Since 1938, lawyers, doctors, homeopaths, historians, and Food and Drug Administration (FDA) officials have questioned the inclusion of the Homeopathic Pharmacopeia of the United States (HPUS) in the Federal Food, Drug, and Cosmetic Act (FDCA). [1 ] The FDCA defines drug in a number of ways, the simplest being: "articles recognized in the official United States Pharmacopeia, the official Homeopathic Pharmacopeia of the United States, or the official National Formulary or any supplement to any of them." [2] Many wonder why a new law that established the first premarketing scrutiny of new drugs, stimulated important new scientific advances in drug discovery, and offered the first glimpses of patient protection policies, simultaneously recognize such a seemingly regressive system of drug therapy as homeopathy [3].
Originally founded by German physician Samuel Hahnemann (1755-1843), homeopathy as a system of therapeutics was brought to the United States in the early nineteenth century by German immigrants [4]. Although homeopathy originated in Germany, there never were any homeopathic hospitals and medical schools there [5]. Rather, homeopathy flourished in the United States in the eclectic medical environment of the nineteenth century. Homeopathy is based on two key principles: the "law of similars" ("let like cure like") and the "law of infinitesimals" (the more dilute the drug, the more powerful its effects). By the early twentieth century, as clinical medicine began to develop and expand into a science-based profession in the United States, homeopathic reformers began to redefine their field as a "complementary" form of treatment-based therapy. A homeopathic product can be derived from any source substance. Such substances, once "discovered," are tested through "provings," in which they are administered to healthy volunteers in concentrations that provoke overt symptoms. The symptoms experienced by these volunteers are recorded and become the basis for the indications the product is used to treat. Employing the "law of similars," substances causing fevers, for example, might be used to treat fevers [6]. The "law of infinitesimals" dictates that the dose be as small as possible, and this commonly translates into doses undetectable by modern laboratory methods. According to the tenets of homeopathy, such minuscule doses impart a healing stimulus. Homeopathy has had its adherents through the years, including some prominent Americans during the late nineteenth century, but it has remained a controversial treatment option.
Senator Royal Copeland (D-NY), sponsor of the FDCA, was a homeopathic physician who undoubtedly supported inclusion of the HPUS in the Act. Little is known about how the provision made it into the FDCA, however. The legislative record is silent, and an examination of Copeland's papers demonstrate that, although he was a dedicated homeopathic reformer early in his career, he had become less involved in homeopathy as his career moved him into the field of public health. Homeopathy does not appear to have been one of his chief concerns in drafting the FDCA. On reflection, this absence of discussion seems to support a more skeptical (or at least more intricate) view of this provision as a mere concession to Copeland.
In 1951, George Harding lamented similarly that there was no discussion of the "causing" provision of the FDCA. The origin of this provision, which sanctioned prosecution of those accused of "causing" a violation of the FDCA, was at least as obscure as the HPUS provision. Even men who worked closely on the bill, Harding remarked, could not remember where or how the "causing" provision came to be included in the law [7]. But Harding rejected the view that the provision was inserted mechanically and without much thought to its meaning in the context of the law.
Such a pragmatic approach might have validity if applied to a bill that slipped through the legislative process in a short time and with little debate. But when one considers the hen-scratching that for five years went on in the Copeland bills it is difficult to believe that a single phrase escaped critical examination [8].
In the case of homeopathy, as in the case of the "causing" provision, food and drug officials had a strategy in mind when they accepted Senator Copeland's inclusion of the HPUS in an early draft of the FDCA. This strategy would have been withheld purposefully from the legislative record and would explain the silence surrounding the provision. In the case of homeopathy, it seems more plausible that FDA officials, principally Charles Crawford, a lawyer and draftsman of the FDCA, agreed to the inclusion of the HPUS in the FDCA. They did so not merely as a concession to Copeland, but rather as part of a strategy they hoped to employ against ineffective products masquerading as homeopathic drugs. Up to the mid-twentieth century, homeopathic drugs were obtained only from homeopathic physicians, who were also trained as regular physicians. As physicians, homeopaths could be counted on to adhere to a code of ethics in assessing and treating patients. Quacks and charlatans peddling homeopathic drug imitations, in contrast and by definition, did not. Thus, in 1934, when the HPUS was added to section 201 of the Copeland Bill, medical quackery, including all proprietary medicines, were of more concern than drugs prescribed by homeopathic physicians.
Once the HPUS was included as an official drug compendium in the FDCA it created some unanticipated regulatory challenges. Premarket drug approvals, first mandated in the FDCA, came to be based on placebo-controlled, blinded drug trials, and as FDA instituted reevaluations of both prescription and over-the-counter (OTC) drugs, homeopathy largely was ignored. FDA was forced to make important regulatory decisions regarding this complementary form of medical practice only when homeopathy began its own resurgence, asserting for the first time that self-treatment was consistent with homeopathic principles.
The nation's first federal food and drug statute recognized the U.S. Pharmacopeia (USP) and the National Formulary (NF) as official compendia of the nation's drug supply [9]. Although the two publications encompassed much that had characterized the eclectic therapeutic and medical practices of the nineteenth century, a move toward therapeutic precision was revising both publications [10]. The selection of these publications as standard references signified not only a commitment to high standards in the nation's therapeutic armamentarium, but also codified the emerging links between laboratory science and professional therapeutic practice [11].
Under the 1906 Act, preparations listed in these two standard references were defined as drugs [12]. Drugs sold under the names employed by the NF and USP either had to conform to the published standards, or state on the label how they differed [13]. The law did not recognize exclusively the standards of the NF and USP. Adopting a broad definition of the term "drug," the law required that all products marketed as drugs conform to a standard to which they could be held accountable [14]. Manufacturers and marketers could establish their own formal standards of quality and purity, but they had to conform to these standards or risk having their drugs deemed "adulterated." [15] The USP and NF, therefore remained more of a model than a mandate under the 1906 Act.
