Cancer Remedies

The promotion of Laetrile in the 1970’s
is completely in character with the his-
torical pattern of the promotion of other
unproven cancer remedies such as the
Koch Antitoxins, the Hoxsey method.
and Krebiozen. These characteristics in-

clude the following:

(1) The proponents “don the mantle of
science while at the same time traducing the
reputable scientists of their day" (R 400 at
3).

(2) The proponents claim that “prejudice
of organized medicine hinders their efforts”

Commissioner's Decision

and they “challenge established theories and
attack prominent scientists with bitter crit—
icism" (R 400, Ex. 2 “Unproven Methods of
Cancer Management—1976" at 3) [herein-
after cited as "Unproven Methods"|.

(3) The proponents "cite examples of phy-
sicians and scientists of the past who were
forced to fight the rigid dogma of their day"
(1d,).

(4) The proponents rely mainly on testi—
monials and anecdotes as evidence that their
remedy is a safe and effective cancer thera-
peutic agent (see R 400 at 4).

(5) The proponents "do not use regular
channels of communication (current, rep-
utable scientiﬁc journals) for reporting sci-
entiﬁc information" (R 400, Ex. 2 “Unproven
Methods" at 2—3). The main channels of
communication are the mass media, popular
journalism, and word of mouth (see R 400
at 4—5).

(6) The proponents' "chief supporters tend
to be prominent statesmen, actors, writers,
lawyers, even members of state or national
legislatures—persons not trained or experi—
enced in the natural history of cancer, the
care of patients with cancer, or in scientiﬁc
methodology." (See R 400, Ex. 2 "Unproven
Methods" at 3.)

(7) The proponents often offer a simplistic
theory for causation of the disease frequently
involving claims that dietary management
can counteract virulent pathologic processes
(R 266. Ex. 3 at 865).

(8) The proponents’ remedy is “easy and
pleasant, compared with the frightening
therapies wielded by orthodoxy, the surgical
knife, harsh chemical drugs, poisonous radia-
tion” (R 400 at 8).

(9) The proponents claim that the mode of
administration of the drug and the method
of treatment can only be learned from them
(R 400, Ex. 2, “Unproven Methods" at 3) .

The record illustrates the remarkable
conformity of the Laetrile promotion to
this pattern:

(a) Mantle of Science—Throughout
history, promoters of unproven cancer
remedies have couched the explanation
for the remedies in pseudoscientiﬂc
terms. “Impressive and plausible to the
layman, such arcane explanations, to
true scientiﬁc specialists, came off as
nonsensical balderdash” (R 400 at 3).
The promoters of Laetrile have pre-
sented a series of shifting theories to ex-
plain the alleged anticancer activity of
Laetrile. These theories have been ex-
amined in detail above. (See, generally,
R 318.)

(b) Attacks on the “Establishment.”—
The proponents of Laetrile have often
accused government agencies and orga-
nized medicine of making untruthful and
irresponsible statements regarding the
experimental evidence of Laetrile's anti-
cancer activity. (See, e.g., R 302, Ex. A at

56

14—16; R 509 at 3—4.) In other instances,
proponents of Laetrile have chastized the
orthodox methods of cancer treatment
and management, i.e., surgery, radiation,
and chemotherapy. (See, e.g., Tr. at 16—
27, 297—316, and 417—426).

The most vocal arguments challenging
established orthodox treatments have
been concerned with the issue of freedom
of choice, discussed elsewhere in this
opinion. These arguments, many of them

from cancer patients or their relatives
and friends, hold that the “bureaucracy”
has no right to interfere with the physi-
cian-patient relationship by withholding
from them a treatment in which they be-
lieve and which they want. (See, gener-
ally, Tr. at 55—56, 255—256, and 454—456.)

(c) Claimed Parallel with Scientiﬁc
Pioneers.—To combat criticism from the
established medical societies and govern-
ment agencies that Laetrile had not been
shown to be safe and eﬁective, its pro-
ponents compare the originators of the
drug and physicians who prescribe Lae-
trile with earlier scientists who were per-
secuted and ostracized for their scientiﬁc
theories: Copernicus, Newton, Freud,
Galileo, and Semmelweiss. (See, e.g., R
318 at 61—63; R 198, Ex. 2 at 3—5).

(d) Reliance on Testimonials.—As
previously discussed, the proponents of
Laetrile rely on testimonials and anec-
dotes as evidence that the drug is safe
and effective in the treatment of cancer.
In reviewing the administrative record,
the Commissioner has not encountered
even one study that meets the legal and
scientiﬁc standards for making a deter-
mination that Laetrile is safe and effec-
tive. Proponents claim that physicians
using Laetrile are too busy treating pa-
tients to be able to maintain the records
needed to document adequately the case
histories they present. (See, e.g., Tr. Ex.
1 at 117.)

(e) Lack of Scientiﬁc Publication——
Good science demands that evidence that
a drug is safe and effective be presented
in a manner whereby that evidence can
be reviewed and evaluated by other sci-
entists. Usually this evidence is published
in scientiﬁc journals and presented for
discussion at symposia and other meet-
ings. Historically, “the main reliance of
unorthodox promoters rests on the an-
ecdotal evidence of testimonials from
laymen, and the main channel for reach-
ing an audience is through the mass me-
dia. In earlier days newspaper advertis-
ing trumpeted the promise of cancer
cures, bolstered by the faces and words

of grateful testiﬁers, not infrequently al-
ready dead of the disease” (R 400 at 4—5) .
The proponents of Laetrile have relied
heavily on popular journalism, adver-
tisements, radio and television, “health”
organizations and word of mouth to
spread their claims that Laetrile is a safe
and effective anticancer drug. (See, e.g..,
R 318; R 302, Ex. A and H; R 198, Ex. 2.)
A number of experts active in the man-
agement of cancer have submitted testi-
mony stating that the scientific literature
contains no reports of adequate, well-
controlled studies upon which Laetrile
can be regarded as generally recognized
as safe and effective. (See, e.g., R 185 at
5; R 186 at 4; R 390 at 6.)

(f) Nonexpert Supports—The propo-
nents of Laetrile are well-organized and,
through organizations such as the Com-
mittee for Freedom of Choice in Cancer
Therapy, have conducted active cam-
paigns to move the discussion of the
safety and effectiveness of the drug from
the scientiﬁc to the political arena. These
organized efforts have encouraged can-
cer patients and others to write their
local, state, and congressional represen-
tatives demanding that Laetrile be “le-
galized.” These efforts are addressed not
to discussions of the scientiﬁc merits of
Laetrile as a cancer drug, but rather to
the issue of “freedom of choice” discussed
elsewhere in this opinion. Such action
on the part of the Laetrile proponents is
typical of other unproven cancer reme-
dies. Failing to win acceptance in the
established medical community, propo—
nents seek sympathetic allies in places
of political power. (See R 400 at 6—7.)

(9) Simplistic Theories of Causation
and Reliance on Diet—The latest claims
being made for Laetrile are that it is a
“vitamin," and that cancer is a vitamin
deﬁciency disease. The basis for these
claims is discussed elsewhere in this
opinion. It is sufficient to note here only
that this simplistic theory of cancer pre-
vention and treatment is common to
other unproven cancer remedies. Can-
cer patients are told that they can cure
or control their cancer by strict adher-
ence to a special diet that includes a spe-
cial “vitamin" even though this “vita-
min" is not recognized by nutritional ex-
perts. (See R 266, Ex. 3 at 865-66.)

(h) A Painless Cure—Laetrile, like
other unproven cancer remedies, is pro-
moted as a harmless cancer remedy free
of the side effects associated with ortho-
dox methods of treatment such as radia-
tion and chemotherapy. Many of the

Laetrile

57

statements submitted by cancer patients
and their relatives and friends reﬂect
the proponents’ claims that Laetrile is
free of side effects. (See, e.g., R 17; R 48:
R 137.)

(1') Only Proponents Can Eﬂectively
Use the Drug.—In common with the sup-
porters of other unproven cancer reme-
dies, the proponents of Laetrile stress, as
did Robert W. Bradford of the Commit-
tee for Freedom of Choice in Cancer
Therapy, that “you” do not and cannot
expect to get results from Laetrile treat-
ment unless you are a trained metabolic
physician” (Tr. at 349). These arguments
are used to explain why orthodox physi-
cians (i.e., those not trained in the prop-
er use of Laetrile) do not see any evi-
dence of Laetrile’s effectiveness as a can-
cer drug.

B. WHY DO PEOPLE USE LAETRILE?

Throughout history persons afﬂicted
with cancer have turned away from the
medical establishment to a series of what
most euphemistically might be called
“unproven remedies.” Laetrile is the most
recently publicized of these remedies,
but, as the discussion above illustrates, it
follows on the heels of other widely pub-
licized therapies such as Krebiozen and
the Hoxsey cure. Thoughtful persons
have questioned the reasons for this
troubling phenomenon. Why do people
bet their lives, or the lives of their loved
ones, on a therapy which is rejected by
almost everyone trained and experienced
in cancer research and treatment?

Much evidence in the record addresses
this question. The answer lies in the fear
that cancer engenders—and that proven
therapies for cancer engender—and the
need of patients and families for hope in
a situation where the hope offered by
the legitimate therapies is often modest.
The use of “unproven remedies” is, in the
opinion of observers, in large part at-
tributable to the loved ones of the can-
cer victim, in whom both fear and the
need for hope are magniﬁed by sympathy
and by the guilt that one feels at being
unable to relieve the suﬁ'ering of a person
one loves. This situation is, unfortunate-
ly, skillfully exploited by the purveyors
of “unproven" cancer remedies, of which
Laetrile is only the most publicized.

1. The Emotional Reaction to Discovery
of Cancer
“[WJhen cancer afﬂicts an individual,
he is frequently faced with a circum-
stance which is virtually without hope.
First of all, the cancer patient must be

Commissioner’s Decision

terriﬁed by the diagnosis ‘ * *. It
would be enough to terrify any lay per-
son to simply be told that he has cancer.
But more important than that is the
fact that once he is told that he has
cancer, he is told by the doctor that the
treatments that we have available are
very often disﬁguring; they can be pain-
ful; they can be unpleasant; they can
even be risky" (Tr. at 204).

