Petition — United States v. Rutherford

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28-605 FILED

No. } OCT 40 I97!

MIGHAEL Re

Iu the Supreme Cunt af the United Stator

OcToBER TERM, 1978

—

UNITED STATES OF AMERICA, ET AL., PETITIONERS

Vv.

GLEN L. RUTHERFORD, ET AL.

PETITION FOR A WRIT OF CERTIORARI TO THE

UNITED STATES COURT OF APPEALS

FOR THE TENTH CIRCUIT

Wapbr H. McCREE, JR.

Solicitor General

JOHN H. SHENEFIELD

Assistant Attorney General

HARRIET S. SHAPIRO

Assistant to the Solicitor General

BARRY GROSSMAN

CATHERINE G. O’SULLIVAN

PETER L. DE LA Cruz

Attorneys

Department of Justice

Washington, D.C. 20530

RICHARD M. CooPER

Chief Counsel

EUGENE M. PFEIFER

Associate Chief Counsel for Enforcement

Food and Drug Administration

Department of Health, Education and Welfare

Rockville, Maryland 20852

Supreme Court, U. S

INDEX

Opinions below _.

Jurisdiction

Question presented

Statutes involved

Statement

Reasons for granting the petition

Conclusion

Appendix A |

Appendix B

Appendix C

Appendix D

Appendix E

CITATIONS

Cases:

Investment Company Institute v. Camp,

401 U.S. 617

Red Lion Broadcasting ( Co. v. FCC, 395

U.S. 367

Rutherford v. American Medical Ass'n,

379 F.2d 641 (7th Cir.), cert. denied,

389 U.S. 1043

Udall v. Tallman, 380 U.S. 1. ee

United States v. ‘An Article of Drug .

Bacto-Unidisk, 394 U.S. 784 __.

United States v. Dotterweich, 320 U.S.

277 ts ee

Page

con Ww WwW FE

10a

lla

45a

“14, 15

Cases—Continued Page

United States vy. New York Telephone Co.,

434 U.S. 159 18

Vermont Yankee Nuclear Power Corp. v.

Natural Resources Defense Council,

Inc., No. 76-419 (April 3, 1978) 17

Weinberger v. Hynson, Westcott & Dun-

ning, Inc., 412 U..S 609 6,11, 14

Statutes and regulation:

Drug Amendments of 1962, Pub. L. No.

87-781, 76 Stat. 780 5

Section 107(c) (4), 76 Stat. 789 3,6

Federal Food, Drug, and Cosmetic Act of

1938, ch. 675, 52 Stat. 1040 et seq.

Section 201(p), 52 Stat. 1041

Section 355(d), 52 Stat. 1052

Federal Food, Drug, and Cosmetic Act, 21

U.S.C. 301 et seq.:

Section 201(p), 21 U.S.C. 321(p) 2.5,7

Section 201(p)(1), 21 U.S.C. 321

oror Oo

20) 6

Section 502, 21 U. S. C. 352 - * 17

Section 502(a), 21 U.S.C. 352(a). 17

Section 505, 21 U.S.C. 355. 3, 8, 11

Section 505(a), 21 U.S.C. 355(a). 11

Section 505(d), 21 U.S.C. 355(d)__.6, 11, 13

Section 505(d)(6), 21 U.S.C. 355

So); hae 17

Food and Drugs Act of 1906, ch. 3915, 34

Stat. 768 . ee ace ER ee 5

21 C.F.R. 5.1(a) Bh, eh antec eat seas eT 5

Ill

Miscellaneous: Page

79 Cong. Rec. 5023 (1935) .. . 14

83 Cong. Rec. 7786-7787, 7789 (1988) . 14

107 Cong. Rec. 5640 (1961) - nant 13

108 Cong. Rec. 17399 (1962) 14

108 Cong. Rec. 17401 (1962) 14

Dunn, Federal Food, Drug and Cosmetic

Act (1938) ie 14

H.R. Rep. No. 2464, 87th Cong., 2d Sess.

| Aree pitta ser ae NU a ley te 15

S. Rep. No. 1744, 87th Cong., 2d Sess.

(1962) AGREE. UPSD A TE Re NR 13, 15

Gu the Supreme Court of the United States

OCTOBER TERM, 1978

No.

UNITED STATES OF AMERICA, ET AL., PETITIONERS

Vv.

GLEN L. RUTHERFORD, ET AL.

PETITION FOR A WRIT OF CERTIORARI TO THE

UNITED STATES COURT OF APPEALS

FOR THE TENTH CIRCUIT

The Solicitor General, on behalf of the United

States, et al., petitions for a writ of certiorari to re-

view the judgment of the United States Court of

Appeals for the Tenth Circuit.

OPINIONS BELOW

The opinion of the court of appeals (App. A, infra,

la-7a) is not yet reported. The opinion of the district

court (App. D, infra, 1la-44a) is reported at 438

F. Supp. 1287. The decision of the Commissioner of

‘the Food and Drug Administration (App. E, infra,

45a-274a) is reported at 42 Fed. Reg. 39768.

(1)

JURISDICTION

The judgment of the court of appeals (App. B,

infra, 8a-9a) was entered on July 10, 1978. On

August 4, 1978, the court of appeals summarily de-

nied a Motion for Clarification or in the alternative

Petition for Re-Hearing filed by respondents on July

27, 1978 (App. C, infra, 10a). The jurisdiction of

this Court is invoked under 28 U.S.C. 1254(1).

QUESTION PRESENTED

Whether the safety and effectiveness requirements

of the Federal Food, Drug, and Cosmetic Act apply

to drugs intended for use by the terminally ill.

STATUTES INVOLVED

Section 201(p) of the Federal Food, Drug, and

Cosmetic Act, 21 U.S.C. 321(p), provides in part:

The term “new drug” means—(1) 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, except thet such a drug not so

recognized shall not be deemed to be a “new

drug” if at any time prior to the enactment of

this Act it was subject to the Food and Drugs

Act of June 30, 1906, as amended, and if at

such time its labeling contained the same repre-

sentations concerning the conditions of its

use * * *

Section 107(c)(4) of the Drug Amendments of

1962, Pub. L. No. 87-781, 76 Stat. 789 (“1962 grand-

father clause’), provides:

In the case of any drug which, on the day im-

mediately preceding the enactment date [October

10, 1962], (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 [21 U.S.C. 231(p)], and (C)

was not covered by an effective [new drug] ap-

plication under section 505 of that Act [21

U.S.C. 355], the amendments to section 201

(p) made by this Act shall not apply to such

drug when intended solely for use under condi-

tions prescribed, recommended, or suggested in

labeling with respect to such drug on that day.

Section 505 of the Federal Food, Drug and Cos-

metic Act, 21 U.S.C. 355, provides in part:

(a) No person shall introduce or deliver for

introduction into interstate commerce any new

drug, unless an approval of an application filed

pursuant to subsection (b) of this section is ef-

fective with respect to such drug.

(b) Any person may file with the Secretary

an application with respect to any drug subject

to the provisions of subsection (a) of this sec-

tion. Such person shall submit to the Secretary

as a part of the application (1) full reports of

investigations which have been made to show

whether or not such drug is safe for use and

whether such drug is effective in use * * *

* * * * *

(d) If the Secretary finds * * * that (1) the

investigations * * * required to be submitted to

the Secretary * * * do not include adequate tests

by all methods reasonably applicable to show

whether or not such drug is safe for use under

the conditions prescribed, recommended, or sug-

gested in the proposed labeling thereof; (2) the

results of such tests * * * do not show that such

drug is safe for use under such conditions; * * *

(4) * * * he has insufficient information to de-

termine whether such drug is safe for use under

such conditions; or (5) * * * there is a lack of

substantial evidence that the drug will have the

effect it purports or is represented to have under

the conditions of use prescribed, recommended,

or suggested in the proposed labeling thereof; or

(6) based on a fair evaluation of all material

facts, such labeling is false or misleading in any

particular; he shall issue an order refusing to

approve the application. * * * As used in this

subsection and subsection (e) of this section,

the term “substantial evidence” means evidence

consisting of adequate and well-controlled investi-

gations, including clinical investigations, by ex-

perts qualified by scientific training and experi-

ence to evaluate the effectiveness of the drug

involved, on the basis of which it could fairly

and responsibly be concluded by such experts

that the drug will have the effect it purports or

is represented to have under the conditions of

use prescribed, recommended, or suggested in

the labeling or proposed labeling thereof.

* * * * *

(i) The Secretary shall promulgate regula-

tions for exempting from the operation of the

foregoing subsections of this section drugs in-

tended solely for investigational use by experts

qualified by scientific training and experience to

investigate the safety and effectiveness of drugs.

Such regulations may, within the discretion of

the Secretary, among other conditions relating

to the protection of the public health, provide for

conditioning such exemption upon—

(1) the submission to the Secretary, before

any clinical testing of a new drug is undertaken,

of reports, by the manufacturer or the sponsor

of the investigation of such drug, of preclinical

tests (including tests on animals) of such drug

adequate to justify the proposed clinical testing

* * *

STATEMENT

The Federal Food, Drug, and Cosmetic Act of 1938,

ch. 675, 52 Stat. 1040 et seq., prohibited the introduc-

tion of any new drug into interstate commerce with-

out the approval of the Secretary of Health, Educa-

tion and Welfare.’ The Act provided procedures for

filing applications for such approval, and directed

the Secretary to deny approval if he did not find,

on the basis of adequate scientific evidence, that the

drug was safe for its intended use. Section 355(d),

52 Stat. 1052. The Drug Amendments of 1962, Pub.

L. No. 87-781, 76 Stat. 780, substantially amended

1 The Secretary has delegated this authority to the Commis-

sioner of the Food and Drug Administration (FDA). 21

C.F.R. 5.1(a). Under the 1938 Act, a “new drug” was one not

generally recognized by qualified experts as safe for its in-

tended use (Section 201(p), 52 Stat. 1041). The Act contained

a “grandfather clause” excluding from the definition of “new

drug” any drug that, before enactment of the 1938 Act, was

subject to the Food and Drugs Act of 1906, ch. 3915, 34 Stat.

768, and that retained representations concerning the condi-

tions of use identical to those it then had. This 1938 grand-

father clause remains in the current Act. 21 U.S.C. 321(p) (1).

the 1938 Act. They redefined a new drug as one not

generally recognized as effective as well as safe

(Section 201(p)(1), 21 U.S.C. 321(p)(1)). And

they directed the Secretary to deny approval of a

new drug application unless he finds substantial

evidence’ that the drug is effective for its intended

use, as well as safe. 21 U.S.C. 355(d). See Wein-

berger v. Hynson, Westcott & Dunning, Inc., 412 U.S.

609, 612-615 (1973).°

This action was instituted by cancer patients on

March 12, 1975,* and seeks to prevent the government

2 “Substantial evidence” is defined as “‘evidence consisting of

adequate and well-controlled investigations, including clinical

investigations, by experts qualified by scientific training and

experience to evaluate the effectiveness of the drug involved,

on the basis of which it could fairly and responsibly be con-

cluded by such experts that the drug will have the effect it

purports or is represented to have under the conditions of

use prescribed, recommended, or suggested in the labeling or

proposed labeling thereof.” Section 505(d), 21 U.S.C. 355(d).

’ The 1962 Amendments also contain a grandfather clause,

excluding from the definition of “new drug” any drug that, on

October 9, 1962 (the day immediately preceding the enactment

of the 1962 Amendments): “(A) was commercially used or

sold in the United States, (B) was not a new drug [under the

19388 Act] * * * and (C) was not covered by an effective

[new drug application].” Section 107(c) (4), 76 Stat. 789.

The action was originally instituted by Juanita Stowe, a

cancer patient, and her husband Jimmie Stowe. After Mrs.

Stowe’s death, an amended complaint was filed by two other

patients, Glen L. Rutherford and Phyllis S. Schneider, and

Mrs. Schneider’s husband, on behalf of a class composed of

cancer patients and their spouses who are responsible for the

costs of treatment. Mrs. Schneider subsequently died. By

order entered April 8, 1977, the district court certified this

case as a class action on behalf of a class composed of ter-

from interfering with the interstate sale or distribu-

tion of a drug called Laetrile. In an order entered

August 14, 1975, and amended October 10, 1975, the

district court enjoined the government from prevent-

ing the purchase and subsequent interstate movement

of a limited quantity of Laetrile for Glen L. Ruther-

ford, one of the plaintiffs. Rutherford v. United

States, 399 F. Supp. 1208, 1215 (W.D. Okla. 1975).°

On appeal, the Tenth Circuit did not disturb the in-

junction, but instructed the district court to remand

the case to the Commissioner of Food and Drugs for

the development of an administrative record address-

ing the questions whether Laetrile is a “new drug”

within the meaning of Section 201(p) and, if so,

whether it is exempt from the premarketing approval

requirements of the Act by virtue of the Act’s 1938

or 1962 grandfather clauses. Rutherford v. United

States, 542 F. 2d 1137 (10th Cir. 1976).°

On remand, the Commissioner concluded after an

administrative proceeding that Laetrile is a “drug”

as defined in the Act, because it is being sold for the

cure or prevention of disease, and a “new drug”

within the meaning of Section 201(p) of the Act, 21

U.S.C. 321(p). App. E, infra. He found that Lae-

trile does not satisfy the premarketing approval re-

minally ill cancer patients, Rutherford v. United States, 429

F. Supp. 506, 509 (W.D. Okla. 1977). The propriety of that

order was not appealed by the government.

5’ The district court subsequently entered similar orders on

behalf of other plaintiffs.

* See notes 1 and 3, supra.

quirements for new drugs in Section 505 of the Act,

21 U.S.C. 355, because it does not meet the statutory

safety and effectiveness requirements. The Commis-

sioner found that there is “an absence of scientifically

sound data upon which experts * * * could base an

opinion that Laetrile is safe for use in man” (id. at

157a), and that “[t]here are no clinical investigations

of Laetrile’s effectiveness, published or otherwise,

which are even arguably adequate and _ well-

controlled.” Jd. at 93a-94a.

The Commissioner further found that Laetrile does

not meet the statutory criteria of either the 1938 or

the 1962 grandfather clause: The drug presently

termed “Laetrile”’ was not shown to be the same drug

used during the applicable prior period; the prior

labeling and representations concerning use are not

identical to the representations associated with the

presently marketed drug; Laetrile was not commer-

cially used or sold on the grandfather date; and ex-

perts did not generally recognize it as safe on that

date. Id. at 163a-211a.

On review of the Commissioner’s decision, the dis-

trict court upheld his determination that Laetrile is

a drug, and further held that “the evidence of record

does not render the Commissioner’s conclusion that

Laetrile is not ‘generally recognized as safe and

effective’ arbitrary and capricious.” App. D, infra,

22a. The court concluded, however, that the drug is

exempt from the Act’s premarketing approval re-

quirements by virtue of the 1962 grandfather clause.

In reaching this conclusion, the court set aside each

of the Commissioner’s factual findings on the issue.

App. D, infra, 26a-34a. The court further con-

cluded that “[b]y denying the right to use a nontoxic

substance in connection with one’s own personal

health-care, FDA has oftended the constitutional right

of privacy.” Id. at 41a (footnote omitted).’

The court of appeals, without addressing either the

statutory or the constitutional ground on which the

district court relied, concluded that the Commissioner

had misinterpreted the safety and effectiveness re-

quirements of the Act as applied to “persons who are

* * * fatally stricken with a disease for which there

is no known cure.” App. A, infra, 6a. In the court’s

view, “[c]learly the terms have no meaning under

these circumstances, and certainly not the abstract

meaning sought to be applied by the Commission-

[er].” Ibid. The court therefore held that “the

‘safety’ and ‘effectiveness’ requirements of the statute

as now written have no application to terminally ill

cancer patients who desire to take [Laetrile] intra-

venously.” Jd. at 7a. The court emphasized that its

decision applied only to the intravenous use of Lae-

trile by terminally ill cancer patients, a group whose

members, it concluded, could be identified without

difficulty by the certification of a licensed medical

7In reaching this conclusion the court expressly rejected

(App. D, infra, 29a n. 18 and 31a-34a nn. 23, 24) the Com-

missioner’s factual finding (App. E, infra, 157a, 162a, 273a-

274a) that Laetrile has a known toxicity that has not been

fully investigated.

practitioner. Jd. at 5a-6a.* The Food and Drug Ad-

ministration was directed to “promulgate regulations

within the above limitations and as if the drug was

found by the Commission[er] to be ‘safe’ and ‘effec-

tive’ for the limited group of persons here considered.”

