Host: Benjamin Thompson
Welcome back to the Nature Podcast. This week: how cooling brown fat could starve tumours of glucose, and learning lessons from record-breaking heatwaves. I’m Benjamin Thompson.
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Interviewer: Benjamin Thompson
Cancer cells are notorious for their ability to divide and divide and divide and divide and divide and, well, you get the picture. But this ability requires something important: fuel. Here’s Yihai Cao from the Karolinska Institute in Sweden
Interviewee: Yihai Cao
Cancer cells, one of the most distinguishing features from healthy cells is that they have a different metabolic programme. They are very hungry for sugar.
Interviewer: Benjamin Thompson
Cancer cells are gluttons for glucose – burning through buckets of the stuff to make the energy and metabolites they need to thrive. And this insatiable appetite for sugar could represent something of an opportunity. What if you could starve tumours of glucose? For inspiration, Yihai turned to another type of glucose-loving tissue – brown fat.
Interviewee: Yihai Cao
What it does actually is help us keep our body temperature when the environment is getting cold. So, brown fat is, in our body, like a radiator to produce a lot of heat.
Interviewer: Benjamin Thompson
When we’re cold, brown fat burns through blood glucose and lipid molecules to help keep our body temperature up, and this gave Yihai an idea.
Interviewee: Yihai Cao
I was curious to know, what if we put experimental animals that have tumours into the cold to activate brown fat, let the brown fat take a lot of glucose, and then create a competitive scenario and maybe the tumour will not have much glucose to take.
Interviewer: Benjamin Thompson
So, that’s what Yihai and his colleagues did. They turned to mice engineered to grow various types of solid human tumour. Then they kept the mice at a cool 4 °C to activate their brown fat and monitored their tumour growth.
Interviewee: Yihai Cao
We tested many different types of cancers, especially those ones that are very difficult to treat, like pancreatic cancer and liver cancer. So, by putting animals into cold, that is +4 °C, after a few weeks we saw very potent anti-tumour effects. Tumours grew more slower and they seem to be less invasive as well. It’s a very good sign. And they live longer, by the way.
Interviewer: Benjamin Thompson
The team showed that cold exposure inhibited growth in the different tumour types and for one type of cancer – colorectal cancer – the survival of the mice almost doubled compared to mice that were kept at warmer temperatures. And it wasn’t just the cold. The brown fat definitely seemed to be playing a role, as the same tumour suppression effect wasn’t seen in mice that’d had their brown fat removed or inactivated. In fact, Yihai’s team tested the role of brown fat in a variety of ways. They showed that mice in the cold had lower blood sugar levels, and that the activated brown fat was taking up much more glucose than the tumours. Increasing overall blood sugar levels in the mice reversed the anticancer effects.
Interviewee: Yihai Cao
Indeed, when we gave a high-glucose drinking water to the mice, tumour growth was largely restored, so that’s really supporting the hypothesis that reducing blood glucose is one of the mechanisms.
Interviewer: Benjamin Thompson
But potentially not the only mechanism. For example, the team showed that in some cases, genes involved in glucose uptake were downregulated in the cold-mice tumours, suggesting it might be a tandem effect of the brown fat using up available blood glucose and the tumours not being as efficient at taking it up in the first place. Yihai says there are other things to investigate too.
Interviewee: Yihai Cao
Because when fat breaks down and produces heat, you also have a lot of metabolites and lots of other growth factors. Cytokines required for tumour growth also get changed. For now, I can only see the competition as a mechanism, but maybe future studies will actually discover many more mechanisms behind.
Interviewer: Benjamin Thompson
But although the exact mechanism is unclear, Yihai was keen to see if he could reproduce the effect he saw in mice in a human cancer patient. And so, he enrolled a person with Hodgkin’s lymphoma who was between chemotherapy cycles in a pilot study, and asked her to spend time in a warm room, and a room kept at 22 °C which, according to Yihai, should be cool enough to activate brown fat. She was then scanned to see what effect this had on her brown fat and tumour tissue.
Interviewee: Yihai Cao
In the warm environments, she did have actually brown fat activation. Maybe some other mechanisms of cancer activated the brown fat. However, when she moved to the cold environment, her tumour glucose uptake was much more reduced, and the brown fat signals became even more boosted. So, that was of course one patient. We cannot make any conclusions. But we want to relate that this thing really exists in humans. That’s the point we’re trying to make.
