Eight-year-old David Manikian has a mutant gene--a small bump on his X chromosome that makes him different from other boys. When he was just a toddler, his parents noticed he was slow to learn. The wonders of modern genetic research revealed that David has Fragile X syndrome, a genetic disorder that impairs mental development.
But modern genetics was as much a curse as a blessing for this little boy, his parents and three sisters. Although it was a comfort to know what was wrong, the same sophisticated blood test that identified David's condition cost this rural New Hampshire family their health insurance after a clerk stumbled across the test results in the boy's files two years ago.
David's mother, Jamie Stephenson, tried desperately to fight the cancellation. As a writer for a political science quarterly and the wife of a dentist, Stephenson knows a little about health care, and a lot about public policy. She bent the ears of anyone who would listen--her state's assistant insurance commissioner, a disability rights lawyer and a U.S. senator.
Fragile X is not a disease; it is a developmental disorder, she told them. Besides, no one else in the family was affected. Surely, she insisted, the insurance company could not do what it had done.
"Well," Stephenson recalled, "everybody I contacted who was in any position of power said: 'They can do this. Our hands are tied.' And then I was faced with the reality that we were not covered. And I had these four little children. We were without insurance for four months, four nail-biting months. It was summer. Every time I took my kids to the beach in the car, all I could think of was, if we had a car accident, we would lose our home."
The Manikian family finally got health insurance, but only after four companies turned them down. Their experience highlights what may become the bitterest irony of the DNA revolution: genetic discrimination.
If the Manikians were held hostage by heredity, they are not alone. Experts estimate that either as a result of sophisticated new genetic tests or a family history of inherited illness, thousands of Americans are being discriminated against because of something over which they have no control: their genes.
Many insurers, observers say, do not want to take the risk of covering someone who may require expensive medical treatment and are laying bare their genetic biases. So too are employers and adoption agencies. All of this is occurring in a legislative vacuum; because the issue is so fresh, only a few states have laws barring genetic discrimination.
And some predict that as genetic tests are developed for more diseases, the number of discrimination victims could explode in the not-too-distant future. As one bitterly complained: "Your credit history has more protection than your medical history."
* A Michigan market research analyst whose two brothers had colon cancer decided to have a colonoscopy--a test to see if she is at risk for the disease, which is known to run in families. Researchers recently pinpointed two genes that they believe cause the familial form of colon cancer. The woman was tested several times. Each test came back fine. But when she attempted to purchase health insurance, she was turned down--the fact that she had been tested at all was a red flag.
* A Louisiana couple had a child with cystic fibrosis, a potentially fatal genetic disorder that leads to chronic lung infections. When the wife became pregnant, prenatal testing revealed that the second baby carried a mutant gene associated with the disease. When the couple said they would have the baby anyway, their health maintenance organization told them it might not cover the pregnancy, and might also withdraw coverage for their first child. The couple threatened to sue; their coverage remained intact.
* An Arizona man was hired for a manufacturing job. During a physical examination, the company doctor asked about blood he spotted in the man's urine. The man said that years before, his family had been tested for Alport's syndrome, a genetic kidney disorder. Although he had been instructed to keep an eye on his blood pressure, he otherwise had no medical problems and was not sure if he had the disease. He lost his job.
* An Indiana woman who is at risk for Huntington's disease, a degenerative brain disorder, did not want to take the chance of passing on the Huntington's gene to another generation. She and her husband decided to adopt. They had completed counseling and were halfway through a pre-adoption home study when the agency they were working with asked them to withdraw because of her genetic history.
"Should I be judged by a disease that I am only at risk for and that may not develop for some years to come?" she wrote in angry response to a survey conducted by researchers studying genetic discrimination. "Does this make me any different than anyone with diabetes or cancer, for example, in their ancestry?"
Dr. Paul R. Billings, clinical geneticist in Palo Alto who collected these and other case histories, sees them as a troubling harbinger. Billings is one of a handful of geneticists who is studying genetic discrimination, particularly in health insurance. He has been outspoken, calling not only for health care reform but for laws to protect the privacy of genetic information.
His work has not endeared him to his fellow scientists.
"A lot of them hate me for it," he said. "It often gets portrayed that I am somehow trying to throw cold water on the explosion in genetic testing and genetic information, that I am trying to bring genetic research to a halt, which is complete bunk."
Genetic research is proceeding at such a rapid clip that it would be nearly impossible to bring it to a halt. Over the last decade, using sophisticated techniques that allow them to examine DNA, scientists are isolating new genes faster than anyone can say "deoxyribonucleic acid." Already, researchers have identified more than 5,000 genes linked to specific disorders. Over the last five years, more than 50 new tests for genetic conditions have been developed.
