This moment, Alex's mile swim, it means everything to him and to all of us.
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Now Alex and his care team have his hemophilia under control with life-saving medication and care management from Evernorth's specialty pharmacy Acredo.
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Nature.
Welcome back to The Nature Podcast.
This week, the deepest ecosystems on Earth.
And how respiratory infections could awaken dormant cancer cells.
I'm Benjamin Thompson.
And I'm Nick Petrychow.
The Nature Podcast.
In the deepest depths of the ocean, where sunlight cannot reach, there is an ecosystem teeming with bizarre creatures.
MUSIC The worms are very long, skinny and bright red blood colour.
The clams are white and quite big.
MUSIC
There are places where there seems to be these white colored microbial mats that form isolated patches on the muddy sea floor.
These organisms form part of the deepest complex ecosystem yet found.
They live at depths over nine kilometers below the surface, discovered on an expedition in a high-tech free-person submersible.
Life at the deepest depths of the ocean, known as the Hadal Zone, is quite unusual, as there's no sun.
Every life living on the surface of the ground, they need to live based on the solar energy.
This is Mengren Du, a researcher of the ocean depths.
So like the plants, they can go through the photosynthesis.
They use energy from the solar sunshine.
But in the deep sea, especially at the halo depths, there's no sunlight at all.
So how can this life survive?
Life requires energy.
And while normally that is ultimately provided by the sun or eating things that use the sun for energy, 9,000 metres below the surface of the ocean in the pitch black depths, that's not possible.
In the 1970s though, it was discovered that organisms can derive energy from things other than sunshine.
Bacteria were found living in the deep ocean around hydrothermal vents.
These bacteria used sulfur and hydrogen as their energy source.
As such, they were dubbed chemosynthetic life as they relied on chemicals rather than the sun.
Other creatures, such as tube worms, were found living symbiotically with the bacteria, allowing them to survive on the dark ocean floor.
This discovery got researchers thinking about what else might possibly be living in the depths.
After decades of this first finding, people still don't know what's the limit.
In 2012, on an expedition to the Mariana Trench, the deepest part of the ocean, researchers found what they thought were dense mats of bacteria at around 10700 metres below the surface.
But there's still a lot researchers don't know about deep life.
A major reason for that is because getting to such depths is no easy feat.
To better understand these mysterious parts of the ocean, Mengren and a team of researchers from around the world have been taking expeditions in a free-person submersible known as Vendojo.
They dive down to the Kurokamchatka and Aleutian trenches of the Northwest Pacific Ocean.
The team surveyed sites across 2,500 kilometres at depths 5,800 metres to over 9,500 metres.
That's about six miles below the surface.
Mengren herself went down in the submersible.
She says that actually diving down is a very valuable experience for researchers, more so than just seeing the footage brought back by the submersible.
When she spoke of her experience, her eyes lit up.
It's amazing.
So it's totally different if you can look through the window and see these animals by your bare eyes.
That's totally different.
And I think when the scientists dive to the bottom, then your observation will give you inspiration.
Many questions will arise when you do the observation or when you do the dive in the water on the bottom.
And when Mengren and the team did these dives, they saw an unexpected diversity of life.
I think it's a remarkable finding to discover a new ecosystem on Earth that was never really conceptualised to exist before.
This is Dominic Papineau, another one of the researchers on the team.
Now this ecosystem is populated by very strange animals as well.
There are no plants.
There's mostly animals that we see with their naked eye and they are all looking very strange.
The worms are very long, skinny and bright red blood color.
The clams are white and quite big, whereas there are places where there seems to be these white colored microbial mats that form isolated patches on the muddy seafloor.
In fact, the team found a variety of different creatures at different depths.
At the greatest depths, around 9500 metres below sea level, they found communities dominated by tube worms.
Whereas in shallower areas, they found communities dominated by clams.
The team believe that many of the organisms they discovered are new species.
And these creatures seem to rely on methane as an energy source.
This is not unusual other species have been found to do the same but typically the presence of methane is marked by bubbles in the water.
