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Hidden Heritage

Tech & Innovation | April 25, 2016

Last summer, a team at New York’s Mount Sinai hospital led by Rachel Yehuda published a study on transmission of trauma across generations. What they found flies in the face of scientific convention: the trauma experienced by a group of Holocaust survivors had been encoded in the genes of their children—trauma that was experienced before the children had been even conceived.

Yehuda’s study is one of the latest and most compelling in the relatively new science of epigenetics: how environmental experiences and conditions—trauma in this case—can activate certain “tags” in one’s genes, and those marginal changes in gene expression can sometimes be passed on to one’s descendants. Research is illuminating the intergenerational effects of things like trauma, diet, and exposure to toxins on health. The choices our parents and grandparents made—and the conditions they were subjected to—may affect us more than we thought.

The full implications of this discovery are unknown, but the existing research raises important questions. What really goes into making us who and what we are? How important is knowledge of one’s ancestral history to answering that? Might the impact of epigenetic changes over generations actually shape society? Certain genetic groups—namely those faced with systemic racism—have disproportionately experienced trauma, everyday stresses, and the deleterious health conditions associated with poverty for generations. What might the cumulative effect of such a history be?

Though the precise mechanism of epigenetic transmission remains a mystery, geneticists have discovered that environmental conditions can elicit certain changes in RNA, a type of genetic material that exists above and separate from our more immutable DNA. Most of those tags get erased at the point of fertilization, but some, it seems, can escape this purification process and be passed to the next generation. “We used to think there was this certain kind of genetic heritability that was everything, that if it doesn’t kill you before you have a chance to have children, then it doesn’t have a biological effect,” said Nick Seaver, an anthropologist of science and technology at Tufts. “And what epigenetics is saying is actually there are things that can happen in your life—things in the abstract sense—that are actually heritable.”

Yehuda’s Holocaust survivor study was the first to concretely identify epigenetic inheritance in humans—an important landmark in the field. The research team compared the activity of a particular protein in a strand of RNA associated with the regulation of stress hormones in a group of 32 Jewish men and women who had survived the Holocaust to the same RNA strand in their children. Previous research had shown that trauma can be passed in humans between generations through social, rather than strictly biological, channels—victims of child abuse often have parents who experienced trauma, for example—but this was the first evidence that someone can actually be born with it. In the children of those 32 Holocaust survivors, this trauma manifested in unusually high rates of depression and other stress-related health disorders.

Yehuda’s study corroborates the findings of several previous studies on rodents. Researchers say we should be cautious in extrapolating animal studies to humans. Yet the strength and consistency of the findings of studies on rodents is encouraging, perhaps hinting at what we could see in people. For example, in December 2013, Kerry Ressler of Emory University and his colleague Brian Dias published their latest research in a series of studies on fear conditioning in mice. They trained mice to associate a certain smell with an electric shock until the mice exhibited a fear response when the smell was pumped into their cages, even in the absence of the shock. Amazingly, their pups also reacted to the smell with fear, despite having never received the shocks, as did the third generation.

Importantly, Ressler and Dias found differences in the brain structures of the descendants of the smell-fearing mice from other mice. In particular, the fearful mice had more neurons that produce the protein used to detect that particular smell, almost as though the mice had evolved within just a generation.

In fact, even the nurturing tendencies of a female mouse can have leave indelible changes in the genetics of her bloodline for generations. “How mother rodents care for their offspring can alter the stress responses of their offspring and their grandchildren,” said Michael Romero, a Tufts biology professor who researches stress responses in animals. In April 2014, a research team at the University of Zurich randomly separated mother mice from their pups and exposed them to stressful situations, such as plunking them in cold water. Not only did their pups show depressive symptoms and unusual activity in the hippocampus, a brain region associated with stress and memory, but these symptoms appeared in subsequent generations as well.

This was not caused by any learned cross-generational change in parenting style: when the researchers collected RNA from the sperm of the second generation of mice and injected it into the eggs of untraumatized mice they found the same result in their offspring. “The current thinking is that this generational transference of behavior and physiology is regulated by epigenetic changes in the brain,” said Romero. The trauma had been stitched into the fabric of their genes before they were even born.

The health effects of toxins, too, may be passed genetically—and may in fact snowball over generations. In 2014, a team led by Michael Skinner of Washington State University found that exposure to the pesticide DDT was associated with only minor health problems in a group of mice, yet nearly 90 percent of mice in subsequent generations had obesity. Likewise, in the United States, DDT was used widely in the 1940s to protect crops from insects, but was banned in the 1970s. Three generations after DDT use became common, the country saw a sudden spike in obesity rate, from below three percent in the 1950s to nearly a third of the population today.

Moreover, by smoking at young age, one may be condemning not only their own health but also that of their children. A 2014 study conducted at the University of Bristol in the United Kingdom found that the sons of fathers who smoked in their early adolescence were much more likely to develop obesity.

And the effects of diet, too, can ripple across generations. The Swedish village of Överkalix, which was genetically isolated for generations and kept meticulous town records, has been vital to research in this area. Researchers found that among the grandsons of men from Överkalix who had been just pre-puberty when a famine struck the town lived, on average, a shocking 32 years longer, adjusting for socioeconomic factors, than those whose grandfathers had lived through a bountiful harvest at the same age. The latter group had unusually high rates of diabetes. Even more bizarrely, the reverse was true for women: the granddaughters of Överkalix women who lived through a famine typically lived shorter lives and were less healthy than those who did not.

The results of all these studies, though they raise more questions than they answer, are forcing us to revisit old assumptions about what contributes to health—and, perhaps, racial health discrepancies. If the effects of poor diet, exposure to toxins, and trauma can be passed genetically between generations, perhaps individuals from historically marginalized groups, such as Latinos and Black Americans, can be born with disadvantages that are not only social, but also biological.

Studies from 2001 and 2010 on the proportionally high rates of hypertension and diabetes in ethnic Hawaiians and Black and Latino Americans concluded that the disparity was directly attributable to discrimination. Darron Smith, an author and researcher of inequalities that pertain to Black Americans and other Americans of Color, believes the categorically poorer health of Black Americans has origins that date back centuries. “Because Black Americans and their forbears have endured over 20 generations of White-imposed race-related inequities in every major sector in society,” he wrote for the Huffington Post, “including persistent race-based discrimination in housing, education, healthcare, jobs, and the prison industrial complex, they carry a higher burden of disease.”

Low birth weight is both an indicator of the mother’s poor health and a predictor of adult health problems in the child, and the literature illustrating the difference between average birth weights in White and Black populations is extensive. A 2008 study co-authored by Grazyna Jasienska argues that genetic and socioeconomic factors alone do not account for this discrepancy. “The low birth weight of contemporary African Americans not only results from the difference in present exposure to lifestyle factors known to affect fetal development but also from conditions experienced during the period of slavery,” she wrote. “I suggest that the several generations that have passed since the abolition of slavery in the United States has not been enough to obliterate the impact of slavery on the current biological and health condition of the African-American population.” Other studies have shown that Black women who live in the United States but were born in countries ancestral to American slaves give birth to babies with significantly higher weights than women with slave ancestry.

Cross-generational effects of systemic marginalization are evident already. But few measures of racism are as starkly, empirically measurable as actual changes in genes. As we learn more about how experience can shape someone’s genes and those of their descendants, we may see that as powerful as the world we’re born into is in determining who and what we are, the world of our parents and grandparents may be just as important. For better or worse, our inheritance is inescapable.