Alright!
This is a sciene talk, so please block the exits,
keep people from escaping and we'll see where we'll end up.
My talk is about evolution and lots of things have been said about evolution,
lots of things have been done.
I want to make one disclaimer:
I've only been given two and a half hours to talk about this by the organisers,
so I have to give a short introduction to some aspects -- to a summary of evolution.
I'm going to skip over things, going to simplify things,
and you're going to have to live with it.
But the points I'm making will hopefully make some sense.
Evolution: everybody knows the theory
or thinks that they know it.
It's a work in progress; that's very important.
There's many things we understand.
There's many facts that tell us evolution is right.
There's not a single scientist
that really works by scientific methods,
that looks at facts and uses theories that doubts the theory of evolution.
That does not mean that the theory of evolution is there, that it's not changing.
We always discover more and we need to adapt our theory.
It's very important. Some people think
that because we sometimes discover something
and we need to make slight changes to our theory
that the theory is not valid.
And instead they come up with a theory for which there is no proof at all
and they think that's a much better option.
I don't think so.
Alright! Let's start with this guy.
As you can tell, very fashionable: French.
Jean-Baptiste Lamarck.
He was one of the first people to come up with a coherent theory of evolution.
He's done many more things, but his theory is quite extraordinary.
And one of the aspects of his theory is that
he believed in the inheritence of acquired characteristics.
What does he mean by that is
that, well, look at these giraffes.
It's a very easy way to explain this idea by Lamarck.
Everybody knows that a giraffe has got a remarkably long neck.
How does it get the long neck? Well --
it's trying to eat leaves on the tree.
And it stretches it's neck.
And therefore the little kiddy giraffes will have slightly longer necks.
And again this repeats, and that's how the giraffe got a long neck.
Seems a bit silly to us but it's actually a great idea.
He was going with the data he had.
Wonderful theory, except it's not right.
In came Darwin.
And enough has been said and done about Darwin
over the last year especially.
He's been great.
One of the things that he did is
he introduced two key concepts
namely variation and selection.
And with variation he just said:
Well, these giraffes don't stretch their neck
-- well maybe they do, but they are born with short and longer necks.
There's just this natural variation amongst giraffes.
And the lucky ones that have the long necks, can reach more leaves.
And as you know, you only think about sex after you're not hungry anymore,
so -- (Laughter)
they're going to reproduce because they're not hungry anymore.
They're going to get little giraffes with slightly longer necks
and that's how evolution happens.
So, this is the selection part
and then there's natural variation.
He didn't really say how the natural variation occured,
he didn't really have answers to that.
He thought about it a lot.
But he really separated the two processes.
This is also what made him so controversial,
because it was very cruel,
it's a very cruel way of having evolution.
There's giraffes dying.
There's poor giraffes with short necks dying here.
Alright!
And this fellow here looks very stern.
He's German. (Laughter)
August Weissmann, great great biologist.
He really -- one of the things he did
is really try to proof that variation and selection
are completely independent.
And one way he did this
-- so he really sort of tried to kill the old idea by Lamarck
that the length of the neck of the giraffe has really nothing to do
with what it did in its lifetime
and its stretching out for trees.
So one of the things he did
-- he's really very famous for this experiment,
although it's not his best experiment --
he took mice as soon as they were born,
cut off the tail then bred more mice
as soon as the little mice were born
cut off the tail again and just repeated this.
And in the end what he noticed was
that all these new mice, these little mice,
even after he's done this for 30 generations
still had tails that were just as long as the original mice.
So it's a great way of disproving Lamarck.
I would say, he should have relaxed, sit back,
thought about looking at the Jewish male population
and we wouldn't even had to do his experiment. (Laughter)
So, he came up with a, I think, much more important finding, though.
And really amazing work that he did.
Where he actually said that,
even early in our lives, and I'm talking about embryo's,
what he called our germ cells,
these are the cells that are used to reproduce,
are separated from the rest of the embryo.
