NATURE PODCAST

Podcast: Lab-made skin grows its own hair

Listen to the latest science news, brought to you by Shamini Bundell and Nick Howe.

This week, a new method to grow hairy skin in a dish, and new research takes aim at the RNA world hypothesis.

In this episode:

00:45 Hairy Skin

Researchers may have developed a way to make skin that can grow hair in the lab, paving the way for treatment of a variety of skin disorders, and perhaps even baldness. Research Article: Lee et al.; News and Views: Regenerative medicine could pave the way to treating baldness

08:56 Research Highlights

How mercury moved during the ‘Great Dying’, and the link between mobile phones and gender equality. Research Highlight: Giant eruptions belched toxic metal during the ‘Great Dying’; Research Article: Rotondi et al.

11:21 Does DNA predate life?

The RNA world hypothesis posits that RNA formed spontaneously leading eventually to life. Now new research suggests that RNA and DNA formed together, before life. Research Article: Xu et al.; News and Views: How DNA and RNA subunits might have formed to make the first genetic alphabet

19:25 Pick of the Briefing

We pick our highlights from the Nature Briefing, including the recent SpaceX launch, and the earliest fossil of a land animal. CBC: Scientists find oldest fossil of a land animal; Nature News: SpaceX to launch astronauts — and a new era of private human spaceflight

Subscribe to Nature Briefing, an unmissable daily round-up of science news, opinion and analysis free in your inbox every weekday.

Other links

Video: We test a home antibody kit for tracking Covid-19 transmission

Never miss an episode: Subscribe to the Nature Podcast on Apple Podcasts, Google Podcasts, Spotify or your favourite podcast app. Head here for the Nature Podcast RSS feed.

Nature Briefing

An essential round-up of science news, opinion and analysis, delivered to your inbox every weekday.

Transcript

This week, a new method to grow hairy skin in a dish, and new research takes aim at the RNA world hypothesis.

Nick Howe

Welcome back to the Nature Podcast. This week, hairy, lab-grown skin…

Shamini Bundell

And did DNA exist before life? I’m Shamini Bundell.

Nick Howe

And I’m Nick Howe.

[Jingle]

Interviewer: Nick Howe

First up, the skin is a pretty important organ. Not only is it what you see when you look at someone else, but it also protects us and helps us regulate our temperature. So, when people have certain disorders that affect their skin, it can be quite a problem. Fortunately, scientists have been able to grow skin in the lab for decades, and more recently, they’ve been able to graft lab-grown skin onto patients. But there’s always been something important missing from this synthetic skin – hair. That may be all about to change, though, as, this week in Nature, Karl Koehler and his colleagues show a way to grow hairy skin in the lab. I called up Karl to find out more and started by asking how he got into the skin game.

Interviewee: Karl Koehler

So, we actually kind of fell into this by accident. When I was a graduate student, my graduate project was focused on trying to take stem cells and generate inner ear tissue – the cells of the inner ear that sense sound or head movements – and we were ultimately successful in doing that and shortly after publication, we noticed that we were not only getting inner ear tissue to develop but we were kind of casting a wide net and getting other things that develop around the ear, including skin. And we noticed that we were getting both layers of the skin developing, both the epidermis and the dermis, and amazingly, after about 20 days in this mouse culture, we saw little hair follicles sprout.

Interviewer: Nick Howe

Do we know why it is such a challenge to make skin in the lab that does grow hair?

Interviewee: Karl Koehler

Yeah, so that’s kind of the million-dollar question, right? We think that what we’ve done works because we’re essentially recreating the entire developmental process of the skin, and both layers of the skin. So, in these culture models that we’ve created of both the mouse and now the human, we are starting from pluripotent stem cells – these are cells that can become any cell in the body – and we create a little ball of cells in a dish and apply these developmental signalling drugs or proteins to kind of mimic developmental signals that these cells see in development of the embryo and the foetus. And over the course of doing these treatments, we’re recreating the development of the epidermis and the dermis, and those cells grow together and they can talk to each other the same way they talk to each other in the embryo and the foetus, and we think that that’s the secret sauce here, the magic, that is allowing formation of these hair follicles.

