Mind Meets Machine

Chris -   A controversy that's even got governments involved! In September 2011, Dutch researcher Ron Fouchier gave a presentation at an Influenza Conference in which he showed how he'd been able to make, relatively easily, a form of bird flu - H5N1 that can transmit readily between mammals which is something that the naturally occurring form of the virus thankfully can't yet do. The results describe the structure of what Ron Fouchier himself describes as 'probably one of the most dangerous viruses that you can make' were sent to the journal Science for publication.  But the paper has been suppressed on safety grounds, that the details could aid terrorists in creating weapons of mass destruction. 

The journal Nature also has a similar bird flu paper waiting in the wings for the same reason.  And now, both papers are currently under review by the US National Science Advisory Board for Biosecurity.  So how should sensitive, but nonetheless very important, scientific results like this actually get handled?  To find out more, I spoke with Mark Peplow, News Editor at Nature which this week asked authorities around the world this very same question.

Mark -   Okay, so this all revolves around some research which has been done on the avian flu virus - H5N1.  Two groups of researchers have basically made a mutant form of this virus which is more easily transmittable between mammals.  Actually, they've tested it in the lab and it's ferrets that they use as it's more easily transmitted, just by ferrets breathing the same air and that raises concerns that these viruses, if they escaped, could also be transmitted between humans and potentially trigger a huge pandemic.

Chris -   There are two aspects to this, aren't there?  One, is should we be releasing the information as to how to make this very pathogenic viruses that transmit very efficiently because there's a question over, whether this is safe from a bioterrorism perspective. The other is, the public health perspective, in order for scientists to be able to work out how to mitigate this threat, they've got to know what the threat is.

Mark -   Yeah, that's right and it's something that sometimes gets lost in some of the news reporting around this and that these mutant strains weren't born out of some reckless desire by mad scientists to push the boundaries of high risk science. 

So the issue is, like you said, should this work be published?  An awful lot of scientists say, "Yes, it absolutely should be published in full because it's important to understand how deadly these viruses are and potentially develop treatment against them."  On the other side, there are some people out within the security community, but even scientists as well, that argue that the benefits that you gain from this sort of work are just not great enough to counter the risk of an accidental release or the possibility that a terrorist could get hold of the recipe, if you like and cook up some of these viruses themselves. 

Those in the security community take a broader issue which is some of the mechanisms for oversight of this sort of work really aren't sufficiently well-developed.  They're saying, "Look, the argument about this is coming up when this work has already been done.  It's about to be published" and the security community is saying, "Look, we need a much more stringent oversight system to make sure that these conversations start happening before the experiments go on and not after them."

Chris -   And where does a journal like Nature stand on this?  You've got some information that you want to publish which is for the good of the scientific community but may have political consequences.  At what point does it become a problem with someone saying, you can't put that out?

Mark -   Well because I'm the News Editor of Nature, I can't actually speak on behalf of the section of Nature which publishes scientific manuscripts, but I know what our Editor in Chief Phil Campbell's position is on this and that is that they acknowledge the concerns about this work and at the moment, there is no decision about whether to publish the papers or whether to publish a censored form of the papers.  What we're waiting for is for the US government to provide details of, if the papers are censored, how it would allow genuine researchers to obtain that detail that would inform their own work.  And as long as there is a safe but efficient system for getting that information, that scientific information, to legitimate researchers who need it, then both Nature and Science have said in statements that they would be happy to publish the papers in a reducted form so you basically outline what the researchers have done, but you don't give any of the recipes in public for how they did it.

Chris -   Mark Peplow.  But what is the work at the centre of this scientific storm?  Ron Fouchier, the author of one of those papers.

Ron -   We've been working on H5N1 viruses that are circulating currently in Indonesia and causing massive outbreaks and we've been studying transmissibility of this virus to humans and between humans.

Chris -   Many people say H5N1 isn't a big worry because if it was going to jump into us, it would have done already.  How do you respond to that?

Ron -   Well, it is a big worry even when it jumps into us now because it kills people.  It killed more than 400 people already and of course so far, there have been isolated cases but the fear is that the virus will adapt and will change genetically, such that it will become transmissible.  And every case of infection of a human is a chance for the virus adapting to the human situation.

Chris -   So when a virus does jump out of one host species like a bird in the case of H5N1, so it gets into humans, what does it actually take for it to grow efficiently in a human, a different host and then spread from one host to the next?

