Killer whales have menopause. Now scientists think they know why

Benjamin Thompson

Welcome back to the Nature Podcast, this week: Making a map of the developing human heart…

Nick Petrić Howe

…and why certain whales have menopause. I'm Nick Petrić Howe.

Benjamin Thompson

And I'm Benjamin Thompson.

<Heartbeat sounds>

Benjamin Thompson

The human heart is an amazing thing. It’s the first organ in our bodies to develop, and it pumps for a lifetime.

And it's this organ’s form of four main chambers with their associated blood vessels and valves that is central to how it works, with multiple parts made up of countless cells working together.

<Heartbeat sounds>

Elie Farah

Each structure has like a very specialized function. So like, for example, the left ventricle, you have these cardiomyocytes, or heart muscle cells, all aligned in almost like a sheet. And they all contract in sync.

Benjamin Thompson

This is Elie Farah from the University of California, San Diego. He’s part of a team focusing on this organ. Because it turns out that even though we know a huge amount about the heart, questions remain.

Elie Farah

Like, what are the cell types that compose the heart? And that's not fully known, especially within the developing human heart. And then how are all these cell types organized? How do you put all these parts together? You can have like all the parts of a car engine, but if you don't know how to put it together, you're never going to form that main engine.

Benjamin Thompson

This week, Elie and his colleagues have got a paper out in Nature looking to help answer these questions. They’ve developed a new atlas of the individual cells that make up the structures that comprise the heart. Specifically, they’ve focused on how the heart develops at the early stages of life, a critical time in development.

Elie Farah

Defects in this process lead to various cardiac diseases, including congenital heart disease, which is the most common birth-defect, as well as adult cardiomyopathies. So understanding how it develops normally will help you understand what goes wrong in disease.

Benjamin Thompson

To make their heart atlas, the team combined two techniques. Their first job was to find out which cells were present. They did this by separating out individual cells found within heart tissue, then extracting and analysing the RNA that each one contained.

Elie Farah

By looking at the RNAs contained within that cell we can determine what type of cell it is. In the end from eight hearts, we captured about 143,000 cells divided into roughly five different major groups. From there we defined 75 what we call cell subpopulations.

Benjamin Thompson

The team were able to say which cells were present and which broad areas of the heart they came from, setting them up for the second stage.

Elie Farah

That part kind of gave us the ‘what’, so the second part answered ‘where’ are the cells within developing human hearts? So to address that question, we use a technique called MERFISH.

Benjamin Thompson

Which stands for “multiplexed error-robust fluorescence in-situ hybridization”.

Elie Farah

And that actually looks at the spatial location of RNA. What's nice is we can essentially pick a group of genes that in combination can help define all the cell types within the heart. So you know, 10, 20 of those genes can define cardiomyocytes. 10, 20 can define fibroblasts, 10, 20 can find endothelial cells, those in combination can then differentiate like all the cell types that we identified within the heart and spatially locate those within the heart tissue.

Benjamin Thompson

So by highlighting RNA specific to different types of cell the team could build up a cross-sectional map of what was where, at an individual cell level.

Elie Farah

Like at that high resolution, if you're zoomed in, you only see like dots, like okay, you have no idea of like what the full picture is. But like when you zoom out, it has all the four major chambers. It has like the valves, to those in the field is almost like a picture perfect cross section through the heart. So it is almost like a Google Maps of the heart.

Benjamin Thompson

With their map in hand, the team could take a tour around the developing heart, working out the different communities of cells that associate together within different areas. This provided new insights into the cellular makeup of different structures, such as the left ventricle.

Elie Farah

One of the structures we had not seen before was that the left ventricle was actually highly organised in almost like a layered fashion, where each layer was composed of like highly specialised cardiomyocytes, or heart muscle cells. And then associated with those were actually specialised, almost like supporting cells like fibroblasts. So that was surprising.

Benjamin Thompson

But in addition to working which cells were where, the team wanted to investigate how structures like this form. They did this by looking in the RNA produced by each cell for genes associated with chemical pathways that help neighbouring cells communicate. And many of these pathways were specific to specific heart regions. For example, a molecule produced by the supporting fibroblasts helped organize the cardiomyocytes into the layered structure the team found in the left ventricle. This molecule is known to play a role in helping neuronal cells move into the correct position, and in in vitro experiments it was involved in getting lab-grown cardiomyocytes to shuffle into place as well.

