Host: Benjamin Thompson

Welcome back to the Nature Podcast. This week, we’ll be hearing about pain, how to cool with crystals…

Host: Shamini Bundell

And learning about the human impact on Mount Kilimanjaro. I’m Shamini Bundell.

Host: Benjamin Thompson

And I’m Benjamin Thompson.

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Host: Shamini Bundell

Now, Benjamin, for this first segment, I’m going to have to punch you in the arm – okay?

Host: Benjamin Thompson

Erm, well, two things: no and what?

Host: Shamini Bundell

I’m sorry, but I’ve done this interview on pain and this is the only way I could think of to lead in to it. You ready?

Host: Benjamin Thompson

Well, hang on, hang on, hang on, alternative suggestion – rather than giving me a whack, why don’t you carefully introduce the topic you’re about to talk about and then maybe let an interviewee explain the science?

Host: Shamini Bundell

Oh, do you think that would be better?

Host: Benjamin Thompson

Yes, I do.

Interviewer: Shamini Bundell

Oh, okay. I’ll do that then. So, there’s a feature in this week’s Nature about how there could be different pain pathways in males and females, with various studies that have looked at certain types of pain in both humans and rodents. The journalist who wrote and researched the feature is Amber Dance, so I called her up and asked her whether people experience pain differently depending on their biological sex.

Interviewee: Amber Dance

The thing is, pain is subjective. If I punch you in the arm and you punch me in the arm, we have no idea who hurts more. If we had to rate it on a scale of one to ten, and I said my pain is a two and you said yours is a three, well what does that mean? There does seem to be indications that women are more sensitive to pain, but the scientists I spoke with said that’s not really the interesting question. The interesting question is what is happening under the skin to create pain conditions, and that their finding is in some cases – not all but some cases – quite different between the sexes, and that’s what has real implications for treatment and clinical studies.

Interviewer: Shamini Bundell

Okay, so let’s say I’m fighting with my younger brother, not that I’d ever do that. I hit him, he hits me, we both go ‘ow’, we could actually be having different physiological physical responses to that pain?

Interviewee: Amber Dance

Right, right, now, I suspect being punched in the arm by a sibling is probably going to use the same pathways. A lot of the scientists that I talked to, what they’re working on is issues more of chronic pain or when you have pain caused by damage or problems with the nervous system that interprets pain.

Interviewer: Shamini Bundell

And when researching basic mechanisms, a lot of the experiments are done with rodents rather than actual people, so how did researchers first start investigating whether chronic pain and things like that, there might be sex differences going on with that?

Interviewee: Amber Dance

Very few researchers were for quite a while. There was just this assumption, well, in mice and rats it’s going to be the same and gosh, it’s so much easier to work with males because they don’t have an oestrous cycle and we don’t have to worry about any hormonal fluctuations, so let’s just look at males and assume it’s the same. That turns out to be a poor assumption because actually males have hormonal fluctuations in testosterone too. The big change has been that the grant funding agencies are starting to say – across biology and not just pain – that you have to consider sex as a biological variable. And so that has kind of pushed more scientists to go, alright, I’ll check in females and sometimes they go wait, it’s different.

Interviewer: Shamini Bundell

And I guess if you’re talking about medicine and testing things that you want to use on humans, that can be a big problem, right?

Interviewee: Amber Dance

So, the implication is, let’s say you go and do all your drug development in male rodents, and then you go and do a clinical trial in half men, half women. If the drug only works in the men and it doesn’t work in the women and you just go and average all your results, you’ll say well that drug’s not very good, let’s not continue with it. So, it’s entirely possible that there have been pain drugs that have been considered failed in clinical trials in the past that might have worked for a subset of the sexes in those trials.

Interviewer: Shamini Bundell

But to come back to the main question, how can such a basic thing as pain be so different? Surely we all have the same nerves and receptors and brains to some extent? What is the difference going on between sexes there?

Interviewee: Amber Dance

Pain is closely tied with the immune system, so a lot of the differences people are seeing between sexes happen when immune cells are involved in the pain pathways and what people tend to point to as a hypothetical explanation is females get pregnant, which means you’ve got essentially a foreign organism in your body for some length of time and you need to not treat that as an invader.

