Podcast: A rapid, multi-material 3D printer, and a bacterium’s role in alcoholic hepatitis

Host: Nick Howe

Welcome back to the Nature Podcast. This week, a super quick multi-material 3D printer…

Host: Shamini Bundell

And the link between gut microbes and liver disease. I’m Shamini Bundell.

Host: Nick Howe

And I’m Nick Howe.

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Sound effect: 3D printer

Interviewer: Nick Howe

This is the sound of a printer, but not your standard office job. This printer prints in three dimensions.

Interviewee: Jennifer Lewis

What’s exciting about three-dimensional printing from a materials perspective is you may be able to unlock a much bigger design space.

Interviewer: Nick Howe

This is Jennifer Lewis, a materials scientist from Harvard University. This week in Nature, she and her team are presenting a new type of 3D printer, one which can print a single high-resolution object that is made of multiple different materials. Now, most 3D printed objects are uniform. They are made of just one type of, for want of a better word, ‘ink.’ So, you end up with and object which is entirely made from one type of plastic, for example. Until now, it has been tricky or slow to print objects made of more than one material, and that is all down to nozzles, the bit where the ink comes out. Now there are some types of printers, like inkjet-based 3D printers, that can already print with multiple inks, but they are limited. They can’t print materials that are too viscous or the droplets of ink won’t form properly and will instead form filaments, making precise printing tricky. Extrusion-based printers, however, work differently. They squeeze fluid inks through a nozzle which then harden, and this process can be used to print a greater range of things. But to change the material being printed, you have to stop the print and change the nozzle – not with Jennifer’s printer though.

Interviewee: Jennifer Lewis

So, we’ve developed these three-dimensional printheads which are multi-nozzle and multi-material, and the really big advance is not only that we can print up to eight different materials simultaneously, but that we can switch between these materials at high speeds, so we can switch between them at frequencies of up to 50 hertz.

Sound effect: 3D printer

Interviewer: Nick Howe

To put that into context, this is the sound of the printer switching between materials, at 50 hertz or 50 times a second. Using this technique, Jennifer’s printer can print objects’ materials, or volume elements to give them their technical name, in exquisite detail.

Interviewee: Jennifer Lewis

We can create volume elements now that are on the order of the length and width of a human hair.

Interviewer: Nick Howe

Multiple nozzles and super quick material switching allowed Jennifer’s printer to rapidly make devices from multiple materials. And Jennifer has made all kinds of stuff – a walking robot, for example, with the legs printed from two materials, a soft one for the bendy bits and a hard one for the stiffer components. We actually have a video of the little bot on our YouTube channel and I’d highly recommend checking it out. It is adorable. But anyway, how does the printer work? Well, the secret is some clever use of pressure.

Interviewee: Jennifer Lewis

We’re taking advantage of the material properties of the ink, so these inks have what are called a viscoelastic response. The viscous part means that it will flow under high pressure, so when we apply pressure to the nozzle, the ink flows, but the elastic part means there’s a pressure that we have to exceed in order for the ink to flow.

Interviewer: Nick Howe

This is kind of like the opposite of that classic school room experiment with corn starch and water. You know the one, the gunk that is solid when you hit it, but runs off your hand if you are gentle. It is called Oobleck – another one to google if you haven’t seen it yet. Anyway, unlike Oobleck, Jennifer’s inks do not flow unless you add the right amount of pressure. So, she rigged up multiple channels, each containing different inks and all connected to one nozzle. By carefully controlling the pressure in each channel she could determine which ink flows through the nozzle.

Interviewee: Jennifer Lewis

So, if we’re applying pressure to one ink, that channel is going to flow, and as long as we prevent backflow of that material through the other channels that are filled with different inks, then we’re allowed to be able to print the material of interest and then seamlessly switch, take off the pressure from one ink, apply it to the next, to then change the material on the fly as it’s coming out of the printhead.

Interviewer: Nick Howe

Johannes Overvelde, an engineer who wasn’t associated with this work, is pretty enthusiastic about the potential of this technology.

Interviewee: Johannes Overvelde

I do think that the whole combination of printing multiple materials at these kinds of rates, being able to precisely control the material properties at a sort of pixel level, I think the whole combination of this is new and exciting.

Interviewer: Nick Howe

He’s particularly interested in possibly using the printer to make soft robots.

Interviewee: Johannes Overvelde

And I mean we build robots in our lab. We built a sort of fluidic circuits to control robots in the lab, and all of these things I think we could immediately print using such a device, which for now, it’s quite a tedious process. It’s not that we can’t do it, it’s that it takes a lot of time and experience of people that are doing it, so for me, being able to design something, press a button, and something like that would come out, I think that would for us also be saving a lot of time.

