Larry Moran rips into the latest hype over epigenetics. Good. There is some valuable biology buried in the field, but I see so much nonsense that even as a developmental biologist who wants to seem more attention to regulative changes in the genome, I’m just seeing so much exaggeration that I think it is doing more harm to our understanding than good (see also Carl Zimmer’s latest discussion of epigenetic over-reach). But this video is just too much.
It’s true — region of the genome can be switched on or off in a coarse way by chemical modification of DNA and associated proteins. It happens all the time. But as Larry points out, this doesn’t just happen by magic. There are regulatory factors that change patterns of gene expression, and they’re probably most responsible as well for triggering the establishment of epigenetic marks.
But here’s my objection: the hype seems to be ignoring development (I know, unforgivable). The problem with assigning too much importance to the inheritance of epigenetic marks is that individual cells and tissues acquire them throughout development and even adulthood…but they don’t matter genetically. Have the proponents never heard of Weismann’s Barrier? Changes in the somatic tissues don’t propagate to the next generation. All that matters are changes in a subset of cells in the gonads, the testes and ovaries. So we’re already dealing with a tiny fraction of our cells that also have unique tissue-specific epigenetic marks, and more importantly, their own specialized patterns of gene regulation.
Then, further, gene expression in the germ line is further refined during maturation of the egg and sperm — both of these cell types are highly specialized and gene expression is honed even more during their development. It’s nice to dream that epigenetics influences neurons in the brain, but you’re not going to inseminate anyone with your neurons, nor are those cells going to migrate down into your ovaries and pass their history on to the next generation.
The video does mention that most epigenetic marks are going to be cleared during gamete formation, and other germ-line-specific marks added, but it just blithely slides past that. It seems to me that the clearest example of epigenetic modification in inheritance is genomic imprinting, which is a consequence of differential gamete-specific modification of sperm and egg, and its main effect is in regulating gene dosage.
It’s strange. I don’t even see the appeal of these epigenetic fairy tales; I certainly don’t see any problem in evolutionary theory that requires patching up with this kind of phenomenon. But Larry includes an excerpt from an interview with the creator of the video, and suddenly all is clear. This bastardized, exaggerated version of epigenetics appeals to people who are uncomfortable with the whole central idea of modern evolutionary theory — who dislike seeing gene transmission uncoupled from the will of the individual.
I came from the world of evolutionary biology. I have always been interested in evolutionary theory but I was never convinced by the neo-Darwinian argument that environmental factors are not a big player in the generation of genetic changes. On the other hand, I never understood the fierce dismissal and often mocking of the Lamarckian ideas in schools and universities; particularly, because Darwin himself never denied Lamarck’s ideas. In epigenetics I found the mechanisms that allow you to understand the action of environmental exposures on the genome.
Whoa. That environmental factors are not a big player in the generation of genetic changes
is sort of true; the environment can influence the rate of genetic changes, but doesn’t play a big role in shaping the direction of that change — that’s all a consequence of changing the frequency of representation of those changes in the population. That he brings up the idea of Lamarck is telling. Lamarckian evolution ain’t coming back, although it’s surprising how often people want it.
Also, Darwin himself never denied Lamarck’s ideas
? Does he know nothing about the history of evolutionary theory? Darwin did not deny them, because his theory of inheritance was all about the inheritance of acquired characters and pangenesis, the generation of a gamete by contributions from all tissues (which, come to think of it, is what you’d need for the epigenetics hype to have any hope of working). He was pre-Mendelian genetics. He was wrong. You can’t defend Lamarck by citing a guy, no matter how influential, who had no viable theory of genetics, and who wrote in the era just before genetics was explored and understood. He might as well support it by announcing that Aristotle didn’t deny Lamarck.
As for the idea that epigenetics somehow explains the effects of environmental exposure to damaging agents…I’m trying to think of any clear examples of how that occurs, and I’m a developmental biologist who has been studying teratology for a few decades. We don’t invoke epigenetics to account for abnormal cell death, or signaling failures, or mismigration, or endocrine disruption, or any of the phenomena that are commonly responsible for non-genetic errors in development. His example is to claim that exposure to DDT in the 50s and 60s somehow led to the current high frequency of obesity.
He’s got no evidence. He has no mechanism, other than to say, “epigenetics!”
The thing to watch out for next is revealed at about 4:00 in the video, where he talks about using diet and behavior to give yourself a “healthy epigenome”, whatever that is. I’m sure some unscrupulous, dishonest someone, somewhere is writing a diet book about super-foods to super-charge your epigenome for you and your baby.
