Return to Science
"You can't go home again" was never truer. It had been ten years since I had, in any sense, been a practicing scientist, ten years of revolution in my very own field of molecular biology. The advent of recombinant DNA and cloning, combined with DNA sequencing, polynucleotide synthesis, and genetic engineering, had broken a long-standing research barrier by permitting the isolation and identification and modification of individual genes from higher organisms. Whole fields of study—some long stagnant, some brand-new—had opened up in developmental biology, cell biology, virology and microbiology, neurobiology, and nearly every aspect of medicine.
In 1977, just prior to becoming chancellor, I had written a review for Annual Reviews of Biochemistry on the then new topic of recombinant DNA. After ten years of sophisticated genetic engineering of recombinant DNA vectors and the development of advanced techniques and instrumentation, that review was wholly obsolete. I had read occasional semi-popular articles in Science or Scientific American, but I had not kept up at all with the technical advances—which, in any case, would be meaningless without actual experience in their application.
Even more profound than the advances in technique were the enlarged perspectives and the deeper insights now available. Biologists have long marveled at the variety of living forms in the world of nature around us. We are now learning that the variety of biochemical mechanisms and processes within these organisms, built on a base of ancient, common strategies and structures, is even more exuberant, even more
extraordinary. Over billions of years, in myriads of species, nature the experimenter has explored and exploited all the changes, the combinations, the cyclic sequences of events to produce programs—cellular dramas—with common themes but of dazzling intricacy and variety.
If I were to reenter science, I needed to travel the usual entry track—as, in effect, a postdoctoral fellow. Caltech seemed the obvious place to do this. I knew most of the people; I knew the structures, physical and organizational; I knew the invaluable ambience. After ten years at UC, I was entitled to a year of sabbatical leave, so I would not need a salary. Caltech was willing to provide me with a small basement office and, most important, access for the year.
However, where would I go after Caltech? My faculty appointment was at Santa Cruz. In light of my own experience with a former chancellor on campus, I felt it would be much preferable not to be a faculty member at the same institution where I had been chancellor. It is awkward for the new chancellor to find a predecessor "popping up," in a sense looking over his or her shoulder. It would be difficult to avoid becoming involved in campus issues in which I had invested so much thought and energy, and I would indeed be pressured to do so by one faction or another. But I definitely should not. They are now the new chancellor's problems, opportunities, and responsibilities.
UC Santa Barbara appealed. It was a young and developing campus, with a growing reputation in the sciences, especially physical science. It had some distinguished biologists whom I knew. The climate was benign. And I had a house there, which I had built in the mid-1970s to use for vacations and which had been rented out all of the Santa Cruz years. The Santa Barbara biologists seemed pleased to have me join them. My appointment would remain at Santa Cruz; I would be on "temporary" assignment to Santa Barbara until my retirement as a faculty member, which would be mandatory in three years.
We rented an older house in Pasadena, near Caltech, and arrived in the midst of a heat wave, just in time for the jolting aftershock of the Whittier earthquake. But Pasadena was still familiar.
Returning to science after an enforced abstinence was a joyous journey. I could savor anew even the process as well as the content: the familiar rhythms and flow of a scientific meeting, the large general lectures and the smaller specialized sessions, the little knots of people, some old friends, some new acolytes, discussing a presentation—or where best to go for dinner—and above all the pervasive sense of progress, of advance, since the prior meeting.
Even the easy rituals of the late afternoon seminars were fresh and pleasing: the faculty largely in the first few rows, the students scattered behind them; the introduction of the speaker, the standard acknowledgments to coworkers and students before launching into substance, the background, the recent results, the future plans; then the discussion period, sometimes respectful, sometimes probing, sometimes brash, sometimes almost harsh, but impersonal. All the familiar and heuristic patterns, time-tested and leading erratically but surely to truth, once again shone and refreshed.
Much of the fall quarter was spent reading, talking to everyone in biology, attending numerous seminars, and catching up on the state of the science. But I clearly needed to get into the laboratory. With recombinant DNA, developmental biology had emerged from a fifty-year slumber. Finally, one could begin to study the genetic and biochemical components, the hierarchy of controls that underlay the intricate processes leading from a single fertilized egg cell to a mature organism. Eric Davidson's laboratory was most active in this field, so I signed on with him as an apprentice postdoctoral fellow.
