Preferred Citation: Sinsheimer, Robert L. The Strands of a Life: The Science of DNA and the Art of Education. Berkeley:  University of California,  c1994 1994. http://ark.cdlib.org/ark:/13030/ft5j49p04r/


 
THE IMPRINTING

THE IMPRINTING


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1—
Boyhood and Youth—
The Molding

"The past is a foreign land."

A child accepts his world as given. Only much later can he look back and see how the twig was bent.

My mind is a time capsule. A memory is stirred, a scene appears with color, sound, and feel as it was fifty years ago, a half century ago. The others in the scene are dead now, some long since departed. Only my images, my impressions remain—for a time.

I am looking at a small, aging photograph of a boy, about five years old, with a thick mop of hair, dressed in overalls and sandals, walking along a dusty gravel road. He is looking down at the road—pensively? With him is a smaller boy, probably three years old, with short curly hair, also dressed in overalls and sandals, walking along head up, eyes forward.

The older boy is—was—me. I don't recall the taking of the photograph, but I know the setting. Summertime on Washington Island off the Door Peninsula of northern Wisconsin, on a gravel road from the farmhouse to the grocery. Washington Island had no electricity then, no telephones or indoor plumbing. Water came from a pump, ice from the icehouse where it was stored up during the winter and insulated with sawdust. It was one of the few remaining sites of nineteenth-century life, lived according to the rhythms of the sun.

I try, to put myself inside the head of that boy, to peel back the layers of years of experiences since accumulated. Of course I can't; the successive years are not simply layered on. They are infiltrated, intertwined,


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and interwoven oven into the very nature of one's being. In some deep sense that boy is stall here, but I can't "access" him. I vaguely perceive that the world was fresher then, more immediate—the tastes cleaner, the smells more direct, the sights sharper, the sounds more distinct.

Life was still a succession of days of sun or rain or snow, of meals and naps, of games with other children and directives from parents. Compared to the life of today, the life of my childhood seems singularly insulated from outside influence. There was school of course and playmates, but the home was the primary influence and was little perturbed or violated by the outside world. No TV screens brought distant scenes to our living room. Radio, in its infancy, brought little of interest. Even the telephone, which required a coin for each call, was used sparingly, and long-distance calls were reserved for calamity. The newspapers and magazines—more decorous in that day—brought in the world, but distilled through the flatness of print and the linear, rational process of reading.

We were all less subject to the seductive commercial values of the media and their induced "peer pressures" but all the more captive of the idiosyncratic, sometimes skewed views of our elders. Thus, parents and, later, teachers by precept and example, through word and action and selected reading provided me with a framework in which to order the myriad events of the vast, confusing outer world—a lens selective of importance, a gate sensitive to values. Indeed, the Midwest in which I grew up in the 1920s and 1930s was still very insular. Europe was a week away, Asia two weeks. International commerce was negligible. Issues of global overpopulation, environmental pollution, and international economic management were unimaginable.

When one is young, at least in America, the world is young. The past, all of history, is telescoped. The constraints the past imposes, the hard-won wisdom it contains, the debt we owe our forebears all seem of little moment. Only later, when our lives have been merged into the stream of human existence, do we better recognize the finite scope of our place in human time. I see now that in my earliest years, the 1920s, I was raised in the America of exuberance. The United States was the greatest, the most advanced nation in the world. We had the most advanced technology, the most advanced political system, and newer was always better. Freed of the palsied hand of Europe with its ancient feuds and antiquated governments and frozen social classes, our democracy had liberated the creativity of the people. Our citizens had civilized a continent and created a great industrial society. Secure between two


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oceans, with no perceived rivals, our destiny was in our hands, and it gleamed. So we thought. Recognition of the side effects of ever more powerful technology or of the social traumas accompanying unlimited free enterprise was yet in the future.

In contrast, my second decade, the 1930s, was gray and grim, a time bleak and foreboding. The Great Depression was psychologically a free fall from the earlier near-euphoria, and the growing menace of Hitler and the war in Europe deepened the gloom.

My forebears on both sides were Germanic and Jewish and thereby melded elements of Teutonic authority and Jewish moral rigidity. My father, Allen, born in 1888 in Chicago, was the elder of two sons. My mother, Rose Davidson, born in 1891 in New York, was the eldest of five children, with two sisters and two brothers. Both of my grandfathers emigrated from Germany to the United States as children with their families, in the 1860s. Their families came for the usual reasons—to escape poverty and prejudice, to seek a better future. Both boys had a limited education; one was for most of his life a salesman in shoe stores, the other a pharmacist who operated a small drugstore. They raised their families in Chicago and New York respectively at only a little above the poverty level, and the education of their children was truncated by economic necessity.

After eight years of grammar school and one year of manual arts high school, my father had to earn a living. After a succession of odd jobs, he discovered a talent for writing. He became a writer for, and ultimately editor of, trade journals. Before and during World War I, he was a feature writer for Automotive Age, a magazine for automobile enthusiasts. During that war, the army's use of motorized vehicles was his principal story, so he was sent to Washington, D.C. There I was born in 1920; soon thereafter however, he returned with his family to Chicago, where I grew up. During most of my childhood, he was editor of a trade journal for retail clothing stores.

Despite his limited education, my father was widely read, a self-taught man. Unguided, some of his reading was enlightening and some quite misleading. He was resolved, however, that his children should at least have the opportunity for more advanced education. He sought to encourage intellectual interests by taking us as children on weekends to the Field Museum of Natural History, Shedd Aquarium, and Adler Planetarium. The Field Museum was endlessly fascinating. I particularly remember the huge reconstructed mastodon and the intriguing, yet eerie, ancient Egyptian mummies.


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After three years of high school, including a final year of secretarial training, my mother was similarly obliged to go to work. However, she intensely disliked office work. She was a very pretty woman and met my father on one of his trips to New York. They were married in 1913 (he was twenty-four, she twenty-one). My older brother, Allen, Jr., was born a year later. In Germanic fashion, my father dominated the household. With three sons (my younger brother, Richard, was born two years after me), my mother played a relatively passive role in the household, occupying herself with projects at the synagogue and social activities such as bridge and mah-jongg.

In our home, there was a strong emphasis on intellectual and cultural development, but at a cost. Emotions were not to be trusted. Emotional display, except through such refined media as music or art, was to be repressed as crude, primitive, and unworthy. A distant mother and the absence of sisters reinforced this atmosphere. We learned to be self-reliant, to make our own way in this world. We could expect some support from the family but not much else. The anguish of the Great Depression confirmed this view as did, later, the "sink-or-swim" attitude prevalent during my years at MIT.

I was also brought up with a strong sense of duty—with the charge to use my talents, which it appeared early were considerable, for the benefit of others in whatever way seemed at the time most propitious, and not to be distracted or seduced from that obligation by transient pleasures. At the same time, my upbringing oddly provided rather little sense of community or belonging to an ongoing stream of human life and endeavor; this has only come to me much later in the global community of science. I was brought up not to expect much from life unless I "earned" it. Perhaps this attitude was simply in the American tradition of "rugged individualism." Perhaps it was the lost contact with our ancestors, buried far away in a decadent Europe from which we were thankfully delivered. Perhaps it was our Jewish identity, which we understood excluded us from the American mainstream. No Jewish boy would ever be president, head of a great corporation, or even mayor of Chicago. America was much freer than Europe and many professions were open to us, but the exclusionary pattern was still there, still real and strong. A Jewish boy would have to be better, we heard, as we hear today for a woman, an African American, or an Asian American.

Much later, I came to realize that, in part, these perspectives reflected, beyond any intrinsic merit, my father's psychology, even pathology. He was a deeply fearful man. He was beset by, and transmitted


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to his children, the convictions that life was a hazardous enterprise, that one could easily make an irreversible mistake that would forever blight one's health or economic or social status, and that the path to avoid such disaster was one of constant caution, moderation, and modesty in behavior and action. Not to dare greatly, not to plunge wildly. He was highly conscious of appearances and highly threatened by possible loss of dignity, or community censure. To become drunk, for instance, was not merely an immoderate act but a disgrace, a blot on one's image.

To me, growing up in his household, all of this seemed reasonable and proper; questioning of parental authority and wisdom was not encouraged. And the apparent correctness of the basic proposition was certainly corroborated by the external events of the 1930s. The Great Depression and the looming abyss of World War II reinforced the concept that one's individual destiny was subject to great and perilous forces far beyond one's control. So it was not until many years later that I came to realize how skewed, pinched, and constrained a view of the world this was and to escape, at least in part, from its thrall.

I am left-handed. Fortunately, my father had read of the traumatic consequences of forced conversion from left- to right-handed use and intervened at school to prevent such a requirement. However, for many years I thought I was clumsy because I had much more difficulty than others with scissors or screwdrivers (and later, corkscrews).

Schoolwork was ridiculously easy for me. I passed the first two grades in one year, likewise the fifth and sixth. Of course, this advancement into an older age group distorted and retarded my social development. Because of this, and because school was mostly boring, I took refuge in reading. I certainly read the majority of books in the children's section of the local branch library.

In my teens, two books markedly changed my view of biological life. In my family, life in the biological sense (much less sex) was rarely discussed. It was a given fact of nature not subject to analysis or human understanding. Our bodies were bequeathed to us and we had limited control over their subsequent fates. But from Wells and Huxley's The Science of Life I first realized that one could regard living organisms as very complex machines, with varied components whose functions and interactions could be dissected and analyzed. Of course, we have now carried that perception down to within the cell, even to the genes, and have found machines within machines within machines to the limiting level of molecular devices.

Except in the crudest sense that like begets like, my upbringing pro-


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vided no appreciation of heredity. Thus, the book You and Heredity by Sheinfeld was a stunning entry to a new world. We are what we are by virtue of our specific, inherited genes. Of course! But how? What wondrous processes could produce this result? Not immediately, but subtly, these new insights gathered deep within me and generated powerful fountains of interest and curiosity that have continually renewed and refreshed a lifetime. Indeed, I seem to have been endowed with an unending curiosity and I have always found that my interest in almost any subject grew in proportion to my knowledge about it. But biology, has had a first claim.

Although the youngest, I was the valedictorian of my grammar school class and went on to high school, a larger world of some five thousand students. At this same age, several other influences affected my life, among them the Great Depression, boys' camp, Sunday school, the World's Fair.

Although the Depression heightened my father's fearfulness, it did not in fact greatly alter our economic status. My father had always lived well within his income and, while his salary was reduced, he was never unemployed and our standard of living changed little. But I well recall grown men coming daily to the back door of our apartment to beg for food; we never turned them away empty-handed.

And I recall a favorite uncle who arrived at our door at a very early hour one morning because he literally had no money to buy food for his family. My father helped out for a time. These images of despair remain sixty years later.

For four summers, my brothers and I went to a boys' camp in northern Wisconsin. Here I was introduced to a more elemental, more natural world. Northern Wisconsin is dotted with clear lakes set in pine forests. In those days, before motorboats and water skiers, the lakes were extraordinarily quiet and tranquil. Paddling across in a canoe, I could imagine a kinship with the Hiawatha of legend.

Camp was also my first interaction, in many aspects of living, with a considerable diversity of other children, many from families much less repressed and with values quite different from my own. The experience was illuminating, although insufficient to raise strong doubts about parental strictures.

I was also introduced to athletics, especially baseball and tennis for which it turned out I had some aptitude and which I greatly enjoyed. Baseball was softball and I pitched reasonably well. I became a fan, following all the major league teams and players and devouring statis-


13

tics. Baseball has remained a lifelong passion, although opportunities to play were always limited by the need to field eighteen players. Tennis became a more readily supported addiction, and I spent countless hours after school and in the summer on the local public courts. If no opponents were about and a court was available, I would practice serving by the hour. I became a good player.

My parents belonged to a reform Jewish synagogue and I had attended Sunday school from an early age. But now, as confirmation age approached, the lessons and sermons took on more significance. The tenets of reform Judaism are morally lofty but leave little scope for human frailty. With its insistent command to consider all the consequences of one's deeds, it was not a creed to encourage spontaneous action or uninhibited emotion.

A World's Fair was held in Chicago in 1933 to celebrate the city's hundredth birthday and was extended to 1934. Its theme was "A Century of Progress," and it featured many exhibits of the latest science and technology. I and a school chum, Jim Flood, went frequently each summer. The advances displayed in science and transportation and communications were exciting. I remember particularly an exhibit featuring samples of all of the chemical elements that had then been isolated, arranged in a periodic table; also a fascinating display of human embryos at the various stages of development. But, surprisingly, the most memorable event was my discovery of Shakespeare. An Elizabethan theater featured a replica of the Old Globe, with a repertory company that daily performed Shakespearean plays. I was mesmerized not so much by the plots, which seemed archaic, even contrived, but by the language. I had never heard such beautiful and poetic language used to express profound thought and emotion. This response was reinforced later in high school when we read Shakespeare. To this day, I am enraptured and inspired by Shakespeare's speech, so soaring and lilting and at the same time so replete with meaning.