You can see them here as little dots.
And they separate and we all know where they end up in the end.
And the strong point in that --
he was totally right about this --
and the strong point about this is that --
pretty much what he was saying is --
when the giraffe stretches its neck, it's not stretching its testicles.
So how can this have any effect on your germ cells.
It's a very strong point, then again,
at least for complex organisms,
he set apart variation and selection.
The forces that will select you
are independent of this variation that you have.
Again a bit later
these two fine gentlemen here, Luria and Delbrück,
were working in Cold Spring Harbor in the U.S.
where they were doing multiple amazing experiments
and one of them got them the Nobel Prize.
And they were working on this virus here,
which looks a bit like a Moon lander
but it's a little bit smaller than it.
It's called a bacteriophage.
This is good news for all of you.
All of you non-scientists might not realize
that these bacteria that make us sick
they actually also get sick, they also have virus infections.
The only organisms that gets away without being sick
are the viruses themselves.
But so, bacteria do get virus infections
and they actually die from it
and that's what these guys were studying.
And they also wanted to look at this idea:
is variation independent of selection.
And they came up with a very smart experiment.
What they did is, they said, "Well, let's start from one bacterial cell.
And let's give it lot of food so it will make lots of little bacteria."
And they always divide as you know,
bacteria they grow or they multiply by just dividing themselves into two
and they make clones of themselves,
genetically identical, and so this is what happens.
And they said --
so these are the bacteria here, always dividing --
and they said, "Well, at some point we're going to introduce a virus
and we're going to see what happens."
Because they've noted that when you introduce a virus to lots of bacteria
there's always a few bacteria that manage to survive.
They are genetically, because their little children bacteria are also surviving,
so it's clearly a genetic trait
something has happened to their DNA, to their genetic material.
So something has happened.
Some of these bacteria are resistant.
And now the question is --
this variation, because that's what it is,
does it occur before the bacteria are ever in contact with the virus?
Or is it when we infect this culture,
this hundred of millions of cells,
that suddenly a few manage to become resistant?
It's a very interesting question.
And they were very smart.
They said, "Well, supose there is a mechanism
by which, when you infect the bacteria with the virus,
it tries to become resistant some way.
There's a mechanism.
Then, if you do this to a hundred million cells,
and you do it a few times to a hundred million cells,
you sort of expect that a similar number of bacteria
will always become resistant
that manage to get there, right? The lucky few.
Whereas, suppose that some bacteria become resistant
while they're multiplying -- the blue dots here --,
You can have vastly diferent numbers when you repeat this experiment.
Because, what can happen is:
here we have a bacterium that becomes resistant to the virus
very late in the reproduction.
And there's only one in this whole population
that's resistant, that's not killed by the virus.
Here though, you have what is called a jackpot event,
and the name comes exactly from what you think it comes from.
Very early in the reproduction of this first cell here
one of two kids becomes --
or maybe the parent becomes resistant
and it starts dividing. And now half of your culture --
but we're talking millions of cells here -- are resistant.
So you have this huge variation.
So they've done the experiment
and what they found was this.
And so they concluded:
Clearly -- and they've shown this matematically --
clearly some bacteria in this population
were resistant to a virus that they've never seen before.
And again, variation must be independent of selection.
Now, I would claim, and other people have claimed,
that the experiment does contain a pretty serious flaw.
And I'm not saying that they didn't deserve the Nobel Prize,
at all, they definitely deserved it.
But one problem with their experiment is clearly
that, well, they introduce a deadly virus
maybe the bacteria have a mechanism to develop resistance
or tolerance to this virus,
but not to one that kills them instantaneously.
Maybe they should have used some milder stress,
some milder selection.
So that's the problem there.
And then of course, later
after Watson and Crick and Rosalind Franklin here
discovered the structure of DNA
and the whole molecular research started taking off
we sort of put everything together of the evolution theory
into what is called 'the new synthesis'.
