Editorial: Can The History of Modern Endocrinology Shape the Future of Obesity?

Obesity is perhaps the most common and costly health problem in modern societies (1, 2). It is also among the most difficult to treat, in part because obesity pathogenesis remains poorly understood. As the diagnosis of obesity is both visually apparent and stigmatizing in ways that other disorders are not, the media coverage devoted to this problem is unparalleled, and weight loss products and services have never been more popular or profitable. The dietary supplement industry alone generates billions annually, despite the absence of safety or efficacy data for its products, and several supplements advertised for obesity treatment were recently shown to contain drugs banned by the U.S. Food and Drug Administration (3). Even major food manufacturers, including Nestle and Unilever (which own Jenny Craig and Slimfast, respectively), have entered the weight loss industry such that multinational corporations that market highly processed, energy-dense, obesity-promoting foods also profit from obesity treatment—treatment that, for the most part, is ineffective and not backed by scientific evidence. Evidently, there is money to be made on both sides of the obesity problem. “If the history of the Endocrine Society tells us anything, it is that rational disease treatment must be based on a sound understanding of the underlying pathophysiological processes.” Of course, some obesity treatment programs operate with the highest of standards and offer an array of health benefits, but such programs are far outnumbered by those of more dubious value and intent. The situation resembles the medical practice landscape of a century ago, when limited insight into disease processes combined with the plight of those affected to create an insatiable demand for whatever therapies might be available. Despite being ineffective and sometimes dangerous, these therapies were often quite profitable, much like many of today's obesity treatments. The story of how the questionable practices of the early 1900s were supplanted by rigorous application of the scientific method, ultimately giving birth to modern endocrinology (4), contains a valuable lesson as we ponder the future of obesity treatment. This story begins with a practice that came to be known as “organotherapy,” in which patients were treated with extracts of various endocrine glands (4). This practice made its way from the fringe to the mainstream of the medical world in 1891, when George R. Murray successfully treated a myxedematous patient with an extract of sheep thyroid (5). Buoyed by this observation, organotherapy enjoyed considerable popularity for the next 3 decades and proved to be highly lucrative for its practitioners. Henry R. Harrower, MD (1883–1934), was a leading practitioner of organotherapy, and he eventually created The Harrower Laboratory in Glendale, California, which produced, marketed, and distributed organotherapy products on an industrial scale. He also authored a series of publications entitled, “Harrower's Monographs on the Internal Secretions” and, eventually compiled them into the books, “Practical Hormone Therapy” and “Practical Organotherapy—The Internal Secretions in General Practice.” These books offer an interesting window into the state of medical science in Harrower's day. They include confidently articulated theories to explain the purported benefits of various “pleuriglandular” extracts, advocated for conditions ranging from reproductive failure to epilepsy, nephritis, “mental deterioration,” and many others. Harrower particularly favored the theory that because dysfunction of any one endocrine gland can cause dysfunction of many others, “… organotherapy contemplates the giving of extracts of many glands” (6). Unfortunately, neither the safety nor the efficacy of these glandular extracts was subjected to systematic study, and, not surprisingly, medical academicians viewed organotherapy with disdain. Seeking greater legitimacy and acceptance, Harrower and his colleagues formed an organization known as The Association for the Study of Internal Secretions in 1916. Charles E. de M. Sajous, MD, LLD, ScD, served as the Association's first president and Harrower served as Managing Editor of Endocrinology for its first 2 issues, after which he resigned his post due to “other business activities” that Council found “incompatible with the purposes of the Association” (7). Harvey Cushing, an acknowledged giant of academic medicine, was invited to serve as the Association's third president. Cushing accepted, and he took full advantage of the opportunity afforded by his Presidential Address to lambaste the practice of organotherapy: “What is there to say of a pluriglandular complex except to acknowledge an abysmal ignorance?… Surely nothing will discredit the subject in which we have a common interest so effectively as pseudoscientific reports which find their way from the medical press into advertising leaflets, where, cleverly intermixed with abstracts from researchers of actual value the administration of pluriglandular compounds is promiscuously advocated for a multitude of symptoms, real and fictitious” (8). To ensure maximum visibility, Cushing arranged for this address to be published not in Endocrinology, the flagship journal of the fledgling Association, but rather in the much more widely read Journal of the American Medical Association. It seems a remarkable coincidence that Cushing's address was delivered in the same year that insulin was isolated from pancreatic extracts by Banting, Macleod, Collip, and Best (9), helping to usher in the modern era of endocrinology. The isolation of a specific hormone for therapeutic purposes marked a sea change that, along with the condemnation of Cushing and others, heralded the marginalization of organotherapy and its advocates. Eventually, The “Association for the Study of Internal Secretions” was renamed the “Endocrine Society,” thenceforth to be presided over by academic devotees of the scientific method. Thus, while the Endocrine Society was given birth by a wealthy and powerful physician who profited from nonscientific approaches to medical practice (4), it quickly evolved into an organization led by academics who championed rational treatment rooted in proven pathophysiological concepts of endocrinology. Which brings us back to today. The leadership of the Endocrine Society recently announced plans to make the problem of obesity a strategic priority for the years ahead. What form will this commitment take? Is there a role that the Endocrine Society is uniquely suited to play in confronting the obesity problem? In doing so, the Society will join perhaps a dozen other professional medical organizations with a similar mission of solving the obesity problem. While advocacy, public policy, and public health, along with the development of diagnostic criteria and treatment guidelines, are all common themes, few of these organizations are specifically dedicated to the study of the biological mechanisms necessary for the development of more rational and efficacious therapies. Propelled by recent technological advances, the goal of identifying neurocircuits that control feeding and energy balance is now being realized (10,–12). Such discoveries have the potential to inform our understanding not only of how pathological weight gain occurs but also how the biologically defended level of body fat stores becomes elevated in obese individuals (13). Until these and other fundamental questions are answered, the pothole-ridden landscape of diets, supplements, and other ineffective therapies that passes for today's obesity treatment—not so different from the practice of organotherapy a century ago—will continue. If the history of the Endocrine Society tells us anything, it is that rational disease treatment must be based on a sound understanding of the underlying pathophysiological processes. Solving complex medical problems through unfaltering and rigorous application of the scientific method has served us well since Cushing's historic Presidential Address. The Society would do well to uphold this tradition as it turns its attention to the obesity problem.