Elie Farah

That one was kind of amazing when we tested this one molecule and I saw it yeah the cells moved into the right place I was like, “Oh my god but they never move”, the fact that it actually responded to this was crazy.

Benjamin Thompson

In vivo experiments in mice also showed the key role for this molecule. Elie says that this is just one aspect of how this layered structure comes about however, and that other molecules made by other cells are involved too, some making sure the cardiomyocytes stay-put when they reach the right place, for instance. There’s a lot more to understand about the processes underlying how cells come together to form structures like the left ventricle, and Elie says the atlas that he and his colleagues have produced of where cells live, and what RNA they make, could help on the road to figuring that out. But there’s a long way to go to fully represent this complex organ.

Elie Farah

What we did was like a 2D map. So the next step would actually be to make a 3D map. And then beyond that, you know you want to look at well how is this changing over time? So we're looking at developing human heart but also like what does the adult human human heart look like, so you better understand like when it goes wrong in disease.

Benjamin Thompson

Incorrect development of heart structures can lead to serious, and sometimes fatal, congenital conditions, and Elie hopes that their insights could ultimately help researchers understand why these occur.

<Heartbeat sounds>

This knowledge could also be used to make more realistic lab-models to test drugs, and perhaps in the long-term could be used to develop cell-based treatments for children that are less invasive than techniques often employed today.

Elie Farah

We tend to use like putting in like a stent or something, but I think the issue with that is they actually need like multiple surgeries. You have to go in and like replace the different parts as the heart grows. So it's like a surgery, six months, two years, like 18 but if you can give like a cell-based one that will grow with the child then it is like a one and done type thing.

<heart sounds>

Benjamin Thompson

That was Elie Farah from the University of California, San Diego, in the US. To read his paper, head over to the show notes for a link. You’ll also find a link to a video we’ve made about the work, where you can see the atlas from the paper.

Nick Petrić Howe

Coming up, how studying toothed whales has helped researchers understand why some of them go through menopause. Right now, though, it’s time for the Research Highlights with Dan Fox.

<music>

Dan Fox

We know that ancient Mesoamerican people like the Maya smoked cigars, but new analysis of ceramic vases suggests that some of these ancient cultures might also have been drinking their tobacco. Researchers analysed chemical residues on seven ceramic vases found at an archaeological site in what is now Guatemala. Three of the vases showed traces of nicotine. And because the vases were probably designed to hold liquids, the findings suggest that the locals consumed tobacco in liquid form. The authors say that the proximity of the vases to sweat baths — bathtub-like structures used for therapeutic and ritual activities — also suggests that tobacco infusions served ritual and therapeutic purposes. You can read that research in full in Antiquity.

<music>

Quantum batteries may sound cutting edge, but they share a problem with regular double As — efficient charging. Now researchers have discovered that charging a quantum battery wirelessly could prevent its efficiency from fading over time. Quantum batteries, which store energy from light in the quantum states of atoms and molecules, could theoretically charge much faster than conventional devices. But interactions between a quantum battery and its surroundings tend to cause the devices delicate quantum properties to break down, reducing its ability to store energy. Now a team of researchers have devised a way to harness those interactions to charge, rather than deplete, the battery. They propose placing the charger and battery in a rectangular metal tube. Then if a electromagnetic field is applied throughout the tube, the battery, charger and tube environment form a single quantum system, allowing the charger to exchange energy with the battery without exposing the system to disturbance. While this setup remains theoretical, the authors think it could work with the battery and charger up to 10 centimetres apart and should result in batteries that don't lose their efficiency over time. You can find that paper in Physical Review Letters.

<music>

Nick Petrić Howe

Next up on the show, why do certain whales have menopause? It’s a bit of an evolutionary puzzle, but some new research in Nature may have some answers. Here’s reporter Julie Gould with more.

Julie Gould

As a woman, I'm used to thinking about menopause as something that all women will go through. Once we get to that age, our hormones start to fluctuate and eventually we'll stop being able to become pregnant. But it's not so common in the rest of the animal kingdom. In fact, outside of humanity, menopause has only been seen to be experienced by some species of toothed whale like beluga whales and killer whales.