But at these depths there were no bubbles, and it wasn't until the team searched that they found it was there.
But the huge pressures at these depths meant that the methane stayed in a liquid form.
The team think this methane is made by microbes feeding on deposited organic matter which seeps out of cracks in the ocean floor.
The team's sampling also suggests that this kind of methane is abundant at these depths, so they think that communities of organisms like these could be more widespread.
These dark depths are still very mysterious.
But the team believe they can learn a lot from what they've found.
For example, the organisms at these depths are under such intense pressures that dealing with oxygen may be a particular challenge.
The problem caused by the pressure to all the head of life is about super saturation with free oxygen ions.
So the way how the head of life is, They adapt to the high pressure, is how they are able to produce more chemicals to remove the extra free oxygen ions, which means it's also an anti-oxidation process.
Understanding how this process works may open the way to helping researchers figure out how to deal with damaging free oxygen ions.
Something that could be useful for humans, as these reactive oxygen species have been associated with ageing and harmful mutations.
Mengren says this is only a preliminary thought which would need a lot more investigation.
The team are planning to do more dives like this one to better understand the Hadal depths.
With UNESCO.
They are launching a global Hadal dive program and are expanding their network of deep sea scientists from around the world to help.
So in the future we may learn a lot more about the unusual life that makes its home at the bottom of the ocean.
And Mengren thinks that every new discovery will bring more questions.
The expedition to new trenches can give us more answers.
All the new findings will bring more questions.
So, more and more.
That was Mengrin Du.
You also heard from Dominic Papineau.
They're both from the Chinese Academy of Sciences.
For more on that story, check out our show notes for some links.
Coming up, how viral respiratory infections could lead to dormant cancer cells reawakening.
Right now though, it's time for the Research Highlights with Dan Fox.
One day in the middle of the Miocene epoch, some 11 million years ago, a nearly 5 metre long caiman ate a terror bird.
Researchers analysed tooth marks on a piece of leg bone of a terror bird, a large apex predator.
With no signs of healing on the bone, it looked like the bird did not survive the bite.
Meanwhile, the lack of gnaw marks hinted at the culprit's identity.
Mammals tend to gnaw, whereas reptiles tend to dismember and swallow.
A 3D model of the jaw of a contemporary black caiman fits neatly into the fossilised tooth marks.
The black caiman's ancient relative Purosaurus, could have killed the bird or scavenged its carcass.
If the caiman did attack the terror bird, the team suggest that the bird may have been stalking a river's edge for aquatic prey before being ambushed by the caiman in the manner of crocodilians throughout the ages.
Snap up that research in Biology Letters.
The universe has an anti-aging secret.
Dark matter.
A new simulation suggests that the mysterious stuff that holds galaxies together might also grant some stars immortality.
The harsh environment near the Milky Way's central black hole doesn't seem suitable for the birth of new stars.
But a crop of stars there have a temperature and luminosity that make them look inexplicably young.
To explain this discrepancy, a team of researchers ran simulations to see whether dark matter might be playing a part.
They found that when dark matter particles collide and destroy one another, they provide a star with an energy boost.
This boost helps to stop the star from collapsing under its own gravity, becoming cooler in the process and therefore more youthful in appearance.
As dark matter supplies replenish, the star remains eternally young.
You can read that paper in full in Physical Review D.
Next up on the show this week new research suggesting that respiratory infections could be an important driver in the awakening of dormant cancer cells in the lungs.
Many types of cancers metastasize, spreading cells from the initial tumor site to other places in the body.
In some cases, these cells can lay in a dormant state, either individually or as small clumps, for years, even decades.
Even if a person is successfully treated for their initial tumor, these cells can awaken and proliferate, and this subsequent relapse often leads to death.
Figuring out what causes this reawakening is thought to be a crucial piece of the puzzle in preventing cancer deaths.
This reawakening is something that James DeGregori and his colleagues have been investigating, and they've got a paper about it in Nature this week.
