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-Andrew Huberman: [OPENING THEME
-MUSIC] Welcome to the Huberman Lab
-podcast, where we discuss science and
-science-based tools for everyday life.
-I'm Andrew Huberman, and I'm a Professor
-of Neurobiology and Ophthalmology
-at Stanford School of Medicine.
-Today, my guest is Dr.
-Oded Rechavi.
-Dr.
-Oded Rechavi is a Professor
-of Neurobiology at Tel
-Aviv University in Israel.
-His laboratory studies
-genetic inheritance.
-Now, everybody is familiar with
-genetic inheritance as the idea
-that we inherit genes from our
-parents, and indeed, that is true.
-Many people are also probably now
-aware of the so called epigenome,
-that is, ways in which our environment
-and experiences can change our genome
-and therefore the genes that we
-inherit or pass on to our children.
-What is less known, however, and what
-is discussed today, is the evidence
-that we can actually pass on traits
-that relate to our experiences.
-That's right.
-There is evidence in worms, in flies,
-in mice, and indeed in human beings,
-that memories can indeed be passed
-from one generation to the next.
-And that turns out to be just the
-tip of the iceberg in terms of how
-our parents' experiences, and our
-experiences can be passed on from one
-generation to the next, both in terms
-of modifying the biological circuits of
-the brain and body and the psychological
-consequences of those biological changes.
-During today's episode, Dr.
-Rejave gives us a beautiful
-description of how genetics work.
-So even if you don't have a background
-in biology or science, by the end of
-today's episode, you will understand
-the core elements of genetics
-and the genetic passage of traits
-from one generation to the next.
-In addition, he makes it clear how certain
-experiences can indeed modify our genes
-such that they are passed from our parents
-to us, and even transgenerationally
-across multi generations.
-That is, one generation could
-experience something, and their
-grandchildren would still have genetic
-modifications that reflect those prior
-experiences of their grandparents.
-Dr.
-Rechavi takes us on an incredible
-journey explaining how our genes and
-different patterns of inheritance shape
-our experience of life and who we are.
-Before we begin, I'd like to emphasize
-that this podcast is separate from my
-teaching and research roles at Stanford.
-It is, however, part of my desire and
-effort to bring zero cost to consumer
-information about science and science
-related tools to the general public.
-In keeping with that theme, I'd like to
-thank the sponsors of today's podcast.
-Our first sponsor is Roka.
-Roka makes eyeglasses and sunglasses
-that are the absolute highest quality.
-The company was founded by
-two all-American swimmers from
-Stanford, and everything about
-Roka eyeglasses and sunglasses were
-designed with performance in mind.
-I've spent a lifetime working on the
-biology of the visual system, and I can
-tell you that your visual system has
-to contend with an enormous number of
-challenges in order for you to be able
-to see clearly under any conditions.
-Roka understands this and
-has designed their eyeglasses
-and sunglasses accordingly.
-Originally, Roka eyeglasses and sunglasses
-were designed for sport, that is, for
-things like running and cycling, and many
-of the features they have reflect that.
-So, for instance, they are extremely
-lightweight, they won't slip off
-your face if you get sweaty, and
-they can indeed be worn for running
-and cycling and things of that sort.
-However, they also come in a number
-of different aesthetics and styles
-that make them perfectly suited,
-not just for sport, but also for
-wearing to the office, to work.
-If you'd like to try Roka eyeglasses
-or sunglasses, go to Roka, that's
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-Again, that's Roka, R-O-K-A.com,
-enter the code Huberman at checkout.
-Today's episode is also brought
-to us by HVMN Ketone IQ.
-Ketone IQ is a ketone supplement
-that increases blood ketones.
-And most everybody has heard of
-the so-called ketogenic diet.
-Most people, including myself,
-do not follow a ketogenic diet.
-That does not, however, mean that ketones
-cannot be valuable because ketones are
-one of the primary sources of brain
-fuel and body fuel that allows us to
-think clearly for long durations of
-time and to perform well physically.
-Which is all to say that even if you're
-somebody who's not on a ketogenic diet,
-such as myself, increasing your blood
-ketones can be immensely beneficial
-for cognitive and physical performance.
-Indeed, that's how I use KetoneIQ.
-I'll take one or two servings per
-day typically, sometimes before a
-workout, but most typically before
-doing a bout of cognitive work.
-So I'm going to sit down
-and prepare a podcast.
-or focus on research for my lab or
-a writing project or anything that
-requires a high degree of concentration
-for a prolonged period of time,
-ingesting ketone IQ prior to that, I've
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-If you'd like to try ketone
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-Again, that's hvmn.com/huberman.
-Today's episode is also
-brought to us by Eight Sleep.
-Eight Sleep makes smart mattress
-covers with cooling, heating,
-and sleep tracking capacity.
-So I've talked about many times
-before on the podcast, there's
-a critical relationship between
-sleep and temperature and indeed
-between waking up and temperature.
-That is your body temperature needs
-to decrease by about one to three
-degrees in order for you to fall
-and stay deeply asleep at night.
-And when you wake up in the morning,
-in order to do that feeling refreshed,
-your body temperature actually needs to
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-Again, that's 8sleep.com slash Huberman.
-And now for my discussion with Dr.
-Oded Rechavi . Oded, thank
-you so much for being here.
-Oded Rechavi: Totally my pleasure.
-Andrew Huberman: This podcast has
-a somewhat unusual origin because I
-am familiar with your work, but we
-essentially met on Twitter, where you
-are known for many things, but lately,
-especially, you have been focusing
-not just on the discoveries in your
-laboratory and other laboratories,
-but also sort of meme type humor that
-relates to the scientific process.
-And we'll return to
-this a little bit later.
-But first of all, I think it's wonderful
-that you're so active on social
-media in this positive stance around
-science that also includes humor.
-But today, what I mainly want to talk
-about is the incredible questions
-that you probe in your lab, which
-are highly unusual, incredibly
-significant for each and all of our
-lives, and very controversial, and
-at times even a little bit dangerous
-or morbid, so this is going to be a
-fun one for me and for the audience.
-Just to start off very basically and
-get everyone up to speed, because people
-have different backgrounds, I think most
-people have a general understanding of
-what genes are, what RNA is, and so on.
-But maybe you could explain to people in
-very basic terms, and I'll just preface
-all this by saying that I think most
-people understand that if they have
-two blue eyed parents, that there's a
-higher probability that their offspring
-will have blue eyes than brown eyes.
-Similarly, if two brown eyed parents,
-higher probability that they will have
-brown eyes rather than blue eyes, and
-so on, but that most people generally
-understand and accept that if they spend
-part of their life, let's say, studying
-architecture, that if they have children,
-that there's no real genetic reason
-we should assume that their children
-would somehow be better at architecture
-because they contain the knowledge
-through the DNA of their parents.
-They might be exposed to it in the
-home, so called nature nurture.
-That's nurture in that case,
-but that they wouldn't inherit
-knowledge or other traits.
-And today I'm hoping you can
-explain to us why eye color, but not
-knowledge is thought to be inherited.
-And the huge landscape of interesting
-questions that this opens up,
-including some evidence that, contrary
-to what we might think, certain
-types of knowledge at the level of
-cells and systems can be inherited.
-So that was a very long winded opening.
-But to frame things up, what
-is DNA, what is RNA, and how
-does inheritance really work?
-Oded Rechavi: Okay, so DNA is the
-material, the genetic instructions that
-is contained in every one of our cells.
-We have the set of genes containing
-the entire set, called the genome.
-And this is present in
-every cell of our body.
-The same set of instructions.
-And genes are made of DNA, and
-they also contain chromosomes.
-Chromosomes are the DNA and the proteins
-that condense the DNA, because we have
-a huge amount of DNA in every cell
-that you need to condense it, too.
-Andrew Huberman: Sort of like
-thread on a spool, right?
-Oded Rechavi: Huge amount
-that you have to condense.
-And we have the same genome, the
-same DNA in every cell in our body.
-Andrew Huberman: Can I just interrupt?
-And I'll do that periodically,
-just to make sure that people
-are being carried along.
-I sometimes find that even remarkable,
-that a skin cell and a brain
-cell, a neuron, for instance, very
-different functions, but they all
-contain the full menu of genes.
-And the same menu of genes.
-Oded Rechavi: No, it is amazing.
-It is amazing.
-And perhaps it's good to have an
-analogy to understand how it works.
-So I hope this is not a commercial,
-but 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.
-So in the kitchen, you want things that
-fit the kitchen, and in the toilet,
-you want things that fit the toilet.
-So you only remove one particular
-page of instructions, which is the
-instructions of how to build a chair.
-And this you place in the living room.
-And the toilet, you put in the toilet.
-So the DNA is the instruction
-to make the genome, is the
-instruction to make everything.
-This is the IKEA book.
-And in every cell, we take just the
-instructions to make one particular
-furniture and this is the RNA.
-This is the RNA.
-This is a set.
-And then in the end, you'll build a chair.
-The chair is the protein.
-So the RNA is our instructions to
-make one particular protein based
-on the entire set of possibilities.
-And this is true for one particular type
-of RNA, which won't be the star of this
-conversation, which is messenger RNA.
-This is the RNA that contains the
-information for making proteins.
-In fact, this is just a small
-percent of the RNA in the cell.
-So we have a very big genome,
-and less than 2% of it encodes
-for this messenger RNA.
-However, a lot of the genome
-is transcribed to make RNA
-that does other things.
-Some of these RNAs we understand,
-and many of them we don't.
-Andrew Huberman: It's a beautiful
-description, and IKEA is not a
-sponsor of the podcast, so it's
-totally fair game to use the IKEA
-catalog as the analogy for DNA.
-The specific instructions for
-specific pieces of furniture is the
-RNA, and the furniture pieces being
-the proteins that are essentially
-made from RNA using messenger RNA.
-Oded Rechavi: Correct.
-Andrew Huberman: Okay, thank you for that.
-So, despite the fact that the same
-genes are contained in all the cells
-of the body, there is a difference
-between certain cell types, right?
-Is it fair to say that there was basically
-one very important exception, which
-is somatic cells versus germ cells?
-And would you mind sharing with
-us what that distinction is?
-Oded Rechavi: Sure.
-So, yes, every cell type is different
-because it brings into action
-different genes from the entire
-collection and assumes an identity.
-We have cells in the legs,
-we have cells in the brain.
-We have in the brain.
-We have cells that produce dopamine,
-cells that produce serotonin, and so on.
-And we can make different separation,
-different distinctions, but we can make
-one very important distinction between
-the somatic cells and the germ cells.
-The germ cells are supposed to be
-the only cells that contribute to
-the next generation, out of which
-the next generation will be made.
-So each of us is made just from a
-combination of a sperm and an egg.
-These are two types of germ cells,
-and then they fuse, and you get one
-fertilized egg, and out of this one cell,
-all the rest of the body will develop.
-And what happens in the soma, which are
-all the cells that are not the germ cells,
-should stay in the soma, should not be
-able to contribute to the next generation.
-This is very important and is thought
-to be one of the main barriers for
-the inheritance of acquired traits,
-the inheritance of memory and so on.
-Because, for example, like the example
-that you gave with learning architecture,
-if I learn about architecture, the
-information is encoded in my brain.
-And since my brain cells can't transfer
-information to the sperm and the egg,
-because the information is supposed
-to reside in synaptic connections
-between different neurons in a
-particular circuit that developed.
-So, what happens is the brain shouldn't be
-able to transfer to the next generation.
-Even simpler, a simpler example,
-if you go to the gym and you build
-up muscles, you know that your kids
-will have to work out on their own.
-This shortcut won't happen.
-This is something that we know
-intuitively, even if we don't
-have any background in biology.
-And this is connected to the fact
-that, as we said at the beginning,
-every cell in the body has its own
-genome and the next generation will
-only form from the combination of
-the genomes in the sperm and the egg.
-Even if you somehow acquire the mutation
-or a change in your DNA in one particular
-brain cell, it wouldn't matter, because
-this mutation, there's no way to transfer
-it to the DNA of the germ cells that
-will contribute to the next generation.
-Andrew Huberman: So despite that, there
-is, as you will tell us, some evidence for
-inheritance of experience, let's call it.
-And here we have to be
-careful with the language.
-I just want to put a big asterisk and
-underline and highlight that the language
-around what we're about to talk about
-is both confusing and at the same time
-fairly simple and controversial, right?
-It's a little bit like in the field of
-longevity, people sometimes will say
-anti-aging, some people say longevity.
-The anti-aging folks feel that longevity
-is more about longevity clinics.
-They don't like that anti-aging is
-related to some other kind of niche
-clinics, sometimes FDA approved or
-government approved, sometimes not.
-And so there's a lot of argument
-about the naming, but it's all about
-living longer and living healthier.
-In this field of acquiring traits or
-the passage of information to offspring,
-what is the proper language to refer
-to what we're about to discuss?
-There is this idea, and I'll say it so
-that you don't have to, that dates back
-to Lamarck and Lamarckian evolution.
-Very controversial, right?
-And maybe not even controversial.
-I think it's very offensive
-even to certain people.
-This idea of inheritance of acquired
-traits, the idea that one could change
-themselves through some activity, let's
-use the example of going to the gym.
-We could also use the example of somebody
-who becomes an endurance runner, then
-decides to have children within another
-endurance runner, and has in mind the
-idea that because they did all this
-running and not just because they were
-biased towards running in the first
-place, but because of the distance
-they actually ran, that their offspring
-somehow would be fabulous runners.
-Okay, this Lamarckian concept
-is, we believe, wrong.
-So how do we talk about
-inheritance of acquired traits?
-What's the proper language for
-us to frame this discussion?
-Oded Rechavi: Right.
-We have to be very careful, as
-you said, and there are many
-complications and many ambiguities.
-Andrew Huberman: And maybe you could
-tell us why Lamarckian evolution,
-for those that don't know, is
-such a stained thing, r ight?
-I t's not polite.
-Oded Rechavi: Right.
-Perhaps we'll start with, just say
-that we can talk about inheritance
-of acquired traits, transmission
-of parental responses, inheritance
-of memory, all of these things.
-And we can also talk about epigenetics
-and transgenerational epigenetics
-and intergenerational epigenetics.
-There are many terms that we need
-to make clear for the audience.
-The reason that is so toxic or
-controversial is very complicated,
-and it goes a long time back,
-even way before Lamarck.
-So even the Greeks talked
-about inheritance acquired.
-Lamarck is associated with the term, but
-it's probably a mistake, although everyone
-talks about including people who studied.
-So Lamarck worked, he published his
-book a little more than 200 years ago.
-And he believed in the
-inheritance of acquired traits.
-Absolutely.
-But just like anyone else in his
-time, just everyone believed in it.
-It seemed obvious to them.
-It was long before Mendel and
-the rules of genetic inheritance.
-And also Mendel was long before
-the understanding that DNA
-is the heritable material.
-So this happened a long time ago.
-Everyone believed in it, including Darwin.
-Darwin was perhaps more
-Lamarckian than Lamarck.
-Andrew Huberman: Really?
-Oded Rechavi: Yes, absolutely.
-Andrew Huberman: All right, now
-we're getting into the meat of it.
-Oded Rechavi: And this is in The Origin of
-the Species . It's in all of his writings.
-Lamarck didn't even really make the
-distinction between the generations.
-He had many other reasons for being wrong,
-but he connected the terms inheritance
-of acquired traits to evolution.
-And this is some of the reasons that he
-was very controversial, even in his time.
-There were other reasons.
-For example, he rejected current day
-chemistry and thought that he could
-explain everything based on Aristotelian
-fluids; earth, wind, fire and water.
-Andrew Huberman: There's still some
-people on the Internet that think they can
-discard chemistry and explain everything
-based on earth, wind, fire, and water.
-Oded Rechavi: And this wasn't
-only biology, it was also
-the weather and everything.
-So that was part of the reason Lamarck
-made many mistakes, but he did have a
-full tier of inheritance, which was a
-big step towards where we are today.
