S3.04 Race to the Bottom

Kat: Hello, and welcome to Genetics Unzipped - the Genetics Society podcast with me, Dr Kat Arney. In this episode, we’re hunting for the ghosts in our genomes, telling the story of the discovery of the double helix in Lego, and finding out how to argue with a racist. 

Before we start, just a reminder that you can find us on Twitter @geneticsunzip or by email, podcast@geneticsunzipped.com - ping us a tweet or shoot us an email, we’d love to hear from you. Also please do take a moment to rate and review us on Apple podcasts, if that’s how you’re listening - it does something happy to the mysterious algorithm and helps more people discover the show. Alternatively, you could share a link on social media or simply tell a friend - it’s all good. Thank you.

Ghosts in the Genome

Kat: Back at the end of October, I went to a fascinating meeting at the Wellcome Genome Campus in Cambridge, all about human origins and evolution.

It was a mind-bending couple of days, listening to geneticists, anthropologists, evolutionary biologists, paleontologists and archaeologists - all the -ologists! - discussing the latest evidence and ideas around where human populations came from and how we’ve changed along the way. 

We’ve already heard from one of the people I spoke to while I was there, Professor Chris Stringer, in our recent episode about the March of Progress - one of the most iconic and misleading images in evolution. Check out episode 1 of this latest series to hear it.

As Chris explains, our family tree isn’t a straightforward linear progression from ancient ape to modern human, but a complex, tangled web of interrelated - and interbreeding - species.

One of the most compelling pieces of evidence for this story can be found in our own human genomes today, in the form of DNA sequences picked up from our ancient ancestors the Neanderthals and Denisovans.

But, as I found out when I spoke with Arun Durvasula, a PhD student at the University of California Los Angeles, there are other ancestral ghosts lurking in the modern human genome - a highly appropriate topic given that I interviewed him on Hallowe’en - the 31st October.

Arun: The main highlights of the past 20 years of genomics research has shown us that we have these Neanderthal populations that have split off from the modern humans, let's say about 600,000 years ago. There was a sister population called the Denisovans which split off about the same time.

What's interesting about these populations is that they have a lot of archaic features, so they're very different from modern humans. So one thing that we'd like to know is what makes them different.

Kat: So, how can you start comparing modern humans, ancient modern humans and these Denisovans and the Neanderthals? What kind of data can you get and look at?

Arun: What we can do is compare patterns in the data, patterns of mutations. We have models that tell us from generation to generation; if these populations split at this time, it will leave this kind of signature in the data.

Kat: Okay, so if you look at their genomes you could say, if you separated this many hundreds of thousands of years ago, what we should end up with now is a pattern more or less like this?

Arun: Right, exactly. So we looked at some of this data in African populations and what we found, is that the current models of human evolution that we have aren't able to explain the patterns that we're seeing.

Kat: So this is like a ghost in the genome. You've got modern humans; we know that there is some Neanderthal and Denisovan DNA in there but then there's something else. What is that?

Arun: Right, yeah. So it looks like there's a lineage that splits off prior to the Neanderthals and Denisovans splitting off. It remained in Africa and interbred with modern humans in the last 50,000 years.

Kat: Hang on, so there was this other population of some kind of human that was around 50,000 years ago and interbreeding with us. Do we know anything about what they might have been like?

Arun: So at this point, we don't. We've been trying to sort of excavate the modern human genomes and try to pull out the chunks of DNA that come from this population. We have some statistical signals, but understanding the actual biology, the differences that this population had from modern humans is still a mystery.

Kat: So we've still got this DNA ghost, if you like - some DNA that is in our genomes today that has come from somewhere. Have you got any top suspects, looking at the fossils that are in Africa?

Arun: At this point we don't. There are quite a few fossils with a lot of interesting, archaic features but at this point it's unclear which one could be the population, and even if it's just one. So the signals that we find could actually be from multiple populations and it's just that our modelling is squishing it into one easy to model situation.

Kat: So also, that means that you don't know if this was just one group of individuals that came across the early humans and were like, ooh, let's have a go with them, or whether it was just one individual or multiple. What do we know about what might have gone on?

Arun: We know that the contribution is fairly substantial. Estimates of Neanderthal DNA in Europeans is about 2 percent, for comparison. Here, we're seeing about 11 percent.

