Podcast: Reviving brains, lightning, and spring books

Host: Benjamin Thompson

Welcome back to the Nature Podcast. This week, we’ll hear how researchers are reviving cells in dead pig brains, learn about the latest spring science books…

Host: Shamini Bundell

And find out the secret structures within lightning. I’m Shamini Bundell.

Host: Benjamin Thompson

And I’m Benjamin Thompson.

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Host: Benjamin Thompson

First up in the show, we’re talking about neuroscience. For obvious reasons, whole brains are difficult things to work with in a lab, and most lab-based neuroscience is done on tissue samples or small cultures of brain cells. But this week in Nature, a paper presents a new way to study brains, by plugging them into a machine that partially restores their function. Reporter Nick Howe has been talking to the researchers involved to find out more.

Interviewee: Nenad Sestan

The idea for this study came about from a very routine observation. We and other scientists have observed that viable cells can be harvested from post-mortem brains and cultured in a dish. This indicates that cells in the post-mortem brain still have the capacity to be revived.

Interviewer: Nick Howe

This is Nenad Sestan, a professor of neuroscience at Yale School of Medicine. The idea he’s talking about is whether it’s possible to restore brains after death. When the heart stops beating, brains lose oxygen and begin to deteriorate rapidly. This deterioration was thought to be irreversible.

Interviewee: Nenad Sestan

We were very surprised by this finding, and that’s why it took us five years before we submitted the paper. We just wanted to be sure that this is what we are seeing.

Interviewer: Nick Howe

The team took brains from pigs that had been slaughtered for food production. Four hours after death, they hooked up the brains up to a machine called BrainEx. BrainEx pumped, or perfused, a blood-like substance into and out of the removed brains and simulated the function of the heart, lungs, kidneys and liver. The artificial blood had chemicals in it that the team hoped would encourage the recovery of the brains, such as compounds that prevent cell death. And indeed, by hooking up the brains to BrainEx, they were able to revive the cells and restore some functions for around six hours.

Interviewee: Nenad Sestan

What we can show is that basically the brain – and that means the cells – is consuming oxygen and glucose, which are two major nutrients and it’s producing CO₂ and other metabolites that are clear signs that cells are viable.

Interviewer: Nick Howe

What’s more, Nenad and his team showed that the brains retained some of their functions. They demonstrated inflammatory responses similar to living brains, their synapses were able to fire, and the brains responded to certain drugs.

Interviewee: Nenad Sestan

And we show that basically the cells in our perfused brains have all the signs that are associated with normal functioning cells.

Interviewer: Nick Howe

This is a striking result says Simone Di Giovanni, a professor of neuroscience at Imperial College London, who wasn’t associated with this study.

Interviewee: Simone Di Giovanni

I think the extent to which they were able to preserve the survival of many cells into the brain and the extent to which they were able also to show that there was some function at the cellular level, also preserved for many hours. So, this was quite surprising and very interesting.

Interviewer: Nick Howe

Having restored functions to cells, Nenad and his team believe that isolated brains could be a useful model system for answering neuroscience questions. Simone agrees.

Interviewee: Simone Di Giovanni

This can be something that we could exploit in the future to understand cellular and molecular mechanisms of disease or physiology.

Interviewer: Nick Howe

So, the brains could be useful models for testing drugs or answering neurological questions. They wouldn’t be able to answer every question though, as the brains were not fully functioning. But, this was by design. If at any point activity associated with consciousness or sensation was detected, Nenad and his team would have stopped the experiment immediately, on ethical grounds. The brains were not alive, but they weren’t exactly dead either.

Interviewee: Simone Di Giovanni

At the cellular level, these brains are very close to being alive, but if we consider life of a brain as the expression of the functionality of the brain, then they are very, very far from being alive.

Interviewer: Nick Howe

In other words, the isolated brains didn’t show the organised activity that we see in living brains – they would be unable to learn, remember or perceive the world. But the individual cells within them showed signs of being alive. Because these brains sit in an in-between zone, being neither alive nor exactly dead, they challenge our assumptions about death itself. Our current understanding is that death means irreversible loss of brain function.

Interviewee: Nita Farahany

This new research study suggests that that may not be the case.

Interviewer: Nick Howe

This is Nita Farahany, a professor of philosophy and law at Duke University.

