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DHS vs. NIH
December 20, 2011 6:30 PM   Subscribe

The U.S. National Science Advisory Board for Biosecurity has asked the journals Nature and Science to publish redacted versions of the studies by two research groups that reportedly created forms of the H5N1 avian flu that could easily jump between ferrets - animals whose response to influenza is similar to humans. posted by 445supermag (101 comments total) 3 users marked this as a favorite

 
It's a good thing the two journals, the two research groups, and the funding sources are all American. Otherwise the US government might not have jurisdiction!
posted by miyabo at 6:36 PM on December 20, 2011 [4 favorites]


“This is a sort of watershed moment,” said Alberts, noting it’s believed to be the first time this kind of secrecy has been sought from legitimate public health research.

That frog boiled yet?
posted by Trurl at 6:37 PM on December 20, 2011 [4 favorites]


Security through obscurity. Always works.
posted by unSane at 6:38 PM on December 20, 2011 [11 favorites]


Otherwise the US government might not have jurisdiction!

Um, jurisdiction isn't an issue. They didn't _order_ anything, they just asked.

Nature/Science can say no. No one is being forced to do anything.
posted by wildcrdj at 6:39 PM on December 20, 2011 [5 favorites]


Eh. I'm kind of okay with this.

Yes it's legitimate public health research, but it's also "How to make a deadly airborne virus".
posted by Grimgrin at 6:39 PM on December 20, 2011 [2 favorites]


It's a good thing the two journals, the two research groups, and the funding sources are all American. Otherwise the US government might not have jurisdiction!

Actually, Nature is British, although owned by a German conglomerate. Not that it makes a difference, really, as wildcrdj points out.
posted by greatgefilte at 6:42 PM on December 20, 2011


Given what's already been released about this, and the fact that the ferret vector/model is (apparently) quite well known, would this really protect anything?

The impression I had was that this was something most virologists and virology technicians with access to ferrets and H5N1(?) could replicate.
posted by Decimask at 6:43 PM on December 20, 2011 [1 favorite]


I think it's too late. The research never should have been performed in the first place... it's simply monster-making for the joy of monster-making. The research team created a doomsday bug just to see if they could, and now they want to make a career out of it. The lecture circuits, the bioterror consultant gigs, oh, how they'll cash in on this.

Either the research is completely suppressed as bad science (which it is), or it needs to be published in full so other can learn something. It leaves a bitter taste in the mouth - the papers need to be rejected, the researchers defunded and blacklisted. Anything less is mealy-mouthed acceptance that mainstream science can and should make gigadeath devices and organisms... go ahead and publish it all.
posted by Slap*Happy at 6:47 PM on December 20, 2011 [3 favorites]


This is an important topic, but your title is misleading. This was an NIH request based on a National Science Advisory Board for Biosecurity recommendation. The NSABB is part of Health and Human Services. They funded the research in question. DHS wasn't directly involved.
posted by demiurge at 6:49 PM on December 20, 2011


sort of a double but maybe just a precursor
posted by xbonesgt at 6:55 PM on December 20, 2011


Everything about this scares the shit out of me. What little I've been able to read about this manufactured virus (which isn't much, like everyone else) paints it as a Class A Existential Threat. We're already primed for a natural wildfire outbreak, we don't need to be going and inventing new ones.

And if we're capable of doing that kind of thing here, now, with the instability and uncertainty we face... yeah, maybe singing the Doom Song isn't inappropriate.

The only silver lining to any of this that I can see would be learning more about how to safely and effectively fight natural viruses.
posted by loquacious at 6:56 PM on December 20, 2011


Either the research is completely suppressed as bad science (which it is)

It's not bad science. Bad science would be putting a ferret and a bird in a cage together to see whether the ferret catches bird flu.

It's actually good science. They did everything correctly and came up with the end result they were seeking.

That isn't the same thing as whether it's science which we should be pursuing from a moral perspective. But then you're getting into a whole field of discussion which can lead to difficult areas. I mean, was Dr. Moreau's explorations in creating human/animal fusings "bad" in and of itself, or was it the fact that he was kidnapping people and experimenting on them against their will?

Or, to be a bit less fictional about it, the background idea I've heard floated about sending someone on a one-way trip to Mars. They would be well supplied, they would have full support from our planet, but we'd have no way to bring them back. Would that be morally-negative, or would it be pushing the frontier?

Science in and of itself isn't good or bad. It can be well done, or badly done. But the moral arguments for or against doing science is something else entirely.
posted by hippybear at 6:59 PM on December 20, 2011 [18 favorites]


Banning publication in scientific journals doesn't mean that the work would not still be carried out by governments with the necessary resources. Scientific papers aren't exactly recipes, anyway. At least publication will increase the amount of knowledge in the public realm, and the possibility that we might know what to do if someone does indeed release this stuff.

Anyway, what would be next? What's the line? When does something become a security threat?
posted by carter at 7:01 PM on December 20, 2011


Slap*Happy, uh, its a bit late for that. They didn't monster make so much as monster unnaturally select and said as much in their correspondence with various news outlets (or maybe just the one, its been a while).

Nothing they do now will put the ferrets back in the cage. They're gone and some madman is sneezing on them (hopefully due to allergies).

On a personal note, as a biochemist myself I'm a little miffed by your tone here. You don't really (unless standards have really fallen whilst I turned my back this evening) 'cash in' on making lectures to random universities. It helps your CV which helps your grant applications and that's the end of it. As for consultancy gigs... we have bigger problems than self-enrichment when someone who makes the minor but not insubstantial leap of logic for people in a public work gets to work on security issues.

As for scientists making giga-death devices... well, there's a long and storied history on that particular topic. We've been inventing things to kill each other with for a long time, a cursory glance around your kitchen and living room ought to turn up a great number of things that have been produced directly or indirectly from some sort of weapon research.

As for this bug being the thing that will kill us... meh. I'd really be worried if someone managed to select for a helper virus that turns HSV1 into a flesh melter.
posted by Slackermagee at 7:02 PM on December 20, 2011 [14 favorites]


Well that, and what evidence do we have that the experimentation/research was done for nefarious and/or selfish reasons? It seems like it would be valuable to carry through with this kind of research, in order to better understand how it could happen outside of the lab. I.e. if this research leads to better preparation against a pandemic, I think it's worthwhile.
posted by Brak at 7:02 PM on December 20, 2011 [1 favorite]


Scientific papers aren't exactly recipes, anyway

Oh my lord, tell me about it. How many times have I seen, "And the protein was homogenized from bacterial pellets as per established protocols (Insert references for eight protocols with conflicting information)"
posted by Slackermagee at 7:04 PM on December 20, 2011 [7 favorites]


Slap*Happy Thank goodness people like you have zero impact on my research funding.
posted by babbyʼ); Drop table users; -- at 7:04 PM on December 20, 2011 [16 favorites]


I'm not really that worried about H5N1, it's got a loooong way to go before it's as scary as AIDS or malaria already is.
posted by mek at 7:05 PM on December 20, 2011


Either the research is completely suppressed as bad science (which it is), or it needs to be published in full so other can learn something. It leaves a bitter taste in the mouth - the papers need to be rejected, the researchers defunded and blacklisted.