Sam Ellis

When you think about how evolution by natural selection works, you're trying to get as many offspring into the next generation as possible. Almost always you'd expect the easiest way to do that is to keep reproducing for your whole life. The 50% of humans do that and in most mammals, that's what females do – they reproduce for their whole life. And so this is actually a really unusual trait that humans seem to share with these whale species.

Julie Gould

This is Sam Ellis, a researcher in animal social behaviour from the University of Exeter in the UK. His research looks into the factors that drive this unusual trait in a few species of toothed whale, in order to better understand how species move from not having menopause, to having menopause, and what this evolutionary process tells us about why it evolved. There are two main theories as to why this trait evolved.

Sam Ellis

One way, it could be that their lifespan is exactly the same as their ancestor, but the reproductive lifespan has dropped back and shrunk. Or it could be that the ancestor didn't live very long, and their lifespan extended, but their reproductive lifespan didn't extend along with it.

Julie Gould

In a research paper published this week in Nature, Sam and his colleagues try to understand which theory is the most likely by comparing the lifespans and reproductive lifespans between different tooth whale species with and without menopause. To study this, Sam used data from whales that had been beached to see when they had reached menopause and what that meant for their lifespan.

Sam Ellis

And we're able to show that species with menopause reproduce for exactly as long as you'd expect for a whale of their size. But they're living on average about 40 years longer than expected for a whale of their size. So what this tells us is it's the what they call the ‘live long hypothesis’, there's some selection pressure has acted to extend females lifespans without also extending their reproductive lifespan.

Julie Gould

This was the first part of that research paper published this week in Nature by Sam and his colleagues. The second part is to explain why lifespans have extended but reproductive lifespans haven't. The reasons Sam and his team believe, are twofold. The first is, as we might understand it, because it takes a village to raise a child. In whale social groups as in human ones, grandmothers are often heavily involved in the raising of grand offspring.

Sam Ellis

One is by leading the group, when resources are scarce. So these– these whales eat resources that have annual fluctuations. And when– when resources are low, if you literally look at who's the group is swimming along, it's the older females at the front, it seems to be the older females they’ve remembered where the resources are, say, ah, yes, when the winds in the east in this kind of year, we need to go here, this is where we're going to find the food. So they seems to be these repositories of long-term ecological knowledge, which allows them to help their group. The other way they seem to be help is by directly sharing the food. So there's been some research that shows that older females they eat these salmon, they eat these massive salmon, and when the older females get them, they almost always bite them in half and half goes to someone else in the group, whereas that's much less extent in the younger females and the males never share their food. So they seem to be both doing this direct sharing of keeping the offspring alive by giving them food, but also this indirect helping by leading the group to places where they can find food.

Julie Gould

The second reason is to do with preventing competition in the group.

Sam Ellis

So we showed that what having menopausal means is that you want to spend much less time reproducing at the same time as your daughters. And what that means, if you're living in a group with your daughters and resources are limited, and you're trying to allocate resources to and offspring, you know, foods limited, you want to feed up all the offspring. If there's your offspring and your grand offspring there, you've got to make a decision, you're taking resources away from the group to give to your own offspring. But if you stop reproducing, your offspring is out of the picture. And then all of the group resources can be allocated towards the grand offspring. And so we call this reproductive competition and we showed that in species with the menopause, the amount of reproductive competition isn't as much as it would be if they carried on reproducing for their whole life. So it seems that menopause is a way to escape this reproductive competition. It's a way for live for a long time, without increasing competition for resources within your group.

Julie Gould

One of the other findings that the group reported was that in toothed whale species, particularly in killer whales with menopause, the males are remarkably larger than the females compared to other species that don't experience the menopause. This could be something to do with an increased investment by mothers in their sons.

Sam Ellis

If you give the resources to your daughter, she will turn it into more grand offspring who will then be in the group and then increase competition within the group. In the social systems of the killer whales, and we think in potentially of some of the other whale species as well, the males they stay with their mother for their whole life. So their sons are still there with their mother, but they reproduce in different groups that when different groups come together, when pods join up, the males go off and reproduce. And that means your son's offspring are somewhere else. They're not increasing your own group competition, they’re someone else's problem. So there's an argument to investing in your sons as a way of lowering in-group competition. In the killer whales, there's an interesting other caveat to that, which is in the killer whales, and this may be the case in other populations, only the two or three oldest males, oldest and biggest males seem to have any reproductive success. There's also a lot of pressure on females, like if you can keep your son alive to become that big, old male, you win the jackpot, you have all of the grand offspring living in other groups.

