The Problem with Potentially Pandemic H5N1

A recipe for an H5N1 flu virus, biosecurity and terrorism, and the deepest deep sea vents ever found...
16 January 2012
Presented by Chris Smith, Helen Scales


In this NewsFlash, we discuss the scientific research that can't be published - a "recipe" for an H5N1 flu virus with pandemic potential that has scientists and governments concerned about biosecurity and terrorism. Plus, the deepest deep sea vents ever found, and a round up of other scientific headlines...

In this episode

Avian H5N1

00:16 - Potentially Pandemic H5N1

Should we publish details of how to make viruses with pandemic potential? We explore the controversy and meet one of the scientists whose work is under question...

Potentially Pandemic H5N1
Mark Peplow, Nature; Ron Fouchier, Erasmus Medical Center, Rotterdam

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. 

InfluenzaThose 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. 

10:41 - The Problem with Potentially Pandemic H5N1

A recipe for an H5N1 flu virus, biosecurity and terrorism, and the deepest deep sea vents ever found...

The Problem with Potentially Pandemic H5N1

In this NewsFlash, we discuss the scientific research that can't be published - a "recipe" for an H5N1 flu virus with pandemic potential that has scientists and governments concerned about biosecurity and terrorism. Plus, the deepest deep sea vents ever found, and a round up of other scientific headlines...

A cigarette. Highly addictive.

13:32 - Quitting Smoking, Exoplanets and Carnivorous Plants!

Smoking cessation, stars and planets, fungi fight lead pollution, and plants making a meal out of worms...

Quitting Smoking, Exoplanets and Carnivorous Plants!
Gregory Connelly, Harvard School of Public Health; Martin Dominik, University of St Andrews; Geoffrey Gadd, University of Dundee; Caio Pereria, State University of Campinas.

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


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.


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.


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.


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