Your issue should be with the NIH for funding this research in the first place. I tend to agree with your sentiment that this specific research is too dangerous to promote. But now that it's been done, why not distribute knowledge that will help with understand transmission, mutation and vaccines?
posted by demiurge at 7:05 PM on December 20, 2011


I'm not really that worried about H5N1, it's got a loooong way to go before it's as scary as AIDS or malaria already is.

Actually, no. There is definitely the potential for the virus to cause catastrophic damage on a much shorter time scale than the other two. If you're interested in learning more about the flu virus, I highly recommend this book.

No disease the world has ever known even remotely resembles the great influenza epidemic of 1918. Presumed to have begun when sick farm animals infected soldiers in Kansas, spreading and mutating into a lethal strain as troops carried it to Europe, it exploded across the world with unequaled ferocity and speed. It killed more people in twenty weeks than AIDS has killed in twenty years;
posted by babbyʼ); Drop table users; -- at 7:09 PM on December 20, 2011 [7 favorites]


We came away with the consensus of the scientists, who probably weren't qualified, that there was already so much out there that could be used by bioterrorists that, I think I can quote, “One more won't make a difference”. We informed the military and we never heard anything back.
posted by a robot made out of meat at 7:09 PM on December 20, 2011 [2 favorites]


This is a goddamn shame.

There is nothing in those papers that is genuinely dangerous that isn't in hundreds of papers scattered in the literature stretching back over the last hundred years. We have been designing pathogens, as well as amplifying both virulence and contagiousness, since the VERY beginning of microbiology. There is nothing new here except for new ways of paying attention that yield incredibly valuable information.

Papers in Science and Nature are, by necessity, incredibly densely written. You can't just go redacting shit without having profound effects on what is communicated. I suspect they are just trying to take a censor's pen to the materials and methods, but to do so would be to ignore that there is nothing fundamentally new there and make the rest of the paper more confusing.

There are real problems that need real funding that these fuckers are taking up, you know, like the coming flu pandemic that has the potential to be the single greatest catastrophe in human history.

"Slap*Happy Thank goodness people like you have zero impact on my research funding."

Amen
posted by Blasdelb at 7:12 PM on December 20, 2011 [7 favorites]


Science in and of itself isn't good or bad.

Yeah. I still can't believe PubMed doesn't have any of Dr. Mengele's research available. So much useful stuff there..
posted by c13 at 7:15 PM on December 20, 2011 [1 favorite]


The worry is that turrists will get their hands on this technique, but isn't what they did pretty straight forward? The press releases contained enough information to do it yourself, just repeatedly select for more virulent forms of the virus.

In another thread, someone talked about engineering a virus that would kill locusts, and having that work for them.
posted by delmoi at 7:16 PM on December 20, 2011


I agree that the 1918 pandemic was crazy-scary but there were some very specific pandemic-promoting conditions at play there, under what circumstance could similar conditions occur again? Hopefully WW3 will be fought with sterile killer robots...
posted by mek at 7:17 PM on December 20, 2011


Science in and of itself isn't good or bad. It can be well done, or badly done. But the moral arguments for or against doing science is something else entirely.

This is emphatically, demonstrably wrong. Science that is unethical cannot, and must not, be trusted - it stems from faulty thinking at the outset, and the only ethical and scientific response must be to discard its results as being tainted by its methods.

Example - medical experiments on POW's, Koreans and Jews during the 2nd world war.

Example - The Tuskegee experiments.

The Scientific Method is not this pure, platonic construct of pure reason - it is a social covenant that allows imperfect humans to divine truth as perfectly as we can. It cannot, must not, be circumvented for expediency's sake - the very minute you do that, for any reason, your science is bogus and untrustworthy, and therefore its results must be rejected. Unethical research is just as bad, just as unreliable, as research with fudged numbers. Worse, IMO, as it undermines the credibility of science as a whole.
posted by Slap*Happy at 7:17 PM on December 20, 2011 [3 favorites]


Hey! Anyone want to make a neutron bomb? You know. For science!
posted by Cool Papa Bell at 7:21 PM on December 20, 2011


delmoi: In another thread, someone talked about engineering a virus that would kill locusts, and having that work for them.

I've wondered for some time if the nastiest bioweapon that you could unleash on North America isn't a micro-organism, but a North American grasshopper selectively bred until it starts exhibiting the social behaviour that differentiates "grasshopper" from "locust". Way beyond me in terms of even understanding if it's possible, but it's been on my list of "damned scary" for a long time.
posted by Decimask at 7:22 PM on December 20, 2011


There was absolutely nothing they did that was unethical.
posted by empath at 7:23 PM on December 20, 2011 [3 favorites]


It's actually good science. They did everything correctly and came up with the end result they were seeking.

That sounds like good engineering. AIUI, good science is asking a question and then doing something that answers it (and not, inadvertently, some other question). Bonus points if it's a question that many people think is interesting.
posted by spacewrench at 7:24 PM on December 20, 2011


Apart from making a known lethal virus insanely contagious for shits and giggles, it was completely ethical.
posted by Slap*Happy at 7:25 PM on December 20, 2011


"The Scientific Method is not this pure, platonic construct of pure reason - it is a social covenant that allows imperfect humans to divine truth as perfectly as we can. It cannot, must not, be circumvented for expediency's sake - the very minute you do that, for any reason, your science is bogus and untrustworthy, and therefore its results must be rejected. Unethical research is just as bad, just as unreliable, as research with fudged numbers. Worse, IMO, as it undermines the credibility of science as a whole."

That's not only wrong, its awfully naive. Most of the women in this thread have directly benefited from the vivisection experiments that J. Marion Sims, father of gynecology, conducted on the women he owned, most of whom lived short and pain filled lives.

You were grinding this ignorant axe in the last thread and its no more informed about their research now, they didn't create a weapon of anything but mass ferret destruction, they didn't create any new techniques, and they did generate incredibly useful knowledge.
posted by Blasdelb at 7:26 PM on December 20, 2011 [13 favorites]


Pure. DHS. Grandstanding.

Does DHS do anything besides theatrics and graft? Oh, right harassment. We could save so much tax money by cutting DHS in favor of asking the NEA to scare us once in a while.

How DHS employs Hollywood to invent terrorism scenarios.

Amen carter, blasdelb, bobby, and slackermagee!
posted by jeffburdges at 7:26 PM on December 20, 2011 [7 favorites]


Example - medical experiments on POW's, Koreans and Jews during the 2nd world war.

Example - The Tuskegee experiments.


