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PostPosted: Thu Feb 16, 2012 6:55 pm 
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niman wrote:
Flu Experts—And One Ethicist—Debate Controversial H5N1 Papers

There's one representative of the Vietnamese lab with which Kawaoka collaborates, and from which he reportedly received the flu sample used in his study.
http://news.sciencemag.org/scienceinsid ... tml?ref=hp

J Gen Virol. 2010 Oct;91(Pt 10):2485-90. Epub 2010 Jun 30.

Pathogenicity of highly pathogenic avian H5N1 influenza A viruses isolated from humans between 2003 and 2008 in northern Vietnam.

Le QM, Ito M, Muramoto Y, Hoang PV, Vuong CD, Sakai-Tagawa Y, Kiso M, Ozawa M, Takano R, Kawaoka Y.


Source

National Institute of Hygiene and Epidemiology (NIHE), Hanoi, Vietnam.


Abstract

Vietnam is one of the countries most affected by highly pathogenic H5N1 influenza A viruses. To evaluate the potential pathogenicity in mammals of H5N1 viruses isolated from humans in Vietnam, we determined the sequences of all eight genes of 22 human isolates collected between 2003 and 2008 and compared their virulence in mice. The isolates were classified into clade 1 and clade 2.3.4 and differed in pathogenicity for mice. Whilst lysine at position 627 of PB2 (PB2-627K) is a critical virulence determinant for clade 2.3.4 viruses, asparagine at position 701 of PB2 and other unknown virulence determinants appear to be involved in the high pathogenicity of clade 1 viruses, warranting further studies to determine the factors responsible for the high virulence of H5N1 viruses in mammals.
http://www.ncbi.nlm.nih.gov/pubmed/20592108

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PostPosted: Thu Feb 16, 2012 6:57 pm 
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niman wrote:
niman wrote:
Flu Experts—And One Ethicist—Debate Controversial H5N1 Papers

There's one representative of the Vietnamese lab with which Kawaoka collaborates, and from which he reportedly received the flu sample used in his study.
http://news.sciencemag.org/scienceinsid ... tml?ref=hp

J Gen Virol. 2010 Oct;91(Pt 10):2485-90. Epub 2010 Jun 30.

Pathogenicity of highly pathogenic avian H5N1 influenza A viruses isolated from humans between 2003 and 2008 in northern Vietnam.

Le QM, Ito M, Muramoto Y, Hoang PV, Vuong CD, Sakai-Tagawa Y, Kiso M, Ozawa M, Takano R, Kawaoka Y.


Source

National Institute of Hygiene and Epidemiology (NIHE), Hanoi, Vietnam.


Abstract

Vietnam is one of the countries most affected by highly pathogenic H5N1 influenza A viruses. To evaluate the potential pathogenicity in mammals of H5N1 viruses isolated from humans in Vietnam, we determined the sequences of all eight genes of 22 human isolates collected between 2003 and 2008 and compared their virulence in mice. The isolates were classified into clade 1 and clade 2.3.4 and differed in pathogenicity for mice. Whilst lysine at position 627 of PB2 (PB2-627K) is a critical virulence determinant for clade 2.3.4 viruses, asparagine at position 701 of PB2 and other unknown virulence determinants appear to be involved in the high pathogenicity of clade 1 viruses, warranting further studies to determine the factors responsible for the high virulence of H5N1 viruses in mammals.
http://www.ncbi.nlm.nih.gov/pubmed/20592108

The above comments essentially confirm that the H5 used in the Kawaoka reassortant is clade 2.3.4.2 that was used in prior publications.

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PostPosted: Thu Feb 16, 2012 7:05 pm 
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niman wrote:
niman wrote:
niman wrote:
Flu Experts—And One Ethicist—Debate Controversial H5N1 Papers

There's one representative of the Vietnamese lab with which Kawaoka collaborates, and from which he reportedly received the flu sample used in his study.
http://news.sciencemag.org/scienceinsid ... tml?ref=hp

J Gen Virol. 2010 Oct;91(Pt 10):2485-90. Epub 2010 Jun 30.

Pathogenicity of highly pathogenic avian H5N1 influenza A viruses isolated from humans between 2003 and 2008 in northern Vietnam.

Le QM, Ito M, Muramoto Y, Hoang PV, Vuong CD, Sakai-Tagawa Y, Kiso M, Ozawa M, Takano R, Kawaoka Y.


Source

National Institute of Hygiene and Epidemiology (NIHE), Hanoi, Vietnam.


