The bird flu outbreak in Wales

Just this month three prominent members of the flu science establishment warned their colleagues that predicting an influenza pandemic was not really possible (Taubenberger, Morens and Fauci, JAMA. 2007 May 9;297(18):2025-7). Not just the time frame is unpredictable, but also the subtype. H5N1 is the bogeyman, and rightly given its horrific case fatality rate (60%), but influenza is primarily a disease of birds. There is therefore a huge reservoir and other subtypes can cause trouble. As if to add an exclamation mark to a well timed warning, this week saw an outbreak of H7N2 in a poultry small holding in Wales (UK) that has spread to humans -- how many it isn't clear. The clinical signs and symptoms for the human cases, mainly mild flu like symptoms and conjunctivitis, are nothing comparable to H5N1 infection. The virus is being described as a "low pathogenic" variety of bird flu and nothing to be concerned about. In the well worn phrases of public officials, there is no cause for panic. Thanks. They should add, "You should never panic. You should be prepared so you won't have to panic." But that's another issue. Let's deal with H7N2 and this outbreak.

Initial reports were that the two proprietors of a smallholding in Wales, a woman who was also the local dog warden and her partner, had fallen ill with flu like symptoms and conjunctivitis. A group of newly imported chickens had experienced deaths in the previous 2 weeks and the pair consulted their veterinarian:

A total of 15 22-week-old Rhode Island Red chickens had been bought by the owners a fortnight ago [11 May 2007], bringing their total number of birds to 45 chickens and 2 geese. It appeared last night that the disease could have been brought on to the small holding after Dr Glossop confirmed that one of the birds died the day after they were taken to the site. [NB. Later it is said that 15 birds died]. Dr Glossop said: "At that time there was no reason to suspect notifiable avian disease. We have no reason to believe that the viral infection is spreading rapidly within this small population. This isn't another East Anglia at the moment.

Wendy Barclay, chair in influenza virology at Imperial College London, said: "Most influenza viruses that infect birds are the 'low pathogenicity' type. These viruses cause mild symptoms in poultry, and do not transmit to humans. Investigations are being carried out to determine where the birds were purchased." (The Guardian via ProMed)

Well, that was then. Next, four people were showing signs of infection:

Four people have tested positive for a mild strain of bird flu, British authorities said.

The cases - which are not the feared H5N1 strain, but the less dangerous H7N2 subtype - were reported after poultry died at a small farm in north Wales.

Tests were performed on nine people associated with the farm, and the Health Protection Agency said in a news release that four people had tested positive for the H7N2 strain of the virus.

Three of the nine were hospitalised, but have since been discharged, the agency said. (AP)

And the latest?

More people have fallen ill after being in contact with farmworkers or poultry sickened by a strain of bird flu in north Wales, British health authorities said Saturday.

The new suspected cases come a day after four people tested positive for the H7N2 type virus -- a far milder form of bird flu than the deadly H5N1 strain.

The Health Protection Agency, which is an independent body, was not immediately able to say how many more people were showing signs of illness, but all had direct contact with sick poultry or farmworkers confirmed to have contracted H7N2, said spokesman Chris Lines. [my emphasis] (AP)

The latest number of flu-like illnesses among the exposed is 11. It's still not serious disease, but the idea that H7N2 causes mild symptoms in poultry, and does not transmit to humans would seem to be "inoperable," as bureaucrats in the US like to say. But that's their story and UK authorities sticking to it.

Even the idea that this H7N2 is "low pathogenic" seems to us at least questionable. The terms Low Pathogenic Avian Influenza (LPAI) and High Pathogenic Avian Influenza (HPAI) refer to birds, not humans. The cardinal feature of HPAI viruses is that they cause serious disease or death in infected birds. Genetically, HPAI viruses also show five or more basic amino acids at the cleavage site of the hemagglutinin protein. Polybasic cleavage sites allow efficient infections at many more tissues than the respiratory and intestinal tracts of birds and lead to death from rapid multiorgan failure. Some strains of H7N2 have been seen with all five basic amino acids at the cleavage site but the belief was that this was still not sufficient to confer HPAI abilities on H7N2: the cleavage site had to be further widened by insertion of additional amino acids (see, for example, Lee et al., Virology. 2006 Sep 30;353(2):388-95). In the case of the outbreak in Wales it is not clear why the virus was declared LPAI, since it appeared to cause serious clinical disease in the birds. After all, they were dying. The announcement was also made fairly quickly, I'm guessing in the absence of sequencing to determine the nature of the cleavage site. The scientific literature does not recognize H7N2 as one of the HPAI viruses, or at least no one has been willing to call any H7N2 HPAI, perhaps because the cleavage sites were not characteristic of HPAI viruses.

