Is it in the genes?

Studies suggest human behavior isn't as predetermined as some thought.

Arthur Allen
June 25, 1999 8:00PM (UTC)

In 1993, a National Cancer Institute researcher named Dean Hamer
made what seemed to be an astonishing discovery about the
genetics of human behavior. He had located a link to male
homosexuality on the X chromosome, Hamer reported in Science. The
story was splashed across front pages around the country. At
last, overly doting mothers and early cross-dressing games were
off the hook and the predilections of everyone from Walt Whitman
to Liberace could be explained by a few errant proteins. Hamer's
article, based on an examination of the DNA of 40 gay brothers,
led to mass-market book deals and minor celebrity. There is only
one small, underreported glitch: Hamer's results have never been
replicated. Two subsequent studies showed much weaker evidence of
a gay gene; a third, published April 23 but overshadowed by the
massacre at Littleton the day before, found no evidence at all.
"There is no hint or trend in the direction of the initial
observation," George Ebers, a Canadian investigator involved in
the study, said in Science.

A quick trawl through the headlines of the 1990s finds a similar
fate for other front-page genetic breakthroughs. Despite much-publicized discoveries of genes for schizophrenia, manic-depression, alcoholism and bipolar disorder, the precise genetic
components of these illnesses continue to elude science. The same
goes for personality traits. The much-trumpeted discovery of a
"novelty-seeking gene" in 1996 hasn't been replicated -- nor have
various "depression genes." This is not to say that progress isn't being made in parsing the biological components of behavior. But in any given person, the interplay of genes and the environment is a horrendously complex story.
Individual genes produce quite subtle effects, and the more we
learn about DNA, the clearer it is that any particular gene's
potential can be shut down or enhanced by complex biochemical
pathways contingent upon things like sleep, nutrition and stress.


A decade ago the field of behavior genetics was aflutter with the
hope that molecular biology would home in on what makes each of
us tick. But "the fog is lifting very slowly," says Kenneth
Kendler, a professor of psychiatric genetics at Virginia
Commonwealth University in Richmond. "We've learned that in
psychiatric disorders, there are no single genes of really large
effect. If there were, we'd have found them already." Genes for certain conditions, such as Huntington's or sickle cell disease, are known as simple Mendelian traits because they follow the straightforward model of inheritance noted by the Austrian monk Gregor Mendel last century. "Mendelian traits are like a trumpet call. The genetic signal blasts right through," says Kendler. "But the genetic effects in [most behavioral disorders
and traits] are like whispers in a busy train station. It's hard to distinguish them from the background noise."

That behavior is a tricky business to predict was elegantly
demonstrated by another study published in Science this month. A
group of researchers at three universities -- in Oregon, upstate
New York and Edmonton, Alberta -- ran a set of identical
experiments on eight different mouse strains, each bred to show
distinct behavioral attributes. The idea was to see whether they
would act according to type. They didn't. In some tests,
genetically identical mice acted differently depending on the lab
that tested them. A strain of mice lacking a receptor for the
neurotransmitter serotonin -- a substance whose imbalance has been
implicated in various addictions and mood disorders -- was expected
to drink more alcohol and show more anxiety than the other mice
strains. But all three teams found that the serotonin-mutants
didn't booze it up any more than the others. And all strains of
mice tested in Alberta, it turned out, were mellower than the New
York and Oregon mice. Must be the weather, eh?

Genetic programming, in other words, isn't nearly as efficient as
scientists might hope. Peter W. Nathanielsz, a Cornell University
obstetrician whose research focuses on the fetal environments of
sheep, writes in a new book that some of the most significant
programming of human health -- and behavior, potentially -- occurs in
the womb. This isn't exactly a new observation, but advances in
neuroscience highlight the fact that the migration of neurons to
the precise area of the brain where they belong during pregnancy
is a dicey business that can be easily disrupted. Even in a
healthy pregnancy, chance has a large impact on the prenatal
formation of the brain. Even twins with identical sets of genes
have brains that look different.


What happens in the womb is one of the new frontiers of the
nature-nurture debate. Epidemiology has already shown how
important the womb can be. Over the past several decades, David
Barker of Southampton University and other researchers have been
studying the outcome of the thousands of Dutch babies conceived
or carried during the hunger winter of 1944-45, when the Nazis
kept food from reaching people in Amsterdam and the surrounding
area to punish the Dutch for the Allied "Bridge Too Far''
invasion. Immediately after the war, this population's nutrition
returned more or less to normal, but 50 years after their births,
hunger winter babies have much higher rates of diseases like
diabetes than controls. Scientists attribute the higher diabetes
rates to the "thrifty fetus" phenomenon -- the fetus' pancreases
were programmed in the womb to process much lower levels of
glucose than became available after birth. "Babies who prepare
in the womb for a thrifty existence after birth pay the price if
they live a life of over-consumption in a situation in which food
is plentiful," writes Nathanielsz, who has observed the same
phenomenon in animal experiments.

Rats whose mothers eat low-protein diets suffer from various
behavioral and learning problems. If the rats are female, they
often pass these traits on to their offspring, even if the
second-generation mother's diet is normal, Nathanielsz writes in
his book "Life in the Womb: the Origin of Health and Disease."
Malnourished rats take many generations of healthy eating to
return to normal, in a kind of Lamarckian pattern of inheritance,
he writes. "The environment of the womb is of extreme importance
in building the body and the brain," Nathanielsz says. "If
things go wrong there can be a permanent price to pay."

Twin studies, which compare the sharing of traits in fraternal
and identical twins, have provided pretty convincing evidence of
a genetic component to most aspects of behavior. They show in
study after study that genetically identical twins, even when
separated for much of their lives, are far more similar than
fraternal twins in everything from IQ to heart disease to
shyness. Twin studies produce statistical estimates of the
genetic contribution traits -- for example, that IQ is 50 to 80
percent genetic. But even identical twins can have remarkably
different womb environments. About a third of all identical twins
are nourished with separate placentas, and in as many as 10
percent of the twins who share a placenta, one twin essentially
steals womb nutrients from the other, a process that has been
called "runting." A few studies that compared the congruence of
the behavior of identical twins nurtured in different types of
womb environments found "significant personality and IQ
differences," says Kendler. Pondering how these studies of womb
environment could skew behavior genetics studies, Kendler admits,
"is enough to make someone like me nervous."


Arthur Allen

Arthur Allen writes on health, science and other issues for Salon. He lives in Washington.

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