The Genetic Labyrinth : A GLOBAL EFFORT TO IDENTIFY EVERY GENE IN THE HUMAN BODY COULD REVOLUTIONIZE MEDICINE. IT COULD ALSO CREATE A CLASS OF GENETIC OUTCASTS.

WHAT MAKES US HUMAN INSTEAD OF, SAY, CHIMPANZEES? What are our physical possibilities and our limits as a species? Can we “perfect” our children? And do we want to? Those questions--as much for philosophers as for scientists--have taken on a greater urgency since the late 1980s, when scientists launched the Human Genome Project--a multibillion-dollar effort to obtain the genetic information hidden in every human cell.

The task is enormous: The human genome contains between 50,000 and 100,000 genes. These genes are distributed in varying numbers through the cores of 23 pairs of different chromosomes housed in the nucleus of virtually every human cell. Genes are strands of deoxyribonucleic acid--DNA--that wind in a double helix, a spiraling ladder whose sides are joined by rungs of chemicals called nucleotides. The order in which the nucleotides appear determines the information carried by DNA--the information that translates into the human form and, more specifically, into blue eyes or tallness or predisposition to a particular disease. Biologists calculate that the human genome contains about 3 billion nucleotide pairs. The genome project will first determine which chromosome holds which genes, and then specify where each gene is located on its home chromosome. Scientists will then figure out the sequence, the order of occurrence, of all the nucleotides in human DNA.

In the United States, the genome project is funded--with a total of $164 million in 1992--by two federal agencies, the National Institutes of Health and the Department of Energy. With work proceeding at dozens of laboratories across the country and in Japan and Europe, researchers hope to complete their basic task by 2005. Although some critics consider that timetable overly optimistic, innovations in genome mapping and sequencing are occurring rapidly enough to expect an enormous amount of information about the human genome by the early 21st Century.

But such information can be gravely misused, with far-reaching and costly implications for consumers, employers and insurers. And research will undoubtedly continue to yield interpretations that may be wrong, misapplied, socially volatile or, if the history of eugenics is any guide, all three.

The basic idea of eugenics was to improve human stock by increasing the number of supposedly desirable human beings (“positive” eugenics) and getting rid of “undesirable” ones (“negative” eugenics). In Nazi Germany, the eugenics movement prompted the state to sterilize several hundred thousand people and helped lead, by equating undesirability with the ethnicity and religion of Jews and others, to the death camps. In the United States, a 1926 American Eugenics Society exhibit included a board on which a light flashed every 15 seconds. With every flash, it explained, $100 of the observers’ money went for the care of people with “bad heredity.” The presentation implied that sterilizing people with deleterious genes would not only benefit the gene pool but reduce governments spending on institutions for the mentally deficient and physically disabled or diseased. The reasoning took hold. Many states enacted sterilization laws, most notably California, where 6,255 people had been sterilized by 1929--twice the number in all other states combined. (A 1942 Supreme Court ruling overturned most such laws, including California’s.)

The shadow of eugenics hangs over the Human Genome Project. Some commentators have suggested that the project may stimulate governments to try positive eugenics--to use genetic engineering to foster or enhance skills in science, math, music, even athletics. Others have warned that the project will more likely spark a revival of negative eugenics.

Economics could easily prompt us to develop such programs, they fear. Today, as health care becomes a public responsibility, funded through taxes, and as the cost escalates, taxpayers may ultimately rebel against paying for the care of those whose genes doom them to severe disease or disability. Governments and institutions may feel pressure to encourage, or even to compel, people not to bring genetically disadvantaged children into the world--not for the sake of the gene pool but in the interest of keeping public health costs down.

In recent years, several governments have developed crude eugenics policies. In 1988, China’s Gansu province adopted a eugenics law, since enacted more widely, aimed at improving “population quality” by banning the marriages of mentally retarded people unless they first submitted to sterilization. As the official newspaper Peasants Daily explained: “Idiots produce idiots.”