Interviewer: Nick Howe

So, is it just a case then of taking these cells and just making them go through the whole developmental process that skin would go through and that seems to be, as you said, like the secret sauce?

Interviewee: Karl Koehler

Sort of. What we’ve done here is we’ve kind of taken an approach where during the first two weeks of guiding the cells to become these different tissues, we’re adding either drugs or proteins to the cells telling them to become different types of cells. And then after that, we put the aggregate of cells into the incubator and essentially just let the tissue develop on its own, and we allow the tissue to develop for up to five months in the incubator, so it’s a very long process. And what we find is that during that hands-off developmental time, the cells produce a lot of the signals that are necessary for that further development of skin with hair follicles.

Interviewer: Nick Howe

And when this process is sort of completed, what do you actually get? What does it look like? Is it a ball of skin? Would you confuse it for human skin? What exactly does it look like?

Interviewee: Karl Koehler

No, it looks like a little ball of pocket lint. Laughs. It doesn’t look like human skin at all. So, one of the weird things about this culture is that the skin develops inside out and then when the hair follicles develop, the root grows outward, so you see these little bulb-like structures growing outward and then the hair shaft will actually grow towards the interior of the aggregate. So, what you end up with is this ball with all of these little tentacle-like structures. It looks like some sort of deep sea creature.

Interviewer: Nick Howe

Laughs. So, one point of growing skin in the lab, as far as I understand it, is it can then go onto be grafted onto patients with skin disorders and things like that, so how could we go from this ball of pocket lint, as it were, to those sorts of therapeutics?

Interviewee: Karl Koehler

So, we’ve been trying to turn it inside out, both in the dish as well as we’ve picked up a mouse model that’s used a lot in the dermatology field. We create a small wound in the back of these mice and their skin, and then tuck the organoids into that wound bed, and after about a month, we found that about 50% of the grafts that we did produced these outward growing human hair follicles on the backs of the mice. Remarkably, the cystic organoids that actually opened up and kind of blossomed within the wound bed and integrated into the mouse skin and produced skin that looks pretty similar to adult human skin.

Interviewer: Nick Howe

How long would this take to produce? You said it takes like five months in the lab to sort of grow. Would that be feasible for people to use them for skin grafts and things like that?

Interviewee: Karl Koehler

Yeah, five months is a long time to wait, and it would take probably a couple of years to produce stem cells from a patient. So, we’re thinking about tweaks to our protocol for inducing skin organoids that can speed up the process and generate hair-bearing skin more rapidly. And we’re also investigating whether or not we can take the skin that doesn’t have hair at an early stage, maybe like a month into the process, and implant that on a mouse and see if it will develop hair once it’s implanted.

Interviewer: Nick Howe

And I have to ask this, is this a cure for baldness?

Interviewee: Karl Koehler

Laughs. I’m surprised you haven’t asked that yet. So, it could certainly be a potential option for patients of baldness. It would be akin to doing a hair transplant where you take hair from the back of someone’s head, hair that’s remaining, and then put that on the top of their head, but you’ve got to worry about rejection from the immune system, and so we’re going to have to think about creative ways to get around that. And we’ve shown in the paper that this hair that develops is actually more similar to the hair that develops on the foetus, so these are not the hairs that we see on the top of your head, but it’s possible that after transplantation these hairs would be converted to scalp hair or back hair or beard hair or whatever site that you put them in.

Interviewer: Nick Howe

And I suppose the other thing is this would allow researchers a model for skin in the lab that they could use to look at different things that affect human skin.

Interviewee: Karl Koehler

Yeah, absolutely. I think that’s where we’re going to make the biggest impact immediately is now we have a new model where we can study the development of human skin, which the mouse is the predominant model within the dermatology field and there really hasn’t been a good way to study developing human skin until this model came along.

Interviewer: Nick Howe

That was Karl Koehler from Boston Children’s Hospital and Harvard Medical School, both in the US. If you want to know more about growing skin with hair, we’ll put a link to Karl’s paper in the show notes, along with a link to a News and Views article.