Id. at Ta.

REASONS FOR GRANTING THE PETITION

The court of appeals’ construction of the Federal

Food, Drug, and Cosmetic Act is contrary to the plain

meaning of the statute, its legislative history, and

its uniform interpretation by the agency responsible

for its enforcement. The court’s decision seriously

limits the Commissioner’s power to protect the public

from unsafe and ineffective drugs. Although the

present ruling is limited to the intraveneous use of

Laetrile by terminally ill cancer patients, the court’s

analysis of the Act would prevent the Commissioner

from concluding that any drug intended for use by

the terminally ill has not been shown to be safe and

effective. The decision thus would make it difficult

if not impossible for the Commissioner to discharge

his statutory responsibility to keep unproven drugs

out of the marketplace.’

* Plaintiffs’ motion for clarification or rehearing, which

requested the court to authorize the class members to take

Laetrile orally, was denied without comment. App. C, infra,

10a.

® The decision is also inconsistent with Rutherford v. Ameri-

can Medical Ass’n, 379 F. 2d 641 (7th Cir. 1967), cert. denied,

389 U.S. 1043 (1968). In that case, a doctor and “hopeless”’

1. The Federal Food, Drug, and Cosmetic Act con-

tains no exemption from its premarketing clearance

requirements for drugs intended for use by the termi-

nally ill. The statute provides that no new drug may

be introduced into interstate commerce unless the -

Commissioner has approved a new drug application.

Section 505(a), 21 U.S.C. 355(a). That approval

requires (1) the submission of reports that include

“adequate tests by all methods reasonably applicable

to show [that] such drug is safe for use,” and (2)

“evidence consisting of adequate and well-controlled

investigations” showing that “the drug will have the

effect it purports or is represented to have * * *.” 21

U.S.C. 355(d).” Nothing in the statute suggests

cancer patients (379 F. 2d at 642) sought to enjoin FDA and

others from interfering with the distribution of another drug

allegedly effective in the treatment of cancer. The court held

that “initial approval or exemption of a drug is within the

primary jurisdiction of the FDA.” Id. at 643. In the absence

of any good faith application to the agency for such approval

or exemption, the court lacked jurisdiction to review the re-

fusal to permit the marketing of the drug. The opinion notes

that Section 355 of the Act establishes a procedure for sub-

mitting adequate scientific information about a new drug

to the FDA to “permit an intelligent assessment of its safety

and efficacy” (ibid.). The court thus indicated that such an

assessment was necessary for drugs designed for use by cancer

patients, even “hopeless” ones; there is no suggestion that the

court believed the standards of safety and effectiveness were

less stringent for such drugs, let alone inapplicable.

10 The only drugs exempted from these premarketing clear-

ance requirements are those that are not “new.” See notes

1 and 3, supra; Weinberger v. Hynson, Westcott & Dunning,

Inc., 412 U.S. 609, 629-630 (1973).

that these requirements are not fully applicable to

drugs intended for use by the terminally ill.” Nor is

it appropriate to read such an exemption into the Act,

as the court of appeals did, whether for terminal

cancer patients or for persons terminaly i!l from

any other affliction.

The court was incorrect in its view that safety

and effectiveness have “no meaning” as applied to

drugs to be used by such persons (App. A, infra,

6a). It is entirely reasonable to give those terms

the same meaning in this context that they have

when applied to any other drugs. Neither term means,

as the court evidently assumed, that the drug will

cure the affliction for which it is taken. Instead, as

the statute makes clear, a drug is “effective” if sub-

stantial evidence” indicates that it “will have the

effect it purports or is represented to have under

11TIn discussing the court of appeals’ holding we assume,

like the court, that the “terminally ill” are an objectively

identifiable group (App. A, infra, 6a). But the term is a pre-

diction concerning the future course of a disease, rather than

an objective description of an ailment, and is thus inherently

speculative. See page 16, infra.

122 The court was not entirely consistent in this view, since

it evidently concluded that there are some appropriate safety

limitations even for Laetrile. Thus, it required that the drug

be administered by a physician and it limited its holding to

intravenous administration, denying a petition requesting

that it amend its order to allow oral dosages. This denial

was unexplained, but presumably reflected a judgment by the

court of appeals on the safety issue. See App. C, infra, 10a;

App. D, infra, 29a n. 18; App. E, infra, 75a, 88a, 157a-162a,

254a-257a, 273a-274a.

18 See note 2, supra.

the conditions of use prescribed, recommended, or

suggested in [its] proposed labeling.” 21 U.S.C. 355

(d); see S. Rep. No. 1744, 87th Cong., 2d Sess. 16

(1962). And a drug is “safe” if its benefits—either

therapeutic or palliative—outweigh any adverse ef-

fects of its use; that is, if it will not gratuitously

harm the person taking it.”

The terminally ill, whether victims of cancer or

any other disease, have as much interest as the gen-

eral public in protection from drugs that are not both

safe and effective. Indeed, as the Commissioner noted

(App. E, infra, 224a-230a), the vulnerable psycho-

logical state of cancer patients may make them par-

ticularly susceptible to unfounded claims and thus

create a special need for protection from ineffective

drugs.

Nothing in the legislative history supports the

court of appeals’ assumption that Congress could not

have intended to impose safety and effectiveness re-

quirements on drugs to be used by terminally ill can-

cer patients. Instead, remarks during congressional

debate on the 1962 Amendments to the Act—which

added the effectiveness requirement for new drugs,

1 That harm may consist of hastening the person’s demise

or of causing less serious physical injury. Even in the absence

of direct physical injury, the drug may cause harm by impos-

ing an unwarranted financial burden on the patient and his

family or by leading him to forego more effective treatment.

See page 15, infra. As Senator Kefauver stated when intro-

ducing the bill that became the 1962 Amendments, “an other-

wise completely safe drug can be dangerous to the patient

if it does not have the therapeutic effect in use which it is rep-

resented to have.” 107 Cong. Rec. 5640 (1961).

see Weinberger v. Hynson, Westcott & Dunning,

supra—reflect an understanding that the Act would

apply to experimental drugs used to treat ‘cancer

in its last stages.” 108 Cong. Rec. 17399 (1962) (re-

marks of Sen. Kefauver, chairman of the committee

reporting the bill).”

Thus, neither the statute nor its legislative history

is ambiguous concerning the applicability of the Act

to drugs intended for use by the terminally ill. But

even if there were some ambiguity, the court’s nar-

row interpretation of the statutory requirements

would be inconsistent with this Court’s repeated

statement of the need to give a broad interpretation to

the Act in order to facilitate the congressionai policy

of protecting the public health. F.g9., United States

v. An Article of Drug . . . Bacto-Unidisk, 394 U.S.

784, 798 (1969); United States v. Dotterweich, 320

U.S. 277, 280 (19438).

2. The consistent administrative practice under

the Act is also contrary to the conclusion of the court

15 Senator Eastland, another proponent of the bill, also

assumed that drugs administered for “fatal diseases, such as

cancer,” would be subject to the Act’s requirements, noting

that approval of such drugs would be appropriate even though

they might only prolong life or alleviate suffering. 108 Cong.

Rec. 17401 (1962).

References to cancer were also made during consideration

of the 1938 Act. See, e.g., 79 Cong. Rec. 5023 (1935) (re-

marks of Sen. Copeland, sponsor of the Act); 83 Cong. Rec.

7736-7787, 7789 (1938) (remarks of Reps. Phillips and Lea).

See also Dunn, Federal Food, Drug and Cosmetic Act 42, 58,

77, 200, 639, 726, 952-956 (1938) (collecting the legislative

history).

of appeals. The Food and Drug Administration has

consistently interpreted the Act to require that drugs

intended for the treatment of terminally ill persons

satisfy the same statutory criteria of safety and ef-

fectiveness that are applied to all other new drugs.”

That interpretation, which was ratified by Congress

when it amended the Act in 1962,” is entitled to sub-

stantial judicial deference. See e.g., United States v.

An Article of Drug .. . Bacto-Unidisk, supra, 394

U.S. at 791-792; Red Lion Broadcasting Co. v. FCC,

395 U.S. 367, 380-381 (1969); Investment Company

Institute v. Camp, 401 U.S. 617, 626-627 (1971);

Udall v. Tallman, 380 U.S. 1, 16 (1965).

Such deference is particularly fitting here, in light

of the Commissioner’s finding (App. E, infra, 270a)

that a decision such as that ultimately reached by the

court of appeals

* * * would lead to needless deaths and suffering

among (1) patients characterized as “terminal”

1° For example, there are approximately forty drugs pres-

ently approved for use in the treatment of cancer, without

regard for whether it is terminal.

The Director of the National Cancer Institute recently an-

nounced that the Institute wishes to conduct controlled clinical

tests of Laetrile use by several hundred advanced cancer

patients. The Commissioner of FDA has indicated that he will

promptly review any application received from the Institute

for approval of such tests.

7In enacting the 1962 Amendments, which adopted the

effectiveness requirement for all new drugs, Congress ap-

proved the FDA’s longstanding policy of requiring a demon-

stration of effectiveness for drugs used in the treatment of

life-threatening diseases. S. Rep. No. 1744, 87th Cong., 2d Sess.

15 (1962); H.R. Rep. No. 2464, 87th Cong., 2d Sess. 3 (1962).

who could actually be helped by legitimate ther-

apy and (2) patients clearly susceptible to the

benefits of legitimate therapy who would be mis-

led as to Laetrile’s utility by the limited approval

program or who would be able to obtain the

drug through the inevitable leakage in any sys-

tem set up to administer such a program.

This finding was supported by expert medical and

technical testimony indicating that there is no way

of distinguishing accurately between “terminal” can-

cer patients and those who will respond to conven-

tional cancer treatment (id. at 267a-268a; see id. at

98a). and that even if such a distinction could be

reliably made, it would be virtually impossible as a

practical matter to restrict the use of Laetrile to the

terminally ill (id. at 269a-270a).

The Commissioner, exercising his statutory respon-

sibility for evaluating medical and technical testi-

mony in this area, adopted this testimony (id. at

269a-270a). The court of appeals nevertheless con-

cluded, without citation of authority, that:

It would not seem difficult to define the group

[of terminally ill cancer patients]. A licensed

medical practitioner can express an opinion as

to whether, under the present state of the art,

a particular person is terminally ill with cancer,

and * * * so certify.

We are well aware of and have considered the

arguments that some patients will be victimized

by unscrupulous persons who will seek to profit

by offering Laetrile as a “cure.” This is how-

ever not a legal matter, but an administrative or

regulatory problem for the FDA. [App. A, infra,

6a-7a. |

This Court recently condemned a similar judicial

interference with the proper exercise of authority en-

trusted to an agency by Congress. Vermont Yankee

Nuclear Power Corp. v. Natural Resources Defense

Council, Inc., No. 76-419 (April 3, 1978), slip op. 35-

36. So here, in what is likewise a distinctly technical

area, the court of appeals should not have substituted

its own judgment concerning the desirability of a

special standard—that is, no standard at all—for

drugs for the “terminally ill” in place of the de-

termination of Congress and the Commissioner that

such an exception from the statutory requirements

is neither appropriate nor feasible.”

Since the court of appeals has misconstrued the Act

in a way that significantly endangers the public

health, we submit that plenary review by this Court

* The court directed the FDA to “promulgate regulations

* * * as if the drug was found by the Commission[er] to be

‘safe’ and ‘effective’ for the limited group of persons here con-

sidered” (App. A, infra, 7a). It is difficult to see how FDA

could comply. In the absence of adequate data, there is no basis

on which to label Laetrile in the manner required by Section

502, 21 U.S.C. 352. Directions for drug use, including indi-

cations, contraindicati ns, dosages and routes of adminis-

tration, warnings, side effects, and necessary collateral meas-

ures are premised on a body of data derived from extensive

testing. As the Commissioner found, such data do not exist

for Laetrile (App. E, infra, 93a-21la, 270a-272a). Neither

court below disagreed with this conclusion. Without such

testing data, the drug cannot be labeled for any use. Any sug-

gestion in labeling that the drug may be safely or effectively

used would misbrand the drug in violation of Sections 502 (a)

and 505(d) (6), 21 U.S.C. 352(a) and 355(d) (6).

is warranted. In the course of that review, respond-

ents can be expected to argue that the judgment of

the court of appeals should be affirmed on the grounds

adopted by the district court but not reached by the

court of appeals. See United States v. New York

Telephone Co., 484 U.S. 159, 166 n.8 (1977). We

accordingly would discuss those grounds in our brief

on the merits. We would argue that neither the 1962

grandfather clause nor the Constitutional right to

privacy precludes the Commissioner’s refusal to per-

mit the interstate transportation of Laetrile. We have

not discussed those issues in this petition because

they do not affect the need for review of the court

of appeals’ decision and they were not dealt with in

that decision. Without regard to those issues, the

court of appeals’ misinterpretation of the extent of

the Commissioner’s statutory authority to protect the

terminally ill should be corrected by this Court.

CONCLUSION

The petition for a writ of certiorari should be

granted.

Respectfully submitted.

WADE H. MCCREE, JR.

Solicitor General

JOHN H. SHENEFIELD

Assistant Attorney General

HARRIET S. SHAPIRO

Assistant to the Solicitor General

BARRY GROSSMAN

CATHERINE G. O’SULLIVAN

PETER L. DE LA CRUZ

Attorneys

RICHARD M. COOPER

Chief Counsel

EUGENE M. PFEIFER

Associate Chief Counsel for Enforcement

Food and Drug Administration

Department of Health, Education and Welfare

OCTOBER 1978

APPENDIX A

UNITED STATES COURT OF APPEALS

TENTH CIRCUIT

No. 77-2049

[Filed Jul. 10, 1978]

GLEN L. RUTHERFORD, individually and on behalf of a

class composed of terminally ill cancer patients,

PLAINTIFFS, APPELLEES,

Vv.

UNITED STATES OF AMERICA, JOSEPH A. CALIFANO,

SECRETARY OF HEALTH, EDUCATION AND WELFARE;

DONALD KENNEDY, COMMISSIONER OF THE Foop

AND DRUG ADMINISTRATION, et al., DEFENDANTS,

APPELLANTS

APPEAL FROM THE UNITED STATES DISTRICT COURT

FOR THE WESTERN DISTRICT OF OKLAHOMA

(D.C. # CIV-75-0218-B)

Barry Grossman, Attorney, Department of Justice

(John H. Shenefield, Assistant Attorney General,

Catherine G. O’Sullivan, Attorney, Department of

Justice, Peter L. De La Cruz, Attorney, Department

of Justice; of Counsel, Richard M. Cooper, Chiéf

Counsel, Eugene M. Pfeifer, Associate Chief Counsel

for Enforcement, and Arnold I. Friede, Assistant

Chief Counsel for Enforcement, Food and Drug Di-

vision, Department of Health, Education and Wel-

fare, with him on the Brief), for Appellants.

Kenneth Coe, of Looney, Nichols, Johnson & Hayes,

Oklahoma City, Oklahoma, for Appellees.

Charles F. Wheatley, Jr., William T. Miller, Grace

Powers Monaco, Robert A. O’Neil, of Wheatley &

Miller, Washington, D.C., on the Brief for Amicus

American Cancer Society.

Before SETH, Chief Judge, BARRETT and McKAY,

Circuit Judges.

SETH, Chief Judge.

The Government appellants seek review of a dis-

trict court holding which set aside a determination

of the Commission of Food and Drugs that Laetrile,

a controversial cancer drug, is a “new drug” within

the meaning of the Federal Food, Drug, and Cosmetic

Act (“the Act”), 21 U.S.C. § 301 et seq., and thus

excludable from interstate commerce due to the ab-

sence of an approved new drug application.

The central question here is whether the plaintiffs,

a class of terminally ill cancer patients, should be

SCID REG SN. San aus anes ~

Bab nm teas

allowed to acquire Laetrile for their own use intra-

venously despite the Act’s requirements that “safety”

and “effectiveness” be established for the approval

of a “new drug.” We conclude as a matter of law

that the “safety” and “effectiveness” terms used in

the statute have no reasonable application to termi-

nally ill cancer patients, and have no established

meaning when considered in that context.

