> While the Murphy group consistently observed this attraction in their assays, the Hunter group generally did not (Kaletsky et al., 2025). The Vidal-Gadea group also observed that worms that had not been exposed to PA14 were initially attracted to it, suggesting that this is an important piece of the puzzle (Akinosho et al., 2025). Indeed, when tested directly, the Murphy group did not observe attraction using the temperature-shift method (Kaletsky et al., 2025). However, whether the omission of azide alone explains the discrepancy between the studies is not clear. In a handful of assays, the Hunter group used azide but failed to see the initial attraction to PA14, or to observe learned avoidance in the F2 generation.
Every time I look into epigenetic inheritance studies I run into a lot of finicky experiments like this, where the outcomes appear to be highly dependent on several variables that aren’t fully understood.
One group of researchers claims to have pinned down the results, but as someone outside of this world trying to interpret the studies it’s hard to know how well they’ve really controlled these finicky experiments to isolate the single effect (epigenetic inheritance) that they claim explains everything.
By waving away the hard parts you’re missing why it’s not a simple question in the context of this paper (what I was writing about).
The behavioral test they used showed different results under different circumstances. Even variables like temperature might impact the behavior exhibited in the test.
> You always have to distill complicated papers that babble about things to a minimum statement.
Disagree. You always have to read the papers and understand the details.
Epigenetics is one of those things that seems wild until you pull the camera back a bit. A cell is affected by and responds to its surroundings - this is not controversial. In eukaryotes, this is usually done by way of altering gene expression - up- or down-regulation by means of chemical markers on the cell’s DNA which are created or removed by enzymes which are activated or deactivated by certain substances in the cell or its environment - in other words, the cell’s environment affects gene regulation within the cell by traceable mechanisms*. All cells, save at least one, are descendent of other cells, and cells split by meiosis, in which the chemical environment within and without the cell is shared by the “descendent” cell - so of course this happens with human embryos as well. Of course the expression of your genes is affected by what happened to your parents (well, your mother, at least), because gene expression is affected by what happens to a cell and you are made up of a lineage of cells descended from your mother’s cells. If you ask how one organism could be affected by something it didn’t experience, sure, that could be a quandary, but looking at a line of cells and wondering how later ones could be affected by environmental pressures on earlier ones isn’t nearly as much of a mystery, and we’re all just extended cell lineages.
(As if first time mothers didn’t have enough to worry about - stop stressing so much, it could lead to long-lasting irreversible changes to your fetus!)
* Standard biology disclaimers: this is not the only way this happens, this varies across species and time, nature has no master plan. “Some of the time some genes have some amount of their expression modified somewhat by some mechanisms that are somewhat responsive to some part of the cell’s environment sometimes.”
>>> (As if first time mothers didn’t have enough to worry about - stop stressing so much, it could lead to long-lasting irreversible changes to your fetus!)
This is plainly not plausible. "Irreversible" doesn't play well with the length of time humans have been a thing.
Ask a parent what they hear when they hear “irreversible” in conjunction with their child. I promise nobody mistook that for “until the heat death of the universe,” but I can add a note if you really think it’s warranted.
3. I've been to a few conferences which mixed geneticists with (human) epigenetics guys, and I have never been impressed with the quality of their work. Lots of different measures of "biological clocks". Lots of multiple hypotheses without much correcting for them. No clear theory. I ended up being very skeptical.
I’d be curious to get to the heart of why we believe heritability in behavior is due to genetic changes. It’s way more likely to be due to mimetic changes.
This relates to policy because it addresses the question of whether we carry epigenetic baggage from prior generations. For example, trauma that our parents, or grandparents experienced could lead to behavior modifications and poorer outcomes in us. If that is the case, it has profound public policy implications.
There is a vast gap between current epigenetic inheritance science in humans and all of the theories that epigenetic inheritance is a substantial carrier of inter generational trauma.
We’re still trying to figure out how much, if any, epigenetic inheritance applies to humans. If we did find some evidence, it wouldn’t be as simple as declaring that the trauma of previous generations harmed offspring. For example, it could be equally likely that offspring of prior generations that endured a lot of stress were actually more stress resilient and therefore received some advantages.
> If that is the case, it has profound public policy implications.