Our genes provide our physical frame, much of the specific basis for our personality, and the raw material for our intellect. Circumstance, environment, and culture, however, map the specific routes for intellect.

In high school, I had two extraordinary teachers, Miss Shoesmith in mathematics and Mr. McClain in chemistry, who surely influenced my future. Miss Shoesmith inspired me throughout geometry, trigonometry, and college algebra through the use of "special credit" problems, all beyond the regular class assignment and of increasing difficulty.


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These interested and stretched my mind and, in a subtle way, generated a growing capacity for innovative problem-solving. Moreover, I enjoyed the challenges.

Similarly, Mr. McClain, by letting us perform "extra credit" experiments in the chemistry laboratory, expanded and strengthened my facility with laboratory apparatus and my capacity to plan an experiment and record and analyze the outcome. One Parents' Night, he let us design a set of demonstrations using liquid air, involving such oddities as a hammer made of frozen mercury and a small steam locomotive that ran by the expansion of vaporizing liquid air.

As a teenager, I discovered the joys of science fiction and eagerly awaited the next issues of Astounding Stories and Wonder magazines. The science fiction of that era was thin on plot and characterization and emphasized technological extrapolation, much of which has, in fact, come to pass. Science fiction today is more literary and indeed much of it is social-science fiction, based on extrapolation of one or another societal facet.

In senior English, in the spring of 1936, the principal assignment for the first semester was the preparation of a lengthy theme, involving library research, on some significant topic. With seeming prescience, I chose "The Transmutation of the Elements." My theme covered the older, misguided efforts to achieve transmutation, doomed to failure by ignorance of the basic nature of the changes required. After this, I discussed the current understanding of the nature of the atom and the atomic nucleus, the achievement of transmutation on a minute scale by nuclear physicists, and the potential source of energy locked in the nucleus. I anticipated that, some day, large-scale transmutation and large-scale energy release would indeed be possible. I did not imagine that day would come within but a few years, to change all our lives.

In grammar school, at about seventh grade, I had become aware that I was, in public, painfully shy. To be called on to speak before the class—or worse, to read to the class an essay I had composed—was an agonizing experience. Yet, from my parents, and somehow from within, I knew this experience could not be averted. In future life, it would be essential to be able to make known my views by speaking in public. So in high school I enrolled in a yearlong course in public speaking. This was learning by doing, for me by ordeal. We were taught some rudimentary, techniques of public speaking and even a few acting skills, but the important lesson was simply the conditioning, the confidence


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gained by repeated public presence without resultant censure. Yet even today, while a technical seminar or lecture on a scientific subject is no problem for me, a speech expressing personal views on a controversial subject generates a tautness, an anxious tension.

I have always been a future-oriented person, a fact that causes some internal conflict now as my future grows increasingly finite. In part, this orientation may have arisen from, or perhaps accounted for, my interest in chess. Chess, of course, requires that one plan and anticipate the consequences of one's moves for several steps ahead. I first started chess with my father, at about age ten. Then, he could defeat me easily and would give me a piece advantage to make the game more even. After a time we became more equal. In high school, I joined the chess club and, with this exposure to other players, soon surpassed my father, a small but psychologically important step. I also began to read chess books. Subsequently, I made the school chess team and in my last year, I was first board. Our team won the Chicago high school city championship. Later, in college, I simply lacked the time to continue with chess; since, I have played only sporadically.

This future orientation likely also derives in part from my rearing in the Jewish tradition with the sense that one should not merely while away one's time here on earth; that one should contribute to and be part of a more enduring human enterprise. And so my life has been spent in education and research, the two ways in which our society most directly invests in the future.

When I graduated from high school, I was not quite 17. Because I was a year younger than most of my classmates and was regarded—to varied reaction—as a "brain," my social development, and particularly my relationship with girls, was quite retarded. It was my serious misfortune to have no sisters. With only brothers and a remote mother, the world of women—their desires, needs, interests, and goals—was foreign and obscure to me and, despite considerable interaction since, has in good part remained so.

It was time to think about college. My older brother had gone to the nearby University of Chicago to study law. My interests more clearly lay with mathematics and science. My mother, reared in New York, had long believed that the Eastern schools were superior to those of the Midwest, and she felt that my talent merited the best education. Stan Jarrow had been my laboratory partner in chemistry and we were good friends. He had his heart set on an engineering education at MIT. MIT,


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or Boston Tech, as it was sometimes called, was held in high repute even in Chicago. It seemed an apt match to my interests, which at the time leaned toward chemistry.

But we knew no scientists. I had no role models.

My father had a limited understanding of science and was unsure about the employment prospects for chemists. Their contribution to, and therefore worth in, society was unclear to him. Even a conversation with Mr. McClain did not help. Chemical engineering, however, seemed to him to be a more practical subject, so it was agreed that I should apply to MIT to enroll in that field.

This was 1936, in the depth of the Depression. Living away at MIT would manifestly be more costly than living at home where I could attend the University of Chicago. But my father agreed that if I could receive a scholarship from MIT (in those days scholarships were primarily merit-based), he would send me there for at least one year. While I was not the valedictorian in my high school class, I was the highest ranking male and am sure I received good letters of recommendation from my teachers. I was awarded an MIT scholarship for full tuition at $500 per year.


This lad with my name, age sixteen, steadily gazing out from his allotted square in the high school yearbook is closer to me today but still indistinct. His features are recognizable, but he himself is yet only half-formed, half-educated, half-emerged from the parental cocoon, still trailing wisps of old myths and superstitions and prejudices, with views not yet his own, skills partly honed, perspectives short and fractured, but an absorbent mind and an endless curiosity. Sure, but quite unsure, and somehow imbued with the stiff determination and internal discipline to "make it," to succeed, wherever the amorphous future would lead.

In 1932, M. Knoll and E. Ruska invent the electron microscope, which extends human vision to the submicroscopic and, in time, to the macromolecular level. Viruses can be seen and essential structures and processes of living cells revealed.

Also in 1932, Curie and Joliot discover artificial radioactivity, the production of radioactive isotopes not found in nature. The use of these isotopes as tracers, substituting for the natural atoms, has been essential to the elucidation of biochemical pathways and structures.

In 1935, Wendell Stanley produces crystals of the tobacco mosaic virus, leading to the possibility of subjecting viruses to detailed physical and chemical analysis.


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2—
Transition 1

Leaving home, truly leaving home, for the first time was a wrenching experience. I had done so before when I attended summer camps, but this was unmistakably different.

It was time. I was becoming increasingly restive under the rigidities imposed by my father's fears—I did not yet realize how much I had by then internalized. But to leave family, friends, the familiar neighborhood and city, the grid of school and stores and movies and sport facilities and transportation systems for a blank—Boston, a dot on a map—was daunting.

I did not then realize that, in fact, I was leaving home forever. Except for a few weeks during college years, in summer or at Christmas, I would never again live in Chicago. My high school friends would tread different paths. Even my place within the family was henceforth to be different, separate, increasingly external, even as the family I had always known lost its structure.


Where was MIT? We had been told it was on Massachusetts Avenue, just across the Charles River. Now we were on the bridge. It couldn't be that six-story red brick building on the left, almost surely a hotel. Was it that massive grey structure on the right, looking more like an industrial plant? It hardly resembled a university campus. As we drew closer and the Great Dome came into view, I recognized the scene from the MIT catalog and realized the truth. Here, for better or worse, was my future.


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My parents had driven with me to Boston to start me off at MIT—a three-day journey in those days. We now located Bemis Hall, the oldest dormitory, where I was to be in room 413. The room was small and sparsely furnished. A bed, a bookcase, a desk and chair, a reading chair. No lamps. A sink and mirror, a small closet. Showers and toilets down the hall. One window looking across a court to another dormitory.

The next day my parents went on to New York, and I moved in. I acquired a floor lamp from the porter, who had a small side business of collecting floor lamps at year end and reselling them the next fall. That evening I looked about the spartan dormitory room with an intense churning mixture of sadness, uncertainty, and eagerness. Sadness because I knew in some visceral way that I was now outside the nest. Home—the only one I had ever known—was a thousand miles away. Uncertainty because an unknown world was all about me and before me. How would I stand up in this strange setting? Of course, I was not wholly on my own, but I had never been quite so much on my own. It was now up to me. And yet eagerness—to explore, to enter the world of science and technology at whose door I literally now stood. In those formidable buildings across the way was the gateway to my life.


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3—
MIT—
The Shaping

"MIT is a place for men to work and not for boys to play."


MIT shaped my mind.

Strangely, it began with a rather farcical freshman camp, off in the woods of Massachusetts. The camp was in some ways a hoax: instant, and brief, camaraderie with faculty and alumni. At a faculty-alumni baseball game, President Karl Compton pitched—I never saw him again until graduation. We heard lectures about the history and traditions of the institute, about its expectations of its students: "MIT is a place for men to work, not for boys to play."

Indeed, MIT was a stern place. Student counseling, psychological help, tutorial sessions were nonexistent. The academic pace was swift and unrelenting. It was very much "sink or swim" save for what mutual care and assistance the students could provide each other. I was very interested in my 625 fellow freshmen, almost all male. While women were, and always had been, admitted, they then made up 1 percent or less of the student body. Most of my classmates were from the East—New England, New York, New Jersey. Many were from New England preparatory schools or elite public schools such as Boston Latin or the New York Academy of Science. A significant fraction were from abroad. Would my Chicago preparation be adequate?

MIT provided a very special kind of education that left its imprint


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on all who attended (and succeeded). It gave us the experience of working "flat out"—at our full capacity, for extended periods—which produced a realization of our capabilities and a confidence in our competence. It taught us, by daily repetition, the art of problem-solving: how to frame a problem, how to find a feasible approach, how to bring to bear any or all of our skills and knowledge upon its solution. This became a life-long habit. It ingrained in us the importance of quantitative thought, the value of a feeling for orders of magnitude, for exponential processes, for precision within "significant figures." This fit us well for the quantitative, practical worlds of science, engineering, and economics, perhaps less well for the qualitative worlds of art, literature, values, and political maneuver.

MIT was little afflicted with self-doubt. It had a clear and distinct sense of its pedagogic mission, rare in academia: technology was the future and it was good and MIT was its leading incubator, a beacon for civilization. And the institute transmitted this sense of worth to its students.

In my day, all freshmen took the same curriculum and much of the second year was common. Two years of physics, two years of calculus and differential equations, one year of chemistry, two years of English and humanities, two years of ROTC, one year of mechanical drawing, one year of physical education or athletics. Laboratories or drafting every afternoon to be followed by an hour of ROTC. Problem sets every. night. An hour quiz every. Friday morning, alternating between mathematics and physics. An unrelenting pace.

Overall, my preparation proved inferior to that of the prep school and Boston Latin graduates. My background in chemistry and mathematics was adequate, but English was deficient and physics was abysmal.

I have always been grateful that MIT required this broad and deep education in the basic sciences and mathematics. For while I have made limited direct use of many aspects, this background has enabled me to follow with interest and understanding the remarkable developments in physics, chemistry, and astronomy over the decades—an outcome that has expanded my range of colleagues and enriched my entire intellectual life.

Faculty were both awesome and remote to freshmen, yet they had recognizable human foibles. The freshman class was divided into twenty-five sections of twenty-five students each. There were discussion (problem-solving) sessions in physics and chemistry for each section in addition to the large lectures. Professor Van de Graaf was assigned to


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teach our physics section. At that time, he was hard at work on his famed electron accelerator. Often on Monday mornings, he would come to class a bit bleary, obviously having worked all weekend on his research and not having looked at the assigned problems. While they were problems of beginning physics, sometimes they were not all that simple, even for him. Chemistry and mathematics came rather easily and obviously to me, but I soon found I had rather little intuitive feel for physics, at least for mechanics and heat, and I had to learn these as abstract, quasi-mathematical science.

English composition almost drove me from MIT. Someone—I was told it was Vannevar Bush—had introduced the notion that a good way to teach composition to MIT students would be to require them to write descriptions of common objects, as for a patent application! This is a formidable task. The objects assigned included a Stilson wrench and a plain, brown-paper grocery bag. These assignments were fiendishly difficult and, to me, basically uninteresting, but they did engender a lasting respect for patent attorneys.

Freshman life at MIT brought varied experiences and required frequent adaptation, even though schoolwork consumed most of the available hours. Freshmen were hazed in those days. They had to wear a special tie in institute colors (actually a good idea as it permitted instant recognition of other freshmen), to run errands for upperclassmen, and generally to be available for sessions of harassment that frequently ended in an enforced trip to the showers. All of this came to a climax on Field Day, immediately prior to Thanksgiving. This event involved several athletic contests between freshmen and sophomores, including relay races and a tug of war and ending with a "glove fight," a more-or-less genteel form of mayhem. All freshmen and all sophomores participated, each class wearing a distinctive glove. Whichever side could get the most gloves off members of the other class and behind their own goal in the time allotted won the match.

