ARE COMPUTER SCREENS SAFE FOR PREGNANT WOMEN ?

More than million video display terminals ( VDT ) are now glowing, scanning, taking instructions and solving problems in many offices and homes. They have become indispensable, but are they really safe? The question arises because of persistent worries that video may pose a variety of health risks from cataracts and muscle strain to miscarriages and birth defects. About a dozen unexplained clusters of miscarriages among video users have been reported since 1980, but so far researchers have not been able to confirm a link. Now a study has found that women who used video more than 20 hours a week had almost twice as many miscarriages as women who did other kinds of office work. The authors emphasize that their findings show an association between heavy VDT use and miscarriages but that they're not sure whether the losses resulted from exposure to the equipment or the workplace itself.

The California researchers, led by Marilyn K. Goldhaber, questioned 1,583 women in the San Francisco Bay Area about their pregnancies and their exposure to various environmental hazards during gestation. While all the women who worked in offices had a higher miscarriage rate than those who stayed home, the only significant finding was among administrative and clerical workers. The women in that category who spent more than 20 hours a week in front of a VDT screen had an 80 percent increased risk of miscarriage, compared with workingwomen who didn't use VDT.

Goldhaber and her colleagues, Dr. Robert A. Hiatt and Michael R. Polen, don't think the link they found is the result of radiation exposure. Extensive testing, they say, has virtually eliminated ionizing radiation as a health hazard for VDT users. And if the very low frequency, nonionizing radiation that VDT' also emit were causing miscarriages, the problem would have occurred in all the occupational groups studied. This suggests to us that it's something to do with the occupation, says Hiatt. Maybe it's not conducive to a good pregnancy to be under a lot of deadline pressure, not to have job autonomy and to sit in a cramped position. The findings could also be explained entirely by distorted recollection, says Goldhaber. When women who had miscarried were interviewed, for example, they might have unwittingly overestimated the time they spent in front of a VDT.

Other research teams are also looking at possible links between VDT and pregnancy problems. One at the National Institute for Occupational Safety and Health is investigating miscarriage rates among 4,000 telephone operators, half of whom work in front of VDT while the other half do not. In the realm of comparing jobs in various industries, they are the most similar we could find, says epidemiologist Teresa Schnorr, director of the study. Researchers at New York's Mount Sinai Medical Center are about to launch the first prospective study, they will follow 8,000 female office workers and determine the effect of VDT exposure on those who conceive. Meanwhile, says Goldhaber, women who work with VDT should not be alarmed, but they can take precautions. Pregnant women who use VDT for more than half the working day, she advises, should take frequent breaks, make sure to sit in an unstrained position and intersperse non VDT work with VDT work. Indeed, that's good advice for anyone who works with a VDT.

HOW TO BUILD IMMUNE SYTEM ?

Need a hand, or perhaps a liver? Scientists are finding ways to help you grow your own. There is a human liver sitting in a lab dish in Madison, Wisconsin. Also a heart, a brain and every bone in the human body-even though the contents of the dish are a few cells too small to be seen without a microscope. But these are stem cells, the most immature human cells ever discovered, taken from embryos before they had decided upon their career path in the body. If scientists could only figure out how to give them just the right kick in just the right direction, each could become a liver, a heart, a brain or a bone. When a team from the University of Wisconsin announced their discovery last fall, doctors around the world looked forward to a new era of medicine-one without organ-donor shortages or the tissue-rejection problems that bedevil transplant patients today.

Doctors also saw obstacles, though. One of them was a U.S. Congress skittish about research on stem cells taken from unwanted human embryos and aborted fetuses. Indeed, last week 70 law makers asked in a firmly worded letter that the Federal Government ban all such work.

Yet the era of grow your own organs is already upon us, as researchers have sidestepped the stem-cell controversy by making clever use of ordinary cells. Today a machinist in Massachusetts is using his own cells to grow a new thumb after he lost part of his in an accident. A teenager born without half of his chest wall is growing a new cage of bone and cartilage within his chest cavity. Scientists announced last month that bladders, grown from bladder cells in a lab, have been implanted in dogs and are working. Meanwhile, patches of skin, the first tissueengineered organ to be approved by the U.S. Food and Drug Administration, are healing sores and skin ulcers on hundreds of patients across the U.S.

How have scientists managed to do all this without those protean stem cells? Part of the answer is smart engineering. Using materials such as polymers with pores no wider than a toothbrush bristle, researchers have learned to sculpt scaffolds in shapes into which cells can settle. The other part of the answer is just plain cell biology. Scientists have discovered that they don't have to teach old cells new tricks; given the right framework and the right nutrients, cells will organize themselves into real tissues as the scaffolds dissolve. I'm a great believer in the cells. They're not just lying there,looking stupidly at each other, says Francois Auger, an infectious-disease specialist and builder of artificial blood vessels at Laval University in Quebec City. "They will do the work for you if you treat them right.

