Live Longer Better: The Historical Roots of Human Growth Hormone as Anti-Aging Medicine

Live Longer Better: The Historical Roots of Human Growth Hormone as Anti-Aging Medicine Abstract In recent years, historians have turned their attention to the emergence of anti-aging medicine, suggesting that this interest group coalesced in the wake of widespread availability of recombinant human growth hormone (HGH) after 1985. We take a longer view of modern anti-aging medicine, unearthing a nexus of scientific, medical, and cultural factors that developed over several decades in the twentieth century to produce circumstances conducive to the emergence of this medical sub-specialty established on the premise of the anti-aging effects of HGH. Specifically, we locate these roots in earlier hormone replacement therapies and in the so-called life extension movement. We reveal the continual tension between, on the one hand, champions of a mainstream medical specialty and a field of biomedical research that aimed to improve health for the aged and, on the other hand, advocates who campaigned for medical endeavors to preserve midlife health in perpetuity, and even to extend the human lifespan. We also demonstrate that the two groups shared a belief in science to solve – or at least to ameliorate – the problems of aging. This commitment to science has been the hallmark of twentieth and twenty-first century prescriptions for living life longer and better. In 1921, scientists postulated the existence of a growth-promoting hormone in the anterior pituitary gland. It took twenty-three years to confirm the identity of this substance, and it took another twelve years after that to isolate it in humans. Human growth hormone (HGH) became available for clinical use from human cadavers in the late 1950s and via synthetically recombinant DNA technology in the 1980s. HGH was, and continues to be, prescribed by physicians to promote growth in children deemed to be pathologically short-statured.1 In 1990, HGH burst onto a different scene: the perennial quest to stave off the effects of aging. Newspapers around the world heralded the preliminary results of a small study published in the New England Journal of Medicine suggesting that treatment with human growth hormone caused men in their sixties and seventies to lose fat and gain muscle. To test the effects of human growth hormone in larger populations, the National Institute on Aging quickly awarded grants to eight groups of researchers. In 1992, before the results of any of these studies were published, two osteopaths founded the American Academy of Anti-Aging Medicine (A4M) to establish and promote a new specialty. Although not recognized by the American Medical Association or the American Board of Medical Specialties, A4M has, since 1999, conferred board certification in anti-aging medicine on thousands of health care practitioners. Some observers have suggested that the origins of anti-aging medicine can be traced to the availability of recombinant HGH in 1985. We take a longer view of modern anti-aging medicine, unearthing a nexus of scientific, medical, and cultural factors that developed over several decades in the twentieth century to produce circumstances conducive to the emergence of this medical subspecialty established on the premise of the anti-aging effects of HGH. Specifically, we locate these roots in earlier hormone replacement therapies of the 1940s and 1950s and in the emerging life extension movement of the 1980s.2 The historical record suggests that members of the life extension movement were not simply individuals dedicated to eluding death and promoting youthfulness through scientific intervention. Rather, these actors sought to alter the dominant culture in terms of knowledge, attitudes, and behaviors about life extension. Their collective vision and mission had many of the features of a social movement. These proponents of the life extension movement, although nowhere near as numerous or influential as the advocates of women’s liberation or civil rights, were happy to proclaim themselves revolutionaries.3 At the height of the group’s popularity in the mid-1980s, the promotional efforts of its leadership often came off as more of a marketing ploy than a medical campaign. However, life extenders did have a shared purpose: to use science to prolong life and promote youthfulness. Even though some of them made fortunes by peddling their regimens, they also went to great and sometimes bizarre lengths to adhere to the protocols they proselytized. They also had shared enemies, namely, the federal government and orthodox medicine who, they claimed, stymied their efforts to transform the health of the nation.4 Together, they were “engaged in a more or less coherent struggle for change,” a defining characteristic of a social movement in the words of sociologists David S. Meyer and Nancy Whittier, and this concept serves as a useful organizing principle for historical analysis of the life extension and anti-aging programs.5 Anti-aging medicine and the A4M brought together traditions from two very different places on the spectrum of medical practice in twentieth-century America. The prescribers of hormone replacement therapies (testosterone and estrogen) in the 1940s and 1950s were orthodox physicians. They reported the results of clinical studies of exogenous hormones and collaborated with the U.S. Food and Drug Administration (FDA) in the regulation of these substances. By contrast, life extension proponents worked at the margins of the mainstream medical professions. They published books targeted to the public, and they viewed FDA oversight of drugs with skepticism and distrust. By the 1990s, the new proponents of A4M had blended aspects of both into an area of practice that mimicked the legitimacy of traditional medicine while appealing to the more fanciful beliefs and promises of the fringe group. In the course of this narrative, we reveal the persistent tension between, on the one hand, champions of a mainstream medical specialty and biomedical research field that aimed to improve health and quality of life for the aged and, on the other hand, advocates who campaigned for medical endeavors to preserve mid-life health in perpetuity and even to extend the human lifespan. What the two groups had in common was a belief in science to solve – or at least to ameliorate – the problems of aging. This shared commitment characterized efforts ranging from research projects conducted by medical school faculty and sponsored by the National Institute on Aging to cryogenic procedures conducted outside of the law. Human growth hormone provided the connective tissue that bound orthodox and heterodox medicine together in the realm of anti-aging therapeutics. The legitimacy briefly conferred upon HGH as an anti-aging medication in the 1990s enabled A4M to claim space within the boundaries of sanctioned medicine while, at the same time, promoting its work on the cutting edge (as opposed to the fringe). Replacement hormones more broadly had opened up this space decades earlier, exposing the porousness of the boundaries erected around mainstream medicine. The intertwined histories of hormones, life extension, and anti-aging medicine in the twentieth and twenty-first centuries demonstrate that lines separating legitimate from unconventional medical practice cannot be easily drawn. Sex hormones, growth hormones, and the fight against aging in the 1940s and 1950s There is a fairly direct lineage between the uses of sex hormone replacement therapies in the 1940s and 1950s and the anti-aging hormone cocktails of the 1990s and 2000s.6 In the earlier era, some clinicians saw the age-related decrease in sex hormone production to be permanent and thus to require long-term replacement therapy. Paul de Kruif, one of America’s best-known science writers, popularized the use of testosterone by men “burnt out between the ages of 50 and 75 … ready for life’s scrap heap …men in whom evidence of hormone hunger has been established.” De Kruif expressed his confidence in scientists: “as in the development of insulin and vitamin B1, increased production and the ingenuity of chemists will in time lower the hormone’s cost until it is within reach of every man who needs it.”7 Another clinical scientist who was an early and vocal proponent of long-term hormone replacement was William H. Masters. Better known for his 1966 book, Human Sexual Response, his research program in the 1940s and 1950s investigated the relationship between sex hormones and aging. His clinical trials led him to conclude that long-term sex hormone therapy could rejuvenate old people and to advocate “‘puberty to grave’ sex steroid support.”8 He blamed the failure of the reproductive endocrine system as “the Achilles’ heel” of the entire endocrine system. “We are essentially intact during our 60’s,” he proclaimed, “and perfectly capable of functioning … as efficiently as much younger persons, except that we are essentially castrates.”9 Replacing the hormones that the sex glands of older people could no longer produce would tackle: one of the greatest public health problems of the present and future … the rapid increase in our aging population. If we can avoid the physical and mental degenerative changes associated with senility, or at least prevent their appearance for many years beyond present expectancy, a major contribution will have been made, not only to the treated individuals but to the economy and potential manpower supply of our country.10 Masters anticipated that hormone replacement therapy would transform not only the social role of America’s senior citizens, but also the science of gerontology and the medical practice of geriatrics. Both geriatrics and gerontology were relatively new fields, formally organized in the 1940s.11 Geriatrics pointed to the older specialty of pediatrics as justification for a field organized around a stage of life (as opposed to an organ system, such as cardiology, or a disease class, such as oncology), but the similarities ended there. Geriatricians struggled to define boundaries between normal and pathological in diagnosing and treating problems of aging; as Laura Hirshbein has noted, their attention to these conditions – whether identified as abnormal or not – served to highlight old age as a time of disability.12 Gerontology also struggled with an identity crisis in the 1940s and 1950s, as the field tried to define itself in terms of research problems, methodological approaches, and boundaries. It was ambitious in scope, including under its umbrella basic biological, medical, psychological, and sociological lines of inquiry into the processes and ramifications of aging. While multi-disciplinarity was a laudable goal, it was in practice difficult to attain, because the different languages spoken by researchers trained in different disciplines impeded the cross-fertilization of ideas. What its practitioners agreed upon was a commitment to scientific inquiry; as W. Andrew Achenbaum notes in his history of gerontology, the field developed in the midst of postwar enthusiasm for the promise of science to solve social problems. The founders made it clear that they wanted to distance themselves from “alchemists, charlatans, con artists, or uninformed adventurers.”13 They saw themselves and their colleagues as serious scientists, who would employ the highest standards of rigorous and reproducible experimentation to expand the understanding of the processes and effects of aging. Indeed, the motto of the Gerontological Society of America was “to add life to years, not just years to life.”14 Masters’ rhetoric was consistent with that of other gerontologists. He pointed out that “there is not the slightest evidence to suggest, nor has any claim been made that steroid replacement increases longevity by one single day.”15 Rather, hormone replacement would enable old folks to live out their lives “happier, better adjusted, and more useful.”16 Since medical science had helped to extend life expectancy so that more and more women lived well beyond menopause, he argued that physicians ought to assume the responsibility of improving the quality of life during those later decades. Although one of his colleagues jokingly referred to him as “a twentieth century Ponce de Leon,” Masters insisted that “steroid replacement … in no sense represent[s] a panacea for the problem of aging.”17 Concentrating solely on the reproductive endocrine system, Masters’ steroid supportive therapy did not include growth hormone.18 Discovered in 1921, growth hormone gained attention primarily for its growth-promoting potential in part because it took academic and industry researchers decades to identify and isolate it.19 First reported by Herbert M. Evans and J. A. Long, the existence of growth hormone was postulated based on the clinical performance of pituitary extract in making people and animals grow.20 For more than twenty years, hormone researchers debated the existence and form(s) of growth hormone. Its most staunch supporter, Evans himself, later admitted that his hunch about a single growth hormone was very tenuous until GH was finally isolated in the 1940s.21 As the debate over the existence of GH entered its second decade, some researchers diverged from studies of its growth-inducing ability and ventured into investigations of its synergistic relationship with other hormones, most notably estrogen and insulin. During the late 1930s, physicians published reports on their successes with the addition of pituitary glands and pituitary extracts to the hormonal therapy given to women for abnormal uterine bleeding. Some investigators hypothesized that growth hormone alone would have been the preferred treatment since it was “luteinizing,” which meant it could spur the production of luteinizing hormone (LH) and therefore help regulate the menstrual cycle.22 Others explored the role of the pituitary gland, and especially the purported growth hormone therein, in the etiology of diabetes. Anterior pituitary extract treatment appeared to cause a permanent diabetic condition in animals. Influenced by sex hormone research indicating that hormone levels varied over the course of the life cycle, these investigators proposed that GH-induced diabetes could occur naturally from the over-production of GH. Menopausal women were considered to be at higher risk because decreased estrogen production increased their susceptibility to unchecked surges of GH.23 It appeared that too much growth hormone could cause health problems in older people.24 This concern about the overproduction of growth hormone was in contrast to Masters’s concern about the underproduction of sex hormones. Clinical research on growth hormone was stymied by the fact that GH is species-specific. It took hormone researchers decades to figure out this association. Once human growth hormone became available, it was used almost solely in clinical research and therapy on young boys. In part, this tightly knit association between growth hormone and growth production was due to strict regulation of HGH in the United States. Except for a few small distributors, a single federal agency, the National Pituitary Agency (NPA), oversaw most of its production and distribution. Researchers and clinicians had to apply for HGH directly to the NPA, resulting in limited use and application in both the clinic and the laboratory. During the next two decades, a few scattered instances of research on non-growth related properties of HGH could be found on the peripheries of basic and clinical research. Several of these studies did explore its regenerative potential. This research looked at HGH’s ability to provide metabolic support for burn victims, its role in insulin production in diabetics, and its potential in treating patients with multiple pituitary-hormone deficiencies.25 When HGH appeared in anti-aging science at the end of the twentieth century, this type of research was unearthed by human growth hormone enthusiasts as the precursors to their work and foundation for their belief in HGH as a youth promoter.26 In the 1960s, however, anti-aging research turned away from hormones, a trend that continued to obscure HGH studies that might have been deemed as breakthroughs in this field. At the same time, a collective belief in science’s ability to promote longer life was strong, and other medical and technological advances captured national attention. Sensationalist articles encouraged optimism about the possibility of extending life with awestruck reporting on vaccines, transplants, and reconstructive surgery that depicted these technological advances as preludes to the ultimate goal of life extension.27 As Frederick Pohl wrote in a 1964 Playboy magazine article titled, “Intimations of Immortality: Scientific Progress Toward Prolonging Human Life and Predictions Concerning its Indefinite Extension,” There is no fiction in the organ transplant that are being performed almost daily – or in the artificial organs that replace or supplement natural ones, on in the vaccines and antibiotics that take the fear out of ancient murderers like pneumonia and smallpox, or in the surgery that can build a new face on what is almost a bare skull, burned to the bone.28 Pohl extrapolated from this narrative to suggest that the “mere process of dying may in 1984 be no longer very important.”29 Aging was becoming just another problem for American scientists to solve. Official steps were taken to create a governmental infrastructure to promote this endeavor. In 1961, President Kennedy convened the first White House Conference on Aging, which recommended the establishment of a federal institute to support biomedical research on aging with the use of federal funds. Ten years later, the second White House Conference on Aging reiterated the call for a National Institute on Aging. By this time, the National Institute of Child Health and Human Development had been established, setting the precedent for an institutional focus on a stage of life rather than a disease (e.g., National Cancer Institute) or an organ system (e.g., National Heart, Lung, and Blood Institute). In 1974, the National Institute on Aging was established “for the conduct and support of biomedical, social, and behavioral research and training related to the aging process and the diseases and other special problems and needs of the aged.”30 However, research on the science of aging was by no means limited to government-supported investigation. “The life extending scene” in the 1960s and 1970s Patrick McGrady, Jr., was a journalist captivated by a wide range of efforts to combat aging. In 1968, he wrote a popular book called The Youth Doctors that documented decades of efforts to promote longevity using modern interventions. Hip to the lingo of the late 1960s, he described these efforts collectively as an emerging “life extending scene.”31 Treatments included cell therapy injections at the La Prairie clinic in Switzerland;32 a sheep-egg embryo, anti-aging regimen developed and popularized by Ivan Popov, a Yugoslavian doctor;33 plastic surgeries sought out by actors and actresses and others who wanted to look like actors and actresses;34 the “specialized service” of amphetamine-prescribing “speed doctors”;35 and the “most coveted youthefier [sic] in Europe”: Romania’s Gerovital H3 (GH-3).36 According to McGrady these interventions evidenced progress in “theoretical and experimental gerontology.” He suggested that, in the near future, “every American family will have its own rejuvenator,” a practitioner to forestall the aging process.37 McGrady, like most participants in the emerging life extension movement, believed fervently in the promise of science to enable people to “live longer better” and encouraged others to seek out anti-aging technologies.38The Youth Doctors imbued efforts from around the world with a sense of importance and further popularized anti-aging therapeutics and interventions. Dr. Frank G. Slaughter, author of Your Body and Your Mind: The New Science of Psychosomatic Medicine (1963) reviewed The Youth Doctors for the New York Times. His review began with McGrady’s assertion that the idea of youthfulness was “the number one obsession of our people in our time” not because of a “fear of death, but sex.” Slaughter was intrigued by McGrady’s claim that women pursued cosmetic interventions while men sought to overcome impotence. While Slaughter agreed with McGrady’s gendered analysis of youth seeking, he was less convinced by McGrady’s belief that science would resolve the problems of aging. Slaughter’s review concluded that The Youth Doctors “introduces the reader to an enthralling world, peopled by colorful individualists” and suggested that it might “not lead you to the fabled fountain, but it will interest and instruct, as well as entertain.”39 Donald W. Goodwin, a psychiatrist at Washington University in St. Louis who reviewed the book for the Journal of the American Medical Association (JAMA), was considerably less amused. He deemed the book “unfortunate” and argued that the treatments it highlighted lacked sufficient proof of legitimacy and efficacy.40 Angered by Goodwin’s assessment, McGrady submitted a rebuttal to the medical journal in the form of a letter to the editor. He described his book as a serious volume “on gerontology, its origins and peripheral landscape” and cited positive reviews by other experts.41 Goodwin stood by his original review, as the scientific press and mainstream medicine were steadfast in their criticism of those who promoted anti-aging therapies. The establishment opinion was best summed up by the author of a 1963 article in Geriatrics titled, “Drug therapy in aging patients:” “the concept of an ‘old age deferred,’ no matter what variation the title assumes, deserves little more than a look askance.”42 While many American clinicians remained cautious and even cynical about the latest rejuvenation therapies, physicians in Eastern Europe were more receptive to these interventions. Perhaps the best-known example was Romanian doctor Ana Aslan, developer and promoter of Gerovital H3, a procaine-based product. Procaine is a local anesthetic, known more commonly by the trade name Novicain. This alleged anti-aging drug was introduced to the global medical community first at conferences in Switzerland and Germany in 1956 and then in the pages of a French publication in 1958.43 Aslan had been using Gerovital to treat arthritic patients since the late 1940s, and she claimed that it also cured them of other age-related conditions, such as loss of muscle strength and memory.44 By the early 1960s, the hype around Gerovital was palpable, even though most American scientists questioned its potency and were frustrated by their inability to examine the chemical composition of the drug, whose formula belonged to the state and was kept secret. Aslan did reveal that, unlike other procaine therapies, hers included benzoic acid and potassium metadisulphite and that the procedure of compounding this preparation was what gave Gerovital its unique potency.45 Unable to unlock Gerovital’s secret formula that had been developed behind the Iron Curtain, the FDA decided to test its principal ingredient, procaine. Procaine was first made in 1905 by the German chemist Alfred Einhorn in search of a local anesthetic less toxic than cocaine.46 The FDA refused to approve the use of