Abstract

Vietnam is one of the countries most affected by highly pathogenic H5N1 influenza A viruses. To evaluate the potential pathogenicity in mammals of H5N1 viruses isolated from humans in Vietnam, we determined the sequences of all eight genes of 22 human isolates collected between 2003 and 2008 and compared their virulence in mice. The isolates were classified into clade 1 and clade 2.3.4 and differed in pathogenicity for mice. Whilst lysine at position 627 of PB2 (PB2-627K) is a critical virulence determinant for clade 2.3.4 viruses, asparagine at position 701 of PB2 and other unknown virulence determinants appear to be involved in the high pathogenicity of clade 1 viruses, warranting further studies to determine the factors responsible for the high virulence of H5N1 viruses in mammals.
http://www.ncbi.nlm.nih.gov/pubmed/20592108

The above comments essentially confirm that the H5 used in the Kawaoka reassortant is clade 2.3.4.2 that was used in prior publications.

Fatal 2012 Guizhou H5 Similar to Kawaoka Reassortant
Recombinomics Commentary 18:15
February 11, 2012

...........Moreover, the paper at Nature involves transmission of an H5 reassortant which was not lethal, and a prior publication on the creation of such a reassortant using a 2009 clade 2.3.4.2 isolate from Hanoi (A/Vietnam/HN31604/2009) on an H1N1pdm09 genetic background (A/California/04/2009) provides methods. Thus, the detail for the creation of the reassortants has already been published, and the requirement for additional changes in this natural isolate is far from clear.

Studies by others have indicated the H1N1pdm09 M gene was critical for the jump of H1N1pdm09 from swine to humans, and all 12 2011 H3N2v human cases have an H1N1pdm09 M gene. Moreover, all 2010 H3N2v human cases have a PB1 change E618D, which is in all H1N1pdm09 isolates implicating this change in human transmission also. The reassortant described in the Nature paper would have both of these changes, which may explain the human transmission.

Although the sequence of A/Vietnam/HN31604/2009 has not been made public, a WHO phylogenetic tree includes this isolate, as well as closely related human and poultry public sequences from 2008 ad 2009 isolates. The most closely related human sequence is A/Vietnam/HN31432M/2008, which was sequenced by the Kawaoka lab and described in a prior publication....................
http://www.recombinomics.com/News/02111 ... waoka.html

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PostPosted: Thu Feb 16, 2012 7:07 pm 
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LOCUS HM114617 1704 bp cRNA linear VRL 20-SEP-2010
DEFINITION Influenza A virus (A/Vietnam/HN31432M/2008(H5N1)) segment 4
hemagglutinin (HA) gene, complete cds.
ACCESSION HM114617
VERSION HM114617.1 GI:295189595
KEYWORDS .
SOURCE Influenza A virus (A/Vietnam/HN31432M/2008(H5N1))
ORGANISM Influenza A virus (A/Vietnam/HN31432M/2008(H5N1))
Viruses; ssRNA negative-strand viruses; Orthomyxoviridae;
Influenzavirus A.
REFERENCE 1 (bases 1 to 1704)
AUTHORS Le,Q.M., Ito,M., Muramoto,Y., Hoang,P.V., Vuong,C.D.,
Sakai-Tagawa,Y., Kiso,M., Ozawa,M., Takano,R. and Kawaoka,Y.
TITLE Pathogenicity of highly pathogenic avian H5N1 influenza A viruses
isolated from humans between 2003 and 2008 in northern Vietnam
JOURNAL J. Gen. Virol. 91 (PT 10), 2485-2490 (2010)
PUBMED 20592108
REFERENCE 2 (bases 1 to 1704)
AUTHORS Takano,R.
TITLE Direct Submission
JOURNAL Submitted (14-APR-2010) Division of Virology, Department of
Microbiology and Immunology, Institute of Medical Science,
University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
COMMENT GenBank Accession Numbers HM114614-HM114621 represent sequences
from the 8 segments of Influenza A virus
(A/Vietnam/HN31432M/2008(H5N1)).
FEATURES Location/Qualifiers
source 1..1704
/organism="Influenza A virus
(A/Vietnam/HN31432M/2008(H5N1))"
/mol_type="viral cRNA"
/strain="A/Vietnam/HN31432M/2008"
/serotype="H5N1"
/isolation_source="throat swab"
/host="Homo sapiens; age: 23; gender: female"
/db_xref="taxon:755285"
/segment="4"
/country="Viet Nam"
/collection_date="21-Feb-2008"
/note="passage history: MDCK2"
gene 1..1704
/gene="HA"
CDS 1..1704
/gene="HA"
/codon_start=1
/product="hemagglutinin"
/protein_id="ADF83650.1"
/db_xref="GI:295189596"

