Descendants of Holocaust Survivors Have Altered Stress Hormones | Hacker News Reader

Descendants of Holocaust Survivors Have Altered Stress Hormones

scientificamerican.com

90 pointsohjeez46 comments

There have been a series of well-reproduced studies, in animals and humans, looking at methylation of genes related to stress hormone receptors in the hippocampus of subjects exposed to stress/abuse.

http://www.nature.com/nrn/journal/v10/n4/full/nrn2629.html

These changes can persist to their offspring.

This may be a pop science article, but the steady stream of these findings suggests that there's some pretty ground-breaking stuff happening here. One of my mentors in residency was betting that Michael Meany will pick up a Nobel Prize for this work.

I wonder why this is not more studied in the black population in the United States.

Totally

You know why...

First let me say that I don't intend to speak for anyone but myself here.

As a black man who grew up in America (though not African-American) I have to say that my immediate reaction to the idea of similar study being done to explain the effects of slavery, Jim Crow, and other forms of institutional racism on the black population makes me nervous.

On one hand I'd love to welcome such studies because they would (could?) explain to many people the lasting effects of over 100 years of horrific oppression on millions of people.

On the other hand it makes me nervous because blacks in this country spent decades fighting not just for freedom but for equality. And not just equality in the eyes of the law but in the hearts of their neighbors. I fear, perhaps irrationally, that a study like this could serve to convince people that blacks are in fact different. That our brains are not in fact the same as other people in this country. That we are not equal.

And if it were possible to have a third hand I'd also have another thought that may be somewhat controversial, particularly in the black community, and it is that I'd be worried that the results of a study like this one would serve to absolve many people today of their responsibility to essentially be good people. The victimization of black people in America is well-documented but I have to say I've often felt uncomfortable by how frequently it is used as something to point to when we are just straight up unwilling to take care of our own communities.

I'm rambling now so I'll stop but I hope some of that made sense.

Methylation is super interesting, but I prefer to keep a broad focus on "what differences in the prenatal/postnatal environment?" for explaining most generation-spanning environmental effects.

In the Netherlands we have a special class labelled 'second generation war victim' which deals with some of the aspects of this: (Dutch link, sorry I could not find any article in English)

https://psychotraumanet.org/nl/tweede-generatie-oorlogsslach...

It explicitly mentions the earliest development as one of the important criteria, but it concentrates on the psychological aspects, not on direct physical links.

And then there is this...:

Male Holocaust survivors have a longer life expectancy compared to those who didn't experience the Holocaust, according to a recent study conducted at the University of Haifa jointly with Leiden University. The results have just been published in PLOS ONE. This is the first study to examine data on the entire Jewish Polish population that immigrated to Israel before and after World War II, using the population-wide official database of the National Insurance Institute of Israel. "Holocaust survivors not only suffered grave psychosocial trauma but also famine, malnutrition, and lack of hygienic and medical facilities, leading us to believe these damaged their later health and reduced life expectancy. Surprisingly, our findings teach us of the strength and resilience of the human spirit", said the leading professor of this research, Prof. Avi Sagi-Schwartz, from the Dept. of Psychology and the Head of the Center for the Study of Child Development at Haifa University.

...

One possible explanation for these findings might be the “Posttraumatic Growth” phenomenon, according to which the traumatic, life-threatening experiences Holocaust survivors had to face, which engendered high levels of psychological distress, could have also served as potential stimuli for developing personal and inter-personal skills, gaining new insights and a deeper meaning to life. All of these could have eventually contributed to the survivors’ longevity. “The results of this research give us hope and teach us quite a bit about the resilience of the human spirit when faced with brutal and traumatic events”, concluded Prof. Sagi-Schwartz.

sounds to me like regression to the mean. In a small population you are likely to find all sorts of extreme scenarios

Wouldn't the simplest explanation be that only exceptionally healthy people have managed to survive a concentration camp?

not really. That's a conjecture that may or may not be true, but it certainly isn't simpler than small sample statistics tending to be extreme.

That would be the simplest explanation, but I think a complicating factor would be that for the Nazi concentration camps, many people were murdered, healthy and unhealthy alike, alongside those who perished by other causes.

