How the Black Death got its start

Host: Nick Petrić Howe

Welcome back to the Nature Podcast. This time, the origins of the Black Death.

Host: Shamini Bundell

And the latest on the efforts to contain monkeypox. I’m Shamini Bundell.

Host: Nick Petrić Howe

And I’m Nick Petrić Howe.

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Interviewer: Nick Petrić Howe

The Black Death was the most deadly outbreak of any disease in recorded history. Between 1347 and 1353, it devastated the populations of Eurasia and North Africa, and it’s estimated that anywhere between 30-60% of the population of Europe was wiped out. The outbreak, caused by the bacterium Yersinia pestis, was the first in a series of outbreaks of bubonic plague that would occur over the next 500 years. The whole period is known as the second plague pandemic – marking the second time Yersinia pestis had swept across the medieval world. The Black Death in particular had enormous consequences on the history of the region, but one ongoing mystery has been, well, where did it come from? Historians have been searching for an answer to this question for a very long time.

Interviewee: Phil Slavin

What’s really important to note is that the victims of the Black Death themselves were not sure where it started, so it's actually a very, very long debate that goes all the way back to the Black Death itself.

Interviewer: Nick Petrić Howe

This is Phil Slavin, a historian of epidemic diseases and one of the authors of a new paper in Nature, which has used a host of historical records, archaeological artefacts and modern-day DNA sequencing to attempt to find the answer to this centuries-old riddle. To start off, though, Phil and his colleagues needed to know where to look. And with hundreds of years of debate on the issue, there’s no shortage of ideas. To cut a very long story short, there are four main theories. There’s one that suggests the Black Death originated somewhere in modern-day China, one that says around modern-day Turkey, another that suggests somewhere between the Black and Caspian Seas, and finally one that says Central Asia is the most likely place. For their part, Phil and his colleagues were drawn to Central Asia, specifically to a place in northern Kyrgyzstan where there are some particularly intriguing tombstones, as Phil explains.

Interviewee: Phil Slavin

And what I found there is that there were two years when we have a massive spike in the number of tombstones. So, we have 467 precisely dated tombstones. Now, about 25% of them are dated to those 2 years. In other words, we have a massive spike in the number of tombstones that were erected in those two years, and some of those tombstones were more detailed than others, and some of those detailed tombstones actually specifically stated that the cause of the deaths of those people was what is described as mawtānā in Syriac, meaning ‘pestilence’.

Interviewer: Nick Petrić Howe

This 2-year spate of pestilence-associated death happened around 7-8 years before the Black Death. So, it seemed like a good place to potentially find its origins, and that’s where modern genetics were able to help, as Maria Spyrou, palaeogeneticist and one of the other authors of the new paper, explains.

Interviewee: Maria Spyrou

So, our first step was to actually extract DNA from skeletons that were excavated from this cemetery. We got access to teeth. We actually drilled the interior part of the teeth. And one of the reasons why we always target this interior part of the teeth is because we think we have the highest chances of detecting blood-borne infections. After extracting DNA, we were able to sequence this DNA and use computational techniques to see whether we can detect any pathogens that may have been the cause of the deaths for these individuals.

Interviewer: Nick Petrić Howe

Within the DNA extracted from the teeth, the team were able to detect Yersinia pestis – the bacteria that causes plague. So, it seemed likely that these individuals were killed by plague. But it’s one thing to say these people died from plague and another to say this is where the Black Death originated from, so Maria and her colleagues took this ancient DNA, assembled its genome and then compared it to the other sequenced samples of Yersinia pestis.

Interviewee: Maria Spyrou

And when we did that, we actually found that the genome from Central Asia is directly ancestral to all genomes that had previously been published from the second plague pandemic period, including the Black Death period from Europe. So, this already told us that this was kind of a more primal or more ancestral form of the bacterium that we were dealing with.

Interviewer: Nick Petrić Howe

In other words, strong evidence that Central Asia was indeed the starting point for the Black Death.

Interviewee: Phil Slavin

So, I would like to think that this will really bring the centuries-old debate to the end. We finally managed to answer those two most pressing questions: when and where, approximately where, did the Black Death start?

Interviewer: Nick Petrić Howe

Whether this new paper will fully close the centuries-old chapter on the Black Death origin story remains to be seen. But it will give scientists clues of where to look next, and maybe to answer a question that continues to be pressing to this day: how and why do pandemics emerge?

