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What Mosquitoes Want
March/April 2004
by Bruce Fellman

Professor John Carlson’s biology laboratory often smells like a barnyard. It’s an occupational hazard of working with a chemical called 4-methylphenol, one of the components of human sweat. In the January 15 issue of Nature, Carlson, graduate student Elissa Hallem, and their colleagues describe their discovery that 4-methylphenol is one of the biggest reasons mosquitoes are attracted to humans.

Female mosquitoes feed on blood. (The males don’t bite.) Many species are quite specific about which animal they’ll dine on and even where on the body they’ll alight. Some feed mainly on birds or amphibians, while others prefer people; of the latter, there are mosquitoes that go only for the ankles or only for the forehead. But until now, scientists have never known how the pests locate their dinner. For the ten percent of the world’s population affected by malaria—the insect-borne disease that kills more than a million people, children primarily, each year—the question is urgent.

Carlson, an expert on insect olfaction who previously discovered how fruit flies sense odors, reasoned that mosquitoes had to be tracking some type of chemical scent. “The insect antenna is the equivalent of the human nose,” he says. In collaboration with scientists from Vanderbilt University, he found genes in the female Anopheles gambiae—a mosquito that can transmit malaria—that are related to feeding: “One of these genes coded for an odor-receptor protein that was found only in females and whose production was turned off after a blood meal,” he explains.

Carlson and Hallem then transferred the mosquito gene into a mutant fruit fly whose antennae don’t normally respond to smells. They exposed the fly’s reengineered nerve cells to various odors and tracked the cells' reactions. Carlson says 4-methylphenol got “a whopping response.”

Carlson is getting queries from would-be investors who hope to back either the ultimate mosquito repellent or the ultimate mosquito lure; 4-methlyphenol is already used in Africa to trap tsetse flies. But he believes more work is needed.
“Human sweat is a complex mixture of many things, and the best substance will no doubt be a chemical cocktail that works on a number of different receptors,” he says. “We’ve only taken the first step. So don’t look for this in your drugstore any time soon.”

Drugs and Money
by Marc Wortman

When psychiatry professor Roger Rosenheck started looking into the merits of one of the latest treatments for schizophrenia, he expected to confirm it was effective. Instead, Rosenheck discovered that the widely used drug, olanzapine, isn’t much better for patients than the older drug it supplanted. “The results really surprised me,” he says.

The finding, published in the November 26, 2003, Journal of the American Medical Association, may result in significant savings. At the Veterans Affairs hospitals where the study took place, olanzapine costs eight dollars per patient per day. The older drug costs six cents.

Rosenheck and colleagues compared olanzapine (marketed by Eli Lilly and Company as Zyprexa) with haloperidol, the older and once popular medication sold as Haldol. “There have been a lot of drug company studies claiming olanzapine was a better anti-psychotic,” says Rosenheck. Much of that claim comes because olanzapine does not cause the muscle contractions and tremors that haloperidol can set off. However, physicians frequently pair the older drug with medications that prevent the side effects. According to Rosenheck, the drug company studies did not take into account these “real-world” treatment practices. “They were asking the question in a way that emphasized the advantage of the new treatment,” he says.

Lilly sold some $3.7 billion worth of the drug last year. The researcher who directed its development for Lilly, Alan Breier, did his psychiatric residency at Yale from 1980 to 1984 and is now Lilly’s chief medical officer. “To have conflicting data in the schizophrenia world is the norm,” he says. “The disease itself is so heterogeneous. There are Roger’s findings, and there are studies that go in other directions. The health outcome data have to be interpreted in conjunction with the study methods used.”

Rosenheck’s findings jibe with recent research by a colleague in the psychiatry department. Assistant professor Bruce Baker reviewed 46 papers—nearly every study ever done—that compared the benefits of Prozac, Paxil, Zoloft, and other selective serotonin reuptake inhibitors (SSRIs) with an older family of antidepressants known as tricyclics. SSRIs are now among the world’s most popular prescription medications. Baker’s conclusion, published in the December 2003 issue of the British Journal of Psychiatry: when a drug company pays for research into a newer medication, the outcome will nearly always favor the new drug. “No matter how you cut it,” he says, “sponsorship is related to outcome.”

The Religion Effect
by Jennifer Kaylin

According to recent surveys, four out of every ten New Haven youths have seen someone shot at or shot, and many have been victims of violence. The aftereffects are well documented: 30 years of studies by psychologists have established that children and teens who witness violence are more likely to get into trouble themselves.

But not all do. By analyzing surveys of 1,703 sixth and eighth graders conducted in 2000 and 2001 in the New Haven public schools, Michelle Pearce, a graduate student in psychology, and her colleagues found two factors that help explain why some remain on the straight and narrow.

