Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • NATURE PODCAST

Podcast: Politician scientists, human genetic 'knockouts' and East Antarctica's instability

This week, politician scientists, human genetic 'knockouts' and East Antarctica's instability.

In this episode:

00:41 It’s a knockout

Rare human ‘knockouts’ – people missing both copies of a gene – help scientists understand the genome. Research paper: Saleheen et al.; News and Views: Human genes lost and their functions found

07:37 Politics and PhDs

A physicist runs for office. Careers: Candidate science; Andrew Zwicker

14:51 Research Highlights

Cephalopods edit their RNA, and a virus may trigger coeliac disease. Research Highlight: Squid and octopuses often edit their RNA; Research Highlight: Virus can spark coeliac disease

16:22 Antarctic alarm bells

Scientists used to think the East Antarctic was stable. Now they’re having to think again. Feature: The threat beneath Antarctica; Nature Podcast: Rising tides; Tas van Ommen

21:16 News Chat

Muon hunt starts at Fermilab, and Cassini begins its final ducks and dives. News: Muons’ big moment; News: Cassini’s science swan-song

Never miss an episode: Subscribe to the Nature Podcast on Apple Podcasts, Google Podcasts, Spotify or your favourite podcast app. Head here for the Nature Podcast RSS feed.

doi: https://doi.org/10.1038/d41586-019-03092-4

Transcript

This week, politician scientists, human genetic 'knockouts' and East Antarctica's instability.

[Jingle]

Interviewer: Kerri Smith

This week: if the human genome is a parts list…

Interviewee: Sekar Kathiresan

…Now we’re basically in the position to understand exactly what lacking each part means.

Interviewer: Adam Levy

And the scientist who became a politician.

Interviewee: Andre Zwicker

Running for public office is and was more difficult than getting my PhD in physics.

Interviewer: Kerri Smith

Plus, how new research on East Antarctica is ringing alarm bells. This is the Nature Podcastfor April the 13th2017. I’m Kerri Smith.

Interviewer: Adam Levy

And I’m Adam Levy.

[Jingle]

Interviewer: Kerri Smith

[Music]The genome is often described as a parts list for building a body. In the human genome, the list has about 18,000 entries. But what if one part is removed – or in the scientific language – knocked out?

Interviewee: Sekar Kathiresan

Characterisation of those knock-outs have actually been one of the main tools for us to understand what any given gene in the genome does.

Interviewer: Kerri Smith

This is Sekar Kathiresanand he’s talking about mice. Scientists can deliberately knock genes out in model organisms like the mouse, but now they’re setting their sights of a knock-out project for humans. Disclaimer: nobody is running around knocking out human genes as part of a grizzly experiment. Geneticists are instead looking for naturally occurring human knock-outs: people carrying genes that are completely non-functional. Cheaper and more widely deployable sequencing methods are making it possible to go looking for people who each have a different part missing.

Interviewee: Sekar Kathiresan

And now we’re basically in a position to understand exactly what lacking each part means.

[Music]

Interviewer: Kerri Smith

Sekar and his colleagues refer to this effort as the human knock-out project. Before it could start there was some detective work to do. They had to find groups of people more likely to be carrying knocked out genes. Every one carries two copies of each of their genes and for a gene to be completely knocked out, both copies of it need to be broken. A good place to look is in groups who are closely related because here the chances are higher of both parents having a mutation in the same gene and therefore passing two wonky copies onwards to their children. Sekar and his team knew that cultures where cousins marry cousins would be good places to look. Geneticists call cousin marriage consanguinity.

Interviewee: Sekar Kathiresan

And if you look at the map of consanguinity rates around the world, the highest ate is actually in Pakistan.

Interviewer: Kerri Smith

The team contacted 10,000 participants and sequenced the bits of their genomes that code for proteins. Nearly 1 in 5 of the participants had at least on gene knocked out. The team also had clinical data available on the heart health and metabolism of their participants and when they looked for traits that correlated with the missing genes, they found a few surprises. Four participants in the study had no working copies of a gene called APOC3. Scientists are already interested in this gene as they know from previous work that one missing copy can reduce the risk of heart disease by lowering levels of a dietary fat. But they didn’t know if anyone could survive with both copies missing. On the line from Pakistan, geneticist Danish Saleheen

Interviewee: DanishSaleheen

These are the first APOC3 that have been discovered in the world.