Experimenting on non-volunteer human subjects without their consent or even knowledge is an ethical issue which doesn't have anything to do with whether the science being done has value or not.
posted by hippybear at 7:27 PM on December 20, 2011 [7 favorites]


Well, that and wanting to publish the instructions on how exactly to go about doing it in the most widely circulated scientific journal.
posted by c13 at 7:27 PM on December 20, 2011


"Apart from making a known lethal virus insanely contagious for shits and giggles, it was completely ethical."

Again, they did nothing of the sort, that took a virus that is lethal in birds and made it lethal in ferrets. In addition to the shits and giggles that are the incredible frustrations of working in a BSL 3 lab, they did it for information that is invaluable to both public health and basic science.
posted by Blasdelb at 7:29 PM on December 20, 2011 [8 favorites]


That took a virus that is lethal in birds and made it lethal in ferrets.



According to the NIH, the manuscripts describe lab experiments in viruses with enhanced transmissibility in mammals. The research concluded that the H5N1 virus has greater potential than previously believed to gain a dangerous capacity to be transmitted among mammals, including perhaps humans, and describe some of the genetic changes that appear to correlate with this potential.


Man, with such reading comprehension skills, I sincerely wish you all the best in your research.
posted by c13 at 7:36 PM on December 20, 2011


I would like to correct a misapprehension I'm seeing on this thread.

This is not just regular old science.

This is Super-Science™.
posted by mikelieman at 7:36 PM on December 20, 2011


So, Slap*Happy is saying they never should have conducted this research in the first place? How would they have known it would have worked before they conducted it? We would continue to live in ignorance, believing it wasn't possible...until someone else figures it out. Now, at least, we know it's possible, and can start considering ways this threat might be combated. We now understand more about the potential dangers of the virus.

But, I guess, it's better to live in ignorance and hope for the best...
posted by Jimbob at 7:37 PM on December 20, 2011 [6 favorites]


"The worry is that turrists will get their hands on this technique, but isn't what they did pretty straight forward? The press releases contained enough information to do it yourself, just repeatedly select for more virulent forms of the virus."

The basic concepts involved have been around since 1890, if we should be angry with anything it should be Robert Koch's grave as well as the DHS and 24 hour news cycle reminding the turrurists of what scientists have been doing since:

In another thread, someone talked about engineering a virus that would kill locusts, and having that work for them.
"

That was me! Talking about Félix d'Herelle's work in 1911 defeating one the four great biblical plagues.
posted by Blasdelb at 7:38 PM on December 20, 2011 [1 favorite]


Linked here because I pressed the wrong button
posted by Blasdelb at 7:39 PM on December 20, 2011


they didn't create a weapon of anything but mass ferret destruction

Wow, deliberate lie. It's not even a good one, as the zoonotic link between ferrets and humans was detailed in the source articles. And insisting that medical research performed on slaves was both necessary and good for science? Really?

I'm not certain you're making your case, here.

At what point does virology research become unethical? When deliberately inflicted on a human population? What if you get some really good data from that?

How would they have known it would have worked before they conducted it?

Ummm - on animals that aren't zoonotic with people?
posted by Slap*Happy at 7:40 PM on December 20, 2011 [1 favorite]


Ummm - on animals that aren't zoonotic with people?

Then how would we gain the same understanding of risks to humans?
posted by Jimbob at 7:42 PM on December 20, 2011 [3 favorites]


But what if PETA rescues the ferrets and releases them into the wild?? WHAT THEN??
posted by mek at 7:45 PM on December 20, 2011 [1 favorite]


Blasdelb: "That took a virus that is lethal in birds and made it lethal in ferrets."

FPP: "According to the NIH, the manuscripts describe lab experiments in viruses with enhanced transmissibility in mammals. The research concluded that the H5N1 virus has greater potential than previously believed to gain a dangerous capacity to be transmitted among mammals, including perhaps humans, and describe some of the genetic changes that appear to correlate with this potential."

c13: "Man, with such reading comprehension skills, I sincerely wish you all the best in your research."

There is nothing in that paragraph that contradicts what I said. Ferrets are mammals, they've got hair and nipples, but please don't freak out the next ferret owner you meet checking. Now I don't mean to scare you, well actually I really should, but influenza infects millions of pigs, which are much closer than ferrets are, on entirely unsupervised farms all over the globe. From an honest public heath perspective there is barely anything notable about a population of less than a hundred ferrets with H5N1, much less when they're under some of the strictest controls there are.
posted by Blasdelb at 7:49 PM on December 20, 2011 [4 favorites]


The FishBike scale of Big Mistakes needs some tinkering, I think.
posted by vidur at 7:51 PM on December 20, 2011


I don't want to get into the good science-bad science argument, but I do want to redirect the comments to the very idea of scientific journals (and two of the most respected ones at that) redacting information at the request of the government. I am assuming that Science and Nature won't play nice, but what if they did? Has this been done before by mainstream journals? How does redacting information work in the context of the peer-review process? How could one possibly assess the merits of said research if the methodology has been redacted from a published paper? The request strikes me as chilling in an Orwellian kind of way.
posted by Seymour Zamboni at 7:55 PM on December 20, 2011 [3 favorites]


Should the new flu stay secret? Or does secrecy kill?
posted by homunculus at 7:55 PM on December 20, 2011 [1 favorite]


Then how would we gain the same understanding of risks to humans?

By studying the zoonotic link between ferrets and people with viruses that aren't lethal.
posted by Slap*Happy at 7:55 PM on December 20, 2011


Apart from making a known lethal virus insanely contagious for shits and giggles, it was completely ethical.

Never before have I been so tempted to deploy a FTFY. Far from being for shits and giggles, they did it to improve our ability to monitor and prevent potentially deadly flu outbreaks:
The research by the Kawaoka and Fouchier teams set out to answer a question that has long puzzled scientists: Does H5N1, which rarely causes human disease, have the potential to trigger a pandemic? ...

Some scientists think the virus is probably unable to trigger a pandemic, because adapting to a human host would likely make it unable to reproduce. Some also believe the virus would need to reshuffle its genes with a human strain, a process called reassortment, that some believe is most likely to occur in pigs, which host both human and avian strains. Based on past experience, some scientists have also argued that flu pandemics can only be caused by H1, H2, and H3 viruses, which have been replaced by each other in the human population every so many decades—but not by H5.

Fouchier says his study shows all of that to be wrong. ...

... The researchers "have the full support of the influenza community," Osterholm says, because there are potential benefits for public health. For instance, the results show that those downplaying the risks of an H5N1 pandemic should think again, he says.

Knowing the exact mutations that make the virus transmissible also enables scientists to look for them in the field and take more aggressive control measures when one or more show up, adds Fouchier. The study also enables researchers to test whether H5N1 vaccines and antiviral drugs would work against the new strain. (source)
By all means, have an argument over whether or not information should be redacted from the papers, or whether or not the benefits from this research outweigh the potential costs. But if you're going to speculate that the only reason this science was conducted was because of moral depravity on the part of the authors, I think you're going to have to provide a little more evidence.
posted by en forme de poire at 7:57 PM on December 20, 2011 [20 favorites]


Jimbob, this isn't about understanding some general " risks to humans". This is like publishing the exact dimensions, shape and composition of the nuke core, along with the exact process and machinery list needed to make one. I'm not talking about the wow factor, just about the difference between general princles and a specific mutations.