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PostPosted: Thu Feb 16, 2012 7:11 pm 
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Five easy mutations to make bird flu a lethal pandemic
26 September 2011 by Debora MacKenzie
Magazine issue 2831. Subscribe and save

Editorial: "The risk of an influenza pandemic is fact, not fiction"

H5N1 bird flu can kill humans, but has not gone pandemic because it cannot spread easily among us. That might change: five mutations in just two genes have allowed the virus to spread between mammals in the lab. What's more, the virus is just as lethal despite the mutations.
http://www.newscientist.com/article/mg2 ... demic.html

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PostPosted: Thu Feb 16, 2012 7:21 pm 
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Dr. Henry Niman PhD
Flu Season

Interview tonight at 10 PM EST
H3N2v and NSABB censorship will be discussed.

http://www.renseradio.com/listenlive.htm

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PostPosted: Thu Feb 16, 2012 7:30 pm 
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Avian flu controversy comes to roost at WHO

16 Feb 2012 | 18:46 GMT | Posted by Declan Butler | Category: Biology & Biotechnology, Health and medicine, Swine flu


Almost two dozen experts kicked off a two-day international meeting this morning at the World Health Organization (WHO) in Geneva, in a bid to find ways to move forward in the controversy over two studies that have created strains of the H5N1 avian flu virus that are transmissible in ferrets. The meeting may reach some consensus on a few immediate issues, such as what parts of the studies should be published, and who might qualify for access to the full papers on a ‘need-to-know’ basis.

But the narrowness of the expertise of those taking part means that the meeting will not even begin to address the far bigger issue of whether such research should be allowed at all in the future, and if so, how it should safely proceed. Key to that question is an assessment of the relative public-health benefits, compared to the risks that a proliferation of such research in labs worldwide would increase the risk of an accidental or intentional release of the lab strains. Ferrets are a good proxy for how flu behaves in other mammals, including humans, so any release could itself spark a H5N1 pandemic, with potentially catastrophic consequences given the virus’s likely high mortality rate (see ‘Death-rate row blurs mutant flu debate‘).

The list of experts attending the meeting — which the WHO made public this morning — shows that the panel is overwhelmingly stacked with academic flu researchers, almost all of whom are strongly in favour of such research, and many of whom would like to see it proceed unfettered. By contrast, there are almost no public-health officials of international stature attending, nor experts in risk assessment, biosafety or biosecurity.

The WHO has explained, however, that the participants were limited to “people who have direct involvement or knowledge about these two studies, their review or oversight, or potential dissemination of results”, and that this meeting has the very limited remit of clarifying “key facts about the two research studies and the most urgent related issues”.



The WHO sees this meeting as the start of a much longer, and more inclusive, broadening of the discussion over the H5N1 studies to a more international level, as anticipated in my Q&A on this with Anthony Fauci, the director of the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, who is also taking part in the WHO meeting (see ‘Open the debate on flu research‘).

To provide some breathing space for discussion — and perhaps avert a ban on such research — researchers on 20 January also declared a voluntary pause in research on making avian flu viruses more transmissible (see ‘Scientists call for 60-day suspension of mutant flu research‘.) But the process of international discussion and arbitration that may ultimately create a framework for inter­national oversight of such research will undoubtedly take far longer than this, so that pause will probably need to be extended. Future meetings will also need to enlarge the debate to include many other interested parties, far beyond the narrow confines of flu researchers.

The two researchers at the centre of the controversy are attending the meeting: Ron Fouchier, a flu virologist at Erasmus Medical Center in Rotterdam, the Netherlands, and Yoshihiro Kawaoka of the University of Wisconsin–Madison. In a study submitted to Science, a team led by Fouchier found that just five mutations allowed avian H5N1 to spread easily among ferrets. In a study submitted to Nature, Kawoaka and his colleagues also succeeded in making the virus transmissible in ferrets, by creating a virus that has the H5 haemagglutinin (HA) surface protein from the H5N1 virus, with all the remaining genes coming from the 2009 pandemic H1N1 virus (see ‘Pandemic 2009 H1N1 virus gives wings to avian flu‘).

