Host: Nick Petrić Howe
Welcome back to the Nature Podcast. This week: uncovering the chemical secrets of mummification.
Host: Benjamin Thompson
And how CAR-T therapy could turbo-charge cancer treatments. I’m Benjamin Thompson.
Host: Nick Petrić Howe
And I’m Nick Petrić Howe.
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Interviewer: Nick Petrić Howe
First up on the show, a new analysis of the contents of some 2,500-year-old pots has provided new insights into ancient Egyptian mummification. If you think of ancient Egypt, I’m going to hazard a guess two things come to mind: pyramids and the people who were mummified and entombed within them. But, as it turns out, mummification wasn’t just reserved for pharaohs.
Interviewee: Salima Ikram
Basically, as far as we can make out, anyone who could afford to be mummified would be mummified.
Interviewer: Nick Petrić Howe
This is Egyptologist Salima Ikram. She says the importance placed on mummification was due to it being a crucial stage of ancient Egyptians’ lives or, in this case, afterlives.
Interviewee: Salima Ikram
The ancient Egyptians believed that your soul lives forever and, being a bit literal, they thought that you also needed your body for your soul to be fully animated, in order to enjoy all the sort of almost earthly delights that you would continue to enjoy in the afterlife. And so, they wanted to preserve your body so your soul could animate it. And that is probably why mummification was carried out because mummification for the ancient Egyptians is basically a transformation and metamorphosis from your being a human being into a divine entity.
Interviewer: Nick Petrić Howe
Despite the importance that the ancient Egyptians placed upon this process, a lot of how it was actually done has been lost to history. It’s understood that the deceased were dried out using salts, and in some cases their organs were removed. But when it comes down to the chemicals, oils and resins that were actually used during mummification, there’s a lot that archaeologists don’t know. To fill this gap, scientists have started doing chemical analyses of mummified people, but it is unclear exactly how various substances that they’ve been identifying were used in the embalming process. Now, though, new research published in Nature has analysed a collection of artefacts from a recently discovered site at Saqqara, some 20 miles from Cairo. Here, an embalming facility has been uncovered, dating to around the sixth or seventh century BC. Near the pyramid of King Unas, it contained areas to prepare the recently deceased for the afterlife, funeral chambers and burial spaces. These finds may help Egyptologists plug some of the gaps in their mummification knowledge.
Interviewee: Maxime Rageot
So, in this site, we analyse actually not the mummies themselves, but the pottery vessels, which were found in the embalming workshop.
Interviewer: Nick Petrić Howe
This is Maxime Rageot, one of the authors of the new paper. Now, the pottery Maxime and colleagues were looking at contained plant oils, tars, resins and animal fats that were used in the embalming process. How did they know what they were used for, you may wonder? Well, these pots were actually labelled. They said what was contained within them or they had instructions on how their contents should be applied. Now, that labelled part is important, as it’s actually the first time that named materials used in mummification have been analysed. And by using modern chemistry techniques, Maxime was able to figure out what was what.
Interviewee: Maxime Rageot
We find some local substance, so animal fats. We found bee products, probably some beeswax. And castor oils, so local plant oils also.
Interviewer: Nick Petrić Howe
These are all local ingredients that you might expect. But the team’s analysis revealed that everything else came from further afield. Now, it’s known that the ancient Egyptians of this period, who lived around 600 BC, had trade networks with nearby regions. And most of the other substances appeared to have originated from around the Mediterranean basin. But then there were two things that were a surprise for the team: plant resins known as dammar and elemi.
Interviewee: Maxime Rageot
Both of these resins are only available in rainforest. For elemi, it could be African or Asian rainforests. But for dammar, it just grew up in Asian rainforests. So, it's at least at the south of India, probably in southeast Asia. So, it's something totally new because we had no idea that Egyptians could have imported some product from so far away.
Interviewee: Salima Ikram
And that is particularly interesting because how did the Egyptians know about it?
Interviewer: Nick Petrić Howe
Salima Ikram, who you heard from earlier, again.
