Podcast: Microbes modifying medicine and kickstarting plate tectonics

Host: Nick Howe

Welcome back to the Nature Podcast. This week, we’ll be finding out how microbes may modify medicine…

Host: Shamini Bundell

And hearing how plate tectonics first got moving. I’m Shamini Bundell.

Host: Nick Howe

And I’m Nick Howe.

[Jingle]

Host: Nick Howe

Ugh, I’ve got such a headache.

Host: Shamini Bundell

Big night last night? You have no tolerance for alcohol.

Host: Nick Howe

You can talk.

Host: Shamini Bundell

Better take some aspirin.

Host: Nick Howe

Aspirin never works for me.

Host: Shamini Bundell

So, you’re rolling on the floor after half a pint of cheap ale but have a high tolerance for aspirin?

Host: Nick Howe

Yeah, it is kind of weird, but people do have big differences in their responses to all sorts of drugs. Things like gender, age, size – they all seem to have an impact, and this week in Nature, there’s another idea.

Interviewee: Michael Zimmermann

Our hypothesis was that the microbiome might play a role.

Interviewer: Nick Howe

This is Michael Zimmermann, a microbiome researcher from Yale University. Since most oral drugs are absorbed in our gut, Michael wondered if the diverse microorganisms that live there could be a major reason people can react so differently to drugs. Michael’s been asking one core question.

Interviewee: Michael Zimmermann

Can microbes metabolise clinical drugs?

Interviewer: Nick Howe

Michael took 271 different drugs and incubated them with 76 different kinds of bacteria commonly found in the human gut.

Interviewee: Michael Zimmermann

The results were quite striking. We found that out of the test of 271, almost two thirds of those tested drugs could be metabolised by at least one of the bacterial species and strains that we tested.

Interviewer: Nick Howe

Drugs were disappearing from the petri dishes, which meant they must be getting altered in some way by the bacteria – in other words, metabolised. And metabolising drugs may change their efficacy or make them stop working completely. Michael wanted to identify which genes in the bacteria could be responsible for all this metabolisation. So, he and his team took one bacterium that was metabolising lots of drugs and chopped up its genome. Then they inserted the chunks of DNA into a bacterium that previously had no effect. If the modified bacteria could metabolise a drug, then the piece of DNA that had been inserted was responsible.

Interviewee: Michael Zimmermann

We were able to identify a total of 30 gene products from the microbiome that collectively metabolised 20 different clinical drugs.

Interviewer: Nick Howe

Seeing things in a petri dish is one thing but seeing them in complex organisms is another, so Michael wanted to test these findings in animals. He used his new knowledge of drug-busting genes to manufacture strains of bacteria that metabolised the drugs and strains that couldn’t. He inserted each of these strains into mice that previously had no gut microbes at all and then gave the mice the drugs.

Interviewee: Michael Zimmermann

We found that the drug reaches the lower intestine where most of the bacteria live and we also found that the genes that we tested also converted the drug in the mouse.

Interviewer: Nick Howe

The test in mice used single bacterial strains. But humans all have unique cocktails of microorganisms in their guts. With all those microbes interacting, could this also be happening in humans? Michael looked for signs of drug metabolism in faecal samples from a range of healthy people.

Interviewee: Michael Zimmermann

And what we find there is actually first of all, there was quite a big difference between communities from different individuals. So, some communities, microbial communities, metabolised certain drugs very quickly, whereas others were very slowly or even incapable of metabolising a given drug.

Interviewer: Nick Howe

The abundance of the genes Michael had identified in the human samples was a good predictor of how quickly certain drugs would be metabolised. For other drugs, though, it was the presence of a particular species or strain of bacteria that had the biggest impact. Melissa Herbst-Kralovetz, a microbiome researcher not associated with this study, thinks this may pave the way for doctors to choose the most effective drug for individual patients.

Interviewee: Melissa Herbst-Kralovetz

These bacterial genes that metabolise particular drugs, we can use that as a way to predict whether a patient is going to respond or not respond to a particular drug as well as potentially if they will have toxic side effects.

Interviewer: Nick Howe

Up until now, most studies have shown correlations between the microbiome and the effectiveness of drugs, but this study is one of the first to dig into how these associations work. Melissa was impressed by the effort to draw causal links.

