Growth hormone — the cadaver-extracted hormone, the CJD tragedy, and the recombinant breakthrough
6 min read · Uplevel editorial
In 1985, a neurologist in California diagnosed a 20-year-old with a disease that typically strikes people in their sixties. The patient presented with dementia and involuntary movements — the progressive and devastating deterioration of Creutzfeldt-Jakob disease, a prion disorder with no treatment and no survival. But this patient was not in his sixties. He had received injections of human growth hormone as a child, for a growth deficiency, through a program that had been running for two decades. He was one of the first. He would not be the last.
The program stopped immediately. All cadaveric human growth hormone was withdrawn worldwide within weeks. Thousands of children who had received the treatment over the previous twenty-six years would have to wait to find out whether they had been infected.
To understand what happened, you have to go back to the beginning of the pituitary story.
Growth hormone was recognized as a distinct pituitary secretion through animal hypophysectomy experiments in the early twentieth century. Remove the pituitary from a young animal, and growth stops. Return pituitary extract, and growth resumes. The logic of what the anterior pituitary was doing — releasing chemical signals that directed growth throughout the body — was established in animal models by the 1920s and 1930s. The specific protein responsible, growth hormone itself, was isolated and partially characterized by the 1950s through the work of Choh Hao Li at the University of California, Berkeley, who spent decades working out the structure of pituitary peptides. By the mid-1950s, growth hormone was available for research use, at least in principle.
The problem was species specificity. Bovine growth hormone doesn't work in humans. Rat growth hormone doesn't work in humans. The GH receptor in primates is specific enough that only primate growth hormone activates it. This was not a problem for insulin, where the bovine and porcine sequences are close enough to human insulin that they functioned adequately for decades. It was an absolute barrier for growth hormone. The only source of GH that worked in humans was human pituitary glands.
Maurice Raben at Tufts Medical School treated the first growth-hormone-deficient child with human pituitary extract in 1958. The treatment worked. The child grew. The problem was supply: a single pituitary gland from a cadaver yielded enough growth hormone for approximately one week of treatment for one child, and treating a severely GH-deficient child for years required pituitary material from hundreds of donors. The mathematics of the situation forced an industrial solution.
The National Pituitary Agency in the United States, established in 1961 under the National Institutes of Health, organized the systematic collection of pituitary glands from autopsy programs across the country. Medical examiners, hospitals, and pathology departments became collection points. Glands were shipped to processing centers, pooled in large batches, extracted, and distributed to pediatric endocrinologists. Similar programs ran in the United Kingdom, France, Australia, and other countries with developed medical systems. At its peak, the American program was collecting and processing tens of thousands of pituitary glands annually. The children who received the treatment grew. Their parents were grateful. The program looked like a public health success story.
What no one knew in 1961, or in 1971, or in 1981, was that some fraction of the donor population was dying of sporadic Creutzfeldt-Jakob disease — a prion disease present in roughly one or two people per million in the general population, often undiagnosed at death because the symptoms could be attributed to other forms of dementia. The prion responsible — the misfolded protein that causes the disease — is extraordinarily resistant to conventional sterilization methods. It survives alcohol, formalin, autoclaving at standard settings, and the processing steps used to prepare the pituitary extracts. It cannot be inactivated by heat at the temperatures used in pharmaceutical processing. When one infected pituitary was pooled with hundreds of others, the prion contamination was distributed across the entire batch. Thousands of children received injections that contained, at levels too small to detect by any method available at the time, the prion that would eventually kill some of them.
The incubation period for prion diseases ranges from years to decades. The first cases emerged in the mid-1980s. Investigations confirmed the link. By 2024, more than 225 cases of CJD had been confirmed in recipients of cadaveric human GH in the United States and the United Kingdom combined, with additional cases in France, Australia, Brazil, New Zealand, and elsewhere. The disease presented in adults who had received the injections as children, often more than twenty years earlier. The incubation period for some cases extended past thirty years. The final number of cases from the cadaveric GH era will not be known for decades more.
The recombinant solution had been developing in parallel. The recombinant DNA revolution of the late 1970s made it theoretically possible to insert the human GH gene into bacteria, turn them into factories for producing the protein, and harvest the result — human-identical GH, biosynthetically produced without human tissue. Genentech began working on recombinant growth hormone in the early 1980s. The FDA approved Protropin — Genentech's recombinant GH product — in October 1985, the same year the cadaveric program was halted. Eli Lilly's Humatrope, using a slightly different recombinant formulation that more closely matched the natural human GH sequence, was approved in 1987. The transition was not coordinated in the way the phrase might imply — the approvals were the result of years of prior work, and the timing was partly coincidental — but the effect was the replacement of a contaminated and supply-limited product with an unlimited, safe, human-identical alternative.
The FDA-approved indications for recombinant GH are specific. In children: growth hormone deficiency, Turner syndrome, Prader-Willi syndrome, chronic kidney disease, children born small for gestational age who don't catch up, Noonan syndrome, and idiopathic short stature. In adults: growth hormone deficiency, wasting in HIV-associated disease, and short bowel syndrome. These are the approved contexts. They involve diagnosed deficiency or specific disease states, documented through IGF-1 testing, stimulation tests, and clinical criteria. They are not optimization contexts.
The off-label use of exogenous growth hormone for athletic performance enhancement and anti-aging began in the 1980s and expanded substantially in the 1990s and 2000s. The pharmacological logic was straightforward: GH promotes muscle protein synthesis, lipolysis, and tissue repair. Athletes took it to build more muscle and recover faster. Wealthy adults took it to pursue the aesthetic and vitality effects associated with higher GH levels. The popular press covered it extensively — Mark Cuban mentioned it publicly; various professional athletes were implicated in supply network investigations; the BALCO scandal implicated GH along with anabolic steroids. The World Anti-Doping Agency banned it for competition in 1989.
The side-effect profile at supraphysiological doses is real and dose-dependent. Fluid retention, carpal tunnel syndrome, joint and muscle pain, jaw and brow growth consistent with acromegalic changes, insulin resistance, and potential acceleration of pre-existing malignancy are among the concerns at doses above the physiological range. The cancer question is the most serious: GH is, broadly, a growth signal, and the relationship between elevated IGF-1 (the primary downstream mediator of GH action) and cancer risk has been studied extensively enough to establish that the relationship exists in some contexts, even if the causal direction and magnitude in physiological-range supplementation are not settled. These risks are meaningful at supraphysiological doses and are part of why the FDA-approved indications are narrow.
The peptide alternative represents a different philosophy, and it emerged partly in response to these concerns. If the goal is to support GH physiology — to address the real decline in slow-wave GH pulsatility that occurs with aging and poor sleep — then the question is whether that can be accomplished without administering exogenous GH. Two peptide families do this by working through the upstream regulatory signal.
GHRH analogs — sermorelin, tesamorelin, and the longer-acting CJC-1295 — mimic the hypothalamic GHRH signal, prompting the pituitary to release its own growth hormone in pulses while leaving the somatostatin feedback loop intact, and ghrelin mimetics like the GHRPs, ipamorelin, and MK-677 reach the same pituitary cells through a separate receptor. What unites them is a philosophy: rather than supplying GH from outside and overriding the body's own regulation, they work upstream through signaling the body already uses. Whether any of them fits a given person is a question for a prescribing provider working from actual lab values rather than a catalog — but the cadaver era and its recombinant rescue are what make the appeal of that more measured, upstream approach legible.
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