- [Announcer] This program is presented
by University of California Television.
Like what you learned?
Visit our website or follow
us on Facebook and Twitter
to keep up with the latest UCTV programs.
- Welcome to a conversation with history.
I'm Harry Kreisler
of the Institute of International Studies.
Our guest today is Svante Pääbo,
who is director of the Max Planck
Institute for Evolutionary Anthropology.
He's a Swedish biologist specializing
in evolutionary genetics.
One of the founders of paleo-genetics,
he has worked extensively
on the Neanderthal genome.
He is the author of Neanderthal Man,
In Search of Lost Genomes.
He is at Berkeley in the fall of 2014
to give the Forester Lectures
on the immortality of the soul.
Professor Pääbo, welcome to Berkeley.
- Thank you.
- [Harry] Where were you born and raised?
- I was born in Stockholm,
Sweden, and grew up there.
- And looking back, how did you parents
shape your thinking about the world?
- Well, maybe my background
was a little unusual
in that I was, when I
was born to my mother,
my father was already married
and had another family.
So we were sort of the secret family.
My mother was a chemist and,
I think, influenced me a lot.
My father was a biochemist.
He had less of an
influence, but he did have
some influence in the background.
He spent, like, Saturdays with us
and always took an interest
in what I did and things like that.
But it was really my mother, I think.
- And he was a Nobel Laureate.
- Yes, he eventually
then got a Nobel Prize.
- And she was very supportive
of all of your interests
as you grew up, and must
have been a powerful force
in shaping your interest in science.
- Yes and, I think, one thing
that influenced me a lot
was that sometimes when I was 13 or so,
she took me to Egypt, and
that's really when I discovered
the ancient history that
became a fascination to me,
as for many young people, I think.
And she really sort of encouraged that.
But also encouraged, I
think, a very, sort of,
quantitative, rigorous attitude to things,
from her chemistry background.
- And did you have an interest in mummies
before you went to Egypt, or
only after you went to Egypt?
- That's really after I went to Egypt.
It was such an experience for me
to realize that, in
Egypt, you can walk around
in sort of old ruined
fields where the ground
almost is composed of pot shards
that are thousands of years old.
And there are, you know,
these dubious antique dealers
that will offer you mummies
or pieces of mummies
that they at least claim
is from Pharaonic times.
That there was so much things preserved
from thousands of years ago
really blew my mind at the time.
- So it was almost
inevitable that you would
become a scientist of some sort?
Or not necessarily.
I mean, was your education
as a young person
very supportive of your
interest in science?
- Well, I think my interest was then
really in Egyptology and archeology.
And I thought I would
become an archeologist
and excavate in Egypt and started
studying those things at university.
And then, I think, it sort of showed
that I had a too romantic idea
about what Egyptology would be.
I thought it would be more
Indiana Jones like things.
So, and it was, at least
in Sweden at the time,
very linguistically-oriented.
You ended up studying, you know,
ancient Egyptian verb
forms and things like that.
So then I didn't really know what to do.
I pursued these studies for what
amounted to almost two years.
- This is as an undergraduate.
- This is at the university, yes.
And then, I think, it was probably
due to my father's influence that I then,
when I didn't know what to do,
decided to study medicine
with an eye towards doing research.
- And was his influence, did it emerge
out of conversation?
Or knowing what he did?
- More from diffusion,
I think, than really,
I mean, both my parents were very good
in supporting me in the
things I wanted to do
and not trying to prescribe anything,
which is probably a recipe
for disaster for young people.
- And you, an idea that
emerges in your book,
which is a very good
account of doing science
and the research that you've done, is,
you have an adventure,
you are an adventurer.
In other words, there's a little
bit of Indiana Jones in you
in terms of exploring new frontiers.
- Maybe, yeah.
I sort of sometimes say to students,
if they wonder if they should pursue a PhD
is that you should only do
it if you really enjoy it,
if you think it's fun, you know?
We're, probably, if we
come that far in life,
all smart enough to work
in an insurance company
or in a bank and earn much more money.
The only reason to really do research
is that you're fascinated by what you do
and enjoy it every day.
- So after undergraduate work,
and realizing that you didn't wanna
just be alone with mummies,
as an Egyptologist,
you decided to go to medical school.
- [Svante] Yeah.
- As the career that
you would pursue first.
And what was it about medicine
that convinced you you had to do more?
