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Man Made H5N1 - Super Version

Re: Man Made H5N1 - Super Version


Mutant-flu researcher backs down on plan to publish without permission


Virologist will apply to Dutch government for export permit before submitting his paper to Science.

Declan Butler

24 April 2012

Ron Fouchier, a researcher at the Erasmus Medical Center in Rotterdam, the Netherlands, whose work on the H5N1 avian flu virus has been embroiled in controversy, told Nature this afternoon that he has now reluctantly agreed to apply for an export permit to submit his work to the journal Science.

Fouchier says that by conceding to the government's request while continuing to contest the need for an export permit, he hopes to have found an acceptable compromise. "By following this parallel track, we hope to publish the manuscript without further delays," he says. But "the government should not consider that this request for a permit sets a precedent for future manuscripts".

Nature
 
Re: Man Made H5N1 - Super Version

Fight Over Dutch H5N1 Paper Enters Endgame

by Martin Enserink on 24 April 2012, 2:41 PM

...The closed meeting was set up to gather additional information and did not result in formal recommendations, says Marianne Donker, head of the Public Health Department at the Ministry of Health, Welfare and Sport, one of eight Dutch ministries involved in aspects of the case.
...
Last night, Donker and Fouchier faced off during a public debate held at the Royal Netherlands Academy of Arts and Sciences here, where Fouchier had trouble hiding his exasperation. "This is pure censorship, as far as I'm concerned," he said. Donker, meanwhile, asked Fouchier "not to let this case escalate." "We would like to continue this process with Ron as we're supposed to," she said.

At the heart of their argument is the government's opinion that Fouchier needs an export license to publish the paper...An annex to the regulation stipulates that the ban includes H5N1 and technologies related to the virus?along with many other human, animal, and plant pathogens. But the regulation makes an exemption for ″basic scientific research," defined as "experimental or theoretical work undertaken principally to acquire new knowledge of the fundamental principles of phenomena or observable facts, not primarily directed towards a specific practical aim or objective."

Fouchier said his study falls in that category, because he's interested in the fundamental question of what makes flu viruses transmissible between mammals...

Donker pointed out that Fouchier himself has always stressed the practical benefits his findings may have -- -from helping prevent pandemics to testing drugs and vaccines against pandemic H5N1 strains. "It's not basic research. It's directly applicable," she said. ...

Full text:
http://news.sciencemag.org/scienceinsider/2012/04/fight-over-dutch-h5n1-paper-enters.html
 
Re: Man Made H5N1 - Super Version

The Netherlands grants export license for mutant flu work

<TIME datetime="2012-04-27T15:38:10+01:00" pubdate=""><ABBR class=value title=2012-04-27>27 Apr 2012 </ABBR>|<ABBR class=value title=15:38:10+0100> 15:38 BST</ABBR></TIME> | Posted by Brian Owens | Category: Biology & Biotechnology, Health and medicine
<!-- before_entry --></HEADER><SECTION>
The Dutch government has agreed to grant an export license to allow Ron Fouchier, a virologist at the Erasmus Medical University in Rotterdam, to publish his work on H5N1 avian influenza in Science.

Fouchier?s paper is one of two reporting the creation of forms of the H5N1 virus capable of spreading between mammals. The other, by Yoshihiro Kawaoka of the University of Wisconsin, Madison, and the University of Tokyo, and his colleagues, has already been submitted to Nature. The risks inherent in the research had led to discussions over whether some details of the work should be censored (see Nature?s news special on the mutant flu saga).

More...
http://blogs.nature.com/news/2012/04/the-netherlands-grants-export-license-for-mutant-flu-work.html
 
Re: Man Made H5N1 - Super Version

Dutch Government OK's Publication of H5N1 Study

byMartin Enserink on <ABBR class=published title="27 April 2012">27 April 2012, 12:24 PM</ABBR>

AMSTERDAM?The Dutch government has given virologist Ron Fouchier of Erasmus Medical Center an export license for his controversial H5N1 transmissibility study, allowing Fouchier to send a revised manuscript of his paper to Science.

The license "is in my inbox," says Fouchier. "Now we can move on."

