The A - Zika of viruses: Preventing Pandemics

A recipe for a soft robotic skin that's sensitive to touch and has the ability to change colour, like an octopus, has been developed by engineers in the US. This could pave the way for blushing robots and 3D phone displays. Rob Shepherd, who led the group behind the invention, told the group how it came about...

Rob - There's a field now called soft robotics and these machines are capable of working around humans safely, which is very important.  But there are some things they can't do since their bodies are required to stretch to large degrees - we need electronics that can stretch with them. Some of the same students that were in my lab were taking a course on engineering with soft materials where I tasked them with coming up with a new device and they, on their own, decided it would be great to impart light emitting particles into these sensors.  So now, they created a device that can sense touch and also emit light in red, green or blue.

Chris - Wow.  So how does this work - talk us through effectively what you have made and how it actually does that?

Rob - So this material is rubber.  There are two different kinds of rubber; there's one that doesn't conduct electricity and another one that does conduct current.  And so, by layering sheets of these, we can create the sensors and the light emitting displays, and because it's all rubber, it stretches like rubber and it's soft like rubber.

Chris - So how do you make the rubber conduct electricity?

Rob - So this technique, actually, was developed a couple of years ago at Harvard. What they did is they put salt water inside of a rubber and we took that material and layered it with an insulating material and that composite is what gives us this new ability.

Chris - How does that architecture then - layers of a conducting rubber and a non-conducting - an insulating rubber - turn into something which a) can detect pressure and b) also make light?

Rob - Well what you've just described, we call a capacitor, and when we can stretch the capacitor, we change the distance between the plates of the capacitor.  That capacitor's change results in a signal that we detect.

Chris - How do you get the light out though?

Rob - Well, in the insulating rubber we put light emitting particles and when we apply voltage across the plates, they emit light.  One of the really cool features about the work is that it's made by casting a liquid and turning it into a rubber.  Depending on how we cast it, we can have as many pixels as we like.

Chris - Then the application of this would be that if I built a robert with a human hand like structure, it would know when it was curving that surface around my hand to shake my hand.  It would know how much it was stretching and, therefore, how much force it was applying to my hand so you wouldn't be in that ignominious situation where you've made a beautiful human-like robot that's capable of taking my arm off?

Rob - That's right.  Since one of the major benefits of soft robots is that they can interact with humans safely.  It's important to also let them feel what they are interacting with and that's what this does.

Chris - How easy is that to achieve thought? You've done this in a small piece of material, but could you extrapolate this to a whole robot?

Rob - That's exactly what we're doing right now.  So our next step is to put this skin onto a larger, more functional robot and test it out and we believe it's very possible.

Chris - And now that you can get this beautiful lighting effect for free. I mean lots of people wear makeup; your robot could almost have light generated, self-made makeup, couldn't it, so it could even blush. What's the application of being able to put the light in there as well?  Why is that helpful?

Rob - Well there's a few reasons.  We make a point in the paper; there's two things this technology enables.  One are robots that can change their colour and another are displays that change their shape and you pointed actually to a very important point - make-up is not useless.  The ability to create an emotional response with the people you are interacting with is important and we believe, as robots work with people more, their ability to communicate information visually is very important and that's what we can do with this technology.

Have you been getting your forty winks? Because researchers have revealed this week that lack of sleep actually gives you the metabolic equivalent of the marijuana munchies, which could lead to unnecessary binge-eating. Erin Hanlon explained her research to Chris Smith...

Erin - There's an association between insufficient sleep, or short sleep, and the increased risk of obesity and there's been some carefully controlled laboratory studies that have shown that when people are sleep restricted, they are reporting feeling hungrier and having a stronger appetite, most specifically for high carbohydrate and high fat foods.  So we wanted to examine what might be causing this increase in appetite and further help to explain the current association with the increased risk of obesity following sleep restriction.

Chris - And just to be clear, the increased appetite that's measured in these people; that's not just because if you're awake longer, you're functioning for longer, you need more energy, therefore you compensate by eating more?

Erin - Correct.  So the energy need of being awake longer is actually quite modest and studies have started to show that people are consuming more calories than are actually needed to maintain wakefulness.

Chris - So something else is going on, driving people who are in a state of sleep deprivation, to overeat?

Erin - Exactly. That's exactly it...

Chris - But we don't know what it is, as yet?

Erin - Right.  Well we're starting to kind of tease those things apart.  It's probably a lot of things working in concert and our current study is adding to this growing literature and suggest one pathway by which this might be occurring.

Chris - What did you do to explore it and what is that pathway?

