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Creating a 'genobility'
Sunday, July 16, 2000 By Byron Spice, Science Editor, Post-Gazette
Genetic insights may extend life, enhance offspring
Today, the only place where all the women are strong, all the men are good-looking and all the children are above average is Garrison Keillor's mythical Lake Wobegon.
But genetic advances may someday make those people a reality, even if Lake Wobegon remains a fantasy.
Scientists who are still struggling to manipulate genes to correct inherited defects say that it will be decades before prospective parents will be able to pick their baby's hair color or athletic skills out of a catalog. Yet every report of cloned sheep and genetically engineered "smart" mice brings speculation that people eventually will be genetically enhanced as well.
Last month's announcement that scientists have largely determined the spelling of the entire human genetic code carries the promise that they might someday understand its meaning. And that has only increased talk about making people who would be uniformly smart, caring, tall, strong, handsome, beautiful and charismatic.
Maxwell Mehlman has even coined a word for them: the genobility, for "genetically enhanced nobility."
Mehlman, director of the Law-Medicine Center at Case Western Reserve University in Cleveland, is no geneticist; he's a lawyer. But he figures it's only a matter of time before the technical barriers to making designer babies fall and society is altered by a growing genobility.
If that seems far-fetched, Mehlman explains that he is "a professional paranoid. I'm paid to think of worst-case scenarios."
Mehlman worries about creating genetic haves and have-nots, which he maintains could destabilize society. And talk of engineering humans contains echoes of the eugenics movement, which led in America to sterilization laws for the "mentally unfit" in the 1920s and '30s before its supposedly scientific underpinnings were discredited.
Eugenics, the attempt to improve the human race through breeding and other genetic means, reached its ugly zenith in Nazi Germany. People deemed physically or mentally unfit were killed, and the Lebensborn program encouraged men and women with desirable characteristics to mate and produce a blond-haired, blue-eyed master race.
Altering the 'germ line'
In the last decade or so, hundreds of medical researchers have attempted to treat disease by replacing defective genes in cells or by adding beneficial genes, an approach called gene therapy. But these experiments have always been performed on "somatic" cells not involved in reproduction, rather than "germ-line" cells such as sperm or eggs that would allow genetic modifications to be passed on to offspring.
Eric Lander, director of the Whitehead Institute/MIT Center for Genomic Research in Cambridge, Mass., said he long assumed that no responsible researcher was interested in germ-line modifications. But the more he talks with fellow scientists these days, the more they tell him it wouldn't be such a bad idea.
Imagine being able to increase intelligence, or stave off the ravages of aging. Could those be bad things?
For now, Lander favors a ban. But if and when it becomes technically feasible, all bets are off.
"I don't know if we can say 'no' forever," Lander said.
"Eugenics of the future won't be government-enforced, but consumer-driven," said Dr. Michael Gorin, interim chairman of human genetics at the University of Pittsburgh. Germ-line changes will occur because parents want a child with enhanced musical talent, or blue eyes, or the height of an NBA center.
The immediate problem is that many genes, maybe most, perform multiple functions. If you change a gene to enhance one characteristic, it could have unintended consequences. It may turn out that engineering a child to be a fast runner might increase his susceptibility to colon cancer, for instance.
"Why do you think we have so many automobile recalls?" Gorin said. "Certainly people know how to build cars by now. But people make changes, often with the intention of making improvements, that have unanticipated effects."
That's one reason that even conventional gene therapy likely will be used only for serious disorders -- diseases and conditions that are disabling or life-threatening and, therefore, worth the risk of side effects, Gorin said.
Germ-line modifications, however, are possible and probably inevitable, said Dr. Arthur Levine, former scientific director of the National Institute of Child Health and Human Development and dean of the Pitt medical school.
"The history of science is that once we know how to do something, eventually we start doing it," Levine said.
A subtle revolution
When we start making inheritable changes, we'll probably back into it, said the Rev. Ronald Cole-Turner, who specializes in the ethics of science and technology at Pittsburgh Theological Seminary.
"I think we will move in such small increments that it will fly beneath the moral radar of the population," he predicted. Sometime in the next decade, perhaps, a germ-line modification may slip through as a side effect of conventional somatic cell gene therapy.
For instance, gene therapy to correct a genetic defect in a girl may inadvertently alter the DNA in the girl's eggs, so that none of her children will carry the undesired trait.
"If that was a side effect of the therapy," Cole-Turner suggested, "most people would say 'Sign us up sooner rather than later.' "
Or there may be a disease that can be treated only by germ-line modification, such as a reproductive disorder.
"Any ethicist looking at that couldn't say no," said Cole-Turner, who recently served on an American Association for the Advancement of Science panel examining issues surrounding germ-line modification.
Religions tend to favor healing and the elimination of pain, Cole-Turner noted, and the line between healing and enhancement is often thin. Would anyone object to boosting the intelligence of a person with Down syndrome or delaying the onset of dementia in an Alzheimer's patient? If not, then at what point do you stop enhancing intelligence?
What is the difference, he continued, between altering DNA to prevent heart disease and administering a vaccine to prevent an infectious disease?
"Is a vaccine a therapy or an enhancement of nature?" Vaccination is now seen as such a societal good that parents can be sanctioned for failing to have their children immunized, he noted.
Perhaps one day genetic enhancement will be considered routine, even expected -- a scenario suggested in the 1997 science-fiction movie "GATTACA," in which children conceived without genetic improvements were called "in-valids" or "faith-births."
"It's going to be extremely hard to know when to stop saying yes," Cole-Turner concluded.