This case is before us for the second time. For a

summary of the facts, see Rutherford v. United

States, 542 F.2d 1137 (10th Cir.), and Rutherford

v. United States, 438 F.Supp. 1287. In Rutherford

v. United States, 542 F.2d 1137 (10th Cir.), we held

that an adequate administrative record had not been

developed by the Commissioner to justify classifying

Laetrile as a new drug. We remanded and said:

“.. To support its determination the FDA in

the case at bar would have to present substantial

evidence to support the proposition that Laetrile

is not generally recognized among qualified ex-

perts as ‘safe and effective,’ and that Laetrile is

not grandfathered by either of the exemptions

discussed above.”

We also upheld a preliminary injunction granted by

the district court which prevented the FDA from in-

terfering with a cancer patient’s personal use of the

drug.

On remand, the Commissioner compiled some 5,500

pages of written submissions and held two days of

oral hearings before making a determination. This

was apparently a rule-making proceeding under sec-

tion 701 of the Act, 21 U.S.C. § 371. The unsworn

material compiled by the agency represents diverse

views but does not appear to be the typical record

which should be formulated to support an agency

determination which is dealing with issues of scien-

tific and medical expertise or in response to our re-

mand. However, we fully realize difficulties in mak-

ing a record when the proponents of a drug are a

group of individuals and not the typical drug manu-

facturer who conducted extensive laboratory tests

and assembled a mass of scientific data. The FDA

was considering what may be regarded as a folk

medicine with no established or organized proponents.

This was difficult to do within the structure of the

agency.

After consideration of the record on remand, the

Commissioner announced that: (1) Laetrile is not

generally recognized by qualified experts as a safe

and effective cancer drug; and (2) Laetrile is not

exempt from the premarket approval requirement for

new drugs by virtue of the “grandfather” provisions

of the Act. Distribution of Laetrile in interstate com-

merce, the Commissioner concluded, is thus illegal and

subject to regulatory activity by the Food and Drug

Administration.

The district court reviewed the administrative rec-

ord and concluded that the decision of the Commis-

sioner was “arbitrary and capricious” with regard

to the 1962 grandfather exemption. The district

court also held that the provisions of the Act violated

a cancer patient’s constitutional right to privacy by

denying him the right to use a nontoxic substance in

connection with his own personal health care. A

permanent injunction was issued by the district court.

While the FDA should make the initial determina-

tion as to “new drug” status, this decision is review-

able under 5 U.S.C. § 706(2). Weinburger v. Hyn-

son, Westcott & Dunning, Inc., 412 U.S. 609. In

reviewing the FDA’s determination the court should

decide inter alia, “all relevant questions of law.” 5

U.S.C. § 706. In Rutherford we remanded to the

FDA for a determination on “safety” and “effective-

ness,” prerequisites which must be established for

new drug approval. However, as these criteria are

applied to terminally ill cancer patients, we noted

some doubt in the application of the terms:

“The FDA argues that a drug offered for use

in a life-threatening disease that is not ‘effective’

is thereby not ‘safe’ either. Thus even under the

pre-1962 law Laetrile would have to satisfy ef-

fectiveness criteria. This argument may lose its

force in the case of a terminally-ill patient or in

the case of a patient suffering from a disease

for which there are in fact no ‘effective’ reme-

dies.”

542 F.2d 1187, 1142, n. 5.

We are considering only cancer patients who are

terminally ill and only their intravenous use of Lae-

trile. Thus in this context, what can be “generally

recognized” as “safe” and “effective” mean as to such

persons who are so fatally stricken with a disease

for which there is no known cure? What meaning

can “effective” have in the absence of anything which

may be used asa standard? Under this record Lae-

trile is as effective as anything else. What can “ef-

fective” mean if the person, by all prevailing stand-

ards, and under the position the Commission takes,

is going to die of cancer regardless of what may be

done. Thus there has been no standard here advanced

by the Commission against which to measure the

safeness or effectiveness of the drug as to the plain-

tiffs. Clearly the terms have no meaning under these

circumstances, and certainly not the abstract mean-

ing sought to be applied by the Commission. This

was an erroneous application of the Act by the Com-

mission. We do not say that anything is safe for the

persons here concerned and nothing is effective, but

it is apparent that no applicable or reasonable meas-

ure exists.

It would not seem difficult to define the group to

which this determination of a legal issue applies. A

licensed medical practitioner can express an opinion

as to whether, under the present state of the art, a :

particular person is terminally ill with cancer, and

to so certify.

We are well aware of and have considered the ar-

guments that some patients will be victimized by

unscrupulous persons who will seek to profit by offer-

ing Laetrile as a “cure.” This is however not a legal

matter, but an administrative or regulatory prob-

lem for the FDA.

Therefore, we hold as a matter of law that the

“safety” and “effectiveness” requirements of the

statute as now written have no application to termi-

nally ill cancer patients who desire to take the drug

intravenously.

We do not reach the constitutional aspects which

were applied by the district court, We conclude,

however, that the permanent injunction granted by

the district court should be continued but be limited

only to permit procurement of intravenous injections

administered by a licensed medical practitioner to per-

sons who are certified by a licensed medical prac-

titioner to be terminally ill of cancer in some form.

We are confident that the FDA with all due dis-

patch will promulgate regulations within the above

limitations and as if the drug was found by the

Commission to be “safe” and “effective” for the

limited group of persons here considered.

The case is remanded for further proceedings con-

sistent with this opinion.

APPENDIX B

UNITED STATES COURT OF APPEALS

FOR THE TENTH CIRCUIT

No. 77-2049

GLEN L. RUTHERFORD, individually and on behalf of

a class composed of terminally ill cancer patients,

PLAINTIFFS-APPELLEES,

v8.

UNITED STATES OF AMERICA, JOSEPH A. CALIFANO,

SECRETARY OF HEALTH, EDUCATION AND WELFARE;

DONALD KENNEDY, COMMISSIONER OF THE FoopD

AND DRUG ADMINISTRATION, ET AL., DEFENDANTS-

APPELLANTS.

Before Honorable Oliver Seth, Honorable James F.

Barrett, and Honorable Monroe G. McKay, Circuit

Judges.

This cause came on to be heard on the record on

appeal from the United States District Court for the

Western District of Oklahoma, and was argued by

counsel.

Upon consideration whereof, it is ordered that the

judgment of that court is affirmed in part and modi-

fied in part. The cause is remanded to the United

States District Court for the Western District of

Oklahoma, with directions to modify its permanent

injunction granted December 5, 1977, so as to limit

it in its future application only to permit procure-

ment of Laetrile for intravenous injections adminis--

tered by a licensed medical practitioner to persons

who are certified by a licensed medical practitioner to

be terminally ill of cancer in some form. Thereafter,

the trial court shall remand the case to the Food and

Drug Administration for further proceedings con-

sistent with this opinion.

/s/ Howard K. Phillips

HOWARD K. PHILLIPS

Clerk

10a

APPENDIX C

MAY TERM—August 4, 1978

Before The Honorable Oliver Seth, Circuit Judge

The Honorable James E. Barrett, Circuit Judge

The Honorable Monroe G. McKay, Circuit Judge

No. 77-2049

GLEN L. RUTHERFORD, individually and on behalf of a

class composed of terminally ill cancer patients,

PLAINTIFFS-APPELLEES

vs.

UNITED STATES OF AMERICA, JOSEPH A. CALIFANO,

Secretary of Health, Education and Welfare;

DONALD KENNEDY, Commissioner of the Food and

Drug Administration, et al., DEFENDANTS-APPEL-

LANTS

AMERICAN CANCER SOCIETY, AMICUS CURIAE

(In support of Petitioners)

This matter comes on for consideration of the mo-

tion for clarification, or in the alternative, petition for

re-hearing filed by appellee Glen L. Rutherford on

July 27, 1978.

Upon consideration whereof, it is ordered:

1. The petition for rehearing is denied.

2. The motion for clarification is denied.

/s/ Howard K. Phillips

HOWARD K. PHILLIPS

Clerk

lla

APPENDIX D

UNITED STATES DISTRICT COURT

W. D. OKLAHOMA

No. CIV-75-0218-B

Dec. 5, 1977

GLEN L. RUTHERFORD, Individually and on behalf of

a class composed of terminally ill cancer patients,

PLAINTIFFS

UNITED STATES OF AMERICA, JOSEPH A. CALIFANO,

Secretary of Health, Education and Welfare;

DONALD KENNEDY, Commissioner of the Food and

Drug Administration, et al., DEFENTANTS

OPINION

BOHANON, District Judge.

The plaintiffs seek judicial review of the Food and

Drug Administration’s (FDA’s) determination that

the substance commonly called Laetrile is a “new

drug” within the meaning of the Federal Food, Drug,

and Cosmetic Act, (the Act); (21 U.S.C. § 301 et

seq.), and excludable from interstate commerce due

to the absence of an approved new drug application

on its behalf. (21 U.S.C. § 355).

On July 29, 1977, the Commissioner of Food and

Drugs announced that: (1) Laetrile is not generally

recognized by qualified experts as a safe and effective

12a

cancer drug and (2) Laetrile is not exempt from the

pre-market approval requirement for new drugs by

virtue of the “grandfather” provisions of the Act.

Distribution of Laetrile in interstate commerce, the

Commissioner concluded, is thus illegal and subject

to regulatory activity by the Food and Drug Admin-

istration. Commissioner’s Decision (R 523 at 1).*

Plaintiffs challenge such administrative decision

and urge that Laetrile is not a “drug,” that in any

event it is not a “new drug,” and that FDA’s en-

forcement procedures against the interstate trans- ©

portation and use of the substance violate plaintiffs’

constitutional rights.

STANDARD OF REVIEW

FDA possesses jurisdiction to initially determine

whether a substance is a “new drug” within the Act’s

meaning, Weinberger v. Hynson, Westcott & Dunning,

412 U.S. 609, 627, 938 S.Ct. 2469, 37 L.Ed.2d 207

(1973), but such determination is reviewable by the

district court under the Administrative Procedure

Act, 5 U.S.C. § 701 et seq., Weinberger, supra. To be

affirmed, the administrative decision must not be

arbitrary, capricious or abusive of agency discretion.’

1In adopting the approach employed by FDA, submissions

to the administrative record are designated by an R followed

by the number assigned to them by the Hearing Clerk. Refer-

ences to the transcript of the oral argument are cited as Tr.

25 U.S.C. § 706 states in part: “To the extent necessary

to decision and when presented, the reviewing court shall

eS OE ae —

is 5

13a

Citizens to Preserve Overton Park v. Volpe, 401 U.S.

402, 416, 91 S.Ct. 814, 28 L.Ed.2d 1386 (1971). The

court in its review must consider whether the de-

cision was based upon a consideration of the relevant

factors and whether there has been a clear error of

judgment.’ Citizens to Preserve Overton Park v.

Volpe, supra.

While the standard of review is narrow, and the

court is not empowered to substitute its judgment for

that of the agency, nonetheless, the reviewing court

possesses a responsibility “to engage in a substantial

inquiry,” and “his inquiry into the facts is to be

searching and careful. . . .”* Citizens to Preserve

decide all relevant questions of law, interpret constitutional

and statutory provisions, and determine the meaning or ap-

plicability of the terms of an agency action. The reviewing

court shall—... (2) hold unlawful and set aside agency ac-

tion, findings, and conclusions found to be—(A) arbitrary,

capricious, an abuse of discretion, or otherwise not in accord-

ance with law... .” (emphasis supplied)

* The Tenth Circuit Court of Appeals has clearly established

previously that Laetrile is not to be considered a “new drug”

merely because the FDA has said so; the agency must proffer

“substantial evidence” supportive of such determination.

Rutherford v. United States, 542 F.2d 1137, 1143 (10th Cir.

1976). “Perhaps agency action which is not based upon sub-

stantial evidence is arbitrary and capricious.” American Pe-

troleum Institute v. EPA, 540 F.2d 1028, 1028 (10th Cir.

1976).

* A court may study the record, hopefully perceptively, even

as to the evidence on technical and specialized matters, and

penetrate to the underlying decisions of the agency, to satisfy

itself that the agency has exercised a reasoned discretion and

has not deviated from or ignored the ascertainable legislative

l4a

Overton Park v. Volpe, supra at 415-16, 91 S.Ct. at

824. Although the agency’s decision is entitled to a

presumption of regularity, this does not preclude a

thorough, probing, in-depth review. Citizens to Pre-

serve Overton Park v. Volpe, supra at 415, 91 S.Ct.

814,

Meaningful judicial review requires determining

that an agency’s course of action flowed from a proper

interpretation of the relevant law and a proper ap-

plication of that law to facts sufficiently well de-

' veloped by agency inquiry as to reflect the truth of

the matter in controversy. The court should intervene

where it apppears from a combination of danger

signals, that the agency really has not taken a “hard

look” at the salient problems, and has not genuinely

engaged in reasoned decision-making.’ Greater Boston

intent. This immersion in the evidence enables the court to

determine whether the agency decision was rational and based

on the relevant factors. Ethyl Corp. v. Environmental Protec-

tion Agency, 176 U.S.App.D.C. 373, 407-408, 541 F.2d 1, 35-36

(1976).

5 Considerable evidence calls into question FDA’s sense of

objectivity in this case.

When this suit was initiated, FDA had declared Laetrile a

“new drug” without ever having constructed an administra-

tive record in support of such designation. See Rutherford v.

United States, 424 F.Supp. 105 (W.D.Okl. 1977). Ideally,

agency decisions and conclusions should flow from a probing

and objective analysis of a carefully amassed and encom-

passing factual record. When ordered on remand to conduct

an appropriate investigation, FDA begrudingly announced its

intentions to do so and then previous to ever having received

the evidence on which its conclusions are ostensibly based,

SR Bee, Be ~

l5a

Television Corporation v. F.C.C., 148 U.S.App.D.C.

383, 393, 444 F.2d 841, 851 (1970).

The exercise of discretionary authority requires a

decision based upon adequate information; to act

without collecting necessary facts is abusive of dis-

cretion. Xytex Corporation v. Schliemann, 382 F.

Supp. 50, 53 (D.Colo. 1974).

After collecting the facts, the appropriate legal

standards must be applied. If administrative con-

struction of a statute is clearly wrong, it is the court’s

duty to correct.’ R. V. McGinnis Theatres and Pay

FDA reaffirmed its same, entrenched positions on the salient

issues in the case. See “Laetrile—Notice of Administrative

Rule Making Hearing,” (R11) (42 Fed. Reg. 10066 (1977) ).

Understandably, many contributors to the administrative rec-

ord expressed skepticism concerning the proceedings’ fairness.

*¢“’When an administrative officer is sitting in a dual role

as judge of the law and trier of the facts, and when he, as

judge, gives himself, as fact-finder, an incorrect instruction

as to the law governing the decision he must make, error is

committed just as there is error if a judge incorrectly charges

a jury. We must assume that the examiner applied the stand-

ard as he stated it; and if he did, he erred, and on a question

of law. The decision, therefore, cannot stand.” Williams Vv.

Ribicoff, 323 F.2d 231-32 (5th Cir. 1963). —

7 FDA errs as a matter of law when it asserts that Laetrile

cannot escape new drug classification unless it is shown that:

“It is currently intended solely for use under conditions pre-

scribed recommended or suggested in its labeling on October

9, 1962.” (emphasis supplied) Under this interpretation, if

someone were suddenly to begin promoting aspirin for some

new or unconventional purpose, all aspirin, regardless of its

use, would ipso facto be subject to being classified a “new

durg” and regulated as such under the provisions of the Act.

The appropriate statutory construction requires that Laetrile

l6a

T.V. v. Video Independent Theaters, 386 F.2d 592,

594 (10th Cir. 1967), cert. denied, 390 U.S. 1014,

88 S.Ct. 1265, 20 L.Ed.2d 163 (1968). Administra-

tive regulations must be consistent with the statute’s

purposes and reasonably adapted to carry out those

purposes. Greyhound Corporation v. United States,

221 F.Supp. 440, 444 (N.D.IIl. 1963).

Having reviewed the Decision of the Commissioner

of Food and Drugs on Laetrile, dated July 29, 1977,

be considered exempt from “new drug” status to the extent

that it is currently being used for the same purposes and

under the same conditions and labeling as on October 9, 1962.

The Act says that the 1962 “new drug” amendments “shall

not apply to... [drugs] when intended solely for use under

conditions prescribed [October 9, 1962] ...” (emphasis sup-

plied) Pub. L. No. 87-781 § 107(c) (4) (1962) reprinted at 21

U.S.C. § 321, n.

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 wrappers, 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, 355 U.S. 345, 347-50, 69 S.Ct. 106,

93 L.Ed. 52 (1948); United States v. Urbuteit, 3385 U.S. 355,

357, 69 S.Ct. 112, 98 L.Ed. 61 (1948). Commissioner’s De-

cision (R 523 at 148).