And that's sort of our current theory of evolution
where you have changes in the DNA code
that are more or less random,
they are independent of selection
and they give you diferences,
that's what's causing all these differences between us
and that's why some of us cannot get AIDS and most of us can.
Which is true, by the way.
And so this is pretty much our theory.
Now, I don't want to end here.
What we've seen is that
more and more evidence is emerging that
the story is a bit more complex.
And maybe variation and selection
are not so completely independent as some people believed.
And I got to know about this
while studying this year
I did my PHD in a beer brewing lab.
You know, it's one of the better places
to start your research as a student.
And I was stuying yeast cells,
great genetic model organism by the way,
so actually one of the frustrations I have
is, try to be taking seriously by the people who need to fund you
or at the conference, when you're working on beer.
And you go like, "Trust me, I'm doing real serious genetic experimenting."
Alright, so one of the things I was studying is
yeast cells that are clumping together.
It's called flocculation.
So what you see here is a bunch of yeast cells
that stick to each other and they settle out in this in this culture here.
This is important for beer because it happens at the end of fermentation.
This is what pretty much makes the difference between a clear beer,
that doesn't have any yeast cells in it,
and what we call a 'witbier' or a 'weizenbier'
that has yeast cells still floating around in it.
And we were trying to find the genetics of this.
What we found is this one gene here
flow one, which stands for flocculation one.
It's a gene, and what is so special about this gene
is that it contains a middle part
that is extremely unstable.
So this gene is of course made of DNA, like any gene.
And the middle part of the DNA is extremely unstable.
It changes much more than any other DNA.
And what it is in particular
is that it contains these things which are called 'tandem repeats'.
It's pretty much a piece of DNA that's repeated time and time again.
It's much longer than what you see here but you get the basic idea.
And what makes it unstable is
that the number of these repeats changes very quickly.
Every time the DNA is copied
you have a pretty high chance that the number will be different from what it was.
This has been known for a long time
except people don't really expected too much within genes.
Usually you find these tandem repeats outside of genes.
But here and in some other genes you find this.
So, what you have here is a piece of DNA
or a particular gene that's changing more rapidly than other genes.
And in this case it means that flocculation is changing,
so this characteristic of the yeast, this specific thing,
compare it to a long neck, if you will,
is changing more rapidly than some other properties of the yeast.
Now if you think that this is
-- well, this doesn't matter --
if you think that this is specific for yeast cells you are wrong.
Pretty much around the same time we were publishing our story,
there was a great story published about dogs.
And I don't know if you've thought about this
but dogs are some of the most variable creatures
on the face of the Earth.
Especially when it comes to their shape.
Just look at, you know,
this Chihuahua and this St. Bernard here.
They're the same species.
In principle. And I say 'in principle.'
These things can breed.
You just hope that the Chihuahua is not a female.
(Laughter)
Now, these are bred by humans.
We have made these dogs by selection and whatever.
But we didn't even use so much time for it.
And in evolutionary terms these things are new.
They are brand new and they were, sort of --
they developed in a very short time.
And one of the things that was found
is that one of the key regulators that regulates --
and again I'm talking about the gene --
it's a regulating gene and it regulates the shape of the skull.
Basically the shape of the dog as well.
And it also has this unstable tandem repeats in it.
And what these researchers found is
that there's a nice correlation between
how many repeats you have in this gene
and how curved your snout is
or how long your snout is.
And they also found that some other changes in another regulatory gene
give you a sixth finger.
Sort of this little extra thumb here.
And, I didn't know this but this is a characteristic
of a specific breed of Great Dane dogs.
And that's why this actually happened.
It sort of happened in a very short time
and now people see this sixt claw, if you will,
as a characteristic.
So clearly it's not just happening in yeast.
And there's more.
One of the other things that people have known for a while
and we are also researching
is that the end of chromosomes
-- chromosomes are basically packages of DNA,
that's how our DNA sits in the cell --
well, the ends of chromosomes -- here,
the very ends -- they change much more quickly.