Interviewee: Nita Farahany

The irreversibility that we thought existed with the loss of brain function from oxygen deprivation may in fact at least partly be reversible. And if that’s the case, our existing definition of death, which is so important to things like being able to declare a human legally dead, so important for us to be able to have that person qualify for organ donation, for example, those things are now fundamentally challenged by the possibility of being able to reverse the damage from loss of oxygen to the brain.

Interviewer: Nick Howe

Another consideration is that restoring function to a brain after death could lead to consciousness and sensation. Whilst in this study there was no EEG activity, which is a marker of consciousness, the study used neuronal activity blockers and anaesthetic. It’s possible that these prevented any form of consciousness arising.

Interviewee: Nita Farahany

There’s still a gap between this study and achieving any kind of consciousness or any kind of sentience-like capabilities, but that doesn’t mean it’s impossible. It just means that there may be more work to do before it could get there.

Interviewer: Nick Howe

This study raises many questions, both scientific and ethical. The study will need to be replicated and attempts made to understand whether consciousness could occur and if it did, how scientists and society should respond to that possibility. Despite the challenging ethical questions, Nita and her colleagues think it’s important that this research continues.

Interviewee: Nita Farahany

We are enthusiastic about this research and think that it’s really important that this research be allowed to proceed. So, we’re excited about the possibilities that this offers, to offer insights into studying the brain, and we also recognise that this research team really is a model for trying to address the ethical questions that research raises, particularly when ethics hasn’t caught up with the science.

Host: Benjamin Thompson

That was Nita Farahany from Duke University. She and group of other ethicists have written Comment pieces in this week’s Nature about this study, which you can find over at nature.com/opinion. You also heard Simone Di Giovanni from Imperial College London and Nenad Sestan from Yale School of Medicine. You can read Nenad’s paper over at nature.com.

Host: Shamini Bundell

As Nick said in his piece, this research raises quite a few questions, and listeners, you might have some of your own. If you head over to the story about this work at nature.com/news, you’ll find a box where you can send in your questions which our reporting team will then try to answer in a follow-up news article.

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Host: Benjamin Thompson

Shamini, spring has very much sprung here in the UK, and that means it’s time for that regular and, dare I say, iconic symbol of springtime.

Host: Shamini Bundell

Oh, daffodils? Cherry blossom? Chocolate eggs? Frolicking lambs?

Host: Benjamin Thompson

No, even more iconic than those – It is, of course, Nature’s spring books selection which picks some of the seasons top science tomes. To find out about some of the books, I spoke to Barb Kiser, Nature’s Books and Arts editor, who told me about the theme that runs through the selection.

Interviewee: Barb Kiser

So, the way that I’ve been conceptualising it to myself is that a lot of science is actually ensemble work. So, we think of science as enacted by these lone stars and what a lot of books are showing these days is how really the lone stars are just part of a constellation. So, obviously, Einstein changed the course of physics and the way we think about the Universe, but even he was part of a larger landscape of scientists who were working to prove his theories, for instance.

Interviewer: Benjamin Thompson

And two of these researchers were Frank Dyson and, in particular, Arthur Stanley Eddington, who’s the subject of three books looking at his 1919 expedition to study an eclipse to test the theory of general relativity, and this is a story we told in a PastCast a couple of weeks back. Barb, what can you tell me about these books?

Interviewee: Barb Kiser

Yeah, so Daniel Kennefick has written No Shadow of a Doubt. It’s a straightforward history, a very rich history, of the eclipse expeditions, and he seeks to quell any doubts over Arthur Eddington’s reputation regarding the proof. The second book is Ron Cowen’s Gravity’s Century, and that looks at all of the developments and discoveries that stemmed from the proof, all the way up to black holes which, of course, are big news now. And Matthew Stanley’s Einstein’s War, is a more generalised history looking at how relativity conquered the world, as the subtitle has it.

Interviewer: Benjamin Thompson

What sort of a sense of the research am I getting from these books?

Interviewee: Barb Kiser

So, these three books sort of encapsulate the derring-do aspect, the difficulties in 1919 of enacting this sort of proof, and it’s interesting really to see how we don’t think instantaneously of Arthur Eddington or Frank Dyson in connection with Einstein and yet they were absolutely essential to establishing his theory of general relativity and making him a world celebrity.