- In Sweden, it's still the situation
that you rather often go to medical school
when you want to do basic research.
That was really why I started.
Then I more discovered, as I went along
and did the more clinical courses,
that I also enjoyed seeing
patients very very much.
And liked interaction with
people from all walks of life
that you get as a doctor.
So I was actually, I had a
little mini crisis about,
should I stay and finish my medical degree
and become an MD, or do research?
And I said, let's try
research, I can always
come back and finish it later.
And that's where it
ended, I never came back.
- And the research you chose to do,
or what you got your PhD in, is?
- Is sort of molecular
immunology, if you like.
How the virus deals with viral
infections and interacts with viruses.
- One of the interesting
themes that emerges
is your many careers, in a way,
in your formative years in education.
Medicine, molecular biology,
with this passion for
ancient beings and artifacts.
You really were drawing on
all of these disciplines
later in life, in a way.
So your education gave you entree
to new worlds that were opening up
that you then applied to this passion
that you had for ancient things.
- Yes, and I think it's sort of
a good thing with a sort
of university system
if it allows you to study different things
that you can then bring together.
It was, of course, quite obvious for me
once I started to learn to manipulate DNA
and clone it in bacteria,
as we did at the time,
to say, well, might there
not be DNA preserved
in all these hundreds
and thousands of mummies
of humans and animals that I knew
were stored in museums around the world
and were found in Egypt every year.
So I started looking in the literature
to see if anyone had done anything,
and to my amazement, seen
that no one had tried it.
So then it was pretty obvious to say,
let's see if this can be done.
- Before we pick up that theme,
I wanna ask you about the skills you think
are required to be an
accomplished scientist.
Obviously, you've suggested
learning many specialties, in a way.
Anything else?
- In some sense, I would say
that science is wonderful thing
because there are many many different
ways of being a good scientist.
There's not just one way.
There are those that are
incredibly knowledgeable
and thoughtful and really think very hard
and then come up and do
the crucial experiments.
There are those that try many many things,
one of them turns out to work out.
And, of course, one way of doing it
is to bring together knowledges that are
normally not combined with each other,
which might be particularly fruitful to do
especially if you're not incredibly smart.
Because, of course, if
you're sort of moving
into a field where many
other very smart people work
and say, I'm going to really
make a contribution here,
you have to be very very smart yourself.
But if you bring things
together from different areas,
you necessarily don't have
to, sort of, be super smart.
- So, in terms of temperament,
you're suggesting,
you suggest in your book, in
a way, being an experimenter,
testing not just in the scientific sense,
but in the sense of
trying different options,
but then really persevering when passion
comes together with knowledge, in a way.
- Yes, and I think one
sort of driving force
was this feeling that it's
sort of very frustrating
to study history purely from,
say, archeological remains,
or even texts that you would
have from ancient Egypt,
but not being able to
really know what happened.
So there was some feeling
there, I think, and still is,
that if we can bring some
kind of rigor to this
and at least study the
population history directly,
not by inferring from
present-day variation
or from old texts or from archeology
what happened in the past,
but actually go back in time
and look at what were the genetic
variants in the population
that actually existed here 1000 years ago
or 10,000 years ago or
even 100,000 years ago,
that that would be fascinating to do.
- It's interesting, because
what paleontology had
before your work, and the work of others
who were moving in this
direction, was really artifacts,
things that were left
by prior civilizations
or prehistoric humans, or whatever.
Whereas what you're really focusing on
is an empiricism that relies on the data
that lies in the bones, in a way.
- Yes.
And I think even today, where
one infers population history
from studying variation
today, under certain models
and ideas of how things change
in populations over time,
it is still extremely valuable to actually
go back and test those things.
And you often, more often
than not, get surprised,
that things have not been as
you had thought in the past.
- A theme in your book,
again, is the moment
where creativity leads to discovery.
And there have been several
points in your career
that one could call wow moments.
And one of them is one you just described,
namely, when the technology came along
and evolved to replicate DNA.
That was a wow moment for you which you
attached to your passion
for studying ancient things.
Talk about that moment.
I mean, was it something
that came suddenly,
or did it evolve after much research?
- A sort of, a theme, all the
way, over 30 years had been,
can we extract and study
DNA from ancient remains?
And this then started when
one extracted this DNA
and multiplied it in bacteria.
So that was the first sort of experiment
I did in the early '80s.