The postdoctoral fellow in science has in many ways an idyllic existence. He or she has no responsibility other than to come in and perform research. The professor provides the laboratory, the facilities, the funds for supplies. Undistracted by teaching, committees, or fund-raising and with such recent training, the fellow is ideally positioned to concentrate for a few years on problems at the most advanced edge of the field. Of course, I had one advantage over the other postdoctoral fellows—I did not have to worry about finding a permanent position in two or three years.
Getting back to the laboratory bench, doing experiments with my own hands, coming in in the morning to see how an overnight experiment had worked out, reviewing results, and exchanging ideas with others in the laboratory was sheer pleasure. Initially, I was quite ignorant of the new techniques, but other fellows and students were most helpful. Once past the early blunders, most of the techniques are actually rather simple to use, save for the occasional total failure due to a mental lapse or, more often, a bad batch of reagents or an equipment malfunction.
Development implies a programmed pattern of controlled differential gene expression in the varied cells of the developing embryo. The research in Davidson's laboratory used embryos of sea urchins—a classical object of embryonic research—which can be obtained in large
numbers and accurately synchronized. The object of the research at that time was to isolate and identify factors—proteins—responsible for turning on and off specific genes at specific stages of development, and then locate the genes responsible for these factors. Ultimately, we hoped to arrange all of these in an hierarchical structure, beginning with the fertilized egg, that could explain the appearance of different functions and organs at the different stages of development. Some genes controlling analogous factors in drosophila had been isolated and sequenced. It was plausible that similar genes existed in sea urchins. If so, techniques existed to identify, and then isolate, these by their homology to the drosophila genes. I set out to do this.
In the laboratory, I was immediately struck by the ready commercial availability of sophisticated biological reagents. A whole ancillary industry had sprung up to provide the many enzymes, polynucleotides, engineered plasmids, viruses, cell lines, and highly purified reagents needed for modern molecular biology. I recalled the era when one had to go to the stockyards to obtain intestines to prepare alkaline phosphatase and thymus glands for DNA. As recently as the 1970s, we had had to prepare our own restriction enzymes. Now a hundred different varieties could be purchased at quite reasonable cost. This development greatly accelerates the pace of research.
Still, as always, the research went more slowly than I hoped, but by summer I had had some success. Now it was time to move to Santa Barbara, where it would be difficult for me to continue this project on my own. But I had mastered a variety of essential techniques.
The biology program at Santa Barbara, because of leaves of absence and pending retirements, needed me to perform some of their essential teaching for a few years. I welcomed the challenge. And it really was a challenge.
The third quarter—thirty lectures—of the required biochemistry course concerned nucleic acids and protein synthesis. This had been my field of interest and research for decades and I had taught varied aspects of this subject at Caltech.
As I prepared to teach this course after a ten-year hiatus, I was astonished and thrilled by the progress made in the past decade. In every sector, the advances had been simply extraordinary: in the intricacies and nuances of DNA structure (no longer the simple rigid double helix); in the still deepening complexities of DNA replication (initiation, strand elongation, termination); in the much expanded understanding of DNA transcription and its control; in the knowledge of the process-
ing of RNA transcripts (capping, splicing, tailing); in the comprehension of amino acid activation and ribosomal structure and the many facets of protein synthesis (initiation, elongation, termination); in the variety and importance of DNA repair processes; in the growing knowledge of chromosomal structure and the enzymology of genetic recombination; and, of course, in the whole world of recombinant DNA with its skillfully designed vectors, the elegant methods of oligonucleotide synthesis and DNA sequencing, the wealth of restriction enzymes, the new polymerase chain reaction, and so on—a true biological engineering.
Practically, I had difficulty in planning the time required to treat each topic, and in the end I estimated that over half of the material I taught in the course had simply not been known ten years earlier.