Julie Gould

For me as a woman in her mid-30s. Menopause is still, I hope, quite some time away. But that doesn't mean I'm unaware of what lies ahead. So I wondered, do these female killer whales and other toothed whale species that experience menopause, experience it in the same way as we do? Night sweats, mood changes, weight gain, hot flashes.

Sam Ellis

Some people have been doing some really great work of collecting killer whale poo. And then analysing the hormones within the poo and the hormone changes happening in the killer whales seem to be very similar to the hormone changes happening in the– in humans. As to hot and cold flushes, we've got no way of telling yet.

Nick Petrić Howe

That was Sam Ellis, from the University of Exeter here in the UK. That piece was produced and presented by Julie Gould. And for more about whale menopause, check out the show notes for some links.

Benjamin Thompson

Finally on the show, it’s time for the Briefing Chat where we of course discuss a couple of articles that have been featured in the Nature Briefing. Nick, why don’t you go first this week? What have you been reading about?

Nick Petrić Howe

So this week, I've been reading a story about how semaglutide, which is a kind of anti-obesity drug, which people may know as Ozempic or Wegovy, how it could help with some of the comorbidities to do with HIV.

Benjamin Thompson

And of course, these drugs are, you know, huge business around the world. And researchers are looking at how they could be maybe reappropriated in other contexts. So yeah, what's the story with HIV?

Nick Petrić Howe

Yeah, so this is an article in Nature and as I said, it's looking at this particular anti-obesity drug semaglutide. And so this reduces weight and fat accumulation. But in HIV, these are particular problems that you can get by taking the anti-retrovirals that control the HIV that help you live a normal life when you have HIV. And so I'll caveat all this by saying these are basically from conference talks so this hasn't been through the peer-review process and that sort of thing – this is very early data. But it seems that in general, they could help with controlling some of the fat accumulation that occurs from taking these antiretrovirals.

Benjamin Thompson

So the drugs are doing what they were kind of designed, developed to do, but are being maybe repurposed for a different area.

Nick Petrić Howe

Yeah that's right. So to give you some examples, the number of people who are obese who also have HIV is increasing as it is in the general population. So one part of this is just trying to mitigate that sort of weight gain and you know, that can help with the people living healthier lives and having fewer other conditions associated. And so, there's been a study where people looked at 222 individuals who have HIV, and they showed that they were able to have a 6.5 kilogram weight loss in a year, so quite a significant amount of weight loss. But another aspect that's particularly HIV is, as I said, these antiretrovirals can lead to certain kinds of fat accumulation. And here they've shown that this semaglutide can really help with some of these conditions.

Benjamin Thompson

And presumably, these comorbidities can be associated with worse outcomes for people taking these antiretrovirals.

Nick Petrić Howe

Yeah, exactly. So one of the things that's very commonly associated with people who have HIV and are taking these antiretrovirals is fat accumulation in the liver. And this can lead to liver failure and cardiovascular disease. So, you know, obviously, quite bad news. And there's no particular medication currently available to treat that. But again, from another conference talk, it seems that people taking a weekly injection, were able to really reduce the effects of this accumulation of fat in the liver, and 29% of them even had a complete resolution of this, so no more liver disease after taking these weekly injections for six months. There is a caveat to this, though, which the drugs and this is true with or without HIV are associated with muscle loss, too. So for older people, this could be a particular problem. Like if you take these drugs, and you also lose muscle, it could make you increasingly frail, which wouldn't be a particularly desirable outcome.

Benjamin Thompson

So clearly, still things to sort of unpick then. But as you say, this is a conference talk, what happens next?

Nick Petrić Howe

Well, they'll obviously be a lot more studies to sort of really identify what's going on here, how these drugs might work, what might be the potential side effects and how to mitigate those side effects? But in principle, if these early results show promise, this could be a way to help treat some of these comorbidities. And one thing that one of the researchers interviewed seemed particularly interested in was that people with HIV can have what's called lipohypertrophy which is lots of abdominal fat, and this is associated with inflammation. And inflammation is not a thing you particularly want. But the semaglutide also seem to help resolve the inflammation as well as reducing the fat in the abdominal area. So that could be really helpful because inflammation can lead to all sorts of organ problems. So trying to nip that in the bud could be a real help to people with HIV.