Ron -   We know pretty much what it takes to infect the first human.  We know very little of what it then takes to be transmissible between humans.  They have to adapt to attach to other cells than they are used to attaching to, these cells express receptors and they have to adapt to new receptors, and they also have to adapt to produce enough virus such that the virus can spread and it does so by making genetic changes in the polymerase complex, and the polymerase complex is responsible for multiplication of the virus.  But really, we don't know anything about what it takes to then become transmissible.

Chris -   Many of the cases of H5N1 we've seen tend to stop with the person that gets infected, so they get it from a bird but then they don't pass it on.  So how come they die of it, yet not pass it on?

Ron -   So many of the human cases of infection, they contract the virus in odd ways - by drinking raw duck blood for instance or by getting the snot out of the beak of a fighting cock.  And so, they get huge amounts of virus in and they get it generally deep down the respiratory tract.  And deep down the respiratory tract, the virus can replicate quite efficiently.  These individuals develop pneumonia and they die as a consequence of that.  The virus is not particularly well adapted to replicate in the upper respiratory tract and we have always said that as soon as the virus gains the ability to replicate in upper respiratory tract of humans, then we might be in trouble.

Chris -   So how are you trying to work out what it's going to take?

Ron -   We borrowed evidence from previous pandemics when avian viruses changed and then caused infections in humans.  And some of the changes that occurred in those pandemic viruses, we have introduced by genetic manipulation into H5N1 virus.  And that H5N1 virus now replicates in the upper respiratory tract of mammals.  Now that virus has many of the hallmarks of a pandemic virus, but we found initially that it's still is not transmitted.  It's very surprising and so what we did then is put it into a mammal and let the virus adapt to the mammal for a few rounds and then take that virus, and then that virus will become transmissible.  And so, by intelligent experiments, we were able to introduce three mutations into the virus and then because we didn't know the rest of it, we let the mammals do the rest of the story, and they accumulated two or three additional mutations or enough to make this virus transmissible.

Chris -   Every time the virus goes into a new mammalian host, it has a new chance to adapt.

Ron -   Yes, that's correct.  So that's the message that we're sending out.  Many of the mutations that we have introduced with genetic modification are already found in the field.  So it's now a matter of chance of a mammal running into a chicken that has a virus with those mutations.  And then in that mammal, it can accumulate the extra mutations and then we would be in trouble.

Chris -   You're saying that the mutations that you put into your experimental virus already exist out in nature if you know where to look for them.

Ron -   Yes.  So far, there have been about 500 million birds infected and we have sequenced the genome of about 1,000 of them and in those 1,000 genomes, we already find the exact same mutations that we find in the transmissible virus, just not in the combination of 5 or 6 that we find in a transmissible virus.

Chris -   Once you put those mutations or changes into H5N1, does it remain as pathogenic, as virulent, as the wild type or does it have to surrender some of that virulence in order to become fit to reproduce in humans instead of its more native bird?

Ron -   Well we had all hoped and also thought that this virus would be reduced in virulence, but the first quick and dirty experiments that we have done suggests that the virus is just as hot as the wild type virus, and it kills a ferret in 3 days.  In humans, kills 95% of the individuals that get infected.

Chris -   What's the moral of the story?

Ron -   To be honest, I think that many scientists have - well not just scientists but also the policy makers are relaxing a little bit too much on H5N1 at the moment.  Many scientists believe that only H1, H2, and H3 viruses can cause pandemics rather than H5, and many scientists think that it has to involve pigs.  Many scientists think that viruses need to shuffle their genes, rather than just build in mutations.  And this investigation really showed that we should not be so relaxed about how to deal with the H5N1 virus, and I think the policy should be, to start stamping out H5N1.

Chris -   And that was Ron Fouchier from the Erasmus Medical Centre in the Netherlands.  He was speaking with me at the ESWI Influenza Conference held in Malta last September. 

Nicotine Replacement not the key for Smokers wanting to Break the Habit...

As many smokers try to fulfil resolutions to quit this month, nicotine replacement therapies have been shown to have no long-term benefits for smokers trying to kick the habit.

Following 787 adult smokers over five years, Gregory Connelly and colleagues from the Harvard School of Public Health found one third of smokers relapsed when trying to quit and saw no difference in this relapse between those using therapies such as nicotine gums and patches to those using other methods, or going cold turkey, in the long term.

Gregory - There's multiple factors for relapse. There's social cues, cigarette-driven cues, and it's probably diminishing over time of the personal will to quit. In the past, studies have looked at laboratory trials and then taken those findings and put them in the real world. What we found when you put it in the real world, and you look at the long term, they're just not having an effect. So what we have to do is combine our laboratory trials with trials from the real world. Combine them, learn, develop better mechanisms, and then make this planet smoke-free

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Planets for Every star in our Galaxy...

