Translator: Amanda Chu Reviewer: Rhonda Jacobs
Memories shouldn't be inherited.
We know this intuitively, also from our experiences.
For example, if you read a book,
you know that your kids won't know its content,
or if you go to the gym,
you know that your kids won't become stronger as a result.
This is obvious.
And acquired traits should not be inherited;
nevertheless, many scientists over the years
tried to examine whether, nevertheless, our experiences in life
do affect the biology of our children.
And I'll tell you very briefly the sad history of this field,
which is filled with controversies and all kinds of crazy stories.
So about 100 years ago,
a scientist named Paul Kammerer,
who was very famous at the time, was working here in Vienna,
was studying a toad that is called the midwife toad
because the males carry the eggs.
And he used this toad in an attempt to show
that acquired traits and memories can transfer to the next generation.
There are two types of toads that Kammerer studies:
one that lives on land and one that lives under water.
And they are different in terms of their appearance,
and also abilities.
He claimed that he can take that toad that normally lives on land
and train it by changing the cultivation conditions
for a few generations
until it evolves to become a toad that lives under water -
and when it did so, it also changed its appearance.
And he claimed that it grew these black nuptial pads -
these structures on the hands for toads that live under water
help the male grab the female without slipping.
This was an amazing discovery,
which questions lots of what we know about how evolution and biology works.
However, his story ended sadly because he was accused of cheating.
He was accused of injecting ink to the hands of the toads.
And he couldn't handle the accusation, and he killed himself.
Then later in the '60s and '70s in the U.S.,
a very different character, James McConnell,
tried to do even wilder experiments to prove that memory can be inherited.
He was studying a worm that is called planaria,
which is the champion of regeneration,
so if you cut off the planaria's head, it grows a new head
after a few days, about a week,
including the brain and everything.
And he claimed that he can teach this planaria certain things,
certain memories,
and then chop off its head,
and the new head that will grow
will still contain the memories that the previous generation acquired.
He did even wilder things.
These planaria are also cannibals, so they eat each other.
So he fed naive worms with worms that he taught certain things,
and he claimed that the memory transferred by digestion.
Since this was very wild, many people didn't believe him,
but that was the least of his concerns
because he received a bomb
from the terrorist known as the Unabomber,
and it exploded,
and this is how I started working on this topic.
(Laughter) (Applause)
Thank you.
(Applause)
The difference was that I decided to study this
using a simpler worm that is called C. elegans,
which is a very important model
for biologists studying genetics and neurobiology.
So after I finished my PhD,
I went to New York to study this with Oliver Hobert,
the famous neurobiologist in Columbia University.
And I'm still in love with this worm.
I still study it today, almost a decade after.
It's a great model for many things,
especially for studying inheritance, genetics, and neurobiology.
The reason that it's such a good model
is that, first of all, it reproduces very fast -
the generation time is very fast,
so you have a new generation every three days.
So you can study many generations fast.
Second, every mother produces something like 250 babies,
so we have large numbers and good statistics.
And the third thing is that its brain is extremely simple.
So it has just 300 neurons in the brain,
300 brain cells.
We have many billions, so it's much, much more complex.
But before I tell you what I discovered using this worm,
you need to understand
why, in theory, memories should not be inherited.
There are a few reasons.
The main reason is that we have two types of cells in our body:
somatic cells,
which are the regular cells of the body,
like blood cells and neurons and the muscles;
and we have germ cells.
These are the sperm and the egg,
and these are the only cells
that can transmit DNA to the next generations.
So for example, if you go to the gym
and you practice and you build up muscles,
since it doesn't affect the DNA in your germ cells -
the sperm and the egg -
it doesn't lead to inheritance.
And this is a fundamental principle;
it's called the second law of biology, the first being natural selection.
And it's also known as the "soma to germline barrier" -
the germline is segregated from the soma.
And the man who discovered this barrier is August Weismann.
That's why it's also called the "Weismann barrier."
And he's one of Darwin's most prominent followers.
He worked in the 19th century,
and he had many seminal contributions, many, many important discoveries.
But he wanted to prove
that what happens in the soma stays in the soma
and that we cannot inherit acquired traits.
And to do so -
Although he was a great biologist,
he did an experiment which wasn't that great.
In fact, even George Bernard Shaw wrote a play that mocks this experiment.
What he did was for many consecutive generations,
he cut off the tails of mice in every generation.
And he suggested that the fact that they kept growing long tails
and that the short tails were not inherited
shows that inheritance of acquired traits can't happen.
Of course we know this also from circumcision -
we didn't need experiments -
but still it convinced the scientific world
(Laughter) (Applause)
and became, really, a fundamental dogma.
Okay?
When I came to study this, I had a different idea.
I knew of course the DNA doesn't transfer
between somatic cells and germ cells.
And what happens in the soma to the DNA -
if you get a mutation in your hand -
It doesn't affect the DNA in your germ cells,
which is the only DNA that counts for the next generation.