Gerovital in the United States when results from experiments testing procaine’s anti-aging ability proved inconclusive.47 Nevertheless, wealthy Americans who wanted to try Gerovital either smuggled the substance into the United States or traveled to Europe, where the drug was readily available.48 For those who chose to travel to the source, Romania was ready. By the early 1970s, the Romanian-Carpati National Tourist Office was featuring the treatment and its anti-aging properties in a travel brochure to cash in on this version of medical tourism.49 In 1972, perhaps due to American citizens traveling to Romania or the continued pressure from the public and the scientific community, US federal government officials decided to reconsider Gerovital. That year, three senators visited the Bucharest Geriatric Institute where they were briefed by Aslan and given tours of the facility.50 The FDA also authorized studies of Gerovital’s ability to treat depression in the elderly. Previous findings had suggested that Gerovital might work as a monoamine oxidase (MAO) inhibitor; MAO is a substance known to cause depression and to increase with age.51 Some of the research conducted blurred the lines between depression and aging, as in the case of a clinical study conducted by Dr. Sidney Cohen and Dr. Keith Ditman. Supplied with Gerovital by Rom-Amer Pharmaceutical Company (at the time located in Los Angeles), these California doctors conducted a Phase II open clinical trial in which forty-one subjects were given 100-200 mg of Gerovital intramuscularly three times a week for four weeks. The goal of the study was to test for safety and efficacy. Although they were studying Gerovital in the treatment for depression, Cohen and Ditman recruited some subjects with “no psychiatric problem.” They also reported that subjects’ main motivation for participating in the study was “a desire on their part to ‘age better’” and that most of the subjects had heard of Gerovital’s promise to combat aging before joining the study.52 Gerovital’s reputation as an anti-aging pharmaceutical persisted through the 1970s, as mass media articles about life extension and scientific research in Europe speculated about how the treatment worked (including a hypothesis that it had an effect on the hypothalamus, which had been identified as a sort of aging clock) and what the treatment could do, if approved, for Americans.53 Journalists also reported on European research suggesting that Gerovital could fight age-related illnesses and conditions, including Parkinson’s disease, depression, and the climacteric in both females and males.54 Not classified as a sex hormone and unable to demonstrate direct results, Gerovital never entered American physicians’ repertoire when it came to fighting symptoms related to menopause and the male climacteric. Although estrogen remained an acceptable treatment for menopause in women through the 1970s (and, indeed until the early 2000s), the use of testosterone as a treatment for aging men vanished from the medical literature after the mid-1950s. Instead, the symptoms that had previously described the male climacteric – fatigue, problems concentrating, loss of memory, restlessness, insomnia irritability, loss of libido – were re-fashioned into a diagnosis of a stress-induced condition. Psychiatry replaced endocrinology as the explanatory framework, and tranquilizers replaced hormones as the preferred therapy. Testosterone would not re-appear as a treatment for male aging until the 1990s.55 Ultimately, procaine was unable to establish itself as a viable anti-aging therapeutic in the United States. As one of its early actions, the National Institute for Aging (NIA) commissioned a review of world literature on procaine treatment. The 1977 report came out strongly against its use. In covering the report, the Journal of the American Geriatrics Society noted that data from “285 articles and books, describing treatment in more than 100,000 patients in the past 25 years” yielded “no convincing evidence that procaine (or Gerovital, of which procaine is the major component) has any value in the treatment of disease in older patients.”56 This definitive meta-analysis ended any chance that Gerovital would be approved for sale in the United States. The FDA’s refusal to approve Gerovital as an anti-aging drug did not quash the optimism held by those who were part of the life extension scene. These believers interpreted Gerovital and advances in biomedical science as life-saving and life-extending technologies. They understood “The Promise of Transplants,” “The New Technology of Bionics,” cloning, genetic engineering, and therapeutics including Gerovital along one continuum.57 In their opinion, it wasn’t the shortcomings of science that made longevity and youthfulness impossible goals; rather, it was the conservative medical establishment and restrictive federal government that obstructed medicine from reaching its full potential. This small but prolific group of believers continued to write about and practice the science of life extension well into the late 1970s and early 1980s. They aspired to alter the way Americans viewed end of life and aging, and they undertook daily regimens to forestall death, which they refused to accept as inevitable. From preparing final instructions for the cryonic preservation of their bodies to taking supplements intended to boost natural growth hormone levels, these practitioners were leading by example in order to bring forth a societal reward. In doing so, these life extenders appeared as a determined, if fringe, social movement.58 By the late 1970s, life-extenders wore their outlier position as a badge of honor and identified themselves as “pioneers” in the “pursuit of an extended human life span” as they fought “the most basic and formidable of our enemies – aging and death.” Their collective frontier was their bodies as they embraced a lifestyle that included practices of “dietary intervention, immunologic engineering, body temperature manipulation, and pharmaceutical therapy.”59 They viewed their self-experimentation with drugs and regimens (many of them untested) as a political stance against oppressive government regulation. Activists and others who disagreed with the government’s decision to outlaw the drug skirted federal law and manufactured, bought, sold, and consumed Gerovital, making it quite popular in anti-governmental regulation circles. In May 1979, there was a showdown between the main manufacturer and distributor of Gerovital in the U.S. and Congress when Rom-Amer Pharmaceuticals Ltd.’s new President and Chief Executive Officer, Marvin Krattner, was called to testify at the Senate Subcommittee on Health and Scientific Research’s hearings on drug regulation reform. In 1977, Krattner had successfully lobbied the state of Nevada to pass legislation allowing for the manufacture and intrastate distribution of Gerovital. Business was booming and had spurred medical tourism to the Las Vegas strip.60 This new tourist trade received national attention and was one of the reasons Congress decided to consider stricter regulations on the federal oversight of interstate distribution of drugs in 1979. Krattner’s testimony at the congressional hearing exemplified the life extension movement’s position on the FDA and federal oversight. He argued that the FDA should not “be permitted to erase and eliminate State lines [making us] one Federal state.”61 He also suggested that increased regulation would infringe on personal rights: The American citizen today appears to be the only one in the world without the constituency of his own body, and, by virtue of the efficacy requirements of the existing law, he is not given the freedom of choice to decide, even with the advice and consultation of his own personal physician, as to whether or not he may elect to have a drug administered or dispensed to him in an attempt by his physician to determine whether or not that particular drug is efficacious for that particular patient in the treatment of one or more various illnesses.62 This interpretation of FDA regulation as stifling personal freedom was shared by others engaged in and advocating for life extension therapeutics. They believed that government agencies were having a “profound and generally negative impact on the progress of aging research” and that the FDA’s “regulatory policies have drastically reduced the amount of pharmaceutical innovation without a measurable increase in either drug safety or efficacy.”63 They also criticized the NIA for its reluctance to fund research on extension of the human life span.64 This anti-establishment stance of life extension promoters did not compromise the movement’s popularity among adherents and in some way may have contributed to it. Activists within the life-extension movement understood aging to be both disability and disease. Aging disabled older Americans by preventing them from participating as fully in life as compared to younger Americans or their own younger selves. And aging was the ultimate life-threatening disease, as its inevitable outcome was death. In combating the morbidity and mortality of aging, these activists had no compunctions about using any and all remedies, regardless of government approval or mainstream medical sanction. Living Longer and Better in the 1980s Interest in life extension grew in the early 1980s as part of the wave of enthusiasm for self-help diet and lifestyle books. An early success of the life extension self-help genre was the 1979 bestselling The Pritikin Program for Diet and Exercise by Nathan Pritikin with Patrick M. McGrady, Jr. (author of The Youth Doctors). Described as a “prescription of health and long life,” the program featured an exercise regimen and a diet low in fats, cholesterol, and protein and high in unrefined carbohydrates. According to Pritikin, exercise and a restricted diet could promote a longer life and reverse debilitating diseases such as diabetes, cardiovascular disease, and cancer. For the affluent looking for a more hands-on intervention, Pritikin opened a chain of Longevity Centers. The centers offered programs for those battling disease as well as for those merely interested in prevention.65 The Pritikin Program was strict compared to dietary standards of the time, as, for example, those issued by the American Heart Association (AHA). It limited salt intake and prohibited sweeteners, caffeine, and alcohol. The Pritikin diet provided five to ten percent of calories in fat, ten to fifteen in protein, and eighty percent in complex carbohydrates; compared to the AHA’s recommendation of thirty percent fat and the typical American diet of forty-five percent fat, the program was panned by some reviewers for being too unrealistic. But to Pritikin it was a matter of life and death. He believed so strongly in his program that he asked the director of the National Heart Lung and Blood Institute (NHLBI), Dr. Robert Levy, to fund research to compare its results with those from the AHA-recommended diet. When Levy refused, Pritikin labeled Levy the enemy and decided to find funding on his own.66 Pritikin accepted and even embraced his outsider status. A college dropout, he made his fortune by developing patents in chemistry, physics, and electronics for companies such as General Electric and Corning Glass.67 In spite of criticism from the medical establishment and competition from other diet developers, Pritikin had a loyal following, which grew during the 1980s and included those who believed in the life extension principles of diet manipulation.68 While Pritikin was not a hard core life extender – his focus was on a restricted diet and exercise to reverse disease and increase longevity, and not on self-experimentation with substances or the promotion of cryonics – his books and centers can be regarded as part of the larger movement to popularize the notion of personal empowerment to defy aging and death.69 Two organizations in particular, the Fund for Biomedical Research (FIBER) and the Life Extension Foundation (LEF), were central to the campaign to challenge the idea that aging had to be inevitable and to the life extension movement. These groups represented the formal, organized wing of the movement. They articulated the movement’s goals and allowed for more cohesive and collective action; as such, they provide structure for this social movement.70 FIBER was the less sensationalist of the two as it worked within the parameters of experimental gerontology specifically and scientific medicine more generally. Founded in 1979 by a senator (Alan Cranston, Democrat-CA) and a physician (William Regelson, a medical oncologist and professor of medicine at the Medical College of Virginia), FIBER was intended to operate as an “institute without walls” by promoting cooperation among scientists working on anti-aging research.71 It did so by coordinating conferences, hosting frequent meetings with experts, endorsing popular books promoting aspects of life extension, and supporting research.72 FIBER experienced some early success and brought some legitimacy to the life extension movement. By 1982, it reported progress in its documentation of geographic variation in death rates, lab research on an organ transplant process that rejuvenated rats, and the discovery of a “death hormone,” which many believed could be responsible for aging.73 In contrast, the Life Extension Foundation (LEF) took a different approach in promoting anti-aging science by focusing on educating the public and fostering a popular health movement. Financially backed by real-estate mogul Stephen Ruddell, LEF was founded in 1980 by mortician William Faloon and science writer and long-time cryonics advocate Saul Kent. A veteran of the life extension movement, Kent was the initial front man of the operation, while Ruddell stayed behind the scenes and Faloon learned the ropes. Kent’s decades-long involvement in the movement reflected its larger developments. He was one of the founders of the first cryonics society in New York in the mid-1960s.74 In 1974, he contributed to the growing science fiction subgenre of life extension with the publication of his book Future Sex.75 Two years later, he published a more technical foray into the science of anti-aging, with an article in Geriatrics titled “Solving the Riddle of Lipofuscin's Origin May Uncover Clues to the Aging Process.”76 In doing so, he remained on trend with his colleagues, as other life extenders also authored scientific treatises on immortality. During the late 1970s and early 1980s, Kent helped to publicize the life extension movement by writing in popular magazines and in a running column, “New Frontiers of Research,” in Geriatrics.77 The jacket of his 1980 book, The Life Extension Revolution, described it as a “definitive guide to better health, longer life, and physical immortality,” and its author as “an activist in the life-extension movement for over fifteen years.”78 LEF would prove not only to be the next chapter in Kent’s career as a life extender but also to provide him with an opportunity to make millions. Headquartered in Hollywood, Florida, LEF sold what it called “nutritional supplements” through its mail-order business. The Miami Times reported that LEF was making four to five million dollars in profit by 1985 through drug sales and membership fees.79 The founders claimed LEF was a non-profit organization focused on providing information about the life-extension lifestyle and laboratory and clinical research on anti-aging. LEF’s major publication was a monthly twelve-page newsletter, Anti-Aging News, featuring the “latest scientific efforts to prevent aging and rejuvenate the aged” and interpreting complex scientific research for its lay subscribers.80 While the official intent of the newsletter was to keep members informed about the latest trends in anti-aging, it also served as a marketing tool. LEF’s efforts blurred the lines between non-profit and for-profit. As public interest in life extension grew, Kent marketed his foundation’s services and products wherever he could. He appeared on television talk shows, such as the Merv Griffin Show. During these staged discussions, Kent not only sang the praises and possibilities of life extension but also encouraged interested viewers to contact LEF for information about services.81 More members meant more profits for this allegedly non-profit venture. There were others who also proselytized self-experimentation in the hopes of “living longer better.” Durk Pearson and Sandy Shaw were two early converts who frequented talk shows on television and radio to spread the gospel of anti-aging therapies.82 Their devotion to self-experimentation in life extension paid off in the early 1980s when their co-authored book made the New York Times bestseller list in 1982.83Life Extension: A Practical Scientific Approach reported in vivid detail the results of their self-experimentation with high doses of nutrients and drugs that they claimed would cheat the effects of aging.84 Pearson and Shaw promoted their book as “an invitation to a personal adventure that may lead to a longer and more vigorous lifetime” by laying out a plan for personal life extension.85 Neither Pearson nor Shaw had graduate training in medicine, pharmacy, or biomedical research (as undergraduates, the former majored in physics at MIT and the latter majored in chemistry at UCLA). Nonetheless, they saw themselves as scientific pioneers; in dedicating their book to James Watson and Francis Crick (the discoverers of DNA), Denham Harman (developer of the free radical theory of aging), and Albert Hofmann (inventor of hydergine, used to improve circulation and cerebral function, especially in the elderly, and discoverer of LSD’s hallucinogenic properties), they sought to locate their anti-aging, Life Extension, lifestyle prescription within a pantheon of important scientific discoveries.86 So successful was their first book that they quickly followed it up with two more: Life Extension Companion (1984) and Life Extension Weight Loss Program (1986). Pearson and Shaw claimed that daily thirty-minute workouts and consumption of a specific regimen of vitamins, preservatives, and drugs could help stave off illness and debility and promote longevity. The experimental drug regimen was lengthy and included vitamin A, beta carotene, vitamin E acetate, selenium, zinc, L-arginine, tryptophan, L-dopa, Deaner (dimethylaminoethanol, Riker), choline chloride, RNA, vitamin B-12, high potency multivitamins with chelated minerals, vitamin B-1, thiamine HC1, vitamin b-2, riboflavin, vitamin B-3, nicotinic acid, vitamin B-5, vitamin B-6, pyridoxine HC1, rutin, hesperidin complex, PABA, L-cysteine, vitamin C, inositol, hydergine (ergoloid mesylates), and diapid (vasopressin). They also advocated sex hormone replacement for post-menopausal women.87 The stimulation of HGH by several of the supplements listed above formed one of the core tenets of Pearson and Shaw’s anti-aging regimen. They argued that restoring growth hormone levels to those of early adulthood was vital to living longer and better. Their advocacy for restoring HGH levels originated with a research proposal written by Pearson in 1976 for private funding titled, “Toward a Possible Life Extension Technology Involving Human Growth Hormone.” Described in Life Extension, the “proposal dealt with the use of GH-releasers…to maintain teenage to young adult levels of GH in adults of any age.”88 Pearson and Shaw were aware of the mounting scholarship that suggested that the release of growth hormone fell off sharply with age and that this deficiency might make older people susceptible to loss of muscle, gain of fat, sleeping problems, slower rates of wound recovery, and compromised immune systems.89 However, they did not advocate the use of exogenous HGH; instead they championed what they claimed to be GH-releasing supplements: L-dopa, bromocriptine, vasopressin, tryptophan, L-arginine, and L-ornithine.90 Missing from their discussion about human growth hormone levels were findings that pointed to the unpredictability of supplements’ ability to elevate HGH levels, some suggested benefits that came with the normal decline in HGH levels, and possible dangers associated with increased HGH levels.91 Some research also proposed the loss of HGH could reverse clinical retinopathy and renal complications of diabetes. Other studies posited that HGH might in fact accelerate the aging process and could be associated with pituitary tumors in aging rodents.92 Instead of acknowledging conflicting reports, Pearson and Shaw sided solely with the literature that suggested increased levels of this hormone would benefit older people. The “evidence” of the effects of increased HGH levels presented by Pearson and Shaw was a series of photographs of themselves showing off their muscles after extensive self-experimentation with growth hormone releasers. Like Pearson and Shaw, most life extension advocates hailed the effectiveness of supplements in promoting longevity and youthfulness through the stimulation of human growth hormone. It is interesting, and somewhat surprising, that Pearson and Shaw and other life extenders did not recommend exogenous HGH, since they were not shy about promoting the experimental use of non-FDA approved substances, such as Gerovital and DHEA, or off-label use of approved pharmaceuticals. Furthermore, exogenous HGH had become more readily available in the 1980s with a change in processing methods and FDA approval of two cadaver-based products manufactured by two European pharmaceutical companies. Even though Pearson and Shaw were aware of these commercial products (Serono’s Asellacrin and Kabi’s Crescormon), they did not advocate the direct use of cadaver-based human growth hormone therapy (cHGH) for life extension purposes.93 Human Growth Hormone in the 1980s Pearson and Shaw not only recommended the intake of numerous vitamins and supplements, they also sold their own line of products. They weren’t alone in this commercial venture. The supplemental health industry targeting older Americans was so robust by the late 1970s that the House of Representatives Select Committee on Aging decided to investigate questionable practices such as anti-aging cures. After a four-year investigation, the report, Quackery A $10 Billion Scandal, found “youth cures … the fastest growing segment of medical quackery” to be entirely without merit and their advocates to be dangerous hucksters. Pearson, Shaw, and the Life Extension Foundation were called out as especially pernicious actors. Pearson and Shaw’s recommendations were criticized as scientifically unsound and possibly lethal, and the LEF was faulted for its evasion of legal and regulatory restrictions on the practice of medicine.94 Although the report condemned numerous anti-aging practices and products, it made no mention of HGH or GH promoters. Meanwhile, many athletes and some scientists started to experiment with cHGH. Used and promoted by bodybuilders, cHGH made a splash at the 1984 Olympics as new doping restrictions did not include human growth hormone.95 One physician, Dr. Robert Kerr, was the focus of a series of articles in the Los Angeles Times leading up to the Olympics. He had practiced family medicine until he got swept up in the performance enhancing drug craze. His book, The Practical Use of Anabolic Steroids with Athletes, helped