During a telephone news conference on Wednesday, Ron Fouchier... said the scientists were lifting the moratorium without waiting for guidelines from the United States.
“How long do you want us to wait?” Dr. Fouchier asked. “If this was the Netherlands, would the U.S. wait? Should all countries really wait for the U.S., and why?”
...
He said other scientists could be given samples of the mutant virus for research only with the permission of Erasmus Medical Center, the National Institutes of Health and virus experts at the Mount Sinai Medical Center in Manhattan.
Nicole M. Bouvier Division of Infectious Diseases and Department of
Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029,USA. nicole.bouvier@mssm.edu
Ian H. Brown Virology Department, Animal Health and Veterinary
Laboratories Agency, Addlestone,UK. ian.brown@ahvla.gsi.gov.uk
Ilaria Capua Istituto Zooprofilattico Sperimentale delle Venezie, Padova, Italy. icapua@izsvenezie.it
Hualan Chen Harbin Veterinary Research Institute, Harbin,China. hlchen1@yahoo.com
Richard W. Compans Influenza Pathogenesis and Immunology
Research Center, Emory University School of Medicine, Atlanta, GA30322,USA. rcompan@emory.edu
Robert B. Couch Department of Molecular Virology & Microbiology,
Baylor College of Medicine, Houston,TX 77030, USA. rcouch@bcm.edu
Nancy J. Cox Influenza Division, Centers for Disease Control and
Prevention, Atlanta,GA30333, USA. njc1@cdc.gov
Peter C. Doherty Dept of Immunology, St Jude Children’s Research
Hospital, Memphis,TN 38105, USA. peter.doherty@stjude.org
Ruben O. Donis Molecular Virology and Vaccines Branch, Influenza
Division, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. rvd6@cdc.gov
Heinz Feldmann Laboratory of Virology, National Institute of Allergy
and Infectious Diseases, National Institutes of Health, Rocky Mountain
Laboratories, Hamilton, MT 59840, USA. feldmannh@niaid.nih.gov
Ron A. M. Fouchier Dept Virology, Erasmus MC, Rotterdam, the Netherlands. r.fouchier@erasmusmc.nl
Adolfo García-Sastre Department of Microbiology, Icahn School of
Medicine at Mount Sinai, New York, NY 10029, USA. adolfo.garcia-sastre@mssm.edu
Yi Guan State Key Laboratory of Emerging Infectious Diseases, School
of Public Health, The University of Hong Kong, Hong Kong. yguan@hku.hk
Jacqueline M. Katz Immunology and Pathogenesis Branch, Influenza
Division, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. jmk9@cdc.gov
Yoshihiro Kawaoka* Department of Pathobiological Sciences,
School of Veterinary Medicine, University of Wisconsin–Madison, Madison, WI 53711, USA.
*Corresponding author: kawaokay@svm.vetmed.wisc.edu
Oleg. I. Kiselev D. I. Ivanovsky Institute of Virology, Ministry of Public
Health, Moscow, Russia. office@influenza.spb.ru
Albert D. M. E. Osterhaus Department of Virology, Erasmus MC, Rotterdam, the Netherlands a.osterhaus@erasmusmc.nl
Peter Palese Department of Microbiology, Icahn School of Medicine at
Mount Sinai, New York, NY 10029, USA. peter.palese@mssm.edu
J. S. Malik Peiris Centre of Influenza Research, School of Public Health,
The University of Hong Kong, Hong Kong. malik@hkucc.hku.hk
Daniel R. Perez Department of Veterinary Medicine, University of
Maryland, College Park, MD 20742, USA. dperez1@umd.edu
Juergen A. Richt College of Veterinary Medicine, Kansas State
University, Kansas, KS 66506, USA. jricht@vet.k-state.edu
Stacey Schultz-Cherry Department of Infectious Disease, St. Jude
Children’s Research Hospital, Memphis, TN 38105, USA. stacey.schultz-cherry@stjude.org
John Steel Department of Microbiology and Immunology, Emory
University, School of Medicine, Atlanta, GA 30322, USA. john.steel@emory.edu
Kanta Subbarao Emerging Respiratory Viruses Section, Laboratory
of Infectious Diseases, National Institute of Allergy and Infectious
Diseases, National Institutes of Health, Bethesda, MD 20892, USA. ksubbarao@niaid.nih.gov
David E. Swayne Southeast Poultry Research Laboratory, USDA/
Agricultural Research Service, Athens, GA30605, USA. david.swayne@ars.usda.gov
Toru Takimoto Department of Microbiology & Immunology,
University of Rochester Medical Center, Rochester, NY 14642, USA. toru_takimoto@urmc.rochester.edu
Masato Tashiro Influenza Virus Research Center, National Institute of
Infectious Diseases, Tokyo, 208-0011, Japan. mtashiro@nih.go.jp
Jeffery K. Taubenberger Viral Pathogenesis and Evolution Section,
Laboratory of Infectious Diseases, National Institute of Allergy