Our galaxy hasas many planets as it does stars according to scientists at the University of St Andrews.

Using gravitational microlensing to find planets located further away from their stars, Martin Dominik and colleagues discovered a large population of planets which calculations estimate to equal the number of stars in the Milky Way and further showed that stars without associated planets could be the exception.

Martin - In the Milky Way alone, we're seeing 100 billion to 300 billion stars in there. Now we took a small sample and we find that another planet is actually comparable to the number of stars or even larger, so that means just in the Milky Way alone, there could be 100 billion planets. Interestingly, we find that the abundance of the smaller planets is much larger than the number of gas giant planets like Jupiter or Saturn and that is quite interesting if you think about places where you're going to look for life.

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Using Fungi to Fight Lead Pollution...

Fungi could hold the key to fighting lead pollution according to research published in the journal Current Biology.

A known environmental pollutant, lead is a widely used structural and industrial material worldwide with previous efforts to contain or control levels in contaminated sites proving challenging.

Now Geoffrey Gadd from the University of Dundee has found that fungi can be used to transform lead into pyromorphite - it's most stable mineral form.

Geoffrey - We made quite a remarkable discovery and that certain fungi can attack the metallic lead which will result in a completely new mineral form - pyromorphite - which is a kind of lead phosphate and in fact, it's the most stable leadmineral that exists in the earth's crust So we've shown that really, activity of living organisms can do this which gives the intriguing possibility that perhaps somehow you could encourage the organisms to do this or act themselves in polluted sites.

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Worming a Plant meal...

And finally, a carnivorous plant residing in the tropical savannahs of the Brazilian Cerrado region uses sticky underground leaves to trap and digest nematodes.

Ciao Pereira from the state university of Campinas fed nematodes labelled with isotopes of nitrogen to the plant Philcoxia Minensis and found significant levels of nitrogen thereafter in the leaves of the plant, proving the plants digestion and absoroption of the worms.

It's thought the plant uses phosphatase enzymes to directly breakdown the nematodes for nutrition.

Ciao - This plant is producing enzymes and digesting the nematodes that gets trapped within the sticky leaves and this suggests that there is more conspicuous ways and more strategies that the plants are using to secure nutrients especially in severely stressed habitats.

The work was published this week in the journal PNAS.

Chris -   Scientists are moving closer to developing ways to interface with the brain and to decode what nerve cells are saying to each other.  Professor Andrew Schwartz is working on this at the University of Pittsburgh and he's with us now.  Hello, Andrew.

Andrew -   Hello.

Chris -   What sort of signals are you trying to eavesdrop on?

Andrew -   Well, we record from a part of the brain called the motor cortex and this part of the brain is thought to have a lot to do with controlling movements.  We're particularly interested in arm and hand movements.  So the neurons we record from seem to be related to aspects of moving the hand and arm, and particularly the direction and speed in which the hand moves.

Chris -   In other words, if you were to look at the surface of the brain and specifically the bit of the brain that we know relates to movements, there's a map of a person, or the body, on the surface of the brain and different bits of that map relate to different body parts.

Andrew -   That's right in sort of a coarse way.  That's a general way of looking at it.

Chris -   So when you are recording from different clusters of nerve cells, what does it sound like?  What sorts of conversations do nerve cells have?

Andrew -   So, we can record from individual nerve cells and the message that they send is the rate at which they fire action potentials.  So action potentials are these little impulses of electricity and the time between those impulses carries the information.  And so, what we've found is that, when you move your arm in different directions, that each neuron has a direction in which it likes to fire fastest in.  We can take account of that to try to decode the way that you intend to move your hand.  And so, over the years, we've built up a rather elaborate decoding mechanism where we can look at the direction and speed of the arm in 3-dimensional space and more recently, the angle of the wrist and now, the shape of the hand and fingers.  So we can get pretty much a complete representation of what you're trying to do with your hand by tapping into these signals.

Chris -   So rather than just turning individual muscles on and off, these motor cells in the motor part of the brain are active when they want to make a part of the body move to a certain position in 3-dimensional space.  So, in other words, if you wanted to hold your hand out at 45 degrees to yourself, there would be a bunch of cells that would fire the most when you're going to do that.

Andrew -   Right and the interesting thing is it's not just the cells that like to fire in that direction but the other cells will actually stop firing when you move against their preferred direction.  So what we do is we look at the entire population because all the neurons carry some information about that movement.  So one of the critical things about all this is that we look at the large population of cells, not just at a few individual neurons.

