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Of mice and men

Posted on Friday, September 21, 2007 at 09:48AM by Registered CommenterScott McPherson in | CommentsPost a Comment

biocryst%20logo.gifA little over a year ago, The Centers for Disease Control and Prevention (CDC) reported with breathless excitement the results of an experiment.  The CDC used ferrets to try and produce a reassortant H5N1 virus.  Under controlled conditions, and using multiple ferret subjects, the CDC was unable to kick-start a reassortant H5N1/H3N2 virus.  Thus, the CDC concluded, it was difficult to imagine such a reassortant occurring naturally.  I cannot tell you why they did not try an H7 or H1 virus.  You'll have to ask them.  The point was, under controlled conditions using the best genetic engineering techniques, they could not produce a reassortant in ferrets.

As one can imagine, the Mainstream Media (MSM) seized upon this as some sort of de facto proof a pandemic could not occur.  It was also seized upon by such people as H5N1 debunker and Amazing Randi wannabe Michael Fumento.  Fumento, who excels at recycling the same anti-bird flu message over and over again, cites this study as a major reason why he thinks H5N1 is much ado about nothing.

In May of this year, BioCryst Pharmaceuticals of Birmingham, Alabama, ballyhooed a breakthrough with its injectible antiviral Peramivir. The study was conducted under the auspices of St. Jude Childrens Research Hospital,  The press release (http://www.medicalnewstoday.com/articles/69680.php)  trumpeted:

A survival rate of 40% to 60% was observed in mice treated with one or two injections of peramivir; however, 100% survival of mice was achieved by two injections of peramivir on the first day followed by once-daily administration for 7 days. The longer duration of peramivir treatment also prevented viral replication in the tissues of the lungs, brain and spleen of the mice at the 3, 6, and 9 day post-inoculation time points.

Another St. Jude study, conducted by Dr. Richard Webby, showed a potential life-saving advantage of today's existing trivalent vaccine in an "N1" pandemic.  Webby's study theorized that the neuraminidase in H5N1 may not have drifted very far from today's H1N1 vaccine, and therefore a modicum of life-saving immunity may be found in people who either had experienced an H1N1 infection, or who had faithfully received a seasonal annual flu shot.  The tests were successful.

Successful, with one important distinction.  Webby remarked to me last year, qualifying the results of his study, "There's the whole mice to men thing," meaning that he personally understood that tests on mice are simply a stepping stone on the road to tests on humans, but they are far from being anything more than promising.

I mention this because BioCryst was the deliverer of bad news Wednesday.  Phase II human trials of its Peramivir injectible neuraminidase antiviral were not statistically any better in human tests than the placebo.  BioCryst postulates that such issues as the subjects' BMI (body mass index) and needle length were factors, but the press is reporting nonetheless that the tests did not go well at all. headlines such as "Flu Drug Misses Goal in Mid-Stage Study" (http://www.clinicaspace.com/news_story.aspx?NewsEntityId=70432) abound.  It is difficult to imagine using calipers to measure body fat and requiring inch-and-a-half needles for injections during a pandemic, but you see where this is going.  It's back to the drawing board for BioCryst.

Trying to create a bioengineered pandemic virus using ferrets has, mercifully, failed.  Big deal: This should show that terrorists cannot just set out and create a pandemic influenza virus.  Tinkering with this stuff in a lab gives me the willies, anyway.  Nor can tests on rodents show anything more than a road map toward further research and experimentation involving humans.  Influenza continues to confound even those who have dedicated their entire lives toward solving its riddles.  And for every innovation or breakthrough, there are several thousand new questions that must be answered and several steps carefully taken backward.

The simple fact is, we know as much about influenza as we did ten to twenty years ago.  "Influenza smoulders" is the best description I have ever heard of the virus' behavior.  Another way to put it is to repeat the words of Dr. Henry Niman:  "H5N1 doesn't read press releases." 

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