“The present moment is always the golden age of science:” An interview with Marty Chalfie

Guest post by Irini Topalidou, Senior Scientist at the Department of Biochemistry, University of Washington, Seattle.

I first met Martin “Marty” Chalfie in January 2004, when I visited his laboratory in the biology department of Columbia University to interview for a postdoctoral position. At this point, Marty was already a professor of biological sciences, studying the development and function of the nerve cells, using the nematode Caenorhabditis elegans. Four years later, he would be awarded the 2008 Nobel Prize in Chemistry, together with Roger Tsien and Osamu Shimomura, for his introduction of GFP as a biological marker.

When I first encountered Marty’s group, I was surprised at how small but international it felt. The warm welcome I received and the intelligent questions asked during the interview made me think that Marty’s lab would be a good fit; the combination of friendliness and challenge felt right. I joined Marty’s lab later the same year and stayed for eight happy years. At a recent encounter with Marty at the International Worm Meeting in Los Angeles, I noticed how people seemed to gravitate toward him and surround him, listening in fascination as he told his favorite stories. This made me think that he might have some interesting insights to share with the world. He happily agreed to do an interview with me.

Marty, were you always committed to becoming a scientist?
When I was an undergrad, I tried working in a lab for a summer, and everything failed. I decided that I had proven to myself that I should never be in science. After graduation I did a whole bunch of other jobs. Fortunately, one of those jobs was working in a lab. There, the experiments worked, and I gained enough confidence to apply to graduate school. In grad school, my advisor, Bob Perlman, was the perfect person for me to work with. I had a desk right outside his office, and he would let me pester him with my many questions all the time. He was always available, and we were constantly talking and interacting. His intelligence, involvement, and friendship were and remain very important to me.

How was your experience working as a postdoc at Sydney Brenner’s lab at the Lab of Molecular Biology (LMB) in Cambridge?
Sydney had the view, especially with postdocs, that each was an independent scientist—a colleague. He never assigned projects; he let me be completely free. But I was not alone; I had lots of spectacular colleagues to talk to. We all talked continuously to each other, so there was no dearth of advice, suggestions, or help. I stayed in his lab for five years, but I had about one conversation a year with Sydney about science. Sydney was doing his own experiments and not even working with worms at the time. Frankly, I was in awe of him and a bit afraid of looking stupid in his eyes. But I knew that he was supportive, and I think, in fact, he liked that I was independently proceeding with my own experiments. Overall, I think this very independent postdoc was a very important step in my development as a scientist, building my confidence in directing my own learning, and developing my science by interacting with colleagues and being part of a larger group.

Sydney Brenner liked being a pioneer in science. What is your approach?
Sydney used to say—and I don’t think this is exactly true—that there were three ways that one could be involved in science. You can be the person that did the experiment that was the crowning touch—the answer to a long-sought problem (e.g., getting the structure of DNA). Unfortunately, opportunities to do so are rare. Sydney said he preferred to work in a second way, at the other end of a problem, and start a project. And he started an amazing number of projects. The third approach, which he somewhat disparaged, was working on, but not starting or finishing a line of research. I think he was unfair because working on problems and adding bricks to the wall often leads to new insights and new discoveries as well. Nonetheless, the idea that you can start projects that other people can pick up had a very strong appeal to me. Although I am certainly not in Sydney’s league, my lab has been fortunate to discover new types of transcription factors, channel proteins (including sensory transducing proteins), and cholesterol-binding proteins, and it introduced GFP. All of these things are wonderful. Other people have and, I hope, will continue to work and use what we have done, as we have done with others’ work.

Is there something that you miss from the “good old days” in science?
The answer is: yeah, I do a bit. I do look back fondly at the time I was a postdoc, but it’s not because of the particular era in science. At the LMB, where I did my postdoc, people loved to talk science; they were excited about what was happening. For most people, you go through a standard sequence of going to grad school, going to do your postdoc, and then going into an academic job. And of those three, the one that is the most carefree is the postdoc. There are no exams, you are not taking courses, and you are doing science but without the responsibilities that you are going to have when you are running your lab. So, of course, we all look back on the times we were postdocs with fondness. You remember it for the wonderful time that it was, even though some of the experiments didn’t work, you were often annoyed, etc. Life doesn’t become this wonderful Eden suddenly with the postdoc. But many people, including me, look back at those years with a sense of nostalgia. But then you remember all the good things that have happened in your own lab, and the nostalgia is not that strong.

Your lab group has a rather international character. Are you purposely selecting people who come from diverse backgrounds?
You take the people that apply and want to work with you, and I have been fortunate that people have come to my lab from all over the world. Each brings their own perspectives and points of view and their backgrounds, and I think that’s wonderful. But ultimately, it’s the science that is important, not where people come from. I want to know that people are excited about their science. I think it is very nice to have people from different backgrounds, but, by and large, the most important thing is how they are committed to science.

