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INFLUENZA PANDEMIC (H1N1) 2009 (116):: ORIGIN
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A ProMED-mail post
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International Society for Infectious Diseases
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Date: Tue 24 Nov 2009
Source: Bloomberg.com [edited]
<http://www.bloomberg.com/apps/news?pid=20601124&sid=ajw2AS.d1wK8#>


Adrian Gibbs, the virologist who said in May [2009] that swine flu
may have escaped from a laboratory, published his findings today [24
Nov 2009], renewing discussion about the origins of the pandemic
virus. The new pandemic (H1N1) 2009 virus, which was discovered in
Mexico and the U.S. in April [2009], may be the product of 3 strains
from 3 continents that swapped genes in a lab or a
vaccine-manufacturing plant, Gibbs, and fellow Australian scientists
wrote in Virology Journal [see comment below]. The authors analyzed
the genetic makeup of the virus and found its origin could be more
simply explained by human involvement than a coincidence of nature.
Their study, published in a free, online journal reviewed by other
scientists, follows debate among researchers 6 months ago, when Gibbs
asked the World Health Organization to consider the hypothesis. After
reviewing Gibbs' initial 3-page paper, WHO and other organizations
concluded the pandemic strain was a naturally occurring virus and not
laboratory-derived.

"It is important that the source of the new virus be found if we wish
to avoid future pandemics rather than just trying to minimize the
consequences after they have emerged," Gibbs and colleagues John
Armstrong and Jean Downie said in today's 8-page study.

Gibbs and Armstrong are on the emeritus faculty at the Australian
National University in Canberra and Downie is affiliated with the
Centre for Infectious Diseases and Microbiology Laboratory Services
at Sydney's Westmead Hospital. While the exact source of the new H1N1
strain is a mystery, their research has "raised many new questions,"
they said. The authors compared the genetic blueprints of flu strains
stored in the free database GenBank and found the pandemic virus's
nearest ancestors circulate in pigs. While migratory birds may have
acted as conduit for their convergence, human involvement in bringing
them together is "by far the simplest explanation," Gibbs said in a
telephone interview today [24 Nov 2009].

Gibbs wrote or coauthored more than 250 scientific publications on
viruses, mostly pertaining to the plant world, during his 39-year
career at the Australian National University, according to
biographical information on the university's Web site. "Knowing
Adrian Gibbs, he will have thought through it pretty logically and
come to that conclusion," Lance Jennings, a clinical virologist with
Canterbury Health Laboratories in Christchurch, New Zealand, said in
a telephone interview. "It's up to someone else to try and prove it
or disprove it."

[Byline: Simeon Bennett]

--
Communicated by:
ProMED-mail <promed@promedmail.org>

[The publication referred to above is entitled: "From where did the
2009 'swine-origin' influenza A virus (H1N1) emerge?" By Adrian J.
Gibbs(1), John S. Armstrong(1) and Jean C. Downie(2), at (1)
Australian National University Emeritus Faculty, ACT, 0200,
Australia, and (2) CIDMLS, ICPMR, Westmead Hospital, NSW, 2145,
Australia.

The Abstract reads: "The swine-origin influenza A (H1N1) virus that
appeared in 2009 and was 1st found in human beings in Mexico, is a
reassortant with at least 3 parents. 6 of the genes are closest in
sequence to those of H1N2 'triple-reassortant' influenza viruses
isolated from pigs in North America around 1999-2000. Its other 2
genes are from different Eurasian 'avian-like' viruses of pigs; the
NA gene is closest to H1N1 viruses isolated in Europe in 1991-1993,
and the MP gene is closest to H3N2 viruses isolated in Asia in
1999-2000. The sequences of these genes do not directly reveal the
immediate source of the virus as the closest were from isolates
collected more than a decade before the human pandemic started. The 3
parents of the virus may have been assembled in one place by natural
means, such as by migrating birds, however the consistent link with
pig viruses suggests that human activity was involved. We discuss a
published suggestion that unsampled pig herds, the intercontinental
live pig trade, together with porous quarantine barriers, generated
the reassortant. We contrast that suggestion with the possibility
that laboratory errors involving the sharing of virus isolates and
cultured cells, or perhaps vaccine production, may have been
involved. Gene sequences from isolates that bridge the time and
phylogenetic gap between the new virus and its parents will
distinguish between these possibilities, and we suggest where they
should be sought. It is important that the source of the new virus be
found if we wish to avoid future pandemics rather than just trying to
minimize the consequences after they have emerged. Influenza virus is
a very significant zoonotic pathogen. Public confidence in influenza
research, and the agribusinesses that are based on influenza's many
hosts, has been eroded by several recent events involving the virus.
Measures that might restore confidence include establishing a unified
international administrative framework coordinating surveillance,
research and commercial work with this virus, and maintaining a
registry of all influenza isolates."

