Norovirus could spread through saliva: a new route for infection?

Host: Nick Petrić Howe

Welcome back to the Nature Podcast. This week: a new route for enteric virus infection.

Host: Benjamin Thompson

And an exotic kind of matter made from only neutrons. I’m Benjamin Thompson.

Host: Nick Petrić Howe

And I’m Nick Petrić Howe.

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Interviewer: Nick Petrić Howe

More than one billion people every year are infected by enteric viruses. These are a group of viruses, including things like norovirus, that infect the gut and typically cause a range of unpleasant symptoms like diarrhoea and vomiting, and in more serious cases can lead to death. Now, these viruses have a specific route of transmission, which has been very well established. Or at least, so has been thought, as this week in Nature, there’s a paper suggesting that researchers might have been overlooking a very important way that enteric viruses spread. I called up one of the authors of the new paper, Nihal Altan-Bonnet, to find out more, and started by asking what the conventional thinking is on the transmission route of these viruses.

Interviewee: Nihal Altan-Bonnet

These viruses infect the intestines and replicate in the intestines, and then shed into the faeces and then spread to the next individual through the faecal-oral transmission route. And what that simply means is the virus in the faeces gets ingested and make their way down to the intestine, and the cycle begins anew.

Interviewer: Nick Petrić Howe

Yeah, and that's sort of the first thing you see when you Google these viruses. And you see stuff like you need to wash your hands, you need to think about sanitation, and that sort of thing. And also, ‘enteric’ means intestinal, so they sort of have it in the name. But you actually saw in your new paper something quite different.

Interviewee: Nihal Altan-Bonnet

Yes, so what we found is that these viruses also replicate very robustly in the salivary glands, and shed in saliva, and that saliva is infectious in itself.

Interviewer: Nick Petrić Howe

And so, the first thing that occurs to me is it's been so sort of well understood that they have this sort of faecal-oral route. I’m wondering why you were looking at the saliva in the first place. How did you get there?

Interviewee: Nihal Altan-Bonnet

We got there in a sort of unexpected way. The animal models to study these viruses are typically very young mice who are still suckling on their mother's breast milk. So, when we were studying these viruses for another question, we would inoculate these pups orally with these viruses, and then put them back to suckle on their mother's breasts. And what we noticed is that their mothers were getting infected with these viruses. But unusually, only the mother's breasts were getting infected. And we ruled out that the mothers were getting infected through, say, licking the faeces of their pups, and we ruled out a number of other scenarios, and what we were left with was that the pups were transmitting these viruses potentially through their saliva during the process of breastfeeding. So, it was really a surprise because the term ‘enteric virus’, our classical way of thinking about these viruses was that only these viruses would replicate in the intestines.

Interviewer: Nick Petrić Howe

And so, what were the sorts of things that you were observing? What were the sorts of like specific things that you were seeing that were telling you that this is definitely happening in the saliva?

Interviewee: Nihal Altan-Bonnet

So, we were seeing the viruses replicating inside the salivary gland cells and being shed in copious amounts into the saliva. And we would collect the saliva from these animals and orally inoculate other animals with just the saliva, so completely bypassing the classical faecal transmission route, and we were able to show that that saliva was actually quite infectious and was able to transmit the enteric infection to other animals.

Interviewer: Nick Petrić Howe

And this work as well, you've discussed it in mice, and obviously, humans, we’re very self-interested animals, so I'm wondering what the sort of likelihood is that a similar transmission route through saliva occurs in humans?

Interviewee: Nihal Altan-Bonnet

We think it's very likely and, in fact, when we look into the literature, there has been many reports of these viruses being detected in human saliva. But it has always been chalked up to being a contamination from a person, for instance, vomiting, and thus getting their oral cavity contaminated. But among these reports, there are instances where the researchers would note that the individual was asymptomatic. There was no vomiting, yet there were copious amounts of these enteric viruses in their saliva. So, little things like that suggest to us that this is likely to take place among humans as well.

Interviewer: Nick Petrić Howe

And do you have a sense of how much of a factor this could be in how the viruses are spreading? Is it equivalent to the faecal-oral route? Is it more? Is it less? Do you have a sort of sense of that?

