The New York Times, by Natalie Angier

By Natalie Angier

A FLIMFLAM ad writer could not have invented more outrageous claims. Here is a diet that extends lifespan by 50 percent or more. It prevents heart disease, diabetes and kidney failure, and it greatly retards all types of cancer. It eliminates or forestalls many of the usual banes of aging, including cataracts, gray hair and feebleness. Adherence to the diet keeps the mind supple and the body spry to an almost biblical old age.

On a microscopic level, the diet protects the genes against environmental insults, keeps important enzymes operating at peak efficiency and cuts back on dangerous metabolic byproducts in the body. And, oh yes, the dieter stays slim. Very, very slim. These claims are not mere snake-oil phantasms, but the results of astonishing studies that lately have captured broad attention among scientists in the fields of aging, toxicology, oncology and other disciplines.

In laboratory experiments, investigators have discovered that animals raised on a meal plan containing all the necessary vitamins and other nutrients, but only 60 to 65 percent of the calories of the animal's normal diet, will live significantly longer than expected.

By nearly all measures, from the health of the creature's organs and the robustness of its immune system to the lustrous appearance of its fur, the animal on the restricted diet maintains the vigor of youth long after the well-fed control animals in the experiment have become weak, sluggish and grizzled, indeed, long after the controls have died.

Laboratory mice fed the restricted diet, for example, have lived to 55 months. The average life span of lab mice eating a normal diet, in which they consume as much as they want to, just as most laboratory rodents do, is about 36 months.

''The outcome of caloric restriction is spectacular,'' said Richard Weindruch, a gerontologist at the National Institute on Aging in Bethesda, Md. ''Gerontologists have tried many things to extend life span, but this is the only one that consistently works in the lab.''

Much to their surprise, researchers have found that it does not matter whether the sharply restricted diet is composed largely of fat or of carbohydrates. As long as the animal receives a minimum amount of protein and enough vitamins and minerals to prevent malnutrition, the creature survives to the same venerable old age.

But researchers warn against people undertaking an ascetic regimen too hastily. They stress that experimental animals are fed carefully measured and planned menus that are difficult to translate into human fare, and that it is easy to become malnourished.

''At this point, I definitely would not recommend a calorie-restricted diet for people,'' said Dr. Angelo Turturro, a biologist at the National Center for Toxicological Research, in Jefferson, Ark., a division of the Food and Drug Administration that is studying caloric reduction. ''There are still too many unknowns about its physiological effects that we have to sort out.''

Nevertheless, gerontologists are excited about the insights they will glean by studying caloric restriction. Initial observations that an extremely low-calorie diet extends life span in animals date back to the 1930's, but they were long shrugged off as mere laboratory curiosities. Only now is the study of dietary restriction receiving wide attention and extensive financial support.

''It's been a sleeping giant,'' said Dr. Weindruch. ''But the giant has awoken.''

As a measure of the new enthusiasm surrounding the field, the National Institute on Aging will spend about $3 million this year on studies related to the effects of calorie restriction on longevity, compared with less than $1 million for 1987. A report on the ability of a low-calorie diet to suppress the growth of breast tumors in lab mice is the lead article in this month's issue of The Proceedings of the National Academy of Sciences, a prominent science journal.

And 400 researchers from around the country and abroad flocked to a recent meeting held in Washington on the physiological consequences of dietary restriction. ''Six years ago you would have had 10 people show up,'' said Dr. Roy L. Walford, a professor of pathology at the University of California at Los Angeles School of Medicine and one of the pioneers in the field.

Primates to Be Tested

Thus far researchers have studied only rats, mice and species even lower on the phylogenetic scale, including fish, spiders, worms, water fleas and protozoa. All creatures fed a restricted diet have had greatly extended life spans.

Studies are now under way to examine the effects of a low-calorie menu on two species of primates, squirrel monkeys and rhesus monkeys, which scientists hope will be applicable to another sort of primate, human beings. The projects were begun within the last three years, and results are too preliminary to draw any firm conclusions. But scientists say that they will not have to wait for the monkeys' deaths - even with a normal diet, a rhesus monkey lives about 35 years - before they will begin to see the impact of caloric restriction on primate health.

Most researchers suspect that the monkeys will reap in years what they are losing in calories, and that, by analogy, reduced food intake probably would prolong the life span of humans as well. ''One argument in its favor is that so far dietary restriction has worked in lower animals across the board,'' said George S. Roth, a molecular geneticist at the National Institute on Aging who heads one of the primate trials. ''If it works in that direction evolutionarily, we should be able to extrapolate out in the other direction, to humans, equally well.''

But Dr. Roth offers an alternative explanation of how caloric restriction might work for lower species but be less effective for animals already endowed with relatively long lives. By this theory, short-lived species such as insects and rodents could possess a built-in mechanism that allows them to withstand a couple of famine years and still survive long enough to reproduce.

But longer-lived species, such as primates, are fertile for so many years that they may not need to have a life-prolonging mechanism set in motion when confronted by a couple of lean years. To resolve the issue, said Dr. Roth, ''we really have to wait and see what we get from the monkeys.''

The most zealous researchers contend that people need not wait for any more data before considering a curtailed diet. Dr. Walford said he believed that humans could live to an extraordinarily advanced age if they were to limit their caloric intake.

The Earlier the Better

''Right now, the maximum human life span is about 110 years, and only a few people live to that age,'' he said. ''But if what is true for other species is true for man, then with a sufficiently vigorous caloric restriction, the maximum life span could be extended to about 170.''

Basing his theory on animal studies, Dr. Walford said he thought that caloric restriction would have a salubrious effect regardless of how old the new dieter was, although he said the earlier the better.

''This may be too broad a statement, but caloric restriction will halve the rate of aging at whatever time you begin,'' he predicted. ''If you start at 50, and you were genetically set to die at 80, then you might live another 60 years rather than 30.''

Dr. Walford himself, who is 65, has been on a low-calorie diet for about five years. He eats between 1,500 and 2,000 calories a day, compared with an average daily intake for men of about 2,500 calories (for women the figure is about 2,100). The bulk of his calories come from vegetables, grains and other foods considered healthy by most nutritionists.

Some of Dr. Walford's colleagues, however, think he may be going too far. ''I wouldn't do what Roy is doing,'' said Dr. Turturro. ''He seems pretty healthy, but he chooses his clothes to conceal his boniness.''

Scientists in the caloric-restriction business have mapped out many of the effects of diet on animals, mostly mice and rats. They have found that animals on a normal diet often die of kidney disease or destruction of heart muscle tissue. Those that survive a bit longer fall prey to tumors, and all die by the age of 32 months.

Rats fed a tightly restricted diet almost never contract kidney or heart disease, and though they, too, develop cancer, they do so at a much later age. They live to almost 50 months, and sometimes die of no discernible cause. ''When we look inside them, they're completely clean,'' said Dr. Edward Masoro, a physiologist at the University of Texas Health Science Center in San Antonio who is considered another leading figure in the field.

Immune Systems Remain Vigilant

Whereas free-eating rodents that had white coats as youths often turn gray and oily by two years of age, the restricted-diet rats keep their shiny white fur, sometimes for more than 40 months.

Rats on restricted diets are able to run mazes more successfully than the well-fed rats at comparable ages. They suffer far less diabetes and cataracts, and their immune system remains vigilant well into old age.

Even when they are exposed to serious carcinogens, diet-controlled animals often fail to develop tumors. And rodent strains that are specially bred to be prone to cancer, hemolytic anemia or autoimmune diseases gain some protection against such disorders if they are assigned a low-calorie diet. ''Any kind of screwed up animal seems to benefit'' from caloric restriction, said Dr. Weindruch.

Researchers have now turned their attention to the puzzle of how dietary restriction works its apparent magic. Dr. Masoro and his colleague in the physiology department, Dr. Byung Pal Yu, are examining the metabolic machinery of the calorie-restricted rats compared with that of animals allowed to feed at will.

Dr. Masoro has focused on the role of blood glucose levels in health and longevity. All animals rely on glucose, which is metabolized from carbohydrates in the food, as a primary source of fuel for the body's tissues. Dr. Masoro has found that animals fed a restricted diet burn as much glucose per gram of tissue as do the plumper control animals. However, the restricted rats have a significantly lower concentration of glucose circulating in their bloodstream than do the controls.

Dr. Masoro believes that the result of a lowered blood glucose level is globally beneficial to the body. He points out that free-floating glucose can promiscuously interact with many important enzymes and proteins in the body, distorting their shape and function. Dr. Yu has examined the contribution of oxygen to the aging process. As a byproduct, food metabolism creates so-called free radicals, highly reactive oxygen molecules that combine with and can damage many parts of the body, particularly the slippery, fat-studded membranes that surround cells.

A Theory on Temperature

Dr. Yu has discovered far less oxygen damage to cell membranes in food-restricted animals than in the controls. He and other researchers also have found that a liver enzyme designed to detoxify free radicals is 50 to 70 percent more active in the dieting animals than in the controls.

Some scientists have detected evidence that in calorie-restricted animals, the enzymes that repair damaged DNA are more robust than in the free-eaters. They say that because mutations in DNA, the cell's information molecule, can lead to cancer, the ability to promptly fix DNA mishaps could explain the delay in tumor growth among dieting animals.

Other researchers believe that dietary restriction works by slightly lowering the body's temperature. ''The whole system in a food-restricted animal cools down,'' said Dr. Turturro. ''And as the fires of metabolism die down, the amount of damage from metabolism is decreased.''

Researchers admit that their understanding of how diet affects lifespan remains embryonic, and a subject of much dispute. ''There are as many theories of aging as there are gerontologists,'' said Dr. Weindruch.

By Natalie Angier

The question of how a single fertilized egg blossoms into a complete human infant is one of the magnificent puzzles of biology, and scientists are just beginning to pinpoint the key genes and molecules that direct the intricate unfolding. But in a rush of new experiments, researchers have made the surprising discovery that one of those crucial impresario molecules of life is not some exotic or arcane compound, but retinoic acid, a familiar derivative of vitamin A. Retinoic acid lately has won fame as the active ingredient in Retin-A cream, a treatment for acne and, more debatedly, the feathery wrinkles of age. The molecule also made news as the main component of Accutane, a more potent anti-acne drug that can cause extremely serious birth defects if women use it during pregnancy. 

Now biologists are finding that retinoic acid plays a pivotal role in normal development as well. In a recent flurry of papers published in Nature, Cell, Development and other scientific journals, they report that retinoic acid helps determine the shape and pattern of a broad array of the body's organs, including parts of the brain and spinal column, the face, the limbs, the heart, the skeleton, and the skin.

The results come largely from studies of chicks and mice, but researchers believe that they are likely to apply to human development as well. ''It's a good bet that this is one of the body's master molecules,'' said Gregor Eichele, a cellular physiologist at Harvard Medical School and a leading researcher in retinoic acid.

The molecule appears to work by flicking on whole groups of genes during key moments of development. Those genes are thought to then stir up other batches of dormant genes, thereby setting off a cascade effect that has the collective might to sculpt an undifferentiated blob of cells into a defined organ.

The apparent importance of retinoic acid to the growing embryo has impressed and surprised many researchers. Lorraine Gudas, a developmental biologist also at Harvard Medical School, said: ''I think this is going to be one of the most exciting molecules in respect to embryogenesis that exists. It's a master regulator that can send a very loud signal at critical points throughout development.''

Dr. Gudas and other investigators also believe that retinoic acid remains important in cell control throughout life, particularly in orchestrating the growth and health of epithelial tissue, which makes up the bulk of the skin, breast and the lining of the lungs, intestines and other organs. They hope that by understanding the mechanisms of retinoic acid, they will better comprehend why certain cells go awry, proliferating into tumors, for example, or simply shutting down and dying.

''I think a lot of this new basic science research into retinoic acid will be of real value to the clinical treatment of cancer,'' said Dr. Gudas.