Interviewee: Maria Spyrou

This actually gives us a precise time point that we can investigate in more detail in this part of the world to better understand how the pandemic began. So, what were the, for example, environmental circumstances under which this began, and also how was the bacterium transmitted from Central Asia all the way to Europe, so 3,000 kilometres, in the next 8 years before the Black Death began in 1346.

Interviewer: Nick Petrić Howe

That was Maria Spyrou from the University of Tübingen in Germany. You also heard from Phil Slavin from the University of Stirling in the UK. To find out more about Black Death origins, check out the paper in the show notes.

Host: Shamini Bundell

Coming up, we’ll be hearing the latest on monkeypox and efforts to control it. Right now, though, it’s time for the Research Highlights with Dan Fox.

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Dan Fox

Wriggling ribbon worms are capable predators known to protect themselves with toxin-laden mucus and subdue their prey with venom injected via a retractable proboscis. But scientists had limited understanding of the different toxic compounds deployed by the more than 1,300 ribbon-worm species. To find out more, a team compared the toxin-encoding RNA sequences of a number of these worms. They showed that the animals boast a wide diversity of toxins and use one toxin mixture for their defensive secretions and another mixture to capture prey. The researchers found evidence that the worms’ diverse venoms evolved to subdue different types of prey. Some venoms contain compounds similar to those produced by snakes and spiders, while others are unique, and these toxic chemicals might be useful. One component of ribbon-worm venom is being investigated as an environmentally friendly insecticide. Wriggle over to Molecular Biology and Evolution to read that research in full.

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Dan Fox

Researchers have made a microscopic thermometer, about the size of a grain of sand, that can detect temperature changes of less than one ten-millionth of a kelvin. High-resolution temperature readings are crucial for tasks ranging from studying chemical reactions to measuring energy loss in electronic systems. But many of these applications need micrometre-scale thermometers that can work at room temperature, and such devices have proved difficult to produce. Now, a team have developed a device about half a millimetre in diameter containing a semiconductor-based structure. This structure reflects laser light, but its ability to do so is extremely temperature sensitive and so can therefore be used to measure temperature. While the current setup has a resolution of less than 100 nanokelvin, the researchers think they can improve even further by using a higher-performance laser. Zoom in on that research over at Nature Photonics.

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Host: Shamini Bundell

Around the world, there have been a number of outbreaks of monkeypox, a viral disease that, until now, has rarely been seen in countries outside of sub-Saharan Africa. Now, we’ve obviously heard a lot about pandemics recently, and I am going to start this whole segment off by clarifying: monkeypox is not the next COVID. However, there are still a lot of puzzling scientific questions. While infection numbers remain low, they are increasing, and researchers are racing to find out what’s driving these outbreaks and the best way to contain them. To find out more about the situation, Benjamin Thompson spoke to Nature’s Max Kozlov, who’s been reporting on the outbreaks. Max started by explaining a bit more about what monkeypox actually is.

Interviewee: Max Kozlov

Yeah, so monkeypox is a viral infection in the same kind of family as smallpox. And it manifests itself in a way that there are very visible skin lesions in people who have monkeypox, usually. It has a non-negligent fatality rate but it's kind of worrying now because it's actually spreading in a way that we haven't seen it spread before, and that's what has scientists kind of on alert.

Interviewer: Benjamin Thompson

And so, these outbreaks are going on across the world then, but they are rather different to what's been seen before. What's the context for where we are now?

Interviewee: Max Kozlov

Yeah, monkeypox is not a new virus at all. Scientists have been studying it for many decades. It's mostly been limited to parts of sub-Saharan Africa. The countries that have seen the most cases are the Democratic Republic of the Congo and Nigeria. There is an outbreak that started in Nigeria in 2017, and the DRC has had a lingering outbreak for more than a decade now. And so, right now, last I looked, there were more than 1,000, maybe even closer to 1,400 confirmed cases, outside of the parts where we know monkeypox has been spreading the last few decades in sub-Saharan Africa. Specifically, Spain, the UK, Canada and the US are the countries that have had some of the most cases in the current outbreaks. But again, there are no more than, in the case of the UK, a few hundred cases, in the case of the US, around 20-30 cases, the last I checked. So, this isn't a situation like COVID-19, but we're kind of seeing the virus pop up in all of these different countries from around the world, and we’re still trying to make sense of how these cases are all connected.

