On April 28, 2011, after their traditional breakfast of pancakes, eggs, toast, hash browns, and bacon, Myron Cohen and his team had their traditional three-hour wait at the National Institutes of Health (NIH). It was the eleventh progress meeting for their blinded clinical trial in the HIV Prevention Trials Network, dubbed HPTN 052. They nervously loitered, with some indigestion, to hear whether treating the AIDS-causing virus with "antiretroviral" drugs reduced the rate at which people transmitted HIV to their sexual partners.
Behind closed doors, statisticians and an oversight board pored over data from 1,763 couples in nine countries—including Malawi, where the work sprouted. Finally, a board member summoned them into a room. Without eye contact, he made a cold, unusual announcement: their NIH sponsor would inform them of a recommendation. Assuming failure, one team member, who had spent more than a decade on the trial, burst into tears. She continued to cry on the way to the airport to return to the University of North Carolina.
But before takeoff, NIH beckoned them back. They returned to a room full of people involved in the study, including the agency’s number two official, who shook his head in fake disappointment. “Guess what,” he said flatly. “It’s a home run.”
Indeed, the result—that treatment blocked 96 percent of transmission, keeping 27 partners from contracting HIV compared to the control group—was a clinical triumph. Science later chose the research as its 2011 Breakthrough of the Year.
Cohen spoke about the project at the February 2012 meeting of the American Association for the Advancement of Science in Vancouver, Canada. Afterward, he shared stories about his path through science with SciCom’s Beth Mole.
How did you get started in global health and infectious disease work?
I’d like to say I have a brilliant, linear answer. I wasn’t a high school whiz waiting to be an expert in sexual disease—nothing like that. To some extent, the answer lies in a combination of timing and carpe diem. I think my evolution started in the 1970s when I was at Yale. I had gone through my medical training and was there working as a scientist—as a pretty serious biochemist. My wife is a China scholar, and Yale sent us to China for a year, where I worked on hemorrhagic fever. That was my introduction to working in global health.
What made you decide to go to China?
My mentor, Richard K. Root, said “go to China for a year.” He was one of my best friends and one of the smartest people I ever worked with. But, it’s the most random thing. I was working on biochemistry. Why did I think it was good idea to go to a country that I had nothing to do with and where I didn’t speak the language? It was frankly crazy. But, had I not gone on that trip, none of this would have happened. I needed to live in another country to understand something about global health.
Do you think your willingness to take chances was important for your career?
I wouldn’t call it a willingness to take chances—I’m a pretty risk-averse person—but to seize opportunity. Each opportunity I see, I force myself to say, “Even a broken clock is right twice a day.” When I think an idea is crazy, I tend to be even more careful not to reject it.
"For everything you want to do, there are a thousand people who say it’s not worth doing. For this study, very famous people told me I was wasting my time."
What would you think now if one of your mentees had an idea analogous to your trip to China?
I would think they’re crazy.
When you came back from China, what made you move to the University of North Carolina?I knew I’d leave Yale when I got back. I ultimately took the job at UNC, in part because of another philosophical point: always like and trust the person who’s your supervisor. At UNC, I’ve only reported to people who I like and trust over my entire career.
At UNC, how did you transition from biochemistry to global health and HIV research?
In Chapel Hill, I was working on oxygen chemistry and white blood cells. The group was very focused on sexually transmitted infections, and the people working on gonorrhea asked me to work on interaction with white blood cells. I became increasingly interested in the transmission of gonorrhea. We took a person with a new infection and we’d count the number of bacteria [in genital secretions]. We showed that when you took an antibacterial drug, gonorrhea disappeared within four hours.
Then, I saw my first case of HIV in 1981. As a physician, I was increasingly taking care of patients with HIV. By 1985, 14% of all the admissions to UNC hospitals had HIV infections. There was no treatment. They all died. You can’t blind yourself from that clinical problem. Around 1988 to 1989, I started to take the gonorrhea experiments and extrapolate them to HIV.
How did that evolve into international work?
A gentleman named Peter Lamptey came to me—because I’d lived in China. I was the only infectious disease person at UNC who had worked internationally. He said, “We’re going to compete for a grant to do HIV prevention internationally, and we want you to go in with us.” We won it and divided up the world.
Why did you choose to work in Malawi—now UNC’s flagship international research site?
