Man Made H5N1 - Super Version

JJackson · May 16, 2012

Re: Man Made H5N1 - Super Version

gsgs said:
you must first run it through the ferrets
and they breath to each other and must be cared for.
That makes it more complicated

And all the lower-tech labs from other countries, that
want to redo the experiments ...

gs all the biological material -virus and ferret - is within the security perimeter of a BSL 3/4 lab and not difficult to sterilise.

I have seen no evidence of anyone wanting to repeat the experiments in anything less than a BSL3 lab. Once the dust settles it may be that only BSL4 labs do this kind of research that is the kind of question that is currently being debated. Here I am talking about research labs populated by academics publishing in the peer reviewed journals. There are 3 other potential problems 1] The garage DIY tinkerer, 2] The terrorist in a cave and , 3] The government sponsored clandestine lab (AKA the military).
1] The technology is not there yet at a realistic price point
2] I do not believe this is a significant threat, they have better things to do with there time.
3] A real danger, and I would be looking a permanent members of the UN Security council rather than less advanced countries who we happen not to be playing nicely with at present. The real danger here is lab escape not deliberate release and the research is probably being done with the best of intentions "we were only working with these agents to produce vaccines because [we are paranoid idiots and] we feared they were, and needed to be prepared".
Never underestimate the stupidity of your own governments.

gsgs · May 17, 2012

Re: Man Made H5N1 - Super Version

lab accidents do happen despite biosecurity.
That's what the experts say. (AFAIK)
One estimated a 1% probability per year.

I assume that many countries want to repeat the experiments,
(now or later ...) but don#t want to use that high,expensive biosafty.

One of the arguments of WHO,NIH for publishing was the desire
of countries like Indonesia to have access to the data,
and who might critisize secrecy as they had been critisized for secrecy
wrt. sequences.
Naturally these countries have also an interest to perform
the experiments by themselves (no dependence on possible future
foreign secrecy). They will be trying to establish their own labs,
once it becomes easier and cheaper, which I assume it will.
Just see how the sequencing costs are dropping.

And there will be international debate, how much safety is needed,
and some countries will think 3 or 2 is enough where others require 4.

And some will do the experiments not publically, so there is no control.

better things to do with their time ??? It's important. And it's new.
Sounds like saying in the 70s that terrorists won't use computers...

I remember decades ago from the SETI discussion,
some people argued that advanced intelligent civilizations
are not viable for long time because they would destruct themselves
by creating biological weapons.
I didn't so much understand that argument at that time.

But now I wonder, how we can even prevent it in theory
in the long run.

The creation of bad viruses/bacteria looks much easier,
fundamentally, than the development of new treatments.
Nature is very restricted with their DNA/RNA and mutations,
evolution as compared to computers and gene-manipulation

JJackson · May 17, 2012

Re: Man Made H5N1 - Super Version

gsgs said:
lab accidents do happen despite biosecurity.
That's what the experts say. (AFAIK)
One estimated a 1% probability per year.

This is also my understanding but it is also a function of time. If you are accumulating 'successful' strains in your freezer and working with them then you are at much greater risk than if you sequence them and then irradiate them. Your 1% becomes .01% if you only have the strain for 3 days while you sequence.

I assume that many countries want to repeat the experiments,
(now or later ...) but don#t want to use that high,expensive biosafty.

One of the arguments of WHO,NIH for publishing was the desire
of countries like Indonesia to have access to the data,
and who might critisize secrecy as they had been critisized for secrecy
wrt. sequences.
Naturally these countries have also an interest to perform
the experiments by themselves (no dependence on possible future
foreign secrecy). They will be trying to establish their own labs,
once it becomes easier and cheaper, which I assume it will.
Just see how the sequencing costs are dropping.

And there will be international debate, how much safety is needed,
and some countries will think 3 or 2 is enough where others require 4.

I do not think Indonesia et al are clamouring to do the experiments - at least not as long as they think nothing is being hidden from them.

I hope they do build more labs but I suspect they will be aimed more at the practical end of things, vaccine, sequencing etc. This kind of more pure research will, I suspect, largely remain in the richer countries domain for the time being.

And some will do the experiments not publically, so there is no control.

I do not worry about this outside of the military domain.

better things to do with their time ??? It's important. And it's new.
Sounds like saying in the 70s that terrorists won't use computers...

What western media and governments normally class as terrorists are passionate believers that their way is right. They have an -ism they want to spread be it religious political or whatever. They are rational actors - within the terms and internal logic of their cause - and a bio-weapon does not help them achieve their aims. Hence they have better - in the sense of more productive - things to do with their time.
Now someone, like me, who thinks the planet has more humans on it than is good for it might be more of a danger (to the governments reading this that was only a hypothetical, no rendition please). I see no comparison with computers which would be very useful to any evangelical organisation, unlike untargetable weapons.

