[Paleopsych] Wired: Whew! Your DNA Isn't Your Destiny

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Sat Sep 3 01:32:02 UTC 2005

Whew! Your DNA Isn't Your Destiny
By Brandon Keim
02:00 AM Aug. 16, 2005 PT

The more we learn about the human genome, the less DNA looks like

As scientists discover more about the "epigenome," a layer of
biochemical reactions that turns genes on and off, they're finding that
it plays a big part in health and heredity.

By mapping the epigenome and linking it with genomic and health
information, scientists believe they can develop better ways to predict,
diagnose and treat disease.

"A new world is opening up, one that is so much more complex than the
genomic world," said Moshe Szyf, an epigeneticist at Canada's McGill

The epigenome can change according to an individual's environment, and
is passed from generation to generation. It's part of the reason why
"identical" twins can be so different, and it's also why not only the
children but the grandchildren of women who suffered malnutrition during
pregnancy are likely to weigh less at birth.

"Now we're even talking about how to see if socioeconomic status has an
impact on the epigenome," Szyf said.

Researchers have already linked some human cancers with epigenetic
changes. In a few years, scientists hope that doctors, by looking at an
individual's epigenome, will be able to detect cancer early and
determine what treatments to use.

The same might be done for other diseases -- and as the effect of the
environment on epigenetic change is better understood, people will be
able to address the environmental aspects of health.

The field, though still embryonic, won't be that way for long.
"Epigenetics is one of the fastest-moving areas of science, period,"
said Melanie Ehrlich, a Tulane University epigeneticist whose lab linked
human cancer to epigenomic changes in 1983.

Back then, Ehrlich's discipline was largely ignored. Walter Gilbert, a
Nobel Prize-winning biologist, famously said that since fruit flies had
no epigenomes, people could hardly need them.

But in the past two decades -- and especially the last couple of years
-- studies have linked the epigenome to disease and development, showing
that it changes in response to the environment and can be passed from
parents to children.

While predicted treatments run from diabetes and heart disease to
substance abuse and schizophrenia, the most promising applications are
in cancer. Research shows that some cancers follow from the deactivation
of tumor-suppression genes. Last year, the Food and Drug Administration
approved the first epigenetic drug, azacitidine, which treats a form of
leukemia by reactivating those genes.

However, using drugs to target specific parts of the epigenome, which
runs in tandem with our 6 billion base pairs of DNA, is extremely

Ehrlich believes epigenetic researchers are better off trying to predict
and diagnose cancer and other diseases.

To do that, scientists need a large-scale map that shows how epigenetic
patterns relate to disease, said Steve Baylin, an epigeneticist at Johns

"If we knew those patterns," Baylin said, "you could predict which
individuals are more at risk -- change their diets, change their
exposures, use prevention. We could detect disease early and predict how
people respond to drugs."

Making that map won't be easy. Not only does the epigenome change over
time, it also differs in every major cell type, of which there are a
couple hundred. Epigeneticists say this will be time-consuming but

In Europe, a consortium of public and private institutions is
collaborating on the Human Epigenome Project, while mapping in the
United States is scattered among a handful of companies and
government-funded scientists.

"We don't have the funding to do a comprehensive, large-scale
epigenetics project," said Elise Feingold, a director of the National
Human Genome Research Institute's ENCODE Project.

The lack of investment is somewhat reminiscent of the Human Genome
Project's early struggles, when James Watson fought for government
money. But at least the epigenomic mapping effort seems to have learned
something from the gene-patenting frenzy that loomed over the Human
Genome Project.

"That was a lesson in how intellectual property should not be handled,"
said John Stamatoyannopoulos, founder of biopharmaceutical company
Regulome. "Everybody patented everything left and right, the lawyers got
rich, the patent office was flooded, and at the end of the day the
patents just weren't valuable."

The absence of patent sniping might diminish some of the urgency, but
the upside is that the epigenomic map is free and available to anyone --
although only a tiny fraction has thus far been made.

"We are well under 1 percent finished; 1 percent would be a massive
overstatement," Stamatoyannopoulos said. "But, ultimately, this type of
knowledge will revolutionize the way we diagnose and treat disease."

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