Sallie Permar, MD, PhD ’04
Karen Thomas spoke with Sallie Permar, MD, PhD '04, who was among 102 researchers nationwide selected to receive the 2012 Presidential Early Career Award for Scientists and Engineers, the highest honor bestowed by the U.S. government on early-stage science and engineering professionals. She is an associate professor of pediatrics at Duke University who specializes in pediatric infectious disease and directs the Laboratory of Neonatal Viral Pathogen Immunity within the Duke Human Vaccine Institute.
Q. How did you become interested in medicine and basic science? Who or what were some of your important early influences?
A. I grew up in North Carolina and went to Davidson College, and knew I was inclined toward science and math. They had opportunities to travel abroad and visit places I’d only dreamed of, so I spent the summer in a Presbyterian mission hospital in eastern Zambia. We arrived very late at night and there was no electricity in most of the village, so it was completely dark. We didn’t even shut the curtains, it was so dark. We woke up in the morning with village children looking through our window!
It was a very stark reality for me to see a place where people were living on so few resources. It was 1996, at the height of the AIDS epidemic, especially in the rural areas. The hospital was full of patients with TB and other opportunistic infections, with very little equipment. There was a measles outbreak, but the village wasn’t set up for that, so they had to dedicate an isolation ward in the hospital that was full to the brim.
We went out in a truck to vaccinate every child we could find. I asked, “if there’s a vaccine available, why is this village still experiencing an epidemic?” I knew I wanted to commit to improving global health for places like Zambia, because poor health was really holding places like Zambia back, and preventing them from achieving what they could be achieving.
Q. What made you choose Johns Hopkins? What did you know about public health before you came to the Bloomberg School?
A. I was really interested in immunology and vaccine development, and the program at JHSPH really stood out to me. Every PI in the Department of Molecular Microbiology and Immunology was focused on a disease, instead of one pathway or arm of the immune system. I really liked that, because my motivation to go into immunology was to solve the challenge of infectious disease.
I was very excited when I got admitted, and didn’t give another thought to any other programs I’d applied to. I wanted to get more international experience, and applied for a Fulbright to return to Zambia for a year, where I worked at the University of Zambia teaching hospital and virology lab with a pediatrician. I called Diane Griffin to ask if I could defer for a year so I could do the fellowship. She said that she was putting together a project on measles vaccines in Zambia at the same university, and she actually came to Zambia during the year I was there, to investigate measles virus in HIV-infected individuals. It worked out great that I was already there and paid for, so I ended up being a research coordinator for Diane’s study, and also worked closely with Bill Moss. So that was a very fortuitous stroke of luck! And that research became my thesis project.
Q. How did completing a PhD in a school of public health shape your research and subsequent career? What is unique about the Department of Molecular Microbiology and Immunology, and what were the most important lessons you carried away from Hopkins about vaccine research?
A. I could take courses in International Health and other public health areas, which I couldn’t have done in other basic science departments. In MMI, we were studying immunology in the context of a school that was looking for broad solutions to global public health problems. Not only did we need to make a better vaccine, we had to think about how to distribute it, how nutrition might affect response to the vaccine, and how we could make sure that the vaccine was effective in all kinds of populations, especially in poorly resourced areas.
Greg Glass taught the infectious disease epidemiology course on how epidemics develop and ways to develop mathematical models to predict the spread of disease. We asked, “if a vaccine is 50 percent or 80 percent effective, will it be enough to end the epidemic?” He showed us all the challenges a new vaccine would face in reducing disease prevalence.
I love working at that bridge between clinical and preclinical studies, that was provided from the work I did at Harvard and Hopkins.
Q. What was it like to work with Diane Griffin?
A. Diane is such an inspiration to young female scientists. She was fearless, and came through when there were far fewer female scientists. She’s developed a research portfolio that really drove two fields, measles and encephalitis. I see her as a pioneer for all women scientists.
Diane was perfectly willing to mentor me from abroad and then have me take on part of their planned studies on measles vaccines in HIV-infected children. People from all different backgrounds came through the lab and told me about patients they would see in the hospital, and then I would come back to the lab and study the viruses.
When I wanted to go to medical school, Diane made allowances for me to fit studying for the MCAT into my schedule. She told me that having both an MD and PhD had opened up a world of opportunities for her, and that was what I needed to do. I got into Harvard Medical School, and Diane really worked the magic for me to find a mentor in Boston so I could continue my thesis work while in medical school. My mentor was Norman Letvin, discoverer of the simian HIV virus and the primate model for AIDS research. Diane came to his lecture in Boston and gave her pitch to enable me to join his laboratory.