Blasdelb, please don't try to appear denser than you really are. You said that all they've done was to make the virus lethal in ferrets. I quoted you that not only did they increase lethality, but they also increased transmissability. If you don't know the difference between these two words, look them up.
posted by c13 at 7:58 PM on December 20, 2011


Do you know what happens when real CIA agents get outed or academic cryptographers discover NSA breakthroughs? Absolutely nothing

If any real security threat appears, the CIA or NSA quietly say "Oops, too bad they figured that out. Please nobody make this worse by confirming its importance."

What does DHS do? "Oh hey, the media covered this biology paper. Let's get ourselves in the news by redacting it!"

And later they argue over who gets dibs on starting the DHS subcontractor to review all biology research before publication. Imagine all those biologists who didn't get accepted into PhD programs being paid per word redacted.   Joking, you think I am, mmm?
posted by jeffburdges at 7:58 PM on December 20, 2011 [13 favorites]


And jeffburdges nails it.
posted by Blasdelb at 8:01 PM on December 20, 2011 [3 favorites]


Oh for the clarity that Kurt Vonnegut gave us in Cat's Cradle. Somehow the real world is so much more complicated. That's why we need fiction.
posted by dmayhood at 8:02 PM on December 20, 2011


Hey! Anyone want to make a neutron bomb? You know. For science!

Gotta nuke something.

That's not any statement about scientists and our innate curiosity, mind you. Just joking around. For science.
posted by Blazecock Pileon at 8:03 PM on December 20, 2011


Sometimes I wish there was a way to flag comments with a "don't worry mate, I got it ;-)" tag…
posted by Pinback at 8:04 PM on December 20, 2011


"And insisting that medical research performed on slaves was both necessary and good for science? Really?"

I insisted nothing of the sort, but the idea that:

"The Scientific Method is not this pure, platonic construct of pure reason - it is a social covenant that allows imperfect humans to divine truth as perfectly as we can. It cannot, must not, be circumvented for expediency's sake - the very minute you do that, for any reason, your science is bogus and untrustworthy, and therefore its results must be rejected. Unethical research is just as bad, just as unreliable, as research with fudged numbers. Worse, IMO, as it undermines the credibility of science as a whole."

is, as I actually insisted, incorrect and awfully naive. You can peruse for yourself the horrendously and gut-wrenchingly unethical research performed in the US that is reliable enough to be quietly used routinely. I didn't say that I think its right that we use techniques derived from those developed on enslaved people, and I don't, but simplistic moral arguments made in ignorance bug me.
posted by Blasdelb at 8:06 PM on December 20, 2011 [9 favorites]


"By studying the zoonotic link between ferrets and people with viruses that aren't lethal."

The potential for zoonotic links between ferrets and people is unimportant except for the comparatively trivial risk of cryptosporidiosis, tuberculosis and listeriosis; and even then that would be a woeful waste of resources when we have genuinely dangerous routes of transmission to study. Viruses that arn't lethal are also not so interesting, because hey, whats the point when you could instead do research that could save hundreds of million of lives.
posted by Blasdelb at 8:07 PM on December 20, 2011 [1 favorite]


Where does it say the DHS was involved? NSABB is not part of DHS. It is part of HHS.
posted by demiurge at 8:17 PM on December 20, 2011 [1 favorite]


Scientific papers aren't exactly recipes, anyway.

Especially not Nature or Science papers -- the space for Materials and Methods is what, 30 square microns each? I wonder if there's really any difference between redacting critical details and the existing practice of burying them into a 90-page supplement nobody reads anyway. One hamburger was prepared as per Sys Rq et al., 2009.
posted by en forme de poire at 8:25 PM on December 20, 2011 [4 favorites]


"Blasdelb, please don't try to appear denser than you really are. You said that all they've done was to make the virus lethal in ferrets. I quoted you that not only did they increase lethality, but they also increased transmissability. If you don't know the difference between these two words, look them up."

Serially transferring a pathogen among a novel host population will inherently select for pathogens more contagious in that population, this has been known for more than a century. So yes, they also increased the transmissibility of their strain of H5N1 among ferrets. This means the strain was some combination of better able to use ferrets to shed more viruses (generally associated with virulence), and more specific to ferret cells, allowing for infections from smaller doses. Some of the trait shifts that made the virus better at infecting ferrets would give it a slight head start at infecting humans, which is why all of this was done in the presence of stringent controls, but that slight head start is REALLY FUCKING NOT unique to those two labs and in no way shape or form a meaningful public health concern next to this.
posted by Blasdelb at 8:25 PM on December 20, 2011 [2 favorites]


This is emphatically, demonstrably wrong. Science that is unethical cannot, and must not, be trusted - it stems from faulty thinking at the outset, and the only ethical and scientific response must be to discard its results as being tainted by its methods.
That doesn't really make any sense, why would an experiment on an unwilling human be less scientifically valid then an experiment on another unwilling ape?

Just to be clear, I'm not at all in favor of doing unethical experiments on humans, the scientists who do them should be prosecuted. But there is a huge difference between doing research on humans and doing research that people who aren't scientists read about in the paper and think might cause the downfall of civilization. I mean by that metric the Large Hadron Collider was 'unethical' because some people thought it might create a black hole and absorb the earth.

As far as the ferret/human thing, once you know that don't terrorist have all the information they need to do this? It's an experiment that's been done before with different animals. The only difference now is that everyone knows that if you do this with ferrets, there's a good chance that your disease will work with humans.
Jimbob, this isn't about understanding some general " risks to humans". This is like publishing the exact dimensions, shape and composition of the nuke core, along with the exact process and machinery list needed to make one.
To extend this metaphor to the breaking point, the process of "making a nuke" has been known for over a century, but people didn't know the exact process by which a harmless ball of plutonium and C4 self-organized itself into a deadly weapon. All these people did was take put the ingredients of a nuke into a bowl and let it form, then they analyzed it in minute detail so they could better understand how it forms and thus how to stop it from forming on it's own, which actually happens on it's own from time to time and actually does kill people.

There's a reason why Metaphors are a bad way to argue. Lets get back to the real world, since diseases aren't even any more complicated then nukes in the first place so why even use an analogy?

People know how to make diseases more virulent. They've been known for over a century. It's a basic application of Darwin's ideas. What people didn't know was the specific mutations that happen that cause bird flu to turn into man flu.

Slap*Happy says we could do the same thing "By studying the zoonotic link between ferrets and people with viruses that aren't lethal."

But, no, the purpose of the research was to study this virus and how it mutates, that work, obviously, could not be done with a different virus. Because this virus regularly mutates into dangerous strains, while at the same time being easily carried around the world by birds.