I disagree. As I said above, anyone jumping to conclusions that epigenetic inheritance could only confer negative traits is trying to force another concept (inter-generational trauma) into a convenient scientific carrier to make it appear to be a more valid policy position.
> trauma that our parents, or grandparents experienced could lead to behavior modifications and poorer outcomes in us
The nurture part of it is already well established, this is the nature part of it.
However, this is not a net-positive for the folks who already discriminate.
The "faults in our genes" thinking assumes that this is not redeemable by policy changes, so it goes back to eugenics and usually suggests cutting such people out of the gene pool.
The "better nurture" proponents for the next generation (free school lunches, early intervention and magnet schools) will now have to swim up this waterfall before arguing more investment into the uplifting traumatized populations.
We need to believe that Change (with a capital C) is possible right away if start right now.
They've discovered that eggs from women with certain medical conditions (including stress and poor diet) produce embryos with shorter telomeres, and in middle age the shorter telomeres lead to premature aging and a raft of health problems.
related: sperm from male rats who drink heavily produces children and grandchildren with reduced brain size and abnormal behavior -- there's an epigenetic male 'fetal alcohol syndrome'
This would require that it's a one-way door, where bad circumstances persist indefinitely across generations but good circumstances don't. It would also require that to not stretch back too far, since bad circumstances were rather universal before the modern age.
In order for this supposed oddly specific effect to have policy implications, it would have to be simple to identify which individuals are impacted and by how much. And it would have to be impossible to identify such individuals except by looking at their family history.
And there would have to be some policy action that is uniquely beneficial to those people.
What policy implications? Obviously wealth, class, race, nationality, and genetics are all highly heritable, what's one more twig on the pile of the birth lottery?
It’s also a good argument for not allowing children to be victims of their parents’ circumstances. Which is the heart of compulsory schooling and school lunch and a whole host of other things.
Yes, unscientific people will misuse it to support their racist ideas of black people inheriting trauma from slavery. They already do, but they're also extrapolating way beyond what research actually shows.
An absurd take. The ‘trauma’ people, baggage handlers de nos jours, have already weaponised the phenomenon for political points, before we even know definitively if it exists. Hey ho.
Incidentally, nobody yet I see has suggested that epigenetics could lead to better outcomes. I wonder why?
There has been aruably a more serious blow to the pure Darwinian evolution (this is all epigenetics, after all): non-random occurrence of useful mutations in populations exposed to particular diseases.
I don’t really see that as anti-Darwinian. Those genes successfully attach themselves to a new organism and provide advantages such that they are selected for in the population.
The selection is classical, but the mutations are supposed to be random, not skewed towards more useful genetic variants. One can speculate that a purely random (and otherwise neutral, say) prior mutation led to this directionality, but the actual resulting mechanism is AFAIK still unknown.
Even if this was going to hold up, it wouldn't make the policies that Lamarck's ideas were designed to promote work. We already empirically know they don't work.
I think that nowadays "gene" refers only to a subset of a nucleic acid. Sequences of ACTG (or ACUG in the case of RNA) only, and only in that organism's chromosomes.
If you inherit a virus from your mother, for instance, I think most would call that non-genetic inheritance, even though viruses have genes too. Same goes for methyl and acetyl markers, transcription factors, nutrients, toxins, and whatever else comes along for the ride in the meiotic cell.
Could you restate this? I believe "genetic" usually refers to only the sequence of linear bases, while epigenetics refers to histone acetylation, and base methylation (And other things perhaps). These are also heritable, and regulate protein expression in a way that, like genetics, affects phenotype.
But there might be other ways that some traits get inherited, eg by changing the cellular environment in the sperm/egg itself which could affect the offspring while keeping the genes the same.
Maybe he's trying to go to the earliest idea of "gen-es" aka the reasons for the traits of an individual. The idea existed before the discovery of cells kernels and DNA right ? so in a way, if there are other mechanisms involved in passing traits to children, it could be termed as gen-something
Yes, that depends on the definition. Lamarck could fit into it, but he had no clue about DNA, genes and so forth; neither had Darwin. He babbled about gemmulae.
Even the definition of a gene is not very accurate. Many important sequences yield a miRNA or another RNA. Only few sequences yield a mRNA. Some "genes" are just integrated viruses/phages/transposons etc... that were modified. One of the most fascinating one was the retrovirus in regards to the mammalian placenta: https://pmc.ncbi.nlm.nih.gov/articles/PMC4332834/ but there are many more examples. We are all DNA hybrids at the end of the day. The whole species concepts makes very little sense these days, IMO. I can see the use case for eukaryotes, but it makes no sense to me for bacteria yet alone viruses.
