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LIFE SCRIPT: How the Human Genome Discoveries Will Transform Medicine and Enhance Your Health.

LIFE SCRIPT: How the Human Genome Discoveries Will Transform Medicine and Enhance Your Health by Nicholas Wade Simon & Schuster, $24.00

TO HEAR NICHOLAS WADE TELL IT, June 26, 2000, marked "the beginning of a new era of medicine." That was the day President Bill Clinton, speaking in the East Room of the White House, announced that biologists had completed a first survey of the 3 billion DNA letters, or sequences, that define the human genome. Clinton compared this accomplishment to "learning the language in which God created life." Wade, with only slightly less rhetorical flourish, assures us that the sequencing of the human genome "provides the basis on which to understand the human body almost as fully and precisely as an engineer understands a machine."

From that understanding, Wade continues, "physicians can hope to develop new ways to fix the human machine and in time to correct most--perhaps almost all--of its defects" Before long, these future fixes might even allow humans to become "effectively immortal," he concludes, speculating that people endowed with such potential might want to separate themselves from lesser beings by establishing a society of Methuselahs on Mars.

If you've just returned from a long visit to Mars, you might be shocked to find a journeyman science writer and editor for The New York Times carrying on with such sci-fi themes. But Wade is hardly alone in his estimation of how profoundly the revolution in genetics will affect the practice of medicine. Controversies rage over who owns the information contained in the human genome, and over the ethics of cloning, gene-therapy trials, and most recently embryonic stem-cell research. But implicit in all these debates is a widespread assumption that genetic research holds the potential not only to produce miracle cures for major diseases, but to prolong the human life span significantly, if not indefinitely. From President Bush, who promises to fund a "medical moon-shot" (even at the expense of federal investment in physics and space exploration) to the man in the street, who hears each day that biologists have discovered a "gene for breast cancer," or a "gene for shyness," the conviction grows throughout the culture that genetics hold the ultimate explanation for most human afflictions, whether physical or mental. Would that it were true.

For those who have failed to keep up with their newspapers, Life Script provides a useful and up-to-date survey of the biomedical headlines you may have missed in recent years. Early chapters rehash the colorful clash between James D. Watson of the National Institutes of Health's Human Genome Project, and J. Craig Venter, the National Institute of Health (NIH) scientist who broke away to undertake his own privately funded quest to map the human genome. Later, Wade introduces us to various figures celebrated for their efforts to create bioengineered drugs, or for their claims to have isolated a genetic basis for diseases such as Alzheimer's or diabetes, or for their success in using stem cells to grow new organ tissue in animals. Wade often writes at a level of detail that presupposes the reader has at least minored in biology, but even those who don't know an SNP from an allele will be able to tough it out. (In a bibliographical essay, Wade helpfully suggests obtaining a copy of the college textbook, The Molecular Biology of the Cell.)

Readers should be aware, however, that Life Script is a deeply misleading book, not in what it reports about recent developments in genetics, but in its neglect of the bigger picture. Despite all the hype surrounding the "completion" of the Human Genome Project, many biologists are disappointed by its results, and there is a deepening suspicion that gene sequences by themselves explain very little about why we get sick and ultimately die. As Harvard biologist Richard Lewontin has recently written, "Now that we have the complete sequence of the human genome, we do not, alas, know anything more than we did before about what it is to be human."

Lewontin isn't making the obvious observation that genetic research can never give us the meaning of life or an understanding of the soul. His thoroughly materialistic point is that the human body isn't programmed by any simple code. Rather, it is a complex adaptive system that both influences, and is influenced by, its surrounding environment on many different scales. If you want to make accurate predictions about how such a body will fare in this world, or intervene meaningfully in extending its life, you're far better off paying attention to what it eats, the cleanliness of the air it breathes, how often it exercises, and even to what indignities it must suffer at the hands of other humans, than you are paying attention to its genes.

As yet, the study of DNA sequences has not led to the cure of a single human disease. Better understanding of genetics has led to the creation of some useful new drugs, such as Herceptin, used to fight some forms of breast cancer, and Glivec, which when used in combination with other drugs, may prove a significant advance in treating one form of leukemia. But gene-based cures for major diseases remain well beyond the horizon, and there are strong theoretical and empirical reasons to believe that they always will. Indeed, genetic determinism is becoming, in the words of the eminent molecular biologist Richard Strohman, "a failing paradigm in biology and medicine."

The more scientists learn about the surprisingly limited amount of information contained within the human genome itself--and its remarkable lack of diversity among individuals--the more it becomes evident how much forces other than genes determine human health. These include everything from the mysterious processes that determine how proteins combine with proteins within the body to global-scale environmental and cultural factors. Trying to explain how the body works by looking only at its genome is like trying to decipher the news in this morning's New York Times by focusing on the sequence of molecules arranged on each page. Perhaps this exercise Would be worth doing for its own sake. And one day it might even lead to a better understanding of how to make print easier to read or some other practical end. But if one's purpose is to understand the meaning of today's New York Times, and to be able to make some useful predictions about what will be in tomorrow's paper (including how the molecules in tomorrow's paper will be arranged) it would be far more effective to shift the scale of perspective and map the code of the English language, while at the same time studying history, politics, sociology, etc.