---

Since people are talking about a 'recipe' let's use a cooking metaphor. Let's say it's been known for years how to bake a particular cake. But, it's known that if you let it sit out to long it turns poisonous. So what these researchers are doing would be like deliberately letting the cake turn poisonous so they can study the actual chemical reactions that take place in order better figure out to prevent it.

Then people are freaking out say "OMG I CAN'T BELIEVE THEY BAKED A POISONOUS CAKE!!! DELIBERATELY BAKED A POISONOUS CAKE FOR SHIT'S 'N' GIGGLES!!!!"
posted by delmoi at 8:33 PM on December 20, 2011 [6 favorites]


"Jimbob, this isn't about understanding some general " risks to humans". This is like publishing the exact dimensions, shape and composition of the nuke core, along with the exact process and machinery list needed to make one. I'm not talking about the wow factor, just about the difference between general princles and a specific mutations."

If you'll excuse the interruption Jimbob,

You know the exact dimensions, shapes, and compositions of nuclear cores have been published for a long time, as well as almost all of the processes and machinery needed to make one right? Besides, the specific mutations involved would be meaningless to someone actually trying to make a monster, the general principles are what might be genuinely dangerous and they've been around for a very long time. Isn't it kind of terrible that the NSABB is doing such a shitty job of keeping those principles out of the public's eye where they might actually do some harm?
posted by Blasdelb at 8:34 PM on December 20, 2011 [1 favorite]


To extend this metaphor to the breaking point, the process of "making a nuke" has been known for over a century, but people didn't know the exact process by which a harmless ball of plutonium and C4 self-organized itself into a deadly weapon. All these people did was take put the ingredients of a nuke into a bowl and let it form, then they analyzed it in minute detail so they could better understand how it forms and thus how to stop it from forming on it's own, which actually happens on it's own from time to time and actually does kill people.

Yes, and they want to publish it, so that whoever wants to, can skip all the hassle and go directly to the good stuff. Hell, according to Blasdelb, all the nuke info is openly available. Of course we won't ask him for any citations or links since he's already stuck his foot so deep into his mouth he's risking a bowel perforation.

Since you want to get back to " the real world" I should remind you that, even though the general knowledge of how to make deadlier bugs has been long known, the details are deeply classified in every country in the world that has a bioweapon program. Much as the nuke details are.
posted by c13 at 8:52 PM on December 20, 2011


Here's another example: it is generally known that spores of Bacillus anthasis will fuck you up if they get into your lungs. It is also generally known that wild type spores tend to clump together into particles too large to stay in the air too long and to get deep enough into the alveoli to cause much havock. Would it be ok to publish the info on how to modify the surface properties in sush a way as to increase the dispersion. So that we can learn more about transmission, epidemiology and all the other fun and beneficial stuff? You know, to help the humankind ans save children and puppies.

Or should we make the remaining stocks of small pox available to any lab that wants to study the Pox viridae family?
posted by c13 at 9:02 PM on December 20, 2011


"Yes, and they want to publish it, so that whoever wants to, can skip all the hassle and go directly to the good stuff. Hell, according to Blasdelb, all the nuke info is openly available. Of course we won't ask him for any citations or links since he's already stuck his foot so deep into his mouth he's risking a bowel perforation."

Since you seem so interested in the contents of my bowels, just look at what is available for the size shape and composition of the Fat Man's core on wikipedia for fucks sake (incidentally the design the Soviets decided to try to copy first), the various processes and machinery lists for enriching uranium arn't exactly secrets either

posted by Blasdelb at 9:07 PM on December 20, 2011 [1 favorite]


Hah hah... So those are the details, eh?
posted by c13 at 9:10 PM on December 20, 2011


c13, your anthrax example already happened. I'm guessing you know that. While writing about the anthrax attacks (which came out of the military vaccine program), I repeatedly had conversations with other reporters about the irresponsibility of publishing information about weaponization materials and methods. It didn't make any difference. There was always some sensation-monger eager to publish "what if" speculation that included information about weaponization.

The only reasons I can figure that we haven't seen more bioterrorism are things like:

a) people smart enough to do this don't seem stupid enough to do this, and

b) biological attacks make people so freaked out that they will do things like invade Iraq just on the off chance that they were involved in an attack.

In other words, doomsday weapons appear to be their own deterrent. Except for when they aren't.
posted by warbaby at 9:14 PM on December 20, 2011


c13: Would it be ok to publish the info on how to modify the surface properties in sush a way as to increase the dispersion. So that we can learn more about transmission, epidemiology and all the other fun and beneficial stuff? You know, to help the humankind ans save children and puppies.

In a controlled lab environment? I'd say yes.

You act like scientists are cooking these things up in their kitchen sinks and assuring us that the Walmart bag they've draped over the top is containment enough. If we weren't able to bring ourselves to trust dangerous research in controlled environments, we'd be depriving ourselves of huge, huge amounts of important research, past, present, and future.

You're arguing like you're willing to throw away huge swaths of human progress just because you're afraid the controls aren't good enough. It's a mother's "you can't be too careful" maxim taken to a staggering conclusion.
posted by gilrain at 9:16 PM on December 20, 2011


Would it be ok to publish the info on how to modify the surface properties in sush a way as to increase the dispersion. So that we can learn more about transmission, epidemiology and all the other fun and beneficial stuff? You know, to help the humankind ans save children and puppies.

You're conflating the publication of information with experimentation.

The experiment discussed in this FPP itself has moved knowledge about transmission and such forward. The publication of the information about this experiment is happening after it's already taken place. This is necessary in science, because non-duplicable results aren't results, they're aberrations in data collection during an experiment.

There is nothing about publishing that information (which likely is already available in publication someplace) which would, in and of itself, be of benefit. If someone had done some process or study which provided new information about these particles which needs to be shared with the scientific community at large so it can be further understood outside the group which originated the new information, then yes, it should be published.

The thing about such things... like anthrax, or atom bombs, or H5N1, or, say, LSD, is that the raw ingredients needed to duplicate the experiments are incredibly difficult to obtain. Anthrax spores in laboratory quantities, uranium or plutonium, H5N1 virus in laboratory quantities, and rye ergot in laboratory quantites... These aren't things you can just purchase with a credit card and an internet connection.

Security through obscurity isn't security at all. If it's not being discussed out in the open, it's being investigated behind our backs where we can't possibly be forewarned, and thus forearmed.
posted by hippybear at 9:17 PM on December 20, 2011 [2 favorites]


"Here's another example: it is generally known that spores of Bacillus anthasis will fuck you up if they get into your lungs. It is also generally known that wild type spores tend to clump together into particles too large to stay in the air too long and to get deep enough into the alveoli to cause much havock. Would it be ok to publish the info on how to modify the surface properties in sush a way as to increase the dispersion. So that we can learn more about transmission, epidemiology and all the other fun and beneficial stuff? You know, to help the humankind ans save children and puppies."

