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 LTS project, but his research is tied to some of the same questions
the LTS 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
"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
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.
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
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
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."
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.
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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