Interviewee: Salima Ikram
Were there also medical types moving between these two areas? Or did the Egyptians come across some of these resins and try and experiment with them and say, ‘Oh, this is great. We could use this for mummification.’
Interviewer: Nick Petrić Howe
Also, because the pots were labelled, Maxime’s work may challenge established ideas about what mummification substances actually are. For example, the team found some pots labelled as what has conventionally been translated as ‘myrrh’. Now myrrh is the resin of some small thorny trees, but when Maxime analysed the pot, it actually contained a mixture of oil and cedar tar – not quite the same thing.
Interviewee: Salima Ikram
So, this label with the ability to identify the materials that they're referring to has been revolutionary because, for once, we're suddenly finding out what these things actually are. So, something that people have said, ‘Oh, this is a resin,’ turns out to be an oil or something completely different. It's a gamechanger in terms of our understanding of how Egyptians were mummifying their dead at this particular time period.
Interviewer: Nick Petrić Howe
Salima, who has written an expert analysis of the new paper, would also like to see analyses on actual mummified people to see how what Maxime and the team found in the pots correlates with what was actually used in practice. Maxime agrees, but he also thinks there’s a lot more to uncover at Saqqara.
Interviewee: Maxime Rageot
There is still also material in Saqqara that we need to analyse, not exactly in this embalming workshop but in the funeral chambers, we need to analyse some pots to trace also the last step of embalming substances which could be used.
Interviewer: Nick Petrić Howe
There are plenty of mysteries that remain about the ancient Egyptians, but now we have a better understanding of a crucial part of their preparation for the afterlife. This is the first analysis, likely of many, of the actual substances that were going to be used to mummify the recently deceased. And their labels provide insights not only into how people were being prepared to be mummified, but also how the ancient Egyptians interacted with the rest of the world. However, these findings only show us a portion of Egypt’s long and complex history of mummification – something that by all accounts changed with the times and fashions. It may be a while into the future before we truly understand the secrets of how these people took their next step into the afterlife long in the past.
Host: Nick Petrić Howe
In this podcast piece you heard from Maxime Rageot from the University of Tubingen in Germany, and you also heard from Salima Ikram from the American University in Cairo. Salima has also penned an expert analysis of the new paper as a News and Views article. You can find that, along with a link to the paper itself, in the show notes.
Host: Benjamin Thompson
Coming up, we’ll be hearing how researchers are modifying immune cells to improve their cancer-fighting capabilities. Right now, though, it’s time for the Research Highlights, read by Dan Fox.
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Dan Fox
A new model can predict how wrinkles form on the skin of fruit as it ages. Natural 3D structures like fruit that grow, shrink or undergo other changes can exhibit a range of wrinkled patterns on their surfaces. But explaining how these patterns form is challenging. Now, researchers have developed a model to predict the patterns on the surfaces of shapes like these. They found that these patterns are influenced by stiffness, the mechanical property related to how objects react under load, with low stiffness leading to dimples across the surface and high stiffness resulting in striped patterns. Another measure related to the object's curvature helps dictate where these patterns appear. The authors say these factors can explain the hexagonal dimpling seen on a dehydrated cherry and the long ripples on a curved shrunken chilli pepper, and confirmed their model by successfully predicting the wrinkling on the surface of 3D-printed resin shapes. They hope the findings will help engineers design surfaces with specific patterns and structures. Read that research in full in Physical Review Letters.
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Dan Fox
Neanderthals collected dozens of large mammal skulls in a cave in central Spain, something researchers say is a unique example of complex ‘symbolic’ behaviour. A team of researchers analysed bone fragments found at a site used by Neanderthals and identified the animal group or species to which the fragments belonged. Among the remains were bones from three extinct animals: steppe bison, steppe rhinoceros and aurochs, the ancestor of modern cattle. The unearthed bones are dominated by skull remnants, nearly all from animals that have horns or antlers, with other types of bones comparatively rare at the site. The team say their findings suggest the skulls were hunting trophies and the cave a shrine in which they were kept. Use your head and read that research in full in Nature Human Behaviour.
