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Interviewer: Shamini Bundell
Welcome back to the Nature Podcast. This week we’re looking at using transgenic stem cells to regenerate an entire epidermis.
Interviewer: Benjamin Thompson
Plus, we’ll be looking at the unexpected disappearance of the axolotl. This is the Nature Podcastfor November the 9th 2017. I’m Benjamin Thompson.
Interviewer: Shamini Bundell
And I’m Shamini Bundell.
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Interviewer: Benjamin Thompson
Well I’m up first this week, talking about a new paper that details the use of transgenic stem cells to treat a condition called Junctional Epidermolysis Bullosa, or JEB. Now, JEB is a genetic condition that affects the skin, making it incredibly fragile, with the top layer – the epidermis – failing to attach to the base layer known as the dermis. There are different severities of this condition and some people experience chronic skin wounds or blistering of the mucosal membranes. There is no cure for JEB and these recurrent skin wounds can lead to infections and a predisposition to skin cancer. 40% of children born with JEB die before they reach adolescence. I wanted to get a sense of what life is like for somebody with JEB so I spoke to Anne-Marie whose daughter Tia has the condition and has had health issues since the day she was born.
Interviewee: Anne-Marie Price
She had literally no skin on her left leg from her knee downwards and bits on her hands and her face and things like that… I literally saw her for five seconds and she got rushed to hospital. Now, obviously because of the effects when she was little, on her left foot her toes are all fused together. When it was so sore and so raw it was hard to heal them separately.
Interviewer: Benjamin Thompson
Life for Tia is different than for most four year olds as the slightest knock can cause her harm.
Interviewee: Anne-Marie Price
When she does try and walk it frightens me. It frightens me that she’ll fall over and hurt herself. She has done it before at school. She tried to walk and she fell over and ripped all her skin off her arm.
Interviewer: Benjamin Thompson
Anne-Marie told me that Tia’s injuries can sometimes take weeks to heal and in some cases not at all.
Interviewee: Anne-Marie Price
She’s four years old and her left leg has never ever, ever been healed. She has always had dressings on her legs and her arms and occasionally on her back and belly, since the day she was born.
Interviewer: Benjamin Thompson
JEB is clearly a very serious condition that severely affects children like Tia and also their families who have to provide constant care. So let’s talk about today’s paper though which perhaps offers some hope for the future. This work began in 2015 when a seven year old boy with a severe form of JEB was admitted to the burns unit of a hospital in Germany.
Interviewee: Michele De Luca
The disease of the child, it was already very severe to start with. It got worse and worse than at a certain point instead of having so-called normal blisters; the patient lost his skin because of the heavy infection he had. He lost 60% of his epidermis and despite all the attempts of the surgeons at a certain point he was losing 80% of his skin and I have to say that the prognosis of the kid was very, very poor because of this.
Interviewer: Benjamin Thompson
This is Michele De Luca, head of the Centre for Regenerative Medicine at the University of Modena in Italy and corresponding author on the new paper. Due to his severe pain, the boy had been placed in a medically induced coma. With treatments failing and options limited, an experimental approach was attempted which began with the team behind the work obtaining a skin biopsy from an area of his body not affected by any blistering. The mutation behind the JEB in this case was in a gene called LAMB3. This is one of three genes that encode a protein called laminin-332, also known as laminin-5. You can think of this protein as an anchor helping to hold the epidermis to the dermis. Michele and his colleagues used this biopsy to establish a culture of epidermal cells which were modified using a virus that introduced the correct version of the LAMB3 gene. These modified cells were then used to grow, essentially, an entire new epidermis that the team transplanted back onto the boy in a series of operations that began in late 2015.
Interviewee: Michele De Luca
In three operations the entire body was covered basically and the kid was going out of the coma, he was in good shape. When he was admitted to the hospital he was 17 kilograms. That was in June 2015 and then in February 2016 the soldiers at the burn unit, they discharged the kid back home and by March 2016 he was back to school.
Interviewer: Benjamin Thompson
It’s been two years since the boy had his first skin graft. I asked Michele how he was doing now.