FLESH AND BONES

Treating bone cells right is what Charles Vacanti, an anesthesiologist and director of the Center for Tissue Engineering, has been doing at the University of Massachusetts Medical Center in Worcester. When that machinist lopped off the top of his thumb, Vacanti took some of the victim's bonecells, grew them in the lab and then injected them into a piece of coral fashioned into the shape of the missing digit. Coral's got lots of interconnected channels for the bone cells to grow in, says Vacanti. It also degrades as bone replaces it. The patch was implanted back on the thumb a few months ago. It looks like he's growing good bone, Vacanti reports. He could get most of his function back.

Moving from the thumb to other hand parts, Charles' brother Joseph Vacanti, a transplant surgeon and tissueengineering pioneer in his own right, has grown human-shaped fingers on the back of a mouse, demonstrating that different cell types can grow together. He and colleagues at Boston's Massachusetts General Hospital shaped a polymer to resemble the end and middle finger bones. These shapes were seeded with bone, cartilage and tendon cells from a cow. Then the medical team assembled the pieces under the skin of the mouse, just like you'd assemble the parts of a model airplane, says Vacanti.

VEINS AND ARTERIES

Blood vessels present a special challenge they must be strong yet flexible enough to expand and contract with each heartbeat. Joseph Vacanti's group has grown a tube of sheep-muscle cells around a polymer, added closely packed lining cells to the inside and stitched it into a sheep's pulmonary-artery circuit. Blood pulsing against the walls gradually strengthens the muscle cells just as weight training builds biceps. To make vessels, Laval's Auger bends a sheet of muscle cells round a plastic tube and reinforces it with an outer layer of stiffer cells. The he removes the tube and seeds the inside with lining cells, which soon grow together. The vessels have worked well in animal tests, and in the lab have withstood blood pressure 20 times normal

LIVERS AND BLADDERS

Anthony Atala, a surgeon who makes bladders at Boston's Children's Hospital, has taken muscle cells from the outside of dog bladders and lining cells from the inside and grown them in his lab. The cells, fed the proper growth -prompting chemicals, happily go forth and multiply. In six weeks we have enough cells to cover a football field, Atala says. He placed a few muscle cells on the surface of a small polymer sphere and some lining cells on the inside. When he inserted the sphere in a dog's urinary system, the artificial bladder began to function like the real thing. Bioengineer Linda Griffith at nearby Massachusetts Institute of Technology is doing similar work with rat-liver tissue.

THE HEART AND BEYOND

One drawback with all these techniques is that it takes time, usually several weeks, to grow organs using the patient's own cells.Although using these cells sidesteps the rejection problem, time is a luxury many patients, particularly heart patients, can't afford. So Michael Sefton, who directs the tissue-engineering center at the University of Toronto, has proposed building a heart in a box complete with chambers, valves and heart muscles from cells genetically engineered to block the signal with which the body marshals cells to attack invaders. Sefton envisions spinoffs along the way-like immune system resistant replacement valves to justify the project’s $5 billion cost.

Replacement hearts-or even cells replacement heart parts are at least a decade off, estimates Kiki Hellman, who monitors tissue engineering efforts for the FDA. Any problem that requires lots of cell types talking to one another is really hard, she notes.Bone and cartilage efforts are much closer to fruition, and could be ready for human trials within two years. And what of those magical stem cells that can grow into any organ you happen to need-if the law, and biologists' knowledge, permit? Using them says Sefton, is really the Holy Grail

DOWN SYNDROME

What is the real significance of Mary Boss? She is 13 years old, a sixth grader at Greenwood Middle School in New and to all outward appearances a human being. You would have to look under a microscope to see that she has an extra chromosome in each of her cells, resulting in the cluster of symptoms including mental retardation, known as Down syndrome. Her speech is slurred in spots but understandable, her ambitions to be a mountain climber and a hairdresser-not that remarkable; yet she walks among us as a living example of the inadequacies of our intellectual categories. Ask a biologist to define a human being and he might begin with the statement that a human being is an animal with 46 chromosomes in his cells. And here is Mary Boss, who has 47. People like her are, literally, expanding our definition of who is human

It is hard to convey just how revolutionary is the sight of Mary Boss playing soccer, let alone Scrabble. Just a generation ago it was considered axiomatic that children with Down syndrome were severely retarded. The state of the art medical advice was to place the infant in a state home at birth, for the good of his siblings and his parents' marriage. Raised amid unspeakable neglect in institutions like New York's Willowbrook, they lived to an average age of about 20, and died, often without so much as learning to speak. Today it is just about out of the question to institutionalize a Down syndrome infant at birth, according to David Rothman, professor of social medicine at Columbia University. And researchers increasingly believe most Down syndrome children fall into the mild- to moderate range of retardation, with a few able to approach if not actually enter that realm whose name parents whisper with awe and trepidation and longing, normal.

Unimagined potential:

There was no great medical breakthrough at work; the revolution was led by parents who rebelled at surrendering their children to places that were near neighbors to dungeons. Its scientific pioneers, observes Lynn Nadel of the science advisory board of the National Down Syndrome Society, were frequently researchers who were studying something else entirely, such as language acquisition. Certain theories could be tested easily on Down syndrome patients, and almost as a by product researchers began to appreciate their ability to learn. Only in the last decade, says Nadel, with the maturing of the first generation raised at home by their parents, has it become clear that Down syndrome children have as yet unimagined and unrealized potential.

