When What We Know Outstrips What We Can Do
Our genes contain information that scientists hope will help in the treatment of many diseases. Huntington's disease provides a window on the choices we face as medicine increases our ability to intervene in human genetics.
Stop pacing, Mom. It'll be all right." Meghan and her mother, Anne, fidget nervously in the waiting area of the genetic testing center.
Anne halts and faces her daughter. "I wish it wasn't this way, Meghan." Anne's family has been haunted by Huntington's since anyone can remember; those who get it always die from it. Her brother Harry was just fine until his mid- 40s—then came the depression, the twitching arms."I need to have this test, Mom," Meghan continues. "I want to know if I'm going to wind up like Uncle Harry. I want to know the chances that my children will inherit Huntington's disease." Meghan and her husband, Rick, want to start a family-a family untouched by Huntington's bizarre dances, frightening mood swings, and untimely death. "I'd rather not have children if it means sentencing them to a death like that," Meghan says.
"I would do anything to spare you," Anne says. "But, Meghan, please understand that I don't want to be tested. 'So far, so good' is my philosophy. I'm only 42. I want to live my life and make my decisions without a Huntington's diagnosis hanging over my head."
"But Mom, you're not the one being tested; I am."
Falling into the chair next to her daughter, Anne pleads, "Don't you see? If your test is positive, it means I've got the gene, too. And I don't want to know. I have a right not to know, don't I?"
Anne and Meghan face a tentative future. Members of families with a history of Huntington's disease have long known that this neurological disorder-with its loss of motor control, personality changes, depression, dementia, and death-might eventually be their fate.
Huntington's is a genetic disease, one that can be passed down from parents to children. The gene for Huntington's is dominant, which means that a single copy of the gene from either parent triggers the disease. Children of people afflicted with Huntington's disease have a 50/50 chance of also having the disease.
Until recently, these people had no way of knowing whether they were in the unlucky 50 percent until symptoms actually appeared, usually between the ages of 30 and 50. Then, in 1993, scientists identified the gene responsible for the disorder and made possible the test Meghan wants to take.
If Meghan is tested and found to carry the gene for Huntington's disease, her mother must also have the gene. Meghan, then, will know what Anne does not want to know. What should Meghan do?
The Human Genome Project
Meghan's problem foreshadows the dilemmas many people will face as scientists learn more about genetics. In 1990, an international effort was launched to decode the language of our genes—the Human Genome Project (HGP). The United States is investing $3 billion over 15 years in this endeavor to map the complete set of genes for humans-the human genome. The project will make it easier for researchers who want to identify the genetic components both of disease and of physical and intellectual traits.
Thus far, the most obvious result of the HGP is the rapid proliferation of genetic information. As the new information pours in, the traditional questions haunt us: What should we do with this information? What does this particular genetic alteration mean personally, medically, and socially? If we can, should we intervene to correct or enhance an individual's genome? And when we cannot intervene, how do we handle diagnostic information in the absence of a cure?
Genetic screening can provide new information, not only for potential Huntington's victims but also for sufferers of the more than 4,000 other diseases of genetic origin. Additional ailments are rooted in the interaction of genes with the environment. All told, genetic disorders are the fourth leading cause of death in the United States.
Discovering the location of a disease-causing gene on a chromosome permits diagnosis before the onset of symptoms. It also allows testing of entire populations to identify carriers as well as those who are affected.
The long-term hope is for a precise molecular correction of the defect so that genetic disease becomes as curable as infectious disease. Such therapy might also prevent genetic pathologies from moving from one generation to the next.
The Rift Between Diagnosis and Cure
Yet despite the progress of the HGP—and, indeed, primarily because of it—disease prediction continues to outpace medicine's ability to treat or cure. The test for Huntington's disease can confirm a mutation in the Huntington's gene, but it offers no treatment for the devastating symptoms. The result is a therapeutic rift between what we know and what we can do.
Meghan and Anne fearfully straddle this crevasse, hoping against hope that it will narrow. However, it seems likely that as information flows from the HGP, this therapeutic rift will continue to enlarge for the foreseeable future. This poses profound and puzzling questions about the limits of medical knowledge and human choice.