advertise his services to athletes looking for a competitive edge. Kerr routinely suggested he was administering anabolic steroids and growth hormone to Olympic athletes from around the world. In the age of the “chemical” athlete, he believed that competitors had to do what was necessary to win.96 In justifying his practice, Kerr described his treatment as a way to make healthy people healthier.97 Researchers who studied the sanctioned uses of cHGH (to treat short stature in children) also self-experimented with injections. In an interview with the New York Times, Dr. Robert Blizzard, a physician at the University of Virginia medical school who played a major role in official cHGH manufacturing and distribution for decades, acknowledged that he and four other unnamed researchers over the age of fifty took it to test its anti-aging potential from 1983 to 1985. Although their experiments failed, Blizzard averred interest in giving it another try with younger men in their thirties. He rationalized that “instead of turning an old Ford into a new Ford, maybe we can preserve the young Ford for a longer period of time.”98 While part of the reason Blizzard experimented with cHGH was that it had become more available due to changes in production, he was also inspired by the pending revolution that was predicted to take place in the manufacturing of HGH. In 1985, the FDA approved the first synthetic version of human growth hormone produced by recombinant DNA technology (rHGH), which further increased the available supply and resulted in an increase in research efforts. One investigator who took advantage of the rHGH was endocrinologist Daniel Rudman, who had begun experimenting with pituitary extracts in the 1950s.99 In the early 1970s, his research focused on the hyper-responsiveness of people with a variety of muscle dystrophies to exogenous HGH.100 In the late 1970s, Rudman compared and contrasted the responsiveness of growth hormone deficient (GHD) children and normal variant short stature (NVSS) children to exogenous human growth hormone and found that some NVSS children were just as receptive as GHD subjects.101 He also documented the high incidence of GHD in children with cleft lips or palates and looked into the clinical outcomes of GH therapy in girls with X chromosome abnormalities.102 In the 1980s, Rudman’s research interests appear to have shifted, as he began publishing articles on endogenous growth hormone secretion in adults. In a 1981 article titled “Impaired Growth Hormone Secretion in the Adult Population,” Rudman and his team described the concomitance of a progressive decline of growth hormone and a hyper-responsiveness to exogenous GH in aging individuals. They speculated about an inverse correlation between adiposity and GH secretion as well as a possible relationship between the “geriatric decline” in “bone formation,” “renal blood flow,” and “stimulus protein synthesis in the lean body mass” and the reduced levels of GH that came with age.103 Although Rudman did not explicitly credit the expansion of his GH research to an increase in hormone supply, it would have been difficult for him to have received any of the hormone for his work with adults and non-GHD children without that greater availability. His publications also reflected an optimism brought about by an increase in supply, especially in his suggestions of potentially new clinical uses for HGH, including the treatment of both NVSS children and aging adults.104 Rudman’s research on growth hormone and enthusiasm for its therapeutic applications made him an ideal participant on a panel of experts convened by the FDA in 1980 to advise the agency on the potential future clinical uses of synthetic HGH.105 In 1983, Rudman began working at the Chicago Medical School and Veterans Administration Medical Center in North Chicago, Illinois. Funded by the Veterans Administration and Lilly Research Laboratories, Rudman examined GH secretion at the end of the life cycle and considered the possibility of treating the elderly with this hormone. He argued that about half of the population over sixty-five was partially or totally deficient in GH and – in a revised iteration of Masters’s hypotheses from the 1950s – that through replacement therapy some aspects of geriatric decline could be reversed.106 He continued this work in conjunction with the Veterans Administration Medical Center in Milwaukee, Wisconsin, when he took a position at the Medical College of Wisconsin in 1988. Rudman and his research team conducted a study on twenty-one men between the ages of sixty-one and eight-one who had low levels of growth hormone (based on low levels of insulin-like growth factor 1). Twelve received growth hormone therapy for six months while nine received no treatment. As he had hypothesized, once growth hormone levels reached a youthful range, the experimental subjects experienced an increase in lean body mass, a decrease in adipose tissue mass, an increase in average lumbar vertebral bone density, and an increase in skin thickness.107 Rudman’s report was published in the New England Journal of Medicine in July 1990, alongside an editorial that emphasized the preliminary status of the research. In the following weeks, the journal also published numerous letters to the editor about Rudman’s findings. His article stirred up debate among the journal’s readers and captured the attention of the popular media; the Wall Street Journal, Washington Post, Chicago Tribune, and New York Times all ran stories with headlines hailing HGH as the new hope for restoring youth.108 Although it might be expected that the life extension movement would have seized the Rudman report as justification for its long-standing claims about the anti-aging benefits of hormone therapy, by 1990 the movement had fallen on hard times. It suffered grave damage from adverse media coverage of its continued commitment to promoting, proving, and participating in cryonics, the practice of deep-freezing dead bodies until science discovered a cure to resurrect them. Two events in particular seemed to have sealed its fate. In the summer of 1987, Paul E. Segall, a researcher who had secured access to a laboratory at the University of California, Berkeley through dubious channels, gave a conference presentation on his success in freezing a beagle for fifteen minutes and subsequently reviving it. The press picked up the story and interest in cryonics heightened until Segall’s story and his status as a Berkeley scientist were both discredited.109 Matters got worse for the life extension movement later that year. In December, Saul Kent’s mother, who suffered from Alzheimer’s disease, became gravely ill with pneumonia. Kent decided to prepare his mother for a sub-zero frozen state, which, following cryonic protocol, included decapitation. In order to avoid law enforcement, Kent kept the whereabouts of his mother’s head a mystery and remained steadfast that his mother wanted to have her head frozen until she could be “reanimated.” Amid debate over what exactly killed Mrs. Kent – an infection or the lethal dose of barbiturates used in preparation of being frozen – the Riverside, California, coroner ruled her death a homicide, but no charges were pressed and the location of the head remains a mystery to this day.110 Meanwhile, the Life Extension Foundation (LEF) found itself in a heap of legal trouble in 1986 when a Hollywood, Florida, police SWAT team raided the office of Stephen Ruddel, the real estate mogul who put up the seed money for the organization. Ruddel was arrested on drug-trafficking charges and then entered into a plea bargain on drug-possession charges. In 1987, the FDA raided LEF’s warehouse, which was located in the same building as Ruddel’s office. A federal criminal indictment was handed down in 1991 to LEF’s Faloon and Kent for allegedly importing unapproved drugs into the U.S. through phony foreign companies, the Longevity Institute and the Hauptmann Institute. Faloon and Kent denied all charges and even set up an anti-FDA museum, which they named the FDA Holocaust Museum.111 Preoccupied with their own defense, they were unable to engage in serious discourse about Rudman’s findings and the implications for HGH as an anti-aging supplement. By 1990, after its humiliation in the media and its run-ins with the law, the life extension movement was essentially defunct. The Not-So-New Anti-Aging Market in the 1990s and 2000s Within the world of mainstream medicine, the reputation of exogenous HGH as an anti-aging therapeutic soared in the early 1990s after the publication of Rudman’s study in one of the most world’s reputable medical journals. HGH was unscathed by either the demise of the life extension movement or the increased federal scrutiny of nutritional supplements and therapeutics promising longevity and vitality; instead, HGH-related anti-aging clinical research received funding from the NIA.112 HGH may have been the beneficiary of the almost universal enthusiasm for another hormone, estrogen, in allegedly forestalling the diseases of aging. In 1992, the American College of Physicians had recommended that “all women, regardless of race, should consider preventive hormone therapy … to prevent disease and to prolong life.”113 That same year, Wyeth-Ayerst’s Premarin (conjugated estrogen tablets) became the best-selling prescription drug in the United States, a position it held for several years through the 1990s. By 1999, some fifteen million American women were taking estrogen replacement therapy.114 With the benefits of estrogen touted in both medical journals and popular periodicals, some physicians began to wonder if aging men might also benefit from hormone replacement. Medical journal articles in the 1980s and early 1990s had reported that testosterone levels decreased steadily in older men, but the effects of this decline were unknown. In 1993, the FDA approved Testoderm, a transdermal testosterone patch from the Alza Corporation, for the treatment of hypogonadism in men. Although the indications for the product made no mention of aging or andropause (the updated term for what used to be called climacteric), physicians were free to prescribe the medication off-label to men concerned about the effects of aging. Testoderm was soon followed by other skin patches, and testosterone prescriptions rose from 122,000 in 1992 to 648,000 in 1999, a more than five-fold increase. FDA medical officer Jean L. Fourcroy observed a “growing realization that the aging male population may also need hormone replacement therapy (HRT).” She concluded that “Androgen delivery systems are therefore a booming business.”115 Given the seeming success of estrogen and testosterone as replacement therapies in aging women and men, respectively, it is not surprising that physicians and laypeople had high hopes for similar results from human growth hormone. The NIA’s support of clinical studies of HGH mirrored – although on a smaller scale – the investment by the NIH in estrogen studies in the Women’s Health Initiative.116 However, preliminary findings from the HGH trial found an absence of anti-aging benefits and the potential for life-threatening side effects, and the study was halted in 1996. The following year the NIA issued a report that stated “side effects of HGH treatment can include diabetes and pooling of fluid in the skin and other tissues, which may lead to high blood pressure and heart failure. Joint pain and carpal tunnel syndrome may also occur.”117 In spite of these warnings, HGH’s popular reputation as the new fountain of youth seemed only to grow in the 1990s. Books about balancing hormones, listening to one’s hormones, and taking hormones in the hopes of slowing down the aging process became best sellers.118 Hormone-enhanced products and anti-aging centers offering hormone replacement sprung up across the nation. Indeed, HGH enabled the principles of the life extension movement to be revived under the guise of a new organization, the American Academy of Anti-Aging Medicine (A4M). A4M was founded in 1992 by two osteopaths, Ronald Klatz and Robert Goldman. They met in the early 1980s at the Chicago College of Osteopathic Medicine where Klatz was a staff physician and Goldman was a medical student. Goldman was a gravity boot enthusiast, and together they researched the risks and benefits of inversion therapy. Their results were published in the Journal of the American Osteopathic Association and received some media attention in 1983.119 A year later, they published a book, Death in the Locker Room, detailing the dangers of drug, steroid, and HGH use by athletes.120 In the late 1980s, their efforts took a turn toward the commercial. They rolled out their own line of fitness equipment, the Ergogenic Pro-Formance system, and created a National Academy of Sports Medicine (NASM) as an entity to certify personal trainers.121 Klatz and Goldman must have chosen this name deliberately, as it resembled the well-established National Athletic Trainers’ Association (founded in 1950). This duo was savvy in creating, promoting, and profiting from their reputation in the world of fitness.122 Klatz and Goldman employed a similar strategy when they ventured into the life extension business. Instead of merely endorsing the use of HGH as an anti-aging agent, Klatz and Goldman formed a medical academy, A4M, to establish and promote a new specialty in (not outside of) medicine. By staking out territory within the boundaries of mainstream medicine, A4M was a marked departure for the life extension movement. Klatz and Goldman purposefully gave their business venture a medical-sounding name and defined its practices and products as a medical specialty. Early on, the “Academy” was marketed through advertisements designed to look like newspaper articles.123 A4M hosted health conferences and published newsletters. Klatz argued that A4M was a pioneering force in scientific research and clinical practice, not a form of alternative medicine. In adopting the NASM business model and attempting to establish A4M as a legitimate medical academy, Klatz and Goldman made plans to establish certification programs, although board certification in anti-aging medicine for chiropractors, dentists, naturopaths, pharmacists, and scientists would not become fully available until 1999. The lack of recognition by establishment groups such as the American Medical Association (AMA) or the American Board of Medical Specialties (ABMS) does not seem to have dampened A4M’s popularity. In 2017, its website proudly claimed a membership of more than 26,000, of whom eighty-five percent are physicians (MD, DO, and MBBS) and twelve percent are research scientists and other health practitioners, and celebrated its twenty-fifth anniversary of leadership in anti-aging medicine.124 The case of A4M raises interesting questions about who gets to define legitimacy in medicine. The 22,000 doctors who have joined the organization, attend its annual meetings, participate in its workshops, and seek its certifications seem not to care whether A4M has secured the imprimatur of the AMA. In the 1990s, human growth hormone gave A4M the legitimacy Klatz and Goldman needed to differentiate their “scientific” anti-aging endeavor from the earlier activities of their predecessors. In spite of the short-lived validation of HGH as an anti-aging supplement, it provided sufficient momentum for its advocates. A4M claimed further validation when the FDA approved the use of HGH in cases of adult growth hormone deficiency in 1996. Since anti-aging practitioners believed that all older individuals experienced growth hormone deficiency due to the natural decline of HGH production, they saw every aging person as eligible for replacement therapy. Unlike their predecessors in the life extension movement who railed against FDA regulations, the latest crop of anti-aging advocates tried to work with the FDA, believing that they were now operating within the borders of regulatory legitimacy. In this way, A4M appears to have brought anti-aging therapeutics back, if not squarely into the mainstream of medicine, then at least to its outer edges. Conclusion Klatz, Goldman, and the A4M membership believed that supplementing growth hormone would solve the problems of aging in much the same way that Masters promoted sex hormones for the same problems fifty years earlier. The battle cry of “live longer better” recapitulated decades-old efforts with a new weapon in hand. The latest band of anti-aging enthusiasts had capitalized on the evidence in Rudman’s 1990 article in the New England Journal of Medicine as justification for their much broader claims about HGH as an effective agent against the disabling effects of aging, although HGH replacement therapy for aging adults never really took hold in mainstream medical practice. Promoted by its boosters as a fountain of youth, HGH did attract a significant following in the broader medical marketplace with the promise of both vitality and freedom from the disabilities that accompanied aging. The anti-aging marketplace of the twenty-first century and the life extension movement in the twentieth century shared a conviction that the decline that accompanies aging is predictable and preventable with the right kind of intervention. While the recommended interventions changed over time, their promises remained consistent. Like estrogen, testosterone, and Gerovital before it, HGH and growth hormone promoters were touted for their potential to reverse or stave off disabling conditions. Amid the historical continuity in anti-aging medicine were changes in its location on the spectrum of medical orthodoxy. Some proponents championed the alternative nature of anti-aging practices; others sought mainstream legitimacy. Whether inside or outside the fluid boundaries of conventional medical practice, anti-aging adherents ascribed to a faith in science. That is, they believed that science could – and should – be marshaled in the fight against aging. From the utopian scientific fiction of cryonics to the more pragmatic off-label prescribing of human growth hormone, anti-aging medicine has been characterized by faith in the power and promise of science. What differed between fringe and mainstream practitioners was the level of commitment to the scientific method, evidence-based medicine, and the sanctity of the randomized controlled trial. While government-funded researchers and board-certified physicians followed the rules of evidence-based medicine and medical research (or at least professed to do so), the life extension and A4M group viewed anecdote and personal experience as sufficient evidence. The story of anti-aging medicine contributes to a blurring of the distinction between the roles of traditional and non-traditional actors in medical practice in late twentieth and twenty-first-century America. While they may have been portrayed as hucksters, the life extenders and anti-aging advocates truly believed in their products and procedures, as evidenced by their own enthusiastic adherence to anti-aging regimens. That faith, combined with a flair for marketing and promotion, has sustained the persistence of the “youth peddlers” for the past seventy years. Our investigation into the deeper roots of anti-aging medicine has brought to light a rogue’s gallery of colorful characters, all of whom –with the exception of Ana Aslan – are white males. We hope this initial inquiry inspires research into the roles of gender, race, and ethnicity among the providers and promoters of anti-aging medicine. This paper has focused on those providers and promoters; more research is needed to learn about the consumers of anti-aging hype and hormones. Finally, the epistemological and rhetorical intertwining of aging as disability and aging as disease, as performed across the spectrum of medical practice, warrants further consideration. Acknowledgments The authors would like to thank researcher Katelyn Smith for her work on this article and Elena Conis, Dorothy Porter, and the anonymous reviewers for their comments on earlier versions of this manuscript. Footnotes 1 Aimee Medeiros, Heightened Expectations: The Rise of the Human Growth Hormone Industry in America (Tuscaloosa: University of Alabama Press, 2016). 2 Courtney Everts Mykytyn, “A History of the Future: The Emergence of Contemporary Anti-ageing Medicine” Sociology of Health & Illness 32 (2010): 181-196. 3 David S. Meyer and Nancy Whittier, “Social Movement Spillover” Social Problems 41 (May 1994): 280. 4 John D. McCarthy and Mayer N. Zald, “Resource Mobilization and Social Movements: A Partial Theory” The American Journal of Sociology 82 (May 1977): 1212-1241. 5 Meyer and Whittier, “Social Movement Spillover,” 278. 6 Of course, the quest to understand aging and relieve its afflictions dates back to ancient times. For examples from the classical era, the Renaissance, the Enlightenment, and the nineteenth century, see Antje Kampf and Lynn A. Botelho, “Anti-Aging and Biomedicine: Critical Studies on the Pursuit of Maintaining, Revitalizing and Enhancing Aging Bodies” Medicine Studies 1 (2009): 187-195, and Carol Haber, “Life Extension and History: The Continual Search for the Fountain of Youth” Journal of Gerontology: Biological Sciences 59A (2004): 515-522. 7 Paul de Kruif, “Can Man’s Prime Be Prolonged?” Reader’s Digest 45 (July 1944): 21-24, quote on 24. In 1945, de Kruif collected the results of his research on testosterone into a book called, simply, The Male Hormone (New York: Harcourt Brace). 8 This philosophy and practice was continued in the 1950s by E. Kost Shelton and in the 1960s by Robert Wilson. See Elizabeth Siegel Watkins, The Estrogen Elixir: A History of Hormone Replacement Therapy in America (Baltimore: Johns Hopkins University Press, 2007), chapters two to four-. 9 William H. Masters and John W. Ballew, “The Third Sex” Geriatrics 10 (January 1955): 2-3. 10 William H. Masters, “Rationale of Sex Steroid Replacement in the “Neutral Gender,” Journal of the American Geriatrics Society 3 (June 1955): 394. 11 Elie Metchnikoff coined the term gerontology is 1908, and Ignatz Nascher coined the term geriatrics in 1909. The Gerontological Society of America filed for incorporation in 1945 and published the first issue of the Journal of Gerontology in 1946. The American Geriatric Society was founded in 1942, and the inaugural issue of Geriatrics was published in 1946. 12 Laura Davidow Hirshbein, “‘Normal” Old Age, Senility, and the American Geriatrics Society in the 1940s” Journal of the History of Medicine 55 (2000): 337-362, 353. 13 W. Andrew Achenbaum, Crossing Frontiers: Gerontology Emerges as a Science (Cambridge: Cambridge University Press, 1995), 128. 14 W. Andrew Achenbaum, Crossing Frontiers: Gerontology Emerges as a Science (Cambridge: Cambridge University Press, 1995), 128. 15 Ibid., 1. 16 Masters and Ballew, “The Third Sex,” 1. 17 Dr. C. Lee Buxton, a prominent New Haven obstetrician-gynecologist, made this comment in the discussion following Masters’ presentation at the eightieth annual meeting of the American Gynecological Society in Hot Springs, VA, in May 1957. The discussion was included in William H. Masters, “Sex Steroid Influence on the Aging Process,” American Journal of Obstetrics and Gynecology 74 (October 1957): 744. The “panacea” quote is from William H. Masters, “Endocrine Therapy in the Aging Individual,” Obstetrics and Gynecology 8 (July 1956): 66. 