and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. taubenbergerj@niaid.nih.gov
Paul G. Thomas Department of Immunology, St. Jude Children’s
Research Hospital, Memphis, TN 38105, USA. paul.thomas@stjude.org
Ralph A. Tripp Dept Infectious Diseases, College of Veterinary
Medicine, University of Georgia, Athens, GA 30602, USA. ratripp@uga.edu
Terrence M. Tumpey Influenza Division, Centers for Disease Control
and Prevention, Atlanta, GA 30333, USA. tft9@cdc.gov
Richard J. Webby Department of Infectious Disease, St. Jude Children’s
Research Hospital, Memphis, TN 38105, USA. richard.webby@stjude.org
Robert G. Webster Division of Virology, Department of Infectious
Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA. robert.webster@stjude.org
__________________ "Safety and security don't just happen, they are the result of collective consensus and public investment. We owe our children, the most vulnerable citizens in our society, a life free of violence and fear." -Nelson Mandela
Statement of Drs. Collins and Fauci concerning intention to lift moratorium
Statement of Drs. Collins and Fauci concerning intention to lift moratorium
January 25, 2013
One year ago, scientists in the H5N1 influenza research community announced that they would voluntarily suspend certain “gain-of-function” experiments involving highly pathogenic avian influenza (HPAI) H5N1 viruses pending a broad international dialogue about the future direction of this research.
That dialogue — which has included experts in the life sciences, public health, biosecurity, biosafety, law, and science policy communities — has been highly productive, with numerous meetings and publications helping to clarify the most critical issues associated with this type of research.
Countries where this research is (or might be) conducted have had the opportunity to review their policies and parameters for funding, conducting, and communicating about this research. In this context, the H5N1 influenza research community has announced their intention and support for resuming their research in those countries with final guidelines in place.
The Department of Health and Human Services (HHS) has worked in a transparent and collaborative fashion to develop a framework for reviewing funding decisions regarding research that might increase mammalian transmission of HPAI H5N1 viruses by respiratory droplets. We anticipate that the final framework for HHS funding decisions regarding HPAI H5N1 gain-of-function experiments will be complete in the next several weeks. In the meantime, U.S.-funded researchers (both those working in the United States, including those in government laboratories, as well as those working overseas) have agreed not to resume these types of HPAI H5N1 gain-of-function experiments pending finalization of the HHS Framework.
Understanding how influenza viruses become human pandemic threats is vitally important to global health preparedness. We applaud the international H5N1 influenza research community for the spirit in which they instituted this extended “pause” on their work, which has provided time for thoughtful consideration of its implications.
Francis S. Collins, M.D., Ph.D.
Director, National Institutes of Health
...
After a year of extensive discussions about how such research should be conducted, the moratorium was finally lifted last week. Professor Wendy Barclay, from the Department of Medicine at Imperial College London, is a signatory on the letter in Nature announcing the resumption of this research. Here she explains why the work was suspended and why it will now continue.
"The moratorium on research with H5N1 highly pathogenic influenza viruses leading to increased transmissibility in mammals was put in place last year by an international collection of influenza virologists. The stimulus for this voluntary pause in research in one specific area was the revelation that two labs had actually generated recombinant viruses with increased transmissibility. Several other labs along with these two had been working in this area for some years, publishing and presenting their work openly, but only when efforts yielded up a positive result did anyone really notice. Then there was a knee jerk response from certain quarters previously naive of this approach, expressing horror that scientists were brewing up deadly diseases. It became clear that the public needed reassurance and justification about these experiments.
