Before You Know It

With my daughter finishing her first year of school this spring I think a lot about what I have offered her—what parts nature and which nurture. Compared to photos of me at the same age in 1984, she could be my twin. My eyes, my nose, my chin. She will be tall, because I am and so is her father. My skin has grown dappled with freckles and moles, and this spring her first few freckles blinked open—one on her cheek, and a minor constellation across her nose.

But I also wonder what else she might have gleaned from her family tree: weak joints, addiction, depression, heart disease? She loves language play and prefers books to people. Is that hesitant perfectionism mine? And is it in the blood, or have I somehow (despite my best efforts) conveyed it in sharp glances and worried frowns?

You want to give your child the best. Better than you got. To somehow manifest a step forward, or a reach beyond your own span. I remember holding my red and birth-tired baby in those minutes after her first breath and wondering: Had I done enough? She was long, scraggly, and full of impossible personality. I'd carried her through those months to term, and the rest was up to genetics. Or so it seemed.

Scientists compare the epigenetic function to an on/off switch for the DNA. If a genome includes inheritable asthma, the epigenome determines if the asthma is “on” or not.

Certain kinds of stresses—famine, war, or pollution for instance—may flip the on/off switch in a way that lasts for multiple generations.

Turns out, a pediatrician can fairly accurately predict a baby's future—Will he succeed in school? Die from violence? Succumb to heart disease?—based on where the child was born.

“Our zip code may be more important than our genetic code in determining our health,” says Larry Wallack, part of a team of sixty researchers and analysts at the Moore Institute for Nutrition and Wellness at Oregon Health & Science University who work in a field called epigenetics, which is the study of the layer of information that surrounds the genetic code. Scientists commonly compare the epigenetic function to an on/off switch for a person's DNA. According to this analogy, if your genome includes inheritable asthma, the epigenome determines if the asthma is “on” or not. The study of epigenetics has demonstrated that certain kinds of stresses—such as famine, war, or pollution—may flip the on/off switch in a way that lasts for multiple generations.

This responsiveness to stress continues to puzzle scientists. Experiences and behaviors that were once believed to affect only an individual are now seen to produce lifelong and inheritable changes in how DNA is expressed. In other words, smoking is bad for your health. If you smoke at a young age, or while pregnant, it may also create changes in your body that your children can inherit.

The scientific community now draws on twenty years of data analysis and research to show that this happens, but they don't yet know why or how. The data say that two moments in a person's life present the greatest vulnerability to these stresses: the first thousand days of life and a phase of prepubescence called the “slow-growth period.”

The team at OSHU is focused on the part of the field that concerns the first thousand days, which is called developmental origins of health and disease (DOHaD). The theory goes that these first thousand days, from conception to age two, may determine not only aspects of that particular child's lifelong health but also inheritable changes in the child's epigenetic structure—which therefore affect the health of that child's children and grandchildren.

“It's the fastest-moving field in all of medicine,” says Kent Thornburg, director of the Moore Institute. “It has put the scientific community in a tailspin.”

In the last two years alone, scientists around the world have begun to look to epigenetic inheritance to explain a growing series of epidemics: rising rates of obesity, ADD, heart disease, depression, stress response syndromes, diabetes, autism, and schizophrenia. The list goes on. Epidemiologists point to stress—from the personal stress of living in a refugee camp or in New York City on September 11, 2001, to the chemical stresses of the plastics revolution, to the nutritional stress of chronic poor nutrition—as potential triggers for otherwise unexplained epidemics in public health.

These discoveries about genetics and inheritance challenge the most basic ideas about when life starts, why life ends, and what our responsibilities are to our children, our grandchildren, and our community. In just two decades epigenetics has radicalized how scientists think about chronic disease and the origins of health. But social understanding, public policy, and actual day-to-day medical practice may be decades away from shifting in any meaningful way. The fastest-moving field in all of medicine may be moving faster than the pace of our ethical, legal, medical, and imaginative faculties.
 

Stress is a trigger for otherwise unexplained epidemics in public health.