Also attending the meeting are Philip Campbell, editor-in-chief of Nature, and Barbara Jasny, an editor at Science, as well as Paul Keim, director of pathogen genomics at Northern Arizona University in Flagstaff, and chair of the US National Science Advisory Board for Biosecurity (NSABB). It was on the advice of the NSABB that the US government in December asked Science and Nature to publish only the broad conclusions of the two studies, and not to reveal the scientific details, so as to limit the risk of uncontrolled proliferation of such research that might lead to accidental or intentional release of similar mutant viruses. (For NSABB’s reasoning see ‘Policy: Adaptations of avian flu virus are a cause for concern‘ and for Keim’s own thoughtful perspective see ‘Q&A: Reasons for proposed redaction of flu paper‘.)


Nature and Science have agreed to the redaction requested by NSABB, provided that a suitable mechanism is established to disseminate the data to flu researchers and public-health officials on a need-to-know basis. Although the WHO has not yet released a meeting agenda, discussion of any mechanism is almost certainly going to be a high priority. Whether any consensus will be reached is another matter.

What seems clear is that the data need to be made available to the H5N1 flu virus surveillance community, in some form, so that they can monitor whether such combinations of mutations appear in the wild. This could, for example, result in intensifying the culling of poultry and other control measures. Genetic surveillance for H5N1 is currently extremely poor: very few viral isolates are collected, and even fewer are sequenced, often only after months or years, with just 160 H5N1 isolates being submitted to GenBank last year (see ‘Caution urged for mutant flu work‘). But we should be increasing the surveillance of H5N1, and other animal and poultry flu viruses with these mutations, to assess their pandemic potential, even if such knowledge is of little practical benefit at present given the lack of surveillance, in particular in pigs. Better funding of real-time surveillance is also needed in affected countries.

But although this data could be useful for surveillance, we should not lose sight of the harsh reality that the next pandemic virus — if it occurs in the next few years — will not be detected in advance, but is likely to be, just as during the 2009 pandemic, present in many countries before we even detect the first case. And even were we to get an early warning, it would mean nothing to the 80% of the planet who will not have access to vaccines.


How to get the data from the two papers disseminated out to those doing the surveillance might be a task that the WHO and the UN Food and Agriculture Organization are well placed to accomplish. Much of the H5N1 surveillance effort is done in collaboration with their networks, such as the WHO’s global influenza surveillance and response system (GISRS) laboratories.

Complicating matters overall is the fact that sharing of avian flu isolates, genetic sequences and other data is a politically charged issue. In 2005, Indonesia refused to continuing to supply these to the WHO flu lab networks, on the very good grounds that it saw nothing in return, in terms of intellectual property, access to vaccines and drugs and technology transfer. It was only after six years of negotiations that the WHO succeeded last year in getting agreement on a ‘Pandemic influenza preparedness Framework‘, which provides for countries supplying viruses to have material benefits in return. It does not want the current controversy over sharing data to jeopardize that hard-won system — it’s no surprise, therefore, that there are three representatives of Indonesia attending the WHO meeting, and that this issue is likely to be a major element in the discussions.

But ultimately answering the question of who should have access to the data from these papers seems inextricably linked to the far bigger question of how such research should be regulated in the future to avoid unnecessary proliferation of such strains, and of what will happen to data from any future studies. Moreover, the Fouchier and Kawaoka papers have already been seen by many researchers, and many labs that are competent in this area would be capable of replicating the work even without having the data from the two papers. So the far more important question is how to develop a framework for regulating this research.

The short-term public benefits of such flu research appear slim (see ‘Facing up to flu‘), whereas the risks of an accidental lab release are not negligible, and the consequences could be a public-health disaster. There is therefore no need to rush headlong into more research to create mammalian-transmissible avian flu virus, and the international community must take the time needed to figure out whether and how such research can be allowed to proceed safely, and how best its proliferation can be checked. It is important that, in considering how this research goes forward, we bear in mind our current inability to deal with any H5N1 pandemic. As such, any proliferation of such research would, as veteran flu researcher Robert Webster at St. Jude Children’s Research Hospital, Memphis, Tennessee, puts it: create an “unacceptably high level of risk to humanity should mammalian-transmissible H5N1 virus be accidentally or intentionally released”.