Already the revelations about retinoic acid help explain why drugs such as Accutane produce the harrowing constellation of birth defects that physicians have observed. Since 1984, Dr. Edward Lammer of the California Birth Defects Monitoring Program in Emeryville has studied almost 90 cases of malformations believed to have been caused by Accutane. He has seen children with misformed hindbrains, or clusters of brain cells in parts of the brain where they do not belong.

Some Don't Survive

Other children are missing the bones of the middle ear or the entire ear canal altogether. Some young patients have hearts in which the two major arteries never separated. Others lack a functioning thymus, the gland where many white blood cells mature, and so they suffer from immune deficiencies. Some of the children do not survive.

Dr. Lammer notes that nearly all the defects occur in those organs believed to be controlled by the body's own stores of retinoic acid during early stages of embryogenesis, usually within the first month or two of pregnancy. He and other researchers suggest that the extra dose of retinoic acid from the acne drug, which the women took before realizing they were pregnant, probably disrupted the exquisite biochemical precision necessary for normal growth.

The basic research and the clinical observations ''all fit together like a nice neat glove,'' said Dr. Lammer. ''Too neatly, unfortunately.'' For biologists, the severity and the pattern of the birth defects provides striking evidence that retinoic acid modulates development in a profound and specific manner.

All vertebrate animals need vitamin A to survive. They get much of it by eating sources of beta carotene, the compound that makes carrots orange, spinach green and lobsters brownish-red. Beta carotene is then metabolized in the body into vitamin A and its derivatives, including retinoic acid. Fetuses obtain their vitamin A from the mother, although they probably transform it into retinoic acid within their own tissue.

Scientists were inspired to explore the role of retinoic acid in organ formation because, among other reasons, studies showed that excess vitamin A caused birth defects in laboratory animals. In other provocative experiments, biologists found that when they swabbed retinoic acid onto cultured cancer cells, the cells stopped dividing wildly and took on the features of more normal cells.

In an effort to begin pulling apart the exact mechanism of retinoic acid, biologists examined its impact on limb development. They demonstrated that if they applied beads soaked in the molecule to particular spots in the growing limb buds of chick and mouse fetuses, the animals developed distinctively defective limbs: twin wings or twin paws extending from a single limb, the two appendages facing one in another in a bizarre mirror image.

Effects Becoming Clear

The results indicated that retinoic acid works as a morphogen, a molecule that helps cells to migrate and form patterns characteristic of mature organs. Researchers believe that, under normal circumstances, the earliest cells of the limb bud release a specific amount of retinoic acid. The signal that dictates the release is not yet known, but the effects of the release are becoming clear. As retinoic acid seeps across the limb bud, different cells receive different concentrations of the molecule. The amount of retinoic acid that reaches a given cell in part dictates its fate.

In the case of the growing mouse paw, for example, cells exposed to higher amounts of the molecule migrate outward to form the equivalent of the pinky, while those receiving smaller doses become the equivalent of thumb cells.

In 1987, Ronald Evans of the Salk Institute in La Jolla, Calif., and Pierre Chambon of the Institute of Biochemistry in Strasbourg, France, isolated the retinoic acid receptor, a protein inside the cell that links up to the vitamin derivative and allows cells to respond to the vitamin derivative. Since then, two related retinoic acid receptors have been identified, and researchers believe there may be others. Importantly, the receptors are equipped with a telltale looping appendage at one end, called a zinc finger, which scientists think allows the proteins to clasp onto DNA, where the cell's genetic information is stored, and ignite a burst of gene activity.

''The receptor is what takes something with a simple structure, like retinoic acid, and translates that into a complicated signal,'' said Dr. Evans. ''The receptor turns on the stereo system.''

Many details of the retinoic acid pathway remain to be fleshed out, but scientists think that the vitamin derivative operates by entering a cell and somehow arousing one or more of its designated receptors. The receptors then glide over the cell's DNA molecule and flick on a battery of genes. The timing and amount of the retinoic acid that infiltrates the cell seem to help determine which genes become activated. Again in the case of the growing mouse paw, those cells in the limb bud that receive a lot of the molecule at just the right time have their genes tweaked to become pinky cells, while the cells that are doused at a later time by less retinoic acid are genetically inspired to form a thumb, although additional signals surely contribute to the process.

With the retinoic acid receptors isolated, biologists have been screening embryonic tissue to see what other budding organs might employ retinoic acid as their sculptor. From studying activation patterns of the retinoic acid receptors, researchers suspect that the molecule works first on cells destined to become part of the spinal column. Soon afterward, it influences the construction of the hindbrain, face, ears and jaw. Later the vitamin is involved in the dispatch of cells to the heart, liver, circulatory system and cartilage.

Scientists are also fitting together retinoic acid with other molecules thought to be master orchestrators of development, including proteins known as growth factors and a class of genes called homeobox genes. ''The field is still in an embryonic stage, but all our findings are starting to converge,'' said David L. Stocum, a developmental biologist at Indiana University-Purdue University at Indianapolis. ''I expect that in the next two or three years we'll make a lot of headway in understanding just what gives a cell its knowledge of what it's supposed to be.''

By Natalie Angier

WHAT do females want? Every man who has ever rolled his eyes heavenward in apparent bafflement at this great enigma might do well to follow the example of evolutionary biologists: stop speculating and start paying attention to the evidence at hand.

In laboratories and field research stations across the United States and abroad, biologists are analyzing an evolutionary force that has long been neglected: the effect of female choice on the appearance and performance of males.

The new results indicate that many of the mysterious and seemingly irrelevant courtship rituals and male displays in the animal kingdom serve a crucial purpose of allowing a female to judge the robustness or health of her potential mate before committing herself to the union.

Biologists have suspected for years that certain flamboyant features among males, like the peacock's Technicolor tail and the bullfrog's booming moonlight sonatas, evolved for no other purpose than to allow males to curry favor with females. But many researchers dismissed the role of female choice as a minor influence in evolution of animal traits compared with the ability to elude predators or defend territory, or with war-like competition among males for access to mates.

Now the female animal is finally coming into her own in the biological arena. Galvanized by new research tools and more sophisticated evolutionary theories, biologists are designing experiments to measure precisely the features that entice females to mate with one male rather than another.

Through elaborate statistical analyses and, in some cases, laboratory manipulations, biologists who study courtship in animals are replacing what Harvard biologist Stephen Jay Gould has called ''Just So stories'' - the old Aesop animal fables - with rigorous data.

''We're trying to do experimental work where we manipulate characteristics, to see how changing these traits changes what the female does,'' said Marlene Zuk, a biologist at the University of California at Riverside. ''In that way we can begin teasing apart what a female is actually choosing, not just what we think makes good sense for her to be choosing.''

The latest findings, published in recent issues of Nature and presented at several international meetings, suggest that females of many species pay particularly close attention to telltale signs of parasitism or disease. As a result, the males often sport skin colorations or feather patterns to signal robust health, which then become accentuated or exaggerated over generations of selection by females.

Some female birds and frogs demand of their suitors in courtship a performance that pushes the males to their cardiovascular limits, perhaps as a test of the hardiness of the males' genes.

In other species, especially insects, a female will refuse a male's sexual overtures unless he offers her some sort of nuptial gift, usually a defensive chemical that she can use to protect herself or her eggs.

The long-term consequences of female choice affect the characteristics of females as well as of their mates, scientists say; daughters presumably inherit from their mothers a predisposition to favor certain masculine traits over others.

Finding Subtle Dynamics

Biologists emphasize that they are just beginning to understand the complex dynamics of female choice, and that the whys and wherefores of female taste remain elusive for the great majority of species. ''Female choice is more subtle than something like male-male competition, because it affects not only the evolution of the male, but of female preference,'' said Dr. Mark Kirkpatrick, a zoologist at the University of Texas in Austin. Nevertheless, he added, ''it's definitely the wave of the future in biology.'' Theory Slighted for a Century Charles Darwin proposed in 1872 that female animals could exert pressure on the evolution of their species in their mating decisions, but the theory was largely slighted for almost a century. It began its comeback in the mid-1970's, when biologists turned away from studies of amorphous group behavior among animals and instead focused on the actions and reproductive strategies of individuals in a species.

Fleshing out the ideas of Darwin and other pioneering naturalists, animal behaviorists proposed that females usually have a larger stake in reproduction than males do. The stake is especially high in female mammals that bear their young and then care for the offspring after birth. But even for insects and fish, which invest far less time in rearing young, the amount of energy needed to produce the nutrients, fat and protein of an egg is greater than that required for generating sperm.

''Eggs are expensive,'' said Dr. Thomas Eisner, an evolutionary biologist at Cornell University. ''Sperm is cheap.''

Given their greater investment in reproduction, say biologists, females have greater incentive than males to seek the best possible mate. Males that want to pass their legacy to future generations must either appeal to females, or suffer a genetic dead end.

Perhaps the most straightforward work on the fine points of female finickiness has come in species where the female seeks material help from the male in the rearing or protection of the young.

Role of One Chemical for Beetles

In ongoing investigations of the courtship behavior of a beetle species called Pyrochroidae, Dr. Eisner, Dr. Jerrold Meinwald and their colleagues have determined why the male beetle goes through the peculiar ritual of displaying to a potential mate a deep cleft in his forehead. The researchers have found that stashed within the cleft is a small dose of the chemical cantharidin, familiarly known as Spanish fly.

The source of the male beetle's cantharidin is still mysterious, though Dr. Eisner suspects that it comes from eating the eggs of another insect, the blister beetle. During courtship, the male exposes his cleft to the female, she grabs his head and immediately laps up the chemical offering. Apparently placated, she allows the male to mate.

The Cornell scientists have determined that the male transfers to the female a much larger quantity of cantharidin during intercourse, and that she subsequently incorporates the chemical into her eggs, which thenceforth are protected against ants and other common predators of beetle eggs.

''The male gives her a little teaser during foreplay,'' said Dr. Eisner. ''It's as though he's showing her a fat wallet and saying, 'There's more in the bank where that came from.' ''

To prove the central importance of cantharidin, the scientists raised male beetles in the lab, where they had no access to the chemical. True to the theory, the cantharidin-free males failed dismally at mating. ''Ninety percent of the males with cantharidin eventually manage to mate, but less than 20 percent of the cantharidin-free males succeed,'' said Dr. Eisner. ''Only the ones that literally rape-mount the female get anywhere at all.''Choosing From Appearance Less obvious than a nuptial gift is what a female seeks when she chooses on the basis of a male's appearance. In an experiment described in a recent issue of Nature, scientists from the University of Bern in Switzerland examined the impact of a male's coloration on female choice among the three-spined stickleback, a small fish.

The researchers knew that in breeding season, the male stickleback turns a bright red and upon changing color, it displays itself before a female in a mating dance of zigs and zags. The biologists also knew that males exposed to parasites turned a dimmer shade of red, even afer shaking off the parasitic disease. Their question: Did females prefer males that possessed the bright red color signaling current and prior health?

To address the problem, they tested female responsiveness to groups of brilliant red males and dimmer, previously parasitized males under natural white light, in which the females could see the intensity of the red color, and under green light, which disguised the relative tones.

The scientists found that when females could distinguish red males from their drearier counterparts, the females almost uniformly paired up with the brighter males, although both groups of suitors performed the zigzag courtship dance with equal zest.

By comparison, females choosing males beneath a green light arbitrarily picked males of either color.

Dr. Zuk believes that female birds also are preoccupied with parasites. In experiments with red jungle fowl, the ancestors of barnyard chickens, she and Dr. Randy Thornhill and Dr. David Ligon, biologists at the University of New Mexico in Albuquerque, identified the specific ornaments that most attracted a hen to a rooster. The biologists found that hens paid closer attention to the condition of the male's comb and wattle than to any other characteristic, including size, weight, the aggressiveness of his strutting, or the state of his feathers.