... Now the scientists suggest it is time to move on, go back to the very safe bench they were working at, taking on board the comments of the past year which will undoubtedly have focused their minds on the key questions they hope now to address. H5N1 has not stood still during this year, but thankfully it has also not made any significant evolutionary jumps either. Evidence suggests the virus continues to drift antigenically especially in places like Egypt, but also that clinical management of patients caught early in the infection is improving their chances of survival. The information learned from the two publications that finally made it into Nature and Science last year has been processed by the influenza community and has been hugely informative, not only for understanding the risks from H5N1 but also for illuminating how other subtypes of flu might species jump and even for assessing the zoonotic risks from other pathogens. The lifting of the moratorium will undoubtedly lead to more scientific revelations that will have direct consequence for human and animal health."
__________________ "Safety and security don't just happen, they are the result of collective consensus and public investment. We owe our children, the most vulnerable citizens in our society, a life free of violence and fear." -Nelson Mandela
strange how they formulate it.
What I recall is, that NSABB first discouraged publishing, then recommended
publishing of a modified paper where the mutations were left out and only
given to a few selected labs, but then
realized that this was not practicable for legal (US) reasons because other
scientists could require the information through a freedom-of-information-act
request.,
Is it too much required, that USA change their laws in this respect ?
How do they handle military secrets or "cables" or such where they are
so sensitive ?
I do not see how publishing the mutations might help those who might become infected
with H5N1 in the current phase. And why even consider this, when the possible H5N1 pandemic affects
billions vs. a few hundred infected each year.
Should we later find an application, that really makes use of there mutations
and that requires publication thereof and international brought cooperation,
then the mutations can still be published
GS
There is a bit more to it, legally, than just the US domestic law.
The WHO concluded a legal framework involving the nation states, pharmaceutical companies and other interested parties after the sequence release stand-off between the poor countries lead by Indonesia and the richer countries - hosting the vaccine producers/antiviral manufactures - lead by the US.
The crux of the issue was that Indonesia, and others, were supplying biological samples and sequences free of charge to WHO - who then gave them to others who sequenced them and used them to develop drugs and vaccines - but Indonesia et al got nothing out of it and could not afford the prices these entities charged for the resultant data and products.
The new system requires Nation States to sign up to participate and if they do so they must provide specimens and sequence data which the participating states can access. Commercial interests and universities can also sign up to access the biological material must return sequences and findings to the database. If they make commercial gain they agree to contribute commensurately. These funds are used to make vaccines available to those members who would not otherwise be able to afford them. All parties sign non disclosure agreements so nothing can be shared outside the closed group of signatories.
This agreement was tortuous to negotiate and failure to let some participating countries, and their universities, access to research results based on submitted biological materials is in contravention of the agreement and could unravel the whole thing.
we're talking about relatively small economical gains as compared to the possible damage.
And this was not the argument of the NSABB why they changed their mind.
> but Indonesia et al got nothing out of it
how much did they require ? Maybe some CSL stocks would have been
appropriate.
> The new system requires Nation States to sign up to participate and if they
> do so they must provide specimens and sequence data which the participating states can access
all of it ? You can't know, what they have
> These funds are used to make vaccines available to those members who would not
> otherwise be able to afford them.
de facto a H5N1 tax, to discourage companies from developing H5-vax.
Better give Indonesia et.al some money directly. You could declare it as H5N1 eradication help or such
> All parties sign non disclosure agreements so nothing can be shared outside the
> closed group of signatories.
this cannot be controlled. Some will be working on it in lower biosafety
> This agreement was tortuous to negotiate and failure to let some participating countries,
> and their universities, access to research results based on submitted biological
> materials is in contravention of the agreement and could unravel the whole thing
modify the whole thing a bit.It cannot be in the interest of either signing party that
those mutations and results become public
The process was still that NSABB first wanted to censor it and wanted the mutations to
be available only to selected groups. Then they figured out that this won't work because
of US-laws, so they changed their minds.
## Osterholm in his bias-criticism letter: http://www.nature.com/news/bias-accu...-board-1.10454
When the US government asked the NSABB in autumn of 2011 to review the papers
for publication, the board suggested that the papers be published in redacted form,
stripped of details that would allow people to recreate the viruses.
...
Before the (deciding 29.-30.March 2012-) meeting, assessments deemed the NSABB’s
proposed redactions too difficult to facilitate. The NSABB had recommended that
only brief announcements of the findings be published and that only qualified,
vetted experts be allowed access to the full data and methods.
