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How Might a Gene Cause Alcoholism?
For a theory to be accepted scientifically, not only must the finding or findings that support it be replicated in rigorously designed research, but also the hypothesized connection between a mechanism and an effect must be plausible and consistent with everything else we know. How, exactly, does the dopamine receptor gene influence the alcoholic's biochemistry and behavior? This connection is not at all obvious, since dopamine receptors are not directly affected by alcohol. Indeed, it is not even known how the Blum-Noble marker affects the dopamine receptors. The alcoholism-associated allele might increase or reduce the number of dopamine receptor sites in brain cells, or affect how well dopamine binds at these sites. One theory is that if the allele reduces the number of receptor sites or minimizes binding at them, then the person's brain might be deficient in dopamine activity. Drinking might compensate for this deficiency by increasing the drinker's levels of dopamine.
But does this complex series of links account for the alcoholic's motivation to drink? Some researchers propose that dopamine is related to pleasure-seeking activity. This is a very long way, however, from explaining how people with the Al allele become alcoholic. Alcoholics often receive negative feedback about their drinking from other people, from their own internal standards, and from physical problems they encounter. Why don't these experiences overcome the presumed pleasurable nature of the dopamine activity and cause the person to curtail drinking? Put in another way, the question is whether a complex behavior can be said to be motivated solely by the pleasure (or comfort or relief) it produces. For example, orgasms are intensely pleasurable and most people can produce them at will, yet relatively few people become compulsive fornicators or masturbators, at least in the long run.
Moreover, dopamine stimulation is simply not so direct or exclusive an effect of drinking that it seems likely to be the root cause of compulsive drinking. Many human activities other than drinking stimulate dopamine release. Some may argue that alcoholics are part of a larger group of people who seek such stimulation, and who therefore experience a higher level of dopamine activity in their brain cells. But why do only some people seek this effect from alcohol?
In an interview about the JAMA study Gordis speculated that the gene marker "may not be specific for alcoholism but it might have a more general influence on appetite, personality, and behavior." Noble has concurred: "The good Lord did not make an alcoholic gene, but one that seems to be involved in pleasure-seeking behaviors." These statements seem skeptical about the existence of a link between the gene and alcoholism. The idea that people with the A1 allele may be predisposed to pleasurable stimulation, of which alcoholism may be one example, also falls short of supporting claims that alcoholics have an innate response to alcohol that dooms them to alcoholism once they begin drinking.
Even if Blum and Noble's finding holds up, most people with the A1 allele will not become alcoholics. According to the study, about 25 percent of the population have this form of the gene. Estimates of the proportion of alcoholics in the U.S. population range up to 10 percent. However, the "virulent" type of alcoholism that Blum and Noble talk about probably occurs in less than five percent of the population. Thus if every full-blown alcoholic had this allele, then only a fifth of the 25 percent that have it would be severely alcoholic. Since only 69 percent of the alcoholics in the Blum-Noble study actually had the allele, even fewer than a fifth of those with the marker will conform to the diagnosis of alcoholism used in the study.
How Can This Discovery Be Used?
Blum and Noble have announced that the identification of a gene that places people at risk for alcoholism should open new treatment and prevention options. The most likely step, given the current cultural climate, would be to tell those with the genetic marker that since they have an elevated risk of alcoholism, they should not drink. But this idea has its problems. In the first place, since less than a fifth of the people with the gene will actually become alcoholics, the warning is unnecessary for most of those with the marker and could make their lives needlessly difficult.
Moreover, unforeseen, and lamentable, consequences might occur. We frequently tell young people not to drink, and they frequently don't listen. But if a person has been told that drinking will lead to alcoholism, the prophecy may ultimately prove to be self-fulfilling. According to Peter Nathan, who was until last year the director of the Rutgers Center of Alcohol Studies, "It has become increasingly clear that, in many instances, what alcoholics think the effects of alcohol are on their behavior influences that behavior as much [as] or more than the pharmacologic effects of the drug." For example, alcoholics have been shown to drink excessively and even behave drunkenly when they are told they are drinking an alcoholic beverage even though the drink does not actually contain alcohol.
In other words, indoctrinating young people with the view that they are likely to become alcoholics may take them there more quickly than any inherited reaction to alcohol would have. In fact a majority of children of alcoholics do not become alcoholic themselves, for whatever reason. No epidemiologic study has ever found that as many as half of such children develop a drinking problem of their own, and most research places the figure at 25 percent or less. That many children don't inherit their parents' alcoholism is indicated by the rapid growth of the "adult children of alcoholics" movement, whose typical member is a woman who has never had a drinking problem. Moreover, adolescents and young adults who have drinking problems often overcome them without abstaining, even if they have an alcoholic parent.
Blum and Noble have also suggested that their genetic finding will lead to medical therapies for alcoholism. That is, if the source of alcoholism is biochemical, then a drug therapy might be designed to eliminate the alcoholic's craving for alcohol. If a vitamin stimulated dopamine activity, for example, or if a drug blocked the binding of dopamine to receptors, then alcoholics could be freed from their biological motivation for excessive drinking and might drink moderately.
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