In 1978 a Johns Hopkins University biophysicist who studied obscure proteins in the membranes of the eye had a crisis of faith and decided to switch to more relevant work -- developing a contraceptive for women that would also stop sexually transmitted diseases.
This, it seemed to Richard Cone, was something the world really needed. His conviction hardened into a crusade as AIDS began taking its toll in the years that followed.
No pharmaceutical company ever pursued Cone's idea. But 70 research groups in the United States and England, including Biofem, are trying to develop what they euphemistically call "microbicides" -- vaginal suppositories containing chemicals that kill germs transmitted through sex, and usually sperm as well.
This approach has tremendous potential for helping women in AIDS-ravaged countries. One advantage is that women could use the suppositories on their own, whether or not their partners chose to wear condoms. But the technical problems are formidable and funding is limited. It is unlikely that an effective microbicide will be on the market anytime soon.
"Microbicides have great promise, but there [was] little interest or funding in the first 20 years of the AIDS epidemic because everyone said we have condoms and we're going to have a vaccine," Cone says. "Well, we eventually realized that men don't like condoms. We eventually learned that a vaccine will take time -- 10 years at least. Meanwhile, women are getting infected by the thousands."
Rep. Connie Morella, R-Md., and Rep. Nancy Pelosi, D-Calif., recently introduced a bill in Congress calling for an expenditure of $425 million on research on microbicides over the next five years. But unless the National Institutes of Health radically overhauls its funding priorities and some political heavies prove willing to lobby for a product that women stick into their vaginas, an effective microbicide is probably more than five years away.
Clinical trials are complicated and expensive. Researchers often have difficulty confirming that women are using the microbicides -- or having sex. Ethically, the researchers must counsel women participating in trials to get their partners to use condoms (because microbicides haven't been proved yet while condoms have). But each time a woman heeds that advice, she is lost to the study.
Compared with AIDS vaccine research, the federal government spends almost nothing on microbicides. The National Institute of Allergy and Infectious Diseases spent $19 million on microbicide testing in 1999, compared with hundreds of millions of dollars spent on AIDS vaccine work. Microbicide researchers also complain that Food and Drug Administration regulators have yet to come up with standards for the safety and efficacy of microbicides, leaving scientists in the dark about what studies are needed to win FDA approval of the product.
It is sad, though hardly surprising, considering the technical challenges, that drug companies have shown no interest in developing a microbicide. What's more, suppositories will never be as uniformly effective as pills would be, raising the specter of lawsuits.
And of course there's always the bottom line.
"If I were a company and someone came to me and said, 'This product could save a lot of lives, why don't you use it?' I couldn't come right out and say, 'Because we can't make a lot of money on it,'" says Polly Harrison, director of the Alliance for Microbicide Development, a nonprofit umbrella group created in 1998 by the Rockefeller Foundation. "So they say they're concerned about protective capacity, birth defects -- and those aren't nutty things to say. Are they the bottom line? I don't think so. The real reason is the amount of profit you can anticipate."
Who might use microbicides? Women whose partners refuse to use condoms. And who are those women? Many are poor, living in Third World countries, and their use of microbicides would have to be heavily subsidized. They also happen to be the population in which AIDS is spreading fastest.
At a conference of the alliance in Washington last month, participants learned of a survey by British researchers, who interviewed officials from 30 pharmaceutical companies. The executives said their firms wouldn't go into microbicides unless there was a guaranteed $1 billion global market, and one official said it might cost $40 million just to research the market for the product.
With little interest from industry, microbicide researchers must rely on NIH funding for clinical trials. But in a Catch-22, many NIH officials see microbicides as something industry should tackle. In NIH's view, the product lacks pizazz. Most microbicides use relatively crude materials -- detergents and simple antibacterial creams -- which contrasts sharply with the elegantly formulated antivirals that are the current gold standard for fighting AIDS in the developed world. And they can't compete with the fascinating immunology that's involved in working on a vaccine.
"The people on NIH study sections that consider grants for these things are interested in molecular biology," says Thomas Moench, whose Baltimore company, ReProtect, has a product, BufferGel, that is entering expanded clinical trials. BufferGel's main ingredient is a polyacylic acid, a common ingredient of household medications like Tylenol.
"Vaccines are a nice clean thing you give a little baby in their deltoid muscle. Microbicide is something you put on people's private parts. No one wants to hear about it."
Roberta Black, who is in charge of microbicides at the NIAID, says the problem isn't lack of interest but lack of information. "What makes one model of microbicides better than another? We don't know that yet," she says.
Microbicides do have some technical problems. The commonly used detergent not only kills germs but can also destroy healthy bacteria and damage the lining of the vagina. The first microbicide candidate tested in a large study, the contraceptive Today sponge, failed miserably when used by prostitutes.
"Instead of getting dishpan hands, they got dishpan vaginas," Cone says. "That made them more susceptible to HIV."
Inner Confidence, a product developed by Larry Ford at Biofem, includes a detergent and lactobacilli -- healthful bacteria in time-release capsules that are intended to recolonize the vagina after the detergent has done its work. It's a "weed and seed" approach.
Michael Hamrell, a respected scientist who has taken over the product's development since Ford's death, says it should enter trials within a few years. But Cone says Inner Confidence is "nowheresville." And Moench speculates that problems with the product might have been behind some of the trouble at Biofem.