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Interviewer: Shamini Bundell
Hello and welcome to the Nature Podcast. Science and art come together this week as engineers program E. coli to see in colour and use it to paint pictures.
Interviewer: Adam Levy
Three papers published together trace the spread of Zika virus across the Americas.
Interviewer: Shamini Bundell
And, what will it take to get microscopic medical bots out of the lab and into your body? This is the Nature Podcastfor May 25th2017. I’m Shamini Bundell.
Interviewer: Adam Levy
And I’m Adam Levy.
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Interviewer: Adam Levy
First, Kerri is here with a story about a super villain and the band of scientists trying to track it down.
Interviewer: Kerri Smith
The story starts around 2013. The super villain is Zika virus and it was always one step ahead.
Interviewee: Bronwyn MacInnis
Unlike other recent outbreaks in the public consciousness, like Ebola for example, or the flu, Zika was relatively off the radar.
Interviewer: Kerri Smith
This is Bronwyn MacInnis from the Broad Institute in Cambridge, Massachusetts.
Interviewee: Bronwyn MacInnis
We all in our own domains scrambled to learn as much as we could about the virus and how it spread and caused disease.
Interviewer: Kerri Smith
They knew that their enemy had a long history. It was first detected in the late 1940s in Africa, but recently all that had been seen of it were a few cases in Asia on some islands in the Pacific. That was before it reared its head in Brazil. Here’s Nicholas Loman, an infectious disease specialist at the University of Birmingham in the UK.
Interviewee: Nicholas Loman
Really what we were trying to do was fill in the gaps between what was going on in Asia, and how we ended up where we are now.
Interviewer: Kerri Smith
Zika had taken everyone by surprise and there were plenty of reasons that it was a fearful foe.
Interviewee: Bronwyn MacInnis
There were so many questions when Zika really broke onto the public and scientific consciousness.
Interviewee: Nicholas Loman
Zika’s kind of difficult, particularly because many symptoms are asymptomatic.
Interviewee: Bronwyn MacInnis
Infections are quite transient.
Interviewee: Nicholas Loman
And when there are cases, it’s very hard to detect clinically whether this is Zika you’re looking at or another virus that is transmitted by mosquitos.
Interviewee: Bronwyn MacInnis
Where and what symptoms and complications we were seeing, and then questions about the evolution of the Zika virus as it spread.
Interviewer: Kerri Smith
The scientists had their work cut out, but they also had secret weapons. They could sequence Zika genomes, fingerprints of the virus left behind in samples from patients and mosquitoes it had infected.
Interviewee: Nicholas Loman
If we get genome sequences and then we can compare them, they’re really like a kind of time capsule. You can peer into them and try and understand how the virus has evolved.
Interviewer: Kerri Smith
They were also going to need to go and get these samples, especially from regions near the north east of Brazil. This is the region where they suspected the outbreak began and where the strongest link emerged between Zika infection in pregnant women and babies being born with abnormally small heads, a condition called microcephaly. To travel around the infected regions looking for Zika in samples, one group of scientists kitted out a vehicle befitting a team of superheroes… [Music end sound effect] … A caravan being towed by a jeep.
Interviewee: Nicholas Loman
The inspiration was Top Gearstyle road trip.
Interviewer: Kerri Smith
Top Gear, for non-Brits, is a BBC TV show about cars whose hosts often do driving related trips and challenges. Nicholas Loman and his team worked long days driving the mobile lab between regional labs in north east Brazil, combing through samples for viruses and generating the sequences to see how they were related. They used every minute of the trip to do it, says project leader Luiz Alcantara who’s based at the FIOCRUZ Research Institute in north east Brazil.
Interviewee: Luiz Alcantara
They took the virus to sequence it inside the bus. During the trip between one state and another state you could sequence the genome inside the bus.
Interviewer: Kerri Smith
Having the mobile lab sped everything up. The team released data online as soon as they could collect it and posted preprints of their work. Their data, plus the work from two other groups, including Bronwyn’s, has yielded the earliest Zika sequence yet found in Brazil from February 2014. Overall, the results published in 3 papers in Natureand one in Nature Protocols, give the clearest picture yet of how Zika emerged.
