Podcast: Carbon-based computing, and depleting ancient-human genomes

Host: Benjamin Thompson

Welcome back to the Nature Podcast. This week, we’ll be hearing how to make a computer processor from carbon nanotubes.

Host: Shamini Bundell

And learning about the costs of sequencing ancient genomes. I’m Shamini Bundell.

Host: Benjamin Thompson

And I’m Benjamin Thompson.

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Host: Shamini Bundell

For decades, computers have been built using silicon. But if we want them to continue getting smaller and more powerful, soon silicon might not be up to the job. So, what could replace it? Lizzie Gibney is here to check out a material of the future.

Interviewer: Lizzie Gibney

At the heart of a computer is its microprocessor – a chip filled with tiny, silicon switches called transistors. These create the computer’s 1s and 0s, and the smaller and more transistors you have, the better the computer’s speed and power. But if we shrink silicon too far, then the chips start to heat up and they become inefficient. To keep improving computers, scientists think we’ll need to replace silicon, and a promising alternative is carbon. Well, carbon nanotubes, to be precise.

Interviewee: Max Shulaker

So, a carbon nanotube, or a CNT, is just a rolled-up sheet of graphene, and graphene is an atomically thin sheet of carbon atoms.

Interviewer: Lizzie Gibney

That’s Max Shulaker from the Department of Electrical Engineering and Computer Science at MIT. His team are interested in carbon nanotubes because they have some pretty unusual properties, like conducting electricity at an incredible pace. CNTs are also semiconductors, which means that this conduction can be turned on or off. Both these properties mean CNTs could be perfect for making transistors. I called Max up to find out what his team have been doing.

Interviewee: Max Shulaker

Here at MIT, we’re trying to use them to replace silicon, which is what all the devices inside of your computer chips are made from, and it’s projected that if we could build a computer chip using carbon nanotubes as the core of these devices that switch inside of your computer, then we can make a computer over an order of magnitude more energy efficient than the computers you’re using today in your house.

Interviewer: Lizzie Gibney

So, because carbon nanotubes are such speedy conductors, I remember that years ago everyone first started getting very excited about the idea that we could use them in computers or in processors that are at the heart of computers, but then nothing really came of that. What were the big issues that scientists and engineers found with actually trying to make processors out of carbon nanotubes?

Interviewee: Max Shulaker

Yeah, so, once CNTs were discovered there was a huge amount of excitement, but the challenge was how can you actually build a billion with a ‘b’, for instance, working transistors which are all perfect and uniform etc., and actually yield a working computer chip?

Interviewer: Lizzie Gibney

And what is it about carbon nanotubes that make it so difficult to do that?

Interviewee: Max Shulaker

Yeah, so, for carbon nanotubes, there are really three major intrinsic challenges with a material. There are what we like to refer to as material defects, manufacturing defects and then intrinsic variability. So, on the material defect side, when we grow our carbon nanotubes, they unfortunately don’t all grow perfectly uniform, and it turns out that if you don’t get the precise, right combination of diameter and chirality, then some of these carbon nanotubes, instead of being a semiconducting material, they will instead be metallic, which means it’s basically just a nanorod of metal and you can never turn it off. So, that’s the material defect. On the manufacturing defect side, when we have all these nanotubes, in order to get them on to the wafer after we grow them, we actually disperse them in a solution and then we pour that solution over the wafer, and when the wafer dries, it leaves behind the nanotubes on the wafer. The challenge is that the nanotubes, while we want them to be perfectly isolated from one another, in the solution, sometimes they’ll actually bundle together. That’s like a manufacturing defect. And then the third challenge with CNTs is variability. So, when we build a computing system, we need to be able to build billions of identical devices across an entire wafer, and we need to be able to tune each of these devices as well. And in the past, we’ve only been able to build one type of transistor using carbon nanotubes. So, in this work, we’ve figured out how we can build many different types and tune all these different transistors across our wafer and make them very uniform as well.

Interviewer: Lizzie Gibney

So, it sounds like they’re some pretty big hurdles to overcome. How did you manage to do that?