The cancer patient must thus cope
with two wounds simultaneously. The
ﬁrst is to the body itself (R 423 at 1).
“The other wound is to the psyche, re-
ﬂected in the loss of the feeling of being
invulnerable, a feeling which is basic to
ordinary day by day living" (id.). The
cancer patient senses suddenly that the
future is limited. Social and work mo-
bility are seen as curtailed; so are the
patient’s functional role in the family
and the community. In addition. the pa-
tient senses a new dependence on others
and may fear that he or she will become
a burden on the family (id. at 2). “The
initial psychological status of the patient
and family is characterized by disorien-
tation, anxiety, guilt, fear of pain and
suffering" (R 421 at 1).

Dr. Robert C. Eyerly, Chairman of
the American Cancer Society’s Commit-
tee on Unproven Methods of Cancer
Management, states that, “Indeed, we’ve
found that the major reason cancer pa-
tients use Laetrile is fear * * * fear
that the disease is incurable, that surgery
or other therapy is mutilating, and that
the medical profession is not to be
trusted” (R 173, Att. “Laetrile: Focus on
the Facts”).

In this climate of anxiety and fear,
the medical establishment—which, un-
like the proponents of “unproven” rem—
edies. feels an obligation to be honest
with the patient and his family—cannot
always offer hope: “ [P]robably the most
important factor [explaining why can-
cer patients choose to use Laetrile] has
been the failure of modern medicine and
technological advances to cure or ade-
quately control some cancers. These un-
fulﬁlled expectations lead patients to
disappointments in standard medicine
and to attempt a cure of their disease by
pseudoscientiﬁc methods” (R 398 at T 9).

Physicians, trained in the saving of
life and the alleviation of suffering but
unable. in some cases, to do either with
cancer patients, may contribute to the
frustration. “Many patients sense a feel-

ing of frustration and hopelessness con-
veyed, perhaps unconsciously, by the
physician who tells them the nature and
probable outcome of their disease—a
natural feeling on the part of the physi-
cian who is discouraged by his recog-
nition that he cannot cure the patient.
Patients sensing this hopelessness fre-
quently are unwilling to ‘abandon hope’
and therefore seek [unorthodox thera-
pies]” (R 190, Ex. 4, Editorial at 327).
Glen W. Davidson, Ph.D., Chairman of
the Department of Medical Humanities,
Southern Illinois University School of
Medicine, testiﬁed that, “" ‘ * when
primary emphasis for treatment is
placed on ‘cure’ and the physician’s abil-
ities, rather than on ‘coping’ and the
patient’s abilities, the patient is placed
in an inappropriate and ineffective de-
pendency relationship. When the physi—
cian can no longer promise ‘cure’ and
then attempts to refer the patient out of
his practice, or leaves the patient to
institutional care of others, the patient
feels abandoned. The patient has al-
ready had his coping abilities under-
mined. And many patients react to un-
fulﬁlled expectations and violated trust
with anger and panic” (R 387 at 2) .

\/ A patient facing cancer and the lack

58

of positive assurance from the physician
that the cancer can be cured may simply
give up hope that what the physician
can do for the patient can work. This
lack of conﬁdence in proven remedies
is tragic in an era when, in the case of
many cancers, a signiﬁcant percentage
of patients can be cured or have their
lives extended. See, e.g., R 173, Att. A08,
1977 Cancer Facts at 3. Laetrile’s pro-
ponents expend great efforts to encour-
age this feeling. Much of the oral argu-
ment of Laetrile proponents in this pro-
ceeding was addressed not to the effec-
tiveness of Laetrile but to the ineffective—
ness of proven remedies (see., e.g., Tr. at

(16 et seq.; Tr. at 228). With real hope

extingished, the use of Laetrile or other
unproven remedies is a way of avoiding
an acceptance on a conscious level of
the consequences of the disease: “The
decision to use Laetrile indicates that,
at the subconscious level, patients and
their families have given up on conven-
tional therapy and, in fact, have ac-
cepted the inevitability of death. On the
more superﬁcial level, patients choosing
Laetrile are persons who believe that
they do not require the use of sophisti-
cated, anti-cancer treatments. This re-
ﬂects an ambivalence which many pa-

Laetrile

tients feel at the time they are required
to make decisions about cancer therapy.
If patients can maintain denial about
the seriousness of their cancer, then they
can permit themselves to experiment
with a bizarre apricot-extract, such as
Laetrile” (R 433 at {I 13) . “Human beings
have become accustomed to using the
psychological techniques of denial in
dealing with real problems” (R 390, Ex.
3 at 386). “The decision to use Laetrile
is, in essence, an attempt ‘magically’ to
avoid the reality of cancer” (R 433 at

119).

2. The Role of Loved Ones

Patients with a diagnosed malignancy
frequently encounter ostracism in their
private, social, and vocational roles (R
387 at 1). At this point, the caring of
loved ones and their sympathetic will-
ingness to continue to associate with and
to share the suffering of the cancer pa-
tient assume great importance to the
patient. This caring relationship, quite
understandably, leads to a dependence
by the patient on the loved one and a
corresponding feeling of responsibility in
the nonpatient: “Many patients in their
initial response to cancer diagnosis sur-
render control to those closest to them,
further complicating the issue of in-
formed choice. Highly anxious relatives
with little or no medical understanding
of cancer as a disease entity fall prey to
the emotional appeal of the proponents
of Laetrile” (R 421 at 2). “Cancer pa-
tients are most vulnerable to the manip-
ulations of others when they feel they
are (1) being abandoned, (2) unable to
control pain, and (3) unable to maintain
a ‘sense of dignity’ by being able to make
decisions for themselves. Attempts at
guarding oneself from all three fears are
often incompatible. Many cancer pa-
tients feel they are in a ‘double-bind.’
If they don’t follow their physician’s
treatment plan, the disease process won’t
be arrested. If they don’t follow the com-
peting, and often contradictory advice
from relatives and friends, they will be
abandoned. And if they assert their own
feelings they will be ostracized by others
at the very time they most need support
from others” (R 387 at 1—2). Thus, some
patients pay the price of what benefits
are available from orthodox treatments
in order not to be abandoned by family
and friends—“a psychological analogue
to the theological concept of being ‘cast
into Hell' " * *” (id. at 2). In many
cases, it is family and friends who, am-

59

plifying the patient’s feelings, try to get
their anger and panic under control by
manipulating the patient into use of
medically unacceptable remedies. (See
id. at 2.) The families of cancer patients,
particularly parents of children with
cancer, are understandably desperate for
anything that will cure cancer. They
often are beset by irrational feelings of
guilt, and seek to assuage these feelings
with the assurance that “ * " ‘ ‘we did
everything for our child’ even to the
point of foolishness in going after an
unproven cure * ‘ *” (R 394 at 2).

The shared responsibility of the loved
ones of cancer patients for the patients’
involvement with Laetrile (or other un—
proven remedies) helps to explain why
these families have been among the most
vociferous proponents of Laetrile. “This
reaction can be understood because such
persons, whether they are family mem-
bers or friends, have to justify the
deceased’s use of Laetrile by suggesting
that the patients were considerably
helped by the drug, that their lives were
prolonged to a significant extent, or, at
the least, that they did not suffer a great
deal of pain during treatment with the
drug. To do otherwise would require them
to acknowledge that they made a mistake
and misled the patients or that they went
along with decisions which were
clearly erroneous. Living with that kind
of guilt is very difﬁcult and the advocacy
of Laetrile is a way of avoiding it” (R 433
at 'U 15). It is only those family members
who did not participate in, or dissented
from, the decision to use Laetrile who,
after the patient’s death, raise their
voices against the drug’s use (see, e.g.,
R 47; R 429; R 300; R 348).

3. Methods of Promotion of Laetrile

As is obvious from the above discus-
sion, the cancer victim and his or her
family are extremely vulnerable to the
kind of persuasion used so skillfully by
Laetrile’s promoters. This persuasion
may take the form of highly polished and
thus convincing ﬁlms and books (see Tr.
at 331) or of personal visits. The fact
that many persons involved in Laetrile
promotion believe strongly in the drug
makes their presentations, because
sincere, all the more compelling. In his
afﬁdavit. one cancer patient, speaking
from his own experience, stated that
“immediately after a diagnosis of cancer,
most patients and family members are
susceptible to something such as Laetrile,
which offers a painless treatment with

Commissioner's Decision

certain results” (R 389 at 2) . The patient
also stated that, somehow, the names of
cancer patients in his area had been ob-
tained by certain persons helping to
spread the Laetrile theory. He indicated
that Laetrile proponents exerted con—
stant pressure on him and his wife to
quit orthodox medical treatment and try
Laetrile. Testimonials from patients who
spoke in glowing terms of their recovery
or successful treatment with Laetrile
were offered to support the proponents’
claim (id.). Laetrile promoters are dili-
gent in searching out persons with
reported cancer to offer their product.
One physician noted that he had a
patient who, within 24 hours of his being
diagnosed as having lung cancer, received
information in the mail telling him he
ought to take Laetrile and where and
how to get it (Tr. at 184).

Laetrile proponents are keenly aware
of the involvement of family members
and friends in decisions to accept un-
proven remedies and actively seek to per-
suade them of the drug’s beneﬁts. One
woman who had had surgery and chemo-
therapy for treatment of breast cancer
commented: “My biggest problem has
been coping with well-meaning relatives
and friends who swallow this propaganda
of unprofessionals and then try to make
me feel guilty because I don’t take their
advice * * *” (R 96).

Laetrile proponents play upon the
victim’s frustration with a medical estab-
lishment that cannot offer the certainty
of a cure. Some patients reportedly turn
to Laetrile precisely because it is “i1-
legitimate,” behavior that appears to be
“an anger reaction toward legitimate
medicine” (R 387 at 3) . This antagonism
toward the medical establishment is
fanned by Laetrile proponents (as it has
been by the purveyors of previous “un-
proven” remedies) to a pitch that most
observers would consider absurd. When a
speaker at the oral argument asked the
audience, which consisted predomi-
nantly of Laetrile supporters, if ”you
really think that a quarter of a million
physicians across the country can let
people die because they want to make a
proﬁt off of them?”, the audience re-
sponse was a loud chorus: “Yes” (Tr. at
191).