If the freshmen won Field Day, hazing ended. Otherwise it continued to the end of the first semester. Being more poorly organized, freshmen rarely won, but, remarkably, our class ('41) did.

Freshman year provided many new experiences, pleasant and unpleasant. Lacking female students, social life at MIT was difficult. "Mixers" were arranged for freshmen with freshwomen at local women's schools such as Simmons College. These were awkward affairs that seldom led to continuing relationships, although it was refreshing to talk with young women who had no preconceived impression of me. For-


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tunately, in time we came to know fellow freshmen from the Boston area who had networks of female acquaintances. This led to dates and friendships.

The Thanksgiving holiday was too brief to return to Chicago, so we remained at MIT. Eating Thanksgiving dinner in a restaurant seemed to me joyless—and still does.

Several students in the dormitories, of German descent, were open admirers of Hitler, had swastika flags and emblems, and affected storm trooper garb. This surprised me and caused several near confrontations.

A group of Cuban students reacted to their first snowfall with palpable delight, rolling in the snow, hurling snowballs, and making snowmen.

Boston, prior to the post-World War II renovation, was yet the old city. From across the Charles it still had a European skyline—no skyscrapers, buildings limited largely to walk-up heights. Historic squares such as Haymarket, Scollay, and Copley retained their old character. Compared to those of Chicago, the streets (old cowpaths, it was said) wound, curved, and changed names in midblock. Much of the city—Chelsea, Somerville, Roxbury—seemed old and beat-up. The area of Cambridge behind MIT was literally a slum. On the other hand, Beacon Hill was charming, as were suburbs such as Brookline, Newton, Lexington, and Milton.

At Christmas I went "home," but it was now no longer home. My bed and bureau were still there, but now I was a stranger: not quite up on family events of the recent past, not included in future family plans. But more significantly, I had entered into a world of science that was foreign to my family and that, sadly, I could not bring home to them. The language was too strange, the concepts too abstract, the images too unfamiliar. While they approved of my direction, the journey could only lead to further separation. I saw old high school friends, and here too the divergence was evident—we were on different paths, and I would not return again for seven months. A long time at eighteen.

We anxiously awaited our first-semester grades. While I felt I had done well, the finals had been difficult, and they counted heavily. In the end, all went very well and I was truly relieved. I could do it. I could compete with the best at an elite, tough school.

At the end of my first year, I stayed on for six weeks to take qualitative inorganic analysis. The technique then was based on the use of inorganic sulfides. So we spent all day, five days a week, in a laboratory reeking of hydrogen sulfide, to which one soon became so habituated


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that it had no odor (except to your friends when you came out of the laboratory).

When I returned home again to Chicago, I was exhausted—by the long year and, I suspect, from the sulfide exposure. I did little but rest for a few weeks. My parents and family (both brothers still lived at home) had moved that spring to a row house near the University of Chicago. It was pleasant but more than ever not my home. My former close friendships were now very tenuous. Even those friends who had remained in Chicago had gone their separate ways to different jobs or different schools.

As I traveled back to MIT that fall, the great hurricane of 1938 swept through New England, uprooting one third of the trees, devastating the shoreline, flooding rivers, and destroying bridges. My train, bound that night for Boston, was rerouted to New York. In New York, no trains were leaving for Boston; the only access was by air, so I had my first airplane ride on TWA from Newark to Boston. I can recall the sensation of being airborne: the sudden absence of jolting, the roar of the engines, the lights of Boston coming into view, the thump of the landing. Boston was hard hit—large sections had no phones or power. But MIT was mostly unscathed.

Sophomore year began my chemical engineering curriculum, and by second semester I was having serious doubts about this choice. I was simply not that interested in pragmatic solutions to practical but often intrinsically trivial problems. I preferred to search for deeper knowledge. I was seriously considering physics when I read in the school paper of plans to revise and revitalize biology at MIT. The seeds planted by Wells and Huxley's Science of Life suddenly germinated.

Biology at MIT had long been a service program, originally for a course in sanitary engineering, arising out of civil engineering. Later, a program in public health had started at MIT in the 1890s. This program had been important in the first quarter of the century, but by the 1930s the scope of the field had expanded, and an M.D. was now required for all important positions.

MIT decided then to phase out this program and to replace it with a program in those areas of biology, biochemistry, and biophysics that could be complemented by other strengths of the institute. They brought Francis Schmitt, a well-known biophysicist from Washington University interested in cellular ultrastructure and nerve function, to be chairman and to recruit a faculty. They also brought John Loofbourow, a physicist from the University of Cincinnati who was interested in the


24

effects of ultraviolet irradiation on cells and who had recently written a comprehensive review of biophysics. They were establishing a five-year program, leading to a combined S.B. and S.M. degree in quantitative biology and also (how presumptuous, prescient, and premature) in "biological engineering," a name that perished after a few years—it was four decades too soon.

I decided to transfer to this new program. What made it so intriguing? As a boy I had read avidly of the great explorers—DeSoto and LaSalle, Coronado, Lewis and Clark. Men who had explored a whole new continent, who saw new worlds and made major and permanent additions to both the global map and the sum of human knowledge. Discovery in geography was now largely complete, but not in science. True, physics and chemistry seemed well established—by no means completed (indeed, synthetic chemistry seems inexhaustible) but in outline well mapped. But biology, beyond the descriptive, seemed terra incognita. Here was the unknown continent within the living cell, and here were new tools, new approaches to the deep and mysterious processes underlying life—and therewith, ourselves.

I was somewhat apprehensive when I broached this subject with my father, remembering his initial concern about a choice of chemistry, but he fully supported me. As I had shown that I could do so well at MIT, he believed that I should be given the opportunity to do what I really wanted to do. Science was becoming a way of life for me. While he could not comprehend or follow where I was going, he admired the direction and respected my choice.

That summer I again stayed on for six weeks to take a course in qualitative organic chemistry. Once again, it was five days per week in the laboratory. The course was enjoyable. Mostly, it consisted of devising procedures to identify unknown organic compounds. This was an excellent means to require the students to learn and think through the application of analytical procedures as well as to become familiar with the great handbooks of chemical compounds, such as Beilstein's Handbuch der Organische Chemie . Some of the compounds were a problem to me because I was sensitized to them to a degree that they caused rashes on my hands. In retrospect, I feel sure that at least several of the unknowns, such as nitroso compounds, were mutagenic and carcinogenic, but in those days we were innocent of such concerns.

All MIT students were required to take a year of economics. I had taken the first semester in the spring. The theory had seemed mathematically rather simple and of limited applicability to the real world of


25

business. I decided to take the second semester by examination, just prior to the fall semester. Regrettably, during the summer I did not find time to read the textbook. As fall approached, the only solution seemed to be to return to MIT a few days early and study. I did so, and in two days I had read and absorbed the text. I took the examination and passed with a B grade. This is not a recommended way to learn a subject. But as a means to fulfill a requirement, I have seen it performed by many, many students in the years since.


My transfer to the new biology program was premature for it was not yet in place. Many of the new faculty would be arriving during that year or next, and the new courses were not yet available; only the older biology "service" courses, many antiquated, were taught. Thus, the course in bacteriology was concerned not with microbial physiology but with the identification and classification of organisms (as appropriate for public health students). The course in invertebrate biology was largely an exercise in the microscopic dissection of various worms and insects.

I was also taking physical chemistry and atomic physics. The physical chemistry was, unhappily, a classical course more suited to chemical engineers than to biologists. Atomic physics was my introduction to the world of quantum phenomena.

Absent new biology courses, I took a variety of potentially valuable courses including crystallography, advanced optics (all geometric in those days), advanced organic chemistry laboratory, and advanced microscopic techniques. A particularly interesting course in X-ray diffraction was taught by Professor Warren. Though the course was largely limited to inorganic crystals of varying complexity, there was some discussion of early work on organic molecules. Dr. Fankuchen, who had recently returned from a year in Bernal's laboratory in London, was spending the year at MIT. I had some discussion with him concerning the possibility of applying X-ray structure analysis to proteins, some of which had then been crystallized. While the potential was clearly present, the difficulties of data collection and analysis seemed overwhelming.

I was greatly intrigued at that time by Vannevar Bush's development (at MIT) of analog computers to carry out differentiation, integration, and numerical analysis. Interestingly, only the future development of digital computers made feasible the X-ray diffraction analysis of protein structure.


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A course in statistical analysis, especially as applied to small sample bases, proved valuable in providing me with a good understanding of statistical variation and its importance in the analysis of data. It also gave me an appreciation of the difficulty and tedium of performing computations and analysis with large data bases using the mechanical calculators then available.

I was taking many interesting courses out of the wealth that MIT offered—but I was not learning much biology.

In biophysics, Professor Horton from the electrical engineering department had become interested in the electrical properties of various tissues at different frequencies and had joined the new biology program. Under his influence, I took the electrical engineers' year course in electric circuits. This was a rigorous, quite mathematical course in circuit theory that provided a thorough grounding in the use of vectors in the imaginary plane to analyze alternating current problems. I also took a laboratory course in electrical measurement—this training in electrical science was to prove useful in a very unexpected way. Professor Horton also ran an electronics laboratory for biophysics students in which we constructed an electronic pH meter, an advanced instrument in those days.


We had a year-long course in biochemistry, along with courses in enzymology and animal physiology. It is difficult today to realize the primitive state of biochemistry at that time despite the fact that the subject dated back to the middle of the nineteenth century.

The living cell was still an object of mystery, a "black box" that performed remarkable feats by unknown mechanisms. Under the microscope, cells could be seen to move, to grow, to divide and thus multiply. Complex movements and rearrangements, called mitosis, accompanied cell division. But clearly much of the mechanism lay in structures and reactions invisible in the light microscope.

We knew that cells required a source of energy: light for those that could perform photosynthesis, nutrient for others. Cells used molecules of nutrients for growth, during which these were digested and converted into more cellular substance. Specialized cells in the body could contract and perform work, or conduct electrical signals, or detect light, or secrete a wide variety of substances.

The major classes of the chemical constituents of cells were also known: the proteins that catalyzed the chemical reactions and that formed major structural elements, the carbohydrates and the lipids, the obscure nucleic acids, and a wide variety of smaller molecules. The path-


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ways of degradation of large nutrient molecules into fragments (intermediary metabolism) were partly known. The processes by which these fragments were synthesized into the larger molecules characteristic of each cell were completely unknown.

The chemistry of inheritance was a profound mystery. Genetic factors could be transmitted unchanged for many generations, or they could mutate and the mutant form could then be similarly transmitted unchanged for many generations. Sometimes the mutant form could revert to the normal version, or it could mutate further. The nature of the genetic factors and their mode of action were completely unknown. What kind of chemistry could account for these observations?

While the stages of embryonic development of various organisms had been described morphologically, the reactions and processes underlying the development of an adult organism from a fertilized egg were completely obscure. Clearly, intricate patterns of control existed: internal control of synthesis and transport within each cell and "social" control, coordinating the actions of cells within an organism. But their nature was totally unknown.

There was much to learn before biology became a deep science, based on broad general principles. To believe that these complex, spontaneous, near-miraculous processes could—and would—be explained in terms of chemistry and physics required an act of faith. To undertake to find such explanations was an irresistible challenge.


By 1940, it was well recognized that most reactions in cells were specifically catalyzed by enzymes. It had finally been settled that enzymes were large molecules, proteins, and not some mysterious "vital force." A few enzymes had relatively recently been purified to a degree from which they could, with difficulty, be crystallized. Crystallization of an enzyme was an important part of the laboratory course. However, while it was known that proteins were made largely of amino acids, no one knew the amino acid composition of any protein, much less the sequence or the spatial disposition of its amino acids. The mechanisms of enzymic catalysis by proteins were therefore completely obscure. Even the molecular weights of the best characterized proteins were known only with considerable uncertainty.

Indeed, this uncertainty permitted the formulation of daring but quite erroneous hypotheses, such as that of Svedberg that the weights of all proteins were multiples of a basic unit. Or that of Dorothy Wrinch, who sought to account for the presumed regularity of protein molecular weights on the basis of a regular crystallographic structure for all indi-


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vidual protein molecules that could be scaled to accommodate the various weights. An ingenious theory, but totally wrong. Nature has its own conception of ingenuity.

No one had any clue as to how the proteins—or most of the components of cells—were synthesized. One problem was scale. Only a few proteins or other molecules could be obtained in quantities suitable for the techniques of organic chemistry. Tracer techniques with radioisotopes and highly sensitive assays were in the future. Most enzymatic reactions were followed either colorimetrically (with human eye detection) or by coupling to some reaction that permitted a gas to be evolved or absorbed. The volume of gas thus affected could be measured, very tediously, in Warburg manometers.

We spent a moderate amount of time in the course on the origins and interconversions of various mold pigments. I ventured the opinion that this did not seem like a central problem in biochemistry. Unfortunately, I thereby unwittingly seriously affronted my instructor, whose research was in that field.

