Critics Skeptical as Flu Scientists Argue for Controversial H7N9 Studies

[tetano]

Editor's Note: Please see our companion thread - Man Made H5N1 - Super Version


Handle with care

The possibility that H7N9 avian influenza may evolve sufficiently to cause a pandemic has scientists turning again to controversial research —they must be careful how they justify the risks taken.
07 August 2013

The H7N9 avian flu virus first reported in China in March has so far infected at least 134 people, and killed 43 of them. Thankfully, there are no signs yet that it can easily be transmitted between people — instead it is sporadically being caught by humans through contact with chickens and other fowl.

Researchers now want to make genetically engineered versions of H7N9 that are more transmissible and pathogenic in mammals. In a Correspondence published jointly this week in Nature and Science (see page 150), 22 scientists, including Ron Fouchier of the Erasmus Medical Center in Rotterdam, the Netherlands, and Yoshihiro Kawaoka of the University of Wisconsin-Madison, argue that such research can help to assess the ‘pandemic potential’ of H7N9. The dilemma is that should such engineered strains be accidentally or deliberately released from a lab, they could spark a flu pandemic.

The announcement is likely to prompt some replay of last year’s debate over the creation by Fouchier and Kawaoka of lab strains of H5N1 that could transmit between ferrets. And it offers the first test of some of the review and oversight structures put in place for this ‘gain-of-function’ flu research. As this journal has said before, scientists who push for such research should be wary of over-selling the benefits to public health, at least in the short term, as a way to justify the risks taken.

..

http://www.nature.com/news/handle-with-care-1.13505

[tetano]

Critics Skeptical as Flu Scientists Argue for Controversial H7N9 Studies

Avian flu: Gain-of-function experiments on H7N9

Ron A. M. Fouchier,
Yoshihiro Kawaoka
& 20 co-authors

Affiliations
Corresponding authors

Nature
500,
150?151
(08 August 2013)
doi:10.1038/500150a

Published online
07 August 2013



Since the end of March 2013, avian influenza A viruses of the H7N9 subtype have caused more than 130 human cases of infection in China, many of which were severe, resulting in 43 fatalities. Although this A(H7N9) outbreak is now under control, the virus (or one with similar properties) could re-emerge as winter approaches.

To better assess the pandemic threat posed by A(H7N9) viruses, investigators from the NIAID Centers of Excellence in Influenza Research and Surveillance and other expert laboratories in China and elsewhere have characterized the wild-type avian A(H7N9) viruses in terms of host range, virulence and transmission, and are evaluating the effectiveness of antiviral drugs and vaccine candidates. However, to fully assess the potential risk associated with these novel viruses, there is a need for further research, including experiments that may be classified as 'gain of function' (GOF).

Here we outline the aspects of the current situation that most urgently require additional research, our proposed studies, and risk-mitigation strategies.

The A(H7N9) virus haemagglutinin protein has several motifs that are characteristic of mammalian-adapted and human influenza viruses, including mutations that confer human-type receptor binding and enhanced virus replication in mammals. The pandemic risk rises exponentially should these viruses acquire the ability to transmit readily among humans.

..

http://www.nature.com/nature/journal/v500/n7461/full/500150a.html

[tetano]

Critics Skeptical as Flu Scientists Argue for Controversial H7N9 Studies

Avian flu: Extra oversight for H7N9 experiments

Harold W. Jaffe,
Amy P. Patterson
& Nicole Lurie

Affiliations
Corresponding author

Nature
500,
151
(08 August 2013)
doi:10.1038/500151a

Published online
07 August 2013


The US Department of Health and Human Services (HHS) announces a new review process for certain gain-of-function (GOF) experiments on the avian influenza A (H7N9) virus, some of which are proposed this week by influenza scientists (R. A. M. Fouchier et al. Nature 500, 150?151; 2013).

Specifically, before being undertaken using HHS funds, any experiments that are reasonably anticipated to generate H7N9 viruses with increased transmissibility between mammals by respiratory droplets will undergo an additional level of review by the HHS.

