On 2014 Nov 22, Arturo Casadevall commented:

There is little that has not been said before in the most recent post by Joshua L. Cherry and thus we do not see the need for additional responses. Interested readers are referred to the original article and the comments above.

On 2014 Nov 20, Joshua L Cherry commented:

The reply above continues with the tactic that I criticized. It embraces and gives the benefit of the doubt to every argument in favor of the GOF experiments, ignores well-known counterarguments, and on this basis declares the other side's rhetoric to be misleading as though this were an additional pro-GOF argument rather than a corollary of the pro-GOF position. I will refrain from engaging in a rehash of arguments that should be familiar, but two specific points deserve brief mention. First, the reply glosses over the differences between laboratory engineered/selected transmission in ferrets and naturally-occurring human pandemic. Second, it makes a logical leap from somebody's intent to act on information to that information having value, as though nobody ever acted on valueless information.

On 2014 Nov 11, Arturo Casadevall commented:

We fear that our position has been mischaracterized in Joshua L. Cherry’s latest comment. For example, nowhere in our article or response do we say or imply that “GOF advocates are right and GOF opponents are wrong”. Although we believe that everyone is entitled to their own opinion, we also think that Joshua L. Cherry most recent comments merit an additional response.

First, we note that the correspondent is in fact invoking the ‘apocalyptic fallacy’ in his opposition to GOF experiments, something that we cautioned against in our editorial. The ‘apocalyptic fallacy’ arises when one side uses the apocalypse to inspire fear without factual data in the hope of convincing others of the correctness of their position. In our prior comment we chided both sides for using apocalyptic arguments but noted that that fallacy applied primarily to the anti-GOF camp because their appeals to fear were based on hypothetical accidents and scenarios, while the pro-GOF camp appeals to risk were based on known past epidemics. In his response Joshua L. Cherry mentions ‘reports of frequent laboratory accidents with infectious agents’ and ‘the return of H1N1 influenza from the laboratory in 1977’ to argue that anti-GOF proponents were in fact justified in their use of apocalyptic arguments. However, there is a problem here. First, while we are the first to agree that there is a need for utmost safety in these experiments, we note that it is guilt by association to aggregate GOF experiments with recent disparate laboratory accidents that range from a shipping error with H5N1 samples to incompletely sterilizing Bacillus anthracis spores. Second, the return of H1N1 1977 has been presumed by some to reflect the escape of that strain from a laboratory, but this has not been proven: that explanation for the reemergence of H1N1 remains a presumption that is not universally accepted among influenza experts. Thus, it is not reasonable to argue that these recent accidents should lead us to fear accidental pandemics from GOF experiments, whereas it is reasonable to worry that naturally occurring mutations in the H5N1 virus could lead to a global pandemic based upon historical evidence of similar such occurrences. Determining the possibility of precisely such events is the point of GOF experiments.

Second, Joshua L. Cherry also states that some ‘would question the likelihood of a natural H5N1 pandemic, and whether GOF experiments tell us much about this likelihood’. I think we can all agree that GOF experiments have shown that H5N1 has the potential to become mammalian transmissible and that that information is new. Since prior to those experiments there was debate among experts in the field as to whether this was even possible, then we must disagree with the statement that GOF do not tell us ‘much about this likelihood’. In fact, those experiments have shown unequivocally that the H5N1 has the biological potential to become mammalian transmissible and that fact alone implies a greater threat from a natural pandemic that we knew previously. At the recent meeting of the National Science Advisory Board for Biosecurity (http://osp.od.nih.gov/office-biotechnology-activities/biosecurity/nsabb), evidence was presented that information obtained from GOF experiments was in fact being used in strain surveillance and vaccine development. Hence, the argument from the pro-GOF camp that this information is in fact useful for preventing a pandemic is more than ‘purely theoretical’.

We agree with Joshua L. Cherry in his concerns about safety. In an earlier essay we took both sides to task for framing the debate in simplistic terms (PMID: 25085113) and we urge the need for careful analysis, rigorous thought and the avoidance of extrapolation and interpretation in framing arguments for and against this type of experimental work during the ongoing debate.

