杏吧原创

UNDER the palm trees on the Caribbean island of St Kitts, monkeys slump in
drunken stupors, nursing hangovers so bad they can鈥檛 look at another
drink鈥攚ell, not until tomorrow. Others are doing what a drunk monkey does
best: falling off their perches and picking fights with anyone who bugs them or
gets between them and the bottle.

Unlike most animals, many of the vervet monkeys of St Kitts will drink by
choice when alcohol is available; no training is needed. And much like humans,
they have different types of attachment to the demon drink. Some are merely
social drinkers鈥攖hey prefer their alcohol sweetened, in moderation and not
before lunch. Others drink heavily. The so-called steady drinkers like their
alcohol unadulterated by anything other than water, and if it is restricted they
will endeavour to drink as much as is available, although they rarely drink
themselves into a coma. Not so the binge drinkers. Mainly male, binge drinkers
would drink the island dry, given half a chance, and shun anything that dilutes
the alcohol. Not surprisingly, they often end up comatose.

Beaches and palm trees notwithstanding, most people would pass up the chance
to study these social misfits of the simian world. But a handful of researchers
believe that the bacchanalian excesses of St Kitts will be the key to
identifying the elusive human genes for alcoholism.

Sure, there are other animal stand-ins for human alcoholism, but none is
ideal. Rats will only drink alcohol disguised with sugar. And although fruit
flies, which are excellent for genetic studies, like humans, stagger then pass
out when drunk, their physiology is completely different.

The St Kitts monkeys, however, have a similar physiology and a disturbingly
human relationship with alcohol. 鈥淭he islanders down in St Kitts discovered that
they could trap monkeys by putting alcohol out for them. That鈥檚 a lot different
than holding an animal down and forcing alcohol down its throat,鈥漰oints out
David Goldman, a geneticist at the National Institute on Alcohol Abuse and
Alcoholism, near Washington DC.

Still, if you鈥檙e after the genes that are thought to be responsible for a
significant proportion of human alcoholism, doesn鈥檛 it make sense to study
humans rather than monkeys? Not necessarily, says Roberta Palmour, a geneticist
at McGill University in Montreal, who studies both.

In humans, a diagnosis of alcoholism covers many different disorders, ranging
from anxiety-induced drinking to drinking associated with violent or criminal
behaviour. This variety may be the biggest barrier to finding the genes for
alcoholism. Each disorder is likely to be driven by its own mix of environmental
and genetic factors. And although attempts are being made to separate the
different types of alcoholism in humans, it isn鈥檛 easy. Experts disagree on the
definitions of the different drinking disorders, and children of alcoholics tend
to marry alcoholics, muddying the genetic waters. What鈥檚 more, a human life is a
complicated thing鈥攁 person can be driven to drink by circumstance (the
stress of war or divorce, for instance), without carrying any of the main genes
for alcoholism.

鈥淭here are so many things going on that you can鈥檛 measure,鈥� says Marc
Schuckit, a psychiatrist at the University of California in San Diego, who as
part of the multicentre Collaborative Study on the Genetics of Alcoholism last
year identified three new regions on the human genome that may be linked to
alcoholism. These regions could contain up to 300 genes, so it may be years
before specific genes are identified.

With monkeys, things are simpler because you can control their environment
and鈥攂y selective breeding鈥攖heir genes. 鈥淗aving a group of monkeys
whose patterns of alcohol consumption are very similar makes it much more likely
that the genes that underlie those patterns of consumption will be similar,鈥�
says Palmour. And as the vervet monkeys share 96 per cent of their genetic
make-up with humans, it is also likely that the same genes underlie alcoholic
overindulgence in both species.

Chin chin

Over the past 13 years, Palmour and Frank Ervin, a psychiatrist at McGill
University, have scrutinised the drinking habits of more than one thousand
vervet monkeys kept in outdoor cages on St Kitts. The monkeys drinking habits
closely mimic their human counterparts. Most are mere social drinkers, but there
are also two small groups of heavy drinkers鈥攖hose that drink steadily, and
those that binge themselves, often into a coma. About 15 per cent of the St
Kitts鈥� monkeys are teetotal. Judicious crossbreeding suggests that those
behaviours are highly heritable.

Later this year, Palmour plans to publish the first map of the vervet
monkey鈥檚 genome, which she will use to work out which genes play a role in
monkey alcoholism. Those genes may then become favourites as potential triggers
for human versions of the disorder.

One candidate for that role is a variant of a gene that controls the levels
of dopamine, a brain chemical that creates a feeling of wellbeing. To ensure we
carry on eating, having sex and doing all the other things that guarantee our
genes鈥� survival, every time we partake a small area in the midbrain sends out a
surge of dopamine. In some alcoholics, so the theory goes, the pleasure dial is
turned down far too low. Alcohol supposedly cranks it back up to its optimal
level. Support for that idea comes from studies showing that some people with
alcoholism have low dopamine activity in their brains, or have less sensitive
dopamine receptors. Unfortunately, for every study that finds such a link,
there鈥檚 another one that fails to do so.

But according to Palmour, too little dopamine certainly plays a role in
steady, heavy drinking among the St Kitts monkeys. Tests carried out on monkeys
that had been forced to abstain for at least 6 months revealed that a breakdown
product of dopamine called homovanillic acid was dramatically reduced in the
cerebrospinal fluid of the steady-drinking crowd, but not the binge
drinkers.

Low levels of serotonin, another of the brain鈥檚 signalling chemicals, have
also been implicated in human alcoholism. But once again, the findings have been
contradictory. And once again, they could be due to the difficulties inherent in
sifting through the different types of human alcoholism.

鈥淔or the binge drinking [monkeys], we are beginning to accumulate evidence
which suggests serotonin may well be implicated,鈥� Palmour says. The levels of a
serotonin breakdown product called 5-HIAA are lower in monkeys that binge drink,
and when the monkeys drink a solution of one of the building blocks of
serotonin, tryptophan, to boost brain levels of the chemical, their alcohol
consumption drops. Tryptophan solutions have a smaller effect on steady
drinkers, and no effect on social drinkers. The implication is that in humans,
just maybe, serotonin underlies binge drinking and dopamine underlies steady
heavy drinking.

Still, Palmour is quick to point out that it鈥檚 going to be a long haul
getting from this biochemistry to the genes that underpin drinking among monkeys
on St Kitts, and from there to the human genes. But Goldman, for one, is
confident that the monkeys will help to track down human alcoholism genes. If
someone hadn鈥檛 already created this animal model, he says, 鈥淚 would probably be
suggesting that they try to.鈥�

In the meantime, the monkeys of St Kitts will be nursing many a
丑补苍驳辞惫别谤鈥