Lasers lure lightning and carbon computing
How hair follicles might hold the key to reversing scars, but not just in skin: in hearts and other organs too. Also, scientists crack how to grow new brain cells in the laboratory dish. And what a mutant from millions of years ago is revealing about how ancient animals mated...
In this episode
00:60 - Hair follicles encourage scar remodelling
Hair follicles encourage scar remodelling
Claire Higgins, Imperial College London
Thanks to evolution, injured tissues usually heal rapidly by necessity, although the payback for this fast fix is often the formation of a scar. But scar tissue, as well as being unsightly in some cases, doesn’t have the same functions as the original tissue it replaced, which means a scar can affect how well a healed body part can work subsequently. Recently, though, Imperial College’s Claire Higgins has made a surprising discovery: hair follicles implanted into scarred skin seem to trigger a repair process that reverses some of the scarring. If she can discover how, it might unlock the door to copying the trick to repair other organs that can scar, like the heart or liver. For Claire, this has meant a trip to the Canary Islands, as James found out…
Claire - We wanted to do an in human experiment as opposed to an experiment in the lab with cells or tissues. And so we contacted a hair transplant surgeon and flew over to Gran Canaria and Dr. Jimenez recruited three patients who had scars on the back of their scalp which were caused by surgeries several years prior. He took hair follicles from areas of the scalp that still contained hair and transplanted them into these scars. And then we isolated biopsies from these three patients prior to the hair follicles being transplanted into the scars, and then two, four and six months after the hair follicles were transplanted into the scar to see if the hair follicle or the presence of the hair follicle within the scar tissue was actively remodelling the scar itself.
James - So, to be clear, this procedure from the surgeon you were in touch with, they were going to go ahead anyway?
Claire - Yes. So the hair transplantation into scar tissue on the scalp is often used to camouflage scarring on the scalp.
James - Got you
Claire - But no one has then looked at whether you actually get changes to the scar tissue other than a cosmetic effect of introducing a hair follicle into the scar.
James - And what did you find?
Claire - So we found that the hair follicle seemed to be actively remodelling the surrounding tissue. We found a doubling in the number of blood vessels back to the levels that we would expect to see in healthy skin - the kind of bulk matrix that you get in scar tissue which is very characteristic and leads to differences in the mechanical properties of scars. We saw a decrease in this bulk connective tissue pushing it towards a phenotype that would be more characteristic of healthy skin.
James - Fantastic. So this treatment would work on other parts of the body as well, other than the head where it's got that cosmetic function as well?
Claire - Yeah. So in our work, as I said, we transplanted hair follicles into scars on the scalp, and so the presence of a hair follicle would be desirable; it helps camouflage the scar. But, of course, you don't want to be transplanting hair follicles into scars on every body site. You do get scars internally and externally, so we think about skin scars, but actually whenever you have tissue injury, you get a scar. So if you have a heart attack, you have fibrotic tissue or scar tissue on the heart, which then impairs the function of the heart. So just as scars in the skin impair functionality there, scarring has impacts elsewhere. So what we're doing now is trying to figure out how the hair follicle actually facilitated this scar remodelling, and then the idea is we will just isolate that component, or take that and try to use it to remodel scars in contexts where we don't want to introduce a hair follicle into the scar. Our work completely challenged this dogma that a scar is for life. We found that you actually can take scars and they can be remodelled, which is quite exciting, I think, for the future.