And it was very frustrating,
because it's a very inefficient process.
And you, above all, you can sort of
retrieve some DNA
sequences and study them,
but you cannot repeat your
experiments, since it's so,
to find the same piece of DNA again,
from that specimen, is almost impossible.
- And explain that.
In other words, in a way,
science was using bacteria,
to ride on the back of bacteria
and its processes to replicate DNA.
- Yes.
So, you take your DNA from, say,
an ancient bone or from a blood sample,
you link it up with a
piece of bacterial DNA
that then gives it the ability to multiply
itself when it's introduced into bacteria.
So you use the bacteria as a
copying machine, if you like,
to make thousands and millions of copies
of these small pieces of DNA.
But it's a random process.
You just happen to pick up some molecules.
And it's very hard to then
find the same molecule again.
And as biologists in general, really,
sort of driven by technological advances,
so then came the
polymerase chain reaction,
which was an invention by Kary
Mullis here in the Bay Area.
That is a possibility in the test tube
to multiply a predetermined piece of DNA,
that you decide which
piece you're interest in
by synthetic pieces of
DNA that you sort of
use to make many copies of it.
And it was obvious from day one
when I heard about that thing
that it might be ideal for
studying ancient remains.
So that's then what I started working on,
first back in Europe and
then over almost four years
as a post-doc here at
Berkeley with Alan Wilson,
which was a fascinating
time, because suddenly
we could go back and actually
reproduce our experiments.
So we could amplify, for
example, a piece of a moa,
an extinct flightless
bird from New Zealand,
and then repeat it again
from the same individual
and from other individuals
to really make sure
that the DNA sequences
we got were correct.
Up to that with these bacteria,
one had never really been able to be sure
if this was a contaminating piece
of DNA that actually came from me
or some museum curator
or something like that,
and in many cases they actually were.
- You quote Jared Diamond as saying
"All specimens constitute
a vast, irreplaceable
"source of material for
directly determining
"historical changes in gene frequencies,
"which is among the most important
"data in evolutionary biology."
So that description, in a way,
is what came to be, really, by your work.
And interestingly
enough, but all this time
you're keeping this passionate
focus on ancient things.
- Yes, it's really this thing
of going back and saying, we should try
to catch evolution
red-handed, if you like,
to be able to actually
see what was in the past.
- Now, in the case of ancient DNA,
there are all kinds of problems,
and I wanna talk about them.
You touched on it a moment ago.
So really, it's not as if, okay,
let's take a DNA sample
from everybody who's living
who's in the room with us.
Let's talk about some
of, go into more detail
with the problems with ancient DNA.
The first problem is really
the contamination that you talked about.
- Yes, what really became clear
over the first years of work with this
was that DNA in an ancient specimen,
even if it's just a few
hundred years old, actually,
is always degraded to short pieces.
It's chemically modified,
which makes it hard to make copies of it.
And there's often very
very little of it there,
So, in the beginning,
when we did, or I did,
experiments, just on the
lab bench in my normal lab,
extracted it from an ancient mummy,
cloned it in bacteria,
and found some human DNA.
In reality, that was almost always DNA
from myself or from some
other people in the room.
It turned out, for example, that dust,
in a room like this
where people move around,
is to a big extent small skin fragments
that actually, each little dust particle
can contain much much more DNA
than what there is in a gram of tissue
from an ancient Egyptian
mummy, for example.
So gradually I sort of came to be
more and more paranoid, if
you like, about contamination,
separating this type of
work in a separate room.
You have UV light at night to destroy DNA,
you wash everything in bleach,
started dressing in protective clothing
that you could discard
after each experiment.
We started saying that you can only
go in there in the morning when
you come to the laboratory.
You should not have entered
any other laboratory
where there are large
amounts of DNA being handled.
And step by step, we slowly
got this under control.
- And the pieces were
very short that you were
able to extract from the ancient material.
- Yes, so whereas, say,
from a blood sample
from someone today,
you can easily retrieve
10,000, 20,000 base pair long of these
letters in the code, long fragments,
here we have things that are 50, 60,
hardly ever up to 150.
- And through time there are
a lot of chemical reactions
acting on the bone fragments,
say, that decompose the DNA.
Water, for example, is one of the things.
- Yes.
So, DNA is a very hydrophilic molecule.
It sort of absorbs water
molecules around it.