Interviewee: Max Shulaker

What it required was innovations in processing, so how do we actually build these chips, new types of processing techniques etc., as well as new circuit design techniques. So, for instance, for the manufacturing defects, these bundles of nanotubes that are particles that end up on our wafer, we found a way that we could selectively wash off just these big bundles, without washing off the good, single, isolated carbon nanotubes on our wafer. And then for the material defects, for the metallic carbon nanotubes, we came up with this design technique where the technique allows us to actually design circuits in such a way that they are immune to any of these remaining metallic CNTs that slips through the processing and end up in our circuit.

Interviewer: Lizzie Gibney

So, using all those techniques, you’ve made this microprocessor. What kind of tasks or calculations can it actually do?

Interviewee: Max Shulaker

So, it’s a 16-bit machine running 32-bit instructions, so we can add or multiply or divide or take the exponent or square root of these 16-bit numbers.

Interviewer: Lizzie Gibney

So, it’s not just some little toy machine – it could do some pretty hefty calculations.

Interviewee: Max Shulaker

Oh yeah, definitely. You can programme this computer just like you would programme pretty much any computer today. So, this is like a microcontroller than you can pick up at a hobbyist shop to programme and control a small robot, for instance.

Interviewer: Lizzie Gibney

Wow, and so I’m guessing it’s probably the biggest processor made of carbon nanotubes that’s out there at the moment?

Interviewee: Max Shulaker

This is definitely the largest and most complex digital system fabricated from carbon nanotubes, and even more broadly than that, it’s the most complex computing system fabricated from any beyond-silicon emerging nanotechnology.

Interviewer: Lizzie Gibney

And the idea with going beyond silicon then, as we started out by saying, is that you want your system to be more energy efficient and maybe faster. Is this system there yet? Is it actually more efficient than silicon?

Interviewee: Max Shulaker

So, right now, what we’ve been able to show is that this technology can work. So, the next step in the process is to focus on performance. We’re not quite all the way there yet, but the progress is really becoming more rapid, and I think we’re quickly approaching now a time and soon you’ll be able to see computer chips made from technologies beyond silicon which can outperform computer chips just made from silicon today.

Interviewer: Lizzie Gibney

So, how easy do you think it will actually be then to transfer this into making a commercial product?

Interviewee: Max Shulaker

We’re actually already partnering very closely with industry in order to transfer carbon nanotubes into their manufacturing facilities so we can actually get these CNT chips out into the real world.

Interviewer: Lizzie Gibney

So, how long do you think it will be before my mobile phone, say, has carbon nanotubes in it?

Interviewee: Max Shulaker

I think if you’d asked me that question a couple of years ago, the answer would be we’re not sure. I think now, given the progress that we’ve made in this work, that it won’t be too long. We’re talking under five years until you’ll begin to see chips that are still built with silicon but also have some carbon nanotube circuits built right on top of them, for instance. So, we’re not talking about science fiction anymore. It’s a matter of when and hopefully not just if.

Host: Shamini Bundell

That was Max Shulaker of the Massachusetts Institute of Technology in the US. You can find his paper over at nature.com, along with a News and Views article.

Host: Benjamin Thompson

Later in the show, we’ll be hearing how the gene-editing tool CRISPR can be used to create smart materials – that’s coming up in the News Chat. Right now, though, it’s time for the Research Highlights, read this week by Josie Allchin.

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Josie Allchin

If elementary particles were split into boxing divisions, neutrinos would be the lightest of the lightweights, and now researchers have given them their most accurate weigh-in yet. These subatomic particles actually come in three possible types, but directly measuring their masses has proved challenging. Now, an international team of researchers has combined data from large-scale cosmology studies – like those looking at the leftover radiation from the Big Bang – with particle physics experiments here on Earth. By feeding information from both types of study into a supercomputer, they estimate that the lightest of the three neutrinos has a mass of at most 0.086 electronvolts, making it at least 6 million times lighter than an electron. The researchers suggest that their finding will help in future experiments investigating dark matter and dark energy. Weigh up that research over at Physical Review Letters.

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Josie Allchin

By the end of 2016, the Zika virus epidemic in the Americas seemed to be declining, but one group of researchers wanted to be sure. Because different countries might have different levels of monitoring and reporting, the team used an unusual method to measure Zika levels. They looked at how many international travellers had caught the virus while abroad in the Americas. They found a large number of Zika cases in people who had visited Cuba, suggesting a hidden outbreak in the country in 2017 that hadn’t been picked up by local reports. This works highlights the way that a virus could be secretly spreading, even after an epidemic is apparently slowing. It also provides a method for monitoring the spread of diseases in countries where the local detection or reporting of cases is difficult. Fly over to Cell for more on this one.