Epigenetic inheritance is a mechanism whereby traits could be passed from one generation to the next without modifying the underlying genetic DNA. The mechanism would alter the expression of different parts of DNA.
It’s a very young field with a lot of open questions. The concept has been adopted and abused in the mainstream so you have to be careful to separate the science from the pseudoscience.
That depends on the definition. But, if we use the modern definition, it emerged (or re-emerged) in the 1990s. It's not old, indeed, but I also would no longer call it "very young". It's soon 40 years in the modern definition, and much older if we include prior discussions.
> While the Murphy group consistently observed this attraction in their assays, the Hunter group generally did not (Kaletsky et al., 2025). The Vidal-Gadea group also observed that worms that had not been exposed to PA14 were initially attracted to it, suggesting that this is an important piece of the puzzle (Akinosho et al., 2025). Indeed, when tested directly, the Murphy group did not observe attraction using the temperature-shift method (Kaletsky et al., 2025). However, whether the omission of azide alone explains the discrepancy between the studies is not clear. In a handful of assays, the Hunter group used azide but failed to see the initial attraction to PA14, or to observe learned avoidance in the F2 generation.
Every time I look into epigenetic inheritance studies I run into a lot of finicky experiments like this, where the outcomes appear to be highly dependent on several variables that aren’t fully understood.
One group of researchers claims to have pinned down the results, but as someone outside of this world trying to interpret the studies it’s hard to know how well they’ve really controlled these finicky experiments to isolate the single effect (epigenetic inheritance) that they claim explains everything.
It can be simplified to this question:
- Do C. elegans offspring show a modified behaviour unrelated to a changed genome sequence?
That is a fairly simple question. The answer to it should be simple too.
You always have to distill complicated papers that babble about things to a minimum statement.
> That is a fairly simple question. The answer to it should be simple too.
This hardly follows.
Agreed. Also, "simple isn't easy".
By waving away the hard parts you’re missing why it’s not a simple question in the context of this paper (what I was writing about).
The behavioral test they used showed different results under different circumstances. Even variables like temperature might impact the behavior exhibited in the test.
> You always have to distill complicated papers that babble about things to a minimum statement.
Disagree. You always have to read the papers and understand the details.
> That is a fairly simple question. The answer to it should be simple too.
"Is P equal to NP" is also a simple question.
The answer should be simple, too -- either yes or no. OP did not imply proving it would be simple.
I'm pretty sure that you won't be able to claim your 1 million dollars from the Clay Mathematics Institute by just answering yes or no.
OP did imply that the paper contained the simple answer, though.
It’s easy to say that the truth is simple if you ignore everything about exploring whether or not a paper is an accurate representation of the truth.
Epigenetics is one of those things that seems wild until you pull the camera back a bit. A cell is affected by and responds to its surroundings - this is not controversial. In eukaryotes, this is usually done by way of altering gene expression - up- or down-regulation by means of chemical markers on the cell’s DNA which are created or removed by enzymes which are activated or deactivated by certain substances in the cell or its environment - in other words, the cell’s environment affects gene regulation within the cell by traceable mechanisms*. All cells, save at least one, are descendent of other cells, and cells split by meiosis, in which the chemical environment within and without the cell is shared by the “descendent” cell - so of course this happens with human embryos as well. Of course the expression of your genes is affected by what happened to your parents (well, your mother, at least), because gene expression is affected by what happens to a cell and you are made up of a lineage of cells descended from your mother’s cells. If you ask how one organism could be affected by something it didn’t experience, sure, that could be a quandary, but looking at a line of cells and wondering how later ones could be affected by environmental pressures on earlier ones isn’t nearly as much of a mystery, and we’re all just extended cell lineages.
(As if first time mothers didn’t have enough to worry about - stop stressing so much, it could lead to long-lasting irreversible changes to your fetus!)
* Standard biology disclaimers: this is not the only way this happens, this varies across species and time, nature has no master plan. “Some of the time some genes have some amount of their expression modified somewhat by some mechanisms that are somewhat responsive to some part of the cell’s environment sometimes.”