Interviewee: Nicholas Loman
Zika in Brazil seemed to be split into several sub-lineages or different clusters but, you know, the ancestor of these clusters all seemed to be from north east Brazil, and as far back as early 2014, so probably introduced into north east Brazil and circulated in north east Brazil for a full year before it was first detected.
Interviewer: Kerri Smith
From north east Brazil it leapt to other parts of the country before finding its way across the Americas to the Caribbean, and from there at least 4 separate times to the US, to Florida.
Interviewee: Nicholas Loman
I mean, we can really get all that from finding genetic information.
Interviewee: Bronwyn MacInnis
It also gives us, at least prospectively, evidence that with more sensitive methods, like genome sequencing for example, surveillance systems could have been able to pick this up.
Interviewer: Kerri Smith
At the end of most superhero stories, the villain is crushed, never to be seen again.
Interviewee: Bronwyn MacInnis
In theory, that’s exactly what we’d love to be able to do.
Interviewer: Kerri Smith
But in this story the end is a little more complicated. This is the real world, after all. Bronwyn said that their data will help pin point where any new hotspots of Zika come from and which sequences they relate to. That could inform when to screen people arriving from particular countries for example. Other colleagues are sequencing genomes from the on-going yellow fever outbreak in Brazil to keep an eye on how it’s being transmitted and help public health officials keep a lid on the outbreak. Meanwhile, the mobile lab is on the move. This week, Luiz and the team are starting the second leg of their project, covering the Amazon. They plan to take the kit to the central, east and south of Brazil in the coming year and there’s good news for the passengers: the bus has had an upgrade.
Interviewee: Luiz Alcantara
It’s a motor home with two labs and you’ll be more comfortable in that bus.
Interviewer: Kerri Smith
That was Luiz Alcantara and you also heard from Nick Loman, and Bronwyn MacInnis. There are three papers that trace the Zika outbreak in Naturethis week. Find them all at nature.com/nature and a News & Views by Michael Worobey, who you’ve heard from before on the show, in the same place.
Interviewer: Shamini Bundell
Later on in the News Chat, experimental Ebola vaccines may be used to tackle the latest outbreak in the Democratic Republic of Congo. Right now, Kerri’s back again with the Research Highlights.
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Interviewer: Kerri Smith
One way of controlling diseases or pests is to handicap them with harmful mutations. But the natural world has a way around, that’s according to a study of a crop pest called the red flower beetle. Researchers tested whether the beetles could evade the effects of an inserted mutation known as a gene drive with their own naturally occurring genetic variation. Many wild beetle groups had mutations that made them immune to gene drives targeting 3 different genes. Previous work from the same team suggests a similar effect in mosquitoes. The paper is in Science Advances.
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Interviewer: Kerri Smith
The sticky feet of geckos have inspired scientists to make adhesives but it’s hard to get them working on 3D surfaces or delicate objects. A team of material scientists spread tiny, stretchy hairs across a flexible membrane and attached that to a solid disk. The gadget has a tube attachment that can change the pressure on the membrane. When they lowered the pressure the membrane got stickier, allowing them to position the device on an object and then grab it. They suspended coffee cups, cherry tomatoes, and a plastic bag – just your regular lab bench debris. More in the journal, PNAS.
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Interviewer: Adam Levy
Christopher Voigt spends his time playing with bacteria. So do lots of biologists, but Christopher’s career path didn’t start like most of theirs with lectures on Darwin and DNA and practicals involving fruit flies.
Interviewee: Christopher Voigt
Well I actually haven’t taken a class in biology, so I, erm…
Interviewer: Adam Levy
Not a single class?
Interviewee: Christopher Voigt
Yeah, I know. Don’t tell them, but I was interested in computer science when I was in high school and I did a lot of programming and I decided in chemical engineering to apply it to problems in the physical sciences, and to me, using biology as a programming substrate is about as hard as it gets and so I took it on as a challenge.