18 http://www.foxnews.com/health/2012/10/19/hormones-needed-for-anti-aging/. Accessed 2 September 2016. 19 GH was identified in 1944 and isolated in 1956. Herbert M. Evans and J. A. Long, “Characteristic Effects Upon Growth, Oestrus and Ovulation Induced by the Intrapertoneal Administration of Fresh Anterior Hypophyseal Substance,” Proceedings of the National Academy of Sciences of the United States of America 8 (15 March 1922): 38-39. 20 GH was not isolated until nearly 23 years after it was discovered. Choh Hao Li and Herbert M. Evans, “The Isolation of Pituitary Growth Hormone,” Science 8 (3 March 1944): 183-184. 21 Transcripts from a 1961 interview with Herbert Mclean Evans, Herbert McLean Evans Biographical Papers, Memorabilia 1946-1970, MSS 92-18, Archives & Special Collections, UCSF Library & CKM. 22 Frederick L Good, “Menorrhagia and Metrorrhagia of Benign Origin in Women Under Forty-Five Years of Age, with a Plea for More Conservative Treatment,” New England Journal of Medicine 215 (29 October 1936): 805-811, quotes on 810. Even though these reports were positive, they were inaccurate. The GH that women received during treatment was not clinically effective because growth hormone is species-specific, unbeknownst to scientists until 1954. During this time, growth hormone for research and clinical care was derived from animals and not humans. 23 Frank G. Young, “The Anterior Pituitary Gland and Diabetes Mellitus,” New England Journal of Medicine 221 (26 October 1939): 636-646. 24 Joseph Rogers, “The Menopause,” New England Journal of Medicine 254 (12 April 1956): 697-704. 25 Examples of this research: Harry S. Soroff, Elinor Pearson, N.L. Green, and C.P. Artz, “The Effect of Growth Hormone on Nitrogen Balance at Various Levels of Intake in Burned Patients,” Surgery, Gynecology, and Obstetrics 111 (1960): 259-73; Elinor Pearson, Harry S. Soroff, John F. Prudden, and Melvin S. Schwartz, “Studies on Growth Hormone: V. Effect on the Mineral and Nitrogen Balances of Burned Patients,” The American Journal of the Medical Sciences 239 (1960): 17-26; James Campbell and Krishna Sudha Rastogi, “Growth Hormone-induced Diabetes and High Levels of Serum Insulin in Dogs,” Diabetes 15 (January, 1966), 30-43; and Harvey G. Goodman, Melvin Grumbach, and Selna Kaplan, “Growth and Growth Hormone: A Comparison of Isolated Growth-Hormone Deficiency and Multiple Pituitary –Hormone Deficiencies in 35 Patients with Idiopathic Hypopituitary Dwarfism,” New England Journal of Medicine 278 (11 January 1968): 57-68. 26 Ronald Klatz and Carol Kahn, Grow Young with HGH (New York: Harper Perennial, 1997), 22. 27 Popular media examples of this type of reporting include: Joan Beck, “Spare Parts for Your Body (Second in a Series on New Challenges to Modern Medicine)” Chicago Tribune (9 February, 1964) H30, H32, H34-35. 28 Frederick Pohl, “Intimations of Immortality: Scientific Progress Toward Prolonging Human Life and Predictions Concerning the Indefinite Extension,” Playboy (June 1964), 79-80, 160-162, quote on 80. 29 Pohl, 79. 30 Public Law 93-296 (31 May 1974). 31 Patrick M. McGrady, Jr., The Youth Doctors (New York: Coward-McCann, 1968), 15. 32 Ibid., 59-86. 33 Ibid., 167-177. 34 Ibid., 193-219. 35 Ibid., quote on 270-271. 36 Ibid., quote on 180. 37 Ibid., quote on 15. 38 Ibid., quote on 324. Dr. Denham Harman coined the term “Live, Longer, Better.” A researcher in the study of aging, Dr. Harman found himself on the fringes of gerontology when he began to champion a more proactive approach in his field. Harman is best known for his “free radical theory of aging.” He posited that aging was caused by reactions among free radicals (atoms and molecules containing unpaired electrons). Damage occurred when a free radical found another molecule and attempted to pair its unpaired electron, which then made the found molecule a free radical in search of another molecule, marking the beginning of a destructive chain reaction. Harman believed that antioxidants would protect against this damaging sequence because they could donate necessary electrons with no adverse effects. Harman published his theory in the Radiation Laboratory Report in 1955, and again in the Journal of Gerontology in 1956. However, it attracted little notice until the late 1960s, with the birth of the field of experimental gerontology, which focused on the processes of aging. Harmon’s Free Radical Theory became one of the foundational principles in experimental gerontology and anti-aging therapeutics. It was also eventually accepted by the field of gerontology. 39 Frank G. Slaughter, “The Youth Doctors,” New York Times (November 17, 1968), BR40. 40 Donald W. Goodwin, “Rejuvenation,” Journal of the American Medical Association 207 (February 3, 1969): 956. 41 Patrick M. McGrady, Jr., Commentary, Correspondence, Journal of the American Medical Association 209 (July 14, 1969): 272. 42 J. T. Freeman, “Drug Therapy in Aging Patients,” Geriatrics March 18, no. 3 (1963): 174-180. 43 Ana Aslan, “Novocain als Eutophischer Factor und die Moglichkeit einer Verlangerung der Lebensdauer” Therapeutische Umschau 9 (1956): 165-172; Ana Aslan, “Eine Neue Methode zur Prophylaxe und Behandlung des Alterns mit Novokain-Stoff H3, Eutrophische und Verjungende Wirkung” Therapiewoche 7 (1956): 1-2, 14-22; Ana Aslan, “La Novocaine H3 dans la Therapeutique de la Vieillesse” Revue Francaise de Gerontologie 4 (1958): 321-330. 44 Rona and Laurence Cherry, “Slowing the Clock of Age: But What if People Live to be 100 or More?” New York Times, (May 12, 1974), SM246. 45 McGrady, 183. 46 Catalog Record, “Novocain,” https://www.woodlibrarymuseum.org/museum/item/118/novocain. Accessed 2 December 2016. 47 Cherry, “Slowing the Clock of Age: But What if People Live to be 100 or More?”, SM246. 48 Gerovital was sold as “H3” in advertisements by supplement suppliers featured in publications, including Let’s Live Magazine, a monthly publication nationally distributed through health food shops and by paid mail subscriptions. See advertisements featured in Hearings before the Committee on Frauds and Misrepresentations Affecting the Elderly of the Special Committee on Aging, US Senate, Part 1: SF, CA January 13, 1964, 38-40. 49 Ruth Davis, “Non-Stop Youth,” Chicago Defender (October 27, 1973), 22. 50 Maxine Cheshire, “Senators Press Search for Eternal Seniority,” Chicago Tribune (December 19, 1972), B3. 51 D. Robinson, J. Davis, A. Nies, C. Ravaris, and D. Sylwester, “Relation of Sex and Aging to Monoamine Oxidase Activity of Human Brain, Plasma, and Platelets,” Archives of General Psychiatry 24 (1971): 536; M. David Macfarlane, “Possible Rationale for Procaine (Gerovital H3) Therapy in Geriatrics: Inhibition of Monoamine Oxidase,” Journal of the American Geriatrics Society 21 (1973): 414-418. 52 Sidney Cohen and Keith S. Ditman, “Gerovital H3 in the Treatment of the Depressed Aging Patient,” Psychosomatics 15 (1974): 15-19, quote on 15. 53 Cherry, “Slowing the Clock of Age: But What if People Live to be 100 or More?”, SM246. 54 G. Untea and G. Bercu, “Considérations sur l'influence exercée par le traitement avec Gérovital H3 (dragées) sur la capacité de travail des personnes actives ayant dépassé l'âge de 45 ans”, Giornale Di Gerontologia 17 (1969): 795-9 ; G. Untea, R. Voinea, and I. Pirvulescu, “Considerations regarding the usage of Gerovital-H 3 during andropause for disturbances of sexual dynamics”, Giornale Di Gerontologia 20 (1972): 62-9. 55 See Elizabeth Siegel Watkins, “The Medicalisation of Male Menopause in America,” Social History of Medicine 20 (2007): 369–388, and Elizabeth Siegel Watkins, “Medicine, Maculinity, and the Disappearance of Male Menopause in the 1950s,” Social History of Medicine 21 (2008): 329-344. 56 Adrian Ostfield, Cedric M Smith, and Bernard A. Stotsky, “The Systemic Use of Procaine in the Treatment of the Elderly: A Review,” Journal of the American Geriatrics Society 25 (January 1977): 1-20, quote on 1. 57 Joel Kurtzman and Philip Gordon, “Contents,” No More Dying: The Conquest of Aging and The Extension of Human Life (Los Angeles: J.P. Tarcher, Inc., 1976), n.p. 58 Meyer and Whittier, 1217-1218. 59 Saul Kent, The Life Extension Revolution: The Definitive Guide to Better Health, Longer Life, and Physical Immortality (New York: William Morrow and Company, 1980), 15. 60 Beverly Beyette, “Gerovital and the Las Vegas Connection: Tours run from the Southland,” Los Angeles Times, January 3, 1980, F1, F9-F12. 61 “Statement of Marvin Kratter, President and Chief Executive Officer of Rom-Amer Pharmaceuticals, LTD.,” in U. S. Senate Subcommittee on Health and Scientific Research, Committee on Labor and Human Resources. Senate; Committee on Labor and Human Resources, Hearings on Drug Regulation Reform Act of 1979 [Hearing Id - HRG-1979-LHR-0067]. May 17-18, 1979, 660-675, quote on 661. 62 Ibid., quote on 663. Although the life extenders were more concerned with the libertarian goal of self-ownership, Krattner’s testimony jibed with contemporary criticism of the FDA’s regulatory machinery for slowing down (and making more expensive) the translation of drugs from bench to bedside. This concern about a “drug lag” in the United States, as compared to Europe, eventually resulted in revisions to the drug patenting system in 1984, through the Drug Price Competition and Patent Term Restoration Act (also known as the Hatch-Waxman Act). (See Jeremy A. Greene and Scott H. Podolsky, “Reform, Regulation, and Pharmaceuticals – The Kefauver-Harris Amendments at 50” New England Journal of Medicine 367 (October 18, 2012): 1481-3. 63 Durk Pearson and Sandy Shaw, Life Extension: A Practical Scientific Approach (New York: Warner Books, 1983), 555. 64 Ibid. 65 Advertisement: “Nathan Pritikin, Director – Announces the Opening of the Longevity Center, Santa Monica, California,” Wall Street Journal, August 22, 1978, 16. 66 Marian Burros, “Getting to the Heart of the Matter: Nutritionist Nathan Pritikin’s Formula for Longer Life Comes up Short with the Medical Establishment,” Washington Post, June 7, 1979, Style section, E1 and E12. 67 Robert D. McFadden, “Nathan Pritikin, Whose Diet Many Used Against Heart Ills” New York Times (February 23, 1985). http://www.nytimes.com/1985/02/23/us/nathan-pritikin-whose-diet-many-used-against-heart-ills.html. Accessed October 10, 2017. 68 Saul Kent, The Life Extension Revolution, 81-82. 69 Jon Leonard, Jack L. Hofer and Nathan Pritikin, Live Longer Now: The First One Hundred Years of Your Life: The 2100 Program (New York: Grosset and Dunlap, 1974). 70 John D. McCarthy and Mayer N. Zald, “Resource Mobilization and Social Movements: A Partial Theory,” in John D. McCarthy and Mayer N. Zald (editors), Social Movements in an Organizational Society: Collected Essays (New Brunswick, NJ: Transaction Publishers, 1987), 20-21. 71 William Regelson and Carol Colman, The Super-Hormone Promise Nature’s Antidote to Aging (New York: Pocket Books, 1996), xiii. 72 James Lardner, Stretching the Limits of Life,” Washington Post, May 15, 1983, G1, G4, and G5. 73 Ellen Hume, “Science Taps Fountain of Aging Mystery: AGING: Scientists May Extend…” Los Angeles Times, July 27, 1982. The term “death hormone” was given to a hypothetical pituitary hormone believed to contribute to the loss of neurons. 74 Homer Bigart, “Group Advocates Freezing of Dead: Life Extension Society Sees Chance for Immortality,” New York Times, January 29, 1967, 58. 75 Saul Kent, Future Sex (New York: Warner Paperback Library, 1974). 76 Saul Kent, “Solving the Riddle of Lipofuscin's Origin May Uncover Clues to the Aging Process,” Geriatrics 31 (May 1976): 128-37. 77 Saul Kent, “The Biologic Aging Clock,” Geriatrics 37 (July 1982): 95-99. 78 Saul Kent, The Life Extension Revolution, sleeve. 79 Saul Kent, Anti-Aging News, August 1985, 5 (8): cover. Steven Almond, “They’re Gonna Live Forever,” Miami Times, June 8 1994. 80 “Cover” Anti-Aging News, 5 (August 1985). This newsletter’s scientific advisory board included W. Donner Denckla, M.D., of the National Institute of Alcohol Abuse and Alcoholism (and originator of the “death hormone” concept), Stanley Fink, Ph.D., Director of Biomedical Research at Orange Medical Instruments, and Ronald Klatz, D.O., of the Human Performance Center in Chicago. Klatz would go on to be one of the founders of American Academy of Anti-Aging Medicine (A4M). 81 Saul Kent, Life Extension Revolution, 13. 82 Durk Pearson and Sandy Shaw on The Mike Douglas Show, c. 1982, https://www.youtube.com/watch?v=5sSKLhTfcpQ&feature=youtu.be. Accessed on 6 September 2017. Durk Pearson on The Tomorrow Show, hosted by Tom Snyder, c.1979, https://www.youtube.com/watch?v=8U-Oxhb8SK4. Accessed on 6 September 2017. 83 People magazine reported that the book sold 275,000 copies in two months. Karen G. Jackovich, “Two Fitness Faddists Have a No. 1 Best-Seller, but Are They Stretching Life Spans or Truth?” People (4 October 1982), http://people.com/archive/two-fitness-faddists-have-a-no-1-best-seller-but-are-they-stretching-life-spans-or-truth-vol-18-no-14/. Accessed on 6 September 2017. According to the New York Times, Life Extension was the sixth-highest bestseller in hardcover general (non-fiction) in 1982. Edwin McDowell, “About Books and Authors: What Sold in 1982,” New York Times (2 January 1983), http://www.nytimes.com/1983/01/02/books/about-books-and-authors-what-sold-in-1982.html?pagewanted=all. Accessed on 6 September 2017. 84 Pearson and Shaw, Life Extension, A Practical Scientific Approach, 7 85 Ibid., xxiii. 86 Ibid., xv. 87 Ibid., 468-469. 88 Ibid., 771. 89 Ibid., 129, 229. 90 There was existing literature that documented increased growth hormone levels after administering L-dopa, bromcriptine, vasopressin, tryptophan, L-arginine, and L-ornithine. See Thomas J. Merimee, David Rabinowitz, Lamar Riggs, John A. Burgess, David L. Rimoin, and Victor A. McKusick, “Plasma Growth Hormone after Arginine Infusion — Clinical Experiences,” NEJM 276 (1967): 434-439; R. F. Knopf, J. W. Conn, S. S. Fajans, J. C. Floyd, E. M. Guntsche, and J. A. Rull, “Plasma growth hormone response to intravenous administration of amino acids,” The Journal of Clinical Endocrinology and Metabolism, 25 (1965): 1140-1144; D. Evain-Brion, M. Donnadie, M. Roger, and J. C. Job, “Simultaneous study of somatotrophic and corticotrophic pituitary secretions during ornithine infusion test, Clinical Endocrinology, 17 (1982): 119-122; A. E. Boyd, III., Harold E. Lebovitz, and John B. Pfeiffer, “Stimulation of Human-Growth-Hormone Secretion by L-Dopa,” NEJM 283 (1970): 1425-1429; Juan J. Gagliardino, John D. Bailey, Julio M. Martin, “Effect of Vasopressin on Serum-Levels of Human Growth Hormone,” Lancet 289 (1967): 1357-1358. And V. Meyer and E. Knobil, “Stimulation of Growth Hormone Secretion by Vasopressin in the Rhesus Monkey,” Endocrinology 79 (1966), 1016-8. 91 Examples of this literature include S. Hontela, N. P. Nair, G. Rosenberg, G. Schwartz, H. Guyda, “Bromocriptine: Effect on Serum Prolactin and Growth Hormone in Psychogeriatric Hospital Patients,” Journal of American Geriatrics Society 2 (1978): 49-52; E. E. Müller, F. Brambilla, F. Cavagnini, M. Peracchi and A. Panerai, * Slight Effect of l-Tryptophan on Growth Hormone Release in Normal Human Subjects,” Journal of Clinical Endocrinology and Metabolism 39 (1974): 1-5. 92 Barry M. Sherman, “Growth Hormone Use,” Science, 235, no. 4784 (1987): 14-15; William Regelson, “Growth Hormone Use,” Science, 235, no. 4784 (1987): 14-15. 93 Pearson and Shaw, The Life Extension Program (New York: Warner Books, 1984): 240. Both commercial cHGH products are listed as part of the MEDLARS search they created to show their readers how to use a computer search in requesting material from the National Library of Medicine. The other prolific life extension author at the time, Saul Kent, did not write about cHGH in his Geriatrics column, nor did he recommend its use when detailing the benefits of increased levels of growth hormone in his book, Your Personal Life-Extension. 94 The Chairman of the Subcommittee on Health and Long-Term Care of the Select Committee on Aging House of Representatives, Quackery A $10 Billion Scandal (Washington: US Government Printing Office, 1984), 94-95. 95 Daniel Duchaine, Underground Steroid Handbook II (Venice CA, HLR Technical Books, 1989), part 11. Duchaine discusses how growth hormone was featured in the first version of the handbook from 1982, which was extremely influential among bodybuilders. 96 Elliott Almond, Julie Cart, and Randy Harvey, “If Athletes Want to Cheat to Get to the Olympics… There’s a Doctor to Help,” Los Angeles Times, December 4, 1983, E1 and E18, E19. 97 Ibid., E18. 98 Sandra Blakeslee, “Supply of Growth Hormone Brings Hope for New Uses: Growth Hormone’s Promise Brings Fear of Abuse,” New York Times, February, 10, 1987, C1 and C11, quote on C11. 99 Daniel Rudman and Floyd Seidman, “Lipemia in the Rabbit Following Injection of Pituitary Extract,” Experimental Biology and Medicine 99, no. 1 (October 1958), 146-150. 100 Daniel Rudman, Samuel B. Chyatte, Joseph H. Patterson, Glynda G. Gerron, Irma O’Beirne, Joan Barlow, Peter Ahmann, Ashby Jorden, and Robert C. Mosteler, “Observations on the Responsiveness of Human Subjects to Human Growth Hormone: Effects of Endogenous Growth Hormone Deficiency and Myotonic Dystrophy,” The Journal of Clinical Investigation 50 no. 9 (1971), 1941-1949; D. Rudman, S. B. Chyatte, G. G. Gerron, I. O'Beirne, and J. Barlow, “Hyper-Responsiveness of Patients with Limb-Girdle Dystrophy to Human Growth Hormone,” The Journal of Clinical Endocrinology and Metabolism, 35, 2 (1972), 256-60; D. Rudman, S. B. Chyatte, J. H. Patterson, G. G. Gerron, I. O'Beirne, J. Barlow, A. Jordan, and J. S. Shavin, “Metabolic Effects of Human Growth Hormone and of Estrogens in Boys with Duchenne Muscular Dystrophy,” The Journal of Clinical Investigation 51, no. 5 (1972): 1118-24. 101 D. Rudman, M. H. Kutner, G. A. Fleming, R. C. Harris, E. E. Kennedy, R. A. Bethel, and J. H. Priest, “Effect of 10-Day Courses of Human Growth Hormone on Height of Short Children,” The Journal of Clinical Endocrinology and Metabolism 46, no. 1 (1978): 28-35; D. Rudman, M. H. Kutner, R. D. Blackston, R. D. Jansen, and J. H. Patterson, “Normal Variant Short Stature: Subclassification Based on Responses to Exogenous Human Growth Hormone,” The Journal of Clinical Endocrinology and Metabolism 49, no. 1 (1979): 92-9. 102 D. Rudman, T. Davis, J. H. Priest, J. H. Patterson, M. H. Kutner, S. B. Heymsfield, and R. A. Bethel, “Prevalence of Growth Hormone Deficiency in Children with Cleft Lip or Palate,” The Journal of Pediatrics 93, 3(1978): 378-82; D. Rudman, M. Goldsmith, M. Kutner, and D. Blackston, “Effect of Growth Hormone and Oxandrolone Singly and Together on Growth Rate in Girls with X Chromosome Abnormalities,” The Journal of Pediatrics 96, no. 1(1980): 132-5. 103 Daniel Rudman, Michael H. Kutner, C. Milford Rogers, Michael F. Lubin, G. Alexander Fleming, and Raymond P. Bain, “Impaired Growth Hormone Secretion in the Adult Population: Relation to Age and Adiposity,” Journal of Clinical Investigation 67 (May 1981): 1361-1369. 104 D. Rudman, M. H. Kutner, R. D. Blackston, R. A. Cushman, R. P. Bain, and J. H. Patterson, “Children with Normal-Variant Short Stature: Treatment with Human Growth Hormone for Six Months,” New England Journal of Medicine 305, no. 3 (1981): 123-31. 105 Arlene Weintraub, Selling the Fountain of Youth, (New York: Basic Books, 2010), 6. 106 Daniel Rudman, “Growth Hormone, Body Composition, and Aging,” Journal of the American Geriatrics Society 33, no. 11 (November 1985): 800-807. 107 Daniel Rudman, Axel G. Feller, Hoskote S. Nagraj, Gregory A. Gergans, Pardee Y. Lalitha,.et al., “Effects of Human Growth Hormone in Men over 60 Years Old,” NEJM 323, no. 1 (July 5, 1990), 1-6. 108 K.A. Fachelman, “Hormone May Restore Muscle in Elderly,” Science News 138, no. 2 (July 14, 1990), 23; Jerry E. Bishop, “Hormonal Treatments Show Benefits for Aging Men and Cancer Patients,” Wall Street Journal, July, 5, 1990, B3; Susan Okie, “Can Drug Help Restore Youth? Older Men Gain Muscle, Lose Fat in Study,” The Washington Post, July 5, 1990, A1; Min Wei Lee, “New Hope for Elderly: Growth Hormone Restores Strength,” Chicago Tribune, July 5 1990, D1; Natalie Angier, “Human Growth Hormone Reverses Effects of Aging,” New York Times, July 5 1990, A1. 109 “Dog ‘Spunky’ After It’s Frozen Test,” Los Angeles Times, March 31, 1987, 3; T. W. McGarry, “Revival of a ‘Frozen’ Dog – Some Cold New Disclosures,” Los Angeles Times, July 6, 1987, 3. 110 Louis Sahagun and Mark Arax, “Coronoer Says It Was Homicide by Drugs in Frozen Head Case,” Los Angeles Times (24 February 1988). Accessed on 6 September 2017 at http://articles.latimes.com/1988-02-24/news/mn-11787_1_saul-kent. 111 Steven Almond, “They’re Gonna Live Forever,” Miami New Times, June 8, 1994 http://www.miaminewtimes.com/news/theyre-gonna-live-forever-6363863. Accessed December 12, 2016. 112 Jane E. Brody, “Restoring Ebbing Hormones May Slow Aging: Researchers Hope…,” New York Times, July 18, 1995, C1. 113 American College of Physicians, “Guidelines for Counseling Postmenopausal Women about Preventive Hormone Therapy,” Annals of Internal Medicine 117 (1992): 1038-41. 114 Adam L. Hersh, Marcia L. Stefanick, and Randall S. Stafford, “National Use of Postmenopausal Hormone Therapy: Annual Trends and Response to Recent Evidence,” Journal of the American Medical Association 291 (7 January 2004): 47-53. 115 U. S. Food and Drug Administration, Testoderm TTS New Drug Application 20-791. Approval package (1997), A-11. Records of the Center for Drug Evaluation and Research, FDA. 116 For more on the Women’s Health Initiative, see Watkins, The Estrogen Elixir, chapter 14. 117 Alex Kuczynski, “Anti-Aging Potion or Poison?” New York Times, April 12, 1998, ST1-2, 2. 118 Examples include: Walter Pierpaoli, William Regelson, and Carol Colman, The Melatonin Miracle: Nature’s Age-Reversing, Disease Fighting, Sex-Enhancing Hormone (New York: Simon & Shuster, 1995); William Regelson and Carol Colman, The Superhormone Promise: Nature’s Antidote to Aging (New York: Simon & Schuster, 1996); Ronald Klatz and Carol Kahn, Grow Young with HGH: The Amazing Medically Proven Plan (New York: Harper Collins, 1997); Ronald Klatz and Bob Goldman, Stopping the Clock: Why Many of Us Will Live Past 100 – and Enjoy Every Minute (New Canaan, CT: Keats Pub, 1996). 119 Ronald Kotulak, “’Gravity Boot’ Cure Criticized,” Chicago Tribune, July 19, 1983, 11. 120 Magda Krance, “’Death in the Locker Room’: Bodybuilder leads anti-steroid crusade,” Chicago Tribune, August 23, 1984, D1. 121 Advertisement: “A Total Breakthrough in Training and Fitness and The Figures to Prove It,” New York Times, April 3, 1989, C7. 122 Ronald Klatz and Robert Goldman, “State of the Specialty Report: Anti-Aging Medicine at Twenty Years (2012): The History of the Modern Anti-Aging Medical Movement,” Encyclopedia of Clinical Anti-Aging Medicine & Regenerative Biomedical Technologies (Chicago: American Academy of Anti-Aging Medicine, 2012), 4-6. 123 Ronald Klatz and Carol Kahn, “Can We Grow Young?” The Washington Post, April 20, 1997, 114. 124 https://www.a4m.com/about-a4m-mmi.html. Accessed October 7, 2017. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of the History of Medicine and Allied Sciences Oxford University Press

Live Longer Better: The Historical Roots of Human Growth Hormone as Anti-Aging Medicine