Consider the effects of genetic information on people who, like Anne and Meghan, confront Huntington's disease. If they discover they do, in fact, have the Huntington's gene, a shadow is cast over the rest of their lives. A slight misstep becomes an omen of uncontrollable muscle movements. Feeling blue is no longer part of everyday life but a precursor of mental collapse. The person's view of life is irreversibly changed by a set of prophecies about affliction and horrifying death.
In Mapping Fate, Alice Wexler describes what it's like to live with this knowledge:
A dancer with Huntington's disease, in her early forties, described how, long before there were any other symptoms, she began having difficulty learning dance sequences; whereas once she had no problem memorizing complicated routines, she gradually found it more and more difficult to master a series of different steps. Later on she found it increasingly difficult to organize a meal, coordinating the different dishes so that they would all come out together. Living at risk undermines confidence, for there is no way of separating the ordinary difficulties and setbacks of life from the early symptoms of the illness. It is not like any other physical illness, where consciousness can at least continue in the knowledge that one is still oneself, despite severe pain and physical limitation. Huntington's means a loss of identity.
But long before the loss of motor control and identity, those who carry the Huntington's gene may face the loss of jobs and health coverage. Many people from families with a history of genetic disorders fear that if they are tested, the results might become public and cause employers or insurers to exclude them. Laws to prohibit such discrimination are not yet completely in place. This is the prophecy of social and medical doom that Anne is resisting.
Responsibilities to the Next Generation
But her daughter Meghan has a different set of concerns. Genetic knowledge is apt to have its greatest impact not on the lives of those who, like the stumbling dancer, are currently stricken, but on the choices to be made by those who, like Meghan, are contemplating parenthood.
If Meghan does not have the gene, then her child will not have the disease. If she does have the gene, any child she conceives has a 50 percent chance of sharing her fate.
Assuming Meghan learns that she has the Huntington's gene, what should she and her husband do? Should they take their chances with genetic roulette? Should they remain genetically childless? Should they undergo prenatal diagnosis?
Prenatal screening and diagnosis can be accomplished through methods such as amniocentesis. Sometimes genetic testing is coupled with in vitro fertilization in a technique called preimplantation genetic diagnosis (PGD). PGD is currently offered in a limited number of research facilities.
In this method, after the egg is fertilized outside the womb, the embryo is allowed to reach the eight-cell stage of development before a cell is removed. This cell is then tested for genetic components that would predispose the child to a particular disease such as Huntington's. Then, only those embryos that do not contain the disease gene are transferred to the uterus, thereby eliminating the chance of having a child with Huntington's disease.
Whatever the promise of this technique, the cost is far from trivial. It includes the fee for IVF-averaging $8,000 per cycle-plus the cost of genetic testing, which adds an estimated $2,000. Even in the rare cases when IVF expenses are paid by health insurance, the genetic component is not covered.
Costs are also likely to be high in the even more advanced procedures now being proposed. In the future, PGD might identify candidates for emerging techniques such as constructive genetic surgery and embryonic cell cloning. Constructive genetic surgery involves removing the affected gene from an embryo and replacing it with normal genetic material. But this is risky business with a failure rate of 80 percent-far too perilous to perform on a single human embryo.
Through cell cloning, however, scientists could make multiple copies of the embryo they wish to modify, increasing the genetic surgical success rate. Indeed, cellular cloning seems to hold the key to the successful genetic engineering of humans. But to what end?
Is Meghan's wish to prune Huntington's disease from her family tree a justified use of this future technology? Suppose parents wish to eliminate the predisposition to alcoholism. What if they want to increase a child's physical stature or intellectual acumen? Would these be reasonable requests for embryonic genetic intervention?
After all, we send our children to soccer practice and tutoring after they are born; why not give them a genetic head start? Is there an ethically relevant difference between genetic therapy and genetic enhancement?
Questions and Guidelines
Reproductive and genetic technologies are opening new medical and moral frontiers, urging us to think in new ways. As the level of medical diagnosis and treatment shifts from bodies and bones to cells and chromosomes, the level of ethical consideration must do the same.