I first heard about epigenetics listening to the syndicated public broadcasting show Radio Lab while weeding my garden. The science program hosts spun the marvelous and confounding story of the Swedish town of Överkalix, which has become the ur-story for epigenetics. In a nutshell: preteen boys who overindulged on the harvest bounty in the 1800s had grandchildren who died an average of thirty-two years earlier—from diabetes, heart disease, and related illnesses—than the grandchildren of those who didn't. The host asked, “So, should I change how I feed my son?”

There is something jarring about the concept of epigenetic inheritance. While I appreciate the weird science at the heart of it, my mind quickens at the kinds of questions it begs: How should I take care of my daughter in her preteen years? How should we take care of all of our children? How do we do that as a society?

While these types of provocative questions naturally follow a story like the boys of Överkalix, Wallack cautions, “This is not ‘news you can use.'”

Thornburg agrees: “We know that stress changes the gene expression. We know that some of those changes are inheritable. But we're not sure how it works.”

The closest researchers have come to a prescription is simple: Eat healthy food, expose yourself to good stresses that strengthen you, and avoid environmental toxins and toxic stress. But these ideals are not equally accessible to or as easily effective for all.

 

A main risk factor for low birth weight is “the level of continuous stress on the mother, the type of intense stress brought on by conditions such as racism, inadequate housing, unemployment, and lack of options and opportunity.”

There's a reason that one of the leading centers of DOHaD research in the world is here in Oregon. David Barker, an epidemiologist from the University of Southampton, risked his reputation and career in the 1980s to establish the science behind the field. He cared about public health and inequality, and he found a welcoming home for those concerns at OHSU with Thornburg.

Our current understanding of the science of epigenetics grew from Barker's simple desire to understand the health and mortality of poor people in England. Statistical maps of mortality in England showed heart disease was a leading cause of death in working class areas. Barker found this information problematic. Heart disease was supposed to be a rich person's disease.
Working with a statistician named Clive Osmond, Barker searched archives and hospital record departments throughout the United Kingdom looking for maternity and infant welfare records from the early twentieth century to see if they could track individuals' health from infancy to death. The researchers focused on the low-income areas where the mortality maps showed high levels of heart disease. In an essay on his work, Barker wrote, “Some records were detailed and some perfunctory. Some were in archives; others were in lofts, sheds, garages, boiler rooms, or flooded basements.”

In 1989, The Lancet published Barker and Osmond's first analysis of the new data, which correlated rates of heart disease with low birth weight. They proposed that an individual's weight at birth might have a greater impact on his lifelong cardiac health than any other behavioral choice. They even went further and speculated that the mother's nutrition and life experiences prior to pregnancy, perhaps even as early as her own adolescence, might be a factor.

The backlash was swift and two-pronged. First, the scientific community refuted the data behind Barker's analysis, stating it couldn't possibly, biologically, be true. Darwinian evolution prescribes a specific view of what is inheritable and how changes take place from one generation to the next. These observations didn't fit. According to Darwin, behavior doesn't influence the genetic code and is not heritable. However, critics of the Barker hypothesis who set to work proving it wrong soon became champions when their research proved the basis in biology was correct. The Barker hypothesis is now widely accepted. In 2003, Time magazine called it “The New Science.”

“We used to use genetics—the gene code—to explain everything, in addition to some behavioral choices people made,” Thornburg says. “It's possible now to rethink the way evolution works.”

While Barker's data challenged major concepts in biology and genetics, the public health community launched an even stronger opposition to his work than the scientific community. A riveting story about Barker in the New Yorker in 2007 describes how the hostility of the health community grew from the challenge that his work posed for agencies that were trying to improve health outcomes in poor communities: “It undermined a decades-long public health message that linked heart disease to adult behavior.”

For decades, the prevailing wisdom had been—and continues to be—that heart disease is a result of behavioral choices that lead to obesity, such as a high-fat or high-sugar diet, sedentary lifestyle, or smoking. In his interview with the New Yorker, Barker summarized an almost philosophical rejection of that prevailing wisdom: “The answer was not going to lie in the way that poor people lead their lives as adults.” Instead, the answer was in their fetal health and their earliest years of life.



