Our Assumptions About What Causes Chronic Diseases Could Be Wrong

      By Laura Wright, OnEarth Magazine
http://www.alternet.org:80/healthwellness/58482/

      Martha Herbert, a pediatric neurologist at Boston's Massachusetts
General Hospital, studies brain images of children with autism. She was
seeing patients one day a few years ago when a 3-year-old girl walked in
with more than the usual cognitive and behavioral problems.
      She was lactose intolerant, and foods containing gluten always seemed
to upset her stomach. Autistic children suffer profoundly, and not just in
their difficulty forming emotional bonds with family members, making
friends, or tolerating minor deviations from their daily routines.
      Herbert has seen many young children who've had a dozen or more ear
infections by the time they made their way through her door, and many others
-- "gut kids" -- with chronic diarrhea and other gastrointestinal problems,
including severe food allergies. Such symptoms don't fit with the
traditional explanation of autism as a genetic disorder rooted in the brain,
and that was precisely what was on Herbert's mind that day. She's seen too
many kids whose entire systems have gone haywire.
      During the course of the little girl's appointment, Herbert learned
that the child's father was a computer scientist -- a bioinformatist no
less, someone trained to crunch biological data and pick out patterns of
interest. She shared with him her belief that autism research was overly
focused on examining genes that play a role in brain development and
function, to the exclusion of other factors -- namely, children's
susceptibility to environmental insults, such as exposure to chemicals and
toxic substances.
      Inspired by their conversation, Herbert left the office that day with
a plan: She and the girl's father, John Russo, head of computer science at
the Wentworth Institute of Technology, would cobble together a team of
geneticists and bioinformatists to root through the scientific literature
looking for genes that might be involved in autism without necessarily being
related to brain development or the nervous system.
      The group scanned databases of genes already known to respond to
chemicals in the environment, selecting those that lie within sequences of
DNA with suspected ties to autism. They came up with more than a hundred
matches, reinforcing Herbert's belief that such chemicals interact with
specific genes to make certain children susceptible to autism.
      Although some diseases are inherited through a single genetic mutation
-- cystic fibrosis and sickle cell anemia are examples -- the classic "one
gene, one disease" model doesn't adequately explain the complex interplay
between an individual's unique genetic code and his or her personal history
of environmental exposures.
      That fragile web of interactions, when pulled out of alignment, is
probably what causes many chronic diseases: cancer, obesity, asthma, heart
disease, autism, and Alzheimer's, to name just a few.
      To unravel the underlying biological mechanisms of these seemingly
intractable ailments requires that scientists understand the precise
molecular dialogue that occurs between our genes and the environment --
where we live and work, what we eat, drink, breathe, and put on our skin.
      Herbert's literature scan was a nod in this direction, but actually
teasing out the answers in a laboratory has been well beyond her or anyone
else's reach -- until now.
      Consider for a moment that humans have some 30,000 genes, which
interact in any number of ways with one or more of the 85,000 synthetic,
commercially produced chemicals, as well as heavy metals, foods, drugs,
myriad pollutants in the air and water, and anything else our bodies absorb
from the environment.
      The completion of the Human Genome Project in 2003 armed scientists
with a basic road map of every gene in the human body, allowing them to
probe more deeply into the ways our DNA controls who we are and why we get
sick, in part by broadening our understanding of how genes respond to
external factors.
      In the years leading up to the project's completion, scientists began
developing powerful new tools for studying our genes. One is something
called a gene chip, or DNA microarray, which came about through the marriage
of molecular biology and computer science. The earliest prototype was
devised about a decade ago; since then these tiny devices, as well as other
molecular investigative tools, have grown exponentially in their
sophistication, pushing medical science toward a new frontier.
      Gene chips are small, often no larger than your typical domino or
glass laboratory slide, yet they can hold many thousands of genes at a time.
Human genes are synthesized and bound to the surface of the chip such that a
single copy of each gene -- up to every gene in an organism's entire genome
-- is affixed in a grid pattern. The DNA microarray allows scientists to
take a molecular snapshot of the activity of every gene in a cell at a given
moment in time.
      The process works this way: Every cell in your body contains the same
DNA, but DNA activity -- or expression -- is different in a liver cell, say,
than it is in a lung, brain, or immune cell. Suppose a scientist wishes to
analyze the effect of a particular pesticide on gene activity in liver
cells. (This makes sense, since it is the liver that processes and purges
many toxins from the body.)
      A researcher would first expose a liver cell culture in a test tube to
a precise dose of the chemical. A gene's activity is observed through the
action of its RNA, molecules that convey the chemical messages issued by
DNA.
      RNA is extracted from the test tube, suspended in a solution, then
poured over the gene chip. Any given RNA molecule will latch on only to the
specific gene that generated it. The genes on the chip with the most RNA
stuck to them are the ones that were most active in the liver cells, or most
"highly expressed."
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