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Oxford University Press
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© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com
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0022-5045
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Abstract

Abstract In recent years, historians have turned their attention to the emergence of anti-aging medicine, suggesting that this interest group coalesced in the wake of widespread availability of recombinant human growth hormone (HGH) after 1985. We take a longer view of modern anti-aging medicine, unearthing a nexus of scientific, medical, and cultural factors that developed over several decades in the twentieth century to produce circumstances conducive to the emergence of this medical sub-specialty established on the premise of the anti-aging effects of HGH. Specifically, we locate these roots in earlier hormone replacement therapies and in the so-called life extension movement. We reveal the continual tension between, on the one hand, champions of a mainstream medical specialty and a field of biomedical research that aimed to improve health for the aged and, on the other hand, advocates who campaigned for medical endeavors to preserve midlife health in perpetuity, and even to extend the human lifespan. We also demonstrate that the two groups shared a belief in science to solve – or at least to ameliorate – the problems of aging. This commitment to science has been the hallmark of twentieth and twenty-first century prescriptions for living life longer and better. In 1921, scientists postulated the existence of a growth-promoting hormone in the anterior pituitary gland. It took twenty-three years to confirm the identity of this substance, and it took another twelve years after that to isolate it in humans. Human growth hormone (HGH) became available for clinical use from human cadavers in the late 1950s and via synthetically recombinant DNA technology in the 1980s. HGH was, and continues to be, prescribed by physicians to promote growth in children deemed to be pathologically short-statured.1 In 1990, HGH burst onto a different scene: the perennial quest to stave off the effects of aging. Newspapers around the world heralded the preliminary results of a small study published in the New England Journal of Medicine suggesting that treatment with human growth hormone caused men in their sixties and seventies to lose fat and gain muscle. To test the effects of human growth hormone in larger populations, the National Institute on Aging quickly awarded grants to eight groups of researchers. In 1992, before the results of any of these studies were published, two osteopaths founded the American Academy of Anti-Aging Medicine (A4M) to establish and promote a new specialty. Although not recognized by the American Medical Association or the American Board of Medical Specialties, A4M has, since 1999, conferred board certification in anti-aging medicine on thousands of health care practitioners. Some observers have suggested that the origins of anti-aging medicine can be traced to the availability of recombinant HGH in 1985. We take a longer view of modern anti-aging medicine, unearthing a nexus of scientific, medical, and cultural factors that developed over several decades in the twentieth century to produce circumstances conducive to the emergence of this medical subspecialty established on the premise of the anti-aging effects of HGH. Specifically, we locate these roots in earlier hormone replacement therapies of the 1940s and 1950s and in the emerging life extension movement of the 1980s.2 The historical record suggests that members of the life extension movement were not simply individuals dedicated to eluding death and promoting youthfulness through scientific intervention. Rather, these actors sought to alter the dominant culture in terms of knowledge, attitudes, and behaviors about life extension. Their collective vision and mission had many of the features of a social movement. These proponents of the life extension movement, although nowhere near as numerous or influential as the advocates of women’s liberation or civil rights, were happy to proclaim themselves revolutionaries.3 At the height of the group’s popularity in the mid-1980s, the promotional efforts of its leadership often came off as more of a marketing ploy than a medical campaign. However, life extenders did have a shared purpose: to use science to prolong life and promote youthfulness. Even though some of them made fortunes by peddling their regimens, they also went to great and sometimes bizarre lengths to adhere to the protocols they proselytized. They also had shared enemies, namely, the federal government and orthodox medicine who, they claimed, stymied their efforts to transform the health of the nation.4 Together, they were “engaged in a more or less coherent struggle for change,” a defining characteristic of a social movement in the words of sociologists David S. Meyer and Nancy Whittier, and this concept serves as a useful organizing principle for historical analysis of the life extension and anti-aging programs.5 Anti-aging medicine and the A4M brought together traditions from two very different places on the spectrum of medical practice in twentieth-century America. The prescribers of hormone replacement therapies (testosterone and estrogen) in the 1940s and 1950s were orthodox physicians. They reported the results of clinical studies of exogenous hormones and collaborated with the U.S. Food and Drug Administration (FDA) in the regulation of these substances. By contrast, life extension proponents worked at the margins of the mainstream medical professions. They published books targeted to the public, and they viewed FDA oversight of drugs with skepticism and distrust. By the 1990s, the new proponents of A4M had blended aspects of both into an area of practice that mimicked the legitimacy of traditional medicine while appealing to the more fanciful beliefs and promises of the fringe group. In the course of this narrative, we reveal the persistent tension between, on the one hand, champions of a mainstream medical specialty and biomedical research field that aimed to improve health and quality of life for the aged and, on the other hand, advocates who campaigned for medical endeavors to preserve mid-life health in perpetuity and even to extend the human lifespan. What the two groups had in common was a belief in science to solve – or at least to ameliorate – the problems of aging. This shared commitment characterized efforts ranging from research projects conducted by medical school faculty and sponsored by the National Institute on Aging to cryogenic procedures conducted outside of the law. Human growth hormone provided the connective tissue that bound orthodox and heterodox medicine together in the realm of anti-aging therapeutics. The legitimacy briefly conferred upon HGH as an anti-aging medication in the 1990s enabled A4M to claim space within the boundaries of sanctioned medicine while, at the same time, promoting its work on the cutting edge (as opposed to the fringe). Replacement hormones more broadly had opened up this space decades earlier, exposing the porousness of the boundaries erected around mainstream medicine. The intertwined histories of hormones, life extension, and anti-aging medicine in the twentieth and twenty-first centuries demonstrate that lines separating legitimate from unconventional medical practice cannot be easily drawn. Sex hormones, growth hormones, and the fight against aging in the 1940s and 1950s There is a fairly direct lineage between the uses of sex hormone replacement therapies in the 1940s and 1950s and the anti-aging hormone cocktails of the 1990s and 2000s.6 In the earlier era, some clinicians saw the age-related decrease in sex hormone production to be permanent and thus to require long-term replacement therapy. Paul de Kruif, one of America’s best-known science writers, popularized the use of testosterone by men “burnt out between the ages of 50 and 75 … ready for life’s scrap heap …men in whom evidence of hormone hunger has been established.” De Kruif expressed his confidence in scientists: “as in the development of insulin and vitamin B1, increased production and the ingenuity of chemists will in time lower the hormone’s cost until it is within reach of every man who needs it.”7 Another clinical scientist who was an early and vocal proponent of long-term hormone replacement was William H. Masters. Better known for his 1966 book, Human Sexual Response, his research program in the 1940s and 1950s investigated the relationship between sex hormones and aging. His clinical trials led him to conclude that long-term sex hormone therapy could rejuvenate old people and to advocate “‘puberty to grave’ sex steroid support.”8 He blamed the failure of the reproductive endocrine system as “the Achilles’ heel” of the entire endocrine system. “We are essentially intact during our 60’s,” he proclaimed, “and perfectly capable of functioning … as efficiently as much younger persons, except that we are essentially castrates.”9 Replacing the hormones that the sex glands of older people could no longer produce would tackle: one of the greatest public health problems of the present and future … the rapid increase in our aging population. If we can avoid the physical and mental degenerative changes associated with senility, or at least prevent their appearance for many years beyond present expectancy, a major contribution will have been made, not only to the treated individuals but to the economy and potential manpower supply of our country.10 Masters anticipated that hormone replacement therapy would transform not only the social role of America’s senior citizens, but also the science of gerontology and the medical practice of geriatrics. Both geriatrics and gerontology were relatively new fields, formally organized in the 1940s.11 Geriatrics pointed to the older specialty of pediatrics as justification for a field organized around a stage of life (as opposed to an organ system, such as cardiology, or a disease class, such as oncology), but the similarities ended there. Geriatricians struggled to define boundaries between normal and pathological in diagnosing and treating problems of aging; as Laura Hirshbein has noted, their attention to these conditions – whether identified as abnormal or not – served to highlight old age as a time of disability.12 Gerontology also struggled with an identity crisis in the 1940s and 1950s, as the field tried to define itself in terms of research problems, methodological approaches, and boundaries. It was ambitious in scope, including under its umbrella basic biological, medical, psychological, and sociological lines of inquiry into the processes and ramifications of aging. While multi-disciplinarity was a laudable goal, it was in practice difficult to attain, because the different languages spoken by researchers trained in different disciplines impeded the cross-fertilization of ideas. What its practitioners agreed upon was a commitment to scientific inquiry; as W. Andrew Achenbaum notes in his history of gerontology, the field developed in the midst of postwar enthusiasm for the promise of science to solve social problems. The founders made it clear that they wanted to distance themselves from “alchemists, charlatans, con artists, or uninformed adventurers.”13 They saw themselves and their colleagues as serious scientists, who would employ the highest standards of rigorous and reproducible experimentation to expand the understanding of the processes and effects of aging. Indeed, the motto of the Gerontological Society of America was “to add life to years, not just years to life.”14 Masters’ rhetoric was consistent with that of other gerontologists. He pointed out that “there is not the slightest evidence to suggest, nor has any claim been made that steroid replacement increases longevity by one single day.”15 Rather, hormone replacement would enable old folks to live out their lives “happier, better adjusted, and more useful.”16 Since medical science had helped to extend life expectancy so that more and more women lived well beyond menopause, he argued that physicians ought to assume the responsibility of improving the quality of life during those later decades. Although one of his colleagues jokingly referred to him as “a twentieth century Ponce de Leon,” Masters insisted that “steroid replacement … in no sense represent[s] a panacea for the problem of aging.”17 Concentrating solely on the reproductive endocrine system, Masters’ steroid supportive therapy did not include growth hormone.18 Discovered in 1921, growth hormone gained attention primarily for its growth-promoting potential in part because it took academic and industry researchers decades to identify and isolate it.19 First reported by Herbert M. Evans and J. A. Long, the existence of growth hormone was postulated based on the clinical performance of pituitary extract in making people and animals grow.20 For more than twenty years, hormone researchers debated the existence and form(s) of growth hormone. Its most staunch supporter, Evans himself, later admitted that his hunch about a single growth hormone was very tenuous until GH was finally isolated in the 1940s.21 As the debate over the existence of GH entered its second decade, some researchers diverged from studies of its growth-inducing ability and ventured into investigations of its synergistic relationship with other hormones, most notably estrogen and insulin. During the late 1930s, physicians published reports on their successes with the addition of pituitary glands and pituitary extracts to the hormonal therapy given to women for abnormal uterine bleeding. Some investigators hypothesized that growth hormone alone would have been the preferred treatment since it was “luteinizing,” which meant it could spur the production of luteinizing hormone (LH) and therefore help regulate the menstrual cycle.22 Others explored the role of the pituitary gland, and especially the purported growth hormone therein, in the etiology of diabetes. Anterior pituitary extract treatment appeared to cause a permanent diabetic condition in animals. Influenced by sex hormone research indicating that hormone levels varied over the course of the life cycle, these investigators proposed that GH-induced diabetes could occur naturally from the over-production of GH. Menopausal women were considered to be at higher risk because decreased estrogen production increased their susceptibility to unchecked surges of GH.23 It appeared that too much growth hormone could cause health problems in older people.24 This concern about the overproduction of growth hormone was in contrast to Masters’s concern about the underproduction of sex hormones. Clinical research on growth hormone was stymied by the fact that GH is species-specific. It took hormone researchers decades to figure out this association. Once human growth hormone became available, it was used almost solely in clinical research and therapy on young boys. In part, this tightly knit association between growth hormone and growth production was due to strict regulation of HGH in the United States. Except for a few small distributors, a single federal agency, the National Pituitary Agency (NPA), oversaw most of its production and distribution. Researchers and clinicians had to apply for HGH directly to the NPA, resulting in limited use and application in both the clinic and the laboratory. During the next two decades, a few scattered instances of research on non-growth related properties of HGH could be found on the peripheries of basic and clinical research. Several of these studies did explore its regenerative potential. This research looked at HGH’s ability to provide metabolic support for burn victims, its role in insulin production in diabetics, and its potential in treating patients with multiple pituitary-hormone deficiencies.25 When HGH appeared in anti-aging science at the end of the twentieth century, this type of research was unearthed by human growth hormone enthusiasts as the precursors to their work and foundation for their belief in HGH as a youth promoter.26 In the 1960s, however, anti-aging research turned away from hormones, a trend that continued to obscure HGH studies that might have been deemed as breakthroughs in this field. At the same time, a collective belief in science’s ability to promote longer life was strong, and other medical and technological advances captured national attention. Sensationalist articles encouraged optimism about the possibility of extending life with awestruck reporting on vaccines, transplants, and reconstructive surgery that depicted these technological advances as preludes to the ultimate goal of life extension.27 As Frederick Pohl wrote in a 1964 Playboy magazine article titled, “Intimations of Immortality: Scientific Progress Toward Prolonging Human Life and Predictions Concerning its Indefinite Extension,” There is no fiction in the organ transplant that are being performed almost daily – or in the artificial organs that replace or supplement natural ones, on in the vaccines and antibiotics that take the fear out of ancient murderers like pneumonia and smallpox, or in the surgery that can build a new face on what is almost a bare skull, burned to the bone.28 Pohl extrapolated from this narrative to suggest that the “mere process of dying may in 1984 be no longer very important.”29 Aging was becoming just another problem for American scientists to solve. Official steps were taken to create a governmental infrastructure to promote this endeavor. In 1961, President Kennedy convened the first White House Conference on Aging, which recommended the establishment of a federal institute to support biomedical research on aging with the use of federal funds. Ten years later, the second White House Conference on Aging reiterated the call for a National Institute on Aging. By this time, the National Institute of Child Health and Human Development had been established, setting the precedent for an institutional focus on a stage of life rather than a disease (e.g., National Cancer Institute) or an organ system (e.g., National Heart, Lung, and Blood Institute). In 1974, the National Institute on Aging was established “for the conduct and support of biomedical, social, and behavioral research and training related to the aging process and the diseases and other special problems and needs of the aged.”30 However, research on the science of aging was by no means limited to government-supported investigation. “The life extending scene” in the 1960s and 1970s Patrick McGrady, Jr., was a journalist captivated by a wide range of efforts to combat aging. In 1968, he wrote a popular book called The Youth Doctors that documented decades of efforts to promote longevity using modern interventions. Hip to the lingo of the late 1960s, he described these efforts collectively as an emerging “life extending scene.”31 Treatments included cell therapy injections at the La Prairie clinic in Switzerland;32 a sheep-egg embryo, anti-aging regimen developed and popularized by Ivan Popov, a Yugoslavian doctor;33 plastic surgeries sought out by actors and actresses and others who wanted to look like actors and actresses;34 the “specialized service” of amphetamine-prescribing “speed doctors”;35 and the “most coveted youthefier [sic] in Europe”: Romania’s Gerovital H3 (GH-3).36 According to McGrady these interventions evidenced progress in “theoretical and experimental gerontology.” He suggested that, in the near future, “every American family will have its own rejuvenator,” a practitioner to forestall the aging process.37 McGrady, like most participants in the emerging life extension movement, believed fervently in the promise of science to enable people to “live longer better” and encouraged others to seek out anti-aging technologies.38The Youth Doctors imbued efforts from around the world with a sense of importance and further popularized anti-aging therapeutics and interventions. Dr. Frank G. Slaughter, author of Your Body and Your Mind: The New Science of Psychosomatic Medicine (1963) reviewed The Youth Doctors for the New York Times. His review began with McGrady’s assertion that the idea of youthfulness was “the number one obsession of our people in our time” not because of a “fear of death, but sex.” Slaughter was intrigued by McGrady’s claim that women pursued cosmetic interventions while men sought to overcome impotence. While Slaughter agreed with McGrady’s gendered analysis of youth seeking, he was less convinced by McGrady’s belief that science would resolve the problems of aging. Slaughter’s review concluded that The Youth Doctors “introduces the reader to an enthralling world, peopled by colorful individualists” and suggested that it might “not lead you to the fabled fountain, but it will interest and instruct, as well as entertain.”39 Donald W. Goodwin, a psychiatrist at Washington University in St. Louis who reviewed the book for the Journal of the American Medical Association (JAMA), was considerably less amused. He deemed the book “unfortunate” and argued that the treatments it highlighted lacked sufficient proof of legitimacy and efficacy.40 Angered by Goodwin’s assessment, McGrady submitted a rebuttal to the medical journal in the form of a letter to the editor. He described his book as a serious volume “on gerontology, its origins and peripheral landscape” and cited positive reviews by other experts.41 Goodwin stood by his original review, as the scientific press and mainstream medicine were steadfast in their criticism of those who promoted anti-aging therapies. The establishment opinion was best summed up by the author of a 1963 article in Geriatrics titled, “Drug therapy in aging patients:” “the concept of an ‘old age deferred,’ no matter what variation the title assumes, deserves little more than a look askance.”42 While many American clinicians remained cautious and even cynical about the latest rejuvenation therapies, physicians in Eastern Europe were more receptive to these interventions. Perhaps the best-known example was Romanian doctor Ana Aslan, developer and promoter of Gerovital H3, a procaine-based product. Procaine is a local anesthetic, known more commonly by the trade name Novicain. This alleged anti-aging drug was introduced to the global medical community first at conferences in Switzerland and Germany in 1956 and then in the pages of a French publication in 1958.43 Aslan had been using Gerovital to treat arthritic patients since the late 1940s, and she claimed that it also cured them of other age-related conditions, such as loss of muscle strength and memory.44 By the early 1960s, the hype around Gerovital was palpable, even though most American scientists questioned its potency and were frustrated by their inability to examine the chemical composition of the drug, whose formula belonged to the state and was kept secret. Aslan did reveal that, unlike other procaine therapies, hers included benzoic acid and potassium metadisulphite and that the procedure of compounding this preparation was what gave Gerovital its unique potency.45 Unable to unlock Gerovital’s secret formula that had been developed behind the Iron Curtain, the FDA decided to test its principal ingredient, procaine. Procaine was first made in 1905 by the German