And so far, H7N2 hasn't easily infected humans. CDC describes only two instances in the US where H7N2 has infected humans, in each case one person:

H7N2, Virginia, 2002: Following an outbreak of H7N2 among poultry in the Shenandoah Valley poultry production area [Virginia, West Virginia, North Carolina], one person was found to have serologic evidence of infection with H7N2.

H7N2, New York, 2003: In November 2003, a patient with serious underlying medical conditions was admitted to a hospital in New York with respiratory symptoms. One of the initial laboratory tests identified an influenza A virus that was thought to be H1N1. The patient recovered and went home after a few weeks. Subsequent confirmatory tests conducted in March 2004 showed that the patient had been infected with avian influenza A (H7N2) virus. (CDC)

The 2002 poultry outbreak was particularly severe and resulted in the destruction of 4.6 million birds. Dr. Michael Gregor's superb Bird Flu Book (available for purchase but also free, online here) has a good rundown of H7N2 and its relation to the US live poultry market:

The University of Georgia Southeastern Cooperative Wildlife Disease Study describes the U.S. live poultry market system as an "intricate web of retail markets, poultry auctions, wholesale dealers, and farm flocks." The study notes that in this system, "birds may change hands up to five times before reaching the consumer," increasing exposure and decreasing trackability. (Gregor, The Bird Flu Book [read the whole section])

Live markets in Europe appear to be no different. The index cases in the Welsh poultry were bought from a market in Cheshire and it now appears more than one farm bought birds there on that day. So we can expect to hear more about H7N2, which can be significantly pathogenic in chickens and spread rapidly (see Lu et al., Avian Dis. 2004 Jan-Mar;48(1):26-33).

In Wales there are indications it has moved to humans readily and human to human transmission may be occurring. The reflex labeling of H7N2 as a Low Pathogenic virus that transmits to humans with difficulty is no longer accurate. Whether this is a mutated H7N2 we don't know as yet, and the clinical illness in humans is so far described as mild.

Still, this is another indication that what we think we know about the veterinary and public health consequences of avian influenza are provisional, at best. We should be cautious about our warnings, so as not to induce undue anxiety. But we should also be circumspect and cautious about our reassurances, the more so as reassurance is a short term expedient but may in the long term be costly in lost credibility.


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Revere, that last paragraph should be carved somewhere on the walls at CDC.

Thanks for saying it.

I would assume that the H7N2 is called low path because it does not have a polybasic cleavage site, which was the case in the H7N3 outbreak in England last year. Since samples from teh current outbreak were collected May 17, there was plenty of time to sequence the cleavage site as "low path" in time for the press confefrence last Thursday.

The cleavage site however, has nothing to do with tissue tropism or host range. H7 (as in last year's H7N3 in England or the outbreak in British Columbia or the H7N7 in 2003 in the Netherlands) has M230I, which is adjacent to the receptor binding domain and matches human seasonal flu (H1N1, H3N2, and influenza B). All of the above outbreaks in poultry led to infections in humans.

Mixing up high and low path, which is based on the abilty to kill chickens, and changes in host range, which is the ability to infect humans, really is mixing up two seperate events, and creates confusion.

This is so classic I don't even want to talk about it.

>The scientific literature does not recognize H7N2 as one of the HPAI viruses, or at least no one has been willing to call any H7N2 HPAI, perhaps because the cleavage sites were not characteristic of HPAI viruses.< Revere

The workings of your mind are clear here, Revere. I haven't seen Niman around here, for a while, but his interest is clearly piqued, too, by this episode. Any preliminary conclusions, that you might care to share with us (you or Niman)?

I took note of what you wrote, above: "The cardinal feature of HPAI viruses is that they cause serious disease or death in infected birds. Genetically, HPAI viruses also show five or more basic amino acids at the cleavage site of the hemagglutinin protein. Polybasic cleavage sites allow efficient infections at many more tissues than the respiratory and intestinal tracts of birds and lead to death from rapid multiorgan failure. Some strains of H7N2 have been seen with all five basic amino acids at the cleavage site but the belief was that this was still not sufficient to confer HPAI abilities on H7N2: the cleavage site had to be further widened by insertion." When I recently encountered several research papers on M230I, I saw the same language, with regard to the "five or more basic amino acids at the cleavage site of the hemagglutinin protein;" if I remember correctly.