Kat: Woah. So one tenth of the modern human genome is this ghost?

Arun: That's right.

Kat: That just blows my mind!

Arun: Yeah, it's pretty surprising at face value, but then when you think about all the different forms that have existed in Africa, all the fossils that we've found, it paints a picture of a really diverse landscape of populations. It's clear that this sort of interbreeding was happening all the time. So I think as we get more samples and as our methods get better at uncovering this stuff, we're going to find that this number could increase.

Kat: There could be more ghosts out there?

Arun: There could be more ghosts. Happy Hallowe’en!

Kat: Arun Durvasula from UCLA, with his scientific ghost story.

Follow him on Twitter @ArunDurvasula

How to argue with a racist

Kat: For a field involving specimens that have been dead for millennia, human origin research is surprisingly fast moving. In an exciting plot twist, just a couple of weeks ago scientists at Princeton University announced that they had discovered traces of Neanderthal DNA in some modern African populations, publishing their findings in the journal Cell.

Coverage in The Guardian, Science Daily, Science, New Scientist

The results contradict the established ‘Out of Africa’ narrative that groups of ancient humans left Africa to spread across Europe and Asia and never went back, instead arguing for more of a Hokey Cokey style in-out-in-out-shake-it-all-about kind of story.

The reason for this complexity, as science writer and geneticist Adam Rutherford likes to argue, is that humans are ‘horny and mobile’. People don’t stay in one place, and they aren’t always picky when it comes to getting into someone else’s pants. Add up the effects over thousands and thousands of years, and it’s easy to see why trying to understand and compare the genetics of modern populations is a challenging task.

The truth is that the more we study human genomes around the world, the more diversity we find. But, as Adam points out in his latest book, How to Argue with a Racist, we should be on guard against those who would wish to crudely slice this rich and complex tapestry of global human genetics for political ends.

As a scientist, he studied at University College London - an institution with a long legacy of genetics, from the dark eugenics work of Francis Galton and his colleagues in the 19th century to modern cutting-edge genomics and evolutionary biology.

Add to that his own mixed anglo-Indian heritage, the massive growth in the popularity of direct-to-consumer ancestry testing and the worrying rise of hardline nationalist and racist narratives in political and public life in many parts of the world, and you’ve got a compelling reason to write a book that separates the facts of genetic diversity from divisive fiction.

Adam: All these things suddenly coalesce. I guess they've been building for a long time, but they coalesced until a point where I was like, well, I can't not write this book now because we now have to seriously address what genetics does and doesn't say about human variation - about race, the history of race science, about eugenics. You know, easy stuff really.

Kat: Just trivial things! It has amazed me really, in the past couple of decades, how much we now know about the human genome. Twenty years ago we thought there were a hundred thousand genes and the human genome was basically six people.

Now we're gathering thousands and thousands of genomes, going back through history, gathering archaic samples and really starting to dig into our human journey across the planet - the ancestors that we gained and lost and mated with along the way and really understanding what is in the human genome and how it varies.

So, how has that knowledge then led to confusion and wrong-headedness? What are some of the most common ways that this new knowledge is being twisted and abused?

Adam: Yeah, I think your description is really accurate, that humans over the last million years, more in the last 100,000 years, we do two things really well; we move and have sex and admixture -

Kat: That's the technical term for bonking.

Adam: Yeah, well basically. Gene flow events, introgression… it's all just sex. But it is a quintessential human characteristic, that different groups of people over time that have been previously separated re-join through sex, through gene flow events. And this concept of "admixture", is just quintessentially human.

So, the idea of racial purity or separation of lineages of humans is not really in line with what we have now discovered, as you say, in the last ten, twenty years in the age of both ancient genomics and just understanding our own genomes of extant, living people better.

So we see that we are -- we talk about family trees and phylogenies, which are sort of tree based descriptions of evolution, and we're not a tree at all. I don't know whether we should completely retire the concept of a genealogical or phylogenetic family tree, but it doesn't describe what humans have done for the last hundred thousand years, for the last ten thousand years. And indeed, in our own family histories over a few generations.

Kat: So we've been using genetic techniques to understand more about the diversity of people. If we go back far enough, we all come from the same small groups of people and we all originally came out of Africa.