So even in an environment
that we think is dry,
there is water around the DNA molecule.
And that leads to reactions, some of them
break the DNA into smaller pieces.
There's others that modify one
of the four letters in
the genetic code, the C,
so that when we study
them, they turn up as,
they look as another base, another, T.
So there are certain types of errors
that you can actually then
sometimes use to your advantage,
to say, I really believe this DNA is old
because I see these types
of modifications in it.
- And so the cleaning process,
help our audience visualize
the cleaning process.
It's one, we see now,
with epidemics emerging,
the way the personnel treating
those suffering from the illness,
the outfits they wear, the
decontamination process
we see there, is what you brought
to the process of looking at ancient DNA.
- Yes.
So it looks, on the surface
of it, very similar.
You sort of dress up in a sort of,
outside the room, you work
in this special clothing.
You work in a hood.
But what we really do is
protect our experiment
from ourselves, from
the DNA we would shed.
But it looks very much like, say,
your chip factory where
you make computer chips.
So the air is filtered so
there is no dust there.
There is high pressure in the room
so that dust cannot come in,
but the air sort of flows out of it.
- Now another problem that
you encountered in this work
is, where are the bones, basically.
And once you know where the bones are,
getting the various bureaucracies at play
that control the bones
to give you some piece of the specimen.
Talk a little bit about that.
Because that was a, as you
describe it in your book,
byzantine maneuvering
and political instincts
were required on your part.
- Yes, that's, of course, very different
in each place and in each country
And my experience, it's generally easy
to deal with the people who have
actually excavated and
discovered the things.
And, of course, I respect very much
that if you discovered
a bone, you sort of,
you feel a sort of
scientific ownership of it,
which is totally appropriate.
What often happens,
though, is that there are
museum curators that sort of inherit
the keys to the cupboard for things
that were found maybe
50, 60, 70 years ago,
and then controls it as if it
were their private property.
And that's what sometimes
makes me a little upset.
So then it's, of course,
they need, of course,
to balance the sort of, that the specimens
are often valuable and should
be preserved for the future
against the scientific knowledge
you could gain by actually studying them.
But it's, of course, also the case
that we can often study fragments of bones
that have very little morphological value.
For example, the bones
we first used to make
the first version of
the Neanderthal genome
were from fragments that
one could not for sure
tell if they came from a cave bear
or from a Neanderthal, for example.
So then there is obviously
very little value
from studying these bones morphologically.
And then it can get frustrating sometimes,
and it's still hard to get
access to these things.
- And, in several cases, the bones were
actually in the countries that were
formerly part of the Eastern Bloc.
The first important set, I
think, were in East Germany,
when that country was still divided.
And then there was a real find in Croatia.
- [Svante] Yes, yes.
- Which probably made the
bureaucracies even worse
to the extent that they were remnants
of the old Soviet system.
- Yes, many of these
things have been found
in former socialist countries.
And, of course, the
structure of how science
works there is partially different.
The academies of science
are very influential,
and things like that.
- Talk a little about science itself,
because it seems that
one element of science
is cooperation, international,
you're working with
scientists all over the
world on the one hand.
As you mentioned, you were here
in Berkeley for several years.
But on the other hand,
competition, basically.
Who's gonna get to the press first
with whatever revelations emerge.
- Yes, so, there is sort of
this tension all the time.
And I think competition, to
some extent, is good, right?
It sort of keeps you on your toes
and makes things go faster
than they would otherwise.
But above all, I think, what
is so great with science
is the cooperation,
the fact that, sort of,
we're analyzing the
genomes we now produce.
We work together with
people all over the world,
but particularly here
in the U.S., actually,
particularly, say, Monty
Slatkin's group here at Berkeley
and David Reich and his
collaborators at the Broad Institute
and at Harvard and many other places.
And that you can really,
with today's technology too,
work very closely together.
You can have video conferences every week,
and actually really have a feeling
you work together towards the goal.
And in this project it
was particularly nice,
because everyone involved
really had a feeling
this was a unique first view
on an extinct form of humans.
So it was amazing how
everybody pulled together
and worked unselfishly to
sort of arrive at things.
- You were fortunate in
the sense that you were
invited to be part of an institute
that was being founded that
focused on evolutionary biology,
the Max Planck Institute.