Interviewer: Shamini Bundell

And what kind of mechanisms are we talking about? How are immune cells involved in pain pathways?

Interviewee: Amber Dance

So, one of the biggest papers in this field came out of Jeff Mogil’s lab in Canada. They were looking at a pain system in these mice, and it’s known that it involves a cell type called microglia, which is sort of the immune cells of the nervous system, and if you block the microglia then it should block the pain. And so, they did this in males and everything worked fine as expected, and then they tried it in females and nothing. No matter what you do to the microglia, it doesn’t block the pain response in females. And what they think is going on is that females don’t use microglia for the pain response – they use T cells instead. So, you have completely different cell types of the immune system contributing to what looks on the outside like the same pain.

Interviewer: Shamini Bundell

And that’s such a major difference – a completely different type of cell. And then of course, that’s really important if you’re trying to target the cell or another part of the pathway to treat pain to know which one it is. But is it that simple? Is it a sort of binary where men have one type of mechanism for pain and women have another?

Interviewee: Amber Dance

So, we know that you can’t just say there’s male and female and that’s it. It’s clear that some people fall somewhere in between. Most of the studies in rodents or in people have just looked at male and female. I did find one study from about 12 years ago where they looked at people who are undergoing gender transition through hormonal treatment, and they asked them about their pain experiences before and after starting the hormone treatment, and they did find that in people who are going from male to female, some people reported more pain after, versus people going from female to male sometimes reported less pain after the transition, suggesting again that hormones make a difference.

Interviewer: Shamini Bundell

And then of course, different people will have different hormone levels naturally, so this also leads into this idea of personalised medicines as something that’s perhaps targeted to an individual even?

Interviewee: Amber Dance

Right, so the eventual hope is that pain medications could be personalised or applied precisely to the person in pain based on what kind of pain they have, what kind of mechanisms are happening under the skin, how they’re experiencing it, genetics, all kinds of factors. In a way, sex is rather a blunt way to divide people, but it could be a start towards that kind of really precision medicine where you get the drug that’s going to work on your pain the first time.

Interviewer: Shamini Bundell

That was freelance science journalist Amber Dance. Her feature includes a lot more details of work by various groups, so do go check it out at nature.com/news.

Interviewer: Benjamin Thompson

Next up on the podcast, let’s talk about being cool.

Interviewer: Shamini Bundell

I did wonder why you were wearing sunglasses in the studio, Ben.

Interviewer: Benjamin Thompson

Well, thank you for noticing Shamini, but actually I was thinking more about cooling things, you know, refrigeration and what have you.

Interviewer: Shamini Bundell

Ah, science stuff.

Interviewer: Benjamin Thompson

Absolutely, but science stuff that’s not without its downsides. The majority of refrigeration around the globe relies on systems that compress and expand gases to suck the heat out of things. But these systems also use a lot of energy, and many of the gases used can be harmful to the environment. They can also be difficult to scale down, which is problematic for things like the computing industry which is looking for more efficient ways of cooling, as microchips are getting smaller and hotter. But there might be another way. An alternative method is called ‘solid-state cooling’, and it relies on a group of compounds known as ‘caloric materials’ that change temperature in response to a force, maybe pressure or a magnetic field. This week in Nature, a team of researchers have published a paper that extends the list of caloric materials, by focusing on compounds called ‘plastic crystals’. They argue that these materials could be a shoo-in for future refrigeration technologies. So, what are these materials and how do they work? Well, I wanted to find out a bit more so I spoke with materials scientist Claudio Cazorla from UNSW Sydney, who’s written a News and Views article about the research. As it turns out, plastic crystals are not, as the name suggests, crystals made of plastic.

Interviewee: Claudio Cazorla

So, yeah, plastic crystals basically are crystals, so solids, that can be deformed mechanically very easily. It’s like if you think of a plastic bag, you can really deform it, right?

Interviewer: Benjamin Thompson

The molecules in a plastic crystal are spaced in a regular lattice. But they aren’t held rigidly and the molecules can rotate around their centre, so there’s a lot of disorder going on within the crystals. But all that changes when you give them a squeeze.