Interviewee: Michele De Luca
Being so inflamed for seven years, you see some difference from normal skin but they are small things, you know. In terms of function of the epidermis – it is fully fiunctional. And as a matter of fact the kid now is behaving as a normal boy. He is going to school. He is doing sports. He is playing football because the skin is functional.
Interviewer: Benjamin Thompson
Now this work is of course rather exciting and has obviously made a huge difference to this young boy but this is still only a one patient study. Work still needs to be done, for instance, to ensure the safety of viruses to deliver genes. Although Michele says that evidence from this and from previous work is encouraging. Having young children have to undergo extensive surgery is also far from ideal. In this case however, Michele says that the approach was justified although he sees the technique being used differently in future and rather than doing a few very large transplants he suggests that multiple small epidermal replacements to a child shortly after diagnosis would be a better way of going about it. Michele and his colleagues are making steps to treating Junctional Epidermolysis Bullosa although it will take time before any treatment is routinely available. I asked Anne-Marie about the future and what she hopes for Tia.
Interviewee: Anne-Marie Price
To be honest, I hope they find something that is going to help her. That is all I want is something to help her… Something to help her to forget the pain she’s in and help her to do normal day to day things that other children do. That’s what I really want for her. But if, obviously, that can’t happen, I hope she grows up to be a happy little girl.
Interviewer: Benjamin Thompson
That was Anne-Marie Foster-Price, a member of the Epidermolysis Bullosa charity DEBRA who had a role in funding this research. You also heard from and from Michele De Luca from the University of Modena. You can read the full paper and a News and Views article at Nature.com/nature.
Interviewer: Shamini Bundell
The News Chat is still to come, where we’ll be learning about a new discovery from ancient Egypt. First though, it’s time for a quick one-two of science, as Emily Banham brings us the Research Highlights.
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Interviewer: Emily Banham
The original poo-artist of the Caribbean left their mark in the caves of Mona Island near Puerto Rico. Chemical analysis of artwork found in dozens of caves reveals that paints were made by mixing bird and bat droppings with plant products. Some of the motifs, depicting things like faces and animals, were carefully crafted by scooping the soft sediments from the cave walls using fingers and tools. Radio carbon dating suggests that the images are almost a thousand years old and that the locals were decorating before Europeans arrived. The guano graffiti extends deep into the bowels of some caves meaning that the ancient artists delved into the dark to work. From Mona Island to Mona Lisa, art has certainly evolved. This excrement piece of research is in Journal of Archaeological Science.
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Interviewer: Emily Banham
Now for something more palatable: wine. Whether you taste wood smoke, cherries or freshly cut grass, the subtle characteristics in a bottle of wine arise from what connoisseurs call its ‘terroir’ – the heady mix of conditions such as grape variety, farming techniques, soil and climate that imparts a unique flavour. Scientists studied samples of Shiraz grapevines from vineyards across Australia’s Barossa region and found that the chemical composition of the vine’s DNA also varies between locations. Such epigenetic changes which can affect gene expression without altering the DNA sequence could help explain the differences between wines grown in different regions. Uncork the full paper over at Frontiers in Plant Science.
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Interviewer: Shamini Bundell
Regular listeners might have noticed my love for weird and wonderful creatures. One such creature is the axolotl, a species of salamander from Mexico. Now, there are lots of cool things about axolotls. My favourite is the fact that they’re essentially baby amphibians; they have gills and live in water and never metamorphose the way other salamanders do into an adult amphibious form. Another top axolotl fact is that they can completely regenerate lost limbs multiple times. So, they’ve ended up being used loads for research into, not just regeneration of tissues but things like organ transplants and cancer as well. And finally, in case you needed any more convincing that axolotls are cool, they just look really funny. Since I can’t show you a photo of one and you might not have access to image search right now, I’ve actually printed out some photos and Benjamin, I was hoping you could help us out by describing for us what an axolotl actually looks like.
Interviewer: Benjamin Thompson
Okay then team, here we go. They look kind of like an amphibian or maybe even kind of a lizard, I guess. They’ve got four limbs; they’ve got quite an elongated body and a bit of a tail there. Like me, they’re very pale skinned. They also have these three little appendages coming out of their head on each side in kind of like a Medusa-head kind of thing going on there, and most importantly they look super cute. They all kind of look a bit smiley.
Interviewer: Shamini Bundell
They do look cute don’t they? That was a good description actually. The Medusa heads are gills if we’re going to be slightly more biologically accurate but, yeah, that’s pretty much what I thought certainly an axolotl looked like. But I actually found out this week that quite a lot of my axolotl facts are wrong. So, first off in the wild they’re not actually white like these ones in the pictures. They’re a dark-brownish colour which presumably blends in with their environment a bit better. And secondly I found out that not everyone pronounces axolotl exactly the same.
Interviewee: Luis Zambrano
Well in Spanish it’s ‘ajolote’ actually.
Interviewer: Shamini Bundell
This is Luis Zambrano, an axolotl expert based in Mexico City. And Mexico City is really the place to be for an axolotl expert since the canals and lakes in and around the city are the creature’s natural habitat. It doesn’t seem like the most obvious place for an unusual salamander to be found. Neither is it the kind of place Luis Zambrano expected his career as a biologist to take him.
Interviewee: Luis Zambrano
Normally in Europe but here in Mexico we have a large area of high biodiversity. As a biologist you normally want to go to a coastal area or a very preserved area. We have a lot of very nice tropical rainforest areas or shore areas and nobody cares about human areas.
Interviewer: Shamini Bundell
But the urban water ways of Mexico City are now something Luis cares about a lot, not just because they’re the only place you can find wild axolotls, but also because of another important fact about axolotls that I didn’t know. Despite being found in pet shops all over the world, they are critically endangered in the wild.
Interviewee: Luis Zambrano
We started to study the population densities of the axolotls. We made that comparison between this population analysis that we made in 2002 and other ones that a previous researcher did in 1998 and we found that the density of the axolotl was reduced six fold. So we made that population probability by analysis to see what is happening with these animals and we found that if we didn’t do anything it would be extinct by 2025 or something like that, in the wild.
Interviewer: Shamini Bundell
It’s not entirely surprising that Mexico City doesn’t create the best home for a rare salamander. The axolotls have to face polluted water, noise, a lack of food, and getting eaten by introduced fish like carp and tilapia. Researchers like Luis need to find ways to combat all these varied threats.
Interviewee: Luis Zambrano
It’s not as easy as that because we are in the middle of a city. It’s not like we are in the middle of a preserved area far away from any civilization. Here we have to work with 20 million people at the same time so after many discussions with other biologists and ecologists we found that the best way to restore the axolotls is to return to the traditional agriculture, to do it properly without pesticides and herbicides, to work with traditional agricultures called chinampas.
Interviewer: Shamini Bundell
It seems that the axolotls in the lakes here have always lived side by side with humans, going back to pre-Columbian times when ancient civilizations such as the Aztecs or Mexica people founded cities here. The Aztec method of agriculture may even have benefited the native salamanders.
Interviewee: Luis Zambrano
The chinampas are Islands that the people built from the model of the lake and so all the time they are completely fertile and they have water all the time and so it’s easy to have two, three or four different crops around. That’s the reason the axolotls established here, because they have food all the time. So these chinampas are these square islands. They generate a lot of shore areas and the shore areas are the perfect place for the axolotls to survive because they need areas to hide and need areas to feed.
Interviewer: Shamini Bundell
Researchers like Luis have started to work with local farmers to create axolotl refuges in the City’s canals and to encourage them to make money from axolotl friendly produce.
Interviewee: Luis Zambrano
People said no, you have to buy a big area and then generate a huge sanctuary for axolotls and I said that doesn’t work because the moment that we leave, then it will be destroyed. So we have to work with people. Actually the idea started to come from the people working there and they said, okay, when we don’t work with pesticides we see that the canals are by far in better shape. So we started to generate common knowledge between local people and the science in order to see how these refuges should be done and how they should sell these products in order to have better income in order to encourage other people to do the same things as they are doing.
