March 15, 2008 (Vol. 28, No. 6)

Playing Cat and Mouse with Genetic “Enhancement”

The well-publicized use by athletes of performance-enhancing drugs including androgenic steroids and human growth hormone has gotten more people than ever before thinking and talking about the subject. But the issue is neither new nor limited to a small number of people.

Few of us are strangers to using chemicals to enhance our mental state. No, I don’t mean alcohol or marijuana—just good old No-Doz caffeine tablets and coffee to stay awake while cramming for a final exam or driving late at night.  Medicine has also made great advances in the use of cognition-enhancing drugs, which doctors prescribe to treat cognitive disabilities and improve the quality of life for patients with neuropsychiatric disorders and brain injury. These prescription drugs are now being used more widely, including for shift workers and for jet lag. The ethical issues and risk-benefit considerations are the subject of a commentary published in December in Nature.

Technology will soon offer even more extreme possibilities for enhancement. Scientists, using gene therapy to increase the levels of a single enzyme, recently created a strain of mice with increased physical abilities by genetically altering a gene that affects metabolism. By injecting an active form of the gene PEPCK-C into an embryo, the scientists found that the mouse more efficiently burns body fat for energy and produces less lactic acid during exercise. 

These “mighty mice” run much faster and longer than their nongenetically engineered cohorts. “They are metabolically similar to Lance Armstrong biking up the Pyrenees,” said Richard W. Hanson, Ph.D., the Case Western University biochemist who directed the research. Although the mice eat 60% more food than controls, they remain fitter and trimmer and live and breed longer than mice in a control group. (Humans share the same gene.)

The appearance of these mice represents a sort of laboratory-created evolutionary balancing act, following by several years, the creation of enhanced cats. (The good news for rodents is that the felines aren’t smarter or faster but they are less allergenic to humans.)

These experiments have reinvigorated a long-running debate about the ethics of creating designer humans. “We’re in an era when breakthroughs in biology and intelligence are outpacing the culture’s capacity to deal with the ethics,” said Joe Tsien, Ph.D., the Princeton University molecular biologist who directed the development of a “smart mouse” almost a decade ago. “There will be issues of access and who can afford it and whether the social wealthy class will have the intellectual advantage over poor people.” As though attending M.I.T. instead of Florida A&M doesn’t confer an intellectual advantage.

Molecular biologist Lee Silver, Ph.D., of Princeton University has written thoughtfully about these issues. He speculates about the emergence of two biological classes, the “Gen Rich” and “Naturals.”  Comprising perhaps 10% of the population, the Gen Rich will include businessmen, musicians, artists, athletes, and intellectuals, all of whom have been enhanced with specific synthetic genes that allow them to perform at levels not possible for those who have access only to nature’s lottery. They might be thought of as the logical successors to Mark McGwire and Marion Jones, who were able to use only crude chemical means to enhance their athletic prowess.

Who then, should dictate when and how such procedures can be used? Economist Francis Fukuyama thinks the answer lies in greater government regulation. In Our Posthuman Future he writes: “The FDA is not set up to make politically sensitive decisions concerning the point at which selection for characteristics like intelligence and height ceases to be therapeutic and becomes enhancing or whether these characteristics can be considered therapeutic at all. The FDA can disapprove a procedure only on the grounds of effectiveness and safety, but there will be many safe and effective procedures that will nonetheless require [additional] regulatory scrutiny.” 

Therefore, Fukuyama proposes “a new agency to oversee the approval of new medicines, procedures, and technologies for human health,” which would exert broader control than current regulation by including “other societal voices that are prepared to make judgments about the technology’s social and ethical implications.” 

This additional interference with decisions that should be left to consumers and physicians smacks of antilibertarian nanny-statism of the worst kind. Moreover, it ignores the fact that our society now affords wide latitude to those who choose to enhance their appearance or health in other ways. For example, drugs are commonly tested and commercialized for relatively trivial indications such as modest obesity, stuffy nose, age spots, and baldness. The injectable drug Botox, widely used to treat nothing more ominous than wrinkles, is one of the best-selling drugs in the U.S., and there have been numerous clinical trials of appetite suppressants, memory- and performance-enhancing drugs, and human growth hormone for hormonally normal but short children.

Gene therapy is an extension of drug and surgical treatments and part of a continuum of medical interventions that introduce or modify DNA or modulate genes’ activity.  Among the therapies on the continuum are organ transplantation (for genetic-deficiency diseases), vaccination (which precipitates irreversible changes in white blood cells’ DNA, initiating the synthesis of antibodies), and drugs (to stimulate the activity of dormant genes in sickle-cell anemia, for example).

For over half a century, these therapies have raised many medical and ethical questions similar to those of gene therapy, and physicians, ethicists, patients, and society at large have had to confront them. Issues such as whether a patient suffers from a condition that warrants treatment, the kinds and magnitude of risks, and equal access to therapy are fundamentally no different for gene therapy than for other interventions. Therefore, even when used for enhancement, gene therapy should not be treated differently from other medical interventions.  

Arguments against testing gene therapy for enhancement should be weighed against society’s permissiveness toward experimental medical and surgical interventions in general and those intended for nontherapeutic purposes in particular.

An array of entities at several levels of government regulates gene therapy. This intensive and highly duplicative oversight offers a stark contrast to the scrutiny of a radical new surgical procedure, for example, which might be completely unregulated or subject only to the approval of a hospital-based committee.

Patients’ psychological well-being and freedom to choose are also important considerations. “Mere” enhancement is not trivial to the adolescent boy who is six inches shorter than anyone else in his class or to many adults of either sex who suffer hair loss.  One need look no further than the huge societal demand for cosmetics, cosmetic surgery, tanning salons, and health clubs to know that people consider it  important to look and feel good.

In a 1992 editorial, The Economist posed the critical question, “What of genes that might make a good body better, rather than make a bad one good? Should people be able to retrofit themselves with extra neurotransmitters to enhance various mental powers? Or to change the color of their skin? Or to help them run faster, or lift heavier weights?” Its admirably libertarian answer: “Yes, they should. Within some limits, people have a right to make what they want of their lives.” 

In view of what people want and what society permits in other realms, should not those limits be very wide?

Henry I. Miller, M.D., a physician and molecular
biologist, is a fellow at Stanford University’s Hoover Institution. From 1979 to 1994, he was an official at the FDA. E-mail: [email protected].

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