There's some confusion though about the populations. I hear the words "population structure" and the characteristics and genetic diversity, and then people say, "Well, that's race." How does this all match up and why do people want to make this such an important thing?

Adam: This is why, I think, the history is very important. In general, scientists are not bad at knowing their own history, but I've always been very interested in the history of genetics because it's short.

Genetics is a subject which is only about 120 years old in any meaningful sense, but of course what genetics is, is a study of inheritance and family trees and sex and those sorts of things - which people have been obsessing about for all of human history. So it's not like quantum physics, in the sense that it has no relation to the experiential.

Kat: We've all got genes; we've all got a human genome.

Adam: Exactly. And that means that we carry a lot of cultural and intellectual baggage about what genetics and inheritance means.

What's happened in the last twenty years, is that many of those ideas about how inheritance works and how genetics works in general, and how genealogy and family trees and how inherited family traits, characteristics are inherited - a lot of these things, we had to radically modify within the genetics community.

You and I know this and many of the listeners who are geneticists will know this, that we no longer cling to ideas about, for example, a single gene for a single characteristic and so on.

So, the transfer of that information from academia into the public domain, I think has been a battle. And a lot of this is on me because this is my job.

Kat: And me as well, yes.

Adam: Yes, and you too. We've failed. We've spent twenty years trying to talk about these things.

I don't think we really have failed, but I think we're contesting against forces which are culturally embedded for thousands of years. So - ideas of racial purity or tribal identity. We are a very ethnocentric species. We like to identify with people who are similar to us in whatever the characteristic is.

That might be football teams or it might be class or it might be geographically based, if you happen to think that South London is better than North London.

Kat: No, it's not.

Adam: Well it is, actually. Or that UCL is better than Kings, which it is.

Kat: It's not.

Adam: It is. Both of those two things are absolutely -- we're going to fall out over this! Anyway, with the advent of ancestry testing kits, which I've written about a lot and talked about a lot in the past, I get almost continuous emails from people telling me that they're descended from Vikings. White people.

White people always want to know that they're descended from Vikings. And that's fine because a) Vikings were super cool and b) everyone in Europe is descended from Vikings. So you don't need to do an ancestry test to demonstrate that. You can just ask me and I will look at you and say, "You're descended from Vikings, well done."

Now, whether that says anything about what your character is like, I find problematic. Everyone is descended from a very small population less than a few thousand years ago. And for Europe, it is a thousand years ago. So that sense of identity that comes out of a misplaced understanding of genetic genealogy, I think is very potent but I don't think it has any explicative power, necessarily.

Now, that's all trivial, wanting to find out if you're descended from Vikings is kind of fun, and then you tell people that you're descended from Vikings. I don't know what you're meant to do with that information other than -

Kat: Get a hat with horns on.

Adam: They didn't have horns.

Kat: Argh.

Adam: Sorry, I can't let that pass. (Laughter) Vikings didn't have horns on their hats. I learned that from Janina Ramirez, who got very cross with me when I suggested exactly the same thing.

Kat: But fancy-dress costumes aside, people maybe want to find out about their ancestry and the journey that they took through history to get here. But where I find it gets a lot more insidious is this kind of idea of categorisation. And the kinds of traits and genetics that people use to divide us up.

Can you explain a bit more about this whole idea of diversity and population structure? Because I've heard things like, the people in two neighbouring villages in Mexico are more different than someone who is European or someone who is Chinese. How does this actually work when we dig into it?

Adam: Right, well, this is where the genetics becomes very complicated very quickly. And it's also where the history is important, because a very brief history of race goes something like this: Humans are ethnocentric. Humans are different from each other.

As we go around the world, we encounter people who look different from each other. You've got Africa which is the birthplace of us as a species and then you've got not-Africa, which is everyone else on earth.

The reason I separate them like that is because there's more diversity within Africa, both phenotypically, physically - our physical characteristics - and genotypically, which means how different we are in our genomes.

There's more diversity in those two things within Africa than there is in the rest of the world put together. But evolution has deceived our eyes because the categorisation tools that we tend to use most obviously are very visual very superficial characteristics such as pigmentation, such as skin colour. And even though there is more variety in skin colour within Africa than there is in the rest of the world put together - so that's relatively recent information but that is factually correct.

We very casually describe people as black, right? So, that's a social categorisation which is meaningful and which people understand, but scientifically, it doesn't hold a lot of water.