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Host: Benjamin Thompson

With advances in genetic sequencing technologies, it’s possible to extract DNA and identify the genes and genomes of ancient peoples. This has allowed researchers to better understand things like how human populations have spread throughout history and how much Neanderthal is present in our DNA. And this research is booming.

Interviewee: Keolu Fox

In the first half of 2019, we have sequenced more ancient genomes of humans than we have in the entirety of history.

Host: Benjamin Thompson

That’s Keolu Fox. He’s an ancient genomes researcher, so you’d have thought he’d be pretty happy about the increasing number of genomes being sequenced. But there’s a cost to these advances. To sequence the DNA, you need to partially destroy the remains. Keolu has written a Comment article in this week’s Nature, saying that human remains need to be used conscientiously. Reporter Nick Howe caught up with him, and asked him what it is about the process that’s damaging the remains.

Interviewee: Keolu Fox

Right, well, there is a particular bone that needs to be accessed in order to get the highest quality DNA, and it actually lives inside of the skull casing, and it involves the partial destruction of the skull in order to acquire this tiny little gyroscope inside of the ear that has a really high density and will give you nice, clean, accurate data. So, the process of getting to that bone requires destruction.

Interviewer: Nick Howe

So, do we have a sense of how many specimens have already been damaged?

Interviewee: Keolu Fox

Yeah, I think it’s really hard to pin that down. I mean, we’re probably in the thousands, but the very clear point is that that number has exponentially increased and it is only going to include more and more destruction of bones in the creation of ancient DNA.

Interviewer: Nick Howe

Are there no sort of checks and balances in place? Do researchers not have to ask permission? How does it work if one wants to use these ancient remains?

Interviewee: Keolu Fox

That’s a great question, and I think that’s one of the central points of the article that we just published, and the idea is that if there is no checks and balance, If there is no ledger system to create accountability, then it’s going to be a wild, wild west cash grab, or what we’re calling a bone rush, where investigators are flying all over the world, getting access to bones from regions where they’re not from or don’t have any sort of historical relationship to and then they are promising participation in a project that will be published in a marquee journal. So, it creates this feedback loop of the destruction of more bones and the creation of more scarcity.

Interviewer: Nick Howe

So, let’s say, hypothetically, I was a researcher doing this. Would I just be able to fly out to a country where there are some ancient remains and take those remains and sequence them and that would just be fine?

Interviewee: Keolu Fox

Well, I think it’s a little more subtle than that, right? It’s sort of like the ‘who you know’ model, and it has to do with who are the individuals that are safeguarding access in museum collections or auction houses all over the world.

Interviewer: Nick Howe

Right, and given that this ancient DNA can give us insights into important questions about our past, what can we do to use the remains more conscientiously?

Interviewee: Keolu Fox

I think you hit it right on the nose, Nick. It’s the idea that the questions should guide the destruction of ancient remains. You have to ask yourself is it worth destroying one of those samples in order to approach a question, and then there’s a larger sort of accountability where we need to think about are the living ancestors of those remains comfortable with us destroying that for the name of science. Is this scientific pursuit actually going to have impact in that community?

Interviewer: Nick Howe

So, if I was to give you ultimate control over how this is decided, what would be the policies that you would implement to try and help safeguard these materials?

Interviewee: Keolu Fox

So, two things. One is we really need to think about slowing down and slowing down this bone rush culture, this wild west culture of people just going through the back door and getting access to ancient remains and not following the proper procedures and protocols and not respecting the wishes of the living descendants of those ancient remains today. So, that involves having stricter sort of regulation for museum collections. This involves journals like Nature requiring stricter consent in access and asking questions about that, and really engaging diverse stakeholders in a way that privileges multiple types of perspectives, potentially having a council of experts that decides when and how much of something can be used to answer a specific question. And the second idea that I think will go a long way is thinking about accountability on the material side of things. Just like timber and minerals are meticulously tracked at truck weighing stations and other venues, we can discourage the sort of illegal acquisition of resources from curators, researchers and others, by openly documenting the passage of those ancient remains from one institution to another. In addition to that, documenting how much of the material is destroyed, what it originally looked like before and after an experiment via a CT scan, and actually publishing the negative results, i.e. results that didn’t work, instead of just focusing on the ancient genomes that were successful.

