Extraction for treatment
Extracted growth hormone was used since the late 1950s until the late 1980s when its use was replaced by recombinant GH.
In the late 1950s, Maurice Raben purified enough GH from human pituitary glands to successfully treat a GH-deficient boy. A few endocrinologists began to help parents of severely GH-deficient children to make arrangements with local pathologists to collect human pituitary glands after removal at autopsy. Parents would then contract with a biochemist to purify enough growth hormone to treat their child. Few families could manage such a complicated undertaking.
In 1960, the National Pituitary Agency was formed as a branch of the U.S. National Institutes of Health. The purpose of this agency was to supervise the collection of human pituitary glands when autopsies were performed, arrange for large-scale extraction and purification of GH, and distribute it to a limited number of pediatric endocrinologists for treating GH-deficient children under research protocols. Canada, UK, Australia, New Zealand, France, Israel, and other countries establish similar government-sponsored agencies to collect pituitaries, purify GH, and distribute it for treatment of severely GH-deficient children.
Supplies of this "cadaver growth hormone" were limited, and only the most severely deficient children were treated. From 1963 to 1985 about 7,700 children in the U.S. and 27,000 children worldwide were given GH extracted from human pituitary glands to treat severe GH deficiency. Physicians trained in the relatively new specialty of pediatric endocrinology provided most of this care, but in the late 1960s there were only a hundred of these physicians in a few dozen of the largest university medical centers around the world.
In 1977, the NPA GH extraction and purification procedure was refined and improved.
A shortage of available cadaver GH worsened in the late 1970s as the autopsy rate in the U.S. declined, while the number of pediatric endocrinologists able to diagnose and treat GH deficiency increased. GH was "rationed." Often, treatment would be stopped when a child reached an arbitrary minimal height, such as 5ft. Children who were short for reasons other than severe GH deficiency were lied to and told that they would not benefit from treatment. Only those pediatric endocrinologists that remained at university medical centers with departments able to support a research program had access to NPA growth hormone.
In the late 1970s, a Swedish pharmaceutical company, Kabi, contracted with a number of hospitals in Europe to buy pituitary glands for the first commercial GH product, Crescormon. Although an additional source of GH was welcomed, Crescormon was greeted with ambivalence by pediatric endocrinologists in the United States. The first concern was that Kabi would begin to purchase pituitaries in the U.S., which would quickly undermine the NPA, which relied on a donation system like blood transfusion. The second offense was Kabi-Pharmacia's marketing campaign, which was directed at primary care physicians under the slogan, "Now, you determine the need," implying that the services of a specialist were not needed for growth hormone treatment anymore and that any short child might be a candidate for treatment. Although the Crescormon controversy in the U.S. is long forgotten, Kabi's pituitary purchase program continued to generate scandal in Europe as recently as 2000.
Recombinant human growth hormone (rHGH)
In 1981, the new American corporation Genentech, after collaboration with Kabi, developed and started trials of recombinant human growth hormone (rHGH) made by a new technology (recombinant DNA) in which human genes were inserted into bacteria so that they could produce unlimited amounts of the protein. Because this was new technology, approval was deferred as lengthy safety trials continued over the next four years.[28]
In 1985, four young adults in the U.S. having received NPA growth hormone in the 1960s developed CJD (Creutzfeldt–Jakob disease). The connection was recognized within a few months, and use of human pituitary GH rapidly ceased. Between 1985 and 2003, a total of 26 cases of CJD occurred in adults having received NPA GH before 1977 (out of 7700), comparable numbers of cases occurred around the world. By 2003 there had been no cases in people who received only GH purified by the improved 1977 methods.
Discontinuation of human cadaver growth hormone led to rapid Food and Drug Administration approval of Genentech's recombinant human growth hormone, which was introduced in 1985 as Protropin in the United States. Although this previously scarce commodity was suddenly available in "bucketfuls", the price of treatment (US$10,000–30,000 per year) was the highest at the time. Genentech justified it by the prolonged research and development investment, orphan drug status, and a pioneering post-marketing surveillance registry for tracking safety and effectiveness (National Cooperative Growth Study).
Within a few years, GH treatment had become more common and competitors entered the market. Eli Lilly
