Progress or Peril?

It's one of nature's most enduring mysteries: What makes human beings tick?

Why are they unique among living things? Do their genes really determine who they are?

Researchers think they are about to deliver some answers. When they do, they could change the world of medicine as profoundly as Copernicus transformed astronomy or Pasteur redirected biology and agriculture.

But this new world of genetic science is proving a crowded one. Researchers and entrepreneurs, engaged in a high-stakes race, are pushing and shoving to conquer the new frontier. It's as if, three years after Columbus discovered America, the land already ran thick with explorers, homesteaders, and Gold Rush entrepreneurs all looking to stake their claim.

Amid the elbowing and jostling, some researchers worry that the technology of genetic discovery has far outrun the public's ability to deal with the thicket of ethical issues it will create. The current debate over human genome ownership is troubling enough. Many more dilemmas lie ahead.

"You ain't seen nothing yet," says Stephen Joseph, president and chief executive officer of the National Center for Genome Resources, a nonprofit research institute in Santa Fe, N.M.

In years to come, he predicts, society will have to figure out whether insurance companies can set premiums based on an individual's genetic predisposition to disease; whether employers can screen new hires based on their genes; and, perhaps one day, whether parents have the right to decide the eye color and IQ of their unborn children.

"This new world is creating many dangers for the consumer," says Keith Wailoo, professor of social medicine and history at the University of North Carolina at Chapel Hill. "The genome project is going to be the microcosm of these larger issues."

Mapping the human genome stands at the center of a medical revolution. Once scientists piece together the human string of DNA - a daunting task involving 3 billion separate pieces of genetic jigsaw - doctors will be able to practice medicine on a new genetic basis. They'll be able to know specifically which genes are affected by a particular drug long before the drug gets tested on people. They'll have new ways of looking at sickness. And instead of prescribing drugs, they may one day insert genes to solve a problem. It "is changing the way we view ourselves," says Robert Waterston, head of Washington University's genome sequencing center in St. Louis.

That is why 14 hours a day, seven days a week, medical researchers here blast apart chromosomes, pick through genetic fragments with toothpicks, run them through computer analyzers, then piece them together again. The center is one of five major publicly funded facilities collaborating to map the human genome. The group already has finished 400 million DNA units and hopes to have a rough draft of the entire human genome by next spring. The complete code should be available by 2003.

But publicly funded researchers are looking over their shoulders because several private entities are racing to conduct their own analyses of the human genome. And, unlike the public effort, which is making its mapping results freely available to other researchers, the private companies are busy patenting large chunks of the genome for their own use.

The idea that someone can own a patent on a piece of generic humanity may sound outlandish. Indeed, the US Patent and Trademark Office doesn't issue patents on discoveries, only inventions that are novel and useful. But the office does grant patents to researchers who isolate plant material in the wild, create a pure form of that material that doesn't exist in nature, and then use it to treat a disease. So it's not a big leap for the patent office to consider pieces of the genetic human code (which don't exist by themselves in nature) in much the same way.

But the process raises several ethical questions. For example, many scientists argue that much of the computer-generated research remains far too preliminary to qualify as an invention.

"I don't want to put so many barriers in the way of industry that they won't use" the research, says Dr. Waterston of Washington University. But "they have to have some insight about that piece of DNA beyond what is done with computational analysis."

Of course, it's difficult to draw the line, because publicly funded researchers are also filing for patents. Researchers are most troubled by companies' push to patent expressed sequence tags or ESTs. These genetic tags give some idea of what a DNA sequence looks like, but no more finely tuned than trying to grasp the meaning of a sentence from a few words imperfectly spelled.

Are such rough clues really useful? Companies think so. They've filed thousands of EST patent applications, often for defensive purposes. Since ESTs partially describe what a full gene might look like, they file the EST applications to prove they're working on particular genes. When they go to patent the full gene, which is far more valuable, they can use the EST application in case someone else claims to have discovered the full gene.

"This is the Golden Age of medical research," says Roy Whitfield, chief executive officer of Incyte Pharmaceuticals Inc. of Palo Alto, Calif. "We're staking claim at the first possible opportunity we have. [But] if it weren't for the patent system, would people be doing all this research?"

Probably not, researchers agree.

Another worry: If would-be monopolists tie up specific genes with patents, they could restrict further research by others. Or they might charge such high license fees to use their gene, that doctors would be unable to use it to cure someone. The potential already exists in medical diagnostics, where firms can insist they alone will conduct tests using a specific gene, says Jon Merz, a bioethicist at the University of Pennsylvania.

Such scenarios seem unlikely, argues Mr. Whitfield of Incyte. "I can't imagine us going after an academic who's doing research on a gene."

In fact, the company encourages such research. The more uses scientists find for its genetic material, the more valuable the company's patent becomes. Incyte already has received patents on some 250 full-length genes, up from about 50 a year ago.

Many observers believe companies will work out cross-licensing and other technology-sharing agreements so that research can go forward. Still, the potential exists for patent holders to create such a thicket of claims and counterclaims that scientists will steer clear of certain genes.

"It becomes a difficult line to draw," acknowledges John Lynch, an intellectual property attorney at Arnold White & Durkee in Menlo Park, Calif. And "it happens in all technologies. There are individuals in the electronics industry ... who are standing there with their palms up when they really haven't contributed to the major advance that's being marketed."

The third worry is more subtle: Will the increasing private-sector funding narrow the scope of scientific inquiry to genes that bring the most profit?

The issue is already bubbling up in agricultural biotechnology. The influx of corporate money is spurring rapid advances in crops grown by farmers who can afford to pay for the new wonder seeds. But there's little incentive for companies to develop new genetic variations for impoverished farmers in the developing world, even though they're in more dire need of the advances.

Earlier this month, for example, Swiss researcher Ingo Potrykus announced a new variety of vitamin-rich rice that should measurably improve the diet of the world's rice-eating poor. But his funding came from foundations and the public sector. Left to the giant seed companies, the research would never have taken place, he says.

"When physicians become researchers, they take a new hat," says Wailoo of the University of North Carolina. When they also become stockholders in a genetics-research company, they put on a third hat. "It poses real dangers for patients who can enter clinical situations not knowing fully what they're getting into." And it may affect how they treat patients, he adds.

"There are dynamic tensions and there are tradeoffs," says Leslie Platt, president of the Foundation for Genetic Medicine, a nonprofit education group affiliated with George Mason University in Manassas, Va. But the best way to minimize the downside is to couple the privileges of the patent system with the obligation to follow recognized best practices in the industry, he adds.

Ethical dilemmas will likely loom larger in the human field than in agriculture, researchers agree. "You can engage in a whole series of failed experiments in the agricultural world until you strike the right approach to applying genetic engineering to plants," Wailoo says. But "human beings are not like tomatoes.... You can't afford those kinds of failures." It's too early to tell if society is striking the right balance, he adds. "We're just lifting up the tent flap.... I'm not sure any of us comprehend what a watershed of change in the human condition we're in."

(c) Copyright 1999. The Christian Science Publishing Society