Interviewer: Benjamin Thompson

Well, the subject of your next book is somebody who I think you’d struggle to describe as a world celebrity, and this is Thomas Harriot. Barb, who was he?

Interviewee: Barb Kiser

Thomas Harriot was a hugely accomplished mathematician living in the sixteenth century who, after his death, left a large box of mathematical papers that have only recently been parsed. So, Robyn Arianrhod’s biography which is called Thomas Harriot and reviewed wonderfully by Georgina Ferry, shines a light on these discoveries. For instance, Harriot produced the first drawing of the Moon through a telescope independently of Galileo and before Galileo, and he did the same in formulating laws of motion and falling bodies.

Interviewer: Benjamin Thompson

So, if he’s made all these discoveries then, why is he not better known?

Interviewee: Barb Kiser

Yeah, so it literally is that evocative rule – publish or perish. Harriot simply fell prey to it and we sometimes forget that in the past, there were scientists who did not publish. The author of the book, Arianrhod, speculates that he simply may have been too busy. He was one of these curiosity-driven greats. There is also some very interesting speculation which is that one of Harriot’s patrons was Sir Walter Raleigh, who was, of course, one of Queen Elizabeth I’s great favourites. Raleigh fell prey to Elizabeth’s, shall we say, quixotic nature and was imprisoned for some time in the tower, of course we know this, but Harriot was also imprisoned for a few weeks, and it could be that for political reasons he was simply keeping his head down.

Interviewer: Benjamin Thompson

So, I guess we’ll never know his reasons for not publishing some of this research that he did, but do you think this book helps to elevate him to maybe where he needs to be?

Interviewee: Barb Kiser

Absolutely. I think it is one of the first, if not the first, books to really emphasise his science.

Interviewer: Benjamin Thompson

Well, let’s do one more then from your selection, Barb. What have you got this time?

Interviewee: Barb Kiser

Yes, so this is Gareth Williams’ Unravelling the Double Helix and, unusually in books that deal with subject, he does not so much focus on Watson and Crick and Franklin and Wilkins, but rather on the precursors, the people and scientists who led up to that.

Interviewer: Benjamin Thompson

So, this is maybe similar in vein to the Einstein books then – we have these kinds of superstars at the top, and then maybe the peripheral figures around.

Interviewee: Barb Kiser

Yes, to some extent, although these are what I think of as collaborations through time. So, he pulls out into the limelight some far lesser known people, such as Walter Sutton, Nettie Stevens and William Cannon, who were all cytologists in the early-twentieth century, and the scientists who were working in X-ray crystallography in the 1920s-1950s.

Interviewer: Benjamin Thompson

So, a fairly exhaustive look then at some of the names involved in the sort of ultimate unravelling of the double helix.

Interviewee: Barb Kiser

Yes, and it counters that kind of tendency that we humans seem to have had since antiquity – we want heroes and we want authority figures and founts of knowledge – but these people got quite a lot of help from their friends and predecessors. It’s fascinating and it really enriches the story of discovery. So, I am discovering that discovery is in many ways a multi-layered and sometimes blurred phenomenon.

Interviewer: Benjamin Thompson

That was Barb Kiser. To read the reviews of all of this year’s spring books, head over to nature.com/news.

Host: Shamini Bundell

Next up on the show, it’s time for the Research Highlights, read this week by Josie Allchin.

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Josie Allchin

Stick insects are renowned for being nondescript – most looking, well, like sticks. But two new species from Madagascar are not sticking to that trend, instead embracing a vibrant colour scheme. Researchers from the University of Göttingen in Germany had originally identified these two insects as unusual examples of existing species. But after analysing the creatures’ DNA, they concluded that they are actually two distinct new species. Achrioptera manga comes in stunning sky blue, while Achrioptera maroloko sports garish green, yellow and red. The latter stick insect can also be around 24 centimetres in length, making it one of the biggest insects around. Quite why these insects are canning camouflage in favour of getting gaudy is unclear, but the researchers suggest that it may help them attract mates or deter predators. Find that research over at Frontiers in Ecology and Evolution.