One might also hypothesize that survivors tend to be more careful, conscious of their health, etc. I don't know if it's a great hypothesis, but it seems plausible.

The headline of this Feb 12, 2015 blog post exaggerates how generalizable these results are likely to be. By the way, do we have a direct link to the published version of the study readily available? I just tried some of the usual online steps for looking up the author's most recent publication on the issue, but what I found was a repost of this Scientific American blog post (which is already a few months old). I study this research with a journal club populated by leading behavior genetics researchers, and any preliminary findings of this kind need a lot more replication before being publishable in an astute journal.

http://www.ncbi.nlm.nih.gov/pubmed/18037011

Considering the incredible psychological impact of the Holocaust on survivors, and how that would affect one's perception of risk in day to day life, I have to imagine that these people probably passed that perspective on to their kids while raising them. If someone were (understandably) raised to always feel under threat, I could see that having an impact on what they're testing.

The "genetics" in epigenetics can actually be quite controversial. That is, how epigenetic markers are inherited isn't very clear. In terms of DNA methylation, there are methylation maintenance enzymes. But for histone modification, how they are inherited (are they being inherited?) isn't very clear. Would enzymes that perform a certain histone modification being passed from mother to daughter cell during division be considered inheritance of the marker? The "information" for the epigenetic marker isn't being passed down, just the machinery is.

Anyways, there are still a lot of things to consider.

As a mechanism though, epigenetics is quite real. My old lab in some soon to be published results found a causal link between some chemicals secreted by an organism and epigenetic traits.

Sure. DNA/histone modifications do seem to serve some kind of purpose in gene regulation.

I just find it a bit amusing that people seem to hold these two specific mechanisms in such high esteem to invent a whole new term, "epigenetics" for them; especially when the inheritance of these mechanisms isn't well established. It's akin to the latest technological buzzword in the tech industry.

I am just being nitpicky here, but semantically, the term epigenetics applies to any mechanism that's not inherently related to the information contained in DNA. Transcription factor binding to DNA is technically "epigenetic". Any non-primary structures formed by DNA that produces some kind of function is technically "epigenetic".

The conventional meaning of the term now in biology seems to only refer to DNA modifications/histone modifications. It's just not a very precise term.

I wonder if this is related to why I have essential tremor. It's something I seem to have inherited from my grandfather, who survived the Holocaust and went back with the US on D-Day. As far as I can tell, it skipped a generation (my dad and his brother don't have it, none of my siblings do, and I don't think my cousins do either).

Perspective (from the comments):

"Is this type of study also being done on the descendants of the Atlantic Slave Trade?"

This is horribly disconcerting. In general the implications are that survivors of severe trauma pass on hormonal alterations to their children, I wonder how many generations this can be observed for.

It's both good and bad. It's more proof that at least some life experiences can produce heritable traits - typically called Lamarckism, and long considered a discredited contender as an evolutionary theory. Whether these traits are good or bad depends on the life experiences I suppose.

epigenetics is the modern science

This is not Lamarckism, though.

It's a bit debated whether modern epigenetics vindicates some elements of Lamarckism or not. Or at least it was a debate in the 2000s; I haven't followed it recently. The consensus is probably no, but the question isn't entirely obvious. Some books by Marion J. Lamb and Eva Jablonka are probably the best-known arguments that results from epigenetics pose a challenge to the gene-centered neo-Darwinian account of evolution, and have stirred debate. One response among many, taking the opposite view, although in a fairly nuanced manner: http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.372...

Thank you for sharing this, fascinating read and interesting viewpoint.

I don't know about humans, but in mice, epigenetic obesity has been observed for 6 generations. (Also, not sure about epigenetic stress response, but I suspect it's similar.)

I'm struggling to find the bit in this[1] set of lectures where something like this was mentioned (I only got to #15 so far); not this study of course, but something about rats being more prone to stress (he was more specific than that) depending on how stressed their mother was (again, that's how I remember it), and that it takes 4-5 generations for that to return to "normal". The logic being that if stress leads to passing on "lower stress tolerance" or however you want to call it, that in turn leads to the offspring being more stressed, which in turn makes their offspring more prone to stress.