Interviewer: Adam Levy
Christopher is interested in programming living organisms to do all sorts of things. This week, he’s got a paper out in Nature Chemical Biologywhich describes how bacteria can be genetically engineered to see in colour and capture images. I asked him how common it is to engineer bacteria to respond to light.
Interviewee: Christopher Voigt
There has been a lot of work to be able to get cells to respond to light. About a decade ago we built bacteria that were able to respond to one colour of light. We had a red light censor and connected it to an enzyme and when that enzyme is expressed it then turns the dish black. So we have a petri dish on which we spread the bacteria. So you can take a black and white image, shine it on the plate and then it would record that image. It’s very stable. I still have about a dozen of them in my office.
Interviewer: Adam Levy
Do you have them up on the wall?
Interviewee: Christopher Voigt
I do.
Interviewer: Adam Levy
Have you got pictures of your family that you’ve done or anything like that?
Interviewee: Christopher Voigt
No, nothing of my family but we have Super Mario.
Interviewer: Adam Levy
So, you printed these pictures back in 2005 by shining an image onto a plate of these light sensitive bacteria. The light triggers them to make pigment and so they gradually build up the picture a bit like a photograph. But now you’ve taken it a step further by inserting 3 light receptors into the bacteria: one for red, green and blue light. And then you’re using those sensors to control production of red, green and blue pigments. So now a plate of these genetically modified bacteria can make colour pictures.
Interviewee: Christopher Voigt
That’s right. What we’ve done here is combined different light sensors that respond to different colours that allow you then to shine a colour image at cells and control different genes with the different wave lengths.
Interviewer: Adam Levy
So that seems like, in some ways, the next logical step, but presumably it’s been quite tricky. It’s taken you over 10 years to get to that stage.
Interviewee: Christopher Voigt
Well we haven’t been working the entire time on this project but it did require a lot of advances to make it even possible. As you increase the complexity of what you’re trying to get a cell to do, it becomes exponentially harder to get all the pieces together, have a working concert and have the cell be happy when you put the DNA in.
Interviewer: Adam Levy
It sounds like a really fun thing. It sounds like a really neat thing to be able to create these almost photographs, but presumably there’s some motivation for it beyond just, hey, look it’s nice, we can create these pictures.
Interviewee: Christopher Voigt
Yeah, so part of the motivation was to be able to control gene expression remotely and quickly and so for example, if you’re looking at the production of a chemical in a fermenter, for example. If it’s in a million litre fermenter then it becomes technically difficult to turn genes on and off when they’re technically needed. And so what this would allow you to do is to use different colours of light to, in real time, change what the cells are doing without having to directly connect with the cells, and so you can imagine having a big fermenter with all different colours of light flashing in it, so we think of it as sort of disco bacteria.
Interviewer: Adam Levy
So here you can control the expression of different genes with 3 different colours of light. Would it be possible to go even further and have an even bigger range of light receptors inserted into the bacteria?
Interviewee: Christopher Voigt
Certainly. I think there’s a bacterium that has up to 50 light sensors in it to respond to all different types of things. But I think what we’re really trying to do with this is not scale up making better photographs, but to scale up genetic engineering. We’re just using this as a toy example of how to do that. And so we envisage a future where we can go from this design that we published to being able to design entire genomes where you have sensing functions that are happening, genetic circuitry that process the information from the sensors and many different pathways that were being controlled so that you could create an organism, that say, makes a much more complex material or chemical than you could do today.
Interviewer: Adam Levy
And are you done with this toy example now – now that you’ve kind of proved the concept? Is that good? You can put they toy back on the shelf or are there more things you want to do with it?
Interviewee: Christopher Voigt
Oh there are lots more things to do, even as a toy system. So I’d love to start thinking about, so, can we put in the ability to respond to particular patterns of light, which are recorded patterns of light. You can really imagine all sorts of things to have the cell do and that would move it towards not just being able to see colours, to see images, but to start to perceive images as well.