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Josie Allchin

When researchers want to know what makes up a complicated system, like a living cell, they often have to break it down and look at individual parts, which can destroy the samples they’re trying to study. Now, a team of researchers from the University of Manchester have developed a new method for analysing results of a common analytic technique – nuclear magnetic resonance spectroscopy (NMR). The method allows a sample to be looked at as a whole. They’ve shown that it works by testing it on beer. Typically, NMR identifies the different chemicals within a sample as peaks on a graph, but when samples are complicated, these peaks overlap. Instead, this new technique – dubbed SCALPEL – allows the NMR measurements themselves to be broken up and analysed individually. This prevents overlap and means researchers don’t have to destroy the sample. When the team used SCALPEL to look at beer, they were easily able to identify the maltose, lactose, glucose and ethanol that makes it up, without having to break it down. Drink in that research in the Journal of the American Chemical Society.

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Host: Shamini Bundell

Next up, reporter Adam Levy brings us a striking scientific story.

Interviewer: Adam Levy

Humans have been marvelling at lightning since, well, since as long as there have been humans. Of course, these days most of us no longer attribute breath-taking thunderstorms to angry gods like Zeus or Thor. We know that lightning is essentially one big electrical discharge – a gigantic version of the spark you get when you shake hands after shuffling around on a carpet for too long. But don’t let this simple analogy fool you – there’s still plenty of mystery around lightning.

Interviewee: Brian Hare

So, like when you see a lightning flash with your eyeballs, it’s very fast. It’s like this very fast flash and a bang and it’s done. But inside of that split second that it happens, there’s tons of things that are going on.

Interviewer: Adam Levy

This is Brian Hare, a lightning physicist, who’s been probing some of these tons of things in a paper out this week in Nature.

Interviewee: Brian Hare

When I was starting my PhD, my advisor just finished a review paper and in the first chapter, he mentioned the top ten questions of lightning and they pretty much went: we don’t know how lightning initiates, we don’t know how it propagates, we don’t know how it connects to ground and we don’t know why it does all the things that it does after that. And thinking about it this way, that’s the beginning, the middle and the end – that’s the whole thing.

Interviewer: Adam Levy

The reason that researchers struggle to answer these pretty fundamental lightning questions is because lightning is so hard to study. As common as lightning is, it’s unpredictable. It’s also dangerous, so it’s hard to get close to, and it involves complex processes over a whole range of space and time scales. One way of investigating lightning is to turn a blind eye to the visible light and instead focus on the pulses of radio waves that the lightning emits as it travels. A so-called ‘lightning mapping array’ picks up these pulses with multiple radio antennas at once. By combining the signals, the array can create a 3D map of a lightning flash’s evolution over time. Lightning mapping arrays typically use ten or so antennas spread out over 100 square miles. But Brian and his team have a different approach for looking inside a flash of lightning. They use the LOw Frequency ARray radio telescope – or LOFAR.

Interviewee: Brian Hare

LOFAR is of a new type of radio telescope that just has a bunch of very simple antennas – they’re not much more complex than just the antenna that comes off your car, and there’s just hundreds of those spread over a very large area. So, if lightning happens anywhere within this large area – it’s like 3,000 square kilometres – then we can measure how lightning develops with metre-scale precision.

Interviewer: Adam Levy

This precision allows for intricate images of both the structure and development of lightning events, as Sonja Behnke, a lightning researcher who wasn’t involved in this study, explains.

Interviewee: Sonja Behnke

My reaction to this is a little bit of awe because my background is in the making of these kinds of lighting maps, and so to be able to see this fine detail in it is breath-taking, I guess. This is the most structure that I’ve seen on a map of lightning.

Interviewer: Adam Levy

But these lightning maps do more than take your breath away. In peering at the data, Brian and his team have been able to spot details that no one has seen before.

Interviewee: Brian Hare

We’re thinking, okay, now we have these really sharp images, what exactly do we want to study? I know, let’s just look at this spot on the lightning. We looked at it, and all of a sudden, we noticed these groupings of radio emissions that looked weird and they didn’t fit with our idea of lightning. It was completely unexpected.

Interviewer: Adam Levy

After lightning initiates, it polarises with positive and negative branches. Each branch grows and splits but in different ways. The unexpected groupings were spotted on the positive branches, which emit fewer radio pulses and so are generally harder to study. And the groupings turned out to provide more than just added detail to the jagged lightning structure that you’re familiar with. Here’s how to picture what the team found.

