Does H5N1 exist?

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.

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Ideally, this would forestall and, perhaps, reduce the risk of inter-species mutation of said virus, when they migrate to and from human population centers or are eaten with gravy and fixin's at the local Kentucky Fried Chicken.

Hank Barnes

By Hank Barnes (not verified) on 03 Apr 2006 #permalink

I know that the estimable Crichton has written that the theory that germs cause disease is not as proven as people think.

Re: Lanka--I hadn't seen that page before. Pretty incredible:

In the past years, however, he stumbled over a breathtaking fact: Not even ONE of the (medically relevant) viruses has ever been isolated; there is no proof of their existence.

outeast--do you have a link for that, or was it in one of his books? Just curious.

Tara says:

outeast--do you have a link for that, or was it in one of his books? Just curious.

Oh, must have been his book. You know...the one where the world-reknown but somewhat jaded scientist (or two) is whisked off to a remote locale in some exotic destination that was laboriously staged, where he (or was it she or they?) meets a group of nerdy and earnest if somewhat argumenative lab-rats - and when something goes horribly awry they run a gamut of various dangerous obstacles until they are finally saved in the end by their unique technical savvy. They may have lost a team member or two along the way (after they were eaten alive), but that's OK because those characters weren't nice any way.

Oh wait...that's all his books.

Uh-Oh -- the latest break-out is on a German Turkey Farm!!!!.

Sorry, about that, but 15,000 turkeys gotta get slaughtered (do they get eaten anyway?)

Also, the scourge includes 3 cats, a stone marten (what's that?) and a dead buzzard on some dude's balcony in Berlin!

Hank Barnes

By Hank Barnes (not verified) on 05 Apr 2006 #permalink

Ack!!

Now, we see that cats are at risk from spreading the dreaded virus from eating said infected birds.

This is a catastrophic development!

Writes virologist Albert Osterhaus and colleagues at the Erasmus Medical Center in Rotterdam, The Netherlands, along with Peter Roeder of the Food and Agriculture Organization of the United Nations:

"[W]e believe that the potential role of cats should be considered in official guidelines for controlling the spread of H5N1 virus infection," they wrote.

Clearly, the avian bird flu is mutating rapidly (as we speak) into the feline cat flu, the turkey bird flu, the Nigerian ostrich flu, all of which constitutes a clear and present danger to our world zoological societies as well as our treasured pets and some of our Thanksgiving Day meals.

When will this madness end.

Hank Barnes

p.s. In case you live in Europe and own a pussy-cat, you will be relieved to know that the European equivalent of the CDC is on the job and has issued an important press release on the matter.

By Hank Barnes (not verified) on 05 Apr 2006 #permalink

Clearly, the avian bird flu is mutating rapidly (as we speak) into the feline cat flu, the turkey bird flu, the Nigerian ostrich flu, all of which constitutes a clear and present danger to our world zoological societies as well as our treasured pets and some of our Thanksgiving Day meals.

Hank, instead of mocking, perhaps you could see why its ability to infect a wide range of animals (including dogs, tigers, pigs, and leopards, in addition to birds and humans) is a cause for concern among scientists?

Hank, instead of mocking, perhaps you could see why its ability to infect a wide range of animals ... is a cause for concern among scientists?

Well, the problem is that the "scientists" aren't acting real scientific. It sounds like they are fueling a potential panic, going off into 17 different tangents, intending to scare people.

What a joke. How does an avian bird virus spread to all these different animals on 3 different continents in a few weeks?

You discussion above on mumps is an excellent counter-example. Human disease, known etiology, unusual cluster -- in same location. Perfect, let's investigate and figger it out. Perhaps, these folks didn't take the vaccine, perhaps its a new strain, perhaps its a result from the vaccine. Who knows?

But, the avian bird flu, again, is rapidly becoming an international joke.

Hank Barnes

By Hank Barnes (not verified) on 05 Apr 2006 #permalink

What a joke. How does an avian bird virus spread to all these different animals on 3 different continents in a few weeks?

I've discussed this several times in a variety of posts here, Hank--plus, it's not "a few weeks."

You sound like you're agreeing with Crowe that H5N1 doesn't exist--what's your opinion on the actual topic, Hank?

what's your opinion on the actual topic, Hank?

It probably exists, although it'd be nice to actually culture the damn virus, purify it, and take an electronmicrograph of it, so we could see it.