05:03 - Manufacturing mature brain cells
Manufacturing mature brain cells
Evangelos Kiskinis & Sam Stupp, Northwestern University
A way to make new brain cells, either for the purpose of repairing the nervous system or studying the mechanisms behind degenerative diseases like Parkinson’s and testing new treatments, has been developed by scientists in the US. Although it’s nearly two decades since researchers discovered how to reprogramme adult cells to make them behave like stem cells again so that they could be turned into other cell types like heart or liver cells, it’s nevertheless been a struggle to make mature nerve cells. Now a team at Northwestern University think they know why: they’ve built molecules that better mimic the environment of the developing brain, stimulating the stem cells in the right way to trigger them to turn into fully fledged neurones. It’s early days, but Sam Stupp, and - starting us off - Evangelos Kiskinis think they are on the right track…
Evangelos - A few years ago, some very smart scientists were able to create stem cells from any given individual. Now we have the capacity to turn these stem cells into the building blocks of the brain, the nerve cells. However, one of the longstanding problems with this technique is that the nerve cells were able to generate resemble nerve cells of a newborn baby. So we're really trying to look for ways that will help us turn the stem cell nerve cells into cells of an adult-like nature.
Chris - Do you know, Evangelos, why you were having that problem beforehand? Why these cells produced this halfway house to being a fully developed adult nerve cell and why they stopped there?
Evangelos - Well, I think although nerve cells are fully created when a baby's born, these nerve cells continue to mature and develop functional capacities as the baby becomes an adult. And when we are doing this process in a dish in the lab, we have had no way of essentially shrinking this timeline.
Chris - And Sam, you're going to argue that part of this is because of the environment that those cells are in.
Sam - Absolutely. When cells in our bodies are making that transition from being babies to being fully mature adults, that process relies on the environment that cells are in. Imagine a mesh of filaments surrounding the cells and the mesh has signals that the cells can understand and translate into action. So it is very important to be able to create a synthetic form of that mesh. And this has been the breakthrough here, our ability to create chemically that mesh that's around the cells; to provide them with the right signals so that they can mature from being babies to age in the dish as they become more mature.
Chris - So, Evangelos, what you have effectively done is to create something more akin to the developing brain for these cells to develop in, so they're fooled into thinking they're in the mature nervous system and they follow suit and turn into the right sort of cell for the right sort of environment.
Evangelos - Yes, that is absolutely correct. So one of the problems of studying human processes in a culture dish is you need all the multitude of different components that exist within the human body. Now scientists have made a lot of progress at creating these different components but, for good reason, the focus has been on the primary components which, for example, in the brain, are the nerve cells. Now what we have been doing is we're thinking about all the additional environmental components that feed onto these nerve cells and allow them to function in a way that allows them to communicate with each other and so on and so forth.
Chris - Sam, how did you work out this was the right cocktail, this is the right environment that we need to make these cells turn into mature nerve cells?
Sam - We asked, how do we create those tiny filaments that normally surround the cell? How do we come up with a molecule that self organises into tiny filaments that look like the filaments that naturally surround cells? So we had to design this compound to do exactly that. But actually we went further. We created molecules that, once they formed the filaments, they could actually move in a certain way. And the reason this is important is because those receptors or parts of the cell that understand those signals are also moving. And so it's very important to make the signals move. Just imagine a filament that has 100,000 molecules, so it's a very long filament, imagine all those molecules jumping around. Those movements turned out to be critical in helping cells achieve their maturity. People usually refer to our work as the dancing molecules because they move.
Chris - How do you know, Evangelos, that you have produced neurons that are, to all intents and purposes, mature? They're not these immature forms that we were getting before?
Evangelos - Well, we know that because we look at their morphology. Baby neurons are rather small, whereas adult neurons have an elaborate morphology with really big sizes and a number of processes that they extend quite far away in order to form a functional connection with another. Another assay allows us to measure the electrical properties of these neurons. And when they're cultured in the dish, in the presence of these new environmental factors, we see that they now resemble those of adult, real neurons that we find in the human body.
Chris - Could you also take the cells and put them back into the brain because you are potentially able to make nerve cells that would be a direct match for a patient? Could you put them into that person's brain and potentially remedy a degenerative state?
Evangelos - Yes, eventually that will be the goal. So cell transplantation therapies are a very promising approach to battle adult onset destructive neurodegenerative diseases. I think one of the problems has been the ability to generate nerve cells that can replace the ones that are being destroyed as a result of these disease processes. And certainly this discovery will facilitate the eventual cell transplantation approaches that are out there.