Stamina Also a Factor

The longer the comb and the brighter the wattle, the more likely the hen was to choose him over a competing rooster. As it turns out, combs and wattles are also the traits by which farmers judge the health of their flock.

''The females didn't seem to care how big the rooster was, or whether his feathers were smooth,'' said Dr. Zuk. ''It's the fleshy parts, the wattle, the comb color and size, that can change in a matter of days depending on parasitism, and that's what the hen seemed to be looking at.''

Beyond resistance to disease, another factor that females seem to find alluring is stamina. Dr. H. Carl Gerhardt, a biologist at the University of Missouri in Columbia, has analyzed the calls of gray tree frogs. Male frogs sit for days attempting to attract females by repeating a series of trilling pulses that they can vary in both length of individual pulses and timing between pulses.

Studying the physiology of the calls, Dr. Gerhardt and his colleagues discovered that male frogs consume an extraordinary amount of oxygen and deplete their body's fuel rations to generate their croons. ''It's energetically demanding,'' he explains. ''The frog reaches the same metabolic rate during calling that you get by forcing him to exercise to exhaustion. It's as though the female was asking him to push against his physiological limit.''

Dr. Gerhardt also has used electronic frog calls in an attempt to determine if females are drawn to artificial sounds that exceed the calling capacity of the hardiest real frog. Generating synthetic pulses through one speaker at a normal song rate and through another at twice that rate, the team has found that female frogs leap wildly in the direction of the fast-trilling speakers, sometimes attempting to embrace the singing machine.

Other species of frog also prefer the most athletic callers, said Dr. Gerhardt. In this way, he suggested, ''thefemales assure that they avoid the obvious wimps.''

Because a male tree frog contributes nothing to the business of reproduction beyond his genes - no defensive chemicals and no caring for the young - a female selecting a male for stamina presumably hopes to gain from the exchange the probability of begetting vigorous young.

Long Tails Chosen by Females

But proving that hardy males sire hardy offspring has been difficult and the subject of great contention among biologists. Some of the strongest evidence supporting the link has come lately from Dr. Anders Moller, a biologist at the University of Uppsala in Sweden. He has studied barn swallows, in which the males have tails that are about 20 percent longer than those of the female.

Dr. Moller first determined that female choice had determined the long tails of the male. He cut feathers off the tails of some male birds, and glued extra feathers to the tails of others.

When permitted to choose between the short-tails and the long-tails, the females invariably selected the more amply endowed males.

Dr. Moller next investigated possible reasons for the female preference. Like other researchers, he found a link between the chosen males and resistance to parasites. The longer-tailed males had measurably fewer blood-sucking mites on their bodies than did the short-tails.

To investigate whether the long-tailed birds had some sort of genetic resistance to the mites the biologist decided to follow the swallows through several generations. More significantly, he switched the eggs that had been fertilized by long-tailed males with those spawned by shorter-tailed males, to offset the contributions of environmental factors.

After making the switches, he infected the nests of all the birds with the same number of mites. Dr. Moller found that, as they grew, young birds of either sex sired by the long-tailed males had significantly fewer parasites on their bodies than did the offspring of short-tailed males.

The chicks' resistance to mites had no correlation to which nest they were in, or to the number of parasites crawling across their foster parents' feathers, but rather was determined by the relative parasite load on the natural father, a strong indication that resistance is hereditary.

Why long tails and resistance correspond remains mysterious, but a female actively chooses the longest-tailed mate around, apparently in an effort to bequeath to her young the best possible genetic legacy.

''About 15 percent of males never seem to get the chance to mate,'' he said. ''And they are almost always the males with the shortest tails.''

Biologists warn that what is true for barn swallows may not turn out to be true for other animals. Many of them believe that many cases of female choice will prove to be somewhat arbitrary - that a female pairs up with an especially loud male, for example, just because he is the one she hears.

''The ultimate question always is, does the female really get anything out of the choice she makes?'' said Robert Gibson, a biologist at the University of California at Los Angeles who studies female choice in the sage grouse. ''Is she really making a choice, or does it just seem that way to us? In so many cases, we still don't know.''

Choosy Female Seeks Robust Mate

When females judge male markings, songs and other mating displays, they may not just be looking for another handsome face. Some biologists say the signs the females look for demonstrate the male's fitness as a father. In wild chickens, for example, a long comb and bright wattle signify a rooster free of parasites. The male tree frog's trilling song needs large pulses of oxygen; a loud serenade proves the male is strong and vigorous. The male pyrochroidae beetle is less subtle. He displays in a forehead cleft a chemical that repels predators. If a female allows him to mate, he gives her a supply of the chemical for her eggs.

By Natalie Angier

IF it is sleep that knits up the raveled sleeve of care, then an overwhelming number of Americans are walking around with distinctly tatty shirtcuffs.

Experts in sleep behavior and sleep disorders have found that a majority of people are sleeping at least an hour to 90 minutes less each night than they should. That discovery may not surprise hard-driving workers who scorn the call to relax, but sleep researchers say that even those level-headed people who think they put in a reasonable stint in bed each night probably suffer from some degree of sleep deprivation.

''People cheat on their sleep, and they don't even realize they're doing it,'' said Dr. Howard P. Roffwarg, director of the Sleep Study Unit at the University of Texas Southwestern Medical School in Dallas. ''They think they're O.K. because they can get by on six and a half hours, when they really need seven and a half, eight or even more to feel ideally vigorous.''

Basing their conclusions on recent surveys, experiments at sleep disorder clinics, trends in the labor force toward shift work and night work, and the swelling number of Americans who suffer from sleep pathologies and chronic fatigue, sleep scientists insist that there is virtually an epidemic of sleepiness in the nation.

''I can't think of a single study that hasn't found people getting less sleep than they ought to,'' said Dr. David F. Dinges, a biological psychologist at the Institute of Pennsylvania Hospital in Philadelphia.

Sleep experts compare sleep deprivation with another common problem, that of excess weight. ''Some people are a couple of pounds overweight, and it's no big deal,'' said Dr. Thomas Roth, director of the Sleep Disorders Center at Henry Ford Hospital in Detroit. ''Others are obese, and that can be life-threatening.''

Likewise, experts say that mild sleep deprivation is not terribly worrisome, although they believe that people would be more productive, good-humored and satisfied with life if they were able to get a full complement of sleep each night. But when sleep deprivation becomes chronic and extensive, they say, it can have serious consequences, leading to gravely impaired judgment and an increase in automobile and industrial accidents.

So apparent are the potential hazards of chronic sleep deprivation that Congress, as part of an omnibus health bill passed in 1988, has asked a panel of a dozen sleep scientists to conduct a comprehensive study of the subject, to be completed by mid-1991. The commission will attempt to gauge the economic and medical impact of sleep disorders and sleep deprivation and suggest ways that the Government might help ease worker fatigue.

''The Government is finally waking up to the problem of sleep deprivation,'' said Dr. Mary Carskadon, a sleep researcher at Brown University and a member of the commission.

There has yet to be a large-scale epidemiological study of the nation's sleep habits, but sleep researchers have gathered insights about sleep deprivation by studying defined groups, particularly young adults and the elderly, and then estimating from those findings how many people over all are getting less than an ideal amount of sleep.

In a new analysis of several health surveys of 21,000 people 65 years and older, the National Institute on Aging found that more than 50 percent reported sleeping badly and feeling poorly rested upon waking. If applied to the older population as a whole, said Dr. Andrew Monjan, a sleep researcher at the institute, at least 13 million Americans are aware enough of their chronic sleep deficiency to cite it as a source of misery.

More revealing of the problem of hidden sleep deprivation is a series of studies of several hundred college and graduate students between the ages of 18 and 30, conducted over the past several years at Stanford University, Brown University and the Henry Ford Hospital.

In one representative experiment with the young adults, who were generally healthy and got an average of seven to eight hours sleep a night, sleep researchers discovered that 20 percent of these apparently normal students could fall asleep almost instantaneously throughout the day if allowed to lie down in a darkened room. That sleep pattern matched ones exhibited by narcoleptics and others suffering from clinical sleep pathologies - evidence, the researchers said, that the students, despite having had what most would consider a perfectly reasonable amount of sleep, were nevertheless sleep-deprived.

The sleep researchers further discovered that even the students who seemed alert and did not quickly fall asleep under test conditions could benefit from more sleep. If they spent one week getting to bed an hour to 90 minutes earlier than usual, the students improved their performance markedly on psychological and cognitive tests.

To sleep researchers, such results strongly suggest that most, if not all, people who think they are sleeping enough would be better off with an extra portion of rest.

As added evidence that people do not sleep enough, Dr. Wilse Webb, a psychologist at the University of Florida in Gainesville and a sleep research pioneer, cites the most pedestrian of bedside staples, the alarm clock. ''Whenever I ask an audience, how many people woke up by an alarm clock that morning, about two-thirds raise their hand,'' he said. ''If that's how you wake up every day, you're shortening your natural sleep pattern.''

Researchers also point out that ever more people are consulting sleep experts and sleep disorder clinics complaining of constant fatigue. Today there are more than 140 accredited sleep disorder centers in the United States, compared with 25 in 1980. About 1,200 clinicians are members of the American Sleep Disorders Association, a professional organization, up from 710 in 1985.

''Every year over the past decade there's been an enormous increase in our number of patients, sometimes as much as 50 percent a year,'' said Dr. Neil B. Cavey, director of the Sleep Disorders Center at Columbia-Presbyterian Medical Center in New York. ''And at least 40 percent of those people are suffering from some sort of extreme sleep deprivation.''

The Causes

After Light Bulbs Came Talk Shows Researchers trace the beginning of the sleep-deficit crisis to the invention of the light bulb a century ago. From diary entries and other personal accounts from the 18th and 19th centuries, sleep scientists have determined that the average person used to sleep about nine and a half hours a night. ''The best sleep habits once were forced on us, when we had nothing to do in the evening down on the farm, and it was dark,'' said Dr. Roffwarg.

According to surveys of school children in California and popular accounts in magazines, say researchers, that sleep schedule had been whittled dramatically, to between seven and a half and eight hours by the 1950's and 1960's. Now social and economic trends are slicing ever deeper into slumber.

Perhaps the most relentless robber of sleep, researchers say, is the complexity of the day. Whenever pressures from work, family, friends, the community and the health club mount, many people consider sleep to be the most expendable item on the agenda.

''In our society, it's considered dynamic, a feather in one's cap, to say you only need five and a half hours sleep,'' said Dr. Cavey. ''If you say you've got to get eight and a -half hours, people look at you askance, as though you lack drive and ambition.''

Also to blame is the increased prevalence of shift work, in which people either toil at night, or alternate between a day and night schedule. Researchers say that the brain has difficulty adjusting to daytime sleep or varying sleep times, which means that shift workers usually suffer a net loss of sleep. According to the Bureau of Labor Statistics, about 22 percent of all employees are shift workers.

The number of workers keyed into some aspect of the international economy likewise is soaring. Last year about 330,000 commercial planes operated by domestic carriers and tens of thousands of foreign-owned carriers took off for international destinations, carrying with them passengers destined for jet lag. Even if they are not traveling, few people in business can afford to ignore markets abroad.

''If you're in finance, the New York Stock Exchange may be closed at night, but if you don't watch Tokyo and London, you're vulnerable in the morning,'' said Dr. Dinges.

Many sleep researchers indict the availability of round-the-clock entertainment, especially the advent of all-night television. They point out that it was not so long ago that television stations signed off at midnight or 1 A.M. with ''The Star-Spangled Banner,'' a prod to many viewers to retire.

Yet another reason for the sleepiness trend is the prevalence of sleep disorders. The National Heart, Lung and Blood Institute estimates that 4 percent of all people suffer from sleep apnea, in which breathing stops repeatedly during the night, waking a person for a few seconds each time and ruining the restfulness of sleep. Researchers say that an unknown but possibly far greater number of people are chronic insomniacs, who spend their nights tossing fitfully and their days in tired misery.