Great writeup!
And as someone less knowledgeable about biological sciences than others, I think learned even more from your disclaimers!
p.s. If you know any good sources for adults to catch up on some biology basics, let me know.
>>> (As if first time mothers didn’t have enough to worry about - stop stressing so much, it could lead to long-lasting irreversible changes to your fetus!)
This is plainly not plausible. "Irreversible" doesn't play well with the length of time humans have been a thing.
Ask a parent what they hear when they hear “irreversible” in conjunction with their child. I promise nobody mistook that for “until the heat death of the universe,” but I can add a note if you really think it’s warranted.
1. Pretty obviously, epigenetics in bacteria provides only very weak support for epigenetics in humans.
2. The case against epigenetics in humans is laid out nicely by Razib Khan: https://www.razibkhan.com/p/you-cant-take-it-with-you-straig...
3. I've been to a few conferences which mixed geneticists with (human) epigenetics guys, and I have never been impressed with the quality of their work. Lots of different measures of "biological clocks". Lots of multiple hypotheses without much correcting for them. No clear theory. I ended up being very skeptical.
here is some reading for you:
https://www.sciencedirect.com/science/chapter/edited-volume/...
https://pmc.ncbi.nlm.nih.gov/articles/PMC12204592/
https://sciencevivid.com/epigenetics/
I’d be curious to get to the heart of why we believe heritability in behavior is due to genetic changes. It’s way more likely to be due to mimetic changes.
This relates to policy because it addresses the question of whether we carry epigenetic baggage from prior generations. For example, trauma that our parents, or grandparents experienced could lead to behavior modifications and poorer outcomes in us. If that is the case, it has profound public policy implications.
There is a vast gap between current epigenetic inheritance science in humans and all of the theories that epigenetic inheritance is a substantial carrier of inter generational trauma.
We’re still trying to figure out how much, if any, epigenetic inheritance applies to humans. If we did find some evidence, it wouldn’t be as simple as declaring that the trauma of previous generations harmed offspring. For example, it could be equally likely that offspring of prior generations that endured a lot of stress were actually more stress resilient and therefore received some advantages.
> If that is the case, it has profound public policy implications.
I disagree. As I said above, anyone jumping to conclusions that epigenetic inheritance could only confer negative traits is trying to force another concept (inter-generational trauma) into a convenient scientific carrier to make it appear to be a more valid policy position.
> trauma that our parents, or grandparents experienced could lead to behavior modifications and poorer outcomes in us
The nurture part of it is already well established, this is the nature part of it.
However, this is not a net-positive for the folks who already discriminate.
The "faults in our genes" thinking assumes that this is not redeemable by policy changes, so it goes back to eugenics and usually suggests cutting such people out of the gene pool.
The "better nurture" proponents for the next generation (free school lunches, early intervention and magnet schools) will now have to swim up this waterfall before arguing more investment into the uplifting traumatized populations.
We need to believe that Change (with a capital C) is possible right away if start right now.
They've discovered that eggs from women with certain medical conditions (including stress and poor diet) produce embryos with shorter telomeres, and in middle age the shorter telomeres lead to premature aging and a raft of health problems.
related: sperm from male rats who drink heavily produces children and grandchildren with reduced brain size and abnormal behavior -- there's an epigenetic male 'fetal alcohol syndrome'
But fortunately “We provide proof-of-concept that DNA resetting can be modulated in embryos where it is deficient, using currently available drugs, to influence telomere length at birth" https://www.adelaide.edu.au/robinson-research-institute/news...
This would require that it's a one-way door, where bad circumstances persist indefinitely across generations but good circumstances don't. It would also require that to not stretch back too far, since bad circumstances were rather universal before the modern age.
In order for this supposed oddly specific effect to have policy implications, it would have to be simple to identify which individuals are impacted and by how much. And it would have to be impossible to identify such individuals except by looking at their family history.
And there would have to be some policy action that is uniquely beneficial to those people.
What policy implications? Obviously wealth, class, race, nationality, and genetics are all highly heritable, what's one more twig on the pile of the birth lottery?
This sort of thing is always a call for generational guilt and reparations.
It’s also a good argument for not allowing children to be victims of their parents’ circumstances. Which is the heart of compulsory schooling and school lunch and a whole host of other things.