Interviewer: Benjamin Thompson
Mariia Yuneva, who researches cancer biology and metabolism at the Francis Crick Institute in the UK and who wasn’t involved in this work, was intrigued by the study, but pointed out that it raises a number of questions too.
Interviewee: Mariia Yuneva
So, first of all, all tumours are different, so it would be very interesting to see how these tumours that they saw an effect on, do they switch to other types of nutrition, right? So, do they use more amino acids, for example? Do they use more lipids? What happens to the tumours who originally rely on other sources more than glucose, and we know those exist, right. And how deep in human patients do you need to go with lowering down the temperature and for how long to have an effect on tumours, given the fact they already don’t have much fat perhaps, and that the condition of their body is already affected.
Interviewer: Benjamin Thompson
Mariia also wants to know how this method compares to attempts to starve tumours of glucose using calorie-limited diets, which has attracted a lot of research.
Interviewee: Mariia Yuneva
They don’t compare this, but perhaps it’s a more efficient way to lower glucose levels down, than using the calorie restriction, for example. And so, there are recent studies demonstrating that, indeed, decreasing glucose levels in the diet and calorie restriction can have an effect on tumour progression, but it’s still not a very clear picture. The picture is quite complicated because different tumours can respond differently.
Interviewer: Benjamin Thompson
It’s clear that metabolism is complicated, and there’s lots to learn about how lab efforts to starve tumours of glucose could translate into the clinic. But Yihai thinks that with proper testing, if the effect that he’s shown is found to be relevant in humans, it could form a simple and useful extra weapon in the arsenal against cancer.
Interviewee: Yihai Cao
In this study, we want to present a concept for a new cancer therapy. We want to make sure this has human relevance. For the future, it does need to be carefully studies by recruiting a large number of patients to see cold, in combination with what kind of therapy, would produce the most beneficial effects. And to see which type of cancer is much more suitable for this type of therapy. And we have no idea at this moment, so we want to do that together with clinical oncologists.
Interviewer: Benjamin Thompson
That was Yihai Cao from the Karolinska Institute in Sweden. You also heard from Mariia Yuneva from the Francis Crick Institute here in the UK. To read Yihai’s paper, look out for a link in this week’s show notes. Coming up, we’ll be hearing about the record-breaking extreme heatwaves that have affected many parts of the world, and what scientists are learning from them. Right now, though, it’s time for the Research Highlights, read this week by Dan Fox.
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Dan Fox
Some 300 years ago, a group of people paddled through the remote, icy channels of the Tierra del Fuego archipelago at the southern tip of South America and landed on a windswept island. There, they established what researchers say is the world's southernmost human outpost before the Industrial Revolution. The site is located on the southern edge of Hornos Island in Chile. There, the researchers found the remains of a hearth, a pile of seashells, two harpoon points and a large number of bones from sea mammals and birds. Radiocarbon dating suggests that the site was probably a hunting camp that was occupied for a short period between 1428 and 1803. On one of the island’s slopes, the researchers also identified the world's southernmost tree. The team say that this plant marks the limit beyond which trees cannot tolerate the harsh environmental conditions of the world's extreme south. Read that research in full in Antiquity.
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Dan Fox
Standing on the edges of a canoe or paddleboard and jumping up and down can propel the craft forwards – and researchers have figured out how. The team behind this work created a simplified model of a canoe subject to a vertical force that represented a person rhythmically pushing down, while standing close to the canoe’s stern. The model showed that the canoe’s bobbing creates its own waves, and when the downwards push is timed right and alternated with a slight forwards and backwards nudge, the canoe can surf on its own waves at speeds of up to 1 metre per second. This isn't the most efficient mode of locomotion, with no more than 17% of the energy expended on bobbing translated into horizontal motion. But the authors speculate that in competitive rowing, the bobbing produced by athletes could help give a canoe a slight extra push. Bob along to Physical Review Fluids to read that research in full.
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Interviewer: Benjamin Thompson
Last month here in the UK, records were smashed as areas baked in temperatures of over 40 °C – the first time this has been seen here since measurements began, beating the previous record set just 3 years ago. Around the world, it’s a similar story too. Climate scientists have long warned that extreme heat and extreme heatwaves will become more frequent as a result of climate change. But these events are happening faster and more furiously than expected. Reporter Alex Witze has written a feature article for Nature about these events and what researchers can learn from them, and she joins me on the line from Colorado.
