Man Made H5N1 - Super Version

[JJackson]

Re: Man Made H5N1 - Super Version

All one would do is release the 'winning combination' for human infections into the global H5 viral reservoir, and with reassortment, how long do you think it would take before other H5 strains (sufficiently genetically divergent to provide no cross immunity whatsoever) also make the jump?

This is the reason deliberately releasing a 'mild' H5N1 is too dangerous. The aim is to build herd immunity by infecting a significant portion of the population.The reasoning being that if a high CFR natural pandemic occurs we then have some protection.
Problem one is HP H5N1 has been around for so long now it has diverged in to a point that its HA - the primary source of antigenic sites - no-longer maintains the necessary % homology across clades to offer adequate protection.
Problem two is the engineered virus will need to sufficiently fit to survive and spread. As part of this it will need to have us solve its airborne transmission problem for it and yet be mild. This would probably be done by picking the most active strain that has caused human infection, use the modification Fourier et al have found to solve the transmission problem and then use the resultant viruses HA and NA with the internal RNA from PR8 or similar. If the resultant virus transmitted between ferrets but did not kill them you would have to find some volunteers to test transmission and CFR. Good luck getting that through the ethics committee, finding global indemnity for the manufacturer and releasing country.
Problem three is V62's. How do you stop nature saying thanks for solving the transmission problem and performing the multiple reassortment in reverse. She has a lot more labs (AKA birds, pigs, humans etc) and sequences than we do.

 

[gsgs]

Re: Man Made H5N1 - Super Version

Gert van der Hoek,
we get ~500000 deaths from flu each year anyway. Does it really matter, what strain ?
As long as it's not so virulent, let alone current H5N1.
Adding a new strain would not increase this so much, the new strain reduces the
other strains by shortterm immunity competition.
We see it each year from the ILI-curve. It goes down when enough people have immunity,
and not when summer comes.

Vibrant,
while seasonal flu still succeeds to circulate each year despite
being there the years before - a pandemic usually only happens
with a completely new HA.
If the existing H5N1 had not the advantage of a new serotype,
it had hardly a chance against long established seasonal flu.

And a widespread pandemic outbreak can even kill all
other strains, even established H3N2, as we saw in 2009/2010.

So a mild H5N1 -or even another strain with widespread outbreak-
would likely prevent a virulent H5N1 wave in that season.
(and then use the gained year to vax everyone with a strain-specific vax)

in a bad H5N1 pandemic, we will reconsider our ethics !

Reassorting: better the mild version reassorts (and thus increases its spread)
than the bad one, expected to come later.
Alternatively use H1N1 or H3N2, this should also work, although maybe
not so well. Key is timing.
JJackson, the exact strain is not so important with this strategy. It's not
the normal B-cell immunity that we know from the split-vax.
When the pandemic starts, then we know the strain and can produce specific
vax against it. Also, we still see bottlenecks, where old H5 dies and a few strains become dominant.
currently Egypt,Indonesia,Mongolia/Japan,China - just one strain in each of those regions
(except maybe China) that is dominant, ~3 years old.
We have that range with seasonal flu as well.

ethics: what's the problem with creating a mild H5N1 ? Using it would be decided later
in a (possible but hopefully not so likely) H5N1-pandemic-changed-ethics environment.

And even if we would never use it, it's still important to know whether the mild H5N1
exists and transmits. First idea: cut the cleavage site and test it in mice ! Has it been done ?

 

[JJackson]

Re: Man Made H5N1 - Super Version

gs
I generally agree that even a poor match is going to give partial immunity. I also agree a bad pandemic will cause a review of ethics and priorities re vaccine funding - sadly this will occur in the post pandemic review stage, i.e. ready for a latter pandemic.
The bigger problem is being sure our mild pandemic does not spawn a sever, and fitter, variant before it has run its course and made us at least partially immune.

 

[gsgs]

Re: Man Made H5N1 - Super Version

run its course with ~50% CFR ? Or even just 10% ?
We would do everything to prevent that.

Is it ethical to forbid some country actually facing a severe H5N1-wave
to use a deliberate spread of another flu ? Be it H5N1 or H1N1 or...
Of course, that flu may reassort and make it even worse but more
likely that it prevents the H5N1-wave.
However that flu may spread to other countries then ...
thus "solving" their ethical problem

 

[gsgs]

Re: Man Made H5N1 - Super Version

the review of ethics and funding priorities may also happen in the prepandemic phase.
When/if the new research more and more shows that the danger
is big, some labs in rogue states repeated the experiments
with low level security, some lab workers died,
terrorist threats to use it and demonstrating that they have it ,...

