Cosmetic Gene Therapy's Thorny TraitsBy Rick Weiss
Washington Post Staff Writer
Sunday, October 12, 1997; Page A01
As a medical researcher, Scott McIvor never suspected that his efforts to develop new cures would lead him to the edge of a brewing bioethical storm. Then, a few months ago, he got an e-mail message from a doctor who wanted McIvor to help him change a patient's skin color.
A similarly disconcerting request recently came to Christopher Evans at his office at the University of Pittsburgh. Evans is helping to devise a genetic therapy for muscle diseases such as muscular dystrophy, in which genes will be added to dying muscle cells to help those cells grow. A sports medicine doctor "put two and two together," Evans said, and asked whether he could get access to the treatment to help healthy athletes grow bigger muscles.
Evans answered with a definitive "no," and McIvor didn't even respond to the skin change request. Changes in skin color and muscle mass probably could be accomplished with current technology, they and others said. But the possibility of harm would be difficult to justify for a cosmetic procedure and, more important, genetic enhancement of healthy people raises a host of difficult ethical questions.
Would cosmetic gene therapy exacerbate racial or other prejudices, for example, by creating a market in preferred physical traits? Might it lead to a society of DNA haves and have-nots, and the creation of a new underclass of people unable to keep up with the genetically fortified Joneses?
The troublesome questions being raised by genetic enhancement are among many now arising as scientists break through long-standing barriers in various fields, such as human reproduction, genetic engineering and animal-to-human organ transplants.
Advances in farm animal cloning, for example, have stirred fears that human adults may also someday be cloned. And the mass production of gene-altered animals with "humanized" organs may bring not only an end to the shortage of transplantable organs but also new epidemics, as deadly animal viruses gain their first entry into people.
Some of these issues remain mostly hypothetical for now, but many are surprisingly close at hand. Given the accelerating rate of scientific advancement, experts said, it's not too soon to consider what limits, if any, ought to be placed on even some seemingly remote possibilities.
Until a few years ago, human genetic enhancement was one of those. But with the rapid-fire identification of genes affecting physical characteristics, such as height and skin color, and behavioral traits such as aggression and sociability -- and recent improvements in the art of injecting genes into people -- many scientists now believe that modest genetic makeovers could become a reality within the next few years.
"Certain types of enhancement will probably be upon us sooner than we'd like to realize," Evans said.
The federal government is taking that prospect seriously. The National Institutes of Health and the Food and Drug Administration convened a meeting last month to consider for the first time what regulations may be appropriate for cosmetic gene therapy. NIH officials organized the meeting so they might be prepared for the first such experiments, instead of reacting to them afterward, as happened when news broke in February that scientists had for the first time cloned an adult mammal.
"We all know it's coming," said Theodore Friedmann, a professor of medicine at the University of California, San Diego.
Public opinion polls suggest that the demand for genetic enhancements may be substantial. Surveys in 1986 and 1992 showed that 40 percent to 45 percent of the American public approved of the concept of using genes to bolster physical and intellectual traits.
Those polls also suggested, however, that the science had gotten ahead of the public understanding about the possible consequences of a free market in genes. Few people realize, for example, that although gene therapy holds promise against inherited diseases and cancer, none of the approximately 2,000 patients treated so far has been cured by the still experimental technique. Meanwhile, the procedure -- which generally uses special viruses to inject new genes into peoples' cells -- has the potential to cause cancer or other problems.
Because of those risks, federally funded scientists who want to put new genes into patients must first convince the NIH and the FDA that the potential for harm is outweighed by potential benefits. Privately funded researchers generally submit their proposals for review as well, although they don't have to.
No regulations specifically preclude the use of genes for cosmetic purposes, and until recently none seemed necessary. But in March, after months of internal debate, NIH officials changed the equation by approving for the first time a gene therapy experiment in people who were not sick.
But as researchers and regulators discussed at last month's meeting, the line between treatment and enhancement won't be easy to draw.
"The central question is, `What is a disease?' " Friedmann said. "Disease is a spectrum, spanning from what we all clearly believe to be disease . . . to someone like me who would clearly benefit from a hair transplant."
Friedmann, at least, may be in luck. A San Diego company that specializes in getting genes into hair follicles already is developing a gene-laden lotion that would be rubbed into the scalp to reverse baldness. It's also experimenting with genes that will make gray hair grow dark again and to make straight hair grow curly -- a truly permanent permanent.
"Genetic enhancement is going to happen," said University of Southern California gene therapist W. French Anderson. "Congress is not going to pass a law keeping you from curing baldness."
Anderson is one of many scientists urging the government to postpone for as long as possible that inevitability. But the ethical arguments against cosmetic gene therapy are not open and shut. After all, no one is against improvements in diet to help children grow taller, or better schools to help them learn. What's wrong with using genes to accomplish those goals?
Moreover, cosmetic gene therapy would not affect eggs or sperm (that kind of gene therapy, in which acquired traits could be passed to children, is technically more difficult and is widely considered to be a decade or more in the future), so arguments against engineering future generations do not apply. And old-fashioned cosmetic surgery has been around for decades with little apparent damage to the social fabric.