Between organizing the lectures, preparing transparencies for projection and Xeroxed handouts for eighty students, meeting with students who had questions, planning the discussion sections with the teaching assistant who would lead them, and giving and grading midterm and final examinations, the course was a ten-week marathon occupying nearly every. waking hour. I learned a lot, and it was truly enjoyable to be able to talk about science and once again interact with students in a nonconfrontational mode.
A series of ten lectures on the cell nucleus in a graduate course in cell biology was a similar, but briefer experience. Quite different, however, was a series of lectures on genetics to a beginning biology course for students who did not plan to major in biology. A popular way to satisfy the science portion of the general education requirement, the course was limited to 475 students only because of the size of the lecture room. The room was actually a concert hall with no blackboard and a sea of faces. In such a course there can be very little direct interaction with students. The presentation must be very largely visual. I used slides, transparencies, films, videotapes (e.g., Nova programs)—whatever I could find that was appropriate. Today's TV-habituated students seem better able to learn from visual presentation than from textbooks. But as they are accustomed to the high technical standards of commercial television, the visual material has to be of a similar quality.
Soon after I arrived at Santa Barbara, I learned of the research of Professor Paul Hansma in the physics department. Hansma had developed an "atomic force microscope" with which he had been able, with favorable substrates, to obtain atomic resolution on surfaces. It occurred to me that this instrument might, just might, be able to resolve the
individual bases in DNA and if so permit one to achieve the direct sequencing of a DNA chain. Such an accomplishment would, of course, greatly advance the Human Genome Project. This was and is a "long shot," a "high-risk" experiment with the possibility of a dramatic result. It was not an experiment that one would give to a graduate student who must complete a thesis and write some papers for his career, but I could take the chance.
Paul Hansma was intrigued with this possibility and together with his wife Helen, who is a biologist, we set out. We have been looking at simple polynucleotides of known sequence. In such research there are always many possible approaches (Should the nucleic acid be dry, under water, under a nonaqueous solvent?) and technical difficulties (What supporting surface should be used? How can we keep the nucleic acid from moving about? Is temperature important? Can we minimize possible damage to the nucleic acid or is that not a problem?) To date we have had modest success. Our resolution has been such that, under favorable conditions, we can detect the presence of the individual nucleotides in a chain but cannot differentiate them. Could we modify them to make them more distinctive? Would other modes of mounting the DNA be more productive?
The research continues, and it is fun. And the reports of progress in each new journal, the new discoveries presented in the weekly seminars, and the new insights that come from reflecting on these all stir the same excitement, the same pleasure and wonder, as always. Science is a glory of the human mind and these are glorious times in which to be a biologist.
"We Happy Few"
I am a scientist, a member of a most fortunate species. The lives of most people are filled with ephemera. All too soon, much of humanity becomes mired in the tepid tracks of their short lives. But a happy few of us have the privilege to live with and explore the eternal, to feel the wind at the ever-advancing edge of human knowledge, and to peer into and progressively reveal the dim shapes of the unknown. Scientists find the natural world endlessly absorbing, a fertile obsession. In the exploration of nature, we can exercise our full imaginations, our most acute logic, our deepest curiosity—and the knowledge we gain will endure throughout time.
In recent years, some humanists have sought to blur the distinction between science and other more ephemeral forms of human activity, to distance science from the "eternal." The "deconstructionists" have claimed that scientific truth is only an outcome of "negotiations" between scientists in the laboratory, that the "natural world" emanates from the "social," and that, as in other human spheres, "truth" in science is not independent of the exercise of power. While such views have gained credence in some circles, they are painfully superficial and do not correspond to the reality of the world of science I know. Science does differ from other human pursuits in that there is an external standard of truth that must be met. There are basic properties of matter and life independent of human intervention. Which areas of nature are explored is, to be sure, socially determined; the framework and language in which the laws and properties of nature are described are of course
human constructs. But there is an external reality, an external truth that cannot be falsified, that is independent of the murky claims of human motivation, and that is as close to "eternal" as humans may approach.
