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How I became a biochemist

2009; Wiley; Volume: 62; Issue: 2 Linguagem: Inglês

10.1002/iub.267

1521-6551

Gerald M. Carlson,

Various Chemistry Research Topics

Recollections of this type tend to be replete with defining moments, profundities, epiphanies, and axioms, usually in Latin. My story, I am afraid, is more a cumulation of small, prosaic, incremental steps leading to the present. I was instructed to focus on my formative stages, which was not particularly helpful, in that they seem to be eternally ongoing. So instead, I will focus on the years between my third grade, when my family moved from a small dairy farm north of Spokane, Washington into that city, and my first academic job as an assistant professor. I was 8-years-old at the time of the move and remember beginning to frequently ponder the three big, ongoing questions of my young life, probably more like the three big fears. The first and most immediate question was would I ever be able to master driving an automobile, matching clutch, brake, gas, and steering, all while computing the probabilities and arcs of the myriad of events occurring around the car in the bustling metropolis of Spokane? That seemed like an impossibly complex set of skills to master, even though I kept reminding myself that many people who did not strike me as particularly competent nevertheless routinely drove cars without careening off the road and maiming themselves and others. The second question was how would I ever find the right person to marry and then somehow convince her to actually marry me? The odds of my achieving that goal seemed nearly as improbable as learning to drive a car. The third and final question, the focus of this recollection was how would I ever decide on what to try to do for a livelihood, so that I could purchase that impossible car and persuade that improbable wife? These three questions occupied most of my quiet pondering time until my sixteenth birthday when, having just received my driver's license earlier that day, I drove my beautiful red 1952 Chevrolet coupe off the steep edge of my former chemistry lab partner's elevated driveway, leaving it teetering, balanced on the open driver's side door wedged into the ground, which is all that kept it from rolling over. Clearly having mastered driving, I could focus my attention on the final two questions, which were progressively being simultaneously answered through the same process, namely, paying attention while working at after-school and weekend jobs. My mother was widowed when I was a year old and raised a family of six children by herself, before eventually remarrying and moving to the city. Not only did she live the example of hard work being necessary for survival, often simultaneously holding down two jobs away from the farm, she also constantly preached the value of hard work in solving life's problems, if not in avoiding them altogether. So, it was naturally expected that her children would also learn to work. Of the numerous childhood jobs I had, the ones that had the largest effect on me, and on answering my remaining two life questions, were delivering newspapers and working in grocery stores. Both of these jobs presented the wonderful opportunity to interact with many customers repeatedly over several years: to get to know them, to observe how they behaved in different situations, and to talk with them. In the process of doing these things, I slowly gained a strong impression of exactly the kind of person I wanted for a wife, the critical first step in answering the second question. Of course, I had not found that person yet, but I consoled myself that it was bound to be easier to find an appropriate person if you knew what you were looking for. The third question, that of career choice, was more complex, especially because I was only beginning to appreciate the differences between a job and a career. Although I did not know precisely what kind of adult job I wanted at that early stage of my life, I had begun compiling a mental list of the type of jobs I certainly didn't want, for instance neither of my parents' jobs in the city. My mother was a clerk at the unemployment office, interviewing people filing for benefits. She did not seem particularly happy with her job, and I often thought of how depressing it must have been for her to see people at their worst every day, instead of at their best, such as when you hand them their newspaper or groceries. My stepfather was an automechanic and he complained about sliding around on his back under cars, often on wet, cold ground. His most memorable complaint though was about his perpetually dirty hands that simply could not be fully cleaned, which embarrassed him. He advised me many times to never have a job where people could tell what you did for a living simply by looking at your hands. That seemed like reasonable advice to me, and I did not particularly enjoy getting dirty anyway. From watching and talking with my customers, the list of negative potential jobs grew rather lengthy; fortunately, some potential positive jobs also emerged. Our home in Spokane was near Whitworth College, and a number of customers who dressed nicely, had clean hands, and seemed happy, gentle, polite, and interesting, happened to be professors there. Although the notion was a bit alien to my background, these people and their career seemed worthy of emulating. I had always hung out at Whitworth anyway, at their library, student center, gym, athletic events, etc., so it was not a huge step to begin imagining what it would be like to actually belong there. The idea of teaching young people who had elected to be at school and were making choices in the formative stages of their own careers, of talking about ideas rather than things, and of having