# Petition — United States v. Rutherford > Briefs, arguments, decisions, and more. URL: https://www.frixlaw.com/law-library/documents/brief%3Amicro_IA40385005_1872%3A01 ## Record - **Collection:** Supreme Court brief - **Document type:** Petition - **Published:** January 1, 1979 - **Citation:** 442 U.S. 544 ## Text ne 28-605 FILED No. } OCT 40 I97! i - 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 10 19 la 8a 10a lla 45a 15 15 10 15 “14, 15 14 Il 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) 2 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 * * * 3 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 4 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 5 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). 6 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- 7 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. 8 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 9 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. 10 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”’ 11 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). 12 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. 13 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). 14 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). 15 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). 16 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. | 17 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). 18 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. 19 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 la 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 2a 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 3a 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 4a 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 5a 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 6a 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 Ta 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. ot 8a 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- 9a 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 v. 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. I 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 II 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 II 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). ee 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 IV x 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 ae 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 V 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. VI “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 (c) (4)). 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. (c) The “Evidence” of Laetrile’s Effectiveness. 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. (c) Lack of General Recognition of Effec- 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.” (c) Claimed Parallel with Scientific Pioneers. (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. ae 55a (a) Proponents’ Claims. (b) Vitamin Experts’ Position. 3. Dangers of Ingestion of “Vitamin B-17.” C. FREEDOM OF CHOICE a 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- [Text truncated at 120,000 characters. The full text is on the page linked above.] --- Source: Frix Law Library, https://www.frixlaw.com/law-library/documents/brief%3Amicro_IA40385005_1872%3A01. Public record. Not legal advice.