Specifically, they've been looking at the role of respiratory viruses, an idea that came about during the COVID-19 pandemic.
Their reports.
They're more really anecdotal of the sort of unexplained rapid progressions of cancers in some people.
And I think that was definitely an impetus to this.
James had been researching the role that aging related inflammation played in waking dormant cancers.
And this got him and the team thinking.
You know, as we're seeing images of people's lungs, we realized OK, if there's anything that's going to be massively inflammatory, it's going to be a respiratory virus infection like COVID.
And so we asked a relatively simple question.
Would a respiratory virus infection lead to the awakening of dormant cancer cells?
Inflammation is a normal and important part of the body's response to infection or injury.
But in previous studies, it has been linked to cancer progression.
For example, one study looked at lung inflammation induced by tobacco smoke, while another looked at inflammation induced by stress hormones, and both found a link with cancer reoccurrence.
To test their idea that inflammation caused by a respiratory infection could also lead to dormant cancer cells reawakening.
The team focused on breast cancer, which is known to metastasize to different organs.
We started with a mouse model of breast cancer, where the cancer within the mammary gland is known to seed the lungs and other tissues.
But we are most interested in the lungs.
And it's known to be a very good model of dormancy, because those cells will sit there for many months before they awaken, sort of spontaneously.
So we're looking at a point way before.
They would awaken and we would infect the mice initially with influenza, virus flu and then, later on, with the mouse-adapted SARS-CoV-2.
When the team infected mice with influenza, they very quickly saw an effect in the dormant breast cancer cells that had metastasised and lodged themselves in the lungs.
Three days after infection, we see awakening of these cells and they're preparing to divide.
You know, the amount of awakening was just dramatic in that typically if you see papers on awakening of dormant cancer cells, it's in the two to seven, eight fold range.
We were getting awakening in mouse models of, you know, a hundred to a thousand fold.
So there's just a dramatic expansion in the numbers of these cells within the lungs within weeks.
But what was driving this process?
The team's work identified a molecule called interleukin 6 or IL-6 as being responsible for starting things off.
Interleukin 6 plays a role in inflammation and orchestrating host immune defences, and it's produced within the lungs in response to an infection.
But interleukin 6 is also known to play a role in cancer progression.
In this instance, it appeared to be activating molecular pathways that are critical in waking the dormant cancer cells.
But once interleukin-6 levels had dropped, after the mice had cleared the influenza infection, the awakened cancer cells stuck around, in part by recruiting one set of immune cells to protect them from being killed by another set of immune cells.
These protected cancer cells linger in a kind of stasis and although their numbers are still relatively low compared to the number of regular lung cells, James suggests this reawakening increases the chances of disease progression.
So what we think this does is it's now increased the risk of that next event that might allow for further metastatic progression.
In some ways, you've awakened the flames, but then it dies back down, but it dies back down.
But now you've got 100 times the embers that you had before.
Experiments using mice infected with SARS-CoV-2 showed broadly the same pattern as was seen in mice infected with influenza, despite them being very different viruses.
But would these findings be relevant in humans?
The COVID-19 pandemic gave the team the opportunity to investigate in a different way an observational study using information from the UK Biobank, a collection of de-identified health data from over half a million people.
And so we could say OK, we wanted people who had previously had cancer and that were in what's inferred remission because they had been diagnosed five or 10 years before.
What would happen to them if they got a positive COVID test versus if they got a negative COVID test?
In total, this included over 4000 people, some who'd had a positive PCR test for COVID-19 early in the pandemic and others who tested negative.
The team looked at what happened to the people in these two groups.
So in the UK Biobank, we saw that there was a substantial increased risk of death from cancer.
In their paper, the team estimates a nearly two-fold increase in cancer mortality in those who tested positive, compared with those who tested negative.
But there were limitations in using the UK Biobank data.
It looked at all cancers and didn't look where a cancer metastasised.
To try and address this.
They next looked at another, more specific set of electronic health records from US cancer clinics.
And that database allowed us to specifically ask for patients with breast cancer.