My sense, here, is that you are clearly indicating that if it "walks like a duck, looks like a duck, and quacks like a duck...then it's a (goddamn duck)???

But the "Authorities," evidently, say that it is not a duck?

HPAI is traditionally defined as a certain score of a pathogenicity index, which is based on the health of 10 experimental chickens injected with the virus being tested. The 10 chickens are monitored and poor health or death are noted. I am not sure of the exact score required, but HPAI almost always correlates with a polybasic HA cleavage site. The number of basic amino acids may be less than 5. Wild type low path only has one basic amino in front of the GLF, such as PQRETRGLF. That cleavage site, RETR is LPAI. The first H5N1 even isolated was from a chicken in Scotland in 1959, and had the cleavage site of RKKR. The consensus for Asian H5N1 is RERRRKKR.

Only H5 and H7 have the polybasic amino acids and only H5 and H7 have been shown to be HPAI.

In this outbreak, I suspect there is no polybasic cleavage site, as was the case last year in the H7N3 outbreak. This year 10 of the 15 chickens died on the farm, but the deaths took almost 2 weeks, so it is likely that the H7N2 woudl alos be low path on the pathogenicity test also.

For HPAI H5N1 like the Qinghai strain, which has a cleavage site of GERRRKKR, all 10 experimental chickens die within 24 hours of infection.

Transmission to humans is based on the receptor binding domain. It is common, recent press releases not withstand, for H7 infections to cause human disease, although the symptoms are mild flu like comditions and/or conjunctivitis.

To date, the only reported avian influenza death that was not HPAI H5N1 was the vet in the Netherlands in 2003 who was infected with H7N7. The past four H7 outbreaks (H7N7 in 2003, H7N3 in 2004 and 2006, and H7N2 in 2007) all produced human cases, with clear H2H in 2003 and the current outbreak.

In 2003, the H7N7 outbreak spread to several countries and millions of birds were culled. Studies of H7 antibodies indicated well over 1000 people were infected, and most were from H2H. The H7 cleavage site in that outbreak was KRRR.

All of the H7 outbreaks above had M230I adjacent to the receptor binding domain, as did five human H5N1 cases in Egypt, all of which were fatal. Those cases were encoded by sequences found in last years H7N3 or H5N1 in northern Germany, establishing a link between the Nile Delta and Germany/England. Thus far, the case fatality rate for M230I in Qinghai H5N1 is 100%, including the Ghabiya cluster.

I've been thinking this is actually good news :
Now we have another serotype of flu with occasional outbreaks as H5N1 , but which never went pandemic either.
Somehow supports the main argument of the optimists:
H5N1 has been around so long .. if it were capable of going pandemic
it had already. Same with H7N2. And it's low path and detected
in UK. How many similar outbreaks may have happened in China
or elsewhere but remained undetected ?
And none of these resulted in an epidemic or pandemic.
Doesn't it indicate that there is a "barrier" towards epidemic/pandemic potential ?


Seriously dude/ette, I've just got back from the dentist -- how real can you get!?! Are you aware that you've written utter drivel which makes no scientific sense in relation to the evolutionary mechanism of transgenic viruses (hyper-stimulated, no doubt, by a dodgy viral promoter shoved into genetically modified crops eaten by wild birds, etc, since the mid 1990s).

Come on, do a bit of research and read previous postings on this site,, and books such as Dr. Michael Greger's Bird Flu: A Virus of Our Own Hatching...

By Jon Singleton (not verified) on 27 May 2007 #permalink

Jon: When you write to anon "you've written utter drivel which makes no scientific sense in relation to the evolutionary mechanism of transgenic viruses (hyper-stimulated, no doubt, by a dodgy viral promoter shoved into genetically modified crops eaten by wild birds, etc, since the mid 1990s)" it is the pot calling the kettle black. You were hyper-stimulated, no doubt, by your trip to the dentist.


I publicly identify myself and don't adopt titles/personas such as "revere" or "anon". Revere hon, surely "anon" is capable of speaking for him/her/itself and doesn't require your speed, speed, speedy and sark, sark, sarky input.