Perhaps the most startling conclusion of the human genome project was the discovery that humans have only about 32,000 genes, which is only about 75 percent more than a nematode worm has, and only 25 percent more than a milkweed. This in itself suggests that the vast differences between humans and milkweeds must be caused by far more than what we can see in their differing genomes. But it also forces the question of how much of a role these 32,000 human genes by themselves can play in determining the organization and operation of the body. As the evolutionary biologist Paul R. Ehrlich points out, human beings have more than 1 trillion nerve cells with as many as 1,000 trillion connections, or synapses, between them. Even if each gene concerned itself solely with the nervous system, each gene would be responsible for the development of an average 3 billion synapses. Other, larger scale forces are obviously at work both within the body and without.

There are, to be sure, some diseases directly caused by specific genetic defects. For example, unless they die of something else first, all persons who have more than 40 repeats of cytosine-adenine-guanine on the short end of chromosome 4 will ultimately die of Huntington's Disease. Such a fate cannot be avoided by change of lifestyle or environment. At the same time, there is no way to contract Huntington's disease except by inheriting this specific gene defect. But true genetic diseases like Huntington's are exceedingly rare, accounting for only about 2 percent of all pathological conditions endured by humanity.

More common are diseases like breast cancer. There is a specific gene defect associated with the disease. But as Strohman points out, many women who carry this defect don't contract breast cancer, and of the 173,000 women who develop breast tumors each year, 95 percent don't carry the defect. Other diseases such as arteriosclerosis may involve as many as 500 genes. None of these genes plays a large role in causing hardening of the arteries, and what role they do play is largely affected by overall body chemistry and by other non-genetic factors such as a person's age, diet, and environment. Because so many non-genetic variables are involved in the diseases that cause the vast majority of human deaths, and because the body in many instances can compensate for specific genetic defects, genetic testing by itself rarely gives accurate predictions of who will get sick from what--a reality unchanged by knowing the complete sequence of the human genome.

Genes, far from determining the incidence and course of most diseases, increasingly appear to play bit roles in concert with other forces ranging in scale from the molecular to the global. The incidence of cancer and heart disease, for example, varies widely around the world, but that's far more attributable to differences in environmental, political, and cultural practices than to difference in genetic endowment, which are minimal among the races. When Third World migrants move to the United States, their susceptibility to cancer and heart disease usually goes up as they adopt the American lifestyle. And when "civilization" comes to the Third World (in the form of McDonalds' chains, belching automobiles, factories, cigarettes, and urban living) so do elevated rates of heart disease and cancer.

Or consider the startling difference in mortality between Utah and Nevada. The populations of these two contiguous states are hardly genetically diverse. Moreover, they are quite similar in their access to health care and average income. Yet infant mortality in Nevada is 40 percent higher than in Utah, and adult men and women in Nevada face a comparably increased chance of premature death. As the health-care economist Victor Fuchs has pointed out, it's hard not to attribute much of the difference to the fact that 70 percent of Utah's population follows the strictures of the Mormon Church, which instructs followers to abstain from tobacco and alcohol and avoid premarital sex and divorce. Nevada, with its freewheeling, laissez-faire culture, has the highest incidence of smoking-related death in the United States, and Utah the lowest. Culture and behavior, this example seems to suggest, are much more important to determining human lifespan than genetic endowment.

The point is a hard one, since most human beings, and especially Americans, would far prefer laboratory solutions to their health problems over solutions requiring wholesale changes in their lifestyles and governing institutions. So we throw money at NIH for molecular-level investigations of the human genome and hope, however naively, that this desperate investment can save us not only from consequences of our individual and collective vices, but from the aging process itself. Yet epidemiologists report that social and behavioral factors such as smoking, diet, alcohol use, and sedentary lifestyles contribute to half of all deaths in the United States, while poverty remains a health threat of incalculable toxicity. And though genetic interventions may one day help a few more people to put off the day they will die, it's unlikely society will ever be able to afford to grow enough replacement hearts, lungs, and other internal organs to make a significant difference in the health status of the population as a whole. With enough money and expertise, one can keep a 1961 Studebaker running indefinitely, too, but the cost of its operation will grow inexorably as time and entropy inevitably cause more and more parts to fail. Keeping the car going by replacing its clutch leaves the car with an elevated chance of being banged up when the brakes fail, and replacing the brakes creates an elevated chance of future transmission problems, and so on forever. At some point, it's time for a new car.

Wade is a journalist with a science beat, and there are few in the business who have covered the daily tick-tock of biomedical advances as well as he. But anyone writing a book on how the genetic revolution is likely to affect medicine needs to apply more skepticism than Wade does to the claims made by the various players in the biomedical-industrial complex, most of whom have deep incentives to exaggerate the promise of their research agendas as they seek to raise funds on Capitol Hill or Wall Street. Many other voices in science and medicine view those agendas as examples of naive reductionism and are calling for greater emphasis on the larger-scale forces that affect human health, from the social organization of medicine itself, to the cultural gene defects that program so many of us to self destruct before our time. At the most, mapping the genome will help us figure out more complex processes, but even most microbiologists would agree, at least when they're not up for an NIH grant, that the human body is nothing like a self-contained machine, and it has no simple blueprint. Wade's readers deserve to know that.

PHILLIP J. LONGMAN is a freelance writer based in Washington D.C.
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Title Annotation:Review
Publication:Washington Monthly
Article Type:Book Review
Date:Sep 1, 2001
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