I remember decades ago from the SETI discussion,
some people argued that advanced intelligent civilizations
are not viable for long time because they would destruct themselves
by creating biological weapons.
I didn't so much understand that argument at that time.

But now I wonder, how we can even prevent it in theory
in the long run.

The creation of bad viruses/bacteria looks much easier,
fundamentally, than the development of new treatments.
Nature is very restricted with their DNA/RNA and mutations,
evolution as compared to computers and gene-manipulation

On your second point I would agree that making a pathogen is currently simpler than making the cure. As depicted in sci-fi the real danger is that some government creates a plague, and the cure, which makes a bio-weapon semi target-able. If released, of course, nature will find a way around the cure and allow it to return-to-sender.

On the first point I would recommend this radio talk in the CBC philosophy of science series by Nicolas Maxwell (episode 24) which Sally posted a while ago. http://www.flutrackers.com/forum/showthread.php?t=86718&highlight=cbc+radio+cod+popper

This is from a resume I made in the thread about that episode.

He argues that there are a hierarchy of assumptions which underpin the supposedly rigorously empirical scientific method. As a starting point he argues that we are fooling ourselves into thinking we are searching for truth when we are starting from the assumption that the answer is basically comprehensible and simple. By simple I mean elegant and to our eyes beautiful. Given the option of a messy complex solution and a clear elegant one human nature will make us take the elegant one despite both fitting the data. He argues that dogma is weakening science by failing to acknowledge some or all of these assumptions. The institutional enterprise of science i.e. the text books, academic institutions, funding, academic promotional systems and criteria for accepting work for journal publication all have a skewing effect. The second, and main, point is much easier to explain it is simply that we should have become wise, or civilised, in parallel with our acquisition of knowledge but the two are out of sync and we have acquired the power to do great harm to our planet and ourselves without the wisdom to know how to control it.

Laidback Al · May 17, 2012

Re: Man Made H5N1 - Super Version

gsgs said:
... The creation of bad viruses/bacteria looks much easier, fundamentally, than the development of new treatments. Nature is very restricted with their DNA/RNA and mutations, evolution as compared to computers and gene-manipulation

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ontFlipMirrorIndents/> <w:OverrideTableStyleHps/> </w:Compatibility> <m:mathPr> <m:mathFont m:val="Cambria Math"/> <m:brkBin m:val="before"/> <m:brkBinSub m:val="--"/> <m:smallFrac m:val="off"/> <m:dispDef/> <m:lMargin m:val="0"/> <m:rMargin m:val="0"/> <m:defJc m:val="centerGroup"/> <m:wrapIndent m:val="1440"/> <m:intLim m:val="subSup"/> <m:naryLim m:val="undOvr"/> </m:mathPr></w:WordDocument> </xml><![endif]--> gsgs makes an important point that is worth repeating and generalizing. We need to be concerned about all kinds of laboratory-based genetic manipulation, not just among viruses and bacteria.

JJackson · May 17, 2012

Re: Man Made H5N1 - Super Version

Laidback Al said:
 gsgs makes an important point that is worth repeating and generalizing. We need to be concerned about all kinds of laboratory-based genetic manipulation, not just among viruses and bacteria.

We can write the code the way we want while nature re-drafts an existing text with random changes, publishes and sees what sells. Our problem is, at present, we can not predict exactly what effect any given edit will have.
The researchers in the two experiments that precipitated this thread did not re-code the RNA they let nature do it at random but with selection pressures selected to favour the desired outcomes. A slightly more high-tech version than plant, and stock, breeders have been doing for generations but in essence purely Darwinian.
This is all about to change. We are now approaching an important nexus linking increased computing power and better sequence databases which will allow a better understanding of - and ability to predict - how sequence changes relate to tertiary protein structure and hence biological activity. We are not quite there yet but it should do wonders for drug development initially but also pathogen manipulation. My concern is it also opens the door to all kinds of well meaning mistakes in the manipulation of, and transfer of, genes. A high tech version of the introduction of rabbits, myxomatosis, cane toads etc. to Australia but with potentially much graver consequences.
At present we can do a bit of reverse engineering in that if it is useful to my research I can cut'n'paste a gene for bioluminescence from one organism into another but I can not sit down and type out a series of ACGTs to create a gene for bioluminescence from scratch, at least not with out cribbing from nature.

gsgs · May 17, 2012

Re: Man Made H5N1 - Super Version

one major method here is reassortment. That's how influenza pandemics are
usually "created" by nature.
This can be really low tech.
While nature must wait for one of the rare coinfections and the suitable
surroundings for spread, we could just infect one swine or ferret
with 2 specially selected strains and wait for reassortments.
Then grow that virus and spread it in crowded places.
Or swine herds.

