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Attacking Alcoholism and Addiction: Waggoner Center unites researchers seeking causes and cures

The effects of alcoholism are devastating: Alcoholism costs society an estimated $148 billion annually. Loss of life from alcoholism and alcohol abuse is greater than that caused by cancer, AIDS or heart disease. About one out of every 13 people is either an alcoholic or abuses alcohol.

Dr. R. Adron Harris, director of the university's Waggoner Center
Dr. R. Adron Harris is director of the university's Waggoner Center for Alcoholism and Addiction Research.

Yet until recently, very few people were involved in alcohol research. It wasn’t until studies with twins in the 1970s showed the genetic influence on alcoholism that it even started being considered a disease. Understanding the cause and determining the treatment of this disease is the mission of The Waggoner Center for Alcoholism and Addiction Research at The University of Texas at Austin.

“[Alcoholism] was traditionally seen as an individual failing of free will,” says R. Adron Harris, director of the Waggoner Center. “If the person were strong enough, they could conquer the alcoholism. That stigma persists. In the area of addiction, in general, people with the disease do not speak out to lobby for research and treatment of the disease. So the afflicted do not have a voice. That is something we’d very much like to change.”

The Waggoner Center was created in 1999 with a $5 million challenge gift from June and Virgil Waggoner, whose son died of alcoholism. Before the creation of the center, people in addiction research were working all over campus: some in pharmacy, some in liberal arts or natural sciences, many in different buildings. Often, they didn’t even realize there were others on campus with similar interests.

The Waggoner Center gathers these researchers together in an interdisciplinary setting. It offers a comprehensive approach to studying alcoholism and addiction, considering the influence of both genes and environment on the disease. (There is no “nature vs. nurture” debate in alcohol research. “They’re both important, they both interact, and we have to study both,” Harris says.)

Studying Genes

Funding has given the Waggoner Center modern instrumentation to allow it to undertake new forms of addiction research. Pharmacy Professor Rick Morrisett uses a high-powered microscope, Molecular Biology Professor Susan Bergeson runs a gene-sequencing facility to determine people’s genotype, and a gene chip facility helps speed up gene mapping.

Researchers study regulation of gene expression
Researchers study regulation of gene expression. “Since this also determines, for example, what is a cancer cell and what is a normal cell, it might be very important for determining what is an addictive brain and what is not,” says Harris.

Humans have about 50,000 genes in each cell of their bodies, and the function of each cell is determined by which genes are turned on and which are turned off. This is called the regulation of gene expression.

“Since this also determines, for example, what is a cancer cell and what is a normal cell, it might be very important for determining what is an addictive brain and what is not,” says Harris. Before the development of gene chips, trying to identify these genes was a painfully slow process.

Through the Waggoner Center, the university’s Molecular Biology Department recruited gene chip expert Vishwanath Iyer. His lab developed gene chips, which, after about an hour’s worth of preparation, allow scientists to see almost all 50,000 genes at once to determine which ones are turned on. The Waggoner Center has published the only research papers on the application of this technology to alcoholism.

The center is bringing together computer sciences and biology to develop new technology and programming to sort the data. “We’re not used to getting 50,000 different pieces of information from one experiment,” says Harris.

Other professors have been recruited to participate in addiction research at the Waggoner Center. Neurobiology Professor Nigel Atkinson is now studying the mechanism of drug tolerance in fruit flies. Biochemistry Professor Andy Ellington, who engineers DNA to do specific things, is now working on “molecular sponges,” properly called aptamers, to soak up cocaine and methamphetamine to treat overdoses.

Waggoner Center gathers researchers together in an interdisciplinary setting
The Waggoner Center gathers researchers together in an interdisciplinary setting.

The center’s ability to obtain relatively quick funding through a grant from the state-run Texas Commission on Alcohol and Drug Abuse has been key in its ability to recruit researchers. What also helps is that Director Harris is a world-class researcher in the molecular genetics of alcoholism. His research focuses on the molecular basis to nerve cell sensitivity to alcohol and anesthetics.

“One of the peculiar things about alcoholism is that we have not known how it works on the brain,” he says.

Most drugs have specific receptors in the brain, proteins with which the drugs interact, but it was widely accepted that alcohol did not have these sites. Harris’ team began searching for sites of alcohol action and found them—key proteins in the brain on which alcohol acts. They mapped out where alcohol acts on the protein and Harris hopes that information is used to design molecules that would block alcohol action.

Treatment is one of the goals of the Waggoner Center. Researchers are mapping out genes that may help determine the best course of treatment for an alcoholic. Most likely, many genes working in concert contribute to alcoholism.

