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.
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Visit evernorth.com slash specialty to learn more.
What's up?
Adam Grant from Work Life, a TED podcast here, and I want to tell you about something exciting.
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I find this not only refreshing, but at some level astounding.
Nature.
Welcome back to The Nature Podcast.
This week, a rubber duck glued to a rock.
And the microbiome of a tree.
I'm Benjamin Thompson.
And I'm Nick Parcher-Chow.
First up on the show this week we've got a story about a powerful new adhesive made of a squishy material called a hydrogel.
Now, when you're developing a new glue, you of course need to test it.
And in this case, the team behind it have done so in a rather unusual way.
As Heilongfan, one of the team behind it, explains.
We want to show our adhesive hydrogel that we can.
Glue the duck on the wet rock.
Yeah, you heard that right.
The team tested their glue by gluing a duck a yellow rubber duck, it has to be said to a rock on a beach where it held fast despite being battered and bashed by the waves.
And this is actually a tough testing environment.
Rough rocks and salty water tend to make it hard to get an adhesive to stick, and hydrogels as a material often aren't the stickiest.
Despite this normal lack of sticking power, researchers are interested in hydrogels as adhesives, as they have good biocompatibility, meaning they could work well as bandages for wounds, glue for surgery or even in making biomonitoring devices.
You see, hydrogels are essentially networks of polymers that contain some kind of liquid, and because of this hydrogels are kind of soft and squishy properties which generally are opposed to the ones that make them sticky.
Designing them to be stickier is a big challenge.
As they're soft, the molecules within them are not in a static arrangement.
They move around.
So you have to account for the interactions between the molecules and with whatever you want to stick them to.
Water and salt can also interfere with these interactions, eroding stickiness over time.
But Heilong and the team managed to overcome these challenges and make a very sticky hydrogel, and one that they reckon could stay stuck for a long time.
We have some other illustrations that show that underwater adhesive hydrogel can glue the two kinds of plates, that is ceramic, glass and titanium.
Even underwater, with a 1kg load hanging from it, their hydrogel, which they call R1 Max, could stay stuck to ceramic, glass and titanium.
So how did the team manage to turn a soft, squishy material into a super glue?
Well, with a little help from AI.
The team started by taking inspiration from nature.
Whilst us clumsy humans can struggle to manufacture glue that works well in saltwater, mussels and barnacles have had this figured out for millions of years.
And then we started to study their adhesive proteins and see the sequence, see the structures.
Then we can get some inspiration.
Heilong and the team were able to identify specific features that made proteins from these sea creatures so adhesive.
The team then looked for similar sticky sequences found in other proteins and used this information to create lots of hydrogels containing these sticky features.
Testing the mechanical properties of these hydrogels and feeding them into a machine learning system enabled the team to iteratively create stickier and stickier hydrogels, ultimately ending up with R1 Max, a hydrogel capable of sticking a duck to a rock.
Why a duck, you may ask?
Well, if you do this experiment, what do you want to use?
Because the duck is cute and the yellow colour is very clear for the video and it's very cute.
But beyond cuteness, the team also showed that R1 Max had some practical applications.
For example, it was able to repair leaks in pipes, so it could be useful for underwater repair, and it could also stick to biological tissues, opening the way for its use in surgeries or in making wound dressings.
Laura Russo, a biomaterials researcher who's been writing a News & Views article on this new paper, was impressed by the work.
The approach that they employed was really fascinating.
She explained that AI approaches like the team developed have been used in other materials design experiments, but typically with hard materials which have a rigid structure that AIs have an easier time working with, unlike the constantly shifting molecules and interactions found in soft materials like hydrogels.
Lauer thinks that this combination of experimental trials and machine learning could help deal with a major problem in materials science.
You can reduce the trial and error method, one of the major problems today.
The trial and error method is expensive, you need time and you are not sure when you start that you will be able to control the final function.
Lara and Heilong believe that this research could help scientists design materials in the future in a more efficient way.
There are challenges ahead though.
Hydrogels are interesting to researchers as they could have biomedical applications.
However, it's unclear how the AI methods would cope with the staggering complexity of interactions between molecules in a human body.
And such methods require a lot of data, which isn't always available for every function you might want.
