Podcast: Mapping childhood mortality, and evolving ‘de novo’ genes

Host: Benjamin Thompson

Welcome back to the Nature Podcast. This week mapping childhood mortality…

Host: Shamini Bundell

And de novo genes. I’m Shamini Bundell.

Host: Benjamin Thompson

And I’m Benjamin Thompson.

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Host: Benjamin Thompson

In 2015, the United Nations adopted targets known as the Sustainable Development Goals. These were intended, in the words of the UN, to ‘ensure that all people enjoy peace and prosperity by 2030’. One of the UN’s targets was to end preventable child deaths by 2030 – a laudable but ambitious target. So, how is the world doing? Well, things are improving, it seems. In 1950, there were almost 20 million child deaths. This has fallen to 5.4 million in 2017, despite a near tripling in world population. But this is just the broad picture of how the world is doing based on national level statistics. Focusing only on these may mean we miss out on what progress is being made at a more regional level.

Interviewee: Simon Hay

If you look at countries like Colombia, Guatemala, Libya, Panama, Peru and Vietnam, they’ve already at the national level reached the Sustainable Development Goal target, but within their boundaries, they have districts or municipalities that did not achieve that goal.

Host: Benjamin Thompson

This is Simon Hay, an epidemiologist from the University of Washington in the US. This week in Nature, he and a huge collaboration of researchers have been trying to get a more granular picture of childhood mortality around the world. They did this by mapping deaths in children under five in 99 of the world’s poorest countries between 2000-2017. To find out more, reporter Nick Howe called up Simon and started by asking him what this mapping has revealed.

Interviewee: Simon Hay

In the 99 countries that we looked at in this paper, mortality rates varied as much as forty-fold at the district level in 2017, so that’s obviously a massive variation between those countries, and even at the national level, so this is within a country, there can be up to a tenfold variation in that under-five mortality rate.

Interviewer: Nick Howe

Were there any places that had shown a lot of progress?

Interviewee: Simon Hay

Examples of exemplars if you like, of countries that have done very well, would include place like Rwanda. The good thing to sort of emphasise about Rwanda is if you look at the highest district level of child deaths in 2017, it was less than half of that of their lowest district level death rate in 2000, so they’ve done spectacularly well. And other countries like Peru and Senegal and Nepal have done incredibly well.

Interviewer: Nick Howe

And what about those countries that perhaps haven’t done so well?

Interviewee: Simon Hay

I guess one of the most depressing notes of this particular piece of work is that although we’ve made this spectacular progress, those areas with the highest concentration of child deaths in 2000, even though they’ve improved and universally I think we can make that statement, so everywhere has improved over that time, those ones that suffer the worst rates are largely the same as those suffering the worst rates in 2017. So, there are definitely areas of Africa, particularly across the Sahel, and other parts of the world where you have a much harder prospect of survival as a child than others.

Interviewer: Nick Howe

And those areas that still have quite a lot of progress to make, is there any unifying thing that is perhaps why they might not be doing so well?

Interviewee: Simon Hay

So, as you might expect, there are some common themes. So, poverty, grinding poverty, undernutrition, lack of vaccination and lack of universal healthcare would be common denominators in all of those places.

Interviewer: Nick Howe

And so, by finding this information where you say this area is doing well and this area maybe not so well, what can we do with that information?

Interviewee: Simon Hay

One of the things that we looked at in this study was not just if every country managed to meet a Sustainable Development Goal. We looked at something that we thought might be slightly more tractable which is could they look at the districts within their own country and say what have we done well in those ones where the mortality rates are the lowest and can we replicate that throughout the country. If each country could achieve that, they would save 2.6 million child deaths a year.

Interviewer: Nick Howe

And do you know of any examples of things that have been done that have made this progress that could potentially be used elsewhere?

Interviewee: Simon Hay

There are myriad different lessons to pick up in these almost 18,000 districts that we track over this period of time, and one of them that I would emphasise, I think, would be Peru. This is a country that’s made staggering progress over that period of time and had very specific policies about targeting anti-poverty and health interventions, using numbers, using metrics, to identify areas of the country that were poorest performing and proportionately send resources to those parts of the country.

