ACTH Dissected

One of the prime puzzles of chemistry is that biological dynamite, ACTH (adrenocorticotropic hormone). Secreted in microscopic quantities by the pituitary gland at the base of the brain, it acts as a concertmaster, controlling by subtle hints of its chemical baton the equally subtle operations of the adrenal cortex. The cortex, properly stimulated, secretes hormones that control many activities of the body, including growth and reproduction.

ACTH, expensively extracted from the pituitary glands of cattle, also helps many a disease, such as arthritis, but the magic compound, unfortunately, is anything but simple. It is a polypeptide, a large molecule (molecular weight 4,500) made up of many amino-acid units arranged in a long chain. Chemists have puzzled over its structure for years, but have learned only bits and scraps about it. Polypeptides (related to proteins) are baffling things to deal with.

Last week the University of California announced that a team led by China-born Dr. C. H. Li has determined the complete molecular structure of ACTH. It turns out to be a straight chain of 39 amino acids arranged in a definite order. After satisfying themselves about the position of each link in the chain, Dr. Li and his teammates broke the chain in two, separating 28 of the links from the remaining eleven. The larger section proved to have all the desirable biological effects of the whole natural molecule. Better still, it lacks certain bad side effects.

An exciting possibility is that the chain can be broken into even smaller sections and that one of them will do the wondrous job of natural ACTH. Other fragments may have other desirable medical effects, and the fragments may be small enough to be synthesized cheaply.

None of this is likely to happen for a considerable time. Work with ACTH is slow, difficult and expensive because of the scarcity of the material. Financed by the U.S. Public Health Service, Eli Lilly Laboratories and the Lasker Foundation, Dr. Li's project took five years, cost $250,000 and consumed the pituitary glands of 360,000 sheep. Many more sheep will have to be dissected before a simplified form of ACTH becomes a standard item on the druggists' shelves.

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