"The glass is half full; the glass is half empty." One can view life either way. I believe you have a choice. In an interview at age ninety, the great dancer Martha Graham suggested that every choice is a sacrifice of the road not taken. But, alternatively, even choice is a cause for celebration—celebration that we of all creatures have the capacity for choice. We are not limited to instinctual responses but can use forethought and will to guide our actions. In all of the known universe, we, Homo sapiens, are the wild card. In all else of nature, the past creates the present, the present creates the future. What is, is because what was, was. But, with us time closes back on itself. The envisioned future affects the present. And science most powerfully permits us to understand the past and the present and to envision the future.
We are all limited human beings with only special innate talents, with only finite perspectives, with depths unplumbed, heights unscaled, and connections never made. We scientists are a type, a breed. We are oriented to things not people, to clean abstractions not messy realities, to reason more than emotion. We are inexhaustibly curious about how things work, but not why, for motive is only real in the people world we eschew.
We scientists inhabit a distinctive culture. We live in both a narrow time frame and a very very long time frame. In our daily work we focus on the near past, the present, and the near future; in our science we range from the beginning to the end of time. But human history is far less real to us. The rapid progress of science renders our past much more distant; unlike many groups, we do not harbor ancient grudges for historic wrongs.
Advances in science are permanent. The knowledge, once gained, is forever ours. In contrast, advances in social affairs, however hard won, seem fragile and temporal—always at risk of the struggle resuming, reversing, or transferring to another arena.
Unlike anthropologists or economists, authors or poets, theologians or politicians, we natural scientists have the luxury of a single truth.
There is only one proton mass, one periodic table, one genetic code. In consequence, science, during my career, has been essentially egalitarian. Nature is the only source of ultimate authority. Before nature, a world outside of man, a reality independent of human design or desire, we are all equal. Nature is not deceitful and nature does not play tricks. We scientists may deceive ourselves, as by our all-too-human quest for a superficial simplicity, and thus for a time we may overlook a deeper truth. But, as research continues, nature alerts us to our myopia.
Critics and revisionists may now argue that access to nature is becoming less egalitarian in this emerging era of intensive instrumentation. We should be consciously concerned that such barriers be minimized.
The purpose of science is to create an inner world that predictably matches the external world. Others create inner worlds for varied purposes, constructive or frivolous, more ordered or more chaotic, more spontaneous or more reflexive. Science requires imagination on which it then imposes discipline. The knowledge that there is an external truth is both a comfort and a trial for the scientist. Unlike the artist who must rely on either an inner voice or an uncertain outer acclaim to validate his work, the scientist knows there is a sure single objective judgment that will be rendered on his experiments: Have they guided us to an accurate perception of a reality? The scientist is therefore more constrained and potentially more vexed. The real world is there waiting to be discovered—if one can find the path—but unlike the artist, the scientist cannot be content with his own "truth." Even imagination and elegance are of little merit if in the end they describe only an unreal world.
One of the values of a life in science is that one does not have to cope—at least not very often—with venal or corrupt people. Scientists are not paragons—ego, vanity, greed are scarcely unknown to us—but out-and-out corruption, lies, deceit, thievery, abuse of power, and bigotry are rare. The discipline and earnestness of the enterprise seem to make such acts too petty, too unworthy. Or perhaps, at least in biology, the true nuggets have been so plentiful and so close at hand as to curb desire to steal from an associate or to gold-plate a common pebble.
Beyond the hours devoted to survival—a need that our society now fortunately satisfies for almost all—how does one live the other hours? I have been fortunate to find true pleasure and excitement in this activity of science, which I can regard as wholesome, deeply meaningful, and enduring. MIT transformed me into a goal-oriented person and equipped me with the means to set and achieve goals. Because I have
thus been goal-oriented, I have had scant patience with those individuals who constantly look back to a past episode—their war experiences, athletic performances, or student "activism"—as the high points of their lives. As a participant in science, one can always believe with confidence that the best is yet to come. For, most remarkably, nature—even biology with its intricacy developed by three billion years of evolution—seems indefinitely penetrable to human reason.
I was fortunate enough to enter a field of transcendent importance—nucleic acid research—at the time of its infancy, when one could actually know everything there was to know about that field, be acquainted with all of the major contributors to the field, and read all of the current literature. Today this would be impossible.