It's not hard to predict that this will happen earlier or later.
It's just what usually happens.

 

[Gert van der Hoek]

Re: Man Made H5N1 - Super Version

Vincent Racaniello has a point: we don't know the CFR of H5N1.

I remember a statement from dr Nidom, Indonesia, saying he expected a very high percentage (50% +) of inhabitants of Jakarta would show H5N1-antibodies.


Should we fear avian H5N1 influenza?

3 JANUARY 2012

Why is there such widespread fear of avian H5N1 influenza virus?

Why did Paul Keim, chair of the National Science Advisory Board for Biosecurity (NSABB) say “I can’t think of another pathogenic organism that is as scary as this one”. What lead Donald McNeil, writing about H5N1 in the New York Times, to conclude that “In its natural form, it is known to have infected only about 600 people since its discovery in 1997, but it killed more than half of them.”

McNeil’s statement is incorrect. Yet it summarizes why Paul Keim, the NSABB, and many others fear the virus.

- snip -

Until we know how many individuals are infected with avian influenza H5N1, we must refrain from making dire conclusions about the pathogenicity of the virus. Doing so has only lead us down a dangerous path of fearing that H5N1 influenza virus might be used as a weapon of bioterrorism, and restricting the publication of scientific papers on the virus.

Read more - Viroloy blog

 

[gsgs]

Re: Man Made H5N1 - Super Version

since we don't know exactly, we must restrain ??
Yes, it is quite possible (~70% ?) that H5N1 in a pandemic
would have a much lower CFR.
But it's also quite possible(~30%?) that not.

And I think we shouldn't just ignore that 2nd possibility
because it's uncomfortable to even think about it.

We have 1918 as worst example with a CFR of 2.5% in USA ~12% worldwide,
~25% were infected, 0.6% of the US-population and ~2.5% of the world population died.

We also saw what flu can do in the 1872 epizootic where almost 100% of horses were infected
in one wave in USA and Canada and ~5% of them died.

 

[gsgs]

Re: Man Made H5N1 - Super Version

ahh, Raccaniello.
Thinks the whole H5N1 is nothing to be afraid of, because
some other people exaggerated the threat.
Incorrectly, as he thinks.
Now the CFR is not 50% but only ... maybe 10%.
Nothing to worry about.

I mean, when you wanted to dismiss H5N1, then you'd argue
about the probability that it happens.

OK, he does that too, the ferrets were different from humans.
Well, maybe, maybe not. He is just looking for small factors to reduce
the threat.

Like saying nuclear war were no big danger since the earlier
estimates of the overkill capicity were too large.
We'd only die 10 times instead of 20 times ...

 

[Pathfinder]

Re: Man Made H5N1 - Super Version

Risk of flu outbreak outweighed by benefits Commentary

By ANTHONY S. FAUCI, GARY J. NABEL, FRANCIS S. COLLINS | Special to The Washington Post
Published: January 08, 2012 Updated: January 08, 2012 - 12:00 AM

Excerpt:

The underlying question, of course, is whether the benefits of such research outweigh the risks. The answer is not simple. A highly pathogenic avian influenza virus transmissible in humans could arise in ways not predicted by laboratory studies. And it is not clear whether the laboratory virus would behave in humans as it does in ferrets. Nonetheless, new data can provide valuable insights that would inform influenza preparedness and help delineate the principles of influenza virus transmission between species.

Along with support for this research comes a responsibility to ensure that the information is used for good. Safeguarding against the potential accidental release or deliberate misuse of laboratory pathogens is imperative. The engineered viruses developed in the ferret experiments are maintained in high-security laboratories. The scientists, journal editors and funding agencies involved are working together to ensure that access to specific information that could be used to create dangerous pathogens will be limited to those with an established and legitimate need to know.



Anthony Fauci is director of the National Institute of Allergy and Infectious Diseases (NIAID), Gary Nabel works in the virology laboratory at the NIAID and Francis Collins is director of the National Institutes of Health.

Full text:
http://www2.tbo.com/news/opinion/20...-flu-outbreak-outweighed-by-benefi-ar-344519/

 

[Shannon Bennett]

Re: Man Made H5N1 - Super Version

The cat is out of the bag people. It evidently is fairly easy to make. There are universities all over the world capable of replicating the results. It is extremely virulent in ferrets. Which sadly translates as probably being extremely virulent in humans. If terrorists do decide to reengineer this virus then we only have a short time to counter. Instead of fighting over what we should have done re. the original manufacture of the virus, we should now be focusing on education, vaccines, etc... The virus mutating on its own was always a threat in any event. The virulence has always been exceptional. The cfr has been abyssmal. The study only highlighted how fast and easy eventual mutation was likely to occur in any event. The only saving grace is if some idiots do release this they are likely to also kill their own people. Detente may be the only deterrent.

