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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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Welcome back to the Nature Podcast.
This time, how iron can derail sex determination in mice.
And uncovering the invisible contributions of small-scale fishes.
I'm Benjamin Thompson.
And I'm Nick Perchichow.
A new study has shown that iron deficiency in mice mothers can sometimes lead to their offspring becoming female when they would otherwise have become male.
In mammals, it's long been thought that genetics plays the key role in determining what sex offspring are at birth.
For example, in one sex determining pathway, a gene known as SRY, found on the Y chromosome, controls the development of testes.
But the new work upends that understanding by showing that an external factor, in this case iron, may play a part in this pathway.
A finding that could indicate it's not just genes playing a role in sex determination in mammals.
Reporter Rachel Fieldhouse, who's been writing about this story for Nature, joins me now to discuss the study.
Rachel, hi, how's it going?
Hi, I'm good, how are you?
I'm good, thank you.
Thank you for taking the time to chat to me about this.
So I think a good place to start would be to talk about the let's call it the normal pathway of sex determination.
How does this tend to occur?
So generally for mammals when sex is determined during development.
So when the unborn animal is in utero it's due to a particular gene.
In the case of mice, it's the SRY gene and it is also connected to the chromosomes XY for male typically, and XX for female.
And this isn't the first time the authors of this study have looked at this sex determining pathway.
What did their previous studies show?
So previously they found that a particular enzyme called histone demethylase is involved in activating SRY and therefore plays a role in sex determination.
Essentially, this enzyme activates the gene.
And basically, if this enzyme is active and it triggers the SRY gene to express, then that causes the mice to develop male sexual organs or gonads.
Okay, so this enzyme seems to be important in this sex determining pathway.
But what brought them to iron as the link doesn't seem immediately obvious?
No, it's not immediately obvious.
But it turns out that this enzyme actually needs iron to activate SRY.
So they started to look at what the effect of manipulating iron levels would do to this enzyme and then, as a result, what it would do to SRY expression and sex differentiation.
So how did they actually go about manipulating these iron levels to see if it had some effect on this enzyme?
So they did it in two main ways.
So In the first way, they had mice and they removed a particular gene that is responsible for incorporating iron into cells.
So because that gene wasn't there, there was less iron available in the cell for the enzyme to function.
And therefore, SRY was essentially deactivated.
And so that resulted in some of the mice that were born from these mutated mice having female sexual presentation, even though they had XY chromosomes.
And the second way they did it was feeding pregnant mice an iron-deficient diet for six weeks, so four weeks before pregnancy and two weeks during.
So when they were looking at the mice in utero during the pregnancy, they saw signs of anemia.
They saw, when again the mice were born, that there was also a switch from male to female in some of the mice.
Oh, in some of the mice.
So how many of the mice was this actually happening to?
So in the first experiment they had four mice that were born with two ovaries and had XY chromosomes.
One actually was partially feminized and it had one ovary and one testy.
In the second experiment, only two of the 43 offspring.
So it was a relatively small proportion then.
Do the researchers then believe that maybe there's a bit more going on than just this iron?
It does seem a lot more complicated than just iron.
It seems like iron intake and iron metabolism is just one of the things that determines sex.
And were the researchers surprised at these findings at all?
Because the thinking has been that, for mammals at least, genetics are the key factor and environment has not really been considered to be that important.
They weren't surprised.
They did note that this is one of the first pieces of evidence to show that, as you said, environmental factors can influence sex determination.
They are also looking...
I guess more further afield into how iron can affect other gene expressions, to see if it's more than just sex determination.
And of course, I'm going to bring this round to humans as we are such a self-interested animal.
Does this have any implications for humans?
Admittedly, mice are quite different, but we are both mammals.
That's true.
It's hard to say what the impact will be because again, like you said, mice and humans are very different.
The authors were quite hesitant to make a comparison to humans because mice are so different, but they do stress that iron plays a really big role in pregnancy and it can have consequences whether you're a mouse or a human, and having low iron can have negative consequences.
Nature reporter Rachel Fieldhouse there.
For more on that story, check out the show notes for a link to Rachel's news article.
Coming up evidence that the contribution to sustainability that small-scale fishers are making has gone underappreciated.