In retrospect, I see that I have had a penchant to choose nonmainstream courses. To minimize competition? Perhaps. In hope that virgin territory would have a greater chance of a rich, undiscovered lode? Perhaps. Or simply because unexplored regions gave one greater freedom to chart one's own path? Perhaps. At each major transition, I have made such a choice. Biophysics was such a choice, as were DNA, f X, and UC Santa Cruz. All proved interesting; most proved felicitous.
The advances in biology since I entered the field were at that time well nigh inconceivable. In the late 1930s, we were nibbling at the edges of the great problems—heredity, development, homeostasis, brain function—grasping at straws to construct ambitious theories in the absence of evidence. Today we are attacking head-on the core of these questions. These advances have brought remarkable insights. Especially, those in our understanding of heredity have been the most profound, the most seminal.
We have long recognized that one of the distinctive features of Homo sapiens is that we, among all the species on earth, are self-aware—aware of our individuality, aware of the mystery of our origin, aware of the future and of our ultimate mortality. Today we are increasingly self-aware in a very different sense, for we are now becoming aware of the intricate machinery within us. No other species knows that it has a circulatory system, a hormonal system, a nervous system. And now we are deepening that awareness to the genetic level, unraveling and exposing the chemical machinery—the complex array of genes—that through controlled expression, repression, and multiple interactions
brings about our growth, differentiation, and maturation and produces (miraculously) the very intelligence that permits us to decipher this extraordinary process. How remarkable!
In the deepest sense, we are who we are because of our genes. Genes provide our physical framework, much of the specific basis for personality, and the raw material for intellect. (Circumstance, environment, and culture map the specific routes for intellect.) If we are ever to find out who we are and how, via evolution, we came to be who we are, we need to understand our genes, our biological inheritance, in detail. When we have it, what then will we do with this knowledge? We cannot escape this question, which is both enthralling and chilling. A species potentially able to plot its own genetic destiny is truly unprecedented. What wisdom can we summon to guide such a venture? Are there principles of increment, rules, or uncertainty, principles to govern manageable rates or size of genetic change?
Ten thousand years of cultural evolution have brought us to this point—unplanned, uneven, the turbulent but continuous history of our species. Much of the continuity has been provided by the continuity of our biological nature—our physical needs, our psychological and intellectual range, our limited life span. Were these to change, what consequences would flow? Such questions, aborning in the laboratories of our time, would seem to beggar the political and socioeconomic concerns that dominate our news.
From the time of the invention of writing, men have sought for the hidden tablet or papyrus on which would be inscribed the reason for our existence in this world, on this planet in this star-lit universe. How poetic that we now find the key inscribed in the nucleus of every cell of our body. Here in our genome is written in DNA letters the history, the evolution of our species over billions of years. The message is faded in places, tattered by the insults of the eons, but of necessity valid and functional in its vital parts. When Galileo discovered that he could describe the motions of objects with simple mathematical formulas, he felt that he had discovered the language in which God created the universe. Today we might say that we have discovered the language in which God created life.
A life in science, a life on the edge of knowledge, can provide endless fascination and intellectual reward. There one finds a continuing sense
of progress, of challenges met and challenges overcome. The scientific problems of my youth have been resolved into a progression of deeper and deeper questions. Most still challenge us, albeit in different terms. To some we have found definitive solutions, but even these often lead on to further, previously unimagined questions.
To know science is to see a wondrous pageant enacted over centuries. The curtain rises, at first slowly, on a scene of mists and strange, indistinct shapes amid the half-light. The protagonist is humankind, a stranger in this strange world, a part of it yet apart from it—puzzled, filled with wonder as to where he is, how he came to be here, what guides this cosmos, and what his destiny is. Gradually, here and there, the mists dissolve, some shapes become clear, some mysteries recede, and some vanish in the clear light of knowledge. Yet others emerge in their wake, formerly hidden in the background. A pageant incomplete, unfolding over the generations.
