Acquired inheritance is proven in nematodes; in humans there is no evidence yet
Textbooks use the Weismann barrier to explain why the muscles you build can't be passed down; but in nematodes, knock out the offspring's own ability to make small RNAs and they still resist viruses their parents encountered — change only the RNA in the brain and you change behavior three generations later.
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The argument · timestamps estimated from transcript position
The genome is the whole book; each cell pulls out one page
Every cell carries the same genome. Rechavi's metaphor is that every room holds an IKEA manual with instructions for building everything in the house; but the kitchen needs different things than the bathroom, so each cell pulls out just one page, and that page is RNA, and the furniture assembled from it is protein. The messenger RNA that actually encodes protein is only a small part of RNA: less than 2% of the genome's sequence encodes messenger RNA, while a great deal of the RNA that gets transcribed does other things, many of which remain unexplained. This distinction is the foundation for everything that follows — DNA determines which instructions can be opened, and the remaining question is whether lived experience can rewrite those instructions.
— Dr. Oded RechaviTwo barriers block the inheritance of acquired traits
Why, by default, can't what you learn in life be passed on? Rechavi attributes it to two barriers. The first is the separation of soma and germline: in the 19th century August Weismann proposed what is now called the Weismann barrier — only germ cells can hand information to the next generation, and what happens in the rest of the body should stay in the body; this barrier has been called biology's second law, the first being natural selection. The second is epigenetic reprogramming: genetic material accumulates all kinds of chemical modifications, but in sperm and eggs, and in the early embryo, these modifications are largely erased — roughly 90% in mammals and humans. The reason for erasing is to return to the original manual, preserving the potential to build all the furniture rather than being locked into the few pieces one room happened to make.
— Dr. Oded RechaviIt was opposed and desired, and not entirely for data reasons
This barrier theory kept acquired inheritance out of favor for a long time. Rechavi describes two sides: one is theory, the barrier is sitting right there; the other is the atmosphere the controversy itself creates. He gives Schrödinger's 1944 book as an example — Schrödinger wrote that acquired inheritance doesn't hold up and doesn't happen, and at the same time wrote that this is sad, because natural selection is bleak: nothing you do affects the genetic information of the next generation, and all you can give your children is money and education. Rechavi says he can psychologically understand why many people want it to be true, because it gives life meaning. But he doesn't push this into ‘because everyone wants to believe it, it has promise’; he only says RNA is a new lead, a candidate molecule that in recent years has come to the fore even in the mammalian field.
— Dr. Oded RechaviA nematode can run hundreds of generations in one PhD
Why should you trust nematodes? The conditions Rechavi lists are concrete: a C. elegans is always 959 cells, 302 of them neurons, and since the 1980s it has had a complete connectome, like a subway map marking who talks to whom; the body is transparent, so you can watch neurons fire directly, and you can switch genes on and off with optogenetics; it was the first animal to have its genome sequenced, earlier than humans; each mother produces about 250 nearly genetically identical offspring, raised in a dish eating bacteria, in a highly controlled environment where nature and nurture can be separated; generation time is 3 days, so one PhD can run hundreds of generations of nematodes. Under these conditions, he says, the inheritance of acquired traits in nematodes already has very clear, indisputable evidence, and almost no one in the epigenetics field disputes it.
— Dr. Oded RechaviOffspring that can't make small RNAs still resist viruses
The experimental design is clean enough to read by color: use a fluorescent virus, and if the virus replicates successfully the nematode turns green, and if it's destroyed it stays black. First let nematodes get infected and destroy the virus, then knock out the machinery for making small RNAs in the offspring — these offspring have no ability to make small RNAs from scratch themselves. Then infect them with the same virus. If they still turn black, the only explanation is that they inherited small RNAs from their parents. That is exactly what happens: all the offspring are black, and the resistance can be passed on for several more generations. Sequencing can directly read those small RNAs matching the viral genome, and only offspring whose parents were infected have them. These nematodes have no T cells or B cells; they defend against viruses with RNA, and this mechanism is RNA interference, which won the Nobel Prize in 2006.
— Dr. Oded RechaviThe brain and inheritance don't speak the same language
The boldest question in this episode is: can the brain leave information for the next generation? Rechavi points out the obstacle is translation — the brain stores information in the three-dimensional structure of synaptic connections, while any heritable information must squeeze through the bottleneck of a single cell, the fertilized egg. He also offers another possibility: learning something may just mean removing a particular odor receptor, in which case one RNA controlling that receptor would be enough to pass it on; such phenomena have been reported in mammals, but he says they haven't been proven convincingly enough, because no one has explained how information gets from the brain to the germ cells. His own route bypasses translation: in a 2019 Cell paper, changing only the production of naturally occurring small RNAs in the nematode brain changed the foraging behavior of offspring, affecting them all the way to three generations later, with the mechanism landing on the germline gene sage-2, and also requiring the protein that physically carries RNA.
