Part II: Genetic Fortune-Telling The Results Are In, Now What? Mike Field ----------------------- Staff Writer Genes may be able to tell our future. But do we really want to know? Last month, a group of 50 internationally prominent doctors, researchers and ethicists met in closed session at a weekend conference in Chicago. The private meetings, sponsored by the National Institute on Aging and the Alzheimer's Association, were held to try to sort out a thorny issue that may, in fact, represent the first volley in the coming wars of genetic testing. At the center of discussion was the test for a specific gene variant--labeled Apo E4--the presence of which is known to increase the risk of heart disease by 30 to 50 percent. Tens of thousands of patients nationwide are currently being tested for the gene, which, in its normal state, produces a protein that reduces cholesterol in the blood. People with a faulty copy of the gene typically suffer from abnormally high cholesterol levels. Those who test positive for the gene will be able to alter their diets, take cholesterol-lowering drugs or pursue other treatment options that, it is believed, will substantially improve their chances of avoiding a heart attack. The trouble is, at the same time cardiologists were linking the Apo E4 gene to increased likelihood of heart attack, a different set of scientists began proposing a startling theory: they produced evidence that individuals with two copies of the Apo E4 gene (one from each parent) may be as much as six times more likely to contract Alz-heimer's disease, and that even one copy of the gene may increase the risk of Alzheimer's dramatically. Further, the gene may also affect the age of onset of disease symptoms, indicating some cases where patients will come down with the debilitating mental disintegration as early as their 50s. Currently, there is no known way to prevent Alzheimer's, and only one drug--with very limited effectiveness--has been approved for treatment of the disease. Even identifying Alzheimer's has proven difficult during the early stages of the disease, and to date, no simple medical test has been developed to aid physicians in making a diagnosis. A genetic test that could confirm a suspected case of the disease would be useful to physicians, families and patients alike. However, as is so often the case in the largely unmapped terrain of genetic fortune-telling, inheriting this particular gene does not guarantee a person will contract Alzheimer's, and there are people who get the disease without inheriting the gene. Furthermore, recent evidence suggests that people with Apo E4 genes seem particularly at risk of developing Alzheimer's after having suffered blows to the head. For instance, many boxers who become demented, it is thought, are likely to have at least one copy of the gene. The dilemma facing the medical researchers who gathered in Chicago was, perhaps, prototypical of the kinds of issues facing medical science as the human genome is unraveled and mapped: should patients tested for Apo E4 by their cardiologists be warned they may also learn unwanted news about an incurable disease? What is the predictive value of the new test, and how should it be employed? Should boxers with the gene be prevented from earning a living at their sport? Or students with Apo E4 prevented from playing contact sports at school? The Apo E4 dilemma highlights the Pandora's Box quality of genetic research, where much new knowledge is being unlocked without anyone's quite knowing what we are going to do with it. Should, for instance, individuals whose genes predict they will contract an incurable deadly disease early in their lives be tested and made aware of the fact right from birth? What is the value of informing individuals they run a high probability--but not a certainty--of developing an illness that can be neither prevented nor treated? And what of the possibility that certain genes might strongly indicate--but not guarantee--a behavioral predisposition to violence or other problems? "The current developments associated with the Human Genome Project will soon enable us to rapidly, and fairly easily, collect tremendous amounts of information about the genetic characteristics of individuals," said university professor of medical genetics Victor McKusick, who has spent more than 38 years in the field. In 1957 McKusick founded the Division of Medical Genetics within the School of Medicine's Department of Medicine, making Hopkins one of the first hospitals in the nation with a clinical practice specifically devoted to hereditary diseases. McKusick has written and spoken widely about the changes that are now occurring. "We are now in the midst of a biological revolution and the information revolution, both of which converge in the human genome initiative," he said. "This creates two big problems: First, it increases the gap between what we know how to diagnose and what we know how to treat. For instance, we can now predict that John Doe will contract Huntington's disease, probably in his 40s, yet we have no way of preventing or treating him for this deadly illness." The second issue has to do with the difficulty in deciphering the real importance of specific gene abnormalities, such as the Apo E4 variant. "There is a gap between what we think we know and what we really know," McKusick said. The one-to-one correlation between a gene and a disease represents only a fraction of all medical illness. In most cases, genes will be a factor, but only one factor in the etiology of disease. "This will be especially true in behavioral traits, where the likelihood is that weak associations will be found between particular genes and certain presumed characteristics such as criminality or alcoholism or elements of intelligence or performance," he said. ----------------------------------------------------------------- Role of genetic counseling ----------------------------------------------------------------- As medical science increases physicians' abilities to make genetic diagnoses, the potential moral and ethical dilemmas in making those predictions grow with it. Increasingly, the task of interpreting genetic test results and helping patients decide what to do with the information has become the domain of genetic counselors, a new type of health-care professional sure to play an increasing role in the medicine of the 21st century. "Counselors work as part of a team with the medical geneticists," said Virginia Corson, assistant professor of gynecology and obstetrics within the School of Medicine. Corson received her master's degree in genetic counseling at Sarah Lawrence College, where the nation's first genetics counseling program was established in 1969. "Our concentration is in working with the family to help them cope with complicated information, understand the risks involved and find support systems that may prove helpful." Corson has spent 20 years at Hopkins, primarily counseling potential and expecting parents in the hospital's Prenatal Diagnostic Center. "Most of the couples I see are anxious about having healthy children," said Corson, who notes that more than 95 percent of her patients do in fact have perfectly healthy babies. "Most people know very little about genetics, so giving them a sense of understanding helps them deal with that anxiety." Even before today's sophisticated genetic tests were available, genetic counselors could provide information about the likelihood of many heritable disorders based on the laws of Mendelian genetics. Parents with a family history of a variety of diseases ranging from dwarfism to cystic fibrosis or sickle cell anemia could be counseled about the likelihood of passing the trait on to their children. Now, with the advent of sophisticated genetic decoding that can identify specific gene abnormalities, parents can also look for diseases in the womb through analysis of cells in the amniotic fluid that surrounds the fetus. Yet as in so many other instances involving genetic testing, additional knowledge leads to a whole new set of questions, many of them profoundly difficult to answer. "In some situations where we have more tests, we create more anxiety, especially when it puts couples in a position of having to make a decision," Corson said. For instance, amniocentesis can reveal a range of genetic information about an unborn child, ranging from anencephaly (absence of the brain), to Down's syndrome to the sex of the child. Even the Apo E4 gene can be discovered this way, although currently it is not looked for. Yet this capability raises a host of thorny issues. Parents might elect to terminate a pregnancy if the child is developing with no brain and will certainly die; but what if it will be moderately or severely retarded through Down's syndrome? Or may be at risk for developing Alzheimer's late in life? Or is a girl when the parents were counting on a boy? "Technology gives us a greater opportunity to make choices, but it doesn't make these choices any easier," Corson said. "The job of the genetic counselor is not to make these choices for patients, but rather, to offer them all the options and discuss all the possibilities and then let them make the decisions themselves. The idea is to give people choices as opposed to cures or treatments. Very often, the cures or treatments simply don't exist." ----------------------------------------------------------------- Next: When your genes say you'll contract a debilitating disease, should your insurance company be told? Genetic privacy and the right to know in the conclusion of "Genetic Fortune-Telling." -----------------------------------------------------------------