Officials essentially took that option off the table, meaning that NSABB members
would have to vote either for full publication or no publication. Osterholm writes
that this all-or-nothing approach merely “kicked the can down the road”, ....
For instance, it was explained that the Government is exploring the feasibility of developing
a mechanism for controlled access to sensitive scientific information for those with a legitimate
need to know, in cases where certain details are redacted from a manuscript, and this would
be a way for the full information to reach relevant communities. However, the Government
noted that there were complex legal and practical issues still to be addressed and thus
such a mechanism was not currently available for communicating information in the H5N1
manuscripts under consideration at the March 29-30 NSABB meeting
## then she added your point mentioned above:
There was also discussion of the
international fiamework for virus sharing recently negotiated by the WHO
and concerns that the
framework could be endangered if the manuscripts were redacted
...“Part of what makes H5N1 so deadly is that most people lack an immunity to it,” explains Marc Lipsitch, a professor of epidemiology at Harvard School of Public Health (HSPH) who studies the spread of infectious diseases. “If you make a strain that’s highly transmissible between humans, as the Dutch team did, it could be disastrous if it ever escaped the lab.”
...
If a transmissible strain of H5N1 escapes the lab, says Lipsitch, it could spark a global health catastrophe.“It could infect millions of people in the United States, and very likely more than a billion people globally, like most successful flu strains do,” he says.“This might be one of the worst viruses—perhaps the worst virus—in existence right now because it has both transmissibility and high virulence.”
Ironically, this is why Ron Fouchier, the Dutch virologist whose lab created the new H5N1 strain, argues that studying it in more depth is crucial. If the virus can be made transmissible in the lab, he reasons, it can also occur in nature—and researchers should have an opportunity to understand as much as possible about the strain before that happens.
Lipsitch, who directs the Center for Communicable Disease Dynamics at HSPH, thinks the risks far outweigh the rewards. Even in labs with the most stringent safety requirements, such as enclosed rubber “space suits” to isolate researchers, accidents do happen. A single unprotected breath could infect a researcher, who might unknowingly spread the virus beyond the confines of the lab.
__________________ "Safety and security don't just happen, they are the result of collective consensus and public investment. We owe our children, the most vulnerable citizens in our society, a life free of violence and fear." -Nelson Mandela
...“Part of what makes H5N1 so deadly is that most people lack an immunity to it,” explains Marc Lipsitch, a professor of epidemiology at Harvard School of Public Health (HSPH) who studies the spread of infectious diseases. “If you make a strain that’s highly transmissible between humans, as the Dutch team did, it could be disastrous if it ever escaped the lab.”
...
If a transmissible strain of H5N1 escapes the lab, says Lipsitch, it could spark a global health catastrophe.“It could infect millions of people in the United States, and very likely more than a billion people globally, like most successful flu strains do,” he says.“This might be one of the worst viruses—perhaps the worst virus—in existence right now because it has both transmissibility and high virulence.”
Ironically, this is why Ron Fouchier, the Dutch virologist whose lab created the new H5N1 strain, argues that studying it in more depth is crucial. If the virus can be made transmissible in the lab, he reasons, it can also occur in nature—and researchers should have an opportunity to understand as much as possible about the strain before that happens.
Lipsitch, who directs the Center for Communicable Disease Dynamics at HSPH, thinks the risks far outweigh the rewards. Even in labs with the most stringent safety requirements, such as enclosed rubber “space suits” to isolate researchers, accidents do happen. A single unprotected breath could infect a researcher, who might unknowingly spread the virus beyond the confines of the lab.
But when Dutch researchers recently created an even more deadly strain of the virus in a laboratory for research purposes, they stirred grave concerns about what would happen if it escaped into the outside world.
Readers of virology blog will know by now that the Dutch researchers did not make an ‘even more deadly strain of the virus’ – they made one that could be transmitted by aerosol, but which had lost its lethality.
The title of the article, ‘The Deadliest Virus’, presumably refers to the H5N1 virus that transmits by aerosol among ferrets. This title is simply wrong, because the virus is not deadly to ferrets.
The first paragraph also contains an equally egregious statement by epidemiologist Marc Lipsitch:
If you make a strain that’s highly transmissible between humans, as the Dutch team did, it could be disastrous if it ever escaped the lab.