There is a reason why we have strict quarantines for inporting pigs
or birds from other continents. And it worked pretty well.
Influenzas from different continents rarely mixes, except in humans
of course. Now the terrorists can smuggle suitably infected swine.
This unlikely creates a pandemic in a single case - but it increases
the risk. And that practice already would be a threat.

Now, why are there almost no Eurasian segments in American birds ?
Terrorist could pick some infected Eurasian birds and mix them
with American ones. In Alaska or Mexico or at sea.
So to "enhance" virus evolution. Not directly identifyable as "terrorism",
but it increases the risks.

In some decades they may be able to combine the "features"
of different viruses. Just add some protein to the RNA.
As immunity-escaping as influenza,
as transmissable as measles, as virulent as H5N1,

That protein can be taken from other viruses
with some adaption in the lab...

We are complacent since historically all these attempts
failed miserably. But there is considerable progress ...

Gert van der Hoek · Jun 20, 2012

Re: Man Made H5N1 - Super Version

Flu researchers don't know when they can restart work

19 June 2012 by Debora MacKenzie

For similar stories, visit the Epidemics and Pandemics and Bird Flu Topic Guides
After six months of dispute, research in the Netherlands that made a deadly H5N1 flu airborne will be published this week. The scientists behind it now want to get on with their work ? but they can't.

read more: New Scientist

Pathfinder · Jun 20, 2012

Re: Man Made H5N1 - Super Version

More from Gert van der Hoek link:

"The US hastily published a new DURC policy in March. It says that if work with any of 15 pathogens increases virulence, transmission, hosts or resistance to defences, researchers must apply a mitigation plan to be agreed by relevant authorities. This may include increased containment, changing the experiment, withholding results, classifying the work under secrecy rules ? or just not doing it."

From an earlier post:

Flu Researcher Ron Fouchier: 'It's a Pity That It Has to Come to This'
byMartin Enserink on <ABBR class=published title="20 January 2012">20 January 2012, 3:42 PM</ABBR>

Source: http://news.sciencemag.org/scienceinsider/2012/01/flu-researcher-ron-fouchier-its.html

Excerpt:

Q: You also want to repeat the experiments with more H5N1 strains?

R.F.: Yes. We did this with one genetic lineage of the H5N1 virus. The question is whether all lineages can become aerosol-transmissible...

sharon sanders · Jun 21, 2012

Re: Man Made H5N1 - Super Version

hat tip Michael Coston

Thursday, June 21, 2012

Science Publishes The Fouchier Ferret Study

BSL-4 Lab Worker - Photo Credit ?USAMRIID

Just over 9 months ago, at the 2011 ESWI Influenza Conference in Malta, Dutch researcher Ron Fouchier described the results of a groundbreaking ? and later, ground shaking ? experiment he?d conducted with the H5N1 avian flu virus and ferrets.

Katherine Harmon?s piece in Scientific American (see SciAm: What Will The Next Influenza Pandemic Look Like?) briefly touched on his work, but it was Debra MacKenzie?s article a week later (see New Scientist: Five Easy Mutations) that really called attention to this experiment.

Fouchier was quoted as saying that he?d `mutated the hell? out of the H5N1 virus in the lab, and then passed it serially through 10 ferrets, during which time it mutated further to become easily transmissible among the lab animals while retaining virulence.

Halfway across the world, Yoshihiro Kawaoka, a highly respected virologist at the University of Wisconsin-Madison School of Veterinary Medicine announced the creation of a comparable H5N1 super flu at roughly the same time.

Quietly at first, and then rising to a crescendo, a number of biosecurity experts began to openly question the wisdom of publishing details of (and in some cases, even conducting) these types of experiments.

Their concerns included the potential for an accidental lab release of the virus, and the possibility that someone could use this knowledge ? if published ? to create a bio-weapon.

The debate within the scientific community was both lengthy and visceral. A recommendation from the NSABB to redact portions of Fouchier?s study for publication was met with heavy criticism.

Those wishing to review that process (some might call it an ordeal) can select this link which will return more than two dozen blog posts on that intense debate.

After much discussion, it was decided that both Kawaoka?s and Fouchier?s (revised) studies should be published in full, and six weeks ago, the first paper appeared (see Nature Publishes The Kawaoka H5N1 Study).

Today the Journal Sciencepublishes the long-awaited Fouchier study in aspecial section that includes an treasure trove of other H5N1 research-related reports, perspectives, news stories, and even an audio podcast.

To great credit to the editors and publishers of Science, all of these articles are being made available ? in their entirety ? to the public.

With well over 100 pages of reports and supporting material, there?s a lot here to read and absorb (and a lot of it, particularly for non-scientists ? is admittedly tough sledding).