12:54 - Ancient trilobites used tridents to joust
Ancient trilobites used tridents to joust
Richard Fortey, Natural History Museum
Dating back over half a billion years, the trilobites were one of the first families of complex animals on Earth. With segmented, flattened bodies, some say they look like a big woodlouse. Some had long appendages projecting from various parts of their bodies, and one species, Walliserops trifurcatus, is notable for the three prongs resembling a trident sticking out at the front of its head. Why these animals had these appendages though, scientists didn’t know. Some thought they helped the trilobite forage for food; others speculated that the trident was an electromagnetic field detector. But now the discovery of a mutant fossil, with a fourth prong, has given weight to a different theory entirely: that these prongs are the first ever instance of animals fighting for a mate, as Will Tingle heard from the Natural History Museum’s Richard Fortey…
Richard - Same sort of thing that happens today with members of the deer family using their antlers for battle was happening already 400 million years ago with the trilobites. So it takes jousting sexual competition of that kind back literally several hundred millions of years older than anybody suggested it before. Some people have suggested that some dinosaurs, which I'm afraid evolved after the Trilobites had gone extinct, some of their head structures might have been involved in similar things, but nothing this old has been suggested before and it shows, if you like, that there's nothing new under the sun. The trilobites got there first.
Will - And your idea of jousting trilobites has been further helped by the discovery, for lack of a better term, a mutant trilobite fossil. It has a malformed trident with an extra tine sticking out the front. How did this specimen alongside the other evidence help further the jousting hypothesis?
Richard - It managed to go to full size. So if it had been the trident had been involved in some critical feeding activity which required perfect adaptation and so on, this animal might have been at a considerable disadvantage and you wouldn't have expected it to achieve full size. But, by analogy with say, those deer, a malformation of those antlers is actually very common. Of course, it doesn't affect their ability to grow to full size, but it does affect their ability to necessarily win in competition with their rivals. This very strange, anomalous trilobite seemed to me to support the idea of this particular function for these tridents in battle. Also, I might say that each individual tine on the trident has a little crest along it. They're flattened, so they're supported by a crest on either side, which is something you very often find in, for example, daggers which are used to have maximum strength. It increases their torsional strength tremendously. So you know everything about it: design of the trident, the anomalous trident and the comparison with the living organisms which suggested that our notion of these as sort of battling equipment was supported. So a mystery, at least if not solved, at least with a plausible explanation.
Will - With all these factors pointing towards the idea that these trilobites use their tridents to fight for a mate, what do you think that kind of activity would look like? How would a trilobite win?
Richard - The second part of our study was to look for a recent analog. Obviously trilobites have no living relatives, but there are arthropods around, lots of them. The nearest analog we could find was a family of beetles, called rhinocerous beetles. They too have an anterior, not perfect, trident like our trilobite, but sometimes bifurcates at the end, for example, which provides at least a model for what the trident might have done. These are used by the rhinocerous beetles for upending their opponent. It's a trial of strength really, in which no party becomes fatally wounded or anything like that, which is obviously ecologically a sensible thing to do. But the defeated party scults off and goes somewhere else. And my co-author and I measured the way these living anterior appendages worked and how they grew and with careful statistical analysis showed that the tridents on the Walliserops grew in exactly the same way. So we made a one-to-one comparison with a living animal that, when they fought, flipped over their opponent and that's what we thought Walliserops probably did when it was a confronting its opponent.
Will - If this is the earliest instance of sexual combat recorded, and there's been nothing since people even thought that it was the dinosaurs a couple of hundred million years later, why do you think then that there has been so little record of sexual combat since? Is it merely because the fossil record is so sparse?
Richard - No, I think probably it's because there are different types of combat that don't necessarily involve something very tangible and very obvious like a trident. The evolution of these things is presumably relatively sporadic. I mean, it's come up in the mammals, as we've said, and in one or two families of beetles, but probably no more. It's just one way of doing things which, as it were, nature invented and then reinvented, which of course is what convergent evolution, that's the technical term for it, is all about. There are many other prising examples in the fossil record of long extinct animals, as it were, anticipating things that are going on in animals that are still alive.