Some experts suggest that genetic enhancement bothers people because it represents a kind of "cheating" more fundamental than that of cosmetic surgery. For example, scientists already know that a gene called IGF-1, which makes muscles grow, could be valuable to an athlete heading for an Olympic meet -- and would be virtually impossible to test for, since IGF-1 occurs naturally in the body. But as with steroid use and "blood doping," gene enhancement would undercut the Olympic spirit of earning rewards through hard work and training, said Case Western Reserve University ethicist Eric Juengst.
Others note that one person's cosmetic concern is another person's medical problem. Obesity, for instance, is a serious medical condition as well as an unpopular aesthetic. How should regulators view gene therapy for weight loss?
That question may soon be more than hypothetical, said Case Western researcher Hunt Willard. Scientists already have identified a gene that, when mutated, causes Prader-Willi syndrome, a disease characterized by a huge appetite and extreme overeating.
"If one copy of that [normal] gene keeps people from overeating, maybe two or three copies of this gene will be the new Jenny Craig," Willard said, referring to the popular weight-loss plan.
In fact, only rarely will cosmetic gene therapy be that simple. Very few traits are encoded by a single gene, and many genes do more than one thing. Researchers announced two weeks ago, for example, that IGF-1 enhances the growth of prostate tumors -- a big price to pay for bigger biceps. Similarly, children with the Prader-Willi mutation are not only obese but also are uniformly extremely cheerful. That suggests the gene plays a role in mood as well as appetite, and that injections of the normal gene may change more than a person's weight.
"The question is," Evans asked, "will you then have people who are very thin but miserable?"
That would run counter to the American Medical Association's position on genetic tinkering, which states that genetic enhancement of traits should be considered only when there is "no trade-off with other characteristics or traits." Those guidelines are subjective and nonbinding, however, leading some to suggest that professional self-policing is an inadequate regulatory option.
Another option is to restrict reimbursement, as Medicare already does, to the "treatment of illness or injury or to improve the functioning of a malformed body part." That would probably limit enhancement procedures, but would not preclude the wealthy from simply paying for the traits they want.
Yet another option is to rely on the FDA, which regulates gene therapy as a biological therapy, said Maxwell Mehlman, director of the law-medicine center at Case Western Reserve. But that agency generally requires less proof of safety and efficacy -- not more -- for cosmetic products, Mehlman noted. For example, the agency ultimately gave up its demands for proof of efficacy of liposuction, concluding that the benefits of the fat removal system are probably best characterized in terms of "patient satisfaction."
Would people be satisfied with cosmetic gene therapy? Or would enhancement just lead to a never-ending escalation of bigger and better?
The example of short stature may provide a clue. Researchers suspect that daily injections of human growth hormone throughout childhood may help many short children attain average heights. The treatment is controversial, however, in part because the enormous number of injections can leave a child feeling even more convinced that short stature is a serious disease. A single dose of growth hormone genes might overcome that problem by providing a lifelong supply of the hormone without the need for shots. But in the end it would simply raise the average height, leave a new group of kids at the bottom of the curve, and perhaps strengthen -- rather than weaken -- bias against shorter people.
To avoid such scenarios, some believe there may be a need for a ban on federal funding of genetic enhancement experiments -- or even a broader legislative ban to include the private sector, as has been proposed for human cloning. Even if gene therapy research were somehow restricted to bona fide medical applications, however, companies might still wend their way into the cosmetic market.
That's the hope among scientists at Anticancer Inc., the San Diego company developing a genetic cure for baldness. Andrew Perry, president of the company's consumer products division, said the company will apply first for FDA marketing approval for hair regrowth in cancer patients who have become permanently bald as a result of chemotherapy treatments. Once it's approved for that medical condition, he said, they will see if they can broaden the market.
Similarly, McIvor said, imagine a company that wants to offer a permanent tan -- a feat that might be accomplished by adding the gene for tyrosinase, an enzyme involved in the production of the skin pigment melanin. "Sunburns can lead to skin cancer, so it could be seen as sort of a melanoma vaccine," McIvor said. "But it may also be seen as a cosmetic thing. Is that enhancement or treatment? Well, it's a little of both."
The reverse example, in which people of color may someday consider the possible social benefits of genetically lightening their skin, carries even greater ethical freight, said ethicist Juengst, who is a member of the NIH committee that examines gene therapy proposals.
"Self-improvement and wanting the best for your children is acceptable and encouraged in this culture," Juengst said. "But would I be complicitous with some unfair cultural values if I chose to change my skin color" to one that offers the best chances of societal acceptance?
That question concerns not only racial minorities but also people who suffer from rare genetic conditions -- many of whom also face discrimination and worry that the field of gene therapy is abandoning them for more profitable cosmetic endeavors.
"There will be many wealthy people willing and eager to pay the price of making their child taller and more beautiful," said Michael S. Langan, a vice president of the National Organization for Rare Disorders. "Eventually there will be discrimination against those who look `different' because their genes were not altered. The absence of ethical restraints means crooked noses and teeth, or acne, or baldness, will become the mark of Cain in a century from now."
© Copyright 1997 The Washington Post Company