[MUSIC]
>>Steve: Welcome to Manifold.
Corey, this week we've got a real treat.
Our guest today is John Hawks, a professor
at the University of Wisconsin.
He is my favorite perhaps — or definitely
one of my favorite — "bone-diggin'ologists"
in the whole world.
And John is actually a triple threat, he's
a very rare talent: he participates on the
physical anthropology side of things, actually
finding new fossils, new bones, new sites
to dig in; he's got the chops to really understand
the computational genomics around ancient
DNA, how to derive knowledge from really complicated
archaic DNA sequences; and third, he's really
a great public speaker.
He's become kind of one of the best-known
people in this field for communicating to
the public.
So really excited to have John as a guest.
Welcome to our show.
>>John: Brilliant, thanks for having me.
>>Steve: I've been aware of John for many
years reading his blog, but also I think we
have some scientific collaborators in common,
so some of the people he's worked with in
the past or people that I've known.
So I want to start with your sort of scientific
biography, maybe talking about what you were
thinking when you were a grad student, what
you did for your PhD, and then after that
where you went for your postdoctoral research.
>>John: Sure, absolutely.
You know, I got into anthropology as an undergraduate
at Kansas State and I Iearned my bones from
a forensic anthropologist, his name was Mike
Finnegan.
He was the forensic anthropologist for the
state of Kansas, great guy, and I was teaching
for him because at Kansas State we had undergraduates
teaching laboratories.
So it was a great way for me to get into the
field.
I was not thinking anthropology at all when
I really started this.
I was an English major and I was interested
in anthropology, but I didn't really know
what that would be as a career.
When I went to graduate school I went to Michigan.
I was a student with Milford Wolpoff, and
he was very famous for his participation in
the modern human origins debate.
He was a big supporter of the idea of multi-regional
evolution, that modern humans had ancestry
from populations that lived in Africa and
other parts of the world, and that was a really
exciting scientific debate at that time.
And so I was really privileged to be able
to do some research on Neanderthals, on other
kinds of fossils to try to address this issue
of human origins.
But this was also the late '90s, when genetics
was becoming a bigger and bigger source of
evidence about human relationships, human
origins; and genetics at that time was clearly
a growth industry.
Finding fossils — some of the really premier
people in in the field were saying look, we
found all the fossils that we're gonna find
and you might as well close up shop because
all of the fossil fields are becoming exhausted.
And so I moved into genetics, went to work
on a postdoc with Henry Harpending at the
University of Utah — great human geneticist,
great anthropologist — and started working
on genetics and population size, and the way
that we could talk about ancient population
sizes and demography by looking at DNA sequences
from today's people.
This was really well before we had useful
information from ancient DNA.
And we did some work on natural selection
in humans, we tried to look at ways that population
growth would affect the pattern of natural
selection, and then did some theoretical work
on the way that you might expect to find genes
from Neanderthals and other ancient populations,
what they would look like and what kinds of
things you would get.
And so that was what I was up to in my early
career.
>>Steve: Henry passed away a few years ago,
and I knew him, and I always thought he was
not only a fine human being but also just
a very, very sharp intellect, and the things
he had worked on in various areas over the
years were just really impressive.
And when I found later that he had done actual
field work in Africa and lived in the, I guess
they would say in the bush or whatever, with
some various tribes, I was just further impressed.
Maybe you could just share maybe one good
anecdote about something that happened with
you and Henry when you were his postdoc?
>>John: You know, Henry, I think he was at
Penn State for many years, and when he went
to Utah he went with a budget, he was a member
of the National Academy and, you know, he
was always a theoretician.
Henry was always concerned with trying to
figure out what you could do with data, and
really pioneered some of the early applications
of principal components analysis to genetics,
to gene frequencies, he thought very deeply
about demography and what you could say from
hunter-gatherer demographies about ancient
humans.
And when I went to work with him I really
feel like he hired me to have somebody to
come down to his office and shake him up once
in a while [laughs], like, you know, he had
been one of the big Out of Africa proponents,
because his genetic work had really focused
on population growth and dispersal and the
idea that we could look at mitochondrial genetics
and look at this Out of Africa event.
And so for him to hire me, I'd come from this
big multi-regional school, I really believed
that he just wanted me to poke him once in
a while.
[laughs] And so I did, you know, it was a
lot of fun.
We'd have some new paper come out, and I'd
go down, and he'd say "Now, doesn't this finally
convince you that you were wrong all along?"
I said "Well, Henry, there's a problem, and
here's what it is."
And by god he would usually walk away and
think about it for a while and then come back
and say "Damn it Hawks!" [laughs] You know,
it was that kind of relationship, it was really
neat.
>>Steve: That hits one of our themes here
on our podcast, which is that you always want
to hear the strongest arguments against your
views, and it sounded like Henry wanted you
there to do some of that for him.
I think for our audience maybe who aren't
so familiar with this field, multi-regionalism
was the idea that humans could have evolved
sort of separately in different places on
earth, whereas Out of Africa was that modern
humans first arose in Africa and then spread
to the rest of the globe.
And that was a very controversial topic, I
guess going back into the '80s, is that correct?
>>John: Yeah, there were basically three views,
and one of them was that you had Neanderthals
and Homo erectus and some African populations,
but we had very little fossil evidence about
them, and they might have progressed separately
and evolved into modern humans separately
from each other.