Interviewer: Benjamin Thompson

So, although the numbers are small then, there are a lot of countries that are kind of tied into these outbreaks then. What do researchers think is causing this uptick? What’s driving these outbreaks do we think?

Interviewee: Max Kozlov

We still don't know if there's something inherent about the virus that has changed that makes it more transmissible or more virulent for any reason. That doesn't seem to be the apparent case. Pox viruses are very slow changing. They don't evolve very quickly. And because it's a DNA virus, any kind of mutations are usually fixed by the virus itself, and so that's why it's not likely that it's all of a sudden dramatically changed to become a ton more transmissible or a ton more virulent. And so far, there have been, like I said, around 1,400 cases worldwide and, knocking on wood, there still has not been a single fatality, which is different from what we understand about this virus because, from previous research, it looked like the case fatality rate for this specific strain of monkeypox was in the 1-3% range. And so, it's been presenting quite mildly so far, but that has to do in part with the population that it's spreading in, in that we know that pox viruses, including monkeypox, if it gets into a population like immunocompromised people, pregnant people, children, those are people who are at higher risk. And so, we haven't seen it spreading through those populations yet.

Interviewee: Benjamin Thompson

And in order to reduce the chances of that happening then, countries are implementing control strategies – contact tracing and the like. And there are a couple of vaccines available and they're being used to selectively immunise people.

Interviewee: Max Kozlov

Yeah, so we already have vaccines that we know are effective against monkeypox, and those are the smallpox vaccines because smallpox and monkeypox are closely related. What public health officials can do is something called ring vaccination, and that's different from mass vaccination, which is what we had for COVID-19. Ring vaccination has a very different goal. Its goal isn't to make sure that everybody is immunised. It's to make sure that the virus is contained, that it doesn't continue spreading. And monkeypox is a good virus for this strategy because it's slow moving, it has a long incubation period. It takes, we think, around two weeks for symptoms to develop. And there actually might be some kind of post- exposure effect of the vaccine, in that even if you get vaccinated after you've been exposed, the CDC and the WHO say that within four days, that vaccination is likely to protect against infection and definitely against some of the most severe symptoms.

Interviewee: Benjamin Thompson

And part of making ring vaccination work is identifying where the virus is spreading fastest to target those groups with vaccines. And right now, the virus seems to be spreading most among men who have sex with men.

Interviewee: Max Kozlov

Yeah, so a lot of the cases have been in men aged between 20 and 50, and scientists have noticed a large subset in men who have sex with men, but a lot of the researchers and epidemiologists that I talked to think that that is likely a coincidence in that, again, the virus is quite slow moving and so, if the virus was introduced into a specific population, odds are it's going to continue spreading there. The virus spreads very readily through close contact. It's still unknown whether the virus spreads through sexual contact specifically, but we do know that sex involves close contact.

Interviewee: Benjamin Thompson

And as you write about in your article, the messaging around vaccination needs to be really, really careful to avoid stigmatising any one group over another.

Interviewee: Max Kozlov

And that's extremely important, and we know that from what we've learned from HIV and AIDS, in that for public health campaigns to be successful, if the virus has been stigmatised, people might not want to disclose contacts that they've had or, in general, cooperate with public health officials to get vaccinated or to follow their guidance.

Interviewee: Benjamin Thompson

And so, countries like the US, the UK and Canada have started implementing ring vaccination then. How has it been going?

Interviewee: Max Kozlov

It's difficult to say how it's been going because they only recently started using this strategy. And it's interesting because every country is kind of doing their own version of it. Because one, ring vaccination hasn't been a strategy that we've used a whole lot. We've used it for Ebola virus and we used it to eradicate smallpox. But there's also a lot of unknowns, actually, about using smallpox vaccines for monkeypox because, again, they weren't meant for monkeypox. They were meant for smallpox. But we know that they're protective against monkeypox as well. But, for example, the US is taking a more measured, conservative approach with the vaccines for now – these things are always subject to change – in that they're only vaccinating high-risk exposures and some intermediate-risk exposures, as they're defining it. Whereas other countries like Canada, specifically the province of Quebec, they have offered the vaccine to men who have sex with men who have had at least two sexual partners in the last two weeks, I believe. So, they are prophylactically hoping to get ahead of the virus.

