There has been much in the news lately regarding two studies in ferrets that resulted in a version of the influenza virus H5N1 that infected and supposedly killed other ferrets. The fear being that if such know how was easily available, then terrorists could make the virus and unleash it on humanity or the virus might get out of the lab leading to the same result. Cross-species virus transmission, sloppy lab personnel, and the threat of terrorism should concern us all but there is another side to the ferret story.
The ferret is held to be the best model for human influenza. This is because the animal uses at least some of the same receptors to recognize the virus, some of the same strains infect humans and ferrets, and the symptoms experienced by ferrets are similar to those experienced by humans. But based on the fact that ferrets and humans are evolved living complex systems, these similarities should not be enough to suggest to anyone that results from ferret studies are likely to predict human response. Such meager similarities between complex systems could result in nothing more than correlations that do not share mechanisms. There would be no causal relationships between the species. Such has been proven empirically many times with animal models. An article by Cohen (Cohen 2012) in Science says essentially the same thing.
Cohen quotes Ron Fouchier, a virologist and coauthor of one of the studies as saying that in many ways the ferret model “is pretty shaky . . . We always have to be really, really critical about what we do. We cannot say [because] it transmitted in ferrets, it must be transmissible in humans.” Fouchier goes on to say that the ferret model can be misleading.
Cohen writes: “Few specifics are known about the work in either lab, but Kawaoka [coauthor of the other ferret paper] revealed an unexpected detail in a commentary online in Nature on 25 January, underscoring the confusion that swirls around these findings and the ferret model: His virus didn't kill the animals. So if nature or bioterrorists created a similar virus—or if it accidentally escaped from the lab, as some fear—does the ferret model predict it would have little chance of causing mayhem in humans? ‘Severity of infection, including lethality, is a complex biologic phenomenon involving pre-existing immunity to pathogens, individual susceptibility, pathogen dose, etc.,’ said Kawaoka in an e-mail reply to Science. ‘With all of these variables it is impossible to declaratively answer this question.’ ”
This is in part why the medical community overreacted to the threat of H1N1 in 2009—the ferret studies were misleading in that they caused scientists to think the virus would be more lethal than previous versions. Cohen: “In another published experiment, the Fouchier group went a step further. They compared pH1N1, seasonal H1N1, and H5N1 in ferrets and found that the pandemic strain was indeed more lethal than seasonal H1N1 (see graph) and less than H5N1. Fouchier now says they made ‘a big mistake’ by concluding that ‘pandemic H1N1 reaches further down the airway than seasonal flu, and, therefore, it's likely to become a severe pandemic.’ ”
Cohen goes on to list more differences between humans and ferrets that confound inter-species extrapolation. I suggest everyone read the entire article.
The ferret studies are yet another example of scientists failing to place their animal model-based results into the context of complexity science. Monozygotic twins do not always respond similarly to drugs and disease yet people whose income and ego are dependent upon animal models want society to believe that animal models are vital. They state or imply that curing cancer in rodents means that the same treatment will also work in humans. When said cure does not work out, they backtrack and say that all they do is basic research and hence should not be held to the predictive standard. They are just studying and discovering fun facts about the living universe. In instances where one strain or species reacts similarly to humans the animal modelers announce to the world that this proves their research is predictive for humans. The duplicity of a community that supposedly is searching for truth astounds.
From my perspective, the above was summarized in principle by Jonah Lehrer writing in Wired: “Although the scientific process tries to makes sense of problems by isolating every variable, reality doesn’t work like that. Instead, we live in a world in which everything is knotted together, an impregnable tangle of causes and effects. Even when a system is dissected into its basic parts, those parts are still influenced by a whirligig of forces we can’t understand or haven’t considered or don’t think matter.”
People applying for NIH grants involving animal models should be forced to take a test on the fundamentals of complexity science. When they fail, they should be removed from the grant pool. The same should apply to the members of the committees that award the grants. If the people deciding where taxpayer money goes are incompetent, then society should not expect informed decisions on life and death matters.
Cohen, Jon. 2012. The Limits of Avian Flu Studies in Ferrets. Science 335 (6068):512-513.