Children with impaired immune systems couldn’t control virus replication as well, and I pursued those studies in his lab. All my holidays were spent in Baltimore, going to my committee meetings or doing research. Between Diane and Norm, they made it possible for me to complete my MD at Harvard and PhD from Hopkins simultaneously in 2004. Looking back on it, I think of how many people have set me up for the career I have now, and Diane was instrumental in convincing me that I shouldn’t let the dream of getting a PhD go by the wayside, and that it would pay off in the end. Norm was a translational investigator who was creative and flexible enough to allow me to join his laboratory.
Q. What made you decide to pursue maternal-infant HIV transmission while you were still a student at Hopkins and Harvard?
A. I transitioned into HIV work in Dr. Letvin’s lab. I’d been studying measles in an HIV-infected population, so it was an easy jump. I also decided to pursue pediatrics, since I was interested in vaccines. I followed the example of the pediatric infectious disease fellows from Diane’s lab.
Mother-to-child transmission had not been well explored, and I used Dr. Letvin’s non-human primate model. Breastfeeding now contributes to almost half of all HIV infection. Drugs have done a good job of preventing transmission in-utero and at delivery, but there’s an implementation challenge in preventing breast milk transmission for as long as two years.
We could develop either an infant HIV vaccine or a maternal vaccine given while the mother is pregnant, like the maternal vaccine developed for tetanus. We had to look at immune responses in both the bloodstream and in breast milk.
Q. What are the results of your latest work on breast milk transmission of HIV?
A. Eliminating breast milk transmission of HIV-1 is a key strategy for achieving an AIDS-free generation. We identified a primary HIV-1 inhibitor in breast milk which neutralizes transmitted/founder HIV-1 variants, which may explain why the majority of HIV-1-exposed breastfed infants are inherently protected against acquiring the virus. This innate mucosal HIV-1-inhibitor is a good candidate for a natural, nontoxic infant HIV-1 vaccine.
Q. What excites you most about working in a laboratory and doing scientific research?
I get this from my family: are you killing monkeys? Is that what you do? But the beautiful thing about a model so close to humans is that you can ask questions in the monkey model that you’d never be able to in the human model. For example, you can ask what arm of immune response is most important, and you can infect the monkeys to see which approach gives the best result.
But human studies also give answers you’d never get from monkeys: are there certain human responses that are more common in people who get infected versus those who don’t? You can get a window into what might be a protective response, and then you can go to the monkey model to prove whether your hypothesis is right.
Q. What led to you winning the PECASE Award?
A. I work at Duke with Sam Katz, one of the original investigators on the maternal vaccine to prevent congenital measles and rubella, which can cause blindness and hearing loss. When the vaccine was introduced, schools for the blind and deaf had to close, because there were no longer enough children to fill them. I decided to try to take on the problem of cytomegalovirus (CMV), a type of herpes virus that affects 40,000 infants in the U.S. and causes lasting neurologic deficits in 25 percent of them. I saw those patients in my clinical work and saw the need for a maternal vaccine, since mothers with CMV have a very high risk of transmitting it to the fetus.
The only existing model for CMV was the guinea pig, with very different anatomy and resistance. The PECASE award was for developing the CMV model in rhesus monkeys and proving that the virus would cross the placenta. We already have good leads on developing a vaccine to prevent fetal transmission of CMV.
Q. How does your experience with pediatric patients, your in-depth basic science training, and your knowledge of public health intersect? Is your inner scientist ever at odds with your inner pediatrician or public health professional?
A. Blending all those backgrounds has only been beneficial, in thinking about areas to pursue and understanding the major health challenges for infants. I’ve only seen all those aspects work together and help me make the right choices about what’s going to make a difference. Norm Letvin would say over and over, “there’s only so many experiments you can do in your life, so you have to think very hard about each one, and whether it’s worth your time. Will it move the field forward and open the door to other things?”
I’ve thought about whether CMV is much of a problem for the developing world, and perhaps CMV is a huge but unrecognized problem in the first year of life. But I’m very well-positioned to work in vaccine development, so maybe I’ll have to leave that behind. I’ve started to realize there is a limit, and you have to focus on what no one else can do. Maybe I’m better suited to stay in the translational epidemiology world. With all these backgrounds, I can envision all these studies that would be great to do, but I can’t do everything, and it’s hard to make the choices.
Q. What do you think are the most important issues that public health scientists will address in the future?
A. There will always be a field of public health. As an infectious disease physician, we try to work ourselves out of business by making vaccines to prevent each disease, but there’s always a new strain or emerging disease. There’s a constant need for strongly public health-minded scientists who can see the full range of challenges in preventing major epidemics. What I’d like to see in my career is an effective HIV vaccine that can work together with ARV drugs and can be applied in a mother-child setting. Prevention is always ten times better than a cure.