The New Viagra for Women

Printer-friendly version

sex up logoThis article is about nasal spray drugs that act as aphrodisiacs. One mimics dopamine in the brain of women. Given the dangerous long-term effects of dopamine agonists on some Parkinson's patients, we can't help wondering whether the questionable short-term gains of this substance justify its production. The other drug, PT-141, makes rats "want it [sex] constantly," which means it never leads to feelings of wholeness or fulfillment. This is a recipe for crazy behavior.

...Will something as mundane as a nasal spray make our society sex-crazed and addicted to lust? Will we be able to have sex without inner composure, perhaps without even being in the mood? It would change society and deprive sexuality of its mystery, conquering and subjugating our libidos....

Increasing Sexual Appetite

By Ralf Hoppe

Can drugs increase sexual desire? Ever since Viagra, the pharmaceutical industry has been dreaming of the perfect aphrodisiac. Now, an American company may have developed a nasal spray that will do just that.

Prowling men and lascivious women, orgasms, odors and sports cars -- they're all nothing but molecules. Just like the world itself -- everything is made up of molecules.

No one knows that better than George Dodd -- indeed, he is a self-described marketer of molecules. He's also about to be the proud owner of a collection of molecules in the shape of a brand-new Jaguar XS in midnight blue with dark leather interior. And why not, he thinks to himself? After all, he's 63 and it's about time he spent some money. Besides, money is about to become plentiful in the life of the Irishman, a biochemist by trade. Dodd, who now lives in Scotland, has designed a brand new molecule.

The molecule Dodd has created resembles dopamine, a substance occurring naturally in the brain and which is associated with feelings of pleasure. Dodd's new product is intended to generate a healthy appetite for sex.

Mass production is already well underway, which explains the midnight blue Jaguar. It also explains why Dodd, on this day, is attending the International Conference of Sexologists in Lisbon. It's a four-day meeting of the world's leading experts on sex -- an assembly of those who seek to learn more about sex and provide mankind with more sex or better sex or just plain sex. And Dodd is now one of them. He's also interested in finding out what the competition is up to these days.

Smelling of goats and cheese

It's shortly after 6:30 a.m. In a few minutes, a biotech firm will give a presentation on a product it plans to market, something very similar to George Dodd's invention -- an aphrodisiac. In fact, everyone's working on an aphrodisiac these days. Massive profits are there to be had for the company that comes up with the next, big sex formula.

Dodd, still red-eyed from not getting enough sleep, is sitting in one of the back rows in the "Berlin" conference room at Lisbon's Marriott Hotel. He's a stocky man, and despite his sandals, full beard and pony tail giving him the appearance of an extra in a low-budget film about the Middle Ages, Dodd is cultured, funny, an opera lover, runs one marathon a year and carries pressed handkerchiefs in his pocket. He pulls one out and makes an elaborate show of cleaning his glasses. Then he motions to one of the waiters for a cup of coffee.

He leans over his coffee and closes his eyes.

So -- how's the coffee?

Nutty, smoky, peppery, nutmeggy, woody, with a hint of soap. He speaks softly and succinctly.

Before studying biochemistry at Oxford University, Dodd completed a training program as a perfume maker. When he was a child, he says, his sensitivity to smell was sometimes frightening. He could smell the bacteria that cause milk to go sour long before the milk turned, and he could sense dogs approaching in the distance before they came around the corner. He suffered when his son entered puberty and suddenly began smelling of goats and cheese, says Dodd.

His house on the Scottish coast, directly on the water, is filled to the brim with scent catalogs, shelves full of tiny glass bottles and aluminum cartridges, vessels containing more than 10,000 different aromas, including Tiara Lily oil, at €29,000 a liter, and the bottled scent of dead salmon. When his odor collection gets to be too much, Dodd steps outside for a whiff of the ocean, of salt and seaweed -- and of the sheep grazing in the surrounding countryside.

When it comes to sex, caution is necessary

Here, in his seaside laboratory, Dodd has developed an aroma similar to the messenger substance dopamine. It's meant to entice the brain into thinking that it's time for sex. But its action is gentle, says Dodd, who believes that caution is necessary when it comes to sex and the brain.

