Ellen spent four years getting her PhD in industrial and chemical engineering. Now, wincing as a company doctor drew a few drops of blood for her preemployment physical, she could hardly contain her excitement about the job she'd been offered at one of the country's foremost metallurgical research institutes. Two days later the phone call came. You are perfectly healthy, the young doctor said. But tests have revealed you harbor a gene that can result in decreased levels of a blood enzyme, glucose-6-phosphate dehydrogenase. Without the enzyme's protection, you have a slightly increased risk of developing a red blood cell disease if you come into contact with certain chemicals in our laboratory. I'm sorry, he said. The job has been offered to someone else. When Frank married at 31, he decided to take out life insurance. A swimmer and avid racquetball player with no previous hospitalizations, he felt certain that his premiums would be low. Weeks later, after a routine physical exam, he was shocked by the insurance company's response. Sophisticated DNA testing had revealed in Frank's tissues a single missing copy of a so-called RB anti-oncogene and minor variations in two other genes. Computer analysis showed the molecular misprints more than tripled his risk of getting small-cell lung cancer by age 55. His application was rejected. These notes from the future illustrate a potential dark side of the biomedical present. The case histories are hypothetical. But the tests already exist -- and so does the threat of genetic discrimination. The recent revolution in molecular biology and genetics heralds a new age in medical science. Ongoing efforts to create a map of the entire human genome -- the DNA blueprint of heritable traits contained in every cell -- promises an ever-widening range of diagnostic and therapeutic benefits. And just last month, scientists received the first U.S. approval to inject genetically engineered cells into human patients. Researchers see the procedure as a forerunner of pending "gene therapy" experiments that may permanently reverse genetic abnormalities. Biochemical cartographers have already located more than 400 genetic "markers," or signposts of genetic diseases, on all 46 human chromosomes. They have mapped the exact or approximate locations of genes responsible for muscular dystrophy, Huntington's disease, some psychiatric disorders and a variety of cancers. But as scientists learn to read the molecular fine print of the genome -- and to interpret and correct the typographical errors that can predestine an individual's medical fate -- others express concern about potential abuse of this technology. Two weeks ago, citing the need for a more complete review of the social and ethical implications of genetic research, activist Jeremy Rifkin turned to the courts to halt the first U.S. human gene-transfer experiments. Rifkin announced the suit during the January 30 meeting of the NIH's Recombinant DNA Advisory Committee, which advises the NIH on matters relating to genetic engineering. He attended the meeting with leaders of advocacy groups for the disabled, including Evan Kemp Jr., commissioner of the U.S. Equal Opportunity Commission. "I'm concerned that as technology and as different cures become available there will be immense pressure on myself and my peers to undergo different forms of treatment," said Deborah Kaplan of the Berkeley, Calif.-based World Institute on Disability. "I'm concerned about social pressure, family pressure, pressure from the medical community and real pressure from the insurance industry" to submit to genetic alterations, she told the committee. Whether or not such treatments are eventually devised, merely testing for genetic traits carries social and ethical risks, experts say. "There are two very broad questions: Who decides whether or not you'll get a test and what happens to that information," says Thomas H. Murray, director of the Center for Biomedical Ethics at Case Western Reserve University. "Clearly there are going to be these tests. The question is how are we going to use them and what social limit we're going to put on them." The Enemy Within Although testing practices are not yet well established, neither are regulations governing their use. Eventually policy-makers may have to confront an apparent discrepancy between the reality of genetic variability and the democratic ideal that all citizens are "created equal." The issue cuts through existing social mores and legal precedents, encompassing a body of information the framers of constitutional and early statutory protections could never have envisioned. "Each new (genetic) test is going to raise slightly different ethical questions," says Murray. These questions, which relate to the overall balance between an individual's rights and those of an employer or insurer, are not new. But as scientists refine their understanding of the more than 3,000 diseases known to have genetic components, the questions "are going to come at us much faster," Murray says. The Constitution protects citizens from government-inflicted discrimination based on immutable characteristics such as race. And to the extent the Supreme Court has ruled on the issue, federal discrimination on the basis of one's genome would appear equally precluded. "If it's the government that wants the information for whatever reason, there are all sorts of constitutional issues that arise," says Mark Rothstein, director of the Health Law Institute at the University of Houston. "The government would seemingly have to make a strong showing to gain access to one's genetic profile because it invades the individual's bodily integrity and privacy." However, says Lori B. Andrews of the American Bar Foundation in Chicago, "the Constitution protects people from the federal government and in some cases from the states, but it doesn't apply to private companies unless there is a specific statute dealing with the issue." "There may be a variety of reasons why an employer may want some of this information, and the legal issues are very unsettled as to whether the employer could make participation {in genetic screening} a valid condition of employment," Rothstein says. A 1982 survey by the Office of Technology Assessment found that only six of 366 responding companies used genetic tests on applicants or employees. Those companies tested for genetic susceptibility to environmental or occupational hazards associated with the workplace. But another 55 companies stated