Interviewee: Nihal Altan-Bonnet

My feeling is that it could be a much more prevalent route of spreading of these viruses, and there are a couple of reasons for this. So, one is we are constantly spewing out salivary droplets when we're talking, when we're coughing, when we're sneezing, and so viruses being in these droplets could get to other individuals quite efficiently, we would think. Secondly, the faeces actually, although it does contain these viruses, it's also quite a hostile environment in the sense that the faeces contain a lot of degradative enzymes, degradative molecules. All of these degradative activities, we have some evidence for actually make the faecal viral population less infectious. And so, in the saliva, we think that the viruses may be more stable and, in fact, more potentially infectious even.

Interviewer: Nick Petrić Howe

So, then, what do you think are the implications of this work?

Interviewee: Nihal Altan-Bonnet

Well, there are multiple implications. One is I think we need to rethink the way we devise our public health practices for preventing the spread of these viruses. And it could be even simply wearing a mask. I mean, we're all used to wearing masks now to prevent coronavirus transmission. It could be that when there is an outbreak in, say, a school or a cruise ship, wearing a mask might be one of the ways to slow down the spread of these viruses.

Interviewer: Nick Petrić Howe

That was Nihal Altan-Bonnet from the National Institutes of Health in the US. To find out more about this research, head over to the show notes for a link to the paper.

Host: Benjamin Thompson

Coming up on the show, after decades of hints of its existence, researchers may have finally created something that is only known to exist in neutron stars, and it may be able to tell us more about the glue that holds matter together. Stick around for that. Before then, though, just time to flag up that we've got a new podcast series beginning on Friday. It's called ‘Nature hits the books’, and unsurprisingly, it's a book show. My first guest will be the science journalist, Ed Yong, and we'll be chatting about his new book An Immense World, which is all about the realm of animal senses. And I'll tell you what, we cover some ground, looking at how our own view of the world is just a sliver of what can be sensed by other creatures and how this blinkered take has affected our understanding of the animal world. Look out for that wherever you get your shows. Back to today's show, though, and here's Dan Fox with this week's Research Highlights.

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Dan Fox

Billions of years ago, as the Solar System was forming, Jupiter became the biggest planet by devouring kilometre-sized space rocks. Until recently, scientists had not been able to peer inside Jupiter and determine its composition. So, to have a look, researchers used data from NASA's Juno spacecraft to analyse the gravitational pull of the gas giant and work out what lies inside. The team assessed various models of the planet's interior and found that the model which best matched the data had surprisingly high amounts of elements heavier than hydrogen and helium. These heavy elements suggest that Jupiter consumed large space rocks as it formed and rules out another theory: that a diet of many tiny pebbles led to Jupiter's size. Read that research in full in Astronomy and Astrophysics.

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Dan Fox

Megalodon, the extinct shark that was one of the largest carnivores ever to have lived, feasted on the flesh of other top predators, according to chemical analysis of its teeth. The relative amounts of two forms of nitrogen in a carnivore’s teeth indicate whether they ate animals that were high or low on the food chain. Researchers analysing the nitrogen in the teeth of several extinct and living shark species found that the ratio within Megalodon teeth suggests that its diet was rich in other large predators. This probably included now-extinct whales and even other megalodons. In fact, it dined on so many big predators that the shark has no analogue among living marine carnivores. This discovery makes the gigantic shark’s extinction 3.5 million years ago even more mysterious. One theory is that megalodon was outcompeted by the great white shark, but this research found that ancient great whites had a diet containing fewer high-level predators than the megalodon, so it may not have competed with the larger shark. Sink your teeth into that research in Science Advances.

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Host: Nick Petrić Howe

Last week, after decades of searching, physicists have found something that’s never been seen before in a lab – a system of four neutrons – a tetraneutron! This is exciting for physicists, as theorists have disagreed wildly on whether tetraneutrons can even exist. And finding out will shape our understanding of the glue that binds an atomic nucleus together – the strong nuclear force. You see, protons and neutrons happily sit within the same nucleus – two of each make a helium atom, for example. But for many years, physicists have wondered whether it might be possible to switch out the two protons in helium for two more neutrons to make a tetraneutron! But it isn’t quite as simple as just kicking out some protons. Although the strong nuclear force draws neutrons together, a quantum rule called the Pauli exclusion principle has the opposite effect. So, putting four neutrons together makes the whole thing inherently unstable. Proving that the tetraneutron exists, even fleetingly, and understanding its properties would help physicists to pin down the interplay between these forces, and even understand the similar rules that underpin neutron stars –the nucleus’ massive cosmic cousin. Now, a group of researchers claim to have done just that. Reporter Lizzie Gibney caught up with one of them, Stefanos Paschalis, to find out more, and started by asking, just how long have physicists been trying to track down the tetraneutron?