We took a map of the globe and we threw darts. We knew nothing about Malawi. But once we got to Malawi, we saw instantly that 50% of the people with gonorrhea are HIV infected. So, the most obvious experiment was to collect semen specimens and count the number of gonorrhea and the number of HIV particles. Treat the gonorrhea and see if the HIV goes down.
In general, we found a pretty big dynamic range of HIV in semen—there could be a small amount or a very large amount. We hypothesized that the lower viral load would lead to less transmission.
When you were designing and launching the HPTN 052 trial, what were some of the big hurdles?
A door opened through the NIH networks, but they said in order to do this study you have to find the drugs yourself. They have to be made in the U.S., and they have to be free. This was a challenge of unbelievable magnitude, because there was no incentive for a company to give away these drugs.
How did you convince the six drug companies to donate HIV drugs?
Negotiating skills—back and forth, iteratively. It took all my energy. I would go to them and say the answer is ‘Yes,’ how are we going to get to ‘Yes?’ For the last drug company representative, who's now a very good friend of mine, I sent her a dozen roses. With that drug, I was ready to go. So, tenacity: it's so much more important than brains. Brains are good, but tenacity is irreplaceable.
At the same time, I had to bring on a team of people that were going to do this study around the globe. This is where trust came in. I had to get all these people and trust them. And they had to trust that I was going to get this off the ground.
In order to develop that trust, did you go to the 13 trial sites and oversee progress?
The last thing we would want was me trying to get under the hood and micromanage. Other, much more competent people were doing everything in the study. The strengths that I brought to the table were optimism and cheerleading. I outsourced all cognitive things. If you were an expert, I would cheerlead you. I would never think I could do a better job than you could do.
It must have been difficult to always be optimistic. How did you manage to do that?
I had to give myself pep talks. I’ve had a thousand moments of fatigue and anxiety. For everything you want to do, there are a thousand people who say it’s not worth doing. For this study, very famous people told me I was wasting my time.
Did you ever think they were right?
Never for a moment. I knew exactly what I wanted to learn from the study: the magnitude and durability [of treatment as prevention]. We assumed that by treating people we rendered them less contagious. Did we really need to know how much less contagious? From my point of view, that was an important consideration.
I’m very concerned about making sure we’re asking important questions and questions that have legs—not dead-end questions. Does it have immediacy and urgency? How important is it to clinical medicine or public health policy? If it’s trivial, why do it?
Have you ever found yourself working on a trivial question?
Yes. In the 1980s, I got involved in one area of science that was absolutely stupid. I started messing around with herbicides that generate free radicals—paraquat [a type of herbicide] is the best example. I loved it. I still think it’s interesting, but, boy, I would never let a researcher do it. Paraquat? I published a whole bunch of articles, which I’m sure no one ever read. Sometimes as a scientist, you get enamored with a pathway, but no one cares about the pathway but you.
Going back to the trial, what did you think of all the recognition you received for HPTN 052?
For me, it’s about the journey and not the outcome. I take great pleasure in small accomplishments. When I came home and told my wife the results, she said, “You prevented 27 cases of HIV.” It's unbelievable, but I was focused on just making sure the trial worked. I hadn’t gone there myself.
After you published the HPTN 052 results, The Economist ran a cover story posing “The End of AIDS?” Do you think this could be the end of AIDS?
No. It’s a sine qua non—without which there is nothing. The work is a cornerstone, but it doesn't guarantee that treatment will serve as prevention. Translating it to a public health intervention takes a lot more. But, I think 96% was a catalytic number. It gives a stronger belief in the power of intervention than could have ever come from aspiration. Next is quality assurance; we have to make the intervention work.
How do you feel about the next stage of your career?
I won the O. Max Gardner award a few years ago [a UNC-based award for “the greatest contribution to the human race”]. In the acceptance speech I gave, I said I can only hope that my most important contributions are still in front of me, not behind me. That's exactly how I feel today.
_________________________
Beth Marie Mole, a graduate student in the Science Communication Program at UC Santa Cruz, earned her bachelor's degree in biology and ethnomusicology from The College of William and Mary and her Ph.D. in microbiology from the University of North Carolina, Chapel Hill. At UCSC, she has worked as a reporting intern at The Salinas Californian, the Stanford Medical School news office, and the San Jose Mercury News. This summer, she'll work in Washington D.C. at The Chronicle of Higher Education.