''You can see how all the causes of sleep deprivation really mount up,'' said Dr. Monjan.

The Effects

On the Night Shift At Chernobyl Whatever the root of a person's sleep deficit, sleep scientists have devised tests to assess its extent and consequences. Researchers agree that the most accurate measurement of relative sleep deprivation is the Multiple Sleep Latency Test, devised by Dr. William Dement, director of the Stanford Sleep Disorders Center in California, along with Dr. Carskadon of Brown. Subjects are hooked up to electroencephalograms, which measure brain wave patterns, to track the precise second at which they fall asleep; they are allowed to lie down for 20 minutes in a dark room every two hours.

Those who fall asleep in under five minutes each time are considered pathologically sleep-deprived, because their sleep pattern matches that of somebody with a known sleep disease, such as apnea. An average score of between 5 and 10 minutes is borderline pathological, that between 10 to 15 is fine but not optimum and those who stay awake 15 minutes or longer are considered at their peak of restedness.

Researchers have also put subjects at sleep disorder centers through a battery of psychological and performance tests, like asking them to add up columns of numbers or to recall a passage that was read to them only minutes earlier. ''We've found that if you're sleep-deprived, performance suffers in many areas,'' said Dr. Charles Czeisler, director of Circadian and Sleep Disorders Medicine at Brigham and Women's Hospital in Boston. ''Short-term memory is impaired, the ability to make decisions is impaired, the ability to concentrate is impaired.''

Sleepy subjects have difficulty discriminating between loud and soft tones, or seeing flashes of light on a board. Because their reaction time is affected, sleep researchers say, sleep-deprived people may be more prone to making mistakes on the job. Experts note that many major industrial accidents, including the ones at Three Mile Island and Chernobyl, occurred at night, when workers who monitor equipment were probably not optimally alert.

Sleep researchers say that sleepiness is second only to drunkenness as a cause of automobile accidents. Reporting to Congress last year, the Department of Transportation said that at least 40,000 traffic accidents a year may be sleep-related, and that more than 20 percent of all drivers have fallen asleep at the wheel at least once. And in new studies, Dr. Roth has found that sleep-deprived people are impaired by smaller quantities of alcohol than are rested people, a factor that could further contribute to automobile accidents.

Dr. Dement of Stanford said he was shocked recently when he met a 30-year-old limousine driver who said he worked from 5 A.M. to midnight seven days a week. ''That man is losing up to three hours of sleep a night, and he knows he's headed for trouble,'' said Dr. Dement. ''He told me, 'I'm so sleepy it's scary.' ''

Sleep scientists have found that one bad night's sleep can make a person less efficient on mental tasks. Worse still, they say, the effects of sleep loss are cumulative. A person who chronically sleeps 90 minutes less per night during the workweek than is necessary will feel far worse on Friday than on Tuesday.

''By the fifth night, you've lost seven and a half hours, or virtually a whole night's sleep,'' said Dr. Dinges. ''That's the day when you're just praying to get through it.''

Sleep deprivation also destroys a person's capacity to feel pleasure or to laugh at a joke, which may be equally critical for getting through the workweek.

Trying To Cope: More Caffeine Is Not the Answer

Sleep scientists say that most people attempt to make up for the sleep deficits of the week by sleeping in on weekends, and that the tactic does help the body recoup vital sleep time. But they warn that in cases of chronic sleep deprivation, a weekend of 10-hour nights is not sufficient.

''I've had businessmen come in who are chronically sleep-deprived complaining of sleepiness they can't understand,'' said Dr. Charles P. Pollak, head of the Sleep-Wake Disorders Center at New York Hospital-Cornell University. ''They say they try sleeping longer on a weekend, but that it doesn't help. Of course a night or two doesn't help. In extreme cases, you may need six weeks of adequate sleep to reverse the effects of sleep loss.''

Scientists say that many people skate through their days on too little sleep by seeking outside stimulation, including banter with colleagues, exercise or the old standard, caffeine. But the stimulation does not solve the sleepiness; it merely masks it temporarily. ''If I start slapping you around, you'll be awake for a little while, but that stimulation is a crutch,'' said Dr. Dement. ''Withdraw it and you're back to where you started.''

Sometimes a severely sleep-deprived brain will try to snatch a break by falling into so-called microsleeps, which last for a few seconds and which may occur without a person's quite noticing it. In Mediterranean and other warm-weather countries, people often take siestas between 1 and 3 in the afternoon, to make up for their traditional late nights. Researchers say that the brain does fall into a lull in the afternoon, indicating an evolutionary predisposition toward napping, but they add that a person who has had a truly full night's sleep will not need a nap.

Sleep experts insist that the effort to squeeze ever more tasks into one's days and nights ultimately backfires. The person who invests in a full night's sleep, they say, will be more than recompensed in heightened productivity, creativity and focus.

But even sleep specialists have trouble taking their own advice. Although Dr. Dement says he is adamant about getting eight hours a night, others, in their zeal to promote the benefits of sleeping, admit that they often work themselves to exhaustion. ''I get by on maybe six, six and a half hours,'' said Dr. Cavey. ''I'm just too busy to get a good night's sleep.''

Correction: May 24, 1990, Thursday, Late Edition - Final An article in Science Times on May 15 about sleep deprivation misidentified a researcher at Columbia-Presbyterian Medical Center. He is Dr. Neil B. Kavey.

By Natalie Angier

AS the human genome project drives steadily forward, the vast new effort to delineate all three billion chemical building blocks of humanity's genetic makeup is arousing alarm, derision and outright fury among an increasingly activist segment of the biomedical community.

The critics argue that the human genome project has been sold on hype and glitter, rather than its scientific merits, and that it will drain talent, money and life from smaller, worthier biomedical efforts.

Matching the pitch of the criticism is the scale of the project and the intensity of support among its promoters. As biology's first foray into big-ticket science, the $3 billion, 15-year human genome project is designed to do nothing less than decipher the complete code of the 50,000 to 100,000 genes that are the genome (pronounced JEE-nome), the blueprint for a human being. Researchers hope to attain their goals by sketching out biochemical maps and sequences of genes.

Its backers insist that a large-scale study of human deoxyribonucleic acid (DNA) will benefit all biomedical researchers, greatly accelerating the search for the genes that cause many diseases, from rare disorders like Huntington's disease to common ailments like cancer. And they argue that the new technology spinoffs will benefit other experiments.

''Our project is something that we can do now, and it's something that we should do now,'' said Dr. James D. Watson, a Nobel laureate who heads the National Center for Human Genome Research at the National Institutes of Health. ''It's essentially immoral not to get it done as fast as possible.''

But opponents of the project argue that the effort is intellectually questionable. They point out that the first phase of the human genome project, a detailed map of all human chromosomes, already is several years behind schedule. They say the delay is evidence that the project, now in its third year of Federl support, is more difficult and tedious than its promoters will admit. They also doubt that the project can be completed in anything close to its original deadline and budget.

Opponents contend that even if scientists manage to finish the genome project, it will have generated enormous reams of uninterpretable and often useless data, essentially a computerized catalogue of genes, subunits of genes, and long stretches of filler material, with few clues about how any of that genetic material works or can trigger disease.

''The human genome project is bad science, it's unthought-out science, it's hyped science,'' said Dr. Martin Rechsteiner, a biochemist at the University of Utah. Some critics have begun aggressive letter-writing campaigns, urging colleagues who harbor similar sentiments to write Congress.

''Everybody I talk to thinks this is an incredibly bad idea,'' said Dr. Michael Syvanen, a microbiologist at the Medical School of the University of California at Davis and a stout antagonist of the genome project.

Opponents say that the battle has shaped up as a fight between prominent scientists, including Nobel laureates like Dr. Watson and Dr. Walter Gilbert of Harvard University, who support the genome project, and less renowned scientists who usually run smaller labs on modest budgets and see the genome project as a threat.

Although critics doubt that they will derail the project soon, they hope that their constant hounding will influence the course of the project, and assure that it does not drain resources from other research.

What It Is: Series of Projects Under One Label

Despite its unifying rubric, the human genome project is not really one project, but a series of related projects, which are now being performed by scientists at universities and institutes around the country.

It is jointly orchestrated by Dr. Watson's office at the National Institutes of Health and an office at the Department of Energy. Congress first allocated a formal budget of $27.9 million to genome-related research in 1988. This year, the N.I.H. and the Energy Department will dispense $87.4 million in genome grants, with the N.I.H. controlling about two-thirds of that money. Together the offices have requested $155.9 million for 1991, and they hope to get up to $200 million within the following year or two and continue getting that amount for the remainder of the project.

That yearly budget, says Dr. Watson, represents a mere few percent of the current $7.5 billion budget of the health institutes, and he stresses that the genome money is newly won money, not funds that have been diverted from the research coffers of the health institutes.

After Hiroshima

Although now staunchly behind the genome project, scientists at the health institutes initially scorned the whole notion. The idea for a huge DNA analysis project first arose at Los Alamos and Lawrence Livermore laboratories, the Energy Department's national weapon research centers. Scientists there were trying to determine whether the offspring of the survivors of the Hiroshima bomb had mutations in their DNA as a result of their parents' exposure to radiation.

''We realized that we didn't have any methodologies sensitive enough to detect the mutations if they were there,'' said Dr. Benjamin J. Barnhart, manager of the Human Genome Program at the Energy Department.

The scientists decided that the only way to pick up the mutations would be to sequence, or spell out, all the three billion subunits that make up the human genome, and then look for individual errors in the subunits.

The weapons laboratories also were seeking novel ways to use their huge data banks and technical resources for civilian projects that would keep them busy in the event military research declined in an more peaceful era.

Thus galvanized, Energy Department experts presented the idea of a national mass-sequencing effort at a scientific conference in Colorado in 1984.

The great majority of scientists dismissed the original proposal with hostility or indifference. They argued that current sequencing technologies are laborious and expensive, costing a biomedical researcher between $3 and $5 to spell out a single DNA subunit, which, multiplied by three billion subunits, would amount to up to $15 billion just to sequence the entire genome.

And they declared that most of the money would be wasted. Scientists suspect that up to 95 percent of human DNA has no function. Nevertheless, a few prominent scientists continued pushing the idea of a genome project. They significantly modified the aims of the project along the way, largely to meet the fierce objections of scientific luminaries like Dr. David Baltimore, a Nobel laureate who will be assuming the presidency of Rockefeller University in New York this summer.

Course Change: Trying to Draw A 'Road Atlas'

Among the biggest of the adjustments was to postpone the idea of sequencing all three billion pieces of DNA in favor of first sketching out a good ''road atlas'' of the genome. That genetic map will feature between 1,500 and 3,000 genetic markers, or distinct biochemical patterns, evenly spaced up and down the chromosomes. Scientists obtain such markers by subjecting the DNA of large families to chemical manipulations and then painstakingly comparing the resulting patterns of the various family members in search of distinct hallmarks.

With those hallmarks distributed around the human chromosomes, researchers can use the patterns as trailblazers, pointing them in the direction of genes that they wish to isolate and study. That map, many researchers concurred, would be a magnificent resource.

As the genetic mapping proceeds, other researchers will strive to create another sort of map known as a physical map, consisting of the human chromosomes chopped into giant pieces and each long piece inserted into a yeast cell or other cell that can be manipulated to reproduce the piece of chromosome. The individual pieces will be lined up end to end in proper order, as they exist in human cells. This operation will essentially create a single photocopying machine for the entire human genome.

In theory, a researcher will employ the genetic map to locate a gene of interest, and then turn to the physical map to actually pull out the gene and copy it into a quantity that can be analyzed.

Trying for Efficiency

Before undertaking the final phase of the project, other scientists will attempt to make sequencing technology 10 times more efficient than it is today. Then they will attempt to spell out the entire human genome to determine if the supposed ''junk'' DNA harbors important insights about human evolution.