Explain your scientific criticism, Revere...

By Jon Singleton (not verified) on 28 May 2007 #permalink

Jon: Please explain your evidence and the meaning of hyperstimulated dodgy viral promoter eaten by wild birds from GMO crops. What is a hyperstimulated viral promoter? What is your evidence that H5N1 is "transgenic" (and what do you mean by it?). What's the evidence that wild birds eating GMO crops pick up viral promoters (which ones? what genes are they promoting? how?). Hand waving insn't scientific evidence. It's hand waving. The breeze is enough to knock one over.

revere, Please. Stop with the personal attacks. You have no background in virology, and put up this thread that proves it. Host range is determenined by thhe receptor binding domain. Virulence is linked to the HA cleavage site. H7N2 is low path because it doesn't have the polybasic cleavage site.

I realize you can't really discuss the science, but you repeated personal attacks under the cover of "revere" is particularly annoying.

Posting your real identity would be quite illuminating to your readers, especially those who are interested in avian influenza.

(And arguing that a rapidly evolving H5N1 can't go pandemic because it hasn't yet, is nonsense).

The real issue with the outbreak in Wales is the human to human transmission. This is really as much of an epidemiological issue as it is a virulence issue. H7 usually is quite mild in humans, regardless of whether it is high or low path in chickens (does or doesn't have a polybasic cleavage site).

The outbreak in Wales is low path H7N2, but it is H7, and H7 frequently causes infections in humans. The media is butchering this story, and public officials are withholding details, but it sounds like 8 of the 11 patients with symptoms have no poultry contact, indicating H2H. This is a high number, because it is linked to a VERY small number of infected birds (ten), yet there are now more humans infected than birds (or at least reported humans and reported birds).

Henry: Thanks for the concise revision lesson.

Jon: While I agree with your position that past pandemics show us that these slow burns do sometimes reach critical mass, is it helpful to attack Anon rather than advance an argument showing the error in the logic that another bullet missed so perhaps they will all miss. As to anonymity Revere(s) is/are an atheist with political views at odds with the current regime which funds the area in which he/they work and has show that it is not above applying pressure to institution to prevent the hiring, funding or promotion of those that disagree with it. I view the blogger as the 21st century pamphleteer, Thomas Paine did not sign Common Sense forcing the focus of attack on what he wrote not the individual. If Anon needs anonymity for a similar reason or is just a member of the public airing an opinion looking for feedback, best not to drive him/her away for fear of ridicule if he/she lacks your breath of knowledge on the subject.

Jonathan Jackson, UK citizen, self employed computer consultant with no fear of TBTB.

Henry: I merely chided Jon for attacking anon, using handwaving arguments. Your own comment was an obvious and blatant personal attack on me. But I give you space here to say what you want, which is more than you do for anyone else on your site, Henry. Afraid to open the door? You have been banned from plenty of sites because of your notorious habit of attacking others personally. I have engaged in "repeated attacks"? Please be specific. What "repeated attacks"?

Scientists, by the way, publish their results in the scientific literature, not as you do, announcing them through a commercial website that allows no comment. Feel free to define "the real issue" in any way that is convenient for you, but don't expect the rest of the scientific community to do so just because you choose to. You are not an epidemiologist, have no training in epidemiology, no expertise in it and apparently no knowledge of it. And your degree in virology is from where? And your publications in virology are where and when? One thing for sure. You are a businessman who is selling a virology product. But a scientist? Scientists publish their science for others to see, criticize, use. They don't just try to sell it without laying it out in detail for others to see. People who live in glass houses, Henry . . .

I obliquely raised an issue about the term "Low Path." H7N2 causes significant pathology in birds, and I wondered out loud about the aptness of the term. The bird CFR was 100%. You are so wedded to sequences that a "Low Path" cleavage site remains Low Path for you despite the fact that it is 100% lethal. I questioned the appropriateness of that terminology and you regarded it as a personal attack on you? It wasn't about you.

Your claim that host range is soley determined by the receptor binding site is pretty strong. What's your evidence? Or is this your business model speaking?

I'm pretty tolerant here, but there is a line. And self promotion under the guise of science is close to crossing it.

