The Wrong Lessons
A few months ago, I was asked by the New York Academy of Science to talk to high school science teachers about my research and particularly the work that I had done with Green Fluorescent Protein (GFP). As I was preparing for the talk I thought about my elementary and high school education in the late 1950's and early 1960's. I was struck by the realization that all the examples of scientists and their discoveries that I learned of then had given me a very incorrect view of who scientists were and how they worked. I also realized that my experience with GFP provided many counterexamples.
So what was I taught and why was it wrong? Actually, no one specifically taught these ideas to me; they were just incorporated in all of the examples that were at hand. First, from stories about Einstein, Newton, Galileo, and others, I learned that scientists were geniuses. They seemed to have an innate ability to think of experiments. In other words, great scientists were born that way, they never developed into the people they became. As a result, when I went to college, I thought I had to know what to do in a lab almost by instinct. I even had the really silly idea that if I asked anyone for held, I wasn't really destined to be a scientist, because asking for help would be a sign of inability. As a result, my first real experience in the lab, one in which I worked alone and did not really ask for help, was a disaster that actually convinced me to finished my major as soon as possible and not take any more science courses in college. But doing well in science, as doing well in sports, the arts, or any other field of human endeavor requires a lot of practice and hard work, as well as a passion for doing the work.
Second, I only heard about the experiments that works, so I was given the erroneous idea that scientists' experiments worked the first time, every time. So when my initial experiments failed, I was convinced that this area was not for me. The truth, however, is that most experiments do not work. Some experiments have to be done several times before you gain mastery over the technique, others have to be modified to make them work, and still other never work (sometimes because your hypothesis is wrong). Very rarely does an experiment work the first time (and, then, of course, you have to repeat it). Osamu Shimomura, the discoverer of GFP, had a terrible time when he started trying to isolate the protein that allowed the jellyfish Aequoria victoria to be bioluminescent. No matter what he did, he could not isolate the light-producing protein. One night after another frustrating day of failure, he threw his protein prep into the sink (the sink had jellyfish remains and seawater among other things in it) and left to go home. As he turned off the light he looked back to see that it was glowing. He soon realized that the seawater in the sink had calcium, something that he had not put into his protein preps. This realization allowed him to purify the bioluminescent protein, which he names aequorin.
Third, I learned that scientists use the scientific method (they think of a problem, devise a hypothesis, design an experiment, etc.), that all of their work is purposeful. The example I just gave from Osamu Shimomura's research does not follow this model. Actually, what he did next also does no fit into this scheme. When he purified aequorin, he had a new problem: when calcium was added to aequorin, it produced a blue light. The problem was that the jellyfish did not produce blue light; they produced green light. He realized that something was missing, and that led him to find a second protein that he initially called the green protein, but we now call the Green Fluorescent Protein. They physicist Enrico Fermi said that when an experiment confirms a hypothesis, you have a measurement, but when it contradicts your hypothesis, you have a discovery. Some of the most profound results in science are these accidental discoveries.
Fourth, I learned that scientists almost never work with someone else unless that is a lab assistant (except for Watson and Crick). My own involvement with GFP, the introduction of the protein as a biological marker was a collaborative effort from the very start. Douglas Prasher cloned the cDNA for the GFP, Ghia Euskirchen, a talented graduate student, put the cDNA into bacteria, Yuan Tu, a technician, put the gene into worms (the main organism we study), and Bill Ward characterized the bacterially make protein. In general, I think that GFP is a very good metaphor for how science advances. GFP absorbs light of one wavelength and converts in to light of another wavelength. As scientists, we take in the observations and ideas of other researchers, modify them by our own thoughts and experiments, and give them off to be modified in turn by other scientists.
Fifth, I learned that (except for Marie Curie) all scientists were men and (including Marie Curie) were European of of European descent. Our experiments succeeded because of Ghia's work. Moreover, although my lab showed that GFP could be used to mark cells and demonstrate gene expression, probably the most far-reaching result with GFP was the demonstration by Tulle Hazelrigg's lab (full disclosure: Tulle is my wife) that GFP could be used to follow protein movements within cells.
Scientific ability has nothing to do with gender, sexual orientation, country of origin, religion, or genetic background. It simply requires the desire to investigate the world around us. It is an equal opportunity enterprise because it requires passion, a willingness to try, and a desire to think about problems, qualities that know no boundaries. And every once in a while, you have to throw things in the sink.
Nobel Laureate in Physiology or Medicine
Department of Biological Sciences