There's higher mutation rates.
The DNA is not as stable.
And so the genes that lie there, again, evolve.
And if you're wondering in humans which genes are lying there.
It's the genes that, for example,
the genes that make us smell.
And of course we have to recognize lots of different smells
and these genes are copying themselves
and they are changing very quickly.
In plants: a whole different mechanism.
And this is a bit more complicated.
I will try to fly through it.
There's this particular protein.
And, this is a bit like your mother.
This protein is the mother of the cell.
It sort of checks all the other little proteins
and it goes like, "Are you okay?
You don't look very good. Here, here's your coat.
You should behave this way, don't behave that way."
It's sort of like a teacher mother.
And, so the protein really takes care
that even if there's small mutations,
changes in other proteins, that they still behave right.
And if they don't behave right, they get degraded.
Now what you see is that, in times of stress
-- and plants also have stress,
stress is a biological word for selection.
It means you're not adapted to a condition.
It means that you feel the burden of evolution
pressing down on you, pretty much.
So, in times of stress, this protein, this function of the mother protein,
gets dialed down a little bit.
And suddenly these plants start disbehaving.
You know, they become weird.
And that's because some mutations that you previously couldn't see
now suddenly emerge.
And, although it's not proven, it seems like a likely theory
that maybe this could serve as a mechanism
to try and escape the stress.
Because suddenly it's good to try and be different
from what your mother was.
And so maybe a few of these plants
are better at surviving the stress.
And they will cope. And maybe this mutation can get fixed.
And this and that.
Another thing, another example comes from bacteria.
And I'm just skimming over it again,
but bacteria -- in times of stress, again
they activate -- and this is just to impress you
it's not very important -- in times of stress
what they do is, they activate a different protein to copy their DNA.
And of course a protein to copy your DNA is a very important protein.
Because it shouldn't make too many mistakes.
Because that's how you get changes in DNA
and that's how you get natural variation.
So you need a little bit of them but you don't want to much of them
because most of the variation is not good.
It wouldn't be so great if a giraffe got a neck that was three times as long
because the heart couldn't cope with it.
But in times of stress, again
it's obvious sometimes you need to chose between dying or gambling.
And bacteria may be gambling.
They activate this gene that's very sloppy.
And so the DNA gets copied, but it has lots more changes in it.
And maybe, although it's hard to prove it,
maybe this is a strategy of bacteria to try and beat the selection,
the evolutionary pressure that's pushing down on them.
An even nicer example, I think, is the waterflea here.
Again, it's pretty mysterious still.
But waterfleas, swimming around, beautiful organisms,
they have predators. And when they get -- you know,
there's a family of waterfleas and dad gets eaten,
there's some chemicals released in the water
and it induces the formation of the stickle here, which is called a 'spina'.
And the stickle makes the waterflea a little bit less attractive for predators.
Now that's all great, thats not so special
a chemical induces some morphological change.
The weird thing is that the kids of this waterflea will also have the spina.
Even if they've never seen a predator.
Even if you take all the predators away.
They will still have this for quite a while,
for a few generations.
So this comes very close to Lamarck, right?
There is something happening in the course of the life of this organism.
It changes something and it's giving that information to its kids.
It's getting pretty close to Lamarck.
So, this is, the conclusion of the talk -- and this is important --
does this mean that our theory of evolution really needs a major overhaul?
I would say: not at all.
And, people have often misunderstood
I guess the things I have said and published.
And it happened recently in this Flemish, or Dutch, magazine here, where I wrote a piece
telling, or writing about the same things that I'm telling you now.
And this is the cover they came up with.
I wasn't so happy because it looks like I'm sort of sawing the ground under Darwin.
No.
Here, this is what Darwin wrote literally
about variation and selection.
He says, pretty much he says,
I have spoken as if this natural variation was totally random in my book.
Like it was just pure chance.