Interviewer: Nick Howe

Now, that’s not to say the printer is without its limitations. At the moment, whilst it can use multiple nozzles at once and swap the materials in the nozzles quickly, the printer can only output one material at a time – all the nozzles have to work in unison. That helps make the prints fast, but it only works with repetitive shapes. It won’t work if there are distinct components in the object being printed. Even so, Jennifer is optimistic about the future use of the printer.

Interviewee: Jennifer Lewis

This technology will enable a huge array of devices, things like flexible electronics, printing rechargeable batteries in three-dimensional architectures, vascularised human tissues that can be used for tissue regeneration and repair. All of these are now possible because many of these devices rely on materials that have limited print windows because they’re either reactive, like epoxies or elastomers, or they contain living cells which can only be printed over about a period of an hour before they start to die, before they lose viability. So, if you have now the ability to construct very complex, three-dimensional objects composed of these reactive or living materials, and do so at very fast timescales, I think the possibilities are really unlimited.

Sound effect: 3D printer

Interviewer: Nick Howe

That was Jennifer Lewis from the University of Harvard in the US. You also heard from Johannes Overvelde from AMOLF in the Netherlands. You can find Jennifer’s paper along with a News and Views article written by Johannes over at nature.com

Host: Shamini Bundell

Later in the show, we’ll be hearing about why ‘megaconstellations’ of satellites are worrying astronomers – that’s coming up in the News Chat. Now though, it’s time for this week’s Research Highlights, read by Dan Fox.

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Dan Fox

Why is ice so slippery? It might seem like a pretty simple question, but it’s taken a team of Parisian researchers equipped with a new ultra-high-resolution microscope and a tuning fork to get to grips with the problem. In the typical explanation for ice’s slickness, objects moving across ice slide on a thin layer of melt water, but this is counterintuitive because normally water makes a poor lubricant due to its low viscosity. The team set out to investigate this using a new microscope equipped with a tuning fork. When the fork’s metal prongs vibrated, it dragged a glass bead back and forth across a layer of ice, measuring the friction generated. The bead also moved into and out of the ice, providing data on the viscosity of the meltwater film between the bead and the ice. Surprisingly, the authors found that this melt water is up to 100 times more viscous than normal water, making it an excellent lubricant. Slide over to Physical Review X for the full paper.

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Dan Fox

If you’ve moved house recently, you probably remember the stress of carefully packing your fragile belongs to prevent them from being damaged. Now, a team of researchers in the US have revealed that some cells go through a similar process. The team found that when squeezing through tight spaces, some cells will protect their nuclei by wrapping them in a wafer-thin layer of a protein called vimentin. Vimentin forms fibres that stiffen under stress, protecting the precious nucleus and the DNA held within. The researchers observed that when cells without this bubble wrap protein wiggled down a narrow passageway, the cells’ DNA suffered 50% more damage than the cells with vimentin packaging. Read that paper in full at the Journal of Cell Biology.

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Host: Shamini Bundell

Next up on this week’s show, reporter Benjamin Thompson has been finding out about the links between a gut bacterium and serious liver condition.

Interviewer: Benjamin Thompson

Long-term alcohol misuse is associated with numerous diseases and one of the most severe is called alcoholic hepatitis, which affects the liver and has a short-term mortality rate of 20-40% after diagnosis. Unfortunately, the treatment options for alcoholic hepatitis are extremely limited and it’s poorly understood. But it seems that microbes living in the gut are involved somehow in this condition, as Bernd Schnabl, a liver specialist and researcher at the University of California, San Diego, explains.

Interviewee: Bernd Schnabl

What we knew from previous, published studies is that alcohol-related liver disease, at least in a preclinical mouse model, can be actually transmitted via faecal microbiota transplantation. So, this means that if you transfer the stool from an alcoholic hepatitis patient to a mouse that doesn’t have any bacteria or any microbes inside their bodies, and if you subject these to ethanol feeding, again in a preclinical setting, these mice develop much more liver disease as compared to conventional mice.

Interviewer: Benjamin Thompson

This week in Nature, Bernd and his colleagues have tried to get a better understanding of what’s underlying this link between the gut microbiota and alcoholic hepatitis. They started by using genomic sequencing to get an idea of the microbial populations within the faeces of people with the condition.

Interviewee: Bernd Schnabl

What was very striking, that a bacterium that is called Enterococcus faecalis is in fact very highly enriched, like 2700-fold higher, in patients with alcoholic hepatitis as compared to the non-alcoholic controls.

Interviewer: Benjamin Thompson

Now, Enterococcus faecalis is found in healthy people, albeit at much lower levels, and it doesn’t cause much harm. But in some cases, this species can cause serious infections and some strains produce a toxin called cytolysin. In this work, Bernd found that 30% of people with alcoholic hepatitis had cytolysin-producing Enterococcus in their faeces, and this was associated with a much poorer outcome when entering hospital.