That point of view was called polygenism,
and by the 1980s nobody believed this.
It was really debunked in the 1960s.
But that idea sort of hung on, because it's
always easier to try to reject an idea that
has these really clear boundaries.
The Out of Africa idea was that the African
ancestors of modern humans were the real important
ones, and they spread throughout the world
sometime within the last 100,000 years and
extinguished Neanderthals and potentially
homo erectus and whatever other populations
there were.
So you had this one source population that
spread throughout the world recently in our
evolutionary history and got rid of all the
others that were there without any interaction.
And then the multi-regional point of view
was that all of these were connected in some
sort of network all the way back into prehistory,
so Africa might have been really important,
but Neanderthals were also important, and
they're all sort of connected and all, you
know...
The extent to which they're different is driven
by distance and not by replacement.
It was really tough to convincingly come up
with evidence that absolutely rejected one
of those, you know, that was really the challenge
that we had from the fossil record was, you're
looking at this stuff and it's like, well,
some people say these look similar and some
people think these look different, and how
do you quantify that and how do you establish
what differences and, right, it always came
down to these real detailed sort of things
that you could argue about.
>>Corey: It's actually unclear to me a little
bit how they're so different.
Is it different time scales that are at issue,
so we're talking about in the regional hypothesis
there are thought to be human populations
there going back three to four hundred thousand
years?
Or only there are human populations there
are a million years before?
Was there clear — there must have been clear
time lines attached to each of these theories,
because it's just hard to get them precise
less you're saying, you know, this group was
there at this point in time or not.
Was it all that clear, was it equally — it
seems like it's a little vague.
How clear were these theories, how clear are
they now?
>>John: The thing is that if I'm sketching
out a picture of what our evolutionary history
looks like, the big picture today it's gonna
be somewhat different from twenty thirty years
ago.
And so and I didn't want to introduce wrong
information now, but I can say that twenty,
thirty years ago, fifty years ago even, our
ideas were so dominated by Neanderthals, because
Neanderthals were a fossil population that
lived in Europe from hundreds of thousands
of years ago up until about 30,000 years ago,
and they don't live in Europe now.
And so both, all of these theories were really
formulated when the Neanderthals were the
major source of evidence about fossil humans,
and the question is, are they us or not?
And if they're not us, what happened to them,
right, why are they gone?
And if they are us, why don't we look like
them?
What is the mechanism of evolution that caused
later Europeans to look so different from
the Neanderthals?
So that was the framework in which these developed,
and it was very end-oriented.
It was really about what happened to these
people that lived 40,000-50,000 years ago,
and in the absence of real evidence about
who else there was.
The way that the world has changed in the
last twenty, thirty years as we know some
more things about who else there was.
Some of this has come in from the rich genetic
record that's accumulated, and some of it's
come in from new fossil discoveries, and while
we haven't filled in every last place — in
fact, I would say we've only really just begun
to fill in the details of these things — nonetheless
it's, we can, we have the luxury today of
not being so focused on Neanderthals.
>>Steve: I seem to recall, Corey, when I was
a kid growing up and reading about this stuff,
that there was a very strong multi-regionalist
hypothesis was literally that modern humans,
like East Asians and Europeans and Africans,
could have actually evolved separately from
different archaic ancestors.
And that would be the really strong kind of
multi-regionals, like you got modern humans
in different places but through different
mechanisms and different lineages, as opposed
to the first moderns appearing in Africa and
then spreading out across...
So those are very different hypotheses.
>>Corey: Well, even the multi-regional hypothesis
— presumably humans are the same species,
right — if you've got them evolving to modern
form in different regions, at some point in
time they had a common lineage, so it seems
to depend upon the time frame.
>>Steve: So you could just draw different
diagrams with different time scales for when
the different divergences happened and things
like that, I suppose.
>>Corey: Does that sound right, John?
>>John: Yeah.
To put this into real chronological perspective,
more than two million years ago we have found
no evidence for any kind of hominins anywhere
other than Sub-Saharan Africa.
Before that we know our origins are African,
but all of those hominins that lived at that
time were fundamentally ape-like: they walked
upright like we do, but they had small brains,
they were, maybe some of them initial tool
users —we have some stone tools that go
back that far — but they didn't have body
shapes like modern humans do, they didn't
seem to be super well adapted for walking
long distances or maintaining large home ranges.
They were apes that walked upright.
After two million years ago two things happened:
one is, we see the first evidence of members
of our genis homo, that have human-like body
shapes and seem to have larger home ranges.
They've got a little bit bigger brains than
their ancestors did, and they seem to be more
sophisticated in that sense.
They seem like food-sharing, hunter-gatherer
looking subsistence pattern, and they show
up outside of Africa — we first find them
in the Republic of Georgia, but we have early
evidence of tools that are about two million
years old in China, there are hominins in
Java before one and a half million years ago
— and so it's clear that there's this dispersal
that happened with very primitive early members
of our genis.
The Out of Africa / multi-regional debate
was about what happened after that point,
and whether these early colonists were the
ancestors of today's people at all, or whether
they were replaced by successive waves of
migration from Africa, and the most recent
of those waves was seen as — probably was
— the most important, the largest, and that
all happened within the last 100,000 years.
