- [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.