On the basis of a wide ranging analysis of the available genome
sequence data, the authors conclude the following. Influenza virus is
a very significant zoonotic pathogen. Public confidence in influenza
research, and the agribusinesses that are based on influenza's many
hosts, has been eroded by several recent events. Measures that might
restore confidence include establishing both a unified international
administrative framework coordinating all surveillance, research and
commercial work with this virus, and also a detailed registry of all
influenza isolates held for research and vaccine production. The
phylogenetic information presently available does not identify the
source of S-OIV [the nomenclature in the paper, ProMED uses pandemic
(H1N1) 2009 virus or H1N1pdm], however it provides some clues, which
can be translated into hypotheses of where and how it might have
originated. Two contrasting possibilities have been described and
discussed in this commentary, but more data are needed to distinguish
between them. It would be especially valuable to have gene sequences
of isolates filling the time and phylogenetic gap between those of
H1N1pdm and those closest to it. We believe that these important
sequences are most likely to be found in isolates from
as-yet-unsampled pig populations or as-yet-unsampled laboratories,
especially those holding isolates of all 3 clusters of viruses
closest to those of H1N1pdm, and involved in vaccine research and
production. Quarantine and trade records of live pigs entering North
America could probably focus the search for the unsampled pig
population. It is likely that further information about H1N1pdm's
immediate ancestry will be obtained when the unusual features of its
PB1-F2 gene are understood.

In the end, thus, the authors come to no firm conclusions, and
perhaps the most interesting part of their analysis is that which
relates to the "laboratory error theory". They claim that there are
clear historical precedents for most of the events described in the
above scenarios. Viruses do 'escape' from laboratories, even high
security facilities. The H1N1 influenza lineage that circulated in
the human population for 4 decades after the 1918 Spanish influenza
epidemic, disappeared during the 1957 Asian influenza pandemic, was
absent for 2 decades, but then reappeared in 1977. Gene sequences of
the 1977 isolate and others collected in the 1950s were almost
identical, indicating that the virus had not replicated and evolved
in the interim, and had probably been held in a laboratory freezer
between 1950 and 1977 and 'escaped' during passaging.

The suggestion that persistently infected cells might be involved is
also not outlandish; influenza virus can persistently and latently
infect MDCK cells, and viruses do travel between laboratories in
cells. Multivalent 'killed' vaccines are widely used to control swine
influenzas, particularly in North American piggeries; indeed, one of
the viruses identified by us and others as closest to H1N1pdm,
A/swine/Indiana/P12439/2000 (H1N2), seems to be the "2000 Indiana
strain" used in commercial vaccines in North America. We also note
that isolates selected from the 3 clusters of viruses we find to be
closest to H1N1pdm would probably make a useful trivalent vaccine for
international use as they would provide a mixture of haemagglutinins
of the swine H3, H1 'classical swine' and H1 'Eurasian avian-like'
lineages.

The patchy occurrence of H1N1pdm infections in piggeries over the
past 6 months is interesting and may be significant. Pigs have been
shown to be fully susceptible to H1N1pdm. They shed the virus and
readily transmit it between themselves, but whereas H1N1pdm has been
reported in humans worldwide, it has not yet been reported from a pig
farm in the USA (October 2009). By contrast, it has been found in 2
piggeries each in Australia, Canada and Ireland, and one each in
Argentina, Indonesia and Japan. In the outbreaks in Argentina,
Australia and Canada, the apparent immunity to H1N1pdm of pigs in the
USA and Mexico, but not elsewhere, may indicate that the swine
influenza vaccines currently used in the USA and Mexico contain an
immunogen that either protects against H1N1pdm infection or mitigates
its symptoms.