So you're looking at this difference between,
maybe human variation becomes established
one-and-a-half, two million years ago, or
— and then after that point there's evolution
so that we become modern humans everywhere
— or modern humans are a recent product,
they evolved in one place, Africa, and after
that point they dispersed and replaced all
these other people, so all of these other
primitive hominins were just gone, because
modern humans which evolved in Africa were
superior, they replaced them.
>>Steve: I guess the, you know the statement
is we sort of know the answer to this question
now, that based on the DNA similarity of all
modern humans around the earth and the evidence
for a very tight bottleneck that they may
have passed through really does suggest the
latter scenario that he's describing, which
is that modernity first manifested in a local
region in Africa, and then those people spread
throughout the world and largely eliminated
— maybe mated with but largely eliminated
— the archaic species that were already
established in Europe and Asia and other places.
And I think that, am I correct in saying that's
a pretty strong consensus view now?
>>John: Yeah, it's very clear that a major
population increase began among African peoples
sometime before 100,000 years ago, and that
growth caused their descendants to spread
throughout the world.
Today your DNA and my DNA and the DNA of everybody
in the world comes 95 to 90% from that initial
African population, and what's at issue today
is, how much difference did the 5% that we
got from other places make?
Is that important, is it significant, does
it signify that these different ancient groups
were different species from us or the same
species?
So there's those questions which remain unresolved.
There's also the question of what happened
in Africa before.
Was this a Africa-wide population, was it
some very small group?
Was there a displacement within Africa before
the dispersal of these people, right, what
was that process?
And that's right now a really exciting scientific
topic.
>>Corey: Do we know, John, what happened about
100,000 years ago to cause the population
to increase so much and to want to disperse
out of Africa?
>>John: No clue.
No clue at all.
I mean you say well, you know, people have
ideas about this, right.
Maybe modern humans evolved language at that
time, they became fully linguistic, and so
that gave them tremendous advantages in symbolism
and in social relationships and in technology:
they became smarter, they were more inventive.
We do see changes in the archaeological record
that indicate that they're making more symbolic
objects and they are maintaining larger social
networks, and they do become somewhat more
inventive and so there's a, you know, maybe
that's a feedback: maybe that's the process,
it's fundamentally cognitive.
Other people say ah, cognition, what — That
depends on population size, it depends on
culture environments, you know, you can't
look at these ancient people and say that
they were impoverished genetically or cognitively
because they clearly had smaller populations
— unless, you know, there's less ideas that
emerge in smaller populations, etc. etc.
So I'd say, while we focus on some things,
we really don't know what the key changes
were that caused this population transition
to happen.
>>Corey: You must be very familiar with the
work of linguists trying to trace the origins
of language and looking at linguistic diversity
in trying to find languages that appear, have
common elements, might be common ancestors.
How does that work line up with the current
work that you're doing on human origins?
Is there a pretty nice map between the language
origin map and human origin map?
>>John: They both converge into the past.
In that sense, there is an alignment, in that
we know that all of today's languages come
from common ancestors that were originally
diversifed, and we know that today's genetics
come from populations that diversified.
what's not clear is whether there is a timeline
that connects them.
And once linguistic reconstruction, you know,
reconstructing ancestral languages — so
English and German and Greek and Italian they
all go back to early Indo-European, right
,and that's a common ancestral language that
gave rise to lots and lots of descendant languages
— that kind of reconstruction in linguistics
goes back quite accurately to that level of
ancestry, which is 6,000-8,000 years ago.
Beyond that, establishing clear connections
between languages becomes more and more difficult.
While it looks like you can create some larger
level groups, tying those groups into ancestral
population origins on the scale of 30,000-50,000
years is controversial, and so it's not clear
whether we can get those way-back points from
language.
It is clear that language is diversified that
came from common ancestors, and genetics did
as well.
In recent times those genetic connections
aligned with the linguistic connections in
in lots of ways, but there are mismatches
also, there are populations that pick up languages
from others that they were not strongly genetically
connected to.
>>Steve: So I wanted to ask you about our
evolution in understanding about the situation
of Neanderthals vis-à vis moderns and how
it evolved, I would say roughly in the last
ten or fifteen years?
So about a dozen years ago I think or ten
years ago Henry Harpending and Greg Cochran
published a book called The 10,000 Year Explosion,
which was mainly about recent evolution I
guess in modern humans, but they also mentioned
in the book — I think it was in the book
— they strongly hypothesized that Neanderthals
and humans had interbred.
I seem to recall that as being a pretty minority
view.
So if you just randomly selected some physical
anthropologists and asked some hey, did humans
and Neanderthals interbreed or did we just
wipe them out without interbreeding and maybe
we're not even the same species in some sense?
people mostly thought the answer was no, we
didn't interbreed with them.
But now the genetic information firmly establishes
that we did, and you can go on 23andMe and
look up your Neanderthal, some estimate of
your Neanderthal DNA fraction.
So can you talk about how it felt, I mean
what, how your views evolved and how the community's
views evolved during that roughly ten- or
fifteen-year period?
>>John: Yeah, I think that, you know, I came
into this thinking that Neanderthals contributed
to human populations a good deal.
You know, if you asked me twenty years ago
what did I think the proportion of Neanderthal
ancestry in living Europeans was, I would
have said well, you know, it could be 10 or
15%, and I viewed that as being a significant
contribution.