Right now, Heilong is working to better understand quite a crucial part of this story.
Why it's so sticky, we need to answer that.
Right now, the team don't know what makes their hydrogel stick so well.
Determining the exact molecular mechanism of the stickiness could help design better adhesives in the future.
But for now, Heilong is hoping that his team's AI-enhanced approach will inspire other researchers to create materials with all sorts of properties.
We want to tell people how to use data mining techniques, experiment and machine learning to produce such kind of bio-inspired materials.
So the pipeline is most important.
That was Hai Long Fan from Shenzhen University in China.
You also heard from Laura Russo from the University of Milano-Bicocca in Italy.
For more on that story, check out the show notes for some links.
And while you're there, you'll also find a link to a video of the duck, if you want to see quite how well it stuck.
Coming up, the hidden microbial ecosystem living within trees.
Right now, though, it's time for the Research Highlights with Katrina Clark.
The characteristic tuber of the modern potato appears to have come from a love affair between potatoes and tomatoes.
The part of the potato plant that we eat, known as the tuber, has always been a bit of a mystery.
As far as appearances go, the rest of the plant mostly resembles wild species of potato from a group called Etuberosum that lack the tuber, but genetically modern potatoes are actually more similar to tomatoes.
To find out what was lurking in the potato family history, researchers analysed the genomes of 450 cultivated potatoes and 56 wild potato relatives.
They found a mix of tomato and ituberosum DNA, suggesting that they hybridised millions of years ago.
The researchers think that genes from each group allowed potatoes to thrive in colder habitats and reproduce asexually, perhaps making them the success story we know and eat today.
Chow down on that story over at Cell.
Osteoarthritis may be driven by a specific set of stem cells, perhaps allowing researchers to target them and treat the condition.
Osteoarthritis is a degenerative joint disease that affects more than half a billion people worldwide.
To better understand the condition, researchers harvested tissue from the top of the shin bones in three people undergoing knee reconstruction surgery.
By analysing the gene expression of the tissue, they found a specific population of stem cells that hangs out in the part between the bones and the cartilage.
These cells had the genetic hallmarks of ageing and receptors that triggered the immune system to produce a protein that partly led to abnormal bone growth.
By blocking this pathway in mice, the team found they could improve symptoms.
They hoped this could help identify a new treatment for osteoarthritis.
Check out that research over in Science Advances.
We talk a lot about microbiomes here on the Nature Podcast and how the populations of microorganisms that live in and on us can have important implications for our health.
We've also talked about the microbiomes found in other animals too, but there's one important group of organisms that we haven't spoken much about – plants.
And that's the subject of our next story this week.
Specifically though, we're talking about trees.
A lot is known about the microbial life associated with plants in general.
Think nitrogen-fixing bacteria in legume roots, or blights and other diseases affecting crops.
But studies looking at microbes inside trees are much more limited.
And that's where this new work comes in.
The team behind it started out just looking for methane-producing microbes that might be living in trees.
But they ended up cataloguing a previously unseen ecosystem of microbial life living within a US forest.
I gave Jonathan Gewertzman, co-lead author of the study, a call to find out more about their findings.
But first, he laid out a big number they've calculated as part of this work.
Namely, the number of microorganisms living in an average tree.
So I think this is both a really cool fun fact and something that bears some hedging and some caveats.
What we found is that there are about 1 trillion prokaryotic microbes, so bacteria and archaea that live inside the above-ground woody tissues of the average tree.
So the simple way to say that is there's a trillion microbes living in a tree.
The complicated answer is one that's not counting the many, many more microbes that live in the roots and the leaves.
Two, that is only the prokaryotes and not the eukaryotes.
So fungi are eukaryotes.
So we were not able to come up with a number for those.
But if you added those, it would increase the number a whole lot.
And the last thing I would say is that trees are very different sizes.
So we went with what we calculated as the globally average size of a tree, the mean size of a tree.
But you'd have a lot smaller number of microbes in a sapling and a much, much larger number in, you know, a giant sequoia.
And let's talk about the rest of the study then.
You were looking for microbes in a particular forest near where you're at university.
Tell me a bit about that.
We did this work all at the Yale Myers Forest, and it's in northern Connecticut.
