Lamarckian sh*t? Why epigenetics is not eugenics

An argument could be made that communicating scientific advances to the public has never been more important. As the NIH budget stagnated, and then was cut by Sequestration, many of us have realized what a poor job we have been doing convincing the public of the importance of basic science research. Neuroscience itself has been under more scrutiny recently. As Adam Gopnik of The New Yorker wrote in a review of three new books bashing brain research, “Neuroscience can often answer the obvious questions but rarely the interesting ones.” If that is the way that the public sees it, then clearly we are losing something in translation. Recently there has been a push to reverse this trend and reaffirm biomedical research as a source of inspiration and hope for the public. The actor and author Alan Alda, who has long held a passion for science, has made it a personal mission to improve communication about science because “How are scientists going to get money from policy makers, if our leaders and legislators can’t understand what they do?”¹

Late last year, Brian Dias, a postdoctoral fellow in Kerry Ressler’s laboratory at Emory, found out just how difficult communicating his work to the public can be. Dias and Ressler had been working on testing whether olfactory fear conditioning would transmit a sensitivity to the conditioned odor across generations. That is, using a mouse model they were exploring whether an experience in your lifetime could affect your children or grandchildren’s response to their environment. They studied the olfactory system because it is extraordinarily well-mapped (thanks in large part to work that Dr. Ressler did in Nobel Laureate Linda Buck’s lab as a graduate student) and shows gross structural changes in mice when they learn to associate an odor with an unpleasant experience¹. Recently, there has been a great deal of interest in understanding how an organism’s environment can affect the way in which genes are expressed via a phenomenon call epigenetics.



Epigenetics refers to chemical modifications to the genome that do not affect the DNA sequence itself. Normally, the DNA molecule of each chromosome is tightly packed in a highly complex yet orderly fashion so that it can fit inside the nucleus of the cell. Several types of chemical modifications can be made to DNA that affect how tightly it packs and in turn, the ability of enzymes to transcribe the sequence and initiate the production of the proteins that it codes for. Epigenetic marks do not affect the letters in the code, just how often it is read. Genes can effectively be silenced or activated by these mechanisms, which are still not completely understood.



Researchers have found that the early life environment can have long term effects on individuals and even their offspring² – so called inter-generational epigenetics³. Lately, interest has even shifted to assessing trans-generational epigenetic effects. In 2010, an Australian group reported that in rodents, paternal high-fat diet can lead to dysfunction in pancreatic insulin-producing β-cells in female offspring⁴. More recently, a study of pre-diabetic mice found that epigenetic marks in the pancreas and, importantly, in sperm persisted for multiple generations as did a pre-disposition to impaired glucose metabolism⁵. Trans-generational epigenetic inheritance has been reported to affect lifespan in the nematode C. elegans⁶, and now some studies suggest that the effects of stress or abuse can be passed to the next generation in mice⁷ and humans⁸.



In this special Neuroethics Journal Club focused on “Neuroscience in the News”, the group was fortunate to get to hear the story of publishing this exciting paper⁹ first hand from Dr. Dias. One of the most interesting aspects of the discussion was the timing of the initial presentation of the results and publication of the paper. Dias gave a presentation at Neuroscience 2013 on November 12^th that created a great deal of buzz, so much so that Virginia Hughes of National Geographic’s “Only Human” blog reported on the presentation and also on the Twitter activity itself. Reponses ranged from “Astonishing if true” to “Crazy Lamarkian [sic] shit”.



The Nature Neuroscience editors themselves may have been thinking something along the same lines as the latter commenter as they made a portrait of Jean-Baptiste Lamarck – the champion of the contentious evolutionary theory that acquired adaptations during life shape subsequent generations – the cover image for the issue with Dias and Ressler’s article. The trouble with associating Lamarck and trans-generational epigenetics is that it could lead to the same type of reasoning that gave rise to eugenics in the early to mid-20^th century. Disadvantaged individuals who have lived with hunger and been exposed to violence or other trauma could be seen as permanently damaged and may be dissuaded from having children to avoid perpetuating some sort of “bad epigenetics”. The fact is, genes simply code for proteins and the jump from the molecular level to behavior is complex to say the least. Dias and Ressler were careful to describe the behavioral phenomenon in the offspring of the fear-conditioned mice as an increased sensitivity, not specifically a fear of the odor. At this point, they were not able to determine a molecular mechanism or specific cause of the behavioral change.