Erin - Right.  So we brought people into the laboratory; we had then sleep either eight and a half hours a night or four and a half hours a night, and we examined a system that is involved in many areas.  It's involved in stress, the immune system, pain, reward and specifically reward driven eating or hedonic eating.  So we explored this system, and it's actually called the endocannabinoid system. Following normal sleep, we found that blood concentrations of lipids that are involved in this system are low overnight and high during the day. When these individuals were sleep restricted, during the day those levels were even higher.

Chris - You are hypothesising then that those are driving the increased appetite that these people display?

Erin -   That's what we think, because the endocannabinoid system has been known to be involved involved in overeating, and actually overeating highly palatable foods.  So it's been thought that this system was involved in brain reward pathways and might affect eating behaviour via reward circuitry.  So seeing this increase in blood concentrations suggests that this system might be overactive following a state of sleep restriction.

Chris - In other words, sleep restriction could be mimicking the marijuana munchies.  The idea that people who use cannabis also tend to report getting hungrier, and eating more, and a tendency towards being overweight.

Erin - Exactly.  So marijuana activates the endocannabinoid system as well.  So we think that perhaps sleep restriction, just like marijuana usage, is activating the endocannabinoid system to cause overeating and overeating of highly palatable, rewarding foods.

Chris - Why?

Erin - I don't know.

Chris - What do we think the benefit of that is?  Is that just because, if you are sleep deprived you're more likely to be a bit less motivated, a bit more tired, a bit sluggish, therefore making sure you feel like you want to keep eating and stay at the top of your energy game, means you're less likely to become someone else's lunch in our evolutionary history?  Is that the idea?

Erin - It was probably protective at some point in a state of feast or famine, when you had to overeat to have energy stores for other times when you might not have access to food, but it's become a little bit maladaptive lately.

Chris - Where does this leave us then? What do we have to ask now, and does this help us to solve the problem for people who do gain weight because they're not getting enough sleep?

Erin - I don't think it will actually solve the problem but I hope it draws attention to the fact that sleep restriction and sleep deficiency is associated with a lot of negative outcomes and increased feeding just happens to be one of them.  So, hopefully, this draws attention to the fact that we need to think of adequate sleep as an important aspect of maintaining good health and just as a byproduct of the day.

There's a disease dubbed the Angel of Death, which has wiped out millions throughout history. Thankfully, it's also famous for becoming the first disease humanity ever managed to eradicate. Georgia Mills spoke to medical historian Mary Dobson to get the story of smallpox.

Georgia - I wanted to hear the story of how smallpox went from being one of the world's deadliest diseases to being one of sciences greatest success stories.  So, I went to meet medical historian and author of the book "Murderous Contagion," Dr Mary Dobson at Cambridge University Farm to find out about this disease...

Mary - It really was a devastating disease.  People would be covered in horrible pustules; they would be exceptionally painful; some would die from a hemorrhagic fever; probably a third of those who contracted smallpox would die;  survivors could be pockmarked for the rest of their lives and, I think, an unknown, not often mentioned is blindness, so again, those who survived could be blind for life.

Georgia - With such a frightening prognosis, smallpox left a significant mark on history. British historian Lord Macaulay made this observation in the 1800s.

"The smallpox was always present, filling the churchyards with corpses, tormenting with constant fears all whom it had not yet stricken, leaving on those whose lives it had spared the hideous traces of its power: turning the babe into a changeling at which the mother shuddered, and making the eyes and cheeks of the betrothed maiden the objects of horror to the lover..."

It affected rich and poor alike, knowing no class boundaries. Ramses V, Abraham Lincoln and even Mozart all contracted smallpox, so how did people try and avoid this dreaded disease?

Mary -  I think smallpox is an interesting case because people were aware that it was contagious, so prevention was one of trying to avoid being close to a contagious person.  Bloodletting was the cure for almost everything in the old days, right up to the mid nineteenth century.  It would have done very, very little good for anyone suffering from smallpox.  So, not a lot that they could do but numerous old remedies are concocted...

Georgia - I think I read one that was powdered horse manure...

Mary - Yes, powdered horse manure is one of those good old fashioned remedies -  anything from garlic to alcohol or herbs.  Around the 10th century in China it was said that they removed scabs from the drying pustules of a smallpox patient, pounded them into powder and then blew a few grains into the nose of people who had not had the illness...

Georgia - Ewh...

Mary - Yes, and one of the things that amuses me is: up the right nostril for a boy and the left one for a girl...

Georgia - Of course...

Mary - Who knows why!

Georgia - This idea of infecting healthy people intentionally with small parts of the virus did actually work to some extent but what came next in the fight against smallpox changed everything - the vaccination.  And it's at this point we meet a key player in the story - the humble cow - or rather we met about 30 of them including one very bold character who wanted to join in with the interview.

It's trying to eat the microphone! No, no...  