Talk a little bit about that,
because in every great
scientific breakthrough
there is a team that's put together,
and you were fortunate enough
to be part of a process
putting a new team together
that drew all sorts of disciplines
together on the one hand,
but also were focused, not on disciplines,
but on the particular that
problem that interested you.
- Yes, I was sort of very very lucky
to be in Germany, happened
to be in Germany then,
at a time when there
was a political decision
to build up science in East Germany,
and particularly the Max Planck Institute
which was focused on basic research,
to the same density in the East
as there was in the old West
German part of the country.
And there was then the
will to focus on things
where German science would
be particularly weak.
And once such area was,
of course, anthropology,
because of the terrible history
in Germany with the Holocaust.
And so, there had been
a sort of predecessor
organization to the Max
Planck Society before the war,
where many, Max Planck and other
very excellent scientists had worked,
but it had gotten very
involved with the Nazi crimes
and had an institute in anthropology
that was involved in the Holocaust.
So since 1945, one had not
touched the subject, really,
for very good reasons.
But now it was a feeling
maybe one should do it again.
And I think it was maybe
even a little easier for me,
as an outsider working in Germany, to say,
we cannot have, sort of,
what happened in the past,
dictate what we can do now.
We have to be able to go forward.
And once one sort of made
that courageous decision,
to found an institute in
evolutionary anthropology,
it turned out to be almost an advantage
to have no traditions to fall back on.
We could sort of sit down the people
that were involved in starting
this institute and say,
how would we today start it,
if we do it from scratch?
And what we ended up doing was sort of
focusing it on a question
rather than a discipline.
So sort of the question,
what makes humans unique
in comparison to other organisms?
So as long as you work on this
and as long as you work empirically,
was the other sort of litmus test,
you could work there, no
matter where you came from.
So there are comparative
linguists, for example,
that study what's unique
about human language.
There are primatologists
that study the behavior
of our closest living relatives,
chimps and gorillas and
orangs, in the wild, in Africa.
There are comparative psychologists
that do experiments in the zoo in Leipzig,
on apes, the children during development,
and try to do the same experiments
in human children as they grow,
to find differences and
similarities in how they evolved.
And there's paleontologists
that then excavate
the remains of Neanderthals
and modern humans.
And there is genetics, where we then focus
on comparisons to our
closest extinct relatives.
- So, in a way,
metaphorically, this is about
building bridges between disciplines,
and then building a bridge to the past
where you can come to understand
the leaps that our ancestors,
the pre-human ancestors,
made to make us what we are today.
- Yes.
And I think the problem is always
to get these bridges between disciplines
to really work, to really
understand each other.
And I think a critical thing there
that sort of made this
work as well as it did
was really to focus on scientists
that do empirical work.
Because I can actually
understand what a linguist does,
although I'm not a linguist at all,
if they just take the time
to explain to me what the data is,
what the hypothesis that
tests for this data is.
And then one can have
a fruitful interaction.
- Science, as you
describe it in your book,
is a social process.
And, on the one hand, there is the process
of interaction with these colleagues
that start in other disciplines,
but on the other hand,
there is the interaction
with your own group, and
bringing to that group
problems that are emerging
as you're doing the research,
and through conversation and
discussion and criticism,
really finding the way forward.
- Yes, I think it's certainly
a social process, science.
And really, in our case,
the crucial thing is really the group.
The group, as an entity,
is much much smarter
than any individual in that group.
And my role is then often just to sort of
catalyze that lots of
ideas are put forward
in weekly discussions we
have about the projects,
and sort of maybe sort of identify
some ideas that come out as
particularly worth to pursue.
But it's really, when
the groups works well,
it's almost impossible to say even
who comes up with the idea,
because it's a process
that you do together.
- And there also is another aspect here
that has both a positive
and a negative quality,
which is that there is the
word conventional wisdom
about this domain and what we understand.
When you're doing innovative
work like you are doing,
then you have to overcome the obstacles
of the conventional
wisdom about what we know.
- Yes, I think that's, almost one quality
that is good in a scientist is
a little bit of an anarchist,
to be able to sort of
almost take a delight
in questioning this
sort of received wisdom
and hope to overthrow it.
You cannot believe in authority
or believe what is in the textbooks.
You must be able to go
back to first principles
and say, how do we actually know the thing
that is there in the textbook?
Could it be wrong?
Could the whole world be wrong
and we be right, actually?