Interviewer: Adam Levy
That was Christopher Voigt. Find the full story at nature.com/nchembio. And, at nature.com/news there’s also a news story…
Interviewer: Shamini Bundell
… Written by our very own Adam Levy. Now, I’ve been finding out about medical microbots which are basically tiny robots that could be designed to move around inside your body doing helpful, medical things.
Interviewer: Adam Levy
Like in the cartoon The Magic School Busor the film Fantastic Voyagewhere the people shrink down to microscopic size and have to swim around through blood and splash through stomach acid and fight white blood cells.
Interviewer: Shamini Bundell
Not really, no.
Interviewer: Adam Levy
Okay, how about the microbots in Big Hero 6or the Borg nanopr-obes in Star Trekor the drones of tiny robots that Prince Charles says are going to turn everything into grey goo.
Interviewer: Shamini Bundell
Oh, yeah, no that last one, that’s actually it, yeah.
Interviewer: Adam Levy
Really?
Interviewer: Shamini Bundell
No.
Interviewer: Adam Levy
Oh.
Interviewer: Shamini Bundell
Look, medical microbots do have the potential to be pretty cool. They could be used to carry drugs around or perform surgery or replace failing bodily functions. But, there’s still plenty of work needed before they’ll be ready to transport cancer drugs to tumours or clear clogged arteries. A Comment piece this week takes a look at the state of medical microbot technology, and so I sat down with NatureComment editor, Jo Baker, to find out more.
Interviewee: Jo Baker
There are many groups around the world who are looking at building these micro machines: different types, different ways of propelling them. They need to overcome a lot of different challenges about the environment within the body. They can be about the size of a cell, so imagine them in the bloodstream and they’ve got to somehow weave their way through.
Interviewer: Shamini Bundell
So at the moment the focus is on designing the basic structure; how they work and how they propel themselves is quite a big issue with that?
Interviewee: Jo Baker
Yeah, so there are various ways to propel them. So the first way is using chemistry. They’re called chemical micro-motors and you can build in catalysts that react when you put them in the liquid and they can move quite quickly and quite well but they are very hard to control and they tend to use really toxic substances.
Interviewer: Shamini Bundell
So, chemical micro-motors is one option with some challenges to overcome: what are the other types of propulsion?
Interviewee: Jo Baker
The other type is you can drive them – if you make them out of metallic materials, so you put something like iron, a layer of iron in them – then you can drive them using magnetic fields. So you can steer them fairly precisely if you want to move them in a straight line from a to b. But if you want to make them go through a blood vessel or something like that, it’s very hard to get them to move more naturally and that’s where the third type of micro-motor comes in, which uses a biological means of propulsion. If you make a synthetic micro-motor and then you can put a sperm cell or a bacterium, then you can use it to drive a little structure.
Interviewer: Shamini Bundell
So, combining artificial components and naturally occurring biological components?
Interviewee: Jo Baker
Yes, because the physical micro-motors are only good at certain tasks and they’re fairly – they’re a little bit clunky, essentially, in what they can do at the moment – whereas, obviously, biology gives us wonderful things like bacteria and sperm which they can do a whole load of other things. They can swim naturally through the body. They can actually perform natural reactions so if you want to fertilise an egg with a sperm, all of those reactions are things which the sperm can do.
Interviewer: Shamini Bundell
So you can use the biological bits for the bits that the mechanical bits aren’t very good at and vice versa when you need some mechanical bits for something that the biology isn’t very good at and one example was trying to help sperm that can’t move very well, which is a big cause of infertility. Can you use a mechanical micro-motor attached to the sperm to help with the propulsion?
Interviewee: Jo Baker
Yeah, so you can basically give it a lift to the egg. The authors of our piece have actually made this metallic helix which they can drive magnetically to move the sperm to the egg directly.
Interviewer: Shamini Bundell
The Comment piece mentions some of the current challenges that we have with micro-motors. What kind of things are currently causing scientists headaches?
Interviewee: Jo Baker
So at the moment everything is pretty much being done in the petri dish in a lab where you can look at it through a microscope and see what’s going on and you can control things and you can use big magnets. You can do what you like. But if you want to bring this into clinical settings then you need other tools. You can’t stick a human under an electron microscope. So these authors are calling for better biomedical imaging.