Laetrile proponents also play upon and
build the cancer patient’s fear of legiti-
mate cancer therapies. (See R 421 at 2:
“The promise of a painless cure through
Laetrile, as opposed to orthodox medical
methods with their side effects capitalizes
on the fear of pain and suffering”.)

60

“Slash (or cut), burn, and poison” are
the code words of the Laetrile supporters
for the proven remedies of surgery, radi-
ation and chemotherapy (see, e.g., Tr.
at 291, 357, 463). A videotape of an
interview with a cancer patient (R 419,
Ex. B; see also R 197 at 'H 7) that is part
of the record shows graphically the costs
of this sort of propaganda. The victim is
a woman who, at the time her breast
cancer was discovered, was given a rea-
sonably good prognosis of recovery after
surgery. Out of fear of surgery she tried
Laetrile therapy. Though the tumor grew
to involve her whole breast she continued
to avoid conventional therapy, even try-
ing, after Laetrile did not help, an “as-
paragus” diet cure, garlic, and ﬁnally a
fruit and vegetable diet with hot baths.
When, nearly at death’s door, she re-
turned to the surgeon, it was too late for
surgery to be effective. She then was
convinced to try radiation therapy, which
she testiﬁed she had avoided because the
negative descriptions of it in Prevention
magazine, to which she had long sub-
scribed. The radiation therapy helped re—
duce the siZe of her tumor and make
her more comfortable. but her expected
survival time was greatly diminished by
her delay in obtaining effective treat-
ment. This kind of disparagement of
conventional therapy, a bulwark of the
campaigns of Laetrile proponents, is per-
haps the most morally reprehensible as-
pect of the pattern of the drug’s promo-
tion.

4. The Sampson Survey

While the conclusions about the rea-
sons for use of Laetrile expressed in the
record are based upon a multitude of
experiences by various witnesses with
patients taking Laetrile, it is interesting
to note the conclusions of the one at-
tempt to survey Laetrile patients about
their reasons for using the drug.

Based upon about 20 interviews with
cancer patients who abandoned ortho-
dox therapy in favor of Laetrile, Dr. Wal-
lace I. Sampson, Clinical Associate Pro-
fessor of Medicine, Stanford University
School of Medicine, stated that about 75
percent of the patients reported that
they had serious problems with their
physicians. About 75 percent believed in
Laetrile’s therapeutic rationale and ef-
fectiveness. About 75 percent of the pa-
tients were involved in other methods
of therapy that included high doses of
Vitamin C, megavitamin therapy, and
immunotherapy given by unqualiﬁed in—
dividuals. Dr. Sampson is of the opinion

Laetrile

that the patients receiving Laetrile were
involved in other types of unorthodox
therapy because of their outlook on life
(i.e., they seek nonrational, magical solu-
tions to the problems of dread and often
uncurable illness) or perhaps because of
difficulties in relating to a standard
physician. A large majority of the pa-
tients believed that there is a conspiracy
to keep Laetrile off the market. Less than
10 percent of the patients tried to inform
themselves about Laetrile from non-
Laetrile sources. (See Tr. at 118—119; R
398 at 4.)

C. THE LAETRILE TESTIMONIALS

Unproven cancer remedies like Lae-
trile are invariably supported by numer—
ous testimonials of persons who pro-
nounce themselves satisfied with the re-
sults they, or their deceased friends and
relatives, have achieved with the drug.
The present widespread use of Laetrile
as an alternative to remedies of proven
effectiveness illustrates the problems to
which such “evidence” of a drug’s effec-
tiveness leads, and it is a legitimate ques—
tion to ask why there are so many such
testimonials.

The Commissioner does not doubt the
honesty or the sincerity of the many
testimonials for Laetrile, but many of
the positive experiences reported may be
accounted for by explanations other than
the claimed effectiveness of the drug. The
placebo effect discussed above undoubt—
edly accounts for some of the reports,
particularly those claiming decrease in
pain and increased sense of well-being.
Experts interested in the question have
provided other explanations. Most of the
patients reporting Laetrile “cures” ap-
pear actually to have had the beneﬁt
of other, proven effective therapies. Some
of those who believe themselves cured
may never have had cancer at all. Others
may simply not be cured, despite their
belief.

Many of the testimonials and anec-
dotes concerning the effectiveness of
Laetrile replay the same scenario. The
cancer patient is told he has cancer and
agrees to surgery, radiation, and/or
chemotherapy. After some time, the pa-
tient, feeling nauseous, weak, and gen-
eral malaise, in desperation turns to Lae-
trile. Within a few days or weeks after
stopping orthodox treatment and start-
ing to use Laetrile, the patient feels bet-
ter, has an appetite, and is able to move
about on his own. The patient in all sin—

61

cerity attributes his recovery and feel-
ing of well-being to his decision to re-
ject orthodox medical treatment and to
choose Laetrile. (See, e.g., R 9; R 35; R
223; R 267; R 315; R 391; R 483.) Many
families of deceased cancer patients
who had orthodox therapy and who then
used Laetrile believe that the patient
beneﬁted from the Laetrile and might
still be alive if they had turned to Lae-
trile earlier. (See, e.g., R 19; R 208; R
2'79.)

It is easy to understand how such a
situation could develop. A doctor may
prescribe 10 applications of a proven
cancer drug, perhaps after surgery. The
cancer may have been totally removed
by the surgery or it may have been to-
tally destroyed by, for instance, the 7th
of the 10 applications of the effective
drug. Because the physician cannot know
this, and because he cannot risk the
chance that some cancer remains, he
has prescribed the recognized treatment
regimen. Use of cancer drugs (referred
to as chemotherapy) or of radiation may
involve unpleasant side effects. The pa-
tient, sickened by the side effects of the
drug and importuned by Laetrile pro-
ponents, may stop the chemotherapy be-
fore the prescribed regimen is com-
pleted. As the side effects clear up, the
patient feels better. If a full cure has
been accomplished. it will be attributed
to Laetrile. If it has not, the surviving
family may well believe that, since the
patient felt better after stopping chemo-
therapy and starting Laetrile, the
therapy was only received “too late.” See
R 184 at ‘i 7:

Testimonials attesting to a feeling of gen-
eral improvement and cessation of pain in
patients upon abandonment of radiation and
chemotherapy in favor of Laetrile treatment
do not indicate that Laetrile is effective in
curing cancer or in relieving pain. The feel-
ing of well being experienced by these pati-
ents derives from two phenomena, one phy-
sical and the other psychological. Chemo-
therapy and radiation treatments produce
unpleasant side effects in most patients.
When such therapies are stopped, the side
effects they produce disappear. This natural
physical effect in the case of these patients
is reinforced when Laetrile is administered
because of the patients' expectation that the
treatment will have a beneﬁcial effect.

Dr. John A. Richardson, himself a major
proponent of Laetrile therapy, stated
that 85 percent of the 4,000 to 5,000
patients treated with Laetrile at his
clinic had previously received some type

Commissioner’s Decision

of orthodox medical treatment (Tr. at
463).

Sometimes conventional and Laetrile
therapies are administered simultane-
ously, with any beneﬁcial effects attri-
buted by patients to the latter. Dr. Emil
J. Frereich is involved in the develop-
ment of cancer drugs. He stated that:
[W]e have numerous patients who are re-
ceiving developmental therapy drugs which
have at the time, real promise, and subse-
quently prove to be useful and are intro-
duced into practice, who unbeknownst to us,
were also taking therapy with iaetrile and
when their disease responds to therapy,
[they] inadvertently ascribe it to the effec-
tiveness of the unproven remedy, whose ad-
ministration is revealed to us subsequently.
When we compare the responses of patients
on a given therapy who have received laetrile
at the same time, with those who received
none, there is no signiﬁcant difference, which
indicates clearly that those observed re-
sponses were due to the cancer chemotherapy
drugs which were being administered by us
and not by the additional use of laetrlle
(R 390 at ii 20).

For other testimony on the propriety of
attributing to Laetrile cures that may be
caused by other, proven effective, drugs.
see, generally, R 1'74 at $1 9 and R 185
at 'H 20c.

“Some people who believe that Laetrile
cured them never had cancer to begin
with” (R 174 t 9). In a number of the
“case histories” submitted to show Lae-

trile’s effectiveness, there is no accepta-

ble showing that the patient ever had
cancer. (See. e.g., R 183, Att. 16, App.
2; R 184, Ex. 2; R 378, Att. “Supple-
mentary Report,” cf. evaluation of case
histories above.)

In one 1955 pamphlet, Dr. Krebs, Sr.,
discouraged biopsy, the procedure often
used to determine whether a tumor is
malignant (cancerous) (R 183, Att. 7 at
14). He urged instead that a special
urine test, not generally accepted by the
medical community as useful, be the
means for diagnosing cancer (id. at 16).
Even where the diagnosis has been done
by someone other than a Laetrile pro-
ponent, a mistake is possible. Some can-
cers which are discussed in reference
to Laetrile are very difﬁcult to diagnose
histologically. Thus, a diagnosis of can!
cer may often on later review be re-
versed. (See Tr. at 141.)

“Many cancer patients have given
testimonials believing themselves cured,
only to discover later that they still have
the disease” (R 174 at i} 9). Since he is

62

involved in the testing of cancer drugs,
Dr. Emil J. Freireich is in a good posi-
tion to follow up on patients who leave
his program to use Laetrile. Dr. Freireich
reports that “[iln virtually every in—
stance, [Laetrile patients treated in our
department and subsequently followed
by our tumor registry, have been] found
to have evidence, not only of progressive
disease, but to have expired after receiv-
ing such unsuccessful treatment, and a
signiﬁcant fraction eventually return to
our clinic for more developmental ther-
apy” (R 390 at ii 20).