Is leadership interesting/important to you?
I’ve always wanted to have my voice heard when I was in committees or discussions in the department. I don’t think anyone likes to be dismissed as not being important. I’ve always enjoyed saying what I felt; sometimes it was completely wrong, sometimes not. I don’t have to be the leader, as long as my suggestions are reasonably thought about and respected. I think this is how you have to work with people when you are leading the group, too. Everybody’s input is important, and you want to share it.

I remember that you spent three years as the department’s chair. How was this experience for you?
Some aspects of being chair were really wonderful. One of those was that I had a little bit of power, and that allowed me to right some wrongs that I thought were happening. For example, in my department the chair decides who gets the merit raises. When I became a chair, I found that some people had been ignored for over 10 years who, in my opinion, had continuously helped make the department better. I could right this omission. What I did not enjoy about being chair was dealing with people who kept demanding more for themselves—the prima donnas. I don’t think I was very good at coping with those people.

How about being the head of a lab? Is this something you enjoy?
I love that other people are doing the work. I’ve never been a good person at doing my own experiments. I did that for some years, but I enjoy thinking about the problems much more, so I enjoy working with others in the lab. But labs don’t always run smoothly. Someone once told me one of the problems of being an assistant professor is that, “We are all asked to practice psychology without a license.” We really don’t know what to do. We are running a small business that has people with their own concerns and needs, and those are sometimes problems that we can’t cope with and need help solving. On the whole, however, I have really enjoyed having people in the lab, working with them and watching them develop.

Looking back on our relationship, one of the main characteristics is that we laughed a lot. How important has humor been in your life and scientific life?
Well, it makes it very enjoyable. I don’t think you plan to have a sense of humor. My father had a wonderful sense of humor. I probably got an element of it from him. Humor breaks down barriers. I have had a lot of strange, funny things happening to me, and I’m basically a storyteller, so I enjoy telling these stories. I don’t know how science would be if I was serious all the time. It’s more enjoyable for me.

In addition to your love for science, you also have a love of music. What role has music played in your life?
My father was a professional guitarist, and I was the oldest of his three sons. When I was 12, my father surprised me by giving me a classical guitar, and the guitar has been my companion ever since. I don’t play it as well as I’d like to or as I used to, but I enjoy it. And I keep learning about the instrument all the time, especially now that I try to make up my own pieces. It’s a great way for me to relax. I have a travel guitar that I can take with me that no one can hear because it doesn’t have the body of the guitar. So I can sit in a hotel room and practice when I’m away from home. The guitar is an important part of my life.

I’d characterize you as a positive and mostly happy person. Where does this positivity come from?
It’s clear that the mask that I present to you is working! I’ve hidden all my anxieties from you. Something I think we all do. To friends, I’m not that private, but for the most part, if I’m worrying about something at home, I usually don’t bring it into the lab. But on the whole my life has been remarkably nice. I realized when the Nobel was given to me that the one thing this honor took away was my ability to complain, because I imagine people would say, “What does he have to complain about?” A lot of the time, I am happy. I do generally enjoy life, and I enjoy being with people, but that doesn’t mean that I don’t have sadness in my life or that I don’t have concerns or anxiety. Over the years I’ve learned that I’d rather be a person who people enjoy being with. I don’t want to make it such that it’s hard on people.

You mentioned once that your favorite author is the Brazilian writer Jorge Amado. What fascinates you about his writing?
I discovered translations of his books in 1980, and I read everything available. His most famous book is probably Dona Flor and Her Two Husbands. Several of his books, including this one, divide people into two groups, which are personified by Dona Flor’s husbands. One is an almost wild man, usually poor, but living life completely and generously. The second, in the book it’s the local pharmacist, is very respectable, very staid, and not a lot of fun, but he gives her security. Together, they provide all the things that Dona Flor needs: security, a love for life, passion. Through all the books, there is this juxtaposition between the rich, arrogant people and the poor people that love life and help one another. The Amado book I like the most is Tent of Miracles. Amado’s opinion was that Brazil’s strength came from the mixing of races, not their segregation, and the book addresses this theme. At one point in the book, a plane lands in Salvador, and out of the plane comes a Nobel Prize–winning scientist from Columbia University! So I was particularly happy to be invited to Salvador several years ago and be the “second” Nobel Prize winner from Columbia to visit.

