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Copyright 1995 April 10 Boston Globe Melatonin Bandwagon Gets Crowded Health Sense JUDY FOREMAN Judy Foreman is a member of the Globe staff Her E mail address, via Internet, is:[log in to unmask] To some, like neuroscientist Dr. Richard Wurtman, melatonin may be "the holy grail of sleep research" a natural hormone with a remarkable c apacity to induce sweet dreams without the drug hangover and other risks of most sleeping pills. To others, like psychobiologist Dr. Dan Oren of the National Institute of Mental Health, melatonin is a potentially "fantastic drug for jet lag" because it can reset the brain's biological clock for time warped travellers. To still others, like Virginia endocrinolo gist Dr. Michael Cohen, it is "nature's con traceptive," a hormone whose greatest promise may be as a component of a new birth control pill. Some even believe it may retard the growth of breast cancer cells, and, as an anti oxidant, may help retard aging.For more than 30 years now, scientists have been quietly probing the mysteries of melatonin, a hormone pumped out at night by the pineal gland tucked just below the brain, because of its uncanny ability to control the sleep wake cycle and keep the brain's biological clock in sync with the rhythms of sunrise and sunset. But a year ago, that quiet quest exploded into the national consciousness when Wurtman, a scientist at the Massachusetts Institute of Technology, published a study documenting that melatonin, given as an experimental drug in tiny doses, dramatically reduced the time it took volunteers to fall asleep, even at midday. Wurtman was besieged with hundreds of calls and letters from desperate insomniacs as soon as his paper appeared in the Pro ceedings of the National Academy of Sci ences. Along with MIT, he has applied for a "use patent" for melatonin and owns $7 million worth of stock in a Lexington based company, Interneuron Pharmaceutical, Inc., that owns the rights to develop the drug. As word spread of melatonin's other properties, especially its potential to reduce jet lag and help shift workers adapt to crazy schedules, other drug companies, among them Eli Lilly & Co. and Glaxo PLC, steppedup their explorations of melatonin products for insomnia or jetlag.Despite all the excitement, melatonin is hardly a new creation of modern biotechnology. In evolutionary terms, in fact, melatonin is an ancient hormone, one so closely tied to the onset of darkness that in animals, it appears to be a major way that animals know when to breed, says Dr. Steven Reppert, a neuroscientist at Massachusetts General Hospital who recently found the gene for human melatonin receptors in the brain."In winter, when days are short," says Reppert, "the duration of melatonin secretion is long, because the nights are long, whereas in summer, when days are long and nights are short, the dark period of melatonin secretion is shorter." "An animal 'knows' how long the melatonin is pumping and what the pattern was in previous days, so it can tell not only what time of year it is, but in which direction the seasons are changing," which lets sheep know, Reppert says, when to breed in winter so that lambs can be born in spring. Wurtman, director of clinical research at MIT, says scientists do not know whether melatonin plays any role in human reproduction, nor why its output decreases with age one reason older people sleep less well than younger ones.Nor do they know where in the brain melatonin acts to induce sleep, though they are increasingly sure it does just that.In his study of 20 healthy male volunteers last year, Wurtman showed to the surprise of other scientists that at almost any dose from 0.1 to 10 milligrams, those who took melatonin fell asleep in five or six minutes, while those on placebotook 15 minutes or longer, when melatonin was given at noon.In a still unpublished paper, Wurtman and his colleague, Dr. Irina Zhdanova, have now also shown that tiny doses (300 micrograms) in the evening induce sleep quickly and do not suppress dream sleep or cause "hangovers." Endocrinologist Cohen, scientific director at Applied Medical Research, Ltd. in Fairfax, Va., has been grving 75 milligrams of melatonin plus 0.5 milligrams of progestin, another hormone, daily to 1,600 Dutch women, not for sleep but as an estrogen free birth control pill.That combination works to prevent ovulation, says Cohen, who has received FDA permission to test the pill in American women.He is less sure, however, about its effects on sleep. When he asked the women to report changes in sleep patterns, "nothing happened," he says, perhaps because they took it at night and were sleepy anyway, or because they were not deficient in melatonin to begin with.Other researchers, among them Dr. Charles Czeisler, director of the laboratory for circadian and sleep disorders medicine at Brigham and Women's Hospital, are ready to test melatonin further.So far, Czeisler has "not yet administered a single pill" and insists it is too soon for people to self medicate with melatonin until clinical trials prove it is safe. But in July, Czeisler will begin studying melatonin as a sleeping pill for NASA astronauts, who often have severe sleep problems.