The Potential—and the Threat—of Genetic Information

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In the spring of 1997, teams of researchers in Houston and New York City reported a discovery that may eventually lead to better diagnosis and treatment of several deadly types of tumors, including brain, breast, and prostate cancer. The two groups, one at the University of Texas Brain Tumor Center and the other at Cold Spring Harbor Laboratory and Columbia University's College of Physicians and Surgeons, found that a particular gene on chromosome 10 is turned off in certain malignant tumors. Apparently, when it is working properly, the gene produces a protein that acts as a brake on tumor growth, helping to prevent potentially cancerous cells from turning malignant and multiplying out of control. But sometimes a mutation deletes the gene from a cell and removes that line of defense. With this information, the researchers hope to devise diagnostic tests that will identify, for example, which prostate tumors need particularly aggressive treatment. Eventually, if scientists can develop compounds that mimic the action of the protein made by this gene, the finding could lead to potent new anticancer drugs.

The discovery of this gene, like countless other biomedical advances made each year, hinged upon the ability of researchers to test DNA from hundreds or thousands of tissue samples, looking for a shared genetic flaw. This ability, which did not exist little more than a decade ago, has made it possible for scientists to trace the causes of any disease that has a genetic basis or component, from Huntington's disease and sickle-cell anemia to heart disease, most forms of cancer, and Alzheimer's. To date, the genetic underpinnings have been identified for only a small percentage of these diseases, but the breakthroughs are coming faster and faster, as scientists accumulate more knowledge and develop increasingly powerful tools for analyzing genetic information. Once the relevant genes are identified, biomedical researchers will have a better understanding of how and why the diseases occur, be able to develop more sensitive and accurate diagnoses, and eventually offer more effective treatments. In the future, researchers hope to use gene therapy to treat and even cure some diseases.

In short, genetic research promises to deliver the most revolutionary improvement of medicine since the discovery of antibiotics, and perhaps the most revolutionary ever. But this advance comes at a price with which many people are uncomfortable: the power of prophecy. Reading a person's DNA has the potential to peek at that person's future. In some cases the prophecy is dead certain. If, for instance, you have the genetic alteration associated with Huntington's disease, then you know that once you reach your 30s or 40s or 50s, your brain will start to deteriorate, you will lose control over your movements, and within another ten to twenty years you will die. In other cases, the predictions are not sure things but instead are statistical statements indicating a predisposition. If, for instance, you are a woman and have an altered version of the BRCA1 gene, your chances of getting breast cancer increase four to seven times more than average. Theoretically, once the relevant genes have been tracked down, genetic analysis should offer probabilistic information about a wide range of afflictions, from how likely you are to suffer from depression or develop cancer to what your risks are for having a heart attack. The predictions, being statistical in nature, would not foretell the fate of any given individual but would be reasonably accurate in estimating, say, how many people out of a thousand with a particular gene would develop diabetes.

That sort of power has tremendous potential for abuse. If an insurance company learned that a woman has the mutated BRCA1 gene, it might refuse to offer her insurance even if she has no prior history of breast cancer. If an employer learned that an applicant was at risk for serious depression, it might look for someone else for the job.

And unfortunately, this is not just a potential problem, Paul Billings of the Department of Veterans Affairs in Grand Prairie, Texas, told the workshop. "Genetic discrimination arising from genetic information available from medical records exists in the United States, and there are real losses and vulnerabilities associated with the participation in genetic research and genetic testing." In the early 1990s Billings published the first evidence of genetic discrimination in insurance and employment matters, and he has now reviewed more than five hundred cases of people reporting discrimination based on genetic information. The degree of this discrimination has not yet been quantified.

"The primary type of genetic discrimination arises from insurance contract issues," Billings said. "The second most common comes when employment benefits are considered . . . The results for some individuals of participation in genetic testing have been uninsurability, unemployability, the lessening of certain other life prospects, and financial instability."

