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The value of influenza aerosol delivery experiments

The Value of Influenza Aerosol Transmission

Saturday, Jul 05, 2014 during 06:45 AM EDT

A Harvard epidemiologist has been on a
crusade to diminish aerosol delivery experiments on avian influenza H5N1
virus since he believes that they are too dangerous and of small value.
Recently he has taken his arguments to a Op-Ed pages of a New York Times. While Dr.
Lipsitch is positively entitled to his opinion, his arguments do not support his

In early 2013 Lipsitch was a theme of a square in Harvard Magazine about
avian influenza H5N1 micro-organism entitled The Deadliest Virus. we have previously criticized this article in that Lipsitch calls
for some-more formidable H5N1 policies. More recently Lipsitch published an opinion in PLoS
in that he called for alternatives to experiments with potential
pandemic pathogens. We discussed this square entirely on This Week in Virology #287. The arguments he uses
in both cases are identical to those in a OpEd.

The Times OpEd is entitled Anthrax? That’s not a real
. The pretension is a anxiety to a probable bearing to anthrax
bacteria of workers during a Centers for Disease Control. Even worse than
anthrax, argues Lipsitch, would be random bearing to a micro-organism that could
transmit straightforwardly among humans. He afterwards argues that such a micro-organism is being
created in laboratories that investigate avian influenza H5N1 transmission.

Lipsitch tells us ‘These experiments use influenza strains like H5N1, which
kills adult to 60 percent of humans who locate it from birds.’ As an epidemiologist
Lipsitch knows that this matter is wrong. The box deadliness ratio for avian
H5N1 influenza micro-organism in humans is 60% — a series of deaths divided by the
cases of tellurian infections that are diagnosed according to WHO criteria. The
mortality rate is utterly different: it is a series of fatalities divided by
the sum series of H5N1 infections of humans. For a number of reasons a H5N1 mankind ratio in humans has
been a formidable series to determine.

Next Lipsitch wrongly states that a idea of experiments in that avian
influenza H5N1 viruses are given a ability to broadcast by aerosol among
ferrets is ‘to see what gives a influenza micro-organism a intensity to emanate a
pandemic.’ The idea of these experiments is to brand mechanistically what is
needed to make an avian influenza micro-organism broadcast among mammals. Transmission of
a micro-organism is compulsory for a pandemic, though by no means does it assure one. we do
hope that Lipsitch knows better, and is simply perplexing to shock a readers.

He afterwards turns to a experiments of Kawaoka and colleagues who recently
reconstructed a 1918-like avian influenza virus and supposing it with the
ability to broadcast by aerosol among ferrets. These experiments are
inaccurately described. Lipsitch writes that a reconstructed micro-organism was
‘both foul and comparably lethal to a 1918 influenza that killed tens
of millions of people worldwide’. In fact a reconstructed micro-organism is less
virulent in ferrets than a 1918 H1N1 micro-organism that putrescent humans. In a same
sentence Lipsitch mixes distress in ferrets with distress in humans —
something even my virology students know is wrong. Then he writes that
‘Unlike experiments with anthrax, formulating such influenza strains in a lab
presents a risk that affects us all, since once it is out, such a strain
would be intensely tough to control.’ This is not loyal for a 1918-like avian
influenza micro-organism fabricated by a Kawaoka lab: it was shown that antibodies to
the 2009 pestilence H1N1 influenza micro-organism can retard a replication. The current
influenza micro-organism vaccine contains a 2009 H1N1 member that would protect
against a 1918-like avian influenza virus.

The crux of a problem seems to be that Lipsitch does not know the
purpose of influenza micro-organism delivery experiments. He writes that ‘The
virologists conducting these experiments contend that by training about how flu
transmits in ferrets, we will be means to rise improved vaccines and spot
dangerous strains in birds before they turn pestilence threats.’ This
justification for a work is wrong.

Both Kawaoka and Fouchier have suggested that identifying mutations that
improve aerosol delivery of avian influenza viruses in ferrets competence help
to detect strains with delivery potential, and assistance vaccine manufacture. I
think it was an blunder to concentration on these intensity advantages since it detracted
from a genuine value of a work, to yield fatalistic information on what
allows aerosol delivery of influenza viruses among mammals.

In a Kawaoka and Fouchier studies, it was found that adaptation
of H5N1 influenza micro-organism from avian to mammalian receptors lead to a diminution in
the fortitude of a viral HA glycoprotein. This skill had to be topsy-turvy in
order for these viruses to broadcast by aerosol among ferrets. Similar
stabilization of a HA protein was celebrated when a reconstructed 1918-like
avian influenza micro-organism was blending to aerosol delivery among ferrets. It is
not simply fluke when 3 eccentric studies come adult with a same
outcome: clearly HA fortitude is critical for aerosol delivery among
mammals. This is one skill to demeanour for in present H5N1 strains, not
simply amino poison changes.

Lipsitch mentions zero about a resource of transmission; he focuses on
identifying mutations for notice and vaccine development. He ignores the
fundamental significance of this work. In this context, a work has tremendous

The residue of a Times OpEd reminds us how mostly accidents
occur in high confidence biological labortories. There are problems with these
arguments. Lipsitch cites a presentation of an H1N1 influenza micro-organism in 1977 as
‘escaped from a lab in China or a Soviet Union’. While is seems clear
that a 1977 H1N1 micro-organism substantially came from a laboratory, there is zero
evidence that it was a laboratory accident. It is equally expected that a virus
was partial of a clinical hearing in that it was deliberately administered to

Lipsitch also cites a countless incidents that start in American
laboratories involving name agents. we advise a reader listen to Ron Fouchier explain on TWiV #291 how a mechanism pile-up must
be available as an occurrence in high biosecurity laboratories, though does not lead
to a recover of spreading agents.

Lipsitch clearly feels that a advantages of aerosol delivery investigate do
not transparent a risks involved. we determine that a experiments do have some risk,
but it is not as transparent cut as Lipsitch would suggest. Although ferrets are a
good indication for influenza micro-organism pathogenesis, like any animal model, they are
not predictive of what occurs in humans. An influenza micro-organism that transmits by
aerosol among ferrets can't be insincere to broadcast in a same approach among
humans. This is a arrogance finished by Lipsitch, and it is wrong.

I determine that delivery work on avian H5N1 influenza micro-organism contingency be done
under a correct containment. Before these experiments can be finished they are
subject to endless examination of a proposed containment and slackening procedures. There is no justification for the
additional law due by Lipsitch.

In my opinion aerosol delivery experiments on avian influenza viruses
are good value a risk. We know zero about what controls aerosol
transmission of viruses. The approach to obtain this information is to take a virus
that does not broadcast by aerosol, get a endemic version, and
determine because a micro-organism has this new property. To interpretation that such
experiments are not value a risk not usually ignores a significance of
understanding transmission, though also fails to acknowledge a unpredictable
nature of science. Often a best initial formula are those that were
never anticipated.

Lipsitch ends by observant that ‘There are dozens of protected research
strategies to understand, forestall and provide pestilence flu. Only one strategy
— formulating virulent, foul strains — risks inciting such a
pandemic.’ Creating a destructive aria is not partial of a strategy. Lipsitch
conveniently ignores a fact that Fouchier’s H5N1 aria that transmits by
aerosol among ferrets is not destructive when transmitted by that route. And of
course we do not know if these strains would be endemic in humans.

I am really unhappy that a Times chose to tell this OpEd without
checking Lipsitch’s statements. He is positively entitled to his possess opinion,
but he is not entitled to his possess facts.

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