-So he had important contributions
-nevertheless, although he was
-mistaken about the mechanism.
-What he believed, like everyone
-else, drives evolution, is the
-transmission of the traits that
-you acquire during your life or
-the things that you do or don't do.
-We talked about use and disuse
-of certain organs that shape our
-organs and eventually also the
-organs of the next generation.
-Andrew Huberman: He sounds
-a little bit like the first
-self-help public figure, right?
-Well, this mean, this is heavily
-embedded into a lot of the health and
-fitness space on Twitter and Instagram
-and on the Internet, which is that,
-it's the idea that we're sold very
-early in life, at least here in the
-United States and probably elsewhere,
-which is that we can become anything
-that we want to become and that that
-will forever change the offspring,
-either because of nature or nurture.
-Oded Rechavi: Right.
-And this is a very dangerous
-idea, as I'll explain in a second.
-And it led to horrible things.
-This is part of the reason
-that this is such a taboo.
-It's not only self-help you're
-helping, or this helping yourself.
-The problem is when you apply to others.
-And this happened in a very, very
-dramatic and horrible way in the
-recent past, as I'll tell in a second.
-So Lamarck, this is what he
-believed and he thought this
-is how evolution progressed.
-And later Darwin showed that
-it's really natural selection.
-The selecting of the organisms that
-already contain the particular qualities
-are selected based on whether they survive
-or not in particular environments, and
-therefore their evolution progresses,
-they are more common and take over.
-This is very different.
-Two different explanations.
-The most common way this is contrasted
-is the neck of the giraffes.
-This is a classic example.
-According to Lamarck, the giraffes
-had to stretch their necks towards the
-trees to eat when the trees were high.
-And because of that, they transmitted
-these traits, long necks, to their
-children, who also had long necks.
-By the way, he only mentioned
-this example a handful of times,
-he didn't really focus on that.
-And according to Darwin, just a
-giraffe that happened to be born with
-a long neck survived because it ate.
-So its genetic, heritable materials
-didn't know about genetics, but take over.
-And the rest of the giraffes that have
-different heritable materials just die.
-So this is natural selection versus
-inheritance for acquired traits.
-So this is natural selection versus
-inheritance for acquired traits.
-There are many reasons why Lamarckism
-and inheritance for acquired
-traits became such a bad term.
-One of the biggest is what happened
-in the Soviet Union under Stalin.
-There was a scientist named Lysenko, who
-thought that Mendelism, normal genetics,
-is bourgeois science, shouldn't be done.
-And whoever did normal genetics was
-either killed or sent to Siberia.
-And he thought that, just like you said,
-not only we can become everything that
-we want, but we can grow everything that
-we want in every field, can take a frozen
-field and grow potatoes there and so on.
-And this led to massive starvation, ruined
-agriculture in the Soviet Union, also
-ruined science for many, many years, and
-put a very dark cloud on the entire field.
-And only probably in the 80s
-or something like this, the
-field started to recuperate.
-For that aside, for that, which is a
-very dramatic thing, there were also
-crazy stories around, and attempts to
-prove the inheritance of acquired traits.
-Despite the realization of many
-scientists, this is something that
-is very rare, or that normally
-doesn't happen, that is not a
-normal way that inheritance works.
-And I can tell you about two such
-dramatic cases that will illustrate it.
-Andrew Huberman: Yeah, please.
-Oded Rechavi: So, in the beginning
-of the 20th century, in Vienna, there
-was a researcher called Paul Kammerer,
-who was a very famous and also very
-colorful figure, who did experiments
-on many different types of animals.
-He did experiments on toads
-that are called the midwife toad
-because the male carries the eggs.
-And there's a beautiful book
-about it from Koestler, telling
-the story of what happened there.
-And there are a couple of types of toads.
-Some of them live underwater
-and some of them live on land.
-And these toads are different in
-their shape and in their behavior.
-So, of course, the capacity to live
-underwater is one thing, but also their
-morphology and appearance changes.
-The toads that live underwater develop
-these nuptial pads, these black pads
-on their hands that allow the males to
-grab onto the female without slipping.
-Andrew Huberman: For mating.
-Oded Rechavi: For mating.
-And the ones on land don't have them.
-He claimed that he can take the toads and
-train them to live underwater, changing
-the temperature and all kinds of things.
-It's a very difficult animal to work with.
-Eventually, according to Kammerer,
-they will acquire the capacity to
-live underwater and also change
-their physiology and develop these
-black nuptial pads on their hands.
-With this discovery, he traveled
-the world, became very famous.
-This was in just the beginning of the
-previous century, as the person who found
-the proof for inheritance of acquired
-traits, despite the controversy and so on.
-In the beginning of the realization of
-how it actually works with DNA and so on,
-not with DNA, but with natural selection.
-DNA came later and people
-didn't believe him.
-He was actually under a lot of attacks,
-but it seemed convincing at the end.
-What happens is that they found
-that he injected ink to the
-toads to make them become black.
-To have these nuptial pads.
-So he faked the results, and he couldn't
-stand the accusations and killed himself.
-Andrew Huberman: Wow.
-Oded Rechavi: In this book by
-Koestler , it suggests maybe it
-was the assistant who did it.
-Andrew Huberman: Who killed?
-Oded Rechavi: No, no.
-Who injected it to sort
-of save him from failure.
-Because the samples lost the
-coloring or something like that.
-So it might be.
-Who knows what happened?
-Andrew Huberman: Well, in science,
-whenever there's a fraud accusation
-or controversy, it's not uncommon
-to see a passing of responsibility.
-Oded Rechavi: Right.
-Andrew Huberman: There are recent
-cases, there are ongoing cases now where
-it's a question of who did what, etc.
-Actually, I have two questions.
-Before the second story, I'm struck by the
-idea that he was traveling and talking.
-I'm guessing this was before
-PowerPoint and Keynote, but also before
-transparencies, which actually were still
-in place when I was a graduate student.
-For those of you who don't know,
-transparencies are basically transparent
-pieces of plastic paper that you put
-onto a projector, and then you can write
-on them and do demonstrations, but can
-show photographs and things like that.
-So how was he giving these talks,
-and would he travel with the toads?
-Oded Rechavi: So he
-traveled with the samples.
-Andrew Huberman: I see.
-Oded Rechavi: And I'm basing this
-on this Koestler book, which is,
-on its own, very controversial.
-It's more of a beautiful
-story than perhaps the truth.
-And according to the story there,
-he had to stand on one side of the
-lecture hall with his hands behind his
-back while others would examine the
-samples and pass them around and so on.
-Andrew Huberman: But he cheated.
-Someone cheated.
-Oded Rechavi: He probably did.
-At least that's what most people think.
-But this wasn't replicated.
-I mean, also, I don't think
-anyone tried to replicate it.
-Andrew Huberman: Interesting.
-This is just a point about replication.
-And actually, another tragic example,
-not but a few years ago, Sasai, who,
-as far as we knew, was doing very
-accomplished work on the growth of
-retinas, literally growing eyes in a dish.
-I think everyone believes that result.
-But then there were some accusations
-about another result that turned out to
-be fraudulent, and Sasai killed himself.
-This was only about
-maybe five, 10 years ago.
-So it still happens.
-Oded Rechavi: Yeah, it happens.
-I think it's rare, but it does
-happen, especially in this
-very high profile situation.
-Andrew Huberman: I would argue.
-I'd love to know what your number
-is, but I would argue that 99% of
-scientists are seeking truth and
-are well meaning, honest people.
-Oded Rechavi: I totally agree.
-And I think that even when people are
-wrong, it's mostly not because they're
-evil and trying to act inflated.
-Maybe they don't really want to believe
-the results, or there are all kinds
-of ways to be wrong and even to bend
-the truth without just blatant fraud.
-But this is, according to the
-story, an example of very bad fraud,
-which, I agree, is rare because most
-scientists, as you said, this is
-also my opinion, are just trying to
-discover truth and do the best they can.
-Andrew Huberman: Well, why
-else would you go into it?
-Because it's certainly not a profession
-to go into if you want to get rich.
-Oded Rechavi: Not for the money.
-Andrew Huberman: And it's probably
-not even a profession to go
-into if you want to get famous.
-If you want to be famous, you
-should go to Hollywood or become
-a serial killer because they'll
-make specials about please don't.
-But please don't do either.
-No, Hollywood, I suppose for some
-is fine, but in any case, okay,
-so Kammerer, around 1907, 1906?
-Oded Rechavi: This is slightly
-before the controversy broke
-out after the First World War.
-Andrew Huberman: Okay, yeah, great.
-Kammerer is gone.
-His toads with their either ink
-or whatever nuptial pads they
-have to go back to mating on land.
-I'd like to take a quick break
-and acknowledge one of our
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-Oded Rechavi: Yeah,
-okay, forget about that.
-We also had the Lysenko episode.
-That's a very big thing.
-And then in the US, there was the
-researcher named McConnell, who
-did very different experiments.
-And he was also a character.
-So he was the joker type of thing.
-And he published many of his results
-in a journal that he published
-that was called Worms Breeders
-Gazette and had many cartoons.
-Andrew Huberman: And so he
-started his own journal.
-Yes, that's one way to publish a lot.
-Oded Rechavi: But he also published in
-very respected journals in parallel.
-He was a psychologist, an American
-psychologist, and he worked on
-a worm, which is a flatworm,
-which is called Planaria.
-This is very interesting.
-This is different from what we'll
-discuss today, a different type of worm.
-You know, worms are very common.
-So four out of five animals
-on this planet is a worm.
-Andrew Huberman: Really?
-Oded Rechavi: Yes, numerically,
-if you just count the individuals.
-So we are the exception.
-But I'll talk about a
-very different worm later.
-This is a flatworm.
-This is called planaria, and
-it is remarkable in many ways.
-It was also a model that many
-people worked on, including the
-fathers of genetics, that people
-who started genetics, like Morgan,
-they worked on it in the beginning.
-But it's very, very hard to study
-genetics in this worm, because
-unlike us, unlike what we explained
-before about how we all develop from
-sperm and egg, these worms most of
-the time reproduce just by fission.
-They tear themselves apart.
-So they have a head and a tail.
-And the part of the head will
-just tear itself apart from
-the tail, grow a new one.
-The head will grow a new tail,
-the tail will grow a new head.
-You can even cut them into 200 pieces.
-Each piece will grow into a new worm.
-Andrew Huberman: Wow!
-Oded Rechavi: And they have centralized
-brains with lobes and everything,
-and even these degenerate eyes.
-He studied these worms and he said
-that he can teach them certain things,
-associations, by pairing them all, I
-don't remember exactly what he did.
-I think it was either lights or
-electricity to shock them, which
-shocked them with other things.
-And he could train them to learn
-and remember particular things.
-Andrew Huberman: Like they might
-get shocked on one side of the tank.
-Oded Rechavi: Exactly.
-Andrew Huberman: And then
-avoid that side of the tank.
-Oded Rechavi: Yes.
-Andrew Huberman: And then I guess
-the question is whether or not
-their ripped apart selves and their
-subsequent generations will know to
-avoid that side of the tank without
-having ever been exposed to the shock.
-Oded Rechavi: Right.
-So without ever being exposed to the
-shock or whether the new generation, the
-new head will be able to learn faster.
-That's another.
-The subtlety that might happen.
-Okay.
-And this is what he said happened.
-He said he can teach them certain
-things, remove, cut off their heads and
-new heads with all the brain will grow
-and that it will contain the memory.
-This was the start of the controversy.
-Not the end of it, only the beginning.
-Then he said something even much
-wilder, which is he can train them
-to learn certain things and then
-just chop them up, put them in a
-blender and feed them to other worms.
-Because they are cannibalistic, they
-eat each other and that the memory
-will transfer through feeding.
-Andrew Huberman: This sounds
-like such a dramatic field.
-Oded Rechavi: And by the
-way, this opened the field.
-So people did experiments not only in
-planaria, but in goldfish and certain
-rodents, and did these memory brain
-transfer assays, implanting brain.
-And this is back when they had an
-idea that some memories could be
-molecular, could have a molecular
-form, which is very appealing.
-It's almost like science fiction.
-You can have a memory in a tube, unlike
-the way we think about memory normally,
-which is something that is distributed
-in neuronal circuits and encoded in the
-strength of particular synapses and so on.
-But the idea that you can take a memory
-and reduce it into a molecule and transfer
-it around is very, very interesting.
-So this is why it
-attracted so many people.
-This ended up in a catastrophe.
-So there was an NIH investigation.
-No one could replicate anything.
-It was a big mess, although there
-were always scientists who said,
-yes, we can replicate this and this.
-So they were in the background.
-The McConnell stuff was different.
-Again, people thought that there
-are problems replicating, but it
-wasn't necessarily, but some people
-replicate, but it wasn't necessarily
-about replicating the whole thing.
-But the question was the memory, the
-transfer, specific, or is it an overall
-sensitization that transmits and so on?
-Andrew Huberman: Right.
-Like you could imagine that what gets
-transmitted is a hypersensitivity
-to electricity, as opposed to
-the specific location that the
-electricity was introduced.
-Oded Rechavi: Or even more than
-that, even just a hypersensitivity.
-In general, you're more vigilant
-and you'll learn anything faster.
-That's also a possibility.
-But his problem wasn't the accusation.
-It was much worse that he was
-targeted by the Unabomber, this
-terrorist who sent letters with bombs
-to many scientists for 15 years.
-And his assistant, again it is
-the assistant, I think, exploded.
-And this is how his line of research
-ended just recently, a few years ago, a
-researcher from Boston, Mike Levin, and
-his postdoc, [inaudible] , replicated
-some of McConnell's experiment with
-the cutting of the head, but using very
-fancy equipment and automated tracking.
-And they could say that they can
-replicate some of his experiments.
-Andrew Huberman: Really?
-And they don't open
-packages in that laboratory.
-Oded Rechavi: [LAUGHS] They
-have interesting stories.
-You should have Mike over.
-Andrew Huberman: Yeah, I'm
-familiar with a bit of his work.
-I didn't realize they
-had done that experiment.
-Oded Rechavi: They published
-it a few years ago.
-And this is very interesting, but of
-course, they don't know how it happens.
-The mechanism is unclear.
-McConnell went a step further than
-this, and what's fascinating is
-that these are experiments that
-were done in the 70s and 80s.
-He said that he can not only transfer
-the memories through chopped animals, but
-he can take the animals that learned and
-break it down into different fractions.
-So just the DNA, just the RNA, just
-the fats, the proteins, the sugars.
-And he said that the fraction that
-transmits the memory is the RNA.
-And this is very, very interesting
-because it was a long time before
-everything that we know about RNA today.
-I'll soon go into my research, explain
-what we do, and then you'll see that
-you can actually feed worms with
-RNA and have many things happen.
-This is, everyone knows this is true.
-Okay, so this is why it was so appealing
-to go back to that and study it.
-By the way, at the time it
-became popular knowledge.
-Everyone knew these experiments.
-There's a Star Trek
-episode about it from '84.
-There are comics, books
-about it, books about it.
-And people were eating RNA because they
-thought that there was RNA in memory.
-This was, of course, complete
-nonsense, but it made a lot of
-noise in these years, which is
-part of the reason it was so toxic.
-Until recently, you couldn't
-touch it because it was considered
-pseudoscience, like Lysenko,
-like Kammerer, and all of this.
-So this was just something you
-didn't want to touch at all.
-And then we go back to these studies
-about inheritance of memory or
-inheritance of acquired traits in
-other organisms, in mammals, in humans.
-And aside from the dark cloud that
-these episodes left, there were also
-theoretical problems of why this
-can't happen, barriers that have
-to be breached for this to happen.
-And you can talk about many different
-types of barriers, and you can also
-narrow it down to two main barriers.
-First barrier, we mentioned it.
-This is the separation of
-the soma from the germline.
-Andrew Huberman: Right.
