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Human Genome: A Blue Plate Special Reviewed by Jeffrey L. Fox ewspaper reports typically refer to DNA molecules as the "blueprint of life." Seeing that tired metaphor so often repeated makes me wonder whether editors might welcome an alternative, such as the "recipe for life's banquet." Food metaphors seem closer to the bone and more succulent—surely more appealing than the jargon of architects for describing biology. Besides, talking about food puts one in mind of family and ancestral matters—in short, genetics. Admittedly with the title, "The Human Blueprint," chemist Robert Shapiro chose a metaphor that is not to my taste. Nonetheless, he serves up a readable account of the human genome project. That project began as an offshoot of more general efforts in molecular genetics and has grown into a major federally sponsored research undertaking. Along the way to describing how that has happened, Shapiro generously peppers his offering with credible, albeit sometimes adulatory, descriptions of the principal characters who helped devise the national—and sometimes international—genome restaurant. The second half of the 20th century has been a boom time for the life sciences. Pure biochemistry, with its emphasis on proteins and how cells make what they need, seemed to reach full stride in the sixties and seventies. Somewhere in those decades, a splinter group of molecular biologists began to gain increasing prominence. They concentrated on DNA and genetics instead of proteins and enzymes. And, perhaps coincidentally, they tended to emulate physicists instead of chemists. Of course, borderlines between these specializations were never strictly demarcated—recipe exchanges and the movement of chefs and sous chefs thankfully are frequent in the modern-day interdisciplinary world of science. Nonetheless, such differences in style helped set the table for the human genome banquet and for its critics. The project, which coalesced in the mid-
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that experts promise will be reduced as new technologies come into play. In support of these efforts, the National Institutes of Health (NIH) and the Department of Energy have become the two lead federal agencies behind U.S. efforts in the genome field, with the National Science Foundation and U.S. Department of Agriculture supporting projects on model organisms and agriculturally important species, respectively. Thus, the U.S. government now sponsors a substantial human genome project, with annual federal expenditures across different departments and agencies somewhere near $200 million. Although smaller in size, efforts also are under way in Europe and Japan. From the outset, the human genome project has kindled controversies. A readable account of the Among insiders, the burning issue was beginnings of the federally usually what federal agency would do which part of the project, how it would fiinded genome project, the be funded, and who would receive that Among outsiders who are bipeople who devised it, and support. ologists, the issue often has been why the disputes that don't end do it at all, or why now at such a cost and at such a risk to other less expensive but more diversified (and arguably "The Human Blueprint," by Robert more imaginative) research. Among Shapiro, St. Martin's Press, 175 Fifth outsiders who watch over biologists, Ave., New York, N.Y. 10010, 1991, 412 the issues often are framed in what are now familiar ethical terms: How will pages, $24.95 factions in society use—or abuse—this promised encyclopedia of human ge1980s, aims to learn first where the full netic information? Although the genome controversies set of human genes is located along the 23 pairs of human chromosomes and more or less continuously change then to determine the full sequence of shape and direction, they never seem human DNA. For a variety of reasons, to abate. Late in 1991, for example, the federal project also promises to do NIH investigator Craig Venter moved the same for other organisms—some of to the head table of notoriety when he them simple, including several model filed a remarkable set of patent applicaviruses, bacteria, and yeast; and others tions covering a wide range of partial more complex, including nematodes, DNA sequences from the human genome. Headlines read: "NIH Researchvarious plant species, and mice. Even if the genome research effort er Patenting Human Genes/' Venter was restricted to the 3 billion nucle- quickly was labeled as a renegade by otide base pairs in human DNA, which many leaders within the genome it won't be, a colossal amount of work project, including James Watson, codisand money will be required to com- coverer of the double helix structure of plete the project. According to current DNA and, at that time, director of the rough estimates, sequencing costs Human Genome Center at NIH. Within months, the tables turned about $1.00 per base pair, or $3 billion for the whole human genome, a figure again. Watson was forced to resign his