Dr. Lipsitch seems to be saying that the Dutch group created an H5N1 virus that transmits among humans. As far as I know, ferrets are not humans.
The article is accompanied by a photograph of two scientists working in BSL4 suits. The legend reads:
The modified H5N1 virus could infect a billion people if it escaped a biocontainment lab like the Canadian facility shown above.
And later Lipsitch is quoted as saying:
It could infect millions of people in the United States, and very likely more than a billion people globally, like most successful flu strains do. This might be one of the worst viruses—perhaps the worst virus—in existence right now because it has both transmissibility and high virulence.
For Lipsitch to say that the virus is both transmissible and of high virulence in humans is a misrepresentation of the Dutch group’s findings. He seems to be making up numbers and scenarios.
Perhaps Dr. Lipsitch does not know that ferret studies are not predictive of how viruses will behave in humans. With so many virologists at Harvard, the writer could have checked Dr. Lipsitch’s statements. But he did not, and the result looks as foolish as the New York Times.
__________________
"May the long time sun
Shine upon you,
All love surround you,
And the pure light within you
Guide your way on."
"Where your talents and the needs of the world cross, lies your calling."
Aristotle
“In a gentle way, you can shake the world.”
Mohandas Gandhi
Amid massive security, bird flu virus research awaits approval
By Karen Herzog of the Journal Sentinel
Feb. 19, 2013
...
Kawaoka is ready to tackle new questions about how avian influenza virus evolves in nature.
He never expected to be thrust into the international spotlight in November 2011, when his research was lumped together with a scientist's research in the Netherlands that - unlike Kawaoka's work - created a deadly H5N1virus strain .
Kawaoka does research only with influenza viruses that are sensitive to antiviral drugs, Moritz says.
Making a virus that's resistant to countermeasures would be a major violation of U.S. government guidelines, she says.
To determine whether H5N1 viruses could be spread among humans, Kawaoka's team generated viruses that combine a gene of avian influenza with genes from a human pandemic 2009 H1N1 influenza virus.
The team used ferrets because the mammals sneeze and cough like humans when infected with a virus. That's how flu viruses are spread among people.
The freezer holding the viruses in the Madison lab is accessible to only a handful of approved personnel. It's kept at -80 degrees Celsius (-112 Fahrenheit), and the virus inventory is checked monthly.
...
As scientists around the world debate the wisdom of creating viruses in labs that could pose serious health threats if accidentally released, or intentionally misused, UW-Madison scientists continue to defend the safety and security surrounding their work.
How would UW researchers know if the virus escaped into the lab?
"That's why we have multiple layers of protection," Moritz says.
__________________ "Safety and security don't just happen, they are the result of collective consensus and public investment. We owe our children, the most vulnerable citizens in our society, a life free of violence and fear." -Nelson Mandela
I don't understand that Racaniello fellow.
It's new for us flubies to deal with people saying
it won't be so bad rather than that it won't happen.
it's hard to prove the "coulds" and "mights" from Lipsich incorrect
but even if, what's the point ? Don't worry about a H5N1 pandemic
because it would likely be not so bad ??
(and thus silently considering that it may well happen ....)
H5N1 is awful. Even if it would be only as bad as 1918, which could
well happen, that doesn't let me sleep well ...
Taking the Fouchier-virus and assuming it behaves similar in humans
and assuming it goes pandemic, how many deaths can we estimate ?
(my estimate 100M, I challenge Racaniello to give his estimate)
| Posted by Brendan Maher |
US government officials have passed two more checkpoints on the long, winding road towards a policy for dealing with risky research. That journey was forced into overdrive at the end of 2011, when a government body recommended against publishing two studies showing how a deadly form of avian influenza H5N1 could be made to pass between mammals.
Today, the US National Institutes of Health (NIH) announced a final framework for vetting specific types of experiments before funding them. The US Office of Science and Technology Policy (OSTP) also published a long-awaited draft policy for how scientists and institutions should monitor and report on a wide range of research that malevolent forces could manipulate to do harm. This type of research, called dual-use research of concern (DURC), is fundable if the potential benefits are deemed significant and the risks deemed manageable.