The techniques and reagents, whatever they are, needed to weaponize anthrax have never been published and are known only by a select group of trusted American researchers and well fed former Soviet ones. You don't need special reagents to change the host range, virulence or transmissibility of a pathogen, just techniques that have been published widely for more than a hundred years. There is nothing in those papers that would be more useful to a terrorist than what is already common scientific knowledge.

You seem to be waffling between the idea that the papers themselves are meaningfully dangerous and the idea that the research itself was meaningfully dangerous. Neither is true.
posted by Blasdelb at 9:23 PM on December 20, 2011 [2 favorites]


I'm not sure what you do for living, hippybear, but I assure you it is not difficult to go to a pasture, pick up some B. anthrasis and then grow as much as you want of it i liquid culture. The problem lies exactly in finding out precise formulation of the solution that would modify the surface charge and lyophylization parameters that would ensure correct dispersal. That's what was done in places like Ft. Detrick or Koltsovo. That's the stuff that is not published, unlike what warbaby thinks.
Likewise, I've presonally grown a strain of flu as a teaching experiment. We've used several dozen eggs. Nothing but the pain in the ass would prevent us getting more eggs (well, they do have to be live) .
Ergot you can pick off store bought rye, apparently.

My point is that saying that mutations in hexoseaminidase and neuraminidase drive the virulence and transmissibility of the flu virus, and saying that mutations X Y and Z at specific locations increase transmisibility N fold ( and here's how we carried them out, samples available on request. ) are not exactly the same.
There's plenty of methodologically sound, important research that's been done. However not all of it should be published in open literature.
posted by c13 at 9:37 PM on December 20, 2011


The Scientific Method is not this pure, platonic construct of pure reason - it is a social covenant that allows imperfect humans to divine truth as perfectly as we can. It cannot, must not, be circumvented for expediency's sake - the very minute you do that, for any reason, your science is bogus and untrustworthy, and therefore its results must be rejected.
I see two sentences. I see no connection between them.

A great deal, perhaps all, of science has been built on bogus foundations and crazy ideas. The thing that makes science work is documentation and repeatability. In that sense, redaction is exactly what shouldn't be done. Redaction is what subverts the scientific method.

Research ethics has very little to do with science and a great deal to do with the world we want to live in. I would strongly prefer to live in a world without unethical experimentation. I want to live in that world because I don't want to experience the harmful results of that research, not because it somehow taints the validity of the science. It doesn't, any more than Newton's alchemic and religious ideas tainted his mathematical and scientific discoveries.
posted by b1tr0t at 9:58 PM on December 20, 2011 [2 favorites]


I'm fairly sure gun assembly design makes a suitable question for an undergraduate course in relativity, c13, although usually you'd teach relativistic electromagnetism instead, probably enough intuition here though.

Can we please lobby for a law that all senior positions in DHS must be filled by former NSA, CIA, or military officers? There are many idiots in the military, and the CIA gave us Bush v1, but surely they cannot be as asinine and corrupt as Michael Chertoff, et al.

There is one upside to this stupidity by DHS though, namely they've provided strong evidence the U.S. does not posses any meaningful biological weapons programs, otherwise they might've spoken with someone who knew anything about biological weapons.

posted by jeffburdges at 9:58 PM on December 20, 2011 [1 favorite]


One of the major differences between H5N1 and anthrax is that anthrax is not likely to spontaneously develop the capacity to freeze-dry itself and then mill itself into a fine powder. The point isn't that they made flu more infectious: the point is that they did it by natural processes that mimic what could easily happen without human intervention outside of the lab.

Also, if you wanted to make real use of this information you would definitely want sequence-level data - flu genomes change relatively quickly and in a monitoring effort you would want to know which mutations are the most likely to be warning signs and which are more likely to be drift. This is why Bruce Alberts is concerned that there be some provision for getting the redacted information to the researchers and governments that need it. Anyway, engineering those specific mutations into flu would be much harder and more expensive than just doing it the old-fashioned way using selection (and to do it by cloning you would need to order some very suspicious looking oligonucleotides).
posted by en forme de poire at 10:02 PM on December 20, 2011 [3 favorites]


Interesting article about this here:

The Loom

It seems that we don't have the ability to make killer diseases, just like that, in the lab. This specific strain was developed by serially exposing groups of ferrets to the disease, with each iteration getting the most contagious version that was found in the previous round. Exposing them in this way led to the natural evolution of the highly contagious disease.

The main point is that the experiment carried out was nothing that couldn't quite easily happen in nature to humans (and has in the past). There has been no discovery of a secret recipe to create deadly epidemics.

I'd recommend reading the article linked - it is much less scary when you understand it.
posted by estuardo at 10:05 PM on December 20, 2011 [2 favorites]


Thanks en forme de poire - said what I was trying to say, but much better.
posted by estuardo at 10:07 PM on December 20, 2011


Well, I'm sorry I brought up the nuke thing. I just hope everyone in this thread can get on a plane after this. If you want to know what the important stuff is, google and read Nuclear Weapons FAQ. It's pretty in depth, talks about the important parameters but contains no classified material. But actually explains what is classified and why.

Back to the topic in question. Now that they,ve made this new strain, how long is it, do you think, until they publish the sequence with the important mutations highlighted?
En forme de poire, do you think site directed mutagenesis is that hard? You could order oligos for 20 bucks a pop 6 years ago.
posted by c13 at 10:14 PM on December 20, 2011


"My point is that saying that mutations in hexoseaminidase and neuraminidase drive the virulence and transmissibility of the flu virus, and saying that mutations X Y and Z at specific locations increase transmisibility N fold ( and here's how we carried them out, samples available on request. ) are not exactly the same.
There's plenty of methodologically sound, important research that's been done. However not all of it should be published in open literature.
"

Heh, if that is something you really don't want out there, you'll have a lot of work to do suppressing the many articles like this that are actually relevant, not these ferret based ones.
posted by Blasdelb at 10:16 PM on December 20, 2011


Incidentally I have institutional access to just about everything as well as my own collection of a lot of the really old literature that is relevant to this, if you'd like a PDF of any journal articles related to this thread just Memail me with an email address I can send it to.
posted by Blasdelb at 10:21 PM on December 20, 2011


Estuaro, the reason we can't make diseases in the lab is because we don't quite know what specific mutations make the bug more or less deadly. That's why they just went with the dumb selection route. But now that they've got the deadlier version, it is much easier to make more via several other methods.

Blasdelb, have I said somewhere that only this particular lab is the problem?
Seems to me that we're a pretty smart species but without a lick of sense sometimes...
posted by c13 at 10:24 PM on December 20, 2011


Thanks for the offer, by the way, but I got a fill of it all in grad school. Way more than I wanted :)
posted by c13 at 10:26 PM on December 20, 2011


Oh, and can somebody explain to me specifically how creating a more virulent strain will help fight the infection?
posted by c13 at 10:30 PM on December 20, 2011


Can we please lobby for a law that all senior positions in DHS must be filled by former NSA, CIA, or military officers? There are many idiots in the military, and the CIA gave us Bush v1, but surely they cannot be as asinine and corrupt as Michael Chertoff, et al.