An illustration of what, in all likeli-
hood, explains most Laetrile testimonials
appears in the record:

Testimonials fail to provide objective evi-
dence that there has been control or regres-
sion of a tumor which is attributable to the
use of Laetrile ‘ " ". To illustrate why such
data are important, let us examine two typi-
cal versions of testimonials from women
who state that their cancer of the breast was
cured by Laetrile. The first testimonial is
from Jane Doe. She discovered a lump in her
breast and based upon the urging of friends
has consumed on her own initiative a num-
ber of Laetrile tablets. It is also possible
that she saw a doctor who administered in-
Jections and prescribed a special diet. In a
month, the lump has disappeared, and Jane
Doe sings the praises of Laetrile. "It cured
my cancer; I am living proof." This is not
credible evidence. The lump detected may
have been caused by a variety of conditions.
Without laboratory confirmation that a ma-
lignant condition existed, there is no basis
to assume that it was cancer and that Lae-
trile contributed to its disappearance. The
second testimonial is from Dorothy Doe.
She had objectively diagnosed cancer, un—
derwent a mastectomy, and postoperative
chemotherapy or radiation treatments. The
physician informs Dorothy that an addition—
Ial surgical procedure may be necessary.
Dorothy decides against further unpleasant
treatment and takes Laetrile, Now. six
months or three years later—time makes
little difference—she, too, sings the praises
of Laetrile. Dorothy’s experience does not
constitute evidence. It is possible that her
orthodox treatment was successful; it is pos-
sible that she still has cancer, but that it
will not manifest itself for another year or,
indeed, as is sometimes the case, for another
dozen years. The point is that there are no
objective data upon which to assess Doro—
thy's condition at the time Laetrile was ad-
ministered and the effects of Laetrile. In the
absence of such data, there is no basis for a
claim that Laetrile was effective (R 191 at
ii 14).

As another afﬁdavit states,

‘ ' * It is a certainty that any substance
without significant toxic or harmful effect

Laetrile

including mystical activities, faith healing
and all other types of non-toxic or non-
harmful remedies will be eii'ective in a small
fraction of the very large population of pa-
tients with hopeless terminal cancer. Those
individuals who fail to respond to such treat-
ment, that is, who have the expected out-
come, which is progression of their cancer
and death, are no longer living and those
rare individuals who have the exceptional or
miraculous outcomes frequently live for long
periods of time. It is obvious that a large
number of individuals can be identified who
have unusual outcomes. These individuals
are of course easily convinced of the effec-
tiveness of such treatments and are free to
testify to their effectiveness for as long as
their disease remains in control. Such testi-
monials contribute no signiﬁcance toward
our understanding of the effectiveness of
any treatment for cancer. Evidence accumu-
lated in the proven, objective, medical and
scientiﬁc fashion is the only evidence that
can be of use in evaluating the potential of
any treatment for inﬂuencing the course of
malignant disease (R 390 at ll 21).

Dr. Melvin Krant, Professor of Medi-
cine and Psychiatry and Director of Can-
cer Programs at the University of Massa-
chusetts Medical Center, reviewed a
number of the testimonials submitted to
the record from patients and relatives
and friends of patients who have been
treated with Laetrile. He stated that the
testimonials “do not offer evidence for ef-
fectiveness because frequently the treat-
ments with Laetrile were taken after
other treatments such as surgery, radi-
ation, or chemotherapy. At times, the
Laetrile was taken in conjunction with
other modes of therapy such as chemo—
therapy. In such instances, it is impossi-
ble to know whether the Laetrile added
anything to the patient’s response. There
are no objective ways to measure the pa-
tient’s response. In many instances, it
seems like the main emphasis of the test—
imonials is on the patient’s emotional
reaction to being treated. Because the
testimonials are not presented in a sci-
entiﬁc manner, it is also impossible to de-
termine if there were any side eifects
from Laetrile administration" (R 453 at
1—2).

V. Omen ISSUES REGARDING LAETRILE

A. USE OF LAETRILE OUTSIDE THE UNITED
STATES

Laetrile’s proponents have sometimes
sought to give the impression that Lae-
trile is in use around the world and that
it is only the United States’ overly re-
strictive drug laws or an evil conspiracy
among drug companies, physicians, and

63

bureaucrats that is preventing market-
ing of the drug in this country. (See, e.g.,
the claim, in a 1963 publication, Control
for Cancer by Glenn D. Kittler, that Lae-
trile was being studied in several coun-
tries in addition to the United States:
Canada, the Philippines, Japan, England,
Belgium, Italy, Union of South Africa,
and Mexico (R 318 at 31) .) The book also
reported that the drug was registered in
Iran in 1962 (id.). (See also the reference
to the use of Laetrile (or Amvgdalin) in
West Germany in the late 1960’s (R 302,
Ex. G).) (Cf. R 198, Ex. 2 at 24, (tran-
script of ﬁlm World Without Cancer);
Tr. at 424.)

The record reﬂects no international
recognition or use of the drug. The State
Department and the United states Mis-
sion to the World Health Organization
made an effort to determine whether
Laetrile, Amygdalin, Vitamin B—17, or
such drug under any other name was
known and approved elsewhere in the
world. The State Department sent in-
quiries to all American embassies in-
structing embassy ofﬁcials to ascertain
the status of the drug in their respective
host countries, and the mission to the
World Health Organization made tele-
phone inquiries of member states
throughout Western Europe. The follow-
ing information was obtained:

The American Embassy in Mexico ad-
vised that in 1974 the Mexican govern-
ment gave provisional approval, contin-
gent upon the presentation of evidence of
Laetrile’s effectiveness in treating can-
cer, to two laboratories in that country
to manufacture the drug. This approval
was cancelled in late 1976 because no
positive results were obtained in research
carried out at the Medical Center Gen-
eral Hospital. The decision to ban Lae-
trile has been appealed by Laetrile pro-
ponents and is now in the Mexican
courts (R 426; see also Tr. at 430).

The mission to the World Health Or-
ganization had been told by some Euro-
pean contacts that “Laetrile" can be
“purchased across the counter in Geneva
without prescription” (R 426). The
American Embassy in Switzerland, upon
inquiry, was told that Laetrile is not sold
on the Swiss market and is not approved
there. One company does sell “small
quantities of Laetrile,” “exclusively to
cancer research scientists" primarily in
Western Europe. The company told the
American embassy in Bern that “laetrile
is not made available commercially, nor

Commissioner's Decision

is it sold as a cancer ‘cure’ ” (id).

In Madagascar, Laetrile is known as
Amygdalin and is considered a poison by
health authorities. Its use is prohibited.
In Chile, Laetrile is also known as azari-
bina and its use is prohibited under any
circumstance. This prohibition followed
receipt of Newsletter 172 from the World
Health Organization which described the
,.“.;ntia1 dangers of use of the drug. The
importation or use of Laetrile (Amyg-
dalin) is illegal in the Republic of Korea
(id).

Health ofﬁcials in Guyana reported
that Laetrile has been used there. The
Minister of Health indicated that he was
not aware of FDA’s prohibition of the
use of Laetrile, however, and that, since
the United States standards are closely
followed in that country, his country
would also ban the drug (R 426) .

The State Department inquiry drew

69 responses from around the world.
Each of the countries not already men-
tioned responded by indicating that
“Laetrile,” “Amygdalin,” and “Vitamin
B—17” were unknown or were not ap-
proved for use for treating cancer or any
other use. The responding countries in-
cluded the Philippines, Japan, the United
Kingdom, Belgium, Italy, South Africa,
and the Republic of Germany, as well as
France, Korea, Taiwan, Hong Kong, In-
dia, and others from every part of the
globe (id.). The United States Mission
at the World Health Organization con-
ﬁrmed that Laetrile “is not registered
and by deﬁnition, unavailable,” in any
of WHO’s member states throughout
western Europe (id.).

3. CLAIMS THAT LAETRILE IS A VITAMIN OR
FOOD

Proponents of Laetrile (or amygdalin)
have in recent years contended that their
product is a vitamin or that it is a nat-
ural food substance rather than a drug.
These claims are properly irrelevant to
the questions this administrative pro-
ceeding was intended to address. How-
ever, in nght of the interest in the vita-
min issue demonstrated by the submis—
sions to the record, the Commissioner
will take this opportunity to discuss it.
The potential safety problems presented
by this concept will also be discussed.

1. A Vitamin or Food May Be a Drug As
Well

This question is irrelevant to the is-
sues in this administrative proceeding
because, even if Laetrile (or amygdalin
or “laetrile”) were a vitamin (or a food),

64

it would still be a drug. Any substance,
including a vitamin or food, is a drug
and subject to regulation as such if it
is intended for use in the “diagnosis, cure,
mitigation, treatment, or prevention of
disease in man or other animals ‘ ‘ t”
(21 U.S.C. 321(g) (1) ). (See Rutherford
v. United States, supra, 542 F. 2d at 1140;
United States v. General Research Lab-
oratories, 397 F. Supp. 197, 200 (CD. Cal.
1975).7 As the previous discussion illus-
trates, there is no question that Laetrile
or amygdalin has been recommended in
the treatment of cancer. In fact, in the
very article in which Ernst T. Krebs, Jr.,
explained his theory that his product was
“Vitamin B—17”, he promoted it for can-
cer treatment. (See R 183, Att. 10c.)

It has been suggested that the claims
that Laetrile (or amygdalin) is a vita-
min or a food are simply an effort to
establish that the substance is covered
by the food requirements of the Federal
Food, Drug, and Cosmetic Act and its
regulations rather than those require-
ments applied to drugs. (See, generally,
Tr. at 216, 225, 405; R 173, Att. “Ques-
tions most frequently asked about ‘Lae-
trile,’ " at l; R 416 at 1116.) One court
has called the attempts by Laetrile pro-
ponents to represent Laetrile as some-
thing other than a drug, “a patently ab-
surd and transparent attempt to avoid
the drug labeling provisions of the Fed-
eral Food, Drug, and Cosmetic Act.”
United States v. Spectra Foods Corp,
Civil No. 76—101 (D.N.J., Jan. 29, 1976)
(R 173, Att.). The Commissioner does

7 Section 411 of the act (21 U.S.C. 350) deals
speciﬁcally with vitamins and minerals. Sec—
tion 411(a) (1) (B) does limit the authority
of the Secretary to classify a vitamin as a
drug “solely because it exceeds the level of
potency which the Secretary determines is
nutritionally rational or useful.” The vita-
min provisions do not. however, affect FDA’s
authority to classify and regulate vitamins
as drugs if they are represented to be for
use in the diagnosis, cure, mitigation, treat-
ment, or prevention of disease. The confer-
ence committee report states, "Except as spe-
ciﬁcally provided, the conference substitute
does not alter the drug or food provisions
of the Federal Food. Drug, and Cosmetic Act.
If a product containing vitamins, minerals
or other ingredients is a drug within the
meaning of Section 201(g) of the Act, the
Secretary may, with regard to such product,
exercise his authority under Chapter V of
the Act" H. R. Rep. No. 1005, 94th Cong. 2d.
Sess. (April 2, 1976); (see also, 122 Cong.
Rec. H3244—H3248, April 12. 1976).