 

[JimO]

Re: Man Made H5N1 - Super Version

Considering that the CFR for the 1917-18 pandemic was only 2-3%, then 10% would be catastrophic.

ahh, Raccaniello.
Thinks the whole H5N1 is nothing to be afraid of, because
some other people exaggerated the threat.
Incorrectly, as he thinks.
Now the CFR is not 50% but only ... maybe 10%.
Nothing to worry about.

I mean, when you wanted to dismiss H5N1, then you'd argue
about the probability that it happens.

OK, he does that too, the ferrets were different from humans.
Well, maybe, maybe not. He is just looking for small factors to reduce
the threat.

Like saying nuclear war were no big danger since the earlier
estimates of the overkill capicity were too large.
We'd only die 10 times instead of 20 times ...

 

[gsgs]

Re: Man Made H5N1 - Super Version

Palese:
> After we published our full paper…researchers poured into the field who probably
> would not otherwise have done, leading to hundreds of papers about the 1918 virus.

those researchers would likely have published papers about other things else.
Less valuable ? That's not clear at all.

> As a result, we now know that the virus is sensitive to the seasonal flu vaccine,

...more than expected. So the danger is small ? Well, we still have seasonal waves each year
despite vaccine and despite partial immunity real infections.
This can be as bad (in terms of spreading) as 2003/4 which was almost pandemic like with
just a new variant of H3N2 only ~5 years of normal evolution away from the vaccine.
And afair the protection is very small, (Palese et.al. paper testing mice, discussed here)
the ****** outbreak should provide larger protection against the 1918 virus.

> as well as to the common flu drugs amantadine (Symmetrel) and oseltamivir (Tamiflu).

this can easily be "undone" by single mutations, as we now know.

> Had we not reconstructed the virus and shared our results with the community,
> we would still be in fear that a nefarious scientist would recreate the Spanish flu
> and release it on an unprotected world. We now know such a worst-case scenario
> is no longer possible.

do we ? The 1918 virus released today would have to compete (via immunity) with ******,
which is more "advanced" wrt. spreading in our modern society.
But this will likely change in some decades or centuries when the 1918 virus may
become a threat again.

> The more danger a pathogen poses, the more important it is to study it (under appropriate
> containment conditions), and to share the results with the scientific community.
> Slowing down the scientific enterprise will not ‘protect’ the public —
> it only makes us more vulnerable.

but is it necessary to make that virus easily available to the masses ?
I'd expected that research to be done as research on nuclear bombs, i.e. nonpublic details,
nonproliferation treaties etc.







http://www.nature.com/news/don-t-censor-life-saving-science-1.9777

Palese:
> We then took an existing influenza virus and, one by one, swapped its genes
> with those from the 1918 virus, eventually recreating a live version

could that be easily redone by terrorists ?

> Giving the full details to vetted scientists is neither practical nor sufficient.

would he be one of those ?

> Once 20–30 laboratories with postdoctoral fellows and students have such
> information available, it will be impossible to keep the details secret.

so do it in military grade labs only ?!

> “Who will want to enter a field in which you can't publish your most scientifically
> interesting results?”

this would only be a small special (sub)field.
I could ask: what research are we,the public, willing to pay for ?

> Knowing which mutations render the virus more dangerous could help on a
> public-health level — if an outbreak of bird flu occurs in Taiwan, for instance,
> and researchers sequence the virus and see those mutations, we would know
> to ramp up the production of appropriate vaccines and antiviral drugs.

ahh, if an outbreak of bird flu occurs in Taiwan, then we should ramp up the production
anyway - no matter if those mutations were included or not

> Incidentally, I believe that the risk of future outbreaks in humans is low: H5N1 has
> had the opportunity to cause widespread pandemics for many, many decades,
> yet it has not done so.

and I remember that's exactly why Palese concluded in 2006 that H5N1 were just not capable
of this. Does he still think so after the Fouchier/Kawaoka experiments ?
****** needed 13 years to take off. Equine H3N8 needed 40 years before it jumped to dogs.
H5N1 had had not enough opportunities yet to evolve 10 or more generations in humans
as Fouchier did with the ferrets.

> Although we know the virus is transmissible between ferrets,
> little is known about how it will behave in other animals, including humans.

so how can Palese conclude :
"Incidentally, I believe that the risk of future outbreaks in humans is low:"
"little is known" is no negative evidence

 

[gsgs]

Re: Man Made H5N1 - Super Version

if they had done Fouchier/Kawaoka like experiments
with triple-reassortant swine flu 5 years ago ,
would they have found the pandemic danger from ****** ?