18:28 - Calculating a computers carbon footprint
Calculating a computers carbon footprint
Loic Lannelongue, University of Cambridge
To computing now and what’s been dubbed ‘the hidden cost of big data’. As computers have become more powerful, they’ve enabled scientists to probe complex problems in new ways, often by building virtual “models”, or analysing huge databases looking for relationships between different pieces of information. It’s given us breakthroughs in weather prediction and ocean currents, and enabled us to piece back together fragments of genetic code from over a million years ago. But all this computer power adds up to a serious energy bill, and that, in turn, means a big carbon cost. Here to explain how big, why and what we can do about it is the University of Cambridge’s Loïc Lannelongue…
Loic - We are a lab working on computational biology. So we use all these big algorithms and it was around the time of the Australian bush fires, part of our lab is in Melbourne, and around the same time a paper came out showing the carbon footprint of an artificial intelligence model. And we thought, well, our models in biology are just as demanding. So we wanted to calculate the carbon footprint of what we were doing. And we thought that would be a one week project, it's going to be really quick and we are just going to move on to what we were doing before. And it turns out, as you said, that no one outside of AI was really looking at it. So we had to first build a tool to do it and then look at it. So two years later, still here.
James - Practically, then, quite a challenge?
Loic - Yeah. Basically, to know how much energy is needed depends on what you're doing and what hardware you're using. And then you need to know what the carbon footprint of getting that much electricity is. Data centres are mostly connected to the power grid, so that depends where you are in the world.
James - And are you able to put some numbers on this, put this into context perhaps for me?
Loic - One striking number we came across is what's called genome-wide association studies. Anytime you come across an article saying, we found the gene for X, that's usually what's done. So you look at a lot of people, you look at the entire genome and you try to figure out what gene is responsible for what disease. We found that if you do it for a thousand different traits (one trait can be height, weight or a specific disease) it can be as much as 17 tonnes of co2. For reference, you could fly to Paris and back every morning to have breakfast there for six months.
James - That's remarkable. What's occurring to me now is to wonder if the current energy crisis and the high energy prices will mean that those areas of research, which are the most resource intensive, whether that will have some knock on effect as to whether that research can carry on at this time?
Loic - I think it may force people to think a little bit more about it. And I know I've talked with academics in charge of data centers who said, yes, we can only use half the data centers because the energy bill is too high. And so what computing used to be considered completely free, and people don't think twice about using computing compared to someone in a lab, in a physics lab where everything costs a lot of money. Uh, computing is, it doesn't cost that much, but maybe if that changes, it'll force people to not waste resources, but hopefully it won't hinder discoveries.
James - So what can we do about this? How can we reduce the carbon footprint of computational research?
Loic - So scientists can maybe use data centres that are more energy efficient, because a lot of the power is actually not used for the computers, but it's used to keep the facilities nice and cool. So if data centres are more efficient, we could reduce the total carbon footprint. Also, things just like using the latest version of a software can work sometimes. And I'm sure everyone has come across the fact that you update windows on your laptop and everything stops working for a week, and it's the same thing in any computational lab. So no one likes updating things, but actually sometimes it can have great effects. But actually just estimating carbon footprints regularly so each user is aware of what their carbon footprint is, but also at institutional levels, so knowing what the total carbon footprint of all the research being done in the department. If you do that over time that's really important because even if you try to be very sensible and make everything more efficient, there's this nasty thing called the rebound effect that means if you make a tool 10 times more efficient, the only result is scientists will use it a hundred times more. And at the end of the day, you didn't save any energy. So it's important to measure things over time to make sure that we'll need to change how we think about computing costs and the cultural changes needed.
James - And, just briefly, on that point of cultural change, could this perhaps be the start of a movement towards science more broadly becoming obligated to acknowledge the carbon intensivity of their research?