Interviewee: Alex Witze
Hi, thanks for having me.
Interviewer: Benjamin Thompson
So, when we talk about extreme heat or extreme heatwaves, what do we mean? What’s the actual definition?
Interviewee: Alex Witze
There's a bunch of different ways you can define extreme heat. It's how much higher your record-high temperature is for that particular day. Heatwaves can be defined by how many days temperatures are above the normal temperature. So, extreme heat is anything and a number of ways in which the temperature records shatter, and a lot of those records are all falling.
Interviewer: Benjamin Thompson
So, what's the picture around the world then? What have we been seeing?
Interviewee: Alex Witze
There’s been a lot of heat around the world for many years and it's getting much worse. So, one of the events that just kind of shattered scientists’ expectations was a huge heatwave in the Pacific Northwest here in North America last summer. That was absolutely off the charts in terms of how hot it got. Canada set a national temperature record multiple degrees Celsius higher than it had ever seen anywhere in the country. And all around the world too. So, China's been having a huge heatwave in the last week or two. Japan, in June-ish, went through some of the highest temperatures it’s seen. There was a massive heatwave in India and Pakistan earlier this year and also the last couple of years. So, basically, every summer, wherever you are around the planet, a lot of these are coming, as you said, faster and more furiously.
Interviewer: Benjamin Thompson
And obviously, there are a variety of impacts of climate change – many of them incredibly serious, of course – but extreme heat seems to bring a particular set of consequences.
Interviewee: Alex Witze
Yeah, it's deadly in a lot of different ways from some of the other consequences of climate change. Extreme heat, I mean, it kills you. It causes people to have heatstroke. Literally, just physically, our bodies can't handle it. So, there's sort of the how do you respond in the day? How do outdoor workers survive? How do people who don't have air conditioning survive? But then there's also these societal consequences, especially on infrastructure. I mean, we've heard about the runways getting soft at Heathrow. We hear about rail lines having to shut down because the trains aren't certain if they can run on the tracks because it might be too hot. You've got electrical grid overload, and this becomes really crucial in super-hot areas where the electricity companies start rolling blackouts, or brownouts as we call them here in the States, where they throttle back because there's so much demand on the grid, and then people aren't able to use fans or air conditioning or whatever is available to them in terms of cooling off. Our entire societal infrastructure is woven in and can be affected by this.
Interviewer: Benjamin Thompson
And of course, heatwaves have been studied for a very long time, right, and the trend is towards more of them and them becoming worse. But these record-breaking events that have been seen around the world seem to have confounded expectations maybe and happened sooner than predicted.
Interviewee: Alex Witze
Yeah, I talked to a bunch of scientists who deal with extreme heat and extremes and what constitutes an extreme for this story. And all of them said, we were expecting extreme heat. We were expecting extreme records. But the sort of record-shattering aspect of it, when you actually see it in front of you and you see it happening, it really sort of crystallises what a lot of warnings that climate scientists have been putting out for the last many, many years. It's one thing if you have a day that's maybe 0.1 °C warmer than your record in the past. But when you're looking at large portions of a country, like during the recent UK heatwave, absolutely shattering records, so like full degrees hotter than previous records, that is what is astonishing the scientists.
Interviewer: Benjamin Thompson
And what's maybe caused the discrepancy between the ‘we're expecting this in the decades to come,’ and, ‘Actually, this is happening right now.’
Interviewee: Alex Witze
We sort of get into that question of what do scientists know and what do they not know. And I mean, climate scientists know a huge fraction of what we need to know. I mean, it's simple physics, right? I mean, there's more greenhouse gases in the atmosphere, the global temperature is going up, the extremes are going to be hotter. There are sort of nuances to that. There are ways in which the climate models don't 100% capture everything about our future and extreme heat. For instance, how we're using the land, how we're irrigating land, that can sort of moderate these extremes that we might be seeing. So, it’s sort of like we know most of it, but we're still sort of fine-tuning exactly how bad it can get. And among the climate scientists I talked to, again, they mostly said, ‘These things are going to happen and they're happening now, and we anticipated these. But the fact that so many records are being broken in so many different ways, all around the world, so quickly. It's like the timescale just kind of moved up.’
Interviewer: Benjamin Thompson
And so, scientists, of course, are scrambling then to learn what they can from what's been going on in the last few months and years. What have these extreme events taught scientists about the way that things are going? What have they learnt?
