As gene map nears, big questions

First draft of the human genome is hailed for its medical promise. But ethics and theology are also at stake.

Not since Charles Darwin put forward his theory of evolution have natural scientists sparked such broad rethinking of that bedrock question: What is man?

Geneticists' unveiling of the first complete sequence of the human genetic code - expected sometime this month - is already causing a stir in the fields of medicine and law. Ultimately, this scientific breakthrough, like Darwin's bombshell, could challenge fixed social and theological ideas about humanity and its place in the universe.

Troubling ethical questions - such as eugenics for the unborn and genetic profiling for health insurance - are only the beginning. In mapping the human body's genetic code, researchers are framing a new context for an age-old debate: Is human nature the product of free will or predestination?

"The mapping information is going to help us rethink a whole lot of issues, such as privacy, confidentiality, ownerships of body parts," says Tom Shannon, professor of religion and social ethics at Worcester Polytechnic Institute and author of a new book on the subject. "It's really going to reshape how we think about each other."

For the medical profession, such changes will take time.

For one thing, the sequence is so long - some 3 billion parts - someone would have to spend more than 47 years round the clock merely to write it out. For another, the sequence that researchers hope to unveil this month will still be a working draft - incomplete and filled with small errors - that might not be finalized until 2003.

Even then, scientists won't understand the genome.

"Imagine that you have the entire works of Shakespeare in front of you, with no spaces and no grammar, and you don't know English," explains Betsey Dyer, a genetics researcher and biology professor at Wheaton College in Norton, Mass. That's what the complete sequence will look like. It could take decades to crack it.

Still, the complete sequence will mark a new plateau in scientific understanding. Two research teams - privately funded Celera Genomics in Rockville, Md., and a much larger publicly funded effort by academic, government, and foreign researchers - are racing to complete the sequence.

"It will revolutionize information about how our bodies work, how our bodies develop. It will lead to drugs and products that cure disease and prevent illness in the first place," says Michael Werner, bioethics counsel for the Biotechnology Industry Organization in Washington.

Already, it is shaking the legal profession, particularly in areas of patents and privacy.

Owning genetic keys

For starters, should companies own pieces of the human genetic code?

"The ability to obtain patent rights on human genome information can be incredibly commercially valuable," says Elizabeth Weiswasser, partner in the international law firm of Weil, Gotshal & Manges, headquartered in New York City.

The United States has offered patents on gene sequences for years. What's new, she says, are mass efforts at sequencing, which portend a flood of patents and court challenges as companies jockey for commercial advantage.

Privacy represents another looming legal tangle.

If doctors, armed with an individual's genetic code, eventually believe they can diagnose that a person in his 20s will incur a life-threatening disease in his 50s, who should know that information? The person? His relatives? His employer or insurer?

"We're not interested in genetic testing," says Herb Perone of the American Council of Life Insurers in Washington. But if such testing becomes routine medical practice, "we don't want to be denied basic information in the future."

Evidence of actual discrimination in the workplace remains mostly anecdotal. When the American Management Association surveyed more than 1,000 of its members last year, only three said they used genetic testing on employees or job applicants.

But already, a national women's advocacy group, the National Partnership for Women & Families, is warning women about how data gleaned from genetic testing can be used against them. In February, President Clinton prohibited federal agencies from using such data to hire, fire, or promote federal workers. At least two dozen states offer spotty protection against genetic discrimination, but there's no federal standard.

Such questions stretch far beyond the legal realm, ethicists say. For people diagnosed with a fatal disease that's years away, "how do you live your life?" Professor Shannon asks. "If this child is fated to die, does that mean the child is going to be rejected - a kind of genetic leprosy? ... It's putting the whole question of human mortality in a much different perspective."

Scanning the unborn

One of the first debates will erupt over the increased use of genetic screening of unborn babies for a new range of deficiencies, predicts Phillip Sloan, director of Notre Dame University's Program in Science, Technology, and Values. Unfortunately, doctors will be able to detect those defects long before they've developed any cures. That could push prospective parents into a thicket of ethical problems. Should they abort those children doctors believe will develop a genetic disease later in life?

As the medical advances of the technology become clearer, society will likely face bigger ethical dilemmas, Mr. Sloan points out.

For example, if medical geneticists one day are able to eliminate certain defects for a generation and all its descendants, what would be the consequences? Would it be ethical to add certain traits by genetic manipulation? What constitutes improvement anyway: Freedom from disease? Being thin? Tall?

The world's unfortunate experiences with the eugenics movement in the 1920s and '30s - including the mass sterilizations of people thought to be genetically defective - make many scientists and medical ethicists uneasy about using technology this way.

Of course, such visions may not come to pass, experts caution. At the very time that popular culture is beginning to contemplate genetic science in very simplistic ways, researchers are uncovering far more complexity.

There is no one gene for blue eyes or alcoholism or intelligence, for example.

Genes don't tell the whole story. They merely punch out a very complex code that gets translated into an expression of proteins which, scientists say, may not act the same way every time. Where they're located in the body, the presence of other genes, personal behavior, and a person's environment may all play a role in health and development, they say.

"It's more complex than we originally thought," says Ari Patrinos, director of the office that oversees the US Energy Department's genome research. Some diseases and physical traits may turn out to be too random to predict with any certainty, he adds.

In fact, so little is known about gene therapy that researchers may have to slow their clinical trials on people, some experts say.

In a clinical experiment last fall, teenager Jesse Gelsinger died several days after University of Pennsylvania researchers injected him with genetic material. The teenager had volunteered for the clinical trial but, according to his father, was not fully informed of the risks involved. Nor was he told that the lead researcher had founded a private company with exclusive rights to discoveries at his university institute.

The case hints at ethicists' concern over commercialization: For all its scientific promise, it may also put patients at risk.

The US Food and Drug Administration has accused the University of Pennsylvania lab of safety violations. Last month, the lab stopped clinical trials.

Meanwhile, the US Department of Health and Human Services is stepping up its monitoring of all clinical trials, and plans to force federally funded researchers to disclose to prospective patients their financial stake in any clinical trial.

Legally speaking, the science may be too new for anybody to properly give consent, suggests Franklin Zweig, president of the Einstein Institute for Science, Health, and the Courts.

The bigger issue

Perhaps the largest implications of the genome project lie with humanity's view of God and itself. Are men and women puppets, genetically destined to live a specific length of time with a certain level of intelligence and temperament? If altruism is predetermined by a special set of genes, does God even exist?

Even many genetic researchers reject such notions. "I don't believe in the excuse: 'My genes made me do it,'" says John Rodwell, acting head of AxCell Biosciences in Newtown, Pa.

"I think that's bad science and bad theology all rolled into one," says Suzanne Holland, professor of religious and social ethics at the University of Puget Sound in Tacoma, Wash. "That is to say that there is no free will - that everything's in the genes."

In fact, the complexity of genetic science may lead thought the opposite direction, she says. "This sort of combination of genes with the interplay of the environment is so magnificent and contains within it so much mystery that to my mind it's more reason for belief in God.... We might come to see God as far more involved in the world than the Newtonian mechanistic view of a God that sets up everything and steps out of the way."

(c) Copyright 2000. The Christian Science Publishing Society