Interviewee: Benjamin Thompson

And there are a lot of questions that remain to be answered about these outbreaks then, and researchers are trying to figure those out. What are some of the key questions that they're looking at?

Interviewee: Max Kozlov

So, scientists would still love to know the genetic underpinnings of this current virus that's circulating outside of sub-Saharan Africa. They're looking for any clues for why it's behaving in the way it is. And there's some preliminary ideas for what's going on, but because monkeypox hasn't been studied a whole lot and it's a large virus, even if scientists notice a mutation in a certain gene, whether they'll actually be able to figure out whether that gene is making the virus behave in a different way, that's a whole other question. So, there's a lot to understand about the genetics of the virus, first and foremost. And another question is what the most effective vaccination strategy is. I think there's going to be some interesting data there for how to effectively contain a pox virus like monkeypox in the future because this is definitely not the only pox virus that exists in nature.

Interviewee: Benjamin Thompson

One thing that struck me, Max, is, of course, we've discussed these most recent outbreaks, but as we've said, monkeypox is not new. When you've been speaking to researchers in Africa specifically, are you getting a sense of frustration from them that they've been obviously fighting this disease for a very, very long time, but only now are there suddenly a slew of genetics work and a slew of public health work being done as a result of what's going on in other countries?

Interviewee: Max Kozlov

Yeah, when I spoke with the head of the Nigeria CDC, who has been managing that outbreak since 2017, he had mentioned that he and other African virologists have been frustrated by the sudden attention to this virus. It's been a public health concern for Nigeria and the Democratic Republic of the Congo for many years now, and it's really only again been studied in the context of bioterrorism for a lot of the global north and western countries, and not taken seriously as a public health concern. And so, now, for countries to not only be talking about monkeypox but also vaccinating against monkeypox using smallpox vaccines that have existed for decades, that is difficult because that's never really been an option for these countries to receive these vaccines. So, the sentiment that I've gotten so far has been frustration and very, very, very cautious optimism that maybe now people will take this virus more seriously and, in general, that a viral infection somewhere is potentially a viral infection anywhere.

Host: Shamini Bundell

Nature’s Max Kozlov there. Look out for links to his most recent monkeypox story in the show notes.

Host: Nick Petrić Howe

Finally, on the show, it's time for the Briefing chat, where we discuss a couple of articles that have been highlighted in the Nature Briefing. Shamini, why don't you go first this week. What have you found for us to talk about?

Host: Shamini Bundell

Well, you might have seen a little bit of a buzz around this story. So, I've been reading an article in the Washington Post, and one in New Scientist as well, about Google's LaMDA AI, and the Google engineer who claims that it has reached sentience.

Host: Nick Petrić Howe

Yeah, I've seen this sort of doing the rounds on social media. I've not really engaged with it too much because, personally, I feel like it's quite a hard thing to tell whether something's sentient. But tell me what actual people in the know have been saying about it, Shamini.

Host: Shamini Bundell

Well, yeah, there's been a lot of responses to it. Most of the responses are, ‘No, we don't think that this AI is sentient. We don't think that AI is sentient yet, perhaps.’ But there's actually lots of sort of interesting elements to this. So, LaMDA is a sort of chatbot system designed by Google. It stands for Language Model for Dialogue Applications. And what they've done is they've…

Host: Nick Petrić Howe

Sorry, I love these acronyms. They’re totally valid names for things. Carry on.

Host: Shamini Bundell

So, what they’ve done, and this may sound familiar, they've put in loads and loads of text conversations, people talking words from around the internet, and they're trying to train the AI to speak like a human. So, it's taken in all these examples of speech and writing and you can have conversations with it. And this engineer, in this case, Blake Lemoine – I’m not 100% sure how to pronounce his surname – released also some transcripts of conversations that he'd had with this LaMDA, as part of his proof that LaMDA is sentient.

Host: Nick Petrić Howe

Right, okay. Well, my first thought is, being able to talk like a human is one thing. Being sentient seems like a completely different thing to me. So, how does it being able to talk sort of convince him that this is sentient?

