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SnakebyteXX
08-08-2005, 06:11 PM
The Coming Boom

Big Pharma has made billions pumping up the male population. Now neuroscientists are reverse engineering the female orgasm

By Annalee NewitzPage



I'm in Newark, New Jersey, in a small room dominated by a large conference table. There are no windows, and no sounds except for the whir of the ventilation system. "This is going to be great," says my host, Rutgers neuropsychologist Barry Komisaruk, grinning.
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A woman walks in with a large black duffel bag and shuts the door. "This is my graduate student Janice Breen," Komisaruk says. Breen opens the bag, unpacks a few electromechanical components, and begins to assemble them using a screwdriver.

"So what do you call this?" I ask. The device looks like a tampon attached to a hefty electric toothbrush, which is in turn wired to a box with a glowing red digital readout.

"It's the, um, contraption," Breen answers distractedly, hunting for an outlet.

"Actually, it's called the calibrated vaginal stimulator," Komisaruk tells me. "It's a modified tampon attached to a transducer for measuring the force that women apply to the vaginal wall."

The tampon looks big enough to be in the supersize range and is connected at a 45-degree angle to the metal handle, which houses the transducer. Scores of women have inserted Breen's contraption into their vaginas (the tampons are disposed of after each use). As I fiddle with the tampon, the pressure from my fingers registers as a few grams of force.

"Women self-stimulate," Komisaruk explains, "and we use fMRIs to look at which parts of their brains respond."

I stare at the instrument in my hands.

"Basically," Komisaruk concludes, "it's a dildo."

The tools are crude, but that's because the science of sexual arousal is still young. Viagra revolutionized the field in the 1990s. The little blue pill that gets blood flowing to the right places at that special moment became a blockbuster for Pfizer, spawning Eli Lilly's Cialis and GlaxoSmithKline's Levitra. Millions now take these drugs to kick-start an evening of private recreation.

Flush with success in the fight against "erectile dysfunction," the pharmaceutical industry set out to develop Viagra for women. First, researchers simply gave women the same pill that worked so well for men. The good news: The drug does pump a woman's genitals full of blood. But it won't necessarily get her frisky.

The results were surprising and frustrating to the pharmaceutical industry, which had assumed that what was good for the gander would be good for the goose. Julia Heiman, a psychology professor and director of the Kinsey Institute, conducted some of Pfizer's Viagra studies and found that while some women "really noticed their genitals" and felt aroused, others "barely paid attention" to them and weren't aroused at all. In other words, signals originating from these women's genitals just weren't translating into conscious desires. That insight put a new target in researchers' sights: the female brain itself. "The brain is where things are made sexual," Heiman explains. "It's the organ that causes us to be attracted to certain body types or looks. That kind of preference isn't processed in the genitals."

Even before Pfizer abandoned the bottom-up approach in 2004, the industry began investigating top-down options. The reigning wisdom these days is that making arousal drugs for women will involve targeting the female brain the way Viagra targets the male vascular system.

The first arousal drugs aimed at women's gray matter are expected to be on the market in the next couple of years. The active ingredient: testosterone, a "male" hormone that is also naturally present in women's bodies in smaller quantities. Procter & Gamble plans to release a testosterone patch, Intrinsa, and Illinois-based BioSante is entering Phase III clinical trials with its testosterone formulation, LibiGel. Even so, most researchers agree that testosterone isn't the end of the story. Testosterone drugs will never have a direct, rapid effect on women the way Viagra does on men, because it's a hormone that fosters an overall sense of strength and well-being rather than specifically catalyzing sexual arousal. More promising is a drug called PT-141, which is being developed by Palatin Technologies in New Jersey. The first in a new class of drugs called melanocortin agonists, PT-141 targets the central nervous system. Early trials show both genital arousal and increased sexual desire in women who take it. But even more precisely targeted drugs are coming - those that won't light up the entire nervous system in the blind hope of hitting pleasure buttons, but actually home in on parts of the brain that are directly connected to arousal and orgasm.

The total market for male arousal drugs is $2.7 billion per year and rising. With a study published in The Journal of the American Medical Association estimating that 43 percent of women are dissatisfied with sex - as opposed to 31 percent of men - a market for a pink Viagra could be even bigger. For now, those future billions are locked up in the labs where scientists are attempting to reverse engineer the female orgasm.

Ken Maravilla is small, dignified, and quiet. He comes across as someone who would never tell a dirty joke, which is why he's perfectly cast in his role as one of the only radiologists in the US to specialize in examining the brain scans of sexually aroused women. But there's nothing prurient here - he's in it only for the magnet.

Nobody in the lab calls it the fMRI machine, and certainly nobody bothers to say "functional magnetic resonance imaging." It's just the magnet. And the part of the room-sized machine that seeks out oxygen differentials in your blood - that's called the doughnut.