The HHS review will consider the acceptability of these experiments in light of potential scientific and public-health benefits as well as biosafety and biosecurity risks, and will identify any additional risk-mitigation measures needed. The review will be carried out by a standing multidisciplinary panel of federal experts with backgrounds in public health, medicine, security, science policy, global health, risk assessment, US law and ethics. This approach, similar to that for certain H5N1 influenza virus experiments (see go.nature.com/vpmplf), allows the HHS to focus special oversight efforts on experiments of concern while allowing routine characterization and other fundamental research to proceed rapidly, thereby enabling a robust public-health response.

GOF studies can provide important insights into how the A(H7N9) virus adapts to mammalian hosts, causes disease and spreads to other hosts, but they may also pose biosafety and biosecurity risks. To ensure that research involving H7N9 virus is conducted safely and securely, the US Centers for Disease Control and Prevention recently re-examined the requisite biosafety conditions for conducting experiments involving H7N9 and, in June 2013, issued interim risk-assessment and biosafety-level recommendations (see go.nature.com/gknn9a).

http://www.nature.com/nature/journal/v500/n7461/full/500151a.html

[tetano]

Critics Skeptical as Flu Scientists Argue for Controversial H7N9 Studies

Science DOI: 10.1126/science.341.6146.601

News & Analysis

Avian Influenza
Critics Skeptical as Flu Scientists Argue for Controversial H7N9 Studies

David Malakoff





Flu scientists are hoping to vaccinate themselves against another outbreak of a crippling controversy.

In a letter published this week by Nature and Science (see p. 612), 22 researchers make their case for launching potentially risky experiments with the H7N9 avian influenza virus, which emerged earlier this year in China and which some scientists fear could spark a deadly human pandemic. The scientists, who mostly work in U.S.-funded labs, also detail the safety and security precautions that they would take to prevent the possibly dangerous viruses they create from escaping from the lab?or falling into the hands of terrorists. In an accompanying online letter (http://scim.ag/fluHHS), officials from the U.S. Department of Health and Human Services (HHS) write that they will require extra review of especially problematic studies.

The communiqu?, the authors say, is intended to head off the kind of global controversy that in 2011 engulfed researchers conducting experiments with another avian flu virus, H5N1, halting certain studies for more than a year (Science, 22 June 2012, p. 1494). Critics charged that those studies?which involved engineering new H5N1 strains able to move between mammals, and not just birds?carried risks that outweighed any benefits and had too little public oversight.

?With H5N1, we were criticized for not being transparent,? says virologist Ron Fouchier of Erasmus MC in Rotterdam, the Netherlands, one of the scientists at the center of the H5N1 storm and a lead author of the 7 August letter. ?So this time we want to be sure the public understands what we want to do before we do it, why we need to do it, and how we are going to do it safely.?

...

http://www.sciencemag.org/content/early/2013/08/07/science.341.6146.601.full

[sharon sanders]

Re: Critics Skeptical as Flu Scientists Argue for Controversial H7N9 Studies

H7N9: Reigniting The `Gain Of Function? Research Debate




BSL-4 Lab Worker - Photo Credit ?USAMRIID


# 7549

Most readers will recall that, beginning in the fall of 2011 and extending well into the summer of 2012, the global scientific community was roiled by controversy over the wisdom of conducting ? and publishing ? Gain of Function (GOF) research on the avian H5N1 virus.

Objections were raised initially after the 2011 ESWI Influenza Conference in Malta, where Dutch researcher Ron Fouchier revealed that he?d created a more `transmissible? form of the H5N1 virus (see Debra MacKenzie?s New Scientist: Five Easy Mutations).

That discovery, along with similar news coming from Yoshihiro Kawaoka, a highly respected virologist at the University of Wisconsin-Madison School of Veterinary Medicine,set alarm bells ringing in the biosecurity community.

By December of 2011 The Biosecurity Debate On H5N1 Research reached fevered pitch, which led to a group of internationally renownedScientists to Announce a 60 Day Moratorium On Some H5N1 Research in January, 2012. That moratorium was subsequently extended until January of 2013 (see NIH Statement On Lifting Of The H5N1 Research Moratorium).