Interviewee: Bernd Schnabl

Like 90% of the patients with cytolysin positivity in their faeces, they died within 180 days, while the patients who were cytolysin negative, there was only like a 5% death within 180 days.

Interviewer: Benjamin Thompson

To get a better understanding of the link between cytolysin-producing Enterococcus and alcoholic hepatitis, Bernd and his colleagues moved from humans into mice. One of the experiments the team performed involved giving germ-free mice an alcohol diet and colonising them with the faeces of people with alcoholic hepatitis.

Interviewee: Bernd Schnabl

The mice which were colonised with cytolysin-positive stool from alcoholic hepatitis patients showed more liver disease than the germ-free mice that were colonised with faeces from alcoholic hepatitis patients who were cytolysin negative.

Interviewer: Benjamin Thompson

While both sets of mice showed liver damage, those with cytolysin-producing Enterococcus were worse off. Other mice experiments in this new paper also showed that cytolysin plays a role in the severity of alcoholic hepatitis, but the team didn’t stop there. To further demonstrate that cytolysin is a key component, they wanted to specifically eliminate the bacteria producing it. Now, targeting an individual bacterial strain in the gut is difficult. Bernd and his team turned to viruses called bacteriophages, or just ‘phages’, to do the job. These viruses are ubiquitous in nature and can infect and kill bacteria. They’re also super specific to their host bacterium, even down to the strain level.

Interviewee: Bernd Schnabl

So, the phages that would recognise and destroy our Enterococcus faecalis which produce cytolysin would not kill and destroy the Enterococcus faecalis which were cytolysin-negative and to add to this, the more astonishing thing was for us was, in fact, that phages that would recognise a cytolysin-positive Enterococcus faecalis from one patient would not even recognise the Enterococcus faecalis from another patient.

Interviewer: Benjamin Thompson

The team then gave these phages to alcohol-fed germ-free mice colonised with human faeces.

Interviewee: Bernd Schnabl

We found that with the phage treatment targeting the cytolysin-positive Enterococcus faecalis, we can actually reduce liver disease in this preclinical model as compared to mice that were treated with a control bacteria phage and that were still colonised with the cytolysin positive stool from alcoholic hepatitis patients.

Interviewer: Benjamin Thompson

The treated mice had lower levels of cytolysin in their livers, which had less damage and lower levels of inflammation. So, it seems then that this toxin is playing an important role in the severity of alcoholic hepatitis. Martha Clokie, a microbiologist who works on phages, has written a News and Views article on this work. She was impressed.

Interviewee: Martha Clokie

Well, I think they’ve combined a very, very careful analysis of what they’ve seen in patients, so although it is correlation, the numbers are large and the statistics are really, really good. And then they’ve also made a really nice link between the humans and mice. So, they’ve got as close to humans without going into humans as you possibly can.

Interviewer: Benjamin Thompson

So, could these phages be used to treat alcoholic hepatitis in humans? Well, that remains to be seen and, of course, much of this research was done in mice. Martha thinks, though, that there’s enough preliminary evidence in this work to suggest that this line of research should be continued. Bernd is keen to eventually move into clinical trials, but says there are still questions that need to be answered. For example, why do some people with alcoholic hepatitis harbour cytolysin-producing strains while others don’t? He also thinks that this current method of isolating specific phages to target specific bacterial strains will need to be adapted to produce phage therapies that can help people with alcoholic hepatitis.

Interviewee: Bernd Schnabl

So, I think in the future, we need to find bacteria phages that have a broader host range. So, there are methods in the literature currently that we can use to do this, but also on the horizon there are these synthetic bacteria phages that cannot only recognise very specific strains of Enterococcus faecalis, but hopefully recognise a broad spectrum, then obviously, this would ease the treatment options for alcoholic hepatitis patients.

Host: Shamini Bundell

That was Bernd Schnabl from the University of California, San Diego in the US. You also heard from Martha Clokie from the University of Leicester in the UK. You can read Bernd’s paper and Martha’s News and Views article over at nature.com.

Interviewer: Nick Howe

Finally on the show, it’s time for the News Chat and I’m joined in the studio by Nisha Gaind, Nature’s European Bureau Chief. Nisha, hi!

Interviewee: Nisha Gaind

Hi, Nick.

Interviewer: Nick Howe

So, this week, we’ve got two stories and the first one is about SpaceX, and on Monday they launched 60 satellites into orbit, and this has caused some worry among astronomers.

