Science Survey: Epigenetics...Understanding Chemicals' Newly Recognized Future Effects

January 15, 2009
dna.jpg

By VALERIE BROWN

The word epigenetics is popping up all over the place. Writers have their choice of many metaphors to describe this emerging field in biology: it's a set of master switches; it's a musical score; it's a Lego construction; it's a string of traffic lights.

Whatever it is, it's scary for journalists, because it's complex. You have to become a bit familiar with molecular biology, where genetics overlaps with biochemistry.

"Epi" means over, above, atop. So whatever it is metaphorically, epigenetics is a phenomenon that transcends, regulates and expands the function of genes. Emerging knowledge of epigenetics is upending dogma that has dominated biology for more than 50 years. Epigenetics is shifting the focus away from genes and onto the apparatus that surrounds a DNA molecule.

The DNA double helix is commonly described as a twisted ladder. It contains four molecules called nucleotides that make up the rungs of the ladder. They cling to two twisting sugar-phosphate backbones, the sides of the ladder.

There are lots of places along the helix where other molecules, called epigenetic markers, can attach themselves. Common hitchhikers on the DNA molecule are known by their chemical monikers and include methyl, phosphoryl, and acetyl molecules. The most widely studied so far are methyl groups.

In addition, there are other structures, called histones and chromatin, around a DNA molecule that act sort of like a moving company – they help compress and package the long helix to the astounding degree necessary to fit inside a cell. Epigenetic markers can block or allow gene expression, and thus prevent or encourage disease. They're part of the timeless vocabulary of replication and reproduction.

For a fertilized egg to turn into an adult, genes must switch on and off in the staggeringly complex process of cell differentiation. And since every cell in a person's body throughout his or her life has a complete set of genes, each cell must allow only certain genes to be expressed, or produce proteins. Liver cells allow different genes to function than nerve cells. Epigenetics apparently governs which genes get switched on and which don't, preventing mix-ups of cell types within organs and tissues.

During fetal development, epigenetic patterns are set up for life. Anything that interferes with the proper gene expression during this critical period of development can have permanent consequences. Plus, any transition in life when cells proliferate or rapidly switch genes on and off – puberty and menopause, for example – is also a high-risk time.

Epigenetic markers can be affected by food, pharmaceuticals and other chemicals. For example, pioneering work by Retha Newbold at the National Institute for Environmental Health Sciences (NIEHS) showed that diethylstilbesterol (DES), a powerful estrogenic chemical given to millions of pregnant women between 1938 and 1971 to prevent miscarriage, altered cell behavior in reproductive organs of those women's daughters. This resulted in vaginal cancers when the daughters grew up. Further research by Newbold and John McLachlan of Tulane University suggested that the harm is passed on to subsequent generations.

The degree to which industrial chemicals in the environment may be influencing epigenetics is a hot topic. Work by Michael Skinner of Washington State University and David Crews of the University of Texas, Austin has supported and extended Newbold and McLachlan's evidence for transgenerational effects. Skinner and Crews exposed pregnant lab rats to high doses of vinclozolin, a fungicide widely used on wine grapes, potatoes and other produce. The vinclozolin damaged male descendants' reproductive anatomy and fertility in three succeeding generations.

A striking aspect of the Skinner team's work is their demonstration that female rats can sniff out the damaged males, and invariably spurn them. This means that transgenerational changes to epigenetic patterns affect reproductive fitness, and therefore natural selection. Philosophers and historians of science find this interesting, since it seems to rehabilitate Jean-Baptiste Lamarck, the 18th-century biologist who believed characteristics a parent acquired could be inherited by offspring. Darwinists scoffed Lamarck's theory into oblivion a long time ago, but epigenetics gives it a new, plausible twist in that epigenetic patterns set before birth can apparently be inherited.

Epigenetic effects on reproductive fitness are also of pressing interest to wildlife biologists, ecologists and the like. If a wild population of a species was exposed to an influence that, like vinclozolin, impaired male fertility for several generations, that population would likely crash unless the females had access to males from another unexposed population.

There's some chance that epigenetic problems can be fixed. Experiments by Duke University researcher Randy Jirtle with bisphenol A (BPA) reveal that nutrients commonly found in foods can dramatically alter epigenetic patterns. Jirtle dosed pregnant mice with BPA, a known estrogen mimic. Their pups had yellow fur and got really fat. Jirtle then repeated the experiment but gave the pregnant rats folic acid, vitamin B12, choline and betaine. Their pups reverted to normal coat color and metabolism. These nutrients occur in food and are easily available in supplements.

Before you rush out to Supplements-'R'-Us, here's a note of caution: epigenetic markers can cut both ways. In many cancers, methyl molecules are stripped from locations where they normally occur. Vitamin D is known to promote methylation. But some cancers feature methylation in places along a DNA helix where it's usually absent, indicating that indiscriminate consumption of substances known to affect epigenetic markers is not a good idea. Not yet, anyway.

So epigenetics is a long-standing natural structure that science has only recently recognized as a rich source of biological information, unnoticed in plain sight as long as all eyes focused exclusively on genes. In short, it's a game-changer.

Keep your eyes on phrases like "fetal origins of adult disease," "transgenerational effects," and the ever-unnerving "endocrine disruption." Emerging knowledge of epigenetics will challenge and clarify our understanding of all these phenomena.

Valerie Brown is a freelancer who changed careers from professional musician to science writer in midlife. After that, even parsing epigenetics seemed easy. For a much more detailed discussion of epigenetics and links to further resources, see her article "Environment Becomes Heredity."
 

VALERIE BROWN