Convocation 2010 - Address by Nobel Laureate Martin Chalfie

Martin Chalfie of the Department of Biological Sciences, Columbia University, won the 2008 Nobel Prize in Chemistry for the discovery and development of the green fluorescent protein, GFP.

He spoke to the 2010 graduating class of Amrita Vishwa Vidyapeetham, from the US through video-conferencing. Reproduced below, is the complete text of his speech to the graduating students.


Martin ChalfieChancellor Amma, President Swami Ji, Pro-Chancellor Abhayamitra Ji, Vice-Chancellor Dr. Rangan, distinguished guests, families, and most of all graduates:

Thank you for giving me this opportunity to talk with you. Graduations are often times for uplifting and inspirational speeches heavily laden with advice. I have usually found that the advice in these speeches is often either what the speaker had been given or wishes he or she had been given, in other words, advice that was useful to the speaker but may not be to anyone else. We are all unique, and each person’s life is, in turns, messy, confusing, complicated, as well as joyful and fulfilling. Thus, I think it is very hard to give advice. As a scientist I like to repeat experiments. Scientist say that we like to increase N, the number of experiments, because a single experiment may give an atypical answer. But life is a single journey, an N of 1, and what has happened in my life may not be important or relevant to any of you. So I do not have any words of advice, but this does not mean that I do not have opinions.

Like many of you, I was the first person in my immediate family to go to college. My father never finished high school and my mother had to quit college because she and her parents could no longer afford the tuition. But they always wanted me to go to college, as did I, mainly because I was interested in science and thought that I was destined for a career in science. During the summer after my third year in college, I had an opportunity to do scientific research. This experience, however, was horrible because I was very ill prepared and had a mistaken idea of how to do research. The biggest problem was that I thought that real scientists (whatever they were) had an innate talent to do experiments. Real scientists just read the protocols, figured out what they were supposed to do, and did the experiments (with spectacular results). But they would never ask for advice. As a result of these mistaken ideas, I spent the entire summer working alone at a bench in an otherwise empty lab, and I had no idea what I was doing. I tried doing experiments, but nothing worked. At the end of the summer I asked the head of the lab what I should do next, and he said I should try the experiment one more time and abandon the project if it did not work. I tried one more time, and the experiment failed again. I did not enjoy failing, so I not only stopped doing the experiments, I decided that I did not have the talent to be a scientist and gave up on that dream. I tried several nonscientific jobs after this, but I wasn’t that successful at those either.

A few years later I was teaching at a high school and had my summer free. A fellow teacher suggested that I spend the time working in the laboratory of a friend of hers. Her friend hired me, and I proceeded to work in his lab. By this time, however, I had learned to ask questions and seek help from others, and this time the experiments worked. This experience taught me several lessons. First, I realized that my previous ideas about how to be a scientist were quite mistaken. I did not have to do everything on my own; seeking colleagues’ advice was both useful and important. In fact, I have found that many of my best ideas come when I have been talking with students and colleagues (and I have not stopped talking since). In addition, I learned that people become scientist in many different ways, as my story shows.

LabSecond, I found that working with others still allowed me to contribute uniquely to a project. In these early experiments, I asked others for advice and ideas, but I designed the experiments. I also found pertinent references that helped our understanding of the results. These days, I think that my main contributions are my enthusiasm for the research, my love of worrying about the problems that it contains, and the experience that I have gained over the years.

Third, I learned that having an experiment work is tremendously exciting and joyful. In fact, although I may seem selfish, having one of my ideas confirmed by an experiment is one of the main rewards I get from being a scientist: the joy of understanding even a little bit about the world.

My daughter echoed this idea six years ago, when I was inducted into the U.S. National Academy of Sciences. The induction ceremony was a rather strange affair: the 80 or so inductees walked across the stage, one at a time, signed a book, and had their picture taken with the Academy President while someone read a few sentences about their research. I thought that my twelve-year-old daughter would be bored silly. Instead she was amazed at what she heard. One woman had discovered a massive black hole in the center of the Milky Way, a man produced evidence that the universe was not curved, and another man had learned how ATP, the energy molecule of the cell, was made. She told me later that what impressed her was that all 80 people had learned something that no one else in the world had known before, that they had accomplished something unique.

I am profoundly grateful for this second laboratory experience, my subsequent graduate education, and my position within a university for giving me the opportunity to think about, explore, and work on problems that I am deeply interested in. I may have always wanted to be able to work in this way. When I was in fourth grade, I was told that a hallmark of civilization was that not everyone had to hunt or produce food; societies could have people who thought about and investigated the world around them. I think that at that time I decided to be a scientist.

GFPMy particular interests are in biology and I have spent the last twenty-eight years at Columbia University tickling worms and studying mutants that are insensitive to touch. At this point some of you may be wondering, “What has civilization come to?” but the research does have a point. The mutant worms fail to respond to touch in two ways: either they fail to produce the touch sensing cells or they make cells that do not work. The first set of mutants lets us study differentiation, how different cell types are made, a central problem in developmental biology. The second set of mutants helps us identify and study the molecules that allow the cells to respond to mechanical signals. Mechanical signaling underlies our senses of hearing, touch, and balance as well as our ability to monitor blood pressure, the stretch of our muscles, and the position of our limbs. Mechanical forces also help mold the shape and function of our tissues. The lack of mechanical pressure on their bones is why astronauts’ bones become weak at zero gravity in space. One hallmark of cancer is that physical forces that constrain the growth and movement of affected cells are no longer sensed by the cancer cells. Although mechanical stimuli tell us much about the world around us and guide our development, the molecules that respond to these stimuli are unknown. By cloning genes identified by our mutations in worms, we hope to learn about molecules underlying these senses. Encouragingly, this approach is working.