Living long and well
The ethical issues aren't confined to the beginning of life. Many conscientious researchers are actively pursuing ways to extend human life span.
"We have to take over from where the process of evolution has left off," said Dr. John Marler, scientific leader of the National Institute of Neurological Disorders and Stroke's neurodegeneration group. Evolution, he explained, may have limited our life spans because there is no species survival value for people to stay alive once they have raised children and grandchildren. That means extending our "health span" beyond the age of 100 may require undoing some longstanding genetic programming.
Marler is not talking about immortality. Instead, "we're talking about the brain functioning as it is supposed to for as long as you are alive."
In one way, then, finding how to prevent or cure degenerative brain diseases such as Parkinson's disease and Alzheimer's disease -- the main thrust of Marler's group -- can be seen as life extension.
But Dr. George Zubenko of the Western Psychiatric Institute & Clinic suspects that staying alert mentally into old age also may involve genes that have nothing to do with a specific disease.
He studies people who have lived to 90 with their mental faculties intact to find out what might lurk in their genome that enables them to age so successfully.
He's been gathering a group of 100 such people, using an array of genetic markers to analyze their genomes.
Zubenko compares the genetic makeup of his successful agers with people ages 18 to 25, a group that presumably includes those who will have both short and long lives. He reasons that some genes -- genes that enhance longevity -- will be expressed more often in the older contingent than in the younger group. Likewise, genes that contribute to premature deaths should be expressed less often in the older group.
The availability of a complete sequence of the human genome should make it easier to identify the specific genes associated with the genetic markers that the study finds significant, Zubenko said.
Mimicking calorie reduction
Maintaining physical health into old age also may be enhanced through genetics, said Anna McCormick, chief of the genetics and cell biology branch of the National Institute on Aging's biology of aging program.
For instance, mice have been shown to live longer when the calories in their diets are cut by 40 percent. It should be possible to use DNA microarrays -- a new tool that enables researchers to determine which genes are turned on in a cell -- to see how the cells of these mice differ from those on a normal diet. Once that difference in gene activation is known, it may be possible to design drugs or isolate a human hormone that can mimic that action.
"I can't see the human population eating 40 percent fewer calories," said McCormick, a Baldwin High School graduate. "I think we need a drug."
A similar technique might be used to find chemical or hormonal means of maintaining muscle mass, which tends to waste in old age.
Marler maintains that this sort of tinkering with evolution is nothing new. "We mess with evolution when we go to the optometrist," he said. Better nutrition also could be seen as altering our genetic inheritance, but "no one asks what you're going to do with the extended life you get from eating a low-fat diet."
Some technical possibilities in the new genetic era may turn out to hold little appeal.
Though the cloning of Dolly the sheep touched off new speculation about cloning humans, people may find that the reality of cloned humans -- or clones of anything to which we feel emotional attachment -- is unsatisfying.
University of Pennsylvania bioethicist Art Caplan believes the wealthy couple that gave Texas A&M scientists $2.3 million to clone Missy, their beloved collie-husky mix, will ultimately be disappointed. Yes, they'll get a clone of their perfect dog with the business-like bark, he acknowledged. But what they really want is for their dog to live forever, and that's not going to happen.
It's a reality that scientists appreciate better than the public: Even though genes have a powerful influence on our lives and our health, environment and upbringing still count for a great deal of who we are and even what our pets are.
Seeking an edge
Still, the benefits of enhancing, rather than duplicating, human offspring will be enticing, Case Western's Mehlman said. After all, people go to great lengths to give their children even small advantages -- private schools, music lessons, football camps, homes in safe neighborhoods.
"Those things will look primitive once it becomes possible to create genobility," he said.
Yet even if the technical barriers to a genobility may fall, the economic barriers are likely to remain. Already, advances such as single-cell analysis -- the ability to genetically screen a test-tube embryo to determine whether it should be implanted in a woman's womb -- are available only to people able to afford in vitro fertilization, which can cost $10,000 per attempt.
If wealthy people are able to concentrate their advantages, not just by sending their children to special classes or schools, but by gaining huge improvements through genetic engineering, the gap between the haves and have-nots will only get worse.
"That's not a democracy," Mehlman said. "That's feudal society, a caste system." If people don't perceive that they or their offspring have a chance of upward mobility, the principles underlying Western democratic society will break down and civil unrest could occur.
As yet, no solution appears obvious. Any attempt by the government to regulate reproduction can become mired in charges of eugenics. Even government subsidies for reproductive enhancements might be suspect.
One solution -- though a pathetic one, Mehlman admits -- might be a lottery. Rather than competing for a cash jackpot, couples would join a lottery that gives the winners access to genetic enhancement.
"Whether you like them or not, lotteries do help maintain social stability," he explained. "They let people feel like they have a chance."
Another answer, Cole-Turner suggested, may be to cultivate "a moral culture" that persuades people to tread carefully with genetic technology and to express disapproval when it is used irresponsibly.
"Instead of enhancing a few through off-shore clinics, let's enhance the health of children worldwide," he said. Genetic technology could be used to increase resistance to many diseases and thus reduce the socioeconomic burden of developing nations.
"Technically, that's a more attainable goal than a child with an IQ of 200 and perfect health," he said. "We don't want a world in which you need to build forts around the enhanced. That's not the world we want."
For more information about the Genetics of Successful Aging project at Western Psychiatric Institute and Clinic, call toll-free at 1 (877) 485-7568 or visit the Web site at www.edc.gsph.pitt.edu/genlab/gensa /
For information on the American Association for the Advancement of Science's Dialogue on Science, Ethics and Religion and links to related sites, visit its Web site at www.aaas.org/spp/dspp/dbsr /
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