But maybe this has all been done. I just haven't seen it.

As to whether it causes a damn thing, well, color me skeptical. This is a classic case of microbe hunters trying to find a germ to explain a disease -- this time, a disease that doesn't afflict humans in any significant way, but only birds, ostriches, weasels, turkeys and now cats -- over 3 different continents, too!

By Hank Barnes (not verified) on 05 Apr 2006 #permalink

Hank says:

This is a classic case of microbe hunters trying to find a germ to explain a disease -- this time, a disease that doesn't afflict humans in any significant way, but only birds, ostriches, weasels, turkeys and now cats -- over 3 different continents, too!

Depends what you mean by "significant". That it's caused death in at least 100 people is pretty significant in my view. Indeed the numbers afflicted are not large by the standards of most diseases (which I assume is what you mean), but the effect of the disease on humans (i.e. death in about 50% of the known infections although this number may not be exact due to undiagnosed cases) is certainly significant. The only missing ingredient is effective human/human transfer.

That it's caused death in at least 100 people is pretty significant in my view

"Cause" is a pretty strong scientific term. If you were to casually say, for example, 100 kids got autism caused by the thimerasol contained in their vaccines, you'd start a big fight.

So, without googling anything, on what basis do you opine that H5N1 caused the death of 100 people world-wide?

Hank

By Hank Barnes (not verified) on 05 Apr 2006 #permalink

Nice evasion Hank. Reminds me of the time you claimed anthrax didn't cause significant injury. Same old, same old.

Well, can't say I didn't try.

Number of deaths in US (polulation 300 million) from anthrax and H5N1 is about 18 and 0, respectively.

Money quote:

In spite of scientific advances, hundreds of animals still die of anthrax each year in the Great Plains, which attests to the virulence of this organism. However, US public health records show only 18 cases of inhalational disease in human beings during the entire 20th century, with the last case reported in 1976.

Feel free to worry about these things all you want:)

However, in 10 years, when you're still a broke, struggling pseudo-scientist, you will wonder whether you shoulda paid a little more mind that old wise geezer, Hank:)

Hank Barnes

By Hank Barnes (not verified) on 05 Apr 2006 #permalink

Sorry Hank. I'm not struggling, broke nor am I a "pseudo-scientist".

And I see nothing wise in your posts. No doubt because there is no wisdom to be found there.

I grant that you may be a geezer though. You would know better than I.

I find it so odd that so many people are trying to deny the existance of a virus. I disagree with the paper and I agree with Tara's comments hers make more sense. I am an undergrad and not up to speed on all of the technology but I really don't understand what the benefit of denying it is. I also don't get those whe reject the germ theory of disease altogether. For example on Lanka's website he said the image of the Ebola virus was never isolated. Tara you wrote a book on ebola have you ever seen the virus? I imagine you have.

For those who deny HIV exists or causes AIDS how can they account for all those who died before the invention of antivirals? Or how they died from the same ailments that those who took AZT did? Since people with HIV died from AIDS prior to antivirals I hardly see how one could say that the antivirals are the cause of death. Not to mention they have extended the average lifespan and the virus has become resistant to some of the meds proving it mutated. So is AZT becoming resistant to other drugs or itself? I doubt it. Maybe I am thinking to simplisticlly but it doesn't seem logical. Am I wrong?

As for H5N1 I realize it has not mutated to infect humans reliably yet but that doesn't mean it never will. I choose to trust the scientists. I know ignorance is bliss but I prefer to be informed and get comfort knowing we are trying to find out more about it. Even if it isn't the next pandemic it still gives us more knowledger of the flu virus overall and will help when the big one does hit.

Laura,

I've never done any experiments with Ebola, so I've not seen live virus. Lanka's assertions are so absurd I don't even know where to start addressing them. I mean, his first assertion that because some are colored, they're fraud--apparently he doesn't realize that even EMs can be enhanced (take a look at this colorization, for example).

Regarding HIV/AIDS, you may want to take a look at some of the comments to these posts--many who deny that HIV causes AIDS have discussed it themselves here.

Re: H5N1--exactly. Whether it is or isn't the "next big one," we'll benefit from the knowledge gained about it and further our understanding of pandemic influenza.

Duesberg's email about bird flu seems to echo the the anti-germ theorists.

The reason why the Flu was so successful in 1918 was primarily the "terrain", namely the millions of immuno-deficient hosts and hostesses starved and stressed by 4 years of war.