1962 labeling characterizes Laetrile as a palliative agent for

use in “cancers beyond aid by standard agents,” and warns

that “it is not to be employed to the exclusion of surgery,

radiation or similar standard modalities so long as they are

indicated.” Affidavit of Robert S. K. Young, Ph.D. (R 201 at

H234) If “generally recognized as safe” by qualified experts,

the “1962 grandfather clause” prevents Laetrile from being

classified or treated as a “new drug” when labeled in sub-

stantially the same manner as previous to October 10, 1962.

See the “1962 Grandfather Clause” Issue, p. 9.

eS ee

17a

(42 Fed.Reg. 39768-39806 (1977)), and the entire

administrative record upon which that decision was

based, and the pleadings and briefs, the court con-

cludes that such decision is arbitrary, capricious, that

it represents an abuse of discretion and is not in

accordance with law. Consequently, it must be set

aside and vacated. 5 U.S.C. § 706(2).

ISSUES

The following issues are presented:

1. Is Laetrile a drug?

2. Is Laetrile a “new drug” within the mean-

ing of §201(p) of the Federal Food, Drug

and Cosmetic Act (21 U.S.C. §321(p) in

that it is not generally recognized, among ex-

perts qualified by scientific training and ex-

perience to evaluate the safety and effective-

ness of drugs, as safe and effective for use

in the cure, mitigation, treatment, or preven-

tion of cancer in man, and in that it is not

“grandfathered” by one of the Act’s pro-

visions applicable to those drugs marketed

before the current “new drug” statutory pro-

vision became effective?

3. Is the agency action in question violative of

plaintiffs’ constitutional rights?

18a

NEW DRUG ISSUE

FDA asserts authority to preclude Laetrile’s im-

portation or interstate transportation on the basis

that it is a “new drug” within the Act’s meaning.

“No person shall introduce or deliver for introduction

into interstate commerce any new drug,” unless an

application on its behalf has been approved. 21 U.S.C.

§ 355(a). It is conceded that no such application in

regard to Laetrile has been approved, but plaintiffs

challenge the Commissioner’s categorization of Lae-

trile as a “new drug.”

Plaintiffs initially question the determination that

Laetrile is a drug, contending instead that it is a

vitamin or food. “Drug” is defined to include “ar-

ticles intended for use in the diagnosis, cure, mitiga-

tion, treatment, or prevention of disease in man or

other animals ... .” 21 U.S.C. § 821(g) (1) (B).

The court need not rule whether Laterile is a food

or a vitamin, since, in any event, its well-recognized

use in the treatment of cancer renders it a drug

within the context of the statutory definition.°

8’ Numerous court decisions have emphasized that it is the

intended use of an article which determines whether or not

it is a “drug” and that even the most commonly ingested

foods and liquids are “drugs” within the meaning of the Act

if their intended use when distributed in interstate commerce

falls within the definition of § 321(g) (1). See e.g. Bradley v.

United States, 264 F. 79 (5th Cir. 1920) (mineral water) ;

United States v. “Vitasafe Formula M,” 226 F.Supp. 266, 278

19a

THE “GENERALLY RECOGNIZED ...

AS SAFE AND EFFECTIVE” ISSUE

If Laetrile’s composition is such that it is generally

recognized among experts qualified by scientific train-

ing and experience to evaluate the safety and effec-

tiveness of drugs, as safe and effective for use in the

treatment of cancer, it is not a “new drug” within

the Act’s meaning and not subject to the asserted

FDA regulation. 21 U.S.C. § 321(p) (1).

Unquestionably, the administrative record in this

case reveals a substantial and well-developed contro-

versy among medical professionals and other scien-

tists as to the efficacy of Laetrile.

Advocates of Laetrile’s use in cancer treatment in-

clude many highly educated and prominent doctors

(D.N.J. 1964) remanded on other grounds, 345 F.2d 864 (3rd

Cir. 1965) cért. denied, 382 U.S. 918, 86 S.Ct. 290, 15 L.Ed.2d

232 (1965) (vitamin and mineral capsules); United States v.

250 Jars ... Fancy Pure Honey, 218 F.Supp. 208, 211 (E.D.

Mich. 1963) affirmed, 344 F.2d 288 (6th Cir. 1965) (honey);

United States v. 46 Cartons, etc., 118 F.Supp. 336, 338 (D.

N.J. 1953) (cigarettes); United States v. Research Labora-

tories, 126 F.2d 42 (9th Cir. 1942), cert. denied, 317 U.S. 656,

63 S.Ct. 54, 87 L.Ed. 528 (1942); Hanson v. United States,

417 F.Supp. 30 (D.Minn. 1976) (Laetrile); United States v.

Article Consisting of 36 Boxes, etc., 284 F.Supp. 107 (D.Del.

1968) affirmed, 415 F.2d 369 (3rd Cir. 1969); United States

v. 3 Cartons, etc., 182 F.Supp. 569, 573 (S,D.Cal 1952).

20a

and scientists’ whose familiarity and practical ex-

perience with the substance vastly exceeds that of

their detractors. To deem such advocacy “quackery”

* Proponents of the use of Laetrile include:

Dean Burk, Ph.D., in biochemistry from the University of

California. A research scientist possessing 35 years’ experi-

ence with the National Cancer Institute, Dr. Burk is the

former head of the Institute’s Cytochemistry Section. (R 302;

Tr. 401).

Charles Gurchot, Ph.D., in chemistry and physiology from

Cornell University, former Assistant professor of pharma-

cology, University of California Medical School at San Fran-

cisco. (R 302 at J-206).

Chauncey D. Leake, Ph.D., former associate professor of

pharmacology at University of Wisconsin. (R 302 at J-200).

Raymond Ewell, Ph.D., in chemistry from Princeton. (R 302

at J-196).

Phillip Binzel, M.D., (Tr. 360); John A. Richardson, M.D.

(R 510, Ex. 1 and Tr. 462); The Honorable Lawrence P.

McDonald, M.D., Congressional Representative from the State

of Georgia (R 509); Ernst T. Krebs, Sr., M.D., and Dr. Ernst

T. Krebs, Jr., (Tr. 228); perhaps as many as 600 American

M.D.’s or more have employed and are advocating the use of

Laetrile in cancer treatment. (R 313 at J-255).

David Rubin, M.D., surgeon at Beilinson Hospital and can-

cer researcher at Hadassah Hospital in Jerusalem, Israel. (R

510, Ex. 12).

Mario A. Soto, M.D., of Mexico, authorized by the Na-

tional Cancer Institute to conduct independent investigational

studies with the Institute’s cancer drugs. (R 286; Tr. 478).

Hans A. Nieper, M.D., Hannover, West Germany; Ernesto

Contreras, M.D., Tijuana, Mexico; Shigeaki Sakai, M.D., of

Tokyo, Japan; Etore Guidetti, M.D., Brazil. (R 507).

Many doctors testify that Laetrile can confer an “improved

quality of life’ even upon patients who ultimately die, by

reducing their pain and discomfort. For example, see P. E.

Binzel, Jr., M.D., (Tr. 362); David Rubin, M.D. (R 510, Ex.

12.)

2la

distorts the serious issues posed by Laetrile’s promi-

nence and requires disregarding considerable exper-

tise mustered on the drug’s behalf.

While the record reveals an impressive consensus

among the nation’s large medical and cancer-fighting

institutions as to Laetrile’s ineffectualness, a discon-

certing dearth of actual experience with the substance

by such detractors is revealed.

Special problems, medical, legal and philosophical,

arise when applying the “generally recognized as safe

and effective” standards of the Act to drugs em-

ployed in the treatment of cancer. There are many

thousands of terminally ill cancer patients each year

whose diseases have progressed to a point where, for

them, no drug exists which can fairly be termed “gen-

erally recogrized as safe and effective.” These are

the persons who have been told they are beyond help

and have been sent home to die. Should further

treatment of these people be precluded by the Act?

Certainly not. Individuals for whom no orthodox cure

is available surely are entitled to select a health-care

approach with which they feel compatible.”

10 Not all members of America’s leading cancer institutions

are unalterably opposed in all context to Laetrile‘s use. “I have

stated before, ... that if the patient has exhausted the bene-

fits of conventional treatment and does not mind the financial

outlay, I see no harm in his taking Amygdalin in the way it

has generally been used.” Affidavit of C. Chester, Ph.D., vice-

president and associate director for administrative and aca-

demic affairs of the Sloan-Kettering Institute for Cancer

Research, New York. (R 195).

22a

Nonetheless, while Laetrile’s use in cancer treat-

ment is widespread, its efficacy may, for statutory

purposes, be inadequately documented. A drug can

be “generally recognized” by experts as effective for

intended use within the meaning of the Act only when

that expert concensus is founded upon “substantial

evidence” as defined in § 505(d), 21 U.S.C. § 355(d).

Weinberger v. Hynson, Westcott & Dunning, supra,

412 U.S. at 682, 93 S.Ct. 2469.*

The current debate is fierce. The issue appears

largely unresolved as to Laetrile’s true effectiveness,

in large part because FDA has prevented adequate

testing on humans. Nevertheless, the evidence of rec-

ord does not render the Commissioner’s conclusion

that Laetrile is not “generally recognized as safe and

effective” arbitrary and capricious.

Significantly, however, a drug not recognized as

safe and effective still “shall not be deemed to be a

‘new drug’ if at any time prior to [this] enactment

[October 10, 1962] . . . it was subject to the Food

and Drugs Act of June 30, 1906, as amended, and if

at such time its labeling contained the same represen-

1 “TT he term ‘substantial evidence’ means evidence con-

sisting of adequate and well-controlled investigations, includ-

ing clinical investigations, by experts qualified by scientific

training and experience to evaluate the effectiveness of the

drug involved, on the basis of which it could fairly and re-

sponsibly be concluded by such experts that the drug will have

the effect it purports or is represented to have under the con-

ditions of use prescribed... .” 21 U.S.C. § 355(d).

23a

tations concerning the conditions of its use....” 21

U.S.C. § 3821(p) (1).”

Many believe that simply administering Laetrile to

tumor-bearing mice, particularly when the results of

such tests are so much in controversy,” is not disposi-

tive of the issue. Laetrile proponents often submit

that it should be utilized in conjunction with a dietary

2 “The effect of this definition is that there is a twofold

grandfather clause exemption which is capable of removing

Laetrile from the new drug category even if it is not recog-

nized by the experts as being safe and effective which, by the

way, does not say it is unsafe and ineffective. The first of

these grandfather exemptions comes from transitional pro-

visions attached to the 1962 Amendments to the Food, Drug

and Cosmetic Act of 1938. The second grandfather exemption

arises from provisions attached to the 1938 Act when it super-

seded the original Food and Drug Act of 1906.” Rutherford v.

United States, 542 F.2d 1137, 1141 (10th Cir. 1976).

18 Knowledgable experts have expressed sharp criticism of

certain prominent Laetrile tests on animals in which the sub-

stance was determined ineffective. Note the analyses of Dr.

Bernard Kenton of the City of Hope National Medical Center,

Los Angeles, California. (R 507 at N249); and Dr. Dean

Burk (R 302 at J-117) also those of Dr. Michael Fox, chair-

man of the Biomathematics Department of the City of Hope

National Medical Center, and assistant professor of bio-

mathematics at UCLA, and Harold Hornsby, research scientist

with NASA and a Fellow of the Royal Statistical Society in

London (R 313 at J-253 and 254). Sloan-Kettering researcher

Dr. Kanematso Sugiura performed at least six different tests

in which he concluded that Laetrile was effective in combatting

certain types of tumors; the Institute subsequently released

other test results reportedly contradicting Dr. Sugiura’s

findings. Dr. Sugiura is quoted as saying: “It is still my belief

that amygdalin cures metastases.” (R 313 at J-241).

24a

regimen essential to the drug’s success.* Significantly,

animal testing sheds little light on the placebo effect,

that is, the healing effect accompanying the psycho-

logical uplight and renewed sense of hope which often

attends administration of a substance in which a pa-

tient strongly believes.” It is only when the sub-

stance is openly used, and its results carefully ob-

served and fully reported that this controversy will

be resolved.

14“T know of no doctor throughout the world who is now

using Amygdalin who does not agree that the maximum bene-

fit from Amygdalin is obtained when it is used in combination

with other vitamins, enzymes and proper diet.” P. E. Binzel,

Jr., M.D. (Tr. 363).

15 “Humans are very susceptible, particularly when ill 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 frequently do just what they

have been told to expect. This effect has long been recognized

in medicine and is termed ‘placebo effect.’ ” Affidavit of Daniel

S. Martin, M.D. (R 185 at 7). One noted expert argues:

“.. the only way to achieve the placebo effect, itself, is for

some authority to indicate that the drug could be effective.

There is no official, no ethical way to do that.” R: Lee Clark, »

M.D., president of the American Cancer Society. (R 307 at J-

228). The record clearly reveals, however, that many doctors

are convinced that Laetrile is capable of playing a legitimate

and significant role in the treatment of cancer, and are per-

fectly willing to administer it on that basis. See n. 6.

25a

THE “1962 GRANDFATHER CLAUSE” ISSUE

If on October 9, 1962, Laetrile was marketed for

the same uses for which it is presently being sold

and if generally recognized by qualified experts as

safe for those uses, the grandfather clause exempts

it from the test of general recognition by experts as

being both safe and effective for its claimed uses.

Rutherford v. United States, 542 F.2d 1137 (10th

Cir. 1976) supra; Tyler Pharmacal Distributors, Inc.

v. United States Department of HEW, 408 F.2d 95,

99 (7th Cir. 1969) .*

Based upon FDA’s own administrative record in

this case and the applicable statutes and case law,

the court concludes that the agency’s classification of

16 “One of the transitional provisions enacted in 1962 was

as follows:

‘In the case of any drug which, on the day immediately

preceding the enactment date (October 10, 1962), (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 (21 U.S.C. Section 321(p)),

and (C) was not covered by an effective (new drug)

application under 505 of that Act (21 U.S.C. Section

355), the amendments 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. Pub. L. 87-781, Section 107(c) (4), reprinted at 21

U.S.C. Section 321 note.’” Rutherford v. United States,

(10th Cir. 1976 supra, 542 F.2d at 1141.)

26a

Laetrile “ as a “new drug” is “arbitrary, capricious,

17The Commissioner’s report concludes that the terms

“Laetrile’ and “Amygdalin” do not refer to the same sub-

stance and cannot be used interchangeably. Such report as-

signed to Amygdalin the chemical formula of D-mandeloni-

trile-beta-D-glucoside-6-beta-D-glucoside, while assigning to

Laetrile, on the basis of a formula derived by Dr. Ernst T.

Krebs, Jr., the designation 1-mandelonitrile-beta-glucoronic

acid. The record reveals that the latter formula has reference

to a theoretical model that Krebs developed but apparently

ei‘her never synthesized or never chose to employ to any ma-

terial extent. (R 183) The substance in controversy in this

case, and with which this opinion is concerned, is described

by the first formula; as recognized by the Commissioner,

Laetrile’s proponents and opponents alike refer to the sub-

stance both as “Amygdalin” and “Laetrile.” Such substance

is that same Amygdalin or Laetrile to which the Commissioner

made reference in his “Laetrile—Notice of Administrative

Rule Making Hearing” (42 Fed. Reg. 10066 (1977)) when

he stated: “Laetrile is the name of a product whose major

component or ingredient is the chemical amygdalin, a sub-

stance that occurs naturally in the pits of apricots, peaches,

bitter almonds and in other plant material .. .” and it “... has

been known, tested, and used [as a cancer remedy] for more

than 25 years... .”

Numerous judicial determinations have been made equating

Laetrile and Amygdalin. See United States v. Spectro Foods,

Corp., Civ-76-101, (Dist.N.J. 1976) affirmed in part reversed

in part, 544 F.2d 1175 (3rd Cir. 1976); United States v. Gen-

eral Research Laboratories, 397 F.Supp. 197 (C.D.Cal. 1975);

Rutherford v. United States, 399 F.Supp. 1208, 1211 (W.D.

Okl. 1975), 424 F.Supp. 105-06 (W.D.Okl. 1977).