In the meantime, after much heated debate, last summer Science Published The Fouchier Ferret Study and Nature Published The Kawaoka H5N1 Study.

In March of 2012 the NIH - which funds many of these research projects - promulgated newDURC Oversight Rules(Dual Use Research of Concern), which also includes some types of GOF research.

For those unfamiliar with the lexicon of biomedical research, DURC in this new policy is defined as:

. . . life sciences research that, based on current understanding, can be reasonably anticipated to provide knowledge, information, products, or technologies that could be directly misapplied to pose a significant threat with broad potential consequences to public health and safety, agricultural crops and other plants, animals, the environment,

Since then the debate has continued, mostly in academia, over what restrictions (if any) should be placed on potentially dangerous gain of function research.

A couple of recent examples include:

Nature: H5N1 viral-engineering dangers will not go away

Morens & Taubenberger - Influenza Viruses: Breaking All the Rules

Today, in a bid to head off the kind of controversy they encountered with the surprise announcement of H5N1 GOF studies in 2011, 22 respected international scientists have published a pre-emptive letter (in the Journal Science and the Journal Nature) calling for gain of function research using the H7N9 virus.

In this letter they outline the benefits they believe such studies will provide along with the biosecurity measures they will work under.

Many of the signatories to this letter are well known to the readers of this blog.

RON A. M. FOUCHIER, YOSHIHIRO KAWAOKA, CAROL CARDONA, RICHARD W. COMPANS, ADOLFO GARC?A-SASTRE, ELENA A. GOVORKOVA, YI GUAN, SANDER HERFST, WALTER A. ORENSTEIN, J. S. MALIK PEIRIS, DANIEL R. PEREZ, JUERGEN A. RICHT, CHARLES RUSSELL, STACEY L. SCHULTZ-CHERRY, DEREK J. SMITH, JOHN STEEL, S. MARK TOMPKINS, DAVID J. TOPHAM, JOHN J. TREANOR, RALPH A. TRIPP, RICHARD J. WEBBY, ROBERT G. WEBSTER

You can read the full letter here or at the following link:

<cite>Published Online August 7 2013
</cite>
Science DOI: 10.1126/science.1243325
Letters
Gain-of-Function Experiments on H7N9

*Corresponding author. E-mail: r.fouchier@erasmusmc.nl (R.A.M.F.); kawaokay@svm.vetmed.wisc.edu (Y.K.)

• Abstract

Since the end of March 2013, avian a influenza viruses of the H7N9 subtype have caused more than 130 human cases of infection in China, many of which were severe, resulting in 43 fatalities. Although this A(H7N9) virus outbreak is now under control, the virus (or one with similar properties) could reemerge as winter approaches. To better assess the pandemic threat posed by A(H7N9) viruses, NIAID/NIH Centers of Excellence in Influenza Research and Surveillance (CEIRS) investigators and other expert laboratories in China and elsewhere have characterized the wild-type avian A(H7N9) viruses in terms of host range, virulence, and transmission, and are evaluating the effectiveness of antiviral drugs and vaccine candidates. However, to fully assess the potential risk associated with these novel viruses, there is a need for additional research including experiments that may be classified as ?gain-of-function? (GOF). Here, we outline the aspects of the current situation that most urgently require additional research, our proposed studies, and risk-mitigation strategies.

But as you might expect, not everyone is in agreement on the value, or the safety, of doing these studies. In an accompanying news and analysis article in Science Magazine, David Malakoff writes:

Avian Influenza
Critics Skeptical as Flu Scientists Argue for Controversial H7N9 Studies

David Malakoff
<EXCERPT>

The openness offensive isn't quieting critics. ?The scientific justification presented for doing this work is very flimsy, to put it mildly, and the claims that it will lead to anything useful are lightweight,? says Adel A. F. Mahmoud, an infectious disease specialist at Princeton University and the former president of Merck Vaccines. And the security precautions are ?insufficient and amazingly lame,? says molecular biologist Richard Ebright of Rutgers University in Piscataway, New Jersey.