chemist Alfred Einhorn in search of a local anesthetic less toxic than cocaine.46 The FDA refused to approve the use of Gerovital in the United States when results from experiments testing procaine’s anti-aging ability proved inconclusive.47 Nevertheless, wealthy Americans who wanted to try Gerovital either smuggled the substance into the United States or traveled to Europe, where the drug was readily available.48 For those who chose to travel to the source, Romania was ready. By the early 1970s, the Romanian-Carpati National Tourist Office was featuring the treatment and its anti-aging properties in a travel brochure to cash in on this version of medical tourism.49 In 1972, perhaps due to American citizens traveling to Romania or the continued pressure from the public and the scientific community, US federal government officials decided to reconsider Gerovital. That year, three senators visited the Bucharest Geriatric Institute where they were briefed by Aslan and given tours of the facility.50 The FDA also authorized studies of Gerovital’s ability to treat depression in the elderly. Previous findings had suggested that Gerovital might work as a monoamine oxidase (MAO) inhibitor; MAO is a substance known to cause depression and to increase with age.51 Some of the research conducted blurred the lines between depression and aging, as in the case of a clinical study conducted by Dr. Sidney Cohen and Dr. Keith Ditman. Supplied with Gerovital by Rom-Amer Pharmaceutical Company (at the time located in Los Angeles), these California doctors conducted a Phase II open clinical trial in which forty-one subjects were given 100-200 mg of Gerovital intramuscularly three times a week for four weeks. The goal of the study was to test for safety and efficacy. Although they were studying Gerovital in the treatment for depression, Cohen and Ditman recruited some subjects with “no psychiatric problem.” They also reported that subjects’ main motivation for participating in the study was “a desire on their part to ‘age better’” and that most of the subjects had heard of Gerovital’s promise to combat aging before joining the study.52 Gerovital’s reputation as an anti-aging pharmaceutical persisted through the 1970s, as mass media articles about life extension and scientific research in Europe speculated about how the treatment worked (including a hypothesis that it had an effect on the hypothalamus, which had been identified as a sort of aging clock) and what the treatment could do, if approved, for Americans.53 Journalists also reported on European research suggesting that Gerovital could fight age-related illnesses and conditions, including Parkinson’s disease, depression, and the climacteric in both females and males.54 Not classified as a sex hormone and unable to demonstrate direct results, Gerovital never entered American physicians’ repertoire when it came to fighting symptoms related to menopause and the male climacteric. Although estrogen remained an acceptable treatment for menopause in women through the 1970s (and, indeed until the early 2000s), the use of testosterone as a treatment for aging men vanished from the medical literature after the mid-1950s. Instead, the symptoms that had previously described the male climacteric – fatigue, problems concentrating, loss of memory, restlessness, insomnia irritability, loss of libido – were re-fashioned into a diagnosis of a stress-induced condition. Psychiatry replaced endocrinology as the explanatory framework, and tranquilizers replaced hormones as the preferred therapy. Testosterone would not re-appear as a treatment for male aging until the 1990s.55 Ultimately, procaine was unable to establish itself as a viable anti-aging therapeutic in the United States. As one of its early actions, the National Institute for Aging (NIA) commissioned a review of world literature on procaine treatment. The 1977 report came out strongly against its use. In covering the report, the Journal of the American Geriatrics Society noted that data from “285 articles and books, describing treatment in more than 100,000 patients in the past 25 years” yielded “no convincing evidence that procaine (or Gerovital, of which procaine is the major component) has any value in the treatment of disease in older patients.”56 This definitive meta-analysis ended any chance that Gerovital would be approved for sale in the United States. The FDA’s refusal to approve Gerovital as an anti-aging drug did not quash the optimism held by those who were part of the life extension scene. These believers interpreted Gerovital and advances in biomedical science as life-saving and life-extending technologies. They understood “The Promise of Transplants,” “The New Technology of Bionics,” cloning, genetic engineering, and therapeutics including Gerovital along one continuum.57 In their opinion, it wasn’t the shortcomings of science that made longevity and youthfulness impossible goals; rather, it was the conservative medical establishment and restrictive federal government that obstructed medicine from reaching its full potential. This small but prolific group of believers continued to write about and practice the science of life extension well into the late 1970s and early 1980s. They aspired to alter the way Americans viewed end of life and aging, and they undertook daily regimens to forestall death, which they refused to accept as inevitable. From preparing final instructions for the cryonic preservation of their bodies to taking supplements intended to boost natural growth hormone levels, these practitioners were leading by example in order to bring forth a societal reward. In doing so, these life extenders appeared as a determined, if fringe, social movement.58 By the late 1970s, life-extenders wore their outlier position as a badge of honor and identified themselves as “pioneers” in the “pursuit of an extended human life span” as they fought “the most basic and formidable of our enemies – aging and death.” Their collective frontier was their bodies as they embraced a lifestyle that included practices of “dietary intervention, immunologic engineering, body temperature manipulation, and pharmaceutical therapy.”59 They viewed their self-experimentation with drugs and regimens (many of them untested) as a political stance against oppressive government regulation. Activists and others who disagreed with the government’s decision to outlaw the drug skirted federal law and manufactured, bought, sold, and consumed Gerovital, making it quite popular in anti-governmental regulation circles. In May 1979, there was a showdown between the main manufacturer and distributor of Gerovital in the U.S. and Congress when Rom-Amer Pharmaceuticals Ltd.’s new President and Chief Executive Officer, Marvin Krattner, was called to testify at the Senate Subcommittee on Health and Scientific Research’s hearings on drug regulation reform. In 1977, Krattner had successfully lobbied the state of Nevada to pass legislation allowing for the manufacture and intrastate distribution of Gerovital. Business was booming and had spurred medical tourism to the Las Vegas strip.60 This new tourist trade received national attention and was one of the reasons Congress decided to consider stricter regulations on the federal oversight of interstate distribution of drugs in 1979. Krattner’s testimony at the congressional hearing exemplified the life extension movement’s position on the FDA and federal oversight. He argued that the FDA should not “be permitted to erase and eliminate State lines [making us] one Federal state.”61 He also suggested that increased regulation would infringe on personal rights: The American citizen today appears to be the only one in the world without the constituency of his own body, and, by virtue of the efficacy requirements of the existing law, he is not given the freedom of choice to decide, even with the advice and consultation of his own personal physician, as to whether or not he may elect to have a drug administered or dispensed to him in an attempt by his physician to determine whether or not that particular drug is efficacious for that particular patient in the treatment of one or more various illnesses.62 This interpretation of FDA regulation as stifling personal freedom was shared by others engaged in and advocating for life extension therapeutics. They believed that government agencies were having a “profound and generally negative impact on the progress of aging research” and that the FDA’s “regulatory policies have drastically reduced the amount of pharmaceutical innovation without a measurable increase in either drug safety or efficacy.”63 They also criticized the NIA for its reluctance to fund research on extension of the human life span.64 This anti-establishment stance of life extension promoters did not compromise the movement’s popularity among adherents and in some way may have contributed to it. Activists within the life-extension movement understood aging to be both disability and disease. Aging disabled older Americans by preventing them from participating as fully in life as compared to younger Americans or their own younger selves. And aging was the ultimate life-threatening disease, as its inevitable outcome was death. In combating the morbidity and mortality of aging, these activists had no compunctions about using any and all remedies, regardless of government approval or mainstream medical sanction. Living Longer and Better in the 1980s Interest in life extension grew in the early 1980s as part of the wave of enthusiasm for self-help diet and lifestyle books. An early success of the life extension self-help genre was the 1979 bestselling The Pritikin Program for Diet and Exercise by Nathan Pritikin with Patrick M. McGrady, Jr. (author of The Youth Doctors). Described as a “prescription of health and long life,” the program featured an exercise regimen and a diet low in fats, cholesterol, and protein and high in unrefined carbohydrates. According to Pritikin, exercise and a restricted diet could promote a longer life and reverse debilitating diseases such as diabetes, cardiovascular disease, and cancer. For the affluent looking for a more hands-on intervention, Pritikin opened a chain of Longevity Centers. The centers offered programs for those battling disease as well as for those merely interested in prevention.65 The Pritikin Program was strict compared to dietary standards of the time, as, for example, those issued by the American Heart Association (AHA). It limited salt intake and prohibited sweeteners, caffeine, and alcohol. The Pritikin diet provided five to ten percent of calories in fat, ten to fifteen in protein, and eighty percent in complex carbohydrates; compared to the AHA’s recommendation of thirty percent fat and the typical American diet of forty-five percent fat, the program was panned by some reviewers for being too unrealistic. But to Pritikin it was a matter of life and death. He believed so strongly in his program that he asked the director of the National Heart Lung and Blood Institute (NHLBI), Dr. Robert Levy, to fund research to compare its results with those from the AHA-recommended diet. When Levy refused, Pritikin labeled Levy the enemy and decided to find funding on his own.66 Pritikin accepted and even embraced his outsider status. A college dropout, he made his fortune by developing patents in chemistry, physics, and electronics for companies such as General Electric and Corning Glass.67 In spite of criticism from the medical establishment and competition from other diet developers, Pritikin had a loyal following, which grew during the 1980s and included those who believed in the life extension principles of diet manipulation.68 While Pritikin was not a hard core life extender – his focus was on a restricted diet and exercise to reverse disease and increase longevity, and not on self-experimentation with substances or the promotion of cryonics – his books and centers can be regarded as part of the larger movement to popularize the notion of personal empowerment to defy aging and death.69 Two organizations in particular, the Fund for Biomedical Research (FIBER) and the Life Extension Foundation (LEF), were central to the campaign to challenge the idea that aging had to be inevitable and to the life extension movement. These groups represented the formal, organized wing of the movement. They articulated the movement’s goals and allowed for more cohesive and collective action; as such, they provide structure for this social movement.70 FIBER was the less sensationalist of the two as it worked within the parameters of experimental gerontology specifically and scientific medicine more generally. Founded in 1979 by a senator (Alan Cranston, Democrat-CA) and a physician (William Regelson, a medical oncologist and professor of medicine at the Medical College of Virginia), FIBER was intended to operate as an “institute without walls” by promoting cooperation among scientists working on anti-aging research.71 It did so by coordinating conferences, hosting frequent meetings with experts, endorsing popular books promoting aspects of life extension, and supporting research.72 FIBER experienced some early success and brought some legitimacy to the life extension movement. By 1982, it reported progress in its documentation of geographic variation in death rates, lab research on an organ transplant process that rejuvenated rats, and the discovery of a “death hormone,” which many believed could be responsible for aging.73 In contrast, the Life Extension Foundation (LEF) took a different approach in promoting anti-aging science by focusing on educating the public and fostering a popular health movement. Financially backed by real-estate mogul Stephen Ruddell, LEF was founded in 1980 by mortician William Faloon and science writer and long-time cryonics advocate Saul Kent. A veteran of the life extension movement, Kent was the initial front man of the operation, while Ruddell stayed behind the scenes and Faloon learned the ropes. Kent’s decades-long involvement in the movement reflected its larger developments. He was one of the founders of the first cryonics society in New York in the mid-1960s.74 In 1974, he contributed to the growing science fiction subgenre of life extension with the publication of his book Future Sex.75 Two years later, he published a more technical foray into the science of anti-aging, with an article in Geriatrics titled “Solving the Riddle of Lipofuscin's Origin May Uncover Clues to the Aging Process.”76 In doing so, he remained on trend with his colleagues, as other life extenders also authored scientific treatises on immortality. During the late 1970s and early 1980s, Kent helped to publicize the life extension movement by writing in popular magazines and in a running column, “New Frontiers of Research,” in Geriatrics.77 The jacket of his 1980 book, The Life Extension Revolution, described it as a “definitive guide to better health, longer life, and physical immortality,” and its author as “an activist in the life-extension movement for over fifteen years.”78 LEF would prove not only to be the next chapter in Kent’s career as a life extender but also to provide him with an opportunity to make millions. Headquartered in Hollywood, Florida, LEF sold what it called “nutritional supplements” through its mail-order business. The Miami Times reported that LEF was making four to five million dollars in profit by 1985 through drug sales and membership fees.79 The founders claimed LEF was a non-profit organization focused on providing information about the life-extension lifestyle and laboratory and clinical research on anti-aging. LEF’s major publication was a monthly twelve-page newsletter, Anti-Aging News, featuring the “latest scientific efforts to prevent aging and rejuvenate the aged” and interpreting complex scientific research for its lay subscribers.80 While the official intent of the newsletter was to keep members informed about the latest trends in anti-aging, it also served as a marketing tool. LEF’s efforts blurred the lines between non-profit and for-profit. As public interest in life extension grew, Kent marketed his foundation’s services and products wherever he could. He appeared on television talk shows, such as the Merv Griffin Show. During these staged discussions, Kent not only sang the praises and possibilities of life extension but also encouraged interested viewers to contact LEF for information about services.81 More members meant more profits for this allegedly non-profit venture. There were others who also proselytized self-experimentation in the hopes of “living longer better.” Durk Pearson and Sandy Shaw were two early converts who frequented talk shows on television and radio to spread the gospel of anti-aging therapies.82 Their devotion to self-experimentation in life extension paid off in the early 1980s when their co-authored book made the New York Times bestseller list in 1982.83Life Extension: A Practical Scientific Approach reported in vivid detail the results of their self-experimentation with high doses of nutrients and drugs that they claimed would cheat the effects of aging.84 Pearson and Shaw promoted their book as “an invitation to a personal adventure that may lead to a longer and more vigorous lifetime” by laying out a plan for personal life extension.85 Neither Pearson nor Shaw had graduate training in medicine, pharmacy, or biomedical research (as undergraduates, the former majored in physics at MIT and the latter majored in chemistry at UCLA). Nonetheless, they saw themselves as scientific pioneers; in dedicating their book to James Watson and Francis Crick (the discoverers of DNA), Denham Harman (developer of the free radical theory of aging), and Albert Hofmann (inventor of hydergine, used to improve circulation and cerebral function, especially in the elderly, and discoverer of LSD’s hallucinogenic properties), they sought to locate their anti-aging, Life Extension, lifestyle prescription within a pantheon of important scientific discoveries.86 So successful was their first book that they quickly followed it up with two more: Life Extension Companion (1984) and Life Extension Weight Loss Program (1986). Pearson and Shaw claimed that daily thirty-minute workouts and consumption of a specific regimen of vitamins, preservatives, and drugs could help stave off illness and debility and promote longevity. The experimental drug regimen was lengthy and included vitamin A, beta carotene, vitamin E acetate, selenium, zinc, L-arginine, tryptophan, L-dopa, Deaner (dimethylaminoethanol, Riker), choline chloride, RNA, vitamin B-12, high potency multivitamins with chelated minerals, vitamin B-1, thiamine HC1, vitamin b-2, riboflavin, vitamin B-3, nicotinic acid, vitamin B-5, vitamin B-6, pyridoxine HC1, rutin, hesperidin complex, PABA, L-cysteine, vitamin C, inositol, hydergine (ergoloid mesylates), and diapid (vasopressin). They also advocated sex hormone replacement for post-menopausal women.87 The stimulation of HGH by several of the supplements listed above formed one of the core tenets of Pearson and Shaw’s anti-aging regimen. They argued that restoring growth hormone levels to those of early adulthood was vital to living longer and better. Their advocacy for restoring HGH levels originated with a research proposal written by Pearson in 1976 for private funding titled, “Toward a Possible Life Extension Technology Involving Human Growth Hormone.” Described in Life Extension, the “proposal dealt with the use of GH-releasers…to maintain teenage to young adult levels of GH in adults of any age.”88 Pearson and Shaw were aware of the mounting scholarship that suggested that the release of growth hormone fell off sharply with age and that this deficiency might make older people susceptible to loss of muscle, gain of fat, sleeping problems, slower rates of wound recovery, and compromised immune systems.89 However, they did not advocate the use of exogenous HGH; instead they championed what they claimed to be GH-releasing supplements: L-dopa, bromocriptine, vasopressin, tryptophan, L-arginine, and L-ornithine.90 Missing from their discussion about human growth hormone levels were findings that pointed to the unpredictability of supplements’ ability to elevate HGH levels, some suggested benefits that came with the normal decline in HGH levels, and possible dangers associated with increased HGH levels.91 Some research also proposed the loss of HGH could reverse clinical retinopathy and renal complications of diabetes. Other studies posited that HGH might in fact accelerate the aging process and could be associated with pituitary tumors in aging rodents.92 Instead of acknowledging conflicting reports, Pearson and Shaw sided solely with the literature that suggested increased levels of this hormone would benefit older people. The “evidence” of the effects of increased HGH levels presented by Pearson and Shaw was a series of photographs of themselves showing off their muscles after extensive self-experimentation with growth hormone releasers. Like Pearson and Shaw, most life extension advocates hailed the effectiveness of supplements in promoting longevity and youthfulness through the stimulation of human growth hormone. It is interesting, and somewhat surprising, that Pearson and Shaw and other life extenders did not recommend exogenous HGH, since they were not shy about promoting the experimental use of non-FDA approved substances, such as Gerovital and DHEA, or off-label use of approved pharmaceuticals. Furthermore, exogenous HGH had become more readily available in the 1980s with a change in processing methods and FDA approval of two cadaver-based products manufactured by two European pharmaceutical companies. Even though Pearson and Shaw were aware of these commercial products (Serono’s Asellacrin and Kabi’s Crescormon), they did not advocate the direct use of cadaver-based human growth hormone therapy (cHGH) for life extension purposes.93 Human Growth Hormone in the 1980s Pearson and Shaw not only recommended the intake of numerous vitamins and supplements, they also sold their own line of products. They weren’t alone in this commercial venture. The supplemental health industry targeting older Americans was so robust by the late 1970s that the House of Representatives Select Committee on Aging decided to investigate questionable practices such as anti-aging cures. After a four-year investigation, the report, Quackery A $10 Billion Scandal, found “youth cures … the fastest growing segment of medical quackery” to be entirely without merit and their advocates to be dangerous hucksters. Pearson, Shaw, and the Life Extension Foundation were called out as especially pernicious actors. Pearson and Shaw’s recommendations were criticized as scientifically unsound and possibly lethal, and the LEF was faulted for its evasion of legal and regulatory restrictions on the practice of medicine.94 Although the report condemned numerous anti-aging practices and products, it made no mention of HGH or GH promoters. Meanwhile, many athletes and some scientists started to experiment with cHGH. Used and promoted by bodybuilders, cHGH made a splash at the 1984 Olympics as new doping restrictions did not include human growth hormone.95 One physician, Dr. Robert Kerr, was the focus of a series of articles in the Los Angeles Times leading up to the Olympics. He had practiced family medicine until