Interviewee: Melissa Herbst-Kralovetz

It’s really exciting how comprehensive this study was and how they utilised a lot of different methods and incorporated these mechanistic experiments to better establish this causal link between how the bacteria are metabolising these drugs.

Interviewer: Nick Howe

Better understanding the causal links in drug responses may mean scientists are able to do more with our gut microbes.

Interviewee: Melissa Herbst-Kralovetz

Unlike out host genome, the gut microbiome is modifiable through diet, antibiotic usage, faecal microbiome transplant, and this could really have important implications for expansion or contraction of the metabolic functions of that community.

Interviewer: Nick Howe

That was Melissa Herbst-Kralovetz from the University of Arizona in the US. You also heard from Michael Zimmerman from Yale University, also in the US. You can read Michael’s paper over at nature.com.

Host: Shamini Bundell

Later in the show, we’ll be hearing about protests in Hungary – that’s coming up in the News Chat. Now though, it’s time for the Research Highlights, read this week by Josie Allchin.

[Jingle]

Josie Allchin

Elephants have a nose for quantity. Several non-human species, including elephants, use sight to identify the greater of two quantities. But what about smell? In the wild, it is thought elephants rely much more on smell, hearing and touch to find food and water. So, scientists developed a simple test to see if their skills were transferable across the senses. They used six captive elephants living on the grounds of a Thai hotel. Each of them were offered two buckets of tasty sunflower seeds. One bucket contained more than the other, but both had lids hiding the seeds from view. The elephants could still smell them though. When they chose to open a bucket, and eat what was inside, on average they opted for the one with the most seeds. The bigger the difference between the buckets, the more likely the elephants were to choose the bigger bounty. According to the authors, understanding how elephants use their sense of smell while foraging might help aid conservation efforts. Sniff out that paper over at the Proceedings of the National Academy of Sciences.

[Jingle]

Josie Allchin

A new AI can identify a person’s activity using only sound. Previous work has used artificial intelligence and video to identify human activity with many promising applications, like alerting caregivers of a medical emergency. But continuous video surveillance raises the possibility of leaks, hacks and loss of privacy. So, researchers turned to high-frequency sound waves. They designed a speaker array that emits a high-frequency signal above the range of human hearing. Surrounding the speakers are microphones that pick up the high-pitched tones as they bounce back from the environment. The reflected sound could be used to work out if volunteers in the room sat, stood, walked or fell, and after training, an artificial intelligence could identify an individual’s activity with up to 97.5% accuracy, all with fewer privacy concerns. Find that paper over at Applied Physics Letters.

[Jingle]

Host: Shamini Bundell

Next up, reporter Adam Levy is taking a look at a surprising story about the surface of planet Earth.

Interviewer: Adam Levy

Science can draw some surprising links between what seem to be completely separate ideas – gravity linking an apple falling from a tree to the motion of the planets, for example. And now, a study linking plate tectonics to the Earth’s climate… maybe. But we’re jumping ahead. The Earth’s crust is broken into huge several-kilometre-thick plates. As many of us learnt in school, these plates move around on the liquid mantle beneath in a process known as plate tectonics.

Interviewee: Stephan Sobolev

So, this is like pieces of ice moving on the river.

Interviewer: Adam Levy

This is Stephan Sobolev, author of the study out this week.

Interviewee: Stephan Sobolev

Plate tectonics is at least one of the most important processes in geology. For me, I think nobody could just avoid thinking about it.

Interviewer: Adam Levy

Our school geography courses may have made it seem like the science behind plate tectonics is done and dusted, but it’s still unclear what allows the plates to move around here on Earth.

Interviewee: Stephan Sobolev

The upper part of the Earth is relatively cold and very strong, very rigid. It should be just absolutely stable, but it is moving.

Interviewer: Adam Levy

Subduction zones – where one plate dives under another – should experience too much friction to allow movement. Something must be lubricating the boundary. Liquid water helps, but it’s not enough to explain the emergence and evolution of plate tectonics. Another option, Stephan suggests, would be sediment – eroded materials from land helping the plates overcome the friction at the boundaries. But how to test this? Some computer models have indicated that sediment could play a crucial role, but Stephan wanted to find evidence from Earth’s distant past.

Interviewee: Stephan Sobolev

Fortunately, there is a lot of data, geochemical data, already about how rock composition was changed during the history of the Earth and what was happening with plate tectonics during the Earth’s history.