-The somatic cells, they can
-change in response to experience.
-The sperm and the egg, the
-so-called germ cells cannot.
-That's the idea.
-Oded Rechavi: Or they are isolated
-from what happens in the soma.
-Okay.
-The man who first thought about this
-barrier is called Wiseman, August Wiseman.
-This was in the 19th century, so it
-is called today the Wiseman Barrier,
-separation of the soma from the germline.
-Only the germline transmits
-information to the next generation.
-And this is also called
-the second law of biology.
-So this is very, very fundamental.
-So natural selection is the first
-one, this is the second one,
-because it's so important to how
-we work, to how our bodies work.
-Wiseman, by the way, thought that
-if you will have direct influence
-of the environment on the germ
-cells, then perhaps this could
-transfer to the next generation.
-So he wasn't as strict
-as his barriers suggest.
-But this is not how
-most people remember it.
-But he thought that this was unnecessary.
-It's possible that natural
-selection can explain everything.
-And he compared it to a boat,
-which is in the ocean, it is
-sailing and it has a sail open.
-So you don't have to assume
-that it has an engine.
-The wind is blowing.
-You don't have to assume other things.
-The natural selection might be enough.
-So this barrier is still
-standing, but not entirely.
-It is breached in some organisms.
-We'll go into that in a second.
-The other barrier is now we have
-to understand the other barrier.
-We have to talk about epigenetics.
-We have to define
-epigenetics and what it is.
-And epigenetics is another term
-which people misuse horribly and say
-about everything that is epigenetics.
-Even people from the fields.
-The word itself, that the
-term was defined in the 40s by
-Weddington, Conrad Weddington.
-And he talked about the interactions
-between genes and their products
-that, in the end, bring about the
-phenotype of the consequences and
-how genes influence development.
-Later, people discovered mechanisms
-that change the action of genes.
-There are different mechanisms and started
-talking about these as epigenetics.
-For example, DNA is built
-out of four basic elements.
-These are the A,T, G, and C, and
-they can be chemically modified.
-So in addition to just the information
-that you have in the sequence of the
-DNA, you also have the information
-in the modification of the bases.
-The most common modification that
-has been studied more than others is
-modification of the letter C of cytosine
-methylation, the addition of a metal group
-to this C, and this can be replicated.
-So after the cells divide and replicate
-their genetic material, in certain cases
-also, these chemical modifications can be
-added on and replicate and be preserved.
-Andrew Huberman: For those who
-aren't as familiar with thinking
-about genes and gene structure and
-epigenetics, could we think of these?
-You mentioned the four nucleotide bases,
-C, G, A, T, but could we imagine that
-through things like methylation, it's
-sort of like taking the primary colors
-and changing one of them a little
-bit, changing the hue just slightly,
-which then opens up an enormous number
-of new options of color integration.
-Oded Rechavi: It's just more
-combinations, more ways, more information.
-There are the modifications of the DNA,
-and also there are the modifications
-of the proteins which condense
-the DNA that are called histones.
-So they are also modified
-by many different chemicals.
-Again, methylation is a
-very common modification.
-Acetylation, even serotonin,
-serotoninlation of histones.
-Andrew Huberman: Serotonin, right.
-Oded Rechavi: This is a
-new paper from nature.
-Andrew Huberman: From a
-few years ago, can change.
-Oded Rechavi: DNA, not the DNA
-itself, but the protein that
-condenses it, essentially.
-Andrew Huberman: How, in the analogy
-I used before, of how the thread is
-wrapped around the spool, essentially?
-Oded Rechavi: Yes, a nd this determines
-the degree of condensation of the
-DNA, whether the gene is now more or
-less accessible, and therefore can
-perhaps be expressed more or less.
-This is one way to affect
-the gene expression and bring
-about the function of the gene.
-There are many additional
-ways, not the only one.
-So then, when all of this was starting
-to be elucidated, people talked
-about epigenetics, they started
-talking about these modifications,
-forgot the original definition.
-And when people said epigenetics,
-they talk about methylation
-and things like that.
-Andrew Huberman: And again, to just
-frame this up so we could imagine two
-identical twins, so called monozygotic
-twins, we could go a step further and
-say that they're monochorionic and they
-were in the same placental sac, because
-twins can be raised in separate Sacs,
-slightly different early environments.
-Let's say those two twins
-are raised separately.
-One experiences certain things, the other
-things, they eat different foods, etc.
-And there is the possibility, through
-epigenetic mechanisms, that through
-methylation, acetylation, serotonin
-production, etc., that the expression of
-certain genes in one of the twins could be
-amplified relative to the other, correct?
-Oded Rechavi: Yeah.
-So we know that even totally
-identical twins, genetically,
-they're identical, but they look
-different, and they are different.
-We all experience it.
-And this can happen because of these
-epigenetic changes, or it can happen
-because of other mechanisms, because
-genes respond to the environment.
-Genes don't exist in a vacuum.
-Genes need to be activated by
-transcription factors, and there's a
-lot of machinery that is responsible
-for making genes function.
-So we are a combination of our
-genetic material and the environment.
-So when people talk about epigenetics
-and talk just about the modification,
-they're also not exactly right.
-My definition of epigenetics is
-inheritance, which occurs either across
-cell division or more interestingly, also
-for this podcast, now across generations,
-not because of changes to the DNA
-sequence, but through other mechanisms.
-I think this is the most robust
-definition that allows you to
-understand what you're talking about.
-And then the question is, if this happens,
-then what are the molecules that actually
-transmit information across generations?
-Are they these chemical
-modifications to the DNA or to the
-proteins that condense the DNA?
-Or are there other agents that
-transmit the information and
-which molecules can do it?
-And I actually think that
-the most interesting players
-today are RNA molecules.
-But before I go into that, I just want
-to say that when we talk about the
-barriers to epigenetic inheritance or
-the barriers to inheritance of acquired
-traits, in addition to the separation
-of the soma from the germline that
-we discussed, the other main barrier,
-it's called epigenetic reprogramming,
-which is that we acquired our cells.
-The genetic material in our cells acquires
-all kinds of changes, these chemical
-changes, modifications we discussed.
-But these modifications are largely erased
-in the transition between generations.
-So, in the germline, in the sperm and
-the egg, and also in the early embryo,
-most of the modifications are removed.
-So we can start a blank slate
-based on the genetic instructions.
-And this is crucial.
-Otherwise, according to the theory, it's
-not clear that's actually true, because in
-some organisms it doesn't really happen.
-We will not develop according to the
-species typical genetic instructions.
-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, some remain,
-which could be interesting.
-Andrew Huberman: So the idea, if I
-understand correctly, is that there's
-some advantage to wiping the slate clean
-and returning to the original plan.
-In the context of the IKEA
-furniture analogy, the instruction
-book is the one that's issued to
-everybody or every cell, right?
-Only certain instructions are used for
-certain cells, say a skin cell or a neuron
-or a liver cell or any other cell for
-that matter, through the course of the
-lifespan of the organism, those specific
-instructions are adjusted somewhat.
-Okay, so maybe like IKEA furniture,
-sometimes they sent you seven, not eight,
-of particular screws, or they sent you
-the proper number, but you put them in
-the wrong place and it sort of changes the
-way that the thing works a little bit once
-that, assuming furniture could reproduce.
-But here in the analogy of the
-furniture as the cell or the organ
-in it mates with another organism
-that needs to be replicated.
-And so the idea is to take the
-instruction, but go through and erase
-all the pen and pencil marks, erase all
-those additional little modifications that
-the owner used or introduced to it, and
-return to the original instruction, right?
-Oded Rechavi: Because if you want
-to bring back the instruction
-book, you want it to have all the
-potential to make all the furniture.
-You don't want it to be restricted to the
-ones that you made in a particular room.
-Andrew Huberman: So it's essentially
-the opposite of acquired traits
-and characteristics, based on
-what we say in biology, geek
-speak, lineage based experience.
-But what your parents experience.
-Right.
-In some ways, we want to
-eliminate all that and go back
-to just the genes they provided.
-Oded Rechavi: Yes, but
-it's more complicated.
-It's more complicated than that
-because we have some very striking
-examples, even in mammals, where
-some of the marks are maintained.
-For example, the classic
-example is imprinting.
-Imprinting is a very
-interesting phenomenon.
-The way DNA works is that you inherit
-a copy for every chromosome from your
-mother and your father, and then you have
-in every cell of your body, two copies,
-if you're a human, of every chromosome.
-So every gene is represented twice.
-These are called alleles, the
-different versions of the genes.
-And the thought is that, in the
-next generation, the two copies
-that you inherited are equal.
-It doesn't matter whether you acquire
-them from your mother or from your father.
-There are some situations
-where it does matter.
-There is a limited number of genes
-that are called imprinted genes, where
-it does matter whether you inherited
-from your mother or your father.
-And this is happening through epigenetic
-inheritance, not because of changes
-to the DNA sequence, but because
-of maintenance of these chemical
-modifications across generations.
-Andrew Huberman: And as I recall from
-the beautiful work of Catherine Dulac
-at Harvard, that, especially in the
-brain, there is evidence that some
-cells contain the complete genome from
-mom or the complete genome from dad.
-Oded Rechavi: And it can
-also switch during your life.
-So her work showed that early on in
-your life, it's different whether
-you express the maternal or paternal
-copy than when you're more mature.
-Andrew Huberman: So parents
-and children take note.
-For those of you that are saying, oh,
-the child is more like you or more like
-me, that can change across the lifespan.
-And if you're thinking about your
-parental lineage and wondering
-whether or not you "inherited" some
-sort of trait from mother or from
-father, it can be, of course, both.
-Or it can be just one or just
-the other, which I think most
-parents tend to see and describe in
-their children from time to time.
-That's just like the father, or that's
-just like the mother, for instance.
-Oded Rechavi: Right.
-But it's important to know that in this
-situation, the environment played no role.
-This was just whether it passed
-to the mother or the father.
-It's not that something that happened to
-the mother or the father affected this.
-So this is slightly different.
-The question is now, can the environment
-change the heritable material?
-So it's very important to understand
-that there is a difference
-between nurture and nature.
-And this is very confusing,
-and people are confused.
-It's a little subtle.
-So, for example, people tell
-me, I'm growing horses for many
-years, and I just know that this
-horse has a particular character.
-It's very different
-from the other horsess.
-And so this is epigenetic inheritance?
-No, it could be just
-genetically determined.
-Yes.
-This horse inherited a different
-set of genetic instructions.
-So it is different.
-Doesn't have to be about epigenetics.
-Epigenetic inheritance means that
-the environment of the parents
-somehow change the children.
-And there are these two main barriers
-that are serious bottlenecks that
-we have to think about what type of
-molecule and how they can be breached.
-So one possibility is that it's
-really this limited number of
-chemical modifications that
-survive, which is about 10% or so.
-That could be very interesting.
-Andrew Huberman: Not a small number?
-Oded Rechavi: Not a small number.
-But perhaps.
-Perhaps.
-Okay, this is one possibility.
-The other possibility is that
-there are other mechanisms.
-The situation now in humans is that it's
-just really unclear what transmits, if it
-can transmit, and which molecule does it.
-We'll talk later about other organisms
-where it is a lot more clear.
-But in humans and in mammals in
-general, there are many examples of
-environments that change the children.
-Whether you need to invoke an
-epigenetic mechanism to explain
-this phenomena, this is unclear.
-First of all, because it's
-hard to separate nature from
-nurture, and second, because the
-mechanism is just not understood.
-So there are classic examples for humans,
-there were periods of famine, starvation
-in different places in the world.
-In the Netherlands, in China,
-in Russia, where people did huge
-epidemiological study to study the next
-generations and saw that the children
-of women who were starved during
-pregnancy are different in many ways.
-They have different birth weight,
-glucose sensitivity, and also some
-neurological, higher chances of
-getting some neurological diseases.
-And this has been shown
-in very large studies.
-Andrew Huberman: Is there ever an
-instance in which starvation or
-hardship of some kind, some challenge,
-sensory challenge or survival based
-challenge led to adaptive traits?
-Oded Rechavi: Yes, there are.
-In different organisms, it could
-be as a result of a trade off.
-So there could be a downside as well.
-But, for example, there are two
-examples that come into mind.
-One of them is that if you stress
-male mice or rats, I don't remember.
-This is the work of Isabel
-Mansuy in the ETH in Switzerland.
-If you stress the males, you can
-do it in many different ways.
-I don't remember exactly how they
-did, but you can separate them
-from their mothers, you can do
-social defeat, all kinds of things.
-Then the next generations are less
-stressed, they show less anxiety.
-Andrew Huberman: So the
-threshold for stress is higher?
-Oded Rechavi: Yes.
-However, I think they have memory
-deficits and other metabolic problems.
-Andrew Huberman: Which may be a n
-advantage for dealing with stress.
-Oded Rechavi: Could be.
-Andrew Huberman: I don't have
-any direct evidence of that.
-But there's some simmering ideas that
-our ability to anchor our thoughts
-in the past, present or future seems
-very adaptive in certain contexts.
-In other contexts, it can keep
-us ruminating and not adaptively
-present to our current challenges.
-Oded Rechavi: Another example
-is that of nicotine exposure.
-This is, I think, the work of Oliver
-Rando from UMass, if I'm not mistaken.
-These are not my studies, but they
-improve the tolerance to exposure to
-similar drugs in the next generation.
-The interesting thing here is
-that it's very non-specific.
-So you treat them with nicotine,
-but then in the next generation they
-are more tolerant to nicotine, but
-also to others, I think cocaine.
-Andrew Huberman: That sort of makes
-sense to me, because obviously nicotine
-activates the cholinergic system, the
-dopaminergic system, epinephrine, etc.
-And you can imagine that there's
-crossover because other drugs
-like cocaine, amphetamine, mainly
-target the catecholamines, the
-dopamine and norepinephrine.
-Oded Rechavi: In this particular
-study, if I remember correctly, they
-show that this happens, this heritable
-effect, even if you use an antagonist
-to block the nicotine receptor.
-Andrew Huberman: Wow.
-Oded Rechavi: So it's something
-more about clearance of xenobiotics
-and hepatic functions that is
-transmitted and is very nonspecific.
-Andrew Huberman: What I love about
-all the examples you've given today,
-especially that one, is, and I hope that
-people, if you're just listening, I'm
-smiling, because biology is so cryptic
-sometimes the obvious mechanism is
-rarely the one that's actually at play.
-And people always ask,
-well, why is it like this?
-And I always say, the one thing
-I know for sure is that I wasn't
-consulted at the design phase.
-And if anyone claims they were, then you
-definitely want to back away very fast.
-Oded Rechavi: And there
-could be so many trade offs.
-So many trade offs.
-So, for example, we studied, and also
-many other people studied effects.
-These are in worms.
-We'll go deep into that in a second.
-But that shows that when you starve
-them, the next generations live longer.
-And this, I think, could be a trade
-off with other things like fertility.
-So the next generations are
-more sick and less fertile.
-And perhaps because of
-that they live longer.
-So it's not necessarily a good thing.
-Andrew Huberman: I don't want to
-draw you off course, because this
-is magnificent, what you're doing
-and splaying out for us here.
-But do you recall there was a few years
-ago, it actually ended very tragically.
-It was an example, I think it
-was, down in San Diego county,
-there was a cult of sorts that
-were interested in living forever.
-And so the males castrated themselves
-in the idea that somehow maintaining
-some pre-pubescent state or reverting
-to a pseudo pre-pubescent state
-would somehow extend longevity.
-The idea that sexual behavior
-somehow limited lifespan.
-This has been an idea that's
-been thrown around in the kind of
-more wacky longevity communities.
-They also shaved their heads.
-They also all wore the same sneakers.
-But then they also all committed
-suicide, right, as the Halle-Bopp
-comet came through town.
-But that's just, but one example
-of many cults aimed at sort of that
-obviously was not life extension,
-that was life truncation, but aimed
-at a kind of eternal life or some
-sort of through caloric restriction.