Because the field is so new, no one can say how far that potential might extend. This much has long been known about Down syndrome: that it is an inherited disorder characterized by a redundant third copy of the 21st chromosom, that it occurs approximately once in 800 to 1,000 births, around 5,000 cases a year in the United States; that it is characterized by a distinctive appearance and varying medical conditions that may include heart and immune defects, and that the brain is always small and some degree of mental impairment is always present. But in at least two areas there have been significant new findings from which parents can take hope.

The first of these is the critical importance of early infant stimulation. There is nothing mysterious about this technique it means talking to, playing with and exercising the infant-activities that are recommended for normal babies as well-but rigorously, for several hours a day. You had to keep winding that mobile, remembers Mary Boss's father, Bill. The mobile is not to teach the baby how to tell a duck from a rabbit; it is a way of literally accessing the physical brain, of forging at an early age the neural connections that are essential for higher thought. There is even a theory that stimulation minimizes selective neuronal debt the natural process in which unused cells in the brain die off in the early years of life. Normal newborns have a surplus of neurons and can afford to lose some. With smaller brains to begin with, Down syndrome infants need to exercise theirs as early as possible. I think most Down syndrome children will be only mildly retarded or learning disabled if we can do early intervention, says Dr. Krystyna Wisniewski of New York's Institute for Basic Research in Developmental Disabilities.

The other discovery is that whether or not you can make Down syndrome kids smarter, you can certainly make it appear that way by improving their language skills. Virtually all Down syndrome children have serious problems with receptive and expressive language. This is partly the result of hearing loss, owing to their propensity for ear infections and partly the result of poor coordination and articulation. But Laura Meyers, a linguist at UCLA, believes there is a deeper problem an inability to perform the rapid auditory processing needed to understand spoken English. They get left out of the dialogue, she says; their brains are not getting the information needed to understand language. In particular, she believes that Down syndrome children simply don't hear short, unstressed words, which include most of the articles and prepositions that hold the language together.

The solution, she believes, lies in the computer, augmented with a voice synthesizer. In one of her studies, toddlers are presented with special keyboards with pictures of toys and actions, they learn to swat the appropriate picture to communicate simple wants and ideas. In another study, school age Down syndrome children have regular keyboards and a more ambitious agenda: to learn syntax and grammar. They say things like Want go Donald Tom, Meyers says. So you have to say, Oh, you want to go to McDonald with Tom. On the screen, the words that slip by so quickly in conversation are captured and made visible; the measured and uninflected voice of the synthesizer renders them a audible. It is a gross heresy in education to proceed from written language to spoken, rather than the other way round. But try telling that to Ralph Bingener, a 17 year old with Down syndrome. Why do you like writing on computers? Meyers asks him; and he replies, My ideas are really fruitful on the computer.

GETTING STARTED

The growing acceptance of programs such as Meyers's has given rise to a new phenomenon, the Down syndrome computer jock. Matthew Costea, six, first started working on a keyboard at three, knew his alphabet at four and scores average on a test of reading recognition. He has been in a trainable class, where he learns simple life skills such as getting dressed and crossing the street, but Wisniewski is urging Matthew's parents to put him in a more demanding educable program. The choice of a program can be a difficult one for parents, torn between wanting their children to learn as much as possible and the need for them to practice buttoning, zipping and tooth brushing. Mary Boss was in regular classes through fourth grade, and then, reluctantly, moved to a learning disabled program; her reading and English have kept up, but she has fallen behind in math.

And for the future? Mary knows she is different, of course, but she doesn't see it as an impediment to happiness. I'll be a mother, of course, she says. When I get older, I'll marry my boyfriend, which is Gary, when we both get older, make that. We stick together, me and Gary, because we both have Down syndrome and stuff. Whether or not she will marry, it is considered unlikely that she-or any Down syndrome patient-will ever be completely independent. I'm not sure that's the goal, says Nadel. The ability to live in their own apartment and balance their checkbook is not the issue. Matthew's mother has what is considered a realistic goal for a Down syndrome child, to live in a supervised group home, help with the cooking and go to a vocational program during the day. Modest, except by comparison to what his fate would have been just a generation ago to sit on a chair in a musty day room and mutely stare at the wall until he died. That they used to institutionalize these guys just amazes me, his mother says. Thank God it didn't happen to him.

THE ESTROGEN DILEMMA

Many women won't take the hormone for fear of cancer. Could new designer drugs be the answer'? Evelyn Levin, an artist in had a tough decision to make. The bones in her hips, thighs and spine were losing mass. But Levin, whose mother also suffered from the general weakening of the bones known as osteoporosis, didn't want to take estrogen. Although the hormone can reverse the bone‑weakening process, it may also increase the risk of breast cancer. So Levin volunteered for a study of an experimental drug called raloxifene, which may confer most of the benefits of estrogen therapy without the risks. Although her doctors won't tell her whether she's on the drug or the placebo, Levin is prettv sure she's getting the real thing, Every time they do a scan, she notes, my bone density keeps improving.