Luckily, I?m sure we?ll be hearing a good deal of expert dissection and analysis emerging over the next few days.

Under the latest H5N1 news, you?ll find the following offerings:

Public at Last, H5N1 Study Offers Insight Into Virus's Possible Path to Pandemic M. Enserink
For Young Scientists, A Wild Ride - M. Enserink

How Much Longer Will Moratorium Last? - D. Malakof

Read all of Science's News coverage of the H5N1 controversy.

A Science Podcast brings us an Interview with Bruce Alberts; Science's Editor-in-Chief.

From Fouchier and his team we get the main event; an 8-page, highly technical report on how they created a genetically modified, mammalian-transmissible, version of the H5N1 virus:

Airborne Transmission of Influenza A/H5N1 Virus Between Ferrets
Sander Herfst, Eefje J. A. Schrauwen, Martin Linster,
Salin Chutinimitkul, Emmie de Wit, Vincent J. Munster, Erin M. Sorrell, Theo M. Bestebroer, David F. Burke, Derek J. Smith, Guus F. Rimmelzwaan, Albert D. M. E. Osterhaus, Ron A. M. Fouchier

(Excerpt)

Highly pathogenic avian influenza A/H5N1 virus can cause morbidity and mortality in humans but thus far
has not acquired the ability to be transmitted by aerosol or respiratory droplet (?airborne transmission?) between humans. To address the concern that the virus could acquire this ability under natural conditions, we genetically modified A/H5N1 virus by site-directed mutagenesis and subsequent serial passage in ferrets. The genetically modified A/H5N1 virus acquired mutations during passage in ferrets, ultimately becoming airborne transmissible in ferrets.

Fouchier also includes 34 pages of supporting material.

Erasmus Medical Center, where these experiments were conducted, at the same time (2pm ET today) released a new Bird Flu Research Q&A that responds to several important questions, including:

What was the purpose of the work?
What experiments were done?
What are the main conclusions?
How does this help public health?

Along with the publication of Fouchier?s study, we also get a major report from C.A. Russell et al., that looks at the potential for these mutations to occur naturally in the wild. The report?s pedigree also includes Albert Ostershaus, Ron Fouchier, and Yoshiro Kawaoka.

The Potential for Respiratory Droplet? Transmissible A/H5N1 Influenza Virus to Evolve in a Mammalian Host

Colin A. Russell, Judith M. Fonville, Andr?E.X.Brown, David F. Burke, David L. Smith, Sarah L. James, Sander Herfst, Sander van Boheemen, Martin Linster, Eefje J. Schrauwen, Leah Katzelnick, Ana Moster?n, Thijs Kuiken, Eileen Maher, Gabriele Neumann, Albert D. M. E. Osterhaus, Yoshihiro Kawaoka, Ron A.M.Fouchier, Derek J. Smith

ABSTRACT

Avian A/H5N1 influenza viruses pose a pandemic threat. As few as five amino acid substitutions, or four with reassortment, might be sufficient for mammal-to-mammal transmission through respiratory droplets. From surveillance data, we found that two of these substitutions are common in A/H5N1 viruses, and thus, some viruses might require only three additional substitutions to become transmissible via respiratory droplets between mammals.

We used a mathematical model of within-host virus evolution to study factors that could increase and decrease the probability of the remaining substitutions evolving after the virus has infected a mammalian host. These factors, combined with the presence of some of these substitutions in circulating strains, make a virus evolving in nature a potentially serious threat. These results highlight critical areas in which more data are needed for assessing, and potentially averting, this threat.

Again, you?ll find copious supplementary information available for this paper as well.

Also included in this special section are related commentaries, policy forum papers, and perspectives, including:

Statement by Science Editor‐in‐Chief Dr. Bruce Alberts Regarding Publication of H5N1 Avian Influenza Research

Regulating the Boundaries of Dual-Use Research - Mark S. Frankel

Influenza: Options to Improve Pandemic Preparation -Rino Rappuoli and Philip R. Dormitzer

Benefits and Risks of Influenza Research: Lessons Learned - Anthony S. Fauci and Francis S. Collins

Evolution, Safety, and Highly Pathogenic Influenza Viruses - Marc Lipsitch, Joshua B. Plotkin, Lone Simonsen, Barry Bloom

Securing Medical Research: A Cybersecurity Point of View - B. Schneier

Like many of you, I?m sure I?ll be spending a good amount of time over the next few days trying to absorb, and understand, this avalanche of new information.

Posted by Michael Coston at <a class="timestamp-link" href="http://afludiary.blogspot.ca/2012/06/science-publishes-fouchier-ferret-study.html" rel="bookmark" title="permanent link"><abbr class="published" title="2012-06-21T14:41:00-04:00">2:41 PM</abbr>

Giuseppe · Jun 21, 2012

Re: Man Made H5N1 - Super Version

It remains a very sensitive issue, about bioethics of such type of experiments and the predictive value of them.