The administrative record clearly establishes that Laetrile

and Amygdalin are equivalent and have been recognized: as

such for over 20 years. The American Cancer Society, in a

pamphlet entitled “Questions Most Frequently Asked About

‘Laetrile’,” answered in response to the question, “What is

Laetrile?”: “The scientific name of the drug is amygdalin;

‘Laetrile’ is a registered trade mark.” (R 173 at 144D) Frank

27a

an abuse of discretion” and as a matter of law un-

supportable. Citizens to Preserve Overton Park v.

Volpe, supra, 401 U.S. at 416, 91 S.Ct. 814; 5 U.S.C.

§ 706(2) (A).

The record and the law reasonably support but one

conclusion: Laetrile (Amygdalin) has been commer-

cially used and sold in the United States for the treat-

ment of cancer for well in excess of 25 years, during

J. Rauscher, Jr., Ph.D., Director of the National Cancer Pro-

gram for the National Cancer Institute equates Laetrile with

Amygdalin in his “Statement Concerning Laetrile.” (R 173

at 222D) So too does Dean Burk, Ph.D., former head of the

Cytochemistry Section of the National Cancer Institute (R 302

at J-60, J-71); Raymond Ewell, Ph.D., former professor of

chemistry at the State University of New York at Buffalo

(R 302 at J-196); Thomas H. Jukes, Ph.D., professor in resi-

dence in medical physics and research biochemist, University

of California at Berkeley. (R 416 at M-77-78).

The affidavit of W. Sherwood Lawrence, M.D., a medical

officer of the Department of Health of the State of California,

the Executive Secretary of the State of California Cancer

Advisory Council, and a Laetrile opponent, clearly establishes

Laetrile and Amygdalin as being one and the same. (R 183).

Numerous “official samples” of Laetrile collected by the

State of California over a period of years and chemically

analyzed have established the substance as Amygdalin. Anal-

ysis by the AMA of the Laetrile employed by the originators

of the term, Drs. Ernst T. Krebs, Sr. and Jr., determined the

substance to be Amygdalin, as did the 1953 report on Laetrile

by the Cancer Commission of the California Medical Associa-

tion. The report stated: “Chemical analyses done independ-

ently for the Commission have identified in the product dis-

tributed as Laetrile only the presence of a natural Laetrile

termed Amygdalin.” (R 183 at 29F) The testimony of both

Drs. Krebs also clearly establishes this fact. (R 183 at 196F;

Tr. 228).

28a

which time it has been “generally recognized” by

qualified experts as safe * for such use.

18 The issue of Laetrile’s safety possesses several different

facets. FDA contends that even if Laetrile were marketed

prior to 1962 it must be shown to have been “effective” as well

as “safe” since it was used in the treatment of a “life-

threatening disease,” cancer, and thus was not safe if ineffec-

tive. Commissioner’s Decision (R 523 at 189). Such legal

premise could be extended to abrogate a!l distinction between

the terms “safe” and “effective” and is unmeritorious; any

ineffective remedy may displace an effective one, regardless

of the disease’s severity, and in that sense is unsafe. The

Supreme Court in Weinberger v. Hynson, supra, stated that

“the 1962 amendments [of the Food, Drug and Cosmetic

Act] for the first time gave FDA power to scrutinize and

evaluate drugs for effectiveness as well as safety.” 412 U.S.

630, 93 S.Ct. 2483 (emphasis supplied). In any event, FDA’s

argument “may lose its force in the case of a terminally-ill

patient or in the case of a patient suffering from a disease

for which there are no ‘effective’ remedies.” Rutherford v.

United States, (10th Cir. 1976), supra, n. 5, 542 F.2d at 1142.

FDA erred as a matter of law when it determined that a can-

cer drug cannot be “grandfathered” on the basis of pre-1962

use unless shown to be effective as well as safe. As to the

danger that Laetrile’s use results in postponement of conven-

tional treatments to the patient’s detriment, it is to be noted

that outlawing Laetrile has not resulted in disuse but merely

in large numbers of Americans traveling to Mexico. It has

been estimated that each year 20,000 Americans afflicted with

cancer travel to Mexico to receive Laetrile treatments. (R 313

at J-242) Thus Laetrile’s illegality actually tends to remove

many patients from the care of their American doctors.

As to selecting Laetrile over orthodoxy, the record dis-

closes that the vast majority of Laetrile patients first under-

went the relevant conventional treatments. While isolated,

tragic instances may have occurred in which Laetrile was used

and conventional treatments avoided, to a patient’s detriment,

29a

Amygdalin was reportedly first isolated from bit-

ter almonds by the French Chemists Robiquet and

Burton-Charland in 1830. The name “Amygdalin”

was derived from the word “Amygdala,” Greek for

almond. Commissioner’s Decision. (R 523 at 23).

Reports of its employment in the treatment of can-

cer were first published in 1845 and 1846.”

In 1949 doctors utilizing Amygdalin as a cancer

treatment in the United States coined the term “Lae-

trile.” *°

Extensive use of the substance, its commercial

availability,” and its recognition as being safe, all

such persons might well have opposed orthodox approaches

and remained untreated even were Laetrile unavailable.

Too, Laetrile may be administered either parenterally or-

orally; the latter method, some contend, is more dangerous

than the former. While the record discloses certain differences

of opinion on this issue, the vast amount of practical experi-

ence of actual experimenters and users, in administering

Laetrile both parenterally and orally, has established its non-

toxicity. See n. 15; also see Tr. 311. One journalist reports

that 50,000 American cancer patients are currently using over

1 million grams of Laetrile per month. (R 507).

19 J. D. Inosemtzoff, in Gazette Medicale de Paris, No. 37

September 13, 1845, pp. 577-582; Journal Chirurgie/Augen-

heilkunde 1846. (R 302, Ex. A, at J-65).

20 “Tn 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.” Affidavit of Ernst T.

Krebs, Sr., M.D. (Apr. 1965) (R 183 at 196F).

21“Use of a drug is investigational, as contrasted with

commercial, when that use is for the purpose of determining

30a

previous to 1962, are well-documenfed in the record.

Any restrictions placed on the commercial avail-

ability or use of Laetrile by FDA previous to July

29, 1977, when the administrative record and Com-

missioner’s Decision were filed, were unsupported by

any competent administrative record whatsoever and

subject to attack as a matter of law.”

The administrative record brooks little real contro-

versy as to Laetrile’s nontoxicity, particularly when

—- -- —— -——

whether, or demonstrating that, the drug in question is safe

and effective.” Commissioner’s Decision. (R 523 at 168).

While the record reveals many instances of investigational

use of Laetrile, extensive use of the substance as a part of

various doctors’ fundamental regimen in treating cancer is

also demonstrated.

The record’s whole tenor reasonably establishes the com-

mercial availability of Laetrile (Amygdalin) during the period

in question. As noted earlier, the substance was extracted well

over a century ago and has long been pharmaceutically recog-

nized. “Of my own personal knowledge, I know that both prior

and subsequent to 1938 amygdalin was readily available to

anyone who wanted it from United States suppliers of chemi-

cals ... [and that] amygdalin was listed and is still listed, as

a purchasable item in various chemical catalogs published in

the United States.” Charles Gurchot, Ph.D. in chemistry.

(R 302 at J-211).

Several documents in the record allude to a controversy in

California in the early 1950’s over variations in the price of

Laetrile (Amygdalin) among sellers. (R 183 at 105F-111F)

Note for example the letter from N. Schneider of Van, Waters

& Rogers, Inc., which clearly establishes the commercial avail-

ability of Amygdalin between 1952 and 1964. (R 183 at 108F).

22 See Rutherford v. United States (10th Cir. 1976), 542

F.2d 1137 supra; Rutherford v. United States, 424 F.Supp. 105

(W.D.Okl. 1977); and the record from the December 30, 1976,

“Hearing to Implement Tenth Circuit Court Ruling” pp. 13-14.

3la

administered parenterally, even at doses greatly ex-

ceeding amounts normally ingested.”

23 In the only laboratory study of record specifically designed

to determine the drug’s toxicity, it was observed: “Amygdalin,

at all doses studied, appears to be completely non-toxic in

laboratory mice.” Harold W. Manner Ph.D., Chairman, De-

partment of Biology, Loyola University, Chicago, Illinois (R

262). Of the various controversial tests studying Laetrile’s

efficacy on animal tumors, none have disclosed toxicity at

reasonable dosage levels.

Among the numerous scientists and physicians testifying

from first-hand experience with Laetrile and its effect on

humans, unanimity exists as to its nontoxicity.

Dr. Phillip Binzel, M.D., graduate of St. Louis University,

testified that he has personally given nearly 4,000 intravenous

injections of Amygdalin using doses up to 9 grams without

any adverse reaction. (Tr. 363).

Daniel S. Martin, M.D., who participated in the same

Sloan-Kettering experiments in which Dr. Sugiura detected

cancer inhibiting properties in Laetrile, and who disputed

Dr. Sugiura’s results, nonetheless concluded that there was

no doubt that Laetrile was nontoxic, at least if administered

parenterally. (Tr. 437).

Charles Gurchot, Ph.D., testified for the record in affidavit

form 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. This Amyg-

dalin was, according to his statement, administered ‘‘on pa-

tients intramuscularly and intravenously.” He further stated

that during this same period Amygdalin was being used to his

personal knowledge by approximately a dozen California

physicians in their treatment of cancer. Gurchot expressed

his belief that Amygdalin was generally recognized by ex-

perts as being safe for use in the treatment of cancer on or

prior to October 10, 1962. (R 302 at J-206).

Chauncey D. Leake, Ph.D., indicated in his affidavit 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

32a

School Hospital in San Francisco. He further indicates that

physicians and other scientists familiar with Amygdalin rec-

ognized it as safe at that time. (R 302 at J-200).

Dr. Dean Burk, former head of the Cytochemistry Section,

National Cancer Institute, Bethesda, Maryland, after testing

Amygdalin on rats, says the substance is “notably less toxic

to animal organisms than ordinary diet sugar,” and that

aspirin tablets are 20 times more toxic than an equivalent

amount of Amygdalin. (R 183 at 166F).

“Investigators have found that intravenous doses in excess

of 20 grams have been without toxic effect in healthy human

subjects, although occasionally a mild hypotensive effect may

be observed. Repeatedly, studies have indicated that pure

Amygdalin, when administered parenterally is astonishingly

devoid of toxic effects.” (R 183 at 166F).

Donald C. Thompson, M.D., of Morristown, Tennessee, testi-

fied as to his personal experience with administering Laetrile

to patients and affirmed the drug’s nontoxicity. (R 515).

In his report entitled “Use of Laetrile in the Prevention and

Treatment of Cancer,” Dr. David Rubin, M.D., surgeon at

Beilinson Hospital and cancer researcher at Hadassah Hospital

in Jerusalem, Israel, asserts: “Laetrile is nontoxic even in

very large injected doses.” (R 510, Ex. 12).

As another example of a practicing physician who has

extensively used Amygdalin and determined it to be nontoxic,

see the letter of The Honorabie Lawrence P. McDonald, Con-

gressional Representative from Georgia. (R 509 at N265-

68).

“Amygdalin (Laetrile) is totally non-toxic systemically,

at commonly applied dosages.” Hans A. Nieper, M.D., Hann-

over, West Germany. (R 302 at J-180).

While a doctor’s inability to control many variables po-

tentially relevant to curing a disease may impugn the credi-

bility of his perceptions as to a drug’s efficacy (see Wein-

berger V. Hynson, supra) his observations as to its toxicity

are much more reliable, since the relevant variables are more

manageable.

“(Laetrile) is totally nontoxic. Its lethal dose in mice and

rats, by injection, is about 25,000 miligrams per kilogram of

body weight. It is so nearly nontoxic that in some studies the

water, used as a dilutant presents a greater toxicity than the

33a

Interestingly, however, Laetrile’s candidacy for ex-

emption from “new drug” status rests less on its

“safeness” in fact than on its “generally recognized”’

reputation in that regard among qualified experts.

Durovic v. Richardson, 479 F.2d 242, 250 (7th Cir.

1973). The record clearly reflects that previous to

1962 Laetrile was generally recognized as safe.™*

vitamin.” The Journal of Applied Nutrition, Ernst T. Krebs,

Jr. (R 302 at J-187).

“|. . All the available facts indicate that Amygdalin is

essentially non-toxic to laboratory animals and to humans.”

Raymond Ewell, Ph.D. in chemistry from Princeton, retired

professor from the State University of New York at Buffalo.

(R 302 at J-196).

24“ Among experts qualified by scientific training and ex-

perience to evaluate the safety‘of chemical substances in drugs,

it is my information and belief that at least since the 1930’s -

pure amygdalin has been generally recognized as safe for use

by human beings either by injection, intravenosuly or intra-

muscularly, or by oral intake. For example, pure amygdalin

may be administered without adverse effect in amounts of

10 grams per day, orally or 3 grams intravenously to a 150

pound man... .” Charles Gurchot, Ph.D. (R 302 at J-211 and

212).

The authoritative publication, The Dispensatory of the

United States (1950 ed. p. 40) emphasizes that “Amygdalin

itself is practically non-toxic... .” Synopsis of Materia

Medica, Toxicology and Pharmacology, C. V. Mosby Company,

1944, p. 33, affirms that “the glucoside Amygdalin, given by

injection, produces no harmful effects.” (R 183 at 166F).

“With 45 years of study and research on the cancer prob-

lem, ... I have found no statements of data on demonstrated,

sustained pharmacological harmfulness to human beings of

amygdalin at any dosages recommended or employed by

physicians in the United States and abroad, up to the high

level of 200 milligrams per kilogram of body weight per day

(equals 15 grams-75 kilogram man-day), administered either

34a

orally or parenterally; and, more specifically no such state-

ments by official opponents of the use by humans of amygdalin,

including comment in their major publications. Few sub-

stances have been so widely investigated regarding non-

toxicity and chemical definition as has amygdalin, by pharma-

cologists and chemists in many countries of the world, for over

125 years. .. . Amygdalin has been known and widely recog-

nized for over one hundred years as nontoxic for man.” Dean

Burk, Ph.D., from the pamphlet Vitamin B-17 ...a Brief on

Foods and Vitamins. (R 302 at J-69 and J-65).

In its 1963 “Report on the Treatment of Cancer With Beta

Cyanogenetic Glucosides (‘Laetriles’)” the only potential

danger discerned by the Cancer Advisory Council of the State

of California was “that the use of one or more of these sub-

stances in early cancer, to the exclusion of conventional treat-

ment might well be dangerous since treatment with acceptable,

curative methods (surgery or radiation) would thereby be

delayed potentially until such time as mestastases were mani-

fest and the cancer might therefore no longer be curable. (R

183 at 246F) No toxicity was reported in the 1953 case study

report of the Cancer Commission of California Medical As-

sociation.

It is only within the context of FDA’s creation of this record

that the specter of Laetrile’s toxicity has even been raised.

The drug’s reputation for nontoxicity, even among its oppon-

ents, is amply documented. See, for example: “Harmless, but

Ineffective Remedies,” The Journal of Pharmaceutical Scien-

ces, Oct., 1975. (R 180 at 190E) FDA allegations of toxicity

appear to be more of an afterthought offered to bolster their

other conclusions, rather than a reasoned conclusion based on

a detached, impartial view of the record.

While apricot kernels can be poisonous if ingested in very

large quantities, such contain enzymes not present in Amyg-

dalin; thus, the toxicity of apricot kernels and Amygdalin are

not comparable. Deposition of Raymond Ewell, Ph.D. (R 302

at J-197).

35a

THE “1938 GRANDFATHER CLAUSE” ISSUE

An added ramification of the Act’s grandfather

clause is that a drug may escape the “new drug”

machinery if it was marketed or officially recognized

as a drug at any time before June 25, 1938, but after

June 30, 1906, if the prescribed conditions for its use

are unchanged. Thus, if Laetrile were marketed or

officially recognized during those years as a cancer

drug, it would not be subject to “new drug” instru-

mentalities of the 1962 amendments even though not

generally recognized as safe or effective. Rutherford

v. United States, (10th Cir. 1976) supra, 542 F.2d

at 1142. ;

While Amygdalin (Laetrile) was indeed employed

in combatting cancer previous to 1938, the record fails

to establish the details of its use during that period

sufficiently to successfully challenge FDA’s denial of

this exemption.

“CONSTITUTIONAL ISSUES”

In plaintiffs’ constitutional challenge of FDA’s pro-

scription they invoke rights fundamental to a free

society and inextricably related to enumerated con-

stitutional concepts.