Homeopaths at the 56th annual meeting of the American Institute of Homeopathy (AIH) in June 1908, resolved to bring their alternative therapeutic perspective into compliance with the new law [16]. Beginning in January 1909, all homeopathic pharmacists would be requested to prepare their remedies according to the HPUS to comply with the 1906 requirement. A statement acknowledging compliance with the HPUS would be affixed to the label of their products, and homeopathic physicians were urged to demand that their pharmacists comply with the HPUS "so that with remedies of a known uniform strength, we may have a more scientific and useful literature." [17] This progressive resolution was merely a prelude to the AIH's ultimate goal: securing an amendment to the 1906 Act that would recognize the HPUS alongside the USP and NF. AIH's reasoning was straightforward:
We would demand this in order that the standards in the Food and Drugs Act may be made complete by providing for the uniform strength and preparation of nearly three hundred fresh plant tinctures which are at present unprovided for and also that justice may be done to thousands of physicians whose scientific remedies are classed among the proprietary or quack remedies [18].
Although the HPUS began publication in 1897, it was not widely employed by most homeopathic physicians and pharmacists. Nonetheless, the very existence of such a compendia must be interpreted as a triumph for the reforming homeopaths, practitioners characterized as "new homeopaths" who were pushing to make homeopathic practice as scientific as possible [19]. American homeopaths during this period shared both the aspirations and the models of scientific medicine and many studied in Berlin [20]. Listerism and the bacteriology of Edward Koch and Louis Pasteur, for example, were embraced by American homeopaths that saw "antisepsis," as consistent with Hahnemann's call for a preventive approach to medicine [21]. Reformers perceived an opportunity to push for further homeopathic therapeutic reforms along the lines sanctioned in the law by the choice of the USP and NF. Thus, the 1906 Act provided homeopathic reformers with both a carrot and a stick with which to persuade fellow practitioners. Once the standards mandated under the law had been accepted and enacted, homeopaths then could petition for recognition of their alternative pharmacopoeia in the federal food and drugs statute.
Chief among the scientific reformers was Royal Samuel Copeland (1868-1938) [22]. Copeland made history a lifelong hobby, but he chose medicine as a profession inspired by a youthful preceptorship with Dr. F.E. Chase, a homeopath and family physician in his hometown near Dexter, Michigan [23]. To support his matriculation at the Homeopathic Medical College, then part of the medical school at Ann Arbor, he taught and his father sold some land [24]. In June 1889, he graduated and like many medical men of the era, did not consider his education complete until he had spent some time in medical institutions abroad [25]. Copeland embarked on a tour of German and European homeopathic institutions where he reportedly was intrigued with a glass eye factory in Halle, Germany [26]. Copeland returned to Michigan in 1890 and settled in Bay City where he spent the next five years establishing himself as an ophthalmologist, an eye and ear specialist, and a surgeon. In 1893, he became Secretary of the Homeopathic Medical Society of Michigan.
Copeland's specialty was a dynamic field for regular physicians and homeopathic physicians at the end of the nineteenth century as both moved into a specialty previously dominated by medical quackery [27]. The earliest homeopathic specialty society under the auspices of the AIH was, in fact, an eye, ear, and throat specialty. Likewise, early delineation of a specialty in ophthalmology among regular physicians ultimately led to the creation of the American Medical Association's (AMA's) first specialty board in that field in 1916 [28]. Copeland secured a place in society and in medicine providing treatment perceived at that time as "distinct," but not "inferior." [29] Copeland, like other homeopathically trained practitioners of the period, regarded himself as a physician first and foremost, albeit one skillfully trained to employ a complementary form of therapeutics [30].
In 1895, Copeland was drawn back to Ann Arbor in a departmental dispute and ultimately was appointed Professor of Ophthalmology, Otology, and Paedology at the Homeopathic Medical College [31]. From 1901 to 1903 he made his first foray into electoral politics, serving a term as the city Mayor. A difficult term of office reportedly "temporarily checked his enthusiasm for political life." [32] In 1904 he returned to medicine and was elected President of the American Homeopathic Ophthalmological, Otological, and Laryngological Society. His presidential address simply entitled "In Defense of the Attenuated Drug" was somewhat lackluster, but as spokesman for an enlightened and growing profession, Copeland wrote as a dedicated homeopathic reformer [33].
In a revealing entry for a Reference Handbook of the Medical Sciences, for example, Copeland wrote a lengthy, defensive, and reformist explanation of homeopathy premised on the simple declaration that "[h]omeopathy is not a system of medicine." [34] Espousing and elaborating on homeopathy as a complementary form of medicine, Copeland defined it as a "method of therapeutic procedure" in which "the facts of the sciences of pathology and pharmacology are brought into correspondence for the purpose of cure when cure is possible." [35] In what a previous generation of practitioners might have considered heresy, Copeland downplayed the significance of homeopathic dosing in modern practice. "The size of the dose prescribed and the repetition of the remedy have little to do with homeopathy. Whether a given prescription is homeopathic or not depends purely and simply upon the means of its selection." [36]
More than any other aspect of homeopathy, it was homeopathy's "law of infinitesimals" that had attracted the derision of regular physicians and others amidst accusations of quackery throughout the nineteenth century [37]. Then and now, it is difficult to convince skeptics that a one part per million concentration (or less) of any substance can produce a therapeutic effect [38]. Reformers like Copeland, however, rejected Hahnemann's concept of a "spirit like force" that maintained and enhanced the potency of homeopathic drug products through successive shakings and dilutions of the source product (percussion and succession). Copeland, in particular, rejected the idea that drugs themselves possessed any mystic force, and instead adopted a quasi-scientific perspective holding that a drug exhibits a dose response [39]. He did not, however, accept the view of critics who charged that homeopathy's minuscule doses were ineffective or that they acted only as placebos.
With a remedy prescribed for symptoms similar to its physiological action, it follows that too large a dose would produce an aggravation of the disease. It is desirable to prescribe a dosage short of one producing actual physiological effect. It is aimed to get what the homeopathist calls the "dynamic" effect of the drug, in contradistinction to its physiological or poisonous effect [40].
Copeland considered dosage less critical than symptomatic treatment. Generally, he treated patients with homeopathic preparations as well as some conventional drugs, but on occasion, he used placebos ("unmedicated pellets") in his practice [41]. In his defense of homeopathy, Copeland was trying to move past what he perceived to be critics' preoccupation with spiritual essences and quantification in homeopathy to promote a more scientific appreciation of the importance of treating a patient's symptoms with a therapeutic substance.