Loic - I certainly hope so. Funding bodies are becoming more aware now that this is an important topic and a lot of them are putting in efforts. Actually, we've teamed up with some funding bodies and some research institutes, and we put together a roadmap of where we think environmental, sustainable professional science should go moving forward. It's coming out in the next couple months. So, yeah, I think scientists are going in this direction. There's hope.
23:47 - Laser lures lightning away
Laser lures lightning away
Aurelien Houard, Paris Ecole Polytechnique
A “virtual lightning rod” that can guide lightning to strike a safe conductor has been demonstrated successfully by researchers in France. Writing in Nature Photonics, Paris’ Ecole Polytechnique scientist Aurélien Houard, has built one of the world’s most powerful lasers. Fired into the air during an electrical storm, it can ionise the atmosphere to produce a short-lived conductive thread through the air that effectively extends the working height of a lightning conductor and lures the lightning bolt to that target. It’s just a proof of principle at this stage, but the long term vision is to use devices like this to protect high value and sensitive sites, like airports or power systems, where lightning strikes can prove highly disruptive…
Aurelien - A lightning rod will concentrate the electric field by bending the electric field around it. But the action of this lightning rod is limited in space. So if you want to protect a very large area, for example, an airport or a power plant, you would need a higher lightning rod. The the idea for our technology is to be able to generate virtually this conductive lightning rod with the laser and hopefully, over several hundreds of kilometres be able to protect.
Chris - So in essence then the laser effectively turns a patch of atmosphere that it goes through into a surrogate extension of that lightning rod for a while, so that you are more likely to make a path of the lightning there rather than in another patch of sky.
Aurelien - Yes, exactly.
Chris - And how does the laser do that? What's it doing to the atmosphere that makes you have an atmospheric lightning rod?
Aurelien - The effect of this laser, which is particularly intense, is that when it's propagatiing the atmosphere it has enough intensity to detach electrons from the molecule. You create what we call plasma, a bit similar to a conductor, and this effect will create a conducting path for any electricity.
Chris - And did your experiment suggest that this can work?
Aurelien - Yes, exactly. Our experiment demonstrated for the first time that this conducting path created by the laser is powerful enough to guide the lightning over more than 50 metres. So it is the first time that people have managed to have an influence on the real lightning with just light and, demonstrated that, on a scale of almost a hundred meteres, you can now control the path of the lightning.
Chris - How did you actually do it? And where?
Aurelien - First we had to develop a specific laser with a lot of power. It is the biggest one in this category. It took us two years to develop this laser, and then one year to test. And finally we installed everything in Switzerland on top of a mountain. And we choose this specific location, which is called Mount Santis because it's one of the places in Europe with the highest number of lightning strikes. And that was successful because we managed to observe several events where we had all the diagnostics working perfectly and the laser generating the conducting path.
Chris - Just speculating about how this might be used in the future in some way: you'd have to fire the laser whenever there were the correct conditions for a potential strike. You just put the lasers on and they would provide this thread through the clouds and the atmosphere towards the lightning conductor that you wanted to be the target. And then you just hope that when lightning does discharge, it's going to come down the pathway, the conduit that you've created with the laser, and you do that whenever you think there's a high risk of a storm strike.
Aurelien - Yes, exactly. You can use a detector to measure the electric field on the ground, and when the value is high enough, you know that the clouds have a possibility to generate lightning, and then you can start to shoot your laser and wait for lightning to develop eventually. If the laser is powerful enough, you could even imagine that it could trigger the lightning before it appears.
Chris - Presumably it's going to cost quite a bit to run a laser of this sort of power. Could you make it self powering by grabbing enough energy from the lightning and tapping it off to then help to offset the power bill for running the laser?
Aurelien - Yeah, that would be a nice idea, to collect the energy from the lightning. But the difficulty actually is that you receive a lot of current in one shot and there is no battery that can support such a large current and that could store it to reuse it later. So, for the moment, there is no real project to harvest the lightning electricity since it's not doable for real application.