DEP.ARIMENT OF HEALTH, EDUCATICN, AND WEIFARE

Food and Drug Administration

lN TEE MATIER OF Docket No. 77N-0048

AFFIDAVIT OF CARL M. LE'VENTEAL, M.D.

earl M. Leventhal, M.D., being first duly S'W'Om, de:pJses and says:

1. I am a physician licensed to practice in the States of Califomia,

Massachusetts, and New York. I received the degree of Doctor of Medicine

from the University of Rochester School of Medicine and Dentistry in 1959.

From 1959 to 1961, I was an Intem and an Assistant Resident in Ward

Medicine at the Johns Hopkins Hospital in Balti.rrore. From 1961 to 1964,

I was an Assistant Resident in Neurology, a Fellow in Neuropathology, and

a Resident in Neurology at the Massachusetts General Hospital. I have

been a Conm:i.ssioned Officer in the United States Public Health Service

since 1963 and presently hold the rank of Medical Director. I am a_Clinical

Assistant Professor of Neurology and Pathology at Georgetown University in

Washington, D.C. I am a Diplornate certified by the National Board of .Medical

Examiners and by the Arrerican Board of Psyc..1-i.iatry and Neurology. My curriculum

vitae is attached hereto as Exhibit 1.

2. From 1966 through 1969, I was a staff neurologist at b.11e National

Cancer: Institute, responsible for the organization and scientific mmagement

of a national collal:::orati v-e clinical trial in t.'1e chenot.'1erapy of brain

tum:i:-s. I have been personally involved in oti'...er scientific studies of

the drug therapy of cancer since 1958 and continue to the present ti..-re a close

interest in progress in t.'1at field of medical research. In 1968, I l:eca-rre

Assistant to t.11e Director of .Lal::oratories and Clinics, a position subsequently

redesignated Assistant to the Deputy Director for Science, of the National

Institutes of Health, in Bethesda, MaJ:yland, a position which I held until

1974. Between Septemt:er 1973 and Februal:y 1974, I was the Acting Deputy

Director for Science of the Institutes.

3. In April 19 7 4, I :t:ecane Deputy Director of the Bureau of Drugs

of the United States Food and Drug Administration, a position which I continue

to hold. As Deputy Director of the Bureau, I share with the Director

responsibility for the coordination, direction, and managerrent of the operation

of the Bureau. I regularly attend m:etings with the Bureau staff ~ in

nedicine and regulated sciences at which the status of drug products for

which the Bureau is responsible is discussed and evaluated. In the course

of rey official duties, I have participated in a numl:er of m:etings at which

the status of the purported but unproved cancer remedy Laetrile (arnygdalin)

has been discussed and evaluated. I am, therefore, familiar with the Agency's

policy relating to Laetrile.

I

FDA Regulation of Laetrile (Arnygdalin)

4. The Federal Food, Drug, and Cosmetic Act prohibits the introduction -

or delivery for introduction into .interstate cormerce of any "new drug"

unless an approval of a New Drug Application filed pursuant to 21 U.S.C.

355(b) is effective with respect to the drug or a Notice of Cla..im:d Investi­

gational Exenption (IND) under 21 U.S.C. 335(i) and 21 CFR 312.1 is on file

for such drug. The Federal Food, Drug, and Cosmetic Act, 21 U.S.C. 331,

also prohibits the introduction or delivei:y for .introduction into .interstate

cc:.irmerce of any food or drug which is adulterated or misbranded.

5. Laetrile contains the chemical arey-gdalin, a substance which occurs

naturally in the kenials of apricots, p:ac..1-ies, bitter a.J.m::,nds, and in other

plant materials. .Anw'gdal.in is a rrerrber of a class of substances known as

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cyanogenetic glycosides. Cyanogenetic glycosides are substances which

contain, in their nolecular structure, a noiety known as the cyanide group

which, upon hydrolysis by certain enzymes, yields cyanide, an ext:renEly toxic

poison.

6. Dr. Ernst T. Krebs, Sr. , a califomia physician, was reportedly

the first to tJ:y apricot pits as a cure for cancer in about 1920. Not

:rruch is known about this early use of ~gdalin. It is reported, however,

that Dr. Krebs gave up t.."lis treat:rrent because it was tco toxic for safe use.