Host: Shamini Bundell

Coming up, we’ll be hearing about which came first – DNA or life? Right now, though, it’s the Research Highlights, read this week by Dan Fox.

[Jingle]

Dan Fox

252 million years ago, the most devastating extinction event in the Earth’s history occurred – the ‘Great Dying’. One possible cause was a series of volcanic eruptions that pumped deadly mercury into the atmosphere, poisoning the planet and leaving a mark worldwide in rocks formed during the period. Now, researchers have investigated how this mercury affected the earth. By modelling the 300,000-year period of eruptions, the team were able to show that the amount of mercury belched into the environment would be orders of magnitude higher than normal. Animals across the Earth would have been exposed to these high levels of mercury, and the team think this could explain the breadth of extinction at that time, when 90% of marine species and 70% of land species were wiped out. Read that research in full at Geology.

[Jingle]

Dan Fox

While we might sometimes worry about the amount of time we spend looking at our phones, a new study has linked mobile phone access to greater gender equality and improved maternal health. Researchers assessed this by comparing prevalence of mobile phone subscriptions in 209 countries with data on women’s health and freedom from 1993 to 2017. They found that countries with more mobile phones per capita have less gender inequality and lower maternal and child mortality, something that even held up when controlling the developmental indicators, such as GDP. Surveys of girls and women between the ages of 15 and 49 in 7 sub-Saharan African countries also support this correlation, with women with mobiles more likely to have decision-making power in their households than women without them. The researchers think more work needs to be done to confirm these observations but say that in the meantime, getting more phones into women’s hands should be a developmental priority. Reserve some screen time to read that research in full at Proceedings of the National Academy of Sciences of the Unites States of America.

[Jingle]

Host: Shamini Bundell

Next up, all of life on Earth today uses RNA and DNA as the long self-copying chains that store genetic information. But how did these molecules come to exist in the first place? Many scientists think RNA arose before DNA but others aren’t so sure. This week, a paper in Nature describes a route for how the first RNA and DNA subunits might have formed on the early Earth simultaneously. Anand Jagatia has more.

Interviewer: Anand Jagatia

Before the dawn of life on this planet, RNA emerged from the primordial soup as the first self-replicating information carrier. That’s according to the RNA world hypothesis, where RNA arose from smaller building blocks. Then due to its properties, it could have facilitated biochemical reactions on prebiotic Earth, eventually leading to life. DNA was formed later, replacing RNA as the core way genetic information was stored and propagated in living things. However, there are some problems with this theory.

Host: Shamini Bundell

First of all, it requires a synthesis of the RNA building blocks that’s plausible on early Earth. Second, you have to think about the transition between the RNA world to a world more resembling of the modern world with DNA and proteins as well, and that transition, I think people have tended to gloss over a little bit. It’s quite a difficult thing to imagine.

Interviewer: Anand Jagatia

This is John Sutherland from the Medical Research Council Laboratory of Molecular Biology in Cambridge, UK. To see if they can replicate the RNA world, his lab has tried to produce the four building blocks of RNA using conditions that would have been plausible on the early Earth – UV radiation and simple starting materials like hydrogen cyanide.

Interviewee: John Sutherland

What we found with the chemistry of hydrogen cyanide was that if you reduce it, the intermediate that’s generated can react with further hydrogen cyanide, and that initiates a cascade of reactions which produces the precursors to the RNA building blocks. What was amazing about that was the fact that the other molecules it produces are actually lipid precursors and amino acid precursors, suggesting that all of the components of modern cells have could have been synthesised in the same place at the same time.

Interviewer: Anand Jagatia

So far, John’s lab has only been able to produce two of the four building blocks needed for an RNA world. That’s because each of these RNA building blocks can exist in a left- and right-handed form, which are mirror images of each other. But all RNA – and DNA in life today – is made up of units of just one-handedness. No one in the field has yet been able to produce the remaining to RNA building blocks with the correct handedness using realistic prebiotic conditions. But this week, John’s team may have solved this problem.

