Louis Picker is not afraid to break with convention. Trained as a pathologist, he was on the front line when the AIDS epidemic emerged in the 1980s. He is now combining his interests in immunology and viruses to pursue an unusual HIV vaccine at Oregon Health and Science University (OHSU) in Portland — a project that was considered a fool's errand by many when he began.

How did you get started in research?

I had always wanted to be a scientist. I started an MD–PhD programme at the University of California, San Francisco, but found it much too slow, rigid and hierarchical. I left that programme, but did a year of research there. Ultimately, I decided to become a pathologist specializing in immunology. It's astonishing how much biology you can learn from looking at hundreds of biopsy slides and by performing autopsies every day. I got a feel for the immune system that you couldn't get by doing graduate research on a mouse.

Credit: OHSU

Describe your first AIDS autopsy.

I was a pathology resident at Beth Israel Hospital in Boston, Massachusetts. The devastation left by AIDS stuck with me. I decided to learn more about the disease so that I could do something about it one day. I had the opportunity to move into HIV research in the mid-1990s and haven't looked back since.

What led you to HIV-vaccine research?

Early in my career, I worked on a flow-cytometry-based assay to measure specific T-cell responses to viral infection in humans. I chose to work with cytomegalovirus (CMV), a virus that infects around 50% of adults in the United States and triggers a T-cell response that lasts throughout a person's lifetime. These factors enabled me to test the specificity of the assay. After studying CMV-specific T cells, I hypothesized that CMV could be exploited to create a vaccine that stimulates an immediate immune response to a variety of pathogens. By incorporating bits of HIV into the vaccine, we could prime T cells to hit the intruding virus early and hard. Our data in non-human primate models show that the vaccine stops infection with the simian counterpart of HIV in slightly more than half of recipients.

What does the next year hold for you?

We will move into clinical trials with our potential HIV vaccine. We are also exploring the use of unconventional viral vectors to manipulate the immune system against tuberculosis, malaria, hepatitis B and cancer at a level heretofore unappreciated.

Why did you choose research over more-lucrative private practice?

I knew that if I wanted to make a difference — and to pursue the CMV-based vaccine while others focused on conventional antibody-led approaches — I had to do lab-based experiments. As a pathologist, I would never have had access to patients. The best way to do relevant science was to test my ideas in a non-human primate model. The job I took at the OHSU was one of two possibilities I had at the time to do that type of work.

How easy was it to pursue your idea?

I was fortunate to have negotiated a start-up package at the OHSU that gave me the leeway to gamble. Either I'd make it or break it. I was warmly welcomed by researchers in the HIV field, which I appreciated. But it took me a while to feel that I fit in. Self-doubt was a powerful driver for me.

How risky was your decision?

To be honest, it helped that I had an MD. I knew I would always be able to get a job as a physician, so the degree allowed me a little more freedom in the early years. In the first crucial years while I was establishing myself, I figured I could always return to pathology. Most people with PhDs don't have that option.

What makes a great scientist?

You have to be a little bit of a lunatic. But your out-of-the-box thinking also has to be right.

This interview has been edited for length and clarity.