Chris -   It's quite clever, so you're looking at things going off as well as things turning on.  How many nerve cells do you record from?  If you want to decode meaningfully what the brain wants to do, how many electrodes do you need?

Andrew -   Well, we've used as few as 30 neurons to get a good representation of X, Y, and Z movement - 3-dimensional movement in space.  But typically, what we do now is record from 100 to 200 neurons and we get a more elaborate decoding.  So now, we can record or decode other aspects of movement as well.

Chris -   So what's the next step?  At the moment you can read those signals off, but translating that neurological chatter into something you want a computer to do or a robot to do, that's a whole different ball game, isn't it?

Andrew -   Well, yes.  Actually, the decoding principle we've known about more or less for 20 or 30 years just from doing basic research.  We study monkeys and when monkeys move their own arms, we can record this activity and then correlate the activity to the monkey's own arm movement.  Now on the last 10 or 15 years, what we've done is taken that signal and instead of using or correlating that to the monkey's own movements, we use that to drive a robot arm and the monkey can actually see that robot arm and control that robot arm without moving its own arm.  So we've sort of taken and tapped this intention out and given it a behavioural meaning to the animal now.

Chris -   And I suppose, one of the things which
Kevin [Warwick] was saying at the beginning is the brain is extremely plastic.  So even if you are not recording from precisely the right cluster of cells to do exactly what you might want to do or want to achieve, with training, the individual, be it a person in the future or monkey today, could still nonetheless learn to think along the right lines.  The brain would maybe rewire itself very slightly in order to achieve the desired movement using the electrodes you've plumed in.

Andrew -   Actually, yes.  That's one of the fascinating things.  I would word it slightly differently.  I'd say that we have to have a model of how this activity works, or what it's being used for, and our model is inaccurate.  As you said, we're only recording from a few of the billions of neurons that fire during every movement.  And so, our decode is rather inaccurate.  But what the animal is able to do is to learn the algorithm that we're using to decode this and actually help us by making his neurons fire more in line with our model.  So essentially, what the animal is doing is learning our model and helping us in that regard.

Chris -   One can obviously see that if you can decode what the brain wants to do in people or individuals who have some kind of injury or an interruption of the flow of information from the brain to the motor centres in the spinal cord that would enable them to move, you could then reconstruct movements for them or enable them to control and interact with their environment better.  What about going the other way though?  What about putting information back into the brain?  Would the same techniques you've developed to listen to neurons also enable you to talk to them?

Andrew -   Well, that's an open area of research but that's exactly what we're trying to do.  We're in process along with several other laboratories.  What that would involve in our particular case is putting sensors on the robot's fingers and joints so that we can impart tactile information and joint information back to the subject.  The way we hope to do that is by stimulating with electrical pulses again in the sensory regions of the brain to try to impart this information back to the subject.

There's been a lot of good research on pain lately and there are a number of what we call "neuromodulatory devices" out there to try to stimulate different parts of the nervous system, both in the brain and the spinal cord, to try to alleviate some of these symptoms.

Markus - So far, I'm seeing patients in the eye clinic who are interested in the technology because they are blind and it gives them the possibility to see things again. So they're highly excited to be part of research and be part of the project, but I would not think that they would consider themselves a cyborg or weird in any way. It's just a different form of camera technology which is connected directly to the eye rather than through the retina indirectly. Chris - Is this something you've come across Kevin? With people feeling a bit strange because they are literally now part man, part machine? Kevin - No, I think one thing that's interesting is that with an implant, even if it's an artificial hip, that sort of implant, very quickly, you regard it as being part of you. It's not like wearing a pair of glasses and you can put them down. When you get an implant, it's you. It's technologically different. I would guess that people with retinal implants, they wouldn't think of this as an implant. Very quickly, they'll think "Oh, it is me. I can do those things now." Which is tremendously exciting, how mentally you take these things onboard, just as much as physically.

Helen - Kevin, you've had a couple of implants yourself. Is the reason that you volunteered because you couldn't find anyone else to do it or because you wanted to do it yourself? Kevin - Actually, we get quite a few volunteers even now, and I actually have three of my undergraduate students who have implants. Not the same type, not the neural type, but to be honest, for me it was quite dangerous what we're doing, particularly the Utah array, the 100 electrodes firing into my nervous system, so there were dangers associated with that but I also wanted to experience for myself what it felt like.

I think to go with reading glasses is probably the much easier way than trying to do any complicated implants in that case!