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Interviewer: Benjamin Thompson
Next up on the show: how researchers are racing to refine CAR-T therapies to make better cancer treatments. Now, the human immune system is amazing, and has evolved to protect us from a range of infections, and also to help when things go wrong inside the body. And there’s one group of immune cells, sometimes called ‘killer’ T cells, that are instrumental at identifying and rooting out things that are rogue, like infected cells or even tumours. But tumours have a number of tricks up their sleeve to outmanoeuvre them, as Avery Posey, a cancer immunotherapy researcher, explains.
Interviewee: Avery Posey
Evasion of the immune system is a common characteristic of cancer, and so the cancer can evade the T cells by cloaking itself or removing the molecules that T cells need to see in order to recognize those bad or foreign cells.
Interviewer: Benjamin Thompson
To overcome this, researchers have been engineering T-cells to turbo-charge their cancer-killing capabilities. Interest in this field has exploded, and a recent feature in Nature has been focusing on an area known as CAR-T therapy, in which T cells are engineered to carry synthetic proteins called chimeric antigen receptors. These molecules essentially have two parts: a section that sticks out from the T cell, designed to recognise a specific protein on the surface of a cancer cell, and a section on the inside that stimulates the cells to divide and attack. These engineered cells are called CAR-T cells, and they originate from regular T cells taken from a person’s own body. Once reinfused, these cells hunt down the tumour cells they were engineered to recognise, and they’ve shown serious success in treating some types of blood cancers. These successes have seen the CAR-T field morph from a relatively niche area of research to one attracting a lot of attention.
Interviewee: Avery Posey
I sit within the field, so it's really hard to see it from the outside. But I can say that over the last decade, I've seen a significant increase in the interest in the field and the number of players in the field – so companies, academic labs – and I think that's been driven by the success of both these types of genetically engineered immune cells and other types of cancer immunotherapies as well.
Interviewer: Benjamin Thompson
But despite their successes, CAR-T therapies don’t always work, and people can see their cancers return. The treatments can also have serious side effects, as Heidi Ledford, a senior reporter here at Nature, explains.
Interviewee: Heidi Ledford
Researchers have learned a lot about how to manage some of the side effects in recent years, but they do still pose quite a few risks. Particularly, there’s a risk of damage to the nervous system that can be quite serious.
Interviewer: Benjamin Thompson
To tackle these issues and even expand the range of diseases that CAR-T could be used to treat, researchers are conducting hundreds of clinical trials and huge numbers of other approaches are being studied in the lab. And Heidi has been taking a look at these efforts for the News Feature.
Interviewee: Heidi Ledford
So, some of them are really trying to figure out how to make this work for more people, make it work for more kinds of tumours, and to make the effects last as long as possible. They’re also looking at ways to make safer CAR-T therapies and to make it easier to manufacture. So, at the moment, they’re bespoke for each individual, right, you engineer their own personal T cells. But there are lots of researchers looking at ways to try to make what are called ‘off-the-shelf’ CAR-T that could be used in many different patients, but the trick is to make it so that it won't be rejected by the body as also being a foreign entity.
Interviewer: Benjamin Thompson
The bespoke aspect also makes CAR-T therapies expensive. In the US, they can cost somewhere in the region of US$500,000. This limits where they’re available and who they’re available to. And while CAR-T has worked for some types of blood cancer, there’s another area where it hasn’t shown much efficacy, and that’s in the treatment of solid tumours, such as those that can be found in the lung or pancreas, and there’s multiple reasons for this.
Interviewee: Heidi Ledford
One of the problems with solid tumours is that they are solid and it's harder for the T cells to penetrate into them, in particular because tumours also have these ways of suppressing T cell responses and so forth and preventing their penetration into the core. And you tend to have a lot more variability within the tumour, so you have just this big mass of cells, some have some mutations, others have different constellations of mutations. If you design a therapy to target just one or even two of those mutations, you're not necessarily going to kill all of those cells. You'll kill some of them, but the ones that remain can then grow and sort of fill in that space.