Copeland's explanation of homeopathy as a complementary medical discipline, while downplaying Hahnemann's "law of infinitesimals" did, however, embrace Hahnemann's first law "similia similibus curentur." [42] Homeopathy, according to Copeland, was a "method of therapeutic procedure" founded on the homeopathic "hypothesis" that the symptoms of disease could be removed by a remedy producing similar symptoms in a healthy person [43]. "Unfortunately," Copeland noted by way of introduction, "disease, as it is met in practice, does not present clear-cut indications for this or that remedy." [44] Rather, "it necessitates us . . . to study our patient carefully in order that we may be led to the selection of the curative drug." [45] A homeopathic prescriber must "forget the name of the disease, and choose the remedy for the one and only reason that it is the similimum for that particular case." [46] In contrast with the average physician, homeopathic prescribers were accustomed to taking into account a patient's "moods" and "mental condition" when choosing a remedy and often prescribed for the removal of "purely subjective symptoms." [47] Copeland noted, for example, the iatrogenic effects produced by drugs with alcohol and morphine (exhilaration and sedation) and suggested that homeopaths would act to counteract these effects and prescribe "remedies to restore normal function to a disturbed mind." [48] In short, Copeland claimed, where the regular physician "elicited" symptoms to identify a disease, the homeopathic physician used them to prescribe a remedy. In an era in which the causes of most disease still were unknown and self-medication had created an appalling number of "toadstool millionaires," Copeland seemed to be offering something that would appeal to those impressed with the potential of scientific medicine but well aware of its practical limitations [49].
Copeland believed that it was in the realm of treatment that homeopaths excelled over regular physicians [50]. At the turn of the century, the distinctions between homeopathy and alternative therapies were clearer, if only because the prevalence of patent medicines and the evils of adulterated drugs were documented well [51]. According to Copeland, homeopathy embodied and represented to the public "faith in therapeutics," and was, in fact, "the therapeutic specialty." [52] Homeopaths, for example, could claim accurately that they created no drug addicts and were early advocates of "pleasant" medicines. Adulteration of homeopathic drugs, delays in filling prescriptions, and carelessness in drug preparation were charges generally not leveled against homeopathic practitioners. Copeland boasted of the breadth and inclusiveness of the homeopathic therapeutic arsenal. In the homeopathic materia medica, according to Copeland, "every possible source of information has been visited -- poisonings accidental or intentional, pharmacological tests, animal experiments, postmortem findings, and [homeopathic] provings." [53] Because the homeopathic physician usually dispensed medicines, this was promoted as a distinct benefit to those who distrusted pharmacists and the "unsatisfactory directions written on the label." [54] Homeopaths promoted this salutary view of their distinctive prescribing methods. Copeland, for example, noted in one speech that not only did this save on drug bills, but it avoided errors because "many a mistake has come from depending on the indirect methods of the pharmacist and the brief unsatisfactory directions written on the label of the medicine." [55]
Many early homeopathic claims citing careful laboratory methods and "exact prescribing," however, seem to have been composed of at least equal portions of scientific ambitions and wishful thinking [56]. In his 1901 address to the Homeopathic Medical Society of Michigan, Copeland chides his colleagues, concluding: "[w]e are not so far in the lead in the procession of successful medical practice as we were a score of years ago. The laboratory and pharmaceutical experts have taught our rivals some very important lessons . . . their speed has become accelerated." [57] Copeland led a campaign for a universal scale of notation in homeopathy beginning in a 1904 speech. By 1906, in a speech to the World Homeopathic Congress, Copeland was specific and practical. In "Homeopathy and Posology: A Discussion of the Potency Problem," Copeland bluntly criticized his colleagues for their lack of a scientific scale of attenuation noting that "unscientific, non-uniform" scales of measurement had evolved so that "one millionth of one equals one tenth of another." [58] Congress then determined that a uniform scale of notation should be used. Thus, in the same year that the USP and NF were adopted in the 1906 Act, homeopaths initiated efforts to standardize measurements used in their drug preparations.
Shortly after the AIH acted in 1908 to strengthen the HPUS, Senator Jacob H. Gallinger (R-NH) a prominent antivivisectionist and champion of various reform causes, sponsored an amendment to the 1906 Act that would have recognized the HPUS alongside the NF and USP [59]. Gallinger was a homeopathic physician with a degree from the New York Homeopathic College and served as New Hampshire's surgeon general before entering politics [60]. Although the amendment was defeated, Gallinger became minority leader of the Senate in 1912. At that time, there was a concerted effort to repeal the variation clause that had authorized standards other than those of the USP and NF under the law [61]. He reintroduced the amendment recognizing the HPUS following hearings on the variation clause. The HPUS amendment was rejected by the medical profession and scorned by Harvey Wiley, father of the 1906 Act, and neither it nor the repeal of the variation clause was enacted [62]. Gallinger's death in 1918 left the AIH without a prominent sponsor to continue the political fight for recognition of the HPUS. It was not until another homeopath arrived in Congress, nearly a decade later, that the initiative was revived.
Meanwhile, in 1908, Copeland took over as Dean of the New York Homeopathic Medical College and its teaching hospital, Flower Hospital in New York City. Copeland was one of the few homeopathic administrators who retained his position in the wake of the 1910 Flexner Report, which paved the way for important reforms in the training of American physicians [63]. Many of his counterparts at other institutions lost their jobs in the wave of controversy, and eventually mergers and closings were set in motion by the highly critical report on medical education in the United States. Inasmuch as any homeopathic institution found any favor with Flexner, New York Homeopathic College did so largely because it was the only homeopathic institution that owned the hospital connected to it. Homeopathic patients generally were not charity patients and this, in particular, made it difficult to train students. The Flexner Report cited the Homeopathic Medical College and Flower Hospital as one of only three homeopathic institutions with the necessary equipment for teaching [64]. Flexner predicted that only four homeopathic schools would survive the coming decades and this institution was one of them [65]. Copeland, in defense of the College, boasted that all of the Flowers' class of 1910 graduates had been placed by graduation day, reportedly receiving three offers for every one available position [66].