__________________ "Safety and security don't just happen, they are the result of collective consensus and public investment. We owe our children, the most vulnerable citizens in our society, a life free of violence and fear." -Nelson Mandela
Deadly new bird flu vindicates controversial research
By Kate Kelland, Health and Science Correspondent | Reuters
LONDON (Reuters) - Scientists in the Dutch city of Rotterdam know precisely what it takes for a bird flu to mutate into a potential human pandemic strain - because they've created just such mutant viruses in the laboratory.
So as they watch with some trepidation the emergence in China of a strain of bird flu previously unknown in humans, they also argue it vindicates their controversial decision to conduct these risky experiments despite fierce opposition.
Above all else, what the world needs to know about this new strain of H7N9 bird flu is how likely it is to be able to spread efficiently among human populations.
And according to Ab Osterhaus, a world leading flu researcher who is head of viroscience of the Erasmus Medical Center in the Netherlands, studies his team and another in the United States have been doing are the best way to find out.
"At the moment we don't know whether we should go for a full-blown alert or whether we can sit back and say this is just a minor thing," Osterhaus told Reuters in a telephone interview.
"(To answer that) we need to know what this virus needs to become transmissible." . . . .
the next round of Fouchier experiments can be found here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3604002/
But they only report about reassortment experiments of normal H5N1 with human viruses,
H5N1 viruses that did not contain the magic 5 mutations.
You have to wonder whether they also tried the same thing with new H5N1 including
the 5 mutations. It would make more sense, IMO.
And then, we have to wonder why we hear nothing about the results of those experiments
with manipulated H5N1 ...
We urgently need reports now to measure pandemic preparedness levels of Erasmus institute
or Dutch government. Whether they increased their Tamiflu stockpile recently or such.
And, since those results are still nonpublic, others will presumably try it ....
it seems likely to me, that they had also done the same experiments with their
mutated H5N1 viruses. That's no big additional effort and they were curious.
But then they must have thought that reporting about it at this time would have been
not good for their projects.
But would they have thought this, if the experiments had yielded no increased transmissiability ?
I do see some evidence for increased transmissiability here, simply by them not reporting
about mutated-H5N1-experiments.
Maybe other researchers can confirm this by not reporting too ...
http://www.cidrap.umn.edu/cidrap/con...913ethics.html
Presidential Commission for the Study of Bioethical Issues (PCSBI).
acknowledged that the commission received the FVR's request but
declined to comment on it further.
The letter says that more gain-of-function studies on H5N1 and other viruses
are on the way. A Chinese group is working with H5N1, and a Dutch group is
expanding its H5N1 studies to include work with the H7N7 avian flu virus and
has plans for similar research with the SARS coronavirus.
(and now they got H7N9 ....)
Also, German
scientists recently did experiments to see what it would take for canine
distemper virus to spread from dogs to humans, the letter states.
> Study: Lab-derived H5N1 virus component binds to human receptors
same Kawaoka-ferret-group as in 2012
> A new study suggests that a lab-derived hybrid H5N1 influenza virus that is
> capable of airborne transmission among ferrets may well be capable of doing
> the same thing in humans.
> ... In some ways, they said, the properties of the mutant HA "suggest that H5 viruses
> could take a similar evolutionary pathway in humans to that followed in 1957 and
> 1968 by avian H2 and H3 viruses.
> ...However, the fact that the mutant virus sacrifices its avian binding ability to gain its
> human affinity "distinguishes it from known pandemic viruses
Racanielli wrote:
> the study offers important contributions but receptor binding is not the only factor
> that determines a flu virus's ability to infect and spread among ferrets and humans.
> the authors find that there is a limit on how many HA–sialic acid interactions can
> occur with one virus particle, and that this explains how modest decreases in the
> dissociation constant [the strength of single HA-receptor interactions] (~15-fold)
> can lead to a complete loss of binding and the resulting effects on receptor specificity.
> I think this is an important contribution which unifies the physical measurements with
> the ability of viruses to infect cells.
> To summarize the important contributions of this work, the ferret transmissible HA
> has a small increase in affinity for human receptors and a large decrease for avian
> receptors; alpha-2,6 sialic acid binds this HA in a way typical of human pandemic
> strains, and different from how wild-type H5 binds avian sialic acids.