-That's right, this cult also was very
-into the whole idea that through caloric
-restriction, we can live much longer,
-which may actually turn out to be true.
-I think it's still debated, hence all the
-debate about intermittent fasting, etc.
-But also it is known that if
-you overeat, you shorten life.
-This is clear.
-It's known that big bodied members
-of a species live far shorter lives
-than the smaller members of a great
-Dane versus a Chihuahua, for instance.
-So there is some sort of, shard
-of truths in all of these things.
-But it seems to me that the real question
-is, what is the real mechanism and
-why would something like this exist?
-Oded Rechavi: Right.
-Andrew Huberman: And why?
-Questions are very dangerous in biology.
-Oded Rechavi: Right, right.
-But very interesting also, when it comes
-to metabolic changes and nutrition,
-there are numerous examples where
-you either overfeed or starve and
-get effects in the next generations.
-Sometimes the effects contrast
-depending on the way you do this.
-Again, we don't do any of that in
-mammals, but people show that starving
-or overfeeding the mothers or the
-fathers changes the body weight of the
-next generation and also the glucose
-tolerance and also reproductive success.
-And so the fact that there's an effect
-that something transmits, this is clear.
-The question is, how miraculous is it?
-And whether you need new biology
-and epigenetics to explain it.
-What do I mean by that?
-If you affect the next generation,
-it doesn't necessarily have to go
-through the oöcyte or the sperm, and
-involves the epigenome, you change the
-metabolism of the animal as it develops,
-and obviously it will affect it.
-When you, for example, starve women
-that are pregnant, as happened during
-the famous starvation studies, the
-baby is already in utero, exposed
-directly to the environment.
-So it's not even a heritable effect.
-The baby is itself affected.
-It's a direct effect, very interesting,
-important, and has many implications.
-And it will be separate from the genetics.
-You'll have to take it into account
-to understand what's going on.
-Doesn't require, necessarily, a new
-biology, a new biology of inheritance.
-Not only is the embryo affected, the
-embryo, while in utero, already has
-germ cells, so it's also the next
-generation, so is directly exposed.
-And you don't need any new biology
-necessarily, to explain it.
-And it doesn't have to involve genetic
-epigenetics or epigenetic gender.
-Andrew Huberman: It's clear to
-me that in the female fetus, the
-total number of eggs that she will
-someday produce and potentially
-have fertilized by sperm exist.
-But in males with a 60 day sperm cycle
-leads me to the question, do fetal
-males, males as fetuses, living as
-fetuses in their moms, already start
-producing sperm, or it's the primordial
-cells that give rise to sperm.
-Oded Rechavi: So I'm not an expert,
-so I don't want to go into the details
-of exactly when in mammals but yes,
-exposure of the mother also has an affect,
-eventually the transmission of genetic
-information through the sperm's father.
-And there are also many examples of just
-stressing the fathers, affecting their
-sperm and affecting the next generation.
-There.
-If you go to the F2 generation, if you
-go two generations down the road, not
-to the kids, but to the grandkids, then
-it is a real epigenetic effect, because
-you examine something that happens,
-although the next generation was never
-exposed to the original challenge.
-So when we say about epigenetic
-inheritance through the paternal
-lineage, through the fathers,
-we talk about two generations.
-And when you go through the mother,
-it's three generations to talk
-about when you need to invoke
-some real epigenetic mechanism.
-And there the evidence becomes
-much more scarce in mammals.
-There are examples,
-more or less convincing.
-The field is evolving and improving a lot.
-So, for example, now many people use,
-the cutting edge is to use IVF, in-vitro
-fertilization, or transfer of embryos, to
-make sure that actually it's the heritable
-information and not the environment,
-and that it goes through the germline.
-So this is something
-that is being done now.
-There are studies.
-Andrew Huberman: You're talking about
-the three parent IVF, where they
-take the DNA from mom, the sperm from
-dad, and they take the DNA from mom
-and put it into a novel cytoplasm?
-Oded Rechavi: No, not at all.
-You just take the sperm and
-transfer it and fertilize an egg.
-Andrew Huberman: So standard IVF?
-Oded Rechavi: Yeah, standard IVF.
-You can do it in many different ways.
-But this idea that you separate
-the environment of the mother from
-the inheritance or the environment
-of the father, and to control
-and separate nature from nurture.
-Andrew Huberman: The environment
-becomes the culture dish.
-Oded Rechavi: Yes, so
-the field is improving.
-People do experiments that have
-a higher end, so more replicate
-and are better controlled.
-And there are some examples
-for effects that transfer.
-And it depends who you ask
-whether people believe it or not.
-Many geneticists do not believe in
-it, and many people do believe it,
-and it depends on the community.
-There is strong resistance
-for many reasons.
-Some of them are justified, some are
-less justified and are part of the
-scientific process and how things work,
-because it's challenging the dogma.
-So this is very interesting on its own.
-If you ask psychologists, many
-psychologists believe that there's
-heritable trauma and things like
-that, population geneticists less.
-So this really depends, and I
-think that we are just at a point
-in time where we don't really know
-whether it happens and to what
-extent, and we need bigger studies.
-Even if you think about normal,
-just genetic studies, where people
-a trying to understand the genetic
-underpinning of complex traits, like
-anything that involves the brain,
-pretty much, we now know that you
-need to study many, many people.
-So now these big genome wide association
-studies, big genetic studies, involve
-hundreds of thousands of people.
-No one did an experiment
-like this for epigenetics.
-It's much more complicated
-because you need to also take
-into account the environment.
-I'm not even sure we know how
-to design such an experiment.
-It's very, very challenging.
-Part of the resistance to the idea
-is based on theoretical grounds
-because of these barriers and
-because of the controversies.
-On the other hand, people
-really want to believe it.
-People really want to believe it because
-it sort of gives your life meaning if you
-can change your biology through changing
-your kids, through changing your biology.
-So psychologically, I can understand
-why many people want this to happen.
-Even Schrodinger, the famous physicist,
-so he wrote a very important book in
-'44, so this was before the double helix,
-and it's called What is Life ? This
-is actually a book that drove many
-physicists to establish molecular biology.
-It's very, very important and he
-talks about the heritable material.
-It also talks about evolution.
-And he said, unfortunately, Lamarckism
-or inheritance of acquired traits
-is untenable, it doesn't happen.
-And he writes, this is very, very
-sad or unfortunate because unlike
-Darwinism or natural selection, which
-is gloomy, it doesn't matter what you
-do, the next generation will be born
-based on the instruction in the sperm
-and the egg, you can't influence it.
-Of course, you can give your
-kids money and education, but you
-can't biologically influence it.
-Andrew Huberman: One thing I'm
-fascinated by for a number of
-reasons, is partner selection.
-I mean, in some ways we think, oh,
-we want to find someone who is kind.
-That does seem to be, by the
-way, the primary feature, at
-least in what the data tell us.
-We had David Buss on the podcast of how
-women select men, that people are kind.
-There's also resource potential.
-There's also beauty or aesthetic
-attractiveness in males and females, etc.
-Male, male, female,
-female, as the case may be.
-But in terms of reproduction,
-sperm, egg, male female, obviously.
-So we're selecting for a number of traits,
-but presumably subconsciously, we are
-also selecting for a number of traits
-related to vigor and in the idea that if
-we were to have offspring with somebody,
-that those traits would be selected for.
-Oded Rechavi: Right.
-And we actually have work on that
-in nematodes that I'll be happy to
-tell you about in a second after we--
-Andrew Huberman: --The dating in worms--
--- Oded Rechavi: The dating in worms , where
-we understand the mechanism, and we'll
-go into that in a second or in a few
-minutes after we dive into the worms.
-But yes, the original calculations
-of how population genetics work to
-simplify things and to do the math, so
-it will be easy, it was random mating.
-Of course, it doesn't work like that.
-So it complicates things because
-we know, and there's research
-about potential capacity to
-somehow sense immune compatibility
-and things like this, which is.
-I don't know, I'm not an expert on that.
-Andrew Huberman: Neither am I, b ut my
-understanding is that, of course, we're
-familiar with the other traits we select
-for, like potential nurturing ability.
-Whether or not someone is
-reliable predicts something
-about their nurturing ability.
-And for offspring, potentially.
-I mean, you can draw lines between these
-things without any direct evidence,
-but they seem so logical, right?
-That somebody kind might also stick
-around or be honest and these kinds
-of things, that it makes sense.
-But that one would be selecting
-for certain biological traits like
-immune function or some other form of
-robustness that we're not aware of is,
-I think, a fascinating area of biology.
-Oded Rechavi: So this is where
-the work in mammals stands.
-However, there's also one additional
-thing to mention, which is that on
-top of chemical modifications to the
-DNA and the proteins that condense
-the DNA, which are called histones,
-there are also other mechanisms that
-might transmit information, including
-transmission between generations of RNA.
-And there are different types of RNA, not
-just the RNA that we mentioned before,
-the messenger RNA, which encodes the
-information for making proteins, but also
-other RNAs that regulate gene expression.
-And this is, and I think that in
-recent years, also in the mammalian
-field, RNA as the molecule that has
-the potential to transmit information
-between generations, took center stage.
-So I think this is the cutting edge,
-a lot more to understand and know.
-But RNA has a lot of potential for
-doing that, as we'll explain soon.
-But we have to go to worms first.
-Andrew Huberman: I'd like to take just
-take a brief moment and thank one of our
-podcast sponsors, which is InsideTracker.
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-Thank you for that incredible overview
-of genetics and RNA and epigenetics,
-and it was essentially a survey of
-this very interesting and on the
-face of a complex field, but you've
-simplified it a great deal for us.
-In our transition to talking about worms.
-I would like to plant a flag in the
-Huberman Lab podcast and say that what
-we are about to discuss is the first
-time that anyone on this podcast has
-discussed so called model organisms.
-I may have mentioned a fly paper here
-or there, or a study on honeybees and
-caffeine and flower preference at one
-point, but typically that's done in
-passing, and we quickly rotate to humans.
-I know that many, if not most, of our
-listeners are focused on humans and
-human biology and health, etc., but I
-cannot emphasize enough the importance
-of model organisms and the incredible
-degree to which they've informed us
-about human health, especially when it
-comes to very basic functions in cells.
-I mean, one could argue, okay, and
-there's been some debate, telomeres
-in mice, did that really lead to
-the same sort of data in humans?
-Okay, there are those cases,
-certainly, but model organisms are
-absolutely critical and have been
-and basically inform most of what
-we understand about human health.
-So before we start to go into the
-description about worms per se,
-could you just explain to a general
-audience what a model organism is?
-Right.
-They're not modeling.
-They're not posing for photographs,
-obviously, what that means and what
-some of the general model organisms
-are and why you've selected or elected
-to work on a particular type of worm
-to study these fascinating topics
-that there's zero question also
-take place in humans at some level.
-Oded Rechavi: So it's a real
-pleasure and an honor to represent
-the model organisms here.
-I'm really happy just for that.
-It was worth it, because, as
-you said, model organisms are
-extremely important, and we learn
-so much about biology through them.
-Model organisms mean that it's an
-organism that many people work on.
-So there's a community of
-people that work on them.
-People work, study many types of
-organisms, but not around every organism.
-There's a huge community of researchers
-that combine sources to create all
-the resources, the tools and the
-understanding that accumulates.
-There are just a handful of model
-organisms in the short history of the
-field of biology, it's not so long.
-We learned about every aspect of
-biology through them, including many
-important diseases, human diseases.
-And these are E.
-coli bacteria, phage - which is a virus of
-bacteria, flies, worms that are called C.
-elegans, and nematodes.
-This is what we studied in the lab.
-Fish which are called zebrafish.
-Andrew Huberman: Danio
-rerio, or something, right?
-Oded Rechavi: Yeah, and of course, there
-are also model organisms, and mouse,
-and also plants, important plants.
-The most studied one is arabidopsis.
-Andrew Huberman: And perhaps
-less so nowadays, but non-human
-primates, macaque monkeys,
-marmosets, squirrel monkeys, mainly.
-Oded Rechavi: These, I don't know
-exactly how the definition is,
-but emerging model organisms.
-There are many model organisms that are
-emerging, and there are communities that
-are formed, including also around the
-planaria that we mentioned before, this
-flatworm that regenerates, this is a
-great model for studying regenerations.
-If we could develop new
-heads, it would be incredible.
-And we can learn from these organisms.
-And the reason that we can learn a
-lot also about humans by studying
-these animals is that we all
-evolved from the same ancestor.
-So we share a lot of our functions
-with them and also a lot of our genes.
-C.
-elegans, and they have, the
-different model organisms have
-different advantages that serve us.
-They sometimes have things that are much
-more apparent in them that we can study.
-For example, learning and memory
-was largely studied in the beginning
-in a snail, aplysia, where many
-of the discoveries were made,
-because it has big neurons that
-you can easily study and examine.
-Andrew Huberman: And yes, snails learn.
-Oded Rechavi: Yes, they learn, even C.
-elegans, these nematodes that we
-study, learn, and they are much
-simpler than another important reason
-to study them, of course, is can
-you actually experiment on them?
-We can't do this to humans, the
-things that we do to these animals.
-And we can change their genes,
-do all kinds of things to them.
-Andrew Huberman: And sorry to interrupt,
-but in some cases, I think you're
-going to tell us, for instance, in C.
-elegans in particular, the presence
-of particular cell types is so
-stereotyped that you can look at
-several different worms and the
-community of people that study C.
-elegans has literally numbered and named
-each neuron so that two laboratories on
-opposite sides of the world can publish
-papers on the same neuron, knowing that
-it's the same neuron in the two different
-laboratories, something that is extremely
-hard to do in any mammalian model, a
-mouse, or certainly in humans, and has
-posed huge challenges that give great
-advantages to studies of things like C.
-elegans.
-Oded Rechavi: Yes.
-So, C.
-elegans, this is the star now,
-and this is what we study.
-These are nematodes, small worms,
-roundworms that are just 1 mm long, so
-you can't see them with the naked eye.
-You have to look under the scope.
-Andrew Huberman: Where do they
-live in the natural world?
-Oded Rechavi: So they used
-to call them soil nematodes,
-but this is not really true.
-They are in many places, but they are
-mostly in rotten fruits and leaves.
-And you can find them
-in the ground as well.
-But you can also find them, and
-they are free living, so they're not
-parasites, but you can sometimes also
-find them in snails, but the best way
-to isolate them is from rotten fruits.
-Andrew Huberman: Okay, I Like the
-idea that they're not parasites.
-I'm one of these people that gets a little
-squeamish about the notion of parasites.
-Oded Rechavi: Yeah, so
-they're not parasites.
-They're really fun to handle
-because they're so small and easy.
-You just grow them on
-plates with agar and E.
-Coli bacteria, this is
-what they eat in the lab.
-You can just pick them with a small pick,
-wire pick, and move them around and change
-their genes and do many things to them.
-But they have many advantages for
-neuroscience and for studying inheritance.
-As you mentioned, they always have a
-certain number of cells in the body.
-So a silicon nematode always has
-959 cells in its body, that's it.
-Andrew Huberman: Not 960.
-Not 958.
-Oded Rechavi: 959, and out of
-which 302 are neurons, always 302.
-There's a huge debate now over
-Twitter on whether it's 302 or 300.
-I don't want to get into trouble, okay?
-But people take this very hard.
-I think it's 302, but let's not get
-into it because I'll get into trouble.
-Andrew Huberman: Well, we can equilibrate
-all things here by, you, say, 302.
-Granted, you're far more informed in this
-model organism than I am or ever will be.
-I'll say 300, and then we're balanced
-in terms of partisan politics in the C.
-elegans community.
-Oded Rechavi: Perfect.
-And it's always the same.
-And each neuron has a name, like you said.
-And not only does every neuron have a
-name, many of them, we know what they do.
