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One on one with… Ron Evans

Ron Evans

Ron Evans

Ronald M. Evans, holder of the March of Dimes Chair at Salk, is best known for discovering a family of receptors found on the nucleus of cells, an advance that's helping to explain the complex molecular systems that are the basis of human physiology.

As one of the lead researchers in the Institute's new Helmsley Center for Genomic Medicine, Evans has teamed up with other Salk scientists to explain how the biological programs coded for in the genome orchestrate our biological rhythms and how glitches in this programming lead to disease.

We caught up with Evans to ask him about the new Helmsley Center, his penchant for embracing cutting-edge technologies and his gift for making the complicated seem simple.

Ron Evans

The Helmsley Center for Genomic Medicine has a strong focus on providing Salk scientists with access to the latest research technologies. Why is this such a large part of the vision for the center?

The Helmsley Center is about an idea and technology that enables ideas. Technology drives science by letting us ask new questions, which in turn lead to new answers. With the ability to sequence an entire genome— whether that of the fruit fly or a human—we suddenly had tools needed to study complex systems like organ physiology, inflammation and chronic illness. And more of those tools are being developed every day, such as high-throughput sequencers, bioinformatics, genome engineering and atomic resolution microscopy. The secret is being able to generate and manipulate massive amounts of data in a rapid fashion. Of course, having technology is no guarantee. Machines do not design experiments. To access the real power of the technology, you have to ask the right questions.

Have you always been an early adopter of new research technologies?

I was exposed early in my career to what were, for the time, really advanced technologies. First it was RNA sequencing, then DNA cloning and then DNA sequencing. That was all in the '70s and was followed by genetic engineering of animals in the early '80s. I learned that you either create it, adopt it quickly or you will be steamrolled. You need to operate at the cutting edge. When I started, there were no biotech companies like Life Technologies or Illumina that provided you with ready-made tools, so we had to make all the reagents and build many instruments ourselves. We were doing DNA sequencing in 1975 before 99 percent of the world was doing it. At Salk, we began engineering the first transgenic mice in 1982. Forward thinking tends to push you forward, and once you get used to that, you get bored if you're not at the frontier. The Salk is the exact right place for pushing the frontier.

Does that extend to your personal life as well?

I've always been into very high-fidelity audio equipment. My brother and I used to build receivers, amplifiers and shortwave radios and set up media rooms with the equipment we built. I really enjoyed working out the electronics. I don't build those systems anymore because the components now are all solid-state electronics that don't work well with the old style of do-ityourself fabrication. But we do have a remote-controlled audiophile sound and media system in our house set up to be controlled in any room through an iPad. It's ridiculously complicated, but fun.

Many of the young researchers trained at Salk have gone on to become leaders in their areas of science. What characteristics do you need to be a successful scientist?

Being comfortable with taking risks is important. When you're working inside the box, there is a lot more information. You know what's safe and what's not. But outside the box there is less information and more danger. You have to develop good instincts and have confidence that the problem is big enough to overcome all the challenges. Francis Crick is a great example of how you can be so ahead of your time, so far out of the box, that it can be very risky. After discovering the structure of DNA, Francis came to Salk to study consciousness, which at the time was an audacious idea. Many scientists at the time questioned whether consciousness was an appropriate problem and, if so, what would be the technical challenges needed to make a breakthrough. Francis was far ahead of his time, but he set the field in motion.

Do you have any burning scientific questions that current technologies are incapable of answering?

Ron Evans

For Watson and Crick, the question was about the structure of the gene. In my era the question became "How is the gene controlled?" and more generally, "What is the mechanism that controls and coordinates the activity of large gene networks?" The nature of gene regulation is very challenging, yet it lies at the heart of normal physiology. When crippled, it is the source of chronic disease. I'm also very curious about the origins of genes. For instance, we know that many genes in our bodies came from primitive organisms like bacteria, mold and yeast. But I work on nuclear hormone receptors, which aren't found in those organisms. Nuclear receptors are integral to human physiology, but where did they come from? Where did we get the genes that tell our cells to produce them? If we could solve that mystery, we'd know a lot more about who we are and how we interact with our environment.

You have a knack for speaking about science in a way that's clear and engaging. Is that something you've cultivated?

I've worked at it. Good presentations take effort. It's one thing to do science and completely another to be able to communicate it. Working in the laboratory is kind of like working in an elaborate kitchen: you're mixing, spinning and making recipes. It's very detailed, and when you tell people what you did, it's easy to get caught up in the description of what you did without tasting the food. Many scientists aren't comfortable talking about their work to nonscientists, in part because the simpler you make it, the more difficult it is to do. But simplifying is important, because that's when you realize the essence of what you've done. That's when you bring the meal together and try to make it smell good, look good and taste good. It's important, but it's not easy.

Is there anything else you'd like to get better at?

I never picked up computer programming, and that interests me. While I do not like the process of writing (because it is difficult), I would like to write a book about the origin of physiology, behavior and the complex biology that makes us humans. In this case, starting is the hardest part. In regards to relaxing, I love playing the guitar, I like the craftsmanship in well-made guitars, and I like the techniques of playing (but mostly for myself and not for groups). While I like big challenges, I am not very efficient. I am easily distracted—by people, by Google, by just about anything. I keep my lab dynamic, and that gives my team room to be creative and ready for surprises. I like seeing the people in my lab take their discoveries and move on to develop their own research programs around the world. And I like bringing in new people and letting them follow their intuition. Truth is, I thrive on chaos.