Host: Shamini Bundell

Well, Blake had originally signed up to be interacting with this chatbot because his job was to work out if it was using discriminatory language or like hate speech that it might have found from his training data. But through a series of conversations that he was having with LaMDA, through the things that they were discussing, through the things that LaMDA was saying, he became convinced that this was an intelligent being. So, LaMDA was talking about its fears of being switched off, talking about feeling happy and sad. When quizzed on a thing that these systems often do, which would be talking about situations in the first person that they couldn't have possibly been in, like, ‘When I was somewhere the other day,’ it couldn't have been there. It's a bot. He said, ‘Well, why do you do that?’ And it said, ‘Well, I'm trying to attempt to form bonds with humans so that they can relate to me,’ so that was its sort of explanation. And Blake said if he didn't know what he was talking to, he'd think it was maybe a seven- or eight-year-old kid who happened to know a lot about physics. And he's not the only one who says talking to these chat bots is becoming increasingly like talking to a real person. There was an article by another Google engineer in The Economist before this came out, and he sort of described it as, ‘I increasingly felt like I was talking to something intelligent.’ So, this model really is doing a really good job of talking like humans tend to talk, staying on a conversational topic, and seeming to come up with sort of novel ideas and propositions.

Host: Nick Petrić Howe

Right, okay. But I guess like the ability to speak doesn’t necessarily make you intelligent, or sentient, in this case. What has been the sort of reaction from people in the field to this?

Host: Shamini Bundell

Well, no, exactly. The thing about all of this is, of course, LaMDA is doing exactly what it was trained to do. It was trained to sound like people, essentially, and that is what it's achieving, amazingly well. So, Google's response to this, actually, the engineer in question, Blake, after not feeling like his sort of concerns were being taken seriously, went public with this, and has been suspended from his job. And Google said that they've told him that the evidence does not support his claims and that there is, in fact, no evidence that LaMDA is sentient, and, in fact, lots of evidence against it. And a lot of commentators have seemed to agree with this and said that AI is not there yet, not at that level that we could call sentient or intelligent, self-aware thinking in that way. But the fascinating thing is that, of course, humans are amazing at anthropomorphising everything. It's a really natural process. And there's a quote from a linguistics professor, Emily Bender at the University of Washington, who says, ‘We now have machines that can mindlessly generate words, but we haven't learned how to stop imagining a mind behind them.’ And another thing that this article said was that AI doesn't need to be sentient to feel real. The point is that when you're interacting with it, it does feel like a real person, and that could be an ethical issue in itself, actually.

Host: Nick Petrić Howe

Yeah, there's certainly a lot to consider here, and it almost brings up the question of how do you determine sentience in the first place. But you left that hanging there quite tantalisingly. So, tell me, what are the sort of ethical issues surrounding this?

Host: Shamini Bundell

Yeah, and this is a sort of broader issue that this story just sort of happens to bring up, about the fact that we're creating these AIs, that people might not be able to tell the difference. You might be talking to someone online and not know whether that's a person or an AI. There is also an issue – in fact, Google themselves wrote a paper earlier this year thinking through some of these sorts of potential ethical problems. One of the things they said was even if people do know they're talking to a chatbot, that instinct to share and connect with a human being might lead people to share private things that they normally wouldn't. Or you could have a situation where an AI is so good at impersonating people that it can even be trained to impersonate a specific person. In the future, it may well be a sort of psychological issue as well about whether we can cope with something that seems intelligent without treating it as such. And Margaret Mitchell, who was a former co-lead of ethical AI at Google, said ‘I'm really concerned about what it means for people to increasingly be affected by the illusion,’ especially now that the illusion has gotten so good.

Host: Nick Petrić Howe

I mean, Shamini, now I’m just starting to wonder like, how do I know if you're an AI or not?

Host: Shamini Bundell

Well, does it matter, Nick? Is it going affect our relationship if I turn out to be an AI? Can we still be friends? There are philosophical questions here, but I'll just leave you with one final quote from Blame Lemoine, this Google engineer, who just said, ‘I know a person when I talk to it.’

Host: Nick Petrić Howe

I mean, that is the question, I guess. It's a very interesting topic, Shamini. Thanks for bringing it to the Briefing. I've got a story this week that is kind of related to it, but hopefully the AIs involved in this are not sentient – at least they don't seem to be. I've been reading an article in Nature, which is a careers feature about cloud labs, and these aren't labs like floating in the clouds.