But what do cows have to do with the smallpox vaccine?

Mary - Well - you could actually say vaccination.  The word vaccination is from vacca which is the Latin for cow.  The discovery of vaccination which is credited to Edward Jenna in 1796 is because he took up a local story that milkmaids who contracted something called cowpox, possibly from infected udders of cows, were immune to smallpox.  And, after some years, he took a very, very brave decision to try out an experiment and there was a young girl, a milkmaid, Sara Nelms who had cowpox.  So he took from one of her pustules from cowpox some of the matter and he then used the son of his gardener, a young boy called James Phipps, and he scratched some of the pus into James Phipps.  Six weeks later, he inoculated smallpox virus (living virus) into James Phipps to see whether the cowpox had indeed protected him, and the result was James Phipps did not get smallpox.

Georgia - Cowpox was a similar virus to smallpox but much let dangerous so, once this boys immune system learnt to recognise it, smallpox no longer held a threat.  Ladies and Gentleman... the world's first vaccine.  After initial rejection from his peers at the Royal Society, Jenna's ideas took off and vaccines made their way all across the world. Starting in Gloucestershire, ending up in Europe, Russia and making it all the way to the Far East.  But, even though these vaccines saved millions, people were still contracting the disease right up until the 1900s.

Mary - So, in the 1960s, we've got about 10-15 million people contracting smallpox a year - probably about 2 million deaths.  So the World Health Organisation took this as a very serious threat.  There was a vote and it only went ahead by two votes to embark on an intensified ten year smallpox eradication programme. Initially, they started with mass vaccinations, so the idea was to just vaccinate everybody.  A new technique was freeze-dried vaccine, which was good for tropical climates and, actually, South America was free by 1972, but Africa and Asia were formidable barriers.  I look back and reading the accounts of those dedicated workers who crossed jungles, rivers, reached outlying rural communities to try and vaccinate communities.  It is an incredible story and they were heroic - absolutely heroic. It was also a campaign that transcended ideological and political boundaries.  It was during the cold war and, actually, the U.S. and the Soviet Union fully cooperated so I think that was really interesting.

1979 - The World Health Organisation based in Geneva announced eradication.  A momentous, absolutely momentous timing and one of the perhaps saddest and ironic twists to the smallpox eradication success is that in 1980, it's eliminated from the list of world infectious diseases.

1981 - a year later, we hear of the first cases of HIV Aids.  I find it really very sad that juxtaposition between this incredible success story and the sadness with which the HIV Aids story broke in the 1980s.

One way that new viruses can appear is if scientists create them in the laboratory. Researchers often genetically modify organisms in order to discover how things work and cause disease at a molecular level. Famously, a few years ago, researchers in the Netherlands made forms of H5N1 influenza - "bird flu" - with a 70% fatality rate and the ability to spread efficiently between mammals, including us humans, so should we be scared and should this even be allowed? Filippa Lentzos is an expert on biosecurity from King's College London and she explains to Kat what the scientists were doing.

Filippa - Hi Kat.  Well broadly, what these two labs were trying to do was to understand the factors that determine the ability of animal viruses to spread to humans. So what they did was to mutate the N5N1 bird flu virus to make it airborne and transmissible to mammals and, as you said, including humans.

Kat - So it doesn't normally travel in the air but they made it so that it could survive in the air and get from animal to person?

Filippa - Exactly right, and that mutated virus was highly virulent and as efficiently transmitted as a common cold.

Kat - Now that sounds like a bad thing to be doing. Why on earth did they even want to try and do this?

Filippa - Well, a lot of this is part of basic science.  New and emerging infectious diseases are also considered some of the biggest threats to national security but we are unable to predict which specific virus subtype will trigger the next pandemic. So it's really in order to address the knowledge gap and to understand flu transmission, aid detection, prepare vaccines, that sort of thing.

Kat - So effectively they were trying to make stuff in the lab that could have happened in real life to work out... okay can we figure out what these viruses might be like if they do arise in the real world out there?

Filippa - Exactly right.  They were trying to work out  what might happen in the future and how we would then respond to that.

Kat - So this does sound quite risky though. How risky is it?  Is there a chance that these kind of things could escape?  Almost you get the impression of a mad scientist in their lab going "I'm going to make a killer virus."  What are the controls and the checks and balances here?

Filippa - There certainly are a number of risks against this and enhanced viruses, as you said, could be accidentally released and they could also be intentionally released from a lab. In that sense, they would potentially expose the surrounding populations to pandemic pathogens.

Kat - What are the mitigations against this? It just bothers me a little bit to know that researchers are building these things in labs. How are they protected?