Interviewer: Nick Howe

Considering the Sustainable Development Goal to end preventable child deaths by 2030, do you think this is an achievable goal?

Interviewee: Simon Hay

The short and honest answer to that is no. What I would say is that we have a massive opportunity to effect that change and we know how to do it. In my humble opinion, there are not any magic bullets that need to be created to massively impact in this domain. It’s essentially scaling up and repeating what we’ve done elsewhere in places that have been neglected. So, it’s a story of bringing success stories from one part of the world to another, rather than having some obstacle to making progress.

Host: Benjamin Thompson

That was Simon Hay from the University of Washington. You can read Simon’s paper along with a World View and an editorial over at nature.com.

Host: Shamini Bundell

Later in the show, we’ll be finding out why Japan is importing Ebola virus ahead of the Olympics – that’s coming up in the News Chat. Right now, it’s the Research Highlights, read this week by Dan Fox.

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Dan Fox

On 30 August this year, amateur astronomer Gennady Borisov pointed his telescope to the heavens and discovered a comet that’s travelled an incredibly long way. After the initial sighting, a team of researchers mined available data and showed that the comet’s orbit originated outside of our Solar System, making it only the second interstellar object observed. The team trained telescopes in the Canary Islands and Hawaii on the object and found it to be reddish in colour with a fuzzy tail that extends from a two-kilometre-wide nucleus. The comet, named 2I/Borisov after its discoverer, appears to look a lot like the comets that orbit within our Solar System. This makes it rather different to the first identified interstellar visitor Oumuamua – a cigar-shaped, rocky object that puzzled scientists when it was detected back in 2017. 2I/Borisov will move closer to the Sun until 8 December, before its orbit begins to take it back into deep space. Astronomers hope that this will give them plenty of time to study the comet in detail. Head over to Nature Astronomy to read more.

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Dan Fox

The extreme snowfall that occurred in northern Greenland in 2018 led to a breeding collapse for animals and plants the area, according to an international team of researchers.

Unprecedented weather led to snow accumulating at the start of the year, which lingered for so long that many species missed their chance to reproduce in the summer. The snow meant that plants flowered late, and there was little breeding among migratory birds or mammals. The researchers say that this is the first time in two decades of yearly monitoring that this kind of ecosystem failure has been observed. They also suggest that while a single non-breeding year is survivable, this event might offer insights into the future as the world’s climate continues to change. Read more over at PLoS Biology.

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Host: Shamini Bundell

Next up, you may be aware of how new genes are formed through the gradual process of mutation and natural selection on existing genes, but this might not be the case for all new genes. Some appear to arise seemingly from nowhere. These de novo genes are the subject of a feature written by Adam Levy, who’s here to explain more.

Interviewer: Adam Levy

The Atlantic cod is one hardy fish. If you’ve ever sampled the quintessentially British dish that is fish and chips, then you’ve most likely met the Atlantic cod. But there’s far more to this species than meets the dinner plate.

Interviewee: Helle Tessand Baalsrud

So, they show a remarkable ability to adapt to different environments.

Interviewer: Adam Levy

This is ecologist and geneticist Helle Tessand Baalsrud.

Interviewee: Helle Tessand Baalsrud

It can come into contact with freezing conditions, which is quite serious if you’re a cold-blooded species. If you come into freezing waters, that is potentially lethal.

Interviewer: Adam Levy

But this codfish has a death-defying trick up its sleeve in the form of an antifreeze protein.

Interviewee: Helle Tessand Baalsrud

They basically prevent ice crystals in their blood from growing, but no one knew how they evolved.

Interviewer: Adam Levy

So, Helle set out to trace the history of the gene behind the protein. Helle knew that all genes come from the material of pre-existing genes that is repurposed or recombined in some way, so she should have been able to see the relatives of the anti-freeze gene in the DNA of the cod’s cousins. But…

Interviewee: Helle Tessand Baalsrud

I couldn’t find any genes in any database that were similar to the antifreeze protein genes, and that was strange to me. I guess I was mostly trying to figure out what I was doing wrong.