I'm not saying that we shouldn't call people black, that is socially accepted -- if that is a socially accepted term that black people want to use -- but to lump together 1.3 billion people in Africa and the millions of people all over the rest of the world who are from recent African descent and have dark skin as one unit type of people, is not reflected by the genetics that underlies pigmentation, or the migratory journeys for the last million years that have seen the dispersal of people around the world.

Now, in the 17th and 18th centuries, where colonial expansion from Europe is occurring, the first attempts to categorise people, to apply a taxonomy to humans, begins. Mostly by European gentlemen scholars, many of whom didn't actually travel. Many of them did this from their armchairs in their living rooms, with reports back from the colonies or potential colonies about what people were like.

So at this point, we begin the scientific attempts - well, actually, the pseudo-scientific attempts in retrospect - but the scientific attempts to categorise people. And they are primarily done by pigmentation.

So we say Africans are black people, Chinese or East-Asians are yellow (this is Linnaeus's terminology). And there have been innumerable attempts by different people to form sharp boundaries of taxonomic categorisations of the people of the earth.

There's never been any agreement on how many races there are, there's never been any agreement on what characteristics, psychological and behavioural traits are associated with those superficial physical traits such as initially, skin pigmentation and secondarily, skull morphology, which comes a bit later in the 18th century with Johan Blumenbach.

But one thing was unanimous and universally agreed on in this era of taxonomy. The one thing that everyone thought was that white Europeans were the best. I know it sounds funny, but -

Kat: We just make the rules!

Adam: It is, in all of those characterisations -- Blumenbach was -- he hedged his bets a little bit. Now, why this is important is not simply that it's pseudo-science because it's unevidenced and it's mostly just opinion based on very superficial characteristics. It's important for two reasons really. One is the concept of "othering", which is a sociological concept. You'd say, we're one group and another group is another group.

Kat: You're not one of us.

Adam: Right. So by othering another group, you separate them away from us, which makes subjugation more palatable. So, if you're going to a country in order to colonise it and you say, "These people are not actually the same as us for the following reasons: they are physically different and they are behaviourally different" - and in some cases some of these people are arguing that they are a different species.

At which point you can say therefore, we can justify enslaving this nation or exploiting this country or their lands because they're not the same as us. That is a standard way of subjugating a people or invading a country.

The second thing I think is important to recognise is that the reason it's pseudo-science and the reason it's important to understand this history, is that it's science or pseudo-science being marshalled, being co-opted into a political view. Not the other way around, which is the way societies work better - we say what the science is and then other people, not scientists but society, the demos, hopefully informed, make decisions about what you do with that information.

The history of race science is the other way around. It is political ambition and expansive political philosophies co-opting science, pseudo-science, in order to make the political machinations and manoeuvres more palatable to the people. I think, and I argue in the book, that we're seeing some of those same patterns emerge in the 21st century, with the application of modern - or the misunderstanding - of modern genetics, especially direct to consumer genetics, to say the same things that we've been through four, three, two centuries ago.

Actually, you're reinforcing these essentialist characteristics of humans which aren't real, or identifying things which are within our genomes, segregating by land mass or by population or skin colour or whatever, and therefore don’t represent the total amount of genetic diversity in a people, but are being used to say these people are inferior or superior, or that there are clear lines of racial delineation between people and therefore, by extension, we can say, “Well, these people are not us.”

Kat: Words to heed from Adam Rutherford, whose book How to Argue with a Racist is available now from all good bookshops and, no doubt, it’s annoying racists everywhere.

Follow him on Twitter @AdamRutherford

Building DNA out of Lego

Kat: I don’t know about you, but I love Lego, and spent much of my childhood constructing strange creations out of the miscellaneous bricks that we had collected over the years. Today’s sets are far more sophisticated and scientific, and my astronomically-minded partner has spent many happy hours putting together Lego versions of the Saturn V rocket, the lunar lander and the Mars rover. But what about Lego for genetics fans? Well, if student Daniel Khosravinia has his way, we could soon be able to make our very own model celebrating the discovery of the DNA double helix. He’s a student at King’s College London, home to Maurice Wilkins’ lab where Rosalind Franklin and Ray Gosling carried out the crucial experiments that helped to cracked the structure. So when Daniel saw an exhibition of some of the equipment that Franklin used, he wanted to dig deeper.