Laetrile

not agree that Laetrile is a vitamin. (See
discussion below.) It is clear, however,
that even if Laetrile were a vitamin (or a
food) it would be subject to the drug pro-
visions of the act.

2. Is Laetrile a Vitamin?

This administrative proceeding was
not intended to address the issue of
whether Laetrile is a vitamin, and testi-
mony on that issue was not solicited.
Nevertheless, a considerable amount of
evidence in the record addresses this is-
sue. It appears that (a) Laetrile pro-
ponents classify amygdalin and certain
related substances as a vitamin under
their own deﬁnition of that term and
(b) experts in the vitamin area, utilizing
the criteria against which each of the
legitimate vitamins have been assessed,
conclude that amygdalin and other ni-
trilosides are not a vitamin.

(a) Proponents' Claims—The idea that
Laetrile could be considered a vitamin
ﬁrst appears in a pamphlet,“ in use in
1965, published by Krebs Laboratories
and entitled “Cancer Is A Deﬁciency Dis-
ease: The Deﬁciency of Cyanide Sugars”
(R 201, Ex. C, No. IV). In that pamphlet,
amygdalin and other “cyanogenetic glu-
cosides” are characterized as pro-vita—
mins for vitamin B—12. This means that
they participate in the formation of vita-
min B—12. It is stated that “during the
process of formation the liver is thor-
oughly fumigated and rendered sterile”
(id.). The real anticancer effect of
amygdalin is said to be not this forma-
tion but the release of cyanide in the
cancer cells by the mechanism discussed
above under “Theories of Action.” It is
interesting to note that another Laetrile
proponent, Dr. Navarro of the Philip-
pines, states that vitamin B—12 should
never be administered to cancer patients
(R 318 at 165).

The pro-vitamin theory had appar-
ently been set aside by 1970 when an ar-
ticle by Ernst T. Krebs, Jr., referred to
previously, “The Nitrilosides (Vitamin
B—17—Their Nature, Occurrence and
Metabolic Signiﬁcance (Antineoplastic
Vitamin B—17),” was published (R 183,
Att. 100). In this article, Krebs, Jr., uses
the term “vitamin B—l'? (nitriloside) " as

8 The Krebs were no strangers to the “vita—
min” area. Ernst T. Krebs, Jr.'s, marketing of
another of his inventions, “Vitamin B—l5"
(“pangamic acid"), led to his plea of guilty
to a charge of causing the introduction into
interstate commerce of an unapproved new
drug in 1962 (R 185, Att. 16, App. 17 at '7).

65

“a designation proposed to include a
large group of water-soluble, essentially
non-toxic, sugary compounds found in
over 800 plants, many of which are edi-
ble” (id. at 75). He indicates that the
compounds “are collectively known
chemically as beta-cyanophoric glyco-
sides. They comprise molecules made of
a sugar, hydrogen cyanide, a benzene ring
or an acetone” (id.). These compounds
could be hydrolyzed by beta-glucosidase
to a sugar, free hydrogen cyanide, and
benzaldehyde or acetone (id.). He states
that amygdalin is one of the most com-
mon of the nitrilosides and that it “oc-
curs in the kernels or seeds of practically
all fruits” (id.).

Mr. Krebs, Jr., in this article, attempts
to build a theory that vitamin B—17 is a
speciﬁc dietary factor that could be used
to prevent and to cure cancer. He ex-
plains that prevention' and cure occur
through the cytotoxic (toxic to cells)
compounds of vitamin B—17—hydrogen
cyanide and benzaldehyde—through
mechanisms discussed elsewhere in this
opinion (id. at 80). He concludes that:
“In nitriloside or vitamin B—l'l we have
a new vitamin in which all of us are
severely deﬁcient” (id. at 84). The
theory that Laetrile (or laetriles) consti-
tutes a vitamin has found another pro-
ponent in the person of Dr. Dean Burk, a
biochemist and president of the Dean
Burk Foundation, Inc. (see, generally, R
302; Tr. at 401 et seq.) .

Clearly, whether or not a given sub-
stance comes within the deﬁnition of
vitamin depends upon the deﬁnition
chosen. In his afﬁdavit, Burk deﬁnes a
vitamin as a substance which is “virtu-
ally non-toxic, water-soluble, an exogen-
ous nutrient or food factor, and active
in relatively small, essentially catalytic,
non-caloriﬁc amounts, and is essential or
beneﬁcial in normal metabolism and/or
physiologic functioning to overcome de-
ﬁciency lesions and symptoms of nutri-
tional disease” (emphasis in original) (R
302 at 4). Dr. Burk continues that in ani-
mal experimentation “‘ ' * the deﬁci-
ency lesions and symptoms of nutritional
disease are best illustrated by the action
of amygdalin in lengthening of animal
lifetime or decreasing development of
metastases, or both, and increase in
health and well-being * * *” (id.). (See
also Tr. at 408 and 465.)

Thus, even by the Burk deﬁnition, the
claim that Laetrile is a vitamin depends
in large part on the substance's ability
to combat cancer, an ability not shown

Commissioner's Decision

'by testing convincing to drug experts in '

general. Proponents of the vitamin
theory claim that the higher the every-
day diet is in nitrilosides. the lower the
incidence of cancer (R 73 at 36). Others
claim that it may not be only high nitril-
oside levels that account for this ob-
servation but that other dietary elements
(e.g., vitamin C) may play a role. (See,
generally, R 318.) These claims are based
upon assertions that in some geogra-
phical areas, where the normal diet con-

tains nitrilosides in abundance, cancer
does not exist. Evaluation of the preva-
lence of cancers requires careful studies
by conpetent epidemiologists and suit-
able cancer registries, which contain re-
ports by professional pathologists (R
399 at 11 9). What evidence does exist in
this area indicates a complete lack of
the correlation between high nitriloside
diet and low cancer incidence that the
:Vitamin 13—17 proponents claim. The
record contains citations to numerous
;reports showing that a variety of can-
cers do occur in populations consuming
nitriloside-containing diets. These in-
clude ﬁndings that cases of most of the
recognized cancers appear in the Kam-
pala Cancer Registry, Uganda (id.) .
3‘3 There are also references to published
) ' papers from the Ibadon Cancer Regis-
try, Nigeria on Burkitt’s lymphosarcoma,
Kaposis sarcoma and breast cancer, can-
cer of the bladder in Kenya, and the can-
cer incidence in Bantu (id.). Some
cancers that are rare or absent in North
America and Western Europe occur in
the populations which consume high
levels of nitrilosides (id.) .
/ In the ﬁlm “World Without Cancer,”
the-peopled the Kingdom of Hunza in
the Himalayan mountains are said to eat
a - diet containing over two hundred
times more nitrilosides than the average
American diet and to prize above all
other foods the apricot seed. It is stated
that “[vlisiting medical teams from the
outside world report that there never has
been a case of cancer in Hunza" (R 198,
Ex. 2 at 8). However, in 1955, a Japanese
medical expedition studied the Hunza
people and reported that they have many
diseases, including cancer (R 173. Att.
“Questions Most Frequently Asked” No.
6; Tr. at 338).

Similarly, the ﬁlm claims that the
Eskimos eat a high nitriloside diet and
are “found to be totally free of cancer"
(R 198, Ex. 2 at 8). The Eskimos have
also-been found to have cancer (R 173,
Att. “Questions Most Frequently Asked”

. v.

66

No. 6; Tr. at 339) . In commenting on an-
other reference to “the diets of the can-
cer-free population" (R 217 at 2),
Thomas H. Jukes, Ph.D., states correctly:
“There are no cancer-free populations”
(R 416 at 11 28(0)).

(b) Vitamin Experts’ Position.—
Numerous nutrition experts and organi-
zations concerned with nutritional
science provide support in the record for
the Commissioner’s conclusions that
“Laetrile,” or “amygdalin,” or “nitrilo-
side,” is not a nutrient or vitamin. (See,

e.g., R 1'73, Att. "Questions Most
Frequently Asked” (American Cancer
Society); R 168, Att. “The Vitamin

Fraud” and R 399 at 11 12(0) (David M.
Greenberg, Ph.D.); R 416 (Thomas H.
Jukes, Ph.D.) ; R 378, Att. Editorial; Att.
American Institute of Nutrition letter; R
169 at {[17 (Vincent T. DeVita, Jr.,
M.D.); R 191 at 11 11 (Philip S. Schein,
MD.) ; R 227 at 3 (National Council on -
Drugs) .) The steps which are necessary
to establish that a substance is a vitamin
are described in the record. These steps
include the publication in reputable
journals of a complete description of the
research procedures, and confirmation,
by other scientists, of the results ob-
tained. If the work cannot be repeated,
the existence of the vitamin is not
recognized (see R 416 at 1115). Addi—
tional steps include demonstrating the
presence of the purported vitamin in
foods, determination of its exact
chemical molecular structure, the
demonstration of its effectiveness, and
its chemical synthesis. After these steps
are completed, the Food and Nutrition
Board of the National Academy of
Sciences sets up Recommended Daily A1-
lowances for the vitamin which then
must be adopted by the Food and Drug
Administration (id.).