There is some delusion of grandeur,
or what you like, there, that sort of,
to be able to instill in the students
and people in your group this feeling
that you actually might be right
and the whole world might be wrong.
- You say at one point,
"I am driven by curiosity,
"by asking the questions
where do we come from
"and what were the important events
"in our history that made us who we are."
So now that we've cut through the brush,
talked about all the obstacles,
talked about the impact of technology
and the problems with the DNA,
help us understand what you and your group
were able to achieve with
regard to Neanderthal man.
- So, there had, of course,
been a debate for decades in paleontology,
what really happened when modern
humans came out of Africa,
starting around 100,000 years ago,
really seriously spreading from
around 50, 60,000 years ago,
when they met Neanderthals, what happened?
Did they mix with each other or not?
Is there a contribution from Neanderthals
to people in Europe today?
And it had been a long long debate
with really no clear resolution of that.
And when we then finally got a version
of the Neanderthal genome,
I could then directly compare that genome
to people living in different
parts of the world today.
And what one found was that there were
pieces in the Neanderthal genome, or,
pieces in the genomes of people today
that were very close to
the Neanderthal genome.
And you found those pieces in Europe,
in Asia, and not in Africa.
And by various sort of analyses,
particularly then by people like
David Reich and Nick Patterson
at Harvard and Monty Slatkin here,
one could sort of show that the only way,
really, to explain that is that we mixed
with Neanderthals rather recently,
around 50, 60, 70,000 years ago.
- That is, humans.
- [Svante] Humans, yes.
Modern humans mixed with Neanderthals.
And so that, in the order
of one or two percent
of the genomes of everybody
outside Africa come from Neanderthals.
So it was clear that we did mix,
but it was also not that one found that
Neanderthal contribution
only when Neanderthals
had existed in Western Asia and Europe.
We found it even in China
and Papua New Guinea and Native Americans.
So the model that has come out of that
is that, when modern
humans came out of Africa,
they rather early mixed with Neanderthals,
and those modern humans may then later,
here and there, have mixed
with Neanderthals again,
but overall, they become the ancestors
of everybody outside Africa.
So that, no matter where people come from,
if they are from outside Africa,
they have at least, say, about
a percent of Neanderthal DNA.
- So what surprised you,
when all the data came in
and all these procedures
had been implemented
to find pure DNA, was
this, you were surprised
and your team were surprised
by this two percent
of Neanderthal DNA in the human genome?
- Yes, I was biased to
think it had not happened,
because we had, earlier in the '90s,
studied just a tiny part
of the Neanderthal genome,
the mitochondrial genome,
which is inherited only
from mothers to offspring
and is a very small part of the genome.
And there, we had found no
evidence of mixture whatsoever.
So I was biased.
I sort of knew, of course, that
that wasn't the full story,
but I was biased to
think we had not mixed.
So, for the longest
time, I sort of thought
there might, after all, be
some mistake in what we do.
We might have some
contamination we overlooked.
But in the end, it was
sort of completely clear
that that was not the situation.
- So you had to confirm by
analysts outside of your group
that what you were doing
and the conclusion you
had reached was right.
- Yes.
I mean, the theoretical
analysis for a large part
done by these other groups I mentioned,
and actually by different approaches,
or at least three different,
independent approaches
that came to the same conclusion.
- What do you think this means,
that we, that our ancestor
was, in some ways,
and in some small parts, Neanderthal man?
Do you draw any larger
conclusions from that?
Other than really impacting the theories
that were out there about the movements
of people in prehistoric times.
- Well, so, it's beginning
now, in the years,
in the few years since we've done this,
it's already becoming evident
that some of this
contribution from Neanderthals
had some sort of real effects.
So, for example, there's
a group at Stanford,
Peter Parham has shown that some genes
that are involved in
regulating the immune system
have been contributed from Neanderthals
and relatives of Neanderthals
in Asia to present-day people.
And one can easily imagine
that that has to do with,
that these modern humans
come out of Africa,
meet these groups that have lived
for several hundreds of thousands of years
in other environments and have
adapted to infectious diseases there.
When they then mix a little bit
and genes come over that are advantageous
to fight those infections,
they rise to high frequency.
There is a risk variant
that was found this January
for type two diabetes, a type of diabetes
you get in old age that is high frequency
in Asia and in Native Americans,
that also comes from Neanderthals.
One can easily imagine
that is an adaptation
to starvation, to store energy better.
