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Vol. LXII, No. 13
June 25, 2010

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Sins of the Grandfather?
STEP Forum Explores Disease Potential Handed Down From Ancestors

On the front page...

Did your ancestors make you sick? Or, more specifically, did something happen to Grammy before she was born that scarred you—health wise—for life? That’s what the science of epigenetics aims to explain. A recent Staff Training in Extramural Programs (STEP) forum, “Blast from the Past: Early Influences on Long-Term Health,” aimed to shed more light on the emerging field and its possible implications in health and society.

So we know certain characteristics—eye color, for instance—are passed down to us through our genes. “She gets that from my dad,” a proud mom might suggest of her daughter’s red hair. Epigenetics, however, seeks to find out what else besides your DNA may cause you to end up with some traits, particularly those abnormalities that can lead to disease.


  Dr. Trevor Archer  
  Dr. Trevor Archer  

Call it your “transgenerational inheritance,” said Dr. Trevor Archer, chief of NIEHS’s Laboratory of Molecular Carcinogenesis. Epigenetics, he explained, looks beyond your genes. It’s what your grandparents may have picked up when they were little more than embryos themselves, and then passed to you through your parents.

“Epigenetics is distinct from, but also dependent on, genetics,” he said.

The field’s extra-genomic influences “are often exposure-induced,” continued Archer, whose own research focuses on chromatin (the combination DNA-protein substance in chromosomes that tells cells how to function) and breast cancer.

British biologist C.H. Waddington coined the term epigenetics in 1942, Archer said, describing what has become a trendy topic in both scientific and popular culture media.

In January, for instance, Time magazine’s cover story featured research done in the 1980s by Stockholm-based preventive health specialist Dr. Lars Byren. He was curious about possible long-term health effects the grandchildren of famine victims might have suffered. That led him to studies documenting conditions in the womb that could affect the health of an infant’s grandkids.

Epigenetics STEP forum presenters included (from l) Dr. Andrew Feinberg of Johns Hopkins School of Medicine, Dr. Kjersti Aagaard-Tillery of Baylor College of Medicine, Dr. Nancy Press of Oregon Health & Science University and NIEHS’s Archer.
Epigenetics STEP forum presenters included (from l) Dr. Andrew Feinberg of Johns Hopkins School of Medicine, Dr. Kjersti Aagaard-Tillery of Baylor College of Medicine, Dr. Nancy Press of Oregon Health & Science University and NIEHS’s Archer.

“An exposure that appears to be directed at one generation can in fact directly influence subsequent generations,” Archer explained. For example, “exposure to one pregnant female actually involves not just one but three generations, not only the embryo inside but also the germ cells that are in it. When we try to understand what’s happening in this very complicated area, we need to remember the initial appearance of the exposure may in fact be a bit more complex.”

The next two panelists built on Archer’s foundation. Dr. Andrew Feinberg of Johns Hopkins School of Medicine talked about “epigenetic epidemiology,” a new field of medicine his group is trying to create. He noted several disorders that may have an epigenetic component, including cancer, diabetes and schizophrenia.

“A lot of common disease has an epigenetic twist to it,” he said. “Much of the fabric of common disease involves some disruption of either development leading to the disease in the first place or of the appropriate response to environmental signals that should take place in that tissue.”

Discussing fetal epigenetic changes, obstetrician-gynecologist Kjersti Aagaard-Tillery of Baylor College of Medicine said there’s one big issue researchers in the field are all grappling with now.

“Where do our genome science and our epigenome science ultimately converge, and what do our understandings in both of those fields mean for very great ethical questions?” she asked, sharing her research on in utero tobacco and maternal high-fat dietary exposures in primates.

“When we put our [pregnant primates] on a high-fat diet there is a rather profound effect on fetal livers,” she noted. In fact, the fetuses develop non-alcoholic fatty liver disease, which, Aagaard-Tillery pointed out, is often a precursor to childhood obesity in humans.

Those results seemed to set up perfectly for the final speaker, Dr. Nancy Press of Oregon Health & Science University, who discussed the ethical, legal and societal implications of epigenetics. She argued that the field uniquely cries out for the concept of team science.

Feinberg and colleagues are creating a new field of medicine called epigenetic epidemiology.
Feinberg and colleagues are creating a new field of medicine called epigenetic epidemiology.

Interdisciplinary collaboration for this particular field, Press explained, should not be a volume of great but individual short stories. Instead, researchers teaming up should produce an individual, unified book composed of great chapters.

“Epigenetics is the point where the myriad facets of the environment and the DNA sequence—nature and nurture—intersect in the organism,” she said. “Not only can no single discipline encompass all these influences and effects, but also I think the disciplines truly have to be talking to each other and listening to each other’s basic assumptions and basic ways of looking at the world to get what is going to be a satisfying picture.”

As an example, she referred back to the studies looking at descendents of malnourished or starving families. Results revealed the children gaining excessive weight, which probably had some kind of a protective effect during their first year of life. Later in the kids’ lives, the state of overweight could end up being deemed unhealthy.

Today’s culture, Press said, seems ready to make us—scientists included—jump immediately to accuse “mothers eating cheeseburgers,” instead of getting, say, the anthropological perspective and determining what is actually occurring long-term with these families.

It’s important that epigenetics not steer society more toward a “blame-the-victim” mentality, she stressed. “Let researchers know how what they’re saying may sound to affected communities.”

Of course, progress in human genome science and stem cell research has only amplified excitement in epigenetics, forum presenters agreed. Mapping an individual’s epigenome, Archer said, could “offer more opportunities for personalized medicine, ways to target drug therapies that are more effective if individuals have different epigenetic types. Then we can easily envision why they would have different responses.”

The challenge of epigenetics, then, is similar to other fields at their outset: Harness the power of the science to improve health without harming in even subtle ways those it’s meant to help.

“An epigenome can potentially provide a readout of an individual’s recent and ancestral environmental history,” Archer concluded. “It provides a way of thinking about the past and present.” NIHRecord Icon

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