Epigenetics: The Controversial Science Behind Racial and Ethnic Health Disparities

Why what we eat, are exposed to, and experience today may shape the health of our descendants tomorrow.

  Research technicians prepare DNA samples to be sequenced in the production lab of the New York Genome Center on Sept. 19, 2013 in New York City. D.C. will need to attract these type of high tech jobs to keep its economy growing.    
National Journal
March 20, 2014, 10:43 a.m.

When pa­tients hop­ing to con­ceive a happy and healthy child vis­it an ex­pert in Ay­urveda — a form of al­tern­at­ive medi­cine that ori­gin­ated in In­dia sev­er­al thou­sand years ago — they are some­times told to fol­low a sur­pris­ing set of or­ders. If either the man or wo­man feels thirsty, hungry, sad, angry, or afraid, the couple is told, they should forgo any po­ten­tial baby-mak­ing activ­ity. Only when happy, sa­ti­ated, and feel­ing con­nec­ted to one an­oth­er should they bathe, dress in fresh white cloth­ing, ap­ply par­tic­u­lar oils to their bod­ies — and then pro­ceed.

To most people with a passing un­der­stand­ing of DNA and hered­ity, all that prep work may sound ut­terly ab­surd. But a fast-grow­ing field of sci­ence, known as epi­gen­et­ics, strongly sug­gests that what we ex­per­i­ence, con­sume, and en­counter from the mo­ment we are con­ceived mat­ters. Epi­gen­et­i­cists study mo­lecu­lar changes in­clud­ing DNA methyl­a­tion, the tech­nic­al term for the way that our en­vir­on­ments and ex­per­i­ences can subtly al­ter our gene activ­ity. The genes turned “on” and turned “off” when we are ex­posed to cer­tain chem­ic­als, man-made pois­ons, or — per­haps most sur­pris­ingly — emo­tion­al ex­per­i­ences, can make us more or less sus­cept­ible to par­tic­u­lar health prob­lems.

“There are con­di­tions and ser­i­ous dis­eases oc­cur­ring in the pop­u­la­tion today at a rate that simply can­not be ex­plained by the rules of mam­mali­an ge­net­ics alone,” says Mi­chael K. Skin­ner, a pro­fess­or at Wash­ing­ton State Uni­versity and the found­ing dir­ect­or of the Cen­ter for Re­pro­duct­ive Bio­logy in the School of Bio­lo­gic­al Sci­ences.

In oth­er words, the rate at which chil­dren in some demo­graph­ic groups are born too soon, the fact that en­tire geo­graph­ic re­gions suf­fer from el­ev­ated rates of obesity and dia­betes, and even the fre­quency with which Amer­ic­an chil­dren today are dia­gnosed with aut­ism can­not be suf­fi­ciently ex­plained by the Pun­nett Squares every high school bio­logy stu­dent must mas­ter, Skin­ner says.

“Ge­net­ics is part of the story, an im­port­ant part of the hu­man story,” says Skin­ner. “But epi­gen­et­ics, that is the oth­er half of the equa­tion.”

The Ef­fects of Chron­ic Stress

An Emory Uni­versity study re­leased last year sug­ges­ted just how large epi­gen­et­ics may loom in one of the coun­try’s most egre­gious ra­cial and eth­nic health dis­par­it­ies — pre­ma­ture births. The United States’ pre­ma­ture birth prob­lem is the worst in the in­dus­tri­al­ized world, es­pe­cially for ra­cial and eth­nic minor­it­ies. About 10.5 per­cent of white chil­dren were born be­fore 37 weeks gest­a­tion in 2012, along with 10.3 per­cent of Asi­an ba­bies. But about 11.7 per­cent of Latino chil­dren, 13.6 per­cent of Nat­ive Amer­ic­an ba­bies, and 16.8 per­cent of black in­fants ar­rived too soon.