he got swept up in the performance enhancing drug craze. His book, The Practical Use of Anabolic Steroids with Athletes, helped advertise his services to athletes looking for a competitive edge. Kerr routinely suggested he was administering anabolic steroids and growth hormone to Olympic athletes from around the world. In the age of the “chemical” athlete, he believed that competitors had to do what was necessary to win.96 In justifying his practice, Kerr described his treatment as a way to make healthy people healthier.97 Researchers who studied the sanctioned uses of cHGH (to treat short stature in children) also self-experimented with injections. In an interview with the New York Times, Dr. Robert Blizzard, a physician at the University of Virginia medical school who played a major role in official cHGH manufacturing and distribution for decades, acknowledged that he and four other unnamed researchers over the age of fifty took it to test its anti-aging potential from 1983 to 1985. Although their experiments failed, Blizzard averred interest in giving it another try with younger men in their thirties. He rationalized that “instead of turning an old Ford into a new Ford, maybe we can preserve the young Ford for a longer period of time.”98 While part of the reason Blizzard experimented with cHGH was that it had become more available due to changes in production, he was also inspired by the pending revolution that was predicted to take place in the manufacturing of HGH. In 1985, the FDA approved the first synthetic version of human growth hormone produced by recombinant DNA technology (rHGH), which further increased the available supply and resulted in an increase in research efforts. One investigator who took advantage of the rHGH was endocrinologist Daniel Rudman, who had begun experimenting with pituitary extracts in the 1950s.99 In the early 1970s, his research focused on the hyper-responsiveness of people with a variety of muscle dystrophies to exogenous HGH.100 In the late 1970s, Rudman compared and contrasted the responsiveness of growth hormone deficient (GHD) children and normal variant short stature (NVSS) children to exogenous human growth hormone and found that some NVSS children were just as receptive as GHD subjects.101 He also documented the high incidence of GHD in children with cleft lips or palates and looked into the clinical outcomes of GH therapy in girls with X chromosome abnormalities.102 In the 1980s, Rudman’s research interests appear to have shifted, as he began publishing articles on endogenous growth hormone secretion in adults. In a 1981 article titled “Impaired Growth Hormone Secretion in the Adult Population,” Rudman and his team described the concomitance of a progressive decline of growth hormone and a hyper-responsiveness to exogenous GH in aging individuals. They speculated about an inverse correlation between adiposity and GH secretion as well as a possible relationship between the “geriatric decline” in “bone formation,” “renal blood flow,” and “stimulus protein synthesis in the lean body mass” and the reduced levels of GH that came with age.103 Although Rudman did not explicitly credit the expansion of his GH research to an increase in hormone supply, it would have been difficult for him to have received any of the hormone for his work with adults and non-GHD children without that greater availability. His publications also reflected an optimism brought about by an increase in supply, especially in his suggestions of potentially new clinical uses for HGH, including the treatment of both NVSS children and aging adults.104 Rudman’s research on growth hormone and enthusiasm for its therapeutic applications made him an ideal participant on a panel of experts convened by the FDA in 1980 to advise the agency on the potential future clinical uses of synthetic HGH.105 In 1983, Rudman began working at the Chicago Medical School and Veterans Administration Medical Center in North Chicago, Illinois. Funded by the Veterans Administration and Lilly Research Laboratories, Rudman examined GH secretion at the end of the life cycle and considered the possibility of treating the elderly with this hormone. He argued that about half of the population over sixty-five was partially or totally deficient in GH and – in a revised iteration of Masters’s hypotheses from the 1950s – that through replacement therapy some aspects of geriatric decline could be reversed.106 He continued this work in conjunction with the Veterans Administration Medical Center in Milwaukee, Wisconsin, when he took a position at the Medical College of Wisconsin in 1988. Rudman and his research team conducted a study on twenty-one men between the ages of sixty-one and eight-one who had low levels of growth hormone (based on low levels of insulin-like growth factor 1). Twelve received growth hormone therapy for six months while nine received no treatment. As he had hypothesized, once growth hormone levels reached a youthful range, the experimental subjects experienced an increase in lean body mass, a decrease in adipose tissue mass, an increase in average lumbar vertebral bone density, and an increase in skin thickness.107 Rudman’s report was published in the New England Journal of Medicine in July 1990, alongside an editorial that emphasized the preliminary status of the research. In the following weeks, the journal also published numerous letters to the editor about Rudman’s findings. His article stirred up debate among the journal’s readers and captured the attention of the popular media; the Wall Street Journal, Washington Post, Chicago Tribune, and New York Times all ran stories with headlines hailing HGH as the new hope for restoring youth.108 Although it might be expected that the life extension movement would have seized the Rudman report as justification for its long-standing claims about the anti-aging benefits of hormone therapy, by 1990 the movement had fallen on hard times. It suffered grave damage from adverse media coverage of its continued commitment to promoting, proving, and participating in cryonics, the practice of deep-freezing dead bodies until science discovered a cure to resurrect them. Two events in particular seemed to have sealed its fate. In the summer of 1987, Paul E. Segall, a researcher who had secured access to a laboratory at the University of California, Berkeley through dubious channels, gave a conference presentation on his success in freezing a beagle for fifteen minutes and subsequently reviving it. The press picked up the story and interest in cryonics heightened until Segall’s story and his status as a Berkeley scientist were both discredited.109 Matters got worse for the life extension movement later that year. In December, Saul Kent’s mother, who suffered from Alzheimer’s disease, became gravely ill with pneumonia. Kent decided to prepare his mother for a sub-zero frozen state, which, following cryonic protocol, included decapitation. In order to avoid law enforcement, Kent kept the whereabouts of his mother’s head a mystery and remained steadfast that his mother wanted to have her head frozen until she could be “reanimated.” Amid debate over what exactly killed Mrs. Kent – an infection or the lethal dose of barbiturates used in preparation of being frozen – the Riverside, California, coroner ruled her death a homicide, but no charges were pressed and the location of the head remains a mystery to this day.110 Meanwhile, the Life Extension Foundation (LEF) found itself in a heap of legal trouble in 1986 when a Hollywood, Florida, police SWAT team raided the office of Stephen Ruddel, the real estate mogul who put up the seed money for the organization. Ruddel was arrested on drug-trafficking charges and then entered into a plea bargain on drug-possession charges. In 1987, the FDA raided LEF’s warehouse, which was located in the same building as Ruddel’s office. A federal criminal indictment was handed down in 1991 to LEF’s Faloon and Kent for allegedly importing unapproved drugs into the U.S. through phony foreign companies, the Longevity Institute and the Hauptmann Institute. Faloon and Kent denied all charges and even set up an anti-FDA museum, which they named the FDA Holocaust Museum.111 Preoccupied with their own defense, they were unable to engage in serious discourse about Rudman’s findings and the implications for HGH as an anti-aging supplement. By 1990, after its humiliation in the media and its run-ins with the law, the life extension movement was essentially defunct. The Not-So-New Anti-Aging Market in the 1990s and 2000s Within the world of mainstream medicine, the reputation of exogenous HGH as an anti-aging therapeutic soared in the early 1990s after the publication of Rudman’s study in one of the most world’s reputable medical journals. HGH was unscathed by either the demise of the life extension movement or the increased federal scrutiny of nutritional supplements and therapeutics promising longevity and vitality; instead, HGH-related anti-aging clinical research received funding from the NIA.112 HGH may have been the beneficiary of the almost universal enthusiasm for another hormone, estrogen, in allegedly forestalling the diseases of aging. In 1992, the American College of Physicians had recommended that “all women, regardless of race, should consider preventive hormone therapy … to prevent disease and to prolong life.”113 That same year, Wyeth-Ayerst’s Premarin (conjugated estrogen tablets) became the best-selling prescription drug in the United States, a position it held for several years through the 1990s. By 1999, some fifteen million American women were taking estrogen replacement therapy.114 With the benefits of estrogen touted in both medical journals and popular periodicals, some physicians began to wonder if aging men might also benefit from hormone replacement. Medical journal articles in the 1980s and early 1990s had reported that testosterone levels decreased steadily in older men, but the effects of this decline were unknown. In 1993, the FDA approved Testoderm, a transdermal testosterone patch from the Alza Corporation, for the treatment of hypogonadism in men. Although the indications for the product made no mention of aging or andropause (the updated term for what used to be called climacteric), physicians were free to prescribe the medication off-label to men concerned about the effects of aging. Testoderm was soon followed by other skin patches, and testosterone prescriptions rose from 122,000 in 1992 to 648,000 in 1999, a more than five-fold increase. FDA medical officer Jean L. Fourcroy observed a “growing realization that the aging male population may also need hormone replacement therapy (HRT).” She concluded that “Androgen delivery systems are therefore a booming business.”115 Given the seeming success of estrogen and testosterone as replacement therapies in aging women and men, respectively, it is not surprising that physicians and laypeople had high hopes for similar results from human growth hormone. The NIA’s support of clinical studies of HGH mirrored – although on a smaller scale – the investment by the NIH in estrogen studies in the Women’s Health Initiative.116 However, preliminary findings from the HGH trial found an absence of anti-aging benefits and the potential for life-threatening side effects, and the study was halted in 1996. The following year the NIA issued a report that stated “side effects of HGH treatment can include diabetes and pooling of fluid in the skin and other tissues, which may lead to high blood pressure and heart failure. Joint pain and carpal tunnel syndrome may also occur.”117 In spite of these warnings, HGH’s popular reputation as the new fountain of youth seemed only to grow in the 1990s. Books about balancing hormones, listening to one’s hormones, and taking hormones in the hopes of slowing down the aging process became best sellers.118 Hormone-enhanced products and anti-aging centers offering hormone replacement sprung up across the nation. Indeed, HGH enabled the principles of the life extension movement to be revived under the guise of a new organization, the American Academy of Anti-Aging Medicine (A4M). A4M was founded in 1992 by two osteopaths, Ronald Klatz and Robert Goldman. They met in the early 1980s at the Chicago College of Osteopathic Medicine where Klatz was a staff physician and Goldman was a medical student. Goldman was a gravity boot enthusiast, and together they researched the risks and benefits of inversion therapy. Their results were published in the Journal of the American Osteopathic Association and received some media attention in 1983.119 A year later, they published a book, Death in the Locker Room, detailing the dangers of drug, steroid, and HGH use by athletes.120 In the late 1980s, their efforts took a turn toward the commercial. They rolled out their own line of fitness equipment, the Ergogenic Pro-Formance system, and created a National Academy of Sports Medicine (NASM) as an entity to certify personal trainers.121 Klatz and Goldman must have chosen this name deliberately, as it resembled the well-established National Athletic Trainers’ Association (founded in 1950). This duo was savvy in creating, promoting, and profiting from their reputation in the world of fitness.122 Klatz and Goldman employed a similar strategy when they ventured into the life extension business. Instead of merely endorsing the use of HGH as an anti-aging agent, Klatz and Goldman formed a medical academy, A4M, to establish and promote a new specialty in (not outside of) medicine. By staking out territory within the boundaries of mainstream medicine, A4M was a marked departure for the life extension movement. Klatz and Goldman purposefully gave their business venture a medical-sounding name and defined its practices and products as a medical specialty. Early on, the “Academy” was marketed through advertisements designed to look like newspaper articles.123 A4M hosted health conferences and published newsletters. Klatz argued that A4M was a pioneering force in scientific research and clinical practice, not a form of alternative medicine. In adopting the NASM business model and attempting to establish A4M as a legitimate medical academy, Klatz and Goldman made plans to establish certification programs, although board certification in anti-aging medicine for chiropractors, dentists, naturopaths, pharmacists, and scientists would not become fully available until 1999. The lack of recognition by establishment groups such as the American Medical Association (AMA) or the American Board of Medical Specialties (ABMS) does not seem to have dampened A4M’s popularity. In 2017, its website proudly claimed a membership of more than 26,000, of whom eighty-five percent are physicians (MD, DO, and MBBS) and twelve percent are research scientists and other health practitioners, and celebrated its twenty-fifth anniversary of leadership in anti-aging medicine.124 The case of A4M raises interesting questions about who gets to define legitimacy in medicine. The 22,000 doctors who have joined the organization, attend its annual meetings, participate in its workshops, and seek its certifications seem not to care whether A4M has secured the imprimatur of the AMA. In the 1990s, human growth hormone gave A4M the legitimacy Klatz and Goldman needed to differentiate their “scientific” anti-aging endeavor from the earlier activities of their predecessors. In spite of the short-lived validation of HGH as an anti-aging supplement, it provided sufficient momentum for its advocates. A4M claimed further validation when the FDA approved the use of HGH in cases of adult growth hormone deficiency in 1996. Since anti-aging practitioners believed that all older individuals experienced growth hormone deficiency due to the natural decline of HGH production, they saw every aging person as eligible for replacement therapy. Unlike their predecessors in the life extension movement who railed against FDA regulations, the latest crop of anti-aging advocates tried to work with the FDA, believing that they were now operating within the borders of regulatory legitimacy. In this way, A4M appears to have brought anti-aging therapeutics back, if not squarely into the mainstream of medicine, then at least to its outer edges. Conclusion Klatz, Goldman, and the A4M membership believed that supplementing growth hormone would solve the problems of aging in much the same way that Masters promoted sex hormones for the same problems fifty years earlier. The battle cry of “live longer better” recapitulated decades-old efforts with a new weapon in hand. The latest band of anti-aging enthusiasts had capitalized on the evidence in Rudman’s 1990 article in the New England Journal of Medicine as justification for their much broader claims about HGH as an effective agent against the disabling effects of aging, although HGH replacement therapy for aging adults never really took hold in mainstream medical practice. Promoted by its boosters as a fountain of youth, HGH did attract a significant following in the broader medical marketplace with the promise of both vitality and freedom from the disabilities that accompanied aging. The anti-aging marketplace of the twenty-first century and the life extension movement in the twentieth century shared a conviction that the decline that accompanies aging is predictable and preventable with the right kind of intervention. While the recommended interventions changed over time, their promises remained consistent. Like estrogen, testosterone, and Gerovital before it, HGH and growth hormone promoters were touted for their potential to reverse or stave off disabling conditions. Amid the historical continuity in anti-aging medicine were changes in its location on the spectrum of medical orthodoxy. Some proponents championed the alternative nature of anti-aging practices; others sought mainstream legitimacy. Whether inside or outside the fluid boundaries of conventional medical practice, anti-aging adherents ascribed to a faith in science. That is, they believed that science could – and should – be marshaled in the fight against aging. From the utopian scientific fiction of cryonics to the more pragmatic off-label prescribing of human growth hormone, anti-aging medicine has been characterized by faith in the power and promise of science. What differed between fringe and mainstream practitioners was the level of commitment to the scientific method, evidence-based medicine, and the sanctity of the randomized controlled trial. While government-funded researchers and board-certified physicians followed the rules of evidence-based medicine and medical research (or at least professed to do so), the life extension and A4M group viewed anecdote and personal experience as sufficient evidence. The story of anti-aging medicine contributes to a blurring of the distinction between the roles of traditional and non-traditional actors in medical practice in late twentieth and twenty-first-century America. While they may have been portrayed as hucksters, the life extenders and anti-aging advocates truly believed in their products and procedures, as evidenced by their own enthusiastic adherence to anti-aging regimens. That faith, combined with a flair for marketing and promotion, has sustained the persistence of the “youth peddlers” for the past seventy years. Our investigation into the deeper roots of anti-aging medicine has brought to light a rogue’s gallery of colorful characters, all of whom –with the exception of Ana Aslan – are white males. We hope this initial inquiry inspires research into the roles of gender, race, and ethnicity among the providers and promoters of anti-aging medicine. This paper has focused on those providers and promoters; more research is needed to learn about the consumers of anti-aging hype and hormones. Finally, the epistemological and rhetorical intertwining of aging as disability and aging as disease, as performed across the spectrum of medical practice, warrants further consideration. Acknowledgments The authors would like to thank researcher Katelyn Smith for her work on this article and Elena Conis, Dorothy Porter, and the anonymous reviewers for their comments on earlier versions of this manuscript. Footnotes 1 Aimee Medeiros, Heightened Expectations: The Rise of the Human Growth Hormone Industry in America (Tuscaloosa: University of Alabama Press, 2016). 2 Courtney Everts Mykytyn, “A History of the Future: The Emergence of Contemporary Anti-ageing Medicine” Sociology of Health & Illness 32 (2010): 181-196. 3 David S. Meyer and Nancy Whittier, “Social Movement Spillover” Social Problems 41 (May 1994): 280. 4 John D. McCarthy and Mayer N. Zald, “Resource Mobilization and Social Movements: A Partial Theory” The American Journal of Sociology 82 (May 1977): 1212-1241. 5 Meyer and Whittier, “Social Movement Spillover,” 278. 6 Of course, the quest to understand aging and relieve its afflictions dates back to ancient times. For examples from the classical era, the Renaissance, the Enlightenment, and the nineteenth century, see Antje Kampf and Lynn A. Botelho, “Anti-Aging and Biomedicine: Critical Studies on the Pursuit of Maintaining, Revitalizing and Enhancing Aging Bodies” Medicine Studies 1 (2009): 187-195, and Carol Haber, “Life Extension and History: The Continual Search for the Fountain of Youth” Journal of Gerontology: Biological Sciences 59A (2004): 515-522. 7 Paul de Kruif, “Can Man’s Prime Be Prolonged?” Reader’s Digest 45 (July 1944): 21-24, quote on 24. In 1945, de Kruif collected the results of his research on testosterone into a book called, simply, The Male Hormone (New York: Harcourt Brace). 8 This philosophy and practice was continued in the 1950s by E. Kost Shelton and in the 1960s by Robert Wilson. See Elizabeth Siegel Watkins, The Estrogen Elixir: A History of Hormone Replacement Therapy in America (Baltimore: Johns Hopkins University Press, 2007), chapters two to four-. 9 William H. Masters and John W. Ballew, “The Third Sex” Geriatrics 10 (January 1955): 2-3. 10 William H. Masters, “Rationale of Sex Steroid Replacement in the “Neutral Gender,” Journal of the American Geriatrics Society 3 (June 1955): 394. 11 Elie Metchnikoff coined the term gerontology is 1908, and Ignatz Nascher coined the term geriatrics in 1909. The Gerontological Society of America filed for incorporation in 1945 and published the first issue of the Journal of Gerontology in 1946. The American Geriatric Society was founded in 1942, and the inaugural issue of Geriatrics was published in 1946. 12 Laura Davidow Hirshbein, “‘Normal” Old Age, Senility, and the American Geriatrics Society in the 1940s” Journal of the History of Medicine 55 (2000): 337-362, 353. 13 W. Andrew Achenbaum, Crossing Frontiers: Gerontology Emerges as a Science (Cambridge: Cambridge University Press, 1995), 128. 14 W. Andrew Achenbaum, Crossing Frontiers: Gerontology Emerges as a Science (Cambridge: Cambridge University Press, 1995), 128. 15 Ibid., 1. 16 Masters and Ballew, “The Third Sex,” 1. 17 Dr. C. Lee Buxton, a prominent New Haven obstetrician-gynecologist, made this comment in the discussion following Masters’ presentation at the eightieth annual meeting of the American Gynecological Society in Hot Springs, VA, in May 1957. The discussion was included in William H. Masters, “Sex Steroid Influence on the Aging Process,” American Journal of Obstetrics and Gynecology 74 (October 1957): 744. The “panacea” quote is from William H. Masters, “Endocrine Therapy in the Aging Individual,” Obstetrics and Gynecology 8 (July 1956): 66. 