And we basically sampled all of the species that are commonly found there.
So about 150 individual trees across about 15 different species.
And so we took tree cores about the size of a pencil from the bark right to the middle of the tree and we separated the wood into two tissues.
So trees have sapwood, those outer living layers of tissue where the xylem and the phloem are that transport sugars and waters up and down, and heartwood, those non-living inner tissues that used to be sapwood but then eventually are replaced by new rings and become just structural support for the tree.
You've looked for evidence of microbial life then using DNA sequencing things like that, and you got this idea of an average number of some of these microbes.
But you actually zoomed in a bit more and looked at different parts of a tree, including the heartwood and the sapwood, and across different trees in the forest.
What did you find there?
So we found that there's a whole lot of variation.
So any two trees, even two red maple trees, right next to each other might have thousands of taxa that are different from each other.
That said, there was grouping or clustering or similarity between the microbiomes of trees within the same species.
So red maples look more similar to each other in terms of their microbiome composition than they look to say, an oak or a pine tree.
And then another thing that we found is that every part of the tree has its own distinct microbiome.
So there's a lot of variability from individual to individual, but there's a different microbiome that lives on the leaves and a different one that lives on the bark and a different one that lives in the roots.
So what lives in the sapwood are mostly aerobic bacteria, things that use oxygen, things that we might be more familiar with.
And there was some more similarity in what lives in the sapwood to what lives in the soils and on some of the tree surfaces.
And the biggest thing, sort of the most difference was found when we look at what lives in the heartwood.
So the microbiome living in those deep, older tissues inside the tree was totally different from what we found anywhere else in the forest.
What lives in the heartwood was dominated by anaerobic bacteria, things that live in oxygen-free conditions.
That includes things like the methane producers we were originally searching for, but also other things involved in fermentation metabolisms.
So the hardwood seemed to be a very unique environment, dissimilar to what we found anywhere else in the forest.
One question that stood out to me looking at your paper is that obviously you found all the different sorts of microbes.
Where are they from?
Because you imagine maybe plant diseases, for example, entering through the roots.
So that might be a path for some of these different species to get in to the different parts of a tree.
Does your work show any influence on how they get to where they end up going?
How the microbes get inside the tree is a really interesting question.
And there's evidence for some microbes being sourced from the environment, as well as some of them even being passed down from the seeds of one tree to the next generation.
In our work.
We didn't do any experimental work to trace the origins.
We used a statistical method that tried to help us infer where the microbes might have come from.
And what we found there was that the microbes in the sapwood looked a whole lot like the microbes in the coarse roots or the bigger roots of the plant.
And so we think that, because of the sort of connectivity through the vasculature of the tree, some of those microbes are probably getting in from the soil and the roots.
We found that?
What was living in the heartwood?
Our statistical source tracking tool told us that it was mostly of unknown origin.
One thing that that could mean is just that they exist in these other environments, but in really, really low numbers, and they only proliferate once they get inside of the tree.
But it could also mean that there are just other sources that we haven't found.
And we're particularly interested in how something that needs to live in an anaerobic environment might pass through aerobic or oxygenated environments on its way to getting into a tree.
So I think there are lots more questions to look into there.
And now you've got an idea of what is there.
Is there a tangible use this can be put forward to later on, do you think?
There's been lots of research that has some very practical implications.
So there are microbes that can confer additional nutrient uptake ability.
There are microbes that can help resist environmental stressors.
And I think that there's good reason to believe that we could see some of the same benefits as we continue to research the sort of wild tree microbiome.
There's also going to be all sorts of complicated interactions between the microbiome and plant disease.
And then, of course, I have to bring in my own personal interest with this, which is that some of these microbes are also likely to be important players in global biogeochemical cycling.
That could help us think about management or species selection for future planting, or even just helping with climate modelling for predicting these emissions under future climate scenarios.
Of course, in this work you've looked at obviously a huge amount of trees, but it is in one forest in one part of the northeast of North America.
Yes.
Your paper shows evidence that there are differences between trees in the same forest.
How applicable do you think these results will be to the rest of the continent?
Will things be wildly different if you go, you know, one state over and look at a forest there?