In 1918, Copeland's perspective on medicine was altered profoundly with his appointment as New York City's Health Commissioner [67]. No longer afforded the luxury of specialization, Copeland became involved with issues as broad and urgent as curbing an influenza epidemic threatening the city, and as narrow and pervasive as ensuring clean milk for the city's tenement babies [68]. His appreciation of public health problems broadened his perspective on scientific medicine considerably and his views became more widely known and influential after he began writing a column on "Your Health." [69] As he left his post in 1924, Copeland advocated health education to "make the American people realize the value of the wholesome plain foods of the earlier days." [70] Citing the values of good bread, fresh vegetables, plainly cooked, and plenty of milk, he concluded that they "are really more essential to the welfare of the American than medicines and drugs." [71]
Copeland was elected to the U.S. Senate in 1924 as a compromise candidate with Tammany support. He brought with him an unusual background in both medicine and public health. Copeland was a striking figure and an "eminently sociable man," easily recognized by the red carnation he wore on his lapel that he once explained as "the emblem of therapeutic perfection." In the words of a biographer, he wore it as a "constant memorial of his youthful idealism." [72] Copeland came to respect and support the work of FDA during its "turbulent twenties" in Congress, and offered a major amendment designed to bring cosmetics under regulation during this period [73]. It was Copeland's well-known sponsorship of a new food and drug law, later enacted as the FDCA, which both culminated and sadly capped his career. Copeland died four days after the bill was passed [74].
The original bill proposing sweeping changes to the original 1906 Act was known as the Tugwell Bill. Approved by Assistant Secretary of Agriculture and prominent Brain Truster Rexford G. Tugwell, the bill was as radical as any New Deal measure proposed at the time [75]. This initial proposal, however, was rejected quickly and decisively by most of the affected food and drug industries [76]. When Tugwell distanced himself from the unpopular bill, Copeland stepped in as a sponsor to try and effect compromises that would create a new food and drug statute acceptable to industry and consumers. It was Copeland, who, in his initial revisions of the Tugwell bill, slipped in the provision originally proposed by the AIH in 1908 -- recognition of the HPUS along with the U.S. Pharmacopoeia, and the National Formulary, as official drug compendia.
Copeland's motives and intent in including the HPUS in the FDCA remain the subject of speculation. It is true that Copeland does not appear to have defended or even mentioned homeopathy on the record [77]. His early medical allegiances only could hurt him as sponsor of a new food and drug statute in 1933, and therefore they were ignored by the bill's supporters. Moreover, Copeland's experiences as Health Commissioner of New York City had made him sympathetic toward much of the work of FDA, especially in the area of pure foods [78]. Copeland's earliest justifications for the proposed new federal statute, however, does contain references to alternative practitioners such as osteopaths, hydrotherapists, and chiropractors. Copeland indicated that he merely wished to protect them from "interference" by regulators [79]. Politically, protecting alternative practitioners was a shrewd move that could have gained new and needed support for the proposed bill. At the very least, it would not have created new opposition from alternative practitioners.
It is clear that Copeland was not a fan of alternative medical practices. Chiropractors, in particular, enraged him as Health Commissioner of New York. He once responded to a query concerning chiropractic medicine by charging that "the average drugless healer (chiropractor) is ignorant of the fundamentals of medical knowledge and has no conception of the science of disease and fights against educational requirements." [80] In another instance, he testified:
I have found them to be a public menace and peril. They have treated typhoid fever patients as well as tuberculosis and others suffering from communicable diseases and have not merely endangered the lives of such patients but by their ignorance and denial of the germ origin of communicable diseases, they have imperiled the health of others and permitted such diseases to spread [81].
In December 1933, as Copeland was preparing his first revision to the Tugwell Bill, he studied a proposal to include a subsection 4(e) of the food and drug bill [82]. Section 4 of the bill defined adulterated drugs and contained references to the USP and NF. Section 8 of S 1944 defined a misbranded drug as one calling itself a cure or "if its labeling bears any representation, directly or by ambiguity or inference, concerning the effect of such drug, which is contrary to the general agreement of medical opinion." [83] Section 9 of the bill on false advertisements, prohibited therapeutic claims "contrary to the general agreement of medical opinion." [84] When Copeland introduced the original draft food and drug bill in June 1933, he had not read it in its entirety, and when he finally did, he found some objectionable features in the bill [85]. One of these features undoubtedly would have been the provision prohibiting therapeutic claims for a drug without the support of "substantial medical opinion" or "demonstrable scientific facts." [86] In the earliest drafts of the FDCA, the term drug also encompassed medical devices [87]. Copeland supported the provision as it would have applied to osteopaths, chiropractors, and hydrotherapists, many of whom used devices rather than drugs, as well as to others considered charlatans or quacks. Yet, as written, it was equally applicable equally to homeopaths.
In December 1933, homeopaths proposed that Copeland include a section 4(e), which would declare that government officials could not determine "therapeutic values" contrary to those pronounced by the U.S. Pharmacopoeia, the National Formulary, or "any medical textbook approved for study in the curriculum of any recognized medical school or college in the United States." [88] This proposal was never enacted.
As important as the proposal's substance was its reasoning. Homeopaths found the therapeutic claims provisions of the bill particularly threatening, noting that "an honest but irresponsible official could exercise his own therapeutic whims to business detriment." [89] Homeopaths cited the case of virburnum, a staple homeopathic drug, in declining use among regulars, but still listed in the 1905 USP. They argued that "no group of officials, medical or otherwise, should have it in their power to say that drugs recorded of value in times past are now obsolete or of no medical worth." [90] Fearing that officials might "get around medical choice in therapy" and pronounce "that some new drug, perhaps synthetic, has supplanted an old, time-tested drug in efficacy and consequently should be used in place thereof," homeopaths pointed out that FDA's Chiefs of Drug Control had all come from the "regular" profession. Furthermore, every Chief of Drug Control to date had shown a tendency toward this "variability of therapeutic determinations." [91]
There is an instance of one chief establishing the therapeutic virtues of salicylic acid in rheumatic trouble; a following chief caused the manufacturer to use aspirin instead of the salicylates; while a third and succeeding chief caused the replacement of the aspirin with the salicylates original to the formula [92].
In addition to such general concerns, the document cites the specific example of a popular homeopathic cold remedy, "Humphrey's No. 77 for Colds."
