Avoid Boring People: Lessons From a Life in Science (6 page)

3. New ideas usually need new facts

Though facts are inherently less satisfying than the conclusions drawn from them, their importance cannot be denied. Darwin's abandonment of the Bible's description of the origin of life came out of the observations that he made as a naturalist aboard the HMS
Beagle.
During its three-year mission of charting poorly known stretches of the western coastline of South America, Darwin spent much time ashore observing and collecting the fauna, flora, and fossils. He noticed among other things that species found in mountainous temperate regions were more similar to those found in nearby tropical regions than they were to species from temperate regions on other continents. Likewise, many South American fossils appeared more related to living South American equivalents than to fossils found, say, in Europe. Crucial to his own acceptance of the origin of species by natural selection was his visit to the Galapagos Archipelago, where each island had its own unique species of finches. Effectively isolated from interbreeding with finches of neighboring islands, each species evolved its own unique coloration and beak shape. Sometimes a new idea can flow from old facts rearranged, but more typically it comes when new things previously unknown and unaccountable for under the old theory are introduced.

4. Think like your teachers

Learning to think should also make your life easier. During my first university years, I crammed far too much for exams, trying to be on top of all the topics given even semiprominence in my syllabi or texts. It would have been much better to focus on questions my teachers were certain to ask, which I could discern if I paid attention to their main take-home lessons. Trying to put myself into my instructor's head became much easier when I began to concentrate on subjects of personal interest, and I proved a whiz while a senior at mastering the ideas of ecological animal geography.

5. Pursue courses where you get top grades

After you've satisfied requirements, choose courses that naturally interest you, not ones someone else thinks you should care about. Then give these courses your all. If your grades in classes you like are not largely As, you have likely not yet found your intellectual calling. As a corollary: if you do take courses that prove to be no fun, don't get upset by less than stellar grades.

6. Seek out bright as opposed to popular friends

Though big-time sports were gone, the University of Chicago still had fraternities that acted as dining and housing centers for students with social aspirations after the war ended. Only one such meal in a house on University Avenue made it obvious to all that I'd better plan to continue dining at the Hutchinson Commons with several undergraduate science oddballs who, like me, could not generate polite words of no purpose. There we could frequently look across its long refectory tables and see Enrico Fermi talking with his graduate students and postdocs. The great Italian-born physicist had elected to be there instead of dining with fellow physics professors in the more stuffy Quadrangle Club. In my senior year, I began moving among zoology department graduate students. With them small talk came easily. I didn't feel like an oddball, as I did among students of other aspirations who were soon to move off into worlds of which I had no interest in ever becoming a part.

7. Have teachers who like you intellectually

Long after I left Chicago, a gathering of its New York alumni brought me into contact with a classmate whom I remembered best for his devotion to bridge games. Cheerfully he told me how, given my social awkwardness, none of my classmates thought I would amount to much. Happily it was my teachers’ opinion, not my classmates', that mattered. After fun classes I liked to stay on to ask questions, and in this way I became well known to them. Because of my enthusiasm, during my senior year the animal behaviorist Clyde Allee invited me to join the weekly meeting of his students at his nearby Hyde Park house. He not only gave me an A but also wrote a compelling recommendation for my application to graduate school. The most effective endorsements are cultivated well before application time. So it was with the human geneticist Herluf Strandskov, who would also praise my keen interest in biology. You don't have to win them all: the impervious embryologist Paul Weiss was ever annoyed at my failure to take notes during his lectures while still getting A's in his exams. I had the sense not to ask him for a recommendation.

8. Narrow down your intellectual (career) objectives while still in college

The University of Chicago was virtually an officers’ training school for intellectuals, and its Zoology Department had no rival in range elsewhere in the United States. Though initially excited by virtually all aspects of biology, by late in my junior year I found myself keenly interested in the gene. If I had not figured out my focus so early, I very likely would have gone to a school such as Cornell or Berkeley that had great programs in biology but not in genetics. In such circumstances I might have grown bored with my thesis research and been obliged to wait until after my Ph.D. was completed, some three or four years, before experiencing true intellectual excitement. And by then I would have left the most thrilling problem of all—the DNA structure—for others to solve.

3. MANNERS PICKED UP IN GRADUATE SCHOOL

I
NDIANA University (IU), at Bloomington in Monroe County, to which I went in September 1947 to become a scientist was waking up from a genteel past that made it still more redolent of a southern state university than the other earnestly progressive Big Ten partners such as Wisconsin and Michigan. Presiding over the emergence of IU as an institution where learning and research were to be as important as weekends of fraternity- and sorority-led fun was Herman B. Wells. He became president in 1937, when he was only thirty-five. Short and heavyset, the Indiana-born small-town boy had prodigious energy and visions of greatness for his university, until then the academic runt of the Big Ten.