There is one upside to this stupidity by DHS though, namely they've provided strong evidence the U.S. does not posses any meaningful biological weapons programs, otherwise they might've spoken with someone who knew anything about biological weapons.


As has twice now been observed in this thread - NSABB isn't DHS. In fact, DHS has just one non-voting representative on the committee (Susan Coller-Monarez, Ph.D.; Deputy Chief Medical and Science Officer, Chemical and Biological Defense Division, Science and Technology Directorate). The current voting members of the committee do include a retired Air Force General who is a Homeland Security Advisor (and who was a deputy director at CIA), but the rest are basically civilian experts in biological research and public health - and there are some pretty heavy hitters in terms of "knowing anything about biological weapons". And, boy oh boy, I would not jump to any conclusions about US bioweapons capability based on this decision.
posted by gingerest at 10:31 PM on December 20, 2011 [3 favorites]


Oh, and can somebody explain to me specifically how creating a more virulent strain will help fight the infection?

It's not that it'll help fight the infection in individuals - it's that it might provide information which will better inform efforts to prepare and defend against the next (natural) pandemic. If we better understand the organism's virulence factors and their interaction with individual host defenses and population susceptibility, we are in much better shape to design both vaccine composition and vaccination strategy.

An interesting article on the research from Scientific American.
posted by gingerest at 10:43 PM on December 20, 2011 [2 favorites]


It's not that it'll help fight the infection in individuals - it's that it might provide information which will better inform efforts to prepare and defend against the next (natural) pandemic. If we better understand the organism's virulence factors and their interaction with individual host defenses and population susceptibility, we are in much better shape to design both vaccine composition and vaccination strategy.

I'm sorry, but that's just arm waving. Might? Better? What do those words mean?
Do we not know how to make vaccines? Will the virus stop mutating and reassorting, obviating the need to continuously make new vaccines?
Presumably they have ( or shortly will) identify key sites affecting virulence. Why couldn't they look for/publish a less virulent strain as it would provide essentially the same information?
posted by c13 at 10:52 PM on December 20, 2011


En forme de poire, do you think site directed mutagenesis is that hard? You could order oligos for 20 bucks a pop 6 years ago.

Don't forget you don't just have to get the PCR to work properly (something that eludes even a lot of biology students), you have to be able to get it to recombine into the viral genome with some kind of selectable marker, then get rid of the marker -- all multiplied by however many mutations there are. Compared to just to passaging the virus in animals it's a lot more technical.
posted by en forme de poire at 10:53 PM on December 20, 2011 [1 favorite]


Why couldn't they look for/publish a less virulent strain as it would provide essentially the same information?

For one, we wouldn't be able to test whether existing antivirals or vaccines had any efficacy on the dangerous strains. Also, we wouldn't know whether new bird flu isolates were accumulating any of the mutations known to lead to airborne transmission.
posted by en forme de poire at 11:05 PM on December 20, 2011 [1 favorite]


c13, when the Washington post asked the Dutch authors about why, their focus to an uneducated audience was mainly on using the mutations they found as markers for figuring out if novel strains are scary bad shit, which is plausible if the research is allowed to be published and continue. Knowing what isn't a horrific pandemic is just as important as knowing what is. In addition to this they were able to characterize how quickly the strain adapted to its new host, which has important implications for how quickly we'd need to freak out about novel flu viruses. Good public health strategies are important and need good data to be based on. It also has potentially important implications for vaccine development, if there are predictable antigen motifs on novel strains as they jump species, we could conceivably develop vaccines against novelness. How cool would that be?

Besides, even if it didn't have direct implications, this is solid basic science that answers interesting questions about an important biological system. That is inherently important.
posted by Blasdelb at 11:21 PM on December 20, 2011


Don't forget you don't just have to get the PCR.....

Or you could make the gene product, add it into the culture in excess so that it gets preferentially incorporated during assembly and then grow subsequent batches as usual.
For example. Bit however you decide to do it, it is much easier with the data on specific mutations you want.
My point is that widely available bugs like flu are different. You've got to be more careful about what you publish about them. Because you can get them anywhere, and there are relatively fewer steps you have to go through to create trouble. The more information you publish about how to make those steps, the lower you set a threshold past which someone will say " shit, this stuff is easy! Death to the infidels!!"

Existing antivirals work by either inhibiting uncoating and release, and act, as far as I know, at completely different sites than those responsible for transmission. Amantadine does not act on H or N, but on a completely different protein.
As far as vaccines, just because of how they work, I don't see how making a new strain in the lab would give you any useful info.

Again, I'm not saying the stuff must not be studied. I'm saying publishing information about an easily available agent in open press that can be used for bioterrorism is irresponsible. Regardless of how cool it is to get your paper into Nature.
posted by c13 at 11:27 PM on December 20, 2011


I'm using the conditional and "arm-waving" because the articles aren't published yet and I'm not privy to the research. Yes, we know how to make vaccines, but if we don't know what's likely to happen in terms of transmission (and we don't, because drift is easy but shift is weird and influenza is a zoonotic freakazoid) we don't know how to plan stocking, whether we need to plan universal vaccination or core populations vaccination (ring vaccination's right out) and frankly this was the only way to answer the million-dollar question, which is whether we need to worry about H5N1 or whether it's unlikely to hop species and become airborne.

The work had to be done. I don't know whether it has to be published in every detail, though. Mind you, in my long-past lab days, I had enormous trouble recreating people's work from their publications without access to their specific protocols, so I don't know whether outright redaction is necessary.
posted by gingerest at 11:37 PM on December 20, 2011 [2 favorites]


And I apologize, "become airborne" is a sloppy Hollywoodism. I really mean "escape and enter the human body via the upper or lower respiratory tract, and survive in nasal secretions, fomites or aerosols long enough to transmit infection."
posted by gingerest at 11:49 PM on December 20, 2011


which is whether we need to worry about H5N1 or whether it's unlikely to hop species and become airborne.

I think we've found this out without the help of these fellows. All they did was to turn something not easily transmittable into one that is. Whoopti doo! Now we have to worry.

As for replicating rexperiments, I had a thought a few minutes ago. My experience is much like yours, and it is pretty damn common, I suspect. So why not make the important dangerous stuff freely available on request by qualified people? How hard would it be to call up, or send them a CV with a pub list when requesting a protocol. I bet people that will try to replicate their results are known in the field, which would go a long way of filtering out undesirables.
I mean, it's pretty damn unlikely that some geology grad student will be hurt by not having this info readily available.
posted by c13 at 11:50 PM on December 20, 2011


Rexperiments, I say!

Experiments are for whimps.
posted by c13 at 11:52 PM on December 20, 2011


Bit however you decide to do it, it is much easier with the data on specific mutations you want.

You could try something simpler, sure, but if people are still doing stuff this complicated in 2011 to generate single gene deletions in flu, I have some reservations without a methods cite. Moreover, even if a somewhat simpler method worked, my main point is that molecular cloning techniques are still never going to be as easy as swabbing a few ferrets in the nose.