I remember the day that you got the Nobel Prize—how unexpectedly surprised we all were. But was it something that you knew or saw coming?
In 2002 Sydney Brenner, Bob Horvitz, and John Sulston—all good friends—were awarded the Nobel Prize in Medicine. During that ceremony, Bob Horvitz, a friend of mine since high school, mentioned GFP in his speech. He told me afterwards that he did that on purpose. It was very nice thought, and at various times since then other people told me that GFP was something that could be awarded the Nobel Prize. Now I’d like to say, if somebody tells you that they think that what you’ve done might earn the Nobel Prize and you are an idiot, you stay up all night thinking that the call might come! You do that once or twice and then you realize you’ve been foolish and you don’t do it anymore. Did I expect it to come? No. Would I have loved to have it? Yes. Was I happy that it did happen? Of course.

Has the Nobel Prize changed you as a person?
I’ve been able to do things I had not been able to do before. I’ve been given opportunities and because of that, I’ve done things. As a consequence of the Nobel, I’ve been on numerous scientific advisory boards. I’ve also been the chair of the US Academy for Science, Medicine, and Engineering Committee on Human Rights, and that has given me a lot of wonderful opportunities to think about something that I wish I had been involved with long ago. I have the ability now to speak out. But sometimes I wonder why I didn’t speak out earlier. Interesting ideas that I have now, I had them back then. Why wasn’t I more active? Now, somehow, I have permission to do them. Has it changed me? Yes, I do a lot more of these things that I wish I had done a long time ago.

I consider you as a relatively humble person. Has the Nobel changed you in that sense?
When I was an undergrad, George Wald had won the Nobel Prize. I read his Nobel Prize talk, and there were a couple of things I couldn’t understand. A professor of mine told me to go and ask him, since his office was a few blocks down. I said to him, “He just got the Nobel Prize; I’m not going to talk to him! I’m just an undergraduate!” “Don’t be an idiot; go talk to him,” my professor said. So I did. I don’t remember what we said, only that I lived through it. Thus, I have a feeling for the unnecessary barriers that can come up between students and laureates. As a result, I try to prevent those barriers from forming. I don’t, however, think I’m being that humble. I think that we imagine that people that get this award have the right to be annoying, but that’s not the case. I am proud of what I’ve done, but sometimes I think I seem humble in comparison to what people think I might be.

In your opinion, are scientists arrogant people? How do you deal with arrogance?
You can say this about any walk of life. All groups have people who are wonderful and some who are not so nice. I’ve been very fortunate to have met many scientists who make you feel good that you know them, and I have an exceptionally long list of people who I’ve looked up to and respected for who they are. Do I also know some stinkers? Yeah! Do I know some really arrogant people? Sure! But this happens, as I said, in all walks of life. No one likes to be belittled; no one likes to have their opinions pushed aside. We all like to be respected for who we are, and if that doesn’t happen, that’s a problem. I’m not sure that science is the problem.

How do you feel about model organisms in biomedical sciences?
I don’t like people using the term “model organism” because, to me, it’s too narrow of a description of what research organisms like Drosophila, yeast, zebrafish, or worms allow us to discover. The term “model organism” seems to imply that these organisms provide ways of investigating and modeling human biology and disease. While such modeling does occur and provides wonderful insights, it neglects the vast majority of things that we have learned and can learn from these organisms. With C. elegans, for example, we learned about cell death genes, RNAi, and microRNAs. So I prefer the term—and I don’t know who came up with it—of “pioneer organisms,” because they pioneer so much about what we know.

How do you feel about impact factors?
I hate them. A couple years ago, I visited two different research institutes in Europe, both had people doing terrific research. I talked with the directors and both said, “You know, this last year has been terrific. We published more papers in journals with impact factor over five than we have ever done before.” But when I asked them, “What was the science?” they both answered, “I don’t know.” They knew the numbers, but they didn’t know the science. It’s easy to talk numbers, but the numbers are meaningless. People don’t seem to have time to judge what people actually do; they want to see what journal the work is in.

What do you think about preprints?
I like them. I find it very encouraging that people are putting their articles on preprint archives like bioRxiv and letting the world see them before they go through all the nonsense of getting them accepted. People around the world are getting the chance to look at the science. I think that this trend is very important. The ASAPbio group (asapbio.org) started to get more people in biology to put their papers on preprint servers, and they have done a miraculous job. They have convinced all the journals that using preprint servers is the right thing to do, and virtually all journals have agreed to let manuscripts be posted on non-profit preprint servers. They have convinced NIH, Howard Hughes, and other funders to accept not only published papers or in-print papers but also papers that are put on bioRxiv as proof of productivity. And preprints are taken into consideration for hiring and promotions. I am excited about these developments because they put the emphasis on the science, not where papers are published.

I observe a lot of anxiety among young people about their future in science. Where do you think this anxiety comes from?
Where I think my generation may have erred is that we complained too much. I think that scientists, in general, love to complain. So, if you don’t get a grant, you get annoyed and let people hear your frustration. But think of the poor students that hear us. They don’t hear about the excitement of science; they are thinking, “Oh, the boss is having trouble! I don’t have a great opinion of myself; I’m going to have even more trouble.” I’m afraid our complaining makes our students and postdocs less confident in their abilities.