The keys, said Pearce, lead author of a study that appeared in the November 2003 issue of Child Development, were the degree of parental involvement in the kids' lives and their degree of what she dubbed “religiousness”—church attendance, praying, reading religious literature, and watching religious programs on television, as well as a more subjective self-assessment of the strength of spiritual belief.

The survey, which was part of the New Haven schools' long-term Social and Health Assessment Project (directed by Mary Schwab-Stone at the Yale Child Study Center), confirmed the behavioral risks of experiencing community violence. “The more they saw or the more they were victimized, the higher their likelihood of getting into trouble,” says Pearce. But some experienced “buffering” from these effects, and—especially for those most at risk—parental involvement didn’t account for all of it. For these children, “religion had unique protective effects.”

It was the more private aspects of religion—praying at home or considering oneself highly religious—that brought the most benefit. “The children who have internalized these values and made them their own are protected the most,” Pearce argues. She acknowledges that because the study depended on self-reporting, the data may be limited

.One confusing finding: among the children who had witnessed the most violence, a higher degree of spiritual belief correlated with an increased risk of problems. “Our theory is that the mismatch between their religious beliefs and their violent surroundings might have led to disillusionment,” Pearce explains.

Limitations and contradictions aside, the study offers some possible directions for prevention and intervention programs. Put simply, says Pearce, “Faith works.”

The Great Vinland Map Debate, Part 476
by Marc Wortman

The Vinland Map, which is either the oldest known map of the Western hemisphere or a magnificent forgery, is back in the news. The map’s authenticity has been in dispute ever since it was unveiled at Yale in 1965. The latest sally is a paper in the December 1, 2003, issue of Analytical Chemistry, which scores a significant point for the believers.

Purportedly created in the early fifteenth century, the faded parchment document, now at the Beinecke Rare Book and Manuscript Library, includes a place labeled “Vinlanda Insula” that is recognizably the north Atlantic seaboard. This, plus the Medieval Latin inscription stating that Viking explorers Leif Ericson and a companion named Bjarni discovered the new land, might be proof that in the race from Europe, Christopher Columbus came in second.

But doubters surfaced almost as soon as Paul Mellon '29 bought the map anonymously for $1 million and gave it to Yale. One of the most damning studies was published two summers ago; it identified traces of anatase, a mineral compound first synthesized in 1917, in the ink. That finding seemed to establish the document as a modern hoax.

But in her Analytical Chemistry report, Jacqueline Olin, a member of the advisory committee of the Smithsonian Center for Materials Research and Education, showed that interactions of the minerals in medieval inks would likely have formed anatase naturally. Moreover, other elements in the map’s ink are “entirely consistent” with medieval ink production methods, Olin says. “For a forger to think about that at the beginning of the twentieth century—before medieval inks had been so thoroughly analyzed—is extremely hard to believe. I’m convinced that it is authentic.”

Others remain unconvinced. John Tully, a Yale chemistry professor who has studied the map, believes the debate will go on. “I don’t know how you would prove it conclusively one way or the other,” he says, “even if you were willing to destroy it for testing.”  

Noted
by Jennifer Kaylin

Scientists have found the oldest known fossilized animal that is definitely male. The pinhead-sized yet proportionately well-endowed ocean-dwelling creature was retrieved from 425-million-year-old rocks in the United Kingdom. Dubbed Colymbosathon ecplecticos, Greek for
“amazing swimmer with a large penis,” the animal is remarkably similar to a group of modern crustaceans known as ostracodes, says Derek Briggs, professor of geology and geophysics and a member of the team that announced the discovery in the December 5, 2003, issue of Science.

Yale researchers are studying the grain that feeds half the world: rice. Over the next four years, they will create an inventory of the expression patterns of every gene in rice. The project is funded with a $4.5 million National Science Foundation grant. Timothy Nelson, professor of molecular, cellular, and developmental biology, said that what’s learned in the rice analysis can be applied to other grain species and may lead to larger crop sizes and experiments on virtual rice plants. Medical scientists have figured out which immune-system cells are involved in skin allergies such as the poison ivy rash and other hypersensitive immune responses. The culprits, according to Philip Askenase, professor of internal medicine, immunology, and pathology at the School of Medicine, are a combination of cells known as T lymphocytes and natural killer cells. The discovery has implications for treatment of autoimmune diseases, organ transplants, and anti-itch creams.

From puberty to menopause, women are twice as likely as men to develop depression and other stress-related mental illnesses. Becca Shansky, a grad student at the School of Medicine, has an explanation—at least for rats. In the March edition of Molecular Psychiatry, Shansky and her colleagues report that when male and female rats take a memory test after experiencing stress, the females do measurably worse—but only if they’re producing lots of estrogen. Take out their ovaries, and the sexes test equal; implant timed-release estrogen capsules in the neutered female rats, and their test performance deteriorates.

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