Sample size considerations for one-to-one animal transmission studies of the influenza A viruses. 
Nishiura H, Yen H-L, Cowling BJ (2013) 
PLoS ONE 8(1): e55358. doi:10.1371/journal.pone.0055358

A very detailed scientific analysis of the number of ferrets needed to generate statistically significant results. 

“The most important caveat in the present study in relation to the common practice is that n = 3 is not enough to show a significant difference as well as Ro>1 for one-sample comparison while it can demonstrate Ro>0. Moreover, comparing a group with n = 3 against a reference group with the same sample size does not allow researchers to demonstrate any significant difference in the transmissibility between two sample groups. If two samples have to be compared, n = 4 would be regarded as minimum, and moreover, k = n for n = 4 and k = n or k= n-1 for n = 5, respectively, would have to be required along with the absence of infected pairs in the control group.”

More prosaically, this says that in an influenza A virus transmission experiment the use of three pairs of ferrets (infected donor and uninfected receiver animal, n = 3) is enough to demonstrate transmission (Ro>0) but not to know whether the virus would spread (Ro>1). If a GOF flu virus is to be compared to a another, say a human influenza virus, a minimum of four pairs of ferrets (n = 4) with all four receiver ferrets becoming infected (k = 4, and hence k = n), would be necessary. If five ferrets were used (n = 5) then a significant result would be obtained if 4 of 5 receiver ferrets were infected (k = n-1 for n = 5).

As n=2 or 3 in the Fouchier and Kawaoka experiments little can be deduced except to say that the viruses were transmitted. Nothing can be said about their potential to spread. In short the conclusions are qualitative.

January 3, 2013

Safety survey reveals lab risks
Van Noorden R.
Nature. 2013 Jan 3;493(7430):9-10. doi: 10.1038/493009a.

The study, which was partly financed by Nature, shows that scientists are overconfident and systematically underestimate risk. This is why scientists need help form outside in assessing risk.

June 7, 2012

Science versus spin: how Ron Fouchier and other scientists miscommunicated about the bioengineered bird flu controversy

For a lucid history of the early phase of the GOF H5N1 flu virus see the story by Peter Sandman, a risk communicator. The contradictions between the early and late versions of the “Fouchier” experiment by Fouchier himself are indeed worrying and highly irregular. This is not representative of what happens in the vast majority of labs.

June 22, 2012

Airborne transmission of influenza A/H5N1 virus between ferrets.

Herfst S1, Schrauwen EJ, Linster M, Chutinimitkul S, de Wit E, Munster VJ, Sorrell EM, Bestebroer TM, Burke DF, Smith DJ, Rimmelzwaan GF, Osterhaus AD, Fouchier RA.

Comment to be posted.

May 2, 2012

Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets

Imai M1, Watanabe T, Hatta M, Das SC, Ozawa M, Shinya K, Zhong G, Hanson A, Katsura H, Watanabe S, Li C, Kawakami E, Yamada S, Kiso M, Suzuki Y, Maher EA, Neumann G, Kawaoka Y.

Comment to be posted.

February 9, 2012

Nature editorial - Facing up to flu
The potential for mutant-flu research to improve public health any time soon has been exaggerated. Timely production of sufficient vaccine remains the biggest challenge.
Nature. 2012 Feb 8;482(7384):131. doi: 10.1038/482131a

“The fact that the risks seem to far outweigh the public-health benefits of the research, at least in the short term, means that there is no need to rush headlong into an expansion of the work. Rather, regulators and flu researchers must take whatever time they need to decide the best way for such work to proceed safely.”

Agreed. However, 2012 and 2013 were essentially wasted years in terms of discussion. Only following what has been called black biosafety year 2014 did anything change.

February 9, 2012

Lab flu may not aid vaccines
Game-changing vaccine technologies are needed to strengthen global pandemic defences.
Butler D
Nature. 2012 Feb 8;482(7384):142-3. doi: 10.1038/482142a.

“Now that laboratory studies have yielded a glimpse of H5N1 flu viruses that might spread rapidly in humans and cause a devastating pandemic, vaccine makers will be better prepared if one develops. Or will they?

It is an appealing argument, and one that some scientists have made in recent weeks as controversy has swirled over two experiments that created H5N1 strains able to spread in mammals. But most experts contacted by Nature say that the work is unlikely to speed up the vaccine response in a pandemic. Jeremy Farrar, director of the Oxford University Clinical Research Unit in Ho Chi Minh City, Vietnam, calls such expectations “a red herring”.”


“But many agree with Richard Webby, a flu virologist at the St. Jude Children’s Research Hospital in Memphis, Tennessee, who says, “I think the research is important, but not for vaccine purposes.””


“Nobody is going to ramp up production of a pre-pandemic vaccine based on these two experimental viruses,” says Webby. “That’s 100% sure.” Ab Osterhaus, a co-author on Fouchier’s paper also at Erasmus, agrees that industry will wait on the actual pandemic strain for any major roll-out, but says that screening for mutations could detect variants that could be used to make new seed strains, which might help with the initial response.”


“Bram Palache, the global government affairs director for vaccines at Abbott Biologicals in Weesp, the Netherlands, says that industry will not switch its limited plant capacity from making the seasonal flu vaccines to making a pandemic vaccine until a human pandemic has actually emerged and government orders are in hand. And once a pandemic is under way, neither industry nor governments will be content to use existing pre-pandemic vaccines — they will insist on one matched to the pandemic strain itself, says Palache.

Given the current technology and infrastructure, developing and manufacturing such a vaccine will take many months. Now that the mutant-flu studies have suggested that an H5N1 pandemic is a real possibility, health authorities should focus on shortening that timescale, says Farrar. He urges much greater investment in better and faster vaccine technologies, including universal flu vaccines — because H5N1 is far from the only possible pandemic strain.”

Making vaccines was one of the claims for doing GOF research work. The above comments are pretty clear. Move on.