Reaching ethical conclusions about the new genetics is challenging for two reasons: First, it is inherently difficult to understand the subtleties of genetics and the wealth of data tumbling out of the HGP. Second, it is next to impossible to foresee accurately the implications and consequences-short-term, long-term, and unintended-of intervening in the genetic "stuff of life."
The following questions may help to clarify key issues as genetic medicine comes of age:
1. What is the purpose of taking a particular genetic test? Who is affected by the results?
Some people undergo genetic screening simply to know their predisposition to a particular disease. Others may hope to fix that predisposition. Currently, the diagnosis of numerous genetic diseases or predispositions is possible; in most cases, however, there is no treatment or cure. Care must be taken to ensure that patients understand this rift between diagnosis and treatment and that their expectations of the testing are realistic.
Since it became possible to test for the Huntington's gene, fewer than 15 percent of those at risk have taken the test, even when it was offered free of charge. Most would rather not know. Anne, like many of us, is reluctant to find out about an inevitable future. Perhaps, out of respect for her mother's wishes, Meghan could wait to take the test, hoping that in a few more years, scientists may make progress toward a cure. Perhaps Meghan is particularly good at keeping secrets.
Traditional notions of confidentiality are profoundly challenged by medical tests that tell patients not only about themselves but also about family members. As genetic tests become readily available, respect must be given to those who, like Anne, claim a right to ignorance.
2. Who has control of genetic information?
In this era of rapid communication and data proliferation, absolute confidentiality of medical information no longer seems realistic. In a hospital, anywhere from 60 to 200 people have access to a patient's medical records. The information is also passed along to insurance carriers and health maintenance organizations. Given that complete privacy is not possible, it is important to consider who has access to genetic information and for what purpose.
People questioned about genetic testing worry that insurers will raise rates or refuse to insure them. They express concern that employers will not hire them. There is a general fear that friends and family will treat them differently or abandon them once they are "tarnished" by a deadly gene. Medicine's obligation to do no harm mandates that genetic information be used in ways that help people, not in ways that stigmatize and marginalize them.
3. What does it mean to offer genetic testing and/or therapy in the absence of universal access to health care?
This is a question of justice. What counts as a fair share of the health care pie for the poor or for those without health insurance? We live in an era of limited access to childhood immunizations and routine preventive care-both of which are relatively inexpensive and medically effective. As we pour health care dollars into genetic research and treatment, we must also seek to provide basic care to those who are most vulnerable to the ravages of disease: the poor and their children.
4. On what basis should someone undertake genetic intervention such as genetic constructive surgery if and when it becomes available?
Two approaches to this question are possible. One is therapeutic; that is, such techniques should be used to correct particular diseases. The other is eugenic; that is, genetic intervention is permissible to enhance specific characteristics (e.g., intellect) or to give individuals capacities they might not otherwise have had (e.g., playing piano).
The distinction between therapy and enhancement may turn on intention. Is the purpose of the intervention to bring a person to a state of health or to go beyond health in the design of someone new or better?
With the fledgling capacity to alter the human genome comes the responsibility to think carefully about what we consider a benefit for individuals and society. Test tube racks filled with "designer genes" hold not only the promise of molecular treatments but also the age-old mischief of discrimination and exclusion. We are not yet free of the specter of forced eugenicsÑwitness reports that up until the 1970s, an estimated 60,000 people had been sterilized in Sweden under government policies to weed out traits such as poor eyesight and "Gypsy features." What some consider desirable traits may not be a benefit in the eyes of either humanity as a whole or the affected individual.
5. For what kind of genetic future are we planning?
Genetics, by its very nature, embodies a concern for coming generations. Genetic diagnosis and intervention hold great promise. However, we need to consider carefully the power conferred on us by knowing our genetic identity and being able to alter it.
With great power comes greater responsibility, asking us to think carefully about the dramatic impact that genetic information and intervention might have on the future. We face not a red light but a flashing yellow as we enter the age of genetic medicine.
Margaret R. McLean is the director of biotechnology and health care ethics at the Markkula Center for Applied Ethics.
This article was originally published in Issues in Ethics - V. 9, N. 2 Spring 1998.
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