The conference room is full, and Dodd joins about 60 other scientists for this morning's session. The subject of the presentation is a substance called Bremelanotide, a so-called heptapeptide -- consisting of eight amino acids, seven of them arranged in the shape of a ring, and making up merely one-thousandth of a protein. This one is named PT-141. The presentation is advertised as the state of the art in current research. He'll believe it when he sees it, he thinks. And the name of the company? Dodd flips through the program. Palatin Technologies, it says. A company from New Jersey.

The speaker approaches the podium. He has long sideburns and sports a silver earring. Dodd takes him for young-looking, 40-something.

The man leans forward and introduces himself. "Good morning," he says. "My name is Jim Pfaus and I'm a professor of behavioral research at Concordia University in Montreal."

Dodd blows on his hot coffee, yawning furtively.

But within 15 minutes, Dodd is as awake as it gets. The substance Pfaus is speaking about -- a new product from Palatin Technologies -- is administered through the nose. That much it has in common with Dodd's idea. But otherwise Palatin's concept is far more radical. PT-141 isn't gentle and it isn't intended to merely lightly stimulate the olfactory system. Instead, the spray quickly enters the bloodstream and is ferried directly into the brain. More than that, according to early test data Pfaus presents, the stuff works -- alarmingly well in fact. Pfaus cites tests on rats that have already been underway for four years, and points to the results of a second test phase involving real-live female humans. The product's success rate is fully 72 percent against just 22 percent in the placebo group. A sensational result.

The Palatin people say that they plan to begin the final phase of their study in a few months, and that they are making headway in their negotiations with the US Food and Drug Administration (FDA), which has to approve new drugs before they can go on the market in the United States. As Dodd's coffee turns cold, the mood in the conference room -- among the endocrinologists, the gynecologists, the biochemists and the andrologists -- becomes worshipfully solemn. The same thought is on everyone's mind: These people could be on to something. An aphrodisiac drug that actually works.

The first sexual revolution began in the late 1960s. It consisted of liberation from the constraints of morality and was triggered in part by a new product developed by pharmaceutical company Schering, the birth control pill. Yearning for a freer life also played a role and young people were the ones who led that revolution -- and the ones who benefited from it.

The second sexual revolution began in 1998, and it too was triggered by a pill -- a small, light blue tablet called Viagra. It liberated men from their performance anxiety and from the unpredictability of their own bodies. But it was mainly the older generation that benefited from this second revolution.

Sex at the push of a button

And now? Do the flickering bar charts and test series involving rats and human subjects being presented on this Friday morning in the Marriott's conference room spell the beginnings of a third sexual revolution? Will something as mundane as a nasal spray make our society sex-crazed and addicted to lust? Will we be able to have sex without inner composure, perhaps without even being in the mood? It would change society and deprive sexuality of its mystery, conquering and subjugating our libidos. This time around, the revolution will benefit both the young, whose stressful and hectic lives have robbed them of the time they need for relationships, and the old with their flagging libidos. It's a revolution that promises immediate sex, sex at the push of a button, sex for everyone and sex for eternity.

While Jim Pfaus, the rat professor, and the other Palatin presenters paint this admittedly hypothetical future, gentle George Dodd sits motionless in his chair. His real purpose in coming to Lisbon was to take a look at what his counterparts in the industry were up to. And now that he's here, he knows that they plan to gobble up the market -- and that in contrast to his product, they won't be taking a gentle approach.

The Marriott Hotel in Lisbon is on Avenida dos Combatentes -- the Avenue of Warriors -- a suitable location for this conference, a meeting delineated by invisible front lines. Sex, after all, is fiercely contested territory.

At first glance, the four-day event, with its 86 presentations and 184 attendees, is nothing but a huge orgy of data. Participants learn a great deal about menstrual cycles, the production of the hormone cortisol in housewives as they watch porn films, and everything they ever wanted to know about cybersex in Portuguese chat rooms. In a conference so jam-packed with presentations, discussions and symposia, it comes as no surprise that attendees want nothing more to do with sex by the time evening rolls around.

But a second glance reveals various subgroups. The front lines run between hard and soft science, between the soul, molecules and the industry. Whose territory is this? Who owns sex?

