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Biology 103
2001 First Web Report
On Serendip

Applying Step One to finding genetic cure for Alcoholism

Charlotte Ford

In Twelve Step groups that aid in 'recovery' from alcoholism (Alcoholics Anonymous) or having loved ones who suffer from alcoholism (Al-Anon), the first step reads: "We admitted we were powerless over alcohol, that our lives had become unmanageable." (11) In Al-Anon literature, this step works to liberate those living with the affects of alcoholism from constant worrying and attempting to control another's drinking. But from a genetic and biochemical standpoint, how powerless are we? Which scientific observations suggest the existence of a genetic component to alcoholism? If these genes exist, how do they work?

These are muddy genetic waters. Human beings are complexly wired products of both their genetic makeup and their environment. Unlike other inheritable diseases or tendencies, alcoholics may become alcoholics for very different reasons. Alcoholism is a disease that encompasses many symptoms that may be secondary or causal; a diagnosis of alcoholism usually includes other disorders such as anxiety, depression and violent or criminal behavior. (5)

It is difficult to locate a specific gene that predisposes someone to alcohol addiction because of the strong environmental influences involved in developing alcoholism; there is no clear-cut cause. It's possible that we inherit genes that directly affect our metabolism of alcohol and our propensity to develop alcoholism, or we may inherit genes for personality traits that create vulnerabilities to diseases like alcoholism. (1) Depending on the person, it could be some or all of the above.

Although scientists have been successful in isolating specific genes or links of genes that appear to predispose one to alcoholism, they have had difficulty duplicating results. Isolating specific genes is difficult because genes are inherited in clumps; a gene containing a predisposition to alcoholism is inherited simultaneously with other genes closely linked on the same chromosome. This is called linkage. (10) How do researchers go about isolating genes that may predispose one to alcohol addiction? Testing genes in human subject, researchers test for genetic predisposition to alcoholism in two ways: with a candidate gene and without. Using the candidate gene approach, scientists test specific genes for linkage that they hypothesize predispose one to alcohol. Without an hypothesized candidate, researchers start by scanning human genomes. They first characterize an entire link of DNA and then look for genes related to alcoholism. (1)

Animal testing has proven extremely useful in locating genes. While animal alcoholic behavior can never encompass the full spectrum of human alcoholic tendencies, they are easier to study cross-generationally and to manipulate genetically. (1) Many studies using animal testing have strongly supported the theory that there is a genetic component to alcoholism. Testing two types of mice at the University of Colorado Health Science center, Dr. James Sikela and colleagues identified forty-one genes thought to predispose mice to alcoholism. (3) Researchers have also been successful breeding rats with high or low alcoholic tolerance tendencies, high or low consumption/preference for alcohol, change in muscular coordination and hypothermia caused by alcohol, and withdrawal symptoms and locomotor activation (which some researchers believe is connected to alcohol's euphoric effects on humans.) (1)

Using human subjects, Pickens and coworkers tested 169 same-sex twin pairs (male and female) when at least one of the twins had sought help for alcoholism. Identical twins, somewhat obviously useful for such a study as they share identical genetic makeup, were more likely to both be alcoholics. However, a difficulty in comparing identical and fraternal twin pairs is that the environment and genetic make-up of identical twins is more similar than that of fraternal twins. (1)

Studies where researchers compared adopted children of alcoholics raised in nonalcoholic homes with children of non-alcoholics raised in similar environments also suggest that alcoholism is inherited. Infants with alcoholic biological parents, when adopted into non-alcoholic environments, are about three times more likely to have problems with alcohol than infants of non-alcoholic parents adopted into non-alcoholic homes. (2)

These studies all suggest that genes predisposing one to alcohol exist, but what exactly are the genes/tendencies inherited, and how do they work? The Dopamine D2 receptor, which in animals seems to be related to motivation, reward, and reinforcement, has been linked to alcoholism. Studies have shown that alcohol abuse increases the brain's production of dopamine, a chemical that makes it possible to feel pleasure and reward. But the more alcohol one drinks, the less dopamine the brain makes. Researchers hypothesized that, in a vicious cycle, alcoholics drink in an attempt to override their constantly depleting levels of dopamine. (4)

Researchers Palmour and Frank Ervin studied the drinking habits of caged vervet monkeys on St. Kitts, which share 96 per cent of their genetic- up with humans. Alcoholic monkeys were forced to abstain from drinking for six months or more, and the "steady drinkers" suffered a reduction of homovanillic acid, a breakdown product of dopamine. This reduction was not found with the "binge drinkers". The "binge drinkers," however, did suffer a reduction in a serotonin breakdown product called 5-HIAA. Palmour and Ervin hypothesize that dopamine may play a role in steady drinking, and serotonin in binge drinking. (5)

Many studies implicate alcoholism with difficulty in dampening excessive neuronal activity. Following benzodiazepine sedative administration (a drug used to treat symptoms of withdrawal,) some alcoholics demonstrated a smaller metabolic change in their frontal brain region than non-alcoholics. This suggests a decreased ability to inhibit behavior. (8) Twin brothers shared preferences for sweets and alcohol in a study conducted by Dr. David Overstreet at UNC Chapel Hill's School of Medicine. Twins who had difficulty controlling how much alcohol they consumed had the same difficulty with controlling their intake of sweets. They were more likely to drink or eat sweets when they were depressed or nervous, and believed both substances would make them feel better. Sweets induce pleasurable responses or positive reinforcement (perhaps related to serotonin and dopamine) and disturbances in the brain's system of positive reinforcement is involved in the development of alcoholism. (9)

Studying alcoholism from a genetic standpoint has yet to come up with a cure, although various treatments, such as the drug naltrexone (ReVia), which quells cravings through Opiad receptors (7) have been fairly successful when used in conjunction with 12 step groups. Researchers have been successful injecting dopamine receptors into rats' brains, although this has not yet been proven safe for humans. (6) Genetic research helps to identify those at risk, and removes some of the stigma from alcoholism by identifying it as a genetic weakness rather than a weakness of character. It also may do more to specify which factors are genetic and which are environmental so that we can try to control our environments to prevent alcoholism. But after a long day at the lab, one still comes home to the effects of the disease, and although some are able to quit alcohol without AA, they usually retain most of their alcoholic characteristics minus the alcohol. (11) The alcoholism of others, like much in life, is something that after a certain point we are powerless over. And learning about alcoholism, like science and again, much in life, is a process of "getting it less wrong." (12) Programs like Al-Anon and AA, while they can't explain the genetic why, help people to find peace in accepting the human condition of "getting it less wrong." These programs also have another concept of "doing the footwork," or going about one's business with the understanding that although one can never get it perfect, one can make progress. (11) (11) My suggestion for the scientific community's "foot work": How much power does a genetic predisposition for alcoholism have in determining one's relationship to alcohol? Can we alter our genetic make-up? Is it worth it?

WWW Sources

1) NIAAA's The Genetics of Alcoholism,

2) Alcoholism and Genetics, UCSF,

3)Join Together Online: Alcoholism: Clinical and Experimental Research,

4)Join gene therapy in alcoholic rats,

5)geroff my tail!,

6)booze ruse,

7)Scientific American: explorations: Closing in on Addiction,

8) Alcohol Alert,

9)Sweet Tooth, Alcoholism Linked,

10) Genetics Information,

11)Al-Anon home page,

12)Biology 103 Homepage,

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