Eliza­beth Cor­win, dean of re­search at Emory Uni­versity’s Wood­ruff School of Nurs­ing, and a team of re­search­ers closely tracked more than 100 wo­men dur­ing the last three months of their preg­nan­cies. They found that wo­men of all races and eth­ni­cit­ies who were poor dur­ing their preg­nan­cies were more likely to suf­fer from chron­ic stress, a bio­lo­gic­ally de­tect­able and quan­ti­fi­able con­di­tion. The same was also true, says Cor­win, of middle-class black wo­men, and all Lat­i­nas ex­cept for those who were im­mig­rants. In fact, the prob­lem was par­tic­u­larly pro­nounced in those last two groups. 

Black wo­men and Lat­i­nas across so­cioeco­nom­ic cat­egor­ies — those with and without in­sur­ance, col­lege de­grees, and ac­cess to the best food and in­form­a­tion — were sig­ni­fic­antly more likely to test pos­it­ive for el­ev­ated levels of stress hor­mones and con­di­tions that those hor­mones can set in mo­tion. This made the wo­men more likely to de­liv­er their chil­dren early. Chron­ic stress, the team de­term­ined, is the reas­on ap­prox­im­ately 30,000 more Afric­an-Amer­ic­an ba­bies are born pre­ma­turely each year than any oth­er group.

“We all ex­per­i­ence stress,” Cor­win says. “Some weeks, who doesn’t feel ut­terly over­whelmed? But what we found was that chron­ic stress is something en­tirely dif­fer­ent. It [is] cre­ated by some com­bin­a­tion of fin­ances, re­la­tion­ships, com­munity, and ex­per­i­ences like ra­cism — ac­tu­al and per­ceived.”

Cor­win knows res­ults like this are not easy for every­one to di­gest or ac­cept. She’s seen the com­ments be­neath on­line stor­ies about her re­search, re­flect­ing what can some­times only char­it­ably be de­scribed as of the “Oh, come on, that’s an­oth­er ex­cuse,” vari­ety. But stud­ies con­firm­ing the neg­at­ive ef­fects that chron­ic stress can have on preg­nancy, in­fant, child and even adult health are, in her words, “vo­lu­min­ous, sol­id, and long known.”

Across the coun­try, Skin­ner’s work at Wash­ing­ton State Uni­versity has gone a step fur­ther. Skin­ner and his team have proven ex­pos­ure to cer­tain chem­ic­als can af­fect the genes likely to ac­tiv­ate in the sperm and egg cells of mice four gen­er­a­tions down the line. His find­ings have been re­peated in oth­er large an­im­als, been pub­lished in peer-re­viewed sci­entif­ic journ­als, and have sig­ni­fic­ant im­plic­a­tions for hu­mans.

In 2013, Skin­ner and his team pub­lished re­search show­ing that dir­ect ex­pos­ure to DDT left mice with a slightly el­ev­ated rate of cer­tain dis­eases. But by the time those mice had grand­chil­dren, more than 50 per­cent of the male mice de­veloped obesity. In fact, Skin­ner’s re­search found that DDT left 90 per­cent of the pro­geny of the mice ori­gin­ally ex­posed more likely to de­vel­op obesity, ex­per­i­ence lower sperm counts, or con­tract oth­er even more ser­i­ous health con­di­tions. This pat­tern con­tin­ued through four gen­er­a­tions, to the great-grand­chil­dren of the mice ori­gin­ally ex­posed to DDT.

In the U.S., farm­ers used DDT widely after World War II to pre­vent in­sects from at­tack­ing crops, and loc­al and state gov­ern­ments used it to drive down the num­ber of dis­ease-car­ry­ing mos­qui­toes. The sub­stance was banned in the United States in the early 1970s. But three gen­er­a­tions after DDT ex­pos­ure be­came com­mon, Skin­ner says, the coun­try saw ma­jor in­creases in hu­man obesity.

Race, Class, and Health

Des­pite these stud­ies, it’s hard to ima­gine poli­cy­makers hear­ing about Cor­win’s re­search and de­cid­ing the na­tion must try to re­duce minor­ity poverty rates or con­front in­sti­tu­tion­al ra­cism to deal with the prob­lem of pre­ma­ture births. Cer­tainly, mem­bers of Con­gress who still doubt the ex­ist­ence of cli­mate change might balk at Skin­ner’s rev­el­a­tions — that the chem­ic­als and every­day sub­stances used or emit­ted in our homes, of­fices, and cars can cause dis­ease-pro­mot­ing genes to ac­tiv­ate in the hu­man body for gen­er­a­tions.