Interviewer: Kerri Smith

Because the team were able to re-contact people that had been sequenced, they could go a few steps further than genetic studies usually can. They got back in touch with one participant living a couple of hours from Karachi in southern Pakistan. Here’s Danish again.

Interviewee: DanishSaleheen

When we called back this participant, we noticed that he was from a small isolated village and the inhabitants of that village had been practising consanguinity for several generations. His wife, who was also his first cousin, was a knockout and as a result all of their 9 children were knock-outs.

Interviewer: Kerri Smith

This village helped the team address a question they had about APOC3. If missing one copy is good for fat metabolism, is missing both even better? To find out, they gave the volunteers a fat challenge.

Interviewee: Sekar Kathiresan

Basically, a big milkshake…

Interviewer: Kerri Smith

… To see how they metabolised fat. Sekar Kathiresanagain…

Interviewee: Sekar Kathiresan

And then measuring their blood for every hour for 6 hours afterwards, we saw that basically the group that completely lacked the APOC3 gene, essentially, there was no budge in the blood triglycerides after a meal, giving us confidence that actually this gene, when completely inhibited, is tolerated, that people are living. And, that they have this favourable phenotype of actually not budging their blood fat after a meal.

Interviewer: Kerri Smith

This study goes to show that not all knock-outs are harmful and it provides the team with a list of possible targets for improving heart disease. The latest study finds similar rates of knock-outs as previous studies done in similar populations. Here’s David van Heel who, last year, published a report on the genomes of people living in Bradford in the UK, of Pakistani descent.

Interviewee: David van Heel

So we sequenced 3,222 people and we found 1,111 genotypes which were loss of function and then we went onto study one single knock-out of interest to us which was a gene called PRDM9. This gene, PRDM9, was thought to be lethal in animal models and we found a healthy mother with PRDM9 knocked out and has 3 healthy children.

Interviewer: Kerri Smith

A cautionary note there for anyone assuming that mice are just little humans. [Music] Sekar Kathiresan thinks it should be possible in the next 5 to 10 years to complete the human knock out project: for every gene in the human genome that can tolerate being absent, to find a person who is missing it. The two groups that have studied Pakistani genomes plus others that have studied elsewhere plan to pool their data into one large catalogue. That would be a boon for the genetics community, but Danish Saleheen, working with the participants in Pakistan can see a couple of ways it already benefits the human knockouts themselves – especially those living with disease.

Interviewee: Danish Saleheen

Sometimes it is very difficult for these individuals to not understand what is causing the high rates of disease in them and in their loved ones so just to know the cause, first of all the relief, then second of all they do tell us that there is something they are going to advocate in their family, their family members as well as the wider community, to reduce this practice of first cousin marriages.

Interviewer: Kerri Smith

David van Heel cautions that studies like his are not trying to make a comment on cousin marriage itself. He points out that it’s only in a handful of cases that knock-outs cause severe disease and other factors like smoking in pregnancy or mothers being older, can lead to similar rates of genetic disorder.

[Music]

Interviewer: Kerri Smith

Thank you to David van Heel and co-authors Sekar Kathiresanand Danish Saleheen. Their paper is at nature.com/nature. So is a News & Views, and the catalogue of human knock-outs will be available soon.

Interviewer: Adam Levy

In the Research Highlights, the creatures that edit their genetic instruction manual on the fly, and how a virus can trigger coeliac disease. But first, scientists all over the world will join the March for Science, taking to the streets to call on politicians to fund research and stand up for evidence based policy making. Scientists have tended to shy away from politics but that could be changing. Things like the election of Donald Trump – a president who questions whether Climate Change is real – as well as talk of alternative facts and fake news are motivating scientists to engage with politics and even run for political office. Noah baker spoke to one scientist who ran a successful campaign and became an Assemblyman.