While the Constitution does not explicitly mention

a right of personal privacy, it is unchallengeable

“that a right of personal privacy, or a guarantee of

36a

certain areas or zones of privacy, does exist under the

Constitution.” Roe v. Wade, 410 U.S. 113, 152, 93

S.Ct. 705, 726, 35 L.Ed.2d 147 (1973). This right

has been discerned within the penumbras of the Bill

of Rights, and specifically within the language of the

First, Fourth, Fifth, Ninth and Fourteenth Amend-

ments to the Constitution, Roe v. Wade, supra. “...

only personal rights that can be deemed ‘fundamen-

tal’ or ‘implicit in the concept of ordered liberty,’

. are included in this guarantee of personal pri-

vacy.”

Mr. Justice Douglas referred to “the freedom to

care for one’s health and person” as coming within

the purview of this right. Doe v. Bolton, 410 U.S.

179, 213 (1973), 93 S.Ct. 739, 758, 35 L.Ed.2d 201

(concurring opinion). “The right of privacy,” Jus-

tice Douglas proceeded, “has no more conspicuous

place than in the physician-patient relationship ... .”

Doe, supra at 219, 93 S.Ct. at 761. He concluded:

“The right to seek advice on one’s health and the right

to place reliance on the physician of one’s choice are

basic... .” Doe, supra.

This right of privacy has been characterized more

than once as simply the right “to be let alone.” Doe

v. Bolton, supra, at 213, 93 S.Ct. 739 (Justice Doug-

las concurring) ; Olmstead v. United States, 277 U.S.

438, 478, 48 S.Ct. 564, 72 L.Ed. 944 (Justice Bran-

deis dissenting). That right includes the privilege of

an individual to plan his own affairs, for “ ‘outside

areas of plainly harmful conduct, every American is

37a

left to shape his own life as he thinks best, do what

he pleases, go where he pleases.’” Kent v. Dulles,

357 U.S. 116, 126, 78 S.Ct. 1113, 1118, 2 L.Ed.2d

1204; Doe v. Bolton, supra 410 U.S. at 213, 93 S.Ct.

739, 758 (concurring opinion).

Many knowledgable and concerned individuals are

questioning the effectiveness and wisdom of our ortho-

dox approaches to combatting cancer. The correct-

ness of their criticisms may not be determined for

many years, and in any event such discussion pro-

vokes controversies largely beyond the realm of the

courts’ function. Nonetheless, it appears uncontro-

vertible that a patient has the right to refuse cancer

treatment altogether, and should he decide to forego

conventional treatment” does he not possess a fur-

25 Such a decision is by no means necessarily indicative of

suicidal tendancies. Dr. Hardin Jones of the University of

California has presented impressive evidence in support of the

thesis that in some instances at least untreated cancer victims

outlive treated ones. (R 507) Conventional modes of treat-

ment, particularly radiation and chemotherapy, can cause

extensive damage to healéfy organs and tissues as well as can-

cerous ones. Some argue that in destroying the body’s natural

defense mechanisms such approaches often destroy important

weapons crucial to an effective fight against cancer and also

greatly increase a patient’s vulnerability to other life-threaten-

ing diseases as well.

Patients possessing particularized complicating factors, such

as old age, frail physical constitutions, or certain types of

religious convictions, might also understandably decide to

forego the rigors of such conventional methodologies.

Even doctors who opposes the use of Laetrile will generally

concede as to orthodox modes of treatment (surgery, radiation

and chemotherapy): “. . . the treatments that are available

are very often disfiguring; they can be painful; they can be

38a

ther right to enlist such nontoxic treatments, however

unconventional, as he finds to be of comfort, particu-

larly where recommended by his physician?

We must carefully distinguish between the consti-

tutional standards applicable to the use of an innocu-

ous substance as a health-care aid, and those stand-

ards which apply to the promotion or advertisement

of that same substance.

Plaintiffs seek to exercise final control over the

handling of their own individual health-care prob-

lems. Numerous cancer patients possess extensive

first-hand experience with Laetrile which has led

them to believe, correctly or not, that the substance

has eased their pain and prolonged their lives. Such

personal convictions are not readily dispelled by gov-

ernment pronouncements or affidavits to the con-

unpleasant; they can even be risky.” Emil J. Freireich, Pro-

fessor of Medicine at the University of Texas, School of Medi-

cine, Houston. (Tr. 204)

In attacking the credibility of “cures” reported to have

been effectuated by Laetrile, FDA argues that in many such

instances the person involved may never even have had cancer.

“Even where the diagnosis has been done by someone other

than a Laetrile proponent, a mistake is possible. Some cancers

which are discussed in reference to Laetrile are very difficult

to diagnose histologically. Thus, a diagnosis of cancer may

often on later review be reversed.” Commissioner’s Decision

(R 523 at 227) This analysis is hardly reassuring to indi-

viduals such as plaintiff Glen Rutherford, whose proposed

surgery, a colostomy, would have unalterably lessened the

quality of his life, irrespective of the ultimate outcome of his

illness. (See Rutherford v. United States, 399 F.Supp. 1208

(W.D.Okl. 1975).

39a

trary.” When deprived of treatment in this country,

they go elsewhere, and in so doing are denied close

contact with their families and family doctors.

Unintentionally FDA has wrought needless hard-

ship and expense to countless individuals required to

travel to Mexico or Germany in order to utilize Lae-

trile. If it were more readily available in this coun-

try, perhaps many patients currently obtaining the

treatment abroad could be persuaded to remain under

their doctor’s care here and use the substance in con-

junction with conventional treatments.

The final consequences are ultimately borne by

those whose bodies are the battleground on which

cancer’s war is waged. Many perceive the drug’s

acquisition as a life and death matter, and are un-

derstandably frustrated and enraged over attempts

by their own government to deny them the right to

decide for themselves questions of such a personal

and grave nature.

Doubtless FDA desires to protect the public. Such

good intention, however, is not the overriding issue.

Many of us allocate time and money and other re-

sources in ways susceptible to just criticism by many

standards. Nonetheless, our political ideals empha-

size that the right to freely decide is of much greater

significance than the quality of those choices actually

made. It is never easy for one who is concerned and

feels himself particularly knowledgable to observe

26 “There can be few patients taking Laetrile in this country

today who do not know that the government and most experts

consider it worthless.” Commissioner’s Decision (R 523)

40a

others exercise their freedom in ways that to him

appear unenlightened.

As a nation, however, historically and continuously,

we are irrevocably committed to the principl> that

the individual must be given maximum latitude in

determining his own personal destiny.

To be insensitive to the very fundamental nature

of the civil liberties at issue in this case, and the fact

that making the choice, regardless of its correctness,

is the sole prerogative of the person whose body is

being ravaged, is to display slight understanding of

the essence of our free society and its constitutional

underpinnings. This is notably true where, as here,

there are no simple answers or obvious solutions, un-

certainty is pervasive, and even the best efforts leave

so much to be desired.”

When certain “fundamental rights” are invoked,

such as the right of privacy involved herein, regu-

lation may be justified only by a “compelling state

interest,” and legislative enactments “must be nar-

rowly drawn to express only the legitimate state in-

271977 Cancer Facts and Figures by the American Cancer

Society estimates that 1977 will have produced an estimated

690,000 new cancer cases; and that over 54 million Americans

now living will eventually have cancer, which is one out of

every four Americans living. The pamphlet also states that

over the years cancer will strike in approximately two of every

three families, that in the 1970’s there will be an estimated

3.5 million cancer deaths, 6.5 million new cancer cases, and

more than 10 million people under medical care for cancer.

Only about 1/3 of all people who get-cancer this year will be

alive five years after treatment, according to the publication.

(R 173 at 113D)

4la

terests at stake.” Roe v. Wade, supra, 410 U.S. at

155, 93 S.Ct. at 728. By denying the right to use a

nontoxic substance in connection with one’s own per-

sonal health-care, FDA™~ has offended the constitu-

tional right of privacy.

This court’s decision in this case in no way por-

tends the return of the traveling snake oil salesman.

As emphasized earlier, the right to use a harmless,

unproven remedy is quite distinct from any alleged

right to promote such. FDA is fully empowered un-

der other statutory provisions to combat false or

fraudulent advertising of ineffectual or unproven

drugs. See the Food, Drug and Cosmetic Act, Mis-

branded Drugs and Devices, 21 U.S.C. § 352 (1976) ;

and the Federal Trade Commission Act, Dissemina-

tion of False Advertisements, 15 U.S.C. § 52 (1975).

The Commissioner’s ‘‘Laetrile” Decision of July 29,

1977, must be vacated. An appropriate Order will

accordingly be entered herein.

ORDER

This action came on for determinatign by the court,

and the issues having been duly considered and a

28 Even if no such right existed generally, it would appear

that Laetrile’s use by terminally ill cancer patients who have

exhausted orthodox approaches of cancer patients interested

in using Laetrile only in conjunction with conventional meth-

ods would be constitutionally protected. While certain prob-

lems may attend exact definitions of “terminally ill,” the term

has a well understood meaning and is of practical significance

to our discussion.

42a

decision having been duly rendered as set forth in

the Opinion of even date herewith,

IT IS ORDERED, ADJUDGED AND DECREED:

1. The action of the Commissioner of Food and

Drugs dated July 29, 1977, is declared unlawful and

such action, findings and conclusions are hereby va-

cated, set aside and held for naught;

2. Laetrile (Amygdalin) is exempt from the “new

drug” requirements of 21 U.S.C. § 355(b) ;

3. The Secretary of Health, Education and Wel-

fare and his subordinates in the Food and Drug Ad-

ministration are hereby permanently enjoined and

restrained from interfering, directly or indirectly, or

acting in concert with United States Customs Service

or others, with the importation, introduction, or de-

livery for introduction into interstate commerce iy

any person of Laetrile (Amygdalin) for the reason

that application has not been filed or approved in the

manner provided by 21 U.S.C. § 355(b) for a “new

drug” ;

4. The Secretary of Health, Education and Wel-

fare and his subordinates in the Food and Drug Ad-

ministration are hereby permanently enjoined and

restrained from interfering with the use of Laetrile

(Amygdalin) for the care or treatment of cancer by

a person who is, or believes he is, suffering from the

disease ;

5. The Secretary of Health, Education and Wel-

fare and his subordinates in the Food and Drug Ad-

ministration are hereby enjoined and restrained from

43a

interfering with any licensed medical practitioner in

administering Laetrile (Amygdalin) in the care or

treatment of his cancer patients;

6. The Secretary of Health, Education and Wel-

fare shall distribute or cause to be distributed to all

personnel within the Food and Drug Administration

and the United States Customs Service concerned or

involved in the enforcement of the Food and Drug

Act copizs of the Opinion and Order herein, and shall

file with the Clerk of this Court within twenty (20)

days of the date hereof his certificate showing distri-

bution as required herein;

7. This Order is binding upon the Secretary of

Health, Education and Welfare, his agents, servants

_and employees in the Food and Drug Administration,

present and future, and upon those persons in active

concert or participation with them who receive actual

notice of this Order by personal service or otherwise;

8. The Clerk of this Court shall serve by certified

mail, deliver to addressee only, return receipt re-

quested, Joseph A. Califano, Secretary of Health,

Education and Welfare; Donald Kennedy, Commis-

sioner of the Food and Drug Administration; and

Vernon D. Acree, Commissioner of the U.S. Customs

Service and their attorneys of record, certified copies

of the Opinion and Order herein;

9. The Court hereby retains jurisdiction for all

further orders appropriate and necessary to enforce

this Order or to adjudicate any dispute arising here-

44a

under. Any complaints arising under this Order by

any party shall be heard by the Court on not less than

five (5) days notice to the opposing party.

45a

APPENDIX E

DEPARTMENT OF HEALTH, EDUCATION,

AND WELFARE

Food and Drug Administration

[Docket No. 77N-0048]

LAETRILE

Commissioner’s Decision

AGENCY: Food and Drug Administration.

ACTION: Notice.

SUMMARY: The Commissioner of Food and Drugs

announces that he has compiled a comprehensive ad-

ministrative 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

experts as a safe and effective cancer drug, and (2)

whether Laetrile is exempt from the premarket ap-

proval requirements for new drugs by virtue of the

“orandfather” provisions of the Federal Food, Drug,

and Cosmetic Act. The Commissioner concludes, after

careful review of this administrative record, includ-

ing oral argument presented at a public hearing,

that: (1) Laetrile 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

46a

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 concerning Laetrile are also set out.

EFFECTIVE DATE: August 5, 1977.

ADDRESSES: The transcript of oral argument pre-

sented at the public hearing, affidavits, written testi-

mony, 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 Administration, Rm. 4-65, 5600 Fishers

Lane, Rockville, MD 20857, between 9 a.m. and 4 p.m.,

Monday through Friday. In addition, one copy of the

administrative record (except two videotapes of inter-

views with cancer patients who had been treated with

Laetrile) is available for public examination at the

following Food and Drug Administration offices dur-

ing regular business hours: 850 Third Ave., Brooklyn,

NY 11232; 880 W. Peachtree St., Atlanta, GA 30309;

483 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., Seat-

tle, WA 98104.

FOR FURTHER INFORMATION CONTACT:

Tenny P. Neprud, Compliance Regulations Policy

Staff (HFC-10), Food and Drug Administration,

Department of Health, Education, and Welfare,

5600 Fishers Lane, Rockville, MD 20857, 301-

443-3480.

CEES SK

47a

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 rulemaking 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 Administration (FDA) was ordered to develop

an administrative record concerning the following two

issues:

1. Whether the product Laetriie (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 quali-

fied by scientific training and experience to evaluate

the safety and effectiveness of drugs, as safe and

effective for use in the cure, mitigation, 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 exempt from the premarket

approval requirements of section 505 of the act (21

U.S.C. 355) in that:

(a) At any time before June 25, 1938, it was sub-

ject 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

48a

its present labeling (“the 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, amcng experts qualified by sci-

entific training and experience to evaluate the safety

of drugs, as safe for use in the cure, mitigation, treat-

ment, or prevention of cancer in man; (3) On Octo-

ber 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 currently intended solely

for use under conditions prescribed, recommended, or

suggested in its labeling on October 9, 1962 (“the

1962 grandfather issue,” Pub. L. 87-781, section 107

The February 18, 1977, notice included detailed

information regarding the submission of testimony.

In response to the notice, over 400 submissions total-

ing more than 5,500 pages were received. These sub-

missions, representing the views of both proponents

and opponents of Laetrile, came from cancer patients,

consumers, experts in drug testing and cancer ther-

apy, physicians, State governments, universities, hos-

pitals, and interested organizations.

The District Court, in directing FDA to develop an

administrative record, suggested that the agency in-

vite the following individuals to participate in the

administrative proceeding: Dr. Dean Burk, Ernst

Krebs, Jr., Mike Culbert, Edward Griffin, and Mike

Spencer, Rutherford v. United States, supra, 424 F.

49a

Supp. at 108. The three individuals whose addresses

could be obtained were specifically invited to give their

views (R 3, 4, 5).* (Kenneth Coe, attorney for plain-

tiff Glen Rutherford, who had proposed that FDA

be required to invite the five named individuals, could

not provide the addresses for Griffin and Spencer and

agreed that invitations to the three individuals whose

addresses he could supply would suffice.) Mr. Griffin

did receive notice of the proceeding and he partici-

pated (see R 404). Written submissions 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 pro-

ceeding, separation of functions requirements were

observed between the Commissioner and persons ad-

vising him and the Bureau of Drugs and persons

advising it (see 21 CFR 10.55).

The February 18, 1977 notice stated that oral argu-

ment would be held in Kansas City on May 2. A sub-

sequent notice published in the FEDERAL REGISTER of

March 25, 1977 (42 FR 16191) set forth the exact

time and place: beginning at 9 a.m. on May 2 at

1 Submissions to the record are referred to by the number

assigned to them upon filing by the Hearing Clerk. When

exhibits or attachments accompany a submission, they follow

the record number of that submission, 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 et the time of oral argu-

ment are referred to as transcript exhibits, e.g., Tr. Ex. 1.

50a

the Radisson Muehlebach Hotel, Kansas City, MO.

Dr. John Jennings, Associate Commissioner for Medi-

cal Affairs, presided over the oral argument. Approxi-

mately 40 persons filed written requests to make oral

presentations; others took advantage of the oppor-

tunity to speak without the filing of such a request as

time allowed. Every person who wished to partici-

pate in, and who was present at, the oral argument

was given a opportunity to express his or her views.

In all, 47 persons made presentations. The transcript

of the oral argument 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, Ken-

neth Coe, Esq., spoke at oral argument (Tr. at 297,

442).

