Electrical stitches show potential, and Nobel prizes

Plus, human DNA is found on the teeth of museum lion specimens...
11 October 2024
Presented by Chris Smith, Will Tingle
Production by Rhys James, James Tytko.

NOBEL PRIZE

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In the news pod, how electrically conductive stitches can speed up wound healing. Scientists find the DNA of human victims embedded in the teeth of two African lions shot in the 1800's. And the Nobel Prizes explained: who’s won what, and what for?

In this episode

Geoff Hinton

- Nobel Prize for Physics: AI takes centre stage

It's the technology that's got everybody talking...

Nobel Prize for Physics: AI takes centre stage

It’s time for the first of our Nobel Prizes. Here’s Will Tingle on physics…

The 2024 Nobel Prize in Physics has been won by two scientists whom the committee say have “helped lay the foundations for modern artificial intelligence”. They are Princeton University’s John Hopfield, and the University of Toronto’s Geoffrey Hinton.

Professor Hinton said that he was flabbergasted to win. But he shouldn't have been. In the course of our lifetimes, his pioneering work on machine learning is likely to change the way that we do almost everything. It has even prompted a huge existential crisis about the power of machines, and seen world leaders gather at summits in a bid to address moral panics. 

In the late 1960s, Hinton read a number of subjects - including natural sciences, the history of art, and philosophy - at the University of Cambridge. This breadth of understanding of the human condition would ultimately lead to his pioneering work on neural interfaces, which helped pave the way for the creation of what we now know as artificial intelligence.

His work on deep learning at Google would see the birth of revolutionary tools that powered the creation of systems like ChatGPT- which is now used by hundreds of millions of people - and helped earn him the nickname the 'Godfather of AI'. But he did not - as has been reported widely in the wake of his Nobel Prize - resign from Google because he was worried about AI. This is what he told our Titans of Science programme earlier this year:

Hinton: People have sort of the wrong story. The media loves to make a nice story and a nice story would've been, I got very upset about the dangers of AI and that's why I left Google. It wasn't really that. I was 75, it was time to retire. I wasn't as good at doing research as I had been, and I wanted to take things easy and watch a lot of Netflix, but I thought I'd take the opportunity just to warn about the dangers of AI. And so I talked to a New York Times journalist and warned about the dangers of AI and then all hell broke loose. I was very surprised at how big a reaction there was.

Geoffrey Hinton speaking to the Naked Scientists earlier this year.

Geoff, of course, is only half of this remarkable story. His co-recipient, John Hopfield, invented a network that can save and recreate patterns. This is of course fundamental to the operation of artificial intelligence. Professor Hopfield - who is based at Princeton University - also developed a network that can use incomplete patterns to find the most similar. A bit like using a computer to fill in the gaps.

John Hopfield doesn’t have a nickname like the 'Godfather of AI' - but we thought we should ask ChatGPT. It suggested the ‘Network Architect’, the ‘Synapse Sage’ or the ‘Neuron Master’. John and Geoff really haven’t done badly at all have they? Congratulations to you both.

Skin close up

00:60 - Electrical stitches make wounds heal faster

Rather than a nasty shock, the results may prove a pleasant surprise...

Electrical stitches make wounds heal faster
Steve Jeffery, Birmingham City University

A new study has found that surgical stitches that can pick up an electrical charge can help speed up the healing of skin wounds. Electrical potentials delivered to the skin by the conductive sutures made new skin cells grow to heal injuries far faster. The findings, published in Nature Communications, are the work of a team of scientists based in China. We asked Steve Jeffery, consultant plastic surgeon and specialist in skin repair at Birmingham City University, to take a look at the results for us…

Steve - This paper from China, they've designed a suture, which is absorbable, but it's got a metal core of magnesium. They put wounds in rats and they sutured up muscle with this suture. Then, they've closed the skin and then they've discovered that when the rat moves, it moves the suture and that generates an electric potential and that acted to improve the healing of the actual wound.

Chris - What's the rationale for thinking that, if one looks at a wound, some local electricity might make a difference?