> They [the authors] suggest that the transmissible H5 would not arise in waterfowl,
> given its lack of binding to avian receptors. These data help guide analysis of viral
> sequences for pandemic potential, and make important links between HA sequences,
> structure, and receptor binding.
> However, it is important to remember that aerosol transmission is far more complex
> than just being able to bind a receptor, and involves other parameters such as efficient
> shed from cells, the ability to replicate, stability, and probably others. For humans,
> the nature of those other changes is unknown.
Wain-Hobson, wrote:
> I express alarm over the findings.
> What I conclude here is that this virus does bind the sugar receptor as would a
> mammalian virus, in which case, as we know it goes from ferret to ferret, it's very
> reasonable to assume this is a novel human virus. The world is a more dangerous place.
> the report says that the virus will replicate in the upper respiratory tract due to affinity
> for the alpha2,6-linked sialic acids—just like any good mammalian influenza virus.
> It also says that as the virus has lost its binding for alpha2,3-linked sialic acids it won't
> get stuck on the mucin surfaces in the airways.
> This means that airborne virus will get down to the upper respiratory tract almost unhindered.
> So it will get into the right place and it will replicate. And because it won't get stuck on the
> mucin, it will get out.
> if Kawaoka's (or Fouchier's) virus escaped from a lab, it might not become a pandemic
> strain immediately, but it could begin spreading in humans and quickly evolve into one.
> So even if this Kawaoka configuration isn't the BIG ONE, it could rapidly lead to it,
Mutant Bird Flu Virus Evolves to Show Pandemic Characteristics
By Makiko Kitamura
April 24, 2013
A mutant version of a bird flu virus created by scientists last year to show its ability to spread between humans evolved to show characteristics of previous pandemic viruses, a study found.
A genetic component of the mutant H5N1 virus developed a 200-fold preference for binding with human over avian receptors, according to a study led by researchers at the MRC National Institute for Medical Research in London. Their paper was published today in the scientific journal Nature.
The study builds on work led by Yoshihiro Kawaoka at the University of Wisconsin-Madison that showed how H5N1 could become highly transmissible if its hemagglutinin gene is mutated and mixed with those of the H1N1 virus that sparked the 2009 swine flu pandemic. As a follow-up, the MRC-led team plans to study the same binding properties of the current H7N9 virus reported in China, John Skehel, one of the study authors in London, said in a phone interview...
As I understand, Racaniello thinks,
that this is an important step in our understanding how to create a devastating pandemic.
But also that the approach is not sufficient yet and that fundamentally new approaches
are needed to complete the task. Mainly because we have only ferret experiments,
so what's needed for humans is unknown.
----------------------------
Now, there are ethical problems with human experiments, but even without these,
they are more and more successful to research around it, find other ways
and I feel that we are close to creating pandemic viruses with lots of new antigenic profiles.
Adapting the virulence of these should be the easier task.
So, should we prepare to let mild versions lose on mankind should someone else
let lose an antinically similar virulent variant ?
So to induce immunity against the evil one by real infections, which still seems to be
more effective then vaccinations.
But I also see the potential of vastly increased different pandemic candidates.
They might be able soon to create many antigenically different HAs, not just
limited to the existing 17 types.and their naturally occurring subtypes.
Once we undestand this, we can "design" many new HA-types and create them
by increased evolution, mutating,selecting,computer simulation,
microscale thermophoresis,surface biolayer interferometry,...(we are just at the beginning)
Then we will have lots of new pandemic candidates and lots of vaccines and antivirals too.
But I feel that constructing new pandemic candidates will be easier than creating
countermeasures against them.
------------------------------------------------
I think they should have addressed this dual-use concern in the paper.
They talk about the possible benefits and importance of their work a lot,
but leave out the risks, although they are clearly aware of that discussion.
That makes the thing incomplete, even somehow unscientific and similar
to a biased advertisement for their work.
-----------------------------------------------------------------
you can purchase the article for $30, but have to agree to some lengthy terms and conditions,
which presumably includes that you maynot quote and discuss it here (?)
profvrr wrote on 2013.May.13 in response to DavidS
> Animal models are not predictors of what will happen in humans.
somehow they are.That's why we are using them, why you say "it's good science"
You probably meant: are not so good predictors (as most think)
> We study infections in animals to obtain mechanistic clues;
you say mechanistic clues, I'd say probability estimates
> conclusions about what happens in people require further testing. There are dozens
> of examples of this in the literature. Drugs and vaccines are tested in several animal models,
> but are the drugs and vaccines then released for humans? Of course not; clinical
> trials are done.
which often however confirm the animal tests. I'd guess in ~70% of cases
> We've had a great deal of experience in this laboratory constructing viruses with
> various mutations, and none have ever been more virulent; most are attenuated.