Interviewer: Noah Baker

So, first off, would you be able to let me know your name and your affiliations so we’ve got that on record.

Interviewee: Andrew Zwicker

Sure, my name is Andrew Zwicker and I’m a physicist at Princeton University.

Interviewer: Noah Baker

And, you have another affiliation as well I suppose.

Interviewee: Andrew Zwicker

I’m also in my first term. I’m an Assemblyman in the state of New Jersey, representing the 16thlegislative district.

Interviewer: Noah Baker

Now, that gets to the core of the beginning of this story which is why… why have you done this? Why have these two affiliations? Why switch from science to politics?

Interviewee: Andrew Zwicker

So – and of course I haven’t switched completely – I actually have this wonderful life where I go back and forth between the world of science and the world of politics, sometimes multiple times in a single day. I got interested in this because there’s a real connection between a government funding innovative things and difficult things – projects that aren’t ready for the private sector – and that as a corollary creating businesses and new inventions. But what I saw also was that this idea which has driven so many inventions in the 20thcentury in the United States, I felt like it had been lost. That was the first thing. The second was that a colleague at Princeton, he ran for Congress in New Jersey and won and became the second physicist ever elected to Congress. When he decided it was time to move on to the next phase of his life, I decided why not run for Congress with no political experience whatsoever. Crazy idea, but I said I could continue to complain or I could try to do something about it. So I did, and I won because of the fact that I’m a scientist, because I have made one promise which is to run on a platform that says I will use evidence to make my decisions. In the end I’m saying I’m going to take a scientific approach as much as I can to politics.

Interviewer: Noah Baker

That’s an approach that’s worked for you in this case but do you think that’s an approach that standardly would be appealing to an electorate, to say that you’re going to go for a scientific approach to the way that you approach the politics and decision making.

Interviewee: Andrew Zwicker

I think it has such appeal. Most of the general public is very frustrated by the political process – feels broken down. Here in the United States it’s felt like Democrats and Republicans no longer can work together on anything and this goes well beyond this current administration and so this idea of saying well let’s at least begin with a common set of facts and then we can have a debate on what the public policy implications are of those facts. While that’s not always easy to do in reality, as a philosophy, it absolutely is appealing across most political spectrums.

Interviewer: Noah Baker

So the question remains then: why are there not more scientists in office? Why do you think you’re one of the trail blazers in this area?

Interviewee: Andrew Zwicker

So I tell people that running for public office is and was more difficult than getting my PhD in physics and it is so different than what we as scientists do on a day to day basis. A scientist makes a presentation of his or her work. They have a PowerPoint presentation behind them. They read the slides. You get some questions; you move on. In politics there’s no slides and people are asking you about their lives. And you’re making decisions that can have an impact on thousands or tens of thousands or more, depending on what level of politics you’re at. So it’s very difficult to makes that transition but it’s so crucially important in my opinion that we have more scientists serving at all levels of government because what a scientist is really good at is taking a large amount of information and trying to solve a big problem – both absorbing it and coming up with a logical, data-driven solution. We just need more of that.

Interviewer: Noah Baker

Do you think that there’s going to be more of a push for scientists to become involved in politics now?

Interviewee: Andrew Zwicker

I think now, certainly. Climate change in particular has driven more and more scientists to start to talk and write about public policy and now we’re seeing more people who want to run for public office. I have, over the last weeks and months actually had people from all over the country calling me – scientists asking how I did it, what I did, whatever advice I could give them, because they’re strongly considering doing the same thing.

Interviewer: Noah Baker

Now, you are currently working in this kind of sweet spot where you’re still maintaining a roll in a scientific institution as well as doing the political work you are doing and that seems like quite a lot to do with your time. Do you think that this sort of conflict of trying to do two things may be a problem for scientists? Are they going to essentially have to leave their career if they want to move into politics?