Interviewer: Benjamin Thompson
Some early clinical trials using CAR-T therapies to treat solid tumours have shown promise, but there’s a long way to go before they’re shown to be safe and effective. And researchers are trying to learn more about the complex push and pull between the immune system and tumour, hoping to pick apart this tug-of-war environment so they can give CAR-T therapies an added boost. And it’s not just immunologists working on this problem. In her feature, Heidi writes about how synthetic biologists – researchers who design specific cellular circuits – are getting involved. In one lab study, a team engineered a T cell to produce both a CAR receptor and a protein called IL-2.
Interviewee: Heidi Ledford
IL-2 is something that's been known for a long time that can stimulate immune responses, but if you administer it to the whole body, it can be quite toxic. But they found that if you have it expressed just by a T cell, you get a stronger response from it. So, that was another way then maybe to facilitate CAR-T cell activity and also to allow it to overcome some of the defences that the tumour has erected that supress immune responses.
Interviewer: Benjamin Thompson
There are a multitude of research avenues like this being explored, some further along than others, which begs the question, which ideas are the best ones to take forward? For Avery, it’s something of a puzzle.
Interviewee: Avery Posey
There’s so many, even within one laboratory, and there's not enough capital to drive all of these forwards to a clinical trial, right. They’re expensive. There are also not enough patients to test all of these different ideas. And we know the majority of them are not going to work going from pre-clinical to clinical. And so, we want to make sure that we're moving forward our best candidates, and how do we that? I think the best way that is we do pooled studies. Usually, we're making one advance and we test it compared to a control and it works better, great. But what if you take 30 of these that have all worked better, and then pick the one that has worked best of all of those.
Interviewer: Benjamin Thompson
Avery also suggests that creating better model systems could improve the success rate of getting promising CAR-T therapies moving from the lab and into clinical trials. But despite these hurdles, work on these therapies continues to expand, and researchers are even trialling whether CAR-T could work for other, non-cancer conditions. A small trial last year, for example, reported promising results when used to treat a form of the auto-immune disease lupus. The human immune system is a fantastically intricate thing and there are many questions that remain unanswered about how CAR-T therapies can be made to work better and be produced in a way that makes them more available. Their ability to treat some blood cancers shows the potential for these therapies, but how many more make it through clinical trials, or even just off the drawing board and into the clinic, remains to be seen. Avery, though, is optimistic.
Interviewee: Avery Posey
So, fortune telling is not my expertise. However, I would say 10-20 years from now, we'll understand this a lot better, and I think we're starting to see some chips into the barrier of solid tumours, and I think this will make larger cracks into increasing the availability of these types of therapies for patients with all cancers.
Interviewer: Benjamin Thompson
That was Avery Posey from the University of Pennsylvania in the US. You also heard from Heidi Ledford, a senior reporter here at Nature. To read Heidi’s feature all about CAR-T therapies, look out for a link in the show notes.
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Host: Nick Petrić Howe
Finally on the show, it’s time for the Briefing chat, where we chat about a couple of articles that have been featured in the Nature Briefing. Ben, what have you got for us to discuss this week?
Host: Benjamin Thompson
Well, Nick, I’m going to start the Briefing chat this week with a very seemingly straightforward question: what time do you think it is right now on the Moon?
Host: Nick Petrić Howe
Oh, that's a good question. Does the Moon have time zones? Like, I'm thinking, what time would we use? But we're here on Earth and we have different times. What time is it here on Earth? I'm so confused. Ben, tell me what time is it on the Moon?
Host: Benjamin Thompson
Well, Nick, you’ve gone straight to the crux of the issue here. Nobody really knows. It kind of doesn't have a time just yet. But I've been reading an article in Nature about how it's super important that lunar time is established, and there are a bunch of reasons why it needs to be done in the not-too-distant future.
Host: Nick Petrić Howe
Okay, well, at the risk of asking a silly question and getting a silly answer, can't we just pick a time on Earth and then use that for the Moon?
Host: Benjamin Thompson
Well, at the moment, everybody seems to be picking kind of their own time, to an extent. So, each lunar mission that goes there at the moment uses its own timescale, right, and that's linked via its handlers on Earth to what's called Coordinated Universal Time, or UTC, which is kind of the standard Earth time. But this is kind of an inexact way of doing it. So, each mission, say, is doing it in a slightly different way, and that can introduce potentially all sorts of problems because, as we've covered on the show quite a lot recently, the Moon is big business right now. It's a hot area, and there are a multitude of missions going up there in the not-too-distant future. And so, for things like efficient communication and positioning, this needs to be sorted out so that everyone can talk to everybody else.
