Indiana Alumni Magazine
Matters of Life and Death, Questions of Right and Wrong
Advances in human genetics lead not only to answers about biological identity, but also to questions about how we use that information.
By Elizabeth Hunt
Just three months ago researchers from around the world wrapped up one of the most significant and ambitious scientific projects ever undertaken. Sequencing the human genome — determining the entire genetic code for the species known as Homo sapiens — began in earnest 13 years ago, with a congressional appropriation for an endeavor called the "Human Genome Project." The origins of this international, multibillion dollar project go back much further, however, to April 1953, when James Dewey Watson, PhD'50, ScD'63, and Francis Crick first described DNA's double helix. It's interesting to note that the completion of the Human Genome Project came 50 years to the month after Watson and Crick's Nobel Prize-winning announcement.
The success of the Human Genome Project means that we have determined "the exact order of the 3 billion DNA letters in the human genetic instruction book," says Francis Collins, director of the National Human Genome Research Institute. And in many ways, the achievement marks a commencement as much as a conclusion. The information generated by the Human Genome Project has provided the starting point for thousands of efforts to detect, treat, and cure diseases from AIDS to alcoholism, malaria to manic-depressive disorder.
But it isn't only scientific investigations that have gained momentum from our new knowledge of the human genome. The human-genetics revolution launched a fleet of ethical considerations with its inception. As we move from understanding the genome to acting on that understanding, these ethical dilemmas are finding new expression — and new urgency.
What happens, for example, to people whose genes reveal that they are at risk for, or will certainly develop, particular diseases? How do we minimize the chance of discrimination against those who have drawn a genetic short straw? Should employers have the right to know about their workers' genetic propensities? Should insurance companies be able to exclude people because of what their genes reveal? And should genetic information collected for therapeutic or research purposes be made available for other uses, such as criminal investigations?
The answers to questions such as these are under deep discussion around the world, as policy-makers, legislators, and scholars hurry to lay the foundation for the ethical use of our emerging genetic identity. But the very same questions have been part of the conversation at Indiana University for many years now, sparked in part by the work of IU researchers on a piece of the genetic puzzle that fell into place well ahead of the Human Genome Project's findings.
That particular puzzle piece centered on Huntington's disease, a devastating, degenerative brain disorder that affects tens of thousands of people in the United States, and many more around the world. The symptoms, which can begin with stumbling, disorientation, and personality changes, typically appear when people are in their 30s. And while the fatal disease was long known to "run in families," there used to be no way of determining who would get Huntington's disease unless and until symptoms appeared.
All that changed beginning with a discovery made in the early 1980s. With a lucky break very early in the history of human genetic mapping, MIT researchers were able to locate the gene that causes Huntington's disease.
"Huntington's disease is caused by an abnormal gene on chromosome 4," says Michael Conneally, Distinguished Professor of medical and molecular genetics at the IU School of Medicine and an internationally recognized expert on Huntington's disease. "That gene was mapped 22 years ago."
Conneally, who was directing the Huntington's Disease Research Roster for Patients and Families at the time, was a member of the collaborative team that went on to find, in 1993, the gene that causes Huntington's disease.
The early breakthroughs into the genetics of Huntington's disease led to reliable predictive tests for the illness. "We can now tell if a person has the abnormal gene," explains Conneally. "If you have the gene, it's certain that you will get the disease at some point in your life."
Because the disease is progressive and incurable, not everyone at risk for the disease — those with a parent or sibling who has been diagnosed with Huntington's — wants to know if his or her genes contain the same ticking time bomb waiting to explode.
"In Indiana, we were able to get state funding to provide testing free of charge for those at risk, and only about 13 percent availed themselves of it," says Conneally. "That's not unusual. Nationally, the rate is about 15 percent."
Conneally believes that psychological stress is probably the main factor in people's reluctance to pursue the test. But there are practical considerations, too, concerns about who might have access to that information and how it might be used. And in many ways, says Conneally, the experiences of those who have been tested for Huntington's disease provide a window onto the future of genetic testing and its ethical implications.
WORKPLACE WORRIES
What if your employer found out that you were going to develop a disease that would affect your job performance, perhaps prohibiting you from undertaking certain tasks or even impairing your thinking? Would your employer have the right to base decisions about your salary or potential for promotion on that information? How about deciding whether you stay on the payroll at all?
These may very well become some of the questions facing people whose genetic propensity for disease is revealed as a result of the Human Genome Project. The questions already confront those with the gene for Huntington's disease.
"Very often, people with Huntington's disease will have a change of personality," Conneally explains. "They become 'ornery,' to use a colloquialism. So there arises an issue about their suitability for managerial roles, for example."
Forgetfulness, too, can plague those in the early stages of the disease. "We worked with an air-traffic controller who had the Huntington's gene," Conneally says. "Of course, any kind of memory lapse in a position like that is a serious problem."
In fact, driving, working with machinery, concentrating for long periods of time — all of these and many other workplace skills can be threatened even in the early stages of Huntington's disease. But, says Conneally, the job-performance problems that workers may face because of their diseases "are separate issues from the important matter of preventing discrimination" against those with any genetic predisposition for disease.
"Those specific questions of whether a person can do this job or that job should be treated separately, one case at a time," he says.
David Orentlicher, a physician, lawyer, and core faculty member of the Indiana University Center for Bioethics, agrees that protecting people from discrimination on the basis of genetic factors is an increasingly pressing issue for society.
