Roanoke Times
Copyright (c) 1995, Landmark Communications, Inc.
DATE: SUNDAY, May 27, 1990 TAG: 9005240502
SECTION: EXTRA PAGE: E1 EDITION: METRO
SOURCE: CHARLES HITE MEDICAL WRITER
DATELINE: LENGTH: Long
She knows this because nine years ago, long before she and Tom were married, she gave birth to a daughter with the disease.
Tom Mack has no idea if he, too, is a carrier of cystic fibrosis. Until last year, the only way he would have known was to see if any of his children developed the disease.
"I definitely would want to know if I am a carrier," says the Bedford County construction worker. "Then I'm sure we would have serious thoughts about having a child."
With the isolation of the cystic fibrosis gene last year, a screening test is now available. From a sample of blood, scientists can determine whether someone carries the gene.
However, the test is conclusive only 75 percent of the time. About 25 percent of cystic fibrosis cases appear to be caused by gene mutations that the screening test can't identify.
The discrepancy has generated a controversy about whether the test should be used and who should be tested.
Some geneticists say the profit motive was a driving factor in an initial rush to offer the test on a mass scale. They warn there aren't enough genetic counselors in place to explain the implications of the test.
If cystic fibrosis screening is botched, then problems are likely to appear when tests come along for other genetic diseases, geneticists say. And those tests are not far away. In the next few years, a massive federal project designed to identify every human gene will be moving forward.
"This technology is really going to touch every individual," says Dr. Neil Holtzman, professor of pediatrics at Johns Hopkins University. "The question we must face is, `What will the benefits be, what will the risks be?' "
One risk, Holtzman says, is that genetic tests could be used to pressure society into a new eugenics: Couples will be encouraged to avoid pregnancies or to abort to avoid the high costs of caring for "defective" children.
That argument doesn't differ much from that of the early eugenicists, who advocated sterilization as a means of avoiding undesirable traits in the gene pool, Holtzman argues.
"I think the cystic fibrosis test is going to force us to confront something which we are going to have to continue to confront with new genetic tests as they come on line and that is: What do we really mean when we say someone has a disability?" says Arthur Caplan, director of the Center for Bioethics at the University of Minnesota.
"It's one thing to say, `You have Tay-Sachs disease and can only survive three to five years in horrible pain and will certainly die,' " Caplan says.
"But cystic fibrosis is a disease where, due to developments in medicine, people can lead a range of lives - from the severely impaired to the pretty well functional. And they can live up to 30, 40, 50 years or more. I'm not sure whether that is a disease where testing and screening the general population makes sense," Caplan adds. "I'm not sure it is debilitating and disabling enough to justify efforts to prevent it prenatally."
Charlene Mack says her 9-year-old daughter, Crystal, looks and acts pretty much like other kids her age. Crystal's cystic fibrosis is most noticeable during coughing spells, and she sometimes tires easily.
Yet even when Crystal is feeling her best, Charlene and Tom Mack know her condition will deteriorate steadily as the disease takes its toll. They don't want to bring another child into the world to face the same struggle.
Several weeks ago, a panel of experts gathered at the National Institutes of Health to recommend guidelines for genetic screening for cystic fibrosis. The panel concluded that the U.S. health care system isn't equipped to handle massive general testing. The test should be limited to people who have a family history of the disease, the experts said.
"It's just a question of us having to go carefully and slowly until we know what the heck we are doing," says Dr. Michael Kaback, president-elect of the American Society of Human Genetics and a pediatrician from the University of California at San Diego Medical Center. "We should not assume we know how to do this on a scale unlike anything we've ever tackled before."
Mass population screening for cystic fibrosis could be very costly and "carry a tremendous possibility for error, confusion, and stigmatization," says Dr. Norman Fost, chairman of the American Academy of Pediatrics committee on bioethics.
Americans have had a hard time grasping the subtle- 12 1 SCREENING Screening ties of the statistics, probabilities and other concepts associated with genetic diseases.
Caplan points to the "disastrous" experience with sickle cell anemia, a hereditary form of anemia that affects almost exclusively blacks. Efforts to screen blacks for the disease led to major misunderstandings about the disease, he says, including confusion about the difference between being a carrier for the disease and actually having it.
"I remember Georgia back in 1976 had a law requiring immunization against sickle cell as an entry requirement for school. But sickle cell is not a disease you can immunize against," Caplan says. "You can be sure that if you do testing and screening without adequate counseling and screening, the first impact of mass genetic testing for anything will be to scare the bejeebers out of everybody."
Information and anxiety
The genetics of cystic fibrosis involves the concept of carriers, people who have no symptoms but have a single gene for the disease. If two carriers have children, there is a 1 in 4 chance that the child will inherit the gene from both the mother and father and therefore have the disease. There is a 2 in 4 chance each child will inherit one gene and be a carrier, and a 1 in 4 chance each child will be free of the gene.
Counseling couples about the cystic fibrosis test means not only getting across the genetics but explaining that the test can detect the gene that causes only about 75 percent of the cases. There is no test yet for the mutations of the gene that cause the remaining cases. In fact, scientists aren't even sure how many mutations exist. So far, they've found more than 20.
All this presents a formidable challenge in explaining even the most straightforward test result, says Fost. Imagine a doctor trying to explain to a couple that each has tested negative for cystic fibrosis, he says.