Sooner or later, every woman of a certain age has to face the question of whether or not to take estrogen. Once she reaches menopause, her body's supply of the natural hormone plummets, triggering such symptoms as night sweats and hot flashes. Decades of research have shown that estrogen is the closest thing to a perfect antiaging potion. It moisturizes the skin, maintains strong bones and protects against heart disease. It may even delay the onset of Uzheimer's disease. There is one big catch, however: estrogen may increase as much as 40% the risk of developing breast or uterine cancer.

Now a new generation of compounds, often called designer estrogens, promises to tip the balance in favor of treatment. Last week the experimental drug that Levin thinks she's taking, raloxifene, became the first of them to win endorsement from an advisory panel to the U.S. Food and Drug Administration, the initial step toward full‑scale approval. Barring any complications, Eli Lilly could bring the drug to the U.S. market in a matter of months.

Raloxifene is one of a group of compounds whose formal name (which only a scientist could love) is selective estrogen response modulators, or SERMS. They are designed to mimic the hormone's good qualities while avoiding its bad ones or at least that's the theory. Although SERMS have been widely publicized and are likely to find a big market, some doctors and women's health groups are sounding a note of caution. To get the best protection against osteoporosis, they note, women might have to take raloxifene for decades. And because the drug has been studied in humans for only a few years, nobody knows what its long‑term effects might be.

Scientists first became interested in designer estrogens in the early 1990s. While studying a powerful new anticancer drug called tamoxifen, which works by blocking estrogen's ability to stimulate breast tissue, they discovered that it also helped prevent osteoporosis. The drug seemed to act like an estrogen in the bone but an anti‑estrogen in the breast. Unfortunately, it also acted like an estrogen in the uterus, dramatically increasing the risk of uterine cancer. So researchers set out to find a chemical cousin of tamoxifen that would be easier on the uterus.

Raloxifene seemed to fit the bill. Studies showed it increased older women's bone density 1% to 2%. It also seemed to reduce the incidence of breast cancer by 58% over the course of a year in one study and to cut the level of so‑called bad cholesterol in the blood. Best of all researchers have found no hint of trouble in their patients' uterine or breast tissue at least not yet.

The greatest unknown, from a scientific point of view, is raloxifene's effect on the brain. The drug is known to increase the number of hot flashes, which are usually triggered by the brain's attempts to deal with falling hormone levels. This suggests that raloxifene might act as an anti estrogen in the brain. Recent studies have shown that estrogen may provide some protection against dementia and other types of nerve disorders. Therefore, taking raloxifene for long periods of time could theoretically increase the risk of developing Alzheimer's disease.

Just as troubling, a woman who has taken raloxifene and then develops breast cancer may reduce her options for fighting the malignancy. Because raloxifene is a distant cousin of the cancer fighting drug tamoxifen, some scientists are worried that any tumor cells that survive are likeiy to be resistant to tamoxifen as well.

Women like Evelyn Levin may be left weighing the poten­tial benefits of the new drugs against their unknown risks. For example, asks Dr. Ethel Siris, an endocrinologist at Columbia Presbyterian Medical Center in New York City, what do you do about the woman whose father had a heart attack and whose mother had breast cancer and also broke a hip? Raloxifene won't make her problems go away, but it may give her a little more room to maneuver.

BEWARE OF MADCOW

A year after the British cattle scare, some scientists fear a broader outbreak of the mysterious disease. Peter Hall did not notice when the proteins in his brain started to change. He noticed other things: a vague depression, general anxiety, sudden mood swings. But blaming any of that on brain chemicals wouldn't have occurred to him.

The proteins in Hall's brain were changing, however. Ordinarily made up of tiny strands of intertwined amino acids the complex molecules had begun to assume a very different shape, collapsing into sticky sheets. Before long, these gummy structures began to clump sloppily together, creating pits and divots where there had once been vital brain tissue. Within months Hall was delusional and bedridden. Not long after, he was dead.

Hall, who was 21, was one of nine Britons felled in 1996 by a brain disorder linked to exposure to bovine spongiform encephalopathy (BSE), better known as mad-cow disease. The appearance of this degenerative disease widely suspected to be contracted by eating contaminated beef organs-set off a panic as Europe slammed its doors to British beef, and travelers anxiously cast their minds back to London vacations, trying to recall whether they had ordered the fish or the sausage.

The scare died down after the British government destroyed tens of thousands of cattle, removed infected feed from the food chain and promised to step up slaughterhouse inspections. Mad-cow disease has stopped turning up in the new generation of cattle, and the crisis is generally considered to have passed.

That conclusion may be premature. While public health officials believe the risks are remote, concern is building in both Europe and the U.S. that the madcow problem may be larger than it seems. This week the science journal Nature published a paper on the possibility that last year's outbreak might be only the tip of an epidemiological iceberg, and that tens of thousands of Europeans are unknowingly infected and could die from the disease. Moreover, a number of researchers in the U.S. aren't convinced that some of the same conditions that led to the mad-cow breakout in Britain might not exist in the U.S, leading to the same spread of the BSE pathogen. Making things even harder, scientists still can't agree on what that pathogen is-a first step in figuring out how to treat the disease if it does surface. The only thing that stands between us and an epidemic, says Robert Rohwer, director of molecular virology at the Veterans Administration Medical Center in Baltimore, is unmitigated luck.