Even so, the po­ten­tial race and class im­plic­a­tions of these find­ings are troub­ling. Four to five gen­er­a­tions ago, the an­cest­ors of today’s middle-class Afric­an-Amer­ic­ans were likely to be en­slaved in bru­tal phys­ic­al and emo­tion­al con­di­tions. Large num­bers of Mex­ic­an na­tion­als came to the U.S. be­gin­ning in the 1940s to work in the ag­ri­cul­tur­al in­dustry and were reg­u­larly ex­posed to chem­ic­als used in farm­ing. Some work­ers were even sprayed with pesti­cides upon ar­rival. Today, Mex­ic­an-Amer­ic­ans make up the largest por­tion of the na­tion’s fast-grow­ing Latino pop­u­la­tion. On top of that his­tory, in­form­al so­cial codes, land prices, and land-use laws of­ten leave poor com­munit­ies closest to loc­al waste fa­cil­it­ies, mines where work­ers rake coal from the earth, or coast­lines dot­ted with re­finer­ies. 

Still some epi­gen­et­i­cists re­main op­tim­ist­ic that the sci­ence and the pub­lic policies that should flow from it will pre­vail. The epi­gen­et­ic changes that sci­ence has un­covered aren’t as dra­mat­ic as hu­mans be­com­ing, say, a spe­cies that glows in the dark, says Car­men Marsit, an as­so­ci­ate pro­fess­or of phar­ma­co­logy and tox­ic­o­logy at Dart­mouth Uni­versity. But they are changes that can shape hu­man health.

“People, par­tic­u­larly in Amer­ica, may be­lieve that fam­ine ex­pos­ure dur­ing preg­nancy could do something harm­ful,” Marsit says. “But it is also pos­sible that chron­ic stress or chem­ic­al ex­pos­ure can also lead to ef­fects, and that sim­il­ar mo­lecu­lar mech­an­isms are at play. There’s really a lot of amaz­ing re­search out there prov­ing that.”

Marsit is also the co­dir­ect­or of the pro­gram in can­cer epi­demi­ology at the Nor­ris Cot­ton Can­cer Cen­ter. His own re­search is fo­cused on de­term­in­ing wheth­er chron­ic low-level ex­pos­ure to sub­stances such as ar­sen­ic — something com­mon to well wa­ter fre­quently con­sumed in New Hamp­shire — can cre­ate neur­obe­ha­vi­or­al de­fi­cits and even car­di­ovas­cu­lar prob­lems.

Some gov­ern­ment of­fi­cials do em­brace the idea that our so­cial ex­per­i­ences and sub­stances to which we are ex­posed may be mak­ing us more sus­cept­ible to cer­tain health prob­lems. Ana Pen­man-Aguilar is the as­so­ci­ate dir­ect­or for sci­ence in the Of­fice of Minor­ity Health and Health Equity at the Cen­ters for Dis­ease Con­trol and Pre­ven­tion. CDC is what Pen­man-Aguilar de­scribes as “very pas­sion­ate” about the fact that the health of the na­tion as a whole can­not be im­proved without mak­ing sig­ni­fic­ant gains in minor­ity health. To do so, CDC has in­creas­ingly fo­cused on pro­jects that identi­fy and ad­dress the so­cial de­term­in­ants of dis­ease, she says.

“We know that no mat­ter what we do, the ge­net­ic re­search — and it is im­port­ant re­search — is go­ing to con­tin­ue,” says Pen­man-Aguilar. “So, we en­sure that there is also a fo­cus on the so­cial de­term­in­ants of dis­ease, the way in­come, diet, neigh­bor­hood — ba­sic­ally how and where we all live, learn, work, and play — can drive health dis­par­it­ies.”

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