Host: Nick Petrić Howe
Right, and so how do you go about deciding what time it is on the Moon? Do you use its rotation or its position relative to Earth? How do you do it?
Host: Benjamin Thompson
Yeah, tough one, actually. Defining lunar time is really hard. I mean, a second is a second, but then gravity comes into play and the special theory of relativity kind of muddies the waters somewhat. And without getting too far into it, what that basically means is that clocks tick slower in stronger gravitational fields, okay. Now, the Moon's gravitational pull is weaker than the Earth's, which means that if you were an observer on Earth looking up at the Moon, it would appear as though the Moon's clock was going faster because the Moon's gravitational pull isn't quite as strong up there. So, from what I understand, from me observing here on Earth, it would gain about 56 microseconds per 24 hours, and that is a problem, right, like this sort of discrepancy. And there are other things as well, in terms of, different parts of the Moon have tall bits, and there's troughs, right, and they can have obviously different effects on gravity as well, so there can be time differences within the Moon as well. So, it all gets quite complicated. But what's being talked about at the minute is that to try and define a lunar standard, like the lunar time, is going to require at least three master clocks that tick at the Moon's natural pace and that are linked via a clever mathematical algorithm to kind of make this virtual accurate timepiece, and that would be lunar time. But then even more questions begin. Would you link that to Earth and have it kind of sync up every now and again, like, check in and link that to UTC? Or would you potentially have lunar time being very much its own time, and just being a standard thing that just keeps on going. And that has some advantages because if you don’t have to check in with Earth, if the comms to Earth go down for any reason, lunar time is lunar time, and satellites and missions can keep in sync with that. Something that will become even more pressing as humanity potentially goes out further into the Solar System and every planet needs to have its own time because obviously, syncing with Earth gets more difficult, the further you are away. So, it's a huge subject. On the face of it, it’s such an easy question, but it just starts spiralling.
Host: Nick Petrić Howe
Well, I mean, I never thought of all these myriad ways it gets very complex, but it makes sense when you tell me about it. So, what are scientists doing now to sort of get on top of this problem?
Host: Benjamin Thompson
Yeah, I think the realisation is that researchers need to get on top of this and soon, right. But there was a meeting in November just gone, where a bunch of different space agencies got together to try and thrash these things out because time is so important for so many things, right? I mean, Nick, I know you've covered on the podcast here before, like GPS systems, positioning systems on Earth, require ultra-accurate clocks in satellites spinning around to be able to work out where you are. And the same thing needs to be done on the Moon as well. Like at the moment, positioning is done by kind of checking into Earth every now and again. And when there become so many missions, that's going to become really, really difficult, so having an in-situ positioning system will be really, really helpful to get missions talking to each other and working out where they are. But of course, that also requires defining that time, right. What time are those clocks set to? But there's a couple of missions that have been in the planning stages, which are going to send up some satellites to orbit different parts of the Moon, and I think there's plans to try and get these in place, if possible, from around 2030.
Host: Nick Petrić Howe
This is a fascinating story. Thanks, Ben. It really makes me think of these sorts of sci-fi futures and things like that. And in that sort of vein, I was looking into something that was very reminiscent of a sci-fi film that I think you may have seen: Terminator 2. Are you familiar with that film?
Host: Benjamin Thompson
A film that I may have seen is something of an understatement here, Nick. I went on my own to watch it at the IMAX like one evening in London. I love Terminator 2. How are we turning this into the T2 podcast, Nick? What’s going on?
Host: Nick Petrić Howe
Well, before we start changing the podcast entirely, I will bring it back to science. So, this is about a metal or a kind of robot that's very reminiscent of the robot in Terminator 2. So, you probably remember from that film, this robot was able to become liquid and then become solid again. And now researchers have made a material that can do just that, and I was reading about this in New Scientist.