Interviewee: Stefanos Paschalis

This has been going on for six decades. So, from the 1960s, people have been trying to detect this particle.

Interviewer: Lizzie Gibney

Wow, that’s a long time. So, for your experiments, you started with a radioactive isotope of helium called helium-8, and that's cool because it basically has a normal helium nucleus at its core, so two protons, two neutrons, but then these four extra neutrons floating about it. How did you go about turning that into your tetraneutron?

Interviewee: Stefanos Paschalis

So, the idea we had is that inside helium-8, it is well understood that there is a well-formed alpha core. The alpha core is made up of two protons and two neutrons, and it's a very compact nucleus that forms the nucleus of normal helium-4 we see around us. So, the idea was that if we suddenly removed this alpha particle, it’s like pulling the carpet underneath, then it will leave these four neutrons in this configuration that they were around this cluster, but without the clustering. And those neutrons there can interact and give us access to study these different neutron systems. So, that's how we generate and we access it, and it's been a pioneering approach which hadn't been tried before.

Interviewer: Lizzie Gibney

So, you did that exact thing. You knocked out the alpha particle. How did you then measure what you saw because neutrons aren't charged, so they don't really interact with anything, right? So, how can you measure what they look like after you've knocked the alpha particle out?

Interviewee: Stefanos Paschalis

The way we performed the experiment was to measure very precisely the proton which constituted the target in our experiment, and the alpha particle that we knocked out. So, those two are charged particles, which means we can analyse them with a very strong superconducting magnet and determine their momenta. Once we measure the properties of those two particles very precisely, we can reconstruct what was the state of the four neutrons that were left behind. And when we did this, we saw, to our surprise, two very distinct structures, one that we interpret to be the decay, the phase-space decay of these four neutrons, and one which we can only associate with this resonance structure of the tetraneutron, so a very characteristic structure that these four systems prefer.

Interviewer: Lizzie Gibney

And why do you call this system of four neutrons together a resonance rather than a tetraneutron?

Interviewee: Stefanos Paschalis

A resonance state is a state that is quantum mechanically well formed, but is not bound enough to form a stable system. This resonance system then lives for a very short time before it decays. And this reflects basically that the system has a certain frequency at which it resonates. It has a characteristic frequency which describes it.

Interviewer: Lizzie Gibney

So, it has a frequency that tells you this is something other than just four free neutrons. There is something going on that binds them together, but it's just kind of gone in the blink of an eye.

Interviewee: Stefanos Paschalis

Exactly, so it’s this characteristic frequency, this natural frequency, that tells us that it's something more than just four particles flying apart.

Interviewer: Lizzie Gibney

And it sounds like an incredibly complex thing to detect. And I think, over the years, there have been some other claims in the past that people have seen something similar. What makes this discovery different, or what makes it a discovery?

Interviewee: Stefanos Paschalis

In this particular case, because of the reaction that we chose to generate these four neutrons, we obtained a very clean signal, standing on what we call a very low background. So, we had a very statistically significant signal in our experimental measurement. The statistics also that we got has been many times greater than what people have used before. So, the previous claims were with four events in 2016, that a lot of people of the community were having trouble to accept that it was a statistically significant result. And in our case, we had about 400 events corresponding to this population of four-neutron system.

Interviewer: Lizzie Gibney

So, now that we have a tetraneutron, can it help us to pin down which of the models that describe the strong nuclear force, the force that binds this temporary system, which of those are correct? What have we learned from this experiment?

Interviewee: Stefanos Paschalis

Well, we've learned that the interplay between the strong nuclear force and the Pauli exclusion principle has to be handled very carefully in order to be able to reproduce such systems. And by fine-tuning these interactions on our models, we can then apply them to other systems, all the way up to astrophysics, astrophysical sites, such as supernovas, where all the elements that we see around us are created. So, understanding and constraining the models through nuclear physics experiments like this can help us build and validate these models and extend them all the way to the Universe and these astrophysical sites like supernovas and neutron stars.

Interviewer: Lizzie Gibney

So, this kind of data could actually give us some kind of data point that helps us to understand what's going on in a neutron star millions and millions of kilometres away.

Interviewee: Stefanos Paschalis

Exactly, yes, it will be an important ingredient for this research field as well.

Host: Nick Petrić Howe

That was Stefanos Paschalis from the University of York here in the UK, chatting to reporter Lizzie Gibney. To find out more about tetraneutrons, check out the paper in the show notes.