In another crucial concession to early critics, genome proponents agreed that some laboratories should study in parallel the DNA of favorite experimental organisms, like worms, fruit flies and mice, comparisons that could allow researchers to better understand the DNA of humans. Thus mollified, a number of early doubters have rallied behind the project.

''I have no objection to the program as it's currently organized,'' said Dr. Baltimore. Dr. David Botstein, a prominent scientist who is currently vice president at Genentech but who will be leaving to head the genetics department at Stanford University Medical Center this summer, says that he initially viewed the genome project with ''extremely negative feelings,'' but that when genome backers agreed to emphasize mapping and technological development for sequencing, he changed his mind.

Money Squeeze: Competition Arises As Cash Shrinks

Grousing about the genome enterprise might have continued to wane had it not been for recent budget limitations on new grants at the health institutes. Between 1987 and 1990, the number of new grants dispensed to young, independent researchers has shrunk from 6,446 to 4,633, largely as a result of administrative changes in financing policy that had nothing to do with the genome project.

But left without support for their struggling labs, many young researchers have attacked the genome project as unfair.

''You can't prove it, but I think it is widely felt that the two are in competition,'' said Dr. Bernard D. Davis, a professor of microbiology and molecular genetics at Harvard Medical School.

Critics have questioned the need for a new enterprise that receives special consideration in the Federal budget.

''If this has validity as a scientific project, why not let it compete with all other grant applications to the N.I.H., instead of saying, this $200 million can only be spent on this particular type of effort?'' said Dr. Ry Young, a professor of biochemistry and biophysics at Texas A & M University in College Station. ''Why should it be insulated from the fray?''

Opponents wonder whether many of the new converts to the human genome project have been persuaded less by the inherent worthiness of the project than by the possibility that they, too, can win genome-related grants. The project has even greater appeal now that the N.I.H. genome office is offering a new type of grant. In the fall, the office will designate four large groups of scientists as the first of a series of so-called genome centers.

These centers will receive around $3 million a year for up to five years, which is about 10 times the average grant given to a university lab. Eventually, the institutes' genome office will distribute about half of its money in giant grants to centers.

Young researchers worry that such financial devices like the big grants will concentrate ever more resources in ever fewer hands. ''I had a brilliant young scientist say to me recently, 'The fat cats are all getting the cream, while I'm sitting here starving,' '' said Dr. Rechsteiner.

Beyond money issues, critics of the program quarrel with its medical and scientific claims. They say that the best approach to understanding human disease is not to thwack away randomly at the thick forest of human DNA, as they say genome researchers will do, but to study one specific disease at a time, as scientists traditionally have done.

To further buttress their position that the genome project is misbegotten, critics note that the early phase of genome mapping already is behind schedule. Project planners had hoped to produce a detailed map by this year or the next, but now that deadline has been extended to 1995. Even genome organizers were concerned enough about the delay in mapping to formally divide up the task of analyzing the 23 chromosomes at a recent meeting at Cold Spring Harbor Laboratory on Long Island.

Mental Factors: Will Tedium Be Another Hurdle?

Critics worry that many jobs necessary to complete the genome project, like identifying biochemical markers on chromosomes, are both so difficult and so numbingly tedious that the students and post-doctoral fellows who will be expected to do the job will rapidly become bored and disillusioned. And though technicians may be able to handle some of the tasks of genome studies, other jobs will require graduate-level training without offering the commensurate intellectual rewards.

''I haven't the foggiest idea how I would inspire my students to work on this sort of thing year after year,'' said Dr. Michael Wigler, a well-known geneticist at Cold Spring Harbor who is not considering genome-related experiments for his group. Opponents doubt that the human genome project will quickly cure any diseases, either. They say that the mere identification of genes responsible for certain illnesses is no guarantee that researchers can easily learn how the genes work or what can be done to correct their defects.

''The gene for sickle-cell anemia has been known for 20 years, and it has yet to lead to a cure for the disease,'' said Dr. Syvanen.

But supporters dismiss the complaints as naive and short-sighted. They say that, while identifying a gene is only the first step toward curing a disease - or understanding how the brain works or how a fertilized egg turns into a human baby - it is a vital first step.

''Most knowledgable people and most eminent scientists are solidly behind'' the genome project, said Dr. James Wyngaarden, who was in charge of the health institutes when it joined the genome project. ''The ones who are critical are journeymen biochemists who may be having a hard time competing themselves.''

By Natalie Angier

For the last 18 months or so Frederick McCullough has been like Popeye, or Tony the Tiger, or some other cartoon character with hyperbolic energy: shinnying up to the roof to put new concrete around the chimney, washing the aluminum siding around the house, and mowing and re-mowing the lawn.

At one point his wife, Rita, peered at her 65-year-old husband and told him his gray hair was turning black again.

''He does appear to have abnormal energy for a man his age,'' she said. ''He never complains of being sick. Every day he feels fine.''

Mrs. McCullough, who is 15 years his junior, added: ''I'm a lot younger, but I don't feel fine every day. I get up dragging sometimes, but he never does anymore.''

Some Indisputable Improvements

Mr. McCullough's hair color has probably not changed, and some of his vigor may be as much psychological as real, say researchers who are studying the effects of human growth hormone on aging. But what is indisputable are the improvements that have taken place in his muscle size, body fat, skin texture and other easily measured traits, all as a result of thrice-weekly injections of human growth hormone.

Mr. McCullough is one of 21 healthy men ranging in age from 61 to 81 who recently took part in a clinical trial examining the effects of growth hormone on older men.

Researchers said in a report published yesterday in The New England Journal of Medicine that six months of treatment with a genetically engineered version of the hormone reversed many of the changes in the body that are wrought by aging.

The men who received growth hormone gained almost 9 percent in lean body mass, dropped nearly 15 percent in body fat, regained a youthful thickness to their skin and had a spurt in important growth-promoting hormone in their blood. In many respects, the treatment cut almost 20 years from their bodies.

''The results are quite amazing,'' said Dr. Lester Cohn of the Veterans Affairs Medical Center in North Chicago, one of the investigators in the study. ''We're dealing with people with an average age of 70, who for 40 years had been losing muscle mass and mass in internal organs. Within a short period of time, through growth hormone replacement, we've moved their bodies backward,'' toward a more youthful state.

But researchers warned anybody who might be on the verge of storming a doctor's office in quest of human growth hormone that the hormone would probably be good primarily for those elderly people who are deficient in the compound, which is produced naturally by the pituitary gland at the base of the brain.

Low Output of Growth Hormone

They say that only a third of those over 65 have almost worthlessly low levels of human growth hormone; the men chosen for the study fall into that category. The other two-thirds have levels of the hormone that range from somewhat low to, in a few cases, surprisingly high.

As a general rule, growth hormone output begins to drop when people reach the age of about 30.

''Some elderly people continue to produce youthful amounts of growth hormone well into old age,'' said Dr. Daniel Rudman of the Medical College of Wisconsin and Veterans Affairs Medical Center of Milwaukee, the leading author on the report. ''For them, the risks of growth hormone treatment could outweigh the benefits.''

Researchers are not yet sure of all the long-term side effects of growth hormones, but they say an excess of growth hormone may lead to diabetes, high blood pressure, enlargment of the face and hands, heart problems and even cancer.

High Leukemia Rate in Children

In some studies, children with a hereditary form of growth hormone deficiency who have been given hormone replacement to help them grow seem to suffer a higher than normal rate of leukemia as a result of growth hormone injections, although researchers say that the statistics are equivocal.

Nevertheless, endocrinologists and gerontologists say the new results are dramatic and promising. The growth hormorne could prove of great benefit for frail, elderly people who need added muscle strength or help in recovering from an operation, experts say.

That was true for Robert Bensing, 72, another participant in the new study. A couple of years ago, before receiving growth hormone injections, he had cataract surgery and needed more than three weeks to recuperate.

Recently, while participating in the hormone experiment, he needed a second cataract operation, and was back up and driving his car again only a week after the operation.

Smoother Skin and Stronger Hands

He also says the skin on his face and hands is smoother, more pliant and less wrinkled than it was before, that he can open jars that once would have stymied him, and that he can work in his garden for several hours longer than in his pre-treatment days.

And, despite being only 4 feet 11 inches tall, he says he now walks quickly enough to cover ground more rapidly than younger and taller people. ''I get irritated when I'm walking behind somebody who is slow,'' he said.

His wife, Alice, who is 57, said: ''He's got more spree in his step. He's been looking fitter and trimmer, too.''

Researchers are now studying whether the gain in lean body mass that added bulk to both the muscles and vital organs like the liver, spleen and kidneys translates into real improvement in organ function. They also must determine whether the loss of fat tissue will help to stem or prevent heart disease, stroke and other diseases associated with obesity.

Nor do they know how long the body changes will last after growth hormone injections have been stopped. Treatment ended a year ago for the men in the new study but, while researchers are still compiling data on the follow-up studies, many of the improvements seem to be lingering.

Other Trials Are Under Way

Other trials of the effects of growth hormone on the elderly are under way at three other medical centers in the United States. Beyond experimental use, the recombinant drug is approved solely for the treatment of growth hormone deficiency in children.

''It's not the sort of thing that you can fill out at your local pharmacy,'' said Edward West, a spokesman for Eli Lilly and Company, a manufacturer of the drug. ''We've tried to restrict its use because we're worried that it may be misused.''

The medication is very expensive, costing about $14,000 a year, although Dr. Rudman and others predict that the price will come down if it proves useful on a broad scale for older people.

''Would I take the drug?'' said Dr. Cohn, the V.A. doctor in North Chicago. ''Well, I'm 67, so I guess I'm the right age. But I'm going to wait a bit longer to see what the studies show.''

By Natalie Angier

O the ancient Greeks, the word ''parasite'' meant one who eats at the table of another. But far from having the decency to sit down for dinner, most parasites in nature suck the blood, sip at the gastric juices of the intestines, pierce into the nourishing warmth of muscle tissue and otherwise leech rudely off the fluids and labors of their unwilling hosts.

Yet for all their repulsive traits, worms, mites, fungi, viruses and a rogues' gallery of other parasitic organisms that derive their nutrients from a larger species hold an increasing fascination for evolutionary biologists. After long dismissing the freeloaders as bit players in the grand theater of evolution, scientists now propose that parasites may explain many of the outstanding features seen in a broad spectrum of animals and plants.

They say that the relentless pressure of a diverse battery of parasitic species ready to colonize and exploit every square millimeter of larger creatures has helped shape many of the traits of the beleaguered hosts. And because parasites breed so quickly and so prolifically, scientists say, their effects on their hosts is particularly powerful.

At a meeting of evolutionary biologists last month in College Park, Md., researchers presented a wealth of new data suggesting that parasitism is what gave birth to sex. They proposed that animals and plants mix their genes together sexually, rather than simply generating clones of themselves, to create diverse offspring as a way of assuring some resistance to parasites. An article on the subject by one of the foremost theoreticians of evolutionary biology, Dr. William D. Hamilton of Oxford University appeared in the May issue of The Proceedings of the National Academy of Sciences.

Other biologists have gathered compelling evidence that the need to dodge parasites may have been the force prodding some species to become migratory or to spend part of every year in isolation from their potentially pest-ridden fellows.

''Historically, the study of parasites has been utterly, completely and egregiously neglected,'' said Dr. Douglas E. Gill, a parasite expert at the University of Maryland in College Park. ''Now that's all changing. There's a great deal of interest at the medical, molecular and ecological level of what parasites are doing out there. It's a new frontier.'' Some researchers are considering the story from the parasite's perspective. They are trying to understand why many species of parasites go through multi-stage life cycles, passing from one host to another. In probing the parasitic reproductive cycle, researchers have unearthed examples of host-parasite relationships that border on the macabre.