Research in biochemistry then was very individual and small scale. No general external sources of funding were available and, in the continuing economic depression, institute resources were very limited. I recall my enzymology instructor telling us how he had had to defend a request to the dean for some one-milliliter pipettes. The dean knew that he already had some graduated ten-milliliter pipettes and did not see why the one-milliliter size was also necessary.

Some of the exciting developments in biochemistry at that time concerned vitamins, viruses, and the beginnings of research on antibiotics. Vitamins (essential nutrients) had been discovered in earlier decades, but additional factors were being discovered and chemically identified. Kögl, in an heroic effort, had isolated a sufficient quantity of biotin (vitamin H) to identify its chemical structure.

The nature of viruses was more obscure. Wendell Stanley had recently startled the field by producing quasicrystals of the tobacco mosaic virus, leading to the hope that these mysterious entities might now be characterized in physical and chemical terms. At the same time, reports of antibacterial compounds from molds were beginning to appear in the literature; penicillin and gramicidin were among the first of the antibiotics.

This was a more leisurely time in the adolescence of the science—Chemical Abstracts was published biweekly, and one could go to the library and literally read through the entire biochemistry section in a couple of hours on a Saturday morning. The Journal of Biological Chem -


29

istry, the leader in its field, did not publish in July or August—the editors, and presumably the readers, deserved a vacation.

In 1940, biological functions were simply observed phenomena that could not be related to underlying structures because of the basic lack of structural information regarding macromolecules or subcellular organelles. The sharp contrast between the rigorous and logically exclusive mathematical analysis of my physics, statistics, and electrical engineering courses and the qualitative and often tenuous experimentation in biology—relying on intuitive art as much as logical projection—disturbed me. Very different intellectual approaches were required for the different subjects. My aim would be to advance biological science toward the levels of understanding achieved much earlier in the physical sciences.


All of this highly technical education, both physical and biological, may seem to have provided a one-sided, if rich, intellectual development. It did.

Not that I had no interest in literature, history, philosophy, or biography. The opening world of science at MIT was so vibrant and alluring, the program so intense, the faculty, especially in science, so competent and eminent, and the value structure so oriented that the more "humane" fields were simply crowded out, ostensibly "deferred." There was a small humanities-type library in the Walker Memorial in which I would very occasionally browse. In particular, I remember being fascinated by a world history written from a perspective different from any I had encountered thus far—that of Jawaharlal Nehru while in prison.

Today, five decades later, MIT is significantly different. Three times as many undergraduates and an equal number of graduates throng a much expanded campus. Thirty-four percent of the undergraduates are female, and fourteen percent are underrepresented minorities. Tutorial assistance, psychological counseling, and other services are readily available. The course offerings in the humanities and especially in the arts have been greatly expanded and diversified. Topics related to the interactions of science and technology with society are prominently discussed. An extraordinary abundance of student organizations offers opportunities to engage in all manner of non- or quasi-academic activities.

As might be expected, this wide diversification has come about at a cost. The depth and intensity of the common basic science education has diminished to accommodate the greater breadth of the curriculum and the greater range of interests of the student body. Today's MIT


30

students receive a broader education that may well better prepare them for the complexities of today's society but that narrows and dilutes their scientific base.

All was not equations and test tubes. In my senior and fifth years I roomed with Art Graham in the Senior House. We shared a suite—a living-study room, a bedroom, and a dressing room. The arrangement of four suites to a floor provided environs a bit more gracious and quieter than had the long dormitory corridors of the three previous years. We looked out over the President's House and the Charles River.

Taking an overload as usual, I was still intensely engaged in studies, but in general it seemed to me that we seniors did not have to work quite as hard as in earlier years. Also, by then we were well acquainted and there was considerable camaraderie. There were long evening discussions about science, about the approach of graduation and the life after that, and inevitably about the war in Europe and the potential of our involvement. There were school dances with the Big Bands—Glenn Miller, Tommy Dorsey, Artie Shaw Some in the group had cars now and so we had greater mobility. During breaks we took ski trips to New Hampshire, where I first learned of the beauty of winter in the New England mountains—and the exhilaration and hazards of skiing. Skiing was more primitive in those days with rope tows, long clumsy skis, and harnesses of questionable safety. But the crisp air and bright skies and the rush of wind in my face and the ski lodge conviviality were joyous breaks in the scholastic routine.

During my senior year, I made the acquaintance of John Loofbourow, a warm, thoughtful, kindly man in his forties with a real affection for people, who became my mentor. Trained as a physicist in spectroscopy, he had become interested in the effects of radiation, especially ultraviolet radiation, on living cells. He was intrigued by the observation that injury to cells or tissues elicits a response to repair the injury, as with the healing of a cut or bruise. To provide a simpler system for the study of this phenomenon, he had demonstrated that yeast cells, damaged by ultraviolet radiation, released into their medium unknown substances that promoted the growth of other, undamaged yeast cells John thought these factors, "wound hormones," might be novel substances synthesized by the damaged cells in response to the radiation. He wanted to isolate and characterize them and sought to understand their effects.

Much later it was realized that this result was not a specific response


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but was primarily a consequence of damage by the radiation to the surface membranes of the yeast cells, greatly increasing their permeability. This caused the cells to leak into the culture medium a variety of vitamins, coenzymes, amino acids, nucleotides, and so on, which accelerated the growth of other yeast in a relatively simple medium.

In addition to his innate kindliness, John had a decidedly pragmatic outlook. Problems were to be solved patiently but with persistence. I hardly ever saw John ruffled or agitated, but nor was he lethargic or insensitive. He became my mentor for much of the next nine years. His wife Dorothea was a physician. They had a teenage son who was already a highly talented pianist. This highly-educated, talented, and urbane family provided a revealing model for me.

John taught me the art of ultraviolet spectroscopy. Nowadays, it is a routine procedure with programmed electronic instruments that can plot out an absorption spectrum within seconds. In those days, to obtain an absorption spectrum involved a tedious photographic procedure. To provide enough light with a near continuum of wavelength, a tungsten spark was used. The light was passed through the specimen, then through a quartz prism to spread out the spectrum, and thence onto a photographic plate. A series of exposures was made with the specimen in the beam and again with a blank in the beam. After development, the plate was scanned with a microdensitometer to find match points at particular wavelengths—regions of equal blackening from sample and blank spectra, taken with different exposure times. From these, the absorption at the selected wavelengths could be determined and the absorption spectrum plotted. It was quite a task to do one complete spectrum in a day. Each newly acquired spectrum was thus a valuable addition to the literature.

The extraordinary improvement of today's equipment—a factor of a thousand in the time required to obtain an absorption spectrum—is an excellent example of the power and role of technology in biological advance.

I learned to perform the "wound hormone" experiment. Growing a sufficient number of yeast cells, irradiating them, incubating the damaged cells for the appropriate period, collecting the culture fluid by centrifugation of the cells, and partially purifying and concentrating the supernatant to a point of stability required a continuous twenty-four-hour stint. More than one night of sleep was lost to this protocol.

Francis Schmitt, the new chairman of the biology program, was a


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very different sort. Aloof, somewhat Prussian in manner, ill-at-ease and formal with students although basically well-meaning, he did not encourage a personal relationship.

In the summer between my fourth and fifth years I worked as a paid assistant with a small research group at the Michael Reese Hospital in Chicago. It was my first paid job. The group was trying to study an unusual protein they had detected antigenically in the sera of rabbits that had been injected with cells of a transplantable tumor. I learned how to bleed rabbits (although I never enjoyed this), how to observe antigen-antibody interactions, and so on. I undertook preliminary purification of the protein by the limited, but then conventional, techniques. Several were ineffective, but I did have some success with ammonium sulfate fractionation.

I learned how slowly research often proceeds, especially when coupled to the physiological time-scales of animals. I learned how difficult it can be to obtain even modest funds for research support, also the great handicaps placed on a small research effort in an institution not really devoted to research or to teaching but to patient care. It was also educational to note how the physicians were in a different caste, with their own exclusive dining room and other facilities.

A research thesis was part of the fifth-year program. I initially had thought to study the recently crystallized tobacco mosaic virus (TMV). Viruses were still mysterious entities. They could reproduce, but not as free-living organisms. It was thought that they were quasicells lacking some essential component. My idea was to look for known vitaminlike substances in TMV to see if there were specific deficiencies. (We now know that all would have been absent!) However, no one at MIT had any experience with TMV, nor were there the facilities (greenhouses) to grow it in tobacco plants. I therefore set out on a far-too-ambitious program to test John Loofbourow's "wound hormone" hypothesis in a very different setting.

It was known that flatworms (Planaria ) could regenerate large parts of their bodies when injured. Indeed, if cut laterally, each half could produce a somewhat smaller whole, the rear half developing a new head and the front half a new tail. My experiment was to test whether flatworms injured (as by ultraviolet radiation) would release factors into the medium to facilitate such regeneration. No one at MIT had worked with flatworms, but they could be purchased and, according to the literature, were easy to raise. However, I did not find this so and indeed had continual difficulties throughout the year in persuading the organ-


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isms to remain alive and reproduce. They could indeed regenerate as reported. But, at least in my hands, the proportion regenerating and the rates of regeneration were highly variable from batch to batch—so much so that I could not obtain what I could regard as a statistically significant effect by application of the medium recovered from injured flatworms.

Thus, empirically, the research was quite inconclusive. Educationally, I learned much about the need to have a biological system under good control before performing molecular experiments with it. I also learned to appreciate the importance of statistical variation and the need for the ability to reduce such variation in order to detect modest effects. And I learned of the need to have available a source of expertise in the "art" of handling any specific biological system—in this case, flatworms.

Research can be humbling, but fortunately one can learn from mistakes.

John Loofbourow's choice of ultraviolet radiation as the means of injury to the cells had an indirect and ultimately fateful consequence. It was a natural agent for a physicist to use, easily quantitated and varied, but it led me into inquiry as to the nature of the damage done to cells by ultraviolet radiation.

It was known that such irradiation could injure cells, slowing their growth rate even to the point of death. In appropriately designed experiments, ultraviolet radiation had been shown to induce genetic mutations. Measurement of the relative effectiveness of different wavelengths of ultraviolet provided clues to the absorption spectrum of the molecules directly affected by the radiation. Less radiation would be needed at those wavelengths at which these molecules absorbed more strongly.

Such data suggested that a poorly known class of molecules in the cell, the nucleic acids, were the immediate target of the radiation and that photochemical injury to the nucleic acids somehow led to mutation or cell death. Because the cellular functions of the nucleic acids—thought then to be fairly small molecules—were completely obscure, these observations led to a mystery, a puzzle of great significance. But this was to be for the future.


MIT was a serious place indisposed to student revels or frolics, which therefore I missed. But it provided a thorough preparation for a life's work.

Looking back, I see with surprising clarity how the twig was bent;


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how the innate talents were fostered, shaped, and channeled by external forces; how, if not the details then the shape and character of my life could have been predicted at age twenty. The pattern was in place—what remained was the unfolding, the evolution and manifold expression of that character.

Science has been a compass in my life, my means of reference to truth and integrity. MIT gave me that compass.

At twenty-two I had now found my calling—that sector of science, the frontier of biology, where I would find a lifetime of intellectual excitement and satisfaction. I was, technically, superbly trained and honed; I had learned some practical lessons in the art of research, in the necessary match between the problem selected and the scale of effort, the facilities, and the skills available. Within science, I had acquired considerable self-confidence and intellectual independence. MIT had shaped my raw talents, girded them with skills, and exposed many paths for their life-long use. Yet socially I was still immature, still enmeshed in the parental ethos. But now my life was to take an abrupt turn.

In 1940, the long-lived isotope of carbon, C14 , is discovered by M. D. Kamen and S. Ruben. The availability of C14 has enabled biochemists to trace, with precision and high sensitivity, the pathways of carbon atoms and groups of atoms through the synthesis and degradation of the multitude of carbon compounds found in living organisms.


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4—
World War II—
The Radiation Laboratory

"Radar won the war, the atomic bomb brought the peace" has become a cliché about World War II. In no other war had technology and technological advantage played such a decisive role.

Quite unpredictably, I spent the war years in the role of a radar system engineer-designer and flight tester. But then war produces many distortions, disrupting many lives.

That technology played such a decisive military role was in part a reflection of the increasingly technological basis of our society. In part, it also reflected the happenstance of recent major scientific breakthroughs that could be adapted to important military purposes. To make such adaptations that needed the latest scientific understanding and to do so quickly required all the recently educated manpower the country could muster. My training was in some ways marginal, but I had the requisite background.

My youth was scarred by World War II. All of my MIT experience had been shaded by the growing threat of war in Europe. Each spring and fall brought a new crisis: Anschluss with Austria, Munich, the Sudetenland, the Soviet-German Pact, and finally, in 1939, Poland and full-scale war. Reared in the Midwest, in the isolationist heartland, I largely shared that view. Europe had been a battleground, an arena for senseless, vengeful conflict for centuries. Many of our ancestors, including my own, had come to this country at considerable hardship to escape for themselves and their descendants the burdens of European


36

history with its recurrent cycles of destruction. Why should we now undo their sacrifice to intervene in these savage squabbles?

