Thanks to the Americans with Disabilities Act and some celebrated cases, public awareness (if not exactly acceptance) of depression has soared in the past decade. But many people don't realize that clinical depression--as opposed to its twin, bipolar affective disorder--is gender-biased. Depression hits women at more than twice the rate as men. And women attempt suicide three times more often than men, according to the National Institute of Mental Health.

A decade ago, Cynthia Bethea began researching the depression gap. She's a neuroendocrinologist at the Oregon Regional Primate Research Center in Hillsboro. Of the eight federally funded primate research centers, OHSU's facility is one of the oldest and most respected. For a university and its biologists, having a primate center is akin to Stanford University having its own particle accelerator: It's a basic research romper room for people who speak restriction enzymes and gene expression, and late at night wonder why.

Most basic researchers, however, chase what speaks to their pure intellect. Bethea has a less abstract motivation. When, at 13, she had her first menstrual period, Bethea had to ask her father to tell her mother. At the time, her mother was in a mental hospital suffering from depression.

"It's not serendipitous that I wound up studying depression," she says, sitting in an armchair in one of ORPRC's lab buildings, nestled among stands of Douglas fir and blue spruce in Hillsboro, where she's spent the last decade seeking a scientific explanation for the illness that has bedeviled her family.

The ash-haired 48-year-old researcher 10 years ago thought that estrogen depletion led to low levels of serotonin in the brain. Serotonin has been proven to be the linchpin in treating depression.

Bethea's thought was that, in women at least, estrogen and serotonin are linked: How else can you explain the prevalence of postpartum depression and depressive episodes that throw some women into suicidal spells during their menstrual cycles?

But a hypothesis isn't valid unless it can be proven, not once but repeatedly. To test her theory, she's euthanized roughly 200 female rhesus monkeys and studied their brains (see story, below).

Rhesus monkeys are so close to humans it's as if, but for a few thousand genes, Bethea were experimenting on humans. From a pure research standpoint, using the closest genetic proxy for humans is essential. But the ethical and political debates around vivisection, killing our biological next of kin, have been among the most intense philosophical conflicts of the past three centuries.

Even moderate groups like the Humane Society of the United States are growing increasingly skeptical of the need for using primates in scientific experiments. "You have to wonder about allowing scientists to experiment on primates," says Martin Stevens, vice president of research for the HSUS. "Is the price too high?"

Bethea is well aware of the debate. She's received her share of outraged email from animal rightists--and she's had the integrity to write them back and answer their questions.

Using monkeys as research vehicles, for Bethea, is not a moral quagmire, despite the renewed pressure on ORPRC and other primate centers such as the Yerkes Regional Primate Research Center in Atlanta, Ga.: The social cost of depression adds up to billions of dollars a year. And her hypothesis has been answered in the affirmative with enough regularity that human clinical trials are now in the offing.

Most important, Bethea doesn't have the option of moving down the chain of being to rats or mice: Their menstrual cycle is four days. Humans and rhesus monkeys: 28 days.

Still, she agrees that ORPRC could take better care of its non-human primates. She'd like the center to house its monkeys socially rather than keep them in individual cages. The only trouble is money. It will cost the primate center $10 million over the next several years to build new monkey housing, money the center has yet to find.

"People always scream at us but they never pay," says Bethea.

Of course, there are people for whom any research using animals is not worth the price. A tortured email exchange between Bethea and a woman in Massachusetts fell apart when the East Coast correspondent insisted that if her own daughter were leveled by an illness that primate-based research could end, then she would rather see her own daughter die than have a monkey being experimented upon.

Cynthia Bethea would prefer that her own daughter know about depression as an abstract concept.

"They Come Out Quite Easily"

By the time Cynthia Bethea gets her monkeys, they've already been subjected to other research in which their ovaries have been removed. For a month, a third of the monkeys are given soy estrogen, a third equine estrogen, a third nothing. Then they are euthanized and Bethea goes to work.

She opens their crania, snips their optical nerves and brain stems and lifts out their fist-sized brains. "They come out quite easily," says Bethea. The highly evolved brain places monkeys a couple of biological steps behind Homo sapiens, down to its thumb-tip-sized medulla.

Bethea focuses on two neurons that control all of the serotonin activity in the forebrain, which is the seat of short-term memory and pleasure--two neural activities rhesus and humans share. After a technician stains the tissue, it is exposed to X-ray film, so the density of serotonin activity can be measured by a statistical program.

In the past four years, Bethea has published four articles on her findings in respected journals such as Neuroscience and the Journal of Neuroscience; each establishes a provable link between estrogen levels and female depression. FDA approval for a forthcoming clinical trial in Portland should be "a cakewalk," as Bethea puts it.