The paper appeared online December 1^st, almost three weeks after Dias’ SfN talk and the ensuing controversy and armchair critiquing. However, during most of that time the authors were essentially handcuffed by the journal’s press embargo policy until the paper was published online on December 1^st. Granted, it is rare that a presentation at a conference would generate this much excitement before the paper was published, but it seems that even with early online publication of articles, peer-reviewed journals have trouble keeping up with 21^st century, 140-character communication. The rapid, yet accurate dissemination of results will likely be an issue that journals continue to struggle with, while occasionally leaving authors in limbo.



In addition to the discussion surrounding publication of a controversial paper, the journal club also delved into some of the ethical issues that may arise from studies such as this one. For example, should the children of veterans who have suffered from PTSD be treated as an “at-risk” group, and what would that entail? Or, should members of the military be screened for a family history of trauma based on the idea that those individuals whose parents experienced traumatic events may be more vulnerable to adverse outcomes during or after their tour of duty? It seemed that there was agreement that when a plausible mechanism for how a fear memory – and particularly one associated with a certain smell – could impact the epigenetic marks in sperm cells in order to be passed on to subsequent generations, and then tested, the field would be better able to understand intervention opportunities. Trauma and stress are major public health issues just based on what we know about how they can shape an individual’s behavioral and physiological responses to later challenges in life^10,11. If in fact trauma and adversity can also shape our children’s sensory experience of the world through heritable, epigenetic changes, then it will be even more important to understand how the effects can be mitigated.



Additionally, accurate and clear communication of results to the public remains as important as ever. While the avenues for communication have changed drastically in recent years, and in many ways have made communicating easier, publishers and authors will likely continue to grapple with the new speed and power of social media. What role, if any, should these platforms play in the communication of science? If one of the goals is to engage the public’s interest then it seems that social media presents a great opportunity to do that but there are obvious concerns. While it may not be possible to fit detailed methods and results into 140 characters, new initiatives such as PubMed Commons may help reduce the formality and finality associated with published papers and increase discussion among scientists. Still, it will be interesting to see how social media is adopted by scientists and whether it helps at all in bridging our current communication gap with the public.





References



1. Jones, S. V., Choi, D. C., Davis, M. & Ressler, K. J. Learning-dependent structural plasticity in the adult olfactory pathway. The Journal of neuroscience : the official journal of the Society for Neuroscience 28, 13106-13111, doi:10.1523/JNEUROSCI.4465-08.2008 (2008).

2. Jirtle, R. L. & Skinner, M. K. Environmental epigenomics and disease susceptibility. Nature reviews. Genetics 8, 253-262, doi:10.1038/nrg2045 (2007).

3. Heard, E., Martienssen, R.A. Transgenerational Epigenetic Inheritance: Myths and Mechanisms. Cell 157, 95-109 (2014).

4. Ng, S. F. et al. Chronic high-fat diet in fathers programs beta-cell dysfunction in female rat offspring. Nature 467, 963-966, doi:10.1038/nature09491 (2010).

5. Wei, Y. et al. Paternally induced transgenerational inheritance of susceptibility to diabetes in mammals. Proceedings of the National Academy of Sciences of the United States of America 111, 1873-1878, doi:10.1073/pnas.1321195111 (2014).

6. Greer, E. L. et al. Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans. Nature 479, 365-371, doi:10.1038/nature10572 (2011).

7. Dietz, D. M. et al. Paternal transmission of stress-induced pathologies. Biological psychiatry 70, 408-414, doi:10.1016/j.biopsych.2011.05.005 (2011).

8. Jovanovic, T. et al. Physiological markers of anxiety are increased in children of abused mothers. Journal of child psychology and psychiatry, and allied disciplines 52, 844-852, doi:10.1111/j.1469-7610.2011.02410.x (2011).

9. Dias, B. G. & Ressler, K. J. Parental olfactory experience influences behavior and neural structure in subsequent generations. Nature neuroscience 17, 89-96, doi:10.1038/nn.3594 (2014).

10. Gluckman, P. D., Hanson, M. A., Cooper, C. & Thornburg, K. L. Effect of in utero and early-life conditions on adult health and disease. The New England journal of medicine 359, 61-73, doi:10.1056/NEJMra0708473 (2008).

11. Murgatroyd, C. et al. Dynamic DNA methylation programs persistent adverse effects of early-life stress. Nature neuroscience 12, 1559-1566, doi:10.1038/nn.2436 (2009).





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Purcell, R. (2014). Lamarckian sh*t? Why epigenetics is not eugenics. The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2014/03/lamarckian-sht-why-epigenetics-is-not.html