— Dr. Oded RechaviMammals lack an RNA amplifier
Why can nematodes do it while mammals are doubted? The mechanism Rechavi gives is blunt: the nematode's secret is that it can keep amplifying these small RNAs, so the signal doesn't get diluted. In mammals there is no known comparable amplification mechanism, so the question becomes — how does a tiny bit of RNA affect the whole organism? One possibility is that it acts only very early in development: when there are just a few cells, perhaps even acting on the placenta formed during pregnancy, and then step by step it steers development off course, and metabolic problems and the like follow. This is the ‘developmental origins of health and disease’ line of thinking. He also frames RNA's role in mammals as a candidate rather than a conclusion: small RNAs are the leading candidate for transmitting protective or harmful effects of stress, but ‘in mammals we don't know, time will tell’.
— Dr. Oded RechaviRNA is more plastic than DNA, so start with diagnostics
The applications come in three layers. The nearest is diagnostics: in Israel, most couples preparing to have children do DNA diagnostics for genetic diseases, but right now no one looks at RNA; if the mechanism becomes clearer, RNA would be another layer, a whole new world, and there may be certain RNAs associated with disease. The advantage is that it isn't fixed the way DNA is — DNA is yours, and if you can't change it you can only choose another embryo; RNA is plastic. Only a step further out is intervention: in rodent experiments, overfeeding causes problems in the next generation, but if you let the mice exercise, this abnormal inheritance gets corrected; when doing IVF, perhaps you could change the RNA composition of the things you introduce. Rechavi is restrained about the timeline: he says this doesn't happen now, it's science fiction, but if it gets figured out, he has also imagined telling someone preparing for IVF ‘you should go run on the treadmill for a while’, which would change your RNA profile.
— Dr. Oded RechaviIn their own words · checked verbatim
This is like the IKEA book that you have in every cell in your body, the instructions to make everything that you need in your house, the chairs, the kitchen, the pictures. But in every room, you want something else.
Dr. Oded Rechavi4:37
The man who first thought about this barrier is called Weismann, August Weismann. … Separation of the soma from the germline, only the germline transmitting information to the next generation. And this is also called the second law of biology.
Dr. Oded Rechavi11:35
So to preserve this, we erase all these modifications and start anew. And this is in mammals and in humans, this is largely true. Most of the modifications in the sperm and in the egg are removed, so about 90% of them.
Dr. Oded Rechavi12:46
In the worm, we now have very obvious and clear-cut proof that there is inheritance of acquired traits. So much so that I don't think that anyone pretty much in the epigenetic field argues against it.
Dr. Oded Rechavi16:20
We demonstrated this very clearly using a fluorescent virus. If the virus replicates successfully, the worm just turns green, and if the virus is destroyed, the worm stays black.
Dr. Oded Rechavi21:20
What we did in C. elegans is we showed that the brain can communicate with the next generations using small RNAs, and that this can change behavior.
Dr. Oded Rechavi28:17
For example, there are experiments in rodents where they show that overfeeding the rodents creates problems for the next generations, for the children. However, if you let the rodent exercise, then it corrects the aberrant inheritance.
Dr. Oded Rechavi31:07
The beauty is that this, unlike DNA, it's plastic. So with DNA, this is your DNA, perhaps we can choose another embryo.
Dr. Oded Rechavi32:22
Figures
| Share of the genome encoding messenger RNA | less than 2% | 4:37 |
| Share of epigenetic modifications cleared in sperm and eggs | about 90% | 12:46 |
| Number of cells in C. elegans | 959 | 16:20 |
| Number of neurons in C. elegans | 302 | 16:20 |
| Number of offspring per C. elegans mother | about 250 | 16:20 |
| Generation time of C. elegans | 3 days | 16:20 |
| Generations of offspring behavior affected by changing small RNAs in the nematode brain | all the way to three generations later | 28:17 |
Glossary
- Weismann barrier
- The separation of soma and germline: only germ cells can pass information to the next generation
- C. elegans
- A transparent nematode with a constant cell number and a generation time of only 3 days, a classic model organism
- small RNAs
- Short RNAs that don't encode protein and can recognize and silence sequence-matched genes
- RNA interference
- The mechanism by which double-stranded RNA triggers small RNAs to degrade messenger RNA and shut genes off
- epigenetic reprogramming
- The process in which most chemical modifications are erased and reset in sperm, eggs and the early embryo
How to listen
People working in reproductive health, IVF diagnostics or epigenetics; and biology readers who want to know whether Lamarck was completely wrong.
The three sponsor segments can be skipped.