Bitter Pills

The AIDS drug Ziagen has brought healthy windfalls to the University of Minnesota and GlaxoSmithKline. But it isn't doing anything at all for the millions who are dying of the disease in Africa.

To Swarr the announcement was a promising, albeit symbolic, first step. But, she contends, unless the university cedes its patent on Ziagen, the school's exclusive deal with GlaxoSmithKline will prevent generic equivalents from reaching AIDS patients in Africa. As Swarr sees it, the Ziagen controversy is only part of a larger debate simmering on campuses across the nation over the increasingly symbiotic relationship between academia and private industry, particularly pharmaceutical and biotechnology corporations. Advocates of licensing arrangements like the U of M's deal with Glaxo argue that they are the only way to move university research from the lab to the pharmacy shelf; critics contend that such deals make universities veritable R & D departments for private corporations--in effect, giving drug companies monopolies over research funded by the National Institutes of Health.

The heart of this debate is intellectual property: If licensing agreements create an unjust monopoly on publicly funded science, are universities still serving the public good? "Why should corporations get to dictate how a university invention is marketed and distributed?" Swarr asks. "And what does it mean for future research? If corporations have this power, does that mean researchers will only work on drugs that are profitable?"

 

Seated in his modest, neatly arrayed office just a few feet from his lab at the University of Minnesota, the man credited with creating Ziagen is flanked by portraits of Albert Einstein and Moe from the Three Stooges. The two figures seem to describe the poles of Robert Vince's professional persona--the combination of a rigorous mind and a strong creative impulse. Though his discovery has made him both famous and wealthy, the 60-year-old chemistry professor retains the stereotypical scientist's slightly owlish appearance and retiring demeanor; he's clearly a man more constitutionally suited to the lab than the public spotlight.

Not surprisingly, the attention his work has attracted in recent months has left Vince slightly wary; when he discusses Ziagen, he chooses his words cautiously and uses them sparingly. But when talk turns to the science behind the drug, he grows animated--a reflection of the passion that drew him from a summer job behind a pharmacy counter to a Ph.D. program in medicinal chemistry. "I was interested in science and medicine from a young age," he explains. "And medicinal chemistry incorporates a lot of basic sciences: You have to know drugs, biochemistry, and pharmacology. It's rare to have all these disciplines in one person."

After completing his doctorate in 1966, Vince was attracted by the relatively new field of antiviral medicine. Scientists had only recently begun to explain the behavior of viruses, and the first antiviral compounds emerged somewhat serendipitously from other research: While working with anticancer agents, scientists discovered that nucleotides--the basic components of DNA--could be chemically altered to disrupt the reproduction of a virus.

Early in his career, Vince also got a hard lesson in the business of science. In the mid-1970s he developed a compound that was effective in halting the spread of the herpes virus. Yet because he didn't obtain a complete patent on his work, it was impossible to interest a drug company in developing the research for market: Since companies couldn't be sure that they alone would have access to Vince's research, they were unwilling to expend time or money testing his new compound. "Without patent coverage," Vince explains, "when we design something, it's hard to engage pharmaceutical companies and get them interested.

"Before 1980 there were a lot of restrictions [on patenting]," he goes on. "It was very rare that anybody would pay attention to what you were doing. It wasn't typical that someone would come to you and want to get involved. Around 1985, though, things started to change. And that also coincided with the discovery of the AIDS virus."

Like most members of the research community, Vince began hearing about AIDS in the mid-1980s. It was clear from the outset that this virus represented a new kind of enemy. As with all viruses, its behavior might be compared to an invading army: HIV inserts itself into human cells, then, with an enzyme called reverse transcriptase, uses the cell's own reproductive machinery to replicate itself as many as 1 billion times every 24 hours. But this organism behaved differently from previously known viruses, depressing the body's immune system and mutating so quickly that attempts to understand its reproductive mechanism--much less confound it--could hardly keep pace.

The few drugs available to treat AIDS--AZT, for instance, and d4T, which were first synthesized in the 1960s--had been developed to fight cancer. But Vince realized early on that the work he was doing with modified versions of basic DNA molecules--compounds known as nucleoside analogues--could be applied to AIDS. After a decade's worth of fundamental research into the behavior of viruses, he knew that altered nucleosides could act as chemical decoys, stopping reverse transcriptase from commencing the replication process, and thus effectively neutralizing the virus without destroying healthy cells. In 1986, with a research grant from the National Institutes of Health, he set out to synthesize the first compound ever designed specifically to combat HIV.

As he recounts the history of his discovery, Vince gravitates toward a chalkboard on one wall of his office and proceeds to diagram the molecular structure of a nucleoside called guanosine. In order to ensure that his compound would target only infected cells, Vince grafted a synthetic sugar to the nucleoside. Evolutionarily sophisticated human cells would recognize the synthetic compounds as impostors and reject them; the virus would not. Pointing to one of the pentagram's corners, he continues, "What we did is replace an oxygen molecule with a carbon. That makes the compound very, very stable." Less stable molecules, Vince explains, are likely to be broken up by stomach acids before reaching their target. To be effective, AIDS therapies, which are often taken in complex, multidrug regimens, must be able to pass easily through the body to the white blood cells and brain tissue where HIV hides.

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