Interviewee: John Sutherland

We’ve been trying to make the other two RNA building blocks for quite a while and we eventually realised that we could come up with a synthesis which was prebiotically plausible of the two missing letters but in the DNA form. So, we’ve ended up with four letters – two in the RNA form and two in the DNA form.

Interviewer: Anand Jagatia

For the RNA or DNA code to work, you need a complete alphabet of four building blocks or letters which are found in complimentary pairs. This is what allows these molecules to encode information. In John’s version, two RNA letters are able to form pairs with two DNA letters to get a working alphabet. This means that these genetic building blocks could have encoded information in a mixed RNA/DNA world before the dawn of life. Importantly, it also provides a potential solution to the problem of handedness.

Interviewee: John Sutherland

And that’s because one of the intermediates in this synthesis has a very interesting property that as it crystallises, if it’s synthesised with a very small excess of one hand over the other, that excess increases during the crystallisation and so that suggests a way in which an excess of one hand over the other could have been increased to give you something that’s completely of one-handed nature.

Interviewer: Anand Jagatia

So, if the building blocks did form in this way, it could explain why they are present in only one-handedness today – a single version of one out over the other. It also suggests that perhaps RNA doesn’t predate DNA after all.

Interviewee: John Sutherland

Well, I think one has to be very careful not to over-claim on the basis of the results we have achieved, but what’s suggested by this work, it’s not proven, it’s suggested, is that neither RNA nor DNA came first, but rather a hybrid of the two came first and gave rise to both of the separate molecules subsequently.

Interviewer: Anand Jagatia

John is quick to point out that they haven’t yet been able to show that these building blocks do actually link up to form a functional DNA-RNA hybrid molecule, which would be the next step. But there are other scientists in the field who fundamentally disagree about what the nature of the first genetic polymer actually was.

Interviewee: Nicholas Hud

Some of us look at the RNA polymer and say, ‘That polymer looks too difficult to have formed spontaneously on the prebiotic Earth.’ We think that maybe a different molecule that could have functioned in some similar ways to RNA would have been much more likely.

Interviewer: Anand Jagatia

This is Nicholas Hud, a biochemist at Georgia Tech in the US who wasn’t involved with this research. I asked him for his perspective and how likely he thinks an RNA-DNA world would have been, based on the work in this paper.

Interviewee: Nicholas Hud

This speaks about possibilities, but I would not say that it speaks to how probable this scenario is. It’s beautiful organic chemistry here, but when you look at each of the steps, what you see is that they are carried out in a particular series. But when you look at each of the steps and say, ‘How probable is it that this step happened after that one and not before it?’ And ‘How probable is it that the UV light shined for the right amount of time without destroying it and only giving it what you want?’ Then I think that the probability of this being the way it happened goes down. I like models for the origin of life where the chemistry is so simple that we say, ‘This is not only possible. This is highly probable.’

Interviewer: Anand Jagatia

So, even though this research presents a plausible picture of RNA and DNA building blocks at the dawn of life, some say it’s still too improbable. But how will we ever know which model is correct, given that we don’t have chemical fossils from this period and we can’t go back in time?

Interviewee: John Sutherland

I think the evidence has to piece together, so each little piece of evidence that we accrue, we gather, has to be consistent with other pieces of evidence we’ve got, and that’s how we approach this problem. So, I think the compatibility of this synthesis with the synthesis of amino acid and lipid precursors is strengthening of the evidence. I think the fact that ultimately, everything derived from hydrogen cyanide, which can be produced on early Earth by lightning in an early atmosphere, we’ve tried very hard to use conditions which our friends in geochemistry and geology tell us are plausible on early Earth. And the aspect of the work which speaks to the handedness on molecules, I think is very important and has not been properly addressed before. As I say, we’ve not fully sorted it out, but we can demonstrate that there is a plausible way of getting around the problem of getting to a single-handed form of building blocks.

Host: Shamini Bundell

That was John Sutherland from the Medical Research Council Laboratory of Molecular Biology in the UK. You also heard from Nicholas Hud from Georgia Tech in the US. We’ll put links to the paper and a News and Views article in the show notes.