We now know that the actual level is about
2 or 3 % and so it's not an order of magnitude
less than I was thinking, but it is a lot
less.
If you asked some other anthropologists at
that time they might have said, you know,
zero, you know, they never interbred; or if
they did inter breed, right, I think the most
common answer you would get from somebody
like Chris Stringer, for instance, who was
really, you know, very Out of Africa focused,
very Out of Africa oriented, he would say
you know, I would never deny that interbreeding
could have happened, but we know that it was
not important, we know that it did not have
an evolutionary impact that mattered to the
development of later Europeans.
>>Corey: Why would he make such a strong statement,
and on the basis of what?
>>John: [laughs] Well, largely on the basis
of looking at a major population transition
that happened.
Neanderthals were the only hominin occupants
of Europe, as far as we knew, before 45,000
years ago, and after 30,000 years ago we see
nothing that is a Neanderthal and only people
that we identify as modern human, and they
differ by a number of traits.
That population of modern humans did have
some low frequency traits that we otherwise
see in Neanderthals, right, so those of us
who thought that there was a contribution,
we had a reason for thinking it.
You find these traits and it's like, you know,
things like the shape of the foramen on the
inside surface of your jawbone — the part
of your jawbone that connects with your skull,
the mandibular ramus — the inside part has
a hole in it, and that hole has a different
shape in some Neanderthals than it does in
most modern humans.
But the few modern humans that look Neanderthal-like
are all European, they're much more likely
to be Europeans 30,000 years ago.
So you look at that kind of evidence and say
okay, there's some evidence of interbreeding.
Stringer knew that evidence.
He's just an example, right, a lot of people
would have the same point of view, look at
that evidence and say yeah, and the fact that
it becomes less and less common shows you
that whatever interaction there was clearly
was not adaptive, it clearly went away, and
so that's the sort of thing that they're thinking.
Explaining that kind of transition, right,
how is it that you end up with nobody in the
world who looks like a Neanderthal today?
It must have been really disadvantageous to
look like a Neanderthal.
>>Corey: Do we know that that is in fact true,
that people today, no one looks like a Neanderthal?
I had a, my advisor at Columbia insisted that
he was at least half Neanderthal.
>>John: A lot of people say this, right, and
I get letters from people — and they're
always women [laughs] — who are, like, I
want to find out if there some way my husband
can participate in your research, because
he has hair on his back, and he has a really
sloping forehead, and I think he is more Neanderthal
than anybody else.
That is the popular stereotype of what Neanderthals
were like, right.
We have no idea whether Neanderthals had hair
on their back right, it's not like there's
a fossil that tells us that, oh yeah, ape
then, you know.
No, it's people's stereotypes. if you think
of the person that you know who has the most
prominent brow ridge, I guarantee you that
looks nothing like a Neanderthal brow ridge.
And the reason why is that Neanderthals have
a brow that is arched over both of their eye
orbits and thick on the outside, as thick
as it is on the, in the middle, right, and
if you saw somebody like that with a groove
between their brow ridge and the rest of their
forehead, I'd say okay, that's exciting right,
that's something that you don't see every
day.
But in fact when you look at the details of
traits like that, they just aren't around
anymore.
>>Steve: But I thought even at the level of
like, the shape of their rib cage or torso,
there were just huge differences between what
Neanderthals looked like and what moderns
looked like.
Is it, am I wrong about that?
>>John: Well there are some differences.
I would say [laughs] those differences have
a way of being exaggerated, right, because
we're comparing a particular group of Neanderthals
that we know about — mostly from southern
France and mostly from the end of their existence
— with living people's skeletal collections
who are mostly indigent and poor, and mostly
collected in the early 20th century from people
who didn't eat very much.
>>Steve: Hmm, I see.
>>John: [laughs] And so while there are differences,
you know, in average stature in the, you know,
the barrel-shapeness of the ribs and that
sort of thing, these are differences that
actually overlap a good amount.
>>Steve: I see.
So, but the question I was trying to get at
is that, okay, so the situation was unsettled
before the DNA results came in, but then the
DNA results came in, and were they just quickly
accepted and people gave up cherished, long-held,
long-defended beliefs in the face of better
data and technology, or was it a kind of battle
with some people going to their graves not
accepting it?
What, just sociologically in terms of the
history of science, how does...
>>John: To simplify a little bit, right, anthropologists
understand numbers [laughs] and yet we have
different understandings of numbers.
[laughs] So some people look at, oh we've
got 3% Neanderthal, oh my god we've proven
at last that we have Neanderthal ancestors,
we were right all along!
And other people say yeah, we're 3% Neanderthal,
god, that's nothing, we've proven that Neanderthals
made no difference to us, we were right all
along! [laughs] And say you got, the same
data have provoked...
>>Steve: Okay.
>>John: ...you know, totally opposite reactions.
>>Steve: Yeah, nobody pinned with a published
prediction of zero that, yeah, like the offspring
would be infertile, for example, like...
>>John: When Svante, when Svante Pääbo who
was, his research team first got a Neanderthal
genome data and they provided the first estimate
of, you know, maybe this is 1 to 4% Neanderthal
ancestry in recent people, he started talking
about this as "leaky replacement."
Okay.
It's mostly replacement.