Steve - We know that there is an electrical potential across the wound. If you put a volt meter from one edge of the skin, the intact skin, down into the depths of the wound, there is a potential. A long time ago, there was a German scientist called Emil du-Bois Reymond who described the nerve action potential, and he actually cut his finger and did that experiment. He measured the current flowing. So we know current does flow from the edge of the wound to the depth of the wound, and we also know that current becomes less as you become older and also if you've got certain comorbidities such as diabetes, etc.

Chris-  What effect does that current have on the tissue, if any? Can the local skin cells detect that and do they use it in some way? Presumably, if it's accelerating wound healing, perhaps they can?

Steve - We think so. We know that when you have an acute wound, the cells at the margin of the wounds start to proliferate and migrate, and they lay down an extracellular matrix and new blood vessels, and the cells migrate through the wound until they meet each other in the middle. It is thought that the electrical potential helps guide the healing cells in order to achieve healing

Chris - In this present study, then, is the electrical conductor of the suture picking up its electricity from the deeper muscle and conveying that into the superficial layer, the skin, and therefore helping it to heal?Is that the sort of mechanism here?

Steve - It is, yes. It's the physical movement of the muscle creating the electrical charge and then that is being delivered to the wound itself.

Chris - How much better was this? When you apply this electrical stimulation, admittedly picked up from the underlying muscle to the wound, how much quicker did they get better? Do you think this is a realistic prospect: using electrical stimulation to heal wounds in this way?

Steve - Yeah, definitely. There's some issues with the paper. So, for example, it's talking about wounds in muscle. We don't normally talk about wounds in muscle. We talk about wounds in the skin. But they had significantly better healing. One side experiment they did was in an infected wound model and they were able to show quite remarkable improvements in fighting the infection. So definitely something to look out for for the future.

Chris - The ultimate aspiration then must be a sort of smart dressing, one day, where we have something that doesn't just cover a wound but is almost actively interrogating the wound, electrically and chemically, to adjust its behaviour. So you basically optimise the wound dressing, which is evolving as the wound changes or heals?

Steve - Exactly. So this has to be something that doesn't have a great big battery pack attached to it. Everything is contained within the dressing. And, as you say, that dressing could detect things that are going on in the wound. So what kind of things could it detect? Is there infection? Is it too wet? Is it too dry? What's the pH, oxygen saturation, the temperature, the pressure? A lot of people are under compression garments, glucose, uric acid, you name it, there's a whole lot of things it could detect. And then to be truly smart, this means the dressing can then act and say, okay, we've got too much of this, we need to change what we're delivering, whether that be delivering electrical stimulation or electromagnetic stimulation or antibiotics or an antimicrobial or growth factors, a light, whatever, so that it detects as a problem and then it treats the problem.

Tsavo Lion

07:33 - DNA reveals the past of man-eating African lions

The study reveals new insights about the Tsavo region of Kenya...

DNA reveals the past of man-eating African lions

The Tsavo Man-Eaters were a pair of large man-eating male lions in the Tsavo region of Kenya, which were responsible for the deaths of many construction workers on the Kenya-Uganda Railway in the late 1890s. The lion pair was said to have killed dozens of people. While the terrors of man-eating lions were not new in the British public perception, the Tsavo Man-Eaters became one of the most notorious instances of dangers posed to Indian and native African workers on that Uganda Railway. They were eventually killed by the British Officer Lieutenant-Colonel John Henry Patterson, and their skulls, and skins, now sit in a museum in Chicago. Recently, researchers in the city have isolated and sequenced DNA from hairs of the lions’ victims lodged inside the animals’ teeth; Alida de Flamingh at the University of Illinois Urbana-Champaign has been telling me what they found…

Alidade - There were these two lions in Tsavo, it's a region in Kenya, and they're interesting because they've been the topic of many movies and books. Most famously they're known for having also preyed on humans. And so those are the two lions that we study in this specific research and they're currently at the Field Museum in Chicago.

Chris - Are they, what, taxidermy specimens? Are they just skeletons? What's there in the museum to see?

Alidade - So at the moment in the museum, there are actually the two stuffed or rearticulated lions, skins on the one side, and their skulls are actually separate from them. So you can see both the skulls but also the lion's skins that have been stuffed, which is great because that means we had access to the skulls without having to damage any of the skins or actual rearticulated lions.

Chris - So confronted with these two lion remains, how did you then progress this? What did you actually test and what question were you asking?