Although it is clearly useful to know at least teoretically the possible mutations that could make transmissible H5N1 virus, it is also important to underline the striking fact that despite the accumulating gene mutations, H5N1 remains a rare event in human.

The precise mechanism behind this substantial specie barrier is - I think - not fully understood by scientists.

Thus, the recent publications are somewhat alarmistic, if one considers the fact that - now - the virus is circulating unnoticed in densely populated area, such as China, India, Bangladesh, Indonesia, Egypt, where it could enter in contact with humans, domesticated animals, cats, dogs as well as swine and poultry.

Since 1997 H5N1 is menacing humans with its unabating circulation but despite the fanfare it remains a sporadic infection.

I suggest to take some distance from the apocalyptic messages now popping up everywhere on the net, even in important news outlets.

We know the virus, and the frenzy we managed during human clusters of H5N1 infections.

The most part of news outlets, opinionists where elsewhere during our endurance...

gsgs · Jun 22, 2012

Re: Man Made H5N1 - Super Version

http://www.virology.ws/2012/06/21/influenza-h5n1-virus-versus-ferrets-round-two/
http://www.virology.ws/2012/05/02/k...ransmission-of-h5-influenza-virus-in-ferrets/

Fouchier:IDN/5/2005(H5N1) + Q222L(4),G224S(4),E627K(1),T156A(4),H103Y(4)
http://www.sciencemag.org/content/336/6088/1534.full

Kawaoka:VNM/1203/2004(H5N1)(4)+Mx(1,2,3,5,6,7,8) + N224K(4),Q226L(4),N158D(4),T318I(4),
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature10831.html

Donis:H5N1(1,2,3,4,5,7,8)+Q196R(4),Q226L(4),G228S(4) + H3N2(6)
http://www.sciencedirect.com/science/article/pii/S0042682211004752#

H5-enumeration: N170D,N236K,Q238L,T331I (?) LIKKnSTY,TRSKVnGqSG,YVKSNRLVLAtGLRNS
Q238L,G240S,T172A,H119Y -- FNDYEELKhLLSRIN,RNVVWLIKKNStYPTI,TRSKVNGqSgRME

Code:

170  1081   -:253 B:2 D:1051 E:2 G:20 K:1 N:3040 S:3 T:1 X:1 
236    22   -:255 D:3 H:15 K:2 N:4097 X:2 
238     6   -:256 K:1 P:1 Q:4112 R:2 X:2 
331     9   -:48 I:1 K:3 L:1 P:1 T:4317 X:3 
-----------------------------------------------------
119     5   -:269 H:4100 P:2 R:1 X:1 Y:1 
172 2141   -:253 A:2066 I:5 K:3 S:62 T:1980 V:3 X:2 
238    6   -:256 K:1 P:1 Q:4112 R:2 X:2 
240    4   -:256 A:1 E:1 G:4114 X:2 
-----------------------------------------------

--------------------------------------------
170 h5z3 1081 -:253 B:2 D:1051 E:2 G:20 K:1 N:3040 S:3 T:1 X:1

D >2002//,A/Ck/HK/YU22/2002
H >2006//,A/chicken/Indonesia/Timika_10/2006
H >2006//,A/Chicken/West Java/PWT-WIJ/2006
H >2006//,A/Chicken/West Java/SMI-CSLK-EC/2006
H >2006/05/01,A/Chicken/West Java/SMI-PAT/2006
H >2006/09/01,A/chicken/West Java/SMI-CSLK-EB/2006
K >2007//,A/Muscovy duck/Vietnam/NCVD-11/2007
H >2007/01/04,A/chicken/Jakarta/DKI-Nurs/2007
D >2007/01/23,A/chicken/Hunan/1793/2007
H >2007/08/,A/chicken/West Java/Smi-Hj18/2007
H >2007/08/06,A/chicken/West Java/Smi-Sud1/2007
H >2007/12/,A/chicken/Indonesia/Sukabumi_10/2007
H >2007/12/,A/chicken/Indonesia/Sukabumi_3/2007
H >2007/12/,A/chicken/Indonesia/Tanggerang_10/2007
H >2008/06/20,A/chicken/West Java/Smi-M1/2008
H >2008/06/20,A/chicken/West Java/Smi-M6/2008
H >2008/07/30,A/chicken/West Java/Smi-Biot/2008
D >2009/05/,A/great cormorant/Qinghai/1/2009
H >2010/06/,A/chicken/EastKalimantan/UT581/2010
K >2010/06/10,A/duck/Egypt/10185SS/2010
236 h5z3 22 -:255 D:3 H:15 K:2 N:4097 X:2