-So there's a few cells that are sensory
-neurons that sense particular chemicals.
-In certain situations, we'll
-know that a chemical will be
-sensed just by one neuron.
-There are other motor neurons
-and interneurons and all of that.
-We know how many dopamine neurons
-there are, and serotonin neurons,
-and we know them all by their name.
-Not only that, we know how they
-are connected to one another.
-We have a map, a connectome since
-the 80s, like a subway map that tells
-us which neuron talks with which
-other neurons, and it is the same.
-People thought that it was exactly the
-same between genetically identical warms.
-Now we know that there are
-slight differences, but by
-and large, it is the same.
-And we have a map, a roadmap
-that we can use to study.
-Andrew Huberman: The so-called connectome.
-Oded Rechavi: The connectome.
-Not only that, the worms are
-transparent, so we can actually see
-the neurons fire using particular
-tools, and we can activate genes and
-silage genes using optogenetics, like
-was discussed here on the podcast.
-We can make the worms go forward or
-backward or lay an egg by shining
-different waves of light on them.
-So we have very powerful tools
-for manipulating the brain.
-On top of that, we have great
-understanding of the genetics
-of the worm, of the genome.
-The C.
-elegans is the first animal to have
-its genome sequenced before humans.
-Before that, of course, there
-were bacteria, and we know that.
-And each worm produces, each mother
-produces about 250 babies, which
-are almost genetically identical.
-And we know where we grow them.
-The environment is very controlled,
-so we grow them in the plate with
-just bacteria, so we can easily
-separate between nature and nurture.
-Andrew Huberman: And one thing that I
-wonder about often is generation time.
-Even though mice are not humans,
-mice have certain advantages
-because they're mammalian species.
-You can't do all the magnificent
-things that you can do in C.
-elegans and mice.
-But one major issue with mice is that
-the generation time is somewhat long.
-You pair two mice, they mate.
-You get a mouse or litter of mice.
-21 days later.
-It might seem like, okay,
-that's only 21 days or so.
-But if you are a graduate student
-or postdoc, trying to do a project
-that can extend the time to do
-experiments out three or four years
-compared to what you could do in C.
-elegans.
-Oded Rechavi: You're absolutely right,
-t his is one of the major advantages.
-The generation time in C.
-elegans is three days.
-Three days.
-So you can do hundreds of
-worm generations in one PhD.
-This is very important.
-Not only that, every worm will produce
-hundreds of progeny that are genetically
-identical, so you will have great
-statistics for your experiments.
-Andrew Huberman: And the worms
-probably don't mind living on these
-agar plates munching away on E.
-coli, where it's the good life.
-It's questionable whether or not mice,
-or certainly, listen, I'm a proponent
-of well-controlled and as long as
-there's oversight, animal research.
-It's necessary for the development of
-treatments of diseases that hinder humans.
-But it is always a little bit of a kind of
-a cringe and go kind of thing when you're
-dealing with mammals that are living so
-far outside their natural environment.
-I'd be lying if I didn't say that it
-gets to you after a while, and if it
-doesn't get to you, you kind of have
-to wonder about your own psyche a bit.
-Oded Rechavi: Right.
-I also think that this is important, but
-for me, it's much easier to work on worms.
-I don't have to feel bad about it.
-Andrew Huberman: Yeah, they're happy.
-Oded Rechavi: They're happy.
-If a worm dies, it's less painful
-to the human than if other,
-more sensitive animals do.
-Andrew Huberman: Yes, I agree.
-Oded Rechavi: So there are
-many advantages for studying C.
-elegans.
-And 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.
-Andrew Huberman: Well, and in large part
-thanks to you and the work you've done.
-So, could you tell us, what was the
-first experiment that you did on C.
-elegans that confirmed for you that
-there is inheritance of acquired traits?
-Because, of course, the best
-experiments and experimenters always
-set out to disprove their hypothesis.
-And when the hypothesis survives, despite
-all the control experiments and poking
-and prodding and attempts to contradict
-oneself, then it's considered a victory.
-But it's one that we all have to
-be very cautious about enjoying
-because of the tendency to
-want our hypotheses to be true.
-So what was the first experiment
-where you were convinced that
-inheritance of acquired traits is real?
-Oded Rechavi: The first experiment I
-did was in my postdoc, which I did with
-Oliver Hubbard in University of Columbia.
-We set out to test whether worms can
-produce transgenerational, prolonged
-multi-generational resistance to viruses.
-Andrew Huberman: Wow.
-This is a very pertinent
-topic, which is relevant.
-Oded Rechavi: These worms don't have
-dedicated immune cells like we do.
-They don't have T cells or B cells.
-They defend themselves from
-viruses very efficiently using RNA.
-So, in fact, when we started these
-experiments, there wasn't any
-natural virus that was known to
-infect clients, which is amazing
-because viruses are very good, as
-we all experience now, in infecting.
-And the worms are resistant to viruses
-because of RNA molecules, short
-RNA molecules that destroy viruses.
-And these are called small RNAs.
-Now, we need to discuss them
-before I explain my experiment.
-In 2006, two researchers
-that were studying C.
-elegans, Andrew Fire and Craig Mello,
-got the Nobel Prize for showing that
-there is a mechanism that regulates
-genes that happens through small RNAs.
-What they've shown is that if you
-inject the worms with RNA molecules,
-which are double-stranded, they
-shut off the genes that correspond
-that match in sequence to this RNA.
-Andrew Huberman: So it's sort of
-like taking the specific instructions
-for the coffee table from your IKEA
-handbook, and you insert a copy of
-that into the book, and in doing
-so, you prevent the expression of.
-You sort of erase the original page.
-Oded Rechavi: Perfect explanation.
-Perfect explanation.
-And they found that double-strand RNA,
-RNA that has two strands is what starts
-the response leading to the production
-of small RNA molecules, which are the
-ones that actually find the messenger RNA
-and lead to its destruction, silence it.
-So you don't get proteins
-in the end for that.
-They got the Nobel Prize after
-people found that this is conserved
-in many organisms, including
-humans, and there are now drugs.
-This was only in 2006 that the Nobel
-Prize, the paper was published in 98.
-There are now drugs that use
-this mechanism also in humans.
-Andrew Huberman: And I'll just
-interject and say that not only is it
-a recent discovery and an incredibly
-important one, but Andy Fire and Craig
-Mello are also really nice people.
-Yeah, they just happen
-to be very nice people.
-And Craig Mello is an excellent,
-I think he's a kite surfer.
-The only time I met him in person was
-at a meeting, and he had a black eye,
-and I thought, okay, wow, I guess he's
-also a pugilist or something, but turns
-out he had done that kite surfing.
-So scientists actually do things
-other than go to the laboratory.
-Nobel Prize winning scientists, that is.
-Okay, I'll let you continue.
-Thanks for allowing that.
-Oded Rechavi: Incredible scientist.
-And there were also studies
-in many organisms on the
-mechanisms of how this happens.
-It is called RNA interference.
-RNA interferes in the expression of a
-gene, in the function of a gene, and it's
-also called gene silencing, because these
-RNAs enforce the silencing of genes.
-Instead of the genes being
-expressed, they are silenced, and
-you don't manifest their function.
-Already in the first paper that they
-published about this, where they've
-shown that double-strand RNA is what
-leads to the silencing of the control.
-They've shown two very important things.
-One of them is that if you inject
-the worms with double-strand RNA,
-you don't only see the action in
-the cell that you injected or in
-the tissue that you injected, but
-you see it all over the worm's body.
-It spreads.
-It wasn't exactly clear what spreads,
-but it was clear that it spreads.
-You see the silencing all over the body.
-This includes also the germ cells.
-So, if you inject the double-strand
-RNA just to somatic cells, even
-to the head, you will also get the
-effect in the germ cells and in the
-next generation, in the immediate
-progeny, the F1 generation, the kids.
-So this was really clear
-proof that this is inherited.
-However, this is just one generation
-in these original studies.
-Later they've shown something which
-will immediately remind you what I
-told you about with planaria, that you
-can just take worms and feed them on
-bacteria that produce this double-strand
-RNA, and that the double-strand and
-the silencing would move from the site
-of ingestion, from the gut where the
-bacteria are eaten, to the rest of the
-body and also to the next generation.
-So before we left, when I mentioned
-these cannibalistic experiments of
-McConnell with the planaria, and
-now you see that it can happen, and
-this is not controversial at all.
-This is being done routinely
-every day by any C.
-elegans biologist in the world.
-This has been replicated a million times.
-Not only that, you can also feed
-planaria, these other worms with RNA.
-You can just put it in chopped
-liver and let them eat it.
-And again, this will
-spread throughout the body.
-Andrew Huberman: Wild.
-Oded Rechavi: And this
-is what we do routinely.
-We always, when we want, we use
-this technique to see what genes do.
-If we want to see whether a particular
-gene is important for a certain behavior
-or a certain something, the way to study
-it is to neutralize the gene activity.
-And we do it by just introducing the worms
-with double-strand RNA that correspond
-in sequence, that match in sequence this
-gene, this will lead to the silencing,
-this activates the gene's activity.
-And if then the effect stops, we know
-this gene is involved in the function.
-And we never want to just examine
-one worm, so we feed the mother
-with double-strand RNA and then we
-examine all of its children, so we
-can have the statistics over hundreds
-of worms or thousands of worms.
-So this is validated and not
-controversial at all and totally routine.
-Andrew Huberman: Is it fair to say that
-McConnell's experiments of chop-blending
-up these worms - [LAUGHS] very graphic
-image - blending up these worms and
-then feeding them to other worms,
-planaria, that those experiments can,
-yes, be explained by double-stranded
-RNA and through RNA interference?
-Oded Rechavi: Potentially.
-It hasn't been done yet.
-We are working on it in my lab
-now in collaboration with other
-labs, but it wasn't published.
-But yes, this could be the explanation.
-So Fire and Mello did these experiments,
-some other people did these experiments.
-When I started my work, I wanted
-to see whether, in addition to
-artificial double-strand RNA, some
-natural traits can also transmit
-across generations because of RNA.
-Because of small RNAs, right?
-Andrew Huberman: Because injecting siRNA,
-or short interfering RNAs, that is, or
-putting worms into an environment with
-an abundance of inhibitory RNAs as an
-experiment, is very different from worms
-experiencing something and then passing
-on that acquired trait to their offspring.
-It's a world apart, in my opinion,
-because one is an extreme manipulation
-that illustrates an underlying
-principle, the other is something
-that, in theory, occurs in the
-passage of generations, Just naturally
-.
- Oded Rechavi: We're going from the
-less artificial to the more artificial,
-the advantages, just like with model
-organisms, that the more artificial
-it is, the easier it is to, you
-know exactly what you did just now.
-Introduce one factor and
-you can follow the result.
-So this is always the trade.
-What I did was, in Oliver's lab, was to
-see whether part of the magic for the
-worms' resistance to viruses is their
-capacity to transmit information in
-the form of RNA molecules, inhibitory
-RNA molecules, to the next generations.
-And it has been shown before in C.
-elegans that the worms resist viruses
-using this mechanism, these small RNAs.
-In fact, this is probably the reason
-that these small RNAs evolved in the
-first place, to get rid of viruses
-and other parasitic genomic elements,
-and this is a mechanism to fight them.
-And what I did is a
-very simple experiment.
-I took worms and I
-infected them with a virus.
-When you do this, this also
-has been shown in the past.
-The worms destroy the virus.
-Okay.
-We demonstrated this very clearly
-using a fluorescent virus.
-So if the virus replicates
-successfully, the worm just turns green.
-And if the virus is destroyed,
-the worm stays black.
-This is very simple.
-It's a clear cut off.
-You don't examine the worm and ask
-whether it feels good, you just see.
-Andrew Huberman: This green
-light binary response.
-Oded Rechavi: Yes.
-And so we took worms, we infected them
-with the fluorescent virus they destroyed.
-This also has been done in the past.
-But then what we did is we neutralized
-the machinery that makes small RNAs
-in the descendants of the worms,
-so they cannot make small RNAs from
-the start on their own, because
-they just don't have the genes that
-you need to make these small RNAs.
-Okay?
-And then we ask, what will happen?
-Will we affect these worms with the virus?
-Will they be green or black?
-They can't make their own small
-RNAs, so they can't protect
-themselves on their own.
-The only way for them to stay black
-for them, not having the virus
-replicate is if they inherit the
-small RNAs from their parents.
-And this is exactly what happens.
-All the worms' progeny, although they
-don't have the gene that is needed
-for making the small RNAs, are black.
-They silence the virus.
-And this also continues
-for additional generations.
-Andrew Huberman: Okay, so the parent
-worms effectively put something
-into the genetic instructions of the
-offspring that would afford them.
-Let's call it an advantage in this
-case, but afford them an advantage
-if they were to be confronted with
-the same thing that the parents were.
-Oded Rechavi: Right.
-And we know exactly
-what this advantage is.
-The advantages are small RNAs that
-match the viral genome and just chop
-up that virus in the next generation.
-And we can identify these small RNAs in
-the inhibitory RNAs in the descendants,
-although they don't have the machinery
-to make it, just because they inherited.
-We can identify them by sequencing, by RNA
-sequencing, which is like DNA sequencing.
-You actually get the actual sequence
-of the RNA molecules, and we can see
-that they correspond to the virus.
-And they inherited small RNAs only if
-their parents were infected with them.
-Andrew Huberman: So
-there's specificity there.
-Oded Rechavi: There's specificity.
-Andrew Huberman: Yeah, it's not just
-some general resilience passage.
-Oded Rechavi: Right.
-Andrew Huberman: I have to be careful
-in drawing an analogy that isn't
-correct, and I want to acknowledge
-that what I'm about to say with
-certainty cannot be entirely correct.
-But the analogy that comes to
-mind in mammals is this idea that
-if one generation is stressed,
-that their offspring may, in
-some cases, have a higher stress
-threshold, a resilience to stress.
-I could imagine why that
-would be advantageous.
-Your parents have a hard life.
-They have offspring, and they want their
-children to have a higher threshold
-to stress because stress can inhibit
-reproduction, etc., and as I always
-say, at the end of the day and at
-the end of life, evolution is about
-the offspring, not about the parents.
-And every species pretty much seems to
-want to make more of itself and protect
-its young one way or another, either
-through nature or through nurture.
-This is a nature-based
-protection of its young.
-Is it fair to say that in the mammalian
-experiment with a passage of stress
-resilience, that it could be RNA-based,
-that that would perhaps set some new
-threshold on glucocorticoid production?
-Here I'm speculating, and I want to
-highlight that I'm speculating, but
-I'm speculating with a reason, which
-is, I think for people that are hearing
-about this in worms, you've done a
-beautiful job of splaying out why model
-organisms are really important, but to
-think about how this may operate in the
-passage of human generations, I think
-is a reasonable thing to entertain.
-Oded Rechavi: Right, and it is true that
-also in mammals now, RNAs and small RNAs
-are a leading candidate for something
-that could mediate the transmission of
-stress protection or also of harmful
-effects that transmit between generations.
-Perhaps RNA does it.
-However, in worms, the RNAs have
-one more trick that we don't know
-the equivalent of in mammals yet.
-This is something very crucial
-that we showed in that particular
-paper, in the first paper.
-Andrew Huberman: Which is?
-Oded Rechavi: So the effect that I
-described, this transmission of resistance
-to viruses through these RNAs, doesn't
-only affect the next generation, it also
-affects multiple additional generations.
-Andrew Huberman: So it gets passed?
-Oded Rechavi: It gets passed.
-And you have to ask yourself,
-how doesn't it get diluted?
-Why isn't it diluted?
-Because everyone produces 250 babies,
-so you dilute by 250, and if something
-is diluted for four generations, so it's
-250 times 250 after four generations,
-it's a dilution of four billions.
-Completely homeopathic, would never work.
-It's just there's nothing left.
-The secret of these worms is that
-they have a machinery for amplifying
-the small RNAs in every generation.