The Africans spread throughout the world,
their DNA replaced the DNA that was there
before, but there was some kind of mistake
in the process that, oh, the Neanderthals
put in a little bit, right.
And I think there's a tendency to look at
small percentages and say yeah that's, okay
sure, it shows that it's there, but it doesn't
establish that there's any evolutionary importance
to this.
>>Corey: What's clear is we're not actually
talking about the functions of these genes,
we're simply talking about the percentages.
There's no discussion it comes down to what
it does.
>>John: Yeah, and in fact, it is totally...
People were totally incapable of looking at
the functions of anything at the time that
the DNA sequences were derived, because they
had no mechanism to identify particular genes
that were coming from this introgression,
and so the only data that they had was the
Sesame Street kind of data.
You can see with, between two people, one
who lives in Sub-Saharan Africa and one who
lives in anywhere outside of Africa, that
one outside of Africa had a little more Neanderthal.
That was the comparison.
But some Neanderthal resemblances in anybody's
genome today, including Sub-Saharan Africans,
come from ancient diverse genes that we inherited
from our common ancestors with Neanderthals.
That's called incomplete lineage sorting and
it, we have incomplete lineage sorting with
chimps, right.
There are genes for which some people resemble
the chimpanzees and other people don't.
So the fact that you have some similarity
doesn't reflect necessarily genetic input
for any particular gene.
>>Corey: So it seems that what you need to
actually have genetic input is to show a diversification
of genes into Neanderthals, and then a reunification
of those genes through interbreeding.
Is there any schematics that exist...
>>John: Right.
So what you have to show is that you have
a haplotype, a long section of chromosome
where variations are linked together, that
existed within Neanderthals and today has
come into modern humans, and it's the difference
across a section of chromosome that tells
us that this came into our population recently,
as opposed to having been retained in the
modern human population for hundreds of thousands
of years.
And we do have that evidence now.
It is possible to look at regions of the genome
where today somebody carries a haplotype that
is never found in Sub-Saharan Africans and
that is found in Neanderthal genetics.
And we know a lot of these now.
Some of them are much more common than they
should be, right.
While the average Neanderthal input for people
outside of Africa is 2 or 3%, there are genes
where, outside of Africa, 40 or 50% of people
have the Neanderthal variation, and those
are genes where we look at it very closely
and say ah, this does something super useful,
this must be advantageous in some way.
>>Corey: Do we happen to know what any of
these genes does?
>>John: Some of these genes are HLA genes,
where we have alleles that have come into
human populations — HLA is human leukocyte
antigen, and these are immune system genes.
They control some of the antigens that are
displayed on the surfaces of blood cells,
and that is an immune defense from pathogens
and sometimes cancers and that sort of thing.
>>Steve: I think it's also claimed, although
I don't know exactly how strong this evidence
is, that some of the Tibetan altitude adaptation
actually may have been due to introgression
from Denisovans, which are a kind of Neanderthal.
I don't know if there's consensus on whether
that's true or not.
>>John: Yeah so this gene EPAS1, which has
a variation, an allele that's very common
in Tibetan and Nepalese and Himalaya living
peoples, that allele came from a Denisovan-like
population, so it came from one of these archaic
groups.
There are other immune system genes besides
HLA, where today people have a Neanderthal
variant that's much more common.
There are metabolic genes.
The most common genetic correlate of type
2 diabetes in Mexico today is a gene that
came from Native American Mexican populations
that was a Neanderthal-derived gene.
So we know quite a number of these now.
It is not yet the case that we know what all
of them do, and that's actually nothing to
do with Neanderthals: it comes from the fact
that we don't know what genes do...
>>Steve: Yeah.
>>John: [laughs] ... and it's a limit on human
genetic information as opposed to understanding
particularly the Neanderthal contribution.
>>Steve: So when the first Neanderthal paper,
DNA papers came out, I think the consensus
view was that okay, the Neanderthals had already
been in Eurasia when the first modern humans
came out of Africa — perhaps in a Middle
Eastern region, that's where the intermixing
perhaps happened — and there was, I think,
a definite view that we were likely to find
more DNA fraction from Neanderthals in Europeans,
and less in East Asians.
But I think the current result is actually
the opposite of that, and so could you comment
on that?
>>John: Yeah, Chinese people have systematically
about a half percent more Neanderthal than
Europeans.
And that's counterintuitive: the Neanderthals
did not live in China.
[laughs] And it's not just Chinese — East
Asian generally, and I don't believe that
that's true of South Asian, I think it's more
Eastern than South Asia.
And so what's going on with that?
It appears that what's going on is that the
differences in different populations today
of Neanderthal ancestry are coming from multiple
mixture events with Neanderthals, potentially
different Neanderthal populations.
Europeans who were of the Upper Paleolithic
time period, who followed the Neanderthals,
also had a higher fraction in some cases.
We've got a European ancient human skeleton
that has something like 8-10% Neanderthal.
>>Steve: How ancient?
>>John: About 45,000 years old.
>>Steve: Okay.
>>John: And this is from Romania.
>>Steve: Yeah.
>>John: So there were individuals that had
a higher fraction, and the fact that those
individuals have not contributed that higher
fraction to later people is in part due to
the fact that today's Europeans are not the
Europeans of 30,000 years ago.