Dr. Manfred E. Rau, a parasitologist at McGill University in Montreal, recently found that two types of closely related parasitic worms can dramatically influence the behavior of mice to suit their own needs. One worm will prompt the mouse to become hyperactive, scampering through fields so frenetically that it attracts the attention of a predatory bird that will eat the mouse and the worm with it. When the bird eats the mouse, it provides the necessary next home for the parasitic larvae.

By contrast, the related worm species will cause a mouse to become sluggish, heightening the chance it will be easily stalked down by the carnivorous mammals this worm prefers for its second shelter.

Other parasitic larvae have been found to drive host snails mad, forcing the creatures to make a suicidal ascent to the top of a blade of grass, rather than hiding underneath the foliage. At the same time, a few of the invading larvae migrate to the snail's antennae, turn bright colors and pulsate, transforming the hapless gastropod's feelers into a reasonable facsimile of a caterpillar. That resemblance catches the attention of birds, which then consume the infested snails. Once in the guts of the birds, the larval worms can mature and reproduce.

''There are fantastically interesting questions to be answered,'' said Dr. Gerhard A. Schad, professor of parasitology at the University of Pennsylvania and the president of the American Society of Parasitology. ''How do these hosts and parasites come to live together? Who's ahead at any given moment in the evolutionary game plan?''

Offshoot of Immune System Studies

Some researchers say the new interest in parasites stems partly from the extraordinary advances in the study of the human immune system. As investigators have deciphered its staggering complexity, they have come to consider the varied spectrum of parasites and pathogens that the immune system evolved to attack.

''Parasites have had a tremendous impact on human evolution, which we're only now beginning to appreciate,'' said Dr. Dickson D. Despommier, a professor of public health and microbiology at Columbia University. ''About half of all people who have ever lived on earth have died from malaria or malaria-related problems, and malaria is caused by the Plasmodium parasite. That's an astonishing notion. The early American colony of Jamestown had to be re-established three times because of malaria.''

Although most people in developed nations no longer suffer from parasitic diseases, the vast majority of the world's people are hobbled by one or more types of parasite. According to one estimate, Dr. Schad said, the amount of human blood sucked by hookworms in a single day is equivalent to the total blood of about one and a half million people. ''It's a parasitized world out there,'' he said. Scientists have no idea how many species of parasites there are or even what exactly constitutes a parasite. By the generally accepted definition, a parasite must derive most or all of its nutrients and resources from another animal or plant species, and it also must be smaller than the host it uses. But while many parasites, like viruses and bacteria, are microscopic or nearly so, some types of worms reach three feet or longer as adults.

Parasites frequently are harmful to their hosts, although the degree of virulence varies widely. Some parasites, like many types of viruses, sicken and even kill the animals they infect. Others cause only the mildest of malaise, while still others are almost completely innocuous.

A number of parasites, like ticks, are generalists, hopping happily from one warm-blooded creature to another. Many more are remarkably specific. There are mites that can survive only in the rectum of a giant tortoise, worms that fit snugly into the quills of a single species of birds, and mites that live exclusively and harmlessly at the base of human eyelashes. Most parasites are themselves burdened with parasites, which prompted the novelist and satirist Jonathan Swift to write in 1733: ''So, naturalists observe, a flea hath smaller fleas that on him prey. And these have smaller still to bite 'em; and so proceed ad infinitum.''

Hosts' Strategies: Evolution of Sex Linked to Parasites

Until recently, parasitologists have studied their subjects largely in an effort to eradicate them. But lately, biologists, stymied in their efforts to solve a few key puzzles in evolution, have turned to parasites in looking for solutions.

The biggest mystery to these researchers has been why sex evolved. On the face of it, scientists say, sexual reproduction is cumbersome and irrational, far less efficient than reproduction by simple clonal copying of the mother organism. Some lower animals and plants do procreate asexually, but the majority of species reproduce through a joining of male and female sex cells, and evolutionary biologists have sought to learn why.

Some researchers have suggested that organisms must create diversity in future generations to guarantee that at least a few offspring will survive changing climate and other unpredictable conditions in the environment. Alternatively, a few scientists have speculated that if babies differ sufficiently from one another, the young will be less likely to compete directly with each other for resources.

''The trouble with these ideas,'' said Dr. Curt Lively, assistant professor of biology at Indiana University, ''is that they aren't supported by any scientific evidence.''

Biologists are finding far greater support for the impact of parasites on the evolution of sexual reproduction. They say that it makes sense for plants and animals to vary their offspring to outwit parasites, because parasites prefer to infest creatures that are similar to the hosts they have exploited before.

Dr. Lively recently studied a type of aquatic snail in New Zealand, called Potamopyrgus antipodarum, which has the unusual feature of some female snails reproducing sexually and others asexually. He wondered what factors in the environment would spur one reproductive strategy over another. Studying about 65 populations of the snail, he found a strong correlation between sex and the prevalence of the most deleterious snail pest, a type of nematode, or worm.

In lakes with a light load of the parasitic worms, there were few male snails, and the females tended to reproduce asexually.

But in lakes awash with nematodes, male snails likewise abounded, suggesting that the females were of the type that required a male for reproduction. ''The evidence isn't conclusive, but it does suggest that parasites were the determining factor in whether it was worth investing in something as inefficient as sex,'' said Dr. Lively.

In another discovery, Dr. Keith Clay, an assistant professor of biology at Indiana University, found that some parasites consider sexual reproduction in their hosts to be such anathema that they will strenuously suppress it. Studying several species of grasses that can reproduce either sexually by producing flowers or asexually by sending out carbon-copy shoots, he determined that parasites wanted no part of genetic variability.

Dr. Clay found that when the grasses became infected by parasitic fungus, the fungus headed straight for the sex cells of the plant and destroyed them, but did no further damage to the host. The result was that the grass could produce only clonal shoots, each of the offspring genetically identical to its forebears and thus vulnerable to fungal infestation.

And in a bizarre story not unlike that of ''Invasion of the Body Snatchers,'' Dr. Helen M. Alexander, a botanist and ecologist at the University of Kansas in Lawrence, has found that when a flower related to the carnation is infected by a fungus, the parasite not only sterilizes the plant, it also transforms that plant into a fungal factory. In the stamen of the flowers, where the pollen of the plant normally would be found, an infected plant displays a bristle of fungal spores. What is more, the flowers of parasitized plants grow bigger and more abundantly than those of normal plants, attracting pollinating insects and assuring the transmission of parasitic spores.

Moving Away: Parasites Linked To Migration

Other researchers have examined the effect of parasites on animal migration and wandering. Over the past decade, Dr. Gill has studied 9,000 red spotted newts in the mountaintop ponds of western Virginia. He found the newts are infested by a type of parasite related to the agent of deadly African sleeping sickness in humans but the parasites seem to do the amphibians little harm.

Dr. Gill determined that the reason for the apparently benign results lay with the newt's migratory habits. At a time when newts harboring a more virulent strain of the parasite might transmit the pathogen, the animals were spending months in solitary roaming through the woods, rather than congregating in ponds.

Those newts carrying a malevolent parasite would die during their migrations. Only amphibians with a mild strain of the parasite would return to the pond to mate.

''It's my general view that it's common for many species to have a phase of life when they're out of contact with a place where they can pick up a parasite or pass a parasite on,'' Dr. Gill said. ''This could at least partly explain bird migration patterns from North to South America, when birds spend nine months not breeding or being in a position of transmitting parasites to each other, or the migration of wildebeest across the Serengeti plains or any number of instances of animal movement.''

Counterstrategies: Clever Life Cycles Open a Path

Nor is life easy even for a parasite that has successfully infected a host. Because the parasite is utterly helpless without a host, the host's death can often mean termination for the parasite, too. Thus, parasites have expended a great deal of energy into evolving methods of guaranteeing their transmission to another host. ''Parasites live in a world of ephemeral islands,'' said Dr. Gill. ''They're absolutely obligated to disperse by any means possible, and that accounts for some of the clever, complicated life cycles we observe.''

Changing the behavior of the host is one way to heighten the chance of transmission to another host. But some parasites go further, demonstrating a spirit of self-sacrifice in their quest to keep their fellows alive. In one of the more remarkable instances of parasitism, a type of liver fluke known as lancet begins its life as eggs laid in the intestines of sheep or other grazing animals. The eggs are expelled by the sheep and are then eaten by land snails that feed on sheep feces. Inside the snails the eggs hatch and develop into larvae, which are once again expelled by the host, this time wrapped within a slimy, mucous-like packet ants find irresistable.

Once ingested by ants, the lancet larvae go to work, some moving into the ant's intestines, where they develop into a new, infectious stage, and a few invading the ant's brain. Those larvae, called brainworms, so disturb the ant that, early in the morning and late in the evening, it does something no sane ant would - climb to the tips of blades of grass, just at the moment when sheep will be grazing.

When safely in the belly of a sheep, the larvae from the ant's abdomen mature, mate and lay eggs, starting the entire cycle over again.

''The brainworms have sacrificed themselves for their kin,'' said Dr. Schad. ''They don't become infective. If there's such a thing as altruism, this is one example.''

But from the ant's perspective, at least, Mother Teresa this fluke is not.

From One Host to Another

Some parasites live in different host species at different times in their life cycles. In some cases, they have have managed to alter the behavior of one host to assure passage to the next. For example, larvae of a parasitic worm, Luco chloridium paradoxum, migrate to the brain of a marsh snail, confusing it and causing it to leave the mud and climb to a leaf top. Other larvae in the snail's antennae turn bright colors and pulsate, making each antenna look like a caterpillar. That attracts the larvae's next host, a blackbird, which eats the snail, parasites and all.

Source: Dr. Gerhard A. Schad

How a Pest Seems to Orchestrate Its Path

The life cycle of the liver fluke Dicrocoelium dentricum begins as eggs are expelled by a sheep. A snail eats the eggs, they hatch within it into larvae and are dropped from the snail in a slimeball tasty to ants. Some larvae migrate to the ant's brain, causing it to climb up a blade of grass. A grazing sheep eats it, begining they cycle anew.

Source: Dr. Gerhard A. Schad 

By Natalie Angier

AH, romance. Can any sight be as sweet as a pair of mallard ducks gliding gracefully across a pond, male by female, seemingly inseparable? Or better yet, two cygnet swans, which, as biologists have always told us, remain coupled for life, their necks and fates lovingly intertwined.

Coupled for life, with just a bit of adultery, cuckoldry and gang rape on the side.

Alas for sentiment and the greeting card industry, biologists lately have discovered that, in the animal kingdom, there is almost no such thing as monogamy. In a burst of new studies that are destroying many of the most deeply cherished notions about animal mating habits, researchers report that even among species assumed to have faithful tendencies and to need a strong pair bond to rear their young, infidelity is rampant.

Biolgists long believed, for example, that up to 94 percent of bird species were monogamous, with one mother and one father sharing the burden of raising their chicks. Now, using advanced techniques to determine the paternity of offspring, biologists are finding that, on average, 30 percent or more of the baby birds in any nest were sired by someone other than the resident male. Indeed, researchers are having trouble finding bird species that are not prone to such evident philandering.

Faithless Females

''This is an extremely hot topic,'' said Dr. Paul W. Sherman, a biologist at Cornell University in Ithaca, N.Y. ''You can hardly pick up a current issue of an ornithology journal without seeing a report of another supposedly monogamous species that isn't. It's causing a revolution in bird biology.''

In related studies of creatures already known to be polygamous, researchers are finding their subjects to be even more craftily faithless than previously believed. And to the astonishment, perhaps disgruntlement, of many traditional animal behaviorists, much of that debauchery is committed by females.

Tracking rabbits, elk and ground squirrels through the fields, researchers have learned that the females of both species will copulate with numerous males in a single day, each time expelling the bulk of any partner's semen to make room for the next mating. Experts theorize that the female is storing up a variety of semen, perhaps so that different sperm will fertilize different eggs and thus assure genetic diversity in her offspring.

