Mixing Nature and Nurture
by Julia M. Klein
JUNE 21, 2011 TAGS:
In the waning months of World War II, the Nazis, angered by Dutch resistance, retaliated with a food embargo. As a result, 22,000 people in western Holland starved to death. And the effects of the famine were not limited to a single generation. The children of malnourished mothers were born undersized. More surprising, studies found that, as adults, these men and women were more susceptible to a wide range of ailments, from diabetes and depression to breast cancer and obesity.
Neither classical genetics nor an environmental explanation suffices to unravel this phenomenon. But the new science of epigenetics – which deals with long-term alterations in gene behavior – supplies a key causal link. Epigenetics involves chemical changes in cells, sometimes random and sometimes environmentally caused. What is even more startling is that these epigenetic “marks,” as they are called, can be inherited – either directly (much like genetic mutations) or in various indirect ways.
Richard C. Francis, a neurobiologist turned science writer, has written what he says is the first popular book on this booming, cutting-edge field. Even so, reading Epigenetics: The Ultimate Mystery of Inheritance (Norton) requires an almost scholarly level of concentration. It helps to have, at the very least, a working knowledge of genetics. If the mere mention of messenger RNA, alleles and methylation (this last was new to me, too) induces panic, then this slim, intriguing volume will provoke anxiety for sure.
To his credit, Francis, relying heavily on analogy and example, does a mostly masterful job of illuminating some very thorny concepts. He introduces epigenetics with a reference to “identical,” or monozygotic, twins. We expect such twins, who are genetic clones, to be biologically similar. But there are powerful exceptions. In the instance that Francis cites, one twin was born with a disorder of sexual development known as Kallmann syndrome, while the other appeared normal.
But that wasn’t quite the case. The twins shared an impaired sense of smell, a symptom associated with Kallmann syndrome, and a signal that both had some form of the malady. In one twin, however, the syndrome was markedly less severe. The difference, Francis explains, was the effect of epigenetics -- which determines the extent to which the genes associated with Kallmann syndrome are expressed.
Epigenetic research has crucial implications for our understanding of genetics, cellular biology, human development and a range of diseases. For Francis, epigenetics upends the classical view – the one many of us learned in our high-school biology classes – of genes as the executive programmers of cellular differentiation. “We would be better served,” Francis writes, “to drop the ‘program’ metaphor altogether, and with it, the temptation to think of genes as software…. Modern epigenetics makes sense only if genes are viewed as hardware, like other cellular constituents.”
By way of explanation, Francis adopts yet another metaphor, of the two-faced “Janus gene.” Genes are acted upon by not just outward-looking causes, but also other chemicals in cells. One mechanism by which that happens is methylation: the attachment of a methyl group, three hydrogen atoms and a carbon atom, to DNA. “The effect of methylation,” Francis explains, “is to inhibit the expression of the gene to which it is attached.”
Environmental forces, from nutrients to bad parenting, can trigger methylation and other cellular changes. Some of these forces – one example Francis gives is the transmission of poor mothering by mice – act by way of complex nature-nurture feedback loops, an indirect form of inheritance. The female offspring of these bad mothers have elevated stress responses and also are less likely to lick their young, even when relatively unstressed. So the problem is perpetuated from generation to generation.
The greatest benefit of epigenetics may well be its potential to supply cures for some of the diseases we dread most. To the extent that cancer is a result of epigenetic problems, in addition to genetic mutations, it may be reversible, Francis tells us. And epigenetic remedies – when they are developed – will be “fine-tuned, compromising fewer healthy cells” than the current toxic chemotherapy arsenal. And there is more good news, according to Francis: Epigenetics, allied with stem-cell research, offers hope for combating conditions involving progressive deterioration, such as Parkinson’s and Alzheimer’s.
Will a branch of science that most of us (so far) have never heard of emerge as our salvation from a host of age-related ailments? That is an idealistic vision, but not an impossible one. And knowing the prospects are so fair transforms the forbidding slog through the scientific quandaries of epigenetics into a walk in the park.