(Continue . . . )

The NIH, responding to today?s letter, has published their position regarding additional oversight they will require for H7N9 influenza virus gain-of-function research.

Extra Oversight for H7N9 Experiments


Harold Jaffe, Amy P. Patterson, Nicole Lurie
The U.S. Department of Health and Human Services (HHS) announces a new review process for certain gain-of-function (GOF) experiments with the avian influenza A (H7N9) virus, some of which are proposed this week by influenza scientists (1). Specifically, before being undertaken using funds from the HHS, proposed studies that are reasonably anticipated to generate H7N9 viruses with increased transmissibility between mammals by respiratory droplets will undergo an additional level of review by the HHS.
(Continue . . . )

Ed Yong ? writing for The Scientist ? has penned an excellent overview of this controversy, including extended remarks from a number of experts, including CIDRAP director Michael Osterholm.

Bird Flu Experiments Proposed

In a bid to avoid the controversy that dogged H5N1 research last year, flu researchers have published a letter proposing how to approach potentially dangerous research on H7N9.
By Ed Yong | August 7, 2013

And for a last stop, we have the always reliable Helen Branswell, who writes:

Flu researchers propose controversial 'gain-of-function' studies for H7N9 virus

By Helen Branswell, The Canadian Press August 7, 2013 10:30 AM

Whether this controversy will reach the contentious levels we saw last year with H5N1 research is difficult to predict, but there are strong feelings on both sides of this issue.

Stay tuned.

Posted by Michael Coston at <a class="timestamp-link" href="http://afludiary.blogspot.com/2013/08/h7n9-reigniting-gain-of-function.html" rel="bookmark" title="permanent link"><abbr class="published" title="2013-08-07T13:56:00-04:00">1:56 PM</abbr>

[Giuseppe]

Re: Critics Skeptical as Flu Scientists Argue for Controversial H7N9 Studies

I reiterate my skepticism on these kind of studies (sometimes known as 'blockbuster' research).

Instead of manipulating organisms in order to make them able to behave in a certain manner, it would be much more urgent a in-depth, multi-disciplinary and international driven research into human host determinants of pathogenicity and to improve therapeutical approaches as a possible pandemic cannot be predicted nor avoided with current science but the world has the obligation to make all the possible to save lives.

Clinical management approaches and vaccine strategy are currently the most urgent needs to be addressed before a natural occurring readily transmissible strain of influenza virus will emerge.

GM

[tetano]

Critics Skeptical as Flu Scientists Argue for Controversial H7N9 Studies

Virologists plan influenza H7N9 gain of function experiments

<abbr class="published" title="2013-08-07">7 August 2013</abbr>

A group of virologists lead by Yoshihiro Kawaoka and Ron Fouchier have sent a letter to Nature and Science outlining the experiments they propose to carry out with influenza H7N9 virus.
Avian influenza H7N9 virus has caused over 130 human infections in China with 43 fatalities. The source of the virus is not known but is suspected to be wet market poultry. No human to human transmission have been detected, and the outbreak seems to be under control. According to the authors of the letter, the virus could re-emerge this winter, and therefore additional work is needed to assess the risk of human infection.
The research that the virologists propose involve gain-of-function experiments which provide the H7N9 virus with new properties. The isolation of avian influenza H5N1 viruses that can transmit by aerosol among ferrets is an example of a gain-of-function experiment.
The proposed gain-of-function experiments fall into five general categories:

• Determine whether viruses with altered virulence, host range, or transmissibility have changes in antigenicity, or the ability of the virus to react with antibodies. The results of these studies would suggest whether, for example, acquisition of human to human transmissibility would have an impact on protection conferred by a vaccine produced with the current H7N9 virus strain.
• Determine if the H7N9 virus could be adapted to mammals and whether it could produce reassortants with other influenza viruses. The results of this work would provide information on how likely it is that the H7N9 virus would become better adapted to infect humans.
• Isolate mutants of H7N9 virus that are resistant to antiviral drugs. The purpose of these experiments is to identify how drug resistance arises (the mutations can then be monitored in clinical isolates), determine the stability of drug resistant mutants, and whether they confer other properties to the virus.
• Determine the genetic changes that accompany selection of H7N9 viruses that can transmit by aerosol among mammals such as guinea pigs and ferrets. As I have written before, the point of these experiments, in my view, is not to simply identify specific changes that lead to aerosol transmission. Such work provides information on the mechanisms by which viruses can become adapted to aerosol transmission, still an elusive goal.
• Identify changes in H7N9 virus that allow it to become more pathogenic. The results of these experiments provide information on the mechanism of increased pathogenicity and whether it is accompanied by other changes in properties of the virus.