But I thought that maybe another type of molecule
would be able to transmit memories between generations,
and the molecules that I thought about were small RNA molecules.
RNA is a close cousin of DNA.
It's a more ancient molecule that evolved before.
The world used to be an RNA world,
and RNA enabled inheritance before DNA existed.
And I had reasons to believe
that maybe small RNAs would be able to move from the soma to the germline
because we knew at least in C. elegans, in these worms,
that they move between cells.
What small RNAs do
is inside cells, they regulate gene activity,
so they decide which genes will function and which won't.
Okay.
So to study this, I did a very simple experiment.
This worm that I'm studying, C elegans, is remarkably resistant to viruses.
There are no viruses that efficiently infect it,
as the reason is that when you infect it with a virus,
the worm produces small RNAs
that match the viral genome and lead to its destruction -
they simply chop it up.
And there was a Nobel Prize awarded for this discovery,
for how these small RNAs work.
What I showed -
this was very new and exciting at the time -
was small RNAs work not only in the parents
but they are also transmitted to the next generation
and to the next generation and to the next generation
to effectively vaccinate the kids,
so if the kids are again challenged with viruses,
they are already protected.
So it's a heritable vaccine, an acquired trait - viral resistant -
that was passed on to the next generation.
This also allowed us to study the mechanism of how it works.
We learned a lot about the genes involved and so on.
The next thing was that we thought that maybe it's not only about viruses.
Maybe other traits can also be regulated using the same mechanism,
and other memories can transfer between generations.
And specifically, I was thinking about the memory of starvation.
And the reason is that the biggest epidemiological study test
that has been done on humans,
on transmission of responses between generations,
was done on people that survived starvations in the past.
In the Second World War,
the Nazis starved large populations in the Netherland.
And people studied the descendants of the individuals that were starved,
and they saw that although there are no changes to their DNA
as a result of the starvation -
because this can't happen -
the descendants suffer more from diabetes
and from other neurological diseases, such as schizophrenia.
Of course this is extremely difficult to study in humans, or in mice,
because they are so complex, but I thought maybe worms can explain it.
Maybe what's being transmitted here are small RNAs,
and this is a different type of inheritance than DNAs -
new rules of inheritance.
To study this,
we can do a really good starvation experiment in worms
because we can really control their conditions.
So what we did is we took worms and we either starved them or not,
and when we starved the worms, we found that they make small RNAs
that regulate the function of nutrition-related genes -
they regulate their nutrition.
But not only that,
the interesting part
was that these small RNAs moved also to the children,
to the grandchildren, and to the great-grandchildren,
and changed their nutrition-related genes as well.
And this had real consequences on the physiology of the kids.
So the descendants of starved worms lived significantly longer.
We now know that they are also more protected
if you challenge them again
with a much more difficult period of starvation -
so it seems adaptive.
One of the Holy Grails of this new field
is to think whether the brain can generate heritable responses,
whether memories formed in the brain are inherited,
because normally when we think of memories,
we think of memories the brain can generate,
and these are special memories.
This sounds crazy that you think about something, you learn it,
and then it will be inherited.
But we wanted to study this in worms, and we show that in fact it happens.
So smaller RNA changes in the brains of worms
lead to transgenerational changes that affect multiple generations.
If you change the population of the production of small RNAs
in the brains of the ancestors,
it changes the physiology and the behavior of the descendants,
even the great-grandchildren.
So we've shown that small RNAs that are made in the ancestors' brains
are needed
so that the kids and the grandkids can search food efficiently;
otherwise, they can't find food, which is obviously very critical.
Over the years, we discovered many types of environments
that lead to transgenerational changes,
and now we want to understand the rules of how it happens
because it's very different
from the normal rules of genetics that we know essentially for 150 years,
since the monk Mendel discovered them.
And so, for example, we want to know, For how long do their responses last?
And we found the mechanism that we call the "transgenerational timer,"
which dictates, which governs the duration of the heritable responses;
and normally responses last only three to five generations,
and then they are erased.
And we found that this clock is constituted from genes,
is built on genes that set the exact time;
and we can manipulate these genes and control the duration of the response,
and also make responses that will just last indefinitely and be stable.
We call these genes MOTEK genes.
It's an acronym
that is short for "Modified Transgenerational Epigenetic Kinetics,"
and also "motek" means "sweetheart" in Hebrew.
(Laughter)
And now, I'm ending here; this is my last slide.
I want to say -
and this is a very important message that has to come across -
that we have no idea
whether this is happening also in humans.
We just don't know, okay?
So there's no need to be worried or anything like that,
because we have no idea.
Many things were discovered in simple organism
and later found to be true in humans,
but we have no idea that this is one of them -
I certainly hope so, but we don't know.
If memories are inherited also in humans,
it might mean you have a greater responsibility for your actions
because you're affecting multiple generations.
But we don't know that's the case.
But I think that regardless of whether memory is inherited in humans or not,
it's probably a good idea to act as if it does.
So thank you very much.
(Laughter) (Applause) (Cheers)