Maravilla's tiny office is in the basement at the University of Washington in Seattle behind two large metal doors emblazoned with the warning: Danger - restricted access - strong magnetic field - the magnet is always on! Working with the Kinsey Institute's Heiman and other psychologists, Maravilla has been monitoring what happens to women's brains when they watch what he calls "visual material."

Heiman is less delicate. "They're erotic videos," she says. "Female-friendly films by Candida Royale."

The point of the experiment is to understand what happens to the female brain during arousal. "A lot of people thought there would be a single sex center in the brain, but that isn't the case," Maravilla says. "In fact, multiple areas are activated."

Women wear video goggles in the magnet so they can see the movies. They watch five minutes of Candida Royale, then five minutes of a flick about mitochondria. Then the process is repeated: five minutes of arousal, five minutes of edutainment. Over a period of roughly half an hour, Maravilla examines what the difference is between a brain on Candida and a brain on Nova.

So can female arousal be quantified? The answer, Maravilla's team concludes, is yes. Brains in the throes of excitement light up in consistent, measurable ways. Furthermore, it turns out that excited women's brains look almost exactly like excited men's brains. Maravilla boots up his laptop and shows me several MR images of brains whose glowing hypothalamuses and cingulate cortices are neural maps of female desire. Then he takes me down a short hall and ushers me into the fMRI's tiny control booth, where I meet Seth Friedman, a researcher and colleague of Maravilla's. We chat about how difficult it is to study cognitive and genital arousal with MRI alone. "They're two parallel responses separated by a couple of feet," Friedman says. Either you stick someone's head in the magnet, or you stick their privates in - but you can't do both at once.

"You'd really need a double doughnut to do it right," Maravilla says wistfully. Friedman laughs, and then Maravilla cracks a smile, the first I've seen on his face all day.

Getting good images of the aroused female brain is easy. It's orgasm that's the problem. In the doughnut, the slightest head movement ruins the scan. Even if a test subject holds her head perfectly still while masturbating, the parts of the brain responsible for motor control are switched on, muddying the picture. "You'll see vaginal sensory input to the brain," Komisaruk says, "but you'll also get motor activity of the arms and hands, as well as sensory input from them." To get clean data, he needed to find someone able to achieve orgasm without touching herself.

Vicky - not her real name - is one of these women. A California college student, she can climax by "thinking off." She contacted Komisaruk after hearing about his work from one of his other test subjects at a party.

"It's amusing to tell people that I jack off in an fMRI for science," says Vicky, quickly adding that the process is more like work than sex. A typical day of research begins with Vicky lying on the fMRI machine's bed; Komisaruk and his team strap down her head. Then she's fed into the doughnut and the machine begins taking pictures, a process Vicky describes as "loud and clunky." She stimulates herself by contracting her vaginal muscles rhythmically and controlling her breathing for 26 minutes.

Vicky and the imaging team worked out a hand signal she can flash when she starts to orgasm. "Basically, my head was strapped to a board in an extremely loud machine, and I had to let them know when I was about to come, so they could mark it on the computer," she laughs. "Whoo - so sexy!"

"We got excellent data from her," says Komisaruk, who adds that Vicky is one of 12 women in his study who can "think off." "Because there is no distraction related to movements and sensory input from arms and hands," he explains, "it illuminates the brain activity involved in producing the orgasm." Certain brain regions really stand out once the noise is eliminated: For example, the nucleus accumbens, associated with the brain's reward system, turns out to be a big player in orgasm. There is also heightened activity in the anterior cingulate cortex, which is linked to pleasure, pain, and craving; and in the amygdala and the hypothalamus, areas that process emotion. "Orgasm is probably incredibly good for the brain," Komisaruk says. "The entire organ is being oxygenated."

At the other extreme are research subjects who were thought to be unable to reach orgasm at all. In the early 1990s a colleague of Komisaruk's, Rutgers professor Beverly Whipple, began a series of studies on women whose spinal cord injuries had left them totally numb below the waist. Many had been told by doctors that they would never orgasm through genital stimulation again, but Whipple wasn't so sure. She had come across anecdotal reports to the contrary since the '70s. "I wanted to validate the sexual responses I was seeing in paralyzed people," Whipple says. So she went to the lab.

An early version of Komisaruk's calibrated vaginal stimulator turned out to be the perfect tool for the job. Because the subjects have no sensation in their genitals, there was the slight but real possibility that they'd inadvertently hurt themselves while masturbating. But using the force-measurement readout as a guide, the scientists could see how much pressure the women were exerting and prevent them from injuring themselves.