The true masters

Sexologists can be divided into three social groups. Members of the first group, psychiatrists and psychologists, share certain identifying characteristics. Most of the women come from the Netherlands or the American Midwest and they often teach gender studies. They tend to wear dark, baggy clothing and ethnic jewellery, and they usually extract their documents from soft leather shoulder bags. They have no qualms about expressing their dislike for a particular presentation by groaning loudly. Their male counterparts have a preference for crepe-soled shoes and poorly fitting tweed sports jackets. They carry cowhide briefcases and they seem to enjoy the sound of their briefcases snapping open. Their studies tend to prove things that were already more or less obvious.

The second group consists of gynecologists, urologists, microbiologists, biochemists and endocrinologists. If they've arrived from Milan or London, they're probably wearing elegant Chanel outfits and pumps or Ermenegildo Zegna suits. They're cool and confident, their presentations are filled with facts, they have a liking for Blackberrys and they've probably never read Erich Fromm.

The third group are men in dark, expensive suits who tend to stand a bit off to the side. They are men with pocket squares and business cards boasting some of the biggest names in the pharmaceutical industry: Pfizer, Boehringer, Procter & Gamble, Eli Lilly. These men are very discreet, and yet it's difficult to escape the impression that they're the ones who own sex, the true masters of this particular terrain.

The schedule on this Friday morning, after the Palatin presentation in the Marriott conference room, includes a little time for questions. Besides scientists, the audience also includes a few sex therapists and psychologists. They stand up when they ask their pointed and critical questions -- questions about social context and the purpose of such a drug. When they sit down again they look around the room, almost expecting applause, and as they listen to the presenter's response, they shake their heads as if to indicate that they find the whole thing somehow distasteful.

Perhaps they're right. They aren't just driven by concerns that the despicable tools of chemistry are being used to intrude upon their own domain of psycho-speak (although experiences with Viagra show this concern to be more than justified). At the root of their concern is the idea that what these drugs are doing is something nature never intended.

A few levels below the heart

But the Palatin presenters are well-prepared. The more critical the question, the more polite is their response. They roll out the argument of therapeutic benefit. They insist that their aphrodisiac spray is no party drug, that it's by no means meant for pure enjoyment, and that it should only be administered as part of a carefully designed program of psychotherapy. They flatter and they expertly dodge questions, but what they don't say is the elephant in the room: Dear colleagues, this product will be more effective than all the world's conversation therapies. We plan to make a lot of money with it, and if you could do the same, you would.

George Dodd has listened to the presentation, quietly and attentively. At the end he applauds politely, sets his cup down and walks out. He seems a bit dejected. Was this the hour of truth?

In the hotel bar, at any rate, it's the hour of myths, a time to tell -- for the 100th time and over beer and peanuts -- the story of the accidental discovery of the "little blue diamond." It happened in the mid-1990s at Pfizer's laboratories in the southern English town of Sandwich, where frustrated researchers working on a drug to treat angina pectoris suddenly and coincidentally discovered that it was also effective elsewhere in the body, a few levels below the heart. When the head of the laboratory tried out the stuff himself he spent a few horrified days walking around with a rock-hard erection.

The story is met with the usual spate of giggles, and someone orders another round of beers.

Annual sales of the stuff have been upwards of two billion ever since, says one person. And then there's the black market, sighs another.

The phenomenal success of Viagra has pointed out new possibilities to the pharmaceutical industry, and it's prompted researchers in many a pharmaceutical lab to search even more fervently than ever for a wonder drug -- especially for women.

Procter & Gamble is working on a testosterone patch under the working title "Intrinsa," but the FDA has yet to issue its approval of the drug. Illinois-based BioSante Pharmaceuticals is also developing a testosterone product, this time in gel form. According to a study conducted by business consulting firm Ernst & Young, there are 1,400 biotech firms in the United States and more than 4,000 worldwide, and each of these firms knows that a drug that promotes sexual desire is the most sought-after in the industry.