The Human Genome Project

Seven years from now, if all goes as planned, scientists will have mapped out every last bit of the human genome—that is to say, they will have written out all of the genetic information that describes how to construct a human. And when that Human Genome Project is complete, it will offer doctors and medical researchers a powerful tool for understanding the human body and mind.

Each cell of our bodies carries 23 pairs of chromosomes, which together hold approximately 100,000 genes along with control regions for turning the genes on and off and also large sections that have no known function. Each chromosome is a long, twisted double strand of deoxyribonucleic acid, or DNA, which in turn consists of millions of the chemical units called base-pairs arranged like letters in a sentence. The base-pairs—which come in four varieties, denoted A, C, G, and T—are the alphabet of the genome, with thousands of them spelling out a single gene. By learning the precise sequence of base-pairs, one can identify not only the gene but the protein that the gene tells the body how to make. Since proteins are both the building blocks of and the construction tools for the body, a compendium of all the genes in the human genome will offer a blueprint, or at least a materials list, for assembling a person.

The Department of Energy began the Human Genome Project in 1986 and was joined by the National Institutes of Health in 1990. The purpose of the HGP is to sequence every one of the approximately 3 billion base-pairs that make up the human genome. To date, about halfway through the projected 15-year schedule, only about 3 percent of the genome has been sequenced, but the first several years were spent mostly in preparation and the actual sequencing has only recently begun in earnest. Experts predict the project will be finished not too long after its scheduled completion date of 2005.

Even now, with only a fraction of the project finished, researchers are rapidly identifying genes involved in various diseases: diabetes, cardiac abnormalities, various cancers, a form of epilepsy, early-onset Alzheimer's disease, and many more. When the entire human genome is mapped, such identification will become much easier and faster. Hopefully, a simple genetic test could allow doctors to learn what maladies a patient is at risk of developing as he or she gets older and to prepare for them or perhaps prevent some of them altogether.

Not surprisingly, such discrimination, or the fear of it, has made many people leery of offering up their own DNA for testing. The fraction of people who should have genetic testing but avoid it for fear of reprisal is not known. Vicky Whittemore of the National Tuberous Sclerosis Association feels fear of discrimination is widespread among those who belong to her association. "The thing that I hear from our members in terms of genetic privacy and all of the issues that are being discussed here is fear—fear of discrimination, fear that release of their medical information or genetic information will have an influence on their eligibility for life insurance, health insurance, or how it will impact them in their jobs." And, Whittemore said, although her association has been successful in recruiting victims of tuberous sclerosis and their family members to take part in research, she has found that the fear sometimes overrides the patients' desire to help find a cure or treatment for the disease. "In the families that I talk to there have been a few who have refused [to take part in genetic research] because of the fear of that information getting out to the public."

Such worries are just one part of the public's uneasiness with genetic testing, said Paul Berg, chairman of the Beckman Center at Stanford Medical Center. "In addition to the concern that the results of genetic testing could be used to deny health care coverage, there are other issues that concern many people. One of these is the psychological impact of knowing of their predisposition to serious disease. One frequently hears, 'How am I going to deal with knowing that I have a predisposition to such and such? I have to worry about my children, and how to deal with my sister who carries the same gene.' And so on and so forth. There are all these emotional issues. Health care is important, but this other issue which is a little harder to put your finger on, is out there. It seems to me that the privacy issue is not only whether somebody else will know, but how the tested individual is going to deal with it?"

The public uneasiness may be understandable, but it is also exaggerated by the tendency of scientists and others to focus on genes to the exclusion of the other things that go into making a person. So perhaps, said Shirley Tilghman, a molecular biologist from Princeton University, the best approach will be to remind the public that although genetic research is an incredibly powerful tool, it is far from omnipotent. "Genes do not determine who we are," she said. "Genes are essentially a blueprint and on that blueprint many, many different houses can be built. I think there is an enormous danger as we head down this road towards defining ourselves by our DNA sequence that we will leave the impression with the public that you are who your genes are. You are not who your genes are. It is a much more complicated dynamic than that, and I think the public acceptance of knowing more genetic information will be directly proportional to the degree to which they understand that basic underlying fact."