Europe seemed remote. Over a thousand miles from either coast, separated from Europe and Asia by thousands of miles of ocean, people in the Midwest felt that the conflicts of Europe or Asia were not their concern. Nor did it matter much who won or lost. International trade was small, and distance seemed to provide an invulnerable barrier. No one envisioned the shrunken postwar world of supersonic flight, intercontinental missiles, and nuclear weapons.

Generally, we believed that the United States' entry into World War I had been a mistake; we had salvaged victory for the French and the British, who had then shunted the U.S. aside and imposed a vindictive peace on Germany. We were now seeing the inevitable revenge. Weekly picture sections in the newspapers reminded us of the endless carnage and torment of World War I and reinforced the conviction, "not again."

Looking back at the countless wars of history, I saw conflict as a futile, feckless endeavor, accomplishing little if anything of lasting benefit to humanity. Through the accretion of knowledge, especially scientific knowledge, humankind had discovered a far more enduring means to achieve progress and enhance human life than that of robbing and slaying one's neighbor. After the outbreak of war in Europe, I was relieved that we were not involved and hoped that somehow this neutrality could continue. The prospect of war was not merely one of unpleasantness and danger; it was a complete and useless diversion, a loss of who knew how many years from the scientific career for which I was single-mindedly preparing.

In retrospect, this attitude toward World War II must seem näive. Today, World War II is regarded as the "good war," the necessary war against the forces of a barbaric fascism that sought to destroy much of Western civilization. But during my student years at MIT, I did not read a daily newspaper, I had no radio, and of course there was no television. My days were principally devoted to study and learning. Major news events penetrated our world, of course—the growing prospect of war, the political campaigns. But, other than in very general terms, I was quite ignorant until after the war of Hitler's depravity, of the campaign of genocide against the Jews, and of the systematic slaughter in the death camps.

The bombing of Pearl Harbor came as an utter and stunning shock. Few of us had paid much attention to events in the Pacific. Asia was


37

even more remote than Europe, both physically and culturally. Japanese industry and its military, unlike those of the Germans, were held in low regard. How could they dare to challenge the United States? The extent of the damage was for a time well concealed, but the bombing of Pearl Harbor needed no exclamation point. It was the bell whose toll had long been dreaded. We were now at war—and for how long? The future was suddenly unpredictable, a new fact of life that quickly became chronic.

Only a few days after Pearl Harbor, air raid sirens wailed across MIT. Students, staff, and faculty crowded into the dimly lit basement tunnels that had been designated as the safest places. I recall John Loofbourow and his wife circulating through the tunnels, trying to provide some reassurance, and I remember saying, "Now it comes to this"—huddling in a basement, waiting for destruction. It seemed a depressing step down from the exhilaration of scientific advance.

After the radio announced that enemy planes were fifty miles from the coast, we expected to hear explosions within a few minutes. No one doubted that MIT would be a prime target in Boston, and we had no defenses. As time passed slowly in the tunnels, confusion and doubt began to mix with fear and bravado. After about two hours an all-clear sounded. In truth, the whole episode was a hoax, concocted by the Air Defense Command to test the state of our preparation, but its effect was counterproductive, leading people to disregard subsequent alerts.

Pearl Harbor created a personal dilemma. I was in the fifth year of a five-year program leading to a degree in quantitative biology. My plan had been to continue further graduate study for a Ph.D. The military draft would now make that plan impossible. In addition, after the shock of Pearl Harbor, despite my convictions of the folly of war, I felt a deep moral obligation to contribute to the nation's war effort. Having completed nearly five years of a high-level technical education, it seemed to me that I should in some role be able to make a more meaningful and significant contribution than I might as an ordinary foot soldier. But biology per se—and, certainly not in that era, the basic biochemistry and biophysics in which I was so interested—seemed unlikely to be helpful in this war.

My problem was resolved in a fortuitous manner. My mentor, John Loofbourow, a biophysicist well trained in physics, was asked to join the Radiation Laboratory at MIT, then rapidly expanding. He in turn asked his two graduate students, myself and Roy Slaunwhite, to join the laboratory. Our training in basic physics and mathematics, and more


38

particularly in electric circuits and electronics, would be useful. The very existence of the Radiation Laboratory, started in 1940, had been a secret kept remarkably well from most of the MIT community. We had, of course, seen sheds and strange-looking domes arise on the roof of the Eastman Laboratory, but their function was obscure. Rumors circulated of research into high-frequency radio waves and even into microwaves. But to what purpose? The strange palindrome radar was mentioned, but its meaning was unknown. Even the presence, as I later learned, of some very distinguished physicists went unnoticed.

All soon became clear. The Radiation Laboratory, in the spring of 1942, expanded from a few hundred personnel to several thousand. New wooden buildings were rapidly constructed on space made available by tearing down temporary buildings left over from World War I. (The temporary buildings of World War II persisted at MIT until the 1980s.) As we soon learned, the mission at the laboratory was to develop microwave radar. Radar—its name an acronym for radio detection and ranging—was a means to detect distant objects such as airplanes, surface vessels, and surfaced submarines by the reflection of radio waves. By emitting such waves in short, microsecond bursts and measuring the time for the reflection to return, one could, knowing the velocity of radio waves, ascertain the distance of the object. By focusing such waves into a beam like a searchlight's and scanning across a sector, one could determine the location of the reflecting object. The more tightly focused the beam, the more precisely the direction could be ascertained. The shorter microwaves could be focused into a narrower beam with an antenna of portable size that could be fitted onto airplanes.

Today radar is commonplace, used for navigation and control of air and ship traffic, for detection of speeders on highways, even for determining the velocity of baseball pitches. But in 1942, the ability to detect and locate planes and ships at great distances at night or through clouds or fog seemed almost miraculous.

Longer-wave, ground-based radar had played a decisive role in the aerial struggle over England during the Battle of Britain. But to use microwaves for radar required an efficient source of microwave radiation. Such a source, the magnetron, had been invented in England in 1940 and, besieged as they were, the British had brought the magnetron to the United States. The Office of Scientific Research and Development, under Vannevar Bush, had then established the Radiation Laboratory at MIT to exploit this breakthrough. Lee DuBridge was


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brought in to head the laboratory, and distinguished physicists were recruited from across the country.

Microwaves not only permitted the development of much higher precision radar but also put us one jump ahead of the Germans, who had no such capability. Thus, they at first were quite unaware of our radar surveillance. But because the Germans would in time surely catch up, the laboratory continually pressed on to new and shorter microwave frequencies. Initially, systems were developed using ten-centimeter radiation (S-band); subsequently, three-centimeter radar (X-band) and finally 1.25-centimeter radar (K-band) were developed, the latter of which, unfortunately, turned out to coincide with an absorption band of water vapor in the atmosphere that limited its useful range in some climates. Each new wavelength required the development of new transmitters, radiation carriers (wave guides), receivers, and antennas. Each new application required the development of a system, involving coordinated transmitter, receiver, antenna, and display devices, all adapted to particular functions and vehicles (plane, ship, truck, and so on).

The constant technological ferment of the Radiation Laboratory was illuminating. It gave me a lasting insight into the modern power of sustained, cumulative technological development performed on a massive scale. In the postwar years, a similar process has led progressively to the revolutions in electronics, communications, computers, and space programs. Many years later, this experience prepared me to conceive of and recognize the existence of the technological potential to sequence the human genome.

An essential and novel component of these radar systems, in addition to the use of microwaves, was the use of feedback circuits for self-correcting control, aiming, and so forth. In such circuits, a portion of the system output is "fed back" to be combined with input in such a manner as to converge the output on a desired goal. If the input changes, the system swiftly self-corrects. The theory of the use of these circuits was then new and increasingly elaborated. I was struck by the analogies between such circuits and various processes such as homeostasis in the biological world and all manner of cyclic phenomena in society in general. Biology was always in the back of my mind.

With its urgent mission, the Radiation Laboratory was organized hierarchically and I was a very junior member, to be assigned where needed. I was arbitrarily placed in Division 9, Airborne Radar. Over the next few years, I was thus assigned successively to three different air-


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borne radar programs—a radar for navy night-fighter planes, a tail-warning system for air force fighter planes, and lastly a general purpose navigational radar, primarily for the Troop Carrier Command. I was involved in the design and flight testing of each system and accompanied its demonstration to the military at various airbases. All of this was a continual learning experience of diverse episodes—many boring, some unpleasant, some dangerous, some triumphant, all crowded into a few years that seemed endless at the time.

The X-band radar for navy night-fighter planes, to enable a pilot to locate and shoot down an enemy fighter plane at night or in heavy fog, was already well along in design. An installation of a laboratory-built model was proceeding into a test plane. A hangar had been set aside for Radiation Laboratory use at Boston's Logan Airport and converted into a somewhat makeshift laboratory. Then and there I immediately came to appreciate the gulf between the theoretical understanding of a device and the practical task of making it work. The latter requires not only understanding but well-thought-out procedures, adequate test equipment, and often experience-based knowledge of the likely causes of malfunction. In a novel experimental system, all of these may well be lacking. Ingenuity and intuition are in high demand.

When I first arrived one morning at Logan Airport—we were taken on a bus from MIT each morning and returned each evening—I found my new "chief," Bill Cady, reflecting in some dismay on the disassembled radar system that had just been brought out from MIT to be installed in the test plane. First it had to be assembled on the bench and made operational. When the rotating antenna was installed in an airport window, everything was out of alignment. The entire apparatus—transmitter, transmit-receive box (a device to shield the receiver during the pulse transmission), waveguides, antenna, and receiver—had to be hand-tuned to the magnetron frequency, which in turn had to be chosen to match a resonance in the magnetron cavity so as to maximize the power output.

Because this was one of the very first X-band systems, for test equipment we had only primitive power meters (in certain ranges only a small neon bulb that glowed when exposed to radiation). The process required systematic adjustment, measurement, readjustment, and remeasurement in a complex cyclic process that gradually proceeded through the system until all the components were optimally aligned and coordinated. If the magnetron failed, we repeated the whole procedure.

Nearly fifty years later, I found myself in a similar predicament in


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seeking to master the operation of a "homemade" version of a very new physical instrument, an atomic force microscope. Lacking appropriate test equipment, the only criterion for alignment was the provision of a clear output, the image. Failure to obtain a clear image could be due to a flaw at any of several stages and alignment was again a delicate reiterative process.

In 1942, the war in Europe and North Africa was going badly. American efforts to resupply Great Britain, Russia, and the Free French were gravely hindered by the German submarine attack. Even along our Atlantic coast shipping was being devastated. The biggest contribution of radar to the war effort at this time was in the detection of submarines by airplanes. The submarines of that era had to surface periodically to recharge their batteries and their hulls then made good radar reflectors. Homing in on these, and undetected because of the use of microwaves, the radar-bearing aircraft were able to substantially reduce the submarine toll on Allied shipping on our East Coast and in the Atlantic.

Spurred on by this example, we felt a real sense of urgency—the military desperately needed this new equipment. Sometimes the contrast between our tasks of performing abstract calculations and machining parts and that of a navy pilot straining in the dark to see an attacking enemy plane seemed bizarre. But such is modern warfare.

We worked Saturdays and often Sundays into the evenings. Finally, the equipment was installed in a two-seater fighter and test-flown. I was then assigned to accompany the plane to the Quonset naval base at Narangansett, to keep the equipment operational while navy pilots conducted tests on simulated missions.

Seldom have I felt so out of place. Life for a civilian at the base was generally unpleasant. I was assigned a room in the Bachelor Officers' Quarters (BOQ). Most personnel were confused as to what a civilian was doing on the base, and I was regarded with understandable suspicion. Why was this civilian wandering about the hangar and into high-security areas? I had no permit to go off base and no transportation to do so anyway.

Evenings were spent with the pilots who were flight-testing the equipment. We had little in common—young, cocky, and seemingly eager to get into combat, they were far from academic types. Their evenings were spent in heavy, drinking and swapping endless flying stories. Apparently, all junior officers were expected at some time in their stay at Quonset to fly their planes in forbidden patterns under the Naragansett Bridge as evidence of their skill and daring. For this they would


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be nominally reprimanded by the commanding officer and toasted with champagne at the Officers' Club.

On weekends the pilots all received passes and cleared out for Providence, Newport, or New York. I was left more or less stranded.

Fortunately (for me), after two weeks a major accident occurred. A portion of the rotating antenna support cracked and the spinning antenna broke loose, damaging not only itself but the radome (plastic covering) as well. This was beyond my capacity to repair, so the plane and I returned to Boston. The navy at that point decided that no further testing was necessary. The equipment was taken out of our hands and put into production and later used successfully.