On 2014 Nov 04, Joshua L Cherry commented:

The response above seeks to justify criticizing "apocalyptic rhetoric" from one side of the debate while ignoring the same sort of rhetoric from the other side. The justification offered is, more or less, that GOF advocates are right and GOF opponents are wrong, so that this rhetoric is justifiable from one side but fallacious when used by the other. A more specific case is, of course, presented, but it is an uncritical summary of pro-GOF arguments that ignores the well-known arguments of critics. The response and the editorial are of no help in deciding which side is right. The editorial misleadingly presents a view that depends logically on a pro-GOF position as though it is an argument that supports a pro-GOF position.

As alluded to in my original comment, much of the GOF debate is about whether the experiments are more likely to cause a pandemic than prevent one. Casadavall appears to have reached a particular conclusion, but critics of GOF experiments would obviously dispute it. They would question the likelihood of a natural H5N1 pandemic, and whether GOF experiments tell us much about this likelihood. Critically, they would question the value of GOF experiments for prevention of such a pandemic, a value that remains purely hypothetical. (In contrast, refraining from performing a GOF experiment assures that this experiment produces no pandemic.) They would point to the return of H1N1 influenza from the laboratory in 1977, and to reports of frequent laboratory accidents with infectious agents, to refute the claim that their fear is purely theoretical.

Would the viruses produced by the H5N1 GOF experiments, if released, be capable of causing human pandemics? If so, then there is a real danger to consider. If not, then these experiments do not provide strong evidence for the likelihood of a natural pandemic, and their general relevance to human pandemics is dubious.

On 2014 Oct 29, Arturo Casadevall commented:

We agree with Joshua L. Cherry that both the pro- and anti-GOF camps have invoked the apocalypse. While pro- and anti-GOF camps invoke the apocalypse in their arguments and emphasize the benefits and risk of such work, respectively, both appeal to fear. However, when it comes to fear there are some significant differences. The fear of naturally caused pandemic comparable to 1918 finds support in the historical record and the available scientific information on influenza virus, including that generated by GOF experiments showing that it has the capacity for mammalian transmissibility. In contrast, fears of a pandemic from resulting from a mishap with a GOF-type of experiment remain a theoretical possibility. We note that such experiments are currently done with a high level of bio-containment and biosafety. Hence, the ‘apocalyptic fallacy’ applies only to use of the apocalypse as a rhetorical device by the anti-GOF camp for the apocalypse is invoked with a vacuum of evidence for this presumed catastrophic event. Given the differences in historically- and theoretically-based fears we do not feel that the use of the apocalypse by pro- and anti-GOF camps as a rhetorical device is comparable.

On 2014 Oct 27, Joshua L Cherry commented:

From the title of this editorial I expected a critique of proponents of controversial gain-of-function (GOF) experiments. Perversely, it levels criticism only at the other side of the debate. According to the editorial, opponents of these experiments have used the possibility of a global pandemic (caused by laboratory-produced virus) as a rhetorical device that is so frightening that it trumps reason. It ignores the fact that proponents of these experiments have always invoked the dangers of a deadly (natural) global pandemic to argue that the experiments are critical for human health.

"In the GOF debate," the editorial states, "the repeated mention of the likelihood of a pandemic is an apocalyptic rhetorical device." Perhaps it is, but who in the debate uses this device? The proponents of GOF experiments clearly do. The specter of a devastating pandemic is central, for example, to Yoshihiro Kawaoka's defense of his experiments. He tells us of the frighteningly high rate of death among confirmed H5N1 infections, and writes that

"Within the past century, 'Spanish' influenza, which stemmed from a virus of avian origin, killed between 20 million and 50 million people. Because H5N1 mutations that confer transmissibility in mammals may emerge in nature, I believe that it would be irresponsible not to study the underlying mechanisms."

Similarly, an Erasmus Medical Center press release about work by Ron Fouchier and colleagues bears the headline "Avian influenza could evolve into dangerous human virus", tells us that "The discovery is important as it could prevent a severe pandemic from occurring", and suggests a 60% death rate for H5N1 infection. A piece by Fouchier and others cites the same death rate data and suggests that the toll of an H5N1 pandemic would exceed that of the H1N1 pandemic of 1918. Many additional examples could be mentioned. This side of the debate repeatedly invokes the danger of a deadly pandemic, and presents GOF experiments as necessary for our rescue from this danger.