Britain's problems began in 1986, when a BSE epidemic struck herds across the country, ultimately leading to the death of up to 1,000 cows a week. To protect the food supply, the government ordered the slaughter of affected cattle and banned the sale of cow brains, intestines and other offal, thought to be the organs likeliest to harbor the disease. And in 1988 it halted the practice of feeding cattle the remains of diseased sheep, which is where the infection is believed to have started. But by that time the damage was done.

The cheapest way to get protein into cattle is to feed them scraps of animals left over from slaughter, says Richard Rhodes, author of the soon-to-be-released book Deadly Feast (Simon & Schuster), which traces the history of BSE and similar diseases. When British cows started to get sick, this practice wasn't banned. Instead industry was merely required to avoid using parts from animals known to be infected. This was hardly foolproof, and it was inevitable that some diseased flesh would be eaten by cows and enter the food chain.

When Britons started falling ill last year, some scientists concluded that that was just what happened. If cattle feed was indeed the indirect avenue of the recent infections, it could spell big trouble, since most Britons ate from a contaminated meat supply for at least 10 years. just how many got bad beef is what the Nature paper tried to determine.

Using a complex epidemiological model, the study concluded that the outlook for the beef-eating population is unclear: at the very least, an additional 75 Europeans will come down with the disease; at the very worst, a chilling 35,000 could fall ill. The researchers caution that too little is known to make confident projections, and in Britain the paper has had little impact. Beef consumption is about where it was a year ago, and although the government last week banned the transplantation of animal organs into humans, saying the risks needed to be studied, no new panic has broken out.

Ironically, the Nature paper generated concern in the U.S. where not one case of mad-cow disease has been diagnosed. I hope we're not on the same course as the British, says Rohwer, but we could be. What concerns Rohwer and others is that the U.S. agricultural industry, like its British counterpart, recycles animal scraps, turning them into both cattle feed and garden fertilizer. Should even one domestic cow develop the disease spontaneously-something that is known to occur in nature-the pathogen could quickly spread through U.S. herds.

In order to prevent that, U.S. Food and Drug Commissioner David Kessler is proposing a new measure-set to take effect later this year-that forbids using cattle parts in animal feed but still permits them in fertilizer. The government concedes that switching to protein substitutes like soy would cost U.S. feed producers up to more $48 million a year, and the industry insists that the final figure would be much higher. Whatever the price, however, Kessler believes it's worth it. The risk of BSE is small but real, he says. If a case did occur in this country, we want to wall it off and not have the amplification that occurred in Britain.

Of course, no regulatory measure will take the place of finding a way to treat or prevent BSE infection. But the disease may at last be starting to give up its secrets. A number of researchers are convinced that mad cow is caused not by a common bacterium or virus but by a vanishingly small crumb of protein known as a prion.

First postulated in 1982 by neurologist Stanley Prusiner of the University of California, San Francisco, prions are thought to be strikingly similar in their amino-acid sequence to proteins found naturally on the surface of certain brain cells but strikingly different in shape. Some types of normal brain proteins form open coils that allow them to be destroyed by protective enzymes when they become damaged. Studying diseased animal brains, however, Prusiner concluded that prion proteins form sticky sheets that are impervious to this defense system. When the two proteins come into contact, the sticky ones seem to induce the coiled ones to assume the new shape, forming the protein clots seen in the brains of mad-cow victims. Prusiner believes diseases like BSE start when a single prion is introduced into the body-either by ingestion or chance mutation-and begins converting brain proteins.

Not all researchers are sold on the prion theory; many believe that a more traditional pathogen like a virus will yet be isolated. Last week this camp got a boost when the journal Science published a study in which a group of lab mice injected with BSE-infected tissue all came down with the disease, yet fewer than half were shown to harbor Prusiner's infectious prions. Opponents of the prion theory say this proves the proteins don't cause disease. Proponents insist that the methods used to detect the molecules were simply not sensitive enough.

Whoever is right, it's in no one's interest for the debate to go on too long. There are more 44 million head of cattle in the U.S., and 7 million are killed for food each year. If just one of those slaughtered cows turns out to be a mad cow, the illness that's now an ocean away could establish its first beachhead on American shores.

PRIONS IN ACTION

Abnormal proteins, known as prions, may trigger mad-cow disease simply by coming into contact with healthy proteins in the brain. A healthy brain protein is made up of strands of amino acids twirled into helices. Prions are thought to be made of the same amino acids flattened into sheets. When a prion touches a protein, the protein flattens out too. A chain reaction of such transformations ravages brain tissue.

MULTY FUNCTION OF THE NOSE

It's well known that women who live in close proximity tend to menstruate on the same schedule. No one knows exactly what triggers this intriguing phenomenon, but it has been documented repeatedly in recent decades, and it could have big implications. It may show that humans, like other animals, communicate subconsciously through odorless substances called pheromones. Scientists have known for more than a century that our noses house a tiny structure known as the vomeronasal organ (VNO).