In about 1952, his son, Enlst T. Krebs, Jr., a biochemist, clai.rred to have

developed a purified fo:rm of arnygdalin safe for injection. Krebs, Sr. , joined

his son in advocating the purified fo:rm as an effective treatment for cancer,

anong other conditions for which it was clai.rred to be beneficial. Krebs,

Jr., contended that Laetrile seeks out a substance which is fotm.d in cancer

cells but not in nonnal cells. This substance, he asserted, causes Laetrile

to release hydrocyanic acid resulting in the destruction of cancerous

cells. According to Krebs, Jr. , nonnal cells contain a different substance

which protects them from the hydrocyanic acid and, accordingly, he clai.rred,

they are not affected. Later, Krebs, Jr~ , changed the theory, claiming that

cancer is a vitamin-deticiency disease, and that Laetrile•is Vitamin B-17.

Serre Laetrile advocates nru say that it prevents, as well as cures, cancer.

7. Scientists have never found any evider1ce that either of the

Krebs' theories are valid. Laetrile is not a vitamin because its absence

fran the diet (i.e., the abse..11.ce of a cyanogenetic glycoside) does not

produce a specific deficiency disease in vertebrate animals, such as man.

Further, no scientifically valid evidence has ever been fotm.d that Laetrile

has any effect whatever on cancer. LT1.stead of well designed controlled

ext:eri.inents _i.l1. animals and hurr.ans, t.1-ie proponents of Laetrile rely upon

testirronials assertions that Laetrile prevents, cures, mitigates and arrests

cancer and pain. Test:L-ronials attesting to a feeling of general irnprove.TI"Ent

and cessation of pain in patients upJn abandonment of radiation and chern:,t...1-ierapy

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in favor of Laetrile treatrrent do not indicate that Laetrile is effective

in curing cancer or in relieving pain. The feeling of well l::eing experienced

by these patients derives from two phenomana, one physical and the other

psychological. Chenotherapy and radiation treatrrents prc:duce unpleasant

side effects in nost patients. When such therapies· are stopped, the side

effects they produce disappear. This natural physical effect in the case of

these patients is reenforced when Laetrile is administered l:ecause of the

patients' expectations that the treatrrent will have a beneficial effect.

The_se psychogenic responses, popularly kno..m as the placebo effect, are well

doet.nnented and have been shown to occur from 30 to 70 percent of patients who are

treated for pain.

8. In 1953, the cancer Commission of the California Medical

Association investigated Laetrile and declared it ineffective. Ten years

later, the Califomia State Cepartnent of Public Health received a report

from its cancer Advisory Council which concluded that Laetrile has·no

value in the diagnosis, treatment, alleviation, or cure of cancer, and

issued a regulation prohibiting its use in that State. Neither t."1.e U.S.

Food and Drug Administration, the canadian Food and Drug Directorate, nor

any other reccgnized exi;:ert on the treatrrent of cancer, ever has found

evidence to justify the use of I.aetrile for any purpose.

9. Several attenpts have been nE.de by pro]?Jnents of Laetrile to

obtain FDA approval to distribute the drug. The last was by t..t-ie M:Naughton

Foundation of Califonria which submitted an L'1.vestigational New Drug .P-..pplication

for the drug in 1970. FDA found the application inadequate and tenrrinated the

IND shortly after it was received. ProPJnents of Laetrile clairred tr.at PDP.' s

action was based on prejudice against Laetrile, not the nerits of the

application. To assure objectivi"bJ, FDA sought the counsel of a special

carrmi ttee of cancer exper'"....s. The COmmi ttee reviettt--ed the application and

supplemental data · required by law, and interviewed Andrew Mc.°l\iaughton. The

Comnittee concluded that the material presented by the McNaughton Foundation

was not adequate to justify clinical tests of the dru.g on humans. A copy

of their report is attached hereto as Exhibit 2.