Women with breast cancer.
And we did a similar study, but here we only had people that had a COVID-19 diagnosis or a diagnosis of the disease.
And those people showed about a 144, so about a 44 increased risk of progression to metastatic disease in the lungs.
So we're able to get much more granular, but with the caveat that probably a lot of those people that we considered this negative actually did get COVID, but it just didn't end up in their hospital records, for example.
Penny Otterwell is a cancer biologist at the University of Sheffield here in the UK who studies the waking of metastases in different parts of the body.
She wasn't involved in this work, but was impressed by the combination of observational studies in humans and mechanistic studies in mice.
They followed everything through, logically seeing that there is a direct correlation between those patients that have had breast cancer and then been infected with COVID-19 and then gone on to get metastases at a later date.
And then, I think, the way that they have scientifically approached this in order to determine the mechanisms that are driving this is very solid.
I think it's something that we can be confident that, certainly under this situation, that the data is something that will bear out.
However, Penny notes that breast cancer isn't one thing and is interested in whether these findings will apply to other types of the disease with different genetic causes and to different types of cancer more broadly.
She also wants to know how applicable the mechanistic findings may be in humans whose immune systems have experienced the virus before, unlike the mice in the study.
While SARS-CoV-2 may have been new to us all, many folk have had flu.
Penny was keen to stress that there's much more to learn about this, and these results shouldn't cause alarm.
Although the science here is very, very solid and I think we can learn a lot from this, I think we need to be quite careful that we're not scaring people who have had cancer.
I would say most people who have had breast cancer.
They come into contact with all sorts of viruses during their normal lives and they do not succumb to secondary breast cancer.
So I would suggest to people that they take this for the science that it's showing, because we use the science in order to make better treatments for people, but to try and not let it affect their normal day-to-day lives.
James also says that there's a lot to learn, particularly around the intricacies of the genetics underlying the process they report.
He also makes the point that mice aren't humans and the human part of the study was observational, looking at correlations and not mechanisms.
Right now, he and his colleagues are continuing to research the role that respiratory virus-related inflammation plays in cancer awakening in the hope that it could ultimately help people in the long term.
Of course we hope to gain a deeper mechanistic understanding of the pathways involved, in part just to understand the meta, but in part because that could lead to interventions that have less of a side effect.
You could imagine that the first thought might be, well, let's just block the inflammation.
But you need your inflammation.
You need it to help clear out the virus in the first place.
So I think coming up with more nuanced interventions and preventative strategies is that can lessen the risk of someone who's a cancer survivor of having their disease progress to metastatic disease after they get an infection.
I think will be just a key goal moving forward.
That was James DeGregori from the University of Colorado and Schutz Medical Campus in the US.
You also heard from Penny Otterwell from the University of Sheffield in the UK.
To read James's paper, look out for a link in the show notes.
Finally on the show, we're diving into the world of quantum physics.
As a reporter, Lizzie Gibney has been writing a feature article on physicists' views of quantum mechanics and what it can or can't tell us about reality.
Lizzie joins me now.
Lizzie, how's it going?
Hello.
Yes.
Good.
Thank you.
Well Lizzie, I think a good place to start would be to just have a little bit of a primer on quantum mechanics.
I've reported on it a few times on the podcast, but it's always one of those things that's a bit confusing.
So can you tell us what quantum mechanics is and what it does?
Absolutely.
It describes the behaviour of everything objects, at a kind of, you know, really fundamental, very microscopic scale.
And what was discovered about 100 years ago was that things behave fundamentally differently at the quantum scale.
And, for example, you have a particle and when it's not being observed, it will behave quite like a wave.
It will kind of spread out.
It can interfere with itself.
And it effectively acts as though it's in multiple states at once.
Now, if you make a measurement, that all changes.
You make a measurement, it is a defined measurement and it has that property.
So that's a big difference between the quantum and the kind of classical type worlds.
So it's a very different world from the one we're used to living in everyday lives.
It certainly sounds like it.
