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Witnesses to a Tragedy

Thirty years have passed since alumnus Michael Gottlieb first identified AIDS. Now, biochemist Eddy Arnold has devised an effective medicine to fight it. 

 

Dr. Michael Gottlieb, and biochemist Eddy Arnold
Michael Gottlieb, left, with Eddy Arnold, photographed at the Center for Advanced Biotechnology and Medicine at Rutgers–New Brunswick. Photography by John Emerson

A yeast infection in the throat. Shortness of breath. A cough. It was a strange mix of symptoms for an otherwise healthy 31-year-old. Dr. Michael Gottlieb, a 33-year-old immunologist and an assistant professor at UCLA, suspected something was up. Lung tissue revealed that the patient had Pneumocystis carinii pneumonia. Gottlieb RC’69 asked for a count of T helper cells, a key to a healthy immune system. The results were astonishing: the patient had none.

It was a medical mystery, and it deepened when Gottlieb learned about another case like it, and then another, among gay men in Los Angeles. Gottlieb wanted to submit the details to a medical journal, but that took time, and this was an emergency—not business as usual. “It was an observation Gottlieb would recite almost daily in the difficult years ahead,” Randy Shilts wrote in And the Band Played On: Politics, People, and the AIDS Epidemic (St. Martin’s Press, 1987), his landmark book about the early days of the AIDS epidemic. “For this young doctor, about to be credited with the discovery of the public health threat of the century, the thought became a grim mantra for the AIDS epidemic.”

On June 5, 1981, Gottlieb’s report about the looming epidemic (“Pneumocystis Pneumonia—Los Angeles”) appeared in a Centers for Disease Control and Prevention publication, the first published report of AIDS. Within days, doctors nationwide were calling Gottlieb with similar cases. Gottlieb’s 31-year-old patient was dead within the year.

The following years were harrowing, with a handful of AIDS cases (and deaths) turning into hundreds and then thousands. Yet many viewed the epidemic as having nothing to do with them. Then, in 1985, actor Rock Hudson revealed he had AIDS; Gottlieb was his physician. Awareness about the epidemic was growing, though there was still much confusion—and inaction. It wasn’t until 1987, six years after the epidemic began, that President Ronald Reagan uttered the word AIDS in public. It was a year of milestones: the group ACT UP (AIDS Coalition to Unleash Power) was founded to confront the crisis, the AIDS Memorial Quilt was displayed on the National Mall, and the first drug to fight HIV—azidothymidine (AZT)—was approved.

During the same year, a 29-year-old researcher at Rutgers by the name of Eddy Arnold was establishing a lab to uncover the microscopic mysteries behind HIV, a puzzle of mind-boggling complexity that would probably take years to solve. To Arnold, a key to developing AIDS drugs would come from understanding the molecular structure and function of reverse transcriptase, an essential part of the virus’s replication. In 1993, Arnold and his team made a breakthrough, describing reverse transcriptase in action and hinting at the clues this held for drug development: “AIDS therapies may be enhanced by a fuller understanding of drug inhibition and resistance emerging from these studies,” the team wrote in an academic paper. It was a time of shifting attitudes toward AIDS, which was now the leading cause of death among young adults in 64 cities in the United States.

As Arnold’s research gained attention, HIV was being fought with AZT and, later, drug cocktails. Yet the AIDS virus was mutating, and resistant strains were a growing problem. How do you develop a drug when your target keeps changing? Arnold had teamed up with Paul Janssen, a legendary drug developer (and founder of Johnson & Johnson subsidiary Janssen Pharmaceutica), and together they worked on developing a drug with enough flexibility to adapt to changes in HIV. And that’s part of the secret behind Edurant, a drug initially developed 10 years ago that only last spring made it through the regulatory gauntlet, the first AIDS drug to be approved by the U.S. Food and Drug Administration in three years. Edurant benefits HIV-positive adults who have not received treatment using other drugs, and preliminary findings are very encouraging. Clinical trials of HIV-positive adults indicated that more than four out of five had undetected levels of HIV in their blood at the conclusion of the 48-week trial. Arnold—a Board of Governors Professor of Chemistry and Chemical Biology at Rutgers–New Brunswick and faculty member of the Center for Advanced Biotechnology and Medicine—had always dreamed of developing new medicines, and he knew he was going to be in it for the long haul. “At times, sprints are required,” Arnold says. “But overall, it has been more like a marathon than anything else.” •       — Allan Hoffman