During its more than thirty-year slumber since 1910, President William L. Bryan had not presided over the construction of even one major new dormitory. So Wells moved quickly to shake things up, recruiting new faculty and using Depression-fighting federal funds to build important new facilities, including a grand four-thousand-seat student auditorium. For science faculty recruiting, Wells tapped Fernandus Payne, who until then had been badly underutilized by the graduate school. A Hoosier born and bred, Payne, like almost all the senior faculty, had gone east to earn his Ph.D., which was awarded in 1909 by Columbia University, where
Drosophila,
the tiny fruit fly, had just been introduced into the laboratory of T. H. Morgan. Payne had the bad luck to return to Indiana just before Morgan and his students Alfred Sturtevant and Calvin Bridges began their seminal experiments, mapping genes to fixed locations along the
Drosophila
chromosomes.

Though never a major player in genetics, Payne knew where the action was. He made offers to major talents not yet adequately discovered or recognized by major institutions. From Goucher, the women's college in Baltimore, he recruited the respected cytologist Ralph Cle-land in 1938 for the Botany Department. A year later he brought to the Zoology Department the extraordinary protozoologist Tracy Sonneborn from Johns Hopkins. Then late in 1943, the bacteriology department acquired the Italian-born Salvador Luria, initially trained as an M.D. but by then exploring the genetics of viruses. Even more spectacular was Payne's ability in 1946 to persuade the already world-famous
Drosophila
geneticist Hermann J. Muller to join ITJ's ranks.

In appointing Sonneborn and Luria, Payne took no notice of the Jewish heritage that had kept Sonneborn from a tenured appointment at Johns Hopkins and Luria from an invitation to join the faculty at the College of Physicians and Surgeons of Columbia University, where he had been given a temporary position upon his arrival as a wartime refugee. Müller, then working with Sewall Wright, the most accomplished of American geneticists, suffered from a double whammy. Not only was he Jewish, but his departure from Texas to Moscow in the early 1930s had indelibly marked him as an unemployable leftist. Upon his return to the States in 1940, only by the intervention of his friend H. H. Plough could he secure a temporary position at Amherst. He had asked many other friends for help, but no major research university made him an offer, even though Müller had by then turned totally against the Soviet government. So it was with great relief that Müller accepted the IU professorship. Soon Indiana would have even greater reason to be pleased when Muller was given the Nobel Prize in Physiology or Medicine.

To get to Bloomington I took the Monon, the railroad most identified with Indiana's past and one whose original tracks went past the Gleason farm near La Porte where my grandmother was raised. Along these tracks Nana saw Lincoln's funeral train as it slowly crisscrossed the Midwest toward Springfield, Illinois, where the president was buried. I had signed up to live and eat at the Rogers Center, a postwar utilitarian dormitory complex located a mile east of the campus center. Its two-story buildings were of necessity built too quickly to have the permanent elegance that comes with Indiana limestone. My $900 fellowship would more than cover room and board fees, leaving me enough for the occasional movie and meal out.

Herman J. Muller, 1941

Some twenty thousand students were then enrolled at IU. All Indiana high school graduates were entitled to enroll there or at rival Purdue, the engineering and agriculture-oriented university a hundred miles north. The state saw its obligation to offer everyone who wanted one a good education. But each year half the freshman class did not go on to be sophomores. Poor grades were behind most dropouts, but a significant number of girls transferred to other schools because of their failure to be accepted by a suitable sorority.

The aged zoology and botany laboratories that dated from the 1880s were in no way adequate for IU's new genetics thrust. Ralph Cleland, upon his 1938 move to the Botany Department, however, had to make do. Tracy Sonneborn had the better fortune a year later of being given space in the relatively new chemistry building. Salvador Luria, coming in 1943, found his new Microbiology Department lab sited in the attic of the early-twentieth-century Kirkwood Hall, originally designed for physics and chemistry, though by then foreign languages and nutrition were taught on lower floors. Hermann J. Muller's lab was hastily created in 1946 in the basement of the equally out-of-date psychology building. As a first-year graduate student, I was given a desk on the top floor of the zoology building, whose original elevator was still operated by pulling ropes to go up and down.

On the first floor of the zoology building were the offices of Alfred Kinsey, much esteemed for his studies on gall wasps, and until recently the teacher of the undergraduate course on evolution. By 1947, however, his focus had turned exclusively to human sexuality, then a daring topic for any university, particularly one almost in the South. Fortunately, Kinsey's recently published book summarizing his findings was so heavily statistical as to be more likely purgative than prurient. In fact, subsequent criticism that Kinsey seemed ignorant of the emotional aspects of sex later led his Institute of Human Sexuality to accumulate a highly restricted library of erotica. This backfired when some books later purchased in France were seized by U.S. Customs and, despite much pleading by Herman Wells, never released for their scholarly aims.

The day after my arrival, I arranged my courses for the coming term. Naturally I signed up for Muller's Advanced Genetics—Mutations and the Gene. I was also urged by Fernandus Payne to take as soon as possible Microbial Genetics with Tracy Sonneborn, since he was zoology's brightest young star. But that term he was only teaching an elementary genetics class, and so I registered for Salvador Luria's course on viruses. Soon I heard faculty gossip that Luria treated his students like dogs. This worried me until I listened to his first several lectures and found them mesmerizing. Less comprehensible to my Zoology Department advisers was my desire to register for Advanced Calculus, a course usually taken only by physics and math majors. But unless I took it, I feared, I would never have the courage to learn more physics, without which I might be precluded from pursuing possible high-powered ways to probe the gene. Ironically, my teacher was to be Lawrence Graves, on sabbatical from the University of Chicago, where I never would have dared enter into one of his courses. But at the more low-key Indiana I would not be competing with real math whizzes— and besides, grades were rather beside the point.