-This is called RNA-dependent
-RNA polymerase.
-It's a complex which uses the RNA
-to find, and once it finds the
-messenger RNA, just create many, many
-small RNAs so they don't get diluted
-and they pass on for additional
-generations, and this is the trick.
-We later also identify genes that regulate
-for how long an effect would last.
-Otherwise, if in the beginning
-we ask how doesn't it stop after
-one generation, now we have to
-ask, why doesn't it last forever?
-And it doesn't typically, we see that the
-responses last not only with the viral
-resistance, but also with other traits.
-For a few generations, three to five
-generations, we found genes that
-function as a sort of a clock that
-times the duration of the inheritance.
-Andrew Huberman: What
-sorts of genes are those?
-Oded Rechavi: So we call
-these genes MoTeC genes.
-MoTeC.
-I don't know how is your Hebrew...
-Andrew Huberman: Not great.
-Oded Rechavi: ...but MoTeC
-means sweetheart in Hebrew,
-but the acronym is Modified
-Transgenerational Epigenetic kinetics.
-There are different types of genes
-like that, and for some of them,
-if you mutate, if you disrupt their
-function, now the effect would transmit
-stably for hundreds of generations.
-It would never stop because their
-role is to stop the inheritance.
-You don't want to carry over something
-forever, otherwise it will no longer
-fit the environment of the parents and
-you'll be prepared for the wrong things.
-So this is important.
-What type of genes are they?
-One gene that we studied, it's
-called Met-2, it's actually a gene
-that functions in methylation of
-the proteins that condense the DNA.
-But then there are other genes that
-also affect production of small RNAs.
-Andrew Huberman: Is there some mechanism
-that controls the duration of passage
-in a way that logically links up
-with the lifespan of the organism?
-So, for instance, I knew
-my grandparents, met them.
-I did not ever meet my great
-grandparents and I certainly didn't
-meet my great great grandparents.
-I could imagine that my great great
-grandparents or my great grandparents
-experienced certain things that
-were passed into their children
-and perhaps into their children.
-But it seems reasonable given that
-humans live somewhere between zero and
-100 years, typically what now, 80 years?
-Is that the typical lifespan?
-More or less, okay?
-That if I were going to design the system,
-and again, I was not consulted at design
-phase, I would want an adaptive trait to
-be passed for two generations, because
-given how long our species lives, and
-certainly given the way the world looks
-now, as opposed to the previous century
-or the turn of the previous century,
-different stressors, different adaptation,
-different life environments, and what I
-would want to pass on to my offspring,
-I can basically hedge pretty well.
-I can place a good bet on the next 100
-years, maybe the next 200, but I don't
-have the foggiest clue what the world
-is going to look like in 300 years.
-Does what I'm saying make
-any sense whatsoever?
-Oded Rechavi: It makes a lot of sense.
-And really we need to talk about two
-things in response to this question.
-First of all, yes, you can imagine
-that the reason that the worms inherit,
-typically for three to five generations,
-is that this is relevant to something
-that happened in their environment.
-For example, we also show that when you
-starve the worms, it affects the next
-generations again for a few generations.
-Andrew Huberman: Which
-in itself is amazing.
-I just want to highlight that you
-can imagine the next generation, it's
-sort of like a genetic version of,
-"be careful, kids, but I'm going to
-give you this extra lunch pack in
-your genome that protects you against
-the possibility of starvation."
-But it's also saying, "And, were you
-to have kids, they have it also."
-Oded Rechavi: Yeah.
-So I have to just make a
-disclaimer that we don't know
-that necessarily, it's adaptive.
-It could also be damaged.
-As I said, when you starve them,
-the next generations live longer.
-But this could be a trade off of a
-trade off for fertility or something.
-So other labs have also shown, following
-our work, that if you starve the
-worms, the next generations are also
-more resistant to harsh starvation.
-This is not our work,
-but this sounds adaptive.
-Okay, but whenever you're talking
-about adaptation, you have to see
-it in the context of evolution.
-There's also this famous saying,
-"nothing in biology makes sense
-except in the light of evolution."
-And so it's very hard to say without doing
-the lab evolution experiments, we actually
-see who wins, the ones that inherit or
-the ones who don't hit, who takes over.
-Otherwise, it's hard to talk about
-whether it's adaptive or not.
-But when it comes to the duration
-of the response, yes, it could
-be programmed to fit something.
-For example, if you're talking about
-starvation, worms transition between
-periods of starvation and periods
-where they have a lot of food.
-So let's say they find an apple for a few
-generations, they will consume the apple,
-and then they will be starved for a while.
-Perhaps this is the number of generations
-that takes them to finish an apple.
-Or perhaps there are other responses
-also to higher temperatures.
-If you grow worms in higher
-temperatures, the options are different.
-They change how they mate.
-What I alluded to before.
-Andrew Huberman: We're going t
-o get back to this because it
-relates to cold exposure, which
-many listeners are interested in.
-Oded Rechavi: And perhaps it is somehow
-correlated with the cycle of the year.
-But to tell you the truth, I don't know.
-As I said, we go from the more
-artificial to the less artificial.
-If double-strand RNA, just synthetic
-RNA, is the most artificial,
-starvation is more natural.
-But it's not starvation in
-the real context of the world.
-In a real apple, it's a
-plate with or without E.
-Coli bacteria.
-But it's not an apple on a tree exposed
-to the elements, with other worms, with
-bacteria, with all kinds of complications.
-And it could be that we will see
-different durations of heritable
-effects the more natural we go.
-It's just much less
-controllable and hard to do.
-And again, when we're talking about
-humans, part of the argument is, why
-people, why the disbelievers, it's
-not about fate, but the critics say
-that this wouldn't happen in humans.
-If they say the worms' generation
-time is just three days, the chances
-that the parents' environment will
-match the children's environment is
-very high because there's not a lot
-of time for the environment to change.
-Plus they can't go very
-far, they're small.
-There are many examples of
-epigenetic inheritance in plants.
-This is a big field where there
-is very established proof for
-inheritance of acquired traits.
-For epigenetic inheritance,
-be more careful.
-Epigenetic inheritance of acquired
-traits is a more loaded term,
-but in plants it also happens.
-And there you also say
-these are sessile organisms.
-They can't run away.
-So the environment is more constant.
-Andrew Huberman: Ideas, maybe just
-a quick example that I've heard
-before, tell me if I'm wrong.
-I very well may be.
-For instance, a particular species
-of plant that grows a straight, maybe
-slightly bent stalk might be exposed to
-some environment where in order to capture
-enough sunlight and other nutrients
-might need to grow in a corkscrew form.
-The corkscrew form can be
-inherited for several generations.
-Oded Rechavi: This is an example
-that I don't know, but perhaps it--
--- Andrew Huberman: something like that.
-Trust me, the one thing we know
-about podcasting and YouTube is
-someone will tell us in the comments,
-and please do, we invite that.
-Oded Rechavi: Right, but there's
-a long history of epigenetic
-inheritance studies in plants, with
-excellent studies, well controlled,
-showing that it happens also there.
-So this is very clear when it comes to
-humans, you could say, maybe my kids
-will go to live in a different continent,
-and they will be on the computer every
-day and everything will be different, so
-it makes less sense to prepare them for
-the same hardships that I experience.
-However, in my opinion, this
-argument comes up a lot.
-It's not the best argument, because
-it depends on the scale of how
-you look at things we experience.
-We meet, for example, I'm not saying
-that this is inherited, but in humans,
-but we experience the same pathogens
-and the same viruses all the time.
-So perhaps it is worth preparing for that.
-Andrew Huberman: Right.
-Oded Rechavi: Again, I'm not saying that
-it happens, but it depends on the scale.
-Andrew Huberman: Well, what you're
-describing makes perfect sense.
-And I do want to acknowledge these
-critics, whoever they may be.
-I do have the advantage that I
-don't work in this exact field.
-And so I'm happy to stand toe to toe
-with those critics now and say that,
-at least in terms of inheritance of
-reactions or adaptive or maladaptive
-traits, to stress or to reward.
-You talked about nicotine
-before, a passage of response
-to drugs of different kinds.
-Not being specific to nicotine.
-It was sort of a more general
-passage of some sort of information
-related to reactions to chemicals
-present in nicotine, but other drugs.
-I have long been irritated and a little
-bit tickled by the fact that people
-say, oh, we have this system for stress.
-That was really designed to keep us safe
-from lions and saber-toothed tigers.
-Sure, but the hallmark of the stress
-system is that it generalizes.
-I mean, if I get a troubling text message
-or if I suddenly see a dark figure in the
-hallway when I go to the bathroom at night
-that I don't recognize, both of those
-have the same generic response, which
-is the deployment of adrenaline in both
-brain and body, changes in the optics of
-the eyes, quickening of the heart rate.
-Stress is, by design, generic.
-And so one could imagine that a passage
-of some sort of stress resilience
-or a maladaptive passage to stress
-would be also somewhat generic, and
-that's actually advantageous overall.
-Same thing with the reward system.
-We essentially have one or two
-chemical systems of reward.
-I mean, there's the opioid system and
-there's a cannabinoid system, but in
-large part, anticipation and reward
-is governed by the dopamine circuits.
-And anticipation and reward of an
-ice cream cone for a kid is the same
-neural circuitry that's going to be
-repurposed when they get to reproductive
-age, and they are anticipating
-creating children with their mate.
-And assuming they want to
-do that, the dopaminergic
-system is going to be engaged.
-So ice cream, sex, stress to
-weather, stress to famine.
-The biology of these more modal
-systems, especially in the nervous
-system, are, again, I have to be
-careful with the words, by design,
-are certainly generic, and so I don't
-see the need for immense specificity.
-I mean, it's not like we're,
-well, COVID just happened.
-So could you imagine that there's the
-passage of a COVID-19 specific resilience?
-No, I think what would probably be
-passed along would be some sort of, if
-it does occur, would be some sort of
-resilience to viruses more generally,
-and that would be advantageous.
-Oded Rechavi: Right.
-So I agree.
-And this opens a question of what
-is the bandwidth of inheritance?
-How specific can it be?
-Does it make sense for it to be specific?
-And in the case of C.
-elegans, the response can be very
-specific through this inheritance
-of RNAs, which are just sequence
-specific, they downregulate,
-they control one particular gene.
-In other cases, it could
-be a very general response.
-And it's very interesting to think
-about it when we talk about inheritance
-of memories, which is the most
-interesting thing we could imagine,
-can brain activity of some sort
-transmit, at least in these worms?
-I said no.
-I said this disclaimer multiple
-times in memories, we don't know.
-Time will tell in worms.
-We know a lot.
-So, can worms transmit brain activity?
-Do they have the specificity to do it?
-Okay, before I'll say that, I'll just
-say that we, over the years, learned
-a lot about the mechanisms that
-shuttle the RNAs between generations.
-We know about genes that are needed
-just for that, about worms, that
-would be perfectly okay, but just
-don't have the capacity to transfer
-the RNAs to the next generations.
-We know about genes that will make
-the responses longer or shorter.
-We know about genes that prevent the
-transfer of RNA between different tissues,
-about genes that make certain small RNAs.
-So we know a lot about that.
-And then the question arises,
-we can finally ask, can memory
-transfer between generations?
-I think that, first of all, we
-need to define memory for that.
-And the broadest definition would be
-any change in your behavior because of
-what happened in the past or in your
-response because of what happened in
-the past or because of your history.
-The more interesting part, of
-course, is to talk about memories
-that are encoded in the brain.
-And the reason is that the brain
-is capable of holding much more
-specific and elaborate memories.
-I think that any tissues that
-transmit, transfer to transmit RNA
-to the next generation and affect
-the next generation is interesting.
-The gut, muscles, everything.
-But the brain can synthesize information
-about the environment and about
-internal state and can also think ahead.
-And the most provocative thing you can say
-is that you could plan somehow the fate
-of your nerve generation using your brain
-after taking many things into the code.
-Andrew Huberman: This is
-without talking to them.
-Oded Rechavi: Right.
-Without talking.
-Andrew Huberman: Right.
-So again, we go back to
-this instruction manual.
-It's like writing something
-into the instruction manual
-based on your own experience.
-Oded Rechavi: Right, and can it
-happen and what is the bandwidth?
-Can we transfer specific things?
-And then I have to agree with you
-that I would imagine that what can
-transfer, and I could be wrong, is
-a general something, sensitivity.
-You can make the analogy to being inflamed
-or not, hypersensitive to pathogens,
-hyper vigilant, something like this.
-But it can also be
-something very specific.
-Now, we have to understand that
-the brain uses a different language
-than the language of inheritance.
-The brain, the way we normally think
-about the brain is that it keeps
-information in synapses, in the
-connections between different neurons.
-When you learn something, you make
-some connections stronger and another
-connection weaker, and you wire the
-nervous system in a different way.
-The information in the brain is
-synaptic, and it is in the connection.
-On the other hand, heritable
-information of any sort has to go
-through a bottleneck of one cell.
-The fertilized egg, because we all start
-from just one cell, so it cannot be in
-the connections, because this cell doesn't
-have any connections with other cells.
-It's there alone.
-So heritable information
-has to be molecular.
-It has to be inside this one cell.
-So the question is, can you or do
-you translate the information, this
-3D structure information of synapses
-and the connection between brains in
-the architecture of the brain, can
-you somehow translate it to heritable
-information to a molecular form?
-Andrew Huberman: It's an incredibly
-important and deep question.
-It brings to mind something that was
-once told to me, which as soon as I heard
-it was obvious, but was very important
-in formulating my understanding of
-biology, which is that a map is just
-the transformation of one set of points
-into another set of points, right?
-So a map of the world, essentially, is
-just, you take what's been drawn out
-in terms of the architecture and the
-coastlines, etc., and divisions between
-states, and you transfer that to an
-electronic map or a piece of paper.
-It seems so obvious.
-It's sort of a duh, why
-are we talking about this?
-But just to make sure that people
-understand what you're really talking
-about is, let's say, the memory,
-and I have a very distinct memory
-for my childhood phone number.
-Phone number doesn't exist anymore, and
-I won't give it out because then some
-other person might get repeated calls.
-But in any case, I remember it.
-It's totally useless information,
-but it lives in my neocortex or my
-hippocampus or somewhere as a series
-of connections between neurons at
-the locations as you call synapses.
-Would my grandchildren
-know that phone number?
-There's no reason.
-Oded Rechavi: Absolutely no.
-Andrew Huberman: Right.
-Would my children know that unless
-there was some adaptive reason or
-some other reason for them to know,
-and this passage of acquired traits?
-And what you're saying is, in order
-for that to happen, there has to
-be a transformation of the neural
-circuit, literally the wiring of
-neuron ABCD, that relates and carries
-the information of that number into
-the kind of nucleotide sequences
-that are contained in DNA or patterns
-of methylation or RNA, more likely.
-So it's a transformation of one set
-of points in physical space to a
-translation of points in genetic space.
-Does that make sense?
-Oded Rechavi: Right.
-And then we have many problems.
-First of all, we don't know of a
-mechanism to translate between the two
-different languages, the language of the
-brain and the language of inheritance.
-We are not familiar with
-a mechanism like that.
-Second, the next generation, if it's
-not a worm, if it's a mammal would
-have a different brain even if it was
-genetically identical to the parent.
-The wiring of the brain and the particular
-neuronal circuits will be different.
-This is true for twins.
-It will always be true because it
-depends, because it's partly random and
-it depends on the environment, even if
-you have the same genetic infections.
-So let's say you somehow had a mechanism,
-a miracle mechanism, to take the 3D
-Information and translate it to the
-magic, to the language of inheritance.
-You would then in the next generation
-have to translate it again to the
-brain, although it is different.
-This sounds very unlikely.
-I'm playing a trick on you now.
-Andrew Huberman: Okay, I'm easy to trick.