Today's Europeans have come in through repeated
waves of immigration with early farming, with
steppe pastoralists who have come in, with
Bronze Age peoples, and so today's Europeans
have got more Near Eastern in them than they
have Upper Paleolithic European by quite a
lot.
>>Steve: So in that last few sentences you
sort of brought in some more recent history
of human migration and evolution, and so I
wanted you maybe to describe for our viewers
the current landscape of work on archaic human
DNA and fossil records.
My impression is that so, for example, David
Reich at Harvard, he specializes in maybe
the last 10,000 or so years of developments,
whereas Svante Pääbo who you mentioned earlier,
he's looking more further in the past, like
hundreds of thousands of years.
Maybe you can just give us an overview of
what people are working on and how the field
is evolving.
>>John: Sure.
Ancient DNA is preserved in bones of all kinds
of eras, right, and not only hominin bones,
obviously, you know, other kinds of animals,
and it's a similar technological process that
you go through for any bone.
Different preservation contexts present somewhat
different challenges.
The oldest hominin bones that we have ancient
DNA from are 450,000 years old.
They're from a site in Spain called Sima de
los Huesos, and the DNA in those bones is
broken up into very small fragments.
By the time you get down to 20 or 30 base
pair fragments, it becomes fairly difficult
to retrieve that DNA and compare it with modern
human DNA to reconstruct sequence.
Even though all ancient DNA is broken up into
fragments, by the time you get down to like
20 or 25 base pairs it's like, wow, the information's
truly gone, it becomes just vastly more time-consuming
and difficult to reconstruct.
And that causes some specialization between
laboratories in terms of what time periods
they're optimized to look at.
Other laboratories who are doing ancient DNA
have specialized on the DNA of various animal
lineages, so you have David Reich's lab, which
is studying lots and lots of Neolithic and
later human specimens, is also studying elephants,
you know, so you've got this sort of looking
at particular groups to pursue scientific
questions.
What's going on now with it, what are the
frontiers?
The exciting stuff that's emerged in the last
year or two has to do with finding, in a much
more systematic sense, bone fragments that
are eligible for sequencing.
Denisova Cave, which is this exciting place,
it's in Siberia, in the low Altai Mountains,
and it's got evidence of ancient Neanderthals
and ancient members of this other population,
the Denisovans, and they, we now know, alternated
in this cave — Denisovans there before 200,000
years ago, Neanderthals coming in for some
period of time, Denisovans coming back — and
we've got a hybrid individual who had a Denisovan
father and a Neanderthal mother, right.
How does all this happen, right, how do we
know all this?
We know all of it because today people are
systematically sampling cave sediments and
retrieving DNA signatures out of them from
the hominins, so you've got hominin DNA inside
of the sediments in the cave, not in bones,
just in the sediments.
You've got a team of people led by Katerina
Douka at the Max Planck [Institute] for the
Science of Human History, who are systematically
going through every bone fragment at the site
that is unidentified — which is mostly red
deer and horse and other kinds of, right,
faunal bone fragments — and doing collagen
sequencing from them, because they have a
method for collagen fingerprinting.
So you do this for thousands and thousands
of bones, and out of this process they find
four or five hominin bones.
And then with bone fragments that you, that
an anthropologist cannot identify, right,
and say oh, here's a hominin, and they take
it and get DNA out of it.
This is where the hybrid came from, here's
DNA and it's half Neanderthal and half Denisovan.
Wait a minute!
What do you mean, half Neanderthal and half
Denisovan?
And they reconstruct this like, No seriously,
one Denisovan chromosome, one Neanderthal
chromosome: this is somebody who had a mother
and a father who were two different populations,
species, something like that, right.
So the retrieval systematic search for ancient
bones, where DNA is the major target, has
become a big thing, and I expect that to be,
you know, sort of worldwide in the near future,
because the promise of this systematic search
is so great.
That being said, there's also people focused
on these historical questions, you know, where
do the Indo-Europeans come from, how were
early farmers connected to anybody else, what
kinds of adaptations were changing in early
farmers, right?
And those sorts of studies are being pursued
by lots of different teams of people.
>>Corey: John, I just have a question about
the environment in these caves.
Is it frozen, is it just, is it 70 degrees
Fahrenheit?
Under what circumstances does ancient DNA
survive for 20,000 years?
>>John: It's a spectacular question, right,
because we don't fully know.
We know that cold is better, and Denisova
Cave has this tremendous preservation in part
because the average temperature year-round
is 5° Celsius in the cave.
You walk into the cave and it's like walking
into a walk-in refrigerator.
That's one aspect, that cold, right.
A cave has the average temperature of the
outside environment over, you know, the year,
and so in areas where I work in Africa, the
caves are much warmer.
The cave where we work is 19° year-round
and that is much less beneficial for long-term
preservation of biomolecules.
So cold makes a difference — dry makes a
difference, drier is better — but beyond
that it's also chemistry.
>>Corey: Are you finding DNA in the cave you're
working in Africa, are you just, are you finding
proteins, are you finding...
What kind of biomolecules are you finding
preserved in that kind of environment?
>>John: So we have attempted to get DNA from
our bones and today's technology cannot get
whatever there is there, we've made no progress
with it.
We do think that it's likely that we'll have
protein preservation in teeth.