I believe that the proposed gain-of-function experiments are all worth doing. I do not share the concerns of others about the potential dangers associated with gain-of-function experiments: for example the possibility that a virus selected for higher virulence could escape the laboratory and cause a lethal pandemic. Gain-of-function is almost always accompanied by a loss-of-function. For example, the H5N1 viruses that gained the ability to transmit by aerosol among ferrets lost their virulence by this route of infection. When these experiments are done under the proper containment, the likelihood that accidents will happen is extremely small.
All the proposed experiments that would use US funds will have to be reviewed and approved by the Department of Health and Human Services:

The HHS review will consider the acceptability of these experiments in light of potential scientific and public-health benefits as well as biosafety and biosecurity risks, and will identify any additional risk-mitigation measures needed.

While I understand that the authors wish to promote a dialogue on laboratory safety and dual-use research, I question the ultimate value of the communication. Because the letter has been published in two scientific journals, I assume that the target audience of the letter is the scientific community. However, the letter will clearly have coverage in the popular press and I am certain that it will be misunderstood by the general public. I can see the headlines now: “Scientists inform the public that they will continue to make deadly flu viruses”. The controversy about the H5N1 influenza virus transmission studies in ferrets all began with a discussion of the results before the scientific papers had been published. I wonder if the publication of these letters will spark another controversy about gain-of-function research.
In my view, science is best served by the traditional process known to be highly productive: a grant is written to secure funding for proposes experiments, the grant proposal is subject to scientific review by peers, and based on the review the work may or may not be supported. The experiments are done and the results are published. I do not understand why it is necessary to trigger outrage and debate by announcing the intent to do certain types of experiments.
I am curious to know what the many readers of virology blog – scientists and non-scientists – feel about the publication of this letter. Please use the comment field below to express your views on this topic.

http://www.virology.ws/2013/08/07/virologists-plan-influenza-h7n9-gain-of-function-experiments/

[Pathfinder]

Re: Critics Skeptical as Flu Scientists Argue for Controversial H7N9 Studies

New China H7N9 strain gives kick to mutant bird flu research

By Kate Kelland, Health and Science Correspondent
ROTTERDAM, Netherlands | Wed Oct 23, 2013 5:55am EDT

(Reuters) - Dutch scientists hidden away in a top-security laboratory are seeking to create mutant flu viruses, dangerous work designed to prepare the world for a lethal pandemic by beating nature to it.

The idea of engineering viral pathogens to be more deadly than they are already has generated huge controversy, amid fears that such viruses could leak out or fall into the wrong hands.
...
Fouchier, who has already done so-called "gain of function" experiments with another strain of bird flu, H5N1, says we need to get ahead of the game with H7N9 since its pandemic risk would rise "exponentially" if it gained in nature what he aims to give it in the lab - the ability to spread easily among people.
...
So far, however, their drive to find out as much as they can about the genetics of bird flu risks rarely wins these world-renowned virologists thanks. More often, it elicits accusations of putting scientific self-interest over security.

Steven Salzberg, a professor of medicine and biostatistics from John Hopkins School of Medicine, accused them of "an outrageous display of chutzpah" and says Fouchier "is deeply confused about the possible benefits of this work", which Salzberg argues are marginal at best.

"The notion of 'gain of function' research on pathogens is very, very dangerous," he told Reuters.
...
Full text:

http://www.reuters.com/article/2013/10/23/us-birdflu-mutations-science-idUSBRE99M06P20131023