Circumstantial evidence must always be treated with caution. One
major uncertainty in trying to determine the origin of H1N1pdm is
that one cannot predict which characters of the parental viruses have
remained or changed during the reassortment process that produced
H1N1pdm. If, for example, the significant infectiousness of H1N1pdm
is an 'emergent' property of H1N1pdm, and not shown by its parents,
then one could conclude that the final reassortment probably occurred
at about the time it emerged in early 2009. However, it is not yet
known whether H1N1pdm's infectiousness is novel; the reassortment may
have occurred a decade ago, and a recent mutation may have enhanced
its infectiousness. Another widely reported feature of H1N1pdm is
that it replicates poorly in embryonated eggs, but again this may be
merely a specific feature of H1N1pdm and not its immediate parents.
Similarly, the fact that the evolutionary rate of all of the genes of
H1N1pdm seem to be 'normal' during their unsampled pre-emergent
period does not prove that the virus or its parents have been
maintained in "unsampled" pig herds and precluded the possibility of
human involvement, as viruses grown for vaccines evolve, and indeed
might be expected to show an increased evolutionary rate, while
adapting to eggs, a new host, although such an increase may have been
offset by the practice of storing 'seed stocks' for use in several
'production cycles' in vaccine production, so that the evolutionary
age of a vaccine virus may be less than its sidereal age, and the
average could then appear to be 'normal'.

Finally, there is the report that the 1st human H1N1pdm infections
were in Perote, a small Mexican town with a very large number of
large piggeries, although it was also reported that none of the pigs
showed signs of influenza. Among the earliest cases were some in
Oaxaca, 290 km to the south [34]. Perote is an unlikely place for an
infected migratory pig to arrive from an intercontinental trip, as
the town is in a remote high valley surrounded by mountains, 200 km
to the east of Mexico City, where there is the nearest major airport,
and 130 km from the nearest port at Vera Cruz. The 4-month difference
between 'The Most Recent Common Ancestor' date for H1N1pdm estimated
from its phylogeny, and its earliest detection in the human
population, makes it more difficult to make specific conclusions
about its provenance.

For a more balanced account, readers are recommended to read the full
paper in Virology Journal, which is freely available on line at:
<http://www.virologyj.com/content/6/1/207>. - Mod.CP]

[see also:
Influenza A (H1N1) - worldwide (26) 20090514.1798]
.................................................cp/msp/lm
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Experts fear escape of 1918 flu from lab
New Scientist
10:33 21 October 2004 by Debora MacKenzie

The 1918 flu virus spread across the world in three months and killed at least 40 million people. If it escaped from a lab today, the death toll could be far higher. "The potential implications of an infected lab worker - and spread beyond the lab - are terrifying," says D. A. Henderson of the University of Pittsburgh, a leading biosecurity expert.

Yet despite the danger, researchers in the US are working with reconstructed versions of the virus at less than the maximum level of containment. Many other experts are worried about the risks. "All the virologists I have spoken to have concerns," says Ingegerd Kallings of the Swedish Institute for Infectious Disease Control in Stockholm, who helped set laboratory safety standards for the World Health Organization....

...The team started the work at the highest level of containment, BSL-4, at Canada's National Microbiology Laboratory in Winnipeg. Then they decided the viruses were safe enough to handle at the next level down, and did the rest of the work across the border in a BSL-3Ag lab in Madison. The main difference between BSL-4 and BSL-3Ag is that precautions to ensure staff do not get infected are less stringent: while BSL-4 involves wearing fully enclosed body suits, those working at BSL-3Ag labs typically have half-suits.