Well, they would have let it reassort with European Swine H1N1
also.
But they could/should have found it ?!?

Seems to me that this is all
just a matter of funding.

What did they pay to Kawaoka,Fouchier groups ?
Who decided that funding and when ?
I mean, H5N1 was a threat since 1997
(triple Swine since 1998)

now H5N1,H9N2, European Swine H1,re-emergence of H2N2

 

[Pathfinder]

Re: Man Made H5N1 - Super Version

Preventing pandemics: The fight over flu


<DL class=citation><DT>Journal name:<DD class=journal-title>Nature<DT>Year published:<DD>(2012)<DT>DOI:<DD class=doi>doi:10.1038/481257a</DD></DL><DL class="citation dates"><DT class="published-online first">Published online<DD><TIME datetime="2012-01-15" pubdate="pubdate">15 January 2012 </TIME></DD></DL></HEADER><SECTION>A proposal to restrict the planned publication of research on a potentially deadly avian influenza virus is causing a furore. Ten experts suggest ways to proceed.

Ron Fouchier & AB Osterhaus: Globalize the discussion

Erasmus MC, Rotterdam, the Netherlands
So far, most of the human deaths from the deadly H5N1 strain of bird flu have occurred in Asia and the Middle East. Many labs worldwide ? including ours ? are trying to understand what makes the virus so virulent, and how to stop it. H5N1 research is thus a global issue, yet the entire research community seems to be following the advice of one country.

We are not questioning the unprecedented recommendations last month from the US National Science Advisory Board for Biosecurity (NSABB) to remove key details from the methods and results sections of published papers, including our own, submitted to Science (see Nature 481, 9?10; 2012). But we do question whether it is appropriate to have one country dominate a discussion that has an impact on scientists and public-health officials worldwide. This discussion should include the perspective of people in regions where H5N1 has infected humans. Will the NSABB also advise on which international researchers and officials have the right to see the full papers, to help implement urgently needed surveillance and other intervention strategies?

It is not clear whether an international discussion would lead to different recommendations. There is no global equivalent of the NSABB, but many European experts that we have seen quoted in the press believe that the research should be published in full. We don't know the worldwide opinion until a group of experts from all parts of the globe is formed. An issue this big should not be decided by one country, but by all of us.

More...
http://www.nature.com/nature/journa...ier-amp-ab-osterhaus-globalize-the-discussion

 

[Gert van der Hoek]

Re: Man Made H5N1 - Super Version

Fear gone viral

By Wendy Orent

January 15, 2012


Despite government alarms bells, recent research with ferrets didn't create flu strains that threaten the world.

If you were paying attention to the flap over two recent flu experiments involving ferrets, you may have come away with the impression that scientists all but waved a red flag in front of terrorists and said, "Here's a perfect biological weapon ? help yourselves."

But there's really not much cause for alarm.

- snip -

But the idea that these laboratory-created mutations could now pop up together in some Asian chicken and launch a lethal pandemic is implausible. That's not how evolution works. Evolutionary biologist Paul Ewald of the University of Louisville predicted in 1993 that packing chickens in factory farms would allow the evolution of lethal chicken viruses. And that's exactly what happened: Chicken viruses evolved that killed chickens.

- snip -

None of this is to say, however, that the ferret experiments weren't important. What they showed is how quickly natural selection can transform a virus.

"You put selection pressure on the system for increased transmissibility, and you quickly get the outcome that you expect to get," says Ewald.

- snip -

The 1918 flu, which killed some 50 million people worldwide, was formed in the massive disease factory of the Western Front of World War I. Why was it a disease factory? Because soldiers were crowded into close quarters that were the perfect environment for the flu to mutate into something highly virulent. When a soldier got deathly ill, there was no place to move him, and he remained packed tightly in among the other soldiers.

The 1918 flu virus eventually lost its virulence as the conditions that gave rise to it abated. When a virus depends on a mobile host to transmit it, as normal human flu viruses do, there's a limit to its virulence. Once humans aren't crowded so tightly together, it's the milder strains of viruses that natural selection favors, because transmission is more easily accomplished if the infected person feels well enough to be out in public sneezing and coughing instead of taking straight to a sickbed where few other people are likely to be infected.


Read more: LATimes

 

[JJackson]

Re: Man Made H5N1 - Super Version

There is no global equivalent of the NSABB

Could that be because there is no Bio-Threat industry outside of the United States?

While I have read of 'nefarious actors' who some in the industry fear are out to cause global Armageddon I am not clear who the industry think they are, nor have seen any evidence that there is a threat of this type.
Here I am talking of the release of an untargetable bio-weapon which would require a significant investment of time and resources by a body of technically knowledgeable people.

