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

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 University.

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 complicated.

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 Hopkins.

"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 possible.

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."

Source: WIRED magazine, August, 2005