And today we get diabetes when we
store energy too well when
we eat well all the time.
And there is a recent paper here
from Berkeley, from
Rasmus Nielsen's group,
that has showed fascinatingly
that people in Tibet
who live on the high plateau in Tibet
and are adapted to living at
a low oxygen tension there
have gotten a variant that
helps with that ability
from relatives of Neanderthals
that we have discovered,
these Denisovans in Asia.
And 80 percent of Tibetans
have that variant today.
So one cat put this sort of,
it's beginning to emerge,
picture of adaptive
introgression, as we say,
saying that genes come over
from these other groups,
some of them are
advantageous and will then
rise to high frequency
and actually have impact.
- Another place where this
has great implications
is the study of the brain and how
it functions and how it evolves.
And, as part of your collaboration
with your colleagues at other disciplines,
I guess you learned and focused a little
on what is called the FOXP2.
Tell us how genes became important
in understanding a small
group of living humans,
and what it might point to with regard
to the connection with Neanderthals.
- Yes, so, there's one thing,
as we discussed so far,
what came over in Neanderthals
to people outside Africa.
But it's another set of questions
that is even more
fascinating to me, almost,
and that is to day, in
what part of our genome
do all humans today, no matter
where we live on the planet,
in Europe, in Africa, or in Asia,
have something in common that's
not there in Neanderthals
and where the Neanderthals look like
the chimpanzees and other apes.
So those things that are actually unique
to all present-day humans, that define
modern humans genetically, if you like.
And that list of things is not very long.
It's a bit over 30,000
changes in our genome.
So, to just expand on that a little bit,
so whereas, say, I differ from you
or from a Neanderthal at, say,
three million positions in the genome,
if we make the requirement that we
all today should share something
and be different from the
Neanderthal and other apes,
it's just 30,000 such changes.
So a dream is that among these will hide
some of the changes that are crucial
for what made modern humans so special,
that we expanded from being a
few hundred thousand people,
that's more like the Neanderthals,
to being seven billion today that made us
able to develop technology that today
is incredibly different
from 100,000 years ago,
to develop art, music, many
many other such things.
Of course, we don't know
what those changes are.
But they presumably have something to do
with how the brain functions.
There's special interest now,
we and others in the
world are particularly
looking at this list of
things, thinking about,
are there things there that
might be important for this?
- And in the case of the FOXP2,
there was a family that
had difficulty speaking.
- [Svante] Yes.
- And you learned about that
from a colleague, I guess.
So then it becomes interesting to see
if any of these differences in the genome
can be attributed to that.
- Yes, so, this gene, FOXP2,
is one of very few genes
that we know have specifically
something to do with language
production in humans.
Because Tony Monaco in
Oxford found this gene
in a family with a severe
language and speech problem.
And that gene turns
out to encode a protein
that is very conserved among all mammals,
but humans have two amino acid differences
in the encoded protein compared to
all other apes and primates.
So we were, of course, very interested
when we got the Neanderthal genome
and this genome of the Denisovans in Asia,
to see, did they share these changes?
And they did.
So they look like us.
So these are changes that happened
before our split from the Neanderthals,
but it's still, they are
very interesting, of course.
So one thing we have done,
which is a model for further work
on this type of human-specific gene,
is to put them into the mouse.
So you then create a mouse that now
makes a human version
of this FOXP2 protein,
and study that mouse.
And amazingly, that mouse actually
vocalized slightly differently.
There are some differences
in how it peeps,
subtle, small small differences.
And you can also study
how the brain functions.
So how electrical signals
are transmitted in the brain,
particularly the part of the brain
that has to do with learning
muscle, motor, behaviors.
And there's some recent unpublished work
that even suggests that these mice
are actually a bit quicker in
automating muscle movements.
A little bit like when
you learn to bicycle, say.
When you think about how
you bicycle early on,
it's very difficult.
When you automate it,
you get very good at it.
And it's a little bit like articulation.
When we learn to speak, initially,
as kids, it's very
difficult to form the words.
And when you get sort of in our age,
it comes rather easily to you.
So you can speculate, of course,
that these changes may have something
to do with this ability to
produce articulate speech.
And there's some evidence
for it from the mouse.
And I think that's how
you need to start working
with many of these human-specific changes.
Try to find animal models that
give you some indications of it.