The lack of scientiﬁc evidence of any.
effect, which has prevented Laetrile from
being recognized by experts as a safe
and effective drug, also prevents recog-
nition of its claimed status as a vitamin.
(See. e.g., R 416 at {I 16: “(T)here are no
data available to show that a disease
state is produced or alleviated by the ex-
clusion from [or] addition to the diet of
amygdalin".) Other experts emphasize
that there is no evidence that (1) lae-
triles (beta-cyanogenic glucosides, vita-
min B—17) are essential nutritional com-
ponents nor that (2) they promote any
physiological process vital to the exist-
ence of any living organism. (See R 168,
Att. at 347; R 395.)

A compelling point made by experts
in this area is that if there were a vita-
min B—17, and if cancer were a vitamin
B—17 deﬁciency disease, then every ani-
mal deprived-ofwthe vitamin would get
cancer while no animal given the vitamin
in suﬂicient amounts wouldget cancer. It
is noted, that “No person given adequate
vitamin C, for example, ever gets scurvy”
(R 198 at 5). Stated another way: “The
key to the term ‘vitamin' is that the
absence otvitamins from-them in an
experimental animal or a human being
must lead to the appearance of a nu—
tritional deﬁciency disease, which is pre—
vented or cured by adding the vitamin
to the diet. Laetrile has no such proper-
ty” (R 416 at 11 14).

It is further stated that “[no vitamin
has] the property of destroying tissue.
such as cancer tissue, that is claimed of
Laetrile. Such a property would be in-
compatible with the action of vitamins”
(Tr. at 223). Other experts in this area
rejected the claimed vitamin status in
part on the grounds, discussed below,
that amygdalin is. or can be, harmful to
the body. It is pointed out that, amygda-
lin properly belongs to the class of com-
pounds termed “toxicants occurring nat-
urally in foods” (R 416 at 'H 27(A) (1) ).

3. Dangers of Ingestion of “Vitamin B—
17"

As has been demonstrated above, the
presence of beta-glucosidase, oxynitral-
ase, and amygdalin together in apricot
pits presents the potential for a combi—
nation that would release cyanide and
cause poisoning of the individual con-
suming an extract of the pits. Addition-
ally, though beta-glucosidase is not pres-
ent in animal tissues, it, and other sub-
stances capable of breaking down amyg-
dalin, may be present in the digestive
track and thus may break down orally
consumed amygdalin to release cyanide
in the body. It is therefore with great
concern that the Commissioner views the
emergence of the theory that human
beings should step up their consumption
of “naturally occurring" nitrilosides such
as amygdalin.

In his vitamin B—17 article, Ernst T.
Krebs, Jr., notes that while the “stupid-
ity” of “political power” may keep pre-
pared vitamin B—17 off the market,
six or seven teaspoonsful of defatted
apricot seed or kernel would supply what
is considered to be an adequate oral
dose of nitrilosides (R 183, Att. 10c at
84). He suggested, “It is best that the

Laetrile

67

beta-glucosidase enzyme be completely
heat inactivated in such material” (id.).
He does not indicate how much heat in-
activation should be accomplished, nor
does he cite any support for the idea that
it can be.

There are documented cases of poison-
ing, some fatal, due to the consumption
of apricot pits or kernels. The toxic ele-
ment in these cases is the hydrogen cy-
anide which is released from the cyano-
genetic glucosides by the action of the
enzymes (including beta-glucosidase)
present in apricot kernels (R 378, Att.
“California Morbidity Reports,” Att.
“Hazards to Health"). The suggestion by
Mr. Krebs, Jr., that the beta-glucosidase
be “inactivated” can be taken as tacit—-
too tacit—acknowledgement that the
kernels and/or pits present a hazard
when consumed unless the enzymes are
ﬁrst destroyed. The Commissioner notes
that other proponents of Laetrile clearly
state that amygdalin products should
never be given by mouth because the
hydrochloric acid in the stomach is capa-
ble of hydrolyzing the drug (R 318 at
158). A 1954 document, “The Rationale
and Clinical Evaluation of Laetrile-Beta—
Glucosidase Palliative Therapy” states,
“CAUTION ' Laetrile (1-mandelonitrile-
beta-glucuronidase) is NOT TO BE
TAKEN ORALLY. It is extremely toxic
by this route of administration, since the
gastric hydrochloric acid acts to hydro-
lize the glucoside with the release of
hydrogen cyanide” (R 388, Ex. 5).

Dr. Burk seeks to support the idea that
Laetrile or amygdalin is a food and,
among other things, may be safely con-
sumed by an allegation that “‘ ‘ ‘ lae-
trile is listed in the HEW—FDA GRAS
list (foods ‘Generaly Regarded [sic] as
Safe’) under the heading of natural ex-
tractive from bitter almond, apricot or
peach kernels" (R 302 at 3; see also Ex.
B). The material to which Dr. Burk re-
fers is “Bitter almond (free from prussic
acid)” which does appear on the gen-
erally recognized as safe (GRAS) list,
21 CFR 182.20. (Prussic acid is another
name for hydrogen cyanide.) The mate-
rial on the GRAS list, however. is an
oil extracted from peach, almond, or
apricot kernels. After cold pressing the
oil from its source, it is processed to
effect enzymatic hydrolysis of amygdalin.
There is no amygdalin present after the
hydrolysis step. The ﬁnal product is es-
sentially benzaldehyde. “Thus the mate-
rial listed for ﬂavor use ‘ ‘ ‘ is not
amgydalin and thus neither is it Lae-
trile” (R 415 at 2). Dr. Burk’s contention

Commissioner’s Decision

is thus incorrect and has no basis in fact.

The idea that foods containing nitrilo-
sides may be safely consumed is also sup-
ported by stories of “non-toxic” nature
of nitrilosides which are found in the
diets of various peoples. This claimed
nontoxicity is not borne out by reality.
In some parts of Africa two important
human diseases—human ataxic neurop-
athy and endemc goitre—appear to be
associated with high cassava intake (R
183, Att. 20 at 161; R 3'78, Att. 6). (Cas-
sava contains linamarin, a commonly
consumed nitriloside (R 217, Att. “Sickle
Cell Anemia” at 51).) It is also reported
that cows have been killed by eating
large amounts of young millet, which
is particularly high in nitrilosides, and
intoxication of other animals has been
reported. (See R 416, Ex. 5 at 302.) There
have been reports in this country of
toxicity and, in some cases fatalities, in
humans from consumption of amyg-
dalin-containing substances (See, e.g.,
R 378, Att. “California Morbidity”; see
also R 378, Att. “Hazards to Health;
Cyanide Poisoning from Apricot Seeds
Among Children in Central Turkey,”
Sayer et al.). Thus there is ample and
clear indication that the consumption of
“nitrilosides” is not without hazard. To
urge the public to consume “apricot pit
milkshakes” or similar foods in order to
be sure to get an ample supply of amyg-
dalin or “vitamin B—17” or “nitrilosides”
is irresponsible and foolhardy.

C. FREEDOM OF CHOICE

The administrative record contains
many comments not directed to the legal
issues of Laetrile’s “new drug” or “grand-
father” status or even to the question
of whether the drug is safe or effective
for use in cancer therapy. Rather these
comments support the proposition that
a person should be free to choose his or
her own cancer therapy, at least if the
drugs involved are not overtly toxic (see,
e.g., Tr. at 33; R 231; R 238; R 242; R
209; R 211; R 283; R 500; R 155; R 272).
The issue of “freedom of choice” is ir-
relevant to the issues remanded to the
agency by the Rutherford courts. Nev-
ertheless, because of the demonstrated
public interest in this issue, the Com-
missioner has given it, and submissions
addressing it, careful consideration.

The very act of forming a government,
of course, necessarily involves the yield-
ing of some freedoms in order to obtain
others, In passing the 1962 Amendments
to the act—the amendments that require
that a drug be proved effective before it

68

may be marketed—Congress indicated its
conclusions that the absolute freedom to
choose an ineffective drug was properly
surrendered in exchange for the freedom
from the danger to each person’s health
and well-being from the sale and use of
worthless drugs. This is in fact the same
decision made by those in government
who have decided over the years that
only those persons may practice medi-
cine who have been certiﬁed by experts '
to be qualiﬁed to actually help the pa-
tients who would choose to seek their
assistance.

Some would argue that the law-
makers’ well-considered decision to pro-
hibit the use of drugs not shown to be
effective was the wrong one. One alterna-
tive suggested is that a drug such as Lae-
trile should be marketed with labeling
which indicates that experts do not con-
sider it to be effective. The present use
of Laetrile vividly illustrates the im-
practicability of such a solution. There
can be few patients taking Laetrile in
this country today who do not know that
the government and most experts con-
sider it worthless. Yet the drug continues
to be used, to the detriment of cancer
patients who might otherwise be helped
by conventional treatment.

The choice to use Laetrile is seldom.
in any case, a free one. As the discussion
above (Why Do People Use Laetrile?)
illustrates, a cancer patient is a person
beset by immense stresses, physical,
psychological, emotional and societal;
and the persuasion that the patient and
his family are subjected to by Laetrile
proponents is seldom limited to a rational
laying out of competing arguments. The
information that the proponents of Lae-
trile provide is false—that the drug
cures, palliates, relieves pain, “controls"
cancer. As Dr. Sampson’s survey, dis-
cussed above, indicates, few Laetrile pa-
tients make an effort to hear the argu-
ment against Laetrile therapy. The idea
that a reasoned free choice is involved in
the selection of Laetrile rather than
legitimate therapy is thus ultimately an
illusion. (See R 421 at 1.)

The record contains the views of many
persons who have considered the issue of
“freedom of choice” in cancer therapy.
Each represents a thoughtful attempt to
deal with this question, which, while ir-
relevant to the legal issues which are the
subject of this opinion, is troubling to
those concerned with the Laetrile prob-
lem. These comments may be grouped
roughly as supporting the two responses

to the “freedom of choice” argument set
forth above: (1) The surrender of an
absolute freedom to choose among cancer
remedies in order to obtain the greater
freedom from the suffering associated
with use of ineffective remedies is' a ra—
tional decision; and (2) the “choice” of
unproven cancer remedies cannot fairly
be characterized as “free."