Host: Benjamin Thompson
And so, you're talking about the T-1000, this kind of robot that is sent back to the distant future of the mid 90s and it can sort of shapeshift. And when this film came out, right, that was impossibly futuristic. So, is it still impossibly futuristic? What's going on?
Host: Nick Petrić Howe
I think what they showed in that movie is probably still quite impossibly futuristic. But there is something kind of like this. So, what researchers have done is they've made this millimetre-sized robots that is made from gallium. And I don't know if you're familiar with gallium, but it's a metal that can melt at around 30 °C, so not that much hotter than room temperature. And what they've done with this gallium is they’ve embedded it with little tiny, microscopic magnetic particles. And then by using magnetic fields, they're able to make it melt and move about basically on command.
Host: Benjamin Thompson
Oh, no way. Alright, so back to sensible world then, like what could this potentially do then?
Host: Nick Petrić Howe
Well, one thing they did is a bit of a reference to Terminator 2, which is why I talked about it, they made it into a little Lego man, and then it melted and went through the bars and then re-solidified on the other side. But for more serious sort of applications, they've got it to do things like go into an artificial stomach, pick something up, and then move out of the artificial stomach with the thing. And they also believe that it can be used to maybe fill in gaps. So, for example, if you're on a spaceship, and maybe a screw fell out or something, it could sort of flow into that hole, and then re-solidify to become a screw there. But yeah, it seems like it could be used for a whole bunch of different things.
Host: Benjamin Thompson
And how does it work then, Nick? How can it sort of have a shape and then then go to liquid and back to the shape again?
Host: Nick Petrić Howe
Well, the way it works is to use something called an alternating magnetic field. And what that does is it generates an electric current between the magnetic particles within the gallium robot-type thing. And with that electric current, it heats up. And so, it goes to 35 °C, which is beyond gallium’s melting points, and so it melts, and then they can just let it go back to room temperature, and it will re-solidify. And the interesting thing about it, when it's solid, it’s actually able to hold 30 times its own weight. So, it becomes really quite strong, but then it can also become a liquid and flow through different things and then go back to being strong again.
Host: Benjamin Thompson
This sounds like one of those things that these researchers have been trying to crack for absolutely ages. What have they said about it?
Host: Nick Petrić Howe
So, one of the researchers who was involved in this research said, ‘No other material I know of is this good at changing its stiffness this much.’ So, they seem quite taken by what it can do. And there's another researcher quoted saying that these melty robots can be used for sort of emergency fixes and things like that.
Host: Benjamin Thompson
So, early work then, I'm guessing, Nick. There is a lot of talk about how this could be used for this and that. Where does it go next?
Host: Nick Petrić Howe
Well, one of the things I mentioned was they were getting something out of an artificial stomach. But as it currently stands, they can't necessarily track the robot if it was inside something. So, the next step would be to sort of be able to track it and work out where it is. Because if you're going to use it inside the body, you probably want to know where it's at. And if you’re trying to pick stuff up, or even deliver things like drugs and that sort of thing, then you want to be able to precisely position it. So, that's where this sort of research will be going next.
Host: Benjamin Thompson
Well, that is a cool story, Nick, and definitely one for us to keep an eye out on. And I can’t wait to find out which 90s sci-fi movie you and I are going to nerd out on next week. But for the time being, let’s leave it there for this week’s Briefing chat. And listeners, make sure to head over to the show notes where you can find links to the stories we’ve talked about today, and a link on where you can sign up to the Nature Briefing to have even more stories like this delivered directly to your inbox.
Host: Nick Petrić Howe
That’s all for this week. But just before we go, we’ve got time to highlight a new video on our YouTube channel. It’s an animation looking at the new technologies that could be the future of COVID vaccines. Well worth a glance at that one. Look out for a link to it in the show notes.
Host: Benjamin Thompson
And don’t forget you can also keep in touch with us on Twitter. We’re @NaturePodcast. Or you can send an email to podcast@nature.com. I’m Benjamin Thompson.
Host: Nick Petrić Howe
And I’m Nick Petrić Howe. Thanks for listening.