Benjamin Thompson

Well certainly want to follow when the actual research is– is peer reviewed, no doubt, but it seems on the face of it a good news story. Let's move on to our second story today and it's my story and it's one that I read about in Nature. And it's based on a study published in the New England Journal of Medicine, and it's looking at how microplastics might be impacting our health.

Nick Petrić Howe

Well, yeah, obviously, microplastics is a topic that we've talked about a little bit on the podcast, but this is about specifically their effects on health, which I don't think is something that we've really talked about before. So what have researchers been finding?

Benjamin Thompson

Yeah, they've been looking at people who have been having surgery to remove fatty buildups called plaques from an artery in the neck. And this procedure can reduce the risk of stroke. And the reason that this paper has kind of come about, I suppose, is that microplastics, and for context, these are plastics that are less than five millimetres across, are kind of found everywhere. Like in the environment, like all over the place, and it seems like it's very likely that we are eating them drinking them and they can be found in human tissue. But as you alluded to there, nobody really knows if they're doing anything bad. Just because they're there doesn't mean that they are doing something unpleasant. So that's kind of where this paper has come in, because that's been really, really hard to evaluate. And the researchers behind it knew that the microplastics are attracted to fat molecules. So they looked in the plaques that were removed from the folk who had this operation. And in some instances, you know, in 150 of the people, in fact, they found these kind of jagged blobs, right, so evidence of microplastics, and even nanoplastics, which are even smaller. And these were, you know, common plastics that are, you know, plastic bags, plastic bottles, that sort of thing. And so what's happened is the researchers have followed that people have had this procedure. And the top line is that, that those with plastics in their plaques were four and a half times more likely to experience a heart attack or stroke or death in the 34 months post-surgery than those whose plaques were plastic free.

Nick Petrić Howe

Wow. So I knew that these microplastics were, you know, getting everywhere, but even inside, like the human body, and inside these fatty plaques, and I mean, obviously, I guess you can't say one causes the other, but there seems to be an association between having these microplastics and, you know, worse outcomes.

Benjamin Thompson

Yeah. And part of the research also showed that, that those were the plastics had higher levels of biomarkers for inflammation. You talked about inflammation earlier on, and that could potentially hint the root at how these particles could contribute to ill health. But as you say, it's absolutely not a smoking gun. Researchers — including the ones behind this paper, the authors of the paper themselves — have said that this work doesn't show that tiny pieces of plastic cause poor health right, there are other factors that could be involved that weren’t included in this study, things like socioeconomic status, which can be an important driver of ill health rather than the plastics themselves. And the study also only included people who needed the surgery, of course, so whether it can be extrapolated out to a wider population. You know, it's hard to say just yet, but it is certainly a start.

Nick Petrić Howe

I mean, I guess it's tricky, because these sorts of things are everywhere. But does this add any weight to the argument that we need to do more to sort of tackle the plastic problem?

Benjamin Thompson

I mean, I think it's certainly well, because at the moment, diplomats are trying to hammer out a global treaty to eliminate plastic pollution, okay. And then the idea is to finalise this by the end of 2024. And no doubt, this finding will feed into that, because I think some researchers are of the mind that the progress on the treaty has been going too slow. But obviously, as I say that there is a lot more to understand about causes and potential effects. There's a little sidebar to this as well, which is very interesting. And that is, how come 40% of the participants in the trial, didn't have any evidence of microplastics in their plaques, because these things are pretty much, you know, ubiquitous around the world. So it's an interesting little avenue of research as well to find out, is there something about their metabolism or genetics that leads to the plastics not being there? So yeah, it's a story that will run around, no doubt. And this is, you know, one step towards working out what the impact of these particles might be.

Nick Petrić Howe

No, definitely. And I think it's something that I'm particularly interested in whenever I eye up my food or anything from the environment and wondering what's in there. So it'll be interesting to see how this one plays out. And listeners, if you’re interested, for more on those stories you can check out the show notes and there will be some links there. And for will also be a link of where you can sign up to the Nature Briefing to get more like them delivered straight to your inbox.

Benjamin Thompson

And that's all we've got time for this week. But as always, send us your comments to podcast@nature.com or fire us a message on X @NaturePodcast. I'm Benjamin Thompson.

Nick Petrić Howe

I'm Nick Petrić Howe. Thanks for listening.