1. Balancing Freedoms

Reverend Allan W. Reed, Director, De-
partment of Pastoral Services and
School for Pastoral Care, Massachusetts
General Hospital, considered the ethical
side of the “freedom of choice” question.
He states “The ethical issues of a group
legislating for an individual, thereby
threatening the principal [of] freedom
of choice, contrasts with the ethical
principal of a government protecting its
citizens from fraud and abuse. In the
case of a drug for which there is no

proven efﬁcacy, the ethical weight is on .‘

the side of protection of the citizens”
(R 418).

Leroy G. Kerney, Chief of the Depart-
ment of Spiritual Ministry at the Clini-
cal Center, National Institutes of Health,
pointed out that, “Freedom of the indi-
vidual is important. But when the free-
dom to accept any drug for treatment
and the freedom to injure oneself collide,
a judgement must be made: Stop signs
or restrictions on turning at certain
corners restrict my freedom in driving,
but, at the same time, they protect my
freedom from hurting myself and others
in traffic” (R 414 at 3).

J. Philip Wogaman is Dean and Pro-
fessor of Christian Social Ethics at the
Wesley Theological Seminary and past
president of the American Society of
Christian Ethics. He noted an “initial
presumption” in favor of freedom from
governmental prohibition but concluded
that Laetrile should be banned for three
reasons: (1) The ban prevents fraud in
the medical marketplace; (2) “[Mlis-
representation in the field of medicine
is particularly serious because it under-
mines public conﬁdence in medicines
that are of real value”; (3) “[Tlhere is
a real danger that persons may be led by
false hopes in a worthless drug to neglect
treatment at a time when it could be
most effective” (R 417 at 2—3).

Dr. James F. Holland of the Mount
Sinai School of Medicine points out that
the freedom achieved by regulation of
drug products is often the freedom to
live: “For the patient ignorant of the

Laetrile

69

inertness of Laetrile as an anticancer
drug, there is an overriding concern that
he not be denied his individual freedom
by untimely death from cancer from
having relied on Laetrile to help. This is
a cruel deprivation of individual free-
dom, since the patient does not get a sec-
ond chance” (R 396 at 2).

James Harvey Young, Ph.D., a histo-
rian of health quackery, discussed the
past use of the freedom of choice con-
cept and phrased his conclusions con-
cerning the validity of application of that
concept to health care in colorful terms.
He states that acceptance of the primacy
of the-freedom to choose medical thera-
pies “leads only toward the license of
those ancient days, when ‘the toadstool
millionaires,’ preaching religion and
spouting patriotism, operating without
restraint, ﬂeeced and often killed their
gullible victims. That is a fate from
which seven decades of constructive leg-
islation, beginning with the Pure Food
and Drugs Act of 1906, has somewhat
rescued the nation. Complex, modern,
industrial, urbanized society, with stand-
ards of medical judgment far more pre-
cise than those existing in the nineteenth
century, cannot afford to let the nation’s
health concerns be governed by a dis-
torted deﬁnition of that great symbol,
‘freedom’, which would return piratical
anarchy to the realm of health” (R 400
at 11—12).

2. The Choice Is Not Free

The discussion above of “Why People
Use Laetrile?” describes the many pres-
sures that induce cancer patients and
their families to make the decision to use
Laetrile. Orville Eugene Kelly is a cancer
patient who has founded an organization
called “Make Today Count,” which now
has 103 chapters in 30 states, to help
other cancer patients and their families
deal with the problems that discovery of
cancer entails. He addressed the question
of “freedom of choice” in an afﬁdavit
submitted to the record (R 389) . He notes
from personal experience that patients
and their families are often susceptible to
arguments that a painless drug like
Laetrile can cure them (id. at 2) and
describes the persistence with which
those arguments are made. He himself
has tried to present the counter-argu-
ments to other cancer patients. “But it is
difﬁcult to convince some of these people
that the substance Laetrile is ineffective
as a therapy for cancer when they have

Commissioner’s Decision

watched a film, listened to tapes, and
heard testimonials from other patients,
quite sincere in their beliefs that Lae-
trile has helped them” (id. at 3) . He asks:
“[Ils it a fair choice if [the cancer pa-
tients] are being pressured by Laetrile
proponents?” (id.).

The constant efforts of Laetrile propo-
nents are emphasized by those dealing
with cancer patients. See, e.g., statement
of Helene Brown, Executive Director of
Community Cancer Control, Los Angeles,
“that far from exercising a free and in-
formed choice patients are confronted
with enormous pressures to use Laetrile
instead of conventional forms of therapy
and that representatives attesting to the
worth of Laetrile make untrue, mislead-
ing and unsubstantiated claims” (R 393
at 5) .

The presentations of the Laetrile pro-
ponents are made, as discussed in more
detail elsewhere, to patients and families
deprived of their normal decisionmaking
abilities. See statement of John J. Daw-
son, M. Div., Director, Patient and Fam-
ily Support, Mountain States Tumor In-
stitute: “Research conducted at the
Mountain States Tumor Institute and
elsewhere indicates that the emotional
trauma of a cancer diagnosis severely
impairs the patient’s and families’ ability
to engage in rational decisionmaking
processes” (R 421 at 1) .

Other submissions reﬂect a similar
conclusion, see the statement of Rev.
Reed: “The ability of [cancer patients
and their families] to protect themselves
is often severely limited by the emotional
situation in which they ﬁnd themselves”
(R 418). (See also R 414 at 4; R 433 at
11 14.)

The Commissioner thus concludes as
follows:

(1) To the extent that any freedom
has been surrendered by the passage of
the legislation which bans from the
marketplace drugs that have not been
proven to be effective, that surrender was
a rational decision which has resulted in
the achievement of a greater freedom
from the dangers to health and welfare
represented by such drugs.

(2) The choice of Laetrile therapy, by
persons under the severe stresses associ-
ated with discovery of cancer and in re-
sponse to misinformation presented
persuasively by Laetrile’s proponents,
cannot be regarded as a choice which is
free.

D. ALLEGATIONS OF BIAS

70

Several submissions charged that FDA
is too biased against Laetrile to conduct

a fair hearing. Aside from general alle-
gations of bias (R 313; R 248; R 353; R
507, R 302; R '73, Att. at 43; Tr. at 444—
45) , these submissions fall into two gen-
eral categories: (1) the administrative
rulemaking proceeding should have been
conducted by someone other than FDA
(R 144; R 505; R 222; Tr. at 12, 29, 75.
444—45) ; and, (2) the drug approval
process administered by FDA is wrong
(R 235; R 258; R 144; R 509; Tr. Ex. 1).

It is difficult for an agency charged
with bias to rebut such charges persua—
sively. Nonetheless, the Commissioner
feels that a complete decision requires
some rebuttal of charges that he regards
as erroneous and misdirected. Insofar as
comments suggesting that the proceed-
ings should have been conducted by
someone other than FDA, it should be
noted that FDA was required by court
order to assemble an administrative rec-
ord and make appropriate determina-
tions therefrom. The task could not have
been delegated to anyone else, and, even
had the agency been able to do so, it is
not likely that any tribunal chosen by
FDA would have satisfied thOSe persons
who are convinced that the agency is
biased. The FDA is, of course, the agency
designated by Congress to evaluate the
safety and effectiveness of drugs and, as
such, it is the agency with expertise in
this area.

The comments charging that the re-
quirements for drug approval adminis-
tered by FDA are wrong contained state-
ments to the effect that testimonial evi-
dence should be accepted as adequate
proof of safety and effectiveness or that
the cost of a clinical trial is too great a
burden for the proponents of Laetrile to
bear. Laetrile proponents place particu-
lar emphasis on the cost factors, stating
that because clinical trials are expensive,
FDA somehow favors only large drug
companies.

As has been discussed above, FDA is
bound by the requirements of law re-
garding drug safety and effectiveness.
Those requirements have been chal-
lenged in court before, by the very drug
companies toward whom Laetrile propo-
nents allege FDA has a positive, favorable
bias. These “favored” groups did not pre-
vail, and the safety and effectiveness
provisions were upheld.

In Pharmaceutical Manufacturers
Ass’n v. Richardson, supra, a trade asso-

 

 

Laetrile

ciation whose membership includes ma—
jor drug ﬁrms sought to enjoin the FDA
regulations establishing the standards of
evidence necessary to demonstrate the
effectiveness of drug products (21 CFR
314.111). Pointing out that Congress
could not have had testimonial evidence,
clinical impressions, practical experi-
ence, or the unsubstantiated subjective
views of medical practitioners in mind
when it deﬁned “substantial evidence,"
the court upheld the regulations. As one
witness in the case pointed out, the ap-
proach which assumed that a collection
of impressions would furnish the truth,
“did not prevent doctors from having
unbounded faith in the curative powers
of leeches for hundreds of years before
scientiﬁc evaluation became the pre-
ferred means of judging emcacy of ther-
apy” (318 F. Supp. at 307).

In Upjohn Company v. Finch, 422 F.2d
944 (6th Cir. 1970) , a drug manufacturer
sought review of an FDA order revoking
marketing approval for seven combina-
tion antibiotic drugs. Stating that testi-
monial evidence was not enough to meet
the standard of substantial evidence, the
court held that “the record of commercial
success of the drugs in question and their
widespread acceptance by the medical
profession, do not, standing alone, meet
the standards of substantial evidence,
prescribed by 21 U.S.C. 355(d)” (422 F.
2d at 954) . Although the cost of develop-
ing the proper scientiﬁc evidence of safe-
ty and effectiveness is high, placing this
burden upon those who wish to sell drugs
is more than justiﬁed by the need to pro-
tect the consumer from harmful, useless,
and fraudulent drugs.

The Commissioner acknowledges that
the FDA is biased in one sense; the
agency is committed to requiring that
drugs meet the standards of safety and
effectiveness required by law. The stand-
ards are designed to protect the public
from drugs which are not both safe and
effective. While the standards are rigor-
ous, they are not mysterious. They are
accepted by the scientific community and
can be applied by any scientists who
seriously wants to prove the value of a
drug. The proponents of Laetrile choose
to attack the standards. They have not
attempted to meet them.