educated colleagues became increasingly attractive, and I slowly, but privately, became convinced that becoming a college professor was the ideal career choice for me. Of course, I did not yet know about deans. I did know, however, that I would need to decide on some subject of interest to pursue. I truly enjoyed all subjects in school, but was probably most intrigued with science. Growing up, anything that could be collected was, especially spiders and insects. In our basement, I often had boxes of spiders brought in from outdoors spinning webs and homemade glass ant-houses. Arguably the angriest my mother ever became with me was when I brought inside a large portion of a termite colony. I also wrote to all the neighboring county extension agents asking for pamphlets on insect and spider pests, which they supplied and I studied. Yes, entomology would have been an attractive career choice, but that was before I learned about chemistry. Like many boys then, I had started out with a chemistry set, this one set up in my “laboratory” under the basement stairs, where I soon successfully synthesized the ever-popular rotten egg gas, which I'm sure most of you remember. My first exposure to real chemistry came in my sophomore year of public high school when I took that class from an outstanding teacher named Gordon Brunette. He really enjoyed chemistry, as did I, although part of the reason for my enthusiasm may have been the identity of my lab partner, a pretty, vivacious girl who was an upperclassman, but alphabetically assigned as my partner. Although she tended to be on the clumsy side, spilling bottles of acid, and breaking glassware, I more than evened things up the following year by driving my car off her driveway. Mr. Brunette's explanations about general chemistry were always enthusiastic and the very idea of the periodic table absolutely enthralled me. Then at the end of the year there were enough days left to expose us to some rudimentary organic chemistry. How exciting it was to see structures of first acetic acid and then amino acids, which brought mention of their polymeric proteins and biochemistry. One of my customers, Robert Bocksch, taught biochemistry at Whitworth, and I started pestering him more often when he came into the store, asking him what sorts of things biochemists studied. He was always gracious and even invited me to stop by his office to talk, which I did. By the time I graduated from high school and customers asked what I was going to study at college, I routinely told them that I was going to become a biochemist because what could be more exciting than to study the actual chemistry that goes on inside our bodies to keep us alive. I said this often enough that summer that it slowly began to sound like a genuine possibility; thankfully, the listeners were uniformly polite and encouraging, no matter how dubious they may have been privately. Thus, it was that in 1964 I enrolled at Washington State University (WSU) in their charter class of B.S. Biochemistry majors; however, the first actual biochemistry class offered in that major was the graduate-level survey class to be taken during one's senior year, which would have made it difficult to determine if this was, in fact, the marvelous major that I had imagined. Fortunately, the academic advisor assigned to me was Ralph Yount, not only an outstanding enzymologist and protein chemist and inventor of AMPPNP, but more importantly, an extraordinary mentor who soon let me begin working in his laboratory. He personally taught me to sacrifice rabbits and remove their psoas muscle, both while being timed with a stopwatch, and to subsequently purify myosin and assay its ATPase activity. I happily spent my undergraduate years and several summers in Ralph's lab and felt like one of his research group, especially because I had been given a desk in his lab, which I could not have valued more highly. It was great fun observing his postdocs and graduate students banter, often provoked by the certitude of Boyd Haley, who has been a friend since. It was Ralph, however, who played a pivotal role in my life for many years during and after this period. As just one example, I had finally found a potential answer to question number two, but our courtship drug on because of seemingly insurmountable differences concerning religion. During one summer when the girl worked at a fish nutrition lab three-hundred miles from Pullman, I would periodically leave Ralph's lab at 5 P.M., drive the three-hundred miles on two-lane roads, see her for an hour or so, and turn around and drive back home in time to pull into the parking lot at work at 8 A.M. After I had performed this feat several times in the same week, demonstrating to all that I had really aced question number one, Ralph called me into his office and said, “Look, Gerry, just marry the girl!” I thought that if someone so wise was not worried, then why should I be, thus solving the second question. Shortly thereafter we became engaged and married after our junior year, freeing me to focus on the final remaining question of a livelihood. Ralph's advice, as always, was good, and Susan and I have managed to build parallel careers together, hers in the relationship of lipid nutrition to infant development. Following graduation, we entered the Peace Corps, and after that returned to WSU to work as lab techs to save money for whatever was to come next. I did not particularly enjoy my tech work in pharmacology and was far from the ideal employee, doing what I wanted to do, rather than what my boss wanted. I naively complained to Ralph about my situation, and he laughed, saying that I really was not cut out to be a lab tech anyway. He did not say much more than that, but a short time later, I received a letter from Dave Metzler at Iowa State University (ISU) asking