Controlling Human Growth

The great Belgian anatomist Vesalius believed that the pituitary gland, a pea-sized protuberance located at the base of the brain, was an organ for the secretion of waste material. He could not have been more wrong. Though one of the smallest of man's hormone producers, the pituitary is the master gland. It exercises control or influence over virtually every biological function--including growth--by manufacturing substances that help control the other glands and organs. Thus an underactive pituitary in a child can arrest bodily development and produce a form of dwarfism. Last week a discovery was announced that could not only enable doctors to treat more cases of this disorder but also produce ways to deal with other illnesses and injuries.

Though no one as yet understands all the workings of the pituitary, Dr. Choh Hao Li, a Chinese-born biochemist and endocrinologist at the University of California, has come closer than anyone to unlocking its secrets. Li and his colleagues have isolated and purified eight of the pituitary's ten known hormones. Now Li has carried his research a major step forward with the laboratory synthesis of one of the most important of these chemical messengers, somatotropin, or human growth hormone (HGH).

Complex Chain. Other pituitary hormones are simpler substances by comparison, some consisting of 30 or 40 amino acids. Analysis showed HGH to be a far more complex molecule, a chain of 188 amino acids with two loops, one containing six subunits, the other 93. To reproduce the molecule, Li and his associates had first to determine the order of the acids in the chain and then reconstruct them from available ingredients. Finally they had to fold the chain and its loops into the precise size and three-dimensional shape of the natural hormone. Li's work was made even more difficult by the scarcity of natural HGH. All of the HGH presently available for either treatment or research must be obtained from the recently deceased. Thousands of cadavers were required to produce the thimbleful of hormone that Li used in his work at the university's Hormone Research Laboratory in San Francisco.

Li, who identified the structure of the HGH molecule in 1966, spent two years learning how to fold his synthetic substitute, two more constructing the chemical bridges between the loops. The result, a synthetic molecule that has about 10% of the growth-producing properties of the natural hormone, more than justifies his efforts. The hormone not only controls growth but also has a profound influence on important bodily functions, including the metabolism of sugar, fats and proteins, and the production of sex hormones. Chemical production of the compound on a large scale would guarantee a plentiful supply for research into the use of an anti-growth hormone for such purposes as countering cancer-cell multiplication and halting uncontrolled human growth.

Li's discovery could also have some immediate applications. Dwarfism and other forms of pituitary deficiency now affect hundreds of thousands in the U.S. alone. Doctors believe that more than 1,000 children a year could benefit from a ready supply of growth-producing hormones. Hormone shots, which can speed up growth by as much as five inches a year, now each require the output of a single pituitary gland. The demand far exceeds the supply of cadavers.

HGH could be a boon to nursing mothers. Twenty-two Mexican women who complained of insufficient milk secretion were given daily injections of HGH for a week. All of their babies recorded significant weight gains during the period --two-thirds of them doubled the weight gains made in a comparable period without HGH.

The next problem for scientists to solve is to convert Li's laboratory accomplishment into a production-line success. The most optimistic estimate is that it will take three years.

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