But genetic scientists know that “idiots” do not necessarily give birth to “idiots” and that mental retardation may arise for reasons not connected to genetics. And political scientists know that reproductive freedom is much more easily curtailed in dictatorships than in democracies. The institutions of political democracy may not have been robust enough to stop the early eugenics movement’s attempts to violate civil liberties, but they did contest them effectively in many places. Britain refused to pass eugenic sterilization laws. So did many U. S. states, and in a number where such laws were enacted, they often were not enforced.

Contemporary democracies are unlikely to embrace eugenics because they contain powerful anti-eugenics constituencies. Most geneticists, and the public, aware of the cruelties of past state-sponsored eugenics, tend to oppose such programs. And although prejudice continues against the ailing and the disabled, today they are politically empowered to a degree that they were not in the early 20th Century. They may not have enough power to counter all quasi-eugenic threats, but with allies in the media, the medical profession and in such quarters as the Roman Catholic Church (long a foe of eugenics), they are politically positioned to block or at least hinder eugenic proposals that might affect them.

With the advance of human genetics and biotechnology, we can try a kind of “homemade eugenics,” to use the insightful term of New Republic commentator Robert Wright--”individual families deciding what kinds of kids they want to have.” Parents can now choose not to have children with certain disabilities or diseases, such as Down’s syndrome or Tay-Sachs. And in the future, they might, via genetic analysis of eggs fertilized in a test tube, choose to have babies that are superior in some sense to those they might have conceived without scientific intervention. If, for example, a cluster of genes for tallness is identified, scientists could check each of the growing eggs for the cluster and implant one that possesses it into the womb of a mother who wants a child with a better chance of becoming a basketball star.

It is quite possible that people will exploit such possibilities, given the interest that some parents have shown in choosing the sex of their child. Further, a 1989 report to the European Parliament on a proposal for a genome project there noted widespread pressure from families for “individual eugenic choice in order to give one’s own child the best possible start.”

Genetic enhancement would inevitably involve manipulating human embryos, and for better or for worse, human-embryo research is restricted in federally funded research programs and powerfully opposed in virtually all the major Western democracies, especially by Roman Catholics. In an effort to frame debate on the issue, a committee of the European Parliament urged in 1989 that genetic analysis “must on no account be used for the scientifically dubious and politically unacceptable purpose of ‘positively improving’ the population’s gene pool,” and called for “an absolute ban on all experiments designed to reorganize on an arbitrary basis the genetic makeup of humans.”

But genetic improvement is not likely to yield to human effort for some time. While the Human Genome Project will undoubtedly make it easier to identify genes for physical and medically related traits, it will not soon reveal how genes contribute to forming the qualities--particularly talent, creativity, behavior, appearance--that the world so much wants and admires. It’s preposterous to think that genetic knowledge will soon permit us to engineer Einsteins.

The prospect and possibilities of human genetic engineering tantalize us, of course, even if they are still the stuff of science fiction. But the near-term ethical challenges of the Human Genome Project come not from private forays into genetic improvement or state eugenics programs, but from something the project will produce in abundance: genetic information. How will we control the spread and use of that information in a market economy? The prospects are deeply troubling.

Many individuals and families already seek genetic counseling before deciding to conceive, but what happens if post-conception tests show that the fetus has lost the roll of the genetic dice? The pregnant couple then faces the only therapeutic choice available at the moment--to abort or not abort. And these tests can be faulty. In 1991, the test for whether an individual is a carrier of the recessive cystic fibrosis gene, for example, was only 75% reliable--it detected the gene in only three out of four of the people who carried it. So, it revealed only 56% (that’s 75% of 75%) of the couples who were truly at risk for bearing a child with the disease.

As technology allows us to pinpoint the genetic causes of more diseases, more people will be drawn, often involuntarily, into the testing network. The potential market for genetic carrier screening and prenatal testing is enormous, said Benjamin S. Wilfond and Norman Fost, both physicians and medical ethicists, in a 1990 article in the Journal of the American Medical Assn. As many as 2.8 million people may be tested each year to learn if they carry recessive genes for cystic fibrosis, they estimated. Many more could be tested for such disorders as sickle-cell anemia, hemophilia and muscular dystrophy. Genetic testing can also let people know that they or their newly conceived children are safe from some specific genetic doom, and in that sense it can be liberating. After tests revealed that she did not carry the Huntington’s gene, one young woman told Joseph Bishop and Michael Waldholz in their book “Genome” that, “after 28 years of not knowing, it’s like being released from prison. . . . To have hope for the future . . . to be able to see my grandchildren.” (Huntington’s usually begins to afflict people in their late 30s, causing mental and physical deterioration and death within 15 to 25 years.)

