If you find yourself battling chronic disease, your DNA and the environment may not be to blame as much as the chemical exposure of your ancestors.
That’s according to an article published this month in the journal Environmental Epigenetics, by a team at the University of Washington.
Researchers exposed three successive generations of rats each to a single toxicant, in a bid to mimic the exposure of humans to different eras of chemicals. The first generation was exposed to the fungicide vinclozolin, a pesticide that kills various diseases on raspberries, lettuce, kiwi, grapes, and turf. A known endocrine disruptor, vinclozolin can affect sex organ development and fertility, as well as delay puberty.
The second generation of rats was exposed to a jet fuel hydrocarbon mixture. And gestating females from the third generation were exposed to the pesticide dichlorodiphenyltrichloroethane, also known as DDT. Marine biologist Rachel Carson famously warned of the dangers of the pesticide, which was manufactured en masse during World War II, in her 1962 book Silent Spring.
Three additional, non-exposed generations were bred before the rats were examined. Washington state researchers looked for changes to their epigenome, which consists of chemicals that modify the genome, telling it “what to do, where to do it, and when to do it”—almost like computer software. The epigenome can be influenced, or “reprogrammed,” by environmental factors like stress, diet, drugs, pollution, and toxicants. Resulting changes can be passed down from cell to cell as they divide, within an individual—and from generation to generation, among family members.
The scientists observed “compounded disease impacts” over time, with toxicant exposure shifting each generation’s epigenetics “dramatically.” The incidence of obesity, kidney disease, and prostate disease increased in each subsequent generation after the first toxicant exposure. By the time the rats were bred out to three unexposed generations, their risk of such conditions had risen by as much as 70%.
Previous research has only examined the impacts of single-generation exposures to toxicants, Michael Skinner, a professor of biology at WSU and the study’s corresponding author, tells Fortune.
“We found that if multiple generations get different exposures, eventually there’s an amplification or compounded effect on some diseases,” he says.
Both the U.S. and Europe have obesity rates around 50% and are three generations down the line from initial exposure to DDT in the 1950s, he points out, suggesting that changes in the epigenome caused by generational exposure to toxic chemicals had created a population that’s more susceptible to disease, including obesity.
A person today who eats a high fat, high sugar diet may very well develop obesity. But their ancestors who weren’t exposed to such toxicants may not have, even if they ate the same unhealthy diet, he asserts.
“What this tells you is that what your grandparents were exposed to is going to give you and your children and grandchildren conditions and will continue to subsequent generations,” he adds. “It’s not your direct exposure, so much.”
The genome as a minor player
Such transmission of diseases through generations is known as epigenetic transgenerational inheritance, a “non-genetic form of inheritance that we now realize exists,” Skinner says.
The impact of various environmental factors—like climate, nutrition, and toxicants—on the epigenome has been shown to extend tens of hundreds of generations in fruit flies and hundreds of generations in plants.
“With mammals, we’ve only been capable of going out 10 or 20 generations,” he says. “But we see transmission as well.”
While a person’s DNA is an important factor in the development of disease, it’s not as crucial as the epigenome, Skinner says. Case in point: Genetic mutations found in the BRCA1 and BRCA2 genes, made famous by Angelina Jolie’s 2013 New York Times op-ed, are found in only 1% to 7% of breast cancer patients who don’t have a family history of the disease.
“It’s not really what is regulating biology that much,” Skinner says of such genetic errors. Of the numerous DNA mutations each person has, only 1% might contribute to disease.
“It’s changes in epigenetics that can give you a disease [presentation] or make you taller or shorter or obese or not obese,” he says.
Case in point again: breast cancer.
Breast cancer is caused by far more than a single gene, he says. “If you take the BRAC2 gene, which is one of the first genes that has a really good association with breast cancer—and you look at 100 people with breast cancer, only one of those 100 people may have a mutation in BRAC2.”
“The idea that a single or even a small number of genes are controlling biology is not accurate,” he adds. “It takes hundreds, if not thousands, of genes” to result in any one medical condition—and all contributing genes must be “turned on” by the epigenome.
The study is a wake-up call as to just how much environmental exposures influence health, Skinner says—if not our generation’s health, undoubtedly the next’s, and perhaps in perpetuity.
“Now we realize that what we’re doing to ourselves in terms of exposure is not so much impacting us, though it can,” he adds. “But it’s having dramatic effects on subsequent generations.”