Interviewee: Brian Hare

So, okay, we have this big jagged line that goes to ground and we have all these little lines sort of coming off the top, and those things are big – those jagged lines coming off the top are five kilometres long. So, zoom into one of those, but keep zooming in, so you zoom in five kilometres to one kilometre to 500 metres, keep zooming in all the way down to 10-100 metres. They’re little tiny like hairs – think of it like needles on an evergreen tree – sticking off of the main channel. We had no idea that these needles existed – none.

Interviewee: Sonja Behnke

Yeah, I would say this is a totally new observation and it’s revealing detail about the part of discharge that we’ve always had a really hard time seeing. The implications of what that means shows us more about the new things about the physics of how the discharge propagates in the first place.

Interviewer: Adam Levy

It seems these needles aren’t just decorations on the positive branches of lightning. It may be said that lightning never strikes twice, but Brian informs me that this saying is not backed up by evidence. A single lightning event can strike the same spot several times in quick succession, and this new discovery could help explain why. The needles seem to be sapping electrical current from the positive lightning branch, causing a portion of it to die off and disconnect, leading to the multiple ground strikes. But spotting the needles on the tree of lightning is just the start of the story. There are plenty more mysteries about the beginning, middle and end of lightning that techniques like the LOFAR radio telescope could help shed light on.

Interviewee: Sonja Behnke

These interesting things that we discover about lightning are usually about looking really close at one lightning flash and seeing something weird, and with this nice, beautiful, fine detail in these LOFAR observations, I’m sure that there’s a lot more that we can learn about lightning from them.

Host: Shamini Bundell

That was Sonia Behnke who’s at the Los Alamos National Laboratory in the US, and before her, Brian Hare of the University of Groningen in the Netherlands, both speaking with Adam Levy. You can find Brian’s study plus a News and Views in the usual place.

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 Holly Else, one of the reporters here at Nature. Holly, hi.

Interviewee: Holly Else

Hi Ben.

Interviewer: Benjamin Thompson

Only time for one story this week, Holly, and we’re going to dive 7,000 metres down into the Mariana Trench to look into the genome of a fish. What’s going on here?

Interviewee: Holly Else

This is a piece of research that looks at the genome of the snailfish, an inhabitant of the Mariana Trench, which is one of the deepest places in the ocean. Obviously, it’s very dark and cold, and the creatures that live there have to endure extreme amounts of pressure. It’s the same as having the Eiffel Tower balance on your big toe, for example.

Interviewer: Benjamin ThompsonWhich is something I resolutely do not want, Holly, but why are researchers trying to sort of unpick the genome of this creature then?

Interviewee: Holly Else

So, they want to get a better understanding of how these creatures have evolved to live under these conditions, so what genes are turned on or off, for example, to help them withstand the pressure and the cold, dark conditions.

Interviewer: Benjamin ThompsonAnd a paper has come out in Nature Ecology and Evolution which is giving an insight into how these fish are doing it.

Interviewee: Holly Else

Yeah, so these researchers took some samples of the snailfish from 7,000 metres down in the Mariana Trench, and compared it to a close relative snailfish which lives in tide pools on the surface, and they found several genetic changes that they think could be linked to adaptations for living in the deep sea.

Interviewer: Benjamin ThompsonRight, and what sort of adaptations did the researchers find?

Interviewee: Holly Else

So, they found the gene for hardening bones was inactive. They also found that they had lost some genes for sensing light. And they had an expanded number of genes that controlled fatty acid metabolism, and they suspect this is to help the cell membranes of the fish stay flexible so that they don’t get all hard under the pressure and become impermeable.

Interviewer: Benjamin ThompsonOkay, right, I mean this sounds like quite an exciting thing – what are researchers saying about it?

Interviewee: Holly Else

Yeah, they’re really excited. This is the first time that an animal living below 6,000 metres has had its genome sequenced, so they’re all really interested to find out how the genes have been affected by this environment, and some of them are keen to get into the lab to use other tools like CRISPR to explore the genes in more detail.

Interviewer: Benjamin Thompson

Well, thank you for joining me Holly. Listeners, for all the news from the world of science, head over to nature.com/news.

Host: Shamini Bundell

Well, that’s it for this week’s show, but don’t forget, if you’ve got any questions about that pig brain story, our reporters would be keen to hear them. Find the article at nature.com/news.

Host: Benjamin ThompsonThere’s no regular show next week, but listen out for an extended News Chat. I’m Benjamin Thompson.

Host: Shamini Bundell

And I’m Shamini Bundell. See you next time.