The torrent of new human genetic information will undoubtedly challenge many socioeconomic values and practices. Employers and medical or life insurers may request the genetic profiles of prospective employees or clients. Employers might wish to identify workers likely to contract disorders that affect job performance or that might be brought on by workplace conditions. Both employers and insurers might want to identify likely victims of diseases that result in costly medical or disability payouts. Employers could use the information to assign susceptible people to risk-free duties or environments--but they might also use it to deny them jobs, just as medical or life insurers might exploit it to exclude them from coverage. Whatever the purpose, genetic identification would brand people with what one American labor union official has called a “genetic scarlet letter” or what some Europeans term a “genetic passport.”

We’ve already seen abuses of genetic information. Around 1970, a fear spread that people with sickle-cell trait--those who possess one of the recessive genes for the disease--might suffer damage to their red blood cells in the reduced oxygen of high altitudes. Such people, the overwhelming majority of whom are black, were prohibited from entering the Air Force Academy, restricted to ground jobs by several major commercial air carriers and often charged higher insurance premiums. More recently, a couple whose first child suffers from cystic fibrosis conceived again and sought to have their fetus tested for the disease. Their insurer agreed to pay for the test--so long as the mother would abort the child if the results were positive. Otherwise, the company would cancel the family’s health plan. (The firm relented--after being threatened with a lawsuit.)

Much of the genetic discrimination so far has been arbitrary, callous and, especially on the job, a product of ignorance. A recent Harvard Medical School survey turned up about 93 instances of genetic discrimination. People with inherited biochemical disorders were denied insurance even though they had been successfully treated and were not ill. An auto insurer refused to cover a man with a genetically based neuromuscular disorder who suffered no disability, and an employer declined to hire a woman after she revealed that she had the same disorder. The study was not designed to determine whether these agencies “have active policies of genetic discrimination,” noted Paul Billings, one of the survey authors and a medical geneticist now at the California Pacific Medical Center in San Francisco, but, he added, the findings “suggest that such policies exist.”

Perhaps, say some commentators, employers and insurers ought to be barred from nosing into anybody’s genome passport. Last year, the California Legislature passed a bill banning employers, health service agencies and disability insurers from withholding jobs or protection simply because a person is at genetic risk for a given disease or disability. Gov. Pete Wilson vetoed the measure, but even if similar laws are enacted in California or elsewhere, insurers could sidestep their prohibitions by setting high common rates and offering discounts to clients with healthy genetic profiles, which such clients would, of course, submit voluntarily. Insurers have a natural interest in information that bears on risk. To them, rate discrimination based on genuine knowledge of risk is neither arbitrary nor illegitimate: It is sound business practice.

The insurance industry’s position is made clear in a 1989 study circulated by the American Council of Life Insurance. If insurers were unable to use genetic tests because of laws requiring that risks be classified on the basis of factors that people can control, wrote Robert Pokorski, one of the study’s contributors, “then equity would give way to equality (equal premiums regardless of risk) and private insurance as it is known today might well cease to exist.”

Industry representatives say that equalizing premiums would hurt not only insurance providers but also their customers. If a client has a high genetic medical risk not reflected in her premiums, then she would receive a high payout at low cost to herself but a high cost to the company. The company would have to pass its increased costs along to other customers, thus forcing low-risk policyholders to subsidize high-risk ones.

To prevent that, insurance companies want to know as much about their clients as their clients know about themselves. They may also decide to go further and require genetic testing so they can tailor rates to risk. The industry expects consumers to resist. “It seems unavoidable that there will be lots of legal battles as this technology unfolds,” says Rob Bier, the managing director of communications for the American Council of Life Insurance. “The insurance industry actually wishes genetic testing had never been developed.”