R >2005/11/11,A/Anhui/2/2005
P >2006//,A/chicken/Xinjiang/27/2006
R >2006/01/14,A/Indonesia/CDC329/2006
K >2011/07/08,A/chicken/Egypt/11506SF/2011
238 h5z3 6 -:256 K:1 P:1 Q:4112 R:2 X:2

I >2002//,A/duck/Guangxi/53/2002
X >2004//,A/Hanoi/03/2004
L >2005//,A/goose/Yunnan/5314/2005
K >2005//,A/Indonesia/239H/2005
P >2005//,A/Thailand/RPNP/2005
K >2005/12/13,A/Indonesia/CDC287E/2005
K >2005/12/13,A/Indonesia/CDC287T/2005
331 h5z3 9 -:48 I:1 K:3 L:1 P:1 T:4317 X:3

-----------------------------------------------------

Y >2002//,A/duck/Zhejiang/bj/2002
P >2004//,A/duck/Hunan/533/2004
R >2006/12/30,A/duck/Henan/1650/2006
P >2011/07/07,A/duck/Vietnam/QT802/2011
119 h5z3 5 -:269 H:4100 P:2 R:1 X:1 Y:1

172 h5z3 2141 -:253 A:2066 I:5 K:3 S:62 T:1980 V:3 X:2

R >2005/11/11,A/Anhui/2/2005
P >2006//,A/chicken/Xinjiang/27/2006
R >2006/01/14,A/Indonesia/CDC329/2006
K >2011/07/08,A/chicken/Egypt/11506SF/2011
238 h5z3 6 -:256 K:1 P:1 Q:4112 R:2 X:2

A >1997//,A/chicken/Hubei/wi/1997
E >2004//,A/chicken/Hunan/41/2004
240 h5z3 4 -:256 A:1 E:1 G:4114 X:2

-----------------------------------------------

Fouchier:
http://www.sciencemag.org/content/336/6088/1534.full.pdf
http://www.sciencemag.org/content/suppl/2012/06/20/336.6088.1534.DC1/1213362.Herfst.SM.pdf

Kawaoka:
http://www.nature.com/nature/journal/vaop/ncurrent/pdf/nature10831.pdf
http://www.nature.com/nature/journal/vaop/ncurrent/extref/nature10831-s1.pdf

Donis:
http://www.ncbi.nlm.nih.gov/pubmed/22056389
http://www.sciencedirect.com/science/article/pii/S0042682211004752#

Pathfinder · Jun 22, 2012

Re: Man Made H5N1 - Super Version

Bird Flu Paper Is Published After Debate
By DONALD G. McNEIL Jr.

Published: June 21, 2012
...
The paper’s publication, in the journal Science, ended an acrimonious debate over whether such results should ever be released. Critics said they could help a rogue scientist create a superweapon. Proponents said the world needed to identify dangerous mutations so countermeasures could be designed.
...
Some of the early alarm was fed by Dr. Fouchier speaking at conferences and giving interviews last fall in which he boasted that he had “done something really, really stupid” and had “mutated the hell out of H5N1” to create something that was “very, very bad news.” He said his team had created “probably one of the most dangerous viruses you can make.”

After the controversy erupted, he claimed the news media had overblown the danger.

Science magazine on Thursday published seven other articles about H5N1. One, by a team at Cambridge, concluded that it was not possible to accurately calculate the likelihood of all five mutations occurring in nature.
...
Asked if a rogue researcher could now try to duplicate Dr. Fouchier’s work, Dr. Fauci said it was possible. But he argued that open discussion was still better than restriction to a few government-cleared flu researchers, because experts in unrelated fields, like X-ray crystallography or viral epidemiology, might take interest and eventually make important contributions, he said.

Full text & comments:
http://www.nytimes.com/2012/06/22/health/h5n1-bird-flu-research-that-stoked-fears-is-published.html

Giuseppe · Jun 22, 2012

Re: Man Made H5N1 - Super Version

[Source: Government of Hong Kong PRC SAR, full text: (LINK).]

Following is the transcript of remarks (English portion) made by the Secretary for Food and Health, Dr York Chow, after attending a public function this afternoon (June 22):

(...)

Reporter: (On whether Hong Kong will have a serious outbreak of bird flu.)

Secretary for Food and Health: We have a contingency plan for pandemics and we have exercised that during the H1N1 emergence in 2009, showing that the plan is workable and suitable for our setting. Of course, every time when we have a new disease, we have to analyse what the characteristics of that virus are, what people will be affected most, what is the pathogenesis that will affect human beings. All these require some analysis before we can deal with them. Our contingency plan is workable and we can always have the support of our laboratories, our tests and expertise in Hong Kong to make a very suitable decision in case. We are well prepared for any type of pandemic and of course we do not wish that would happen in Hong Kong.

