Epigenetics In D.C.

At the end of last week, I witnessed a few dozen scientists and regulators with expertise in a dizzying diversity of disciplines—among them toxicology, epidemiology, molecular biology, public health, toxicology, genetics, pharmacology, reproductive biology, and exposure biology—confront the likelihood that an emerging arena of science, called environmental epigenetics, might change plenty about how they understand the relationship between public health and environmental conditions ranging from exposures to specific chemicals to child abuse. The conference, held in the Keck Building in downtown Washington, D.C., had a long title: “Use of Emerging Science and Technologies to Explore Epigenetic Mechanisms Underlying the Developmental Basis of Disease.” It was one of several workshops organized by the National Academies at the request of the National Institute for Environmental Health Science (NIEHS). “The objective is to gain understanding of what research is most needed to inform public-health decision-makers about chemicals that cause epigenetic effects,” the organizers wrote in a brochure for the workshop. In his engaging overview of just what epigenetics is and where in the scientific landscape it came from, Richard Meehan, program leader of the Human Genetics Unit at the Medical Research Council in Scotland (and bleary eyed from what turned out to be something like 20 hours of travel involving 6 boarding passes) shared a widely used definition of epigenetics with the group: “Epigenetics is the study of heritable changes in gene function that occur without changes in sequence of nuclear DNA.” The details behind these changes in gene expression requires drilling deep into the bedrock of molecular biology, but the basic idea is that there are mechanisms by which the macromolecular home of genes, chromatin, becomes chemically modified in such ways that genes can get switched on or off. This has consequences. Switch off a tumor-suppressor gene this way, for example, and you might be set onto a course that has cancer along the way. At least that is one way researchers are thinking about things. It seems that for just about any environmental input that these and other researchers have looked for epigenetic effects, they have found such effects. Among the specific, measurable epigenetic changes are methylation of certain cytosine bases along the DNA of chromatin and methylations, acetylations and other chemical modifications of histone proteins that comprise reel-like nucleosomes in chromatin around which DNA winds. Everything from exposure to nickel and estrogenic compounds such as bisphenol A to child abuse and maternal care (as in a rat mom’s licking and grooming of her pups) appear to elicit epigenetic changes. Much harder to nail down is whether these changes are, in fact, biologically consequential. Among the take home messages was that characterizing the epigenetic landscape on a genome scale for normal and diseased cells of as many tissue types as possible would be valuable. There are efforts along those lines in the works. There was some noticeable handwringing about the dynamic nature of epigenetic changes compared to the permanent alterations emblematic of gene sequence changes, otherwise known as mutations. It could be that many or most epigenetic changes that researchers have associated with, say chemical and other environmental exposures, do not, in the end, actually last that long (they become undone) and may not have much to do with health consequences associated with the exposures. That is, epigenetic phenomena may not have as much of a causal role in disease as many now suspect they do. One left the workshop with a sense that this group of researchers viewed epigenetic phenomena as harboring the potential to, in fact, provide powerful causal stories that underlie myriad statistical associations that toxicologists, epidemiologists, medical researchers and others have been filling journal articles with for decades. These would be the kinds of science-based stories that ultimately could guide public health policy as well as data-gathering efforts, such as screening programs for the tens of thousands of chemicals in commerce today, for guiding such policy. That in particular was on the minds of Linda Birnbaum, director of NIEHS, and her colleagues at the workshop. But surrounding the field of epigenetics now is an atmosphere of uncertainty about how biologically consequential epigenetic changes really are and whether this new science will have an important bearing on public policy and regulatory practice.  Check out the workshop web site for more information: http://dels.nas.edu/envirohealth/epigenetic.shtml The presentations and recordings of the talks will be available there in the near future.

Author: Ivan Amato

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