A Chief of Drug Control of the Regular School, unless inhibited by some provision of the new law, could absolutely throw out such a medicine as totally inert; yet probably hundreds of thousands use that particular remedy and have so used it for years because of the results as given in aborting or shortening the duration of colds [93].
The proposed remedy, the "textbook provision" to be included as a subsection 4(e) in the bill, does not mention homeopathy by name. It would have sanctioned homeopathy alone, however, because none of the alternative medical practices -- chiropractic, hydropathy, or osteopathy -- was recognized through a text adopted by a recognized medical school [94]. Only homeopathy had a text (Hahnemann) used in its own medical schools [95]. Copeland, however, rejected this provision and could have done so for a number of reasons -- its provisions were rather transparent; alternative groups would have discovered the ruse rather quickly and the bill already had enough enemies without creating new ones; if enacted, the provision might have encouraged alternative practitioners to author and seek adoption of a textbook, which was not Copeland's intent.
Copeland introduced S 2000 in January 1934. In his introductory remarks, he stated his opposition to "interference with various schools of healing such as chiropractic, osteopathy, hydrotherapy and the like." [96] Copeland rejected the homeopaths' "textbook" provision in favor of the simpler solution of recognizing substances in the HPUS as drugs in section 4 of S 2000 [97]. Copeland's proposal, however, and FDA's acceptance, may have been based on entirely different premises and understandings.
In addition to recognizing the HPUS as an official compendia, section 4 specifically provided that where a drug was recognized in both the USP and the HPUS, that the USP standards would prevail unless the drug specifically was labeled and sold as a homeopathic drug. This provision could have arisen from the example of virburnum and other substances listed in both the USP and the HPUS that was supplied to Copeland by the homeopaths. More likely, however, it protected and clarified a legal strategy that FDA officials hoped to employ against a particular group of quack products peddled by William Frederick Koch, for the treatment of cancer.
According to a recent article by historians James Harvey Young and Richard McFadyen, Koch possessed legitimate medical credentials [98]. Nonetheless, he devised three "synthetic antitoxins" in his laboratory and in 1923 began to distribute them to "restore natural immunity" in fighting human cancer, as well as other diseases. Glyoxylide, Malonide, and Benzoquinone all were diluted with distilled water to "about a trillion times their original volume" following Koch's consultation with, and ultimate employment of, the Dean of the Homeopathic Department at the University of Michigan [99]. FDA could not persuade either the Post Office or the Federal Trade Commission (FTC) to take on Koch, and FDA did not feel that the 1906 Act or the Sherley Amendment of 1912 allowed them to prosecute Koch [100]. His products bore no claims and were sent only to licensed physicians [101]. Young recalls that the records indicate that at one point the homeopaths and FDA worked together, ultimately unsuccessfully, to discredit the Koch Cancer Treatment's claims to cure cancer [102]. Had the HPUS been recognized as a legal drug compendia, action might have been initiated against Koch for marketing a nonstandard homeopathic product [103]. FDA agreed to Copeland's insertion into the law and kept silent about it to establish a means to act against Koch.
Although Copeland had rejected the homeopath's "textbook provision," he sympathized with at least some of their concerns. Copeland's revisions in S 2000 indicate his overall agreement with the homeopaths' admonition to him that the new bill "in its every part must carry self-contained justice, as far as possible leaving nothing to favorable or unfavorable misconstruction by agents executing the law." [104] Homeopaths, however, were far from unique in criticizing this aspect of the original proposal. In fact, the chief concern about the original Tugwell bill was a perception that extraordinary powers had been vested in the Secretary of Agriculture as administrator of the act [105]. For example, in section 4 of the original bill, under the definition of a drug, the Secretary was permitted to establish what later was explained to be "emergency tests" for purity, quality, or strength, to supplement those of the USP and NF [106]. Copeland's first revision, S 2000, was aimed primarily at meeting widespread industry concerns about "dictatorships" and "bureaucratic whims." The so-called "emergency" drug standard provision was modified, along with other similar provisions throughout the original draft [107]. All references to "consensus of medical opinion" were replaced with "general agreement of medical opinion" after it was astutely perceived by nearly everyone that it was unlikely that medical experts ever would achieve a consensus on anything [108]. Copeland's subsequent draft, S 2800, dropped all references to "medical opinion." [109] At that point, Copeland also announced that he had confined "regulation-making power" to those "few instances where the problems are so complex and so changing with scientific progress" that they were necessary to protect the public [110]. Elsewhere, he said he had added "definite" court review provisions, as well as a system of checks by "non-partisan committees of scientists whose members are affiliated with neither the enforcing agency nor the regulated industries," to satisfy all lingering concerns about excessive bureaucratic powers [111].
Did no one challenge such a seemingly important insertion -- recognition of the HPUS as an official drug compendium -- in the draft food and drug bill? Apparently not. The HPUS appears to be the only organized group to have tested section seven of the 1906 Act that allowed self-professed quality standards [112]. Homeopaths undoubtedly were elated at their success. Ultimately, inclusion of the HPUS in the new 1938 statute became more significant when the final bill eliminated the variation clause and made HPUS alongside the USP and NF, exclusive rather than optional drug compendia [113]. Now, all drugs had to conform to the standards of one of the law's three recognized pharmacopeias, or state their deviations on the product label. The AMA, according to its then-president, Dr. Morris Fishbein, had no problems with Copeland or the recognition of the Homeopathic Pharmacopoeia because Fishbein believed, much like Flexner, that the more science that homeopaths learned, the less homeopathy they practiced [114]. Also, the AMA and the homeopaths at this time found themselves in a new posture of unity as they opposed the New Deal and proposals for "socialized medicine." [115] Copeland, a conservative Democrat, often was at odds with many New Deal measures, and his differences with the President at times made passage of the FDCA look remote [116]. Moreover, it seems that almost everyone, except homeopaths themselves, felt that homeopathy eventually would be absorbed into the mainstream of medicine [117]. Statistics supported this view: there were more homeopathic physicians in the AMA at that time than in the AIH and the children of many homeopaths who remained in medicine chose regular routes of study [118]. In 1934, as the Copeland Bill was debated, the eminent physician, Henry Sigerest characterized homeopaths in his book American Medicine as "thoroughly trained physicians," noting that "there are many competent practitioners among them." [119]
There was no need to test the new HPUS provisions of the act in prosecuting Koch after the law was enacted. Recognition of the HPUS merely ensured that Koch could not claim that his product was homeopathic because his allegedly active ingredients were not listed in the HPUS. FDA had several options under the new law for prosecuting Koch, however, and it ultimately used both its new authority to conduct factory inspections and its new drug authorities to proceed against Koch. FDA's early experience in conducting factory inspections and its successful use of factory inspection reports in court cases made this the simplest and most straightforward approach to gathering evidence against Koch [120]. Because nonofficial drugs under the FDCA had to declare all active ingredients on their labels, something that Koch proved both unwilling and unable to do, FDA acted against Koch beginning in 1940 [121]. There was no need to test the HPUS provisions, and in the end, the FTC took the lead in suppressing Koch's illegal activities [122]. Because FDA did not employ the HPUS provision against Koch, and does not appear to have tested it against any other product, homeopathic or otherwise, in court, the provision remained untested as a strategy against medical quackery.