Often PhD students and postdocs have difficulties dealing with failure. What would you advise them?
I have a stock answer to this. It’s not good, but it’s my answer. When, during my postdoc, I started working on mutants defective in touch, two sets of mutants came out: the animals in one set were defective in developing the sensing cells; those in the other were missing a component needed for the actual sensing. And it’s been throughout my carrier that sometimes one aspect works wonderfully and other times the other aspect works wonderfully. So for me, one of the things of really coping with failure—and no one wants to hear this as a coping mechanism—is doing even more. Do two things instead of one, because one of them will work. Why are the students in the lab miserable, but the head of the lab is happy? It could be because the head of the lab has several students or postdocs working on multiple projects, and usually at least one is working. So working on multiple projects is a very useful defense against depression.

The real question is: When do you stop? When do you decide that you have actually tried enough and that the frustration in the lab is not something that you enjoy? And why should you torture yourself doing something that you feel frustrated with? I can’t make that determination. I don’t know when this point is. I probably let people go far too long when their experiments aren’t working.

What would you advise PhD students when seeking labs to do their postdoc?
Focus on the science, and come as a colleague to begin with. I often suggest to people that they can get almost any postdoc they want if they would write a proposal of what they are thinking about. They shouldn’t just write, “Do you have space in your lab?” Instead, write only two or three people saying, “I’ve read your work. I’m excited about your work, and here are the things that I would feel excited about being part of.” And tell them what are the next experiments that you would do from their published work. They might have done the experiments already, but it doesn’t matter. You are just telling the person how you think and what you are excited about. That is, I think, very important. After that, the advisor will ask the recommenders their opinion on the person and the applicant should go and ask the people in the lab and find out if this is the right place. But I don’t think it should be the right place because this person has a lot of funding or this person gets papers published in this journal or that journal. It should be, “How can I develop as a scientist? Am I going to enjoy it? Am I going to learn? How well can I work with these people?” These questions are very important.

What advice would you give to young faculties?
Basically, this is advice that I found useful: ask other people for help and concentrate on the science. One of the first things I did when I wrote my first grant was to give it to a senior faculty member to give me feedback. In general, I still do this. When there are things I don’t know about, I ask somebody and get their opinion. I think that, very often, people feel that they should do everything on their own. That certainly hasn’t been the case for me, and I benefited from that. In fact, just this morning, I sent an email to other Nobel laureates that were listed on a website of a meeting that I had been invited to, asking their opinion of the meeting. I routinely ask advice from others, and their input always helps me. I find people whose opinions I really respect, and I go to them. I think the most important thing in setting up the lab is going for the science, not letting other concerns distract you. In my experience, the people that really concentrated on their science tended to fare better than those who were concerned about networking or where their papers were accepted.

Does Columbia University have a system of helping young investigators?
We do have an official procedure where we assign every new member a committee of two or three senior faculty. Sometimes the committee also evaluates the person rather than advising them, but usually people find these committees useful. In addition, some professional societies have programs to help new faculty. Every two years, for example, the Society for Developmental Biology runs a “boot camp” for beginner professors. I’m very glad they do this. For me, it was always a very informal thing; I always went to the people I thought would give me good advice, and I asked them.

If it were up to you, what would be the first thing that you’d change in academic culture?
In general—and I think one feels this post-Nobel—I don’t like hierarchies. I think it’s better in a lab—at least for me—to interact with people as colleagues. Now, they might be colleagues who need to learn a lot of things, but respecting a person only because of a position in a hierarchy is detrimental to science. It’s been my experience that the very best grad students are people who act like colleagues and not students. We are working together as team, and this working together is the most fun for me.

Do you think that academia has become more difficult due to more competition and less funding?
When I became an assistant professor, they lined up at the door and they gave us bags of money and they said, “Please do what you want to do!” (Only in my dreams.) Doing what we do is not easy. We are trying to be the first people in the world to do what we do, and as a result, we fail a lot. It’s part of the game. When I get a paper that gets rejected, I swear at the screen, reading the reviews on the first day, but on the second day, I realize that the reviewers made some pretty good suggestions, although I hate that they did. Is there competition out there? Yes! Is there more now than before? Not so sure. Do I think things have gotten worse? Not really. NIH is not funding the top 27% like they used to. The percentage has gone down. But I really see some terrific science out there being done by a wide variety of people. What we need, of course, is to give more opportunity. People often talk about the golden age of cinema, and I realize that the present moment is always the golden age of science. We can do more experiments and consider more problems than people even imagined 10 or 20 years ago. We always have problems and have to deal with them. Life is not fair all the time. Nonetheless, I hope we can give opportunities to as many people as possible to see what they can do.