Until recently, scientists could also take satisfaction in the thought that their activities were an unalloyed good—that knowledge was good and more knowledge better. Human intelligence has been the principal agent of human progress. And science, the disciplined search for new knowledge, has, at least in recent times, formed the leading edge of intellectual advance. Yet strangely, in our time, as scientific knowledge has advanced in every field, as the powers of applied science have multiplied again and again, the public perception of science has markedly darkened. Science, once the Promethean reliever of toil, the bringer of light and health, the transcender of space and time, the enabler of so many human dreams, has become science the handmaiden of pollution, the abettor of overpopulation, the fountain of apocalyptic military technologies.
Science is a mutator gene in our society. Could it mutate itself out of existence by mutating the society to become resistant to its product—resistant and fearful of innovation, or so comfortable that few will choose to enter such a demanding career? Some portents are already clear. Many futuristic novels such as The Time Machine by H. G. Wells and Brave New World by Aldous Huxley envision a world with two distinct classes of people—a technologically advanced, dominant class and a more primitive, naturalistic class living a simple but hazardous life.
Once I thought that these scenarios merely reflected British class distinctions. But one sees the same bifurcation occurring in the United States, between a scientifically literate, technology-prone culture and an antitechnology, back-to-nature cult opposed to "the rape of the earth,"
"research on animals," and "technological enslavement." The technical illiteracy of most of our people has led to a growing alienation from the "incomprehensible" manmade world and a growing passion to return to the romanticized, intuitively grasped world of nature (to be sure, as tamed and made accessible by technology). From our beginnings, humans have sought to leave an imprint on the earth, an evidence of their existence—as cave drawings or pyramids, as statues or portraits, as castles or factories. Today, for the first time, we have a generation that seeks to remove human imprints, to return the earth to a more primitive state.
Most scientists recoil from the evidence of these perceptions that their work is not universally admired. They respond with the argument that their role is to discover knowledge, that they are not responsible for its use or abuse. Partly, this is true. Indeed, one can hardly foresee the longer-range uses of a basic discovery. When Einstein formulated his famous equation relating matter and energy, he could hardly have foreseen that it would find application in an atomic weapon. But as research has become more and more rapidly the source of industrial development, that excuse has become an evasion. Such evasion is clearly evident in the approach of scientists to the setting of priorities within science. The issue tends quickly to gravitate to the lower brain centers, numbing the mind and inflaming the emotions.
Scientists believe they serve, in their discipline, an inherently noble cause. They believe that a multitude of minds including their own, working more or less independently, is much more likely to piece together the truth than is a central, if more "efficient," directorate. They can cite the numerous historical instances in which the greatest discoveries were totally unexpected and unpredictable and thus would have eluded planned research. Thus, discussion of limitations on the resources to be made available to science elicits alarm but little intellectual interest and no sympathy. And discussion about the allocation of finite resources is met with avoidance responses.
But when the cost of basic scientific research is measured in tens of billions of dollars, other social institutions are certain to raise questions. For society, basic scientific research is, like education, an investment in the future, a diversion of resources in money and minds that could otherwise be used to meet present needs. Therefore, society is entitled to ask: What are the prospects, however tenuous or remote, of future benefit? On what time scale and of what magnitude are these benefits, however large the standard degree of error in prediction? And to what
extent are such factors considered in the allocation of research resources? Because of apathy, or even antipathy, toward such questions in the scientific community, the answer to the last question would have to be "precious little." Broad resource allocations are based on historical precedent, on political pressure by interest groups (e.g., AIDS activists and pro-agriculture groups), on indigenous cost elements such as expensive instrumentation, and on general public appeal or concern over issues like health, defense, and space exploration.
Is this problem, once confronted, really so intractable? Can weighting factors be devised to be applied, not within disciplines, but over broad domains of science to help design a more rational means of allocation? Implicitly or explicitly, such intellectual discipline is of necessity applied in other costly areas of national importance such as defense, health care, and education. Science can hardly expect to be exempt. And the continued possibility of an engrossing life in science will depend on finding solutions to this allocation problem and to the much greater problem of developing widespread scientific literacy, the only secure basis for informed support of science.
