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Earthfile: Toxic ills’ genetic roots
Homing in on complex gene-environment interactions
A new government project is aimed at finding genetic variations that make
people susceptible to reactions from environmental triggers such as
pollution and food additives. The findings will help doctors develop
therapies that target the responsible genes, preventing illness in
vulnerable people and curing the sick.
IMAGINE THE DAY when we’ll know exactly which components of air pollution
make some people sick, or which of thousands of chemicals we have to be
especially vigilant about keeping out of our drinking water.
The answers may begin trickling in within the next decade, say
researchers orchestrating the Environmental Genome Project. The goal of the
EGP is to identify variations in genes which, triggered by substances
milling around in the environment and hidden in our food, predispose people
to diseases and disorders.
Environmental factors, including micronutrients in our food, dust in
the air, chemicals in our water and cigarette smoke, cause a broad range of
maladies. Although it may be the first ailment to come to mind, cancer is
but one entry on the roster of diseases the investigators at the National
Institute of Environmental Health Sciences-sponsored project hope to
address. Whether or not we develop cleft palate, AIDS, mental retardation or
have a heart attack are but a few examples of conditions dependent on
gene-environment interactions.
In the past, scientists studied the health impact of environmental
factors independently of genetics. “It’s only been in the last couple of
years, with lots of genes and the ability to rapidly genotype people, that
we can put the two together,” says Dr. Jack Taylor, head of molecular and
genetic research in the laboratory of molecular carcinogenesis at the NIEHS
in Research Triangle Park, N.C.
There are, of course, cases where specific carcinogens have been
shown to cause disease. We know, for example, that cigarette smoking causes
lung cancer. But depending on his or her genetic makeup, one may be more or
less susceptible to smoking-associated lung cancer.
Genetic variation also may determine whether a smoking woman has a
child with birth defects. By genotyping — homing in on the genetic makeup of
a specific person — researchers have identified an association between
smoking and cleft palate, a physical deformity that occurs when the two
parts of the roof of the mouth fail to grow together completely during
prenatal development.
WORKPLACE AILMENTS
Genetic variation also influences which employees become ill from
industrial pollutants in the workplace, Taylor says.
Take the metal beryllium, which is used in industries such as
high-tech ceramics, nuclear weapon production, aerospace and electronics.
Depending on the industry, anywhere from 2 to 15 percent of workers exposed
to beryllium develop the lung disease called chronic beryllium disease, or
CBD.
New studies have shown that the chance of a worker developing the
disease is greatly increased if he or she carries a faulty gene that, when
normal, makes a protein that is involved in helping immune cells rid
beryllium from the body. The flawed gene allows beryllium to proliferate,
and CBD develops.
About one-third of healthy people carry this gene variation, or
allele. And almost all — 97 percent — of people who work with beryllium and
have the disease also carry the harmful allele.
But about 30 percent of workers who have the allele and have been
exposed to the metal do not develop CBD. Therefore, some other factors must
be at work, Taylor says. Homing in on these unidentified factors is one of
the goals investigators hope the EGP will achieve.
PROJECT DESIGN
The first step of the EGP is to decide which 200 of the more than
100,000 genes in the human genome to study. Then, DNA will be collected from
about 1,000 people so that alleles of the genes can be cataloged.
One of the issues facing the researchers is deciding whose DNA to
sample.
“We could take a representative sample of the U.S. population, which
would be predominantly Caucasian,” Taylor says. “But that doesn’t give you a
lot of variation.”
Exactly which ethnic groups are going to be included in the study
remains to be determined, but the researchers hope to decide and begin
recruiting people within the next few months, according to Dr. Samuel
Wilson, deputy director of NIEHS.
Ironically, it is just this sort of thinking along ethnic lines that
the study may help eliminate. “We will come to think of people in terms of
genetic identity rather than as members of a specific racial or ethnic
group,” Wilson says. And knowing our genetic identity will help protect us
all from environmental hazards, he says.
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