The legal battles could grow more heated as the Human Genome Project accumulates more data. As we better understand the links between genetics and disease, companies may be able to determine an individual’s risk to the point where risk becomes certainty and lifetime medical costs can be exactly calculated. In those cases, medical insurance premiums would amount to payment for lifetime medical care on the layaway plan.

Alternatively, the more we learn about the human genome, the more will it become obvious that everyone is susceptible to some kind of genetic disease or disability; everyone carries some genetic load and is likely to fall ill in one way or another. Of course, the cost and severity of the illnesses will vary, but if everybody were aware of their genetic jeopardy, we might well see more interest in a risk-rating system that expresses what the Europeans call solidarity. In Europe, according to G. W. de Wit, a professor of insurance economics at Erasmus University in the Netherlands, if parents with a genetically diseased fetus choose to have the child, “all medical expenses for that child will be borne by the insurer. It seems fully justified to have the other policyholders contribute (solidarity),” he said in a paper delivered at a human genome meeting in 1990, “because otherwise the free choice of the parents is jeopardized.” De Wit doubts that European insurers will demand genetic information.

Suggesting that it costs too much to provide care or coverage for those with genetically based disorders casts a shadow over people who suffer from them. Already, those who would abort a fetus with such afflictions have been attacked as stigmatizing the living who have those ailments. Barbara Faye Waxman, an activist for the disabled who herself has a neuromuscular impairment, was quoted in a New York Times article as criticizing her fellow workers in a Los Angeles Planned Parenthood clinic for displaying “a strong eugenics mentality that exhibited disdain, discomfort and ignorance toward disabled babies.”

Some advocates for the disabled have joined the anti-abortion movement. But it seems to make little sense to try to preserve the dignity of one group by limiting the reproductive freedom of another. We’d do better to recognize that values of social decency compel us to live with conflicting principles: We can endorse using genetic information in personal reproductive choices while upholding the rights and dignity of the diseased and disabled.

There are many ways people with purported genetic disorders have been demeaned, but the most reckless have involved claims linking genes and behavior. The early eugenics movement declared immigrant groups from eastern and southern Europe to be biologically inferior in intelligence and inclined to criminality, alcoholism, prostitution and the like. Eugenic science then was obviously riddled with social prejudice, but even purified of bias and vagueness, behavioral genetics poses difficult problems. Not only must we distinguish between nurture and nature but, equally important, we need to define behavioral traits, measure them, and recognize spurious correlations. Typical of dubious behavioral genetics is a 1990 study co-authored by the Harvard psychologist Jerome Kagan, who reported that among a group of 379 students, those who suffered hay fever also scored high on a shyness index. “We think there is a small group of people who inherit a set of genes that predispose them to hay fever and shyness,” Kagan said.

Finding the genetic origins of human behavior is a legitimate goal, but it is also socially and scientifically treacherous. In recent years, for example, several family studies reported the discovery of specific genetic susceptibilities to manic depression and schizophrenia, but follow-up studies failed to confirm the findings.

Personality traits are so hard to specify and explain that we need to use considerable caution in spreading the claims of behavioral genetics, yet such caution has tended to be lacking in the media. It was Page 1 news in April, 1990, when researchers at UCLA and in Texas jointly announced that, having examined the brains of only 70 corpses--half of them severe alcoholics, half of them not--they had detected a gene for alcoholism. But it was Page 10 news in the New York Times when, eight months later, scientists at the National Institutes of Health reported that they could not confirm the UCLA/Texas results. Reporters often take as firm conclusions what scientists announce as tentative conclusions, and scientists encourage the process when they hold press conferences to proclaim attention-getting findings--however fragile they may be--linking genes to behavior.

The fears that the genome project will foster a drive to produce superbabies or to callously eliminate the unfit are grossly exaggerated. They also divert attention from the scientific and social issues that the project actually raises--particularly how human genetic information should be used by geneticists, the media, insurers, employers and government. Clearly, we can use our new knowledge to help reduce human suffering, but one thing is equally clear: We cannot allow ourselves, as West Virginia Rep. Bob Wise noted at a 1991 hearing on the issue, “to create a new genetic underclass.”