This research has taken up most of my time and that of my students, but probably the most influential discovery I have been associated with, had nothing to do with touch sensitivity in worms. Several years ago, while listening to a seminar on bioluminescence, the ability of organisms like fireflies to make light, I heard of a jellyfish protein that was inherently fluorescence. This protein, called the Green Fluorescent Protein or GFP, didn’t make light, but it glowed green when irradiated with ultraviolet or blue light. Since the worms I work on are transparent, I immediately started thinking of the experiments I could do if I could put GFP into worm cells: we could see which cells had activated a gene, simply by looking for cells that were green because they made GFP or we could see where in a cell a protein went because it brought GFP along with it. Most importantly, we could watch cells and proteins dynamically in living animals and plants. These thoughts began a research project that introduced GFP as a general biological marker. Today GFP and it derivatives are essential tools in molecular and cellular biology being used to study many biological processes. For example, making green bacteria and viruses has allowed investigators to follow the process of infection. And having a mouse tumor cell fluoresce because of GFP allows researchers to investigate tumor growth and metastasis. Each year brings new adaptations and new uses. The efforts and thoughts of a great many people have developed uses for fluorescent protein well beyond those I first imagined.

GFPIn fact, I have often thought about GFP as a very nice metaphor for how we do science. Just as GFP absorbs light of one color and converts it to that of another, scientists take observations and discoveries of others, add their own contributions, and produce new findings that others can use and modify, in turn.

GFP has been used in tens of thousands of investigations in the 16 years since my colleagues and I introduced it as a method to label organisms, cells, and proteins. Some of these studies have involved basic biological problems, whereas others have focused on applications to human health and well-being. To my mind, both types of studies are important. But in recent years in the United States and elsewhere, I feel that too much emphasis has been placed on the importance of what has been termed “translational research.” Translational research is research that applies (or translates) observations and discoveries made in the laboratory into treatments for human diseases. I am not against translational research (actually I become more enthusiastic for it as I get older), and I feel that scientists are obligated to think about the implications of their research. Nonetheless, I am bothered that a disproportionate emphasis has been placed on translational research recently and that many feel that translational research is the only reason people should do biological research. (A similar problem occurs in nonbiological sciences, when people try to justify scientific research by saying what products will be produced or explaining how the products of research will help stimulate the economy.)

I have three main objections. As many people have said, one needs to have something to translate to have translational research. One of the finest examples of translational research that I know of was done by my friend and colleague Qais Al-Awqati. Approximately 40 years ago as a young doctor, he was sent to an Iraqi village that was having a cholera epidemic. Cholera is a horrible disease that causes such a massive loss of fluids that people die of dehydration. Drinking water does not help. Giving intravenous solutions can treat the dehydration, but these are very expensive and not always available in poor countries. Qais, however, remembered research on how nutrients are taken up by the intestine and realized that he could rehydrate people simply by having them drink a solution with some salt and some sugar. This procedure allowed for a safe and inexpensive way to successfully treat the disease. I think the important lesson here is that basic research on how the body works was the necessary beginning of the development of a wonderful procedure.

This example also supports my second objection: the usefulness of a basic research is almost never obvious. The development of a treatment for cholera used basic findings to address a disease that the original researchers had not been studying. GFP provides another examples. This protein, which was discovered by Osamu Shimomura because he was curious about the problem of why particular organisms produce light, not because he was studying a disease, has been extremely important in the study of the mechanisms underlying several human diseases. If we narrowly focus on human diseases and well-being, we miss the information that may ultimately help us understand and treat human afflictions.

LabFinally, translational research or the usefulness of research in general is not the only (and I do not believe the best) justification for scientific studies. I would like to read two quotes that similarly speak of a different importance of studies in science and math. The first quote comes from the mathematician G. H. Hardy. The geneticists among you may know him as the Hardy of the Hardy-Weinberg equation in population genetics; others of you may recognize his name as the Englishman who recognized the genius of the Indian mathematician Srinivasa Ramanujan, with whom he collaborated for many years. In a book that he wrote in his sixties (The Mathematician’s Apology), Hardy after explaining and in fact reveling in his contention that mathematics is useless, writes the following to justify his life as a mathematician:

“The case for my life, then, or for that of any one else who has been a mathematician in the same sense in which I have been one, is this: that I have added something to knowledge, and helped others to add more; and that these somethings have a value which differs in degree only, and not in kind, from that of the creations of the great mathematicians, or of any of the other artists, great or small, who have left some kind of memorial behind them.”

My second quote comes from Robert R. Wilson, the physicist, architect, and sculptor, who designed and was the first head of the FermiLab Accelerator in the United States. Until a few months ago FermiLab had the world’s most powerful particle accelerator. Wilson was asked to testify before the U.S. Congress in 1969, when it was deciding whether the government should fund such a large and expensive scientific project. One senator wanted to help Wilson and gave him what he thought was an easily answered question that could convince the members of Congress to fund the project: How would the work from the new accelerator help national defense? Wilson replied that it would not. The senator persisted and finally Wilson replied,

“It has only to do with the respect with which we regard one another, the dignity of men, our love of culture. It has to do with whether we are good painters, good sculptors, great poets. I mean all the things we really venerate in our country and are patriotic about. It has nothing to do directly with defending the country except to make it worth defending.”

I love both of these quotes because they speak to a different way to contribute to society. As I said at the beginning of this speech, our lives are an N of 1, and we all contribute in our own ways. So I do not have advice to give, but I do have a wish: I wish that you enjoy this uniqueness and see where it takes you. And don’t listen to too much advice. Congratulations.

August 28, 2010
University HQ, Coimbatore

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