Salk Institute for Biological Studies: InsideSalk

One on One with... Ron Evans

Ron Evans, a Howard Hughes Medical Institute Investigator and a Salk professor in the Gene Expression Laboratory, is credited for the discovery of nuclear hormone receptors, which have since led to more than a half-dozen drugs for cancer, diabetes and heart disease. Earlier this year, he reached two major milestones: his 60th birthday and the 30th anniversary of his laboratory at the Institute – both were celebrated with a one-day symposium and a party that drew 145 of his former students. Throughout his career, Evans has received some of medical science's most coveted awards and has published more than 250 papers, many of which are among the most cited in the world.

It must have been an overwhelming feeling of nostalgia to see so many of your former students gathered at the same time.
Having them all come back together was like being whole again. Seeing everyone and reliving the work and the camaraderie ... it's not just about the science. The science is born out of the intensity and the hard work. While the paper represents hard and cold facts, it's the product of people who are putting in 100 percent effort for weeks, months and years at a time. So getting back together after all this time was just so enriching and moving for me – really one of the best days of my life.

It must have been a joy to see how the progression of your lab's discoveries was represented in each of the people who were there to celebrate with you since each of them contributed their part to the research.
In a way, they each had a small part and a big part in the evolution and progression of the lab. People joined my lab to work with me and advance their own aspirations. While they changed and evolved, I changed and evolved both as a lab head and as an individual. The lab environment was and continues to be an ever-dynamic process. We are solving problems that by finishing one it illuminates the next. That dynamic of change and challenge and having people at your side to pick up that gauntlet and run with it is such a wonderful part of science.

In your career so far, what has been the discovery that has fascinated you most?
The growing realization that so much of body physiology, endocrinology and behavior is really about the control of gene networks. My initial interests in the early '80s were to study the mechanics and logic of how the genome is controlled. Our interests in cloning hormone receptors ultimately provided us with a key to unlock the secrets of the genome. In the beginning, science is about overcoming technical challenges, which in the end open new avenues of approaching complex problems.

The thing for me is that Salk is an amazing environment where people ask bold questions and being able to bask in the glow of people like Francis Crick, Roger Guillemin, Renato and Sydney Brenner. I think all of us here aspire to not only carry on that legacy but to take Salk to the next level. It takes that kind of imagination that they have to learn from it and pass it along to the next generation.

Is that what keeps you passionate about science?
Science to me is like the ultimate chess game where the opponent is Mother Nature. You're trying to win secrets in a never-ending duel. There's nothing that is more thrilling than pitting yourself against problems that are not yet solved. It's fun, it's challenging, it's often competitive and it's one of the ultimate things that I think you can do as an individual because it's curiosity driven. The process of science tells us about the process of life and that was really brought home by seeing the cadre of people who have been with me over the years and who have gone on to become leaders in their own right. We are one golden age that dissolves into the next. The people who have come through the lab really reflect what can be done by individuals. Science is driven forward by the imagination, and the people that come through the lab bring in the spirit and energy to power discovery.

I know you play guitar. What do you get out of playing that science doesn't provide?
Research is intense and it's frustrating because it's hard to solves the unknown problems for which you're seeking answers. So you have to have a way to pull away from it and often times the only thing that dissolves one intensity is something that you're passionate about in another part of your life. So for me it's the guitar. I love the guitar and I can lose myself in it. It refreshes the spirit.

Any particular genre you enjoy playing?
Guitar for me is a little bit like science. It's ever evolving. In my early days, it was finger picking and folk music. That progressed to blues, then to jazz then that progressed to classical. I like guitars themselves. I like the artistry of the craftsmanship in the wood.

You're a sports fan, right? And you recently received an honorary degree from Mt. Sinai School of Medicine along with Earvin "Magic" Johnson. What was that like?
He is just like he is on television, which is that he seemed just like a big 6-foot 10-inch, 300-pound Teddy bear. You know what I mean? He's a very engaging, interactive and interesting guy.

In what way?
Firstly, Magic is very friendly. He extended his hand to me and congratulated me for receiving my honorary degree. I congratulated him and told him now he can be the real "Dr. J," which he liked (laughs). He was completely accessible which is nice because he's a celebrity and celebrities are often not that way. He's done a lot in his career, he's overcome a lot and he's a leader. He's done just as much off the court as he's done on the court. In addition to the honor of meeting him, I love the Lakers so it was a double bonus.

Your lab drew worldwide media coverage last summer with the "Exercise in a Pill" study. While the research was conducted on mice, how plausible is the idea that one day those who cannot physically exercise because of disease, frailty or obesity will be able to get the benefits of physical activity by taking a pill?
I think the work clearly demonstrates, that in mice, it is possible to develop drugs that have the capacity to enhance muscle performance with out actually exercising. That is a major advance. It also identifies two key drug targets for which the next generation of more effective muscle-enhancing drugs can be produced for people. In fact, the drugs that we used have already been in people. So now I would say it's going to take a large pharmaceutical company to develop the right type of program in muscle biology.

You never really know, but my guess is that probably within four to five years we'll see the next generation of drugs, while the current generation of compounds is being explored for this purpose. The challenge in bringing this forward is getting the FDA to agree that frailty and obesity can be treated with muscle-enhancing drugs. You have to cure disease to get a drug approved. We think we can make people a lot more healthy. But making people healthy is not an FDA approval end point. We need to educate the public and the medical community to move the FDA toward accepting the benefits that can be achieved by this kind of program.

What's the one scientific question in your field you'd like answer in your lifetime?
Since we are in the bicentennial of Charles Darwin's birth, I would like to know the origin and evolution of physiology. Understanding the origin would give us a much deeper insight into how general physiology goes bad. When physiology itself is not controlled, it's highly destructive to the body. When it is controlled, it's everything that we call life. We want to get a handle on that. We would like to exploit all of that for the purpose of developing a new generation of drugs that control metabolic disease. That includes diabetes, heart disease and using our understanding of genomics and genomic control to develop muscle-enhancing drugs.

InsideSalk 07|09 Issue | © Salk Institute for Biological Studies