At the National Institutes of Health, the genetic equivalent of Christopher Columbus' voyage is under way as scientists race to map the entire genetic blueprint of the human body. The Human Genome Project, a 15-year, $3-billion effort, is set for completion in 2005.
The research holds great promise for diagnosing, averting--and, scientists hope, eventually curing--myriad inherited afflictions. Already, the magic of genetics is changing lives. The incidence of Tay-Sachs disease, a fatal brain disorder common among Ashkenazi Jews, has declined more than 90% since 1971, when genetic screening became available.
So far, more than 1 million people have taken tests for the disease, which occurs when both parents carry the Tay-Sachs gene and which usually kills children by age 3. Many couples have terminated pregnancies to avoid bearing Tay-Sachs babies. And in a novel program run by Orthodox Jews in Brooklyn and Israel, young people who are tested for the Tay-Sachs gene submit the results to a central registry. When they are dating or considering marriage, they can phone the registry to see if the match is compatible.
Thus far, most conditions for which genes have been identified are, like Tay-Sachs, Huntington's disease and Fragile X syndrome, relatively rare. But researchers recently isolated two genes for colon cancer, and they are closing in on a gene for a highly hereditary form of breast cancer.
Experts warn that as genes are identified for such common illnesses, the general population could become a target of discrimination.
"We are at the watershed point," Billings said. "We are at a point where the basic science is (such) that we are going to see an explosion in genetic tests which are applicable to a large number of people. Either this is going to mean real improvements in people's health . . . or the incidence of discrimination, segregation and what I call mismanaged care will increase enormously."
Martha Volner is health policy director for the Alliance of Genetic Support Groups, an umbrella organization that represents more than 200 associations. She says there is a not-so-funny joke running around the genetics community today:
"One day, we will come to the point where only one person in the United States has insurance anymore, and the reason is he was the one person who had never been tested."
It is black humor, she admits, but it may not be too far from the truth.
Scientists engaged in genetic research face a terrible irony: After painstaking years of laboratory work, their efforts might hurt the very people they are intended to help. For those at risk for a genetic disease, the specter of discrimination creates an agonizing dilemma: to test or not to test?
Melissa Aylstock is a Roseville, Calif., woman whose son has Klinefelter's syndrome, a chromosomal abnormality that gives boys the physical characteristics of girls and is often linked with mental retardation.
"It's a Catch-22," she said. "If you don't find out that your child has this, then you are not going to get the services that you need. And if you do find out, and your insurance cancels you, then you are not going to get the services that you need."
The Catch-22 is a frequent topic of discussion among genetics counselors, who make their living by advising people who are considering testing. Most tell clients to get their personal affairs in order--health and life insurance, potential career moves--before getting tested. They often suggest that patients keep insurers in the dark by paying for tests themselves.
One genetic counselor at Cedars-Sinai Medical Center in Los Angeles describes an elaborate dance he performs with insurance companies that ask for too many details. He sends only a letter confirming that the patient had a genetic test. Never does he send medical records containing results.
"When they say: 'I need more information in order to pay this bill,' I say: 'What information do you need?' " said the counselor, who asked not to be identified. "They say, 'Everybody else just sends us medical records.' Well, if you send them medical records, you are sending them a lot more information than they really need. They do not need to know what's going on to pay the bill."
Theresa Morelli, an Ohio civil rights lawyer, has become a crusader for legislation to protect genetic privacy. She receives so many phone calls from people who have lost health insurance and other benefits as a result of genetic testing that she has taken to calling herself "the Ann Landers of genetic discrimination."
"I get at least two calls or two letters a week from people all over the world saying, 'This happened to me. What can I do about it?' " she said. "People come up to me in the grocery store, the bank. One person told me she was going to flee to Europe."
But most do not want any publicity. They are afraid to talk openly about their genetic status. Morelli and others lament this reluctance, saying it contributes to a "dirty little secret" atmosphere reminiscent of the days when people were afraid to talk about cancer.
"When I need people to testify in front of the legislature, it's horrible," Morelli said. "Most people refuse to go--not that I blame them. They say, 'My employer will find out. My family will find out.' The trouble is that the legislators want to see faces. They think you're being anecdotal unless you present a few horror stories."
At the root of many of these "horror stories," experts say, are deep misunderstandings about what genetic tests mean. Insurance carriers, and the public, equate having a gene for a certain disease with an automatic doomsday sentence. Often this is not the case. Like nearly everything else in life, illness can be a function of both nature and nurture. Genes can predispose people toward certain diseases, but lifestyle may play an equally important role.
"For most conditions where you find a genetic marker, you can't predict the severity of the disease or when the disease is going to occur," said Jonathan Beckwith, a Harvard University geneticist who advises the Human Genome Project on ethical issues. "It is not precise information. And yet insurance companies are already using that information to deny insurance or hike insurance rates."