Interviewer: Benjamin Thompson

Last Friday, the US Supreme Court struck down the constitutional right to abortion. In the wake of this ruling, Nature has been turning to research to ask what we can expect in the coming weeks and months. And joining me to discuss this is Lauren Wolf, Nature's Americas Bureau Chief. Lauren, hi.

Interviewee: Lauren Wolf

Hey.

Interviewer: Benjamin Thompson

Before we get into the science, could you just lay out in practical terms what this decision means for people in the US?

Interviewee: Lauren Wolf

Well, what this decision means at its most bold is that the federal right to an abortion in this country is no longer protected, and that means that the Supreme Court has now handed over decisions about abortion rights to individual US states. And ever since Roe v. Wade, which is the decision from 1973 that protected abortion rights, states have tried to chip away at it and gotten sued, and we've kind of gone back and forth. And up until now, there's never been a time when Roe was really, really threatened. But now that this has happened, it goes back to the state's decision in terms of what the abortion rights are for people living in that state. And a lot of states had what are called trigger bans, so there were about 13 of those states that have trigger bans, which means immediately upon Roe being overturned, those states ban abortion or severely restrict it in some way, and we've already seen a lot of those go into effect. For a lot of other states, they're likely to either ban or severely restrict abortion. And there are some states that actually protect abortion rights. And so, you get this patchwork of rights, and people will have to make a decision about whether to continue their pregnancy or pay the expense and travel to a state that allows abortion to go get one there.

Interviewer: Benjamin Thompson

And this decision was not unexpected. It was leaked several weeks ago. What have researchers been saying since then?

Interviewee: Lauren Wolf

Yeah, we talked to people when it was leaked by Politico, and we talked to people just on Friday, when the official ruling came down, and I think, for a lot of people, it's not that it was unexpected but when you actually see it on paper, it's still really hard to come to grips with for a lot of people for whom might seek abortion, but also for people who have been studying abortion and who have shown through research that it's an important right for people to have.

Interviewer: Benjamin Thompson

And scores of researchers, so economists, folk working in the public health sphere and what have you, submitted evidence to the Supreme Court last year when it heard the case Dobbs v. Jackson Women's Health Organization, which is ultimately what led to Roe v. Wade being overturned.

Interviewee: Lauren Wolf

Yeah, so we did a story about this, the fact that these researchers were submitting evidence to the court, when the court decided to take this case or hear it. And all of these researchers, as you noted, hundreds of them, submitted what are called amicus briefs to the Supreme Court ahead of time. And the important thing to say here is that the court doesn't have any obligation to take into consideration these briefs, and people from all sides can submit them, but basically, their evidence or opinions etc. that could help in the weighing of the case. And so, because this is such an important case and because there are decades of research about what the right to an abortion means to people and what it means to them in terms of their health and the economics of the country, these researchers supported that evidence.

Interviewer: Benjamin Thompson

And maybe you can lay out some of that evidence then that researchers did submit?

Interviewee: Lauren Wolf

Maybe as a baseline, the important thing to think about is, who are the people who usually get abortions? Those are some of the most fundamental pieces of research that are done. And some of these studies have shown that in the US, one in four women will get an abortion by age 45, at least in the time before Roe was overturned. 75% of those women who choose to have an abortion come from a low-income bracket, and almost 60% of them already have children and can't afford or don't want any more. Usually, the people who don't have access to birth control and who might be in a position to need an abortion are younger people or poorer people. And people below the poverty line have a five times higher rate of unintended pregnancies than people in higher-income brackets. So, that's kind of a baseline level. And when people look at the safety of a legal abortion procedure, what they see is that the death rate involved with abortion is actually, for the person receiving it, much lower than then it would be if they had gone through with a birth. It's just a fact that death during childbirth is a thing that happens. Another headline, though, is that in the US, maternal mortality is actually quite high compared to a lot of other high-income countries. And what is being predicted, based on a post Roe world, is that those numbers in the US are now going to get worse. And we're going to see, I should note, that they're going to go up disproportionately in minority groups, right. So, also in the US, the maternal mortality rate for Black people, it is a lot higher than white people. And so, those are the people who are often affected by seeking an abortion, and so we're expecting that those numbers are going to go up here too.

Interviewer: Benjamin Thompson

And abortion rights can very much impact on other health care and economic aspects as well, right?

