The Burden of Generations

The sins of the father revisited?

I had the privilege recently of taking part in a family constellation exercise. The supposed objective of this is to uncover trauma or events experienced by previous generations, that have caused discordance in the family dynamic, which are then inherited by the present individual resulting in problems or difficulties. While this was entirely based on psychological concepts and maybe some pseudoscience (I went in with my usual dose of healthy skepticism), I was surprised to learn much later on that such a concept does exist biologically. It is called transgenerational inheritance.

We all inherit our genes from our parents, and they inherit them from theirs. Our genes determine our characteristics, as we all know. The influence of the environment however, has always been an intriguing element in determining who we are, the eternal Nature vs (and?) Nurture debate. But what if the environment our great grandparents were exposed to also has a part to play in our lives right now?

Scientists have discovered that several factors, including environmental factors, ageing, diet, and exposure to toxins, can cause alterations in the chemical composition of chromatin. These alterations outside the sequence of genes, like DNA methylation patterns, histone modifications amongst others, are called epigenetic changes. This in turn modulates expression of certain genes. And these modifications have now been shown to be inherited between generations (1), and are thought to be a driver for natural selection.

However, traumatic stress can also transmit adverse effects in the downstream generations in mice and rats, like nutritional metabolic risk (2). Studies have shown that environmental or metabolic factors including high fat diet, diabetes, undernourishment and trauma, have resulted in inheritable epigenetic changes, resulting in altered metabolism and behavior in the later generations. These persistent changes have been seen in reproductive, nervous, endocrine, and recently the immune system (3).

While this effect is clearly shown in plants and mice, evidence in humans however remains sparse (4). There is some criticism against the existence of this, especially in light off the fact that the genome is “reprogrammed” during gametogenesis, essentially erasing epigenetic changes. So is this real? The jury is still out, but there are many groups working to answer these controversial questions. The burden of proof is high, as the author of review (2) points out: not only should cultural, genetic and ecological inheritance be ruled out, scientists should also identify the epigenetic factor in germ cells.

Meanwhile, the question I suppose becomes philosophical: are we born doomed by the actions and traumas experienced by our grandparents, great grandparents and maybe even beyond? The science, at least, is trying to figure it out.

References

1. Transgenerational inheritance: how impacts to the epigenetic and genetic information of parents affect offspring health. Hum Reprod Update. 2019 Sep 11;25(5):518-540. doi: 10.1093/humupd/dmz017. [https://www.nature.com/articles/srep18952]
2. A critical view on transgenerational epigenetic inheritance in humans. Nature Communications volume 9, Article number: 2973 (2018) [https://www.nature.com/articles/s41467-018-05445-5]
3. The Ancestral Environment Shapes Antiviral CD8⁺ T cell Responses across Generations. iScience Volume 20, 25 October 2019, Pages 168-183 [https://www.sciencedirect.com/science/article/pii/S258900421930352]
4. Transgenerational Epigenetic Inheritance: myths and mechanisms. Cell. 2014 Mar 27; 157(1): 95–109.doi: 10.1016/j.cell.2014.02.045. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4020004/]
5. https://www.bbc.com/future/article/20190326-what-is-epigenetics

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