I had intended to entertain no thought of marriage until I completed graduate study, but the war promised to postpone that time indefinitely. Most of the Radiation Laboratory personnel had families; the laboratory did not provide the comradeship of classmates. I had become close to Joan Hirsch, from Chicago, then in nurse's training, whom I had met a few summers earlier. In August 1943, we were married in Chicago. After a very brief honeymoon in New Hampshire, we found a small apartment in Cambridge and Joan soon found a job as a laboratory technician at Boston City Hospital. Our marriage produced two daughters and a son. Some twenty-eight years later, however, our interests having greatly diverged, it ended in divorce.

After the night-fighter project, I was assigned to a small project to explore the possibility of an automatic radar tail-warning device for air force fighter planes This design brought me in contact with the diversity and wealth of talents and skills that had been assembled.

The Radiation Laboratory was a remarkable place. It was perhaps the first laboratory to undertake research and development on such a grand scale. Also extraordinary was the virtually unlimited availability of resources. The stockroom was free! And the stock was swiftly replenished by knowledgeable purchasing agents. One simply went to it and took whatever resistors, capacitors, vacuum tubes, and so on one needed. At MIT, in the chemistry stockrooms, every item, every test tube, beaker, and bunsen burner had been charged against one's account and returned for credit if still in "good" condition. The difference in paperwork was revealing.

Expert help on any aspect of radar theory and technology could be readily obtained. Specialists were continually seeking to improve transmitters, receivers, antennas, display devices, and so on. The laboratory


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had brought together an extraordinary group, mostly young physicists, who were applying their theoretical knowledge and their native ingenuity to a single multifaceted goal—advancement of microwave radar. Within the laboratory, knowledge was, with a few security exceptions, shared freely. Weekly evening seminars were held to disseminate the more recent advances. Project reports (classified) were written and available in the laboratory library. A few projects were, for unclear reasons, regarded as more highly classified, but the knowledge of their existence and parameters inevitably spread within the community.

All the work at the Radiation Laboratory was under security clearance, and a photo badge was needed for admission. Shortly after Pearl Harbor, a military guard was placed at the laboratory. Secrecy was taken seriously—I did not discuss the nature of my work outside the laboratory, even in my family. This created an unfortunate habit of reticence, which in part has persisted long after the reason for it disappeared.

The military presence guarding the laboratory persisted until 1943 when an associate director was shot while leaving the laboratory, one evening, for failing to halt. Less security, was then deemed sufficient.

In 1943, the Eighth Air Force began its major bomb attacks on Germany. A key laboratory project at this time was the construction of a dozen advanced X-band terrain-scanning radars to be installed in the Eighth Air Force bombers in England. These were to be used as lead planes to guide bombing missions over Germany in the frequent bad weather or at night. A number of laboratory personnel accompanied these to England to oversee their installation, maintain the equipment, and suggest modifications in use.

Outside the laboratory, life was becoming increasingly unpleasant for everyone, albeit much less so than for those in combat. Increasingly stringent food rationing restricted our diet. We had no car and could not have found gas if we did. All transportation was overwhelmed with troop movements, and any travel became arduous. When my father-in-law died in Chicago, the trip to the funeral required two twenty-four-hour stints in overcrowded train coaches that gave me a severe bronchitis.

As draft registration had begun while I was a student, I was registered in my home district of Chicago. The draft board there, understandably, regularly sought to draft me Each time, the laboratory filed an appeal on grounds of the national importance of our work and, each time, the appeal was granted whether at the state or national level. However, only


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a six-month deferment was granted, so every six months the process started over again. As the appeal often took several weeks, I was repeatedly required to take the standard physical exam for draftees in Boston and on one occasion even received orders for induction before the appeal was finally granted. This apprehension—the recurrent threat of imminent major upheaval—was disconcerting.

Actually, it later became evident that it was not possible to leave the laboratory even if one desired. A few of the younger scientists decided they would rather serve in the military and signed up. Imagine their surprise when they were immediately assigned back to the laboratory, only now in uniform.

The tail-warning system was a technical gamble from the beginning. Given the weight and power limits that fighter planes could afford, quick calculations suggested that the ability to detect an enemy plane at a useful range would be marginal. Nevertheless, the importance of the problem suggested that it was worth a design and feasibility test and assembly of a prototype. Bob Taylor, a scientist of similar age, and I were assigned this project.

The only hope of providing a radar reflection of sufficient strength to be unambiguously and automatically detectable seemed to lie in an integrative approach that would rely on the repetitive character of the returning echo contrasted to the sporadic character of the background circuit "noise." Because, however, the pursuing plane would be closing in, the time available for integration of successive echoes was strictly limited. With today's computers and electronics, this would be a far more feasible task. Using the electronic techniques then available, we were in fact able to detect quite weak signals and use these to activate a bell or light for the pilot in the cockpit. We then assembled a prototype that (barely) fit within the weight limits and installed it in a Cessna aircraft for flight testing.

Testing was somewhat hampered because it always required two planes, our own and a target plane We also soon learned that the pilots had very limited ability to judge the distance of a second plane. So we had to modify our equipment, which had no readout other than a warning signal, with a test monitor to provide range information. We also had to automatically limit the range of detection to a distance less than the plane's altitude or else the radar reflection from the ground would trigger the warning.

We soon discovered yet another problem. It had long been known that some clouds, especially cumulus clouds involved in thunderstorms


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that accumulated electric charge, could give weak, diffuse radar echoes. Indeed, this property is now used in meteorology. On a radar screen this caused little problem; however, with our increased sensitivity and our designed ability to integrate echoes over a wide sector, we found the thunderheads were not infrequently setting off our alarm. When we reported these results, it was generally agreed that the project, if feasible at all, would be more likely to succeed at longer, submicrowave frequencies (for technical reasons having to do with antenna effectiveness and lesser reflection of clouds). The problem, in any case, did not require the narrow beams for which microwaves provide a significant advantage. The project was thus terminated and I was assigned to a new one then being initiated, the design of a general purpose terrain radar, initially intended for use by the Troop Carrier Command in locating their drop zones.

This experience illustrated a negative aspect of work at a junior level within a large laboratory. One may be assigned to a problem and work on it with great diligence, energy, and imagination only to be informed that one's solution will not be implemented. In basic science, the goal is simply knowledge. In applied science, the goal is practicality as measured by military, economic, or political criteria.

The years of war dragged on. Coping with the daily minutia of system design, airplane installation, and test flights repeatedly postponed because of weather or aircraft maintenance delays, it was difficult to sustain the earlier sense of urgency. The work was challenging, requiring improvisation and ingenuity, but now connected through some lengthy channel of time to the military struggle. And my real interests were elsewhere.

By now, early 1944, the invasion of Europe was expected within the year. We were more knowledgeable of the time and scale of effort required to design, test, and shepherd into production each new radar system. Was it sensible to launch entirely new projects? The response was that Washington expected the war might continue as long as ten years. Success in Europe might require two to three more years, to be followed by, it was expected, a battle of near extermination against the Japanese army, which would never surrender. It was a grim prospect. While my situation was surely better than that of those in combat, it appeared that my entire youth would be spent in an unwanted war, doing development research in a field of only secondary interest to me.

The ability of radar to distinguish features of terrain was evident early on. Water was a poor reflector, but coastlines and the shores of lakes


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were readily detected. Structures, too, and clusters of structures were good reflectors, though at low altitudes hills and ridges created obscuring radar shadows. The finer beams of three-centimeter radar permitted more precise resolution of details.

The immediate aim of the new project, dubbed APS-10, was to use the most advanced techniques available to develop a sophisticated, lightweight, relatively low-power radar to be used by the military for general navigation and by the DC3s of the Troop Carrier Command for specific troop drops at night by following previously established radar "maps." The APS-10 was also conceived to be a prototype for possible postwar radar for civilian aviation.

Design and assembly of the system went relatively smoothly. I was familiar with every aspect of the system and was subsequently given responsibility for installation of the first test system into a DC3. The Radiation Laboratory had outgrown its facility at Logan Airport and was now using Bedford Airport near Lincoln, Massachusetts. It was a longer busride and there was no alternative means of transport should I miss the bus.

DC3s were manifestly not designed to accommodate radar equipment. To provide a radar plot of forward terrain, the scanning antenna had to be located in a plastic dome beneath the fuselage. Aerodynamic consultants indicated that a dome of the size needed would probably not threaten the craft's airworthiness.

By May 1944, installation was at last completed, the equipment was operational, and all was ready for our first test flight. When we arrived at the airport, however, we learned that disaster had struck. Our air crew had without authorization taken our plane that morning to an airbase in New Hampshire to pick up some parts needed for maintenance of another plane. Unfortunately, visibility was poor at the New Hampshire base, and our plane had somehow struck the side of a mountain, killing the crew, disintegrating the plane, and demolishing our radar installation. This shock reminded us of the hazards of our occupation.

But flight testing of the radar design was still required. Assembly of another radar system would take but a few weeks. Acquisition of another DC3, its modification with a radome, and installation of the radar would need three months or more. We therefore made an impromptu installation of the radar in the nose cone of an A25 fighter-bomber. Normally, this site was occupied by the gunner. We crammed in the radar antenna, transmitter, receiver, and display unit. As the operator, I had


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to sit in the nose cone just behind the antenna. Remarkably, this all worked surprisingly well. While regulations prohibited anyone to be in the nose cone during takeoff and landing, the equipment made getting in and out during flight much too onerous a task. The landings were quite exciting with only the dome of clear plastic between myself and the runway a few feet away.

When the second DC3 installation was complete and operational, we took the equipment to the military for scrutiny by its personnel. Our first assignment, in November 1944, was to the Troop Carrier Command in Indianapolis. Shortly after arriving there, we discovered that a crucial piece of test equipment needed to keep the system operational at near peak performance was not available. When I was sent back to Boston to bring one out a bizarre incident resulted.

On my return, an air force general who had been visiting the Radiation Laboratory was flying back to Wright Field in Dayton, Ohio, and it was arranged that I would carry the equipment on board his personal plane. We arrived at Wright Field late in the evening, and I was put up for the night at the BOQ. My equipment was left on the plane. Next morning, I sought to retrieve the equipment to take it by train from Dayton to Indianapolis. Once again, I was an odd civilian poking about high-security hangars. I was quite certain as to which hangar held the plane in which I had arrived. To my dismay, it had been moved. When I inquired, no one had any knowledge of the plane. Remarkably, there seemed to be no record of its arrival.

It was clear that my inquiries were breeding dark suspicions of my interest and perhaps my sanity. Finally, on the verge of being turned over to the MPs, I persuaded an unbelieving sergeant to call the general's office. With some difficulty, I was able to reach the general, who with evident annoyance was able to resolve the situation and arrange for the return of my equipment. I thereupon as quickly and boldly as possible strode out through the airfield gate, suitcase in one hand, equipment in the other, to catch a bus to town. That I was able to simply walk off the military field with a piece of classified electronic equipment with no pass or identification still mystifies me.

This incident notwithstanding, secret war research on applications of high technology to defeat a sophisticated foe was not as glamorous as one might expect. The reality, at least in our roles, far removed from the levels of decision, was often tedium.

In Indianapolis, the weather was, as might be expected in November, miserable. We could fly perhaps every third day. On the days we could


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fly, we went up two or three times at troop carrier drop altitudes of about five hundred feet to avoid enemy radar. At such altitudes, the turbulence was constant—every gust, every thermal, jolted the plane. It was a good test for the equipment, which performed well, and for us who did not perform as well. I became airsick nearly every flight but "carried on." After about three weeks, the Troop Carrier Command seemed well satisfied with the equipment and when the weather cleared, we returned to Boston. This was my first extended night flight and I marveled at the lights of the cities and towns against the deep blackness of the countryside. Greater New York was a vast sea of light.

Our next demonstration, to be held in Orlando, Florida, seemed more promising. We took off from Bedford early one frigid January morning (it was minus ten degrees) and, after the serious mishap en route, described in the Introduction, arrived at balmy Eglin Field in Orlando. As a northerner, I had frequently read about or seen pictures of Florida in the wintertime, but the reality of this sunny, lush land less than a day away from the frozen gloom of New England was startling. Today, with television and jet travel we are accustomed to these contrasting realities. In 1945, this was a novel, almost bewildering experience. At the same time, I was shocked and offended by my first exposure to the segregated restrooms and drinking fountains of the South. And these were, of course, but the most superficial evidences of racial discrimination.

Compared to those in Indianapolis, demonstration flights for the air force at Orlando were easy. We flew over sea to the Bahamas and over land in Florida. The equipment performed well and the air force personnel seemed pleased. Except for the exceptional size of the cockroaches, life in Orlando seemed idyllic. After two and one half weeks we returned uneventfully to Boston.

Next, the APS-10 had to be put into production. The General Electric plant in Schenectady, New York, had in some way been selected as the manufacturer and I was sent to there as liaison to the engineers. Here was yet another unfamiliar and hectic milieu. As I soon learned, the problems of mass production of a few thousand radar sets, plus spare parts and technical manuals, to be operated by military personnel, are very different from the construction of a few prototypes to be operated by highly trained scientists and engineers. Cost factors, simplicity of controls, ease of maintenance and repair, adaptation of design to production-line manufacture, even aesthetics of appearance, all became important elements that could not, however, be allowed to compromise


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performance. I am sure the GE engineers were very good at their jobs—as an academic researcher, however, I was not always fully sympathetic with their problems or solutions.

