Tuesday, August 20, 2013

The Ghost in your Genes

The Ghost in Your Genes is a 50-minute documentary produced by the BBC in 2006 (http://topdocumentaryfilms.com/the-ghost-in-our-genes/). It elucidates something astonishing about inheritance that counters what we have been taught in recent years—i.e. that our approximately 30,000 genes control everything about who we are. Instead, we learn that the lives of some of our forebears—what they ate, what they breathed, perhaps even what they saw—can directly affect us years later. In other words, though we get our genes directly from our parents and grandparents via sperm and egg, we are also affected by their experiences—which can determine which of our genes are expressed, and how. The latter is a short version of what is now called “epigenetics”—changes in the genome that do not involve structural changes or mutations in the genes themselves, but rather in how existing genes are expressed and at what level. As Dorothy Roberts explains in her excellent work, Fatal Invention, where she referred to The Ghost in Your Genes, “Scientists call each epigenetic change a mark, and the total set of epigenetic marks in an organism are the epigenome.” Most importantly, the “epigenome can be modified by the environment,” and those changes can last beyond a single life. Hence, not only what our grandparents were genetically, but even what they experienced can affect us many years later.

            This is (or was when it was discovered) truly paradigm-shifting stuff, because it means that the environment, the conditions that we all experience, can be passed on to our offspring and to their offspring. If we undergo certain kinds of stress—and scientists have already done research on the effects on unborn children of parents going through the horror of Nazi concentration camps, the collapse of the Twin Towers on 9/11, the effects of famines and pesticides—those stressors can affect our unborn heirs years later. We are not born with a blank slate of genes, protected from outside influence in their cozy DNA packets, as scientists once thought. We are also born with the experiences of generations that preceded us, experiences that can, and often do, leave their epigenetic marks. And if those who commit atrocities such as the bombings of Hiroshima and Nagasaki or the 400-year horror that was slavery and then Jim Crow and now mass incarceration in the allegedly free and equal United States of America—if they think that their evil is visited only upon those who directly experience it, then they must think again. For epigenetics is now telling us that the effects of evil (and good) actions are passed on to the generations.

            The Ghost in Your Genes starts out with the insight of a mild-mannered, and very appealing (he actually came near tears when explaining some of his discoveries) British geneticist named Marcus Pembrey, who noticed something strange in his work with children. He noticed that a rare genetic disorder, known to be caused by a deletion in a specific chromosome (#15), expressed itself differently depending on whether the gene came from the father or the mother. If the father passed the deletion on, the child was afflicted with Prada villi syndrome—a condition marked by severe overweight. If the mother passed it on, the child was afflicted with Angelman’s syndrome, a condition where children lack speech but seem exceptionally happy. Pembrey was shocked by this: the exact same genetic deletion resulted in two wildly different expressions in the human body. In the documentary, Pembrey says, “It was as if the genes knew where they came from.” This was unprecedented and altogether unexpected. Pembrey wrote up his results and published them, but received little response. Until one day he received an email from a researcher, Oluv Bygren, doing work in a remote town in Sweden near the Arctic Circle, which had the peculiarity that its archives recorded not only births and deaths, but also conditions in the lives of the people involved, particularly relating to the harvests. This was because being so remote, the harvests were critical: too little grain and there would be famine. Pembrey and Bygren subsequently were able to match the records of the recurring famines that occurred due to natural climate fluctuations with the deaths of inhabitants—specifically death from diabetes. To their great joy as scientists, they were able to plot the births during famines with records of death from diabetes, to find almost perfect matches over the years. In other words, if a woman gave birth during a famine year, her child would be more likely to later suffer from diabetes, and so would her grandchildren. The change in the expression of genes from an environmental event was passing on to subsequent generations. Prof. Michael Skinner, another researcher from the state of Washington, comments as follows:

What this means is: an environmental exposure that your grandmother had could cause a disease in you, even though you never were exposed to the toxin, and you will pass it on to your grandchildren. You are directly affected by the stress your grandmother experienced.

Again, this is astonishing stuff in light of the standard view of genetic inheritance, which says that genes pass untouched (except by mutation) from one generation to another; they are protected, essentially unaffected by our experience as individuals. But now, we must consider the contrary view that what we experience is, or can be passed on to not just one but several succeeding generations, to our biological heirs.

            Dr. Michael Pembrey calls this “genomic imprinting.” Genomic imprinting means that genes have a memory of where they came from—in the cases he first discovered, whether the gene deletion on chromosome #15 came from the mother or the father. This is one answer to the question sought by the researchers in the documentary: if the activity of genes is controlled by a switch, and if this switch controls the critical decision of whether a given gene is turned on or off—then what turns such genes on or off? To further answer this, the documentary shifts to a couple, the Mullins’, who after many years without a child turned to in vitro fertilization. It was successful and resulted in the birth of their first son, Keiran. But Keiran, even in the womb, showed signs that something was amiss: he displayed symptoms of something called Beckwith-Wiedemann syndrome. Such children tend to be very large, have protruding tongues, and have a tendency to develop cancerous tumors. It turned out that Keiran did have the syndrome, had several operations to fix some of the problems, and underwent recurring examinations for cancer. But the question was, what might have caused the disease? Another researcher named Wolf Reik came up with the answer, derived from his work with lab mice. Reik noticed that placing mouse embryos in a culture dish for a short time tended to affect the gene switch. He researched the records of babies with Beckwith Wiedemann’s and found the correlation: those who had been fertilized with IVF were 3 to 4 times more likely to have the syndrome. Something about altering the environment—having the embryo or the egg outside the womb—was causing an epigenetic change leading to the syndrome. Moreover, Reik found from experiments that mice with environmentally-altered gene switches also passed the condition on to several subsequent generations. Reik’s comment: “A simple environmental event could affect the way genes worked, and it could be passed on.”