Yes, unscientific people will misuse it to support their racist ideas of black people inheriting trauma from slavery. They already do, but they're also extrapolating way beyond what research actually shows.
An absurd take. The ‘trauma’ people, baggage handlers de nos jours, have already weaponised the phenomenon for political points, before we even know definitively if it exists. Hey ho.
Incidentally, nobody yet I see has suggested that epigenetics could lead to better outcomes. I wonder why?
The consequences could be terrible if it were intentionally weaponised by a government looks at the Russian empire.
So Lamarck wasn't entirely incorrect either. Darwin would have been fascinated by these results.
There has been aruably a more serious blow to the pure Darwinian evolution (this is all epigenetics, after all): non-random occurrence of useful mutations in populations exposed to particular diseases.
https://pubmed.ncbi.nlm.nih.gov/40854136/
I don’t really see that as anti-Darwinian. Those genes successfully attach themselves to a new organism and provide advantages such that they are selected for in the population.
The selection is classical, but the mutations are supposed to be random, not skewed towards more useful genetic variants. One can speculate that a purely random (and otherwise neutral, say) prior mutation led to this directionality, but the actual resulting mechanism is AFAIK still unknown.
In Lamarkian evolution features that organisms use either accentuate or attenuate. That's not how epigenetics works in general.
Even if this was going to hold up, it wouldn't make the policies that Lamarck's ideas were designed to promote work. We already empirically know they don't work.
Honest question: isn’t all inheritance transgenerational?
Sure, but epigenetics is inheritance that does not have an associated genetic sequence change. The DNA sequence is identical.
If it's inheritable wouldn't that make it by definition genetic?
I think that nowadays "gene" refers only to a subset of a nucleic acid. Sequences of ACTG (or ACUG in the case of RNA) only, and only in that organism's chromosomes.
If you inherit a virus from your mother, for instance, I think most would call that non-genetic inheritance, even though viruses have genes too. Same goes for methyl and acetyl markers, transcription factors, nutrients, toxins, and whatever else comes along for the ride in the meiotic cell.
Got it. I had thought that actual genes were only a part of what was considered "genetics."
Could you restate this? I believe "genetic" usually refers to only the sequence of linear bases, while epigenetics refers to histone acetylation, and base methylation (And other things perhaps). These are also heritable, and regulate protein expression in a way that, like genetics, affects phenotype.
No. If the change happens without altering the DNA (or RNA) sequence it's not genetic it's epigenetic.
epi- = outside
It’s not a tautology. Check out the work of Michael Levin (easily accessible on YouTube) for examples of non-genetic heritability.
Genetic would mean that genes get modified.
But there might be other ways that some traits get inherited, eg by changing the cellular environment in the sperm/egg itself which could affect the offspring while keeping the genes the same.
Maybe he's trying to go to the earliest idea of "gen-es" aka the reasons for the traits of an individual. The idea existed before the discovery of cells kernels and DNA right ? so in a way, if there are other mechanisms involved in passing traits to children, it could be termed as gen-something
Yes, that depends on the definition. Lamarck could fit into it, but he had no clue about DNA, genes and so forth; neither had Darwin. He babbled about gemmulae.
Even the definition of a gene is not very accurate. Many important sequences yield a miRNA or another RNA. Only few sequences yield a mRNA. Some "genes" are just integrated viruses/phages/transposons etc... that were modified. One of the most fascinating one was the retrovirus in regards to the mammalian placenta: https://pmc.ncbi.nlm.nih.gov/articles/PMC4332834/ but there are many more examples. We are all DNA hybrids at the end of the day. The whole species concepts makes very little sense these days, IMO. I can see the use case for eukaryotes, but it makes no sense to me for bacteria yet alone viruses.
Epigenetic inheritance is a mechanism whereby traits could be passed from one generation to the next without modifying the underlying genetic DNA. The mechanism would alter the expression of different parts of DNA.
It’s a very young field with a lot of open questions. The concept has been adopted and abused in the mainstream so you have to be careful to separate the science from the pseudoscience.
> It’s a very young field
https://en.wikipedia.org/wiki/Epigenetics#Definitions
That depends on the definition. But, if we use the modern definition, it emerged (or re-emerged) in the 1990s. It's not old, indeed, but I also would no longer call it "very young". It's soon 40 years in the modern definition, and much older if we include prior discussions.
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