I would say that because we work in a fairly diverse mixed temperate forest, the genera we sampled have sort of global distribution.
And so we did sample a fair amount of sort of plant diversity.
And that being said, yes, it was one forest in one place in Connecticut sampled during one summer.
There is probably all sorts of spatial and temporal dynamics that we have not begun to touch yet.
That said, I think that there are commonalities with work in other places.
So some of the things that we found, like methanogens and anaerobes living inside the heartwood, have been found in individual species in a handful of other papers that have come out in recent years.
And I expect that some of these are going to be commonalities across globally distributed trees.
And we also saw how many things are unique to individual species.
And so there's a lot more to work on there, too.
Jonathan Gewertzman from Yale University there.
To read more about the work, look out for a link to the paper in the show notes.
One of the biggest science stories of the year so far happened back in April, when the company Colossal Biosciences claimed to have de-extincted direwolves, a species that last roamed North America during the Ice Age that ended some 11500 years ago.
Nature's Ewan Calloway has written a feature article about this and the field of de-extinction more generally.
And he joins me now.
Ewan, thanks for being here.
Thanks for having me.
It's always a pleasure.
Well, I've given an idea of the story there, but maybe you can get us up to speed on what happened, because the news kind of came out of nowhere.
Yeah, where do we begin?
De-extinction is a kind of a catch-all term invented by a science fiction book from the 70s.
For all we can tell, it means bringing extinct animals back to life or things like them.
And I mean, I guess this story starts maybe in 2021 with the founding of a company called Colossal Biosciences, with the stated goal of de-extincting animals.
First, the woolly mammoth, then the thylacine or the Tasmanian tiger, dodos.
And these were all, you know, much announced, discussed a lot.
And then, out of nowhere, in April, they announced that they had de-extincted this species called the dire wolf, which is kind of a distant relative of today's grey wolves that went extinct around the time of the last ice age.
I mean, there's been fierce debate about whether this is a dire wolf or not and indeed how accurate it is or was to what came before.
Yeah, so de-extinction doesn't really have a clear definition.
So some people say that nothing's de-extincted unless you've got a complete copy of it.
Other people say you just need something that kind of fills the same ecological niche as something that existed before, never mind how similar or not it is.
What Colossal is doing is, I guess, somewhere in between.
What they're doing is they're taking...
Ancient genomes from extinct animals.
We'll keep it to the dire wolf here and sequencing them and looking for variants that distinguish them from their nearest living relative, gray wolves in this instance.
And that analysis identified something like more than 10 million variants.
That's too many to put into words. a genome to engineer.
And so they tried to identify variants that they think are important for key traits of dire wolves.
So what they do is they take basically the cells of a gray wolf and edit the genomes of those gray wolf cells to introduce key traits of dire wolves.
They made 20 edits in total, 15 of which were to replicate variants identified through these ancient dire wolf genomes.
And then what they did was take this gene-edited gray wolf cell, pluck its nucleus out and put it into an egg cell from a domestic dog.
And then these cloned embryos, basically, were then transferred into domestic dog surrogates.
And they gave rise to three gene-edited gray wolf puppies.
You can call them direwolves.
Some people wouldn't call them direwolves.
They're direwolf-adjacent, maybe.
Proxy direwolves is a term that I've heard people use, including Colossal's chief scientist.
But Colossal has been very bullish in saying the direwolves are back.
This is the first successful de-extinction.
And it's caused a lot of controversy, to say the least, because of the shaky definition of what the extinction is.
It means different things to different people.
And I think a lot of people were unhappy about the secrecy.
You know, they didn't really talk about that they were doing it before.
And, you know, some people say that this is a technology that could alter our planet.
And maybe we should be giving a little more thought and consideration to its debut, whether you agree that this is its debut or not.
Colossal, of course are central to your article, then because they are this huge player not the only player in this field, it has to be said but really they are at the vanguard of these attempts.
They are definitely at the vanguard of these attempts.
You know, this is a company that's valued at more than 10 billion dollars.
They've raised hundreds of millions of dollars in funding from celebrity investors.
People like to talk about paris hilton and peter jackson, lord of the rings director, but they've got a lot of venture capitalists supporting them, And they're not the only people doing this.