That there are people who hate all I stand for and are willing to kill my ilk in quantity, given a chance, I don't doubt but that is not what we are talking about if you are censoring H5N1 research or worrying about re-animating H1N1(1918) from its sequence data.

Looking at the list of members of the NSABB I see many good scientist for whose work I have much respect. I also however see a list of institutions who collectively get a significant chunk of funding which might evaporate if the threat was down graded.
Not really the group I think should be leading this discussion.

These are my personal views and not those of any other body.

 

[mixin]

Re: Man Made H5N1 - Super Version

For those who may not know exactly what and who NSABB is:

The NSABB is a federal advisory committee chartered to provide advice, guidance, and leadership regarding biosecurity oversight of dual use research, defined as biological research with legitimate scientific purpose that may be misused to pose a biologic threat to public health and/or national security.

The NSABB is charged specifically to:

Recommend strategies and guidance for enhancing personnel reliability among individuals with access to biological select agents and toxins.

Provide recommendations on the development of programs for outreach, education and training in dual use research issues for scientists, laboratory workers, students and trainees in relevant disciplines.

Advise on policies governing publication, public communication, and dissemination of dual use research methodologies and results.

Recommend strategies for fostering international engagement on dual use biological research issues.

Advise on the development, utilization and promotion of codes of conduct to interdisciplinary life scientists, and relevant professional groups.

Advise on polices regarding the conduct, communication, and oversight of dual use research and results, as requested.

Advise on the Federal Select Agent Program, as requested.

Address any other issues as directed by the Secretary of HHS.

The NSABB is chartered to have up to 25 voting members with a broad range of expertise including molecular biology, microbiology, infectious diseases, biosafety, public health, veterinary medicine, plant health, national security, biodefense, law enforcement, scientific publishing, and related field. The NSABB also includes nonvoting ex officio members from 15 federal agencies and departments.

(member list is included at the link)
http://oba.od.nih.gov/biosecurity/about_nsabb.html

 

[Pathfinder]

Re: Man Made H5N1 - Super Version

<IFRAME height=315 src="http://www.youtube.com/embed/0yS1ur24j40" frameBorder=0 width=560 allowfullscreen></IFRAME>
Uploaded by NIHOD on May 12, 2010

Dual Use Research: A Dialogue

This educational video was produced by the National Institutes of Health (U.S. Department of Health and Human Services) to raise awareness and understanding about the issue of dual use life sciences research. The video offers a conceptual introduction to the issue and features interviews with some of the country's leading experts who discuss the need to ensure scientific progress while ensuring appropriate oversight. The target audience includes life scientists, trainees and students, research administrators, and the general public.

http://www.youtube.com/watch?v=0yS1ur24j40&feature=player_embedded#!

 

[Laidback Al]

Re: Man Made H5N1 - Super Version

from this article post by Gert above.

But to become a world-destroying pandemic, a virus would need a so-called human disease factory in which to refine its mutations. . .

The 1918 flu, which killed some 50 million people worldwide, was formed in the massive disease factory of the Western Front of World War I. Why was it a disease factory? Because soldiers were crowded into close quarters that were the perfect environment for the flu to mutate into something highly virulent. When a soldier got deathly ill, there was no place to move him, and he remained packed tightly in among the other soldiers.

According to Ms. Orent it was densely packed soldiers in Europe in 1918 that allowed the virus to mutate and spread. This is a naive view of the pandemic. The spread of the infectious disease, as measured the R0, is primarily a function of the transmissibility of the novel virus, not the density of potential victims. If that were true, H5N1 would have already caused a pandemic.

At the time of the H1N1 pandemic in 1918 the population in all of Europe was 250 million people (Mortality burden of the 1918?1919 influenza pandemic in Europe). Today, Europe has a population of over 840 million (link). And there are four countries in the world with current populations that exceed 200 million people, China, India, United States, and Indonesia (link). Of these, China and Indonesia have already reported human H5N1 cases, and human H5N1 case are likely to have occurred in India but have not been officially reported. The density of people in some areas of these countries greatly exceeds the density of Orent's 1918 "disease factories".

Countries such as China, Indonesia, and India could already be "disease factories" for human H5N1 mutations. So far, we are lucky that the virus has not yet become sufficiently transmissible to break out of local clusters.

 

[gsgs]

Re: Man Made H5N1 - Super Version

yes, and it was worst in countries not at war.

Maybe the increased traffic with military ships contributed
to the spread, though.
But then, as we know now, less naval traffic would only have delayed it.