Duesberg also seems to get a lot of things wrong about influenza which is surprising after reading some of his early classic papers on the virus.

Please correct me if I'm wrong but the 1918 flu is not believed to have been a new recombinant but an avian flu that made the jump to infect humans.

Seasonal variants of the flu are due to genetic drift not genetic shift involving recombination events.

Duesberg also goes on about how real epidemics behave. Somehow I don't think viruses pay much attention to his ideas about epidemiology.

In my view the situation is similar to living in a town on the side of a volcano. The volcano hasn't erupted for 200 years but records show that on average there has been an eruption every 200 years. The chances of an eruption this year are small the probability that at some time it will erupt again approach 100%.

Given this it would be insane not to extensively research the volcano and develop an emergency evacuation plan.

There will undoubtably be "skeptics" that complain about wasted research dollars and unfounded scaremongering if no eruption occurrs that year.

By Chris Noble (not verified) on 06 Apr 2006 #permalink

Please correct me if I'm wrong but the 1918 flu is not believed to have been a new recombinant but an avian flu that made the jump to infect humans.

You're correct.

Seasonal variants of the flu are due to genetic drift not genetic shift involving recombination events.

Correct again.

I was going to write up a response to the Duesberg email when it was published, but I was just too burned out. And I like the volcano analogy.

I checked the number of citations for Duesberg's 1968 paper on the RNAs of influenza virus.

It's been cited 159 times.

The last two citations are by Bialy and Duesberg himself.

Duesberg attempts to use influenza as a model to support his aneuploidy theory.

Explaining the high mutation rates of cancer cells to drug and multidrug resistance by chromosome reassortments that are catalyzed by aneuploidy

"The high mutation rates of influenza virus via reassortments of subgenomic RNA segments (54, 55) versus the extremely low mutation rates of viruses with singular genomic RNAs (56) are an exact precedent for our model."

References 54 and 55 are his papers
54. Duesberg, P. H. (1968) Proc. Natl. Acad. Sci. USA 59, 930-937
55. Duesberg, P. H. (1969) J. Mol. Biol. 42, 485-499

The reference for "extremely low mutation rates of viruses with singular genomic RNAs" is Fenner's book from 1974. It seems that Duesberg cites this book whenever he needs to pull a factoid out of thin air.

56. Fenner, F. , McAuslan, B. R. , Mims, C. A. , Sambrook, J. & White, D. O. (1974) The Biology of Animal Viruses (Academic, New York).

Hang on what about HIV, poliovirus, VSV and FMDV? Extremely low mutation rates?

Maybe this explains Duesberg's overemphasis of recombination in influenza.

By Chris Noble (not verified) on 07 Apr 2006 #permalink

Tara,

I think you should admonish these "AIDS zealots" about hijacking unrelated threads:)

Hank

By Hank Barnes (not verified) on 07 Apr 2006 #permalink

Hank,
Think before you post.
If you go back to the top and read you'll find the thread has been placed in the AIDS/HIV category.
The vast majority of posts including my own have concerned people that deny/rethink the pathogenicity or existence of viruses other than HIV such as influenza. As Tara pointed out there is often an overlap between the HIV "rethinkers" and the influenza "rethinkers".

Some HIV "rethinkers" also "rethink" polio.

Polio-Rethink

This one is a bit contorted because she "rethinks" poliovirus pathogenicity but claims that SV40 does cause disease.

At least Stefan Lanka is consistent in his "rethinking"

By Chris Noble (not verified) on 07 Apr 2006 #permalink

Hank, why don't you start your own blog and do this?

Dave S,

Why not butt out?

Hank B

By Hank Barnes (not verified) on 10 Apr 2006 #permalink

Now that wouldn't be the blogging spirit, would it Hank?

Of course you are free to comment or not to me as you see fit. I'm fine either way.

Of course I saw it--Harvey still spams my email with links, even if he's stopped doing it on the board.

Of course I saw it--Harvey still spams my email with links, even if he's stopped doing it on the board.

Well, I've never e-mailed you, and don't know what all e-mails you get.

But, differences aside, Don't y'all pretty much agree with him that the War in Iraq is an unmitigated disaster?

Sounds like room for common ground or, at the least, an interesting thread discussion. War on AIDS/War on Iraq, similar dynamic, similar poor results -- something like that.

Hank Barnes

By Hank Barnes (not verified) on 10 Apr 2006 #permalink