Most have dismissed it as an idle vestige of our evolutionary past, but that consensus is eroding. Some now view the VNO as a sensory organ an with its own pathway to the brain. They believe it may affect everything from mood to sex and though the evidence is still sketchy, entrepreneurs are racing to exploit it. Pheromones pervade the animal world. They're pollenlike chemicals that, when emitted by one creature, have some effect on other members of the same species.

And as the Dutch psychologist Piet Vroon makes clear in his recent book Smell: The Secret Seducer (226 pages. Farrar, Straus.), they can pack a wallop. The pheromones produced by queen bees stall sexual development in other females (who then become workers). Male mice use pheromones to promote the sexual development of nearby females and, when it's convenient, to induce abortions. The effects are subtler in large mammals but no less remarkable. If a sow or a cow is in beat, a whiff of the pheromones contained in male urine will send her into a mating stance. Conversely, a male rhesus monkey loses libido if you block his VNO.

It's not clear whether humans produce actual pheromones, but our body fluids contain sex-specific chemicals called androstenes and copulines, which can have pheromonelike effects. Researchers have synchronized women's menstrual cycles with those of complete strangers, simply by exposing them regularly to extracts from the strangers' perspiration. Studies have also shown that women have less variable periods if they're routinely exposed to male sweat. And when researchers have sprayed human androstenes on seats in a theater or waiting room, women have become more likely and men less likely to sit in them.

Most experts regard these as hints, not proof, that pheromones affect people. But David Berliner, an anatomist turned entrepreneur, has no doubt. He and his colleagues think they have identified a dozen human pheromones. Since 1994 the California-based Erox Corp has peddled three of them in pricey perfumes called Realm Men, Realm Women and Inner Realm. The fragrances allegedly transcend the five senses and awaken the sixth-but don't get the wrong idea. The makers say they're not designed to send lewd signals, just to enhance the user's own sense of comfort, security, well-being and confidence

Do they work? Studies have shown that their patented chemicals stimulate the VNO and that people who sniff them in a lab experience a slight drop in heart rate, respiration and body temperature. Whether that translates into anything psychologically meaningful is another matter. Berliner's group claims that participants in an unpublished study felt happier and less tense after sniffing Realm's patented ingredients, but other experts are wary. Their findings need to be replicated in other laboratories, says Wysocki, a neuroscientist.

Until that happens, Realm won't revolutionize neuroscience. But it may still shake up the fragrance industry. Erox CEO William Horgan hopes to license the ostensible pheromones for use in everything from fabrics to air fresheners. When you're rubbing your nose into a pillowcase be says, imagine there's something soothing we could impregnate into that pillowcase. By all means, imagine.
Sweet dreams.

HEADACHE

As doctors learn more about our throbbing heads, they are uncovering amazingly effective ways to kill the pain before it starts. For Henry Schipper 49, of Venice, California, the first warning signs are mild and almost pleasant a giddy light headedness that evolves into what he describes as a happy series of energetic moments.Then for about 15 minutes his eyes play tricks on him, and a wall of shimmering light obscures his field of vision. There's no pain at that point, says Schipper, who produces docu­mentaries for the History Channel. But once the shimmer starts, the countdown begins. If Schipper can't get to his medication quickly or if it doesn't kick in, he will experience a neuro­logical event that million people in the world know all too well about the migraine.

For Schipper the pain is sudden and sharp. The front quarter of my head begins to pound and throb, he says. In extreme cases, he vomits violently every 20 minutes. His senses of smell and hearing become agonizingly acute. All I want to hear is gentle white noise at most and no movement, please. If there's a car alarm that goes off nearby, it's unbearable. It was not that long ago that migraine sufferers like Schipper had no choice but to retreat to their darkened bedroom and wait, often for days, until the agony passed. Doctors could prescribe heavyduty painkillers, but regular use often triggered even more painful episodes Making matters worse, friends and co-workers tended to treat headache sufferers as the punch line of a bad joke, as if they were having headaches on purpose to avoid work or sex or some deeply repressed memory.

That bleak state of affairs is changing rapidly. Now physicians have at their disposal a growing arsenal of headache drugs medications that can stop an accelerating migraine in its tracks, reduce the risk of recurrence or, in some cases, keep one from happening in the first place but scientists are starting to uncover subtle defects in brain chemistry and electrophysiology that lead not just to migraines but to all kinds of headaches. Indeed, many neurologists now believe that most severely disabling headaches are actually migraines in disguise and so are more likely to respond to migraine medications than to standard analgesics such as aspirin, ibuprofen or acetaminophen.

What it all adds up to is a revolutionary view of extreme headaches that treats them as serious, biologically based disorders on a par with epilepsy or Alzheimer's disease. Before, patients got shipped around from doctor to doctor until eventually they wound up at a psychologist, says Dr. Joel Saper, director of the Michigan HeadPain and Neurological Institute in Ann Arbor. Now their headaches are seen as the result of wayward circuits and molecules, not personality disorders.

The revolution in migraines was very much in evidence last week in London as more than 600 scientists from 32 countries gathered for the biennial symposium of the Migraine Trust (whose patron, the late Princess Margaret, suffered from migraines). A ripple of excitement followed reports of progress in blocking a key neuropeptide called CGRP (more on that later). But the biggest headlines came from a seemingly unlikely source, the anti-epilepsy drug topiramate. Dr. Stephen Silberstein of Thomas Jefferson University in Philadelphia presented a study of nearly 500 patients showing that topiramate significantly reduced both the occurrence and duration of migraines offering hope that a whole class of existing anti seizure drugs could someday help migraine sufferers put an end to attacks before they occur.