10. A m.mb:r of the clinics dispensing laetrile are located just

across the califomia border in Tijuana, Mexico, where the drug is used

.in the "treatrrent" of cancer. Thousands of cancer-stricken Arcericans,

fran as far away as Alaska, have reportedly gone to clinics .in Tijuana.

sane of those persons may l:e in the terminal stages of their illness,

although no docunentation to that effect erists l::ecause of the failure of

the Mexican clinics to conduct an adequate diagnosis or, for that matter,

any diagnosis, of .incoming patients as well as suitable pathological

tests. Other cancer victims, misled by •the false promise held out by

Laetrile's prorcoters, reportedly have fonns of cancer that could l::e

controlled by available effective treatnent. These clinics, and the •

amygdalin they dispense, offer victims of fo:r:ms of cancer that can l::e

controlled by effective therapy, false hope and the prospect of certain

mistreatrrent.

11. One of the principal proponents of Laetrile in Mexico is

Dr. Emesto Contreras of Tijuana, B.C., Mexico. In 1971, at FDA' s

invitation, Dr. Contreras submitted a numl::er of.clinical histories

which he felt derrcnstrated that Laetrile is useful in treating cancer.

FDA in"'ilestigated these cases and secured from the National Cancer Institute,

an evaluation of tl1ose cases which could l:e assessed. None of the cases

studied were fmmd to provide any objecti"'ile evidence whatsce"'iler that

Laetrile is effective in treating cancer. A full account of FDA I s

.investigation and its findings is set forth in our letter to Dr. Contreras

of February 10, 1975, a copy of which is attached hereto as Exhibit 3A.

12. The National Cancer Institute tested Laetrile .in animals on

five separate occasions between 1957 and 1975. The results ·of eacl1 of

triese tests confinn Laetrile' s total worthlessness as a caneo._r cure. And,

indepe.l'ldent cancer research centers which investigated Laetrile in 1975

found it carpletely lac.ting in t.'"l.e.rapeutic effectiveness. The published

results of tv.o such tests are attached hereto as Exhibits 3B and JC,

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respectively. After vigorous, scientifically sound, and fully docunented

testing, the investigators in these studies were COill)elled to a:,nclude .

that Laetrile was "inactive" against the cancer systems tested and that

"no successful chenotherapy" resulted from its use. I am also aware

that the National Cancer Institute recently has a:,mpleted another study

in which mice with transplanted human tum:::>rs were administered Ia.etrile

and other ,agents. A a:,py of this study is attached hereto as Exhibit 3D.

12A. Laetrile is currently the nost widely publicized and popular

unproven cancer renEdy in Amsrica. It is contrary to the public interest

and a potential threat to the public health to permit use of the channels

of interstate cormerce for distrib1:1tion of this worthless drug. Its

distribution, whether here or in Mexico, adversely affects thousands of

Anericans who go abroad seeking treatnEnt, who attempt to bring it back

from Mexico, or who seek out and find laetrile on the "black narket" at home.

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II

Laetrile (Amygdalin) Is A New Drug

13. Laetrile is not now, nor was it on Cctaber 9, 1962, generally

re<D3'Illzed anong e~rts qualified by scientific training and experience

to evaluate the safety and effectiveness of drugs intended to be used in

cancer therapy, as either safe or effective for the prevention, cure, mitigation,

or treatnent of any fonn of cancer or pain associated with cancer. It is,

therefore, a "new drug" as that term is defined in 21 U.S.C. 32l(p) for

which there is not naw on file with FDA an approved New Drug Application

or an acceptable Notice of Clailted Investigational Exenption for New Drugs.

14. Under Section 107(c) (4) of P.L. 87-781, the 1962 Anendm:nts to

the Federal Fcad, Drug, and Cosmetic Act, Laetrile would not be considered

a "new drug" subject to the requirei:rents of an approved New Drug Application

under 21 U.S.C. 355, if each of the follawing conditions are met:

a. On October 9, 1962, Laetrile was not a new drug as

defined by Section 201(p) of the basic Act as then in force

(21 u.s.c. 321(p));

b. On Cctober 9, 1962, Laetrile was com:rercially used

or sold in the United States;

c. On October 9, 1962, Laetrile was not covered by an

effective (new drug) application under section 505 of tl1e

basic Act then in force (21 U.S.C. 355);

d. Laetrile, as used on October 9, 1962, was th~

ide."ltical drug entity it presently is;.. and .

e. The labeling for Laetrile represents it as being

intended solely for use under conditions prescribed,

reccmt'Ended, or suggested in its labeling on October 9, 1962.