-[LAUGHS]
-Oded Rechavi: But if this is how it
-happened or if this was required, it
-could never happen, in my opinion,
-which means, and I still think that
-there are certain memories that cannot
-transfer transgeneration and these
-complex and things that you learn about
-the environment that are arbitrary.
-None of our listeners' kids
-will remember this conversation.
-No way.
-This is impossible.
-Andrew Huberman: Unless they're
-listening with them [LAUGHS] . There
-are some families or parents that
-tell me they listen with their kids.
-Oded Rechavi: But it cannot transmit
-because it's random and these are
-connections that are arbitrary.
-So this seems to be a
-limitation on what can transfer.
-On the other hand, perhaps more general
-things could pass, these types of things.
-I doubt they could pass.
-However, you can nevertheless imagine
-that some things that are very specific,
-some memories that are very, very specific
-could nevertheless transmit from the brain
-after learning to the next generation.
-I'll give you an example.
-You can teach worms, even though they
-have just 302 neurons, you can teach
-them simple things about the world.
-For example, you can take
-an odor that the worms like.
-The worms have thousands of
-odorant receptors and they can
-recognize many, many molecules.
-They can smell them so they
-can find food or avoid enemies.
-You can take an odor that
-the worms like and pair it to
-something bad, like starvation.
-And then the worms will
-learn to dislike this odor.
-We don't know that this learning
-involves necessarily changing
-the strength of synapses.
-It's a possibility, but it
-doesn't have to be the case.
-It could be that just the receptor
-for this particular odor is being
-removed and this is how they live now.
-They won't have the receptor.
-They won't smell.
-They won't like the odor.
-This is a possibility.
-This type of thing, you can perhaps, not
-that anyone has shown it convincingly,
-transmit to the next generation because
-all it would take is an RNA that will
-control this particular receptor.
-So this is possible.
-People have shown things
-like that not in C.
-elegans, but people have shown
-things like this in mammals.
-They said that you learn a certain
-thing, and then just in the next
-generation, thus a particular receptor
-would be methylated or would change,
-and this would transmit the response.
-And on the one hand, it could be true.
-On the other hand, you need to
-understand, they'll need to prove, and
-this wasn't done convincingly enough
-yet, how exactly does the information
-transfer from the brain to the germ
-cells, and then in the next generation,
-from the germ cells back to the brain
-to where the receptor needs to operate?
-And this is a challenge.
-This is the current state of the
-field, that this is something
-that needs to be proven.
-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.
-And it doesn't require any
-translating between any language.
-It is very simple.
-What we've shown is that if you take
-a worm and you change the production
-of small RNAs just in its brain, in
-the next generations, their behavior
-will be different, even though
-you don't mess with their brains.
-This is a paper that we
-published in 2019 in Cell.
-We show that you just manipulate the
-production of endogenous natural RNAs
-in the worm's brain that are always
-made, but you change their amount, and
-this changes the capacity of the worms
-in the next generation to find food,
-to find not only in one generation,
-but three generations down the road.
-And the way that it works is that
-perturbing the production of these small
-RNAs in the brain affects, in the end,
-the expression of a gene in the germline.
-One gene, it is called SAGE-2, we
-don't know how it works, but we can
-do all kinds of controls where we
-manipulate activity of the gene and
-see that this also affects behavior.
-And this gene works in the germ cells.
-The information needs to go from
-the brain to the germ cells.
-It doesn't need to go back from the germ
-cells to the brain to affect behavior.
-And this depends, we know that this
-is a true epigenetic effect because it
-goes on for multiple generations, and
-also because it requires the machinery
-that transfers RNAs between generations.
-If you don't have the protein that
-physically carries the RNA between
-generations it doesn't happen.
-Andrew Huberman: So it has to be RNA.
-Oded Rechavi: It has to be RNA.
-We can also find the RNAs in
-the next generation that change.
-We sequence the actual RNAs that
-change in the next generation.
-Andrew Huberman: You mentioned that you
-don't know what SAGE, this gene SAGE
-does, but is it reasonable to assume that
-it does something in the context of the
-nervous system or, that's unclear as well?
-Oded Rechavi: It is possible.
-It is possible, but we have reasons to
-believe or experiments to show, although
-there could be alternative explanations,
-that it functions through the germline.
-Now, you may ask, how can you affect
-behavior just by changing the germ cells?
-Right?
-Andrew Huberman: Well, it would have to
-change the germ cells in very specific
-ways, because, as people probably recall,
-the germline, germ cells are where the
-inheritable information is contained.
-But you can imagine it, for instance,
-adjusting the gain or sensitivity, rather,
-on some sort of sensory foraging system.
-Oded Rechavi: Right.
-The interesting thing is it,
-again, can be quite unspecific.
-So it sounds weird that you
-change germ cells and it changes
-behavior, sperm and egg, but if
-you think about it, it's trivial.
-If you castrate a dog, it
-behaves differently, right?
-Andrew Huberman: Sadly, yeah, I
-did that to my dog and I ended up
-putting him on testosterone therapy
-later and it brought him back.
-Just as an aside.
-Oded Rechavi: Yes.
-This is because the germ cells
-affect the soma, including the brain,
-in many ways by secreting certain
-chemicals, and also because the other
-cells develop from the germ cells.
-So some information could be transmitted
-over development, or the course of
-development could be altered because of
-changes that occur in the germ cells.
-For example, in mammals, one of the
-explanations for how heritable information
-transmits is that it just affects
-something very early on in development.
-I told you that the secret to worms'
-inheritance is that they have the capacity
-to amplify these small RNAs all the time.
-This is what keeps it going
-and prevents the dilution.
-In mammals, we don't know of
-such an amplification mechanism.
-So you ask, how can a little bit of
-RNA or something without amplifying
-affect the entire organism?
-And it could be that you just perturb
-something in the very beginning when
-you just have a few cells or even in
-the placenta that develops in pregnancy,
-and this later throws everything off.
-And because of that, you have many
-problems in metabolism and so on.
-And this is called, it's an
-idea of the developmental
-origin of health and disease.
-Many of the functions occur
-early on in development.
-Andrew Huberman: So you've raised a number
-of incredibly fascinating aspects to this.
-I do have a question about one particular
-aspect, and feel free to pass on
-this for a future episode if it's
-going to take us too far off track.
-But something you said, it really
-captured my attention, although I was
-listening to all of it, which is that
-the germ cells so in the case of males,
-it's going to be sperm, and in the
-case of females, it's going to be eggs.
-Something perhaps not coincidental about
-those cells and the environment that they
-live in is that, yes, they contain the
-genetic information of past offspring.
-Of course, you explain how that works.
-But also those cells live in a region
-that is rich with hormones that can be
-secreted and in fact, are secreted, and
-through so called endocrine signaling,
-communicate with other cells, not just
-at the level of receptors on their
-surface, but also can enter the genomes
-of those cells and modify those cells.
-In other words, it seems to me that
-the microenvironment of the germ
-cells, the testes and the ovaries
-are rich with information, not just
-for the passage to next generations,
-but also for all the, as you said,
-all the somatic cells of the body.
-They're telling the somatic cells of
-the body what to do and what to become.
-And the best example I can think
-about this would be puberty, right?
-I mean, I would argue that one of the
-greatest rates of aging and transitions
-we go through in life is from puberty.
-I mean, a child becomes a very
-different person after puberty.
-They look at the world differently,
-they think about it differently.
-It's not just about the growth
-of the hair and the jaw and the
-Adam's apple and breasts and so on.
-It's a transformation of the somatic
-cells from the same microenvironment
-that the DNA containing cells reside.
-Oded Rechavi: Right.
-So once you think about it like
-this, it becomes obvious that just
-by affecting the germ cells, you
-can affect the rest of the body.
-And in C.
-elegans, there are experiments
-that show it very clearly.
-So, for example, if you just take
-worms and prevent sperm production,
-it changes their capacity to smell.
-These are experiments done by others,
-which is obviously a brain function.
-Andrew Huberman: And in a castrated
-dog, you're not just eliminating the
-possibility of transfer of DNA information
-to subsequent generations, you're also--
-Oded Rechavi: --Limiting
-their personality.
-Andrew Huberman: Without question, my
-bulldog Costello changed after castration,
-and it was a wonderful dog, but at some
-point developed some health issues.
-The introduction of a small amount of
-testosterone every other day changed
-him fundamentally, in that case, for
-the better, back to a version of himself
-that I had only observed earlier, but
-also a different version of the same dog.
-And no, he wasn't humping everything,
-maybe the occasional knee?
-[LAUGHS] Particular people,
-whose names I won't mention.
-But it was absolutely clear that
-the hormone was not just taking
-a system and amplifying it.
-It was actually modifying the system.
-So, anyway, I just wanted to highlight
-that and then now, thank you for indulging
-me, if you will, let's continue down this
-path that we were going on, because I want
-to make sure that we absolutely get to
-this issue of transmission of information
-about sex, choice of offspring.
-Oded Rechavi: So the worms are
-hermaphrodites, which means that they make
-both sperm and an egg, but they are also
-males, which are much more rare, and they
-can choose to mate with the males or not.
-When they mate with a male, it's a
-huge decision because it's very costly
-energetically, and they also risk
-predation and all kinds of troubles.
-The males hurt them and reduce their
-lifespan when they mate with them.
-Andrew Huberman: People are going
-to draw all sorts of analogies
-here, but it's inevitable.
-But, hey, here we go.
-Oded Rechavi: And most importantly
-for evolution, when you mate with
-another animal, you dilute your genome
-in half, because the worms can just
-self fertilize and transmit the exact
-same genome to the next generation.
-But when they mate,
-they dilute it in half.
-So this is a big price to pay.
-On the other hand, when you
-mate, you diversify your genome.
-So maybe some combination
-of genes will be good.
-Andrew Huberman: And
-we know that in humans.
-I mean, it's kind of interesting that
-the brain circuits that are associated
-with aversion and with approach
-are fairly hardwired for a number
-of things, like a puddle of vomit,
-almost everybody kind of cringes.
-Plate of cookies.
-If you like cookies, you move towards it.
-But there's one particular word in the
-English and presumably Israeli language
-that ought to evoke disgust, and that's
-incest, because incest is actually
-not just disgusting as a practice,
-but it's dangerous genetically, right?
-Because of inbreeding, it
-creates a deleterious mutation.
-Oded Rechavi: Right, so there are
-studies on how people in Israeli
-kibbutz, for example, where they all grow
-together, the children live together.
-It used to be like that,
-don't date each other.
-This is the classic thing.
-I talked to some of whom the
-kibbuti told me that's not true,
-but yes, there are studies like
-this that say, but it makes sense.
-Andrew Huberman: And in some countries,
-Scandinavian countries, or in Lapland
-and Iceland, where populations are
-small, they keep exquisite records of
-lineage in order to avoid inbreeding.
-Oded Rechavi: Right?
-So you're absolutely right.
-But the worms, the safe choice
-for them is to self mate.
-And if they mate with a male, they
-take a risk, but they diversify.
-Okay, what we found is that if you
-take the hermaphrodites, we can call it
-the female for just one second and you
-stress it with high temperatures, then
-the next generations of worms, for three
-generations, mate much more with males.
-And they do it because the female
-starts secreting a pheromone
-that attracts the males.
-Andrew Huberman: It's a
-very cryptic mechanism.
-It's not that she somehow changes
-and then goes seeking males.
-It draws males.
-Oded Rechavi: It draws males.
-And we know how it works.
-We think we know how it works.
-What happens is that the stress, the
-high temperatures, compromise the
-production of sperm in the hermaphrodites.
-So the hermaphrodites don't, they
-make sperm enough to make next
-generations, but the sperm, because
-of defective small RNA, inherited.
-Because the RNAs are not inherited, okay?
-The sperm is not made optimally,
-so they make less sperm.
-And when they don't make a lot
-of sperm, they feel that they
-don't self-fertilize correctly.
-So they call the males by secreting
-the pheromones so that it would
-provide its own sperm and they
-can continue to make babies.
-And we know this also from experiment.
-You just take hermaphrodites and you
-kill its sperm, it starts secreting
-pheromone and the males come.
-Andrew Huberman: It's a need-based system.
-Oded Rechavi: Exactly.
-Andrew Huberman: Incredible.
-And I hope people can appreciate as
-they're hearing this, that none of this
-we assume, I don't know how to speak worm.
-None of this, we assume, is a conscious
-decision in these animals, much like
-human mating behavior, which to us
-always seems so conscious, but is
-being governed by both conscious
-and subconscious decision making.
-None of this is an active decision to
-secrete the hormone to draw in more males.
-It's simply a biasing of probabilities.
-The hormone is now secreted in greater
-quantities or greater frequency.
-The males therefore approach more.
-So it's just increasing the
-probability of interactions.
-Is that right?
-Oded Rechavi: Right.
-What happens naturally, normally, if
-you don't stress the ancestors, is
-that the worms start secreting the
-pheromone only when they are old.
-This is also people will--
-Andrew Huberman: --When they're
-running out of their own fertility.
-Oded Rechavi: Exactly.
-Because they only make the sperm
-at a particular time and then
-they run out of self sperm.
-They can't self-fertilize.
-So they have to call the males
-if they want to continue to mate.
-Andrew Huberman: Well, this is sort
-of the plastic surgery approach.
-Okay, I'll take the heat for that one.
-But it's true, I think as certain
-people age to a certain point and they
-feel that their fertility is waning.
-If they want offspring, they need to
-take any number of different approaches.
-Here we're talking about a female,
-but we could also do the reverse.
-Right.
-Sperm donor.
-Oded Rechavi: Right.
-Andrew Huberman: But if they want to
-attract a lifelong mate or co-parent
-with somebody, oftentimes they will do
-things to adjust their attractiveness
-in any number of different ways.
-Psychological attractiveness
-or physical attractiveness.
-I'm not afraid to bring this up because
-I think that the parallels are very
-important, because I do think that
-every species and individuals within
-a species, of course, decides whether
-or not they want to reproduce or not,
-but has an inherent understanding,
-conscious or subconscious, about where
-they reside in the arc of their lifespan.
-I do believe that not
-just based on experience.
-Some people are very attuned
-to the passage of time being
-very fast, others very slow.
-I think that knowing how long
-your parents and their parents
-lived makes a big difference.
-I have friends whose fathers in
-particular died fairly young.
-And all these guys basically got
-married and had kids really young.
-Oded Rechavi: Right.
-So here, luckily for me, I don't have
-to get into the psychology of the worms.
-The explanation is just like an instinct.
-When they run out of sperm,
-they start secreting the
-pheromone and attract the males.
-There are studies also in Newman's
-about older fathers, that children
-of older fathers have a higher
-chance of becoming autistic.
-There are studies--
-Andrew Huberman: --40 and up, basically.
-Oded Rechavi: However, in this case,
-it's not clear that this is something
-in epigenetics, could be just because
-of DNA damage, because it accumulates.
-Andrew Huberman: And actually nowadays,
-we have an episode on fertility
-coming up, both male and female
-fertility, and there are actually
-DNA fragmentation kits for at home.
-DNA fragmentation kits or sperm analysis.
-You send the sperm back
-in, you don't do the DNA.
-People pipetting semen at home would
-be an odd picture, let's not go there.
-But there are clinics that
-do this for a nominal charge.
-But I did want to ask about autism
-and human disease in particular.
-Another thing that you hear
-sometimes, and here I want to
-acknowledge, autism is on a spectrum.
-Some people get upset if
-you call it a disorder.
-There are some adaptive
-autistic traits, etc.
-But one thing that often comes up is this
-idea that two people who are more of the
-kind of engineering hard science, if you
-will, of phenotype mate and have children.
-Higher probability of the offspring
-being on the spectrum, some people
-would argue, but that's already
-selecting for people that might have
-already been partially on the spectrum.
-So maybe it's a gene copy issue.
-I'm not asking you to comment on autism
-in particular, but when you hear things
-like that, that the children of older
-fathers born from older fathers tend
-to have a higher probability of autism.