Quote:
<TABLE border=0 cellSpacing=0 cellPadding=6 width="100%"><TBODY><TR><TD style="BORDER-BOTTOM: 1px inset; BORDER-LEFT: 1px inset; BORDER-TOP: 1px inset; BORDER-RIGHT: 1px inset" class=alt2>If you look at the report from overseas regarding the manipulation of a virus so that it can change to a more villainous virus, the World Health Organization has a very strong stand that such methodology should not be publicised.</TD></TR></TBODY></TABLE>

(...)

-
-----

Emily · Jun 23, 2012

Re: Man Made H5N1 - Super Version

Bird flu mutations may make it more contagious, less deadly

By Maggie Fox
[snip]
Bird flu is still out there and mutating into dangerous forms, but there?s good news too ? the changes that could make it spread more easily could make it less deadly, researchers reported on Thursday.
[snip]
Now here?s the reassuring part ? the mutations that make the virus pass easily from one animal to another also make it a little less dangerous. Instead of taking root deep in the lungs, causing a hard-to-treat pneumonia, the mutated version of H5N1 likes to live in the upper respiratory tract.

?And so it's less likely to cause pneumonia,? said Ron Fouchier of Erasmus Medical Center in Rotterdam, the Netherlands. And, Fouchier and colleagues reported in Science, drugs used to treat flu worked against the mutant version...

Giuseppe · Jun 23, 2012

Re: Man Made H5N1 - Super Version

I am usually really dumb but if the mathematical model made for establishing the likelihood of the specific gene constellation supposed to enabling aerosol transmission in mammals has failed to compute this value, what is really the issue?

if one calculate the chance of an event to happen as:

p = number of the events matches a particular value (f) / total number of all possible events (t)

p = impossible when t=0 or infinite (?)

Laidback Al · Jun 23, 2012

Re: Man Made H5N1 - Super Version

Now here?s the reassuring part ? the mutations that make the virus pass easily from one animal to another also make it a little less dangerous. Instead of taking root deep in the lungs, causing a hard-to-treat pneumonia, the mutated version of H5N1 likes to live in the upper respiratory tract.

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aunPenh; mso-bidi-theme-font:minor-bidi; mso-bidi-language:AR-SA;} </style> <![endif]--> I don?t think we should be reassured. What is the definition of less dangerous? The fact that the mutated version of H5N1 establishing itself in the upper respiratory tract may cause fewer cases of hard-to-treat pneumonia does not make the mutated virus less dangerous.

It is highly likely that an H5N1 virus in the upper respiratory tract will be much more transmissible, causing even more cases, perhaps in short periods of time which could overwhelm the health care system. The real question is - what is the overall virulence of the strain, not where it lodges itself in the human body.

gsgs · Jun 23, 2012

Re: Man Made H5N1 - Super Version

what do we know ? they just tested one strain

let it reassort a bit ...

gsgs · Jul 1, 2012

Re: Man Made H5N1 - Super Version

http://www.flutrackers.com/forum/showthread.php?p=458976#post458976

http://alandove.com/content/2012/06/unleashing-the-ferrets-of-fear/

http://www.virology.ws/2012/06/21/influenza-h5n1-virus-versus-ferrets-round-two/

none of these people does sequencing
can you decide the threat without comparing the sequences,
the mutations ?
and other experts are more concerned

and now we have the additional danger of terrorists and lab-escapes

gsgs · Jul 2, 2012

Re: Man Made H5N1 - Super Version

?You can?t put a number on it,? said Fauci

if Fauci "can't", others can and hopefully will.
That just means, we will not so much consider
Fauci's opinion on this issue, sigh.

-------------------------------------------

Derek Smith said :
> But asking whether a five-mutation strain could evolve in human hosts,
> was like asking if it could ever snow in the Sahara ? unlikely, but not inconceivable.

comparing it with weather events means that experts "can"
and will put numbers to it.

January 20, 2012 ? BECHAR, Algeria - Snow fell Tuesday in the Sahara Desert in western Algeria.

-----------------------------------------------
> Asked if a rogue researcher could now try to duplicate Dr. Fouchier?s
> work, Dr. Fauci said it was possible. But he argued that open discussion
> was still better than restriction to a few government-cleared flu
> researchers, because experts in unrelated fields, like X-ray
> crystallography or viral epidemiology, might take interest
> and eventually make important contributions, he said.

sure, but what is more likely ? I don't count on the X-ray people
to save us. 80 years of flu research didn't achieve a lot so far.
Best achieved is presumably antibiotics against bacterial pneumonia.
And how shall knowing these special mutations help flu-research ?
The only thing that comes to mind is surveillance and watching
and concentrating on the dangerous strains.
But that doesn't need publishing.