Alidade - So we wanted to see if we can identify the prey from the hairs that were compacted in tooth cavities from these two lion skulls, so from their lower jaws. To do this, we used both microscopy, but we also looked at genetic material that was contained in hair fragments that were in these tooth cavities.

Chris - So are you saying, when the lions chowed down - for want of a better phrase - on whatever they were preying, on bits of the hair were ending up embedded in the teeth, and because they don't have toothbrushes, that stuff just stays in there?

Alidade - That's exactly what happened, right! We don't know exactly how old they were when this happened, but both of them had parts of their lower canines broken off and this created a cavity or a hole in which hair was compacted as these lions were eating. So the hair would get stuck in there and would kind of compact up.

Chris - And what's the preservation of the material like? Can you get meaningful amounts of, I presume you're going for DNA, from the hair that's in that cavity?

Alidade - Yes, and this is one of the interesting things is a lot of people are aware that to get a really large quantity of DNA, if you've watched any type of CSI show, right, they usually want to have the follicle of the hair shaft of your hair present. But in this case, because we are focusing in on a specific type of DNA that's called mitochondrial DNA, it's a type of DNA that's really well preserved in hairs without follicles. And so that's why we targeted this type of genetic material.

Chris - So what you just grind up the hair and out comes the DNA? you can separate that off?

Alidade - It's a little bit of a complicated situation where we have to work in a really, specialised laboratory, and that's at the University of Illinois, where there's absolutely no external DNA or DNA other than the ones that you're interested in present. And so we take those hairs and we actually dissolve them in a combination of different chemicals and that breaks open the cells and releases the DNA. And that's what we use to start out this process of DNA analysis.

Chris - And then you read the DNA sequence which, presumably, because the mitochondrial DNA of different species is very different, you can begin to pinpoint what sorts of things these animals had been eating?

Alidade - Exactly, so each individual species has a unique type or sequence of mitochondrial DNA. And so you can use this to identify the different types of prey that these lions were eating.

Chris - How do you know, though, that someone didn't contaminate the skull, the tooth, the environment that they were in, and that's what you are picking up? How do you know this genuinely was prey?

Alidade - There's multiple lines of evidence that point towards the accuracy of our data. The number one is that we've never analysed anything like wildebeest or zebra or giraffe in this specialised facility that's at the University of Illinois. The second is, when we did this analysis, the type of mitochondrial DNA that we got when we compared it, for example, for the giraffe or zebra to known mitochondrial DNA from across Africa, we find that the lions, the hair DNA, matches most closely with other giraffe or zebra that were actually from Kenya and not from the rest of Africa. So that's a good support or validation that the DNA that we're extracting is actually authentically from animals that used to live in Tsavo.

Chris - What about the human remains? Could that be mapped to Kenya? Were the locals being picked on or was it colonists coming in and and being picked off?

Alidade - Yeah, so we are refraining to infer to any type of ethnic identity from this really small piece of DNA that we analysed. We do however know that this DNA that we got from the hair had specific damage patterns. So your DNA degrades over time and it had damaged patterns that are characteristic of what you would expect from ancient DNA or DNA that's really old and have degraded over time.

Chris - We've known that we could do this for mitochondrial DNA in related ways for some time. What is new about this study and what does it add?

Alidade - So I would say two things. First is, methodologically, this is interesting because where folks have used ancient hairs to do any type of research, usually you know what type of animal you are actually sequencing or getting DNA from. A good example is, people have analysed hair from Siberian mammoths. In our case, we didn't know what the hairs were from. And so we took a backwards approach and said, we have a bunch of DNA, can we identify the actual animals that they're from? So that's a type of novel way of interpreting palingenetic data or ancient DNA data from animals or from hairs. The other kind of interesting aspect of this project is, it also gives us kind of insights into the historical ecology or interactions that these lions had with their environments. For example, the presence of wildebeest in the area, which is, until we did the study, folks hadn't reported wildebeest at least from that specific area in Tsavo. So it does give us some insights that we didn't have before.

