Triumph of a Naturalist

It would be churlish indeed to argue that Watson and Crick’s elucidation of the double helical structure of DNA in 1953 was anything less than one of the great scientific achievements of modern history. Yet, in a curious way, this discovery differed from other revolutionary events in science by its doubly conservative nature. First, it seemed to confirm the canonical view of genetical systems as rows of beads (genes) on strings (chromosomes), and its implication that evolution proceeds slowly and gradually, based ultimately on the generation of new genetic variation (mutation) by pinpoint changes within the beads (substitution of one nucleic acid base for another yielding a different amino acid in the translated protein).

Second, it represented the greatest modern triumph of the standard methodology that has ruled orthodox science ever since Descartes: reductionism, with its particular claim (in this case) that the complex forms of completed organisms could be explained, ultimately, as the translated products of an inherited program coded by a simple mechanism of four bases variously arranged in groups of three. Had not Watson built his double helix as a tinker-toy machine based on the sizes and fits of constituent parts? And had not Crick, soon afterward, proclaimed the “central dogma” (his words) of the new biology—that DNA makes RNA and RNA makes protein, in a oneway flow of information, a unidirectional process of mechanical construction?

It is a credit to the power of Watson and Crick’s model and to the fruitfulness of good science in general that, thirty years later, this Cartesian view of molecular genetics has been superseded, as a second revolution transmutes our view of inheritance and development. The genome, a cell’s compendium of genetic information, is not a stationary set of beads on strings, subject to change only by substituting one bead for another. The genome is fluid and mobile, changing constantly in quality and quantity, and replete with hierarchical systems of regulation and control.

Genes come in pieces, and the shuffling of their segments can produce new combinations. Some genes can excise themselves from a chromosome and move to other locations in the genome; if these “transposable elements” operate as regulators to turn adjacent genes on and off, their movement to other places (and near different genes) can have major effects on the timing and control of development. Other genes make copies of themselves, and these identical daughters can then either reside next to their parent or move to other chromosomes. In this way, hundreds or thousands of copies of the same gene may be repeated within an organism’s genetic program. The multiple copies of this “gene family” may then diverge in function, thus providing a solution to the old conundrum of how anything novel can evolve if all genes make products necessary for an organism’s construction and well-being. (Original copies may continue to make the required product, while new copies are “free” to alter and experiment.)

If these processes replace a static with a more mobile genome subject to rapid and profound rearrangement, the central dogma with its one-way flow of information from code to product has also been breached. A substance called “reverse transcriptase” can read RNA into DNA and insert new material into genetic programs by running backward along the supposedly one-way street of the central dogma. A class of objects, called retroviruses, uses this backward path, placing new material into chromosomal DNA from the outside. In short, a set of new themes—mobility, rearrangement, regulation, and interaction—has transformed our view of genomes from stable and linear arrays, altered piece by piece and shielded from any interaction with their products, to fluid systems with potential for rapid reorganization and extensive feedback from their own products and other sources of RNA. The implications for embryology and evolution are profound, and largely unexplored.

Barbara McClintock is the godparent and instigator of this second revolution. Her discovery of transposable elements in maize—so-called jumping genes—first presented in the early 1950s before her field had any language to express such a heterodox idea, was, in retrospect, the beginning of modern molecular genetics. She suffered the fate of many pioneers—incomprehension and bewilderment from most colleagues who could not read her maps of terra incognita. But by tenacity, the blessings of long life, and continuous fruitful activity, she has avoided the maudlin ending of most tales in the annals of exploration, and has lived to savor her triumph in the midst of an active career. Now in her eighties, and committed as ever to research on maize in her laboratories at Cold Spring Harbor, she has won every major award that science and an adoring public can bestow, from MacArthur laureate to Nobel prize. And, as a supreme irony, this intensely private woman, who has worked all her life for personal and intellectual reward, can only view such recognition as a bother and impediment. (Most of us, so honored, feel compelled to make some public comment to the same, selfless effect, but we love the accolade and bask in the notoriety; I believe that Barbara McClintock may be unique in truly feeling more discomfort than vindication.)