As far as vaccines, just because of how they work, I don't see how making a new strain in the lab would give you any useful info.

Vaccines can sometimes offer partial protection against diverged strains and there is at least one existing vaccine against H5N1; if it has any effectiveness against this strain that's a good sign and could be useful in slowing down an outbreak. As for antivirals, Tamiflu targets neuraminidase and is apparently the most effective drug for H5N1 according to the CDC, so if that doesn't work against this strain that's something we want to know. Both of these are totally empirical questions that are tough to answer from first principles (especially without knowing which specific residues are mutated).
posted by en forme de poire at 12:29 AM on December 21, 2011 [2 favorites]


I think you're missing a point here. (well, maybe I am missing a point). This strain they've created, it's not in the wild. It will never be in the wild, so we hope. As such, it does not matter whether the existing vaccine is more or less effective against it. If for no other reason than even if it is effective, it says nothing about effectiveness on the next wild type that comes along. This is why they're having to come up with a new vaccine every year just about anyways.
If they are doing what you say they are, not only are they prearing to fight the last war, they're searching for WMDs in Iraq.
But again, I'm not saying the reaserch must not be done.
posted by c13 at 12:56 AM on December 21, 2011


Regarding your link, all I could pull up was an abstact from pubmed, but they are Trying to express a foreign gene, which is much harder, no doubt.
Doing a quick search, I mean something like this:

Characterization of Neuraminidases from the Highly Pathogenic Avian H5N1 and 2009 Pandemic H1N1 Influenza A Viruses

To study the precise role of the neuraminidase (NA), and its stalk region in particular, in the assembly, release, and entry of influenza virus, we deleted the 20-aa stalk segment from 2009 pandemic H1N1 NA (09N1) and inserted this segment, now designated 09s60, into the stalk region of a highly pathogenic avian influenza (HPAI) virus H5N1 NA (AH N1). The biological characterization of these wild-type and mutant NAs was analyzed by pseudotyped particles (pseudoparticles) system.

Except done not with pseudoparticles, but with live virus.
posted by c13 at 1:07 AM on December 21, 2011


Or this:

Disruption of the viral polymerase complex assembly as a novel approach to attenuate influenza A virus.

AuthorsMänz B, et al. Show all Journal
J Biol Chem. 2011 Mar 11;286(10):8414-24. Epub 2010 Dec 23.

Affiliation
Department of Virology, University of Freiburg, 79104 Freiburg, Germany.

Abstract
To develop a novel attenuation strategy applicable to all influenza A viruses, we targeted the highly conserved protein-protein interaction of the viral polymerase subunits PA and PB1. We postulated that impaired binding between PA and PB1 would negatively affect trimeric polymerase complex formation, leading to reduced viral replication efficiency in vivo. As proof of concept, we introduced single or multiple amino acid substitutions into the protein-protein-binding domains of either PB1 or PA, or both, to decrease binding affinity and polymerase activity substantially. As expected, upon generation of recombinant influenza A viruses (SC35M strain) containing these mutations, many pseudo-revertants appeared that partially restored PA-PB1 binding and polymerase activity. These polymerase assembly mutants displayed drastic attenuation in cell culture and mice. The attenuation of the polymerase assembly mutants was maintained in IFNα/β receptor knock-out mice. As exemplified using a H5N1 polymerase assembly mutant, this attenuation strategy can be also applied to other highly pathogenic influenza A virus strains. Thus, we provide proof of principle that targeted mutation of the highly conserved interaction domains of PA and PB1 represents a novel strategy to attenuate influenza A viruses.

posted by c13 at 1:09 AM on December 21, 2011


There's a podcast at This Week in Virology that has an interesting discussion of this issue.
posted by carter at 4:50 AM on December 21, 2011 [1 favorite]


Yes, and they want to publish it, so that whoever wants to, can skip all the hassle and go directly to the good stuff.
Again dude, people already know how to get the 'good stuff' what was unknown before, was what the specific mutations were. The genetic code itself? Not that useful to terrorists. You can go online and download the genetic code to SARS if you want.

Their research won't let anyone skip any steps. If the turrists had the ability to synthesize viruses from genetic code, they could simply make SARS or any other virus who's data is online. I'm guessing H1N1 is online as well.

What this research does is specify what happens to the genome when you go through the steps that everyone already knows.

I don't know why people are so desperate to hang on to an obviously incorrect understanding of what was going on.

This has nothing to do with weaponization, which is what happens when researchers try to create bioweapons, which would never happen in nature, but rather about emulating what happens in nature to cause these viruses to start infecting humans.
until they publish the sequence with the important mutations highlighted?
All the mutations are already public.

From Carl Zimmer's Loom blog:
As Martin Enserink reports in Science, the new experiments on bird flu were similarly effective. They turned H5N1 into a ferret flu in just 10 generations. By the time the scientists were done, they no longer had to ferry the flu from one ferret to the next. A healthy ferret just had to be placed near a sick one; the virus could travel through the air. When they examined the new strain, they discovered five mutations in two genes. All five mutations have been found in natural H5N1 viruses–just not all in one virus.
I'm sorry, but that's just arm waving. Might? Better? What do those words mean?
You don't know what the words 'might' and 'better' mean? One way it could be helpful is that scientists could track when these mutations start to show up in order to prepare for a pandemic that hasn't even started yet. Or if you see a new strain you can tell by looking at the genome how bad it will be.
I think you're missing a point here. (well, maybe I am missing a point). This strain they've created, it's not in the wild. It will never be in the wild
All the mutations that showed up in the new strain had already shown up in the wild. So, it's possible that all five could someday show up in the wild together.

The scientists did not end up creating anything new.
posted by delmoi at 5:07 AM on December 21, 2011 [3 favorites]


c13, both of those papers required transfecting HEK 293T cells with 4-8 separate plasmids (4 for the pseudoparticles, 8 for the virus) to reconstitute the flu genome with a mutant gene, which is similar to what you have to do for the gene knockout.

If the flu virus they made had several or even a few brand new mutations, I would tend to agree that its genotype might not bring much to bear on flu strains that are likely to arise in the wild. And indeed if you re-ran the experiment you might get different evolutionary trajectories. But we now know from this study that the evolutionary path to airborne transmission is very short, and relatedly, as Delmoi just pointed out, we know that the individual mutations making this strain so potent are already out there. Getting existing mutations into the same virus is a much easier walk down the fitness landscape than, e.g., selecting for a brand-new allele. These facts together are a pretty strong indication that we should be on the alert for flu strains having these mutations in combination (meaning monitoring them and testing the efficacy of known treatments).

I don't know if they've tried yet to make reversions in their virus, in order to see whether certain combinations of the mutations are necessary and/or sufficient to cause airborne transmission, but that would be one of the logical next steps.
posted by en forme de poire at 11:10 AM on December 21, 2011 [1 favorite]


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