But of course I didn't mean to imply that.
It just means that I don't really know what's happening.
And maybe there is a mechanism It's much more complex.
Darwin was extremely clever. He thought about his theory.
He knew exactly where the holes were
and where he shouldn't really speak for one possibility or the other.
So he actually incorporated --
it's only later that maybe we've gone a bit too far away from Lamarck.
He didn't really dislike Lamarck's theory that much.
Although, this is not to say that Lamarck's theory was right.
I mean, I still think that it's mostly random
but there's some small changes here and there
that make it a little less random than completely random.
So, what I'm saying is that through evolution, mechanisms
have developed that make evolution not a complete chance.
And then you might start wondering
how can this be right.
And there I would argue this just happens through the process of evolution.
Suppose a gene becomes very unstable
and it's a housekeeping gene
it's a gene that doesn't need to change.
Or it doesn't need to change as quickly.
Or when it changes it's mostly detrimental.
Now, if such a gene becomes unstable
it's going to be a huge disadvantage for the organism that has it.
And so it will be selected away.
However, if a gene
for example, a gene that makes your skull a bit more flexible,
like in a giraffe, and maybe you can, you know,
you get more giraffes with longer necks.
If such a gene arises, by pure chance --
and this is pure chance.
Maybe it becomes an advantage for the organism and it stays there.
It stays unstable like it was.
And maybe that's how these things have evolved.
Now again, like I said, my work sometimes gets misinterpreted.
Sometimes it's quite funny. Especially when it's the people
that believe in creationism as a more intelligent design that take our work.
This was [one of] the more funny things.
This is a website called 'uncommon descent.'
And if you think about it, you know,
the title says it all. These people don't believe in the common descent,
that's of course at core of our evolution theory.
So we published a paper,
a coleague in the U.S. -- when I was still working in the U.S. -- and I.
And we were, again in this paper, it's a more in-depth discussion of what I'm telling you know,
and we were aware of the fact that some people might misinterpret this.
So, in the abstract, in the summary of the paper,
which is pretty much the thing that everybody will read,
we wrote, specifically, that our ideas do not go against Darwin.
And then these guys here read the article,
still wanted to use it for their ideas.
And they said, "Well, to publish this in a reputed scientific journal
the authors needed to write something that their ideas do not go against Darwin,
but they don't mean it.
It's just a secret handshake to get into this good journal."
So that's the secret handshake here.
So luckily there was --
oh, then it becomes quite funny because there's reactions on this forum
of people, and, well, I can barely read it myself, but I'll try.
So this is one of the people reacting to this, and he says --
they quote some of the parts that we write in the paper --
and he says like: "Error-prone DNA copying enzymes
produce bursts of variability in times of stress.
These mechanisms seem to tune the variability of a given characteristic
to match the variability of the selection."
That's something that we wrote.
And he says, "Gee, it almost seems like a built-in response mechanism.
Who would've thunk. Darwin is sooo dead!" That's what he writes.
Anyway, so there's some people who did not misunderstand our paper
and they reacted to this.
And it's also fun to read this discussion
because then the 'intelligent design' people get on.
It's all one great family.
It's kind of fun to have this -- I really like these discussions.
I have nothing against people who come up with different theories.
They're just wrong, but, you know,
it makes it fun to discuss with them.
Alright, this brings me to the acknowledgements.
And I have to acknowledge pretty much all these people here,
which are the people who are doing all the hard working in my lab,
probably as we're speaking now they're getting more results
so I can give another great talk and, you know, be the hero for this audience.
They are chained to their benches.
I have to remember to feed them tonight.
But, they really are the heroes of the lab.
And there are many more of them, of course,
our group is definitely not the only one doing this work.
For people who are scientists and want to know more about this
these are some of the publications.
This is the major one, where we really sort of discuss all these things.
There's more information on the website.
And this is very impotant as well,
these are the people that are paying us.
Well not me, but, more, the research.
Thanks.