Interviewee: Claudio CazorlaWhen you apply pressure, what you do is stop those molecular rotations, right. So, you actually go from a very disordered system to something that is very ordered because now the molecules are not rotating any more. So, because of that change in the state of the disorder, you can get some kind of transfer of heat.

Interviewer: Benjamin Thompson

As the molecules become more ordered and the rotation stops, the crystal heats up. But how could you use a warm crystal to cool something down? Well, a few more steps are needed. First, you need to draw this heat away from the crystal using a heat sink or a fan. This drops the temperature of the plastic crystal back to where it started, even though it’s still under pressure.

Interviewee: Claudio CazorlaAnd now you remove that pressure, right, if you do that carefully, your system will cool down. So, it cools down below the initial temperature from what we have started with our cycle, so by putting into contact that cold system with something that we want to cool down, like for instance it can be a CPU in a computer, we can extract heat from that hot source.

Interviewer: Benjamin Thompson

This is broadly how the fridge in your kitchen works too, but instead of using a crystal, your fridge uses a cycle of compressing and expanding a gas. An international team of researchers wanted to explore the potential of plastic crystal cooling. They looked at the performance of a variety of plastic crystals, measuring the change in molecular disorder under pressure, and the cooling performance. For example, they have found one crystal that showed a temperature change of around 50 Kelvin when squeezed, and that surprised Claudio.

Interviewee: Claudio CazorlaThe numbers that they have got for that particular change of state on plastic crystals are very, very large, so they are practically within an order of magnitude larger than what we are used to finding out in other crystals.

Interviewer: Benjamin Thompson

Claudio says that plastic crystals like these could be a good alternative to gas cooling in the future. They only requires a small amount of pressure and function at near room temperature while other caloric materials require more extreme conditions to work in. And they have other traits which could be useful too.

Interviewee: Claudio CazorlaThese materials are not toxic generally because they don’t contain heavy metals. Also, on top of that because plastic crystals are highly deformable, they are especially well suited for being implemented on small devices.

Interviewer: Benjamin Thompson

But it’s going to be a while before we see plastic crystals being squeezed to cool microchips. Claudio says that a lot more research needs to be done on plastic crystals to find out if they’d work in the real world.

Interviewee: Claudio Cazorla

This has been a kind of fundamental discovery, right, whether in a few years we could have some new technology based on these materials, that’s something I don’t really know because there are many technical aspects that we are not thinking of now. So, there really has to be a lot of testing and a lot of prototyping in order to get some new technology out of that.

Interviewer: Benjamin Thompson

That was Claudio Cazorla from UNSW Sydney in Australia. You can read his News and Views, and the research paper on plastic crystals over at nature.com.

Host: Shamini Bundell

Coming up in the show, we’ll be hearing about an exchange programme for physics students between Italy and North Korea. But first, here’s the Research Highlights, read this week by Noah Baker.

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Noah Baker

Scientists have 3D printed mini-tumours-on-a-chip in the hopes of personalising cancer treatment. Researchers in South Korea focused on the most common type of brain tumour – glioblastoma. First, they created a range of ‘bioinks’ containing tumour cells from glioblastoma patients. Then they used a 3D printer to deposit the inks onto glass, mimicking the structure and biochemistry of the actual glioblastoma. When treated with radiation and chemotherapy, the tumours-on-a-chip reacted in a way which mirrored the cancers they came from. Higher success rates were seen if mini-tumours were derived from patients responding well to treatment, while there was less success with mini-tumours from patients whose cancer couldn’t be controlled. This suggests that the tumours-on-a-chip could be a good model for the patient’s cancer, and the researchers hope that they can use this to better tailor glioblastoma treatments in the future. More on that study over at Nature Biomedical Engineering.

