Occasionally when discussing HIV and folks like Duesberg, etc., I’ll get a question along the lines of, “do these people deny the entire germ theory of disease?” Certainly Duesberg has written that he doesn’t believe HPV causes cervical cancer, or prions cause kuru, for example, and many of the arguments they make (expecting 100% attack rate in people who are HIV-positive, meeting Koch’s postulates as initially outlined, even though no infectious agent does, etc.) would, if applied universally, not allow us to attribute causation to any infectious agent, not just HIV. A recent paper by David Crowe in Medical Hypotheses (“Avian flu virus H5N1: No proof for existence, pathogenicity, or pandemic potential; non-“H5N1″ causation omitted”) shows at least that he’s consistent in his application of skepticism. More after the break…
From their paper, they ask 4 questions:
1. Does H5N1 exist?
2. Is it pathogenic to animals?
3. Is it transmissible and pathogenic to humans, and does it have pandemic potential?
4. Have other causes for observed disease been studied?
Their objections to the literature they’re provided to answer their questions are as follow. For 1, they’re referred to the fact that infectious clones have been made of H5N1 entirely from molecular genetics–that is, the squence of the virus is made from scratch via PCR, added to cell culture, and infectious virus can be isolated (even though no live H5N1 virus was added). They argue this doesn’t prove the existence of the virus, stating: “However, PCR cannot be used to identify viruses which have not been previously sequenced.” I know Crowe has read this blog before and left comments, so perhaps he can elaborate on that statement, because it makes little sense to me. H5N1 has been previously sequenced, and even during the initial isolation primers which are conserved (that is, they bind to sequences that are identical or similar in all influenza viruses) can be used for PCR.
They also received a response from Robert Webster, who “informed [them] that stock viruses ‘are classified as select agents’ and ‘we are not at liberty to release this information'” (regarding “the composition of the stock virus.”) As such, Crowe and his co-author, Torsten Engelbrecht, “cannot accept that stock virus is pure and fully characterized.”
For 2, again we come to the problem of animal models. In one of the papers referenced, the mouse was used as the experimental animal model. Crowe and Engelbrecht object, saying:
Papers describe the use of natural routes, but disease was only achieved with extraordinary concentrations, up to 10 million EID per animal. None of the experiments used controls or blinding. The Science paper is highly abstract molecular science, employing elevated concentrations of chimeric variants.
First, I assume they mean PFU (“plaque-forming units,” a typical measure of virus titer) instead of “EID”. Second, this high titer of virus infecting mice is pretty typical–mice aren’t generally infected by influenza, and even with “normal” influenza viruses, high viral doses are often used. (There is at least one influenza virus that’s been mouse-adapted by multiple passages through a mouse). So no surprise here to influenza virologists.
Regarding controls or “blinding.” This isn’t a clinical trial. One goal in any animal study is to use as few animals as possible to get your results, and animal studies aren’t often “blinded” in the way drug studies are. (For one: animals ain’t gonna tell you they’re feeling better even if they’re on a “placebo” such as PBS [Phosphate Buffered Saline, a typical benign control substance used], and the attitude of the researcher isn’t going to affect if they die or not). And indeed, no such PBS (or distilled water, etc.) controls were used–but in both studies, a variety of different influenza viruses were tested, each containing different mutations. As such, the goal was to compare the virulence amongst them and see which ones were more efficient killers–again, a common practice in animal studies.
For question 3, they again decry “anecdotal” studies (case reports), and the fact that in one, “The scientists found evidence of aspergillosis, and the boy was treated with toxic agents (broad-spectrum antimicrobial and antivirals) before he died.” They also suggest this it is contradictory to warn of the pandemic potential of this virus, when elsewhere scientists have stated: “There is no scientific forecasting method that can evaluate the possibility that an influenza virus induces a new pandemic.” And indeed, there’s not. We simply have too few data points to accurately predict what influenza viruses may have pandemic potential, and there are very few people who’d stake their career on H5N1 being the next pandemic. But at the same time, as I’ve mentioned, it’s just a strange virus capable of infecting a much wider variety of species than any other influenza virus known–and it’s deadly to those infected. It’s certainly within the realm of possibility that it could become a pandemic–and hence, warning of the pandemic potential. This is not a contradiction.
Finally, regarding question 4:
Question 4 (non-“H5N1” causation). Neither the Subbarao et al study nor the FLI references consider reasonable, competing theories for disease causation, e.g., environmental and pharmaceutical factors.
Is H5N1 also caused by poppers, I wonder? Or Tamiflu?
So, their conclusion? Wanna guess?
Our analysis shows the papers do not satisfy our four basic questions. Claims of H5N1 pathogenicity and pandemic potential need to be challenged further.
Though I disagree with the first statement–I think H5N1 pathogenicity has been pretty well established–I agree with the latter. I’d wager most people do, and it’s something that’s re-assessed with every new piece of information. Will it ever become human-to-human transmissible–something that’s necessary for a pandemic? Some scientists argue that because it’s not done so yet, it won’t. I think that’s a bit overconfident, personally, but whether it gains the ability or not, the knowledge we receive from watching this one closely will help us understand–and ideally predict–future threats.