The proteins in teeth, because they're bound
up in the enamel and dentin matrix, which
is harder and a little more protective, they
have a longer duration, and folks have been
successful getting protein sequence out of
some of these specimens that are 1.8, 2 million
years old.
So I think there's a good chance that we'll
have protein preservation.
That's a vastly smaller source of information
than DNA.
You said yeah, there's lots of proteins, but
actually very few of them are expressed in
bone and teeth, and so you're only looking
at very particular amino acid sequences — which
is sometimes, you know, gives you really interesting
information, but it's not a genome, you know,
so...
>>Corey: Sounds like, John, we're looking
at kind of a difference in, across the world,
right?
If it's far north enough, we're getting information
about DNA but further south we're not.
Is there a line you could draw, say the DNA
line across the globe, or above that, you're
getting...?
>>Steve: Depends on technology.
>>Corey: But current technology?
>>John: Yeah, it's...
If you look at sites before 30,000 years ago,
they are nearly all — I think all, actually
— above a line that runs from Spain to northern
China, and so — and in southern Africa we
have nothing that old.
In Africa generally the oldest sequences that
we have are about 20,000 years old.
That's probably not a preservation limit,
that's the limit of what has been investigated
and what people are willing to invest today's
technology to do.
That willingness comes on two sides, right.
One of them is based on somebody — there's
always DNA people who will try, but the fact
is that the best DNA people sort of know where
their limits are and know it's worth trying;
and there's also a forward look to it, right,
what might be at the very edge of possible
today is probably going to be easy the ten
years from now, and don't destroy something
now if 10 years from now it's gonna be with,
easily within our reach.
So people are very, I think most people are
very thoughtful about when to try something.
And the other side of this obviously is the
museum institutional side, right: these bones
have curators who are responsible for them
as world heritage objects, and we don't destroy
things willy-nilly, you know, we think very
carefully about whether examining something
is going to be justified in terms of the science
it produces, whether today's techniques are
the best or whether we should really let the
technology develop.
So Africa sampling is complicated for that
reason.
We know that it's at the edge in many cases
and the edge is exciting to be at, but also
not the place to take your most valuable specimens
and destroy them.
>>Steve: So let me switch gears a little bit,
and I want to talk a little bit about what
I call the David Reich controversy.
And so David Reich is a leading figure in
this field, I think focusing— correct me
if I'm wrong — at least recently more on
the sort of last 10,000 years than way back,
probably deserves, I guess, credit for sort
of really working out the waves of Indo-European
settlement that people modern-day Europe.
I think it was about a year ago he wrote an
editorial in the New York Times which caused
a huge kerfuffle [John laughs] and, you know,
I do some work on the genomic prediction of
human height, and so we now kind of in a way
have almost solved that problem.
If you look at northern European populations,
they tend on average to have more of the plus
alleles for height, and southern European
populations have more of the minus allele.
And so there is actually a genetic contribution
to a group difference.
The group difference in height is, between
northern and southern Europe, is about a standard
deviation.
And so this seems to have been — this is
a little bit more speculative — but it seems
to have arisen in the last 10,000 years or
so, so it's a relatively recent, perhaps natural-selection-driven
group difference on a complex trait.
And Reich wrote an editorial warning people
that — and he, I think he's actually published
on this topic as well — he warned people
that we should get ready in some sense to
discover more genetically driven group differences
between populations that could have arisen
relatively recently.
Now, he took a huge amount of blowback for
this.
I think there was a huge petition signed by
many people — I don't know if you signed
it or you know people who signed it — so
many genomicists signed a petition against
his editorial.
And then much more recently in a way there
may be two David Reich controversies: so there
was that one, and then recently there was
a big New York Times Magazine perhaps hit
piece, but anyway negative profile in some
sense of David Reich, which also then got
into some of his research practices having
to do with treatment of maybe DNA obtained
from indigenous peoples and things like this.
So I would just like to get your overall opinion
of everything that I've just discussed.
>>John: [laughs]Well it's a big topic, right
— I mean, the fact is that we're really
privileged to have information about the most
intimate details, at least in biological terms,
of ancient people who cannot tell us what
their wishes are.
And I have for a long time studied Neanderthals
and have always felt like, you know, by trying
to understand their biology, by trying to
understand their lives, I am bringing them
back into the present in some way, right,
I'm restoring in some sense their heritage
that has been lost because they're not with
us, right, they're extinct; and I've always
thought about the work that I do that way,
you know, in the sympathetic kind of vein.
I want to understand past people in part because
it helps us to understand ourselves and the
diversity that's in the world, and the way
that that diversity emerged, it's important
to be scientifically accurate about it, because
a lot of people think about diversity in racial
terms that fundamentally is not scientific.
And so I think about things that way.
Part of that practice when you get to remains
that are clearly more connected to some living
people [than] others, right —, as you have
with Native American remains in the United
States, as you have with Native American remains
throughout the Americas, as you have with
Khoisan-affiliated remains in southern Africa,
Polynesia, and affiliated remains in Polynesia
— you know, there's lots of areas of the
world where you're studying bones that may
or may not have living descendants, right,
you may not be looking at the ancestors, but
you're clearly looking at cousins of theirs
that are closer to them than you.
And my attitude in that situation is, in those
situations you have to be communicating with,
and making a role for, the people in your
research who are more directly connected than
you are to them.