Interviewee: Andrew Zwicker

This is one of the biggest problems. I was already not in a full-time research career when I did this. I was doing a lot of science education work as well as public outreach, so for me, from there to politics, I had already taken a major step towards that. This is one of the biggest issues. You will have to give up a piece of your scientific career to do this and for many scientists who have spent their life studying what they love, that’s too much to ask. The flip side is you don’t have to give up your entire scientific career and the potential both personal rewards and the impact that you can have on your community, or your state or country or society is enormous. And so there are risks and there are rewards and each person’s going to have to balance that and consider that carefully.

Interviewer: Adam Levy

That was physicist and politician Andrew Zwicker. You can read more about his route to office and how other scientists are engaging in politics in this week’s Careers section.

Interviewer: Kerri Smith

Coming up, the region everyone thought was dependable and stable, until they took a closer look. Before that, this won’t take a minute. It’s the Research Highlights with Shamini Bundell.

[Jingle]

Interviewer: Shamini Bundell

If DNA is an instruction manual, most animals follow it to the letter. They have to stick to it pretty closely as they use it to make RNA and then proteins. But some cephalopods, the group including squid and octopuses, they rip the manual apart. Scientists know they use enzymes to edit RNA, producing proteins that look quite different to those encoded by the DNA. Now, scientists have found that this editing is particularly common in the more complex, cleverer cephalopods, and in RNA sequences associated with brain function. The creatures can evolve, not by rewriting the DNA itself, but by keeping the genome more static and tailoring it on the fly. That paper is in Cell.

[Jingle]

A common virus could be partly to blame for coeliac disease where eating gluten triggers the immune system to attack the gut. Researchers have fed mice a component of gluten and also infected some of them with a gastric bug called reovirus. The infected mice had higher levels of inflammatory immune molecules in their intestines. When the mice also had a genetic predisposition to coeliac disease, the reovirus brought on gluten intolerance. The immune molecules seemed to mistake gluten for a virus and that triggers the intolerance. The journal Sciencehas that paper.

[Jingle]

Interviewer: Adam Levy

What happens in Antarctica over the coming years will shape the world. Vast amounts of ice sit on top of land and so there’s enormous potential for sea level rise. For many years, all of eyes have been on the West Antarctic Ice sheet where many glaciers are rapidly retreating. In contrast, East Antarctica seemed…

Interviewee: Tasvan Ommen

Inert, cold, high, thick ice sheet on top of mountainous bed rock.

Interviewer: Adam Levy

This is Tas van Ommen of the Australian Antarctic division in Tasmania. He’s been studying the icy continent for years.

Interviewee: Tasvan Ommen

I started with the Antarctic division in 1994, so that’s quite a while now.

Interviewer: Adam Levy

And in that time researchers have discovered that East Antarctica, a region the size of the United States of America, may not be as secure as previously hoped. Tas shared his thoughts on how the East Antarctic and our understanding of it have evolved.

[Music]

Interviewee: Tasvan Ommen

We’ve been flying airborne surveys now for nearly every year since 2008, building up and filling in the gap, if you like. We now have a picture where large portions of East Antarctica are more similar to the West based on bed rock that goes deep below sea level. So that raises the prospect, like West Antarctica, of an ice sheet that can’t retreat from a warming ocean without the ocean following it in land. I didn’t expect that in just a decade or so, for my career to go from this quest for knowledge through to a very acute question.

[Music]

Interviewee: Tasvan Ommen

It really made us sit up and open our eyes wide. I think the more we flew, the more we saw these extensive canyons and fjords, in fact, deep in land which showed that the ice sheet had once upon a time been much smaller. That raises the clear prospect that if it’s retreated in land in the past, that that’s clearly possible in the future. More to the point, we can tell from the geology that once you move past a certain coastal margin where it is now, retreat is really quite rapid in geological terms before it reaches an inland stable position. And we’re talking about sea level contributions of well over a metre; two metres to three metres of sea level rise in this one catchment alone. That’s comparable of course to the sea level rise potentially in all of West Antarctica which is around three to three and a half metres. It would make a radical impact that over a time scale that we still can’t define very well at all. I mean, one of the problems we have is that policy makers are asking for information about what to expect over to the end of this century and the IPCC report said that it was up to a metre or so but then covered the uncertainties by saying there could be a few tens of centimetres more than that sea level rise by the end of the century if processes we don’t understand really well cut in and they’re actually the very processes that we feel that we’re seeing in West Antarctica at least at the moment.