Right now though, it's time for the Research Highlights with Dan Fox.
Climate change is extending the period when conditions are ripe for the formation of dust storms in some regions.
As temperatures have risen, snow has tended to melt earlier in the year, but the date at which vegetation starts to grow hasn't necessarily kept pace.
This has resulted in longer periods when the ground is mostly bare, dry and vulnerable to wind erosion perfect conditions for damaging dust storms to whip up.
Researchers analysed data gathered in the northern hemisphere between 2001 and 2019.
During this period, they found that the gap between the end of snowmelt and the start of the growing season widened in 44 of North America and 53 of Eurasia.
In the Inner Mongolia region of China.
The team saw that both weak and severe dust storms were more likely to occur during this gap than the periods before or after.
And in years in which the gap was unusually long, dust storm activity was higher.
You can read that research in full in Global Change Biology.
A study of a boy who was unable to feel pain could lead to innovative new therapies.
Researchers conducted extensive genetic testing of the boy who died suddenly at the age of 16 to determine the cause of his symptoms.
They identified a single mutation in a gene that encodes an enzyme called USP5, which is involved in regulating the activity of neurons that transmit pain sensations.
To understand the mutation's effect, they used CRISPR to give mice an equivalent mutation.
These mice were less good at sensing acute pain than normal mice and also developed resistance to inflammatory and chronic pain, an effect that was more pronounced in male mice.
The results suggest that the mutation changes the structure of USP5, sharply reducing its activity.
You can find that paper in the Journal of Experimental Medicine.
Next up, how research is helping shine a light on an invisible contribution to sustainable fishing.
Reporter Julie Gould is here with the story.
The 2025 United Nations Oceans Conference taking place next week has a heavy focus on sustainability.
But there are many factors that threaten the sustainable use of the oceans.
Illegal fishing, habitat destruction, climate change and overfishing are just a few examples.
To make fishing sustainable.
Researchers and policy makers need to understand the contribution of everyone involved here.
But one group of people have, until recently, been described as invisible, small-scale fishers.
Mitchell Ley is a small-scale fisher based in Antigua and Barbuda and has been a fisher for most of his adult life.
I grew up associated with the ocean.
So the ocean is a sort of place where there is a certain sense of tranquility.
It is also, you know, fairly challenging sometimes, but excitingly so, enjoyably so, in that you actually control your movements.
You are not restricted by anyone.
If you decide to go a particular location today, you do that.
Mitchell uses his own panga boat that he has adapted to catch mostly red snapper, with equipment that he makes himself.
But his livelihood is threatened by the unsustainable use of the oceans.
Whenever your livelihood is threatened, I feel I have a responsibility to respond and to defend it.
But this is how I feed my family, and my family is important.
The idea to support small-scale fishers like Mitchell is what drives Javier Basurto's research at Stanford University in the US.
When Javier was an early career researcher studying the oceans, he had the opportunity to go to Canada, where overfishing was transforming daily life and fishing communities.
And so I realized wow, they have so much knowledge about the ocean and they produce so much out of it that if we want to really use the coast sustainably, They need to be part of the conversation, because they have so much knowledge, because they have so much at stake that for me it was very clear that partnering and working with fishers was a way to become better stewards of the ocean and the coasts.
Over the last eight years Javier, the Food and Agricultural Organization, or FAO, and World Fish have been working closely with small-scale fishers in 58 countries to collect data that demonstrates how impactful they are on a global scale.
We were very interested in capturing the multi-dimensional contributions of small-scale fisheries.
Not only what it means for catch and the value of that catch, but what small-scale fisheries means in terms of bringing nutrition to marginalized people around the world, what it means in terms of employment or for their livelihoods more broadly, who are dependent in the employment of this fisher, or the involvement of women.
They worked on the assumption that a lot of the data already existed, so they enlisted and trained local experts in each of the 58 countries to find the data, and only in a few cases did the team go to the field to collect data from observation.
This data then needed to be compiled and analysed together with other sources, explains Nicole Franz, another researcher from Stanford who worked on the project.
While the study is really grounded in the evidence from these 58 country and territory case studies, we also used other sources of data.
We call it a tapestry of methods.
