The Second Messenger

Dr. Earl Sutherland Jr. was hardly fazed when newsmen bearing rumors descended upon his home in Nashville, Tenn., last week. A professor of physiology at Nashville's Vanderbilt University, he remained calmer than the newsmen while a Swedish journalist in the group placed a transatlantic call to a colleague who was waiting outside the room at Stockholm's Royal Caroline Institute where the Nobel Prize Committee was voting. After a while, the Swede suddenly turned from the telephone and gave Sutherland the news: he had been awarded the Nobel Prize in Medicine and Physiology for his long study of hormones, the chemical substances that regulate virtually every body function.

The news was worth $90,000 in cash and invaluable prestige in his profession. But Sutherland, a physician turned researcher who is more at home in a trout stream than an ivory tower, received the tidings with candid nonchalance. He made unassuming remarks about the award being "terrific" and "an honor and a pleasure." Then he observed: "I've known that I've been under consideration for a long time. My friends were saying, 'Maybe this year or maybe next year.' "

Slow Worker. Little known in lay circles, Sutherland has for years been a recognized leader among his colleagues. They believe that his findings are basic to any understanding of body chemistry. Last year his experiments brought him the Lasker Award, the 22nd time since 1946 that this distinction has presaged a Nobel. Though he became interested in hormone studies 25 years ago, Sutherland considers almost everything he did before 1960 merely preparation for his recent research, which established the importance of his earlier findings. "I guess I'm just a slow worker," he says.

His first discovery, published in 1955, was the means by which the hormone adrenaline regulates the breakdown of carbohydrates stored in the liver. He learned that adrenaline works by activating the enzyme phosphorylase. a chemical catalyst that triggers the release of energy-producing glucose. This explains how the body produces additional energy under stress. Then, in 1958, Sutherland isolated a previously unknown chemical called cyclic adenosine 3'5'-monophosphate, or cyclic AMP, that functions in an intermediary role in many hormonal processes.

The discovery was significant. The newly identified substance proved to be a missing link in a long series of biological control mechanisms. Tests showed that hormones do not act directly on their target organs. Instead, they trigger the production of cyclic AMP, which in turn regulates body functions, increasing the rate at which some take place, slowing down the rate of others. "I like to call it a second messenger," said Sutherland of AMP. Subsequent research showed that his description is apt. Studies have established, for example, that when adrenaline output is increased by fear or anxiety, it is not the adrenaline itself that speeds up the heart; rather, the adrenaline activates cyclic AMP, which stimulates the heartbeat.

Cancer Key? Cyclic AMP also plays a role in the digestive and reproductive processes as well as in the brain's system of message transmission. More recent findings indicate that cyclic AMP may also be involved in the transmission of genetic information and in abnormal cell growth. When cyclic AMP is added to cancerous cells, it returns them to normal. Though Sutherland points out that further research is necessary before the clinical implications of this discovery can be evaluated, doctors have already found it tremendously valuable in diagnosing and treating obscure disorders of calcium metabolism, for example. Some of his colleagues believe that the chemical may hold the key to the cure of certain types of cancer.

Sutherland's work has provided a base for most of the research now being done on the body's endocrine system. But Sutherland, now 55, admits that the pace of his own research has slowed considerably since his breakthrough. "When I got to the bifocal stage," he said, "I decided to give up the 61-day week."

Sutherland does seem to work in a more relaxed manner than many other researchers. He gives much of the credit for his accomplishments to his research assistant, James Davis, who has been with him for 20 years, and to other members of his team. He also believes in getting away from the office whenever he can. "All my life I've insisted on taking a vacation," he said. "I feel you lose ground if you don't." Sutherland, who sometimes calls hormonal research his hobby, regrets that he will be unable to participate in another avocation when he goes to Stockholm in December to accept his prize. Just returned from a fishing trip when his Nobel was announced, he fears that it will probably be too cold by then to cast his line in Sweden.

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