Juggler: Q&A with Richard Kolodner

What did it feel like when you realized that you had tracked down the gene responsible for the most common form of inherited colon cancer?
Fundamentally, it was a new approach to looking at the development of cancer but I didn’t appreciate how important it was until after the fact. The realization that there was a gene in which defects cause an inherited cancer susceptibility syndrome was exciting. The fun was in doing the work, a lot of which I did myself. The most rewarding aspect  of doing the work itself was in learning new ways of doing science and new ways of doing experiments—that’s what scientists live for. One of the most memorable moments was when we heard that some of our early genetic data were used to identify an asymptomatic patient with a genetic defect who on re-examination was found to have a previously undetected cancer, possibly saving a life.

Our understanding of cancer and the current approaches for studying it are completely different now than they were three or four decades ago. What has it been like to be a part of this conceptual evolution?
My scientific career has spanned a transformative period in cancer research. It’s bridged the formative years of molecular biology and now it’s my extraordinary luck to be working in a revolutionary period in genetics.
So it’s been amazing to be a part of the progress that has directly impacted our understanding and treatment of human diseases. But, to me, what’s even more interesting is that we’re starting to study mammalian cells in ways that we used to only be able to study microorganisms. Now we can apply insights from these studies to understand the genetics of human cancer susceptibility.

You wear many hats: director of Ludwig’s San Diego Branch, member and head of the Laboratory of Cancer Genetics in the San Diego Branch, Distinguished Professor in the Department of Cellular and Molecular Medicine at University of California, San Diego, and Scientific Review Council Head for the Cancer Prevention Research Institute of Texas. What is your secret to juggling all these roles?
No sleep. Seriously, I guess my secret is to break things down to discrete tasks so that I can complete them and cross them off my list. It’s important for me to organize my work so I’m not being pulled in multiple directions all at once, which is easier said than done. Managing the flow of email is particularly challenging. As the new branch director, I’m very fortunate because during Web’s tenure a lot of very talented, self-sufficient lab heads and staff were brought in. We also have a great administration in place and, maybe most important, we all get along. That coupled with the support we receive from Ludwig makes it a very comfortable environment in which to work and allows the branch to run smoothly on a day-to-day basis.

Many students and postdocs struggle with the decision to choose a career path in research, industry or academia. Do you think there are certain characteristics that make a person well suited for a position in one environment versus another?
A career is often an intersection of talent, personal choices and, to some extent, luck. I look for people who are passionate about conducting experiments and solving interesting problems. And no matter what path a member of my lab takes, it’s my responsibility to ensure that they have a solid foundation in conducting experiments and writing papers. I try to learn what it is that excites and energizes them, what their specific talents are and how to best utilize them, and where they see themselves going. But ultimately,
I counsel them that what makes them valuable to any organization is the fact that they are accomplished scientists. So whether it’s pursuing a career in research, academia or industry, all require a platform of significant, high-quality scientific training and accomplishments. Those are the elements that will offer the most options and choices.

You obviously enjoyed science right from the beginning, but you must have met challenges along the way. Do you have any advice for junior scientists facing challenges?
Once upon a time, people thought the earth was flat and if you went out to the edge you’d fall off. To me, the best scientists are the ones who—when confronted—want to go out to the edge and jump off. When you’re out there in the unknown you can’t predict everything. You’ll do experiments that don’t work, but failed experiments are simply a part of lab life. You’ll try things that are risky because great opportunities often come from risk taking. You’ll be faced with obstacles and setbacks so you’ll need a lot of patience, persistence and perseverance to succeed.

What would our readers be surprised to know about you?
I have a pet border collie named Levi who I train to compete in agility trials, which consist of running through timed obstacle courses. They’re tough because he has to weave through poles, clear jumps, sprint into tunnels, run over elevated walkways and run up and down a teeter-totter—all without making a mistake. And it might surprise people to know that he’s better at it than I am. So far he’s earned seven different agility titles, and because of the great weather in Southern California, he competes about a dozen times a year.

What new directions are you headed in now?
Right now we’re trying to identify and develop therapeutic targets whose inhibition might selectively kill cancer cells. We’re also continuing our work on studying the pathways that prevent genome instability and the inherited defects in human recombination and repair genes to better understand how such defects cause cancer susceptibility.

In a 1994 interview you’re quoted as saying, “I like to do experiments. That’s what I like most.” Is that still true today?
I do love to do experiments. They give me great joy. Unfortunately I don’t really have the time for the hands-on aspects of doing experiments. There are a few that I would like to do but, right now, I’m only involved in designing and critiquing experiments and interpreting the data.

What has been the most satisfying part of your research?
The long-term success of the people who have been students and postdocs in my lab. That’s the legacy you leave to the world. Over time even the most important scientific discoveries are relegated to the textbooks and become part of our baseline knowledge to the extent that they seem like trivial facts. I’m not saying it’s easy to make those discoveries, but when I go to a meeting in my field and find that many of the invited speakers are people who trained in my lab, I’m reminded once again that their success is my most important contribution to science.

What’s missing from a technical perspective that would help move your field forward?
We’re not suffering from many technical limitations. One of the biggest challenges in science today is how best to use all the technology that’s available right now. The question becomes, how can we exploit all these new insights and technologies, how do we gain access to them, and how do we learn to use them? And, maybe most important, can we afford them, and afford to use them properly? As the technology has become more complex and more costly, we often want or need to work with scientists in other labs who can offer resources or technical expertise that complements what’s available in my lab in order to move the work forward. But as you increase the number of labs working on a specific project, it’s not only tougher to manage the collaborations but it’s tougher to manage the quality of the work.