And so you've been writing a feature which has essentially surveyed physicists on their views on quantum mechanics.
And well Lizzie, I must say, after reading your feature, I've come to the conclusion that quantum mechanics is bonkers.
Is this the right interpretation to take from this?
You're not alone in taking that interpretation.
So, I mean, that's something that people may have heard of about quantum physics, right?
There's a famous quote from Richard Feynman, which is if you think you understand it, you don't understand it, or something along those lines.
So you're certainly in good company if you think, hang about some parts of this, don't make total sense.
Now, the reason I wanted to do this survey is because what is really the case is that physicists think very, very differently about reality, about the real world behind the maths of quantum mechanics.
And so that's kind of why you get all these different explanations.
You know, you may have one physicist saying or in this experiment the particle is in two places at once, and another would be like that's not true.
Or they would just describe it in a completely different way.
And that's because there are fundamental disagreements about how to interpret the mathematics of quantum mechanics, which I should say works incredibly well.
You know, we can use quantum mechanics to make predictions that are so incredibly well experimentally verified.
So it all works.
But what exactly that means is something that is a bit more up for debate.
Right, yes, because quantum mechanics is behind, you know, some real world technologies.
So it works.
It's just that these interpretations seem to differ.
So, as you said, you've done this survey of quantum physicists and you sent this out to 15000 people.
Got more than a thousand replies about it.
So it's a mammoth survey.
And a lot of what you're asking was about people's different interpretations of quantum mechanics.
Can you tell me about what these different interpretations are and what physicists thought about them?
So a lot of the time when we're talking about the reality that underlies quantum mechanics.
These are a coherent set of ideas that haven't been given a name.
So there's one that people may have heard of, which is called Many Worlds, which is this idea that you can have a particle effectively is in this superposition of different positions say, and then when you measure it?
It's actually not that we just get only one of those outcomes occurring.
Both outcomes do occur, but in different universes.
The universe branches off in different directions and we stay in one of them.
So we just see one outcome.
Now that may seem wild as an idea that there are, you know, an unfathomable number of these universes branching up all the time.
But actually, that is a valid way of explaining the mathematics, as valid as any other.
So we ask people which the interpretation are at best.
So many worlds is one.
The main one is the Copenhagen interpretation, which is kind of an amalgam of the views of some of the founding fathers of quantum mechanics.
And it's a little bit stitched together.
Those views weren't always consistent, but it's generally the idea that measurement plays a really important role in having an object's quantum state.
And it's kind of just a very useful practical interpretation that focuses on what is observable right.
So it's kind of saying this is what we see in experiment.
Well, that is what my philosophy will then be.
Yeah.
And so, looking at the results of the survey, it seemed that, as you said, most people adhere to this sort of Copenhagen interpretation.
And then the next most popular one were epistemic or information-based approaches, which seems like quite a few different things, but essentially where physicists consider quantum mechanics as not really talking about a real property.
Rather, it's just talking about information.
And then there's many worlds, as you said.
And then there's a few other theories, but maybe more edge cases that people adhered to as well.
But the interesting thing is no one was particularly confident in any of them.
And the other thing I noticed when I was reading your feature was there seemed to be a bit of a divide between theorists and experimental physicists.
So the people who think about the sort of underlying physics and the people who like try and use it in practice, I guess.
That's right.
So we asked a lot of demographic questions and we didn't find many great patterns.
But the only kind of slight ones that we did see was that there was a slight tendency for experimentalists more to favour this Copenhagen interpretation versus theorists.
And people who have done research in quantum foundations, which is basically studying this.
Like what are the assumptions beneath the way that you interpret quantum physics?
Those people as well were less likely to have the Copenhagen interpretation as their favourites.
So there is perhaps a suggestion that the people who do these really probing thought experiments and think really really deeply about this topic tend to have decided that some of the others are their favourite or that they find a more satisfying approach.
And I guess for the experimentalists as well, it kind of just works this interpretation, so they don't really need anything else.
That's it.