Interviewee: Alex Witze
There's sort of two answers to that question, I think, and one is like, what are the statistics of what it means to be extreme and how bad are things? And in one sense, it's very interesting because you can sort of quantify just how bad things are. So, by some measures, there were only 5 others in history that were worse than this enormous Pacific Northwest heatwave in 2021. And then people are sort of quantifying exactly how bad the recent European and UK heatwaves were and how bad that is. And honestly, from my perspective as a journalist, that seems to be just kind of like figuring out the numbers for like, how bad something is. Like, we know, they're bad, right? How bad do we have to know? But then, I guess the more important thing is the message that a lot of climate scientists are trying to get across, that, number one, the most important thing to do is for society to cut emissions. And beyond that, how can we start to adapt? How can we start to introduce practices into our daily lives that allow us to survive these extreme heatwaves?
Interviewer: Benjamin Thompson
And in terms of adaptations then, what sort of things are being discussed? Certainly, when we live in a city environment, it can be really, really hard to find any respite, for example.
Interviewee: Alex Witze
There are a number of cities around the world that actually are very proactive about developing heat plans. So, when you've had a really bad heatwave, you can start to prepare to not have it be as bad the next time. For instance, in France, and across most of Europe, in 2003, there was a heatwave that killed tens of thousands of people, perhaps 70,000 people, and as a result, a lot of changes were introduced. And in 2006 when a heatwave came through, it wasn't nearly as deadly. Now, these things are super easy to do. It's like introducing cooling centres in a city. So, maybe you keep a library open that's got air conditioning, and people who would be on the streets otherwise are able to come in and cool off. These things have huge impacts on people just being able to make it through a heatwave. There are other cities that do this really well. So, Phoenix in Arizona is the hottest major city in the US. It's in the desert in the southwest. And they've done a lot of simple things like putting shade at bus shelters, introducing recreation centres where people can go and cool off. This is also true in Southeast Asia, particularly in India, there are a number of cities that have adopted heat action plans. And again, really straightforward things – keep the park open, close stuff down that doesn't need to be open – very common-sense approaches that reduce death tolls significantly.
Interviewer: Benjamin Thompson
And it seems from what you're saying there, Alex, that some of these measures were put in after the fact. What about planning in advance? Are scientists modelling where future extreme events might be more likely to occur so that steps can be taken there?
Interviewee: Alex Witze
Yeah, so there's places around the world where extreme heat is common, and we know it's going to get worse, so, again, some of the sort of tropical cities in Southeast Asia. But Western Europe is an interesting case study because they had a very bad heatwave a couple of weeks ago, and they've had a number of heatwaves this year already. And over the last couple of years, records have been broken somewhere in Europe every single year for the last couple of years. And there’s a new study in the study that we talked about in the feature, where Western Europe was identified as being basically a hotspot for heatwaves – sorry for the not really bad pun. Essentially the jet stream that comes across the North Atlantic splits into these two strands and the breakup of that jet stream into these two strands allows heatwaves to develop and persist over Western Europe. And the bottom line is that extreme heat is increasing in Western Europe three to four times faster than in other comparable places around the Northern Hemisphere.
Interviewer: Benjamin Thompson
And what of the future, Alex? As these extreme heat events become more frequent, it looks like the trend really isn't going in the right direction.
Interviewee: Alex Witze
It's definitely not and everything sort of lies on how we manage to bend that line of emissions downward, right. So, if we're able to bring those emissions down and keep that temperature increase down, then that will help bend that curve away from these extreme events. But it feels like we're in this little sort of interim point right now, where we are experiencing some of the most dire consequences of climate change, and we can still do something about it. And maybe one example is just this week, the US Congress, the Senate, passed a major climate bill. And in the reporting, a number of people are saying that some of the politicians, some of the senators, might be starting to be swayed by these extreme weather events that they're seeing. So, it's hard to draw a line between this particular heatwave and the Senate passing this climate bill, but there's no question that as we live through these record-shattering events, that it's having an impact, I think, on people's conception of climate change and politicians’ willingness to do something about it finally.
Interviewer: Benjamin Thompson
Alex Witze there. To read her feature article, look out for a link in the show notes. And that's all we've got time for this week. As always, you can reach out to us on Twitter – we're @NaturePodcast. Or you can send an email to podcast@nature.com. I'm Benjamin Thompson. See you next time.