Males Retaliate

Most efficiently energetic of all may be the queen bee, who on her sole outing from her hive mates with as many as 25 accommodating, but doomed drones.

Scientists also have gathered evidence of many remarkable instances of attempts by males to counteract philandering by females. Among Idaho ground squirrels, a male will stick unerringly by a female's side whenever she is fertile, sometimes chasing her down a hole and sitting on top of it to prevent her from cavorting with his competitors. Other squirrels simply use a rodent's version of a chastity belt, topping an ejaculation with a rubber-like emission that acts as a plug.

The new research, say scientists, gives the lie to the old stereotype that only males are promiscuous. ''It's all baloney,'' said Dr. Sherman. ''Both males and females seek extra-pair copulations. And what we've found lately is probably just the tip of the iceberg.'' Even mammals, which have never been paragons of virtue, are proving to be worse than expected, and experts are revising downward the already pathetic figure of 2 percent to 4 percent that represented, they thought, the number of faithful mammal species.

''It was believed that field mice, certain wolf-like animals and a few South American primates, like marmosets and tamarins, were monogamous,'' said Dr. David J. Gubernick, a psychologist at the University of Wisconsin in Madison who studies monogamy in mammals. ''But new data indicate that they, too, engage in extra-pair copulations.''

Scientists say their new insights into mating and the near-universality of infidelity are reshaping their ideas about animal behavior and the dynamics of different animal social systems.

''It's been a bandwagon,'' said Dr. Susan M. Smith, a biologist at Mt. Holyoke College in South Hadley, Mass. ''Nobody can take monogamy for granted anymore, in any species they look at, so we're all trying to rewrite the rules we once thought applied.''

Old Assumptions: Darwin's Misconceptions

Biologists say their new research suggests that many animal social systems might have developed as much to allow animals to selectively cheat as they did out of a need for animals to divide into happy couples. They propose that pair bonds among animals might be mere marriages of convenience, allowing both partners enough stability to raise their young while leaving a bit of slack for the occasional dalliance.

More than anything else, say biologists, they are increasingly impressed by the complexity of animal sexuality. ''It seems that all our old assumptions are incorrect, and that there's a big difference between who's hanging out with whom and who's actually mating with whom,'' said Dr. Patricia Adair Gowaty, a biologist at Clemson University in South Carolina and one of the first to question the existence of fidelity among animals. ''For those of us in the field, this is a tremendously exciting time.'' 

Researchers say that many of the misconceptions about monogamy and infidelity began in Darwin's day, when he and other naturalists made presumptions, perhaps understandable, about mating based on field observations of coupled animals. Nearly all birds form pairs during the breeding season, and biologists assumed that the pair bond was necessary for the survival of the young. Without the contributions of both males and females to feed and protect the young, experts thought, few offspring would make it to the fledgling stage. And that demand for stability, biologists assumed, likely included monogamy as well.

But as field researchers became more sophisticated in their observation techniques, they began spotting instances in which one member of a supposedly monogamous avian couple would flit off for a tete-a-tete with a paramour.

''Extra-pair copulations are called sneakers, and they really are,'' said Dr. Robert Montgomerie, a biologist at Queens University in Kingston, Ontario. ''They're not easy to observe because the birds are very surreptitious about such behavior.''

Such sightings inspired biologists to apply DNA fingerprinting and other techniques used in paternity suits to help determine the parentage of chicks. They discovered that between 10 percent and 70 percent of the offspring in a nest did not belong to the male caring for them.

Explanations: Females Look Up

Redoubling their efforts in the field, biologists began to seek explanations for the infidelities. In some cases, the female clearly was the one seeking outside liaisons.

Dr. Smith has studied the familiar black-capped chickadee of North America. She had found that, during winter, a flock of chickadees forms a dominance hierarchy in which every bird knows its position relative to its fellows, as well as the ranking of the other birds.

In the spring breeding season, says Dr. Smith, the flock breaks up into pairs, with each pair defending a territorial niche and breeding in it. Though she has determined that infidelity is rare among the chickadees, it does occur ''and in a very interesting way,'' she said. On occasion, a female mated to a low-ranking male will leave the nest and sneak into the territory of a higher-ranking male nearby.

''In every single case of extra-pair copulations, the female wasn't moving randomly, but very selectively,'' said Dr. Smith. ''She was mating with a bird ranked above her own mate.''

Dr. Smith suggests that the cheating chickadee may have the best of both worlds: a stable mate at home to help rear the young, along with the chance to bestow on at least one or two of her offspring the superior genes of a dominant male. ''This fits into the idea that the female is actively attempting to seek the best-quality genes,'' she said.

Selectivity of Barn Swallows

In similar studies, Dr. Anders Moller, a biologist at the University of Uppsala in Sweden, has found that female barn swallows likewise are very finicky about their adulterous encounters. When cheating, he said, the females invariably copulate with males endowed with slightly longer tails than those of their mates. Dr. Moller has learned that, among barn swallows, a lengthy tail appears to be evidence that the birds are resistant to parasites; this trait would be beneficial to a female's young. ''Females mated to very short-tailed males engage in these extra-marital affairs the most,'' he said. ''Short-tailed males attempt to have affairs themselves, but they're rarely successful.''

Some females that mate promiscuously may be gaining not so much the best genes as enough genetic diversity to assure that at least some of their offspring thrive. Biologists studying honeybees have found that the queen bee will leave her hive only once, to mate with as many as 25 drones patrolling nearby. Tabulating her wantonness is easy: to complete intercourse, the poor drone must explode his genitals onto the queen's body, dying but leaving behind irrefutable evidence of an encounter.

And while the queen bee does have considerable reproductive demands, needing enough sperm to fertilize about four million eggs, researchers have determined that any one of the drones could provide enough sperm to accommodate her. They, therefore, suspect that her profligate behavior is intended to insure genetic diversity in her brood.

The Devious Males: Strategies For Success

But biologists say there are evolutionary counterbalances that can keep cheating in check. Females that actively seek outside affairs might risk losing the devotion of their own mates. Researchers have found that among barn swallows, a male that observes his mate copulating with other males responds by reducing his attention to her babies. Of course, males themselves are always attempting to philander, say biologists, whether or not they are paired to a steady mate at home. In an effort to spread their seed as widely as possible, some males go to exquisitely complicated lengths.

A Kind of Betrayal

Studying the purple martin, the world's largest species of swallow, Dr. Gene S. Morton, a research zoologist at the National Zoo in Washington, has found that older males will happily betray their younger counterparts. An older martin will first establish his nest, attract a mate and then quickly reproduce, both parents again being needed for the survival of the young.

His straightforward business tended to, the older bird will start singing songs designed to lure a younger male to his neighborhood. That inexperienced yearling moves in and croons a song to attract his own mate, who is promptly ravished by the elder martin. A result is that a yearling male manages to fertilize less than 30 percent of his mate's eggs, although he is the one who ends up caring for the brood.

''The only way for the older males to get the younger females is to attract the young males first,'' said Dr. Morton. ''The yearlings end up being cuckolded.''

Older males often try to appropriate a younger male's partner. Studying mallards and related ducks, Dr. Frank McKinney, curator of ethology at the Bell Museum of Natural History at the University of Minnesota in Minneapolis, has found that males often try to force sex on females paired to other males. The females struggle mightily to avoid these copulations, he said, by flying away, diving underwater or fighting back.

''Our finding is that it's usually the older, experienced males that are successful in engaging in forced copulation,'' he said. They have more skills, and capturing females is a skillful business.''

Guarding the Females

Driven by evolutionary pressures, males have developed an impressive array of strategies to fend off competitors and keep their females in line as well. ''In almost any animal you look at, males do things in order to be certain of paternity,'' said Dr. David F. Westneat, a biologist at the University of Kentucky in Lexington. Mate-guarding is one widespread strategy, he said, with males staying beside females during her fertile times. But other strategies result in what biologists have called ''sperm wars,'' a battle by males to give their sperm the best chance of success.

Among many species of rodents , the last male's sperm is the sperm likeliest to inseminate the female, for reasons that remain mysterious.

Hence, several males may engage in an exhausting round robin, as each tries, repeatedly, to be the last one to copulate with the female.

In studies of the damselfly, Dr. Jonathan Waage, a biologist at Brown University in Providence, R.I., has learned that the male has a scoop at the end of his genitals that can be used before copulating to deftly remove the semen of a previous mate.

In other species, natural selection seems to have favored males with the most generous ejaculation. Over evolutionary time, researchers say, this has resulted in the development of some formidable testicles.

The more likely a female is to mate with more than one male, they say, the bigger the sperm-producing organs will be.

Comparing the dimensions of testes relative to body size among several species of primates, biologists have found that gorillas have the smallest. Among the great apes, a dominant silverback male manages to control a harem of females with little interference from other males, biologists say.

Chimpanzees have the largest testes of the primates relative to body size. They are the ones that live in troupes with multiple males, multiple females, and considerable mating by all.

Human beings have mid-sized testicles, further evidence, biologists say, that our species is basically monogamous, but that there are no guarantees.

One Exception: A Paragon Of Fidelity

But lest everybody cynically conclude that nothing and nobody can be trusted, a study has unearthed at least one example of an irrefutably monogamous animal: Peromyscus Californicus, or the California mouse, found in the foothills of the Sierra Nevada.

Dr. David Ribble, of the University of California at Berkeley, and Dr. Gubernick of the University of Wisconsin have performed extensive tests to prove the rodent's fidelity. DNA analysis has shown that, in 100 percent of the time, the pups are fathered by a female's lifelong mate.

The scientists also have coated the female in fluorescent pigment powders to see with whom the female has contact. ''The powder only shows up on her mate and offspring,'' said Dr. Gubernick. Mother and father split child-rearing duties 50-50 he says.

''This is an extremely unusual animal,'' said Dr. Gubernick. ''It may be one of the only truly monogamous species in the world.''

The Human Urge to Cheat

THE most intrepid biologists are trying to apply the new insights about infidelity among animals to the study of humans. Some say that we are basically a monogamous species, but that the urge to cheat might have an evolutionary basis.

Babies need long-term care, which probably led to pair-bonding among humans early in our evolution, biologists say. But they suggest that a man might be driven to stray from his partner to slip a few more of his genes into the pool. For her part, a woman might philander to mate with a man who has hardier genes than those of her husband.

Dr. Robert L. Smith of the University of Arizona in Tucson, believes that lapses in monogamy helped spawn male sexual jealousy.

''There are nasty cultural manifestations of male jealousy,'' he said. ''Female genital disfiguration, , foot-binding in China - these are mechanisms by which males have controlled female opportunities to run off and mate with other males.''

But women are not entirely helpless, Dr. Smith says. He suggests that evolution has provided them with ways of avoiding being too closely monitored by men, for example, by giving no clue of when they are fertile.

''If males don't know when their mates are ovulating, they can't be so diligent about guarding their partners during that time,'' said Dr. Smith. ''That allows women to exercise their reproductive options,''

Another way that women may exercise such options, Dr. Smith suggests, is by having breasts. ''In great apes, conical breasts are a signal that a female is lactating and thus has low reproductive value,'' he said. ''By having perennially enlarged breasts, women make it ambiguous to males when they're fertile and when they're lactating,'' again confusing men about when to guard their partners.

Nature's Peyton Place

The closer they look, the more biologists are finding that for male and female animals alike, infidelity is not merely the rule, it is practically the law.

THE OLD ROUE

Among purple martins, experienced males mate with their own partners early so they may devote themselves to cuckolding neophyte males later.

By singing distinctive tunes, elders attract younger males, who attract more females. Elder males then sire extra offspring with the debutante females, but leave the job of rearing the chicks to the younger males.

QUEEN FOR A DAY

The queen bee departs her hive only once to collect all the sperm she needs for a lifetime of fecundity. Rendevousing with drones nearby, she mates with up to two dozen, each one sacrificing himself explosively to donate sperm. Biologists think that the queen needs the variety of semen to assure that future bees possess genetic diversity to weather disease and hardship.