18 http://www.foxnews.com/health/2012/10/19/hormones-needed-for-anti-aging/. Accessed 2 September 2016. 19 GH was identified in 1944 and isolated in 1956. Herbert M. Evans and J. A. Long, “Characteristic Effects Upon Growth, Oestrus and Ovulation Induced by the Intrapertoneal Administration of Fresh Anterior Hypophyseal Substance,” Proceedings of the National Academy of Sciences of the United States of America 8 (15 March 1922): 38-39. 20 GH was not isolated until nearly 23 years after it was discovered. Choh Hao Li and Herbert M. Evans, “The Isolation of Pituitary Growth Hormone,” Science 8 (3 March 1944): 183-184. 21 Transcripts from a 1961 interview with Herbert Mclean Evans, Herbert McLean Evans Biographical Papers, Memorabilia 1946-1970, MSS 92-18, Archives & Special Collections, UCSF Library & CKM. 22 Frederick L Good, “Menorrhagia and Metrorrhagia of Benign Origin in Women Under Forty-Five Years of Age, with a Plea for More Conservative Treatment,” New England Journal of Medicine 215 (29 October 1936): 805-811, quotes on 810. Even though these reports were positive, they were inaccurate. The GH that women received during treatment was not clinically effective because growth hormone is species-specific, unbeknownst to scientists until 1954. During this time, growth hormone for research and clinical care was derived from animals and not humans. 23 Frank G. Young, “The Anterior Pituitary Gland and Diabetes Mellitus,” New England Journal of Medicine 221 (26 October 1939): 636-646. 24 Joseph Rogers, “The Menopause,” New England Journal of Medicine 254 (12 April 1956): 697-704. 25 Examples of this research: Harry S. Soroff, Elinor Pearson, N.L. Green, and C.P. Artz, “The Effect of Growth Hormone on Nitrogen Balance at Various Levels of Intake in Burned Patients,” Surgery, Gynecology, and Obstetrics 111 (1960): 259-73; Elinor Pearson, Harry S. Soroff, John F. Prudden, and Melvin S. Schwartz, “Studies on Growth Hormone: V. Effect on the Mineral and Nitrogen Balances of Burned Patients,” The American Journal of the Medical Sciences 239 (1960): 17-26; James Campbell and Krishna Sudha Rastogi, “Growth Hormone-induced Diabetes and High Levels of Serum Insulin in Dogs,” Diabetes 15 (January, 1966), 30-43; and Harvey G. Goodman, Melvin Grumbach, and Selna Kaplan, “Growth and Growth Hormone: A Comparison of Isolated Growth-Hormone Deficiency and Multiple Pituitary –Hormone Deficiencies in 35 Patients with Idiopathic Hypopituitary Dwarfism,” New England Journal of Medicine 278 (11 January 1968): 57-68. 26 Ronald Klatz and Carol Kahn, Grow Young with HGH (New York: Harper Perennial, 1997), 22. 27 Popular media examples of this type of reporting include: Joan Beck, “Spare Parts for Your Body (Second in a Series on New Challenges to Modern Medicine)” Chicago Tribune (9 February, 1964) H30, H32, H34-35. 28 Frederick Pohl, “Intimations of Immortality: Scientific Progress Toward Prolonging Human Life and Predictions Concerning the Indefinite Extension,” Playboy (June 1964), 79-80, 160-162, quote on 80. 29 Pohl, 79. 30 Public Law 93-296 (31 May 1974). 31 Patrick M. McGrady, Jr., The Youth Doctors (New York: Coward-McCann, 1968), 15. 32 Ibid., 59-86. 33 Ibid., 167-177. 34 Ibid., 193-219. 35 Ibid., quote on 270-271. 36 Ibid., quote on 180. 37 Ibid., quote on 15. 38 Ibid., quote on 324. Dr. Denham Harman coined the term “Live, Longer, Better.” A researcher in the study of aging, Dr. Harman found himself on the fringes of gerontology when he began to champion a more proactive approach in his field. Harman is best known for his “free radical theory of aging.” He posited that aging was caused by reactions among free radicals (atoms and molecules containing unpaired electrons). Damage occurred when a free radical found another molecule and attempted to pair its unpaired electron, which then made the found molecule a free radical in search of another molecule, marking the beginning of a destructive chain reaction. Harman believed that antioxidants would protect against this damaging sequence because they could donate necessary electrons with no adverse effects. Harman published his theory in the Radiation Laboratory Report in 1955, and again in the Journal of Gerontology in 1956. However, it attracted little notice until the late 1960s, with the birth of the field of experimental gerontology, which focused on the processes of aging. Harmon’s Free Radical Theory became one of the foundational principles in experimental gerontology and anti-aging therapeutics. It was also eventually accepted by the field of gerontology. 39 Frank G. Slaughter, “The Youth Doctors,” New York Times (November 17, 1968), BR40. 40 Donald W. Goodwin, “Rejuvenation,” Journal of the American Medical Association 207 (February 3, 1969): 956. 41 Patrick M. McGrady, Jr., Commentary, Correspondence, Journal of the American Medical Association 209 (July 14, 1969): 272. 42 J. T. Freeman, “Drug Therapy in Aging Patients,” Geriatrics March 18, no. 3 (1963): 174-180. 43 Ana Aslan, “Novocain als Eutophischer Factor und die Moglichkeit einer Verlangerung der Lebensdauer” Therapeutische Umschau 9 (1956): 165-172; Ana Aslan, “Eine Neue Methode zur Prophylaxe und Behandlung des Alterns mit Novokain-Stoff H3, Eutrophische und Verjungende Wirkung” Therapiewoche 7 (1956): 1-2, 14-22; Ana Aslan, “La Novocaine H3 dans la Therapeutique de la Vieillesse” Revue Francaise de Gerontologie 4 (1958): 321-330. 44 Rona and Laurence Cherry, “Slowing the Clock of Age: But What if People Live to be 100 or More?” New York Times, (May 12, 1974), SM246. 45 McGrady, 183. 46 Catalog Record, “Novocain,” https://www.woodlibrarymuseum.org/museum/item/118/novocain. Accessed 2 December 2016. 47 Cherry, “Slowing the Clock of Age: But What if People Live to be 100 or More?”, SM246. 48 Gerovital was sold as “H3” in advertisements by supplement suppliers featured in publications, including Let’s Live Magazine, a monthly publication nationally distributed through health food shops and by paid mail subscriptions. See advertisements featured in Hearings before the Committee on Frauds and Misrepresentations Affecting the Elderly of the Special Committee on Aging, US Senate, Part 1: SF, CA January 13, 1964, 38-40. 49 Ruth Davis, “Non-Stop Youth,” Chicago Defender (October 27, 1973), 22. 50 Maxine Cheshire, “Senators Press Search for Eternal Seniority,” Chicago Tribune (December 19, 1972), B3. 51 D. Robinson, J. Davis, A. Nies, C. Ravaris, and D. Sylwester, “Relation of Sex and Aging to Monoamine Oxidase Activity of Human Brain, Plasma, and Platelets,” Archives of General Psychiatry 24 (1971): 536; M. David Macfarlane, “Possible Rationale for Procaine (Gerovital H3) Therapy in Geriatrics: Inhibition of Monoamine Oxidase,” Journal of the American Geriatrics Society 21 (1973): 414-418. 52 Sidney Cohen and Keith S. Ditman, “Gerovital H3 in the Treatment of the Depressed Aging Patient,” Psychosomatics 15 (1974): 15-19, quote on 15. 53 Cherry, “Slowing the Clock of Age: But What if People Live to be 100 or More?”, SM246. 54 G. Untea and G. Bercu, “Considérations sur l'influence exercée par le traitement avec Gérovital H3 (dragées) sur la capacité de travail des personnes actives ayant dépassé l'âge de 45 ans”, Giornale Di Gerontologia 17 (1969): 795-9 ; G. Untea, R. Voinea, and I. Pirvulescu, “Considerations regarding the usage of Gerovital-H 3 during andropause for disturbances of sexual dynamics”, Giornale Di Gerontologia 20 (1972): 62-9. 55 See Elizabeth Siegel Watkins, “The Medicalisation of Male Menopause in America,” Social History of Medicine 20 (2007): 369–388, and Elizabeth Siegel Watkins, “Medicine, Maculinity, and the Disappearance of Male Menopause in the 1950s,” Social History of Medicine 21 (2008): 329-344. 56 Adrian Ostfield, Cedric M Smith, and Bernard A. Stotsky, “The Systemic Use of Procaine in the Treatment of the Elderly: A Review,” Journal of the American Geriatrics Society 25 (January 1977): 1-20, quote on 1. 57 Joel Kurtzman and Philip Gordon, “Contents,” No More Dying: The Conquest of Aging and The Extension of Human Life (Los Angeles: J.P. Tarcher, Inc., 1976), n.p. 58 Meyer and Whittier, 1217-1218. 59 Saul Kent, The Life Extension Revolution: The Definitive Guide to Better Health, Longer Life, and Physical Immortality (New York: William Morrow and Company, 1980), 15. 60 Beverly Beyette, “Gerovital and the Las Vegas Connection: Tours run from the Southland,” Los Angeles Times, January 3, 1980, F1, F9-F12. 61 “Statement of Marvin Kratter, President and Chief Executive Officer of Rom-Amer Pharmaceuticals, LTD.,” in U. S. Senate Subcommittee on Health and Scientific Research, Committee on Labor and Human Resources. Senate; Committee on Labor and Human Resources, Hearings on Drug Regulation Reform Act of 1979 [Hearing Id - HRG-1979-LHR-0067]. May 17-18, 1979, 660-675, quote on 661. 62 Ibid., quote on 663. Although the life extenders were more concerned with the libertarian goal of self-ownership, Krattner’s testimony jibed with contemporary criticism of the FDA’s regulatory machinery for slowing down (and making more expensive) the translation of drugs from bench to bedside. This concern about a “drug lag” in the United States, as compared to Europe, eventually resulted in revisions to the drug patenting system in 1984, through the Drug Price Competition and Patent Term Restoration Act (also known as the Hatch-Waxman Act). (See Jeremy A. Greene and Scott H. Podolsky, “Reform, Regulation, and Pharmaceuticals – The Kefauver-Harris Amendments at 50” New England Journal of Medicine 367 (October 18, 2012): 1481-3. 63 Durk Pearson and Sandy Shaw, Life Extension: A Practical Scientific Approach (New York: Warner Books, 1983), 555. 64 Ibid. 65 Advertisement: “Nathan Pritikin, Director – Announces the Opening of the Longevity Center, Santa Monica, California,” Wall Street Journal, August 22, 1978, 16. 66 Marian Burros, “Getting to the Heart of the Matter: Nutritionist Nathan Pritikin’s Formula for Longer Life Comes up Short with the Medical Establishment,” Washington Post, June 7, 1979, Style section, E1 and E12. 67 Robert D. McFadden, “Nathan Pritikin, Whose Diet Many Used Against Heart Ills” New York Times (February 23, 1985). http://www.nytimes.com/1985/02/23/us/nathan-pritikin-whose-diet-many-used-against-heart-ills.html. Accessed October 10, 2017. 68 Saul Kent, The Life Extension Revolution, 81-82. 69 Jon Leonard, Jack L. Hofer and Nathan Pritikin, Live Longer Now: The First One Hundred Years of Your Life: The 2100 Program (New York: Grosset and Dunlap, 1974). 70 John D. McCarthy and Mayer N. Zald, “Resource Mobilization and Social Movements: A Partial Theory,” in John D. McCarthy and Mayer N. Zald (editors), Social Movements in an Organizational Society: Collected Essays (New Brunswick, NJ: Transaction Publishers, 1987), 20-21. 71 William Regelson and Carol Colman, The Super-Hormone Promise Nature’s Antidote to Aging (New York: Pocket Books, 1996), xiii. 72 James Lardner, Stretching the Limits of Life,” Washington Post, May 15, 1983, G1, G4, and G5. 73 Ellen Hume, “Science Taps Fountain of Aging Mystery: AGING: Scientists May Extend…” Los Angeles Times, July 27, 1982. The term “death hormone” was given to a hypothetical pituitary hormone believed to contribute to the loss of neurons. 74 Homer Bigart, “Group Advocates Freezing of Dead: Life Extension Society Sees Chance for Immortality,” New York Times, January 29, 1967, 58. 75 Saul Kent, Future Sex (New York: Warner Paperback Library, 1974). 76 Saul Kent, “Solving the Riddle of Lipofuscin's Origin May Uncover Clues to the Aging Process,” Geriatrics 31 (May 1976): 128-37. 77 Saul Kent, “The Biologic Aging Clock,” Geriatrics 37 (July 1982): 95-99. 78 Saul Kent, The Life Extension Revolution, sleeve. 79 Saul Kent, Anti-Aging News, August 1985, 5 (8): cover. Steven Almond, “They’re Gonna Live Forever,” Miami Times, June 8 1994. 80 “Cover” Anti-Aging News, 5 (August 1985). This newsletter’s scientific advisory board included W. Donner Denckla, M.D., of the National Institute of Alcohol Abuse and Alcoholism (and originator of the “death hormone” concept), Stanley Fink, Ph.D., Director of Biomedical Research at Orange Medical Instruments, and Ronald Klatz, D.O., of the Human Performance Center in Chicago. Klatz would go on to be one of the founders of American Academy of Anti-Aging Medicine (A4M). 81 Saul Kent, Life Extension Revolution, 13. 82 Durk Pearson and Sandy Shaw on The Mike Douglas Show, c. 1982, https://www.youtube.com/watch?v=5sSKLhTfcpQ&feature=youtu.be. Accessed on 6 September 2017. Durk Pearson on The Tomorrow Show, hosted by Tom Snyder, c.1979, https://www.youtube.com/watch?v=8U-Oxhb8SK4. Accessed on 6 September 2017. 83 People magazine reported that the book sold 275,000 copies in two months. Karen G. Jackovich, “Two Fitness Faddists Have a No. 1 Best-Seller, but Are They Stretching Life Spans or Truth?” People (4 October 1982), http://people.com/archive/two-fitness-faddists-have-a-no-1-best-seller-but-are-they-stretching-life-spans-or-truth-vol-18-no-14/. Accessed on 6 September 2017. According to the New York Times, Life Extension was the sixth-highest bestseller in hardcover general (non-fiction) in 1982. Edwin McDowell, “About Books and Authors: What Sold in 1982,” New York Times (2 January 1983), http://www.nytimes.com/1983/01/02/books/about-books-and-authors-what-sold-in-1982.html?pagewanted=all. Accessed on 6 September 2017. 84 Pearson and Shaw, Life Extension, A Practical Scientific Approach, 7 85 Ibid., xxiii. 86 Ibid., xv. 87 Ibid., 468-469. 88 Ibid., 771. 89 Ibid., 129, 229. 90 There was existing literature that documented increased growth hormone levels after administering L-dopa, bromcriptine, vasopressin, tryptophan, L-arginine, and L-ornithine. See Thomas J. Merimee, David Rabinowitz, Lamar Riggs, John A. Burgess, David L. Rimoin, and Victor A. McKusick, “Plasma Growth Hormone after Arginine Infusion — Clinical Experiences,” NEJM 276 (1967): 434-439; R. F. Knopf, J. W. Conn, S. S. Fajans, J. C. Floyd, E. M. Guntsche, and J. A. Rull, “Plasma growth hormone response to intravenous administration of amino acids,” The Journal of Clinical Endocrinology and Metabolism, 25 (1965): 1140-1144; D. Evain-Brion, M. Donnadie, M. Roger, and J. C. Job, “Simultaneous study of somatotrophic and corticotrophic pituitary secretions during ornithine infusion test, Clinical Endocrinology, 17 (1982): 119-122; A. E. Boyd, III., Harold E. Lebovitz, and John B. Pfeiffer, “Stimulation of Human-Growth-Hormone Secretion by L-Dopa,” NEJM 283 (1970): 1425-1429; Juan J. Gagliardino, John D. Bailey, Julio M. Martin, “Effect of Vasopressin on Serum-Levels of Human Growth Hormone,” Lancet 289 (1967): 1357-1358. And V. Meyer and E. Knobil, “Stimulation of Growth Hormone Secretion by Vasopressin in the Rhesus Monkey,” Endocrinology 79 (1966), 1016-8. 91 Examples of this literature include S. Hontela, N. P. Nair, G. Rosenberg, G. Schwartz, H. Guyda, “Bromocriptine: Effect on Serum Prolactin and Growth Hormone in Psychogeriatric Hospital Patients,” Journal of American Geriatrics Society 2 (1978): 49-52; E. E. Müller, F. Brambilla, F. Cavagnini, M. Peracchi and A. Panerai, * Slight Effect of l-Tryptophan on Growth Hormone Release in Normal Human Subjects,” Journal of Clinical Endocrinology and Metabolism 39 (1974): 1-5. 92 Barry M. Sherman, “Growth Hormone Use,” Science, 235, no. 4784 (1987): 14-15; William Regelson, “Growth Hormone Use,” Science, 235, no. 4784 (1987): 14-15. 93 Pearson and Shaw, The Life Extension Program (New York: Warner Books, 1984): 240. Both commercial cHGH products are listed as part of the MEDLARS search they created to show their readers how to use a computer search in requesting material from the National Library of Medicine. The other prolific life extension author at the time, Saul Kent, did not write about cHGH in his Geriatrics column, nor did he recommend its use when detailing the benefits of increased levels of growth hormone in his book, Your Personal Life-Extension. 94 The Chairman of the Subcommittee on Health and Long-Term Care of the Select Committee on Aging House of Representatives, Quackery A $10 Billion Scandal (Washington: US Government Printing Office, 1984), 94-95. 95 Daniel Duchaine, Underground Steroid Handbook II (Venice CA, HLR Technical Books, 1989), part 11. Duchaine discusses how growth hormone was featured in the first version of the handbook from 1982, which was extremely influential among bodybuilders. 96 Elliott Almond, Julie Cart, and Randy Harvey, “If Athletes Want to Cheat to Get to the Olympics… There’s a Doctor to Help,” Los Angeles Times, December 4, 1983, E1 and E18, E19. 97 Ibid., E18. 98 Sandra Blakeslee, “Supply of Growth Hormone Brings Hope for New Uses: Growth Hormone’s Promise Brings Fear of Abuse,” New York Times, February, 10, 1987, C1 and C11, quote on C11. 99 Daniel Rudman and Floyd Seidman, “Lipemia in the Rabbit Following Injection of Pituitary Extract,” Experimental Biology and Medicine 99, no. 1 (October 1958), 146-150. 100 Daniel Rudman, Samuel B. Chyatte, Joseph H. Patterson, Glynda G. Gerron, Irma O’Beirne, Joan Barlow, Peter Ahmann, Ashby Jorden, and Robert C. Mosteler, “Observations on the Responsiveness of Human Subjects to Human Growth Hormone: Effects of Endogenous Growth Hormone Deficiency and Myotonic Dystrophy,” The Journal of Clinical Investigation 50 no. 9 (1971), 1941-1949; D. Rudman, S. B. Chyatte, G. G. Gerron, I. O'Beirne, and J. Barlow, “Hyper-Responsiveness of Patients with Limb-Girdle Dystrophy to Human Growth Hormone,” The Journal of Clinical Endocrinology and Metabolism, 35, 2 (1972), 256-60; D. Rudman, S. B. Chyatte, J. H. Patterson, G. G. Gerron, I. O'Beirne, J. Barlow, A. Jordan, and J. S. Shavin, “Metabolic Effects of Human Growth Hormone and of Estrogens in Boys with Duchenne Muscular Dystrophy,” The Journal of Clinical Investigation 51, no. 5 (1972): 1118-24. 101 D. Rudman, M. H. Kutner, G. A. Fleming, R. C. Harris, E. E. Kennedy, R. A. Bethel, and J. H. Priest, “Effect of 10-Day Courses of Human Growth Hormone on Height of Short Children,” The Journal of Clinical Endocrinology and Metabolism 46, no. 1 (1978): 28-35; D. Rudman, M. H. Kutner, R. D. Blackston, R. D. Jansen, and J. H. Patterson, “Normal Variant Short Stature: Subclassification Based on Responses to Exogenous Human Growth Hormone,” The Journal of Clinical Endocrinology and Metabolism 49, no. 1 (1979): 92-9. 102 D. Rudman, T. Davis, J. H. Priest, J. H. Patterson, M. H. Kutner, S. B. Heymsfield, and R. A. Bethel, “Prevalence of Growth Hormone Deficiency in Children with Cleft Lip or Palate,” The Journal of Pediatrics 93, 3(1978): 378-82; D. Rudman, M. Goldsmith, M. Kutner, and D. Blackston, “Effect of Growth Hormone and Oxandrolone Singly and Together on Growth Rate in Girls with X Chromosome Abnormalities,” The Journal of Pediatrics 96, no. 1(1980): 132-5. 103 Daniel Rudman, Michael H. Kutner, C. Milford Rogers, Michael F. Lubin, G. Alexander Fleming, and Raymond P. Bain, “Impaired Growth Hormone Secretion in the Adult Population: Relation to Age and Adiposity,” Journal of Clinical Investigation 67 (May 1981): 1361-1369. 104 D. Rudman, M. H. Kutner, R. D. Blackston, R. A. Cushman, R. P. Bain, and J. H. Patterson, “Children with Normal-Variant Short Stature: Treatment with Human Growth Hormone for Six Months,” New England Journal of Medicine 305, no. 3 (1981): 123-31. 105 Arlene Weintraub, Selling the Fountain of Youth, (New York: Basic Books, 2010), 6. 106 Daniel Rudman, “Growth Hormone, Body Composition, and Aging,” Journal of the American Geriatrics Society 33, no. 11 (November 1985): 800-807. 107 Daniel Rudman, Axel G. Feller, Hoskote S. Nagraj, Gregory A. Gergans, Pardee Y. Lalitha,.et al., “Effects of Human Growth Hormone in Men over 60 Years Old,” NEJM 323, no. 1 (July 5, 1990), 1-6. 108 K.A. Fachelman, “Hormone May Restore Muscle in Elderly,” Science News 138, no. 2 (July 14, 1990), 23; Jerry E. Bishop, “Hormonal Treatments Show Benefits for Aging Men and Cancer Patients,” Wall Street Journal, July, 5, 1990, B3; Susan Okie, “Can Drug Help Restore Youth? Older Men Gain Muscle, Lose Fat in Study,” The Washington Post, July 5, 1990, A1; Min Wei Lee, “New Hope for Elderly: Growth Hormone Restores Strength,” Chicago Tribune, July 5 1990, D1; Natalie Angier, “Human Growth Hormone Reverses Effects of Aging,” New York Times, July 5 1990, A1. 109 “Dog ‘Spunky’ After It’s Frozen Test,” Los Angeles Times, March 31, 1987, 3; T. W. McGarry, “Revival of a ‘Frozen’ Dog – Some Cold New Disclosures,” Los Angeles Times, July 6, 1987, 3. 110 Louis Sahagun and Mark Arax, “Coronoer Says It Was Homicide by Drugs in Frozen Head Case,” Los Angeles Times (24 February 1988). Accessed on 6 September 2017 at http://articles.latimes.com/1988-02-24/news/mn-11787_1_saul-kent. 111 Steven Almond, “They’re Gonna Live Forever,” Miami New Times, June 8, 1994 http://www.miaminewtimes.com/news/theyre-gonna-live-forever-6363863. Accessed December 12, 2016. 112 Jane E. Brody, “Restoring Ebbing Hormones May Slow Aging: Researchers Hope…,” New York Times, July 18, 1995, C1. 113 American College of Physicians, “Guidelines for Counseling Postmenopausal Women about Preventive Hormone Therapy,” Annals of Internal Medicine 117 (1992): 1038-41. 114 Adam L. Hersh, Marcia L. Stefanick, and Randall S. Stafford, “National Use of Postmenopausal Hormone Therapy: Annual Trends and Response to Recent Evidence,” Journal of the American Medical Association 291 (7 January 2004): 47-53. 115 U. S. Food and Drug Administration, Testoderm TTS New Drug Application 20-791. Approval package (1997), A-11. Records of the Center for Drug Evaluation and Research, FDA. 116 For more on the Women’s Health Initiative, see Watkins, The Estrogen Elixir, chapter 14. 117 Alex Kuczynski, “Anti-Aging Potion or Poison?” New York Times, April 12, 1998, ST1-2, 2. 118 Examples include: Walter Pierpaoli, William Regelson, and Carol Colman, The Melatonin Miracle: Nature’s Age-Reversing, Disease Fighting, Sex-Enhancing Hormone (New York: Simon & Shuster, 1995); William Regelson and Carol Colman, The Superhormone Promise: Nature’s Antidote to Aging (New York: Simon & Schuster, 1996); Ronald Klatz and Carol Kahn, Grow Young with HGH: The Amazing Medically Proven Plan (New York: Harper Collins, 1997); Ronald Klatz and Bob Goldman, Stopping the Clock: Why Many of Us Will Live Past 100 – and Enjoy Every Minute (New Canaan, CT: Keats Pub, 1996). 119 Ronald Kotulak, “’Gravity Boot’ Cure Criticized,” Chicago Tribune, July 19, 1983, 11. 120 Magda Krance, “’Death in the Locker Room’: Bodybuilder leads anti-steroid crusade,” Chicago Tribune, August 23, 1984, D1. 121 Advertisement: “A Total Breakthrough in Training and Fitness and The Figures to Prove It,” New York Times, April 3, 1989, C7. 122 Ronald Klatz and Robert Goldman, “State of the Specialty Report: Anti-Aging Medicine at Twenty Years (2012): The History of the Modern Anti-Aging Medical Movement,” Encyclopedia of Clinical Anti-Aging Medicine & Regenerative Biomedical Technologies (Chicago: American Academy of Anti-Aging Medicine, 2012), 4-6. 123 Ronald Klatz and Carol Kahn, “Can We Grow Young?” The Washington Post, April 20, 1997, 114. 124 https://www.a4m.com/about-a4m-mmi.html. Accessed October 7, 2017. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

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