Interviewee: Lauren Wolf

So, one of the biggest studies over the years that has delved into some of those issues is called the Turnaway Study. And, as I explained earlier, right, there have been states that have challenged Roe v. Wade over the years and tried issuing our own laws and restrictions, kind of setting up maybe depressingly the perfect situation for researchers to study what happens when a person is able to get an abortion versus when someone is ‘turned away’. And you adjust for age and all the other different factors and you can see that the health care for people who have to go through with an unintended pregnancy, they have negative health outcomes, their children have negative outcomes. But if you just look at the economics you can see, I'm just looking at one Turnaway Study result, but after five years of watching these two groups of people, you could see that the group that was turned away experienced a 78% increase in overdue debt and an 81% increase in financial events like bankruptcies and evictions, compared to the other group, which didn't see any kind of change, in terms of they were able to get their abortion and then went on with their lives. And they've done a lot of studies looking at also mental health because that's one of the arguments that anti-abortion critics have made, is that when people have an abortion, that they have some mental-health issues such as depression or anxiety, and what these studies have shown is that that's not true. The two groups don't marry in that way.

Interviewer: Benjamin Thompson

And one of the things you mentioned, Lauren, is that there is this kind of patchwork aspect to the US now, in terms of where someone can access an abortion and where they can't. And there's been a lot of research into what effect this will have for people who want or need to travel to a clinic.

Interviewee: Lauren Wolf

Yeah, for sure, and those researchers have predicted that about 54% of US women seeking abortions will have to travel further than they would have previously to get to their nearest abortion provider. And in terms of mileage, their travel distance would increase from about 36 miles on average to 274 miles, which, of course, can be a real financial burden. And so, you'll see that, I saw this statistic, maybe three quarters of the people who are seeking one will still find a way to get it, but the barrier will be enough to turn a quarter of people away from it.

Interviewer: Benjamin Thompson

And one of the potential consequences of restricting access is that people will end pregnancies without clinical supervision. What is the research saying about that?

Interviewee: Lauren Wolf

What researchers have said is what we're going to start seeing is, for people who don't have the option of going to an abortion clinic to have the procedure, they will more often seek a medication abortion, and this is available. Places like the World Health Organization say that a medication abortion is safe and effective, used correctly, guided by people who know what they're doing. And so, researchers are predicting that they're going to see more of that, and we are, I've already read articles today, just showing that these pills are getting sold out and people are hoarding them, especially in states that are already seeing bans going into place. And I think then there's also the prediction that we're also going to see more laws put on the books to try to prevent people from gaining access to those types of pills. And, of course, I think one other concern that researchers have is that for people who don't understand what a medication abortion is, or know that it is available to them, or where to get one, that they might try to take matters into their own hands in a different way, right, self-manage an abortion in a different way. Researchers have definitely seen people who have tried taking other substances that are not safe, or inserting things into their vaginas and then end up having some serious harm to themselves or to the child if they weren't successful. And so, I think that's another concern about what is to come.

Interviewer: Benjamin Thompson

So often in our chats we end with, ‘And so, what now?’ And in this case, it's such a huge issue. What are researchers thinking about as they move forward?

Interviewee: Lauren Wolf

Yeah, I think some of the researchers who have been studying this for years and years are going to keep doing that. They're going to keep looking to examine the effects of denying someone abortion rights because we have a whole new, unfortunately, set of experimental conditions, so that in the future, when more policy decisions come up, that there will be even more evidence to be able to recommend what should and shouldn't be done. And separately from that, there's also just the issue of researchers, research organisations, research institutions, and how they can now, going forward, support the students and staff that they have who might now find themselves at a university in a state that doesn't allow abortion. And so, I think that there's lots of questions in the coming days and months. And if you kind of look at this from a global perspective, in the past 25 years, you've seen 32 other countries have expanded abortion access, based on the fact that you see this research and that it's good for society in terms of the wellbeing of individual people, their reproductive rights and equality. And so, I think, right now, what we're all kind of struggling with a little bit is that the US has now taken this step backward instead of forward with these other countries.

Interviewer: Benjamin Thompson

Well, thank you for joining me today, Lauren. And listeners, we'll put links to all of our stories relating to this ruling in the show notes.

Host: Nick Petrić Howe

That's all for today for the podcast. But there's a new video on our YouTube channel. It's part of the inequality special that we featured on last week's show. It's all about the stats and figures that illustrate the unequal toll of the pandemic. You can find that on our YouTube channel, and we'll put a link to it in the show notes. I’m Nick Petrić Howe.

Host: Benjamin Thompson

And I’m Benjamin Thompson. Thanks for listening.