if I might be interested in working toward a Ph.D. in Biochemistry there. Inasmuch as Ralph had earned his Ph.D. at ISU working with Dave, it seemed like a rhetorical question; so, we soon loaded all of our possessions into a 4 ft. × 6 ft. U-Haul trailer, threw our 9-month-old son in the back seat of our car, and drove off to Ames, Iowa. Years later I learned that in his letter to ISU, Ralph had guaranteed that I would be either their very best or very worst graduate student and nowhere in between, but that he had absolutely no idea which of the two extremes would attract me. The years in Ames were marvelous, filled with personal growth and self-discovery. The more biochemistry I learned, and there were many outstanding professors at ISU, the more I liked it. Although we were typically poor, so were all our friends in married student housing, which led to co-ops and sharing and getting to know neighbors. So, life was good at home and at work. For my major professor, I chose Don Graves, who had, and still does, a contagious enthusiasm for research, which made you want to work with him. It is not surprising that two of Don's sons, Lee and Paul, have become biochemists themselves, both having worked in his lab as children while I was there. Don had a large family and he and his lovely wife Marge opened up their home to everyone in the research group, making all of us feel welcome as part of their extended family. It has been a special pleasure to become adult friends with Don and Marge, who are shining examples of how to live life to its fullest. By the time I defended my dissertation, I was certain that biochemistry, especially proteins and enzymes, was indeed right for me. So, after hearing him speak, I decided to do postdoctoral work with Henry Lardy of the Institute for Enzyme Research at the University of Wisconsin. Shortly before leaving Ames, Dexter French, the highly respected former chairman of the department, called me into his office and handed me five-hundred dollars, saying that he knew graduate students were usually strapped for money and that it might come in handy for the move or until my pay in Wisconsin started and that I could repay him whenever I felt able. His generosity was a complete surprise, in that I really did not know him personally–it had nothing to do with anything I had said, but was simply an outpouring of his sensitivity and kindness. When I asked how I could possibly repay that kindness, he said that perhaps one day I would be in a position to provide similar help to others, which is nearly word-for-word what Ralph Yount had previously told me when I had asked him the same question. Both the subject of biochemistry and its practitioners continued to convince me that I had chosen the right career path. The urgency of reality began to crowd in at Wisconsin, as I realized that no matter how much I enjoyed enzymology, it was not the hottest area in the job market in the mid-1970s. Henry Lardy's group had grown large from postdocs not leaving and I had to persuade him to accept me, because there was not an empty lab bench available. I was assigned a room with a desk in the old unoccupied side of the building; we called this “the bullpen,” and there I sat working on a review article until a bench opened up about 6 months later because of another postdoc's visa problems. I gratefully occupied it and began learning protein chemistry to find a niche on an ongoing project on phosphoenolpyruvate carboxykinase. Listening to Henry at group meetings, I was in awe of his encyclopedic knowledge of metabolism, as if he had one of those confounding metabolic charts glued to his eyelids. He was also adept at synthesizing unifying hypotheses from seemingly unrelated facts. Perhaps the most important thing I learned from Henry is that there is no such thing as a bad idea, especially if it's testable and the person who thought it up is willing to do the testing. Unfortunately, I still have to remind myself of this periodically as I listen to students and postdocs hypothesize. Another person I met during my postdoc years who has had a big influence on me ever since is Dick Hanson of Case Western Reserve. I first met him when he came up to my poster at a national meeting and flattered my work–those of you who know him will immediately recognize that Dick can find something nice to say about nearly everyone's work. His generosity made me feel special and encouraged me to keep at it. To this day, every time I encounter him, I feel better afterward. I consider him to be a true ambassador of our profession. In 1978, I decided that it was time to determine if I had learned enough to survive on my own and started applying for academic jobs. Picking up protein chemistry turned out to have been valuable, for I found my first job in a chemistry department, where I began doing affinity labeling, hoping the chemists would appreciate that technique. Looking back over my career, it is clear that it has been guided and enriched by a steady stream of invaluable mentors who inspired by the examples they set. Not only was each kind and generous, but each showed an obvious passion for our discipline. As it turned out, my journey of incremental steps toward this career led to exactly the right destination for me. I have always told students that our discipline is ideal because you can contribute valuable knowledge working either inductively or deductively, quantitatively, or qualitatively, that you can be a bioCHEMIST or a BIOchemist, with each being equally valuable. Of course, this does not take into account the incredibly valuable additions of biophysics, molecular biology and genetics, bioinformatics, computer modeling, the various “omics,” etc. What an exciting time it is to be a biochemist! I cannot possibly give enough thanks to those who showed me the way.