The HPUS provision appeared in the Copeland Bill in 1934, a year before the first sulfa drug, Prontosil®, came on the market. Prontosil® launched a therapeutic revolution that called into question the therapeutic efficacy of all preceding drug products, homeopathic or otherwise. At the time the 1938 Act was enacted, sulfanilamide's revolution was underway. In the decades that followed, however, the "wonder drugs" began to revolutionize drug therapy and FDA's campaigns against both nutritional and medical quackery shifted the agency's entire perspective on effective medical therapy. In such a new therapeutic environment, regulators and skeptics found it increasingly incomprehensible that the FDCA formally recognized the HPUS.
Under the FDCA, homeopathic drug products in the HPUS were stipulated to be drugs, and as with products in the USP and NF, they were subject to the drug requirements of food and drug law. The most revolutionary drug feature of the FDCA was the final-hour provision requiring that new drug marketers file applications demonstrating their safety to FDA prior to marketing them [123]. This provision, enacted in the wake of the Elixir Sulfanilamide tragedy in 1938, virtually reinvented drug regulation in the United States [124]. In its charge to ensure the safety of all new drugs, however, the agency virtually ignored homeopathy. No one had charged that homeopathic drugs were unsafe and there were few, if any, "new homeopathic drugs."
As early as 1938 FDA differentiated between drugs that could be obtained only by a physician's prescription and those available for self-medication "over-the-counter." It was not until 1951, however, with the passage of the Durham-Humphrey Amendment, that the distinction was enacted into law [125]. In the wake of Durham-Humphrey, virtually all homeopathic drugs became prescription drugs. The AIH persuaded regulators that the tenets of homeopathy dictated that treatments were highly individualized. Most homeopathic drugs should be dispensed by a practicing homeopath, and therefore the AIH believed that they were categorized best as prescription drugs. Taken by surprise, FDA informed inquirers in 1953 that although Durham-Humphrey did "not appear to directly encompass homeopathic preparations as prescription drugs,"
The agency had no objection to their distribution with the prescription legend [126]. The agency did note, however, that it would not act against homeopathic products "without the prescription legend which are offered to the laity for minor ailments." [127] In defending the prescription requirement for homeopathic products, FDA generally advised inquirers that "it is our position that adequate directions for lay use of Homeopathic preparations cannot be devised." [128] Homeopathic drugs were restricted to sale on the written or oral order of a practitioner licensed by law to administer such drugs, and like other prescription drugs, they were required to be labeled [129]. The prescription labeling requirement for homeopathic drugs, however, was not enforced strictly, reportedly because some FDA officials believed that use of the Rx symbol lent undeserved credibility to homeopathic drugs [130].
While the safety of homeopathic drugs under the FDCA drew no regulatory scrutiny, passage of the 1962 Kefauver-Harris amendments in the wake of thalidomide, did generate questions about the extent to which homeopathic drugs should be required to conform to the law's new efficacy provisions [131]. Once the National Academy of Sciences and FDA had begun the Drug Efficacy Study Implementation (DESI) project, however, FDA felt that the expert criteria governing that study -- "generally recognized among qualified experts as safe and effective" -- would be difficult to apply to homeopathic remedies [132]. Because the HPUS was recognized in the FDCA, homeopathic drugs would have to be evaluated for efficacy by homeopathic experts according to homeopathic standards [133]. Homeopathic leaders did not believe that this was possible, and FDA was not inclined to establish a separate review panel or process for homeopathy [134]. Much of the literature on homeopathic drugs was written in the nineteenth century, and "provings" did not begin to resemble adequate and well-controlled double blind drug trials. Homeopathic practitioners themselves agreed that "because of the theories of various homeopathists and the individualized nature of their prescribing practices," evaluations of efficacy would be virtually impossible because "there is no real unanimity of opinion among homeopathists as to what remedies are specific for a particular symptom complex." [135] In short, without the assistance of homeopathic experts, an efficacy review of homeopathic products was deemed not feasible.
Technically, the agency was justified in not looking at homeopathic preparations during the DESI process because the 1962 Drug Amendments required re-review only of drugs originally approved between 1938 and 1962 on the basis of safety alone. Because they posed no safety concerns, homeopathic drugs had not been approved by FDA between 1938 and 1962. During this period, the agency began a policy of deeming some "safe" substances "unsafe" when promoted for serious and life-threatening conditions, such as cancer. This policy was not applied to homeopathic remedies or homeopathic practitioners, however, because there did not appear to be a problem with homeopathic drugs making serious curative claims [136].