In t...1-ie event that Laetrile does not rreet each and every one of these

conditions, it is not e.t1.titled to the section 107 (c) (4) grandfath.er exerrption

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£ram the new drug provisions of the Federal Food, Drug, and Cosnetic Act.

Laetrile, however, fails to meet even the threshold test of not being a

"nev drug 11 , as that tenn was defined on Cctober 9, 1962.

15. On Cctober 9, 1962, Section 20l(p) defined the te:on "new drug"

to nean "any drug • . • the catp:)Si tion of which is such that such drug is

not generally rea::,g:nized, anong exi;:erts qualified by scientific training

and experience to evaluate the safety of drugs, as safe for use under the

oonditions prescribed, recormended, or suggested in the labeling thereof".

16. On Cctober 9, 1962, Laetrile was not generally recognized as

safe for the prevention, cure, mitigation or treatnent of any fonn of cancer

or pa.in associated with cancer and was therefore a "new drug" under the Act

as then in force. There are several factors which compel tbis conclusion.

They are discussed in the following paragraphs.

17. General recognition of Laetrile' s safety as a cancer drug on

October 9, 1962, requires that there then have existed substantial evidence,

oonsisting of adequate and well-controlled studies, derronstrating that

Laetrile is not toxic to humans. This is especially significant because

a.Ir¥gdalin, the principal CO!t1f0nent of Laetrile, is, as previously noted,

a cyanogenetic glycoside, which, upon hydrolysis by certain enzyrres, yields

hydrogen cyanide, an extrerrely toxic poison.

18. I am familiar with the scientific literature dealing with the

toxicity of cyanogenetic glyoosides, suc..11. as the amygdalin contained in

Laetrile. whlle there is a widespread belief that Laetrile is non-toxic,

there are not nCM, nor were t.11ere on Cctober 9, 1962, any adequate and well­

controlled short or long term toxicity studies upon whia.11. it could be concluded

that amygdalin, as prese.11.t in Laetrile, is not toxic. In the absence of such

studies, Laetrile cannot be regarded as having been shown to be safe and, thus,

generally recognized as safe on October 9, 1962.

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19. The question of whether Laetrile is now, or ever was, generally

recognized as safe gees beyond the absence of any evidence indicating the

lack of .toxicity of the drug. The safety of a drug for hunan use depends,

in large neasure, on the therapeutic effectiveness of the particular c:L.--ug.

When patients forego effective fonns of therapy and tum instead to v.0rthless

potions and nostrums, their disease may progress while effective therapies

are foresaken. In the case of ·cancer, treat:nent with an ineffective drug

will inevitably and inexorably 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.

20. Laetrile is a totally ineffective drug for use in preventing,

curing, mitigating or treating any fonn of cancer. The corrplete ineffectiveness

of Laetrile should be distinguished from the relative success achieved in

treating cancer with :recognized therapeutic rn:::xialities, such as radiation

and cherrotherapy. Attached hereto as Exhibit 4, and rrade a part hereof,

is an excerpt from a publication by the National Institute of Health .

showing the five year survival rates in nen and wonen afflicted by cancer

in various sites at various stages of the particular cancer. The chart

shows, for exarrple, that nen afflicted with a localized fonn of cancer

of the prostate have a 68 percent chance of surviving for a five year

period when undergoing recognized fm:ms of cancer therapy. Similarly,

wcm:n afflicted with localized breast cancer have an 84 percent chance

of survival for a five year pericd when conventionally treated. These

success rates should be distinguished from the certain deaths which await

the nen and wonen afflicted with these cancers were they to abandon

conventional tr..erapy and tum instead to Laetrile. Seen in this :p:rspective,

Laetrile cannot be regarded as now, or ever, l::eing generally recognized as

safe for use in the treatrrent of any fonn of cancer and, therefore, it

is not entitled to t...1:.e Section 107 (c) (4) grandfather exemption.

