Pandora's Helix

by Dan Richardson


It has been compared to the moon landing and to the detonation of the first atomic bomb, even to the invention of the wheel. Given its profound implications, people almost cannot help but speak in historic terms when the subject is the Human Genome Project.


The comparisons began in earnest last February, when scientists working for the U.S. National Institutes of Health, Department of Energy and the private company Celera Genomics published in Science and Nature the working draft of the human genome, the description of our genetic code.


The genome is sometimes called the "book of life." Its mapping represents a great leap forward in medicine, promising eventually to help cure terrible diseases and enhance life even before birth.


In the same month the Human Genome Project's draft made headlines, politicians were apologizing for an 80-year-old perversion of genetic science. That's because the Human Genome Project is not the first widely hailed and popular use of genetics. Early in the 20th century, governments in the United States and Europe attempted to breed away chronic social problems like drug addiction, crime and mental illness. It didn't work, but for years the idea remained ingrained in public policy.


Americans called this misuse of genetic theory "eugenics," and the result was that 30 states forcibly sterilized thousands of citizens. Some sterilization laws existed until the early-1980s. So it was that two weeks before scientists published the genome working draft to worldwide acclaim, the Virginia House of Delegates passed a resolution expressing the state's "profound regret" for its sterilization of 8,000 "defectives."


The program caused, the resolution said, "incalculable human damage done in the name of eugenics."


Conspicuously absent from the resolution: an apology.





The Human Genome Project generates not only


information on our genetic code, but also ques-


tions about how that information should be used. A massive coordination of U.S. and international scientists, the genome project is the work of U.S. government agencies, research laboratories and private corporations. The cost is projected at around $3 billion over the project's 15-year span, ending in 2003.


The goal is nothing less than a detailed map of the human genome. A genome is all of an organism's genes, which carry in their DNA the information for making the organism's proteins. The proteins determine individual characteristics ranging from hair color to one's susceptibility to cancer.


"If I were going to pick five things that changed man, it would be one," Dr. Michael Donlan says of the project. "I think it's going to be up there with the wheel."


Donlan is the former director of pediatrics at Sacred Heart Medical Center, and also former director of the Inland Northwest Genetics Clinic. He is one of several speakers at a conference in Spokane this weekend where physicians, theologians and philosophers will discuss the ethical implications of the Human Genome Project.


So far, the genome project has raised far more ethical questions than it's answered. They include:


Who should have access to personal genetic information -- family members, employers or insurance companies? And how do we prepare physicians for the new genetics?


Even with most of a genetic map drawn up, scientists know just the tiniest fraction of how human genes interact.


"It's like a book in a foreign language that you don't understand," says Fred Sanger in a Science article. Now retired and living in England, Sanger performed pioneering work on DNA sequencing in the late-1970s. "That's the first job, working the language out."


Many scientists and critics say that, with the Humane Genome Project, our knowledge of genetics is outpacing our ability to wisely use it.


"Right now, science is moving a lot faster than social ethical practices," says Mark Alfino, professor of philosophy at Gonzaga University and a panelist at the Spokane conference.


The genome project opens a huge amount of information to examine and experiment with, says Alfino. Often, though, that information is more about possibilities than certainties, like the possibility that a child might be born with a tendency toward alcoholism, or the possibility that an adult may develop cancer.


"We don't know morally how to deal with that information," he says.


Ethical questions about genetic information affect Inland Northwest residents today, here and now -- anywhere, in fact, where genetic testing takes place.


Genetics medicine raises emotions like no other, because "it gets to the question of who we are," says Julie Hanna, Sacred Heart's director of cytogenetics. (Cytogenetics is diagnostic testing based on a person's genetic information.)


Genetics testing does not reveal information just about a given patient, but also about the patient's family, Hanna says. Consider a woman whose genes show the probability of her developing breast cancer. That could mean her sisters are at higher risk, too. But there is no rule or generally accepted guideline that says she has to tell them.


Or consider a young adult for whom genetic tests even before birth may have shown a high risk for some irreversible and fatal malady, says Alfino. "If I'm a kid and I'm staring down a genetic illness, is it better not to know until the symptoms develop?"


As the Human Genome Project and its follow-up advances reveal human genetics in detail, these kinds of ethical dilemmas are going to multiply.


"It is a problem right now," says Alfino, "and it's a problem doctors can't solve for you."





If the Human Genome Project raises


so many unanswered and painful


questions, why pursue it? The lure of increased genetics knowledge is powerful. Scientists and doctors say the project will vastly advance medical practices.


Doctors' abilities to handle emergencies -- a broken leg, a burst appendix -- are impressive, but medicine still struggles mightily with chronic ailments, from back pain to diabetes. Genetic knowledge might help medical workers better address those ailments.


The technical advances in the genetics era are undeniable. In 1990, for example, all clinicians had at their disposal were four genetic tests for diseases, according to cytogeneticist Hanna. Last week, there were 876 such tests.


In 1990, manually examining a patient's DNA sequences took one to several days. Today, computers can read them in several hours.


The most amazing advances will come in the future, as scientists learn better how to read the book of life they're recording. Many physicians look forward especially to "pharmacogenetics," or the use of a person's genetic information to individually tailor drugs to their ailments. That could mean more effective drugs with fewer side effects.


"It's going to be a real stride forward," says Donlan, the former pediatrician and genetics director.


Genetics information could eventually also help treat mental disorders and similar chronic problems where current approaches fall short, he says.