Maybe introduce them in stem cells
to in vitro differentiate
cells, nerve cells say,
and see how they function.
- There's an irony here,
because you left medicine
to go back to the past, to
make an important discovery,
and now we're getting
feedback back into the future
in medicine and understanding
the genetic basis for some ailments.
Fascinating.
Let's briefly talk about this
discovery of the Denisovans.
- Denisovans.
- Because that came late in this process
that we've discussed, and
this was just a eureka moment.
So this is another group of people
that was found in Russia, but who,
their virtue was, the DNA
was really amazingly intact.
- Yes, so, we're very
lucky to work with people
in Novosibirsk, particularly
Anatoly Derevyanko,
a very influential archeologist in Russia,
who excavated many sites in Siberia.
And in 2008, his team had
found a tiny little bone
in this cave called Denisova Cave,
in the Altai Mountains in Southern Siberia
on the border to Mongolia and China.
And this was a piece of a
last phalanx of a pinky.
And we got a sample of
that, and it turned out
that the DNA was, there was a rather a lot
of DNA relative to bacterial DNA in there.
So we were able, then, in 2010 already,
to sequence a large part of that genome
and compare it to the Neanderthal genome
and present day people's genomes.
And we were very very surprised.
I was sure that this individual
would be either a modern
human in that area
or a Neanderthal sort of at the eastern
extension of the Neanderthal distribution.
And it turned out to be something else.
So it has a common
ancestor with Neanderthals,
but very far back, in the
order of 400,000 years back,
much older than any divisions
between present day living humans.
And then a long independent history.
So these are some sort of
Neanderthal relatives in Asia.
So we needed to come up
with a name for this group.
So we said, yes, like Neanderthals
are called Neanderthals
after Neanderthal site
where they were first found,
we call these guys Denisovans after
the Denisova Cave where
they were first found.
And it turns out that
they have contributed,
also, to present day people,
all over Asia to a small extent,
but particularly in the Pacific.
So people in Papua New Guinea,
Aboriginal Australians,
contain up to four or five percent
of DNA from these Denisovans.
- And in this cave, you found evidence
that Neanderthals were
there, this group was there,
but also humans were there at one time.
- So we have also found
other bones in the cave
that come from Neanderthals.
So this is an area where
at some times Neanderthals have lived
and at some times Denisovans have lived.
- In this work and as
you reflect on your work,
have you done any thinking about
the implications of all this
for the position, the place, of humans
in this whole picture of creation
in terms of who we are
and where we're going?
- Well, of course, it
is fascinating to me,
in a way, that these groups of humans,
Neanderthals and Denisovans,
humans who are not here
any more, that are extinct,
that they still live on a little bit
in many of us today, if we
have our roots outside Africa.
So they're not totally
extinct, if you like.
They have contributed a bit to us.
Of course, it's fascinating also to say
that Neanderthals were here
just 3000 generations ago.
It's not that long ago.
So sometimes I like to sort of speculate
and say, what if they had
made it 3000 generations more?
What would that really
mean for our sort of
ideas about human uniqueness?
Would we, if you're sort
of pessimistically minded,
you'd say we would just experience
even worse racism against Neanderthals,
even worse that what we
experience among us today,
because they were truly
a bit different from us.
If you're more positively inclined,
you might say, if we had
other groups of humans here
that were a bit different,
better in some respects,
but also less sophisticated in others,
maybe we would not be able to make
this enormous dichotomy that we do
so automatically today
between humans and animals,
that we would see that there's
more diversity to life than that.
Who knows.
It's sort of just something
you can speculate about.
- One final question.
How would you advise students to prepare
for a future if they're
interested in science
and are fascinated by the potential
breakthroughs that you
just described to us?
How should they think
about their own future
and preparing for a future in which
they are part of this
scientific discovery?
- It's sort of a difficult question,
because we cannot
anticipate the breakthroughs
of the future, of course.
But I would, of course, say,
follow the things you are fascinated by,
because it really comes
rather automatically
that, if you really like something you do,
you tend to be good at it.
And just get a rigorous
training, at least,
in one discipline, so that you
really know the basics of it.
And then you can bring in
other types of knowledge too.
- Well, on that note, I
wanna thank you very much
for taking us on this intellectual journey
and helping us understand the remarkable
discoveries that you and your team make.
Thank you very much.
- Thank you, pleasure.
- And thank you very much for joining us
for this conversation with history.