The H5N1 evolution story is pretty straight forward. H5N1 is rapiidly evolving. In 2004, there was only one version in circulation that was infecting humans (Clade 1 in southeast Asia). Today there are four (Clade 1, Clade 2.1, Clade 2.2, and Clade 2.3). Moreover, Clade 2.2 (Qinghai strain), has spread out of eastern Asia and now has been reported in almost 50 countries in Europe, the Middle East, and Africa. This Clade 2.2 has since formed multiple subclades with distinctive regional markers that are mxining and matching via recombination.

In Egypt, M230I, was reported in human Qinghai H5N1 for the first time this season, including the Gharbiya cluster, the largest cluster reported to date in Egypt, which not only had acquired M230I (also in H7 like the H2H H7N2 in Wales), but also another change in the receptor binding domain (V223I) and Tamiflu resistance (N294S). The resistance was present prior to Tamiflu administration, indicating the resistance was flying around Egypt. Similarly, human Qinghai H5N1 was reported for the first time in Nigeria, where the isolate had regional markers from west Africa, Egypt, and Germany. Surveillance in Nigeria is lacking and even though the mother of the index case died with bird flu symptoms, only "inconsistant" results have been found in samples, so the real extent of human cases in Nigeria is unknown. Similarly, Vietnam just reported its first human case since 2005, and the relationship to prior isolates is unknown. In addition, the mamalian PB2 E627K has become fixed in the Qinghai strain.

Thus, the H5N1 continues to evolve and pick up mammalian polymorphisms and continues to infect more mammals (cats, dogs, foxes, stone martins, civet cats, pigs) allowing for more mammalian acquistions (in Egypt there are actually two versions of M230I in both human and bird H5N1 isolates).

H5N1 has evolution down to a science. This isn't Kansas, and the announcement of the decline of H5N1 in wild birds is utter nonsense, spoon fed to a VERY guilible press.

Maybe this would be a good place to ask this.

What exactly is it that distinguishes one HA subtype from another? I recall the discussion on the Shortridge paper, and the criticism that the assay method (single radial hemolysis) was too weak to distinguish between (say) H5N1 and H5N2. I understand that antigenic evolution (or is it origin?) can cause one strain of (say) H5N1 to be quite different from another, yet they are both H5N1. There are 16 known HA subtypes; could there be more? Could a 17th type evolve out of one of the existing types? What would identifying H17 consist of? Would it involve a judgement call on somebody's part? I've read about Wiley and Skehel, and I've looked at ribbon diagrams and whatnot, and I'm pretty much stumped.


As noted, you focus on personal attacks and not science, as do the anonymous posters at some of the sites you mentioned. Personal attacks by anonymous posters are quite annoying, but the science I post is quite straight forward (which is why the anonymous posters focus on personal attacks).

I have presented data on my analysis of avian influenza sequences at the Vaccine Meeting in Boston last fall, and the Northern California ASM meeting in San Ramon this spring. Both were invited presentations, and I am on five abstracts at the upcoming influenza meeting in Toronto (three with US NAMRU-3). The presentations have bene well recieved by the scientific community and I am collaborating closely with US NAMRU-3 in Cairo including publications which are at various stages of the peer review process. However, much of the data is public, either in patent filings or at the recombinomics website (can be accessed via link above - if I put a link in the text, the post "disappears").

The acientific arguments I make are actually quite straight forward, and the anonymous posters really don't argue the science. They use personal attacks, as you just did.

Make PhD was from USC and was on RNA Tumor VIRUSES, and I regularly presented at JD Watson's RNA Tumor VIRUS meeting at Cold Spring Harbor - my first presentation was in 1976 in the opening session chaired by David Baltimore and Howard Temin, who had both won the Nobel Prize the year before. My presntation was published in Nature, which was my first publication, in 1977. I have published in VIROLOGY, Journal of VIROLOGY, as well as Nature, Science, Cell, and PNAS. The flu monoclonal I made at Scripps (in collaboration with Ian Wilson, who solved the stucture of HA while in Don Wiley's lab at Harvard) is among the most popular in the world (a google search fo the monoclonal returns 160,000 hits, mostly from the mention of teh monoclonal in peer reviewed publications). I also held a joint appointment at Harvard / Mass General, while at the Shiners Burn Center in a city that you should know well.