The decision by Henk Bleker, Minister for Agriculture and Foreign Trade, was announced this afternoon in a press release (Dutch) posted on the ministry's website. It comes four days after a closed meeting in The Hague, where government officials discussed the risks and benefits of the research with an international group of scientists and security experts.

More...
http://news.sciencemag.org/scienceinsider/2012/04/dutch-government-oks-publication.html
 
Re: Man Made H5N1 - Super Version

Racaniello video (lecture) about H5N1, about one hour:

https://s3.amazonaws.com/w3310/026_W3310_12.wmv


since journalists often simplify and exaggerate things to attract attentition
he _concludes_ that H5N1 can't be that bad.

He said it won't transmit from human to human (never heard about the Karo-cluster ?)
Kocyigit,Garbija,Garut,...
and ferrets were not a very good model (so it would be less severe in humans).

And then the ferrets did not even die (well, if they had died it wouldn't have mattered anyway
since they are a bad model)

And so many poultry workers have antibodies, so much fewer than 60% of poultry workers
would die in a H5N1-pandemic.

He compares it with seasonal flu, where so many are not tested.
But, of course, if someone was exposed to H5N1, he/she is likely to get tested.

And most seasonal cases won't get antivirals.

He says H5N1 is lethal in waterfowl, but most strains aren't. So ducks usually can spread it
without severe disease.

most who die from seasonal flu are elderly people and the attributed cause is
cardiovascular, so they aren't tested. But when H5N1 is suspected, they would
likely test.


at the end he says there were no examples where science should be kept secret or such
(I can't easily replay it)
But all the military science, atombombs etc. is secret. No public recipes how to build bombs


"noone can predict how severe a H5N1 pandemic would be"

ahh, again that.

so it needn't be tried, and we can just ignore it

why all the science then ? We must try to estimate the treat and prepare for the most
likely, most severe disasters. And we must pronounce the threat in probability estimates
and damage expectation values to improve communication, threat assessment
and scientific discussion.

said, we are all immune to 1918-flu now
(hmm, why didn't that help in 1977 ? why do we get seasonal waves each year despite immunity ?)
 
Re: Man Made H5N1 - Super Version

Life Sciences at a Crossroads: Respiratory Transmissible H5N1
Michael T. Osterholm1* and Donald A. Henderson2
Published online 19 January 2012; 10.1126/science.1218612


We can?t unring a bell; should a highly transmissible and virulent H5N1 influenza virus that is of human making cause a catastrophic pandemic, whether as the result of intentional or unintentional release, the world will hold life sciences accountable for what it did or did not do to minimize that risk.


[...]
http://www.sciencemag.org/content/early/2012/01/18/science.1218612.full.pdf
 
Re: Man Made H5N1 - Super Version

The Kawaoka paper finally is published

Yoshi.jpg


Laurie Garret on the Kawaoka paper

may 2, 2012

- snip -

WHAT IMPORTANT QUESTIONS WERE ANSWERED?

In the end Kawaoka showed that a contagious form of bird flu could be generated in the lab, or through a reassortment process akin to that which occurs in nature. Offering comfort, he also showed that currently available experiment H5N1 vaccines could block that mutant virus.

But the Kawaoka experiment fails to answer the sorts of questions a politician or policymaker needs to know in order to decide what steps should be taken to prevent a global H5N1 human pandemic.

Firstly, Kawaoka acknowledges in his paper that the particular set of mutations he produced is probably not the only way nature could transform a bird flu into a human one. He lists other potential mutation sites, and other routes to viral evolution. Therefore, it would be dangerous for any policy flowing from this paper to assume it is now possible to narrow humanity’s surveillance or threat assessment to the mutant Kawaoka developed.

Kawaoka points out one especially worrying set of mutations now seen in strains of H5N1 found in the Middle East, especially in now-chaotic Egypt. These H5N1 strains show four mutations that affect sialic binding to mammalian cells and another part of the virus entirely, called PB2. Combined, the mutational drift seen in wild Middle Eastern strains prompt Kawaoka to say, “we cannot predict whether the four mutations in the H5 HA identified here would render a wholly avian H5N1 virus transmissible,” but the changes seen in the Middle Eastern viruses, “may be several steps closer to those capable of efficient transmission in humans and are of concern.”