When humans first emerged on the earth out of the shadowed millennia of the preconscious, they were intellectually newborns. They had no idea of their origins or their potential. Their internal and external worlds were simply given to them without explanation. All was mystery—birth, death, disease, famine, light, dark, the stars, and the tides—all occurred as if staged by unseen hands.
Science has provided the key to explain with ever deeper, more general, and more complete concepts the origins and workings of the planet, of the cosmos, of ourselves and all the other creatures of earth. The biologist, peering ever deeper into the machinery of life, is caught between a growing wonder at its beautiful complexity and adroit ingenuity and a growing conviction that we too are but remarkable machines—a most extraordinary, perhaps unparalleled creation, yet a transient assortment of atoms playing a role in a drama whose point we can never fathom.
Just as living is a daily denial of the ultimate reality of death, an absorption in the accessible events of daily life while avoiding the intractable issue of mortality, so is science a denial of the ultimate questions of human or cosmic purpose by absorption in the accessible mysteries of the natural world around and within us.
Why does it seem so strange to have reached an age when one can no longer view death with the detachment of youth? In January 1990, for the seventh time I changed the decade as I wrote the date. How could another decade have slipped by so quickly? Will there be another?
To the students in my classes, World War II is ancient history, quite as remote as the Civil and Revolutionary Wars, if not those between Rome and Carthage and Athens and Troy. The living memory of that cataclysm is fast dying and yet, beyond their ken, that vast conflict shaped my world and theirs as well. From the times of the Greeks and Romans, the elders have looked askance at the mores of the young. Knowing this, I nevertheless feel out of place in an age of lotteries, rock stars, and television violence. Was it better in my youth, with bootleggers and the Teapot Dome and Hollywood scandals? Somehow, I think so. The mindless spectacle, tawdriness, and criminality were much less pervasive and much further from general acceptance.
I feel out of place in a society in which self-actualization support groups and telephone hotlines have replaced the senses of duty, selfreliance, and personal responsibility, in which "society" and "the system" are always the culprit, as if the individual had no free will. Human actions derive from some mixture of genetic determinants, social determinants, and volition. The middle set currently receives much attention. And of the first, we will in the near future know much more. But, it is the third, the capacity for voluntary action, that makes us human and most distinguishes us from all other species. Human society has been built, and properly so, on the concept of personal responsibility, and the more our research clearly defines the roles and strengths of the biological and social determinants, the more we must develop an internal recognition of volition with its possibilities of choice and associated responsibilities.
In the spring, as graduation day approaches at MIT, there will be a time of alumni reunions, and the fifty-year class will be a center of attention. When I was a student, this knot of elders seemed truly ancient—they had graduated in the 1880s, the remote past. Two years ago, I attended the fiftieth reunion of my own class, the fossils of '41. No doubt, we seemed just as ancient to the students of today—our era just as remote, our hopes, dreams, and concerns just as antiquated, however much they still pulse in our memories.
The cycle of life tempers hopes and dreams with harsh reality. Some prove too remote, some illusory. Some come to fruition tinted with a far less roseate hue. I think of television, of how, when I was a student, we dreamed it would bring enlightenment, education, the great wonders of nature, and the great human achievements to all the world. And how, with seeming inevitability, television has been trivialized and suborned by the truly dominant forces of commerce and politics, the sources of power in a secular age. Could it have been otherwise in our society? Fortunately, new generations arise with their new dreams. For, as reality, tempers dreams, so in a crucial counterpoint do dreams temper reality.
I sit here in my study, surrounded by the ghosts of science past. These are not ethereal ghosts, undulating gently and silently in the soft air. No, they are solid and weighty tomes—textbooks, journals, conference proceedings, reviews, reports, theses—arrayed on shelves, stacked in piles, and filed in cabinets. They are the mute but viable record of fifty years of biology, of once-lively discussion, of questions now mostly resolved or identified as mirages, of brilliant concepts dashed on reality and major discoveries unexpectedly stumbled across. Of advances in knowledge year by year by year. They are the record of a golden age in biology, when the search for understanding of living processes finally reached the basal genetic level and began to find the ultimate evolutionary explanations.