Demis Hassabis

Nobel Prize for Chemistry: Predicting and producing proteins

Will Tingle is back with more Nobel Prizes. Three of them have scooped the next award. Although, as we'll find out, it’s not been shared equally…

The 2024 Nobel Prize in Chemistry has been won by two researchers from the AI company Deepmind, its co-founder, Sir Demis Hassabis, and research scientist John Jumper. They share the award with the University of Washington’s David Baker.

All three have worked in one way or another on the structures of proteins, the three dimensional molecules that make life possible. Baker won for his work on creating entirely new synthetic kinds of proteins not found in nature but which can operate as drugs, vaccines and sensor molecules.

Meanwhile, the Deepmind duo are recognised for their pioneering work cracking the “hard problem” in biochemistry: predicting the structures of proteins from the sequence of the gene that encodes them, or the amino acids that compose them.

It’s a key nut to crack because knowing the shape of a protein molecule is critical to understanding its behaviour and contribution to life processes, role in health and disease, and potential as a drug or therapeutic target.

Hassabis and Jumper achieved their breakthrough by harnessing the artificial intelligence muscle they’d developed at Deepmind. Their tool, called AlphaFold2, achieved what scientists had tried and failed to do for decades.

According to the Nobel Prize Committee, the work has revolutionised chemistry, and led to the mapping of the structures of around 200 million important protein structures globally.

Interestingly enough, the Nobel Prize for Chemistry hasn’t been split evenly. Hassabis and Jumper will share half of it, and the other half goes to Baker. I’m not sure they’ll mind though. Hassabis has come a long way since his days of writing computer games: before joining Queens’ College, Cambridge as a student he took a gap year and wrote the blockbuster “Theme Park” simulation game. This is what he told Chris Smith on this very programme in 2009:

Demis: Although I had been in the games industry for a long while, underlying all the games I'd been involved with designing and programming actually composed a lot of AI in those games. Most of the games were big strategy.

Chris: Artificial Intelligence for the non-initiated like me.
Demis: That's right. All the games I wrote like Theme Park and Republic and Evil Genius. They all involved simulations. Most of them involved hundreds of little computer people coming in and getting involved with the game environment. Most of the games, like Theme Park, involved you manipulating that environment and seeing how these autonomous agents reacted to what you were doing. Those were the kinds of games I found fun to play and they were the kinds of games I found fun to create. But so underlying all of this was my passion. My main passion is actually in artificial intelligence and related to that (as soon as you start thinking about what artificial intelligence is) then you start thinking about - how is it the mind achieves these end-goals?
He wasn’t wrong was he? It goes to show that you can indulge your interests and have a successful career. It might even help you win a Nobel Prize, or at least a share of it.

Urine sample

18:57 - How kidneys protect themselves from bacterial infection

The finding significantly develops our understanding of infections like UTIs...

How kidneys protect themselves from bacterial infection

Researchers at the University of Cambridge have found that webs of DNA help protect the kidneys from bacteria that cause common urine infections. The webs - which are called neutrophil extracellular traps - NETs for short - are produced by white blood cells called neutrophils which are attracted to the kidneys and then persuaded to spew out their DNA into the urine stream where it acts as a defence against microbes trying to gain a toehold. Andrew Stewart is part of the Cambridge University team that conducted the study, and I went to meet him at Addenbrooke’s hospital…

Andrew - The question we were asking had nothing to do with what this project turned out to be. So we were trying to work out what in urine we could see to diagnose kidney disease, and mysteriously we found there was lots of DNA in people's urine, healthy people.

Chris - Whose DNA?

Andrew - It was the patient's DNA, but in fragments within their urine. There's a phenomenon known where cells can eject their DNA as a defence mechanism. So we speculated that this might have something to do with it.

Chris - So, it's cells from somewhere in the urine producing system basically chucking DNA out into the urine?

Andrew - Yeah, exactly. So in order to work out what cell it is, because all cells contain the same DNA, we looked at the proteins on them, and these proteins suggested it was coming from a white cell, and a very important white cell called a neutrophil that fights bacteria which causes urinary tract infections.

Chris - But you said these are healthy people?

Andrew - They are. So this was really surprising that healthy people seem to be undergoing some sort of chronic defence mechanism. And given this is in the urine, it's logical that maybe urinary tract infection was important here.

Chris - Is this some kind of defence then. They're healthy, they haven't got an infection and this is why?

