In December 2021, Francis Collins stepped down as head of the National Institutes of Health—a position he had held for a record 12 years—only to be tapped a few months later to serve as acting Science Advisor to the President of the United States. Yet even in the national spotlight, Collins has always preserved a private lifeline to his first love—the trenches of genetic research.

In the 1970s, with a doctorate in chemistry and an M.D., Collins found himself drawn to the field—even when peers said genetics would never be practical, “except perhaps in pediatrics.” His career has consisted of proving those critics wrong. Collins’s early laboratory at the University of Michigan pioneered work in cystic fibrosis, and in 1993 he was asked to head the Human Genome Project, an unprecedented global collaboration that completed a map of the sequence of human DNA in 2003. As NIH director, Collins oversaw and nurtured the revolution in genetics that project helped spark.

Q: Had you ever planned on a life in public service?

A: Not really. When I got the call to join the NIH, there was some resistance on my part because I was enjoying myself. I was running a research lab, taking care of patients and teaching. Part of my negotiation for the job was a request to continue my own research at a modest scale. And I’ve run that research lab at NIH for 28 years.

Q: One focus of your lab has been progeria, a rare disease that causes accelerated aging. How did that come about?

A: When I was a fellow in training at Yale in 1982, I was assigned the care of a patient with progeria. Nothing was known about the cause. Much later I met a White House fellow whose son had just been diagnosed.   I had a postdoc in 2001 who was looking for a new project. The genetic cause of progeria would be really hard to discover, since it didn’t recur in families, so many of the tricks we had access to at the time didn’t apply. But we said, “OK, let’s give it a year.” In less than a year, we had it. It’s a single base pair misspelled in the middle of exon 11 of the lamin A gene.

Q: Did that lead to any therapeutics?

A: Yes. Soon after discovering the mutation and studying the biology of lamin A, we thought, “Maybe this could benefit by treatment with a drug developed for cancer,” a farnesyl transferase inhibitor. Lonafarnib is now an FDA-approved treatment, capable of extending life by a few years. But that’s not good enough—we’re currently exploring two other, much more targeted approaches. One tries to block the abnormal RNA from getting translated. That’s looking really promising, and in our mouse model, it extends life span by a factor of almost two.

Even more dramatically, we are exploring in vivo gene editing in a collaboration with David Liu at the Broad Institute of MIT and Harvard. To our amazement, a single intravenous infusion of a gene editor carried by the AAV9 vector almost cured the disease in our mouse model. So we are now very fired up to work toward a human trial.

Q: You’re also looking at type 2 diabetes—a much more common condition.

A: Yes. The disease has very clear hereditary contributions, which you can tell just by examining family pedigrees. But when we started to study it, it was resistant to any simple models that Mendel would have appreciated. It had to be polygenic.

Well, now we know just how polygenic it is. There are at least 243 regions in the human genome that carry variants that increase the risk of type 2 diabetes. Currently we understand how those variants work for maybe a third of those. But five years ago, we understood almost none. So we’re making real progress, and each clue leads us to potential therapeutic targets.

Q: Any advice to researchers about leaving their labs to engage in public life?
A: I would say—don’t be afraid to get out in public. It’s challenging, but it’s much needed. At our current moment, there’s a distrust of science at a level that I have not seen before. So we all have a responsibility to go out and counter that. Scientists have a great story to tell. If you can learn to talk about the work you do in terms that anyone can understand, you’re going to see people’s eyes light up.