THE FIRST SIGN OF TROUBLE CAME in May 1996, when Angela Christiano went to her hair salon for a highlight job. "Did you have a biopsy?" asked the stylist, examining her luxuriant brunette mane. "You have a big bald spot back there." Soon afterward, when a dermatologist diagnosed Christiano, 32, with alopecia areata—a common disorder that in extreme cases can cause the loss of all body hair—he suggested that her condition might improve if she would avoid stress. "How can you relax when your hair is falling out?" says Christiano. "How can you not obsess about it?"
Obsess she did—so much so that Christiano, a scientist specializing in dermatology, spent the next 17 months working full-time to unlock the secret of human hair loss at the genetic level. "It's kind of weird to start studying something you have," she says, yet the result was edifying: a breakthrough that may at some point open the way to cure certain forms of hair loss. Dr. Vera Price, a hair-loss expert at the University of California at San Francisco, says Christiano is the first researcher to pinpoint a single gene responsible for any type of baldness. "It is," she says, "a very important discovery."
Coincidentally, just six months before the appearance of three palm-size bald patches on her scalp, Christiano had moved from Philadelphia to take her first full-fledged job, as an assistant professor of dermatology at Columbia-Presbyterian Medical Center in New York City. Like many of America's 2.5 million alopecia areata sufferers, she immediately began a regimen of painful cortisone injections. She considered a wide range of other treatments but was stunned, she says, when she realized how little was understood about the causes of the disorder.
As it happened, Christiano was looking for a problem to research, so she put her three-person lab crew on the case. First she began looking for an extreme case of hair loss that might yield significant clues. Soon she came across a study of a Pakistani family in which seven of 36 members suffered from a rare form of alopecia that causes the complete loss of all hair in both men and women. "The women are so conscious of their appearance, they won't leave the house," Christiano says of the family, who live primarily in the isolated town of Chakwal, a four-hour Jeep ride from Islamabad. Pakistani researchers who had studied the family agreed to collaborate with her. "We thought her own alopecia would motivate her to try harder," says Wasim Ahmad, who mailed Christiano blood samples from the afflicted villagers in October 1996 and then came to New York City in July 1997 to work with her. But isolating the baldness gene in the vast range of the genetic material available was a daunting challenge. "It's the equivalent of standing on the moon and trying to find one person on the face of the earth," says Christiano.
Then, last April, she found the key to her research while attending a dermatology conference in Washington. A scientist giving a talk about sun protection happened to show a slide of a hairless mouse of the type often used to test skin products. It struck Christiano that the tiny creature—which naturally loses its baby hair soon after birth and never grows adult hair—might provide a model for the disease she was studying. "On a long shot," she says, "we decided, 'Well, it looks like our patients, why not?' "
Christiano and her colleagues set about the painstaking task of comparing the mouse's genes to those of the Pakistani villagers. By July she found the human version of the gene responsible for the hair loss in the mice. In September, she found that a mutation in the same gene caused hair loss in the Pakistani villagers. "It was just one of those moments," she recalls of the discovery. "You just stare at it and you know it's like a gift from God."
The gene causes a disease that affects only a handful of people. Yet Christiano believes the discovery could help pave the way to treatments that will benefit people suffering from other forms of hair loss. "This is the first gene in the pathway," she says. "[It should] lead us to the next gene and the next after that, and give us a better understanding of how the hair cycle actually functions."
The discovery generated worldwide attention when it was revealed in the prestigious journal Science in January. But Christiano's peers are not unanimous in their enthusiasm. Dr. Madeleine Duvic, a dermatology professor at the University of Texas, says Christiano's discovery primarily helps to explain the rare Pakistani disorder. "This is not going to lead to cures for male pattern baldness in two years," she says. "That would be overstating it completely."
"We never said anything about a cure," rebuts Christiano. "We only say this is the first understanding of any gene that controls hair growth—just the first foot in the door. At the very least, it would take five years to begin to understand the genetics of male pattern baldness."
Still, the news brought a degree of hope to people affected by severe hair-loss disorders—particularly women who suffer from forms of alopecia. "I have people crying on the answering machine," says Christiano, "women saying, 'We knew it would take a woman to figure out this disease.' "
Growing up in Nutley, N.J., the only child of a beautician and an Amtrak conductor, teenage Angela ran a small tea salon in the beauty parlor where her mother, Maria, worked. Maria, though, had higher hopes for her. "I was always interested in her education," she says, "that she grow up to be a professional."
A diligent student, Angela was in eighth grade when a National Geographic article about DNA captured her attention. "I thought it was the most interesting thing I'd ever read," she recalls. She went on to study biology at Rutgers, where she was working toward her doctorate in microbiology. when she met a young physician, whom she married in 1989. But after she went on to postdoctoral work at Philadelphia's Jefferson Medical College, the couple grew apart and divorced in 1996. Christiano says the consuming nature of her work makes it difficult to contemplate another relationship. "I'm hopeful that some day it'll happen," she says, "but it's hard to find people who will put up with this lifestyle."
Yet the rewards are so gratifying that she finds the work almost addictive. "I really think it's the ultimate in medicine, to learn how disease happens at the DNA level and then go in and fix it," she says. Getting her research funded is difficult, since medical insurers and foundations don't consider hair loss a priority compared to life-threatening diseases. Still, says Christiano, the problem shouldn't be taken lightly. "It never kills you," she says, "but it devastates you psychologically and makes you feel like you're ugly and worthless." (Her own case of alopecia areata was arrested by the cortisone injections, though her hair remains thinner than before.)
In the future, she hopes to expand her research into more common forms of alopecia, including male pattern baldness. She hopes one day to find the elusive cure, but believes that in the meantime, by focusing attention on disorders such as alopecia, her work will help ease the stigma felt by its sufferers and bring them a measure of psychological relief. "Then it will have done its job as good science," she says, "because it will have made people think a new thought."
NANCY MATSUMOTO in New York City
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