This week’s meeting at the WHO will not even begin to address such wider issues. But one can hope that it will provide for a serious and thoughtful analysis of the studies and the issues they raise, which will help inform wider debate. As Fauci points out: “We need to get people in the same room discussing the pros and cons rather than having duelling soundbites. That doesn’t help anybody.”

http://blogs.nature.com/news/2012/02/av ... t-who.html

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PostPosted: Thu Feb 16, 2012 11:01 pm 
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niman wrote:
Dr. Henry Niman PhD
Flu Season

Interview tonight at 10 PM EST
H3N2v and NSABB censorship will be discussed.

http://www.renseradio.com/listenlive.htm

Interview starts in a few minutes. Will also cover today's meeting in Geneva.

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PostPosted: Fri Feb 17, 2012 12:05 am 
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The editor of a leading scientific journal has said he is prepared to publish full details of controversial research into the bird flu virus, unless progress is made on how to circulate details of the findings to scientists.

The World Health Organization is expected to announce later its view of how to circulate the research safely to scientists studying the H5N1 virus in humans.

Dr Bruce Alberts, editor of Science, was asked by US security advisors not to publish parts of the work due to concerns it could help terrorists to develop a biological weapon.

But he says it was important to get the research out quickly to scientists and health officials monitoring the virus.

Speaking at the American Association for the Advancement of Science meeting in Vancouver, he said: "Our position is that, in the absence of any mechanism to get the information to those scientists and health officials who need to know and need to protect their populations and to design new treatments and vaccines, our default position is that we have to publish in compete form."

'Academic freedom'

The controversy is centered on two research papers - one of which was submitted to Science, the other to another leading journal, Nature, last year.

They showed that the H5N1 virus could relatively easily mutate into a form that could spread rapidly among the human population.

The studies prompted the US National Security Advisory Board for Biotechnology (NSABB) to ask both journals last November to redact some sensitive parts of the research, which it believed could be used by terrorists to develop such a virus.

The request caused outcry among some scientists who believed that it was an infringement of academic freedom.

Some pointed out that the scientists had given presentations about their work at conferences and the details were already widely circulated, so redaction would have little purpose.

The scientists who carried out the research, and the journals concerned, have been considering the request and listening to suggestions as to how the research results could be redacted in the scientific journals, but distributed to bone fide researchers who urgently need the information.

The information is vital to develop a vaccine to any human form of bird flu, and it would enable surveillance teams to see if the bird flu virus was mutating into a form that could be transmissible to humans.

But such efforts have been put on hold for four months as governments, scientists and the journals decide what to do.

'Wake-up call'

The latest stage is a meeting this week held at the WHO's headquarters in Geneva.

Bruce Alberts says that the research shows that it is very easy for lethal bird flu to develop and it should act as a "real wake up call to the world".

He added: "This is likely to happen at some point in the wild because these viruses are mutating very actively in the wild."

The NSABB comprises a group of US scientists and government security officials.

Its role is to identify research that might pose a security threat and recommend redaction where appropriate.

It is the first time that it has done so since it was created in 2005.

Dr Alberts supports the NSABB mechanism because it enables government security advisors to be informed by the scientists who sit on the board.

He suggests that for him and the editor of Nature, Dr Phil Campbell, to simply ignore the recommendations of the NSABB would undermine a system which could be considerably worse.

"Both Science magazine and Nature would both of like to support the mechanism because it's the best mechanism we're ever going to get to get," he says.

The sticking point though is that the scientific community and governments can not agree the process by which an applicant for redacted material is deemed to be worthy of receiving it and who should make that judgement.

Initially the US government had suggested that US scientists, with the input of some foreign researchers, should administer the distribution process.

But this week at the WHO, international health bodies have said they should be more intimately involved and it would not work to run it through the US government.

"It is our hope that that meeting will lead to an international resolution as to how to get the information selectively to those that need to know and that would allow us to adhere to the NSABB recommendation," says Dr Alberts.

http://www.bbc.co.uk/news/17066147

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PostPosted: Fri Feb 17, 2012 12:22 am 
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niman wrote:
Bruce Alberts says that the research shows that it is very easy for lethal bird flu to develop and it should act as a "real wake up call to the world".

He added: "This is likely to happen at some point in the wild because these viruses are mutating very actively in the wild."

http://www.bbc.co.uk/news/17066147

Yes, the Science paper (5 changes in 2 two genes) is definitely a wake-up call and the papers should be published in full immediately.

The NSABB lacks the expertise to understand that any serious bioweapons program can now generate a transmissible H5N1 without the papers. The censorship only limits scientists who are not actively engaged in transmission studies.

The NATURAL H5N1 is clearly VERY close to transmitting.

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