Daniel: So as I continued my research and I learned more about the history and the people who were involved, I thought that creating a Lego model of DNA would not only be very fun, which it was, it would also inspire many young people - and even not young people, because everyone loves Lego - to pursue a career in science - and to try and contribute to this beautiful field.

Then when I learned more about the history and I discovered about Rosalind Franklin who intrigued me the most, I felt that this would be a very good way for people to recognise her more and for people in general to know about the efforts that led to the discovery of a very important piece of information that is now regarded as common knowledge.

Kat: Just describe it to me because I think it's absolutely incredible. What does it look like, what does it show and also, who is in it?

Daniel: Well first of all, thank you for your compliment. Secondly, regarding the model itself, as best I could I tried to make it a real replica of the DNA molecule.

It's a double helix with it turning a complete 360 degrees around itself. It has the base pairs all being connected to each other in complementary pairs and it also has the phosphate groups. The sugar groups were put on as best they could be - obviously, since this is a Lego model, the structure of the model also has to be taken into consideration. These were from the structure itself.

One interesting thing, at first I was going to do only the structure, but then I thought to myself, why don't I work with some of the history of the structure as well. So to make the entire structure, I made it into a two-sided laboratory, with one side being the Franklin and Wilkins lab and the other side being the Watson and Crick lab.

These labs contain some of the most famous devices used for the discovery such as two microscopes such as Rosalind Franklin used in her lab. It also includes minifigures – which is the technical term for Lego people – of Rosalind Franklin, Maurice Wilkins, James Watson and Francis Crick. So those four figures are also included in the Lego set.

Kat: So, now you've designed this model, what happens next? I know it's up on the Lego Ideas website. What do you need to make this a reality that people can actually buy and build themselves?

Daniel: Whenever a model reaches 10,000 supporters, the Lego group will consider those ideas to be made into an official Lego set which can be bought in any of the stores around the world or even online. So right now I just need to get to those 10,000 supporters. I’m happy to say I've already got more than 1,000, so there's 9,000 left to go.

Kat: And how long have you got to get to that 10,000?

Daniel: Currently I have around ten months.

Kat: Excellent. So, hopefully in about a year or so we'll come back to you and find out whether you hit your target. 

Daniel: Hopefully, yeah. And hopefully by then it will be in Lego stores.

Kat: Head to the Lego Ideas page to see pictures and vote for Daniel’s model. You can also watch this short video about the model:

Picking where to publish

Kat: And finally, it’s time to round things off with a clip from the Heredity podcast, the journal of The Genetics Society. Host James Burgon is running a series of interviews with the journal’s editors to find out what makes them tick and - more importantly - extract some top tips for successfully publishing scientific papers. Here’s his latest guest, Dr Marc Stift from the University of Konstanz, who’s not only spent three years as an editor at Heredity, but has authored five papers in the journal to date. He explains what to look for when it comes to choosing where to submit your next scientific paper. 

Marc: I think everybody is using Impact Factor as a prime decision maker for where to submit. And I don't think I'm an advocate to abandon them, but I'm an advocate to also look at the reputation of journals and to ask older colleagues which journals they, just off the top of their heads, know have been around for a long time and are signals of good quality science.

So, I think I'm an advocate of publishing in society journals, not only Heredity, but in general the experience you get as an author from these journals. It's much more personal and you can get much better and potentially more honest feedback. And you're supporting the scientific community.

Kat: You can get more of Marc’s good advice by listening to the full interview in the latest Heredity podcast - just search for Heredity in your favourite podcast app.

That’s all for now. Next time we’ll be taking a look at the naming of nucleotides.

You can find us on Twitter @geneticsunzip and please do take a moment to rate and review us on Apple podcasts - it really makes a difference and helps more people discover the show.

Genetics Unzipped is presented by me, Kat Arney, and produced by First Create the Media for The Genetics Society - one of the oldest learned societies in the world dedicated to supporting and promoting the research, teaching and application of genetics.

You can find out more and apply to join at genetics.org.uk  Our theme music was composed by Dan Pollard, and the logo was designed by James Mayall, transcription is by Viv Andrews and production was by Hannah Varrall. Thanks for listening, and until next time, goodbye.