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Noah Baker

Palaeontologists have found the 4,000-year-old remains of a monkey that was given the same burial rights as a human, suggesting it was a treasured pet. The monkey – a rhesus macaque – was buried in the vast cemetery of Shahr-i Sokhta, an ancient city near modern-day Zabol, Iran. Like human infants, it was interred in a simple pit along with traditional pottery. For Middle Easterners of the time, pet monkeys were a status symbol imported from the near east. This monkey might have been bestowed upon its owners as a luxury gift, and it’s one of the earliest known examples of a pet primate. Dig up more over at the Journal of Osteoarchaeology.

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Host: Shamini Bundell

Next up this week, our reporter Nick Howe has been finding out how human activity may be impacting ecosystems on Mount Kilimanjaro.

Interviewer: Nick Howe

If I asked you to picture a mountain, what would you think of? Maybe the cold and ice of Mount Everest? Or the impossibly steep faces of the Matterhorn? Perhaps the lava-filled slopes of Mount Doom? Well not all mountains – fictional or otherwise – are barren of life. In hot and dry regions, mountains are great sources of water and since temperatures cool the higher you go, parts of the mountain are often the perfect temperature for crops and great places to farm. Of course, this means a lot of human activity on these wet and warm mountain slopes, which raises the question, what impacts are humans having? Marcell Peters and his team have been trying to find out. Their new study in Nature this week looks at looks at Mount Kilimanjaro in Tanzania, and how its ecosystems have been changed by human activity.

Interviewee: Marcell Peters

On Mount Kilimanjaro, we find that the areas, the lowlands where we naturally find savanna ecosystems, that they are largely transformed to maize plantations. If you go higher on the mountain, you find naturally tropical montane rainforests, and these ecosystems are increasingly transformed to coffee plantations, for example, to grasslands for feeding cattle.

Interviewer: Nick Howe

The team observed 60 sites across the mountain. Some of these sites had high amounts of human impacts, like farming, and some had none at all. Then, they looked at how the plants, animals and bacteria differed between the sites. Using all that information, the team were able to get a picture of how humans may be impacting both biodiversity – the number of plants and animals in an area – and also ecosystem functions, processes like pollination, soil acidity and carbon dioxide emissions.

Interviewee: Marcell Peters

So, if you look at the biodiversity, we found that the strongest effects on both plants and animals were found in the dry lowland ecosystems, and when we look at the ecosystem functions, we found the strongest effects of land use again in the lowland ecosystems, the dry lowlands and in the montane forest, so that’s the area where the temperatures are already very low, but there’s still a lot of rain and these two ecosystems where you have a quite harsh climate, they were also the ones which were most affected in terms of ecosystem functions by land use.

Interviewer: Nick Howe

So, humans seem to be impacting different parts of the mountain in different ways and in the hot, arid lowlands, life is particularly harsh for plants and animals. Usually when things get very hot, the organisms will hide from the heat, but when humans come along and dig up all their hiding places to plant their crops, the biodiversity is left to bake. For ecosystem functions, they again were most affected in the arid lowlands, but also in the cold montane forests near the top of the mountain. These harsher climates are already difficult places for ecosystem functions, but with the addition of humans, the balance could be tipped. On the other hand, more temperate areas in the middle part of the mountain have much easier climates to deal with.

Interviewee: Marcell Peters

They have a temperature not so extreme, so animals and plants which are living there, they don’t come near to these extreme temperatures.

Interviewer: Nick Howe

That’s not to say there weren’t effects of humans in temperate areas.

Interviewee: Marcell Peters

You find quite the same number of species but they are totally different species.

Interviewer: Nick Howe

Marcell and his team found that the kinds of plants and animals thriving in the temperate parts of Mount Kilimanjaro had changed and different species had taken their place. This study involved a huge amount of data and with so many different factors to consider – temperature, elevation, human activity, all of which are not necessarily independent of one another – Marcell had to be strategic to disentangle what was causing what.

Interviewee: Marcell Peters

So, what we did is we tried to disentangle the influences by looking, for example, at subsets of data. So, we did some analysis also where we just used data from study sites where you still find agriculture.

