October 23, 2014

Nature editorial – A ripe time for gaining ground

After three years of heated debate, the advocates and critics of gain-of-function research must work to agree on how best to regulate work.

Nature. 2014 Oct 23;514(7523):403. doi: 10.1038/514403a.

“And the revelations over the past few months of serious violations and accidents at some of the leading biosafety containment labs in the United States has burst the hubris that some scientists, and their institutions, have in their perceived ability to work safely with dangerous pathogens.”

October 22, 2014

Meeting of new NSABB. For agenda see here.

Two news reports in Science and Nature written within hours of the meeting.

We learn that “Such GOF studies are "crucial" for the selection of each year's candidate vaccine strain because they help WHO identify the riskiest strains in the wild, Schultz-Cherry said.”

Consultation with two senior flu researchers familiar with the selection process of strains for the annual flu vaccine revealed that they disagree with this statement.

October 17, 2014

The US National Academies announced that they would be holding a workshop on GOF research. 
It will take place at the National Academies of Science building in Washington DC on December 15-16.

October 17, 2014 (Bis)

White House statement on funding new GOF research:
Doing diligence to assess the risks and benefits of life sciences gain-of-function research

A pause in new funding of GOF virus research is implemented. It concerns influenza, SARS and MERS viruses. The document clearly excludes work on natural influenza SARS and MERS viruses. During the time, a review and discussion process is to be initiated so that a considered opinion as to the risks and benefits of GOF virus research can be forged.

It “encourages those currently conducting this type of work – whether federally funded or not – to voluntarily pause their research while risks and benefits are being reassessed.”

October 16, 2014

Improving pandemic influenza risk assessment.
Russell CA, Kasson PM, Donis RO, Riley S, Dunbar J, Rambaut A, Asher J, Burke S, Davis CT, Garten RJ, Gnanakaran S, Hay SI, Herfst S, Lewis NS, Lloyd-Smith JO, Macken CA, Maurer-Stroh S, Neuhaus E, Parrish CR, Pepin KM, Shepard SS, Smith DL, Suarez DL, Trock SC, Widdowson MA, George DB, Lipsitch M, Bloom JD.
Elife. 2014 Oct 16;3:e03883. doi: 10.7554/eLife.03883.

“Abstract 
Assessing the pandemic risk posed by specific non-human influenza A viruses is an important goal in public health research. As influenza virus genome sequencing becomes cheaper, faster, and more readily available, the ability to predict pandemic potential from sequence data could transform pandemic influenza risk assessment capabilities. However, the complexities of the relationships between virus genotype and phenotype make such predictions extremely difficult. The integration of experimental work, computational tool development, and analysis of evolutionary pathways, together with refinements to influenza surveillance, has the potential to transform our ability to assess the risks posed to humans by non-human influenza viruses and lead to improved pandemic preparedness and response.”

Predictions are extremely difficult while the genotype-phenotype relationship (how to understand biological potential from genetic data) is a very tough call.

The conclusion starts with:
“It is currently not possible to predict which non-human influenza A virus will cause the next pandemic. Reducing the impact of the next pandemic will rely on early detection and mitigation strategies that slow the early spread to allow more preparatory work to be done.”

The first sentence is in keeping with what others have said (Morse et al., 2012; Morens et al., 2013; Wain-Hobson 2013). It undermines the claims that GOF research would help with pandemic preparedness. If the next pandemic cannot be predicted, this means that the strain cannot be identified. In turn this means that preventive vaccines and drugs cannot be made. The second sentence is more pragmatic and can be readily adhered to.

The paper is interesting for three authors of this eLife paper have been proponents of GOF influenza research while one has been against.

References
Prediction and prevention of the next pandemic zoonosis.
Morse SS, Mazet JA, Woolhouse M, Parrish CR, Carroll D, Karesh WB, Zambrana-Torrelio C, Lipkin WI, Daszak P.
Lancet. 2012 Dec 1;380(9857):1956-65. doi: 10.1016/S0140-6736(12)61684-5.
http://www.sciencedirect.com/science/article/pii/S0140673612616845

Pandemic influenza viruses--hoping for the road not taken.
Morens DM, Taubenberger JK, Fauci AS.
N Engl J Med. 2013 Jun 20;368(25):2345-8. doi: 10.1056/NEJMp1307009. Epub 2013 Jun 5. 
http://www.nejm.org/doi/full/10.1056/NEJMp1307009

Pandemic influenza viruses: time to recognize our inability to predict the unpredictable and stop dangerous gain-of-function experiments.
Wain-Hobson S.
EMBO Mol Med. 2013 Nov;5(11):1637-41. doi: 10.1002/emmm.201303475. Epub 2013 Oct 24. 
http://embomolmed.embopress.org/content/5/11/1637.long

October 14, 2014

Rules of engagement
Johannes Rath
EMBO Reports doi 10.15252/embr.201439281

A discussion of problems associated with risk-benefit analyses. It is interesting for alternatives to risk-benefit analyses have never been mentioned by scientists familiar with the GOF controversy. It refers to the precautionary and proportionality principles that are widely known and used in other fields.

October 14, 2014 (bis)

A cluster of seven papers on GOF research in the scientific journal mBio came on line. There are three contributions and three replies from the mBio editors and ASM representatives, the publisher of mBio. The ensemble is covered by an overarching editorial:

The apocalypse as a rhetorical device in the influenza virus gain-of-function debate
Arturo Casadevall, Don Howard, Michael J. Imperiale

The authors note that the “central nugget in the controversy is a disagreement on the risks and benefits of such experiments”. It is fair to say that nobody has squarely addressed this duo, so there is agreement. This is quickly morphed into a dichotomy whereby pro-GOF proponents stress the benefits and the anti-GOF group concentrate on the risks. While risk is an important issue it is not the only one. Some opponents of the work have focused on the virology and concluded that the touted benefits were overblown. Others who have not taken explicit stands, or who cannot be considered opponents have argued that predicting a pandemic is extremely difficult, if not possible. For such a discussion, see:

• http://www.nejm.org/doi/full/10.1056/NEJMp1307009
• http://www.sciencemag.org/content/342/6156/310.2.long
• http://www.atsjournals.org/doi/abs/10.1164/rccm.201305-0914ED?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&#.VEQ1I4dAyTc
• http://embomolmed.embopress.org/content/5/11/1637.long