Schenectady was not so far from Boston, so I shuttled back and forth. Thus, I was at the Radiation Laboratory on VE Day in May 1945. It was a joyous celebration, taking off from work, at least informally. A group of us gathered at Art Solomon's house to hail the victory. Many whose interests were more focused on Europe seemed to feel the war was over. Others of us still thought of Japan and the blood yet to be shed. Nevertheless, from that day on, we could begin to foresee the end of the Radiation Laboratory and to envision the return to a postwar world.

Soon, we learned that the long-held secret of the Radiation Laboratory was at last to be told. Our activities and the important role of radar in the war effort were to be made public. At last I could let my wife and family know what I'd been doing for the past three years, although it did indeed seem strange to have (selected) reporters prowling about the laboratory, asking questions, taking pictures, and so on. The release date for the story was, for obscure reasons, repeatedly postponed. It was finally set for the first week of August—as it turned out, the day of the bombing of Hiroshima.

Rumors of some kind of atomic development had spread from time to time around the laboratory. Several of the senior people—Luis Alvarez, Robert Bacher, and others—had rather abruptly disappeared. When asked, we were simply told they had "gone West." I was aware of some large projects in Tennessee and in Washington State. I was unaware of Los Alamos, and my imagination conceived only of an atomic-powered engine that might power an airplane or a submarine for unlimited range—not a bomb!

Thus, Truman's announcement on 6 August was a stunning surprise, although I immediately appreciated its epochal significance. Nagasaki, on 9 August, answered the question of whether we had more than one bomb, and VJ Day truly ended the war.

As we now know, many of the scientists who worked on the development of the atomic bomb anguished over the invention of such a devastating weapon of mass destruction. I would today have similar concerns about the development of biological weapons.

Since Vietnam, many scientists have questioned the morality and ethics of the application of science to military pursuits, but during World War II I had no such qualms. We had been wantonly attacked.


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(While there are revisionist historians that maintain that President Roosevelt's policies invited such attack, I believe this to be a misreading of history. The America I knew did not want war.) We had no choice but to defend ourselves. If the application of our science and technology could shorten and help to win the war, save lives and punish aggressors, and thereby perhaps deter future aggression, then we should surely use our talents toward that end.

Radar is, to be sure, a relatively passive and defensive technology that provides information. In war, radar per se never killed anyone. But one cannot escape the fact that in war the lines between offensive and defensive are constantly blurred. The radar that guided bombers to German cities at night certainly had a part in the resultant deaths. I had no qualms, because the end—a just end—necessitated the deplorable means. Hiroshima and Nagasaki frightened me as a portent of the future, but they did not revolt me. From all that I knew and know, they spared hundreds of thousands or more American casualties. And that was enough. We cannot always choose the world in which we live.

I know that for some who survived, World War II was the greatest adventure, the most vibrant time of their lives. Not for me. I've always felt, in a sense, cheated by World War II. By luck, I did not have to endure the agony and danger of combat, but four of the potentially most creative, most carefree years of my life—irretrievable years of greatest imagination, of highest energy, of most recent training—four years of intense and draining effort had to be spent in an alien pursuit.

Detoured from a nascent career in biophysics, my reactions to the Radiation Laboratory were atypical. Most of the scientists were physicists, Ph.D.'s of varying degrees of professional maturity. For them, the Radiation Laboratory was an opportunity to advance, at a very accelerated rate, a sector of their science, as well as an opportunity to utilize to the fullest their training and skills in a project of great importance to the war effort. While recognizing the latter, I, in a much junior role, could utilize only a portion of my training and aptitudes.

My entire generation had been forced to wage a war we never sought. Never again could I know the simple, secure Midwestern insularity of my youth. The war was an epic of courage and national will, but it also forever destroyed the youthful illusion that one had ultimate control over one's individual destiny.


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In 1944, in the midst of the carnage of World War II, Avery, McCarty, and McLeod at the Rockefeller Institute demonstrate that the "transforming principle"—a substance extracted from one strain of Pneumococcus that could, hereditarily, alter the properties of a second strain, so as to make it resemble the first—is, in fact, composed of DNA. This most surprising and significant result provided the first direct evidence that DNA played a major role in the transmission of hereditary information.


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5—
Transition 2

The war was finally over.

The future was now open, but which path to choose? I had been away from biology for four years. I had of necessity acquired a considerable and valuable expertise in some of the most advanced areas of electronics. This skill was soon recognized. Major electronics firms—RCA, General Electric, Bell Laboratories—were gearing up for the return to a civilian economy. Realizing the considerable pool of talent at the Radiation Laboratory, recruiting teams soon appeared. Also, new electronics companies—some small and others not so small—were being organized, several by the new Radiation Laboratory alumni. I was interviewed by several of these companies and offered employment at salaries approaching ten thousand dollars per year, a quite handsome sum in those days and three to four times my Radiation Laboratory salary.

My alternative was to return to graduate school to obtain a Ph.D. But how would I and my wife be supported? It seemed unreasonable to ask my family to provide my support again, since I was approaching the age of twenty-six. For the interim, the Radiation Laboratory had undertaken to provide a written record of its accomplishments and thereby make publically available all of the technical knowledge the laboratory had collectively acquired. The Radiation Laboratory Series ultimately came to twenty-eight volumes. I agreed to stay on a few months to provide two chapters: one on the conception and design features of the APS-10 radar, one on radar altimeters.


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The money from industry certainly was tempting and to discard four years of hard-learned expertise was grievous. But in my heart I was a biologist. I wanted to explore the mysteries of living organisms, not to design sophisticated electronic gadgets. Manifestly, a life in the electronics and communications industries over the past four decades would have been exciting and surely more financially rewarding, but I have never regretted my choice.

I became aware, through Art Solomon, of a proposal for the American Cancer Society to provide fellowships to make possible the entry, or re-entry, of several of the younger scientists at the Radiation Laboratory into biology. I applied for this program; others included Bob Taylor and Ed McNichol (later director of the National Eye Institute). Approval of the proposal and award of a fellowship of two thousand dollars followed. Where should I study? I briefly considered other institutions, including Caltech. But we had a place to live, Joan had a job, and my mentor, John Loofbourow, was returning to MIT. There seemed no especial advantage to going elsewhere and several disadvantages, so in February 1946 I enrolled as a graduate student in biology at MIT.


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6—
Graduate School

The hour could not be over. I had only completed two of the four test problems. And this was my first examination in graduate school.

After Hiroshima and Nagasaki, it seemed clear that nuclear physics—isotopes, radiation—would be an important aspect of biophysics, so I had enrolled in Robley Evans's course in introductory nuclear physics. I went to class, read the assignments, understood the subject matter, and thought I was doing well until the first test. Disaster. I knew how to do the problems in principle. But in four years of pragmatic experiment and development, my advanced mathematical skills had rusted. I barely completed half of the test and received a deserved D.

This abrupt failure (a D grade is failing in graduate school) singularly shocked my self-confidence. Had I been out of school too long to come back? Had I made the wrong choice and taken an impossible path? The problem-solving approach came to my aid. Manifestly, I had to review and revive my calculus, differential equations, vector analysis, and so on. And quickly. I also decided I should know more advanced mathematics and subsequently took a year of advanced calculus. By the end of Robley Evans's course, I was doing much better.

Returning to the academic schedule as a student, after four years' absence was not an easy task. The routine of fifty-minute classes, nightly assignments, and reading initially seemed very confining and required considerable self-discipline.

I was not alone. MIT was besieged by returning students. Courses and classes ran year-round and leisurely summer vacation periods were


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totally discarded. The Boston climate was unchanged, however; our small apartment opened only onto a narrow court, so some stifling summer nights we slept on the building roof for a bit of breeze. Air conditioning was still in the future.

One of the casualties of the war was the network of friends established during my undergraduate years. While graduation would have frayed the network in any case, the war dispersed my set of friends in all directions and made it impossible even to maintain contact. Now, after four years, the strands were severed and the relationships lost. As if in compensation, our apartment building now housed several couples of returning students, enrolled in graduate programs at MIT or Harvard, among whom a natural camaraderie soon developed. It was a diverse and interesting group of future scientists, engineers, lawyers, physicians, historians, literary scholars, and the like.

The MIT Biology Department had changed considerably in personnel. Frank Schmitt had filled out his faculty, including Dick Bear who did X-ray crystallographic studies of fibers (actin, tropomyosin), electron microscopist Cecil Hall, a surface chemist named David Waugh who was interested in cellular membranes, and Stanley Bennett, an M.D. interested in embryology, among others. I enrolled in the new biology graduate courses—embryology, genetics, biophysics—and started on a thesis under John Loofbourow.

Graduate school is normally a time of specialization and apprenticeship—of learning, under a mentor, the arts and standards of research in preparation for one's future independent career. One's mentor usually proposes one or more research problems in the field of his interest for which he can provide background knowledge, technical expertise, and the necessary facilities and equipment. The wise mentor will also select problems that can reasonably be resolved within a normal period of graduate study.

My graduate experience was, however, anomalous. Four years at the Radiation Laboratory had taught me the ways and vagaries of experimental research, albeit in a very different mode and with extraordinary support and resources. And so, while adapting to a different field, I was already sufficiently prepared and confident to engage in novel, relatively independent research projects. In this mode, I came to know John Loofbourow much more intimately. Thoughtful and pragmatic, he also had a deep compassion for people and empathy with their concerns. Frank Schmitt made John the executive officer for biology as he was much better able to cope with the personalities of faculty and students.


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John's "people skills" similarly led him to become active in the MIT faculty senate and he was chair of the faculty in 1949–50. Unfortunately, all of this valuable citizenship took him away from his science.

He loved to tinker, and his pride and joy and diversion was a lathe at which he would turn out often ingenious "gadgets" for laboratory use. He had a long-standing interest (from boyhood?) in the South Pacific and regularly subscribed to the Pacific Island Quarterly, a gossipy journal devoted to the economics and politics and personal idiosyncrasies of planters and other characters among the South Pacific islands. In "bull sessions," we would occasionally rhapsodize about taking over an island in the South Seas and, using modern methods, developing its agricultural and mineral resources. A form of Shangri-la.

I resumed my interest in things ultraviolet. This resulted in my first published paper and, more important, naturally extended to nucleic acids as one of the principal ultraviolet absorbing components of cells. A dramatic experiment conducted during the war by Avery, McLeod, and McCarty at Rockefeller Institute had suggested a most significant role for these previously obscure substances. They had shown convincingly that the "transforming principle," an extract of some strains of pneumococcus that had the property of transforming certain characteristics of other strains of pneumococcus in a stable, inheritable fashion, was composed of deoxyribonucleic acid. This result, consistent with earlier indirect evidence, strongly implicated DNA as a genetic factor, at least in these organisms.

This result was a solid fact in a bog of speculation. The proteins, it was clear, were the catalysts, the machines of the cell and the body. But whence came the proteins? What created these complex molecules? How did some cells in the pancreas know how to make pepsinogen and trypsinogen (digestive enzymes) and other cells in the pancreas know how to make insulin? This "know-how" clearly was inherited from generation to generation—but not, it seemed certain, by the simple passage of (say) insulin molecules to serve as models. What then was inherited? The concepts of information theory were still nascent in the fields of electronics and communications and their application to biology was yet to emerge.

A few scientists had pondered this problem qualitatively and speculatively. Max Delbrück, reflecting on the faithful replication of genes (whatever they were) over many generations, had wondered whether new, unknown physical laws might be involved. Erwin Schrödinger, in his 1944 book, What Is Life?, followed Delbrück in his quest for a


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mechanistic explanation for genetic phenomena but achieved only the somewhat paradoxical notion of an "aperiodic crystal." (It is of historical interest that Friedrich Miescher, who had discovered the nucleic acids in 1869, proposed in the 1890s that the templates for inheritance might somehow be provided by an appropriate string of asymmetric carbon atoms. The chirality [handedness] of tetravalent carbon had only recently been elucidated.)

The Avery experiment pointed to DNA as the substance of the genes. Recent experiments by Beadle and Tatum at Stanford had demonstrated that the genes specified not only such complex traits as wing shape and bristle pattern in drosophila but much more discrete characteristics such as the presence or absence of one or another enzyme needed to make essential cell components. Genes, enzymes, proteins—an amorphous pattern of hints and glimmers was emerging. The nucleic acids, as yet so ill-defined, could be the key.

My first published paper, appearing in 1947, was only a short note in Nature, but I felt a deep satisfaction that it had been accepted. Now I had joined the ranks of those who had made some enduring contribution to human knowledge, my work was part of the stream (today one would say flood) of scientific publication. It was certainly not a major, nor I fear particularly useful, contribution but it was novel. It illustrated well my capacity, at that stage of my career, to define and resolve an unsolved technical problem by bringing together a variety of information and skills.

