Gene Machine

CHAPTER 1

An Unexpected Change of Plans in America

WHEN I LEFT INDIA, I had my heart set on becoming a theoretical physicist. I was nineteen years old and had just graduated from Baroda University. It was customary to stay on to get a master’s degree in India before going abroad for a PhD, but I was eager to go to America as soon as I could. To me, it was not only the land of opportunity but also of rational heroes like Richard Feynman, whose famous Lectures on Physics had been part of my undergraduate curriculum. Besides, my parents were already there, as my father was doing a short sabbatical at the University of Illinois in Urbana.

Since this was a last-minute decision, I had not taken the GRE exam that is a requirement for American graduate schools, and most universities would not even consider my application. The physics department at the University of Illinois initially accepted me, but when the graduate college found out I was only nineteen, they said that at best I could join as an undergraduate with two years of college credit. No middle-class Indian then could afford the cost of tuition and living in America. In the meantime, my department chairman in Baroda showed me a letter from Ohio University asking him to let prospective graduate students know about its program. I had never heard of Ohio University before but saw that the department had an IBM System/360 computer and a Van de Graaff accelerator and that its faculty had been trained at some of the best universities; that seemed good enough for me. They waived the usual GRE requirement and accepted me with financial support. After the typically nerve-racking interview for a student visa at the U.S. consulate in Bombay, I bought my ticket to the promised land.

As soon as I had finished my final exams, I left the sweltering heat of India and set off for America. I had caught a fever and the flight seemed interminable, stopping at Beirut, Geneva, Paris, and London before landing in New York. I boarded a plane for Chicago and then took a short flight to Champaign-Urbana. As I stepped out onto the tarmac on the evening of May 17, 1971, I felt a blast of the coldest wind I had ever experienced.

My sudden immersion into American college life came as something of a shock. College life in India was fairly staid. Students were conservative in their attire and focused on their studies; many, like me, still lived with their parents. Dating, and especially premarital sex, was quite unusual. I arrived as a geeky student with a crewcut, glasses with thick black plastic frames, and orange suede shoes two sizes too large, into an America that in 1971 was a continuation of the sixties. American students seemed to belong to an entirely different species: the males in tattered jeans and hair even longer than the females, who in their hot pants and halter tops seemed almost naked compared to the Indian women I had just left behind. Campuses throughout America were protesting the Vietnam War. One afternoon, out of a mixture of curiosity and sympathy, I attended a peace rally. I stuck out like a sore thumb but then found two older guys at the back, who like me had short hair and were dressed in the same cheap polyester pants and shirts. I walked over to them and tried to be friendly, but they were rather curt and suspicious. Only later did I find out that they were FBI agents keeping an eye on the antiwar troublemakers.

I spent the summer taking courses at the University of Illinois, filling gaps in my education from Baroda. At the end of the summer, I drove with my parents and sister to the pretty and hilly university town of Athens in southern Ohio, which was to be my home for the next few years. The first problem was finding any home at all. Since I had to live on my teaching assistantship and was a vegetarian, I thought it would be best if I rented a small apartment where I could cook my own meals. We scoured the newspaper for rental ads with little success. In one case, the landlady said the apartment was available, but when we showed up to look at it only a few minutes later, she took one look at me and said it was “just taken.” That was my first experience of racism in America. Unable to find an apartment that weekend, I signed up for a dorm room and spent the first year living primarily on cheese sandwiches at the cafeteria.

Notwithstanding its culinary disadvantages, the dorm room had the great benefit of allowing me to instantly acquire a group of friends and avoid the feeling of isolation and ghettoization so common to foreigners. My dorm mates quickly helped me assimilate into American college life. The first Saturday, we went to a football game. The pomp, with cheerleaders, bands, and the loud PA system, seemed to dwarf the game itself.

The dorm also had the advantage of being close to the physics department, and several fellow graduate students lived in rooms nearby, so we were able to form a friendly study group and get used to graduate school together. Physics graduate students generally have to do a year or two of coursework followed by a comprehensive exam before they begin serious research. Although I finished my coursework and the written part of the comprehensive exam without too many problems, the oral part at the end gave me the first inkling that I did not have a burning desire to be a physicist. I was asked what recent interesting discoveries in physics I had read about. I couldn’t name even one, and only after some prodding could I even name an area I found interesting. They passed me anyway, and I decided to work under the supervision of Tomoyasu Tanaka, a well-regarded condensed matter theorist. By then, I had already become intrigued by biological questions, and I included some biological problems in my thesis proposal. Since neither Tomoyasu nor I knew the slightest thing about biology, these proposals were pure fantasy and I soon abandoned them.

As I began my thesis work, I realized that I could not quite see how to identify key questions, let alone how to approach them. Even worse, I didn’t find my work interesting. I retreated into my social life, playing on the university chess team, going hiking with my friend Sudhir Kaicker, learning about Western classical music from another friend, Tony Grimaldi, and generally doing anything except making progress on my graduate work. Tomoyasu was an almost stereotypically polite Japanese who would occasionally come into my office to delicately inquire about my progress, and I would tell him in a roundabout way that there hadn’t been any. This continued for a couple of years. I’ve often said that if I’d had students like me, I would have fired them!

