What makes a man? This is the perennial question of mankind. In recent years, advancements in biology and medicine have given us a thousand new ways to ponder that question. We may have stopped looking for a literal soul, but the line between nature and nurture is a fun one to skim.
Our genetic code, often analogized as a blueprint to the body is a great compendium of designs for biological machinery, fluids, and sundries that make our body work. The human genome was fully sequenced a mere 13 years ago, but in many ways it was a short-lived victory. The genome is not the end of our biological instruction books. Epigenetics, a nebulous term that describes the factors involved with reading the genetic code. Analogously: the blueprints (genetic) may dictate that the kitchen gets two standard windows, but when the misses finds inspiration during the construction, those two regular windows become one large bay window. Our inspired woman is an epigenetic factor. She has modified the blueprints. Now, she does not herself install the bay window. First, she consults her husband. In both real life and in biology, this process is know as feedback. The husband, if the system is functioning normally, will indicate that this alteration is acceptable (positive feedback). But it could happen that there is an issue with the man, and he will object to the alteration (negative feedback). From there, the handyman will be alerted to the suggestion. He says it will cost more money, and the wife takes this information back to the husband for deliberation (more feedback). They get back to the handyman, and say go ahead anyway. The handyman orders a new window and tells his assistant to install it. None of these changes are listed in the blueprints.
There’s a sequence of events, and changes at any one of the junctions can affect what goes on down the line. If the window breaks the budget, maybe it doesn’t happen–or maybe the bathroom gets a downgrade. A house is complicated enough. The entirety of the human body is quite a beast to understand in its entirety. When you through something as nebulous as the human mind into your examination, it becomes harder still. So the genetics and epigenetics analysis of human personality is a rather Herculean task. I’m sympathetic to the daunting challenge of the research. On the other hand, a task being challenging doesn’t give anyone a pass on having to deal with challenges.
Enter
Holocaust exposure induced intergenerational effects on FKBP5 methylation. That sounds confusing.
Here’s how it looks after the media does a rinse. “The Holocaust was so bad that even their unborn children got screwed by it!” You want to be the person who says on the record “Uh, pretty sure that’s bullshit”? There are very few people in this world paid enough to deal with the kind of shitshow that would fall out from a public criticism like that. Fortunately, I’m still obscure, so I’ll go for it. Epigenetics is a very contentious subject. The extent to which epigentics factors are inheritable is very contentious. The role of biology in general on human personality is very contentious. Also, complicated. So any evidence that there’s even something worth looking into for a given epigenetic factor should have some very convincing data behind it. Maybe that day will come, but it is not this day. The data here are pretty much worthless. Scroll down to the Tables, starting on page 18. It’s a nice display of data. We have 32 Holocaust survivors, defined as anyone who was “interned in a Nazi concentration camp, witnessed or experienced torture, or had to flee or hide during WWII”, most of whom have highlighted mental health issues. For contrast, there is a control group… of 8 people. FKBP5 is a gene. It’s the gene these researchers have been looking at in their careers, and they’re doing so again here. We’ll look at it too. Their term “risk-
allele” is what we’re looking at in particular. Simplistically, the researchers think this variation in the gene (the “risk”-allele) is potentially responsible for contributing to a risk of psychological issues such as PTSD. It’s an epigenetic trait, not a genetic one, so if it can be inherited, that’d be a neat discovery.
So what do the numbers say? Well, 58% of the Holocaust group has the allele, while 38% of the control group does. So right off the bat, that similarity is a red flag. The difference between the groups is only about a fifth just even before you look at the kids. If the allele makes any difference, it’s going to be a minor roll, otherwise the control group would have similar pathologies to the Holocaust group, and they don’t. The allele is already fairly common within a general Jewish population–probably others too, but, you know, why bother checking? Let’s go to the kids. 64% of the Holocaust-parent kids have the allele and 44% of the control-parents kids do. The kids of
both groups increased by the same rate (6%)–the control group was actually about a percent higher if you stretch it out to 3
significant figures. So suffering through the Holocaust makes, based on their data, literally 0% difference in the rate of “intergenerational FKBP5 methylation”. Their own data indicate that the comparison makes no difference. So why does the title mention the Holocaust? So people in the media can write “Holocaust survivors may have passed on traumatic stress to offspring” as a headline. That will grab your attention. “
No difference in induced intergenerational effects on FKBP5 methylation from Holocaust exposure” will not let anyone write a catchy headline. They get to keep it in the title because technically there was a higher prevalence of the allele in the offspring compared to the control group. The Holocaust group
started with a higher prevalence, so it’s not a meaningful result.
The authors of the paper have published numerous articles on the FKBP5 gene, particularly with how it relates to mental health issues like PTSD.
Here are a
couple. Those articles reference other authors in the Holocaust study too. Their push seems to be that the gene plays a role in pathways that are involved in PTSD. Digging through all those articles to figure out what precisely they have found out and how would be massively time consuming. And I’m fairly obsessive. The average Joe sure isn’t going to go digging. And that’s what this Holocaust paper gets them: more earth to throw on the pile. “Of course we’re sure this is how it works! Just look at all these papers we’ve cited!” Now, some of the papers may be perfectly insightful. This one gives me a lot of skepticism about the rest of their work, but I can concede that this one may be the fluke. But this paper adds nothing valuable to the conversation of epigenetics and mental health.
The discussion is an interesting bit. What these particular authors won from this study was finding offspring having “methylation changes on the same site in a functional intronic region of the FKBP5 gene, a GR-binding sequence in intron 7, but in the opposite direction.” Basically, one of the sections of variation in the gene was inherited in some of a group. That should have been the lead of the paper, but it’s buried. Because it’s tedious and tenuous. It hardly proves that the “trauma of the Holocaust” is a heritable trait. It is at the absolute best, a lead for a far better designed study. The rest of their discussion talks about how most of their findings are insignificant and the many ways in which better studies would need to be designed to test any of this more thoroughly. Which I think I mostly agree with.