Interviewer: Nick Howe

So, Marcell split up the data and by only looking at sites where there’s loads of agriculture across the whole elevation of the mountain and doing the same for when there was no agriculture, he could see whether temperature or humans were causing the impacts. Another factor that helped separate what was causing what is that Kilimanjaro is not like other mountains. Normally, there are the most people near the bottom and as you move up there are less and less. Since temperature decreases as you move up a mountain and so does human population, it's often hard to discern whether it’s people or temperature that are causing the observed effects. On Kilimanjaro, there are the most people in the middle of the mountain, so it’s a bit easier to see whether temperature or human activity are driving the effects. They found that humans were the driving factor for impacts on ecosystems but climate modified the effect, making it stronger in certain areas, like the arid lowlands. Altogether, Marcell thinks that the results of this study will be important to understand how best to protect these mountain ecosystems. He also thinks that it helps show how climate and human activity will impact biodiversity in the future. Typically, studies will look at one or the other, but this study was able to look at both. As we don’t have a crystal ball to help us predict the effects of climate change, studies like these can help us understand what the impacts might be, as you can use the different temperatures on the mountain as a proxy for future climates and it could help inform conservation efforts on tropical mountains worldwide.

Host: Shamini Bundell

That was Nick Howe talking to Marcell Peters from the University of Würzburg in Germany. You can check out Marcell’s paper and an accompanying News and Views over at nature.com.

Interviewer: Benjamin Thompson

Finally on this week’s show, it’s time for the News Chat and I’m joined here in the studio by Nisha Gaind, Nature’s European Bureau Chief. Hi, Nisha.

Interviewee: Nisha Gaind

Hi, Ben, thanks for having me!

Interviewer: Benjamin Thompson

Well, Nisha, for our first story let’s head back to last Saturday and a fairly big march that went on here in London.

Interviewee: Nisha Gaind

Yes, this is something that listeners in the UK will probably know lots about already. There was a march over Brexit and hundreds of thousands of people descended on London to call for a people’s vote – they want another referendum on Brexit, and scientists were there with them.

Interviewer: Benjamin Thompson

Well, our reporter Holly Else was at the march, and she was asking scientists why EU membership was important for science. Here’s what a couple of them had to say.

Susan Lea

I’m Susan Lea from the Sir William Dunn School of Pathology in Oxford. Europe and movement of scientists is absolutely the core of everything we do in science. The trivial things are funding, but mostly it’s about the people and about the fact that our department is more than three quarters non-Brits, and that’s going to get hard. We’ve had huge issues with recruitment. We’ve had several people pull out shortly before interviews for jobs from the level of chair down. It’s huge issues.

Stephen Serjeant

My name’s Stephen Serjeant. I’m a professor of astronomy at the Open University and I am involved in many big European Union projects. It’s very, very important for us – free movement of people, also large research collaborations, international funding – it’s so, so very important. We get so many benefits.

Interviewer: Benjamin Thompson

So, there we go Nisha, and there are more quotes on similar lines.

Interviewee: Nisha Gaind

Yeah, so this is just a small example of the types of arguments that researchers make against Brexit. The scientific community in the UK and in Europe seem to be overwhelmingly against Brexit. The European Union is a really, really important part of the scientific enterprise because it gives out lots of money to researchers, collaboration is really easy to do because people can move freely across the continent and that is all threatened by Brexit and those are a couple of reasons that researchers either want to see Brexit reversed or for it to do as little damage as possible.

Interviewer: Benjamin Thompson

Well, Nisha, there’s a lot of machinations going on in the UK Parliament right now, and politicians are still trying to thrash out how the UK will leave the EU. It seems like we’re getting maybe quite close to an end game, but nobody knows what that end game is going to be. The no-deal scenario where no deal is reached with the European Union seems still a very plausible thing that might happen. What do we know that that might do to science?

Interviewee: Nisha Gaind

Yes, that’s right. The no-deal scenario is something that lots of people want to avoid – politicians and scientists included. The reason is because it will probably cause a lot of chaos. It means that Britain would leave the European Union in a very abrupt way and have no trade or migration agreements in place. Now, what will that do for science? It would immediately cut Britain off from certain EU research funding streams, it would disrupt clinical trials, it would disrupt data collection and even the imported lab supplies, which might just get stuck at the border. So, those are the reasons that scientists are so keen not to have this no-deal scenario happen.