Interviewer: Shamini Bundell
Because if we are going to put a lot of very small, very fast moving things in our body, and want to see whether they’re working or not, we need to be able to see what they’re doing and that’s not something current technology can manage. What kind of things might be able to help with visualisations of micro-bots inside the body?
Interviewee: Jo Baker
The authors highlighted a few techniques that look very promising. They think combining different types of imaging techniques and taking the good bits from all of them is the way forward. So, for instance, ultrasound. If you combine it with different forms of infrared imaging and optical imaging, you can get both high contrast images and sensitivity and you can also get really good sharp images with good spatial resolution as well.
Interviewer: Shamini Bundell
And it’s not just imaging technology – there are still a lot of challenges with microbot technology as it stands currently?
Interviewee: Jo Baker
When you’ve finished using these things in the body, then what do you do with them?
Interviewer: Shamini Bundell
But the authors of the Comment piece did seem quite optimistic about the speed with which this could develop.
Interviewee: Jo Baker
I think they’re quite bold in their ideas and their experiments.
Interviewer: Shamini Bundell
They are talking about within the next decade we could have use for non-invasive, therapeutic microbots.
Interviewee: Jo Baker
Yes, I think they believe that if we find a few specific cases where these technologies can be used, so such as the assisted fertilisation, then you can really try and start to bring everything together. It gives people a focus.
Interviewer: Shamini Bundell
That was Jo Baker, talking about the Comment piece she edited, that was written by Mariana Medina-Sánchezand Oliver G. Schmidtand it can be found at nature.com/news along with some images of microbots including the sperm-bots mentioned in the piece.
Interviewer: Adam Levy
Time now for the latest news and Amy Maxmen is on the line from the NatureSan Francisco office. Amy there’s been an Ebola outbreak in the Democratic Republic of Congo, DRC. What’s the situation? How many cases have there been reported?
Interviewee: Amy Maxmen
So far there are 34 suspected cases. There’s been 4 deaths but only 2 of these deaths have been confirmed as testing positive for Ebola and the reason why there’s only two that are confirmed so far is that the samples have to travel from this area where there’s no roads at all. So the sample has to be taken by motorbike, by foot, to a health centre there and then transferred, I suppose, by car, on a lot of unpaved roads, to the capital in Kinshasa and that’s where they can be tested. So, so far only two have been confirmed and there are about 400 people who had contact with the people who are suspected of having Ebola that are being monitored.
Interviewer: Adam Levy
How much fear is there that this incidence of Ebola could spread more widely?
Interviewee: Amy Maxmen
On the one hand, the WHO was quick to say that they are taking it very seriously. That said, this is the eighth outbreak in DRC – at least the eighth break out. Maybe there’s more we don’t know about. And they have burnt out themselves and that’s just because people stay in their areas often because there’s not a lot of roads. So they’ve previously not spread like wild fire. Nonetheless there’s always a concern that it could spread and so people are taking it quite seriously.
Interviewer: Adam Levy
And in this case part of that taking it seriously is plans to potentially use a vaccine to protect against spread.
Interviewee: Amy Maxmen
Exactly, and that’s because during the last outbreak, sort of towards the tail end of the last outbreak in Guinea, there was a vaccine that looked pretty good in clinical trials in Guinea. Actually it looks really good. Even though it’s not yet been approved by any regulatory agency, the WHO put together a working group and that working group in April recommended that if there’s another Ebola outbreak, this vaccine be promptly deployed, as long as it’s the same strain and indeed it is the same strain.
Interviewer: Adam Levy
Well in that case, why not start giving out the vaccine as soon as possible? What’s stopping things progressing right now?
Interviewee: Amy Maxmen
That’s a great question. So, back to the remoteness of the area. It’s going to be very expensive and require a lot of person hours and efforts to get the vaccine to people. It has to be kept at minus 80 which is a really big deal in a tropical country. So it will have to go inside of freezers that stay cold and there’s not a constant source of electricity anywhere so it’ll have to be inside portable freezers, within helicopters, maybe on the backs of motorbikes. It’s logistically really, really hard to get there. I mean, to give you a sense, Doctors Without Borders, as of Friday still hadn’t got to the epicentre within the province in the north where the outbreak was. So logistically it’s going to be extremely complicated. It seems like the World Health Organisation and Congolese authorities and others are all on board to help this happen but it’s not going to be simple.