•
NIH post—purportedly because cer tain of his investments represented po tential conflicts of interest, but more likely because he disagreed volubly with NIH director Bernadine Healy on this matter. Venter is being champi oned by Watson's former bosses at NIH as well as by others there who are charged with transferring technology from the public to the private sector. Meanwhile, ethicists say they are ap palled at the prospect of NIH's capital izing on human genetic sequences. In taking this position, they have forged an unusual alliance with a group of patent attorneys, who argue that this patenting effort is an ill-advised at tempt to control the means of making discoveries instead of the discoveries themselves. However, the possibilities of human gene patents leading to prof its has revived the interests of venture capitalists in the genome project. Some of them doubtless are already dream ing of worldwide genome franchises. Although the Venter patenting con troversy is too fresh to have found a way into Shapiro's account, the book is chock-full of other recent instances of similar caliber, and he does a good job of providing the background and con text in which these issues arose. For example, Shapiro takes good ad vantage of personal interviews with some of the principals, including Wat son, Walter Gilbert, Fred Sanger, Charles Cantor, and Nancy Wexler. His conversations with and descriptions of these actors in the genome drama are vivid, entertaining, informative, and reasonably accurate. To understand the impetus behind the genome project, it helps a great deal to appreciate the characters who have helped propel it. As a group, they are awash with intel ligence, foibles, egos, and hubris. Sha piro presents a fair sampling in "The Human Blueprint." Perhaps one of Shapiro's most pro vocative contributions comes in Chap ter 12, "A Public Undertaking." Here he usefully summarizes many of the viewpoints argued among leading par ticipants over whether the genome project should go forward at all. Sha piro emerges as an undeniable partisan for the project. But he does not try to disguise his own beliefs and how they were derived, and he is fair in repre senting the views of others. Shapiro's candor extends to his vision of the future and how he thinks that ge
nome information and, eventually, ge netic therapies may serve to refine hu man culture. Here again, his views are extraordinarily optimistic. Although he describes the potential obstacles to that future with fairness and clarity, ulti mately he seems to overcome them for himself on the basis of hope rather than an analysis of human history. "By applying our consciousness to evolution, we should be able to make our position and that of life, in general, not only more secure, but ultimately
much better," Shapiro writes near the end of his book. For that vision to take shape, surely humankind will need to learn a good deal more than the ar rangement of genes and aggregate se quence of its DNA bases—the main in sights that the leaders of the genome project expect to deliver. Jeffrey L. Fox, a free-lance science writer based in Washington, O.C., is current topics and features editor for ASM News of the American Society for Microbiology and a contributing editor to Bio/Technology. •
Powder Technology Handbook. Koichi Iinoya, Keishi Gotoh, Ko Higashitani, editors, xi + 794 pages. Marcel Dekker, 270 Madison Ave., New York, N.Y. 10016. 1991. $150 U.S. & Canada, $180 elsewhere.
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Practical Fluorescence. 2nd Ed. George G. Guilbault, editor, χ + 812 pages. Marcel Dekker, 270 Madison Ave., New York, N.Y. 10016. 1991. $185 U.S. & Canada, $222 elsewhere. Principles of Environmental Toxicology. Sigmund F. Zakrzewski. xiii + 270 pages. American Chemical Society, 1155—16th St., N.W., Washington, D.C. 20036. 1991. $59.95 hardback, $44.95 paperback. Protective Groups in Organic Synthesis. 2nd Ed. Theodora W. Greene, Peter G. M. Wuts. xvi + 473 pages. John Wiley & Sons, 605 Third Ave., New York, N.Y. 10016. 1991. $59.95. Protein Immobilization: Fundamentals and Applications. Richard F. Taylor, editor, χ + 377 pages. Marcel Dekker, 270 Madison Ave., New York, N.Y. 10016. 1991. $110 U.S. & Canada, $126 elsewhere. Purification and Analysis of Recombi nant Proteins. Ramnath Seetharam, Satish K. Sharma, editors, xiv + 314 pages. Marcel Dekker, 270 Madison Ave., New York, N.Y. 10016. 1991. $99.75 U.S. & Canada, $114.50 else where. Safety of Chemical Batch Reactors and Storage Tanks. A. Benuzzi, J. M. Zaldivar, editors. 439 pages. Kluwer Aca demic Publishers, 101 Philip Dr., Assinippi Park, Norwell, Mass. 02061.1991. $144, £74.
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Transition Metal Nuclear Magnetic Resonance. Studies in Inorganic Chemistry. Vol. 13. P. S. Pregosin, editor. 364 pages. Elsevier Science Publishing Co., P.O. Box 882, Madison Square Station, New York, N.Y. 10159. 1991. $169.
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