Such heroic tales are the stuff of simplistic mythology, and McClintock’s catapult into public recognition has fostered vulgar versions of what she did, thereby obscuring a more subtle story and, in a perverse if unintended way, degrading McClintock’s formidable achievements. The vulgarized accounts try to use her as an exemplar for one of two archetypical stories in the sociology of science, either (1) the woman in science, a brilliant mind rejected by prejudice against the color or sex of the body housing it, or (2) the maverick genius who, despite heroic efforts, obtains no hearing because colleagues simply cannot hear a different drummer. The story is never so simple, never a clear-cut contrast of unblemished individual genius and benighted establishment. Just as McClintock’s work helped to break the central dogma and establish interaction between code and product, so must the complex tale of her long rejection be cast as an interplay between her own idiosyncracies and the reactions of her colleagues.

The strength of Keller’s fine book lies in her successful attempt to avoid the myths and capture the subtleties, thereby providing a rare and deep understanding of a troubling, fascinating, and general tale in the history of science—initial rejection (or, more frustratingly, simple incomprehension) of great insights. Keller, who has written with much force about the trials of women in science (see her previous book, Working It Out), understands especially well why this theme cannot provide a central explanation for the career of so special a person as Barbara McClintock.

Yet, in a kind of Catch-22, the uniqueness that makes McClintock such a fascinating subject, and that prevents her from serving as a prototype for any standard tale, has also limited Keller’s achievement for reasons utterly beyond her control. If McClintock has prevailed because a remarkable ability to work for her own satisfactions rather than for approbation of peers kept her going with equanimity and fortitude through all the years of rejection, then the same love of privacy makes her a most unforthcoming subject for a biography. She provided Keller with precious little material of the sort that makes a good story—a few factual tidbits here and there (but little beyond the public record) and almost no account of her feelings and motives.

The first theme, the woman in science, fails to explain her long years of intellectual loneliness after the discovery of “jumping genes” in maize. I do not say, of course, that she suffered no prejudice on the basis of sex; such discrimination was pervasive and affected every stage of her developing career to her practical disadvantage. Yet it would denigrate her remarkable achievements to attribute her experience of isolation, a key event in her intellectual history, to blind prejudice over which she had no control. For Barbara McClintock, in her distinctive and personal way, had overcome these pervasive prejudices by the acknowledged brilliance of her work long before she discovered transposable elements in maize.

Great achievements often wipe out the public’s memory and restart a person’s professional clock. Darwin, for example, had a successful career as a geologist before he published a word on the origin of species, but how many of his admirers and denigrators know that he solved the problem of the origin of coral atolls? Since McClintock has been so honored for the jumping genes that ushered in the second revolution in molecular genetics, many commentators do not realize that transposable elements were not the discovery of a brash young investigator, but a further step built upon a recognized and distinguished career.

Since a scientist cannot look consciously for the unexpected, McClintock found transposable elements while probing another question then largely ignored by geneticists, but of central importance to the study of development and particularly suited to her talents. She wanted to learn how some genes affect the timing of development by regulating activity of other genes that build parts of the body. Maize is particularly well suited for such studies because differences in timing often translate into clear effects in the color of husks and kernels. Her reductionist colleagues, who avoided such complex creatures and tried to get closer to molecules by manipulating the simplest of unicellular organisms, were not then studying problems of regulation—though many molecular geneticists do today because the issue is so fundamental to what Aristotle recognized as the central problem of biology: the development of organic form. McClintock found regulatory elements in maize and then, incidentally while probing their inheritance and expression, discovered that they move.

McClintock could study the difficult problem of regulation successfully because she had already spent a career as one of America’s most distinguished students of cytogenetics—the branch of biology that investigates the physical basis of inheritance by linking observed genetic patterns with the structure of chromosomes and other components of the cell. McClintock had ushered in the modern era of maize genetics in a series of careful studies that developed techniques for naming, visualizing, and characterizing the ten pairs of chromosomes that carry the DNA program of corn. She also performed a series of classic experiments in cytogenetics that established the physical ground for basic principles of heredity. Most famous was her proof, published with Harriet Creighton in 1931, that chromosomes really do carry genetic programs in the linear order that traditional breeding experiments with Mendelian pedigrees had indicated. (She did this by studying the process called “crossing over,” in which chromosomes paired during meiosis—cellular divisions that form eggs and sperm—exchange genes. She proved that this genetic crisscross corresponds exactly with the breaking off and mutual exchange of chromosomal segments.)

For this elegant and pathbreaking work, and in the face of continual impediments raised by prejudices against women in science, McClintock was abundantly recognized and honored by her colleagues. She served as vice-president of the Genetics Society of America in 1939, and as president in 1945. In 1944 she reached the pinnacle of peer recognition in American science and became the third woman ever elected to the National Academy of Sciences. At that time, she wrote to Tracy Sonneborn in the only contemporary, explicit reference she ever made (In Keller’s citation) to the problems of women scientists:

It was both thoughtful and generous of you to write me as you did concerning the National Academy. I must admit I was stunned. Jews, women and Negroes are accustomed to discrimination and don’t expect much. I am not a feminist, but I am always gratified when illogical barriers are broken…. It helps all of us.

McClintock surely suffered from all the prejudices, subtle and overt, directed against women in science, but she overcame them by dint of personal genius and an awesome inner strength that few of us can hope to posses. She will not serve as an exemplar of this troubling theme, and it will not explain the primary event of her public life—the stony silence that accompanied her most important discovery of transposable elements.

The second theme—genius so far ahead of her time that no one can understand—also contains a partial truth but will not suffice because it foists all explanation upon external reception beyond McClintock’s control. Her transition from peerless scientist to pariah owed as much to her personal style as to any inability of colleagues to grasp a radical new idea.

McClintock has always worked for herself and in her own way, never tailoring her efforts to win acceptance, or even to promote understanding among those who might need a little extra prodding or clarity to appreciate an unconventional notion. She lost the only regular academic job she ever held (at the University of Missouri, where women could, and occasionally did, win promotion) largely as a result of her personal preferences (her disinclination to teach formal classes, and her contempt for what academic departments call “good citizenship”—primarily a euphemism for submission to myriad, meaningless hours of soul-sapping committee work). Some of the idiosyncracies that Keller describes are certainly mild ones, and we must therefore accept her argument that the combination of woman and maverick, in synergism, ultimately led to McClintock’s dismissal. (One day, for example, arriving at her lab without keys, she climbed up the side of the building and crawled in through a window, all in the unsuspected presence of a hidden photographer. But what else could she do? Who wouldn’t try acrobatics in such a frustrating situation? I certainly would, and have.)

More importantly, she never did all she could to promote her chances in the admittedly tough battle for acceptance and understanding of transposable elements. She planned a minor campaign, writing an introductory paper and presenting a seminar to key people at Cold Spring Harbor. But when these initial forays met with little response and general incomprehension, she folded her tents. With her usual fortitude and self-reliance (though not, of course, without bitter disappointment), and using her own version of the immemorial phrase “bugger them,” she pressed on in her own way, knowing that she was right and that the rest of the world would eventually catch up. She published most of her subsequent work in the annual reports of her laboratory, surely an inauspicious place to launch a scientific revolution. I have read her main papers and they are, to put it mildly, tough slogging. With their unrelenting passive voice, and their compression of complex reasoning and experiment into single paragraphs, they are marvels of their genre but not models of optimal communication.

Keller argues, I think correctly, that a third reason eclipses gender and collegial obtuseness as a primary explanation for McClintock’s years as vox clamantis in deserto—her unconventional style of scientific thinking. Her different inspiration transcends mere empirical contention and embraces a mode of reasoning quite foreign to the procedures of most experimental science.

First, and more general, McClintock does not follow the style of logical and sequential thinking often taken as a canonical mode of reasoning in science. She works by a kind of global, intuitive insight. If she is stuck on a problem, she will not set it out in rigorous order, write down the deduced consequences and work her way through step by step, but will take a long walk or sit down in the woods and try to think of something else, utterly confident that a solution will eventually come to her in extenso. This procedure makes scientists suspicious and has often led colleagues to label her as a “mystic” in the pejorative, not appreciative, sense.

Nothing could be more inappropriate than the word “mystic” applied to this style of reasoning. It is a common procedure for some people, though perhaps rare (and certainly not generally appreciated) in science. It is neither mystical nor, in another vulgar misrepresentation, feminine as opposed to masculine in character. We dub it mysterious because we have neither good words nor concepts in our largely linear language to express such a modality. I am particularly sensitive to its denigration because it happens to be my own style of working. (I am hopeless at deductive sequencing and can never work out the simplest Agatha Christie or Sherlock Holmes plot—the best stereotypical representations of this conventional mode. I never scored particularly well on so-called objective tests of intelligence because they stress logical reasoning and do not capture this style of simultaneous integration of many pieces into single structures. The difference, of course, between McClintock and me is that she is a genius who can depend upon integrative insight for the solution to major scientific problems; I can only be sure that the “correct” outline for an article will eventually come to me in toto.)

I think that the best description of this style was presented not by a psychologist or neurologist, but by another mystery writer, Dorothy Sayers, who, I am convinced, worked this way herself and established Lord Peter Wimsey as a conscious antidote to the Sherlock Holmes tradition of logical deduction. Now Wimsey was no intellectual slouch, and (in his impeccable upper-class style) was certainly not a fuzzy romantic mystic. But he solved his cases by integrative insight (and these I usually do figure out). In the first Wimsey novel, Whose Body, Sayers describes the process explicitly:

And then it happened—the thing he had been half-consciously expecting. It happened suddenly, surely, as unmistakably, as sunrise. He remembered—not one thing, nor another thing, nor a logical succession of things, but everything—the whole thing, perfect, complete, in all its dimensions as it were and instantaneously; as if he stood outside the world and saw it suspended in an infinitely dimensional space. He no longer needed to reason about it, or even to think about it. He knew it.

Second, and more specifically but more importantly, McClintock practices a style of biology quite foreign to the norms of molecular biology and genetics (and often denigrated, sometimes explicitly, by leaders of these professions—though less so now than before, as appreciation and recognition mount). Keller captures this style in her well-chosen title—“A Feeling for the Organism.” The experimental sciences (like molecular biology) generally work in the reductionistic mode, trying to establish simple and linear chains of cause and effect. They prefer explanations rising from the lowest level of molecules and their physico-chemical properties. To reach this “basic” level, they work with the simplest organisms and try consciously to avoid the individuality of any particular creature. They concentrate instead on the repeatable properties of large groups (so that a clone of bacteria becomes the analogue of a population of atoms with no individuality by definition).

This style has had remarkable triumphs in the history of biology, though I believe that it has now reached definite limits in the attempt to understand genetic systems and their complex interactions with the developing form of organisms. It must also be admitted that, although McClintock first found transposable elements with her different manner of working, the discovery that proved her right and elevated her to heights of peer and public recognition came from molecular biologists working with simple unicellular organisms as physical objects.

McClintock’s style is not uncommon; it just isn’t widely used in her own subfield of biology. It is, in fact, the procedure of my own discipline—evolutionary and taxonomic biology. We work directly with complex organisms and their interaction with each other and their physical environment in growth and adult life. We accept the individuality of each organism as fundamentally irreducible, as the definition of biology’s uniqueness and complexity. (This individuality is, for example, the source of Darwinian evolution since natural selection cannot operate unless populations present a wide spectrum of variation among their constituent members.)

McClintock chose an organism that most molecular geneticists would shun as recalcitrant and hopelessly complex for discovering anything fundamental about genetic systems. Maize grows only one generation per year, and its many parts are subject to a baffling array of non-coded modifications responsive to local environments of growth. (Bacteria may divide in twenty minutes. Populations of billions, with no discernible individuality—save for valued new mutants that can then be cloned by billions themselves—can be readily generated.) But McClintock has always believed that one must follow the peculiarities of individuals, not the mass properties of millions. She is a true taxonomic biologist, a naturalist not a mystic, working in a field unfamiliar with (and often alienated from) this approach. She said to Keller that one must understand

how it grows, understand its parts, understand when something is going wrong with it. [An organism] isn’t just a piece of plastic, it’s something that is constantly being affected by the environment, constantly showing attributes or disabilities in its growth…. No two plants are exactly alike…. I start with the seedling, and I don’t want to leave it. I don’t feel I really know the story if I don’t watch the plant all the way along. So I know every plant in the field. I know them intimately, and I find it a great pleasure to know them.

I see a happy lesson in McClintock’s story, and in the triumph of her unconventional style. She chose to work as a naturalist with a complex organism that most colleagues wouldn’t touch. With maize, she could study basic problems that bacteria do not well exemplify—genetic regulation of timing in growth and morphogenesis, for example. But when she made her unanticipated and greatest discovery of transposable elements, confirmation and generalization required the different procedures of reductionistic molecular genetics. Biology is a unity, and we will not solve Aristotle’s dilemma of morphogenesis, the origin and development of organic form, until we marry the distinctive styles of natural history and reductionistic experiment. Barbara McClintock, with her “feeling for the organism” and her uncanny ability to perform the most rigorous and elegant experiments, points the way better than any other scientist I know.