-At the level of intuition, does that
-strike you as an epigenetic phenomenon,
-as a nurture mishmash or the possibility
-that it's RNA passage or anything?
-Does anything sort of trigger
-the whiskers, your spidey sense?
-Oded Rechavi: So in that case, I
-would go with the most parsimonious
-explanation, which is it's just
-less fidelity, less DNA maintenance
-and some damage that passes on.
-It doesn't have to be an epigenetic thing.
-Andrew Huberman: But the sperm are
-generated once every 60 days, so the
-damage must be at the level of the germ
-cells not having the proper machinery.
-Oded Rechavi: Right.
-Andrew Huberman: Mitochondria
-or something like that.
-Oded Rechavi: Or the DNA repair machinery.
-The DNA repair machinery could be
-defective or could work less well in older
-people, leading to the constant production
-of germ cells with more mutation.
-This is a possibility.
-Andrew Huberman: Do we know exactly
-what the DNA repair machinery is?
-Oded Rechavi: Yes, there are
-many types of DNA repair.
-There's one that use other
-copies of the DNA to correct.
-There are ones that just recognize all
-kinds of lesions on the DNA and remove it.
-It's a very elaborate
-and complicated system.
-Andrew Huberman: And is it a system
-that is now tractable, that can
-be modified through pharmacology
-or through anything like that?
-Oded Rechavi: So I don't know about
-drugs that correct that, improve it.
-Maybe they exist and I'm not aware,
-but it's very well understood and many
-people are studying this direction.
-Andrew Huberman: Yeah.
-One thing that came across in the
-exploration of the fertility work is
-that what I'm about to describe is not
-legal in the US, it is illegal, but is
-legal in the UK and in other countries,
-is this notion of three parent IVF,
-where it does seem that some of the eggs
-that persist in older females, even if
-fertilized, don't produce healthy embryos.
-They have chromosomal abnormalities,
-replications, and deletions that are
-problematic for the development of the
-embryo, such as trisomy 21 aka down
-syndrome, in part or in large part because
-of deficits in the mitochondrial genome.
-So what they now do is they take the,
-because the mitochondrial genome resides
-mainly in the cytoplasm, they'll take
-an egg from the mother, the sperm
-from the father, but they'll take the
-nucleus from the mother and put that
-into a cytoplasm of a younger woman
-whose mitochondrial DNA is healthy, then
-use the sperm to fertilize that egg.
-And that's why it's called three parent
-IVF, then implant that into the mother.
-And this has been done several times
-in cases of mitochondrial damage or
-mutations in the mother, it works.
-The question is whether or not those
-offspring will grow up to be healthy.
-So this, of course, is not
-just a pure divergence.
-It raises a bigger question
-that I have for you, which is in
-terms of the work in either C.
-elegans or in other model
-organisms, but in particular in C.
-elegans.
-Where do you see this going next?
-And if you would indulge us, I
-would love for you to tell us a
-little bit about the admittedly
-unpublished work that you're doing on
-temperature exposure and environments.
-I mean, how malleable is this system?
-Because to me, it just
-seems incredibly malleable.
-And yet a lot of it's
-still cloaked off to us.
-There's still a ton to learn.
-Oded Rechavi: So, assuming that
-we will discover similar things in
-humans, which we don't know that this
-is the case, but let's say we find
-it, I think there are many things
-you can do before you change it.
-For example, you could also change
-a parent inheritance by having
-the parent exercise, for example.
-Some things like this have been done.
-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.
-So this is one possibility.
-And you can also manipulate
-it at the source.
-You can change, if it's RNAs, let's say
-you could, in the future, perhaps, if we
-understand how it works, actually change
-the composition of the heritable RNAs.
-Andrew Huberman: By eating RNAs,
-just like the worms RNA sandwich.
-Oded Rechavi: No.
-So the RNA sandwich will be
-difficult because it's not.
-I don't know.
-But if you do IVF, if you do any
-vitro fertilization, you can perhaps
-change the composition of the RNAs
-in the stuff that you introduce.
-But way before that, what you could
-do, perhaps even in the not so far
-future, is use this for diagnostics,
-DNA based diagnostics for every
-couple that wants to have a kid.
-In Israel, this is done for most couples.
-You can look at the DNA and look
-for genetic disease, but no one is
-looking at the RNA at the moment.
-If we understand how it works
-better, we'll have another level,
-a whole new world to look at.
-And perhaps there will be some RNAs
-that correlate with disease that
-will say, okay, the beauty is that
-this, unlike DNA, it's plastic.
-So with DNA, this is your DNA,
-perhaps we can choose another embryo.
-But here you could say,
-perhaps again in the future.
-This is science fiction, it doesn't
-happen now, but if we understand this
-and it's true, we can say, maybe you
-should run on the treadmill a little bit.
-This will change the profile of your
-RNAs, and then we will use it for IVF.
-This seems more, because it correlates
-with healthy profiles of RNAs.
-This is a level that no one looks
-at now and holds great potential.
-Again, with a disclaimer that we don't
-know how it works in humans at all yet.
-But, of course, this is
-why it's so interesting.
-Andrew Huberman: Yeah, it's super
-interesting, incredibly promising.
-So, along the lines of things
-that one can do in the short
-term and your experiments on C.
-elegans, I'd love for you to share
-with us what you're observing
-about cold exposure and how that
-impacts subsequent generations of C.
-elegans.
-And if you would indulge us with the
-story of this discovery, like some of
-the earlier stories you told us, it
-is a surprising and fascinating one.
-Oded Rechavi: I'll
-gladly tell you about it.
-This is not a story about
-transgenerational inheritance.
-It's a story about memory
-within one generation.
-Andrew Huberman: Excuse me.
-Oded Rechavi: Within one generation.
-Okay, and as you said, the story of how
-it happens is it's totally by accident.
-It's a funny story.
-And I'm bringing this up because I know
-Dana Lanchev, who's a huge fan of your
-podcast, will really be happy, that this
-is her work and this is unpublished work.
-We didn't even finish it,
-so we're working on it.
-Andrew Huberman: Okay, well, when
-it's published, we will feature the
-paper, Because I love this story.
-Oded Rechavi: Great.
-What happened is that we talked about
-transgenerational memories, and I
-said that in worms, there are very
-long transgenerational memories.
-If a generation time for C.
-elegans is three days, some
-memories last for many generations.
-So way beyond the lifespan of the worm.
-The lifespan of the worm is three weeks.
-You have a new generation
-every three days, but every
-worm lives for three weeks.
-But there's a lot of research that
-shows that unlike heritable memory,
-which can be very long, the memory
-that the worms acquired during
-their lifetime Is very short lived.
-So if you teach something
-after 2 hours, it forgets.
-So, for example, you can teach the
-worm, you can take an odor that it
-likes and pair it with starvation,
-and then it would dislike the odor.
-And then there's a simple test.
-You just put it in a plate.
-You put the odor in one side and a
-control order in the other side, and
-you see whether it prefers this odor
-or not, and it stops preferring it.
-Okay.
-There is 30 years or more of research
-or 40 years of research on this showing
-that the worms forget after two hours.
-The reason I went to study C.
-elegans is that I wanted to
-understand memory because of
-such a simple nervous system.
-Maybe I have the potential to
-actually understand how it works,
-but this is slightly disappointing
-because they forget after 2 hours.
-So what is it exactly?
-Okay, my idea was, and I tried to
-convince students to do it for ten years,
-is to take the worms, teach them this
-assocIation to dislike the odor that
-they innately like, and then just put the
-worms in -80 and freeze them, freeze them
-completely, thaw them and see whether
-they still remember after they are thawed.
-Andrew Huberman: The Han Solo experiment.
-Oded Rechavi: And I didn't w ant to
-do it because of cryopreservation
-or something like this.
-I wanted to do it because as you know
-better than me, many theories about
-memory say that you need electrical
-activity to maintain the memory.
-You need to reverberate it in the brain.
-Andrew Huberman: During dreams or
-replay of the thing or whatever.
-Oded Rechavi: And if the memories
-will nevertheless be kept even
-though the worms were frozen in -80
-it would mean that it was kept in
-the absence of electricity because
-there's no electricity in -80 degrees.
-This was the idea.
-I asked many students, no one
-wanted to do it because it's not
-so easy and also a little crazy.
-Andrew Huberman: Well, and when
-the PI, the principal investigator
-or lab has a pet experiment, no
-one wants to do that experiment.
-[LAUGHS]
-Oded Rechavi: That is universally true.
-And then Dana agreed to do it.
-Dana Lanchev I was very happy only
-later to find out that she ignored me
-completely and did a different experiment.
-The experiment that Dana did instead
-is to just take the worms, teach them
-the association and place them on ice.
-She wanted to see how the
-kinetics of memory and forgetting
-change in low temperature.
-Because maybe whatever memory
-is, the breakdown of the memory
-is affected by the temperature.
-A very simple idea, we
-know, different experiment.
-A different experiment, but
-a cool experiment, very cool.
-And what she found is that when you
-place the worms on ice after you teach
-them, they just don't forget even ten
-times longer than control worms at
-that point, after 24 hours, if normal
-worms forget after 2 hours, after 24
-hours, the worms will become sick.
-So normally we do shorter experiments,
-but for 2 hours, the worms don't forget.
-This is cool, but it was only the
-beginning because the boring explanation
-is just what I just said, that everything
-slows down in low temperatures.
-So the breakdown of memory again, we
-don't know what it is, but whatever it
-is happens slower in low temperatures.
-But this is not the case.
-It's not merely the physical.
-It's the response.
-It's the changing of the
-internal state of the worms which
-affects the memory kinetics.
-How do we know this?
-There's been beautiful work over the
-last year on cold tolerance in C.
-elegans nematodes.
-If you take the worms and you
-place them on ice like she did, but
-longer, for 48 hours, they all die.
-However, if you take the worms, acclimate
-them to lower temperatures for a few
-hours, 5 hours is a minimum, and then
-place them on ice, they all survive.
-They become cold tolerant.
-And people who study this show
-that this involves changes in
-lipid metabolism and many things.
-So Dana took the worms, acclimated them
-to slightly lower temperatures, made
-them cold resistant, and then taught them
-the association and placed them on ice.
-And now they forgot immediately, which
-means that when they change their internal
-state to become cold tolerant, they no
-longer extend memories on ice, which means
-it's not only the temperature, because
-the temperature was in any way low.
-Now they know the memory.
-We took this as a starting point
-to understand which genes change
-when the worms are becoming
-cold tolerant on and off ice.
-And we found genes that when you mutate
-them, the worms just remember longer,
-always, even when they're off ice, because
-these are the genes that normally change
-when they are surprised on the ice.
-And these genes are expressed just in one
-pair of neurons, just two out of the 302.
-Andrew Huberman: Notice
-he said 302, not 300.
-Oded Rechavi: And we can manipulate
-the activities of these genes in
-these neurons to extend memory.
-And then the punchline of everything
-that happened is that we found
-out that this neuron, where these
-genes function, this one pair of
-neurons, is the only neuron in C.
-elegans which is sensitive to lithium.
-And lithium is a drug that has being given
-to bipolar disorder patients for decades.
-Although it's not entirely clear how
-it works, it's very, very interesting.
-It is also interesting,
-there's an episode, of course,
-in your podcast about this.
-You know more about this than me, a lot.
-But it's also interesting because
-it's just an atom created in the
-Big Bang, yet it works on our
-brains in such a fundamental way.
-And we wanted to see whether it
-works also on the worms, because
-this neuron was tied to this memory
-extension phenotype that we found.
-So Dana grew the worms on lithium,
-removed them from lithium, taught them
-the association, and found out that they
-remember a lot longer than control worms.
-Not only that, if you first make the
-worms cold tolerant and then lithium
-doesn't work on them, lithium switches
-this forgetfulness mechanism on and off.
-Andrew Huberman: Amazing.
-Oded Rechavi: And it's all
-connected to cold tolerance.
-Andrew Huberman: Amazing and
-amazing for a number of reasons.
-And so, at risk of being long winded
-in my response, I just wanted to
-highlight something that I think
-will be of relevance to most people,
-which is when, at some point,
-we did a few episodes on memory.
-And I highlighted a review that was
-written by the great James McGaugh, one
-of the great mammalian memory researchers
-who's worked a lot on humans and mice.
-And I was shocked, pun intended,
-and amused to learn that in medieval
-times, if people wanted children
-to remember lessons, they could be
-religious lessons or school doctrine
-or whatever it was, mathematics, they
-would take children, teach them, and
-then throw them into cold water to
-introduce a memory instilling event.
-And we now know that the memory instilling
-event is the release of adrenaline in
-the body, which makes perfect sense
-if you think about traumatic events.
-But this whole general mechanism
-also applies to the learning
-of other types of information.
-And so, if I understand correctly about
-the role of lithium and the role of
-cold in the experiments that you just
-described, there's some general state
-switch, some internal state switch that
-says, what happened in the minutes or
-hours preceding this was important.
-It acts as sort of like a highlighter
-pen in the Book of Experiences.
-And I'm absolutely curious to
-know whether or not this is an RNA
-dependent mechanism in some way.
-So, is this literally like the
-highlighter in the IKEA instruction book?
-Oded Rechavi: This we don't know.
-This we don't know, and as I said,
-this is not even a finished work.
-It's not peer reviewed.
-It's just the state that I told you about.
-But it's very exciting for me to go
-into this new field, and once it's
-out, I'll be happy to talk more about
-it and think about the implications
-and the connection to other things
-and more about the mechanisms.
-Yeah.
-Andrew Huberman: Well, thank
-you for sharing it with us.
-Despite the fact that it's
-not finished, people now know
-that it's also not finished.
-And I love a good cliffhanger.
-So we await the full conclusion and
-interpretation of these results.
-Today, you've taken us on an
-amazing journey through the genome.
-RNA, short interfering RNAs, a ton
-of history of prior experiments,
-some of which ended tragically, many
-of which, unfortunately, did not.
-They were true triumphs, and
-in particular, the work in your
-laboratory, which is just incredible.
-And also this introduction
-of model organisms.
-And I only mentioned a short
-handful of the things that
-you've taught us about today.
-So, first, I want to extend thanks
-for the incredible teaching.
-I also want to say thank you for
-something equally important, which is
-that absolutely came through, but is what
-initially brought me to explore you and
-your work more, although I had certainly
-heard of you, which is that your spirit
-and kind of approach to biology is an
-extremely unique and intoxicating one.
-Oded Rechavi: Thank you.
-Andrew Huberman: Even I
-venture to call it seductive.
-I do believe that whether or not it's
-music or poetry or science or mathematics,
-that the spirit behind something dictates
-the amount of intelligence and precision
-with which that thing is carried out.
-And it absolutely comes through.
-So if I'm making you feel on the
-spot about this, I've succeeded.
-Oded Rechavi: Thank you.
-Thank you very much.
-Andrew Huberman: But I know
-that the listeners can feel it.
-It's a felt thing.
-So thank you.
-There are many scientists out there,
-fewer with this phenotype and even
-fewer that I think that can communicate
-with such articulate precision.
-So thank you so much.
-Oded Rechavi: Thank you.
-Andrew Huberman: It's
-been a real pleasure.
-Oded Rechavi: Pleasure was all mine.
-Thanks a lot.
-Andrew Huberman: Great.
-Well, we'll do it again, and we'll learn
-about all the incredible things you're
-doing trying to transform science, as
-it were, at the level of publishing,
-at the level of social media, because
-there's a whole other discussion there.
-Meanwhile, we will, of course,
-point people in the direction of you
-and to learn more about your work.
-And I look forward to hearing
-the conclusion of Dana's studies.
-Oded Rechavi: Thanks a lot.
-It's been a real pleasure.
-Andrew Huberman: Thank you for joining
-me today for my discussion with Dr.
-Oded Rechavi about genetics,
-inheritance, the epigenome and
-transgenerational passage of traits.
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