Researchers aren't yet sure whether they have identified all the pieces of the puzzle or if they know the order in which those pieces fall. Does it all fit together in a cogent picture? asks Dr. K. Michael Welch, a migraine researcher at the University of Kansas Medical Center in Kansas City. I don't know. But we know a bell of a lot more than when I started in this field 25 years ago.

First, let's define a few terms. Doctors divide headaches into two broad categories: those that are self-contained (primary headaches) and those that result from another illness or accident (secondary headaches). The best treatment for a secondary headache depends on its origin. For example, an antibiotic may be prescribed for a headache caused by a bacterial infection.

The most common type of primary headache is the familiar tension headache, which is usually stress related. (Doctors now label it a tension-type headache to counter the idea that knotted muscles are the principal cause.) In most cases, a couple of aspirin and a good nights sleep are all that's required to get rid of one.

Not so the mercifully uncommon cluster headache, so named because an attack, typically repeats itself, often daily, with each episode lasting anywhere from an hour to an hour and a half. Cluster headaches usually strike their victims, generally men, at fixed times of the year. The pain is so searing that they are also known as suicide headaches. Immediate treatment with oxygen and migraine drugs given intravenously can sometimes provide relief.

Somewhere between tension and cluster headaches are migraines. Typically, the pain from a migraine is a throbbing one, restricted to one side of the head that gets worse with movement and lasts from four hours to three days. Migraines are usually accompanied by either nausea and vomiting, as they were for TV producer Schipper, or extreme sensitivity to both light and sound. By contrast, patients suffering from tension type headaches may react badly to either light or sound but not both.

It is a mistake, however, to stick too rigidly to these definitions. At one time people thought that migraine was a disorder all its own and that tension-type headache was totally separate, says Dr. Ninan Mathew, director of the Houston Headache Clinic. Now we realize that headaches are not that clear cut. Indeed, Mathew says, nearly any recurring headache that is debilitating enough to keep you away from work or the things you enjoy is probably a migraine.

As far back as the 1600s, the prominent English physician Thomas Willis suggested that headaches are caused by a rapid increase in the flow of blood to the brain. He theorized that the suddenly bulging blood vessels put pressure on nearby nerves and that these in turn trigger the pain. A variation on Willis' idea became the favored explanation for the cause of migraines (An important network of blood vessels at the base of the brain bears Willis'name.)

Two things have occurred in the past couple of decades to alter that view. First, several imaging techniques were developed that allowed doctors to study blood flow in the living brain. Second, scientists learned a great deal more about the nerve endings that are embedded in the dura mater, the fibrous outer covering of the brain. Armed with these tools and that information, researchers concluded that the order of events in a migraine is not as straightforward as they had been taught. The nerve endings in the dura mater appear to act first, releasing proteins that cause the blood vessels to open and prime the nerves to maintain a state of alert. In other words, swollen blood vessels are the result of a growing migraine, not its cause.

Tracing the pathway of the affected nerve endings deeper brain led researchers to the trigeminal nerve, a complex network of nerves fibers that ferries sensory signals from the face, jaws and top of the forehead to the brain. During the course of a migraine, scientists discovered, the trigeminal nerve practically floods the brain with pain signals. The more researchers learn about the trigeminal nerve, the more they believe that it is involved in all types of primary headaches, including tension and cluster headaches. The differences in the headache types seem to stem from what activates the trigeminal nerve and how it responds.

So much is happening all at once during a migraine that it has been hard to pinpoint what sets off the trigeminal nerve. Some scientists are focusing on a wave of electrical activity that spreads across the brain just before a migraine and triggers the aura-the shimmering light show experienced by I in 5 migraine patients. Others wonder whether there is some kind of migraine generator buried deep within the brain stem. Even when researchers think they know the order in which different parts of the brain turn on during an attack, they can't always be sure if one section is initiating an action or anticipating the need to respond.

What seems clear, however, is that the brain of a migraineur (as sufferers are is primed overreact to all sorts of stimuli that most people can easily tolerate. The brain receives input from a wide variety of triggers-stress, hormones, falling barometric pressure, food, drink, sleep disturbances, says Dr. David Buchholz, a neurologist at the Johns Hopkins University School of Medicine in Baltimore, Md. Each of us has his own stack of triggers and his own personal threshold at which the migraine mechanism activates. The higher the trigger level climbs above the threshold, the more fully activated the migraine system-and the more pain.

In this view, people who are prone to migraine have a low threshold for activating the trigeminal nerve. Those who suffer only an occasional tension-type headache have a much higher threshold. Persistent treatment of acute attacks and prevention of additional ones may reset the brain I s threshold point at a higher level.

Researchers are exploring the possibility that migraine sufferers are not just hypersensitive to various triggers but that their brains have lost some of their natural ability to suppress pain signals. To find out more, scientists are studying a part of the brain called the periaqueductal gray matter, which, says Dr. Welch in Kansas City, switches off the pain response so that you can focus on the fight to survive. It's the reason why if you have a cut that you don't remember getting, it doesn't start to hurt until you actually look at it.