The required text of Muller's course was the lucid and still highly relevant
Introduction to Modern Genetics
(1939) by the English biologist C. H. Waddington. The heart of the course, however, was Muller's lecture account of his career starting from his days as a student in the “fly room” of Columbia University between 1910 and 1915. Emanating from a short, heavyset man almost the shape of a
Drosophila
himself, Muller's lectures were streams of consciousness rather than prepared orations. His agitated speech mingled clever genetic reasoning with details of his frustrations over, say, not initially being accepted into T. H. Morgan's lab, and later when finally a member having his ideas given short shrift. Much less absorbing were the lab sessions, in which we were chaotically run through an increasingly complex set of genetic crosses. The insights of such experiments seemed rather arcane, pointing to a truth that could not be avoided:
Drosophila's
days as a model organism were over. Indeed, a new one would soon supplant it as the premier tool for studying the gene.

Through Luria's virus course lectures, I saw the genetic wave of the future unfolding. The key would be microorganisms, whose short life cycles would permit genetic crosses to be done and analyzed in a matter of days instead of weeks or months. Luria was particularly excited about the future of research using the common intestinal bacterium
Escherichia colt
and its parasitic viruses, the bacteriophages (or phages for short, as they were more often called). Soon after his 1943 arrival in Bloomington Luria, then thirty-one, was the first to systematically show that both
E. coli
and its phages gave rise to easily identifiable spontaneous mutants. Only three years later, in 1946, was genetic recombination between different
E. coli
strains demonstrated by the precocious twenty-one-year-old Joshua Lederberg, then a medical student in Edward Tatum's laboratory at Yale. The same year Alfred Hershey at Washington University found genetic recombination for the
E. colt
phages T2 and T4 and soon constructed the first genetic maps of phage chromosomes.

Until Luria's first lecture, I had no idea what a virus was. Soon I knew they were very small, infective agents that multiplied only within living cells. Outside of cells, viruses are essentially inert. But once they enter a cell, a multiplication process is initiated that leads to a generation of hundreds to thousands of new progeny viral particles identical to the original parent particle. Unlike bacteria, viruses cannot be observed using conventional microscopes. Their sizes and shapes first became known following the invention of the much more powerful electron microscope in Germany just prior to the start of World War II. The first phages so examined had unexpected tadpole-like shapes, with polygonal heads attached to much thinner, tail-like appendages.

More than two decades earlier, H. J. Müller had speculated that viruses were, in fact, naked chromosomes that had acquired special structures for being transported from one cell to another. Supporting his conjecture was the finding in the mid-1930S that DNA, a soon-to-be-discovered major component of all chromosomes, also was a major component of the phages. Even more important was the 1944 discovery by Oswald Avery and his coworkers at the Rockefeller Institute in New York that DNA could transmit genetic markers in pneumonia bacteria. Conceivably much, if not all, of the genetic specificity of phages also resided in their DNA components.

Luria's lectures were also particularly exciting for me because they frequently described his collaborations of the past six years with the German-born physicist Max Delbrück, whose ideas about the gene in the mid-1930S provided the essence of Erwin Schrödinger's
What Is Life?
How a gene is copied to yield an identical replica was now being extended by Luria and Delbrück to ask how a single phage particle gives rise to hundreds of identical progeny. In learning how phages multiply, Luria and Delbrück thought the fundamental mechanism of how genes are copied would also become known.

A key requirement of Luria's course was the term paper, which I chose to write on the effects of ionizing radiation on viruses. Luria had used X-rays to estimate the size of the then still submicroscopic phages when he worked in Paris in 1938-40, where he had fled when Mussolini, in an attempt to curry favor from Hitler, had begun his first serious persecution of Italy's Jews. Because only a single ionizing event is necessary to kill a phage, a minimal size of a phage can be calculated from the number of phage particles killed as a function of X-ray dose. The so-called target theory approach was previously used in 1935 by Max Delbrück to give an estimate of the size of
Drosophila
genes, and so I had no difficulty finding enough material to fill out my paper, as no original thought was expected. I was more worried I would be penalized for bad handwriting, but I got an A.

Not so easy was my math course, whose text was
Advanced Calculus
by Harvard's David Widder. Fortunately, Graves began to appreciate the much lower math aptitudes of his Indiana students in comparison to those he had been used to teaching at the University of Chicago.

What had threatened to be entirely above my head got easier, even occasionally satisfying toward the end. Helping matters was the presence in the class of a small, neat blonde with whom I could compare homework answers at the IU Union cafeteria. A grade of B was more than encouragement enough to continue the course through the spring term. Being able to pass a real math course was a big step forward for me, not only for its own sake but also for allowing me to hold my own with the growing number of physicists moving toward biology to find the secrets of the gene.