Similarly, all but the HA bulb section of Kawaoka’s mutants came from the relatively benign HiN1 swine flu that spread worldwide in 2009. Most of humanity was exposed to that virus – including the individuals who got the H5N1 vaccine and donated cells that proved impervious to super mutant infection. Were the cells impervious because the mutated HA bulbs from bird flu triggered an immune response, or because the entire rest of the reassortant viruses were H1N1?

http://www.lauriegarrett.com/index.php/en/blog/3186/#&panel1-1
 
Re: Man Made H5N1 - Super Version

Publishing risky research

Nature 485,5(03 May 2012)doi:10.1038/485005aPublished online 02 May 2012

This week sees the online publication of the paper 'Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets' by the Japanese–US team headed by Yoshihiro Kawaoka at the University of Wisconsin-Madison (M. Imai et al. Nature 10.1038/nature10831 (2012). See also pages 7 and 13, and H.-L. Yen and J. S. M. Peiris Nature http://dx.doi.org/10.1038/nature11192; 2012). Kawaoka's paper was one of two submitted last August, reporting mammalian transmissibility of avian flu as a result of artificial genetic manipulation, the principal scientific interest of which arises from the small number of mutations found to be necessary. The other paper, by a team headed by Ron Fouchier at the Erasmus Medical Centre in Rotterdam, the Netherlands, is expected to appear soon in Science.


More...

http://www.nature.com/nature/journal/v485/n7396/full/485005a.html
 
Re: Man Made H5N1 - Super Version

Lab Security Standards Raise Chances of Mutant-Bird-Flu Catastrophe

By Brandon Keim
May 2, 2012 | 2:08 pm
...
The May 2 publication of Kawaoka’s study in Nature, and the Dutch government’s green-light of Fouchier’s paper, signal that bioterror fears have been allayed. According to the prevailing view, potential benefits outweigh the risks. The conclusion is that for bioterrorists to use the findings would be very hard, while scientists can learn from them immediately.

But many epidemiologists and public health experts say poor handling inside laboratories, rather than bioterror, is the real threat. More than 100 accidents in high-security labs took place between 2003 and 2009, involving everything from flu-infected ferret bites to dropped vials of encephalitis, slips with Ebola needles and lost shipments of bubonic plague. The 1977 “Russian flu” epidemic may have involved a lab escape. Less accidentally, anthrax used in the 2001 attacks almost certainly originated in U.S. military laboratories.

Such events have been downplayed during the current the engineered-flu controversy. Nature‘s “independent review” of risks associated with publishing Kawaoka’s research doesn’t even mention accidental release, and supporters of the controversial experiments say the researchers are careful. But dozens of labs and hundreds if not thousands of researchers may eventually handle the new flu strains and others like them.

“There’s too high a probability of escape if there are 40 or 50 labs working on something,” said Lynn Klotz, a senior science fellow at the Center for Arms Control and Non-Proliferation. In a commentary published in January in Nature, Klotz estimated a 1 percent chance of accidental release per year at each lab working on SARS, the 1918 influenza or the new H5N1 strains. “We are creating a risk that is much greater than that posed by nature. Laboratories need stronger precautions,” wrote Klotz.
....
Of the pathogens currently handled at BSL-4, including hemorrhagic fevers, ebola, tick-borne encephalitis and hantavirus, few are contagious. They primarily threaten people who work directly with them. “If they get out into the environment, most of them are fortunately not very transmissible,” said disease epidemiologist Stephen Morse of Columbia University. With more-contagious pathogens, “you’d want to be very concerned about lab accidents and how they’re being handled in the laboratory.”

“They should use Biosafety Level 4. It’s what BSL-4 was developed for,” said geneticist Steven Salzberg of Johns Hopkins University. “The avian flu people have been saying this disease is incredibly dangerous, kills about 60 percent of the people it infects, and could infect hundreds of millions of people if it goes pandemic — but they don’t say it needs BSL-4? How could they say those two things?”

Full text:
http://www.wired.com/wiredscience/2012/05/engineered-h5n1-security/#more-108455
 
Re: Man Made H5N1 - Super Version

[Source: Nature, full text: (LINK). Abstract, edited.]

Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets


Masaki Imai,<SUP>1 </SUP>Tokiko Watanabe,<SUP>1, 2 </SUP>Masato Hatta,<SUP>1 </SUP>Subash C. Das,<SUP>1 </SUP>Makoto Ozawa,<SUP>1, 3 </SUP>Kyoko Shinya,<SUP>4 </SUP>Gongxun Zhong,<SUP>1 </SUP>Anthony Hanson,<SUP>1 </SUP>Hiroaki Katsura,<SUP>5 </SUP>Shinji Watanabe,<SUP>1, 2 </SUP>Chengjun Li,<SUP>1 </SUP>Eiryo Kawakami,<SUP>2 </SUP>Shinya Yamada,<SUP>5 </SUP>Maki Kiso,<SUP>5 </SUP>Yasuo Suzuki,<SUP>6 </SUP>Eileen A. Maher,<SUP>1 </SUP>Gabriele Neumann<SUP>1 </SUP>& Yoshihiro Kawaoka<SUP>1, 2, 3, 5</SUP>
<SUP></SUP>
<SUP></SUP>
Journal name: Nature - Year published: (2012) - DOI: doi:10.1038/nature10831

Received 18 August 2011 - Accepted 09 March 2012 - Published online 02 May 2012



Highly pathogenic avian H5N1 influenza A viruses occasionally infect humans, but currently do not transmit efficiently among humans. The viral haemagglutinin (HA) protein is a known host-range determinant as it mediates virus binding to host-specific cellular receptors. Here we assess the molecular changes in HA that would allow a virus possessing subtype H5 HA to be transmissible among mammals. We identified a reassortant H5 HA/H1N1 virus?comprising H5 HA (from an H5N1 virus) with four mutations and the remaining seven gene segments from a 2009 pandemic H1N1 virus?that was capable of droplet transmission in a ferret model. The transmissible H5 reassortant virus preferentially recognized human-type receptors, replicated efficiently in ferrets, caused lung lesions and weight loss, but was not highly pathogenic and did not cause mortality. These results indicate that H5 HA can convert to an HA that supports efficient viral transmission in mammals; however, we do not know whether the four mutations in the H5 HA identified here would render a wholly avian H5N1 virus transmissible. The genetic origin of the remaining seven viral gene segments may also critically contribute to transmissibility in mammals. Nevertheless, as H5N1 viruses continue to evolve and infect humans, receptor-binding variants of H5N1 viruses with pandemic potential, including avian?human reassortant viruses as tested here, may emerge. Our findings emphasize the need to prepare for potential pandemics caused by influenza viruses possessing H5 HA, and will help individuals conducting surveillance in regions with circulating H5N1 viruses to recognize key residues that predict the pandemic potential of isolates, which will inform the development, production and distribution of effective countermeasures.
-
-------
 

Attachments

Re: Man Made H5N1 - Super Version

Capua on super virus: 'The research should not be financed'



Publish it or publish it? For months the debate
of experts, scientists, publishers was monopolized by the question whether it was right to make known the research on the super
virus H5N1, created in the laboratory and potentially lethal for the human race, or if, on the other hand should be futile, considering the very real danger of bioterrorism.
"
At the end, it went in the only way in which it could go: the study was published," observes
Ilaria Capua, director of the department of research and development of the Istituto
Zooprofilattico Sperimentale delle Venezie.
But there is not, in the sentence, the tone exultant that you expect from her, the
champion of science open source.
Capua is famous because in 2006, in full overall alarm on avian influenza, I defy the World Health Organization, by refusing to deposit in archives reserved the sequences of H5N1 virus and fought against the interests of pharmaceutical companies to the public accessibility of the data.


..


"
The problem is upstream," says the researcher: "
millions of euros have been spent to support research whose goal was stated at the outset: change the virus of avian flu because acquired the ability to transmit from human to human.
It would have been the case of thinking more for the consequences to the safety of the population. It is clear then that, once you have obtained the results, it is inevitable that they should be published".

...

"
I have my doubts that the mutations induced in viruses for a jump of species will have some usefulness for the development of any vaccines or antiviral drugs," says Capua.

..