Each time a migraine occurs, Welch and others have found, the periaqueductal gray matter fills with oxygen, which triggers chemical reactions that deposit iron in that section of the brain. As the n builds up, the brain's ability to block out pain decreases. That may explain why many migraineurs become more sensitive to pain with each episode. If overly sensitive M, nerve cells are the problem, it makes sense to try to calm them down- and that's exactly what the first drug tailored to block an oncoming migraine was designed to do. Approved in the U.S. in 1993, surnatriptan mimics the action of a neurotransmitter called serotonin, which plays many roles in the brain, including regulation of mood and pain. In the case of migraines, the drug prevents nerve endings in the dura from releasing their stimulatory proteins. No proteins, no pain.

Sumatriptan's success launched a new class of drugs called triptans that provide most migraineurs substantial relief. Like the painkillers before them, the triptans deliver their best results when taken early in an attack. Unfortunately, their effect is often temporary (drug companies are working on longer-lasting versions). Also, the drugs can trigger certain cardiovascular side effects, which means they should not be used by patients who have an increased risk of heart attack or stroke.

Still, triptans have dramatically changed the lives of millions of migraine sufferers and opened up promising areas of research. Scientists have discovered that triptans, besides affecting serotonin path ways, also directly block one of the stimulatory proteins released by the nerve endings in the dura. New compounds that target this protein, dubbed CGRP, are being tested in Europe. One big problem, says Lars Edvinsson of Lund University in Sweden, is that the drug can be given only intravenously. We need a CGRP blocker that works as a tablet.

Pain relief isn't the only reason to stop a migraine before it goes too far. When the illness goes untreated, there is some evidence of a mechanism in the central nervous system that makes traditional medications less useful, says Dr. Michael Moskowitz, a neurologist at Harvard Medical School in Boston. How that resistance develops is the subject of intense investigation.

Ideally, you'd like to prevent a migraine from occurring in the first place. There is a lot you can do to help yourself. Identifying individual triggers-such as chocolate or fluorescent lights-and keeping away from them as much as possible is an obvious first step. You should also avoid relying too heavily on quick fixes.

People with severe migraine headaches can enter a cycle of taking medications on a daily or near daily basis, says Dr. Sonja Potrebic of the Pain Management Center at the University of California in San Francisco. Initially it helps, but over time the headaches get worse. Painkillers that contain caffeine are the most common cause of such rebound headaches. Taking baby aspirin to prevent a heart attack does not seem to be a problem.

Many migraineurs swear by various nonpharmacological methods of keeping their headaches at bay, such as yoga, meditation and biofeedback. These techniques probably work best for patients whose headaches are triggered by stress or tense facial muscles. One of the surprises of the past couple of years is the effectiveness of botox, which is now being injected into facial muscles to temporarily erase wrinkles. Migraineurs have reported that botox seems to banish their headaches as well. Studies are under way to see if those observations hold up. Lifestyle changes, however, are sometimes not enough to prevent migraines. In such cases, doctors may turn to beta blockers, drugs that were designed to treat high blood pressure. Although these medications open up the blood vessels, which would seem counterproductive if you're trying to prevent a migraine, they also turn out to have a soothing effect on nerve cells.

Similarly, antidepressants have been used to help prevent migraines. If antidepressants were discovered to day and we didn't know they were antidepressants, we'd call them analgesics, says Dr. Seymour Diamond, director of the Diamond Headache Clinic in Chicago. Intriguingly, the pain-fighting effect of antidepressants takes just three to 10 days to kick in, less than half the time needed to alleviate depression. This suggests that depression and migraine are triggered by different, though related, neural pathways.

As helpful as beta-blockers, anti depressants and even anti-epilepsy drugs may be in preventing some migraines, they don't cure the condition. Eventually scientists hope to discover therapies that address the brain's overly sensitive circuits more directly. For what it's worth, getting older seems to soften the blow. Studies show that migraine attacks peak between the age of 35 and 45 and decline after that.

Meanwhile, it may be a process of trial and error for most migraineurs and their physicians. Chances are, however, that more and more of them will, like Schipper,eventually hit on the combination of medications and lifestyle changes that works for them. In his case, careful attention to his triggers along with judicious use of a powerful painkiller has kept his headaches to a minimum. It's a tricky thing to navigate a migraine, Schipper says. You have to be adept at knowing your own patterns. But it can be done. And sometimes knowing that relief is within reach is half the battle.

HOW WE HURT

The first step in treating a headache is to determine what kind you have

M I G R A I N E

This type lasts from four hours to three days, with pulsing pain on one side of the head, nausea and sensitivity to light and sound

T E N S I O N

Diffuse, viselike pressure throughout the head. Attacks last from 30 minutes to a week

C L U ST E R

Also known as suicide headaches, these are the most painful kind. They occur in groups-as often as eight times a day-and are experienced as a searing pressure in one eye

O T H E R

Any number of medical conditions, from viral infection to brain tumor, can cause a headache. Treating the disease usually relieves the pain