Interviewer: Adam Levy
And how would actually giving out the vaccine, once it’s in the correct location, work? Can you give it to people who’ve already been exposed?
Interviewee: Amy Maxmen
Well, what they would do is they would do the same sort of design that was taken during the outbreak in Guinea where they would vaccinate anybody who had contact with people who had had Ebola and also the contacts of those people. So this is called the ring design. So if they had already been infected, it’s too late, most likely, but the idea is if they had not been, then they’ll be protected.
Interviewer: Adam Levy
Is the protection pretty universal or is there still a chance people might catch Ebola even after the vaccination?
Interviewee: Amy Maxmen
There’s a lot of unknowns about how long the vaccine lasts for, however in the trial in Guinea, nobody who was vaccinated got Ebola. But the check point was 10 days after vaccination. So this doesn’t answer how long the vaccine lasts for but it does suggest pretty highly that there is some great coverage at least soon after the vaccine
Interviewer: Adam Levy
Elsewhere, in Chile actually, there’s been another experimental intervention that has been sparking controversy. Now, this isn’t about disease. What is this intervention looking to affect?
Interviewee: Amy Maxmen
So there’s a Canadian foundation who has proposed to the Chilean government to revive Chilean fisheries by releasing iron into the Pacific Ocean. And the idea is this iron would stimulate phytoplankton and I suppose that’s what fish would eat.
Interviewer: Adam Levy
Well, has this kind of idea ever been attempted before?
Interviewee: Amy Maxmen
Yes, there’s been at least 13 iron fertilisation experiments since 1990 but there’s been some kind of worrying side effects that it could possibly lead to toxic algal blooms. So actually because of these experiments, the UN convention on Biological Diversity put a moratorium on all but the smallest ocean fertilisation projects quite a while ago, but this group still would hope to do it.
Interviewer: Adam Levy
So how are they hoping to carry this out if there’s been this moratorium?
Interviewee: Amy Maxmen
Because the planned experiment takes place in Chilean waters exempt from those rules.
Interviewer: Adam Levy
And what are they actually hoping to learn from this experiment?
Interviewee: Amy Maxmen
I think previous studies aren’t very clear about possible benefits and the draw backs and so for that reason the Chilean government recommended that there should be input from the Chilean Academy of Science. So they’ll be meeting to discuss this and look at the evidence and to see if it should go forward.
Interviewer: Adam Levy
So why scientists should be concerned that this experiment might not be worth doing in the first place?
Interviewee: Amy Maxmen
They’re concerned because of the geology of the Chilean coast and the pattern of ocean currents there. It’s very difficult to see what an input in one place does in that specific place if the currents are moving, so the timing and the place of the iron input might shift over time. It’s hard to tell what came from where.
Interviewer: Adam Levy
So even if it was having an effect it would be hard to really observe what that effect was?
Interviewee: Amy Maxmen
Exactly. What worries scientists is that the foundation in 2012 had another fertilisation project that they carried out off the coast of British Columbia. And in that project, the group dumped iron sulphide into the ocean and in the years since scientists haven’t seen any evidence the experiment worked.
Interviewer: Adam Levy
Do we know when this might happen if it were to?
Interviewee: Amy Maxmen
So, we don’t know about when it will be approved but the foundation hopes that this happens as soon as 2018 and they would dump 10 tonnes of iron particles off the coast.
Interviewer: Adam Levy
Thank you Amy, our reporter based in San Francisco. Find all the latest science news over at NatureNews’ site, nature.com/news.
Interviewer: Shamini Bundell
That’s all we have time for this week but look out for Backchat, landing in your podcast feed in the next couple of days. I’m Shamini Bundell.
Interviewer: Adam Levy
And I’m Adam Levy.
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