Interviewer: Adam Levy

The information from rocks suggests that plate tectonics hasn’t always operated at the same pace. There have been times when it’s been more and less active.

Interviewee: Stephan Sobolev

And what you find is that sometimes it was a period of active plate tectonics and then it was a time of where not so much was happening and again, something was happening and again, nothing was happening.

Interviewer: Adam Levy

More geochemical data from rocks suggests that the active periods did indeed coincide with increased amounts of sediment. So, what was causing such a fluctuation in sediment over Earth’s history? Well, Stephan’s surprising answer is climate. There have been periods when the Earth has been much colder than it is today, such as the proposed period of ‘snowball’ Earth, around 700 million years ago. When the ice during this period gradually retreated, it would have caused huge amounts of erosion.

Interviewee: Stephan Sobolev

And according to our study, this was the kick-starting of a new phase of plate tectonics which we can call the modern phase of plate tectonics.

Interviewer: Adam Levy

Stephan thinks a similar kick-start to plate tectonics might also have taken place some 2 billion years ago, but could sediments from glaciers really have led to the emergence and evolution of our planet’s plate tectonics?

Interviewee: Bob Stern

This is kind of like a court case, and interrogating the historical record is fraught with uncertainty.

Interviewer: Adam Levy

This is geoscientist Bob Stern, who didn’t work on this study. Bob is sceptical that the circumstantial evidence we currently have from rocks is strong enough to demonstrate such a crucial role for sediments.

Interviewee: Bob Stern

I think it’s clear that once plate tectonics gets going, the role of sediments is very important. I don’t think sediments started plate tectonics.

Interviewer: Adam Levy

Stephan, on the other hand, thinks there’s over 50% chance that his sediment hypothesis is correct.

Interviewee: Stephan Sobolev

Which is not too bad for the processes of the early Earth.

Interviewer: Adam Levy

Bob remains firm in his scepticism. When we spoke, I asked him, do you think there’s some magical bit of data or something that could be shown to you, that you’d be like, oh hang on a second, it looks like sediments might be able to…

Interviewee: Bob Stern

Yeah, that’s an interesting question. I’d have to think about that more, probably with a few more beers.

Interviewer: Adam Levy

For Stephan, though, the study opens up whole new areas of research. For one, the list of processes to include when simulating plate tectonics has just got a little longer.

Interviewee: Stephan Sobolev

We need actually to build a kind of new type of Earth system model which will include deep processes, plate tectonics, surface erosion processes and even climate.

Host: Shamini Bundell

That was Stephan Sobolev, who’s based at the German Research Centre for Geoscientists in Potsdam. You also heard from Bob Stern at the University of Texas at Dallas in the US. Read the study plus a News and Views in the usual place.

Interviewer: Nick Howe

Last up on the show, it’s time for the News Chat and I’m joined once again by Nisha Gaind, Nature’s European Bureau Chief. Nisha, hi.

Interviewee: Nisha Gaind

Hi, Nick.

Interviewer: Nick Howe

Thanks for coming to join me. As always, we’ve got a couple of interesting stories to discuss, but I wanted to start by talking about some protests in Hungary. Nisha, can you tell me what’s happening here?

Interviewee: Nisha Gaind

Yeah, so this is a story we’ve been following for quite a while at Nature, and it’s to do with academic freedom in Hungary, which seems to be the target of some efforts by the government, possibly to oppress academic freedom, or at least that’s what the international community is saying. Now, on Sunday, scientists in Hungary marched through the streets of Budapest and they were marching specifically to protest against a law, a proposed law, that would give the Hungarian government direct control of the country’s top research institutes and that, they say, is problematic because it erodes their academic freedom and their autonomy.

Interviewer: Nick Howe

So, what else has the government been doing that may impact academic freedom?

Interviewee: Nisha Gaind

So, we’ve been seeing this sort of battle between the Hungarian Academy of Sciences and the government, that has been going on for quite a few months now, and it’s important to understand that in Hungary a lot of research is done by institutes that are run by the Academy of Sciences. And what we’ve been seeing is this effort by the research ministry, firstly to take control of the institutes, and also to take control of the budget of the institutes and redirect it to other places. Now, the research ministry says that this is part of an effort to increase and improve the amount of innovation that the country does, but researchers say this is a worrying restriction on their academic freedom, that they should be free to do the kind of research that they want without being guided by the government.