“There are probably different versions of these multiple genes, called polymorphisms, where there is a difference in the gene sequence,” Harris says.

Because not everyone responds to treatment in the same way, scientists believe there are subtypes of alcoholics. By coordinating genetics and clinical psychology, Bergeson and University of Texas at San Antonio psychiatrist Bankole Johnson are trying to map out these types genetically, which would help determine which treatment is best for whom.

Harris' team began searching for sites of alcohol action and found them
Most drugs have specific receptors in the brain, but it was widely accepted that alcohol did not have these sites. Harris’ team began searching for sites of alcohol action and found them.

Harris believes science will one day be able to recommend treatments for alcoholism based on a person’s genetics, something he calls the “medicine of the future.”

Studying Behavior

Some students may claim they’re going to “the lab” when, in fact, they’re off to a local bar. At the Waggoner Center, they don’t have to lie. Associate Professor Kim Fromme created and heads the Sahara Lab, a lab dressed up as a fully functional bar.

“Everything people see, hear, smell, tells them that they’re in a bar,” says Fromme.

Researchers at the Sahara Lab most recently studied subjective reactions to alcohol, that is, people’s perceptions of how alcohol affects them. Students of all ethnicities, 21 and older, were carefully screened. Research assistants, acting as bartenders, gave them enough drinks to cause them to have a .06 blood-alcohol level. They were then given some sort of stress-inducer, such as being told that they would have to give a speech on what they do and don’t like about their bodies. Then they were free to drink however much they wanted while preparing their speeches, during a so-called “ad lib” period.

Fromme and Bergeson are compiling the results of the genetic portion of the study, but they have found some interesting behavioral results. The less intoxicated a person feels, they say, the more likely he or she is to drink more and thus have a greater risk of developing alcoholism.

Jianwen Liu, a molecular biology graduate student
Jianwen Liu is a graduate student in molecular biology.

They based their tests on research by Marc Schukit, who showed that those people who feel the influence of alcohol less, though they may be just as intoxicated as people around them, have a higher chance of becoming an alcoholic 15 or 20 years later. Fromme and her researchers wanted to test this empirically.

“Could we show that indeed, people with lower subjective intoxication self-administer more alcohol given the opportunity?” says Fromme. “Yes, they do drink more in this laboratory setting. That supports the hypothesis that they drink more in their daily lives.”

Fromme’s interest is not necessarily in alcoholism but in alcohol use and abuse, which affects a much larger group. She also studies how to identify these individuals who abuse alcohol early and intervene before they develop alcoholism.

“College students, for example, tend to mature out of these heavy binge-drinking patterns,” she says. “We know college is a developmentally limited period of excess. That’s the good news: Most of them at graduation will go on to get jobs, get married, stop their binge drinking. My real interest is during that developmentally limited period of excess, the problems that can arise via the misuse of alcohol and engaging in hazardous behaviors caused by binge drinking.”

Another study in the lab has been investigating alcohol’s influence on the perceived risk and perceived benefit of engaging in risky behaviors, such as drunk driving or unprotected sex. Alcohol reduced perceptions of risk but did not alter the perception of benefit.

Research assistant Macy Brown
Research assistant Macy Brown works in the lab of Dr. Harris.

“In other words,” says Fromme, “alcohol didn’t mush your brain and dampen all of your cognition, but it seemed to selectively influence the perception of risk by making you feel less vulnerable.”

They also have investigated the success of various prevention programs and are trying to figure out why so many don’t work.

Researchers also taught basic behavioral skills, such as alternating each drink with water, and showed subjects that alcohol reduces their perception of the danger of risky behavior. They even did this while the subjects were drunk in the bar lab, but the preventions didn’t work.

“That suggests that we need to know more about the kinds of factors that are motivating that kind of high-risk behavior,” Fromme says.

As the Waggoner Center continues to make strides in approaching the disease of alcoholism from various standpoints, it may uncover these factors and many others that contribute to the disease. Its most powerful tool is not its instrumentation or its labs, but the fact that it enables experts from a variety of disciplines to work together toward a common goal: understanding the cause and finding the cure for a devastating disease.

“It’s just such a wonderful entity to be able to bring together this kind of multi-disciplinary research,” Fromme says, “and it’s just so phenomenally rare, in my experience, that molecular biologists and clinical psychologists would even be in the same room together, much less be doing collaborative research.”

Excerpted from the May/June 2002 Alcalde article by Cora Oltersdorf

Portrait of Dr. Harris: Bob Nagy

Lab photos: Marsha Miller

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  Updated 2014 October 13
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