Filippa - Well, currently they work under biosafety containment precautions but in response to the experiment we were talking about - the H5N1 experiment that was done a few years ago.  What happened was the scientists broke the news, pre-publication, pre-review, in the media and it was met with substantial alarm from the scientific community...

Kat - Not surprising...

Filippa - No.  I mean the New York Times went with the headline " An Engineered Doomsday" - this was really a big deal.  The advisory body in the U.S. that was looking at this advised against publishing the methods section; they said they could go ahead and publish the experiments but they weren't allowed to publish the methods section because that might give information to people who would misuse it.

Kat - Nefarious people. Then I understand that funding was stopped for this kind of research. Where are we now with attitudes towards doing and funding this kind of  research?

Filippa - Initially there was a self-imposed voluntary moratorium by the scientific community on this; that was lifted and work resumed in 2013. That then became entangled with safety concerns and there were a couple of high profile lab safety breaches at the time and, eventually, the U.S. government stepped in in October 2014 and pulled their funding on this gain of function research, of concern.  So it was a particular subtype of gain of function research that they pulled their funding on and they started this deliberative pause and that's really what we're coming to the end of now.

Kat - So there's a debate, I understand, happening in Washington this week to say - so should we do this, how do we go forward. What's going on there?

Filippa - Well the debate is really about risk assessment of this gain of function work and about who should be making those assessments. Should it just be scientists, should it be their institutions, should it be funders, should it be publishers or, much more broadly, should it be regulators, vaccine manufacturers, ethicists?  You know, these are big questions.

Kat - Because, I guess, we've also got to balance the benefits of find out how these viruses could potentially happen and work with the risks we might accidentally cause a pandemic.  So should researchers be allowed to do this?  What are the things that we need to consider when deciding whether this kind of research (engineering these effectively new super-viruses) should be allowed to go ahead.

Filippa - Well, there will be cases where the risks outweigh the benefits and there are experiments which simply should not be done.

Kat - What kind of things would that be?

Filippa - So, for instance, making ebola airborne, making influenza viruses resistant to vaccines or antivirals. So I think we need clear red lines like this and we need a regulatory framework that also applies to the military and to commercial sectors and that isn't just limited to those in receipt of NIH funds, which is the current situation in the United States.

Kat - So this is like a global - okay guys do not do this kind of thing?

Filippa - Absolutely! Clear red lines!

Smallpox was eradicated in 1980. But, 30 years later, the virus that causes it is not gone at all. It exists in two labs, one in Russia and the other in America. Georgia Mills spoke to Professor Geoffrey Smith, to hear the end of smallpox's story. 

Geoffrey -   It might sound logical that at the end of a disease eradication programme, that the virus that causes that disease should also be eradicated and many people took that view.  Other people, however, argued that we didn't really understand why that virus was able to cause such a devastating disease in man and, if we conducted further research on that virus and gained that understanding, that would be helpful not only for perhaps treating and preventing other poxvirus infections, but other virus infections in general. So in 1996, The World Health Assembly adopted a recommendation made by the orthopoxvirus committee that advised the WHO that all remaining virus should be destroyed.  So that recommendation was made in 1996 and the World Health Assembly debated it and passed that resolution.  The date for destruction was set in 1999, and that date came and went and the destruction did not take place.

Georgia - So what happened? Well there was a postponement so that three lines of research that needed the virus could be continued.  These were producing diagnostic test for future cases of smallpox, creating a safer vaccine and making antiviral drugs so the disease could be treated.  But, if the virus that cause smallpox, called variola, was destroyed, why would we need drugs to treat it?

Geoffrey - The reason that some nation states wanted to develop drugs was the fear that actually the virus, even if it were destroyed at the two collaborating centres, might exist somewhere else.  And I think it was following the attacks in the U.S.A. in 9/11 that the U.S. government, for instance, felt that if people were prepared to fly aeroplanes into densely populated buildings, then would they stop at using a virus of this type as a bioterror weapon if they were able to get their hands on it.

Georgia - So are there any risks to having these remain in the U.S.A. and Russia?

Geoffrey - Well there is certainly a finite risk in keeping a virus.  I mean you have to maintain the security.  I have to say that the security is very good and both these facilities are inspected regularly by WHO authorised teams and I think the chances of the virus getting out of either place is remote.  More of a concern would be that it's out there somewhere else that we don't know about already or that it could be remade.

Georgia - Some argue that if the virus could be remade anyway, there's no reason not to destroy the samples but others argue this would be premature and we still have a lot to learn from them. Geoffrey Chairs the WHO's Advisory Committee on Variola Virus, who meet to discuss the need to continue this research so I asked him - will we ever be closing the book on smallpox for good?

Geoffrey - The decision to destroy the virus is taken - it's not a case of if, it's only a case of when.