Andrew - Absolutely. So we then move to look at mice because we can give mice urinary tract infections. So you get a very small catheter and you put it into the mouse's bladder and you put some bacteria in and the mouse gets a urinary tract infection. So when we did this, we then looked for these nets in the urine that we were seeing in healthy humans and we could see the same thing.

Chris - But the mice have got an infection unlike the humans. So can you stop the mice having these nets and see if they're more prone to infection?

Andrew - Absolutely. So there's a drug that isn't used for anything clinically at the moment in the hospital, but it stops these nets from forming. So we gave some mice this drug versus some mice who didn't have the drug and we found that the mice who had the drug were much sicker. So in the absence of these nets, they got an infection that went from their bladders, which is usually mild up into their kidneys, which in humans can be life threatening.

Chris - Where are the white blood cells that are making these defensive nets hanging out then? Have you now gone and profiled through the urinary tract to see where they're starting out from?

Andrew - We don't really know the answer to it, but there's good evidence from the lab that the kidney has chemicals that pull these white cells towards it in normal healthy humans. And this is then probably increased in infections.

Chris - A million questions now running through my mind because as you say, UTI is a big common clinical problem. If these are so good at fending off infection, if we turn them up, can we cut down the rate of infection? And are people who are more prone to infection deficient in these?

Andrew - We actually did look at this question. So we looked at some genetic information and we found that there was an association between the enzyme that we were inhibiting to prevent these nets from forming, and infections, but also autoimmune diseases. And essentially it's a trade off of one versus the other. So if you have increased risk of infection, you can reduce your autoimmune disease and vice versa. So if you turn them up in your genetics, you're probably actually going to get more autoimmune disease and less infection and vice versa.

Chris - When people go to the doctor, usually women, and they say, I've got some symptoms of a urine infection, the first thing we do is we reach for these sticks that you dip in the urine. One of the things we look for is evidence of leukocytes, white blood cells. So are we finding these things and it's a good thing if they're in there, it doesn't mean they've got an infection?

Andrew - That's a really interesting question and we thought the same thing. Well what does this urine dipstick test actually tell us and what does it mean? This test is 70 years old now. So we actually thought, let's have a look at that test and see what it was doing. So we took some neutrophils from blood from a healthy person and did this several times and found that actually, lots of neutrophils did not activate this test. So that's kind of contrary to what we've thought for 70 years. So then we took those neutrophils, the same neutrophils, and triggered them to do the net formation and they activated the test straight away. So this kind of demonstrates that actually what this test that we've been doing and using on millions and millions of people all the time, probably the commonest test we do, after some simple blood test is actually detecting the DNA being ejected by these cells, not the cells themselves.

Chris - It's detecting the defence not the infection it's designed to prevent. So it could be misleading us?

Andrew - Exactly. So some things, some types of infection are good at triggering net formation and some are bad. And there are many reasons why nets may form independent of infection, and therefore this test is actually much more complicated and this is probably why this test is so difficult to interpret in our population.

Chris - So where next then?

Andrew - So I think we've disrupted them and we now need to understand what drives their formation and what doesn't. One interesting characteristic of this cell is it's quite unstable. It likes to do this, but a lot of the cells weren't doing it. So working out what makes them do it, what makes them not do it, how that changes from person to person and whether that changes in disease, I think are really interesting avenues.

RNA polymerase

24:27 - Nobel Prize for Medicine: microRNA explains how cells differ

Coaxing out the correct gene expression from DNA is crucial for complex life...

Nobel Prize for Medicine: microRNA explains how cells differ

For the final Nobel Prize winners, it’s the turn of US duo Victor Ambros and Gary Ruvkun who have scooped the gong for medicine. Here’s Will Tingle again…

The 2024 Nobel Prize in Physiology or Medicine has been awarded to the University of Massachusetts' Victor Ambros, and Harvard's Gary Ruvkun, for the discovery of a key process that controls which genes are turned on or off in different cells in our bodies.

This matters because there are more than 200 different types of cells doing very different jobs all around the body. Yet they all carry a complete and nearly identical copy of our individual DNA code.

So whether it's a liver cell breaking down the booze consumed by a Nobel Prizewinner after they popped the champagne cork, or a cone cell in the retina enabling us to see, these different cells are all dipping into the same DNA recipe book for the instructions that make them work.