Written submissions presented at the time of oral

argument were made part of the record and consid-

ered 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 con-

sidered as part of the record. The Commissioner’s

opinion is based entirely upon the administrative

5la

record and does not reflect information brought to

FDA’s attention subsequent to the closing of that

record.

No legal memoranda were solicited by the Commis-

sioner 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 become a genuine public

health problem. Increasingly, doctors dealing with

cancer 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 Lae-

trile instead. The question has become one of life and

death for these patients and for others vho may be

convinced to use Laetrile in the future. For this rea-

son the Commissioner has considered not only the

evidence in the record addressed to the specific legal

issues remanded to FDA by the courts, but also the

great amount of evidence submitted by both pro-

ponents and opponents of Laetrile regarding other

issues of importance to the controversy over the use

of the drug. Since the Commissioner’s discussion of

these issues is necesarily detailed, he is setting forth,

for the reader’s convenience, an outline of that dis-

cussion as follows:

Ot m go fo

= pee

PSePre*

52a

I. LAETRILE

A. DEFINITION OF CANCER

B. 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?

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 Malignancy.

Sickle Cell Anemia.

Parasitic Diseases.

Regulating Intestinal Flora.

Hypotensive Effect.

D. THEORIES OF LAETRILE’S ACTION

Il. THE “NEW DRUG” ISSUE

A. GENERAL RECOGNITION OF EFFECTIVENESS

. Objective Evidence of Effectiveness.

(a) What are the Required Studies?

(b) The Need for Controlled Studies.

Se eee ee

al dt edt

SE pees nr ee

53a

(i) 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 “GRANDFATHER 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.

(i) Lack of General Knowledge of Use.

(ii) Lack of General Knowledge of For-

mulation.

(iii) Lack of General Knowledge of Con-

ditions of Use Suggested.

(iv) Lack of Safety Data in Scientific

Literature.

(v) Lack of Showing of Safety by Ade-

quate Testing.

(b) Statements by Experts.

tiveness in 1962.

- 9h

54a

IV. THE POPULARITY OF LAETRILE

A. LAETRILE AND OTHER UNPROVEN REMEDIES

The History of Cancer Quackery in the United

States.

Similarities Between Laetrile Promotion and

That of Other Recent ‘“Unproven” Cancer Reme-

dies. ~

(a) Mantle of Science.

(b) Attacks on the “Establishment.”

(d) Reliance on Testimonials.

(e) Lack of Scientific Publication.

(f) Nonexpert Supporters.

(g) Simplistic Theories of Causation and Reli-

ance on Diet.

(h) A Painless Cure.

(i) Only Proponents can Effectively 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 LAETRILE TESTIMONIALS

V. OTHER ISSUES REGARDING LAETRILE

A. USE OF LAETRILE OUTSIDE THE UNITED STATES

B. CLAIMS THAT LAETRILE IS A VITAMIN OR FOOD

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

2. Is Laetrile a Vitamin?

———- ———_ —_—__—_- - -—

Bia an. Ree tite 4

hate abana a2 Jt.

55a

(a) Proponents’ Claims.

(b) Vitamin Experts’ Position.

3. Dangers of Ingestion of “Vitamin B-17.”

C. FREEDOM OF CHOICE

Balancing Freedoms.

2. The Choice Is Not Free.

D, ALLEGATIONS OF BIAS

E. LIMITING USE TO TERMINAL PATIENTS

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, recommended 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 in-

clude “* * * all malignant neoplasms regardless of

the tissue of origin including malignant lymphoma,

Hodgkins disease, and leukemia” (R 173, Att., “Laws

and Regulations Relating to the Diagnosis and Treat-

ment of Cancer,” State of California, Division 2,

Chapter 7, Section 1705). For an almost identical

56a

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. Malignant neoplasms are “neoplasms that are

characterized by unregulated, uncontrolled, and un-

restrained growth and proliferation” (R 190 at

7 14; R 194 at 8; R 195 at § 11). It has been said

that the “distinguishing feature of cancer is its

ability to invade, erode and to metastasize to more

or less distant parts” (R 183, Att. 7 at 15). Metasta-

sis, 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 entities 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 100

at § 14; R186 at § 7-9). The cause of cancer 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 irri-

tation (e.g., a high frequency of cancer of the groin

in textile workers whose jobs required straddling a

metal shaft) (R 318 at 37), with cancer-causing

chemical substances called carcinogens (e.g., a nigh

frequency of lung cancer in chimney sweepers and

57a

coal miners probably caused by inhaling dust parti-

cles) (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 espoused by Laetrile’s proponents to

explain how cancer is caused. The first of these

theories is said to have been first developed by Pro-

fessor John Beard of Scotland. In 1902. Professor

Beard announced 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 charac-

teristics 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 be-

lieved that trophoblast cells could be expected to

develop at various places in the body from precursor

cells distributed throughout the body during the em-

bryonic stage. If the pancreas gland were function-

ing properly it would, in his theory, produce en-

zymes which destroy these trophoblast cells. If such

enzymes were not produced, cancer would occur (R

318 at 58-59).

The proponents of Laetrile have more recently

taken the position that cancer is a metabolic defi-

ciency or dietary disease (cf. R 302, Ex. H at 76-

77). It is claimed that cancer is a “* * * systemic,

58a

chronic, metabolic deficiency disease” (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 refuted by at least

one expert (Tr. at 223).

B. COMPOSITION AND IDENTITY OF “‘LAETRILE”

Several terms, such as “Laetyrile,” “laetrile(s),”

“amygdalin,” “nitriloside(s),” “vitamin B-17,” and

“Sarcarcinase” have in many instances been used in-

terchangeably by both proponents and opponents of

Laetrile. There are, however, distinctions among

these terms, which must be understood in order to

deal with the issues in this proceeding. The Commis-

sioner will discuss in detail what the record indicates

about the meaning of the terms “amygdalin,” “Lae-

trile,” “laetrile’ and “Sarcarcinase.”

1. Glossary

The following glossary provides a definition or de-

scription of the above terms and others that will be

used in this opinion:

Amygdalin: A specific chemical entity having the

chemical formula:

Whee

D-asalelonlte il e-bets-9-g locos ido 6 -beta-D-z luc oside

Gurch totes, Mh £4. ot 61).

59a

beta-Cyanogenic glucosides; beta-cyanophoric gluco-

sides; beta-cyanogenetic glucosides: Terms used

interchangeably in the record. In general, they are

used in the record to include compounds which can

break down to yield cyanide and glucose. The terms

are used to refer to amygdalin, a glucoside present

in kernals or seeds of practically all fruits (see,

e.g., R 302, Ex. H at 75; R 173, Att., California

Administrative Code, Section 10400.1 at 16; Tr. at

272). beta-Cyanogenic slucosides belong to the

large class of chemicals know as beta-cyanogenic

glycosides. (See definition of glucosides and glyco-

sides below.)

beta-Glucosidasc: An enzyme present in plants that

participates in the metabolism 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

mandelonitrile. The enzyme is found only in trace

amounts in animal tissues (R 173, Att., “The Vita-

min Fraud in Cancer Quackery” (hereinafter

“Vitamin Fraud”) at 345).

beta-Glucuronidase: An enzyme present in animal

tissues that participates in the metabolism of glu-

curonic acid derivatives (also called glucurono-

sides). The enzyme reportedly catalyzes the

breakdown of “Laetrile” (1-mandelonitrile-beta-

glucuronic acid) to free glucuronic acid and man-

delonitrile.

60a

Enzymes: Chemical compounds (all of them pro-

teins) produced by living organisms that serve as

catalysts in metabolic reactions. The suffix “‘-ase”

is given to most enzymes.

Glucoside: A term applied to any glycoside having

glucose as its sugar constituent.

Glucuronide; glucuronoside: Terms used in the rec-

ord to refer to chemical derivatives of glucuronic

acid. As an example, Laetrile is identified as 1-

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 encompasses gluco-

sides. Not all glycosides are glucosides (cf. The

Condensed Chemical Dictionary, 7th Ed. at 455).

Laetrile: A specific chemical entity having the chemi-

cal formula:

—Tosndel nltelte-dete-sioesronie acd CSerch Paden, fh

Bde at 702). The ame ““aetvile” vee perzortesiy sselgned

te this coupoced by Erest fT. Ecobs, Ir. (2 319 at 73)6

laetrile: A term used interchangeably with ‘Lae-

trile,’” “amygdalin,” “nitriloside,” and “vitamin B-

17” (R 302, Ex. A; R 183, Att. 10c). The term

is also used to include a number of compounds, in

which case it may appear as “laetriles.”

6la

Mandelonitrile: A specific chemical entity having the

chemical formula:

HO — at \

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

Nitriloside: A term proposed by Ernst T. Krebs, Jr.,

for all cyanophorioglycosides of dietary significance

(R 302, Ex. H. at 75).

Prunasin: A _ specific chemical entity having the

chemical formula: }

W208 cN

9 ‘

P aan&,

Mandelonitrile-Glucoside

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

Sarcarcinase: The name given to an enzyme prepara-

tion developed by Dr. E. T. Krebs, Sr., and de-

scribed by him in a 1933 patent application as a

mixture of the following enzymes—amygdalase,

prunase, oxynitrilase, catalase, peroxydase, 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-soluble, essentially nontoxic,

sugary compounds found in over “800 plants” (R

62a

302, Ex. H at 75) used interchangeably with

“nitriloside,” “Laetrile,” “amygdalin,” “beta-cyano-

genic glucosides” and “‘cynophoric glucosides” (e.¢.,

R 302, Ex. H at 75; R 302, Ex. A).

2. Whatis Amygdalin?

Amygdalin was reportedly first isolated from bitter

almonds by the French chemists Robiquet and Burton-

Charland in 1830 (R 178, Att., “Vitamin Fraud” at

345). The name “amygdalin” was derived from the

word “amygdala”, Greek for almond (R 302, Ex. L

at 7 9). Amygdalin is a chemical compound composed

of two glucose molecules and one molecule of man-

delonitrile. 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 prepara-

tion (later called emulsin) from bitter almonds was

capable 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 enzymes (beta-D-glucosidase and

beta-oxynitrilase) which are present in emulsin

(id.). The beta-D-glucosidase hydrolyzes the beta-D-

glucoside bond and thus frees the two glucose mole-

cules from the mandelonitrile, beta-Oxynitrilase is the

catalyst for the breakdown of mandelonitrile into

benzaldehyde and hydrogen cyanide (id.).

Amygdalin may be extracted from apricot kernels

(id.), and is present in seeds of other members of the

RI Se OR Se ee MES ho Dt

63a

rose family (R 416 at 931A). The Commissioner

concludes that amygdalin, a cyanogenic glucoside, is a

chemical having the chemical name D-mandelonitrile-

beta-D-glucosido-6-beta-D-glucoside (Merck Index, 9th

Ed. at 81, compounds 630; R 183, Att. 10b). The

cheinical structure of amygdalin is:

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

The term “Laetrile” has been used interchangeably

with “amygdalin,” “laetrile,” “vitamin B-17,” “nitril-

osides,” and “beta-cyanogenetic glucosides” (R 173,

Att., Laws and Regulations Relating to the Diagnosis

and Treatment of Cancer 10400.1 at 15; R 302, Ex.

A; Tr. at 405, 272, 465). It appears, however, that

the term “Laetrile” (with a capital L) has been used

by the drug’s proponents to refer to a particular sub-

stance. There are essentially two versions of what

that substance is:

(a) The term has been used to refer to a specific

chemical compound which was prepared in 1952 by

Ernst T. Krebs, Jr., who is said to have derived the

name “Laetrile” from the compound’s chemical 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 laveo-mandelonitrile-

64a

beta-glucuronoside was derived by Ernst T. Krebs,

Jr., while working with the apricot extract his father

had prepared and studied some 20 years earlier (R

318 at 70-73). The chemical structure of this mate-

rial 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

Ht 0 CN

i }

o—CH

EXO

H OH

(b) In a 1965 affidavit, however, Dr. Krebs, Sr.,

stated that the name “Laetrile’ was devised in 1949

by his son, Ernst T. Krebs, Jr., for a form of amyg-

dalin which Dr. Krebs, Sr., was producing at that

time (R 183, Att. 13). As can be seen from the dia-

grams set out in this opinion, the chemical structure

of amygdalin 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 ‘mandelonitrile,’ 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

CR CR a 8S ND we 6 + ered Lae

65a

result of a desire on the part of promoters to continue

to use drugs containing amygdalin while justifying

the use of the arugs by theories associated with the

Laetrile of Krebs, Jr. For example, in a February 17,

1953 letter to Dr. Ian Macdonald, the Chairman of

the Cancer Commission of the California Medical

Association, Ernst T. Krebs, Jr., advised that he was

forwarding “* * * samples of the biosynthetically de-

graded amygdalin in which one dextrose was removed

by prunasin and the resulting compound, in the

presence of platinum black, was oxidized to the cor-

responding glucuronoside” (R 183, Att. 14). (Note:

the compound thus obtained should have been 1-

mandelonitrile-beta-glucuronoside or “Laetrile’’ as de-

scribed by E. T. Krebs, Jr., R 318 at 73.) The Cancer

Commission of the California Medical Association, in

its 1953 report, stated: “Chemical analyses done inde-

pendently 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 material dis-

tributed as “Laetrile” arose again in the early 1960’s

when the Carcer Advisory Council of the State of

California was gathering information on Laetrile in

order to enforce the 1959 California law dealing with

cancer quackery. In 1963 the Council reported that

the California State Department of Public Health had

examined different varieties of Laetrile and found

that the products were markedly different in com-

position but did contain varying percentages of amyg-

66a

dalin (R 183, Att. 16, App. 7 and 8). A Canadian

Medical Association report published in 1965 found

that the United States and Canadian versions of the

drug were different—a larger percentage of the Ca-

nadian version than of the United States version was

found to be made up of amygdalin (R 189; see also

R 378, Att., “Supplementary Report by the Cancer

Advisory Council” at 1-2).

The record reveals a number of references 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 identifies the product as “Laetrile

(Amygdalin) 400 mg capsules” (R 183, Att. 10a;

see also R 183, Att. 10d). The National Cancer In-

stitute, in its October 1975 “Background Statement

on Laetrile’ notes the fact that supporters of the

drug have used the names “Laetrile” and “amygda-

lin” interchangeably. The report then correctly iden-

tifies 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 Cancer

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

67a

reports by Dr. Manuel Navarro of the Philippines

stated that the Laetrile of Ernst T. Krebs, J r., was in

use (R 313 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 (Laetriles) Their Rationale and

Clinical Utilization in Human Cancer (December

1962),” by Ernst T. Krebs, Jr., and Dr. N. R. Bouzi-

ane, in which the authors report on their use of “non-

toxic nitrijosides (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 “cyanophoric glucosides and cyanophoric glu-

curonosides” (id. at 189), the authors do not identify

the “Laetrile” they had been using and about which

they were reporting. 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 iden-

tity of material called “Laetrile’ would be a severe

drawback to anyone seeking to show through testing

that Laetrile was safe and effective, this lack of uni-

formity has been adopted by Laetrile proponents as

a means of discounting data showing the drug to be

ineffective and thus unsafe. An example is found in

the statement by Ernst T. Krebs, Jr., that “The * * *

single negative report on Laetrile, which is based

upon the observations of unidentified investigators in

unidentified institutions administering a purported

Laetrile not obtained from the only source of the

68a

material, is to be found in California Medicine, 78 :320

(1953)” (emphasis added) (R 318 at 251). It should

be recalled that at least some of the material sup-

plied to the California Cancer Commission was sent

by Ernst T. Krebs, Jr., himself (R 183, Att. 14).

In May of 1971, Mr. McNaughton of the pro-Laetrile

McNaughton Foundation, in a meeting with FDA’s

Ad Hoe 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 Hoe Committee of

Oncology Consultants” at 1). See also statement of

Robert Bradford, President of the Committee for

Freedom of Choice in Cancer Therapy, Inc.: “As an

aside, an important aspect of animal tests, and in-

deed, 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 materials, 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 identity of the drug tested makes the test results

obtained questionable. The Committee stated that

because of the variability in composition of early

preparations, doubt was cast on the bulk of the 1970

McNaughton Foundation Notice of Claimed Investi-

gational Exemption for a New Drug (IND) for Lae-

trile, which was based almost exclusively on such

69a

early material (R 173, “Report of the Ad Hoc Com-

mittee of Oncology Consultants” at 1). The Commit-

tee further suggested that any protocol for study

contain a full description of the drug (formulation,

stability ete.) (id. at 4).