I know this may be something totally unrelated, like comparing a jpeg to a wav file, I have no clue about this subject really. It's just this "similar thing that this reminded me of" :)

[1] https://www.youtube.com/playlist?list=PL848F2368C90DDC3D

edit, this was the bit I was thinking of: https://www.youtube.com/watch?v=e0WZx7lUOrY&t=50m11s

A pop science article talking about how "a researcher in the growing field of epigenetics and the intergenerational effects of trauma" found ... intergeneration effects of trauma kind of sets of my https://xkcd.com/882/ alarm.

ETA: especially considering this theory in general has been massively disproven twice (as Lamarck-ism and Lysenko-ism).

If you don't like pop science here is her research - http://www.ncbi.nlm.nih.gov/pubmed/?term=Yehuda%20R[Author]&...

It sounds like their research is a little more robust than that:

http://www.ncbi.nlm.nih.gov/pubmed/18037011

It's not like Lamarck or Lysenko proposed specific persistent markers on DNA, the failure of their ideas doesn't do a lot to discredit the possibility of epigenetic effects.

This is a variant of 'I don't understand [something]...therefore I must be right'.

You really can't discount the study of epigenetics as a modern field, simply because Lamarck and Lysenko were incorrect over a century ago.

I wouldn't discount it. But the more a published scientific finding spins a narrative that would confirm people's existing sensitivities, the more evidence it takes for me to be convinced it is true. Because of all false scientific findings (which most are: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1182327/), the ones that are most likely to virally propagate despite being false are the ones that people want to be true.

So the more I can imagine someone nodding their head and saying "yeah, that totally makes sense," the more I am skeptical of the study until I see some pretty solid evidence.

(I haven't looked at the evidence for this at all, so have no opinion on it).

No, but I definitely can discount one study because two other people that claimed similar things were proven wrong (and Lysenko was less than a century ago). Although I can't tell in this case whether they're claiming anything other than hormone levels in the mother during pregnancy might impact development (which is another reason I'm extremely skeptical of any stronger claims made in the article)

There was a radiolab episode awhile ago about a study in Sweden. They had records going back centuries, of family trees and each years harvest. They found that grandchildren of people who starved at the age of 9 had significantly better life outcomes.

http://www.radiolab.org/story/251885-you-are-what-your-grand...

Indeed, there seems a casual assumption in some pop accounts and discussions that such 'inherited stress' must be bad, a continuation of the ancestral tragedy. In fact some evidence, like that Swedish data, suggests the opposite can also be true.

That sounds like a textbook case of p-value hacking and hypothesis fishing. Is there a solid statistical analysis on the space of hypotheses considered and the size of effects measured?

Fascinating. Also entirely consistent with genetic determinism by the usual natural selection story - 9 year olds who survive starvation have bad-ass genes, etc.

Kids were not dying of starvation, just malnourished. And it fits with the epigenetic theory because 9 years old is when your sex cells form.

If it was just selection, the effect wouldn't be as strong, and should happen regardless what age the starvation happens.

Dying vs. merely damaged is a red herring. Interesting fact re: 9 yo => making eggs/sperm - good comment overall. "Effect wouldn't be as strong" why?

Re: 'regardless of age': you can't rule out genes that influence near-starvation thrive/fail differentially at young vs teen ages. Nevertheless I agree that this is suggestive evidence for "it's not just regular genetics". Good analysis if it indeed applies to this case!

Yeah, this was the first thing that came to my mind, but I couldn't remember where I read this (I thought it was posted on HN recently), but I guess I heard it on Radiolab. I also found a more recent study about the same phenomenon:

http://newsroom.cumc.columbia.edu/blog/2014/07/17/effects-of...

While I enjoy calling epigenetics "Lamarck's Revenge", it's not correct, and I'm well aware of that (I'd even call it part of the joke, at least for myself). Lamarck was wrong about the dominant way in which traits are passed down, full stop, and no future discoveries are going to change that. Epigenetics is more limited, more nuanced, and also, to some extent, now inevitable that it's doing something.

Remember, the genetics you learned in school were just scratching the surface of what was known even then, and the science has been progressing by leaps and bounds since then. Everywhere they look there's another complicated mechanism doing complicated things for complicated reasons. It's terrible and awesome, in the original meanings of those terms.

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