Faculty Q&A With Martin Chalfie
When he received his A.B. from Harvard in 1969, Martin Chalfie wasn’t sure what he would do next. His worst grades had been in physics and chemistry, and a summer research project had failed, so science seemed out of reach. He had a series of short-term jobs and then spent two years teaching high school algebra, chemistry and social science in Connecticut. The need for a summer job after his first year of teaching and the suggestion of a fellow teacher sent him back to biology: a job in a Yale Medical School laboratory.
There, the success of a project and the support of colleagues led him back to Harvard for a Ph.D. in physiology. After another suggestion from a friend, he went off to the MRC Laboratory of Molecular Biology in Cambridge, England, where he developed his current interests in nerve cell development. He has called his career “a rather undirected and surprising trip.”
Today, Chalfie is a Nobel laureate, having shared the 2008 prize in chemistry. As of this month, he is also one of Columbia’s newest University Professors, an honor that goes to faculty members for exceptional scholarship and service to the University. Only 13 Columbia professors hold the title, the highest academic rank. His years in a lab, the last 31 at Columbia, have never been boring. “The wonderful aspect is that it’s not an isolated, solitary occupation,” he said. “Often we have no idea where the research is going to go.” In an interview with The Record, Chalfie discusses why not knowing where your research will go is a good thing.
Q. What’s the importance of basic research?
Basic research is important because it provides new knowledge and a greater understanding of our world. But basic research is also very important because it provides us the building blocks that allow for applications, whether they’re applications for engineering, biotechnology or medicine. People often talk about translational medicine, of translating what’s learned in the laboratory into work that will apply to cures or preventive measures, bringing it to the bedside. And that’s an important thing to do, but of course you have to have something to translate first.
And that’s where the study of basic problems of biology is very important. But the other aspect of basic science is that we don’t always know what’s going to come out from our experiments. In fact, maybe it’s a good idea that we don’t. Enrico Fermi had this wonderful line about experiments: “There are two possible outcomes: If the result confirms the hypothesis, then you’ve made a measurement. If the result is contrary to the hypothesis, then you’ve made a discovery.” Of course, it’s the discoveries that drive so much innovation and so many new ideas in biology.
Q. Do you see a wavering in the commitment to fund basic science today?
I’m certainly concerned about it, and not just in the United States but in many other countries. These days there is an idea that if we just put the money on this particular problem or that particular problem, then we will be able to solve that problem. And that’s misguided. Yes, you should have directed research and look at specific problems, but you also have to have background research that will give the insights that will then allow us to be able to have new approaches to solving disease-related problems, for example, or other issues. Every year we learn more things that we had no idea existed before. We never actually know when the consequences of what we discover will come to fruition, or what those consequences will be. When [Columbia Physics Professor] Charles Townes in the 1950s worked on what became the laser, he had no idea that it would eventually allow us to have DVDs or CDs or the types of surgery that have helped millions of people.
Q. That’s a nice segue to green fluorescent protein. Did you have any idea, when you first started working with it, where it would take you?
I was in my lab studying a series of genes, and I was interested in knowing where those genes were activated. And I happened to listen to a seminar where the speaker was describing this protein from a jellyfish. Because it was fluorescent, shining light of one color on it allowed it to convert that light to another color. You could see wherever that protein was by seeing where that second color was. I realized if we could put GFP under the control of the genes we were studying, wherever those genes were turned on, we would see GFP. Moreover, if GFP was attached to the protein made by the gene, that protein would take GFP as a lantern along with it wherever it was in the cell.
This idea was first demonstrated by my wife, Tulle Hazelrigg, who is also a professor here at Columbia. Then it became an explosion. Hundreds, thousands of people have used this protein and invented wonderful new methods based on the fact that they could watch something happen in living organisms. Most of these applications were never on my radar. I hadn’t thought of them.
Q. You shared green fluorescent protein with hundreds of other researchers, who went on to make their own discoveries using it. Do you worry about whether science will become so focused that the unexpected discoveries might become rarer?
This is an important issue, how scientific knowledge is shared. Patents are issued for use, but should the knowledge also be somehow sequestered away from people? And the answer to that for me is absolutely not. The gain in science is when one shares information. GFP itself was an accidental discovery. In the early 1960s, Osamu Shimomura was studying an interesting biological problem that had absolutely nothing to do with human health: Why did organisms like fireflies, glowworms and jellyfish generate light? What was the enzyme? After many failures, he finally purified the protein. But he had a problem: The protein produced blue light, not the green light of the animal. Reasoning that another protein changed the light to green, he looked for and found the protein we now call GFP. He never started off to discover a fluorescent protein, it wasn’t even something he was thinking about. He just wanted to find out what protein generated light. That unexpected result led him to wonder what was missing. And what was missing was something terrific.
Q. What are you working on now?
Before I was working on GFP, and since then, I’ve been researching the sense of touch. Biologists understand the molecules that allow us to see. We also have a very good idea now, from work by many people, including notably [Nobel laureate] Richard Axel at Columbia’s medical school, how chemical signals can lead to a sensory perception. But some senses are still mysteries. Many are what we call mechanical senses. We have five different cells in our skin that allow us to sense touch, we have the hair cells in our inner ear that allow us to hear, or to detect acceleration, we have sensors in our bones and in our muscles that tell us whether there’s tension on the bones or stretch in the muscles. All of these are mechanically driven senses and we haven’t a clue as to how they work.
Q. So much of science is funded by grants from foundations and the government. Does that put constraints on your research?
I often joke with people that when we write grant applications, everybody is lying. Not literally, of course. We write in an application, “Here are the four or five areas that we want to do research in, and here are our ideas about how we should proceed.” But it’s understood by the granting agency, by the investigators, by everyone involved, that if a better idea comes up tomorrow, we would be foolish to stick to the old method. So what we really are saying when we write a grant proposal is what we believe at the moment are the most important things we can do. And if you believe as we do that these are important, then you should fund us. But after that, if something better comes along, if a new insight makes us veer off in a different direction that may be more fruitful, we’re going to do that. I never wrote a grant application to study GFP, I just wanted to do the experiments.
Q. What is the advantage of doing research at a university?
I’ve particularly enjoyed the freedom that I have of working in a university because I make the decision of where the research is going to go. That means I can make mistakes, but it also means that I can pursue ideas as they occur to me. And I find that very rewarding. If I get funding, I’m able to do research on what I think is important. This is different from working in industry, where if they decide a project isn’t important for the company, they may stop it, even if the research is going wonderfully, even if there are exciting new results.
Q. You often hear how professors get as many ideas from their students as they give to them. Can you give an example of that?
Oh, easily. I have several students that I’m struggling to catch up with. One was in the process of cloning and identifying a gene. He cloned it, brought me the result, and it reminded me of a gene that my wife has worked on in a different organism and a good friend of mine has worked on in the organism that we study. And I think, “My student won’t know any of this.” So I tell him who to email and what strains to get so we can do our own tests. Without hesitation, he says, “the strains are already on my desk.”
Q. So even a Nobel laureate can be humbled by his students?
All the time.