SOCIAL CLIMBING

Every spring, black-capped chickadees break up into pairs that are stable and monogamous - most of the time. On occasion, a female will flit from her nest for what biologists call a ''sneaker,'' a clandestine mating with another male. The female invariably chooses a mate who ranks above her partner on the chickadee pyramid, perhaps in an effort to receive his superior genes.

THE JEALOUS HUSBAND

Male Idaho squirrels will chase their mates down a hole to prevent the females from dallying with others.

OZZIE AND HARRIET

Researchers have shown that the California mouse may be one of the very few monogamous species.

EACH day in a healthy human body, at least a trillion cells divide. White blood cells proliferate into fresh legions of T cells, B cells, macrophages and other gladiators of the immune system. The cells that line the stomach divide daily to keep a seamless seal around the belly's caustic juices. As the uppermost layer of the skin sloughs off, newborn dermal cells poke their way up from below. Hair grows; nails grow. Cell division is synonymous with life.

The mystery of how a cell knows when to divide and when to cease division is one of the fundamental puzzles of biology. And lately, through an extraordinary convergence of research from a broad spectrum of disciplines, scientists have made enormous progress in unraveling the pivotal molecular events that control cell division.

Some of the new results were reported last week at a conference at Rockefeller University in New York presented by the General Motors Cancer Research Foundation.

"So many things are coming together from fields that have been developing on their own for years," said Dr. Raymond Erikson, a molecular biologist at Harvard Medical School who attended the meeting. "There's a new synergism that is really exhilarating."

Biologists believe they are close to a deep understanding of the cell cycle, the intricate dance that begins when a cell awakens from its normal state of rest and glissades with balletic precision through the replication of its chromosomes and the apportioning of them into two progeny cells.

This knowledge has coalesced with a swiftness exceptional even for basic biology, which has grown accustomed to a dizzying pace ever since the advent of recombinant DNA technology.

"Our knowledge of the cell cycle compared to just two or three years ago is really the difference between day and night," said Dr. David Beach of Cold Spring Harbor Laboratory on Long Island.

As part of the new dawn, biologists have identified two types of proteins that are indispensable to beginning and completing cell division. Either species of protein on its own is useless -- "a little lump of clay," said Dr. Joan Ruderman of Harvard Medical School, a pioneer in the field.

But when the proteins clasp together they take on the vitality of young lovers, galvanizing a cascade of changes in the cell that culminates in division. The paired proteins seem to work by altering the shapes and duties of a string of other proteins in the cell, and scientists have identified many of those target proteins.

But the coupling is short-lived: researchers have discovered that after each cycle of division, one of the two proteins rapidly disintegrates, an event that seems to protect against untrammeled cell growth.

So exquisitely do the master molecules perform their job that nature has decided to make wide use of them. Among the many exciting findings about the cell cycle is this universality of the central players: the same proteins commanding cell division in primitive cells like yeast are also at the helm in human tissue.

"From my point of view, one of the most astonishing realizations has been that nature used the same elements over and over to control different parts of the cell cycle," said Dr. Steven Reed of the Research Institute of Scripps Clinic in La Jolla, Calif. Clues to Cancer

Scientists are also beginning to knit together the findings about the cell cycle with recent studies of the hormones and peptides in the bloodstream known to stimulate cell growth.

By combining discoveries about the growth signals that bombard the cell from the outside with knowledge of the internal machinery that orchestrates growth, scientists hope to form a complete and finely detailed portrait of the dividing cell. That information will in turn permit them to better understand cell division gone awry, the hallmark of cancer.

"I got into this business for the intellectual satisfaction of it," said Dr. Ruderman, "but I really believe it will tie into something useful."

<> <> Some scientists say an understanding of the nuts and bolts of the cell cycle could provide novel ways to attack cancer cells. They point out that however aggressive and deranged tumor cells become, they still must proceed through the steps of cell division. Hence, they theoretically could be blocked at particular points in the cycle.

But scientists in the cell cycle field say that for all the satisfaction they derive from their work, the pace is beginning to exhaust them. "It's a little frightening," said Dr. Reed. "The ground is always shifting under your feet, and what's true today may be tomorrow's old news. You have to spend a lot of time on the phone or plugged into the rumor mill." The Process Signals For Division

Far from being a fledgling specialty, the study of the cell cycle is among the classic problems of biology, though until recently it interested only a small corps of scientists.

Researchers realized that cells of any sort do not divide willy-nilly, but rather must work their way through defined stages. And before a cell progresses from one stage to the next, it takes a break, apparently to assess whether all the major chores of the previous stage have been completed.

During division, said Dr. Tim Hunt of Cambridge University in England, "the cell comes to a couple of checkpoints, when it asks a number of questions that have to be answered. It may ask, 'Have my chromosomes been replicated? If not, hold off and let me know when it's done so I can move on to the next phase.' " Researchers sought to pinpoint the precise signals that allowed the cell to progress from one phase to the next.

The first wedge into the conundrum came in 1970, when scientists discovered a compound that, when injected into immature frog eggs, forced the egg cells toward maturity by pushing them from one stage of cell division to the next. Scientists purified the protein and experimented with it, but nobody knew quite what it was doing.

In an unrelated pursuit, Dr. Ruderman and Dr. Hunt were analyzing protein production in clam eggs, and in 1980 they made a dramatic discovery. During each cycle of cell divison in the eggs, one protein was created en masse and then destroyed en masse. The scientists named the mysterious protein "cyclin," because it rose and fell with the cell cycle.

They quickly found cyclin in other primitive marine organisms, but at first they had difficulty spotting the same class of proteins in higher animals. "We could see it clearly in clams, starfish and sea urchins, but when we were depressed we thought maybe only the weird sea creatures bothered to have it," said Dr. Hunt. At the Center of the Process

But eventually cyclins were found in other families of animals, and scientists realized that cyclins were somehow at the center of cell division. Only when a fresh batch of the protein is created within the cell can division proceed, and only when that batch is destroyed can division end. The Ringmasters Proteins Act In Concert

In yet another line of research, geneticists identified a peculiar mutation in yeast cells that stopped the cells cold at a particular stage in division: after the chromosomes had been replicated, but before the double set of chromosomes had been divided into two cells. The mutation indicated that a critical protein, needed to catalyze the splitting up of the cell, had been deactivated.

The scientists called the protein CDC, for cell division cycle, and appended a different number to the end depending on who was doing the appending.

The disparate threads of research have come together only within the last couple of years. Scientists have learned that the CDC protein in yeast cells is the same as the protein that prods frog eggs toward maturity. What is more, the same protein has been identified in mammals, including humans, and seems to be crucial to cell division everywhere.

But scientists studying it at first were perplexed, because the protein always seemed to be present in the cell. How then could it know the difference between a quiet cell, a dividing cell, or a cell somewhere in between? Two Proteins Must Mate

The answer proved to be cyclin. Scientists have lately discovered that the CDC protein must find its mate in cyclin before it can do anything about cell division. Cyclin seems to spark CDC to life and allow the colossal task of masterminding cell division to begin.

Somehow, a signal that has yet to be identified spurs the production of cyclin in the cell. That cyclin then joins with the CDC protein, and the division machinery starts up.

More intriguing still, the same CDC protein unites with a different cyclin at different stages of the division process. That molecular fickleness is indispensable and explains why cyclin must be degraded rapidly at every step of the complex cycle: to free the CDC protein for mating with a new type of cyclin.

The various cyclins are created afresh at every point in division, whether before the moment the cell must make new DNA, or during the time when the engorged cell is ready to split down the middle.

"Nature is using a single molecular system to carry out totally different mechanisms" in the cell cycle, said Dr. Beach. "Why keep one subunit around and simply change its specificity subunit? Why not use an entirely new system at each point? We don't know. We haven't found another example of that yet in the cell." Supporting Players Cadre of Proteins Gets Into the Act

What those different mechanisms may be is also becoming clearer, as researchers locate the subordinate proteins in the cell that heed the commanding couple's call to action. Regardless of the stage in division or which type of cyclin is participating in the union, the protein complex does its job of prodding the cell through division with the same technique.

The couple coaxes other proteins into the cell division process by adding phosphate molecules to the deputy proteins, which changes their form and function.

Among the proteins that the CDC-cyclin complex transforms early in cell division are ones that can help generate a new copy of DNA to bestow on a daughter cell. These proteins include molecules that latch onto the existing strand of DNA and help untwirl it, a crucial first step in the replication of its prized genetic information.

Other proteins, when catalyzed by their new phosphate accessories, also clamp onto the DNA and switch on huge batteries of genes, which then perform specialized duties in the baroque operation of synthesizing more DNA.

At a later stage in the cell cycle, once the genetic material has been duplicated, CDC, together with a new cyclin mate, activates important proteins shaped like little spindles. These help yank apart duplicated chromosomes in preparation for division.

The same basic cascading events, with the powerful protein couple doling out phosphate molecules to its minions, seems to apply from yeast to humans, although the complexity soars as the evolutionary ladder is scaled.

"There could be as many as eight different cyclins in mammalian cells," said Dr. Tony Hunter of the Salk Institute in La Jolla, Calif. "And there are probably multiple, parallel pathways that all have to be modulated and regulated before a cell takes its next step in the cycle." Outside Influence The Body And the World

Researchers' big task now is to work their way from the inside of the cell back out to the world around the cell, where signals to divide originate in blood hormones and other growth-promoting molecules in the body.

Here, too, scientists are fast gathering clues. They have begun to understand how certain genes that seem to tune in to growth signals from the bloodstream or from neighboring cells may then communicate with the executors of the cell cycle buried within.

Some of these liaison genes have been found to help spawn cancer when mutated.

"What's really wonderful is that we can begin to think about how all these family members in the cell are talking to each other," said Dr. George F. Vande Woude of the Frederick Cancer Research and Development Center in Maryland. "Some work before cell division, some during, but all are common partners in the dialogue."

In one especially provocative discovery, Dr. Ed Harlow of Cold Spring Harbor Laboratory has focused on a gene called the retinoblastoma gene, known to become mutated in a wide variety of human cancers, including tumors of the eye, bone, breast and bladder.

In its normal state, the retinoblastoma gene acts as an anti-tumor gene, preventing wild cell divison. Dr. Harlow's work suggests that the gene could operate in healthy cells by listening to a wide array of external signals. If the combined messages do not suggest the need for division, the gene could keep the cell in repose by repressing the activity of the CDC protein, among other functions.

Should the outside world signal division time, the retinoblastoma molecule could free the protein to mate with a stimulating cyclin partner. Search for the Full Story

The retinoblastoma gene is an important component of cell growth, but it is only one link in the chain.

Scientists will not be able to boast a complete mastery of cell division until they understand the signals, from the first, faint whisper that new cells are needed, to the end point, when one cell obligingly becomes two. Tracing the pathway back to the original signal that set cell division in motion is a formidable task, but scientists have a rough idea of the sequence.

Initiating signals must come from hormones or other growth-promoting factors in the blood. For example, wounded tissue might release growth hormones to spur surrounding cells to proliferate into a scab.

The hormones would prompt a cell to divide by linking to receptors, proteins studding the surface of the cell that are designed to catch signals from the outside.

Stimulated by the hormones, the receptors would then begin relaying the division signal inward, perhaps by jostling other proteins located a bit deeper within the cell. Like a bucket being passed along a fire brigade, the signal would be carried further and further into the heart of the cell. At some point, the signal must ignite the rapid production of cyclins. The cyclins then meet with CDC proteins and kick the division machinery into action.

But this is little more than a model. Researchers must still identify the vast lineup of proteins between the outside world and the interior machinery of the cell cycle.

"A lot of our understanding of where signals go in the cell and how they're interpreted has been a black box," said Dr. Reed. "But there are plenty of creative people in this field and it's very trendy. So give us a few more years and maybe there won't be any black box left."