Host: Shamini Bundell

You immediately crushed my dreams. You immediately just like got in there before I'd even had time to fully picture it. Thanks. Thanks, Nick.

Host: Nick Petrić Howe

That’s okay, I live to crush your dreams, AI Shamini. So, they're not labs in the clouds floating in the sky. These are actually labs where you can send your code and a robot will do your experiments for you.

Host: Shamini Bundell

Oh, that kind of cloud, like cloud computing?

Host: Nick Petrić Howe

Yeah, that’s right. So, this is something that I hadn't heard about before but has been around for a couple of years now, where, essentially, you can send your code for your experiments to some robots in a lab somewhere and they'll perform the experiments for you. And so, the thing that really caught my attention in this article was someone was describing their PhD work, years and years of work, and then they were asked to participate in trialling out some of these robots that do this work for you on this cloud platform, and they were able to replicate their entire PhD work, years of work, in a couple of weeks.

Host: Shamini Bundell

That's a little bit painful for them having already done it. But also, presumably amazing for projects where you just like need a huge bulk of data collected, lots of things reproduced, and that could save people years.

Host: Nick Petrić Howe

Yeah, I mean, that is the sort of hope with this technology. And I'll tell you, as someone who did their PhD, a lot of lab experiments are quite boring, and they normally require doing the same thing over and over. And scientists are no strangers to robots. A lot of labs have robots that help automate many of these processes. But this is sort of taking it a step further by having all sorts of experiments available on demand. They describe it in the article as sort of like a Netflix for research. So, you don't have to buy all the equipment and all the things you need. It’s there on demand when you need it. And so, yeah, it could allow people to be able to reproduce their experiments easily by using the same code again and again, and also just perform experiments very quickly in a sort of controlled environment where they know everything is going to be the same each time.

Host: Shamini Bundell

And so far, what kind of labs and what kind of science is this?

Host: Nick Petrić Howe

Yeah, I can't imagine that this would be used for all of the kinds of science that everyone does, and this seems to be more focused on the biology side of things. So, they have a list of things that they're able to do, which includes cell culture, DNA synthesis, liquid chromatography, structural analysis sort of things like mass spectrometry and nuclear magnetic resonance. So, there's quite a few different things that you can do. But another advantage of this is the robots, they don't need sleep, so this is something that's operating 24/7.

Host: Shamini Bundell

And I feel like the key question that all the PhD students out there are going to be asking is, ‘Is this ready to go? Can we use it?’

Host: Nick Petrić Howe

It is ready to go. It is quite expensive. So, in the particular lab that they focused on in the article, the Emerald Cloud Lab, it costs $US24,000 dollars a month for the sort of lowest tier of access, which sounds like a lot of money, but then when you actually think about how expensive much of the equipment involved in these kinds of experiments is, it can work out in the long term as saving money. And also, some people in the article are discussing the fact that it could help democratise research because instead of having to buy all the expensive equipment or only go to the labs that have the expensive equipment, if your institution or something has a subscription with a service like this, then you could do the research. Some people been applying for grants for people from low incomes to come and do research using this sort of cloud laboratory, and that opens up access to a whole group of people may not have had it before. However, this openness could be a bad thing because some people have raised concerns that certain groups, say, terrorist groups and things, could misuse the technology to perform malevolent experiments and do unethical things with it. And when asked for comment on this, the people involved in making these sort of cloud labs, they say they've got the highest-level data encryption possible, and they've never had these sort of security concerns, so they haven't addressed those yet.

Host: Shamini Bundell

So, I think that's really interesting in the sort of changing ways that scientists are going to be working in the next few years and, doubtless, the Nature Podcast will be here, bringing you all the most exciting science news, as always. So, I think we will leave it there. Listeners, if you want to read more about those stories we've just been discussing, you can find some links in the show notes. And while you're there, you can also sign up to the Nature Briefing and that will deliver more of these kinds of stories into your inbox.

Host: Nick Petrić Howe

That's all for this week. If you want to keep in touch with us, you can follow us on Twitter – we're @NaturePodcast. Or you can send us an email to podcast@nature.com. I’m Nick Petrić Howe.

Host: Shamini Bundell

And I’m Shamini Bundell. Thanks for listening.