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, ci "new drug" subject to the requirenents of an approved New· Drug Application .r.

under 21 U.S.C. 355 if it was ItErketed, or recognized in an official

cc:mp:ndium, as a cancer drug after June 30, 1906, and_before June 25,

1938, and if at such time its labeling contained the same representations

concezn:ing the conditions of its use as it presently contains.

22. Ia.etrile is not now, nor has it ever been, recognized as a cancer

drug by either the United States Pharmacopeia or the National Forrm.ll.ary.

23. Official rea:,rds of the Food and Drug Administration under nw

care, custody and control, reveal that Laetrile was not marketed as a cancer

drug after June 30, 1906, and before June 25, 1938. Indeed, on Decerrber 12,

1952, Dr. E. T. Krebs, Sr., and his son E. T. Krebs, Jr., two of Laetrile's

principal proponents, infonred Gove.rnm:nt investigators that the Laetrile

they were then administering was first used on humms by a Dr. Han:y Pincus ·-

Jacobsen in June 1952. (See Exhibit 5, attached hereto and made a part

hereof). Thus, by their own admission, the leading proponents of the drug

have conceded that it was not cormercially marketed between 1906 and 1938

as a cancer drug for humans and that it is not therefore entitled to grand­

father protection under the transitional provision as between the 1906 and 1938

Acts.

24. Further, Dr. Krebs, Sr., in an affidavit executed in April 1965

(see Exhibit 6, attached hereto and made a: part hereof) , himself stated ti.t-ia.t

in his 1936 e~ircents, Laetrile contained 66 percent amygdalin while Laetrile,

as he purified it in 1960, contained 99.8 percent arey-gdalin. _Thus, the

quantitative corrposition of the drug en~ty kncwn as "Laetrile" changed

1:etween 1936 and 1960. Whatever Laetrile was in the period 1906 to 1938,

it is not naw the sanE drug. Indeed, Laetrile as it presently exists,

lacks unifonnity in dosage fo:ans, indications for use, nethcd and route of

administration and in recomrendations by its proponents as to whether it

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Because of the ~ges in th~ drug and th~ drug 1 s present non-confoJ:ntl.ty, . . .

the 1906 to 1938 Laetrile, if it existed at all, differs fran any existing

fot:m of Laetrile and the transitional provision as between the 1906 and 1938

Acts does not apply.

III

CCNCLUSION

25. In addition to violating the new drug provisions of the Federal

Food, Drug, and Cosmatic Act, Laetrile is also misbranded within the meaning

of 21 U.S.C. 352(f) (1) • .Eecause Laetrile lacks safety and effectiveness it

is inp:)ssible to prepare adequate directions for its safe and effective use

as a drug. In United States v. Spectra Focds Corp. , et al. , Civil Action

No. 76-101 (D. New Jersey, January 25, 1976) the Court held that prorrotion

and sale of Laetrile (aiey-gdali.n) for any drug or food use is unlawful and

constitutes a fraud on the public. A copy of the Court's findings are

attached hereto as Exhibit 7. These findings are entirely accurate and

correct.

26. To find that Laetrile is not a "new drug" w--ould 1:::e to reject

every scientifically established principle of drug testing. It would result

in untold thousands of needless deaths and would elevate quackery and deception

above science and reason. ~7e all recognize the tragedy of cancer to the victim

and his family. This tragedy is terrpered hcwever by the realization that

nedical science has progressed to the po.int where rrany fo!ltlS of cancer are

treatable by scientifical],y established rrethods · so t.~at the length of

the cancer victim's life and its quality can be enhanced. But, the

tragedy wtmld be unnecessarily tu:r:ned into a catastrophe if victims of

cancer are ~tted to resort, on the basis of enotionalisrn only, to a drug

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wnose tnerapeuoc errect.J.veness is m.1. No-c on .cena.i..r: or: t:ne ~l..Jfi, u:ie

Amsrican Medical Association nor any other established group, but on the

cancer victim's behalf, do I argue that use of Laetrile not be legalized.

County of Montgonery ) State of M.ai:yland ) ss

} , : ---

CARL M. LEVENTHAL, M. D.

Subscril:ed and swam to before m:: this day of March, 1977. ----

Notary Public My Comnission Expires:

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