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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