Science is frequently said to be a young person's game by those who point to the relative youth of those scientists who most often make the greatest discoveries. The reason for this is that science is the art of the feasible or, at the frontiers, the barely feasible, for the readily feasible most often has been done. A young scientist quickly learns what experiments are feasible, barely feasible, or infeasible, and these last are usually mentally discarded and removed from consideration. With time and invention, such experiments may indeed become feasible later. But the barrier against even considering them often remains strong in the older scientist's mind, who thus appears—and is—less creative.

This need, especially in periods of swift advance, to unlearn what "cannot be done" accounts in large part for the advantage of freshly trained minds.

The idea was to make a simple but adjustable filter to isolate various portions of the ultraviolet spectrum for use in studies of the effect of ultraviolet radiation on biological objects. Monochromators, using


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quartz optics and prisms or gratings, could accomplish this but were expensive and generally required the use of narrow slits at entrance and exit that restricted the energy available and the size of the area to be irradiated.

Christiansen had described a set of very simple filters for the visible region of the spectrum. These consisted of small rough chips of a transparent glass immersed in an appropriate transparent liquid, all contained in a transparent cell. The liquid was so chosen that its refractive index matched that of the glass at a specific wavelength. At this wavelength, the cell containing the chips and liquid was completely transparent to a beam of light. At other wavelengths, the refractive index of the chips and liquid would differ and the light would be reflected and scattered out of the beam at each chip-liquid interface. The further the wavelength from the matching wavelength, the greater the scattering and the lower the transmission of the cell. In principle, the cell could be of any size.

While such Christiansen filters had been made for all visible wavelengths, none had ever been designed for the ultraviolet region of the spectrum. I set out to make one.

First, I required chips of a material transparent to ultraviolet. Second, I needed a liquid, transparent to ultraviolet, with a refractive index to match that of the chips only at a desired ultraviolet wavelength. I preferred to use a mixture of two liquids so that, by varying the composition of the mixture, I could change the selected wavelength of complete transparency. Data on refractive indices of liquids and crystals at ultraviolet wavelengths was scarce, but by literature research and extrapolation, I was able to eliminate most combinations. Only saturated hydrocarbons would be expected to be transparent in the ultraviolet regions and the larger molecules would have the higher refractive indices.

It finally appeared that ground fluorite, which was ultraviolet transparent, could be used for the chips and that its refractive index could probably be matched at ultraviolet wavelengths by an appropriate mixture of the hydrocarbons cyclohexane and decalin (decahydronapthalene). When purchased, the cyclohexane was transparent to ultraviolet but the decalin was strongly ultraviolet-absorbing. No ultraviolet absorption spectrum for decalin had been published, but the measured absorption seemed implausible to me. I decided it must be due to unsaturated hydrocarbon impurities and undertook to purify the decalin


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by passage through a column of activated silica gel, which I believed would preferentially absorb unsaturated molecules.

The column worked. The eluate was ultraviolet transparent. When mixed, with cyclohexane, combinations were obtained that, when added to a cell with fluorite chips, produced the desired filtering effect at chosen wavelengths. I had solved the problem.

Unfortunately, in practice the filters are not very useful. The drawbacks are that the wavelength bands emergent from the filter are quite broad (about 10 nanometers at half-maximum intensity) and, more seriously, that the filtering action is never complete. Transmission is still 1 percent or so at wavelengths far removed from the maximum. Since the biological effectiveness of different ultraviolet wavelengths can vary by more than a hundredfold in some applications, such a degree of wavelength contamination is often unacceptable.

John Loofbourow's long-standing interest in the ultraviolet absorption of biological substances was revitalized by the wartime work of Caspersson in Sweden, who had combined ultraviolet microscopy with spectroscopy to determine the ultraviolet absorption spectra of specific cellular structures. Technically, this work was, even by 1940s standards, rudimentary. The optics, dating back to Köhler and von Rohr in 1904, were monochromatic (uncorrected for wavelength dispersion), the photographic measurements tedious and imprecise. However, the potential utility of the technique suggested that it would be worth a significant effort to improve the instrumentation and then apply an improved instrument to a variety of biological questions.

John gathered a diverse group of people around him for this project. Paul Lee undertook the design of a reflecting microscope that would be inherently achromatic. I undertook to design an electronic, self-compensated photoelectric system for measurements. Jesse Scott, an M.D. who had joined us, undertook to develop techniques of specimen preparation for observation. Because I was accustomed to the facilities and services of the Radiation Laboratory, this project seemed to proceed very slowly on all fronts—which was just as well, as I had to prepare for the dreaded Ph.D. examinations.

These examinations are both written and oral and are expected to be comprehensive and challenging. As the first postwar crop of four candidates in a virtually new department in which precedent was lacking, we students were quite unsure of what to expect; I realized later that the faculty was similarly unsure of what level of performance could rea-


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sonably be anticipated. The resultant examinations were in fact very difficult and I was the only one of the four to pass without condition.

Development of the ultraviolet microscope continued to be delayed by the time required for design and fabrication of the mirror optics. (Today's computers would have greatly accelerated this work.) My attention was drawn to some papers demonstrating the sharpening of the ultraviolet absorption spectra of benzene and similar aromatic molecules, as vapors, at very low temperatures ( - 190°C, the boiling point of liquid nitrogen) with the attendant revelation of fine detail in the spectrum. Would the same be true of the purines and pyrimidines of DNA? Could the utility of absorption spectroscopy for biological research, at either the macro or micro level, be enhanced at very low temperatures? Would sharpening permit greater discrimination among the absorbers of ultraviolet irradiation within a cell? (Simple cells could be quickly frozen, irradiated, and revived.)

Jesse Scott and I undertook such experiments, initially with purines and pyrimidines. We had first to find a way to pass ultraviolet light through such molecules at low temperature. They would not vaporize at low temperature; simply freezing aqueous solutions would result in an opaque polycrystalline mass. We developed two methods. One involved solution in a mixture of ether, isopentane, and alcohol (EPA), which would dissolve purines and pyrimidines and which froze to a transparent glass at liquid nitrogen temperature. As an alternative method, we learned how to sublime purines and pyrimidines onto a quartz slide by moderate heating in a high vacuum. The absorption spectrum of the resultant thin film was readily measured.

We had made a quartz Dewar vacuum flask with plane entrance and exit windows for transmission of ultraviolet light. After filling it with liquid nitrogen, we could suspend, into the ultraviolet beam, either the EPA solution in a quartz cell with plane windows or the thin films of purines or pyrimidines on the quartz slides. Very appreciable sharpening of the absorption spectra was obtained.

Unfortunately, neither of the techniques was applicable to nucleotides or to DNA. Our only recourse was to dry down samples onto quartz slides. These absorption spectra regrettably showed little effect of low temperature. (We prepared our own DNA, directly from calf thymus glands. The DNA available commercially at that time was often badly degraded. Much elegant physical chemistry performed on DNA in those early years was worthless because the DNA preparations employed were so degraded.)


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It seemed desirable to go to still lower temperatures to look for an effect. At that time, liquid hydrogen (at - 252°C) was available at MIT, but in another building, several hundred yards away. We had to resort to a double vacuum Dewar—the outer Dewar to be filled with liquid nitrogen to insulate the inner Dewar, which would hold the liquid hydrogen. Both Dewars had plane quartz entrance and exit windows so that, when all was aligned, an ultraviolet beam could be sent through the apparatus. The equipment was mounted on a wooden board. Both Dewars were filled with liquid nitrogen. I then carried the apparatus by hand to the source of liquid hydrogen, displaced the nitrogen in the inner Dewar with hydrogen, and returned to our laboratory to insert the specimens and measure their absorption.

We had several successful runs, but the lower temperature did not produce appreciably sharper spectra than we had previously obtained. A disastrous accident (described in the Introduction) subsequently terminated this research.

Because of the constraints of this apparatus, relatively small beams of fairly high intensity were passed through the specimens. In some instances, examination of the specimen after the experiment suggested irradiation damage. This recalled the much earlier observations that ultraviolet irradiation of cells, most likely affecting the nucleic acids, resulted in cell injury and genetic mutation. What was the chemical basis for these effects? What did ultraviolet irradiation do to nucleic acids? I thought it might be possible using our low temperature techniques to obtain clues to at least the nature of the primary radiation effect.

I began with irradiation of the simpler pyrimidines and purines in aqueous solution and quickly obtained a surprising result. On irradiation of the pyrimidine uracil, its ultraviolet absorption largely disappeared then very. slowly reverted to the original spectrum. This reversal could be greatly accelerated if the solution were made acid. By the spectroscopic criteria, this spontaneous reversal recovered, almost quantitatively, the original compound. At just this time, Albert Kelner described the phenomenon of photoreactivation of ultraviolet damage in bacteria. We naturally speculated that our reversal phenomenon could be related to his biological reactivation. (Actually, there is no simple relation.)

It was time to leave the scholastic nest. I had passed my examinations and had done more than enough research for a thesis. The thesis needed to be written, the Ph.D. acquired, and a suitable position found. It felt quite strange. I was twenty-eight. Since the age of five, save for the war


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years (which seemed an unplanned, nightmarish interlude), I had been a student. Each year had followed the pattern of the previous in simple progression. Each year, I had known where I would be and what I would do in the next. The academic cycle had governed my life. I now came to an end of formal education, to a new and uncertain stage.

And now, even more startling, no academic positions appeared. The biology department received letters from departments in other schools around the country that were seeking faculty, but there was simply no demand for biophysicists, only for the more conventional zoologists or botanists or microbiologists. The possibility of unemployment had never occurred to me. To have done so well academically and then find there was no interest in my services was jarring. My problem was that I was a molecular biologist before there was such a discipline.

Another factor was that Joan and I were expecting our first child. In consequence of all of this, it was decided that I would stay on at MIT for another year as a (minimally) paid research associate to continue work on the microscope and ultraviolet spectroscopy projects and await a better season of job opportunities. During this year, Jesse and I wrote up the low temperature spectroscopy work and, after some editorial difficulty (what has this to do with biology?), saw it published in the Journal of Biological Chemistry .

All of these research projects may seem opportunistic, lacking a master plan. We were not at that time able to attack directly the key biological questions surrounding the nucleic acids. We were searching for a foothold, for ways to further exploit the scant clues we had, such as their specific ultraviolet absorption and its relation to the significant effects of ultraviolet irradiation.

The approaches we employed were novel. Each of the researches was a completely original foray into a previously unstudied area. Such studies are risks. They may produce important results or results of no value at all. But if well done they are definitive. Indeed, some twenty years later, a distinguished physical chemist told me that he had recently become interested in the absorption spectra of complex molecules at low temperatures and had been astonished to find that the best previous work had been done in the MIT biology department in the 1940s.

Of the three projects that comprised my graduate thesis, the reflecting ultraviolet microscope was later completed. It provided useful if not pathbreaking results. The low temperature spectroscopic studies of nucleic acids led no further. The study of the effects of ultraviolet irradi-


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ation on nucleic acid did open—directly and serendipitously—into much more fruitful paths, as will be seen.

By the following winter, at least two reasonable academic openings had appeared. One was in the biology department at Washington University in St. Louis—Frank Schmitt's former department. The other was a biophysics position in the physics department of Iowa State College at Ames.

I visited both places. Washington University had clearly changed little since the 1930s or even the 1920s, with a good but conventional biology, department and little modern equipment or technical facilities. It did not seem well suited to my kind of biophysically oriented, instrument-dependent research. In contrast, several of the faculty of the physics department at Ames, including the chairman, Gerry Fox, had been at the Radiation Laboratory during the war. The theorists Julian Knipp and Frank Carlson and the solid-state physicist Gordon Danielson were also Radiation Laboratory. alumni. The physics and chemistry departments at Iowa State had been involved with the Manhattan Project during the war, and now the AEC had established a permanent laboratory at Ames. A variety of excellent instruments was available, as were a fine machine shop and an understanding attitude with at least moderate resources.

In addition, there was a small but distinguished tradition of biophysics at Iowa State. Fred Uber, who had done the best studies of ultraviolet-induced mutation, had been in the physics department before the war but had moved to Missouri. And Iowa State was willing to recognize my Radiation Laboratory experience as a relevant part of my resume in deciding a salary level.

I was on my way to Ames.


Because few biologists came to biology with such background, I have been able throughout my career to bring a somewhat different perspective to bear on the problems of biology—an approach more quantitative, more analytically rigorous, more unrelentingly reductionist, perhaps more imaginative as to the ever-expanding potentials of ever-newer techniques. I became a laboratory biologist, but one always aware of a perspective external to the field.


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THE IMPRINTING
 

Preferred Citation: Sinsheimer, Robert L. The Strands of a Life: The Science of DNA and the Art of Education. Berkeley:  University of California,  c1994 1994. http://ark.cdlib.org/ark:/13030/ft5j49p04r/