E. LIMITING Use TO TERMINAL PATIENTS

There has been concern expressed in
the submissions to the record that
Laetrile might be approved for use by
“terminal” cancer patients. Such an ap-

71

proval would be theoretically justiﬁed
only on the grounds that since such pa-
tients might be considered beyond the
help of other therapies, Laetrile cannot
hurt them. Approval of a drug for use
by terminal patients is not possible un-
der the act; however, in light of the in-
terest in this issue the Commissioner
will discuss the evidence relating to it.
One submission objected to the pos-
sible use of Laetrile by terminal patients
on the grounds that approval of such
use constitutes sanction of an inhumane
fraud upon the patients involved, one
which wastes the ﬁnancial resources of
the patients and their families uselessly
(R 190 at if 1'7). Two other arguments
were expressed by a number of submit-
ters: (1) there is no such thing as a
“terminal” patient and (2) allowing use
by a subgroup of cancer patients would
lead to increased use by patients who
could be helped by legitimate therapy.

I. Who is Terminal?

Dr. Peter H. Wiernik, Chief of the
Clinical Oncology Branch of the National
Cancer Institute’s Baltimore Cancer Re-
search Center, states, “One major difﬁ-
culty in making a particular chemical
available for terminal patients only, is
that no one can prospectively deﬁne the
term ‘terminal’ with any accuracy. A
patient can be said to be terminal only
after he dies. Many patients who are
critically ill respond to modern day
management of cancer" (R 200 at 11 18).

D. Joseph F. Ross, Professor of Med-
icine at the University of California
School of Medicine at Los Angeles, is
actively involved in the medical care
of cancer patients. He states, “[Tlhe dis-
tinction of ‘terminal’ patients from ‘non-
terminal’ patients may not be reliably
determined and an assumption that
Laetrile may be given to such patients
with impunity may deprive such pa-
tients of therapeutic measures which
could help them” (R 190 at if 17). Cf. R
393, Ex. 1 at 2: “Medical history is full
of miracles.” “No one knows if and when
any patient is going to die.” (Helene
Brown, Executive Director of Cancer
Control/Los Angeles); see also R 173,
Att. ”Questions Most Frequently Asked
* * "’ at 2).

2. Eﬁ‘ects on other Patients

Approval for use of Laetrile by “ter-
minal” patients, assuming some way
could be found to deﬁne that class of
individuals so as to exclude all those who

Commissioner's Decision

might be helped by legitimate therapy,
would still pose a risk to other patients
who could be helped. This effect would,
the evidence in the record shows, occur
in two ways. First, approval for even this
limited use would encourage illegitimate
use of the type now occurring in this
country.

Historian James Harvey Young, based
upon his study of past “unproven” med-
ical cures, states, “Permitting Laetrile’s
use in terminal cases gives it a credence
among the public at large that will ex-
pand its use in early cases, for people
will prefer taking a ‘vitamin’ to con-
fronting the surgeon’s knife” (R 400
at 11).

Dr. Samuel C. Klagsbrun, a psychi-
atrist who works with cancer patients at
St. Luke’s Hospital in New York, states,
“Permitting Laetrile to be used by any
population of cancer victims would have
the correlative effect of creating the mis-
impression in the minds of other can-
cer victims that the drugs is, in fact,
safe and effective for a broader popula-
tion” (R 433 at ‘i12).

A second danger from such a limited
approval of Laetrile is that the limitation
would be extremely difﬁcult to enforce.
Kenneth A. Durrin, Acting Director, Of-
ﬁce of Compliance and Regulatory Af-
fairs, Drug Enforcement Administration,
submitted an affidavit describing the
detailed and costly regulation of “con-
trolled substances” under the Controlled
Substances Act (CSA) and then consid-
ered the possibility of approval of
Laetrile “for terminal patients only”
(R 435). He stated his conclusion as to
the practicality of preventing the di-
version of Laetrile from “terminal” pa-
tients, if approved for such patients, to
others who might be helped by legitimate
therapy: “Absent the kinds of controls
available under the CSA—and indeed
even with such controls—it is my opinion
that a drug such as Laetrile could not
effectively be restricted to a class of ter-
minally ill cancer patients. For example,
absent a quota on production, manufac-
turers would not be limited to producing
an amount of Laetrile suﬂicient only to
provide a source of supply for terminally
ill cancer patients. Manufacturers would
not be restricted in the channels in
which they could permissibly distribute
the drug. They would not be required
to report transactions in Laetrile. The
amount of Laetrile which could be im-
ported into this country would be un—
limited.

72

“Given such unrestricted and unfet—
tered availability of Laetrile, it is my
opinion that there would be no practical
way of limiting access to the drug to
terminally ill cancer patients only. It is
completely unrealistic to suggest that
any other result would occur” (id. at
i 18—19).

The Commissioner concludes that ap-
proval of Laetrile restricted to “termi-
nal” patients would lead to needless
deaths and suffering among (1) patients
characterized as “terminal" who could
actually be helped by legitimate therapy
and (2) patients clearly susceptible to
the beneﬁts of legitimate therapy who
would be misled as to Laetriles' utility
by the limited approval program or who
would be able to obtain the drug through
the inevitable leakage in any system set
up to administer such a program.

F. USE CONCURRENTLY WITH OTHER
THERAPY

Some persons not familiar with the
problems of drug interactions have sug-
gested that Laetrile might be approved
for use concurrently with legitimate
cancer therapy. This theory would logi-
cally extend to allow any worthless drug
to be used as long as effective therapy
was also utilized. Such a limited use
program would, of course, involve the
problems of administration discussed in
the previous section. Particularly in light
of the Laetrile proponents’ practice of
dissuading patients from what they
characterize as the “cut, burn, and poi-
son" techniques of legitimate therapy,
any seeming government sanction of
Laetrile would inevitably involve en-
couragement of use of “painless” Laetrile
therapy alone and thus would result in
needless suffering and loss of life (cf.
R 191 at il17).

More important, it simply has not
been shown by any sound scientific evi-
dence that the administration of Laetrile
along with other therapy may not either
make such therapy more dangerous or
interfere with its effects. Dr. James F.
Holland states (R 396 at 2), “That Lae-
trile is inert as an anticancer drug does
not mean it may not interfere with the
metabolism of and compromise the ef—
fects from known anticancer treatments.
This would require years of study to
elucidate, and it is not a worthwhile un-
dertaking since Laetrile itself has no
anticancer activity. One does not seek
further information on why not to use
Laetrile. If there is no good reason to

 

do something, the best reason exists not
to do it” (emphasis in original). Thus,
the same reasons that justify the law’s
ban on use of drugs not shown to be ef-
fective form an equally strong basis for
the ban on that use where the use will
be concurrent with other therapy.

VI. CONCLUSIONS

The Commissioner, after careful re—
view of the administrative record
amassed in this rule making proceeding,
makes the following conclusions:

(1) Although the terms “Laetrile,”
“laetrile,” “amygdalin,” “Sarcarcinase,”

Laetrile

“vitamin B—17,” and “nitriloside” have ‘

been used interchangebly, the chemical

identity of the substances to which these ,

terms refer has varied over the years.
The identity of material referred to or
called by any of those names is often not
known. All too frequently terms have
been used haphazardly or imprecisely by
proponents, as well as opponents, of
Laetrile:

“Laetrile,” as described by Ernst T.

Krebs, Jr., is: L~mandelonitrile-beta-
glucuronic acid.
“Amygdalin” is: D-mandelonitrile-

beta-D—glucosido-6-beta-D-glucoside.

“Sarcarcinase” is the name given by
Dr. E. T. Krebs, Sr., to a mixture of 6.
possibly more, enzymes extracted from
apricot pits.

(2) Neither Laetrile nor any other
drug called by the various terms men-
tioned above nor any other product
which might be characterized as a “ni-
triloside” is generally recognized by ex-
perts qualiﬁed by scientific training and
experience to evaluate the safety and
effectiveness of drugs to be safe and
effective for any therapeutic use.

(3) Animal studies conducted to date
show that Laetrile has no anticancer ac-
tivity in laboratory animals. Even if such
activity were shown, the data would not
be relevant to the issue of whether Lae-
trile is generally recognized by qualiﬁed
experts as a safe and effective anticancer
drug in humans.

(4) Neither Laetrile, amygdalin, nor
any other drug called by the various
terms set out in conclusion (1) is ex-
empted from the “new drug” deﬁnitions
of the act (21 U.S.C. 321(p)) by virtue of
compliance with either the “1938 grand-
father clause” (21 U.S.C. 321(p)(1)) or
the “1962 grandfather clause" (section
107(c)(4) of Pub. L. 87—781).

(5) The history and promotion of Lae-
trile are characteristic of other unproven

73

cancer remedies. Laetrile’s popular ac-
ceptance by laymen lies not in credible
proof of its effectiveness, but rather in
the fears of orthodox medical treatment
and the false hope, fostered by Laetrile’s
proponents, that suffering and eventual
death can be avoided through Laetrile.

(6) Laetrile is not in general use as
cancer therapy anywhere in the world.

('7) There is no evidence that “Vita-
min B—l-7” is generally recognized among
experts in theﬁeld of nutrition or nutri-
tion research as a vitamin. Even if there
were such recognition. “Vitamin B-17”
would still be subject to regulation as a
drug under the Federal Food, Drug, and
Cosmetic Act because of the claims made
for its use in cancer therapy.

(8) The safety of ingesting amygdalin,
Laetrile and/or apricot or peach kernels
or pits has not been established. There
is, in fact, evidence of frank toxicity from
ingestion of the kernels or pits.

(9) There is no basis in law or in fact
for the use of Laetrile or related sub-
stances in the treatment of cancer.

The foregoing opinion in its entirety
constitutes the Commissioner's ﬁndings
of facts and conclusion of law. Distribu-
tion of Laetrile, amygdalin, or any other
substance called by the various terms set
out in conclusion (1) in interstate com-
merce is in violation of the Federal Food,
Drug, and Cosmetic Act and subject to
regulatory action.

Dated: July 29, 1977.

DONALD KENNEDY,
Commissioner of Food and Drugs.

[FR Doc.'77—22310 Filed 8—4—77;10:00 am]

U. S. GOVERNMENT PRINTING OFFICE : 1978 O - 246-920

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