In 1972, FDA's Chief Counsel, Peter Barton Hutt, met with homeopathic officials to consider review of homeopathic drugs under the OTC drug review process announced January 5, 1972 [137. Representatives of the AIH, the American Foundation for Homeopathy, and the American Association of Homeopathic Pharmacists (AAHP) agreed that about one-third of homeopathic drugs sold at that time were sold OTC [138]. By 1971, officials recognized that homeopathic preparations were attracting new OTC sales among laypersons. Health food stores, for example, provided a new outlet for homeopathic products. FDA's campaign against nutritional quackery encompassed these new outlets, and although officials questioned the "usefulness" of these products, FDA appears to have taken little action against OTC homeopathic drugs at the time [139]. Officials did, however, insist that imported homeopathic drugs meet the requirements of U.S. law. In 1971, for example, FDA informed a Canadian importer that his products did not meet the law's requirements because they contained ingredients not in the HPUS. Citing as "one of the fundamental principles of homeopathy" that the selected remedy should be administered singly, an official noted that "although several of the ingredients of each of the drugs [offered for import] are indeed recognized in the Homeopathic Pharmacopeia of the United States, not one of the combinations of the ingredients is recognized in that compendium." He concluded "the drugs [thus] appear to contravene one of the fundamental principles of homeopathy and would therefore require approved new drug applications before they could be imported." [140] In 1977, the U.S. District Court for the District of Nevada upheld the agency's detention of misbranded homeopathic drugs [141].
In a May 1972 commentary published in the Federal Register, FDA responded to the AIH's request for exclusion of homeopathic drugs from OTC review. "Because of the uniqueness of homeopathic medicine, the Commissioner has decided to exclude homeopathic drugs from this OTC drug review and to review them as a separate category at a later time after the present OTC drug review is complete." [142] This was not a difficult decision. In the context of a massive review of somewhere between 100,000 and 500,000 OTC drug ingredients, homeopathic drugs seemed trivial at best. FDA also was immersed in what would become a debacle over the regulation of vitamins and minerals [143]. Homeopathic drugs appeared to pose no direct health threat, and if they were being prescribed for serious or life-threatening diseases, however, this had not come to FDA's attention. In short, they enjoyed only a limited market. The decision made during this era to treat homeopathy as a special case was made under the continuing assumption that homeopathy was a dying specialty [144]. As FDA noted, "in light of competing regulatory priorities, homeopathy was a medical back-water." [145] The last class of homeopathic physicians graduating from a homeopathic medical school graduated in 1960 from the Hahnemann Institute in Philadelphia and few states had statutes recognizing the practice of homeopathy [146].
In the proposed 1979 Drug Reform Act, mention of the HPUS was omitted from the proposed rewriting of section 5 of the FDCA. Because the bill was defeated and no House hearings were held, it is unclear whether the omission was deliberate or inadvertent. Nonetheless, homeopathic organizations noted and protested the exclusion. Following meetings with these organizations, FDA announced that it would move to classify homeopathic drugs as prescription items [147]. Beginning in 1981, FDA surveyed twelve homeopathic drug manufacturers and was concerned to note that there had been tremendous growth in the market for OTC homeopathic preparations, some sold for treatment of serious medical conditions [148]. FDA no longer was regulating a few old, established firms such as Boericke and Taffel marketing a few hundred exclusively homeopathic products. Homeopathy was no longer an exclusive specialty of physicians that Henry Sigerest had pronounced "competent" in 1934. Far from a dying therapeutic practice, homeopathy as self-help appeared to be experiencing a worldwide regeneration [149]. Traffic in imported homeopathic drugs, for example, had increased exponentially. Attention was drawn to imports when FDA seized a shipment of homeopathic drugs imported from Switzerland in 1984 [150]. FDA officials charged that the drugs were imported illegally because they did not bear the Rx legend. The imports eventually were released when the Swiss Embassy claimed that the seizure violated a provision of the General Agreement on Tariffs and Trade (GATT). Officials initiating the seizure were chagrined to learn that FDA's requirement that homeopathic drugs bear the Rx legend had been unenforced since it was enacted. The AIH, moreover, reversed its previous position supporting the marketing of most homeopathic drugs through homeopathic practitioners and argued, instead, that the great majority of homeopathic drugs should be allowed onto the market as OTC drugs, just as cold, cough, and headache remedies were allowed on the market [151]. The AAHP was revising the HPUS, subjecting it to modern drug provings [152]. Such profound changes in the homeopathic marketplace invigorated discussions about establishing an agency policy regarding homeopathic drug regulation.
After considering a wide range of options, FDA's Center for Drug Evaluation and Research (CDER) issued a formal Compliance Policy Guide (CPG) in 1988 establishing new guidelines to govern the agency's regulation of homeopathic drugs [153]. Officials considered requiring homeopathic drugs to bear warnings similar to those it imposed on medical gases [154]. In the end, however, this was rejected in favor of accepting the AIH's request to have some homeopathic preparations bear the Rx legend, while others were allowed to be marketed as OTC products for mild and self-limiting conditions [155]. In distinguishing prescription from OTC homeopathic drugs, the CPG stated that "those products that are offered for treatment of serious disease conditions must be dispensed under the care of a licensed practitioner. Other products, offered for use in self-limiting conditions recognizable by consumers, may be marketed OTC." OTC homeopathic remedies were required to have labels listing the ingredients and dilutions, as well as instructions for safe use [156].
The CPG did warn, however, that a homeopathic drug offered or promoted "significantly beyond the recognized or customary practice of homeopathy" would be subject to the agency's priorities and procedures with regard to the prosecution of health fraud [157]. Pursuant to the new policy, FDA did act against several start-up homeopathic manufacturers marketing products to the public, including injectable products for such conditions as AIDS, strokes, and cancer [158]. Overall, the CPG complicated regulation of homeopathic products. The CPG was regarded, in the words of one anonymous industry official, as a "how-to-manual" that quickly spawned an entirely new industry [159]. OTC drug manufacturers, in particular, began to protest the easy market access enjoyed by homeopathic products. Popular smoking cessation aids, for example, were sitting next to homeopathic products on store shelves, sporting similar claims and similar packaging, but with strikingly different price tags. Concerns about unfair competition were the subject of several citizen petitions submitted to FDA during the late 1980s and early 1990s.
