SIXTH SPECIAL AWARD 365 that the body could make dopa from tyrosine by oxidation, since dopa itself could not be found free or bound in tissue. Aaron and his collabo- rators solved the problem by proving that mammalian tyrosinase indeed did exist. It was a copper-containing enzyme that required traces of dopa to be activated. In nature the small amounts of dopa required are formed autocatalytically. Once started, the reaction forms new dopa as fast as it is used up in the series of reactions culminating in melanin. Probably dopa works by reducing the cupric ions of inactive tyrosinase, thereby converting it to the active enzyme. Having completed his military obligations, Aaron went to Western Reserve University where he hoped to learn isotope techniques in the Department of Biochemistry, headed by Dr. Harlan Wood. How well he succeeded is illustrated by the fact that he worked out the complete metab- olism of tyrosine in that year of 1948-1949. Faithful Marge, having spent two years at Johns Hopkins, enrolled at Western Reserve, and there earned her M.D. degree. So:•etime during that year, Aaron decided he really wanted to combine laboratory and clinical work. Accordingly, he went to the University of Michigan as an assistant professor of dermatology. Here he ran a research laboratory and completed three years of residency, enabling him to take his boards in dermatology. Not to be outdone, Marge finished medical school, a year of internship, and a year of residency in dermatology during these years. In 1952, Aaron and another brilliant young dermatologist, Dr. Thomas B. Fitzpatrick, with whom Aaron had worked at the Army Chemical Center, went to the University of Oregon--Dr. Fitzpatrick as professor, and Aaron as associate professor, of dermatology. At this university, Aaron and his collaborator, Dr. T. H. Lee, isolated the two melanocyte-stimulating hormones, now known as a-MSH and g-MSH, using hog pituitary glands as a source. These remarkable hormones cause the melanocytes of various animals to darken as a result of dispersion of their pigment granules through- out the cytoplasm. These substances were shown to be polypeptides. The complete structure of g-MSH was worked out by Dr. J. I. Harris at the University of Cambridge. About this time (1955), Aaron went to Yale University as Professor of Dermatology. He went to Cambridge for a short time, during which he and Dr. Harris worked out the detailed structure of a-MSH. During these years, there was controversy revolving around the MSH- activity of ACTH. Some scientists doubted the existence of MSH, at- tributing the ability of pituitary extracts to darken melanocytes to their content of ACTH. When the structures of a- and /•-MSH were known, the mystery was solved. A considerable portion of the peptide chains of the two forms of MSH was found to be duplicated in the peptide chain of

366 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS ACTH. Thus, pure ACTH has some MSH-like act}vity, although the converse is not true. Aaron isolated and determined the detailed structure of human ACTH and showed that it also had MSH-like activity. The relationship of MSH to human skin pigmentation was brought out in further experiments done in Aaron's laboratory. These studies showed that human skin could be darkened, both in vitro and in vivo, by contact with MSH. The next advance came in 1958, when Aaron and his collaborators at Yale reported the presence in the pineal glands of cattle of an agent that, in contrast to MSH, caused lightening of melanocytes. This substance was named melatonin. Aaron has shown that it occurs also in human pineal glands. He and other scientists working with him at Yale and at the Upjohn Company proved that melatonin was the relatively simple compound, N-acetyl-5-methoxytryptamine. Aaron's laboratory has found melatonin in the peripheral nerves of man, monkey and cow. He has suggested that it may play a role in the transmission of nerve impulses and in the patho- genesis of vitiligo and malignant melanomas. Aaron recently has published some interesting observations on the mech- anism of action of MSH. When this hormone is added to pigment cells, the melanin-containing granules clumped around the nucleus stream throughout the cytoplasm so that the cell becomes darkened. These granules also contain tyrosinase. When they are dispersed, the active surfaces containing tyrosinase are increased and the rate of melanin for- mation increases, leading to an increase in the actual amount of melanin present. The important speculation is that MSH probably accomplishes this without penetration into the cell. It may change the permeability of the cell wall, allowing ionic exchanges to be altered. This, in turn, may lead to a gel-sol change in the cytoplasm, with resulting dispersion of granules. It is easy to show, for example, that the granules of frog melan- ocytes disperse in solutions of low pH or low osmotic activity. Hence, for this hormone at least,the intact cell is required to demonstrate activity. Marge and Aaron Lerner have other interesting accomplishments. For instance, although Marge completed her residency and her boards in derma- tology, and works part time as Assistant Clinical Professor of Dermatology at Yale, the couple have four delightful children, ranging in age from 3 to 8 years. Marge has published several successt•l children's books dealing with medical subjects. I understand several more are in the offing, in- cluding one on pigmentation! Aaron enjoys making things with his hands and repairing his children's toys. The Cenco-Lerner laboratory jack is becoming standard equipment in most laboratories. Interesting varia- tions of this useful gadget, including a micro model and a power-operated one, are in the developmental stages. Truly this is a unique couple!