Interviewee: Nisha Gaind

Yeah, that’s right. This is a story that’s been simmering for a while and it’s about these plans by SpaceX and some other companies, including Amazon, to launch what are called ‘megaconstellations’, and these are huge networks of satellites that will hopefully provide internet to the entire globe, including to places that are very underserved. But there is a problem that comes with this and it is for astronomers, and they are fearful that all of these satellites in the sky will basically mess up their astronomical observations.

Interviewer: Nick Howe

In what sort of ways might this affect their observations?

Interviewee: Nisha Gaind

So, there are a couple of different worries here. One is that these satellites are basically pretty bright, and they might create streaks in the night sky that would interfere with data collection, and the other is that the orbit area around Earth is already quite congested, and we’re talking about huge numbers of potential satellite launches here – somewhere in the order of the tens of thousands. 50,000 is one number that has been thrown around. So, all of these extra things in what they call low Earth orbit could increase the risk that satellites and other craft that are up there could start bashing into each other, which obviously isn’t great.

Interviewer: Nick Howe

So, there’s obviously a few different problems there, and presumably, satellites need to communicate with the ground in some way. Would that cause problems for radio astronomy?

Interviewee: Nisha Gaind

Yes, exactly. That is another problem. Radio astronomers use these huge dishes to try and capture radio signals from deep in the Universe and there is a concern that these communication satellites will be using a band of frequencies that will interfere with radio astronomy observations, potentially rendering some astronomical data useless.

Interviewer: Nick Howe

So, these satellites have already been launched, but as we said, there are future launces planned – are there any different things planned for the future that may help mitigate some of these problems?

Interviewee: Nisha Gaind

Yeah, so these companies – SpaceX and others – are currently engaging in conversations with the astronomy community because it’s not just this launch that happened yesterday. There will be potentially tens of thousands of these satellites in the years and decades to come, so mitigation conversations are a very important part of what is happening now. One, which is to mitigate this brightness issue, would be to actually paint the underside of satellites, i.e. the side that faces Earth, a sort of dull black to literally make them appear fainter, and another approach that’s being discussed is to look carefully at the frequency bands that satellites will be using. These are regulated by a body and there are some discussions about shifting the frequency bands that the satellites might use or, in fact, turning off satellites in certain frequencies as they pass over radio astronomy observatories.

Interviewer: Nick Howe

So, moving back down to here on Earth, we’ve got another story and this one is about a huge study that has shown that there is a gender gap in chemistry publishing. Nisha, what can you tell me about this?

Interviewee: Nisha Gaind

So, it’s a study that has found that across a huge number of papers, women are less likely to get papers accepted for publication in chemistry journals than their male colleagues are.

Interviewer: Nick Howe

And who was this study conducted by?

Interviewee: Nisha Gaind

So, this was done by the Royal Society of Chemistry, which is a British learned society that has a huge number of chemistry journals, and they publish all sorts of research in the chemical sciences.

Interviewer: Nick Howe

Right, and this was looking at corresponding authors. What specifically did it find?

Interviewee: Nisha Gaind

So, it found that although 36% of authors on submitted manuscripts were women, only 23% of the papers that were accepted for publication had female corresponding authors, and it also found that work that had a female corresponding author was less likely to be cited than work that had a male corresponding author.

Interviewer: Nick Howe

How much less likely was it to be cited?

Interviewee: Nisha Gaind

So, papers authored by men, on average, were cited 7 times and papers authored by women were cited just over 5 times.

Interviewer: Nick Howe

So, if I was to put my devil’s advocate hat on for a second, that doesn’t seem like a huge disparity.

Interviewee: Nisha Gaind

Yeah, in absolute figures it might not seem like a large disparity, but it’s important to remember that these disparities exist in every part of the publication process and they have been shown to exist across fields, in paper acceptances, in citations, in invitations to peer review, so over a long career as a scientist, these are all things that add up and disadvantage women.

Interviewer: Nick Howe

Does this new study offer any clues as to why this disparity exists?

Interviewee: Nisha Gaind

Well, this is something where there will be a really complex interaction of subtle biases and these are difficult to pin down exactly, but we all know that they exist, and as well as that, there are fewer women chemists to begin with and there are a set of issues that underlies that as well. But importantly, the RSC, the Royal Society of Chemistry, says that it will be taking action to address gender bias and it will be doing that through things like unconscious-bias training for its editorial staff, recruiting more women to be peer reviewers and to be editorial-board members.

Interviewer: Nick Howe

Well, thanks for joining me, Nisha. Listeners, for more on those stories, head over to nature.com/news.

Host: Shamini Bundell

That’s all for this week, but don’t forget, if you want to see that 3D printer in action, then we’ve made a video just for you. You can check it out over at youtube.com/NatureVideoChannel. I’m Shamini Bundell.

Host: Nick Howe

And I’m Nick Howe. See you next time.