Universal access to health insurance, the centerpiece of President Clinton's health care reform plan, is one possible fix. In a report issued in May, Beckwith and other members of a group called the ELSI (Ethical, Legal and Social Implications) Committee of the Human Genome Project favored universal insurance, which would require insurers to provide coverage whatever a person's medical condition. But the ELSI group did not endorse the Clinton plan.
State laws are another answer. In the absence of health care reform, Ohio and Wisconsin have laws prohibiting health insurance firms from using genetic information to deny medical coverage. California and New York have similar laws on the drawing boards.
The Americans With Disabilities Act, adopted in 1990, offers some protection against discrimination on the job, but Billings and others say it does not go far enough.
The insurance industry insists it has the right to use genetic information to deny applications for certain plans, particularly disability and life insurance, where payouts are often large and where a purchaser may buy a policy knowing he or she has a serious genetic disorder and will need to make a claim. The industry's response is less clear with regard to health insurance.
The Health Insurance Assn. of America, an industry trade group, supports health reform and universal coverage--a move that would effectively prevent companies from considering genetic information for health insurance.
But, spokesman Harvie Raymond said, the group opposes state laws that would do the same, on the grounds that they are premature and will only attack the problem in piecemeal fashion. Raymond said that until health reform is in place, his group believes it is "inappropriate and unfair" for insurers to be prevented from using genetic information in decision making.
Meanwhile, medical ethicists, geneticists and legislators are grappling with even stickier questions: Should genetic information be used to deny applications for disability plans or life insurance, which are not considered as much of a "right" as medical coverage? Should employers consider genetics when hiring? Should adoption agencies use genetics in selecting prospective parents?
"We are really looking at the technology zooming ahead of public policy," said Nachama Wilker, executive director of the Council for Responsible Genetics, a Boston-based group that is trying to draft laws to combat genetic discrimination. "The big issues that are out in front of us right now are: How is our society going to deal with genetic information? How important is it going to become, and who is going to have access to it?"
In New Hampshire, Jamie Stephenson is asking herself the same questions.
She worries, in particular, about her daughters, ages 6, 10 and 12. They, too, carry the mutant gene for Fragile X syndrome, although their sex spares them the condition. (Unlike boys, who carry one X and one Y chromosome, girls have two X chromosomes, which enables the chromosome with "good" genes to cancel out the bad.)
"My daughters have this on their medical records," Stephenson said. "What's going to happen to them when they become adults and they try to get jobs, or health insurance?"
She remembers a conversation she had with Nobel laureate James Watson, former head of the Human Genome Project who, as co-discoverer of the structure of DNA, helped spawn the genetic revolution. She met him at a conference on the science of genetics, and when she asked him about the future, the picture he painted was bleak.
"He said he fears a new underclass evolving of people with genetic conditions who are going to be discriminated against, just like people with the wrong skin color used to be discriminated against," Stephenson recalled. "Is this what my daughters will be? When they get to be adults, are they going to be the new underclass?"
NEXT: How insurance companies decide what to cover.
Once scientists discover a defective gene that causes disease, they are able to test for it. Since the late 1980s, more than 50 new genetic tests have been developed. Some can be done prenatally, or almost immediately after a baby is born. Here is a partial list of genetic disorders for which tests are available:
* Amyotrophic lateral sclerosis (Lou Gehrig's disease). A degenerative disease of the nervous system.
* Beta-thalassemia. Prevalent in the Mediterranean, the Middle East and Southeast Asia. Causes a breakup of the red blood cells, leading to anemia, spleen enlargement and sometimes abnormal growth of bones. Fatal in early childhood if untreated.
* Charcot Marie-Tooth disease. Causes foot and hand deformities.
* Cystic fibrosis. The most common lethal genetic defect, causing chronic lung infections and an inability to absorb fats and other nutrients.
* Duchenne muscular dystrophy. Major form of muscular dystrophy in children, which causes progressive degeneration of the muscle fibers.
* Fragile X syndrome. Chromosomal disorder causing mental impairment, ranging from subtle learning disabilities to severe retardation and autism. Symptoms are generally more pronounced in boys.
* Gaucher's disease. A disorder common to Ashkenazi Jews. The most severe form appears in infancy, causes central nervous system impairment and death within the first year.
* Huntington's disease. A degenerative brain disorder.
* Marfan syndrome. Disease of the connective tissue that often strikes athletes.
* Myotonic dystrophy: Most common form of muscular dystrophy in adults.
* Retinoblastoma. Inherited eye tumors in children.
* Tay-Sachs disease. A brain disorder common among Ashkenazi Jews. Causes death in early childhood.
* Coming soon: A genetic test for familial colon cancer. Researchers recently identified two genes that account for more than 90% of this inherited form of cancer.