            There is more to this splendidly informative documentary—including research on births to women pregnant during 9/11, indicating the affects of major stress on their offspring—so I recommend that anyone with even the slightest interest in the subject should watch it. What I would feel remiss in not mentioning, though, is one more episode, of lab research done by Dr. Michael Skinner of Washington. Skinner exposed pregnant rats to large doses of pesticides commonly used on our crops. Not unexpectedly, 85% of the exposed rats displayed symptoms of tumors, kidney damage, and immune dysfunction. What was unexpected was that after the third generation, the rats’ offspring showed the same degree of toxic effects: 85% of the third generation individuals were affected by tumors, kidney damage, and immune dysfunction! This was a new phenomenon in Skinner’s experience: an environmental toxin affecting not just the individual exposed, but extending its effects to several subsequent generations. The voice-over narrative made the point: “the exposure of a single animal to a toxin was causing a whole range of diseases in almost every individual of the following generations.”  And Skinner himself generalized as follows: “What your grandmother was exposed to when she was pregnant could cause a disease in you, even though you had no exposure, and you’re gonna’ pass it on to your grandchildren.”

            For Dorothy Roberts, and for us, these findings bear critical importance. What they mean is that the environment in which we live, and the stressors from that environment, can have direct and long-lasting effects on our bodies. Harvard biologist and public health expert Nancy Krieger has studied just this, and she calls it “embodiment:”

            “Embodiment to me refers to the many many, many different ways that we literally incorporate the world outside of us in us, in the expression of our biology….My focus is on how inequity becomes embodied and harms health.” (Roberts, p. 130)

Specifically, Krieger has studied the relationship between environmental stress and birth weight. In a 2004 study of 352 births, Krieger found that women reporting high levels of racial discrimination were almost five times (5X) more likely than those reporting no racial discrimination to deliver low-weight babies, and had three times (3X) the risk of preterm birth. In other words, stress leads to low birth weight, and low birth weight is often a predictor of such later-occurring maladies as diabetes, cardiovascular disease, and immune system dysfunction.  This is the key point that Dorothy Roberts emphasizes again and again: “Epigenetics may masquerade as genetic difference, but its biological effects stem from the environment, not mutations of the genetic code.” The new racism cloaked in the “objectivity” of science often, wittingly or not, takes part in this “masquerade.” Characteristics that have long been touted as an unalterable product of genetic difference—that is, the consequence of being born a certain race—are actually more often a product of the environment, which is to say, of society and the practices it dictates for the people it governs. It is a product of how people are treated—of what place they are allowed to occupy in a given society, of what access to that society’s goods they are allowed to have. And that treatment—particularly if it involves frequent humiliation and stress—affects not just them, but their offspring for generations and generations to come. When we reflect that even a single stressful event—such as 9/11—can affect generations of offspring, imagine what a lifetime or several lifetimes of stressors can do to a people’s epigenetic genome, to the way its genes are expressed.

            The good news, of course, is that environments can change. Societies can wake up to the burdens they are imposing on some classes of people. The only question is whether, and to what degree, a given society wishes to change, or if it wishes to perpetuate the epigenetic condemnation it imposes on its victims and their heirs in perpetuity. 

addendum, 8.16.13: A recent study at UCLA’s Cousins Center for Psychoneuroimmunology (see www.biosciencetechnology.com <http://www.biosciencetechnology.com> ) provides a fascinating gloss on the above discussion. Steven Cole and others, after many years studying the negative effects of stress on gene expression, studied the positive effects of happiness on gene expression (epigenetics). They studied two types of happiness: 1) eudaimonic well-being—the kind derived from having a deep sense of purpose and meaning in life; and 2) hedonic well-being—the kind that derives from self-gratification and pleasure. Though there is certainly overlap (both can be exhibited by people with strong social connections, and the presence of one can influence the other when people who “feel good” find more meaning in their lives), the differences when measured at the epigenetic level were striking. People with high levels of eudaimonic happiness displayed highly favorable gene expression in their immune cells: they had low levels of inflammatory gene expression, and powerful antiviral and antibody activity. People with high hedonic happiness, by contrast, had an opposite profile—one exhibiting high inflammation (the kind that can lead to cardiovascular and other diseases) and low antiviral and antibody gene expression. This despite the fact that, outwardly, eudaimonics and hedonics exhibited very little difference in their apparent emotional well-being.

            Professor Cole concludes that this study has important implications for the age-old question of what constitutes “the good life”: feeling good, or doing good. Though on the surface it appears that “feeling good” and “doing good” have the same effect on most people, at the level of health as measured by gene expression, they differ quite a bit. “Doing good” leads to a healthy immune system response, whereas “feeling good” can lead to the opposite. “Apparently,” says Cole, “the human genome is much more sensitive to different ways of achieving happiness than are conscious minds.” The genome may also provide a more “objective approach to moral philosophy rooted in the utility of health and the basic biology of human nature.”

            It is striking that this initial research displays a remarkable correlation with the wisdom traditions that have counseled human groups for millennia. As just one example, the Tibetan Buddhist teacher Matthieu Ricard, in his book on Happiness, advances a very simple and anti-modern formula. Happiness, he says, stems from serving others rather than from caring predominantly for oneself. Countless other spiritual teachers have said the same thing. Now, it appears, the heretofore inscrutable biology of the human genome seems to be supporting the same wisdom, this time from deep within the workings of the human body.

Lawrence DiStasi

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