[Music]

Interviewee: Tasvan Ommen

The latest estimates we’re seeing put the plausible upper – low probability – but plausible upper sea level rise at 2 metres or even more by the end of this century. Now, this is at a very low percentage probability, but of course we insure our houses against low probability events and I think as we look at the future of the planet we have to absolutely consider what is plausible by the end of the century and beyond.

[Music]

Interviewee: Tasvan Ommen

It’s sort of a little bit split brain at times. So, you’ve got this simultaneous curiosity and relevance drive, but then you step back from time to time and look at the implications of what you’re learning from the planet and it’s quite a sobering thing.

[Music]

Interviewer: Adam Levy

That was Tas van Ommen. For more on the East Antarctic, make sure to check out the Feature in this week’s Nature, and check out the Nature Podcastfrom the 31stMarch 2016 for a discussion on how scientists are trying to pin down Antarctica’s role in future sea level rise.

Interviewer: Kerri Smith

Finally this week it’s the News Chat and two amazing physics stories brought to us today by Lizzie Gibney.

Interviewee: Lizzie Gibney

Hello Kerri.

Interviewer: Kerri Smith

Now first we are up for a bit of muon magic, as you told me. The subject line of the email was – as it was circulating around – as you were writing this story. What is a muon, first of all, before we guess why they’re magical?

Interviewee: Lizzie Gibney

Great question. So, a muon is very much like an electron, which people are probably more familiar with except it’s much, much heavier. So, it’s 200 times heavier than an electron. It’s kind of like a cousin to the electron.

Interviewer: Kerri Smith

And are they hard to spot? East to spot? All around us?

Interviewee: Lizzie Gibney

They don’t exist very naturally on earth but you do get them coming in in cosmic rays and you can produce them in accelerators.

Interviewer: Kerri Smith

And why are they magic, then?

Interviewee: Lizzie Gibney

Well, because, when we’ve been doing studies of muons over the years, a very particular property called its magnetic moment, doesn’t seem to match up with theoretical predictions, and one possible reason for that is because we’re not taking into account some whole other new particles that are out there. So this might actually be a lever that we can use to crack open the standard model which you’ve probably heard me talk about before, which is a great theory – very, very successful theory that describes particles and all their interactions, used basically throughout particle physics, but which we know is incomplete, which doesn’t account for dark matter, which doesn’t really account for gravity – really quite important things. So, we’ve got the standard model. It’s not enough. We’re looking to go beyond it and muons may help us. And physicists have tried to look at them before and analyse their moment, their properties, to see if they could shed any light on the standard model.

Interviewee: Lizzie Gibney

Exactly, so, measurements of the muon have been going on since, I think, the late 1950s and they’ve been getting better and better. At the same time the theoretical predictions have been getting better and better. And, about 15 years ago, the Brookhaven experiment which was a very similar set up to this muon that we’re going to be talking about, found that when they did all their calculations there was quite a difference between the experimental results and the predicted results. Now, because of the statistics involved, the number of muons they could use – that wasn’t statistically significant. It was about 3.4 for those who care about that kind of thing. So there was a chance of, I think, about one in a thousand that it could have just cropped up in the noise and it doesn’t actually mean anything but now we’re in a position where we have a new experiment ready to go which should be able to take data from many more muons and it’s more precise. At the same time, theoretical predictions have got a lot better. So there’s a chance now that if that anomaly remains, we’ll be able to show it beyond doubt and then we’ll know something really weird is going on.

Interviewer: Kerri Smith

This new experiment is at the Fermilab facility in the states and it is launching, starting, heating up next month: May.

Interviewee: Lizzie Gibney

Exactly. So, muons will start circulating in May. They’ll have a little bit of time for commissioning, calibrating the experiment, and then they hope that by the end of 2018, end of next year, they may well have something exciting to report. And can I tell you a bit about the crazy way in which these muons are telling us something?

Interviewer: Kerri Smith

Yes please.

