The Business of Medicine

Five Questions

A conversation with Darren Higgins

portrait of Darren Higgins
Darren Higgins, professor of microbiology in the Blavatnik Institute at Harvard Medical School

What drew you to studying how bacteria invade cells and cause disease?

I am fascinated by the fact that microorganisms we can’t even see with the naked eye can cause so much death and disease in so many different ways.

Who has influenced your career?

There have been a few. My PhD adviser Victor DiRita, now chair of microbiology and molecular genetics at Michigan State, was formative for my development and, in many ways, continues to be. Then there was Dan Portnoy, my postdoctoral adviser at UC Berkeley, who taught me not only how to be a better scientist but how to be a better person. He taught me that in life, but especially in science, one has to be gracious and be generous.

What was your most memorable eureka moment?

One of the major challenges in vaccine development is making vaccines that can stimulate both arms of the adaptive immune system—antibodies and T cells.

As a postdoc, I was working on a technology that could express and target every protein from an infectious pathogen for delivery into host cells for presentation to T cells. If we could do this, then we could rapidly identify which proteins would be the appropriate components to make vaccines better at stimulating T cell immune response. But the technology just wasn’t working.

Then I realized we had a Goldilocks problem: too much of one of the delivery system’s components killed the cell; too little failed to trigger any T cell response. We finally got to the sweet spot. The system, ATLAS, is now being used commercially to develop vaccines for cancer.

How do you stay curious?

I like to solve problems. I like to build things. Kids do this naturally. One time, I was walking with my twin daughters—they were 3 or 4 at the time—and one of them stopped to look at a flower. As I tried to hurry her along, it hit me: we adults get so fixated on the need to get things done that we forget to focus on the basic details and ask the right questions. In every facet of my life, I phrase things in the form of a question. If you ask questions instead of just making statements, the dialogue is much better.

What are the most daunting challenges in the field of infectious diseases?

By 2050, infectious diseases will kill more people than cancer, partly due to antibiotic resistance and partly due to the resurgence of old diseases and the emergence of new pathogens. There’s a dire need for new therapies, but also for new prevention strategies. Another aspect, of course, is social acceptance of vaccines, especially the timing of prophylactic vaccines for children, and combating vaccine hesitancy. Public education and public engagement are critical.

Ekaterina Pesheva is the  director of science communications and media relations in the HMS Office of Communications and External Relations.

Images: Sam Peasley (top); John Soares (portrait).