Interviewer: Adam Levy

No matter how hard she looked, nothing turned up. And then Helle found something surprising, a body of literature from a field only a few years old that suggested that genes can be built from scratch from non-coding DNA, the DNA that doesn’t encode for useful molecules.

Interviewee: Helle Tessand Baalsrud

At first I thought I don’t have a story here because I can’t find their relatives and then that became the story.

Interviewer: Adam Levy

The cod’s antifreeze protein is an example of a de novo gene, a gene that’s born new rather than through changes to the code for well-oiled, pre-existing proteins. The first papers presenting the case for specific de novo genes only date back to 2006. Geneticist Aoife Mc Lysaght, one of the earlier researchers to publish in the field, still remembers how much scepticism there was for her work.

Interviewee: Aoife Mc Lysaght

Someone wrote, ‘When I saw the title of this paper, I couldn’t believe it was possibly true.’ Thankfully they read on and were convinced by our data, but that was the general attitude – you don’t get genes this way. It was just considered such an improbable route to the origin of a new gene.

Interviewer: Adam Levy

It took so long for researchers to convince themselves and others that genes really could be built from scratch because it’s so easy to overlook something. If you have a gene in one species but no relatives of that gene in the DNA of the species’ relatives, that could mean any number of things. Maybe your search just wasn’t good enough or maybe the species where the gene is missing just lost its copy of the gene.

Interviewee: Aoife Mc Lysaght

And so, in order to be confident that you’re looking at something that really is a de novo gene, you want to have positive evidence of the absence of the gene, not just that you can’t find it.

Interviewer: Adam Levy

Researchers want to be absolutely sure that the gene really did arise from non-coding DNA, so if they can find the non-coding DNA in related species that would have given rise to the gene in question, then they can be pretty certain that they have a de novo gene on their hands – the code for a molecule where no code used to be. But the field is still full of questions. How? There are plenty of ideas, including evidence of a grey area between gene and not gene, giving room for de novo genes to be beta tested before launch. How often? Estimates vary widely with one study identifying 15 in primates and another finding 60 in humans alone. And of course, why? Why would evolution do this? Why would a gene evolve from scratch rather than through tweaking the pre-existing code for carefully crafted molecules? Well, the very novelty of de novo genes could allow them to perform completely novel tasks.

Interviewee: Aoife Mc Lysaght

One possible idea is that a gene that originates this way is more radically different than a gene that originates by other routes, so every now and again it produces something that is different and useful.

Interviewer: Adam Levy

I’ve spoken to a lot of researchers working on this newly born field and while they’re generally certain that genes can be born de novo, there’s still plenty of disagreement about some of the fundamentals. But one thing everyone seems to agree on is that there’s plenty more to learn about these oddball genes.

Interviewee: Aoife Mc Lysaght

I think it’s going to be very interesting to see what happens in terms of de novo genes moving on to their next stage. So, we are confident now that they exist and they’re real and now we want to know a lot more about how they contribute, how they have made a difference in the evolution of organisms and how they have contributed to evolutionary innovation.

Host: Shamini Bundell

That was Aoife Mc Lysaght of Trinity College Dublin in Ireland. You also heard from Helle Tessand Baalsrud of the University of Oslo in Norway. You can increase your knowledge of how genes can form de novo over at nature.com, where you’ll find the feature written by Adam.

Interviewer: Benjamin Thompson

Finally then on this week’s show, it is of course time for the News Chat and I’m joined here in the studio by Heidi Ledford, senior reporter here at Nature. Heidi, thanks for stopping by.

Interviewee: Heidi Ledford

Thanks for having me, Ben.

Interviewer: Benjamin Thompson

For our first story today then, we’ve got a story about vaping, about e-cigarette use, and that’s something that’s becoming increasingly popular around the world, but in the US, there’s something of a health epidemic going on which has been linked to vaping.