Answers to stark disparities in the health and wellness of poor and marginalized communities are what public health advocates and activists seek. These solutions take the form of policies, such as funding for healthier school lunches and regulations on air pollution. They also take the form of education, such as public service announcement billboards posted throughout Oregon that illustrate seventeen packets of sugar in a bottle of soda.

Public health focuses on improving the health of populations, not individuals. However, most of our cultural, medical, and policy norms set up health as an experience and responsibility of an individual, not a population. Wallack, who is the former dean of the College of Urban and Public Affairs at Portland State University, spent the first three decades of his career working on precisely this problem. He is a nationally recognized leader on reimagining the concept of health.

One key concept in his work in public health is the metaphor of the stream. When he lectures, Wallack inevitably starts with a simple but illuminating anecdote: One day people notice that citizens have fallen in the river and are drowning. They hasten to pull them out. But there are so many drowning, and more are coming down the river all the time. Finally, someone decides to go up the stream to stop people from falling in the river in the first place.

“Unless we link what's going on downstream with what's going on upstream, we'll never get ahead of the game,” Wallack says.

For years, Wallack and many public health advocates throughout the United States have focused on discovering and tackling the upstream factors that affect health. Poverty, educational attainment, and social connectedness correlate so closely with health and disease that they have come to be seen as determinative of a person's well-being. But Wallack shifted his career course three years ago when he met Thornburg and learned about epigenetics and DOHaD, saying, “This redefines what constitutes upstream.”

Now he's working to create public policies that focus on women's and children's health at those moments when epigenetic triggers might cause multigenerational health disparities. If focusing on the health of populations is challenging because it raises questions about individual responsibility, focusing on the health of future populations is challenging in a very different way: It raises questions about our collective responsibility for the next generation.



Since the discovery of the developmental origins of health in the 1980s, researchers have begun articulating a tricky question that could change how the medical community thinks about genetic and chronic diseases: What if disease starts earlier than we had ever imagined, in a fetus or in a bundle of cells a generation or more before a fetus was ever conceived?

Barker, Thornburg, and Wallack have also raised another, equally difficult problem: If rates of disease in low-income communities aren't primarily a result of how poor people lead their lives, how do we understand and reverse trends in community health? “Fundamentally, the distribution of health and disease in our society is not random,” Wallack says.

By random, Wallack means randomly distributed. “Wherever you are on the social ladder the group above you will tend to have better health, and the group below you worse health,” he says. But he also stresses that in societies that have the greatest levels of inequality, health outcomes are lower across the board.

As with the prevalence of heart disease among poor communities in England, in the United States, chronic diseases are more common in specific populations: racial minorities, immigrants, and the poor.

Take, for instance, heart disease. African Americans face the highest risk of death due to heart disease among all racial and ethnic groups. About half of all African American adults develop some form of cardiovascular disease. Compared to white Americans, African Americans are 1.3 times more likely to develop heart disease, 1.8 times more likely to develop diabetes, and 1.5 to 2 times more likely to have hypertension that leads to stroke.

Poverty, educational attainment, and social connectedness correlate so closely with health and disease that they have come to be seen as determinative of a person's well-being.

Epidemiologists have offered many theories about the cause of heart disease in the African American community. The theories basically fall into the two categories that Thornburg attributes to the scientific worldview before epigenetics: genes (i.e., African American genes predetermine a weak cardiovascular system) and behavior (i.e., African American diet and exercise cause obesity, diabetes, stroke, and heart disease). As a result, the preventive approach to reducing these chronic illnesses in the African American community focuses on helping adults change their lifestyles, because cause and treatment are linked.

But the Barker theory would contend that infant development in the womb is more likely than adult lifestyle choices to be the cause of these illnesses. A major indicator of poor development in the womb is low birth weight. As it happens, low birth weight in African Americans is a well-documented and widely researched fact: low birth weights are twice as high among African Americans than whites, and average weights are lower for both full-term and pre-term births. If infant development is the cause of illness, interventions focused on adult lifestyle might be healthy but still ineffective in lowering rates of heart disease.

Researchers have now begun to connect low birth weight and cardiovascular weakness in the African American population with an epigenetic trigger: significant levels of toxic stress experienced only three generations ago in slavery. Other researchers point to levels of toxic stress experienced directly by African American mothers throughout their lifetimes, and particularly as preadolescent girls, as a result of racism and the systems of inequality that have persisted since slavery was abolished.



