"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
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
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-
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
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
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
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.
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-
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-
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 -
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
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
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
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-
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;
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.