Viagra was rather primitive compared to what's in the pipeline today. Instead of acting in the brain, an erection-inducing drug's modus operandi is essentially hydraulic. Viagra inhibits an enzyme called phosphodiesterase-5, or PDE-5. The function of PDE-5 in the body is to regulate blood flow by breaking down messenger substances that signal an increase in blood flow.

If the enzyme is inhibited, the messenger substances, especially a substance called cGMP, are able to send their signals without obstruction, allowing more blood to flow, increasing erections and market share. In order to have an erection, however, a man must be sexually stimulated. If this isn't the case, Viagra is ineffective, producing headaches and diarrhea at best. But what if we could not only smooth the way for sexual desire, but also generate it?

Why do we get aroused?

Sex takes place in bed, at least most of the time. But where and how do people decide whether to have sex in the first place? Is it his aftershave, his money or his smile that excites a woman? Is a man aroused by a woman's voice, her breasts, her mouth?

That decision, a compendium of many individual decisions, is made in lump of cells weighing an average 1,300 grams and located beneath the top of the skull, between the limbic system and the large regions of the neocortex.

The sensory organs -- the eyes, ears, nose and skin -- don't feel, taste or see anything. Sound, light and smell mean about as much to these organs as an e-mail does to a laptop. Instead, they translate them into electric impulses, which are transmitted to the brain, which then develops a neuronal correlate to the perception of a sunrise or the sensation of touching a woman's breast.

Nothing happens without inspiration. Someone who feels no desire for sex doesn't want to have sex. Although one can establish the right conditions, such as locking an office door, drinking a glass of red wine or lighting a romantic fire, the rest must happen on its own. After all, the brain isn't exactly capable of telling itself what to do. We are hostages to this organ -- and it forbids us from meddling in its business.

But that's exactly what those in the business of generating desire, people like George Dodd, the biochemist from Scotland, and the Palatin researchers, are after: finding the right trigger.

The reward system for sex is located in the limbic system, in the teaspoon-sized hypothalamus, an ancient area of the brain in terms of evolution. This is where hormones like alpha-MSH, testosterone and estrogen are dispatched to the cells. And it is here that messenger substances like dopamine and serotonin act, transmitting arousal through the spinal cord to the sex organs. If the blood pressure and the heart are able to keep pace, the arousal cascade continues on its own, ending in the expected fireworks, followed by peace and quiet, with everything under control once again.

Desire versus inane chatter

Every adult is familiar with a few tools to stimulate arousal and remove inhibitions. Alcohol makes us less inhibited, but it also causes drowsiness and loss of sensation. A joint, with the tetrahydrocannabinol it contains, can trigger sexual desire, but it can also produce nothing but inane chatter. Cocaine, though considered a reliable sex drug, is expensive and illegal.

Dodd, for his part, doesn't believe in drugs. Instead, he believes in the gentle power of aromas. He occasionally drinks red wine, together with his son. Once a year he buys a bottle for £300 pounds (€450), which the two drink almost ceremoniously.

Dodd's aphrodisiac, registered under patent number 2386555, is an aroma that should be inhaled repeatedly over a 24-hour period, if possible. Its molecular structure is similar to that of dopamine, the messenger substance that controls sexual desire. The difference between PT-141 and Dodd's invention is the aroma's relative instability. It docks only briefly and gently and then either disintegrates or is discarded.

As the Lisbon conference continues -- problems of estrogen treatment, psychosexual profiles of women with genital pain, brain activity while listening to music and its effect on sexual desire, one presentation after the next -- Dodd searches for Jim Pfaus, the scientist from Palatin. He finds him that afternoon at the coffee table, and soon the two men are deeply engrossed in animated conversation, with Dodd talking about operas and aromas and Pfaus telling the story of how PT-141 was discovered.

It was at the University of Arizona's Health Sciences Center, a place where the sun burns relentlessly nine months of the year and where researchers were trying to develop a sunscreen that would stimulate pigment production in light-skinned men. They were working with a substance that resembled melanotropin, a human hormone, and they called it Melanotan II.

Stumbling across desire

Melanotropin stimulates the tanning process. And the subjects in the study did indeed develop dark tans, but that wasn't all. The researchers also observed that the drug suppressed appetite, had anti-inflammatory properties, triggered sexual desire and produced what Pfaus calls "fantastic erections."

