By David A. Kindig, MD, PhD
A while ago I presented a cautious population health perspective on the potential impact of modern genomics, ending with the observation that:
It is not anti-scientific to worry that our American belief in technology and venture capitalism could result in much waste, while less expensive investments we already know to be effective are ignored. The problem is that it is hard to predict the future, and decades from now there will certainly be important benefits from genomic research, including both treatments and preventive interventions. We can only insist that the most careful evidence on population health cost-effectiveness be used to guide investments, rather than the potential for profit from very expensive therapies that benefit few.
But what to make of this quote I came upon the other day from Duke University geneticist Randy Jirtle?
When you have a mutation in a gene, you are stuck. You feel like you have a death sentence. There is no way of treating that unless you do gene therapy which has had very few medical successes to date. The epigenetic basis of health and disease might open up other routes of intervention. You might develop drugs that target the epigenome to prevent or reduce susceptibility to disease; you might even leave drugs behind and treat yourself simply by varying your diet or the way you live (1).
What is the epigenetics he is referring to? Wikipedia defines epigenetics as:
The study of heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence – hence the name epi- (Greek: επί- over, above, outer) -genetics. It refers to functionally relevant modifications to the genome that do not involve a change in the nucleotide sequence. Examples of such changes are DNA methylation and histone modification, both of which serve to regulate gene expression without altering the underlying DNA sequence. Conclusive evidence supporting epigenetics show that these mechanisms can enable the effects of parents' experiences to be passed down to subsequent generations.
Doesn’t this sound like the old debunked Lamarckian inheritability of acquired characteristics that got a really bad name under the Soviet geneticist Lysenko? What is the epigenetic evidence to date? Wikipedia reports that more than 100 cases of trans-generational epigenetic inheritance phenomena have been reported in a wide range of plants, and animals; for example, mice given some dietary supplements have epigenetic changes affecting expression in offspring of the agouti gene, which affects their fur color, weight, and propensity to develop cancer. Another leading researcher notes that studies in rodents “have demonstrated the transgenerational impact of nutrition and indicate that prenatal protein restriction can exert effects on growth and metabolism of offspring and grand-offspring through changes in DNA methylation.” She concludes that “there is clear evidence that environmentally induced changes in brain and behavior can influence offspring and grand-offspring with implications for research perspectives on the inheritance of risk and resilience in response to social interactions” (2).
What is the relevance of this for population health? We know that stress-inducing factors in the social and economic environment get “under the skin” via biological mechanisms. Until recently, most researchers and practitioners -- even those taking a life course and developmental perspective to health improvement -- have approached genetics from a clinical (rather than a population) perspective. Additional research demonstrating the multigenerational impact of environmental influences could fuel environmental interventions to improve the quality and length of life for our children and grandchildren. Of course this research is quite new, and its full implications are yet to be demonstrated. But while we need to carefully evaluate the cost effectiveness of genomic investments, we need to also track the potential of epigenetics as a possible mechanism for population health improvement.
1. Amato, Ivan. Genes Take a Back Seat. Science/Technology April 6, 2009, p 28-32.
David A. Kindig, MD, PhD is Emeritus Professor of Population Health Sciences and Emeritus Vice-Chancellor for Health Sciences at the University of Wisconsin School of Medicine and Public Health. Follow him on twitter: @DAKindig.
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