they might begin genetic testing within the next five years. A 1988 OTA report, "Biology, Medicine and the Bill of Rights," says "little is known about whether the incidence of genetic screening has increased in the last five years." But other sources suggest such a trend is a near-certainty in coming years. Sharing the Risk "Employers are obviously worried about health insurance and health-care costs," says Lawrence Miike, a project director at OTA. "My guess is that a lot of employers, if they had no restraints on them, would obviously want to do some kind of testing for increased probability for disease." In her book, "Medical Genetics: A Legal Frontier," Andrews cites studies indicating that industrial physicians sometimes reject job applicants with mild diseases that have no effect on job performance. "Employment discrimination against people with potential health problems has been widespread and is likely to further increase," she writes. "The availability of genetic diagnostic technologies now raises questions about whether laws should be passed protecting people against genetic discrimination by private entities." She concedes that genetic tests may someday prove a legitimate means of screening out some workers with health-endangering sensitivities to particular workplace conditions. But, Andrews warns, today's genetic profiles do little to assure an employer that the best person has been hired -- especially when, given our incomplete understanding of genetics, job applicants at even higher risk may well be hired simply because their particular genetic weaknesses have not yet been mapped. Andrews and others also express concern that employers may simply filter out all but the most genetically hardy applicants rather than cleaning up an otherwise unhealthy workplace. Gene mapping and testing "could challenge or overturn a lot of our traditional legal notions about the role of such things as occupational health and safety laws," Andrews says. Rothstein notes another interesting twist: Employers, while free to hire the most capable applicant, cannot discriminate against the handicapped. "It remains to be seen whether an individual who is currently healthy and asymptomatic but has an atypical genetic trait might not be covered under the definition of handicapped under state or federal law," he says. Insurance companies, too, have a substantial financial stake in knowing an individual's propensity for illness or early death. Already some insurers are under fire for requiring AIDS-antibody tests as part of their underwriting procedure. While AIDS testing falls short of screening one's genetic profile, it differs from standard blood tests in revealing an individual's exposure to a virus that years later may cause disease. Some states -- led by California -- have made it illegal for insurance companies to require AIDS tests. So some insurance companies now require specialized white blood cell counts that provide indirect evidence of AIDS infection. "This gives a clue as to what's going to happen in the area of genetics and how hard it is to prohibit the acquiring of information," Rothstein says. "Maybe you can ban the use of genetic information, but it's hard to prohibit people from getting information." Indeed, Andrews suggests, "increasingly sophisticated genetic diagnostic tests may force a total rethinking of the concept of health insurance." She notes that insurance companies already exclude from their coverage -- or at best charge extra for -- health-care costs associated with preexisting disorders. If one's genome becomes recognized as a preexisting template for future disease, genetic predispositions may be excluded from coverage. Moreover, as insurance companies learn to make more detailed assessments of an individual's particular health risks, premiums will probably become prohibitively expensive for the most at-risk individuals. "Insurance will thus lose its social value as a means of spreading risk across groups," she concludes, adding that the apparent injustice of that situation "will provide the impetus for the development of a national health system." "The ramifications for the insurance industry are just startling," Rothstein says. "I can see 20 or 30 years from now that life insurance policies will be essentially accident policies, because everything else is foreseeable. The essence of insurance is you assess a risk against the unknown. If there's no medical unknown, the only unknown is whether you're going to get hit by a bus, right?" The Selection Factor Meanwhile, underwriters are frightened by the prospect of individuals performing genetic analyses on themselves -- and keeping the results secret. The home-diagnostics market in the United States already boasts more than 60 do-it-yourself kits for detecting such conditions as pregnancy and indirect evidence of colon cancer. Home testing for DNA markers could amplify the effect of the insurance industry's arch nemesis -- "adverse selection." Adverse selection refers to the probability that people privately aware of a medical problem are more likely to seek medical insurance. That, insurers say, can result in their insuring too many high-risk individuals, thus throwing off the statistical tables upon which they base their charges. Today, OTA's Miike says, most home tests monitor chronic conditions, such as blood sugar levels in diabetics. "But I think it's eventually going to cause a lot of problems, and I think that it will be an additional pressure on the insurers. For example, there's an HIV (AIDS antibody) spot test now that, even though it's not supposed to be used by consumers, is pretty simple to use." Still, he notes, genetic tests are "a little more complicated, because genetic disease seems to depend mostly on a combination of factors rather than any one thing. So those tests are less likely to be done so easily or as cheaply on a mass scale." In the long run, it will fall upon legislators and the courts to codify the proper use of genetic information. In "Medical Genetics," Andrews writes that "The legal scheme created to handle genetics will also create the blueprint for a particular type of society." At one extreme, she says, "we could take an approach that would take us back to feudal times where you're born into your occupation and that type of thing." Or "we could take a more 'individual rights' approach where people could use this information individually to make better decisions about things like where they should live and work."