But this broad range of effects was a significant problem. After all, no one is interested in taking a drug that causes half a dozen unwanted side effects. The FDA was not impressed.

Melanotan II had been born but no one wanted it -- not until Palatin came along, that is. The small New Jersey-based company with only 20 employees at the time (compared to more than 3,000 people at Pfizer's facility in Sandwich) decided to take on the challenge.

Palatin's founder and president, molecular biologist Carl Spana, and his laboratory director, Annette Shadiack, saw their chance. The drug could be altered to treat the lack of sexual desire suffered by some women. According to a major European study involving 2,467 respondents, one in 10 young women experiences major libido problems -- a number that jumps to 48 percent in post-menopausal women over 50. The number of unreported cases is even higher, the scientists believe.

In other words, the scientists saw a potential Viagra for women. The Palatin researchers began working on modifying the peptide structure of Melanotan II. They spent seven years subjecting the substance to all kinds of molecule-changing procedures, until finally the invisibly tiny peptide shape fit into a single receptor shape -- like a key into a lock. All other signals were switched off: the tanning effect, appetite suppression and anti-inflammatory activity. All that remained was the stimulation of the limbic system.

They named the new drug PT-141. Its nickname was "passion."

"They want it constantly"

In 2001, Palatin researcher Shadiack and rat expert Pfaus met in San Diego. Pfaus vividly recalls the encounter and Palatin offered him an extended research contract. But, says Pfaus, he insisted that he would never stray even an inch from his scientific objectivity. "Palatin wants clean data," he says. "They would be stupid to order fudged studies -- and I would be even more stupid to provide them with that kind of data."

Pfaus developed special cages in which female rats were able to make decisions about when to have sex. The results, he says, are astonishing -- a four to six-fold increase in sexual appetite. "Believe me, I know these animals. They want it constantly," he says.

But what does this mean for people?

"Rats are different creatures, of course. But there are major similarities between our brains and theirs," Pfaus explains. "I would say that if my female rat responds to an agent, we can be pretty sure that people will respond in almost exactly the same way."

PT-141, or bremelanotid, has since been tested on more than 1,000 human subjects. The tests were performed by neutral, third-party companies, secretly and using a double-blind, placebo-controlled approach. According to Pfaus, 72 percent of the women tested experienced a sensation of general arousal, while 67 percent reported a significant increase in their sexual appetite. Even when the reactions of the placebo control group are taken into account, the results are still encouraging enough to lead the people at Palatin to believe that the drug will be a major success in one or two years. Just under 1,000 people have participated in development to date, and the research, says company President Carl Spana, has cost Palatin about $150 million.

Will it really work?

Palatin needs money constantly, especially now that the drug is in its final phase of development. Once or twice a week Carl Spana meets with bankers, venture capital investors, analysts in New York, San Francisco and London, and between meetings he prepares for hearings at the FDA. Procter & Gamble may have lost its first battle for "Intrinsa," but Carl Spana intends to win his.

Pfaus also mentions a few unofficial assessments of the drug he says are from an earlier test phase. In that phase, older subjects claimed to have had sex several times in a row after using the nasal spray. Women raved about sudden attacks of sexual desire, and test subject 041, when asked to rate his erection on a scale of zero ("nothing") to five ("outstanding"), gave it a grade of six.

Is this nothing but PR, or is the truth? It could be true. After all, the brain is an isolated system. But once we're inside, we can easily manipulate it.

On his last evening in Lisbon's Marriott Hotel, George Dodd, the bearded perfumer and biochemist, leaves the conference a little early. He skips the last presentation of the day, takes the elevator to his room on the fourth floor and puts on his dark blue business suit and stylish black sandals. He's meeting investors and licensees for a business dinner, where he'll be expected to explain to them why his aromatic agent is gentle but effective.

The conference presentation Dodd has decided to skip is on premature ejaculation and how it affects the level of sexual satisfaction of the woman involved. Perhaps not an especially uplifting topic. But a new market segment to be sure.

Translated from the German by Christopher Sultan

Original article, SPIEGEL ONLINE - May 19, 2006