In 1990, FDA's Center for Biologics Evaluation and Research (CBER) took a very different stance from CDER on homeopathic products by refusing to sanction homeopathic poison ivy extract oral pills manufactured by the Washington Homeopathic Pharmacy in Washington D.C. Rhus toxicodendron, or rhus tox for short, is an extremely popular homeopathic tincture [160]. In 1966, under unusual circumstances related to the regulation of pharmacies in the District of Columbia, the Washington Homeopathic Pharmacy had been licensed under the Public Health Service Act to manufacture homeopathic poison ivy extract pills as a biologic [161]. In 1972, however, when responsibility for biologics (serums, vaccines, antitoxins, etc.) was transferred from the National Institutes of Health (NIH) to FDA, all biologic products became subject to additional provisions imposed under the FDCA [162]. When CBER reviewed test results from allergenic extracts, reviewers found "no evidence of effectiveness for either prophylactic treatment or treatment of active disease" in the case of rhus tox [163]. Although the reviewers noted that "FDA may wish to consider this product differently because it is a homeopathic remedy," CBER did not elect to do so, insisting that its regulations made no separate provision for standards of effectiveness for homeopathic drugs [164]. CBER placed rhus tox in category IIIB -- subject to revocation until safety, potency, and effectiveness are proven [165]. In the end, a compromise was reached on the issue. Washington Homeopathic Pharmacy petitioned for a revocation of its license under the Public Health Service Act to avoid compliance issues related to that statute [166]. So far, however, CBER, has not taken steps to remove the rhus tox product from the market and it still is available as an OTC homeopathic drug.
In 1994, a citizen petition was submitted to FDA requesting that it hold homeopathic drugs to the same standards of safety and efficacy as other drugs regulated by the agency [167]. In the interim, the petitioners requested that consumers be warned that FDA does not consider homeopathic drugs effective. The petition called homeopathy a $250 million a year scam "equivalent to a car with no engine or a phony stock certificate."[168] The petition did not stimulate immediate action. For one thing, at only two pages, it was short on details as to how such a sweeping indictment might be issued or implemented. For another, its timing was particularly poor. In the late twentieth century there has been substantial growth in all fields of alternative and complementary medicine, not merely homeopathy [169]. In 1997, it was estimated that there were more visits made by patients to alternative medicine practitioners than to primary care physicians in the United States, and that more than sixty percent of patients did not report use of alternative therapies to their primary physicians [170]. In 1996, the industry estimated sales of homeopathic drugs to be between $100 and $200 million a year [171]. The effectiveness and value of such alternative and complementary therapies, however, are increasingly disputed, evidence is contradictory, and confusion rampant [172]. In the case of homeopathy, for example, a 1998 survey of pharmacists found that 27.4% of respondents deemed homeopathy "useful" while 18.3% found it "useless," and 54.3% were unsure [173]. Such confusion led some scientists and consultants to recommend more critical scientific evaluation of homeopathic therapeutic treatments [174].
At the time the citizen petition on homeopathy was submitted to FDA, Congress already had taken a controversial step in establishing an Office of Alternative Medicine (OAM) at the NIH. In January 1995, Dr. Wayne B. Jonas, a physician who believed in the efficacy of homeopathy, was appointed to head the office. Under Jonas' leadership, the NIH's OAM (now the National Center for Complementary and Alternative Medicine) expressed confidence that homeopathy could demonstrate some true scientific merit [175]. As Congress continued to increase the OAM's budget, the number of studies of homeopathic remedies increased, but results of the few published scientific studies to date have remained controversial [176].
In 1994, Congress passed the Dietary Supplement Health and Education Act (DSHEA) [177]. DSHEA indicated that Congress wanted consumers to have broader rather than more restricted access to dietary supplements. Congress defined dietary supplement and established a regulatory framework to ensure that product labeling is accurate, and that FDA can remove products that are adulterated or pose a "significant or unreasonable" risk to consumers. Unlike new drugs or food additives, Congress did not subject dietary supplements to premarket review requirements, except where the supplement contained a "new dietary ingredient." DSHEA did require nutrition and ingredient labeling to provide guidance for consumers and sanctioned the establishment of good manufacturing practices for dietary supplements. One of the most revolutionary provisions of DSHEA, however, was the provision allowing dietary supplements to bear "structure or function" claims on labels, provided that a firm could substantiate that the claim was truthful and not misleading and that the claim was accompanied by a disclaimer [178].
Although DSHEA dealt only with dietary supplements, it was interpreted largely as a harbinger of a new era in regulation. In March 1999, FDA Commissioner Dr. Jane Henney testified before the House Committee on Government Reform that since 1994 the dietary supplement industry had grown "exponentially," with $12 billion a year in sales and over half of U.S. adults take dietary supplement products [179]. Although often marketed in the same fashion and through the same venues, the homeopathic drug market has not grown as spectacularly as have dietary supplements, per-haps because homeopathic products still are regulated as drugs. The public, however, perceives little distinction. An issue of Time, devoted to visions of the new century, discusses "ginseng, ginkgo biloba, and homeopathic potions" interchangeably [180]. In language reminiscent of that used by medical reformers during Flexner's era then speculating on the future of homeopathy, it has been predicted that "any alternative therapy that can be proved valid will swiftly be incorporated into mainstream medicine," but any medicine "based on myth, irrationality and deception will eventually be rejected." [181] As for homeopathy, the public will become disenchanted with it when consumers "finally wise up to the fact that in many cases they are paying big bucks for a highly diluted mixture that is essentially pure water." [182]
Today, the HPUS is published by the Homeopathic Pharmacopeia Convention of the United States, a private nonprofit organization. It contains hundreds of monographs for homeopathic ingredients. Although the organization requires that certain homeopathic drug products be marketed only by prescription, including those from dangerous or toxic sources, not all homeopathic drug ingredients are recognized in the HPUS. So long as there is some official documentation that an ingredient generally is considered homeopathic, it can be marketed in a homeopathic drug product. In recent years, in fact, few new homeopathic ingredients have been added to the HPUS, indicating that the modest monograph requirements imposed by the HPUS for new homeopathic drugs are not being met [183]. The entire regulatory system governing homeopathic drugs has been defended as appropriate to a class of drugs posing few safety concerns. Nonetheless, it stands in marked contrast to the well-honed new drug application/investigational new drug process applied to all other new drugs in the United States. There are some indications of increasing concern, but in the end, Royal Copeland may be judged to have succeeded in his quest to keep homeopathy from being regulated to the "quack heap." [184]
Dr. Junod is an FDA Historian at the FDA History Office, Rockville, Maryland. This article won Society for History in the Federal Government (SHFG) Thomson Prize.