Our public health, medical, and legal systems may be unprepared to address the needs and rights of those harmed by toxic stress. For example, consider that the rates of obesity and diabetes have doubled in the last fifteen years in Oregon. The collective hand-wringing about this epidemic has included a lot of collective finger-pointing as to the root causes of this increase and the best way to handle it. While Wallack and Thornburg, like many in the medical community, promote healthy diets and exercise as partial solutions, they also see the trajectory of causality that began generations ago. “If you get educated, middle-class people together and get them to eat right, you can improve their health,” Wallack says. But for populations that have inherited the epigenetic changes from generations of poor nutrition, the solutions are not so simple.

In another example, consider pollution as an epigenetic trigger. If a company knowingly dumps chemicals in a watershed, and residents develop skin diseases associated with those chemicals, the causality and responsibility are clear: the company pays for the damage it caused. As the field of epigenetics grows, when will we be able to establish which activities trigger negative health outcomes over the course of multiple generations? Could a plastics manufacturer be considered a point-source polluter of human DNA? Could that company be sued? Which agency would regulate toxins that cause epigenetic shifts, the EPA or the FDA? Discovering and attributing financial value to the harm experienced over multiple generations would be difficult.

A pediatrician can fairly accurately predict a baby's future based on where the child was born.

In a secular democracy, laws are citizens' expression of ethics and values. We set policies, establish authority to regulate, and require that companies pay or that governments offer reparations. But the ethical and legal language, precedent, and logic to address intergenerational health disparities are unclear. This is where the questions outweigh the answers three to one.

The trouble with shaking a culture's ethical framework to see where the joints give out is that they don't necessarily all collapse in the same direction. These are complex ethical and legal questions because they raise liberty, individual responsibility, collective security, harm, and the value of health as competing concepts that vie for precedence. At this point, our current understanding of epigenetics highlights a new need for enhanced protection of certain groups of people: pregnant women, infants, and preadolescent youth. Will we as a society act with more urgency to address inequality now that we know it has multigenerational, biological consequences?

The care and health of pregnant women is now definitively connected with the wellness of multiple generations of citizens. In recent testimony to the Oregon House Committee on Health Care, Wallack explains a main risk factor for low birth weight is “the level of continuous stress on the mother, the type of intense stress brought on by conditions such as racism, inadequate housing, unemployment, and lack of options and opportunity.”

This understanding suggests the need for new definitions of liability for those that do harm to these classes of people, such as powerful corporations and governments that fail to prevent experiences that flip the epigenetic switch. But while it seems relatively to simple to point to responsibility when we're talking about a company dumping toxins into the air or water, it's more complicated when we're talking about a community in which racism and discrimination create toxic stress.

And more complex again when we consider that protecting a fetus requires defining that fetus as a life. How do our laws simultaneously protect the health of an individual from conception through age two and also protect the freedom of women to choose when and if to have a child?

Could we imagine a world in which our society limits certain freedoms now to protect the health of those more than a generation in the future? Which activities would we regulate? Would preadolescent girls and boys, whose biology is highly vulnerable to environmental and nutritional stresses, experience more regulation on their play, nutrition, and activities? Would a pregnant woman enjoying a glass of wine be fined? And, further, in a society where mothers currently earn fifty-eight cents on the dollar when compared with men and motherhood is the single greatest indicator of poverty in old age, how do we ensure that protections for pregnant women and new families—such as restrictions on work, activities, or diet—would not create new forms of economic inequality?

Obviously, these are provocative questions. The science is far from dictating specific changes in lifestyle, never mind broad social or policy changes. But Barker, who passed away last year, was impatient: “He saw where the science was heading, and he knew the work was too urgent to wait,” Wallack says.

The story of the developmental origins of health is not yet complete. It may not be for decades to come. Much remains unanswered—both scientifically and for our culture. In Oregon, the research is focused now at the cellular level: the lining of the placenta. Chances are, the science will continue to advance ahead of popular imagination and far ahead of the laws and policies that will be needed to address the disparities in health that Barker wanted to understand twenty years ago. But this is how the change begins.

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