Interviewer: Nick Howe

So, what specifically are the academy’s problems with the government’s position?

Interviewee: Nisha Gaind

There are a couple of things. So, one of the main parts of the law is giving the ministry control of the institutes, which they object to on academic freedom grounds, but there’s also a second part of the law that seems to give the government ownership of the Hungarian Academy of Science’s properties. The academy says that that part in particular is unconstitutional.

Interviewer: Nick Howe

And how does this compare to academic freedoms that other countries have?

Interviewee: Nisha Gaind

So, this is precisely the problem. It seems like academic freedom is being particularly oppressed or suppressed in Hungary, and it seems to be by a government that is run by Viktor Orbán, which has been quite a controversial government and has been at the focus of criticism from the international community. So, researchers in Hungary really want to be left alone in a way. They want to their academic freedom to be retained as it has since the fall of communism 20-some years ago, and that’s what they’re protesting to keep.

Interviewer: Nick Howe

And has the government responded at all to the protesters?

Interviewee: Nisha Gaind

So, that’s something that we don’t know yet. The protests happened just a couple of days ago, but we understand that there are some negotiations happening between the Hungarian Academy of Sciences and the government. The government says that they want to introduce this draft law into parliament very soon, so it seems like they are forging ahead with their plans, regardless of this outcry.

Interviewer: Nick Howe

Well, Nisha, it sounds like we’re going to see more of this story in the future so we’ll have to keep an eye on that, but for our next story, I wanted to move on to an anaesthetic journal that have tried a new thing where they had two sets of conclusions. What’s happening here?

Interviewee: Nisha Gaind

This is a story from the realm of reproducibility, which is something that many people in the science community are passionate and interested in because there is a reproducibility crisis. Now, anaesthetics research is one field in which this crisis seems to have been building in the past few years. There have been lots of questions over the reliability of anaesthetics research, so one journal – The British Journal of Anaesthesia – is trying this quite unusual experiment, and they have asked two sets of researchers to review a scientific study and write their own conclusions.

Interviewer: Nick Howe

Did the conclusions agree, did they disagree? How did it play out?

Interviewee: Nisha Gaind

So, this is the really interesting thing. The original study investigated a link between stronger doses of anaesthetic with earlier death in older patients, and it ruled out that link. But the second independent discussion said actually, the trial on which the study was based did not include enough patients to make that conclusion about death.

Interviewer: Nick Howe

So, why might this be a good tool to help this reproducibility crisis?

Interviewee: Nisha Gaind

So, reproducibility experts who have looked at this approach say that it’s actually a really positive approach and the reason is that many efforts in reproducibility mostly look at methods and results sections. They look at papers explaining each part of their methods section properly so that they can be replicated by others and things like that. But so far, there has been little focus on discussions sections, but the people who are running the trial say that that’s a really important part because of bias, spin and the over-interpretation of results.

Interviewer: Nick Howe

And what has been the response of researchers?

Interviewee: Nisha Gaind

So, not everybody thinks that it is a positive way forward. One person that we spoke to said that this type of independent discussion would inevitably draw on the same people who are already asked to review papers, and they suggest that a better solution to trying to get rid of this type of bias is to enforce existing rules that are laid out in author guidelines for journals – for example, to make studies’ weaknesses clearer and to avoid speculation in discussion sections.

Interviewer: Nick Howe

So, this example was in an anaesthetic journal – are we going to see this in other journals more widely?

Interviewee: Nisha Gaind

Yeah, so at the moment, it’s just being trialled in one journal and it’s very much the push of the editor of this journal. We don’t know yet whether it will be picked up by other fields and other journals but certainly, the people involved in the trial and reproducibility specialists say it is something that other fields should consider.

Interviewer: Nick Howe

Well, another one to keep an eye on then. Nisha, thanks for joining me. Listeners, for more on those stories head over to nature.com/news.

Host: Shamini Bundell

That’s all from the podcast for this week, but you might be interested in a new video we’ve got on our YouTube channel. It’s a tale of three lizards and what happens when you introduce a new top predator. Go to youtube.com/NatureVideoChannel for that. I’m Shamini Bundell.

Interviewer: Nick Howe

And I’m Nick Howe. See you next time.