There is, quite simply, no one answer to the ques-

tion “What is Laetrile?”. In the glossary to this

opinion, the chemical composition of Laetrile is con-

sidered 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 “Lae-

trile’ and “amygdalin” to mean different substances,

uniformity of definition will not be possible in dis-

cussing the evidence in the record. For this reason,

the Commissioner will not, in quoting or citing parts

of the administrative record, attempt to define or to

determine the identity of the material under discus-

sion but will simply use the term as it appears in

that portion of the record. Attempts to identify the

material referred to will be made only when necessary

for a rational resolution of an issue, e.g., a reference

to Sarcarcinase as amygdalin or as Laetrile will not

be accepted blindly.

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

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. 10e;

70a

R 378, Att. 6). The term has, however, also been used

to describe a class or group of compounds. For ex-

ample, amygdalin and prunasin are described as

“two common Laetriles”’ (R 1738, Att., “Vitamin

Fraud” at 345). It has been stated that: “The term

LAETRILE is used to designate the laevorotatory

containing glucosides in general and the correspond-

ing 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 § 9 which defines natural laetriles as beta-

cyanogenetic glucosides and glucuronosides.) The

Commissioner concludes that the term “laetrile” is an

imprecise term and that it does not imply a specific

chemical compound. 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 “Sarcarcinase” in 1926 (R 183, Ait.

13). “Sarearcinase” is stated to be a registered trade-

mark in the United States and 10 other countries

(with registrations dating from Marck 1923 to Janu-

ary 1934) (see R 260; R 259). The process for pre-

paring 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”

7la

used within the United States as well as several for-

eign countries (id.).

Ernst T. Krebs, Jr., stated at oral argument that

as early as 1932 his father “* * * observed the use of

amygdalin, or laetrile; made it available across the

country and abroad under the term ‘Sarcarcinase’ to

physicians, to researchers” (Tr. at 233). He also

stated, “* * * the first amygdalin was used—1932—

it was labeled 7s “ ‘Sarcarcinase’” (Tr. at 246). Sar-

carcinase was not, however, amygdalin nor did it con-

tain amygdalin in any quantity. Rather, in the words

of Dr. Krebs, Sr.’s 1933 patent application, Sarcarci-

nase was “an enzyme for treatment of malignant

growths.” The patent application actually describes

the product as “an enzyme complex” containing

“amygdalase, prunase, oxynitrilase, catalase, peroxy-

dase and proteolytic enzyme” plus a suggestion of

“isomaltase and 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, enzymes are chemicals which

catalyze the breakdown of other chemicals and which

are often named by attaching the ending “-ase” to

the chemical which they attack. Thus, “amygdalase,”

stated by Dr. Krebs, Sr., to be part of his enzyme com-

plex, may have been meant to describe 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, how-

ever, that much or all of the small amounts of amyg-

72a

dalin in the apricot kernels used in making Sarcarci-

nase would be destroyed by enzyme action when the

kernels are ground up and that only a small fraction

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 scientific sense or in a legal sense.

There is some indication that Dr. Krebs, Sr., had

abandoned Sarcarcinase even at the time when the

patent applications were being obtained. One submis-

sion by a Laetrile proponent states that Dr. Krebs,

Sr., “* * * resigned himself to the fact that there was

no sense continuing this particular research to iden-

tify the toxic element or elements in the apricot ex-

tract he prepared (sometime after 1926) until he

acquired the additional knowledge necessary to under-

stand the mysteries that were occurring in his test

tubes. He put his extract aside and returned his

books” (R 318 at 42). Krebs himself states that in

1936 he developed a new product, whose “active prin-

ciple” was amygdalin of 66 percent purity (R 183,

Att. 13). (The inactive ingredients of this prepara-

tion are not identified.) It is not clear whether it is

Sarcarcinase or this new product about which Krebs,

Sr., speaks when he states that his “apricot extract”

was “so toxic that he and colleagues who were experi-

menting with him were reluctant to continue its use,

except in dire circumstances” (R 183, Att. 7 at 23).

Its was apparently these toxicity problems that led

73a

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

Sarearcinase in the 1930’s is patently erroneous.

C, CLAIMS FOR LAETRILE

Laetrile (or amygdalin) has been recommended

over the years primarily for use in the treatment and,

more recently, “control” of cancer. The claims ap-

pear to vary in relation to the sophistication of the

intended audience. Thus in the 1962 new drug ap-

plication (NDA) for Laetrile submitted by Ernst T.

Krebs, Jr., to FDA, the drug was claimed to be a

palliative (ie., a drug that mitigates the symptoms

of a disease without curing it) to be used with other

recognized therapies (R 201, Ex. B at 102). By con-

trast, in a pamphlet in use in 1965, apparently ad-

dressed 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 concurrently is discouraged (R 201,

Ex. C., # III). The following claims have been made

for Laetrile (amygdalin) :

1. Treatment (Cure or Mitigation) of Cancer

The pamphlet discussed above and others obtained

from Dr. Krebs, Sr., by FDA investigators at the

same time recommended Laetrile for treatment of

cancer (see, generally, R 201, Ex. C). Dr. Krebs,

Sr., in a pamphlet entitled “The Treatment of Breast

74a

Cancer with Laetrile by Iontophoresis” promotes the

drug for treatment of a number of cancers (R 183,

Att. 7 at 26-27 and 30).

A label for 400 mg capsules of “Laetrile (Amyg-

dalin)” claims that the “nontoxic cyanide glucoside

is used for specific treatment of cancer by physicians

or under 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 1738, 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 pallia-

tion. (See, e.g., R 216 at 348; R 318 at 175; Tr. at

238.) Recently, Laetrile has been touted as a “con-

trol” 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 en-

tirely clear from the record whether “control” means

palliation. Laetrile therapy is said to be responsible

for increased appetite and weight gain and an in-

creased “sense of well-being” among treated cancer

patients (R 318 at 158 and 165).

2. Analgesic (Pain Killer)

An information booklet for physicians about amyg-

dalin 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

75a

claims that the oral route is the most convenient

route of administration for both patient and physi-

cian.

NoTe.—The Commissioner points out that both pro-

ponents and opponents have warned against oral

use of amygdalin 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 178, 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 hydrogen cya-

nide.” “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-

cer-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).

8. 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), pro-

76a

ponents of 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) ; ef.

Tr. at 465). (See also R 178, Att., United States v.

Spectro Foods, supra, Findings 16 through 23.)

While proving that Laetrile (or amygdalin) did not

prevent cancer would be extremely difficult, the rec-

ord does contain evidence that at least one person tak-

ing it as a preventative did contract cancer (Tr. at

120).

4. Facilitation of Other Cancer Therapy

While, as noted above, some labeling recommends

against use of other cancer therapies with Laetrile,

it has been stated that “* * * if you combine toxic

chemotherapy 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 neucophenia (leukopenia?) and you don’t

get chromositophenia (chromocytompenia?)” (Tr. at

480).

5. Hemoglobin Index

One set of labeling for “Laetrile (Amygdalin),”

which appears at two points in the record, recom-

mends the product “for raising hemoglobin index and

red count * * *” (R 183, Att. 9; R 201, Ex. C. No. 1).

6. Reduction of Odor Associated with Malignancy

It is also claimed that topical application of Lae-

trile relieves fetor (odor) resulting from the second-

77a

ary infection of ulcerated carcinoma and that par-

enteral administration takes care of fetor associated

with internal cancers. This action is ascribed to the

“antiseptic” properties 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 (Laetrile) might be

of value in the treatment of sickle cell anemia because

of the release of cyanide and the subsequent forma-

tion of thiocyanates (R 217, article by R. G. Hous-

ton). (See also Tr. at 465.) This claim is reportedly

refuted by experts in sickle cell hemoglobin (R 416

at 23).

8. Parasitic Diseases

The Houston article also references a report by

Navarro and others of the clinical control of schisto-

somiasis (a snail-borne infection) with nitriloside

(Laetrile) (R 217, Houston article at 58). The possi-

bility of using Laetrile to treat parasitic diseases

such as schistosomiasis or malaria is discussed in the

book Control for Cancer but there are no reports of

actual use in the book (R 318 at 111-12).

9. Regulating Intestinal Flora

It has also been suggested that amygdalin has some

utility in regulating intestinal flora (Tr. at 476).

78a

10. Hypotensive Effect

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 refer-

ences to or claims for its therapeutic effects as a

cancer cure or as a preventative. There are also ref-

erences to relief, attributed to Laetrile, from other

ailments unrelated to cancer, e.g., arthritis (R 391).

D. THEORIES OF LAETRILE’S ACTION

A thorough understanding of the manner in which

a compound achieves its therapeutic or beneficial ef-

fects is highly desirable. A cancer drug which had

been shown to be safe and effective would not, how-

ever, be denied marketing approval 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 suc-

cess; neither does a weak theory, or even what turns

out to be a totally incorrect theory, mean certain

failure.

Some cancer patients may be turning 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”

79a

theories associated with Laetrile (see, generally, R

413.) The Commissioner finds from the record that

the theories advanced for Laetrile’s supposed action

are based on false or questionable assumptions. An

understanding of these theories, furthermore, points

up important differences between the “Taetrile”’

whose use is “justified” by the theories of Krebs, Jr.,

and the amygdalin-containing products actually 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 man-

ufactured in the cells of the body which help the

cells perform chemical reactions involving other com-

pounds. As an example, trypsin, a common enzyme,

aids in the metabolism of proteins in food by break-

ing these large molecules into smaller, easier-to-

handle pieces. Enzymes generally are very specific in

the types of chemicals they will attack. Frequently,

the name of an enzyme is derived from the com-

pounds that enzyme will break down. The ending

“ase” is often used to indicate an enzyme.

The chemical “beta-gluosidase” appears frequently

in the Laetrile record. The name of this chemical

indicates that it is an enzyme (-ase) and, further-

more, the name indicates that it attacks glucose-

containing compounds (glucosides) from which it

will liberate glucose molecules. As an example, beta-

glucosidase liberates two molecules of glucose from

_ 80a

amygdalin. If the chemical compound does not con-

tain glucose molecules, beta-glucosidase will not at-

tack it. In a similar vein, beta-glucosidase will attack

chemical compounds that contain glucuronic acid.

(These chemical compounds are called “glucuronides”

or “glucuronosides” or “glucuronic acid derivaties.” )

The original theory of Ernst T. Krebs, Jr., for

Laetrile’s action involved two enzymes, rhodanese and

beta-glucosidase (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-gluosidase to liberate cyanide and

benzalderhyde. In normal cells, the enzyme rhodanese

converts the liberated cyanide to the less toxic thio-

cyanate. 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 gonadotropic hormone

that efiectively blocks the action of rhodanese (R 318

at 153). In later versions of the theory, the benzalde-

hyde is also considered to be responsible 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 oxi-

dation. Cancer cells are said to oxidize the benezalde-

hyde at a slower rate than normal cells, making it

8la

toxic to cancer cells and nontoxic to normal cells.

(See Krebs, Jr., “The Nitrilosides (Vitamin B-17)—

Their Nature, Occurrence and Metabolic Significance

(Antineoplastic Vitamin B-17)” (R 183, Att. 10c

at 80.)?

In fact, it has been reported that only traces of

beta-glucosidases have been found in animal tissues

and even less in experimental tumors than in such

organs as liver and spleen (R 173, Att., “Vitamin

Fraud” at 345). Apparently for this reason, Krebs,

Jr., at one time modified his theory. In the modified

version it is beta-glucuronidase rather than beta-glu-

cosidase 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-glucuroni-

dase, which bathed the cancer cell, because of its

affinity for sugar split the glucoside (or sugar radi-

cal) from the Laetrile molecule” (R 183, Att. 7 at

24). (See also R 318 at 151-53.)

?In his 1933 patent application for Sarcarcinase, Dr. Ernst

T. Krebs, Sr., discussed his own theory of cancer, apparently

now abandoned by Laetrile proponents. He perceived a malig-

nant protein (“* * * a so-called abnormal glucosido-protein

* * *”) in cancer cells and explained why his enzyme extract,

prepared from apricot kernels, should be effective against

those cells (R 424). He believed that the enzyme would break

up the abnormal gluco-protein and thus be an effective treat-

ment 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).

82a

The change in theory is important. beta-Glucuroni-

dase hydrodyzes (breaks down) beta-glucuronosides

(or “beta-glucuronic acids” or “beta-glucuronides” )

but does not hydrclyze beta-glucosides (R 318, Att.

16 at 24). Thus, beta-glucuronidase will hydrolyze

“Laetrile”’ of the formulation devised by Krebs, Jr.

(i.e., laevo-mandelonitrile-beta-glucuronoside), but it

will not hydrolyze amygdalin (D-mandelonitrile-beta-

D-glucosido-6-beta-D-giucoside) or other “nitrolo-

sides” found in nature. What this means is that

amygdalin, which has been sold as “Laetrile,” would

not be hydrolyzed by the body to liberate 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 reported to have stated in a manuscript that

“the natural laetriles have been abandoned for the

more specific synthetic laetrile tailored as specific glu-

curonsidie substrates for the tumor beta-glucuroni-

dase” (R 183, Att. 16 at 14).

The specificity of beta-glucuronidase for glucuro-

nides (or glucuronosides) and its lack of activity

against gluecsides (such as amygdalin) is rigorously

addressed in the record:

Numerous glucuronides are hydrolyzed by beta-

glucronidase. * * * 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 ques-

tion (beta-glucuronidase) not hydrolyze the beta-

83a

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 Cancer Commis-

sion of the California Medical Association had deter-

mined that the material labeled “Laetrile’” was in

fact amygdalin—a glucoside and not a glucuronoside

(R 183, Att. 15 at 326.)

The conclusion seems justified that the pres-

ence of the terminal carboxyl group on position

6 appears to be the important factor in deter-

mining a specificity which is markedly different

from that of B. Glucosidase * * * (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 molecule).)

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 “preparea enzyme.”) He

does claim that the two enzymes react with Laetrile

in the same manner (R 183, Att. 7 at 24).

There is some indication that Ernst Krebs, Jr., in

later years abandoned his attempt to develop a Lae-

trile that could be broken down by beta-glucuronidase

and began treating beta-glucuronidase and beta-glu-

84a

cosidase as equivalent. In a 1962 letter, Krebs, Jr.,

seems to refer to the former as an example of the

latter: “beta glucosidases (e.g., beta glucuronidase)”

(R 183, Att. 16, App. 12 at 2) and seeks, in describ-

ing an experiment with water fleas he had designed,

to extrapolate results obtained with beta-glucosidase

to results with beta-glucuronidase he feels is found

in malignant lesions (id. at 4). (See also Krebs’ 1970

article “The Nitrilosides (Vitamin B-17)—Their Na-

ture, Occurrence and Metabolic Significance (Anti-

neoplastic Vitamin B-17)” in which he again equates

beta-glucosidase with beta-glucuronidase (R 183, Att.

10c at 82).)

Three other problems with this theory are quickly

identifiable: (1) there is evidence that beta-glucuro-

nidase is not particularly abundant in malignant tis-

sues. The record shows that “* * * beta-glucuroni-

dase is found in all tissues of the animal body and

in particularly high concentrations in spleen, liver,

and endocrine organs, as well as in plasma and in

tumors arising from estrogen-influenced tissues. Per

gram of tissue, the spleen and liver have a higher

concentration 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 ma-

lignant 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 defi-

cient in the enzyme rhodanese. In reviewing the rec-

ord, the Commissioner has not found any support for

85a

the bald assertion by the Krebs and other Laetrile

proponents that cancer cells are deficient in the pro-

duction of a hydrogen cyanide-inactivating enzyme

called rhodanese. If there is any scientific support

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 rec-

ord shows, in fact, that: ‘There is no evidence of

pronounced differential between the rhodanese con-

tent of comparable normal and cancerous tissue” (R

378, Att. 9 at 346).

(3) The complete breakdown of Laetrile into cy-

anide may require an enzyme not found in animal

tissues. Hydrolysis of Laetrile by beta-glucuronidase

(and hydrolysis of amygdalin by beta-glucosidase)

only represents the first step in breaking down the

molecules to release hydrogen cyanide and benzalde-

hyde (which are supposed to kill the cancer cell). The

first reaction in each case would yield mandelonitrile

plus (for Laetrile) glucuronic acid or (for amygda-

lin) glucose. Mandelonitrile must then be

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