In any event, the issue is the science and high and low path are well defined. The definition is based on a well controled patogenicity test that measures the effect of the virus on experimental chickens. That test correlates well with the HA cleavage site. An audio of the press announcement on the outbreak in Wales clearly indicated the low path was based on sequence, and I believe 10 of the 15 birds died over a 10 day period (May 7-17). in contast, H5N1 infected birds can appear healthy in the morning and be dead in the afternoon. Sudden death is a hallmark of HPAI H5N1.

The H7N2 almost certainly doesn't have a polybasic cleavage site, which gives a quick answer. HPAI only applies to H5 and H7, and only H5 and H7 have reported polybasic cleavage sites.

I didn't call the H7N2 low path. Weybridge did and I told you (and your readers) why.

In contrast, the host range is determined by the receptor binding domain, which is on H and upstream from the cleavage site. H7 infections in birds frequently leads to human cases, as was seen in the past 4 H7 outbreaks, regardless of pathogenicity in chickens. H7N7 in the Netherlands was HPAI and led to the death of millions of chickens and infections of over 1000 people (mostly H2H). H7N3 in British Columbia in 2004 switched from low path to high path and led to reported infections in a few people. H7N3 low path in England in 2006 was fairly contained and led to infections of a few people. H7N2 low path in England in 2007 has already been linked to more sick people than sick birds. Only one of the H7 human infections was fatal (the only bird flu fatality that was not H5N1).

H2H is the issue, and that is largely controled by the receptor binding domain, which nis well accepted by VIROLISTS.

The epidemiology of the H5N1 H2H (as well as H7) is pretty straight forward, as is the spread of H5N1 by Qinghai infected wild birds. BOTH are quite straightforward, although readers of this board may be a bit surprised at how obvious the data is (ALL cases of H5N1 west of China are tehn Qinghai strain, and there were ZERO HPAI Asian H5N1 reported cases west of China prior to the Qinghai Lake outbreak in May, 2005.

Well, well, emotions (((ARE))) "hyper-stimulated" are they not -- I feel a tad like Rock Hudson "chided" by Big Daddy in Cat On A Hot Tin Roof!?! JJ was correct in that "anon" required some backgrounder rather than a boo-hiss for writing in a muddying manner -- "H5N1 has been around so long.. if it were capable of going pandemic [it would have] already."

Indeed JJ, it'd be much more sensible if I were to point toward what I was actually reading back in the early years of this century! Scientific literature alluding to the "evolutionary mechanism of transgenic viruses (hyper-stimulated, no doubt, by a dodgy viral promoter shoved into genetically modified crops eaten by wild birds, etc, since the mid 1990s)."

Backgrounder on the "dodgy viral promoter (ie. CaMV 35S)" @ article, "Whos Afraid of Horizontal Gene Transfer? (originally published Mar 05, 2002)

Let's not forget what I was writing that same year, the same year in which Centrelink (Australian social security) would order me in for an interview and have some Howard gov administration homophobe inquire if I were mentally ill... 2002, the year where no one in British, American or Aussie governments heard of H5N1.

Date: Fri, 19 Apr 2002 03:17:00 -0700
From: "Jon Singleton"


Personal feelings re: the precautionary principle and good science:

To paraphrase ISIS' Dr. Mae-Wan Ho, "With transgenic DNA, nature becomes a huge uncontrolled experiment for generating horizontal gene transferred and recombinant superviruses and superbugs (ISIS ARTICLE


Brian Stableford's novel THE CASSANDRA COMPLEX (C) 2001, appears to be the first substantive work of hard science fiction referring to and warning of transgenic generated viral [pandemics]...

C21*S*E*Research -- The Politics of Horizontal Gene
Transfer (How did H2H H5 evolve!?!)

I suspected genetic engineering was dangerous way back
in the late 90s when first digesting a tv news item on
H5N1 contamination in Hong Kong -- six people (adults
and kids) "cytokine storm" died of this transgenic flu
during a late 1997 outbreak in Hong Kong's Special
Administrative Region.

Even a major pharma company, Roche, was worried back
in 1997 bout the global implications -- in its Media
News 16 (May 2006) Roche says:

"Roche has been in discussions with governments as
early as 1997 regarding pandemic preparedness..."

So how did H5N1 get here?

