| 摘要 | How should we set priorities in medical research? Officials at the National Institutes of Health will grapple with this question as they allocate billions of dollars from the agency’s budget this year.
Two geneticists, Dr. Kathleen Merikangas of the National Institute of Mental Health and Dr. Neil Risch of Stanford University, have taken on this challenge by introducing an intriguing framework for setting priorities for genetic research.
The best candidates for genetic research, they believe, are disorders whose emergence and course cannot be derailed by changes in personal habits or manipulation of the environment. Examples are autism, Type 1 diabetes and Alzheimer’s disease.
In contrast, lower priority on the genetic research hierarchy should go to conditions like Type 2 diabetes or alcohol or nicotine addiction, they argue. Type 2 diabetes, after all, can be largely avoided through exercise and weight loss, and teenagers will buy less beer if taxes on alcohol are high enough. Similarly, a combination of smoking bans, social pressure and taxes have had an impact on smoking.
Not surprisingly, the geneticists’ proposal, published in Science, drew fire from their colleagues who study addiction, including Dr. Nora Volkow, director of the National Institute on Drug Abuse. In a published rebuttal last June, they insisted that addiction deserved a much higher ranking for genetic-research money, noting that the health and social costs of alcohol and drug addiction exceed $500 billion a year.
No one can dispute addiction’s high cost. But is genetic research the best way to reduce it? Probably not.
Environmental approaches may not be as sexy as high-tech gene-based solutions, but they work. In the past 20 years, California has reduced smoking to 16 percent of adults from 26 percent through higher cigarette taxes, closer monitoring of sales outlets, restrictions of smoking in public places, endorsement of antismoking attitudes in the general public and better decisions about health by current and prospective smokers.
”Californizing” the country in a public health sense would reduce smoking to a much greater extent than a comparable investment in genetics research. Within a generation, most of those who continued to smoke despite every environmental barrier would be those at high genetic risk; the rest would be a small cohort who are not interested in quitting. At that point, investigating smokers’ genes might warrant a greater investment because they would be a more highly genetically determined group. But for now, resources could be better directed toward diseases where society has no similarly potent environmental tools.
Could genetic screening prevent addiction? Ideally, people of legal age could refuse cigarettes or alcohol if they knew that their genes put them at higher risk for progressing from casual to compulsive use. But screening can backfire: fraternity members, for example, might be more likely to go on a drinking binge if they knew their genetic risk for alcoholism was low.
In its defense, genetic research may one day improve addiction treatment. In response to Dr. Merikangas and Dr. Risch, addiction genetics researchers noted that therapeutic response of alcoholic patients to the medication naltrexone, an agent first developed for heroin users, might be associated with a variant of a gene that codes for a specific brain receptor. If replicated, this finding might allow clinicians to use genetic information to decide whether to offer naltrexone to a particular patient.
But future improvements in treatment from genetics research are unlikely to have much effect because, research shows, most addicts who recover do so without formal treatment. A survey by the National Institute of Alcohol Abuse and Alcoholism, for example, found that three-quarters of adults who had once been alcohol-dependent but no longer have alcohol problems never received treatment.
As Dr. Merikangas and Dr. Risch emphasize, addiction is malleable under the right circumstances. Only 12 percent of American soldiers addicted to heroin in Vietnam maintained the heroin habit after returning home. That is a striking example of a physiological process (drug dependence) interrupted by psychological and environmental processes–less need to manage the anxiety or boredom of a war zone, reduced availability of inexpensive heroin and increased recognition of the personal cost of continued drug use. Less startling examples of environments’ changing addictive behavior abound: when is the last time you saw a heavy smoker light up at a religious service?
Finally, much of the harm to public health from drug and alcohol use has nothing to do with addiction. In 1986, Len Bias, the basketball star, died not because he was addicted but because cocaine can induce sudden cardiovascular death. Improved treatments for alcoholism would not make our highways safe: of the 32.3 million Americans who acknowledge driving drunk in the last year, most were non-addicted people who made bad choices after drinking too much.
Genetic research on addiction could have benefits. There is a distant possibility of improving treatment, and it might help in understanding related traits, like impulse control and anxiety. But unlike benefits from research into more intractable diseases, major cuts in drug- and alcohol-related harm depend not on genes but on choices by policy makers and individual citizens.
Keith Humphreys is an associate professor of psychiatry at Stanford. Sally Satel is a resident scholar at AEI and an unpaid advisory board member for the Substance Abuse and Mental Health Services Administration. |