You know there's a nonprofit group called Revive and Restore that's working on restoring the passenger pigeon.
They were working on the mammoth with one of the co-founders of Colossal.
That's George Church.
But then that project got spun off to Colossal.
You know, they're not the only game in town, but they're definitely the biggest game in town.
And I get the sense from your article that this really is quite a divisive field.
And people kind of swing maybe one way or the other about whether this is a good idea or a bad idea, whether it even is a thing or not.
Yeah, opinions differ.
I mean some people think that this whole pursuit is a waste of money.
That detracts from conservation.
You know, instead of resurrecting this or that, we should be spending money on saving habitat.
But a lot of people point out that these are different pots of money, you know.
And then even amongst the community of people who really think that genetic technologies like gene editing, stem cell technology cloning, have a role to play in conservation.
They're not so sure that this was the way to debut this technology to the world.
I guess there's a real concern from some people.
I'd say that by doing it in this way, making a big splash, putting it out there, saying these are dire wolves, we're kind of confusing the public as to what this technology is and as to what it can achieve.
And technology seems to be quite central where we are with extracting ancient DNA and cloning animals.
And of course, CRISPR gene editing.
These things have kind of come together to really allow attempts to be made that couldn't be tried before.
Definitely.
I mean, it's the confluence of three of the great biotechnology discoveries of the last few decades.
And it's come together to create a pathway towards, air quotes, de-extinction.
And I suppose the question is, should we?
And if we should, when and how?
And I think some people are a little bit uncomfortable with that one company basically calling the shots on this.
But I should say they have a lot of scientific outside advisors, a lot of people with a lot of expertise in all these technologies, in conservation, in bioethics, etc.
So you know, you could argue that they are doing this carefully and cautiously and responsibly, and some people do.
And one thing that struck me in your article is how useful this technology could be, because i think it's been touted as a way to undo a lot of the damage that humans let's be honest have caused to the world throughout history.
But you say that this technology won't necessarily work for all extinct species, for example I mean Colossal themselves talks about how expensive this is.
I don't think this is a solution to the biodiversity crisis.
And I think Colossal would agree with that.
I think they would say this is a toolkit to help deal with the biodiversity crisis.
I think they're interested in applying these technologies not just to bringing back extinct species but to existing species that maybe have very low genetic diversity.
And maybe you could use CRISPR to introduce some lost genetic diversity that's sitting there in museums.
But the flip side of that is a lot of folk will say this is just for show and it really serves little to no purpose potentially.
Yeah, there are definitely people who will say that.
The colossal proxy direwolves, genetic gray wolves, whatever you want to call them.
They are sitting on a big reserve surrounded by a 10-foot 3-meter fence.
They're never going to be released into the wild.
They're never going to form a wild population.
And for some people, that's not de-extinction.
That's Jurassic Park, basically, they would say.
This isn't contributing directly to species conservation.
There's that argument out there as well, that they're created for spectacle.
In your feature, you spoke to a huge amount of people, it has to be said.
Where do you get a sense that this field is going?
Because we hear now.
Obviously there's a lot of debate about the dire wolves and mammoths are being looked at and all sorts of other things.
Where do you think this leads?
That's a good question because this took me by surprise.
Not the fact that they could do this because a lot of the technologies were there.
We've been cloning dogs for two decades, or something like that, and CRISPR is getting better and ancient genomics is flying.
And I think that changes the game.
It almost allows somebody to define de-extinction how they want to suit what they can do.
Some people would call that moving the goalposts.
In Colossal's defense, they would say well, we needed only these 20 edits to recapitulate what we think are the key traits for dire wolves.
When we start thinking about applying these technologies to animals that are intended to live in the wild, that'll be crossing an important threshold.
Can we create something for lack of a better word that can thrive in the wild, that can perform a function that was lost?
I think that's an open question.
Well, Ewan, thank you so much for joining me today.
And we'll put a link to your feature in the show notes.
Yeah, thank you very much for having me.
That was Nature's Ewan Calloway.
That's all for this week.
As always, you can keep in touch with us on BlueSky or X.
We're at Nature Podcast or you can send an email to podcast at naturecom.
I'm Nick Petrichow.
And I'm Benjamin Thompson.
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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