(It should be noted that the high death rate for H5N1 infection has been called into question. Some defenders of GOF experiments have used diminished estimates of lethality to downplay the danger of the laboratory-produced viruses, usually failing to note that they would also weaken the original argument for the importance of the experiments.)

It was quite reasonable for critics to ask whether GOF experiments are more likely to cause a global pandemic than prevent one. The critics' discussions of pandemics have generally been no more apocalyptic than those of the proponents, such as those referred to above. The editorial's accusations concerning misleading rhetoric are at best one-sided, and arguably are pointed in exactly the wrong direction.

On 2014 Oct 27, Joshua L Cherry commented:

From the title of this editorial I expected a critique of proponents of controversial gain-of-function (GOF) experiments. Perversely, it levels criticism only at the other side of the debate. According to the editorial, opponents of these experiments have used the possibility of a global pandemic (caused by laboratory-produced virus) as a rhetorical device that is so frightening that it trumps reason. It ignores the fact that proponents of these experiments have always invoked the dangers of a deadly (natural) global pandemic to argue that the experiments are critical for human health.

"In the GOF debate," the editorial states, "the repeated mention of the likelihood of a pandemic is an apocalyptic rhetorical device." Perhaps it is, but who in the debate uses this device? The proponents of GOF experiments clearly do. The specter of a devastating pandemic is central, for example, to Yoshihiro Kawaoka's defense of his experiments. He tells us of the frighteningly high rate of death among confirmed H5N1 infections, and writes that

"Within the past century, 'Spanish' influenza, which stemmed from a virus of avian origin, killed between 20 million and 50 million people. Because H5N1 mutations that confer transmissibility in mammals may emerge in nature, I believe that it would be irresponsible not to study the underlying mechanisms."

Similarly, an Erasmus Medical Center press release about work by Ron Fouchier and colleagues bears the headline "Avian influenza could evolve into dangerous human virus", tells us that "The discovery is important as it could prevent a severe pandemic from occurring", and suggests a 60% death rate for H5N1 infection. A piece by Fouchier and others cites the same death rate data and suggests that the toll of an H5N1 pandemic would exceed that of the H1N1 pandemic of 1918. Many additional examples could be mentioned. This side of the debate repeatedly invokes the danger of a deadly pandemic, and presents GOF experiments as necessary for our rescue from this danger.

(It should be noted that the high death rate for H5N1 infection has been called into question. Some defenders of GOF experiments have used diminished estimates of lethality to downplay the danger of the laboratory-produced viruses, usually failing to note that they would also weaken the original argument for the importance of the experiments.)

It was quite reasonable for critics to ask whether GOF experiments are more likely to cause a global pandemic than prevent one. The critics' discussions of pandemics have generally been no more apocalyptic than those of the proponents, such as those referred to above. The editorial's accusations concerning misleading rhetoric are at best one-sided, and arguably are pointed in exactly the wrong direction.

On 2014 Oct 29, Arturo Casadevall commented:

We agree with Joshua L. Cherry that both the pro- and anti-GOF camps have invoked the apocalypse. While pro- and anti-GOF camps invoke the apocalypse in their arguments and emphasize the benefits and risk of such work, respectively, both appeal to fear. However, when it comes to fear there are some significant differences. The fear of naturally caused pandemic comparable to 1918 finds support in the historical record and the available scientific information on influenza virus, including that generated by GOF experiments showing that it has the capacity for mammalian transmissibility. In contrast, fears of a pandemic from resulting from a mishap with a GOF-type of experiment remain a theoretical possibility. We note that such experiments are currently done with a high level of bio-containment and biosafety. Hence, the ‘apocalyptic fallacy’ applies only to use of the apocalypse as a rhetorical device by the anti-GOF camp for the apocalypse is invoked with a vacuum of evidence for this presumed catastrophic event. Given the differences in historically- and theoretically-based fears we do not feel that the use of the apocalypse by pro- and anti-GOF camps as a rhetorical device is comparable.