----------------------------------------------------------------------
> The only groups who might logically consider using such
> a weapon are those for whom humans are the problem,
> such as environmental extremists and animal-rights activists,
> or apocalyptic sects, such as the Japanese terrorist cult
> Aum Shinrikyo, which released sarin gas in the Tokyo underground
> in 1995. Then there are those who do not care about casualties,
> such as a state or a regime that believes it faces imminent
> existential threat, or suicide fighters.

or any group who is desperate enough. E.g. in a war, when the
world knows that the country/dictator has H5N1 panflu weapons, they
will not allow it to become desperate enough to use it.
So it makes sense to have such weapons, and that bares the risk
of lab escapes.
And normal terrorists can also well make use of it.
They can threaten to use it so to press the world to
fulfill conditions. They don't want to use, but will make
it almost automatical if the conditions aren't met.
So they can be realatively sure that the conditions are met.
--------------------------------------------------------------------
Tim Trevan:
> Precise calculation is not possible, but the evidence strongly suggests that the
> increase in risk is quite small.
-------------------------------------------------------------------
> ?There is always a risk,? Dr. Anthony S. Fauci, the director of the National Institute
> for Allergy and Infectious Diseases, said in a telephone news conference held by
> Science. ?But I believe the benefits are greater than the risks.?

I think it will turn out in the next years, that he overestimated the benefits ...
----------------------------------------------------------------
> ?done something really, really stupid? and had ?mutated the hell out of H5N1?
someone suggested this was maybe incorrectly translated. Any Dutch-speakers here ?
------------------------------------------------------------------
> up to three in a single human is ?a possibility,? said Derek J. Smith,
> ?Five mutations is pretty difficult, but we don?t yet know how difficult it is

reminds me to Fujian H3 in 2002. Suddenly 11 mutations in HA out of nowhere.
T31C,C121A,G156T,T273G,C511A,A512C,G648A,G1011A,C1044T,T1149C,C1642T
only 3 nonsynonymous, though.
We've seen multiple mutations in prolonged infection in immunodeficient people
-------------------------------------------
has someone read the paper ? 6 ferret sequences at genbank with many common
mutations, I haven't yet found which viruses went to which ferrets, can't be that
all these 14 multi-mutations developed independently ?!?!
Also, they started with a different,special variant of A/IDN/5/2005(H5N1) , why ?
-------------------------------------------------------------------------
?It?s possible that the chances are one in a thousand, and we?ve just gotten lucky,?
Dr. Smith said. ?Or it?s possible that the chance is one in a million and it might not
happen for a long time.?
--------------------------------------------------------------------
> No one knows the probability that H5N1 would reassort with a human flu.
everyone has a subjective probability
-----------------------------------------------------------------------
> ?We really don?t talk about it, because so little is known about the probability of it,? said Dr. Smith.
we should.
---------------------------------------------------------------------------
Fauci ,
> hopes scientists will be able to amass a longer list of potential mutations,
> and even find a common denominator in how they alter H5N1. It might then be
> possible to monitor emerging strains for signs that they are about to cross over into humans.
> That may be the real home run for surveillance,
OK, but we could vaccinate people in countries with more dangerous strains and concentrate on those.
If e.g. it turns out that Indonesia is dangerous, but -Qinghai,Fujian,Vietnam are not,
then we could concentrate on IDN. ~Half of efforts saved
Or we could even increase our efforts to eradicate that one strain.
Or even introduce another H5N1 to that country hoping that it will
replace the more dangerous one
We needn't make the mutations public now, though.
---------------------------------------------------------------------------
Fouchier adds.
> Very little has gone wrong so far, so why would that be different now??
because things have changed. Now we have reverse genetic
---------------------------------------------------------------------
> In 2002, for reasons that are still unclear, the viruses started hopping back into wild birds
ahh, wasn't it in wild birds all the time ? AFAIK it didn't go from poultry to wild birds ((?))
except occasional, e.g. one of the Qinghai strain components afair
----------------------------------------------------------------
2.3.2.1, is of great concern to Webster.
--------------------------------------------------------------------
Palese suspects that the severe cases have simply inhaled high doses of the virus.
But Peiris says that this cannot be the sole explanation.
-------------------------------------------------------
Wendy Barclay,
> not quantify the odds or reassortment. If you force the event, it'll happen, but I haven't seen
> anyone do the experiment in a more natural way,
nature does. We have much data to estimate the likelyhood of double infection
and reassortment.
-------------------------------------------------------------
Farrar:
I think the great worry is that a purely avian virus somehow crosses over to us,
H5N1 tops the list of concerns
-----------------------------------------------------------

gsgs · Jul 25, 2012

Re: Man Made H5N1 - Super Version

can they please figure out now, which mutations reduce
its virulence while keeping it transmissable ?

Man Made H5N1 - Super Version

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