Capua disagrees. "We do not know
if those changes in super viruses can really occur spontaneously and even if they are the only ones that would make the pathogen the possibility of transmitting from human to human. It was already known, in any case, that H5N1 has the right gear to become a race car.
It is a real risk, an endemic virus in at least six countries, including Egypt, and it would be a much more urgent, rather than playing with fire, and the need to strengthen surveillance, monitor the natural mutations in order to prepare a quick response, in the event of an alarm".

..


http://daily.wired.it/news/scienza/2012/05/03/virus-h5n1-scienza-open-31451.html?page=1#content
 
Re: Man Made H5N1 - Super Version

A letter from NSABB member Michael Osterholm to Amy P. Patterson, M.D. Associate Director for Science Policy at National Institutes of Health



Summary

In short, the NSABB March meeting should be a very important learning experience for the USG, the journal editors, and life scientists in general as to the need for a much more effective system to address DURC issues. One primary lesson that I believe is critical: The Board must involve disinterested subject matter experts to provide technical advice. I believe that the relative lack of subject matter expert input from those without a direct interest in the Board’s decision be viewed critically by the larger policy and life science communities as the decision is debated over the upcoming days.

As I stated before, I believe our recent experience is just the beginning, not the end of this type of scientific and policy conflict. As a said to Dr. Collins toward the conclusion of the March meeting, I wouldn’t want to be in his shoes sitting before a Congressional hearing trying to explain why the NSABB and likely the USG supported the full Fouchier publication when we heard at the meeting that he has done more work and found one additional mutation that now confers H5N1 transmissibility between mammals without ferret passage. How will we justify one more “incremental finding paper” that now is a pretty complete cookbook when we didn’t recommend redaction for the vast body of his work? If we believe redaction of the current manuscript is problematic in terms of international agreements, I think the next mutation paper will prove to be the straw that breaks the camel’s back. It is unfortunate that the current NSABB action just kicked the can down the road to the next manuscript. I hope these comments are helpful as the NSABB moves forward. As someone who will soon be rotating off the Board after 7 years of service, I believe now, more than ever, of its importance.

Thank you for the honor and opportunity to participate.

Sincerely,
Michael T. Osterholm, PhD, MPH
Director, Center for Infectious Disease Research and Policy

http://news.sciencemag.org/scienceinsider/NSABB%20letter%20final%2041212_3.pdf


Here is the response from the US gov. It is the biggest smack down I have ever seen in print from a government official to anyone. The tone is degrading. And I thought the dungeon was bad.......

http://blogs.nature.com/news/files/2012/05/Response-to-Dr-Osterholm-04-25-2012.pdf
 
Re: Man Made H5N1 - Super Version

I would like to apologize on behalf of FluTrackers for the bash that appeared on this thread yesterday. We have removed that post.

All of us occasionally rant. Sometimes I write a post that contains hundreds of words and some of them are not appropriate for children!... and then (usually) I click on the backspace button instead of the reply button.

This thread is discussing a tough subject and these are very stressful economic times for all of us. We are all volunteers and I am honored to work with each and every one. :applause:

Thank you to everyone who views us. :tiphat:
 
Re: Man Made H5N1 - Super Version

why do you think it's a "smack down" ? I didn't feel so.
I'd rather prefer people saying what they think than
keeping quiet and the opinions and texts coming out
at other places eventually anyway.

What I was missing in the process was a systematic
access of the risks and an attempt to weight them.

As was recommended in the books about the 1976 swine flu decision.

BTW. why are these letters in .pdf ? They are plain text.
Is it to make quoting and discussing them in internet harder ?!


can I have the removed "bash" in email ?


--------------------
googling for the text of the letter ... I cannot (yet) find it online in google-text-cache
----------------------

so it all depends on who (secretly) selects the speakers
who at what occasion and in what context is allowed to present arguments
what arguments are more often "presented"
arguments are not being weighted and listed independently

---------------------------------
 
Re: Man Made H5N1 - Super Version

Kawaoka paper, explained by Ed Young. Excellent reading.

Haemagglutinin_mutant_flu.jpg


Mutant flu paper is finally published, reveals pandemic potential of wild viruses

For several months, people have worried about experiments that artificially produced more transmissible strains of flu. Yes, this research has genuine risks, but the point is that similar experiments are already going on all around us – in the tissues of wild birds, pigs, and other animals. They’re the ones to worry about, and they don’t require regulatory approval. The lab experiments could help us to understand how the natural ones are going to play out.

