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  The following article was written by Elizabeth Gold and appeared in the Spring 2002 edition of the Coloradan, the University of Colorado's alumni magazine. It highlights Professor Allan Collins, who is on faculty at the Institute for Behavioral Genetics. Professor Collins does not work directly on the CAP project, but his research is tied to some of the same questions the CAP seeks answers to, mainly what genes may be responsible for drug and alcohol addiction.
Alcoholism and the smoking gene

In the early 1600s England's King James wrote a treatise on the health problems related to tobacco.  Not one to mince words, he also declared that the worst smokers were the drunken sots.

The King's conclusion that alcohol abuse and nicotine addiction were related came from his observations rather than from any kind of scientific research.  But, in the same way your mother could always tell when you were lying, his sense was correct.

Almost four centuries later, the link between the two addictions has been scientifically documented and put under the microscope for further study.  Even before the association was confirmed, however, a CU professor mixed his own theories about genetics and the two drugs in a test tube.

And after 30 years in the lab, Allan Collins of the Institute for Behavioral Genetics has uncovered what no one anywhere has been able to discover.  His research has isolated one of the genes that seems to play a major role in determining the predisposition for addiction to both alcohol and tobacco.

"We've identified a candidate gene that appears to make a difference in the addictive behaviors of a mouse," Collins says, referring to the Alpha 4 nicotinic receptor gene.  "We're now trying to determine what the normal function of this gene is." He adds that his discovery has opened the door to studies that will determine if the findings also apply to humans.

The simple story of Collins' research begins with the premise that genes make proteins, and drugs affect those proteins.  The protein that is made by the Alpha 4 gene contains one of two different amino acids.  Out of the 670 amino acids in the Alpha 4 gene, the difference between the two strains can make the difference between a non-smoking tea drinker and someone addicted to nicotine and/or alcohol.

Collins observes that environmental influences carry equal weight in determining the choices someone with the predisposition to addiction makes.  If people are never exposed to the drugs, they can side step the addiction, regardless of which amino acid their genetic make up carries.

But for those who get both the genetic influence and the environmental influence, addiction probability runs high.

The impacts of butts and booze

According to the National Mental Health Association, 10 million Americans suffer from alcoholism and 10 million more are problem drinkers on their way to the full-blown impact of the disease.  The American Heart Association estimated that 420,000 Americans die annually from the effects of tobacco.

No one would dispute the health problems both drugs can cause.  In addition, alcoholism contributes to lost wages from excess sick days, domestic abuse and traffic accidents.  Many children grow up in single-parent homes as a result of divorce or death of one of the parents who was an alcoholic.  The sociological, psychological and financial impacts of this kind of childhood are immeasurable.

Collins is convinced that a new angle for dealing with the problems of addiction is imperative.  "In the 1950s, 75 to 80 percent of young kids explored tobacco.  That number is actually the same now if not higher."

He explains that what has changed in recent years are the social pressures for quitting.  "In the '60s, 60 to 65 percent of adult males used tobacco.  In 2001 that number was reduced to 24 percent.  We've found the environmental interventions that work to make people quit but we need to know more about the addiction process to be able to affect the number of people who start."

Collins adds that 80 to 90 percent of alcoholics smoke.  With this one gene influencing both addictions, he wonders if alcoholics who are in rehab to quit drinking would fare better if they were required to quit smoking as well.  "Would their alcohol withdrawal be more severe or less severe if they stopped using nicotine at the same time?" he asks.

"As a pharmacologist, I think in terns of coming up with a drug that could alter the activity of this particular Alpha 4 protein product," Collins says.  "Since we now have a target to attack, if we wanted to change behaviors, we could even put different genes in people."

Impulsive mice turn to drink

Collins refers to his wife, who is also with CU's Institute for Behavioral Genetics, as the star of the show behind his discoveries. Jeanne Wehner, whose research focuses on how genes affect learning and memory, used mice to study impulsivity.

She determined that mice with the strain of Alpha 4 that points to an addictive tendency for alcohol and nicotine had a harder time focusing on tasks. Their reduced attention and increased impulsive behavior inhibited their ability to learn the task.

That alone gave Collins food for thought. But the clincher came when the impulsive mice were given a choice to drink water or alcohol and they chose alcohol. The mice with the other strain of Alpha 4 were better at learning the tasks because of their increased attention and ability to restrain their behavior long enough to learn something new. Interestingly, they chose water over alcohol.

Alpha 4 also seems to be the gene responsible for stimulating the release of dopamine and GABA (gamma-aminobutyric acid), according to Collins. In short, these two chemicals create pleasurable feelings and a sense of well-being. They also reduce unpleasant feelings, like anxiety. Nicotine activates the receptors for the release of these chemicals, and alcohol enhances the action of nicotine - like a "dirty" anti-anxiety drug, according to Collins.

He refers to the pleasant feelings as the "smilies." "The problem is that the smilies don't last, and the sedative effects of alcohol bring on depression. Then the people who are insensitive to the intoxicating effects of alcohol have to drink more to get the smilies to last longer."

The people who are sensitive to the intoxicating effects tend to be the ones who hug the toilet before getting very far in their drinking spree, he adds.

More than a lifetime

Collins recognizes that the research he has devoted his life to won't reveal all the answers needed to fully understand the genetic components of these addictions in his lifetime. He says that because this type of research is so slow and tedious, few people pick up the challenge to study it.

This is one reason the National Institute on Alcohol Abuse and Alcoholism and the National Institute of Drug Abuse go to great lengths to keep him in the lab. He's one of the few researchers in the world who have been given a research scientist merit award. That means his funding is automatically renewed for 10 years at a time, freeing him up from the task of resubmitting annual grants.

The grant mandates that he not be required to teach but Collins opts for the classroom anyway, teaching a class in neuropharmacology.

"People are always surprised when they learn that there are only six professors here in the Institute for Behavioral Genetics," he says. "Every one of the faculty members here are world-class. We're all leaders in what we do."

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