By Rich McManus
On the Front Page...
As the world prepares to reap what is certain to be a bountiful harvest of new health-improving knowledge from the Human Genome Project (HGP), it is heartening to realize that there are strong precedents already in place promising that the breakthroughs will conform to the public's great expectations: that prevention of disease will be enhanced, that access to new therapies will be wide, that quality of life will improve and that patients will remain able to chart their own fates by using their decision-making skills.
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But it's that latter category — what to do with new facts that research will inevitably uncover — that's the wild card, according to Dr. Wylie Burke, who discussed "Using Genetic Tests To Promote Health: Evidence and Values," at the June 2 Wednesday Afternoon Lecture. Burke, who is professor and chair of the department of medical history and ethics at the University of Washington, Seattle, demonstrated that there are likely to be occasional gulfs between the medical profession's judgement of what is best to do in certain instances and the opinions of patients.
Case in point: Research has shown that mutations of the BRCA1/2 genes in families with a high risk of breast cancer are strongly predictive of future cancers, and that a procedure known as prophylactic mastectomy, or removal of the breast before there is any indication of disease, can dramatically lower risk of getting breast cancer. But what is "slam dunk" evidence in favor of the procedure in the eyes of science is not necessarily convincing to patients. Despite the fact that prophylactic mastectomy is the single most effective tool for preventing breast cancer known to medicine, Burke showed evidence that patients frequently reject it as an option, often with the subtle cooperation of their own doctors.
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Now about 30 years old, PKU screening — which involves blotting a dot of a newborn's blood on a piece of paper that is then tested for phenylalanine — is used to identify affected infants so that dietary intervention can prevent mental retardation. That the test is mandated in every state in the union is evidence of its wide accessibility. Burke concedes that the test, often done without formal parental consent, does, technically, violate the standard of autonomy currently recognized in most medical care, by omitting an informed consent process and limiting parents' opportunities to refuse testing. PKU testing nonetheless "preserves the child's opportunity to realize future self-determination, by preventing retardation...Patient preference is, in this case, a secondary concern."
Despite its status as a "gold standard" prevention tool, PKU testing has had some adverse effects, Burke cautioned. Doctors have learned that it is inappropriate to treat mildly elevated PKU — some babies suffered neurological consequences as a result of unnecessary dietary intervention when testing was first introduced. Burke's message is that the evidence for benefit is crucial in any intervention.
Burke predicts a coming onslaught of genetic testing in which it will get tougher to determine what evidence is persuasive. Already, commercial web sites purport to offer personalized profiles of an individual's disease risk, for a sum of money and a cheek-swab that picks up some of his or her DNA. "Web sites outside the health care system are offering personal profiling, diet advice and other tests. But on what evidence are they recommending testing?"
One of the main purposes for acquainting oneself with risk information is to take action, Burke explained. But data can be ambiguous, as likely to generate hope in a patient as dark fatalism. And even in cases where knowing one's risk can't possibly lead to amelioration of a disease — such as having the APOE4 mutation associated with Alzheimer's disease — studies show that patients find a use even for that grim knowledge; while they can't take any medicine or therapy that would turn things around, they can nonetheless get their affairs in order, plan vacations sooner, etc. Personal values unrelated to health outcomes come into play, Burke showed.
Data from the genome project indicate that multiple genes contribute to risk in many diseases, in a complex interaction with environmental factors. Diabetes, heart disease, Alzheimer's disease and asthma have all been linked to gene variants that seem to be associated with a small increase in risk. But, Burke asks, how good is the testing that established the link? And how reliable is the test in specific patients?
Burke said the health care industry has many cultural and economic questions to answer, in addition to purely scientific ones, in the future. "What tests should be offered? What purposes should testing serve?" she asked. "When does the harm of a genetic label outweigh its benefit? What messages are conveyed by genetic information?" Her advice is to broaden our research goals to include such subtleties as how patients perceive benefit, and how to identify the social and cultural contributors to health and well-being. It is a field rife with complication, but history shows that medicine can be up to the task, Burke optimistically concluded.
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