Comment by klmr | Hacker News Reader

Comment by klmr | Hacker News Reader

Nick is a former colleague, and I’ve co-authored one of the relevant papers with Isabelle, and with the greatest respect to the two of them I need to caution anybody against taking away the wrong message from this misleading article: these findings are fundamentally not translatable to humans — and even in most cases to mammals, research in mice notwithstanding.

Furthermore, most, if not all, transgenerational effects of epigenetic inheritance even in C. elegans is transient. Meaning, the effect attenuates over just a few generations and then vanishes completely.

To be absolutely clear: Learning is not inherited in humans. There are good reasons to make this a categorical statement. What’s called “learning” in C. elegans is completely different from “learning” in humans, and adaptive changes in mouse behaviour are, so far, still not clearly demonstrated to be caused by epigenetics, and there are good reasons to be sceptical, as summarised by Kevin Mitchell: http://www.wiringthebrain.com/2013/01/the-trouble-with-epige..., and by Bernhard Horsthemke: https://www.nature.com/articles/s41467-018-05445-5

Isn't there a similar mechanism in humans though? Like this:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127768/

""" One the most provocative observations regarding Holocaust offspring was the report that Yom Kippur war veterans were more likely to develop post‐traumatic stress disorder (PTSD) in response to combat if they had a Holocaust survivor parent25. A higher prevalence of PTSD, mood and anxiety disorders was also observed in Holocaust offspring, largely selected from a convenience sample of people seeking treatment for Holocaust‐related problems, compared with controls26. These findings were replicated in a study assessing the relationship between PTSD in offspring and their own parents, assessed directly by clinical interview of the parent (s)27. """

> Isn't there a similar mechanism in humans though?

No. That review paper doesn’t discuss an actual mechanism, with good reason: the authors don’t have a mechanism. At the risk of sounding harsh, the underlying research has been throughly rubbished by the community [1, 2]. It uses a tiny sample size, tenuous correlation and, as mentioned, utterly fails at highlighting a plausible mechanism. It’s bunk: there’s absolutely no need to invoke the spectre of epigenetics to explain why children of traumatised parents may likewise be jumpy, just as there’s no need to invoke epigenetics to explain why children of English parents speak English. In fact, even the review you link to acknowledges as much:

> studies in humans have not yet demonstrated that the effects of trauma are heritable through non‐genomic (i.e., epigenetic) mechanisms

[1] http://sciblogs.co.nz/code-for-life/2015/08/28/epigenetics-a...

[2] https://www.theguardian.com/science/blog/2015/sep/11/why-im-...

Here are some mechanisms by which that could be true without any sort of biologically-inherited learning being involved.

1. "Holocaust offspring" may have been told by their parents about their experiences, and that could sensitize them in various ways (e.g. more inclination to envisage very bad worst cases; vivid examples of terrible things available to their imaginations; some sort of unconscious fear of losing their parents; feelings of guilt at being upset about something less bad than what their parents went through).

2. "Holocaust offspring" are, necessarily, offspring of people who survived the Holocaust. Those people might be different genetically from the population at large, in all sorts of ways. Maybe some of them happen to correlate with greater susceptibility to PTSD.

3. "Holocaust offspring" might have a greater tendency to put themselves into the sort of situations that produce PTSD. (Either for #1-like reasons -- e.g., their parents' example makes them feel a greater obligation to put themselves into danger if they think it may save others -- or for #2-like reasons -- e.g., maybe people who survived the Holocaust tend to be braver or show more initiative or something like that.)

And a couple of other reasons to be cautious about interpreting these findings.

4. "largely selected from a convenience sample of people seeking treatment for Holocaust-related problems". That seems like an extremely fruitful source of selection bias.

5. PTSD is a thing that has to be diagnosed. The people making the diagnosis know their patients' history, or ought to. It's possible that a psychologist may be more inclined to diagnose PTSD if they know that their patient is the child of a Holocaust survivor.

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