"It can be easy to point the finger at those with relatively uncommon disorders and to ignore the burden placed on them," he says. "It's a majority versus minority dynamic in many ways, a case of haves and have-nots."
But as pieces to the human genetics puzzle continue to be put into place, says Orentlicher, Samuel R. Rosen Professor and co-director of the Center for Law and Health, we will see fewer and fewer "haves," people whose genes reveal no propensities for disease. "It's believed that every one of us has from three to five genetic abnormalities," he says.
"There are lots of health conditions with genetic components that we would never imagine letting employers use as the basis for making discriminatory decisions — conditions like hypertension, Type II diabetes, and obesity," he points out. "I think that's because those are the diseases that are, in fact, quite common in corporate boardrooms and executive offices across the country."
Orentlicher, who deals with both political and ethical issues as a member of the Indiana House of Representatives, believes that much of the workplace discrimination that people may face on the basis of their genetic makeup is "a consequence of the absence of universal health care" in the United States.
"If it weren't for the issue of health insurance, employers would be far less concerned in most cases about having an employee with a predisposition to disease," he says.
INSURANCE ISSUES
Insurance, in fact, is another focus of concern for ethicists and others grappling with the implications of the human genetics revolution. These concerns begin with ensuring the availability of health and life insurance for those whose genes reveal a future of health problems, a likely early death, or both.
"Among the people we work with, we have already seen a situation in which a man with the gene for Huntington's disease was told he couldn't be insured because of that," Conneally says. "Fortunately, the man was an attorney, and the insurance company soon thought better of that decision."
Like Orentlicher, Conneally believes that our increasing understanding of genetic warning signs for all kinds of illnesses may help reduce the focus on people with uncommon diseases or risk factors. It may change the way insurance companies do business, too. "Insurance companies can't rule out everyone with a genetic predisposition for disease," Conneally says. "They'd have nobody left to insure."
Forced genetic testing raises another area of concern centered on insurance companies. For example, because it is known that the children of a person with Huntington's disease have a 50 percent chance of harboring the defective gene themselves, some insurers have discussed the feasibility of requiring testing for anyone whose parent or sibling has been diagnosed with Huntington's.
"It's absolutely unethical," says Conneally.
"Insurance companies want what they term 'a level playing field,'" he says. "They want to be sure that all insurance companies play by the same rules and thus have access to the same information about the people they insure."
PRIVACY PROBLEMS
Insurance companies aren't the only ones concerned about access to genetic information. Policy-makers, biomedical ethicists, and law-enforcement officials are also weighing in on the important matters of privacy and confidentiality and how these can be balanced against the benefits of making certain types of genetic information available for certain uses.
On one hand is the possibility of creating a giant genetic database, a powerful tool for apprehending violent criminals and for identifying victims of accidents or violence. On the other hand, say many ethicists and civil libertarians, is the potential for breaches of privacy and abuse of genetic information.
Genetic databases are hardly the stuff of futuristic fantasy. For more than a decade, people who enlist in the U.S. military have been required to give a blood sample for the purposes of creating a "DNA fingerprint" to be used, if necessary, to identify their remains. And already, the armed forces' repository of more than 3 million specimens not only has served its stated purpose — supplying genetic information used to identify victims of the Sept. 11 Pentagon tragedy, for example — but is also regularly asked to supply information for a number of other uses, from criminal investigations to paternity suits (although it doesn't comply with requests for the latter).
Another large-scale database is being created in Iceland, where the country's entire citizenry is providing genetic material as part of a research study. "The company doing the study, deCODE, hopes to identify the genes for complex diseases," Conneally explains. "Iceland was chosen because of the size of the population and the excellent medical records and family histories of the people."
But for Conneally, the key question is, What else can and should we do with this information? "If a rape occurs in Reykjavik, the information to identify the assailant would be available, and there would be many who would say finding a rapist is a laudable use of that information," he says.
"But what if it's a broken window, on which the perpetrator left some blood? Or a theft? Do we want to use genetic information in those cases? We have to think carefully about where we draw the line. We don't want to be living in an Orwellian society."
That vision, of a society in which genetic information is used to the detriment of society and humankind, has prompted one of the most common metaphors for human genetics research. "It's often compared to a Pandora's box," says Eric Meslin, director of the IU Center for Bioethics, whose training is as a philosopher. "There's a strong sense that the positive uses of this research are linked to potential for horrific abuses."
How do we prevent winged pests — or even monstrosities — from flying out of the box that appears to hold so much promise? Despite their disparate disciplinary backgrounds and perspectives, Conneally, Orentlicher, and Meslin find common ground in at least part of the answer: greater understanding of the issues at stake, including, if not especially, among the general public. Informed lay people, say these experts, have a better chance of protecting themselves against genetic discrimination and breaches of privacy.
"When people don't understand a scientific or medical matter, it often makes them needlessly fearful," Conneally says. "And that never leads to good results."
Just as important, those who understand the scientific and ethical dimensions of these issues can contribute to the social and political decision-making that will shape genetic policy and law.
"From an ethical perspective, the more people feel empowered to participate in the debate, the better," says Meslin. "You don't have to have a Ph.D. to have an opinion about these issues, or to have an opinion that matters." 
Elizabeth Hunt, BA'88, will become editor-in-chief of Indiana Alumni Magazine on July 7.