Interviewee: Heidi Ledford

Yeah, so there’s been an outbreak, it’s been recognised over the past few months, of a very acute lung illness. It’s sickened about 1,300 people so far, and of those about 26 have died. It’s really sort of shaken up the United States and particularly those who use e-cigarettes, in part because many of the people who have been sickened by the outbreak are quite young and quite healthy, so even physicians, when they first started coming in, thought what is this because it was so unexpected to see these kinds of problems in people so young.

Interviewer: Benjamin Thompson

And what sort of problems are we talking about?

Interviewee: Heidi Ledford

They’re coming in, they’re having trouble breathing. Some of them have had to go on assisted breathing, so ventilators, for example. Some people have been discharged, it seems like they’re doing well and then they come back and they’ve got another serious episode, but researchers don’t quite know specifically what’s causing it. What they do know is that the people who are coming in have vaped, typically within the last couple of months, and a lot of them have vaped e-cigarettes that have contained THC, which is the active ingredient in marijuana and cannabis. Not all of them – so I think it’s somewhere around 70-80% of them. There’s some question that maybe some of the others just aren’t willing to admit it because that’s not legal in every state, but at this point it’s still unclear.

Interviewer: Benjamin Thompson

Well, it’s certainly a thorny one and there’s a paper that’s come out recently in the New England Journal of Medicine that’s maybe been trying to look at the molecular mechanisms behind some of these health problems.

Interviewee: Heidi Ledford

The paper was really interesting because it kind of undercut a really popular hypothesis. Early on, public health investigators recognised this possible link to THC and quite a few of those e-cigarettes also had a high concentration of vitamin E acetate, which is a very oily substance, and then we’re thinking okay, this is probably used to dilute the THC basically, so whoever sold this to you was trying to get more for their money and just diluting the product. That seemed to connect well with early reports that some of the people who had become sick from the outbreak had symptoms that were similar to what’s called lipoid pneumonia, which is a very rare condition and it happens when people breathe in oil, basically, and there are certain characteristics of that. You’ll see, basically, oily droplets in the lungs and in certain cells that kind of scavenge up debris in the lung. This report that came out earlier this month sort of undercut that. It was a pathologist who was looking at tissue slides from tissue taken from some of the patients who’d become sick and said no, ‘I don’t think that’s oily droplets, actually, and this doesn’t really look like lipoid pneumonia to me,’ and what he concluded then is that what we’re seeing is essentially just lung damage from exposure to something toxic.

Interviewer: Benjamin Thompson

And so, two schools of thought already then, I mean where do we go from here?

Interviewee: Heidi Ledford

Yeah, it’s tricky. I mean it was a relatively small sample size that they were working with – I think about 17 different patients contributed samples for that particular study. And that’s just kind of indicative of what happens in an ongoing investigation like this. It’s very tricky to track everything down and people are trying to use the data as it comes in. So, one person I was talking to said what I tell you this week may be totally wrong next week because we just don’t know yet what’s happening and things are changing so quickly.

Interviewer: Benjamin Thompson

And I guess with studies like these, they need to be done properly and take time as well.

Interviewee: Heidi Ledford

Yeah, I mean I think to get a solid answer probably on a lot of this it may take a lot of time. I think public health officials, from what I have heard, have largely given up the idea that they’re going to be able to find one single smoking gun for all of these people who have become sick and that in reality, there’s going to be some sort of complex causes or maybe if they’re lucky they can find a process such as, as an example, that dilution perhaps of the THC with some sort of oily substance, that gave them some hope that they had found a process that might be implicated, but now we’re not quite sure of that. But that’s the sort of idea that maybe we won’t find this one chemical that’s causing the damage but maybe there’s some something else that people are doing that is causing the damage. For public health officials, it’s really hard right now because they have to sort of tell people: ‘Be careful.’

Interviewer: Benjamin Thompson

A lot of people do use e-cigarettes, use vaping, as a way to cease using regular cigarettes. Do you think that this new study might affect people doing that and maybe make them not want to vape anymore?