Julia M. Klein, a cultural reporter and critic in Philadelphia and a contributing editor at Columbia Journalism Review, is a frequent contributor to Obit.
Neither classical genetics nor an environmental explanation suffices to unravel this phenomenon. But the new science of epigenetics – which deals with long-term alterations in gene behavior – supplies a key causal link. Epigenetics involves chemical changes in cells, sometimes random and sometimes environmentally caused. What is even more startling is that these epigenetic “marks,” as they are called, can be inherited – either directly (much like genetic mutations) or in various indirect ways. Richard C. Francis, a neurobiologist turned science writer, has written what he says is the first popular book on this booming, cutting-edge field. Even so, reading Epigenetics: The Ultimate Mystery of Inheritance (Norton) requires an almost scholarly level of concentration. It helps to have, at the very least, a working knowledge of genetics. If the mere mention of messenger RNA, alleles and methylation (this last was new to me, too) induces panic, then this slim, intriguing volume will provoke anxiety for sure.
To his credit, Francis, relying heavily on analogy and example, does a mostly masterful job of illuminating some very thorny concepts. He introduces epigenetics with a reference to “identical,” or monozygotic, twins. We expect such twins, who are genetic clones, to be biologically similar. But there are powerful exceptions. In the instance that Francis cites, one twin was born with a disorder of sexual development known as Kallmann syndrome, while the other appeared normal.
But that wasn’t quite the case. The twins shared an impaired sense of smell, a symptom associated with Kallmann syndrome, and a signal that both had some form of the malady. In one twin, however, the syndrome was markedly less severe. The difference, Francis explains, was the effect of epigenetics -- which determines the extent to which the genes associated with Kallmann syndrome are expressed.
Epigenetic research has crucial implications for our understanding of genetics, cellular biology, human development and a range of diseases. For Francis, epigenetics upends the classical view – the one many of us learned in our high-school biology classes – of genes as the executive programmers of cellular differentiation. “We would be better served,” Francis writes, “to drop the ‘program’ metaphor altogether, and with it, the temptation to think of genes as software…. Modern epigenetics makes sense only if genes are viewed as hardware, like other cellular constituents.”
By way of explanation, Francis adopts yet another metaphor, of the two-faced “Janus gene.” Genes are acted upon by not just outward-looking causes, but also other chemicals in cells. One mechanism by which that happens is methylation: the attachment of a methyl group, three hydrogen atoms and a carbon atom, to DNA. “The effect of methylation,” Francis explains, “is to inhibit the expression of the gene to which it is attached.”
Environmental forces, from nutrients to bad parenting, can trigger methylation and other cellular changes. Some of these forces – one example Francis gives is the transmission of poor mothering by mice – act by way of complex nature-nurture feedback loops, an indirect form of inheritance. The female offspring of these bad mothers have elevated stress responses and also are less likely to lick their young, even when relatively unstressed. So the problem is perpetuated from generation to generation.
The greatest benefit of epigenetics may well be its potential to supply cures for some of the diseases we dread most. To the extent that cancer is a result of epigenetic problems, in addition to genetic mutations, it may be reversible, Francis tells us. And epigenetic remedies – when they are developed – will be “fine-tuned, compromising fewer healthy cells” than the current toxic chemotherapy arsenal. And there is more good news, according to Francis: Epigenetics, allied with stem-cell research, offers hope for combating conditions involving progressive deterioration, such as Parkinson’s and Alzheimer’s.
Will a branch of science that most of us (so far) have never heard of emerge as our salvation from a host of age-related ailments? That is an idealistic vision, but not an impossible one. And knowing the prospects are so fair transforms the forbidding slog through the scientific quandaries of epigenetics into a walk in the park.
Julia M. Klein, a cultural reporter and critic in Philadelphia and a contributing editor at Columbia Journalism Review, is a frequent contributor to Obit.
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