Host: Nick Howe

Finally, it’s time to look at some other non-corona science news and, as ever, Shamini and I have turned to the Nature Briefing – that’s Nature’s daily pick of science news and stories. Shamini, what’s interesting to you in the world of science this week?

Host: Shamini Bundell

So, this week, I am very excited about people going to space, which in and of itself is not too unusual – people go to space a lot – but this week, they’re going in a whole new kind of spacecraft and, significantly, one that was built by a private company.

Host: Nick Howe

You’re referring to the SpaceX launch then, I’m assuming?

Host: Shamini Bundell

Yes, exactly. So, SpaceX, which is Elon Musk’s company, have designed and built this Crew Dragon capsule, designed to go up into space, and NASA has used it to send two NASA astronauts to the International Space Station.

Host: Nick Howe

And what might be the significance of this being a commercial enterprise doing this?

Host: Shamini Bundell

Yeah, so this is the first time that it’s not been, for example, NASA’s own space shuttles that they used for a long time and then, more recently since the NASA space shuttle retired in 2011, they’ve been using the Russian Soyuz craft to take people to the International Space Station. So, NASA has been very keen on getting private companies to develop the equipment that they can use and there are a couple of companies having a go at this and SpaceX has kind of got there first. And the idea is that then, in future, NASA won’t be putting all their efforts into building space shuttles and can focus on other areas, such as the science that is going on up in the ISS.

Host: Nick Howe

So, might this be a brave new era of commercial space flight?

Host: Shamini Bundell

Yeah, so quite possibly, this is the future now, where it’s all going to be commercial. But it is also interesting in the history of space flight because there haven’t been that many different designs for spacecraft to take you up into orbit. There’s the Soyuz capsule and there was the Space Shuttle. There were the Apollo missions. But this Crew Dragon spacecraft is only the ninth new design that’s been made and tried out, so people were a little bit nervous about the first time that humans were using it as well, but it’s been taking cargo up there for ages so it’s not like it was completely untested.

Host: Nick Howe

Cool, so it will be interesting how this new era of space flight goes. So, for my story this week, I’ve been looking into a 425-million-year old millipede-like creature that may be the oldest fossil of a land animal that’s ever been discovered.

Host: Shamini Bundell

Well, I don’t know how old 425-million- years is, but if there were no other land animals around at the time, I’m guessing pretty old.

Host: Nick Howe

Yeah, so it’s pretty early on. Plants only moved onto land around 450 million years ago, so it is quite early on in the process of life encroaching onto land.

Host: Shamini Bundell

So, this is sort of way before vertebrates and fish sort of called from the sea onto the land. We’re sort of talking invertebrates at this stage. And was this millipede-like thing really the first to ever sort of live on land? How would we know that?

Host: Nick Howe

Well, maybe not. Scientists think that these were these soil worm-like creatures that existed before, around 450 million years ago, but we just don’t have any fossil evidence of them, so this is the earliest fossil we have so far.

Host: Shamini Bundell

Well, congratulations, millipede, for as long as it manages to hold onto that title.

Host: Nick Howe

Yeah, let’s see how long that lasts. Thanks, Shamini, for chatting to me, and listeners, we’ll put links to the stories we discussed in the show notes, and if you’re interested in more, but instead as an email delivered daily, then make sure you check out the Nature Briefing. We’ll put a link to that in the show notes as well.

Host: Shamini Bundell

That’s all for this week. Don’t forget, if you’re interested in what’s happening with science and coronavirus, then on Friday we have another episode of our weekly Coronapod for you. You can find that podcast wherever you found this one. Do check out our YouTube channel as where – NatureVideoChannel – for an insider look at a new trial of home antibody kits that could be used to battle COVID-19. I’m Shamini Bundell.

Host: Nick Howe

And I’m Nick Howe. See you next time.

Subjects

Sign up to Nature Briefing

An essential round-up of science news, opinion and analysis, delivered to your inbox every weekday.

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing