Essay review: Portraying molecular biology

Essay Review: Portraying Molecular Biology* JAN

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Rockefeller University 1230 York Avenue New York, New York 10021-6399

Molecular biology has been portrayed from various points of view. It has been celebrated for its rigor, the elegance of its DNA molecule, the glamour of its technological prowess, and its crowning achievements: an account of DNA replication, the synthesis of macromolecules, and their regulation. It has been criticized for its fast-paced competitive style, its arrogance, its lion’s share of funds and glory, and the winner-take-all mentality of post-World War II biology. It is also a story about successful and failed collaborations in science (Watson and Crick, Jacob and Monod, Franklin and Wilkins, etc.), about scientists moving across disciplines and beginning new careers after World War II, about different ways of imagining nature, about the opening and closing of controversies. All of these issues are addressed in the books briefly reviewed below. Francois Jacob’s The Statue Within takes the reader on a romantic journey down a literary trail to discover the drama-laden life of one of France’s leading biologists. Much of this memoir is devoted to Jacobs life before becoming a scientist. It tells of his relations with his family, his lovers, literature, and politics, his identity as a French Jew, his training for a medical degree, and his wartime activities with the Free French. Later we learn of his life as a member of the Institut Pasteur. An injury during the war prevented him from becoming a surgeon; searching for an altemative, he turned, and fell into biology. Jacob retraces and examines

* Fraqois Jacob, The Statue Within, trans. Franklin Philip (New York: Basic Books, 1988); Francis Crick, What Mad Pursuit (New York: Basic Books, 1988); Anthony Serafini, Linus Pauling: A Man and His Science (New York: Paragon House, 1989); Arthur Kornberg, For the Love of Enzymes (Cambridge, Mass.: Harvard University Press, 1989); Lily E. Kay, Molecules, Cells, and Life:

An Annotated Bibliography of Manuscript Sources on Physiology, Biochemistry, and Biophysics, 1900-l%O, in the Library of the American Philosophical Society (Philadelphia: American Philosophical Society Library, 1989). Journal of the History of Biology, vol. 25, no. 1 (Spring 1992), pp. 149-l 0 1992 Kluwer Academic Pub&hers. Printed in the Netherlands.

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the inner workings of his collaboration with Andre Lwoff on lysogeny, and his collaboration with Jacques Monod on gene regulation for which they were awarded a Nobel Prize in 1965. One would have to search hard to find a finer autobiography, a more literary work, a more introspective and moving memoir. The Statue Within does not present us with the usual account of an early life and later scientific career where the rest of the world is shut out. There is no such dichotomy - rather, this is an account in which everything outside of science is brought inside. Jacob also offers an insider’s view of the rituals and personalities of the Institut Pasteur. When describing his early preference for genetics over biochemistry, he points to an issue of some importance for the rise of molecular biology. Certain kinds of knowledge about the natural world could be invented. Biochemistry, he asserts, could not be: one had to learn formulas and reactions; but genetics constituted a logical system that worked like an exact science. His preference for genetics over biochemistry was further enhanced by several American researchers, physicists or physical chemists who were attracted to the biology of phage, and who were also ignorant of biochemistry. All of them were interested in genetics, in which they saw the only specialization in biology whose logical structure permitted speculations somewhat similar to those in physics. Jacob here describes science with the same clarity and deftness to be found in The Logic of Life. This time, however, it is not snapshot images of science across hundreds of years, but science in action. “Science,” he writes, “is above all a world of ideas in motion” (p. 318). Science in the works has two aspects, which he calls “day science” and “night science.” The former employs a mechanical reasoning; it is ordered, integrated, progressive, and self-confident. The latter is cautious, skeptical, emotional, and reflexive; it’s “a sort of workshop of the possible” (p. 296). One can watch science go from night to day and back again. Jacob emphasizes the rhetorical nature of scientific “stories” told in articles, chapters, and monographs, and he underscores the importance of style in science - a way of looking at the world, and of questioning it, as in art and literature. There is an infinite variety of scientific styles: “A workman’s style or a cavalryman’s. An eagle’s or a mole’s A visionary’s or a follower%. A great lord’s or a shopkeeper’s. A paranoiac’s or a melancholic’s” (p. 290). Jacob compares the way he conceived of nature and interpreted experiments to that of Monod, who, he argues, imagined nature to be logical, functioning according to strict rules: having found a “solution” to some problem, it had to stick to that

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solution from then on. While Monod ascribed a “Cartesianism and elegance to nature” (p. 320) Jacob did not find the world so strict and rational: “What amazed me was neither its elegance nor its perfection, but rather its condition: that it was as it was and not otherwise” (p. 320). Nature for Jacob was “rather like a good girl. Generous, but a little dirty. A bit muddle-headed. Working in a hit-or-miss fashion. Doing what she could with what was at hand. Hence, my tendency to foresee the most varied situations” (p. 320). This last theme is also emphasized by Francis Crick, who argues in What Mad Pursuit that “what is found in biology is mechanisms, mechanisms built with chemical components and that are often modified by other, later, mechanisms added to the earlier ones” (p. 138). While Occam’s razor is a useful tool in the physical sciences, Crick warns that it can be a very dangerous implement in biology. It is very rash to use simplicity and elegance as a guide in biological research. Physicists, he points out, “are all too prone to look for the wrong sorts of generalizations, to construct theoretical models that are too neat, too powerful, and too clean” (p. 139). What Mad Pursuit chronicles Crick’s early interest in science, his training as a physicist, and his work on weapons during World War II; his switch to biology, in his thirties, to study X-ray diffraction of proteins; and his part-time, unofficial collaboration with James D. Watson on the molecular structure of DNA and subsequent work on the genetic code. In the midst of this, Crick takes the opportunity to express his own views on some of the major themes discussed in articles, books, and films dealing with the discovery of the double helix. Crick denies the competitive race for the “secret of life” as illustrated in Watson’s Double Hefix. He addresses the importance of Rosalind Frankin’s excellent X-ray diffraction work, but protests against viewing Franklin as a champion for the cause of feminism. Nonetheless, he acknowledges the institutionahzed sexism in science, and at Cambridge in particular, and he argues that there were other, “more subtle handicaps,” such as Franklin’s suspicion that Maurice Wilkins wanted her to be an assistant rather than an independent researcher (p. 69). Many writers have commented on the tremendous sudden impact of the discovery of the double helix. Some have argued that style and showmanship were as important as content. Gunther Stent and Peter Medawar, for example, suggested that if Watson and Crick had not revealed the structure, instead of being discovered in a flourish it would have trickled out, and its impact

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would have been far less. For this sort of reason, Stent argued that a scientific discovery is more akin to a work of art than is generally admitted. Again, Crick disagrees. He claims that the discovery of the double helix was scientifically commonplace. What was important was not the way it was discovered, but what was discovered. In other words, Watson and Crick did not make DNA; rather, the structure of DNA made Watson and Crick. In Crick’s view, the major credit that he and Watson deserve, considering how young they were in their scientific careers, is for selecting the right problem and sticking to it. What is remarkable in this saga, to Crick, is that the structure of DNA remained in dispute for so long. He argues that it was not until the early 1980s that the double-helical structure of DNA was finally confirmed. “It took 25 years for our model of DNA to go from being only rather plausible, to being very plausible (as a result of the detailed work on DNA fibers), and from there to being virtuahy certainly correct. Even then it was correct only in outline, not in precise detail” (p. 73). Thus Crick suggests that the double helix might serve as a useful case history, showing one example of the complicated way in which theories become “fact.” Yet, the speed at which controversies in molecular biology were opened and closed was all too apparent to Crick. The mid1960s marked the end of what he calls the “classical period” of molecular biology, when all the major questions that had interested him when he started biological research in 1947 were answered, at least in outline: What a gene is made of, how it replicates, how it is turned on and off, what it does. At this time, he shifted research directions and entered the field of brain science. Crick offers a personal account of the state of the field of brain science and argues for the essential need of theory for any explanation of the brain. Issues of style and showmanship in science are highlighted again in Anthony Serafini’s Linus Puuling: A Man and His Science. This engaging narrative, based on personal letters, manuscripts, discussions with Pauling, and interviews with his contemporaries, offers the first book-length account of this remarkable scientist. Serafini takes the reader through many facets of Pauling’s turbulent life, from his early student days, his pioneering work in the application of quantum mechanics to chemistry, for which he was awarded a Nobel Prize in 1954, his work on the chemistry of the brain, and his Nobel Peace Prize in 1962, to his later work on nutrition and vitamin C. Serafini offers a very readable exposition of Pauling’s chemistry, and a critical commentary on his theoretical style and highly

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speculative lines of reasoning. “It is well known in the scientific community,” Serafini writes,.“that Pauling had never relied very much on exhaustive laboratory research to verify his theories” (p. 237). He characterizes Pauling’s style in terms of a frontiersman, a shoot-from-the-hip cowboy. He describes his social relations at the California Institute of Technology and later at San Diego and the Linus Pauling Institute, his thirst for an audience, and his political prowess. He also examines the charges against Pauling of self-glorification and power-seeking, charges that grew to thunderous levels as Pauling entered the political arena. Pauling’s career was persistently surrounded by controversy, particularly during the postwar years when he used his scientific prestige and credibility to crusade for peace, organizing protests against nuclear weapons testing, and when he stood up against McCarthyist witch-hunts, himself accused of being a Communist under discipline because of his left-wing politics. Serafini explores Pauling’s political activities and examines the tensions with the American scientific community. He details Pauling’s struggles with representatives of the Atomic Energy Commission and his conflicts with H. J. Muller and several other leading members of the scientific community sympathetic to the U.S. policies of the cold war. He highlights the hostility of the American Chemistry Society, and the poor reaction of the chemists at Caltech to Pauling’s winning the Nobel Peace Prize; Pauling subsequently retired from both institutions. Serafini also offers a general outline of the stakes in the contest surrounding the effects of vitamin C: the struggle against the medical establishment, and the controversial data - some data suggesting that mega-doses of Vitamin C may have curative effects against cancer, and other data suggesting that such doses may actually cause cancer. He describes the falling-out between Pauling and his collaborator Arthur Robinson over the vitamin C data, and further suggests that the death of Pauling’s wife, Eva Helen, from stomach cancer may have resulted from her heavy use of vitamin C over many years. While Francis Crick only halfheartedly suggests that his own interest in consciousness was perceived as a sign of approaching senility, this was certainly true of the perceptions of Pauling’s promotion of vitamin C. Serafini, however, does not attribute Pauling’s obstinacy to senility. Instead, he would rather compare Pauling’s crusade in the vitamin C controversy to Einstein’s quest for a unified field theory. Arthur Kornberg’s For the Love of Enzymes is a book of a completely different kind. It is not a story of the fast-paced life of a leading scientist, nor is it a glamourous tale of the search for the

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secret of life. Much of it is a personal account of how advances in biochemistry and the study of enzymes have enabled an understanding of heredity, and of much of life, as chemistry. It is a dry, rather factual account of Komberg’s career which does not stray too far from the laboratory bench. Komberg mixes his own experiences with existing accounts of the history of biochemisry; he describes his biochemical work on nutrition, vitamins, and the purification of enzymes, culminating with his work on the synthesis of DNA for which he shared a Nobel Prize in 1959. Subsequently he worked on spores as agents of disease (anthrax, tetanus, botulism) between 1962 and 1970. We also learn of Komberg’s development of the Department of Biochemistry at Stanford, which he headed for ten years. For the Love of Enzymes lacks deep introspection, but there are enough personal anecdotes and biographical information for the reader to catch a glimpse of Komberg’s scientific style, or at least his rhetoric. Komberg presents us with the calculated image of a naive empiricist, whose work is driven solely by the facts; a plodder, guided only by hard-won knowledge of biochemical processes; someone who believes that good science is 90 percent perspiration and 10 percent inspiration; someone who had to work hard for everything that he received. Yet, as the title of Komberg’s autobiography indicates, it is as much a celebration of enzymes and an apologia for biochemistry as it is a celebration of his scientific career. Komberg argues that 40 pecent of all Nobel Prizes in both biology and chemistry have been awarded to work in biochemistry - and yet biochemistry seems to remain as unpopular and unappealing today as it was to the founders of molecular biology. He claims that “Biochemists deserve to share in the glory of the golden age of discoveries of genetic chemistry and molecular immunology often attributed to others who are indifferent to biochemistry” (p. 274). He points out that genetic engineering, understood in its euphemistic term, “biotechnology,” owes its origin to biochemistry; yet, the popularity and power of genetic engineering and molecular biology have eroded the important roles of biochemistry. In the exciting rush toward mastery over DNA, enzymes - and biochemistry generally - are being neglected. Lamenting what he sees as the unjustified depopulation of biochemistry departments, Komberg makes a plea for more research on the chemistry of metabolism, and the brain. Indeed, in the true spirit of a biochemist, he asserts that all life processes must be understood in the language of chemistry. Lily Kay’s Molecules, Cells, and Life is a thoughtful analysis of

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the manuscript holdings of the Library of the American Philosophical Society in the history of physiology, biochemistry, and biophysics for the period 1900-1960. These holdings comprise twenty-four manuscript collections, including those of such wellknown figures as Erwin Char-gaff, Milislav Demerec, Simon Flexner, Alexander Hollaender, and Arrhenius Svante. Kay’s book contains an historical overview which helps place the archival materials in their historiographic contexts. She also provides some suggested research topics based on the annotated sources. This publication nicely complements the previous guide to the APS Library’s collection on genetics, compiled by Bentley Glass. Kay’s essay is entitled, “A Survey of the Life Sciences in the Twentieth Century”. It is shaped by archives of the American Philosophical Society and as such has a double restriction: to life sciences in the United States, and to certain individuals and disciplines represented in the APS archives. I will conclude then, on a cautionary note: we should be wary of having our problems, theories, and views of history be determined by the availability of certain archives.