Interviewer: Nick Howe

So, who would be responsible for holding people to account? Would it be journals, would it be funding bodies – how would it work?

Interviewee: Keolu Fox

Regarding who holds people accountable, I think this is a collective issue, so it’s not just journals, it’s not just regulatory bodies, it’s not just funding bodies, it’s not just policymakers, geneticists, bioinformaticians, archaeologists – it needs to be a collective decision around the regulation of who gets access to these materials because right now, it’s only serving a handful of people.

Host: Benjamin Thompson

That was Keolu Fox of the University of California, San Diego. You can find his Comment piece over at nature.com/opinion. And speaking of ancient remains, there’s a research article in this week’s Nature about the discovery of a fossil hominin skull that’s millions of years old, and that’s the topic on today’s News Chat. I’m joined in the studio by Ewen Callaway, senior reporter here at Nature and resident hominin expert. Hi, Ewen.

Interviewee: Ewen Callaway

Hello, how are you?

Interviewer: Benjamin Thompson

Very, very well. Thank you so much for joining me. Well, first question then – what do we know about this skull? Why is this find so important?

Interviewee: Ewen Callaway

Yeah, this skull belongs to a species called Australopithecus anamensis. Australopithecus is a genus of early Homo. It’s the same genus from which the famous fossil Lucy is part of, but Australopithecus anamensis – what this skull belongs to – is a little bit older.

Interviewer: Benjamin Thompson

Yeah, so Lucy comes from the different species then – Australopithecus afarensis – and she’s pegged as being 3.2 million years old, as I understand. Where does this new fossil fit in?

Interviewee: Ewen Callaway

So, this new fossil, it’s about 3.8 million years old and it was found in 2016 in Ethiopia, and it probably belongs to an adult male. What’s so interesting, I think, about this fossil is what it tells us about the relationship between the species Australopithecus anamensis and Lucy’s species. For the longest time, based on incomplete fossils really, we thought that this older species, anamensis, was a direct ancestor of Lucy’s species, but what this skull shows us is that that might not be the case at all. It could be, and it seems likely, the authors say, is that these two species kind of coexisted at the same time, and so it’s thrown some confusion into an area which we thought we knew, which is what these fossils often do.

Interviewer: Benjamin Thompson

Well, it sounds like there’s a lot of information then sort of held in this fossil skull. I mean you and I have talked before about how rare it is to find more than a few fragments of bone. What did this skull look like and how is it giving so much information?

Interviewee: Ewen Callaway

Yeah, I mean this is a relatively complete skull, kind of a once in a decade or more sort of find, and there’s a couple of things to say about this skull. First off, it’s primitive both in its shape and its size – it’s got a small brain – and in some ways, the authors say it looks a bit like some of these very early possibly hominin fossils. I say possibly hominin because we’re at the boundary where the common ancestor – humans and chimpanzees – exists five or six billion years ago, and there’s a lot of controversy over which fossils are on this lineage. So, this fossil, which is, we think, definitely on the hominin lineage, it’s starting to look like those primitive things. The authors are hopeful it could shed some origins on hominins. It’s also got some, I don’t know if modern features is the right term, but some unusual features that you don’t see even in Lucy’s species, and that’s how we actually know that it wasn’t a direct ancestor of Lucy’s. It’s got kind of flared cheeks, which you see in I think much later species of Australopithecus and even in other later species. So, it’s a riddle, it’s a piece of a puzzle, but I think the authors and commenters agree that this is a really important find that’s going to give people a lot to chew over for decades to come.

Interviewer: Benjamin Thompson

What I will say is n = 1 in this case. It seems like the more puzzle pieces we find, the more confusing the puzzle gets, and from what you’re saying, maybe it’s muddied the waters. It’s not a to b to c then, sort of direct species lineage. I mean where do we need to go maybe to try and uncover this or to try and clear this up a bit better?

Interviewee: Ewen Callaway

Well, fundamentally, there is – if we draw from humans all the way back – a straight evolution, but that’s only one part of it, so we’re dealing with a very bushy tree and incomplete fossil evidence, and just because something isn’t on this straight line that goes to you or me, doesn’t mean it’s not important and it’s not revealing about our species and our early history.