Interviewee: Lizzie Gibney

So, what we’re doing is – as I mentioned – is measuring the magnetic moment of the muon. It’s influenced by these things called virtual particles which are any kind of regular particles – think photons, quarks. They can pop in and out of existence as long as they do it in a very, very short time – blink of an eye. And that’s happening all the time around us. And when they do these calculations, when the theorists put pen to paper to figure out what this magnetic moment should be, they have to take into account all of those virtual particle processes. The question is, is there some other particle, or some other particles, which are in that virtual particle soup that we should be taking into account in our calculations but we’re not.

Interviewer: Kerri Smith

Here they still have a question – the identity of the particle – but they will at least be able to sort of tell if it’s missing.

Interviewee: Lizzie Gibney

They can tell if something’s missing. So they will say for sure we know there’s something going on that we can’t account for.

Interviewer: Kerri Smith

And then we’ll have to wait another 15 years to build another piece of kit to find out.

Interviewee: Lizzie Gibney

Well, who knows. The LHC might directly find them. There are lots of theories that say, for instance, they maybe exist at energies that the LHC can find but they are very rare so they are only going to crop up when the LHC’s been running for a decade or whatever. They might slowly work their way out of the statistics.

Interviewer: Kerri Smith

Virtual, missing particles, buried in a pile of statistics. Now we’re going to move on – you were saying the way they’re looking for these muons is looking at them wobble rather than smashing them into each other, but we are going to go back to some other physicists smashing something into something else because the space craft Cassini is just now starting its final descent to crash into Saturn.

Interviewee: Lizzie Gibney

Exactly, so Cassini’s been there for 13 years and now it’s the 5 month countdown and we’ve got a great story this week from my colleague Alex Witze which is looking at the science that it’s going to do in the next 5 months. And as we’ve seen with previous missions is when you’re coming to the end anyway, you can do things that are a little more daring, that you might not do at the start of a mission. And in this case, Cassini is actually going to fly between Saturn and its inner rings and hopefully find out the answers to a whole load of mysteries in doing that.

Interviewer: Kerri Smith

What has it been able – in the brief highlights so far – what has it been able to find in the time it’s been orbiting the planet thus far?

Interviewee: Lizzie Gibney

Well it’s taken some fantastic pictures. There’s a high resolution camera on Cassini. In fact, one picture was really nice. It took, looking back through Saturn, backlit by the sun, with earth as a little pale teeny-tiny plae dot very far away. And it studied Titan, Saturn’s largest moon which has these bubbling methane lakes, and the planet’s magnetic field and a whole raft, really, of measurements.

Interviewer: Kerri Smith

And what will it be able to do in the next 5 months then, as it descends towards the planet itself?

Interviewee: Lizzie Gibney

One thing it’s going to look at are these strange propeller shaped gaps in the rings which they think might be cause by little tiny moonlets, so it’s going to take some pictures of those. Saturn’s got loads and loads of moons, of all different shapes and sizes. It’s going to look at the chemical make-up of the rings. They’re mainly made of ice but there are some other substances in there, and then the big question that they want to answer is how old are the rings? And how did they form? And a way in which they’re going to do that is they’re going to get the gravitational field of Saturn and the mass of the rings and use that to figure out how big was this object that probably disintegrated to create the rings?

Interviewer: Kerri Smith

All that and more to learn as Cassini dives around and towards Saturn in the coming months. Thanks Lizzie for those updates. Follow our on-going coverage of Cassini’s grand finale and find out more about muons at nature.com/news.

[Jingle]

Interviewer: Adam Levy

That’s all for this week. Thanks for tuning in. if you enjoyed the show, why not recommend us to a friend or leave us a little review or rating on iTunes so that we can reach even more people who might like a weekly shot of science.

Interviewer: Kerri Smith

Next week we’ll be taking a little break for Easter so our next show will be dropping on April the 26th. If that’s too long to wait, why not check out the entire Nature Podcastarchive on our website nature.com/nature/podcast. Until next time, I’m Kerri Smith.

Interviewer: Adam Levy

And I’m Adam Levy.

[Jingle]

Subjects

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing

Search

Quick links