Interviewer: Benjamin Thompson

And so many scientists attended this march calling for a people’s vote. What might happen next?

Interviewee: Nisha Gaind

Well, that’s the million-dollar question. Politics in the UK seems to be moving at a mile a minute. At the moment, we are still watching to see whether politicians might accept this deal which was forged by Teresa May and EU officials, which has been really divisive among UK politicians and they’ve rejected it a couple of times. Approving that deal would allow the UK to leave the European Union in an orderly fashion but politicians are trying to find alternative arrangements that might be more satisfactory. And then of course, there are the people who have been calling for a people’s vote, which is a second referendum that could have a remain option, i.e. the UK doesn’t leave the European Union, but these are all options. They’re all up in the air and there is just no certainty about where this will go.

Interviewer: Benjamin Thompson

Well, collaboration between the UK and European Union has been central to this discussion, For our next story, Nisha, though, we’re talking about a different collaboration. What’s going on here?

Interviewee: Nisha Gaind

Yeah, so we’ve got this really unusual and interesting agreement between North Korea’s top university and an institute in Italy that will see the exchange of students and lecturers.

Interviewer: Benjamin Thompson

And how will this collaboration work?

Interviewee: Nisha Gaind

So, this agreement will allow physicists from this university – the Kim Il-sung University in Pyongyang – to come to the Institute for Advanced Study in Trieste, Italy, to be trained in the field of neuroscience. Now, it sounds a little odd – physicists being trained in neuroscience – but this arrangement has come about because UN sanctions against North Korea aimed at supressing the nation’s nuclear programme forbid scientists around the world from training North Korean researchers in physics, but they are allowed to train them in other fields.

Interviewer: Benjamin Thompson

So quite a unique setup then?

Interviewee: Nisha Gaind

Yeah, it’s a very rare kind of agreement and it’s been approved by the Italian foreign ministry. It covers all types of collaboration in research in fields related to cognitive neuroscience and it’s valid for five years.

Interviewer: Benjamin Thompson

Okay, well how did this come about in the first instance?

Interviewee: Nisha Gaind

So, three years ago when these sanctions against North Korea were put in place, an Italian newspaper reported that there were four physicists who were studying at the Institute for Advanced Studies. Now, that wasn’t allowed under the sanctions. So, the leaders of these institutes arranged for these students to change the topics of their PhDs from physics to other topics that would be allowed under the sanctions. Two of these students went to study neuroscience and the other two changed to studying mathematics. And the agreement has sort of grown out of this situation and has now kind of formalised this process so it makes it easier for students from North Korea to come to this particular institute.

Interviewer: Benjamin Thompson

So, that’s the set-up then, what are people involved saying about it?

Interviewee: Nisha Gaind

The really interesting thing about this is that the people on both sides of this agreement – those in Italy and those in North Korea – are really excited and they’re really happy to be able to make this kind of exchange and to build these expertise for students in North Korea. So, the head of the department of physics at Kim Il-sung University says that this agreement is totally independent of politics and it’s only to do with science and that’s the only thing they’re motivated by. And the leaders at the Institute for Advanced Studies say that they’re really happy to be able to help these students and that this arrangement has benefits not only for science diplomacy but also to help others to gain expertise in these fields that they wouldn’t otherwise be able to have.

Interviewer: Benjamin Thompson

It seems like good news there then, but what about movement in the other direction – are Italian scientists going to be going to North Korea anytime soon?

Interviewee: Nisha Gaind

Yes, that is allowed by the agreement, and in fact, some researchers from Italy have already gone to North Korea and this agreement will make it much easier for that to happen.

Interviewer: Benjamin Thompson

Great stuff. Well, thank you for joining me Nisha. Listeners, head over to nature.com/news for more on these stories.

Interviewee: Nisha Gaind

That’s all for this week’s show, but if you have enjoyed this podcast, why not tell your friends about it? Tell your dog about it! Just tell everyone about it! In the meantime, we’ll be back next week with more from the wide world of science. I’m Shamini Bundell.

Interviewer: Benjamin Thompson

I’m Benjamin Thompson. See you next time.