Sure enough, some of the women experienced what seemed to be orgasms. "One woman hadn't tried stimulation for two years since her accident. She was crying and I was crying - it was very moving," Whipple says. The conventional wisdom held that these were "phantom orgasms" - more like a memory or a dream than the real deal. But Whipple and Komisaruk had an alternative explanation: that the anatomy textbooks - which had all the vaginal nerves routing to the brain via the spine - were wrong. "I hypothesized that the vagus nerves [which travel up the front of the body] bring sensory input from the G-spot and the cervix to the brain," Komisaruk says, "bypassing the spinal cord."

To test the theory, they turned to the magnet, comparing the so-called phantom orgasms of paralyzed women with the orgasms of ambulatory women. They got a match. "Even though they could not feel the stimulus in their genitals," Whipple explains, "they had orgasmic response in the same area of the brain as women without spinal cord injury. These were not imaginary orgasms. They were real." Whipple and Komisaruk had fMRI proof, the scientific equivalent of a smoking gun.

Komisaruk's grad student, Breen, continues to investigate the vagus nerve. Not only is it a pathway to orgasm, it might also modulate pain signals. I learn this the hard way.

I'm messing with the vaginal stimulator when Breen shows me another contraption. analgesy meter is stenciled across its side. "It's used to measure pain," Breen explains.

Though she never offers to let me test-drive the tampon, Breen suggests I give the analgesy meter a spin. It looks sort of like an old-fashioned postal scale, except instead of a little dish for your mail there's a piece of pointed plastic with a cap on it. The soft part of my finger rests on the pointed bit, and the cap presses down on my nail. As Breen moves a slider that goes from 1 to 20, my finger is pushed down harder and harder. "Tell me when it gets to be too much," she says.

It reaches about 13 before I yelp. "OK, too much!"

Breen's eyes are shining. "One of the things Dr. Komisaruk discovered is that women who are stimulating the anterior vaginal wall can take 50 percent more pain than they can when they're not," she tells me excitedly. "If they have an orgasm, their pain threshold rises 100 percent."

Unfortunately I'm neither stimulating nor orgasming and my finger is still squashed. "Could you take my finger out please?" I gurgle.

"Oh, sorry!" Breen says, releasing me and warming again to the topic. Her doctoral work indicates that a woman with lingering soreness from a back injury can get up to a full day's relief by using the stimulator once a day for several minutes.

Komisaruk and Breen hope to someday develop a painkiller based on this quirk of the female body. Komisaruk has even patented a small sequence of amino acids associated with the pain-dimming effects of vaginal stimulation. "In rats we've determined that our analgesic is more effective than morphine," he says.

A new drug for pain is great, but I'm looking for orgasm in a bottle. When am I going to get my pleasure pill, and how will it work? The person with the big picture, and with the closest thing to an answer, is Gemma O'Brien. Perhaps the only orgasm theorist in the world, O'Brien is an Australian biomedical researcher at the University of New England in New South Wales; she has spent the last decade tracking down every study available on orgasm and the brain. She has a kind of unified field theory of female orgasm, summed up by an elaborate Venn diagram. Its three overlapping circles represent emotion, pleasure, and euphoria, along with their associated hormones and regions of the brain.

O'Brien is convinced that there's no reason why women shouldn't be as sexually satisfied as men. Because orgasmic brains look nearly the same across gender lines, she believes that inorgasmic women may be suffering due to early social experiences. Sexually repressive environments "may affect the growth of brain pathways in girls," O'Brien says.

She suggests that there may also be a genetic reason why certain women enjoy sex less than others. Just as some people are depressed because their brains reabsorb too much serotonin, some may be less sexually charged because their brains reabsorb too much oxytocin or dopamine. Researchers could "provide a fix for that with drugs," she says, sketching out plans for a pill that keeps the oxytocin from getting absorbed too quickly. If the fix works, "you might experience bliss instead of having just an OK sort of time."

Andreas Bartels, a brain researcher at the Max Planck Institute for Biological Cybernetics in Tübingen, Germany, has done research that seems to back up O'Brien's theory. He's imaged the brains of women thinking about their sex partners. Bartels says the hypothalamus appears to be a key indicator of romantic love, and it's also a main area in the brain where oxytocin is absorbed. The chemical is released during orgasm and other sorts of mating rituals.

"Love is just a biological mechanism," says Bartels with laugh. He's certain that a drug that tinkers with oxytocin isn't far down the road. "You can inject an animal with oxytocin and make it pair bond with a stranger," he says. "All we need to do is apply it to humans."

Most experts believe a truly effective aphrodisiac for women will hit the market in the next decade. Meanwhile, researchers are following new neural pathways and disproving the conventional medical wisdom about orgasm. They're investigating regions of the brain whose paradoxical roles as pleasure enhancers and pain modulators may yield more than one kind of drug. Komisaruk is even suggesting a technological fix for arousal problems - a neurobiofeedback machine that could help women learn to be superorgasmic. The future can't come soon enough.

web page (http://www.wired.com/wired/archive/13.07/female.html)