One promise of genetics testing is that physicians would not have to wait until symptoms appear to diagnose these problems. More and more of them could be detected in babies, or even in the unborn. Say a person's genes will code for a cancerous tumor somewhere between ages 20 and 30. Having that knowledge from the person's infancy could mean that the application of a low dose of individually tailored medicine might prevent the tumor from ever developing.


Of course, there's many a malady doctors could still do little about, just as AIDS still kills people in the world's most advanced health systems. Knowing that a person is predisposed to an early death could mean loss of employment or higher health insurance premiums, some observers predict.


Those are valid concerns, even if the problems are far off, says Alfino. Some large employers (including Alfino's, Gonzaga University) self-manage their health insurance, meaning they pay their employees' health bills. An employer doing so could conceivably discover a person's genetic information, he says. If a certain employee has a 40 percent chance of developing a fatal illness in the next five years, perhaps there's a better candidate for promotion?


That's science fiction now -- more or less -- but with the advances of the Human Genome Project, perhaps not for long.


Says Donlan, "There's little question that in a practical way, it's going to affect people."





If you talk ethics and genetics with


physicians, you're talking about


making people better, more ideal. There's much to that, like new cancer therapies and prevention of birth defects.


Eventually, however, the conversation winds its way to eugenics.


Eugenics is what Americans and Europeans used to call the science of breeding better people. Very often, that meant sterilizing criminals, the mentally ill, even immigrants from certain countries. The Nazis called it "race science," and in their most extreme legacy, eugenics ideas were the underpinnings for the mass murders of the Holocaust.


American eugenics was not much kinder or gentler. Some 30 states, including Washington, Idaho and Oregon, passed laws allowing the state forcibly to sterilize men and women for reasons ranging from sex crimes to epilepsy. "Three generations of imbeciles are enough," was how Chief Justice Oliver Wendell Holmes put it in his U.S. Supreme Court's 1927 decision that upheld forcible sterilization.


By the late-1930s, Oregon alone had forcibly sterilized 1,000 people, Washington 200, and Idaho 26, says Mark Largent, a history professor at Tacoma's University of Puget Sound.


Progressive reformers, often the same people who supported women's suffrage and temperance, saw eugenics as a public health measure, says Largent. So the most active sterilizers were "states that invest more money into public welfare."


Contrary to one historical "myth," says Largent, the Nazis' Holocaust did not turn Americans off from sterilization and other aspects of eugenics, like laws forbidding interracial marriage. American sterilizations peaked in the 1940s and '50s and only fell out of favor with the patients' rights movements in the 1970s.


Eugenics of old was about weeding out the "unfit" or the "feeble-minded." Many physicians and ethicists believe genetic advances will create a new eugenics, backed not by state coercion but by social pressure. On the one hand, people have a natural desire for healthy babies, but on the other, they could become less tolerant of supposed defects.


People might want to be parents of a six-foot, blonde, blue-eyed beauty and be willing to order gene therapy to achieve that, supposes Donlan, the former Sacred Heart geneticist. He calls the idea "dial-a-child" or the "perfect baby syndrome."


Already today, some people visit genetic advisors before having children, notes Largent. Those advisors don't have government power, of course, but they can give seemingly neutral information in a socially coercive way, he says.


"If you tell people they have a 63 percent chance of having children with Downs Syndrome," he says, "you're saying they have a high chance of having a child you consider to be inferior."





The human thirst for knowledge is as


ancient as the secret of fire. So is


the idea that knowledge can burn the unwary. When Mary Shelley wrote Frankenstein in 1818, her novel's subtitle -- The Modern Prometheus -- referred to the ancient Greek myth about the titan who was said to have stolen fire from heaven to give mankind. Victor Frankenstein, his monster and Prometheus all met bad ends.


If history is any guide, the Human Genome Project and similar development will open us to undreamed-of advances, while posing the threat of unlooked-for consequences. There is some evidence that scientists and public health officials are treading somewhat more carefully than their predecessors. Government agencies' funding for the project are setting aside 3 to 5 percent of their budgets for debate on the ethical questions, according to the Department of Energy's Human Genome Project Web site (www.ornl.gov/hgmis/).


Still, the idea of human perfectibility that some might see within genetics research is a hypnotic one. The 20th-century eugenicists thought they were perfecting society by removing its ills. In this century, many individuals may hope to perfect their own bodies, or their offspring's, by altering their genetic functions.


"The cautionary tale should be about enthusiasm for science and technology," says Largent, adding, "I don't want to stop research, but we need to talk about it."


Perfectibility will remain impossible, physicians say. But the Human Genome Project has given one answer on the old nature vs. nurture debate: "It's both," says Alfino.


In other words, genes are not destiny, says geneticist Hanna. "It doesn't mean we don't have choices. People can still choose to exercise or not to exercise, or to smoke or not to smoke."


Meanwhile, those black-and-white certainties scientists do draw from genetic mapping will create their own gray areas, ethical dilemmas and moral choices.


"There's still going to be gray out there," despite a wealth of new knowledge, says Donlan. "The gray's going to have to do with who gets access to it."


Even if we settle the question of how to handle genetics information and then apply it with precision unimaginable today, the world will still be wracked with human woes.


"Every one of us has genetic disorders," says Hanna. "No matter what we do, there will always be babies born with mutations."





The Human Genome Project conference begins Friday at 7 pm at Sacred Heart Medical Center's Providence Auditorium. Ticket prices for the evening are $20. The conference continues Saturday starting at


8 am through lunch for $60. Among the


other speakers will be Dr. Victor McKusick, namesake of the McKusick-Nathans


Institute of Genetic Medicine at


Johns Hopkins University.