Interviewer: Shamini Bundell
This is clearly going to be a big challenge for Luis and for other axolotl conservationists and it’s really important work. Axolotls are on the brink of extinction in the wild and although there will be plenty left in labs and aquariums, a huge amount of genetic diversity will be lost. Captive axolotls are extremely inbred, being descended from only a small group of wild animals. They suffer from various mutations including ending up with the wrong number of digits and are very susceptible to diseases. Supporting the wild populations could be vital for future research. It’s not an easy task but Luis is prepared.
Interviewee: Luis Zambrano
This challenge is one of the things that I like a lot. It’s a very highly complex system and we have to consider which are the important variables here – social, ecological and economical – in order to see how we solve this very complex system.
Interviewer: Shamini Bundell
That was Luis Zambrano of the national autonomous University of Mexico. He’s been interviewed for a feature that’s coming out in next week’s issue of Natureand which includes even more fun facts about axolotls. Keep your eye on nature.com/news for that. Benjamin, that was an excellent description of an axolotl there, so I just wanted to say, thanks-olotl.
Interviewer: Benjamin Thompson
Mmmm.
Interviewer: Shamini Bundell
Sorry.
Interviewer: Benjamin Thompson
Time now for this week’s News Chat, and I’m joined in the studio by Jo Marchant, one of the news editors here at Nature.
Interviewee: Jo Marchant
Hello.
Interviewer: Benjamin Thompson
So our first story today, we’re going to be talking about weakly interacting massive particles or WIMPs as they’re known, which are something that physicists think dark matter is made of?
Interviewee: Jo Marchant
Yeah that’s right, this is one of physicists’ favourite theories for what dark matter could be. Dark matter of course is the explanation for why galaxies don’t fly apart. We think they should given the amount of matter they’ve got in them and how fast they’re spinning but they don’t, so what’s holding them together? And yes, physicists’ favourite explanation for what that dark matter might be are these particles called WIMPs. The trouble is they’re just not seeing them.
Interviewer: Benjamin Thompson
This news story comes out of Italy then, and what’s happened?
Interviewee: Jo Marchant
So there was a big result that came out of the Gran Sasso National Laboratory in Italy last week. It’s the first run of an experiment called XENON1T. This is the world’s most sensitive detector looking for dark matter and it is made of a tank of 3.5 tonnes of extremely pure liquid Xenon and the idea that if dark matter interacts with any of the atoms in that tank, physicists will see flashes of light but unfortunately in the first results that were announced they didn’t see any evidence for dark matter and we’re seeing this as well in other experiments. There were results that came out of China last week as well: they saw nothing. Space-based telescopes and experiments at CERN, the European Particle Physics Laboratory, also haven’t seen any dark matter. So this is quite bad news really for the theory of WIMPs.
Interviewer: Benjamin Thompson
So if WIMPs are physicists’ favourite dark matter theory, does this mean that other theories are getting more of a look in?
Interviewee: Jo Marchant
Yes, absolutely. So there are several other theories. One possibility is that dark matter consists of exotic axion particles which are described as being like strange massive photons. There’s also the idea that dark matter might not interact with known particles at all and might just exist in a completely hidden sector. And of course this is also encouraging for the minority of physicists who think that actually, dark matter doesn’t exist and we can explain all the anomalies that we see, just by modified versions of gravity.
Interviewer: Benjamin Thompson
So if there are other theories then floating about, what do we need to do to prove it? Is it just a case of we need some more time or we need to build a bigger detector?
Interviewee: Jo Marchant
Yeah, pretty much. That’s what physicists are doing. So versions of detectors – the next generation of this Xenon tank – are under development at the moment so it may well be that we need to wait for those to really close the door or not on WIMPs. But ultimately, most physicists think that some form of dark matter is out there and eventually we will find it.