The difference is that the liver cell will be reading and making a different repertoire of recipes than the retinal cell.

So how is that achieved?

Before Ambros and Ruvkun came along, the explanation centred mostly on signals called transcription factors. These are small molecules made inside cells that can lock onto DNA and physically turn groups of genes on and off.

But what  Ambros and Ruvkun showed, using microscopic worms called C.elegans, is that pieces of genetic material also do this job.

Cells "transcribe" genes from DNA into a temporary intermediary called mRNA. This is a bit like jotting down a copy of a recipe on a piece of paper to avoid having to take the entire Jame Oliver tome into the kitchen.

It's this mRNA copy that's shuttled out to the part of the cell that turns recipes into reality and effectively cooks the cake prescribed in the DNA.

But the mRNA can be ambushed en-route, Ambros and Ruvkun found, by other short pieces of genetic material called "micro RNAs".

These resemble the mRNA made from working genes, except that many of them are the genetic "mirror images" of parts of those genes. And if they meet their mRNA mirror image, they can bind on, triggering the cell to rip up the recipe and blocking the expression of the gene.

Initially the scientific community were sceptical and regarded the findings as a peculiar foible of the worms the scientists had been studying.

But in the years since, the phenomenon has been confirmed to be operating across the tree of life, at work in even bacteria through to our own cells. It is arguably one of the most important ways in which genes are regulated, and also offers us new ways to get a handle on important diseases.

Because this system is disrupted by conditions like cancer, which can make cells grow in ways they shouldn't; and infections like the herpes simplex virus exploit these mechanisms to cause repeated painful cold sores.

But thankfully, for the majority of the time, thanks to this system the 37 trillion cells in an adult human know their places and roles. And that liver cell knows that it needs to turn on the alcohol dehydrogenase gene: very important when you've just won the Nobel Prize and are celebrating with a glass or two of bubbly!

A spine from neck to pelvis

When I pinch my knee, why do I feel a tingle in my shoulder?

James - Thanks for your question, Jim. You've touched on something that's actually quite common there. In the nervous system, nerves receive activation at the level of our skin. They send their signal all the way to the spinal cord where they're processed, and the signals then go on an ascending pathway to the brain to be interpreted. That critical point in the middle there, at the spinal cord, is probably the source of this confusing phenomenon. Here's Mark Hoon, senior investigator of the neuroscience of sensation at the National Institutes of Health in the US.

Mark - Along the spinal cord, there's something called a dermatome, which is just a fancy word to say that there's different units all the way along the spinal cord. And each of those correspond to a grouping of nerves that go to a specific part of the body. It's a very defined area of the body that goes to a single part of the spinal cord. And that unit of information then goes up to the brain where there's this discrimination of location.

James - So what's happening in Jim's case where the stimulus is occurring in one part of the body, but he's feeling the sensation in another? Is it literally a case of the wires or the nerve pathways getting crossed?

Mark - In some ways, yes, you could refer to it as that. It's basically that there isn't a separation of some nerves coming into very precise locations, and that's called referred pain. And a very good example of referred pain is people who have pain that's actually the result of something going wrong in their heart. So a heart attack patient will often not feel the pain close to where their heart is, but will actually feel the pain in the shoulder, the neck and the back. And very often, if you have a shoulder pain for instance, the doctors will be quite alarmed and also have to test you to see that you haven't got a heart problem.

James - And this is why, as you say, there are parts of the body that are more commonly mixed up with each other. The dermatomes for the parts of the body they relate to happen to sit next to each other in the spinal column?

Mark - Yes, that's exactly how it is.

James - Jim's feeling, he referred to as more of a tingling than a pain. Some people might have an itch. Do we have a handle on the distinction between them?

Mark - A tingling sensation is better described as paraesthesia. And that is something that most people will recognise as something that happens, for instance, when they sleep on their arm and you're actually cutting the blood flow and the nerves are actually affected by that blockage. When you wake up with your tingling arm it's when the blood flow starts to go back to the nerves and they all start to have fire. And so you get activation of nerves that produce the sensation of pain, itch and also touch neurons. So it's a funny little activation that causes a tingling sensation.

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