Interviewer: Benjamin Thompson

Well, Ewen, let’s move on to our second story today, and it’s one that you’ve written for nature.com/news, and well, it’s about CRISPR, but maybe not the usual sorts of ways that CRISPR is used, and I know we talk about that technique a lot on the show, but maybe before we begin, can you just give me an overview of what CRISPR is?

Interviewee: Ewen Callaway

Yeah, CRISPR the disruptor. CRISPR is a lot of things. I mean it’s most famous for being a gene-editing tool, a tool that people are using to make transgenic animals and unfortunately, some humans, but it’s a bacterial immune system or defence system that bacteria use to defend against viruses and basically, it’s a system that has an enzyme that can recognise a specific piece of DNA and cut that DNA, and very smart people have taken advantage of it for all sorts of applications.

Interviewer: Benjamin Thompson

Yeah, certainly, gene editing is the thing that I think of when I hear the word CRISPR, but it seems like this kind of cutting technique has been used in maybe a new way that I certainly hadn’t considered.

Interviewee: Ewen Callaway

So, the latest twist is using CRISPR to make smart materials – that is materials that can respond to some stimulus, some genetic signal, and change their shape in response, which is pretty crazy.

Interviewer: Benjamin ThompsonIt is quite out there. What sort of materials are these then and how are they made?

Interviewee: Ewen Callaway

So, the materials in this paper, which were developed by a group at MIT and the Wyss Institute at Harvard, they were using materials called hydrogels, and as the name suggests, they are mostly water but they’re also based on polymers like polyacrylamide or polyethylene glycol. And in recent years, people have been incorporating DNA into these hydrogels, so they call them DNA hydrogels, and in many cases the DNA serves as kind of a scaffold that holds them together, and DNA is great because it’s easily synthesisable, you can make it into lots of different neat structures, and so there’s been a lot of exciting things going on in this area of DNA hydrogels.

Interviewer: Benjamin Thompson

And what then, pray tell, could these hydrogels be used for with their scaffold of DNA?

Interviewee: Ewen Callaway

DNA hydrogels have existed before, and people have tried to and I think succeeded in turning these DNA hydrogels into kind of smart sensors that change their shape. The advance that this paper does is to use CRISPR, and the way this works is that if you’ve got a DNA hydrogel, you can input a sequence in it that CRISPR recognises, and they used a specific form of CRISPR that once it recognises this target sequence, it cuts that and then it goes on and cuts like all the other single-stranded bits of DNA that hold this thing together, and that can do something in response to it. It could release, say, an antiviral molecule. The authors show that you can release human cells. They even created electronic circuits that go on or off when a biological signal is triggered.

Interviewer: Benjamin Thompson

Wow, so a myriad of possibilities then – has anything actually been created using this technology yet?

Interviewee: Ewen Callaway

Yeah, they’ve got, I wouldn’t say it’s a prototype – it’s more of like a test – but some of the authors of this paper are interested in using CRISPR technology as a disease surveillance mechanism, and they’ve worked on this tool that when a virus such as Ebola is present, you get a colour change and they kind of adapted this using these CRISPR hydrogels. And in one application they coupled detection of Ebola genetic material to a wireless signal and so I think in the experiment, a student or a scientist with a wireless detector was able to put this detector next to a testing chamber that had this smart hydrogel in it, and in the presence of a very tiny quantity of Ebola DNA, it sent a wireless signal and said ping, Ebola, and when there was no Ebola it did not send a ping. So, you could see that you could turn this into a wireless diagnostic lab that could be run with your smartphone or tablet or something like that in an actual outbreak zone. So, instead of having to look for a colour change on something, you can just get a readout on your phone. That’s one of the possible applications, but I think this is something that, I talked to a few materials scientists or people who are experts in materials, and they say this is a genuine advance. They’re excited to get to work on this and just see because CRISPR is making things possible that didn’t seem possible before.

Interviewer: Benjamin Thompson

Well, Ewen, thank you so much for joining me. Listeners, of course, head over to nature.com/news for more on these stories.

Host: Shamini Bundell

That’s all for this week. If you’ve enjoyed what you’ve heard, don’t forget you can leave us a review. You can do that on Apple Podcasts or on most other podcast providers. I’m Shamini Bundell.

Host: Benjamin Thompson

And I’m Benjamin Thompson. Thanks for listening.