And what we found, for example, was that it is very useful to look into labor force surveys or household surveys and to look at them through the lens of small scale fisheries.
The results of this major data collection and analysis effort have now been published in a recent Nature paper, and it's highlighting the contribution and impact that small-scale fisheries are having.
For example, the livelihoods of one in every 12 people depends directly or indirectly on small-scale fishing, and that 40 of the global catch is generated by small-scale fisheries, and that this catch provides nutrition for approximately one quarter of the global population.
Despite their importance.
What was surprising is how invisible the sector has been for society, for the global society, for policymakers around the world.
Like how is it possible that this sector that provides so many nutrients, so much cash, that is all over the world, has been practically invisible to decision makers?
This invisibility at national and global levels means there is little to no legislation or support programmes for fisheries, nothing to stop the people on the ground falling into poverty, for example, particularly in the developing world.
And one of the things that makes small-scale fisheries invisible is that not all fishing activities go through the markets, said Mitchell.
Subsistence fishing, where people fish for direct consumption for the household, is a big part of how their communities operate.
And small scale fisheries is not just about generating revenue.
It's also about community.
It's about families.
This is a social issue, which is extremely important in my view, and often on the low.
Not anymore, said Nicole.
The research reflected the importance of this type of fishing.
We found the estimate that it's about 53 million people that engage in one way or the other in small-scale fisheries for subsistence.
So that's an important contribution to livelihoods that that has been even less visible than some of the other dimensions.
There's also the issue of how and how often small-scale fisheries engage in the governance and management of their activities to ensure their sustainability and so that their interests are represented at national and global levels.
The central government or central authorities are doing the management, if there's management at all.
In many cases, there's just no management.
And I've been in many meetings with fishers that that's one of the things they constantly ask for.
We need more management so that there's less problems, less conflicts, less legal fishing, less some of the issues that bring overfishing to the sector and put in peril their livelihoods as well.
But Mitchell says that even though fishers want to get involved in the governance, the lack of involvement is difficult for them to overcome due to the nature of their work.
So we typically prepare the boat in the evening before I leave.
And then I'll probably leave the shore at 5am or earlier, depending on the weather conditions.
And then I'll fish for the day until we get in before dark or at sunset.
And so trying to defend interests and promote livelihood is challenging.
So what Javier and Nicole hope will happen next is that the data that they've collected will help make small-scale fisheries more visible.
What we would like to see in the future is that countries actually are able to produce those numbers at the national level so that they can really inform how they're managing and how they're supporting those small-scale fisheries.
A second pathway for follow-up is in relation to advocacy and empowerment of small-scale fishers themselves.
So what we hope is that we have created a tool for small scale fisheries organizations around the world to use these findings, to use as evidence for advocacy and for engagement in policy making, in decision making, using these facts that were maybe missing or not as substantiated as before.
So that would basically prepare the ground for a new generation of decision makers, of researchers, of practitioners that have all of these dimensions already established included from the beginning in their work.
Although Javier and Nicole will not be attending the 2025 United Nations Oceans Conference, other members of their team will be flying the flag for their project.
And what they're most excited about is that the small-scale fishers themselves will be attending, sharing their perspectives and having an opportunity to take part in the discussions.
So there will be representatives attending the UN Ocean Conference and they will also have that dedicated side event to emphasize the role of small-scale fisheries in terms of food security, poverty eradication and so on, and the important need to secure their role and their access in using the ocean space.
So that would be an opportunity to also highlight the findings in Nature Collection and the information that has been generated through this initiative.
I mean we got to remember that, in terms of numbers, small school fishers are some of the largest users of the ocean space, right.
And so it's only fair that such a large sector of users of the ocean needs to have a seat on the table.
And for the most part, fishers have been invisible to policymakers.
So.
So what we hope is that they have an increasing place at the negotiating table, a table that determines the futures of their livelihoods.
And for Mitchell, as one of those small-scale fishers who has been somewhat invisible in the past.
More fishers being involved in advocacy would help highlight their important contribution to sustainability.
The research on a whole paints the kind of picture that says to us We must stop and pay attention to small-scale fisheries.
Yes, the reality is that small-scale fisheries are not just important, they're vital.
That was Mitchell Lay from Antigua and Barbuda.
You also heard from Javier Basuto and Nicole Franz from Stanford University in the US, and reporter Julie Gould.
For more on that story, we'll link to a collection of articles on this topic in the show notes.
Finally on the show, it's time for the briefing chat, where we discuss a couple of stories that have been highlighted in the Nature Briefing.
Ben, what have you been reading this week?
Well, I've got a story that I read about in Nature, and it's based on a paper in Angavanta Chemie.
And it's about an ambidextrous protein, one that can function in two mirror forms.
And this is quite rare and it could be a relic of a time when the molecules of life on Earth looked rather different.
Oh, interesting.
So when you're talking about in both ways, this is chirality, right?
Absolutely right, Nick.
So yeah, chirality is essentially handedness.
Molecules can be left-handed or right-handed.
They're mirror images of each other.
You can put your two hands together, but you'll never be able to twist them.
So they are exactly the same shape.
And life tends to stick to one or the other, right?
DNA is right-handed, so if you look at it down the barrel, down the axis, its double helix twists to the right.
But proteins tend to be left-handed, right?
They sort of twist the other way.
And that's sort of just the way it is.
Nobody really knows why.
Having this preference might have helped maintain stability and function of biomolecules in life's evolution.
But that's unclear.
But what's happened now is that a researcher was looking at a protein fragment, a peptide, and it's a peptide that binds to DNA, often found in DNA repair enzymes.
Now the researcher noticed the structure of this peptide was symmetrical around its central axis, and he suspected that maybe both a left or a right-handed version of this could bind DNA, so it could work in either mirror form.
Oh, that's super interesting, because the one thing that I think is pretty consistent is often like enzymes and stuff will only work with a certain form of this.
But in this case, this one's working either way, but binding to DNA at least.
And this segment is found in all sorts of proteins.
It turns out that either manipulate or bind to DNA or RNA, which suggests that this particular peptide, this sort of part of a protein, existed in a very early ancestor of all cells.
Now, this was just a hunch.
So the team behind this work tested it out.
They made a right-handed version and this could bind to regular DNA, the sort of DNA that exists now.
And what's more is a regular version of the peptide could bind to a mirror version of DNA, right?
So it could work both ways.
So it really doesn't matter to this protein, like, which way anything is, really.
Absolutely right.
Now, obviously, that's not the way the world is now.
And most likely is that this, this adaptability, this flexibility, I suppose, lets this peptide bind to DNA if it's folded in different ways.
It's not about mirrorness or handedness.
It's just it adds a bit of flexibility to DNA binding.
But what it might mean underline the might there, I think is that This binding peptide may have evolved when mirror life may have existed on Earth.
So left handed DNA and right handed proteins, the reverse of what we have now.
And this kind of ambidextrous nature may have evolved to be able to bind to these different bits.
So can this tell us something about that early, early world and early, early life?
I think that's what's hoped, but it's going to be really tough to do, according to this article.
Really, what will be required is looking at other potentially ancient DNA binding domains and seeing do they work in an ambidextrous way which may give a bit more insight into what may have been going on on Earth a long time ago.
Because Luca, the last universal common ancestor that all of today's cells ultimately kind of came from.
Nobody really knows exactly what that looked like, or even what it looked like before life.
As we know, it branched off from luka, so it's kind of an interesting one.
But mirror life is something that's getting a lot more attention now.
Last year there was a big report about it and so a bunch of news articles, because it's not possible to make it now, but it might be possible for researchers to make it in the future, and there's a lot of interest in this because you might be able to make biomedical molecules that last a lot longer because they're not the right handedness for the body to break it down.
But conversely, there is some concerns that if you were to make mirror bacteria say, our immune system is based on left-handed proteins, right?
Like it's evolved to work that way.
It may not work at all against future right-handed molecules, which obviously could be quite bad.
You could make a superbug.
I mean, potentially.
And this is all very sort of hypothetical.
It's estimated that doing this is...
10 years away plus, right?
But it's something that we don't know a huge amount about.
And this research is maybe shining a bit more light on that.
Well, I'm interested to see what will happen in the next few years as researchers shine more of a light on that.
And speaking of shining lights on things, seeing things more clearly.
My story this week is about vision, and it's about whale vision.
And as it turns out, humpback whales may be short-sighted.
I mean there's a lot going on here Nick.
I must confess I don't know a huge amount about whale vision.
I imagine whales can dive quite far under the sea so I'm guessing they've got quite big eyes?
They do have quite big eyes and so because of that it has been thought that they have quite good vision, because one way to make your vision better is to have a bigger eye so you can have more focal lengths and you can focus more light and see things more clearly.
That is something that happens in nature.
But for humpback whales, at least, that doesn't seem to be the case.
So this is a story I was reading about in Discover magazine, based on the paper in the Proceedings of the Royal Society B.
And yeah essentially, if these whales were human, their vision would be so bad they would be legally blind.
How on earth do you go about testing this?
I mean, I've been to the opticians recently and they put up the chart and you know you'd say the letters from top to bottom.
I'm guessing it's hard to do that under the sea.
Yeah.
It is quite hard to do that under the sea.
The way that they've looked at this is they've looked at an eye that has come from a stranded whale.
And an interesting tidbit about this story is this has been in a lab for about 10 years before someone's had a look at it.
And then an undergraduate, for their honours project, decides to look at this eye and try and figure out how well these whales can see.
So what you do if you have an eye is you can measure the focal length.
So that's the distance from where the light rays enter the eyes to where they are then bent to the retina.
And you can also look at the peak density of the retinal ganglion cells.
And these are neurons in the eye that get info from photoreceptors, and based on these two factors, you can come up with a number that gives you an idea of the acuity of the vision, which is how well you're able to resolve two different objects clearly.
So you know if you can read text 20 meters away, then you've got good visual acuity.
For example, and what they found by doing this is that the humpback whales they had a measure for the security in cycles per degree cpd of 395, which is quite low.
Humans range from 60 to 100, for example.
So our vision is much, much better.
But does being short-sighted have an impact on whales and how they live in their lives?
Do we think For a long time?
No, because what whales needed to see is just big schools of fish and big objects that they need to avoid.
And they can see that.
They can see silhouettes of things quite well.
And once they get close enough, they can determine exactly what it is.
But in recent times...
Humans.
Humans have come about.
And one of the problems may be that the whales are not able to see our fishing gear very well.
And it's known that a leading cause of death of these whales is getting tangled up in fishing gear.
And it could well be because they can't see it very well.
Like the nets are quite small.
They're quite hard to see, especially if you can't resolve things very well.
But this is one eye.
Right, this is one eye.
It's very hard to get samples like this to test in the lab, like this was from a stranded whale, and that's normally where you get anatomical bits of whales to then assess in the lab.
And that is a relatively rare occurrence.
And even when it happens you have to act very quickly because the whale carcass very quickly degrades.
So we don't have many studies on this, but there was a previous study on a juvenile humpback whale which also showed that the vision was not great.
So more work will need to be done to make sure that this isn't just a particularly short-sighted whale, or the juvenile, and this were particularly short-sighted whales.
But it seems that, yeah, they may well struggle to see clearly, despite their big eyes.
And so now we have more evidence, then, that whales potentially need glasses.
Yes.
What do we do with this information?
Well, I think it would be tricky to put glasses on all the humpback whales in the world.
But one thing that the researchers have proposed is we could borrow what's been done to protect birds.
So we know that birds can see ultraviolet light.
And so researchers have proposed made basically ultraviolet warnings to stop birds colliding with objects that they normally collide into so we could do something similar with whales making something that they're able to see now that we know that they have this visual acuity the other thing that will need to be determined is how maneuverable whales are because it's one thing to warn them is another to know how soon we need to warn them to make sure they can steer out the way in time and that is something that we don't really understand Well, I absolutely love that story and I'm always fascinated by the things we didn't know about animals and anatomy and the world around us.
But let's leave it there for this week's Briefing Chat.
If you've enjoyed hearing about those stories, we'll put links to them in the show notes, where you can find out a bit more and where you can sign up for the Nature Briefing to have more stories like this delivered directly to your inbox.
That's all for now.
In the meantime, if you want to keep in touch with us, you can follow us on Blue Sky or X, or you can send an email to podcast at naturecom.
I'm Nick Pettichow.
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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