One thing that I didn't like about David's
book is that he sort of takes this attitude
of, you know, what business is of these other
people who are descendants or relatives to
say anything about these individuals who lived
in the past, right, what right do they have?
And I look at that and I'm like, that's sort
of tragic, you know.
It's tragic a) because if we actually incorporate
people into this research we have the potential
of building something really positive and
getting people onto the same page, right:
our science has to be built by involving people
and not by saying hey, we're doing science
over here and guess what we're gonna tell
you about your ancestors next, you know, I
don't get people who have that kind of attitude.
But also that the number of ancient bones
that we have in the world is limited.
There are not going to be thousands and thousands
of new ancient skeletons that are unearthed
by archaeologists.
We don't do work like that anymore.
This is a, fundamentally a limited resource.
You say well, you know, but you're making
new discoveries all the time.
It's our goal to leave our new discoveries
in the ground as much as we can, because we
recognize that when we dig a site we're actually
losing evidence, and our choices about what
to dig are shaped upon a trade-off between
building science and building evidence today,
and retaining something for future scientists
who are gonna have much better techniques
than we have now.
And when I look at a laboratory that is just
sampling thousands and thousands of bones,
I know that that constitutes a very high fraction
of the bones that there are; and the bones
that there are, there's not gonna be twice
as many in the future, right, the bones that
there are, are sort of what we have.
>>Steve: You're saying in a sense these, maybe
his lab and maybe some other labs have become
so dominant that they're getting their hands
on all the best samples, and they're maybe
processing them in a way that's irreversible,
that leaves, you know, some future developments
unable then to use those bones, and that is
a sort of major criticism, maybe, of what's
going on right now.
Is that a fair summary?
>>John: I think so.
You know, my attitude toward this is, I want
to see us make the responsible choices so
that tomorrow's scientists do not look at
us and say: How could they have done this?
And one thing that you do is, you maximize
the value for building science of everything
that you destroy.
>>Steve: Yep.
>>John: That to me is like the prime directive.
>>Steve: It's a difficult optimization because
it involves future progress in technology,
right.
>>John: And the pressures that are on you
in the moment...
>>Steve: Yes.
>>John: ...right, I've got to get that new
nature paper, and the nature reviewers say
that my sample is too small; and I know that
I can build up my sample by destroying twice
as many inner ears, [laughs]and so, you know,
I have to do what I have to do, because they
tell me that I have to do it.
>>Steve: Right.
>>John: And what we need, I think, is an effective...
This has all developed without a real conversation
among scientists of many fields saying: Hey,
where is this going, guys?
When I read that David Reich's lab had sequenced
something like 3,000 or 5,000 bones, I said
wait a minute, how did this happen? you know,
and I follow the field [laughs] right; so
the fact that this has really emerged, it's
burgeoned, I know that many archaeologists,
bio-archaeologists, people who study ancient
remains have been approached and thought,
you know, if I do this my name's gonna be
on a nature paper; or if I don't do this maybe
I'm not gonna have another chance because
they're interested in my sample today but,
you know, next week they might...
You know, there's a lot of people who are
trying to optimize things.
Very few of them are thinking about optimizing
what science looks like 40 years from now.
>>Corey: Is anyone having that discussion
kind of on a broader scale?
>>John: There are discussions that are happening.
I am involved in a few of them with people
who are geneticists, who are interested in
optimizing or improving the interactions that
folks have with indigenous societies, indigenous
peoples, and increasing consultations, you
know; I'm involved in lots of conversations
about optimizing genetic information versus
other kinds of biomolecule information.
>>Corey: But also the love of the whole field
right?
Are people actually having discussion — I
don't know what the organization of physical
anthropology is called — but is there a
policy discussion about these very issues
saying look, you know we're basically, we
have to carry out research now we don't want
to mortgage the future of our field for our
current interests.
It's a little like the global-warming debate
except it's actually in some sense much more
severe because...
>>Steve: We can't even organize ourselves
to stop getting gouged by Elsevier on journal
subscriptions, and you're asking us to coordinate,
you know...
>>John: There's reality that... and there's
also reality to the fact that these conversations,
right — You say, what's the association
of physical anthropologists and I say, well,
the American Association of Physical Anthropologists,
and that's the problem: it's American, and
the problem is global, and while those of
us who are in the American association — it's
the largest, without question, association
in the world — can have that conversation,
the fact is that the people who are crucially
important to that conversation are not American
researchers who are coming into other countries
and doing research as guests.
They're people like me who are engaged year-round
in the countries where we work, and the people
who are in the countries and responsible for
the remains, right, and that's a much broader
group but also more difficult group, because
they're more pressed by the need to have impact
come from your collections, more pressed by
the lack of funding for the work that they
do, and so more inclined to bring in large-money
collaborators, you know, there's a...
It's very difficult, and I don't know that
— I don't know, right, I think we do, all
of us do what we can.
That's where it has to go.
>>Steve: I think we're running out of time.
We have a whole set of other things that we
want to talk about, so, you can come back?
>>John: Yeah sure, of course.
>>Steve: Okay, awesome.
So thanks a lot, it's been really fantastic.
So we don't want to keep you from your class,
and I don't want to get beat up by the Provost,
so...
>>John: [laughs] All right, that sounds great.
>>Steve: ...I guess we'll just stop now.
[Music]