Interviewer: Benjamin Thompson
Alright, well let’s change tack enormously. Let’s move away from outer space and to the great pyramids of Giza and what I would say is that this is a story that did come out last week but we like this one so much we really wanted to cover it. So what’s happening then in one of the Seven Wonders of the World?
Interviewee: Jo Marchant
Well this is physicists and actually there is a link with outer space because physicists have used particles that are created when cosmic rays hit air in the upper atmosphere to scan the Great Pyramids of Egypt, to see through the stone and reveal the existence of a hidden chamber.
Interviewer: Benjamin Thompson
So this is the first new piece of architecture that’s been discovered since the nineteenth century, so I understand. How do you go about using outer space physics to find it?
Interviewee: Jo Marchant
So they’re looking for muons which are particles that are produced when cosmic rays strike atoms in the upper atmosphere and so they placed muon detectors in previously known chambers so that the King’s chamber, initially, of the pyramid which is sort of in the centre of the stone and just looked for muons coming from above. It’s a bit like X-raying the pyramids. So, muons are partially absorbed by the stone of the pyramid so if there’s a chamber then more muons than expected will strike the detector from that direction and that team saw what they’re calling a void, a large void at least thirty metres long and then they got two other teams in using different types of muon detector and putting them in different places in and around the pyramid. All three teams independently saw this same void.
Interviewer: Benjamin Thompson
So what does a void mean then?
Interviewee: Jo Marchant
Well the researchers are being very careful. They’re just using the word void meaning it’s a space. They don’t know what the purpose of it would have been. I reported on this story for Natureand I rang around a fair few different Egyptologists to find out what they make of it and they all thought that this would be an intentionally created space, so we had described it as a chamber. But it’s very unlikely to be containing any treasure. Nobody thought that it would be part of the burial arrangements for the King, for example. We already have the King’s chamber. There was a sarcophagus found in there. So this is probably much more likely to be to do with the construction of the pyramid.
Interviewer: Benjamin Thompson
So what might it be doing then in kind of a structural way?
Interviewee: Jo Marchant
Well I should emphasize first that all of this is speculation, so the chamber hasn’t been directly seen. We’ve just got this information from the muons. But essentially it looks like a long space, at least thirty metres long and it looks very similar to a known space in the pyramid called the grand gallery, a sloping corridor with a lovely stepped or corbelled roof that leads up towards the King’s chamber. This space looks very much like that but directly above. One Egyptologist I spoke to thought that it might be a relieving chamber to take weight away from that grand gallery. An engineer suggested well we might want to look at the end of that space; the grand gallery leads to the King’s chamber… maybe there’s another chamber at the end of this one and the third theory that was suggested to me was that this could be part of a giant counterweight system. So, one theory for the grand gallery is there would have been a cable running down it with weights at the end that would have, as the weights fell, that would have hauled big blocks up the other side so perhaps this was part of another counterweight system further up.
Interviewer: Benjamin Thompson
So, much like the dark matter story there – so we’ve got a number of competing theories. What happens next to try and work out which is the correct one? Can we do it at all?
Interviewee: Jo Marchant
Well, I mean it’s tricky because it is completely surrounded by stone. We don’t know of any way in. The researchers have suggested that it might be possible to drill a small hole through from the grand gallery and then you could even send a fibre-optic cable, but they even suggested flying robots through to go and have a look, so who knows. Maybe in a few years’ time we’ll get a first proper look at the space.
Interviewer: Benjamin Thompson
I guess it’s a case then of watch this space or perhaps even watch this void?
Interviewee: Jo Marchant
Yeah, watch this void.
Interviewer: Benjamin Thompson
Thanks for the update there, Jo. For all the latest science news, head on over to nature.com/news.
Interviewer: Shamini Bundell
So that’s it for this week. If you’ve enjoyed the show it would be great if you could leave us some stars or a review wherever you get your pods, and don’t forget to follow us on Twitter. We’re @NaturePodcast. I’m Shamini Bundell.
Interviewer: Benjamin Thompson
And I’m Benjamin Thompson. Thanks for listening everyone. See you all next time.
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