Things suddenly changed when I met Vera Rosenberry, a recently separated woman with a four-year-old daughter. Some mutual friends decided that the two of us should meet, perhaps because we were both vegetarians—an oddity in 1970s southern Ohio. I was completely oblivious that our first meeting was a setup because we were part of a large Thanksgiving gathering. Observing my cluelessness, my friends decided I needed additional help and invited me to a dinner party with just one other couple. Vera struck me as both intelligent and classically good looking, but I assumed someone like her would be out of my league and couldn’t possibly be interested in me. So I tried to introduce her to a friend by inviting him to dinner along with Vera and her daughter, Tanya. I spent some of that time playing with Tanya so that my friend and Vera could be free to chat. It was my friend who had to point out that she seemed interested in me, not him, and if anything, she probably became even more interested when she saw how well I got along with her daughter. Despite this comically inept start on my part, we began a stormy courtship that lasted less than a year and got married soon after her divorce became final. At the age of twenty-three, I found myself married and the stepfather of a five-year-old girl.

Marriage, however, focused my mind on my career. Vera wanted to have another child, so I faced the prospect of supporting a family without any idea of what I would do next. There seemed no question that if I stayed on in physics, I would spend the rest of my life doing boring and incremental calculations that wouldn’t result in any real advance in understanding. Biology, on the other hand, was undergoing the sort of dramatic transformation that physics had in the early twentieth century. The revolution in molecular biology that began with the structure of DNA was still going strong, and we were beginning to get fundamental insights into the molecular basis of biological processes that had puzzled us for centuries. Almost every single issue of Scientific American would report some major breakthrough in biology, and it seemed as if it could be done by mere mortals like me. My problem was that I knew only the most basic biology and had no idea what biological research entailed. So even before I had finished my physics PhD, I made the difficult decision to attend graduate school all over again, this time in biology, taking heart from the fact that illustrious scientists like Max Perutz, Francis Crick, and Max Delbrück had made a similar transition.

I wrote to several top-tier universities, but many of them did not want to accept someone who already had a PhD into graduate school. Two replies were particularly memorable. The first, from Franklin Hutchinson at Yale, was a friendly letter saying that although they couldn’t accept me as a graduate student, he would send around my CV to his faculty in case someone was interested in hiring me as a postdoctoral research fellow. Two of them wrote back: Don Engelman and, ironically (in hindsight), Tom Steitz. I thanked them both and said that I didn’t have enough background to be useful to them as a postdoc and would try to acquire some training first. At the opposite end of the spectrum from Hutchinson was James Bonner of Caltech. In my applications, I had written that because I was only twenty-three, I was young enough to go to graduate school again. Bonner berated me for bragging about my age, adding that he, too, was only twenty-three when he received his PhD, and he was considered backward in his family. He also said that the areas I had mentioned—allostery, membrane proteins, and neurobiology—were hardly surprising because they were the most fashionable areas of biology. If I wanted to work in them, he wrote, I had to first show that I could actually be competent in those areas, and certainly Caltech would not accept me as a student. Perhaps he had never read Catch 22. Fortunately for me, Dan Lindsley of UC San Diego was willing to accept me into the biology department as a graduate student with a fellowship. Even more fortunately, Vera and Tanya were game to move to California and continue living on a meager graduate student’s stipend with the added burden of an infant—all without a car.

Somehow, I scraped together enough work to produce a passable thesis just in time. Our son Raman was born just a month after my PhD exam. A couple of weeks later, a friend and I drove from Ohio to California in a Ryder truck with all our belongings, and Vera and the children flew in with my mother-in-law a week later. Once we had settled in, I began my studies in earnest in the fall of 1976.

The thing that immediately struck me about biology was how many facts you have to know. The introductory lectures for new graduate students were full of jargon I didn’t understand at all. To catch up, I took a full load of undergraduate courses in genetics, biochemistry, and cell biology, in addition to doing first-year graduate student rotations, which are short six-week projects that American grad students typically do before they settle into a lab for their PhD research. Because my physics research had been entirely theoretical, I was totally ignorant of laboratory work. This was brought home to me during a rotation in Milton Saier’s lab, which worked on sugar uptake by bacteria. The experiment entailed adding a certain amount of radioactive glucose to a culture of bacteria at time zero, and then measuring how much glucose had entered the bacteria at various time points. The amount of the glucose to be added was much smaller than anything I had encountered before—only about twenty microliters (less than 1 percent of the volume of a teaspoon). How could you measure such a small volume? I asked. The technician who was training me very pleasantly showed me a device called a Pipetman, which is essentially a tube with a piston that can be set so that it can go up or down by a precise amount. She showed me how to set the volume on the dial, how to draw up the right amount, and how to give the knob a little extra push at the end to make sure all the sample had been ejected. That was all there was to it, she said. I took the device and plunged it into the radioactive glucose, and she exclaimed, “What the hell are you doing? You have to use tips!” The devices were so commonplace that she’d forgotten to mention the narrow disposable plastic tips that needed to be attached to the end of the Pipetman so that it never got contaminated by contact with the sample.

Moving with a young child and an infant was not exactly conducive to learning a new field. However, I was extremely lucky that Vera, who was starting her own career as a children’s book illustrator, could work from home. She did almost all of the childcare and housework, allowing me to focus on my studies. I ended the first year feeling optimistic that I had a broad enough background in biology and fairly varied lab experience. In my second year, I began work with Mauricio Montal, who was studying proteins that let ions pass through the thin membranes of lipids that envelop all cells. As it turned out, I wouldn’t stay in his lab very long. Almost entirely by chance, I would move across the country yet again to begin work on one of the oldest and most central molecules of life.