One Night in San Diego:
Tragedy of Alcohol Abuse Drives TSRI Researcher's Work

By Jason Socrates Bardi


That which hath made them drunk hath made me bold;
What hath quench'd them hath given me fire.

——Macbeth Act II, scene 2

An affluent man in his 60s, drunk, pushes past his pleading wife, gets in his late model Cadillac, guns it out of the gas station where the two have been fighting over the keys, and drives the wrong way up the freeway off ramp, running head-on into a car, killing the driver, and injuring himself.

At around the same time, a prominent member of a San Diego community, blind-drunk, crashes his family minivan into several parked cars along his street. Nobody is hurt, but after the story breaks, he will be forced to resign.

A few hours later, some teenagers are drinking and blasting around in their old Ford pickup truck. A momentary lapse or some loose gravel and they plunge off the road and down a canyon. Luckily, they are not hurt, but they have to wait until morning before an emergency crew can climb down and haul them out.

According to The Scripps Research Institute (TSRI) Neuropharmacology Professor George F. Koob, these three stories—based on actual events that transpired on a single night in San Diego last year—highlight how problems related to alcohol cut across nearly all social, financial, and age-related strata.

Koob has been studying the neurobiology of alcohol and alcoholism for several years, and he has developed models of normal and excessive drinking to study the neurophysiological correlates of alcohol consumption. His studies start with the brain and the neurobiology of alcohol in the brain—some of which we understand, and some of which is only now coming to light.

"Despite many years of independent study of the biochemistry, physiology, systems, and processes hypothesized to be involved in alcoholism, the mechanisms are still unclear," says Koob.

An Enigma in a Bottle

Of all the legal and illegal drugs, alcohol is both one of the most readily available and one of the most toxic. It holds an enigmatic place in American society.

On the one hand, alcohol is regularly or occasionally consumed in various forms by nearly two thirds of all American adults, and there are few who have not consumed alcohol on occasion. According to United States Centers for Disease Control and Prevention statistics, four fifths of the U.S. adult population have been regular or occasional drinkers at one time.

Alcohol is the great "social lubricant" that humans have imbibed for at least 7,000 years (the age of the oldest known wine jugs ever found by archeologists). The Egyptians loved wine so much that they imported grapes. The Greeks celebrated the joys of inebriation through their god of wine, Dionysus. The Romans called the same god Bacchus.

On the other hand, alcohol extracts a heavy toll on society.

Drunk driving is a major scourge in the United States—about a third of the approximately 40,000 traffic fatalities every year involve drunk drivers. Thousands more die each year from accidental or deliberate alcohol poisoning, and from alcohol-related degenerative conditions like gastritis, cardiomyopathy, and liver disease. In 1999, according to the Centers for Disease Control and Prevention (CDC), a total of 19,171 persons in the United States died from such causes. And fetal alcohol syndrome, caused by alcohol consumption by pregnant women, is the leading cause of mental retardation in the United States. The CDC estimates that as high as one out of every thousand babies born in the United States each year suffers from fetal alcohol syndrome, and they report that the heath costs related to these children was $1.9 billion in 1992—the last year for which they report such statistics.

One of the most terrible costs of excessive drinking is, of course, alcoholism—the chronic compulsive use of and loss of control over alcohol intake. For reasons that are not entirely clear, some portion of the people who drink suffer from some form of alcoholism.

In addition to its enormous toll on families and society at large, alcoholism is devastating to an individual's health because of the damage that excessive amounts of alcohol cause to the system over time. Whether it is the liver or the heart or some other organ, says Koob, "Ultimately, alcoholism gets you as some part of your body goes."

The direct and indirect public health costs of alcoholism are estimated to be in the hundreds of billions of dollars yearly. Currently, there is no cure for alcoholism, and the neurobiology of the disease is not completely understood.

"Why does 10 to 15 percent of the population become alcoholic and the rest of the population does not?" asks Koob. "For instance, we know that the children of alcoholics are four to five times more likely to become alcoholics themselves, but we do not know what the neurological basis for this trait is."

A Consortium Seeks Answers

Last year, the National Institute on Alcohol Abuse and Alcoholism (NIAAA) funded a multi-year consortium headed by Koob to identify the molecular basis of alcoholism. The aim of the Integrative Neuroscience Initiative on Alcoholism consortium grant is to address the basic science of alcoholism and to establish a platform upon which future treatments can be built.

The grant supports the combination of physiological, molecular, and cellular models to derive the genetic and environmental factors that form the basis for individual differences in developing excessive drinking. A large portion of the funding is dedicated to setting up shared facilities to centralize and enhance some of the tasks common to the researchers with independently funded research projects.

"The goal is to figure out what makes people vulnerable to excessive drinking," says Koob. "What is the genetic loading and how does that interact with environmental determinants?"

A neuroinformatics group, for instance, will make use of the newly solved human and the soon-to-be-completed mouse genomes to interpret "gene chip" screens needed to identify the genes involved. Certain gene clusters are regulated by alcohol and may be differentially regulated during the development of excessive drinking.

Another group will establish animal models of alcoholism that will be used to study these genes in action.


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Professor George F. Koob studies the neurobiology of alcohol and alcoholism. Photo by Kevin Fung.