Interviewee: Heidi Ledford

It’s a really tricky question, isn’t it, and it’s one I can’t really give people advice on what to do and I think public health officials are really struggling with that as well. It’s also something that depends a lot on where you live. So, this outbreak, so far, seems to be limited to the United States. I know that in the UK, for example, they’ve really tightly linked e-cigarette use and vaping to their smoking cessation efforts overall as a public health effort. They seem to be very worried that the outbreak in the US is going to send vapers in the UK back to their cigarettes, which is not something that public officials here in the UK want. But within the United States, maybe that question is a bit more complicated because of this outbreak and they don’t know yet what’s caused it. Again though, I certainly would not want to tell people yes, go back and embrace your cigarettes.

Interviewer: Benjamin Thompson

Let’s move on to our second story for this News Chat, Heidi. It’s just over 280 days at time of recording until the 2020 Olympics, which is of course being held in Japan, and the government there is doing some biosafety preparation.

Interviewee: Heidi Ledford

That’s right, so for the first time, they have imported a number of very dangerous viruses into the country for study. The most familiar to listeners will probably be Ebola, but there are four other quite dangerous viruses that they have brought in, including Marburg virus, Lassa virus and so on. And the idea is to help researchers develop ways to react if there is an outbreak during the Olympics.

Interviewer: Benjamin Thompson

Well, I guess these viruses require some pretty stringent handling sort of equipment.

Interviewee: Heidi Ledford

Yeah, it’s fascinating. So, apparently, they’re being brought in for study into a facility that was built in Tokyo back in 1981, but until this import did not actually handle pathogens of this level of security. Listeners may be familiar with the concept of biosecurity levels and this is biosafety-level-4, so this is as high as it gets. This is the first time in 38 years since the facility was built that it will actually be used for what it was intended for.

Interviewer: Benjamin Thompson

And what specifically is it going to be used for then?

Interviewee: Heidi Ledford

I think researchers have a number of studies planned, but one of the examples is to develop ways to tell if someone has become sick or infected with one of these viruses and is in the hospital, how can you tell when it’s safe to release them back into the public again.

Interviewer: Benjamin Thompson

I mean I’m sure this has caused some debate locally about whether this is necessary to import these incredibly dangerous viruses.

Interviewee: Heidi Ledford

Yeah, I mean as you can imagine, it’s typically the case around facilities like this. A lot of the residents of the neighbourhood surrounding it are quite concerned. Some have raised questions as to whether or not it was even necessary to bring in these pathogens or are the researchers just using the Olympics as sort of a pretext, an excuse to bring them in finally.

Interviewer: Benjamin Thompson

I guess, though, that this laboratory isn’t going to shut down after the Olympics but will keep researching?

Interviewee: Heidi Ledford

I think certainly researchers are hoping that they’ll be able to continue their research in this laboratory with these sorts of high-risk pathogens in the future. In the past, they had to apply to do this kind of work in special laboratories overseas, and that could be quite difficult. Often, they’re in high demand and with long wait times. And then Japan is also building a second laboratory that could handle these sorts of pathogens, and that one’s due to be completed in 2022.

Interviewer: Benjamin Thompson

Well, finally then, Heidi, on this one, do researchers think that it’s more likely that there will be an outbreak of a disease during the Olympics?

Interviewee: Heidi Ledford

No, not really. I think the consensus there is that the risk of an outbreak during the Olympics really isn’t much higher than at any other time, but as the researchers gain experience working with these viruses and have access to working with these viruses, they’re hoping that it’ll boost the country’s capacity overall to handle outbreaks.

Host: Benjamin Thompson

Thanks, Heidi. Listeners, for more on those stories, head over to nature.com/news.

Host: Shamini Bundell

And that’s it for this week. We’ll be back next week with all the latest from the world of science. I’m Shamini Bundell.

Host: Benjamin Thompson

And I’m Benjamin Thompson. Thanks for listening.