By 1993, Merck had all but scuttled its AIDS vaccine project and shifted Emini to the head of a team developing a protease inhibitor against HIV. (Protease inhibitors don’t prevent infection but quell the ability of an infected person’s cells to make new viruses, slowing-and for a time even reversing-the disease.) In 1997, one year after Merck marketed the bestselling protease inhibitor Crixivan, Emini turned back to the AIDS vaccine project. In a remarkable flip-flop, Merck quietly began a new program that completely ignores HIV’s surface proteins and antibodies. “Now it seems like a reasonable thing to do,” Emini says. “Will it seem like a reasonable thing to do two years from now? I’ll let you know two years from now.”
And Merck’s reentry into the field with an intensive, methodical new program has buoyed spirits tremendously. Researchers are excited because Merck makes a habit of backing its scientists-and has ample cash with which to back them. In 2000, Merck grossed $40 billion and funneled nearly one-third of its $6.8 billion net back into R&D. In short, if Merck wants something, it does not need help from the government or philanthropies. It just takes out its checkbook.
Consider how Merck responded to Emini’s decision to build the new AIDS vaccine program around studies in monkeys, which are in short supply and notoriously expensive. Ordinarily a company that does such experiments relies on academic collaborators who have access to government-funded primate research centers, or it hires a private firm that raises the animals. Merck simply bought its own monkey-breeding colony in 1999 and since has supplemented it with hundreds of additional animals. Anthony Fauci, director of NIH’s largest AIDS branch, the National Institute of Allergy and Infectious Diseases, notes that Merck has a long history of converting basic research insights into products. “Merck’s record speaks for itself,” says Fauci.
Emini and his right-hand man, John Shiver, first unveiled Merck’s monkey data to their scientific colleagues at a prestigious AIDS vaccine meeting in spring 2001 in the ski town of Keystone, CO. Merck came to the meeting in full force, sending 30 of its scientists, accounting for nearly 10 percent of the total participants. No other company even has 30 scientists devoted to AIDS vaccine R&D. When Shiver and Emini showed a slide at the end of their presentations that listed nearly 50 senior investigators with their own teams working on the project, there were audible gasps from the audience. Merck towered over the other companies with its mountain of new scientific data.
When it came time for Shiver to speak, he showed a head-to-head comparison of five different vaccines in 21 monkey experiments. Asian monkeys develop an AIDS-like disease when infected with simian immunodeficiency virus, a monkey cousin of HIV, or with a laboratory-made hybrid virus that combines the monkey virus and HIV. Researchers can vaccinate monkeys and then challenge their immune systems with an injection of either of the two viruses to test the worth of the vaccine. Merck created its test vaccines by stitching a gene that codes for a protein from the interior of the monkey AIDS virus into five different “vectors” that carry the gene into the body. Three of the vectors were simply circular pieces of bacterial DNA, or “naked DNA”; the other two were harmless viruses commonly used in vaccines.
Merck’s best results in these monkeys closely resembled those seen by some of the academic researchers at the meeting: vaccinated monkeys became infected when challenged with the hybrid virus. But unlike unvaccinated animals used as controls, the vaccinated monkeys remained healthy. The researchers linked their protection not to antibodies but to a less famous contingent of the immune system, killer cells. Antibodies and killer cells work in concert. Antibodies glom onto invaders and prevent them from infecting cells; killer cells clean up, targeting and eliminating cells the invader manages to infect. Merck’s research showed an edge over other groups’ work in such subtle parameters as killer-cell production and levels of the hybrid AIDS virus found in the protected animals. More importantly, Merck had moved quickly to begin testing the most promising vaccines in humans, a feat that none of the academics could match.
Everyone acknowledges that the monkey results may not translate into humans. Ronald Desrosiers, head of Harvard University’s primate center and a pioneering AIDS vaccine researcher, emphasizes that researchers still are guessing whether a vaccine needs to crank up production of killer cells, antibodies, a combination of these responses, or some other immunologic warriors. “Believe it or not, we have no frickin’ clue what one needs for an effective immune response,” Desrosiers says.
Another huge problem is that different labs often test their vaccines against different challenge viruses, each of which has a different potency. “You can get basically any result you want based on the challenge virus you use,” says Desrosiers, who believes that the hybrid AIDS virus used in Merck’s tests is relatively easy to thwart. “Nothing against Merck, but it’s going to be damn tough to protect against viruses in the field,” he says, where much more robust strains of HIV run rampant.