So we've also argued in an editorial that goes along with this that we do think it's worth thinking about.
Because the thing is, it does work.
And you can have the Copenhagen Interpretation in your head while you are doing research, and it won't change anything about the results that you expect.
But if what we're thinking about is probing beyond, you know, quantum physics can't describe gravity right now.
Right, that's a huge thing.
We have this whole other like area of physics which is not compatible, and so some people are trying to come up with theories of quantum gravity and, and you know, when you're doing that kind of attempt to push forward or shift or overhaul the science that we have right now, you know really pushing to its limits.
What you think is going on is a good way of intuitively coming up with new experiments or of really testing the validity of how you're thinking about it in any given time.
So, I mean, it is very practical.
And if you're developing technology like we've got a great quote in the future from someone who studies quantum foundations saying like look, if everyone was like me, we wouldn't have quantum computers, because sometimes you just got to be in the lab, you know, pushing forward the technology and the experiments.
But I would argue that actually thinking at this deeper level can.
I was wondering though, how do you think it is that you know, all these physicists who've spent years dedicated to problems like this can end up disagreeing so much on something that seems quite fundamental?
So, you know, what is there to divide them really?
It comes down to often philosophy or logic or people's like almost instincts.
So for some people, we just have to be trying to describe the real world.
They just cannot get on board with the idea, this epistemic idea, that what we're describing is just knowledge or information.
For them, that is not science.
So, again, it comes from somewhere almost deep within.
And similarly, if you don't like many worlds, some people just say.
Some of the responses are literally like oh, come on.
Can we really have this number of universes just branching off all the time?
That's just silly.
It's effectively what they're saying.
There's no...
I mean, there have been well-constructed arguments against it, but it almost comes from a case of personal belief or instinct, as much as anything else.
I'm sure that the kind of training that people have had, you know, a lot of the time the Copenhagen interpretation is just wrapped into physics education.
So people don't even know, but they're kind of being taught Copenhagen interpretation now without it being explicitly put that way.
So with each one there are sacrifices.
I would say, from having studied all of these, that none of them are perfect.
Gun to my head, I still don't know which one I would say I'd adhere to.
That was going to be my next question.
Well, I'm so sorry.
It's so hard.
I think yeah, it's really about.
It really does come down to kind of what you're willing to give up and what appeals to you.
I guess ultimately science kind of thrives on a healthy debate.
So I wonder, does it even matter that people don't agree on all this?
I would say not.
I would say it's a sign.
The fact that there is disagreement means...
Quantum physics, it is hard to make sense of with your intuition.
It just is.
We are these poor macroscopic evolved creatures.
You know, we're used to sitting on chairs and looking at computers.
You know, the quantum world is something else.
So we have the tools to use math to describe it.
And then when it comes to the interpretation...
Right now, I don't think it does matter.
I think it's kind of healthy.
And we maybe, maybe we shouldn't expect that we agree because yeah, it's something, it's something pretty out there.
And we're only 100 years in, you know, maybe that's that's not a lot in the history of science.
So give it another couple of hundred years and we'll see where we are then.
Well, here's to not knowing.
Thank you so much, Lizzie.
Thank you very much.
That was Nature's Lizzie Gibney.
For more on quantum mechanics, check out the show notes for a link to Lizzie's feature.
And that's all for this week.
As always, you can keep in touch with us on Blue Sky or X. We're at Nature Podcast.
Or you can send an email to podcast at nature.com.
I'm Benjamin Thompson.
And I'm Nick Parcher-Chow.
Thanks for listening.
This moment, Alex's mile swim, it means everything to him and to all of us.
At Evernorth Specialty Services, we help providers make sure patient care doesn't get interrupted, especially for rare, chronic and complex conditions.
Now Alex and his care team have his hemophilia under control with life-saving medication and care management from Evernorth's specialty pharmacy Acredo.
So Alex can be the last one out of the pool.
Evernorth Specialty Services.
Because every moment counts.
Visit evernorth.com slash specialty to learn more.
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