Kawaoka told New Scientist that the decision to move down to BSL-3Ag was taken only after experiments at BSL-4 showed that giving mice the antiviral drug oseltamivir (Tamiflu) in advance prevented them getting sick. This means, he says, that if all lab workers take oseltamivir "they cannot become infected"...

...Michael Katze at the University of Washington at Seattle is planning to expose monkeys to aerosols of 1918-type viruses at BSL-3, a step down from BSL-3Ag. The recent SARS escapes were from BSL-3 labs.

"We would have to do any such work at BSL-4," says John Wood of the UK's National Institute for Biological Standards and Control. In the US, the differing standards applied by different groups are due to the fact that experiments on engineered viruses such as the 1918 flu are approved on a case-by-case basis by Institutional Biosafety Committees (IBCs), composed of local scientists and officials. Critics say these are free to interpret the official guidelines in a way that suits them.

"There is no effective national system to ensure consistency, responsibility and good judgement in such research," says Edward Hammond of the Sunshine Project, a biosecurity pressure group in Austin, Texas. In a review of IBCs published this month, he found that many would not provide minutes of recent meetings as required by law.

He says the IBC that approved the planned 1918 flu study at the University of Washington considered only one scenario that could result in workers being exposed to airborne virus - the dropping of samples. Its solution: lab workers "will be trained to stop breathing".

http://www.newscientist.com/article/dn6 ... m-lab.html

_________________
If your leaders tell you the Kingdom is in the heavens, the birds will get there before you.
If they say it's beneath the ground, the fish will get there before you.
It is within you and outside you..P.Oxy 654

Bird flu mix-up could have spelled disaster
New Scientist
05 March 2009 (17 March 2009 was the first known onset of flu in a patient. As was March 11 in 1918)

IT'S emerged that virulent H5N1 bird flu was sent out by accident from an Austrian lab last year and given to ferrets in the Czech Republic before anyone realised. As well as the risk of it escaping into the wild, the H5N1 got mixed with a human strain, which might have spawned a hybrid that could unleash a pandemic.

Last December, the Austrian branch of US vaccine company Baxter sent a batch of ordinary human H3N2 flu, altered so it couldn't replicate, to Avir Green Hills Biotechnology, also in Austria. In February, a lab in the Czech Republic working for Avir alerted Baxter that, unexpectedly, ferrets inoculated with the sample had died. It turned out the sample contained live H5N1, which Baxter uses to make vaccine. The two seem to have been mixed in error....

http://www.newscientist.com/article/mg20126983.400

If science can do good, it can also do evil.

_________________
If your leaders tell you the Kingdom is in the heavens, the birds will get there before you.
If they say it's beneath the ground, the fish will get there before you.
It is within you and outside you..P.Oxy 654

Abstract from the Virology Journal 2009, 6:207doi:10.1186/1743-422X-6-207
Published: 24 November 2009

http://www.virologyj.com/content/6/1/207



I would very much appreciate it if Dr Niman would comment on this.

This is an old story and was pretty obvious before it was detailed. Almost anyone who ran the pandemic H1N1 sequences saw it was a swine triple reassortant with the expected constellation of 1 human, 2 avian, and 5 swine flu genes (with human and avian contributing the three polymerase genes, including 1993 human PB1), but had a bit of an evolutionary gap with sequences in the database. These gaps are rather common, because the swine flu database is much smaller than human or avian.

There was nothing unsual about the gap, but Professor Gibbs decided that the gap indicated the virus had evolved to some extent in a lab developing a swine vaccine. He has yet to show any credible data to support his hypothesis and the vast majority of scientists who have a looked at influenza sequences and done phylogentic analysis would adhere to the "unsampled herd" explanation (especially since pandemic H1N1 is asymptomatic in swine) and I was in that camp within seconds of running the sequneces.

_________________
www.twitter.com/hniman

Can anyone comment of the coincidence of these articles?

Govt. funded institution and homeless in Poland.

Does anyone have any idea if the 2 could be connected to a trials and what was contained there in?

http://www.cdc.gov/eid/content/15/12/pdfs/08-1644.pdf

http://tinyurl.com/6r7amq

Are our state and govt facilities being used like Tuskegee again?