> The same applies for research done in other laboratories. We have little clue how
> to make a more virulent virus.
but there are many papers demonstrating just this increase of virulence.
I don't know much outside influenza, but especially with reassorting influenza viruses :
we have 256 possible children, some are usually
more virulent than the parents, some are less virulent. Only ~10% do survive and replicate
and most transmit worse than in nature. But now I feel that we are getting close to successfully
create/detect and filter the potential candidates. We are clearly better than nature here,
which requires a (rare in humans) double-infection and competition (through immunity) with other viruses,
while we can learn and design and select to specifically target and optimize the outcome.
Since above study is not public and already starts with a HP-virus,
let me select this as an example instead, to demonstrate what I mean Sun et.al., 2011: http://www.pnas.org/content/early/2011/02/23/1019109108
[ For an overview of other reassortment studies see http://www.flutrackers.com/forum/sho...d.php?t=203696 ]
While most (46 out of 127) [H9N2+pH1N1)-reassortant viable children had lower pathogenicity
than the parents, there were still 8 out of 127 that had higher pathogenicity in mice than both
parents.Researchers and terrorists will learn how to create higher pathogenicity by reassortment
or passaging or combinations of both. And how to enhance it to ferrets,pigs,...,humans.
This was for reassortment experiments, but also for single mutations and passaging
there are many papers how these may increase virulence.
Some keywords that come to mind:: N66S in PB1-F2, E627K in PB2, H5N1 in mouse-brain
after passaging, chicken-adapted,quail-adapted H9N2, D225G in HA of pH1N1 and 1918-H1N1,
search "virulence mutations", "influenza"
> Part of the problem is that we focus on amino acid
> changes in isolation; in nature these are accompanied by hundreds of other changes
> which are eventually selected in various hosts to make the final pathogen.
in flu it's often just one mutation. And the mutations usually accumulate one by one.
Each of the viruses in that chain must be viable. We have many influenza sequences
meanwhile, so we can study the chains. And in the labs they can create these mutations
by passaging.
> We don't have a chance at duplicating this and I've never seen any laboratory come close.
Palese,Fouchier,Kawaka,...I feel they are pretty close
> Just take a look at the scientific literature on viral pathogenesis.
> My beliefs are indeed relevant. They are based on 30+ years of doing research in the
> laboratory on viral pathogenesis, and keeping up with the literature.
but things have changed a lot recently. Now we have reverse genetics, better organized
labs with rooms full of ferret-cages, 200000 flu sequences at genbank, 70000 flu-papers at pubmed.
Next Generation Sequencing
profvrr wrote:
> I firmly believe that laboratory-constructed viruses do not have what it
> takes to be a human pathogen: only viral evolution in nature can
> produce the right combination of RNA segments and mutations.
> ... I can find plenty of virologists who would have the same view.
> We are talking about humans, not animal models.
laboratory-constructed viruses do have what it takes to be a ferret pathogen ?
Humans are animals. We are not so special from the virus' POV.
Why might it work in different animals but not in humans ?
Presumably only because we can't test it in humans for ethical reasons.
There is no magical difference that separates humans from ferrets
but not ferrets from mice or guinea pigs. We cannot be 100% sure
before we tested it in humans - but maybe 80%, and that's still useful.
So lab-viruses probably often do have "what it takes to be an animal or
human pathogen" but tests to confirm this for humans are rarely available.
Mouse-adapted H9N2 influenza A virus PB2 protein M147L and E627K mutations
are critical for high virulence
http://jvi.asm.org/content/77/6/3816.full H5N1,mousebrain,2001
all five genotypes of the H5N1/01 viruses were of low pathogenicity in mice
(MB variants) were isolated from the brain by culturing virus-positive brain homogenate
in 10-day-old embryonated hens' eggs for one passage.
The MB variants ... were markedly more virulent than the original viruses
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Re: Man Made H5N1 - Super Version
Re: Man Made H5N1 - Super Version 
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