In mid-October, researchers in California published a study of Civil War prisoners that came to a remarkable conclusion. Male children of abused war prisoners were about 10 percent more likely to die than their peers were in any given year after middle age, the study reported.
The findings, the authors concluded, supported an “epigenetic explanation.” The idea is that trauma can leave a chemical mark on a person’s genes, which is passed down to subsequent generations. The mark doesn’t directly damage the gene; there’s no mutation. Instead it alters the mechanism by which the gene is converted into functioning proteins, or expressed. The alteration isn’t genetic. It’s epigenetic.
The field of epigenetics gained momentum about a decade ago, when scientists reported that children who were exposed in the womb to the Dutch Hunger Winter, a period of famine toward the end of World War II, carried a chemical mark, or epigenetic signature, on one of their genes. The researchers linked that finding to differences in the children’s health later in life, including higher-than-average body mass.
The excitement since then has only intensified, generating more studies — of descendants of Holocaust survivors, of victims of poverty — that hint at the heritability of trauma. If these studies hold up, they would suggest that we inherit some trace of our parents’ and even grandparents’ experience, particularly their suffering, which in turn modifies our own day-to-day health — and perhaps our children’s, too.
But behind the scenes, the work has touched off a bitter dispute. Critics contend that the biology implied by such studies simply is not plausible. Epigenetics researchers counter that their evidence is solid, even if the biology is not worked out.
“These are, in fact, extraordinary claims, and they are being advanced on less than ordinary evidence,” said Kevin Mitchell, an associate professor of genetics and neurology at Trinity College, Dublin. “This is a malady in modern science: the more extraordinary and sensational and apparently revolutionary the claim, the lower the bar for the evidence on which it is based, when the opposite should be true.”
Investigators in the field say the critique is premature: The science is still young. “The effects we’ve found have been small but remarkably consistent,” said Moshe Szyf, a professor of pharmacology at McGill University. “This is the way science works. It’s imperfect at first and gets stronger the more research you do.”
The debate centers on genetics and biology. Direct effects are one thing: When a pregnant woman drinks heavily, it can cause fetal alcohol syndrome. This happens because stress on a pregnant woman’s body is interfering directly with the fetus’ normal development. But no one can explain how, say, changes in brain cells caused by abuse could be communicated to fully formed sperm or egg cells before conception.
One theory is based on animal research. Scientists at the University of Maryland School of Medicine, led by Tracy Bale, have raised male mice in difficult environments, by periodically tilting their cages, or by leaving the lights on at night. This kind of upbringing, effectively a traumatic childhood, changes the behavior of those mice’s genes in a way that alters how they manage surges of stress hormones.
And that change is associated with alterations in how their offspring handle stress: The young mice are numbed, or less reactive, to the hormones compared with control animals, said Bale, director of the university’s Center for Epigenetic Research in Child Health and Brain Development. “These are clear, consistent findings,” she said.
Perhaps the best explanation for how such trauma marks could be attached to a father’s sperm cells comes from Oliver Rando at the University of Massachusetts. His studies, also in mice, have zeroed in on the epididymis, a tube near the testicles where sperm cells load before ejaculation. There, they learn to swim over a period of days, and their genes can be marked, he said.
The molecules that affect the changes appear to be “small RNAs,” fragments of genetic material that scientists are still learning about, Rando said. “This tube produces small RNAs and ships them to the sperm as they develop, suggesting that there exists a place that senses the dad’s environmental conditions and can change the package RNAs delivered.”
Other researchers have attempted to fill out the picture. Once those RNA packages arrive at the epididymis, the hypothesis goes, they prompt a cascade of changes at conception that evade the stripping, or rebooting, process and the subsequent reshuffling during early development.
The critics are far from persuaded. “It’s all very nice work, and yes, there are changes in the testicular cells,” said John M. Greally, a professor of genetics, medicine and pediatrics at the Albert Einstein College of Medicine. “But … the story that’s often told is overblown relative to the results, and too much causality is claimed.”