"Here's the information he's got to convey: `I've done a test and it's negative, which means there is a 75 percent chance that you and your wife do not have a gene, which if you did have, there would be a 1 in 4 chance that you would have a baby who could die in infancy or could live to be age 50.' Now if you track that sentence, you are a lot smarter than I am," Fost says.
For some couples, a screening test will create even greater anxiety, says Dr. Thaddeus Kelly, chief of the genetics division at the University of Virginia.
For every 1,000 couples tested, Kelly says, the test will turn up one couple in which both partners are positive. But in that same 1,000 couples, the test also will turn up about 55 couples in which one person tests positive and the other tests negative. The risk for those couples having a child with cystic fibrosis is about 1 in 400.
Aside from increasing their anxiety, there really isn't much more the test can do for those 55 couples, Kelly says. Until the test is accurate enough to dispel this added worry, Kelly believes mass screening should not be done.
Others disagree.
"Our position is, why deny the test to the people who are going to get a conclusive answer out of it?" says Anne Maddalena, director of the molecular genetics laboratory at the Genetics and In Vitro Fertilization Institute in Fairfax. "The people who get a positive test will know they are carriers."
Physicians at the institute have been offering the cystic fibrosis test for several months to all couples who come in for genetic counseling. They feel justified in doing so, she says, because the ramifications of the test are fully explained.
"I fully agree that this shouldn't be a test that you can get done at any old doctor's office and just get a yes-or-no answer without getting the counseling that needs to go with it," she says. "It's not like getting your cholesterol count."
A potential windfall
Should genetic testing become widespread, there's no doubt a lot of money could be made.
"Some private companies are poised and ready to start doing testing on large numbers of people because there is an enormous profit to be made," Kaback of the American Society of Human Genetics says.
"The first person out in the market is going to reap quite a windfall," says UVa's Kelly. "Once you've got people coming in and asking about screening and testing, then the medical profession will try to figure out how to get the most from that blood sample."
The cystic fibrosis test alone has the potential to spawn a billion-dollar industry, says Fost of the pediatrics academy. That figure can be reached simply by multiplying the number of women who get pregnant each year - 5 million - times the $200 testing fee charged by some companies.
Genetic screening also has a tremendous potential to help people. Ultimately, scientists hope to be able to fix defective genes, not just identify them.
In the meantime, even identifying faulty genes could be invaluable to certain people.
It will probably be possible in the next five to 10 years to identify genetic factors that predispose people to developing certain conditions later in life, says Kaback.
Certain types of cancer, heart disease, mental illness and neurological disease could be identified through pre-symptomatic screening, he says. It then might be possible to prevent or delay onset of the diseases through drugs or changes in diet and behavior.
Who gets the results?
If screening tests become commonplace, who should be given the results? Is a patient obligated to tell family members that they may be at risk for a disease? Can employers demand the results of such tests? Can insurance companies?
"People ask me, `Gee, I wonder whether employers and insurers will have access to the test results?' To which my response is, `Are you kidding?' Please. It will become an absolutely mandatory element of applications for jobs and insurance coverage," says Caplan of the University of Minnesota.
Attempts may be made to pass laws limiting access to genetic tests, Caplan says. But the legal precedent for requiring the tests already exists.
"Since we've been engaged in a frenzy of insisting upon testing for drugs, the laws are on the books that pretty much guarantee that genetic testing will be seized by police, courts, insurance companies and employers," Caplan says.
Once employers and insurers gain access to genetic information, it could give them tremendous power over people's lives. Businesses could force employees to retire early. And insurers could force people into treatments or procedures they don't want.
Medical geneticists tell of a pregnant woman who had her fetus tested for cystic fibrosis because her first child had the disease. The test was positive. The second child also would have cystic fibrosis.
The couple's insurance company decided it would not provide medical coverage for the child. The parents faced a terrible choice: either abort the fetus or face the financial burden of raising a child with cystic fibrosis.
After pressure from the couple's employer, the insurance company reversed its decision. But the case illustrates the agonizing decisions that genetic screening can lead to.
"Increasing numbers of people are being confronted with the necessity of making decisions about having children," says UVa's Kelly.
Raising ethical issues
Twenty years ago, the health of an unborn child was something couples had no way of measuring. The development of amniocentesis - a procedure in which a sample of the fetus' amniotic fluid is tested - and now screening for genetic disorders has changed that.
People now have a responsibility to be aware of risks and to make informed decisions, Kelly says.
"These are questions that people ought to ask but many of us don't," says Nancy Wexler, who heads the ethics, legal and social issues working group advising the federal project to identify the estimated 100,000 human genes in every human cell.
Here are some of those questions: Would I marry another carrier? Would I use prenatal testing? Would I abort a fetus if it's discovered to be at risk for a disease? What risk would I take with the health and lives of my children?
Many people are reluctant to discuss those questions because genetic screening links directly to the national debate over abortion, Caplan says: "That seems to pretty much effectively end all discussion of this as a public issue."
But cystic fibrosis is such a widespread disease that the public eventually is going to get caught up in the debate over testing and screening, says George Annas, a professor of health law at Boston University.
The debate already has led the federal human gene project to "get more serious" about ethical issues, Annas says. The project has an active advisory committee on ethics, law and social policy and recently appointed a full-time ethicist.
He adds, "I think the debate over cystic fibrosis testing has had a lot to do with this, because everyone recognized we weren't ready for mass genetic screening."
by CNB