Now, in this field little as read or is worth reading that is more than five years old. And so my own articles now sit with these others, unattended, buried ever deeper by the unending flow of new literature. But the old records speak to me yet, for I can hear the voices of the seminar speakers, I still recall the late-night discussions, I still feel the excitements, the disappointments, and the wonder as the tale continually unfolded and the mysteries continually receded into the newer unknown—as they do today.
Some twenty years ago, I visited Sinsheim, the dwelling-place of my ancestors. In the early 1970s, it was still a small German village of perhaps four to five thousand persons some fifty kilometers southeast of Heidelberg. It had been spared much of the destruction of World War
II; the seventeenth-century town hall, the old church, and many medieval buildings and dwellings were still in use. Nestled along the tree-shaded Elbenz River, Sinsheim is located in a rolling countryside of small farms and orchards. On a hill some two or three kilometers away are the ruins of an old castle-fort that once protected the inhabitants. My ancestors lived here, for how many centuries? They must have farmed the soil or tended the orchards. Their world was small and bounded. The nearest town, Heidelberg, was two days' journey.
I, their descendant, have lived a very different life, in laboratories and classrooms, part of the worldwide community of science. As part of that community my travels have taken me to most of the continents of earth. I have had so many more opportunities than they. I have been permitted a life of investigation, a life of investment in the future through science and education. I expect they too invested in the future, to the extent then possible, and I know with gratitude that their investment made possible my life and my contributions.
Writing this book has been a pilgrimage to faces and scenes of long ago, to dates once future and now past. To seek order in a life, to find meaning in a trajectory. Looked at as the life-span or a scientist-scholar, there are two abrupt shifts or zigzags in the arc. One, to the Radiation Laboratory, was imposed on me and reversed when feasible. The other, to be chancellor at UC Santa Cruz, I chose out of a näive if lofty idealism. It was too late in life to ever fully reverse.
I find it as yet difficult to assess the decade at Santa Cruz. I learned so much—perhaps that is its own reward. I tried to use all that I learned and all that I knew before to guide the campus toward its true potential. Was my role good for the institution? I firmly believe it was. Was it good for the students and the future of education? I like to believe so, but only history will tell. In that decade, Santa Cruz sought to educate in some degree between ten and fifteen thousand students. How can one measure that impact?
Was it worthwhile for me personally? I have to acknowledge that, for many reasons, much that I had hoped to do was not accomplished. Could I have accomplished more, for my personal satisfaction or for the long-run benefit of humanity, had I remained within science? Who can say? Surely, I became wiser in the ways of the world. Perhaps that is enough.
Both deviations gave me broader experiences, which I treasure, but both I believe diminished my overall scientific productivity—what I might have accomplished in science. Science has given my life a continuity and a thrust. Whatever disillusion has accompanied its triumphs has not dimmed my appreciation of its beauty and power—it has only deepened my compassion for the plight of our species which can both conceive it and so misuse it. Some deep impulse of social concern, some underlying bent of conscience has repeatedly nudged me out of the happy cloistered world of science. To add to knowledge was not enough. Knowledge is not inert; it is a seed that will be used for good or ill. A scientist cannot and should not control that use, but to ignore or pretend ignorance of its potential is to abdicate a central part of one's humanity.
We have only scratched the surface. The great mysteries remain. The mysteries of the cosmos, of the origin of the universe, of"dark matter," of quasars and all the quandaries of galaxies. The mysteries of matter: What lies beyond the quarks? What determines the mass of the proton? The mysteries of evolution, of the origin of life and the origin of man. The mysteries of the mind, of the origin of consciousness and the neurobiology of thought and sensation. They beckon the human spirit and they summon us to endless adventure, to the "endless frontier."
What we have in my lifetime learned about genetics, and what we are today learning about our own human inheritance, will endure. It will endure as long as humans ask questions, as long as we seek some control over our destroy, as long as we know wonder. I have no desire for immortality, but I would love to return in a century or two to see where science stands and to learn what questions they are asking in the Sinsheimer Laboratory.