LINK
 
Re: Man Made H5N1 - Super Version

Science journal could give recipe for deadly avian flu virus

Posted: 5:36 AM
Libby Lewis, CNN Radio

Excerpt:

Well, now what?

These experiments lay a path to a whole new area of genetic engineering in flu research.

The government and supporters of the controversial experiments say more research will lead to a better understanding of the genetic mutations that could lead to a viral pandemic.

But other scientists say this is the wrong road to take.

Sir Richard Roberts, a molecular biologist who's won the Nobel Prize, spoke out at a recent National Academies workshop on the bird flu experiments.

"Someone is trying to make the most dangerous virus we can think of," Roberts said. "I don't understand how one can justify that, unless there is no other way of getting the data that you're interested in.

"And the way you get data is surveillance, and to see what is going on in nature, and to respond to it accordingly. And you go out of your way to find a universal vaccine. I would much sooner see money spent on that than on creating the most dangerous virus imaginable. I find it indefensible."

Roger Brent, a biologist at the Fred Hutchinson Cancer Research Center in Seattle, said he believes these experiments create more danger than benefit.

Brent told CNN that in order to be valuable -- that is, to reliably show the ways that bird flu could evolve to infect humans -- these experiments would require more experiments that could generate recipes for more, and different, man-made viruses -- all of them dangerous.

"Scientists must ask: Do we really want to do these experiments?" Brent said. "If we're generating knowledge that we feel dodgy about, do we really want to generate 20 or 100 additional (engineered viruses) that create something that most people would believe to be bad?"
...
Read more: http://www.abc2news.com/dpp/news/he...cipe-for-deadly-avian-flu-virus#ixzz1ur3X9Z4p
 
Re: Man Made H5N1 - Super Version

Brent told CNN that in order to be valuable -- that is, to reliably show the ways that bird flu could evolve to infect humans -- these experiments would require more experiments that could generate recipes for more, and different, man-made viruses -- all of them dangerous.

This is absolutely true, and misses the point completely. The viruses are dangerous if they escape the lab but we do not really need the viruses. What we need is the sequences and these are only dangerous if you believe there are mad scientists out to make bio-weapons. If the later exist they probably are not in a cave but in a military facility of a G8 country and will not be thumbing Nature looking for ideas. As soon as the viruses are sequenced they can be destroyed. The useful information is knowing if there are many solutions to this problem, or only a few. The later points to target vaccine candidates and increases the value of spending on rapid sequencing, and publishing, of currently circulating clades so we know which need the closest watching.
In short it is worth rerunning the experiment many times - but not keeping the virus - so we know what we are looking for/at in the wild type sequence data.
 
Re: Man Made H5N1 - Super Version

if it were so easy to destroy the viruses then H5N1 were long be gone.

And nowadays the viruses can be re-created from the sequences.
And it's not hard to predict that many will try that (secretly).

And this is just the beginning, starting from natural viruses.
Later we may be able to "design" viruses or bacteria
or whatever directly.

What made SARS,EHEC,MRSA,... so bad ?
They'll figure it out and combine it with features
of other bugs to create more "successful" ones.
 
Re: Man Made H5N1 - Super Version

if it were so easy to destroy the viruses then H5N1 were long be gone.
I am talking about destroying the newly lab created viruses which are easy to kill. Lab release risk is very low if the virus is not stored once created.

And nowadays the viruses can be re-created from the sequences.
And it's not hard to predict that many will try that (secretly).
And this is just the beginning, starting from natural viruses.
Later we may be able to "design" viruses or bacteria
or whatever directly.

What made SARS,EHEC,MRSA,... so bad ?
They'll figure it out and combine it with features
of other bugs to create more "successful" ones.
Not that easy unless you have a well equipped lab and no oversight, which is where the debate/regulation needs to be focused. If a developed Nation State wants to develop Bio weapons there is little we can do about it apart from show them they are untargetable and therefore a useless weapon.
 
Re: Man Made H5N1 - Super Version

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 ...
 
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