I’m calling it. There are already plenty of pseudoscientific books that mangle the concept of epigenetics. I’m sure the ones that will turn it into a marketing fad are coming up soon. We’ve already got a lot of books touting the microbiome as the cure-all for everything — I can easily imagine the fusion of the epigenome and microbiome hype machines popping up on Amazon.
Can I claim royalties for predicting it?
You could maybe patent it and sue anyone who tries to use or publish the method, but that’d be basically patent trolling.
Take a wild guess…
While you’re about it, patent Weismann’s Barrier Cream.
Greenfieldism, or pointer theory, raises its head again: I point to DDT and I point to obesity, that is all.
I’ll take that…
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“Have the proponents never heard of Weismann’s Barrier? Changes in the somatic tissues don’t propagate to the next generation. All that matters are changes in a subset of cells in the gonads, the testes and ovaries.”
True for most, but not all, animals, and mostly not true for other organisms.
The Trump Epi-Plan. People are loving it. It works. Believe me. Remember that.
Yes, TED audience, remember to avoid the choices made by those dumb babies in Flint.
Where’s Trofim Lysenko when you really need him !!
No, but if you’re unscrupulous you can cash in on it.
You know enough about biology to bamboozle the gullible with big words.
There appears to be a bit of Big Name Scientist worship going on here. If Darwin believed something about evolution, it must be true because he’s the biggest name in the field! An argument that completely omits the fact that there has been 150 years of research since his day. We might as well say that the sun is the center of the universe and planetary orbits must be circular, because Copernicus said so and he’s way more famous than any modern astronomer.
Holms: did you know Isaac Newton was a Christian? Ergo…
BTW, I believe Deepak Chopra has jumped on the epigenetics bandwagon.
You and Larry may think that but there is plenty of experimental evidence to show that the ability of many/most of those regulatory factors to bind to DNA is influenced by the (epigenetic) state of the chromatin. Not to mention all the experiments from the 70s showing that inhibition of DNA methylation activates the expression of many genes.
chris61, it amuses me that you imagine your point somehow contradicts the claim you quoted.
As a layman my takeaway from this is that epigenetic inheritance is my sperm passing on all my balls have learnt over my lifetime. You’re welcome, offspring.
Indeed.
I have strong feelings about the possibilities of epigenetic inheritance, but I do take steps to keep them feelings about possibilities. I’ve phrased my feelings in terms of “placing my bets” or “it’s not a widely held view” depending on the context because I know that there is currently no strong, direct evidence of transgenerationally inherited epigenetic changes to things like behavior in humans. There are some interesting things: in model organisms in terms of inherited epigenetic changes, brain anatomy differences in humans with conditions like ADHD and Tourette’s Syndrome (with imprinting as part of TS inheritance), inherited predispositions to ADHD when grandmothers are smokers (indicating a molecular system involved in inherited changes)… but there is currently no connection between these things that paint a clear picture that links experiences, choices, or modes of life to inherited epigenetic changes in something like behavior through development. I know what I would try to study if I had a lab though.
I’m embarrassed to admit that if I had heard of Weismann’s Barrier, I have since forgotten about it. But there are some places where I would look for exceptions in germline tissues involving the fact that most epigenetic marks are cleared. If an organism were able to pass on information about the environment that it lives in it makes sense to have a system for preventing marks irrelevant or contrary to the current environment, or for changing marks if the environment changes.
The current “state of the organism” is reflected in circulating chemical messengers like hormones and if I were running a lab I would be looking for evidence of things like hormone driven changes in, or preservation of epigenetic marks in germline tissues. Especially in molecular systems that have connections to “current state” like stress responses. Or maybe changes related to disposition like introversion/extroversion which have a strong inherited component (if such changes have been found).
As for anatomical changes that could be investigated for connections to epigenetic inheritance an example would be the enlarged amygdalas or frontal cortex regions in children with Tourette’s Syndrome (that end up smaller in adults), or the enlarged hippocampi in ADHD. But the fact that the developmental space between conception and when these structures are detected is large is a big problem.
I could still easily lose my bet though. Life will be what it will be. Even if the possibilities I dream of end up true that would still not make such changes a matter of anyone’s will being expressed in transmission of gene expression. There would be very little choice involved in things like environmental response driven epigenetic changes. Maternal stress is related to likelihood of Tourette’s Syndrome and mothers don’t choose stress.
“His example is to claim that exposure to DDT in the 50s and 60s somehow led to the current high frequency of obesity.”
Haven’t seen the video but I’m a graduate student at a UC School whose research is pretty much exactly how DDT exposure in utero increases risk for obesity, type 2 diabetes/ insulin resistance, and other metabolic disorders via epigenetic mechanisms. if anyone would like to discuss the epidemiology and/or molecular work behind this research feel free to ask!