H5N1 is a transgenic polymorphic pathogen -- a highly
mutable cross species multi-strained virus probably
CaMV 35S promoter gene flow originating from genetic

Since the mid 90s, dietary consumption of GM
(genetically modified) crops by birds, animals and
humans (who eat crops, birds and animals) has
increased dramatically. It is very probable GM crops
containing CaMV 35S transcription promoter are the
horizontal gene transfer (HGT) causation vector thru
which transgenic viral pathogens (eg. H5N1) are
recombining (homologously) into existence with such
ease, speed and spread.

The "homologous recombination" process has, according
to, always been the explanation for
viral evolution and not "random mutation". But, the
thang bout the technology of potpourri tweaking GM
organisms sees "hyper-acceleration" entering natural
DNA evolution -- thangs move a durn sight faster...

Recombinomics -- Random Mutation Explanation of Flu
Genetics Is Fatally Flawed (March 30, 2006) @

The defence against evolving polymorphic viruses is
rather simple and has been repeated many times by
numerous scientists worldwide -- cease the corporate
controlled release of genetically modified organisms
within the global environment.

Prior to the end of 2005, efforts in sequence tracking
the genesis of H5N1 were criminally lackluster -- we
now know transgenic strains are present in birds and
mammalian populations...

But still, the question remains unanswered, how did a
transgenic virus appear out of nowhere?

One possible cross species vector is GM/GE feed fed to domestic fowl from the mid 1990s to present, HGT recombining (evolutionary mechanism) H5N1 (via CaMV 35S promoter) into a transgenic polymorphic pathogen, now infecting and killing humans...

So, basically I'm saying gene flow has occurred as a
consequence of transgenic crops doing a CaMV 35S
promoter recombination hotspot remix in the bellies
(and bodies) of all organisms, including wild birds, consuming such crops.

Prof. Joe Cummins was the first to warn against using
the CaMV 35S promoter or any viral genes in plants
because it had been shown that such viral transgenes
in plants could gene flow recombine with naturally
occurring viruses to generate, in some cases,
super-infectious viruses.

Subsequently, the CaMV 35S promoter has been found to
substitute for the promoter of many plant and animal
viruses to produce infectious viruses.

* Remixed excerpt ISIS Press Release 29/11/04 -- Fluid
Genome & Beyond @

By Jon Singleton (not verified) on 28 May 2007 #permalink

Influenza serotypes are called serotypes because they are based on serology. Viruses are tested against ferret antibodies. If they don't react with any of the known 16 H antibodies, they are given a new number, as happened with H16 a few years ago.

However, within each serotype there are many clades and subclades, which is based on phylogenetic analysis.

Revere, I received my BS at UC Santa Barabara in 1974 and my PhD at University of Southern Califiornia in 1978. I then did a post doc at Scripps and went on staff there in 1980. My first publication was in Nature in 1977. All graduate and post graduate work was on viruses. My PhD these was on gene expression of two cat retroviruses. The program included the largest contract in the US as part of Nixon's war on cancer. My chief competitor was Ed Scolnick, who bowed out of cat research (focused on rats and RAS) after I published in Nature. He eventually left NCI to head Merck research. Most of my early patents are on combining monoclonal antibody and synthetic peptide technology.

Now why don't you tell your readers where your appointment is, and what kind of training you have in virology. Since you wish to remain anonymous, it would not be appropriate for me to release the info, but I think it might be useful for threads like this which are focused on VIRUSES (and you suggestion that they be reclassified based on who knows what).

So the subtype distinction is essentially an artifact of the tools used in observation? Sort of like "gram negative/positive"?

Racter: Yes, in a sense you are right. The serotyping of HA is done with a technique called double immunodiffusion and uses hyperimmune sera, usually, I believe, from rabbits. I think it goes too far to call it an artifact, however, as that implies it isn't of genuine interest. Remember, gram neg/pos has both a biological and clinical interest. Influenza serotyping is based on a specific method that distinguishes broad classes of HA (currently 16; still others may be determined by this method). The classification depends on the fact that reactions to these 16 different hyperimmune sera don't overlap (cross react), although we know that cross reactivity between serotypes does occur for other kinds of immune reaction measures.

Henry: I appreciate that you are not divulging information I revealed to you in confidence long ago, so you know quite well that I am a credentialed epidemiologist with a university appointment and that I publish in the scientific literature; I look forward to reading your publications on influenza recombination, which no one to date has been able to do. I have no idea why you decided to attack me as you did, but I responded in kind. I didn't pick a fight with you. You picked a fight with me and did it in a most offensive way, as I am sure you intended.

This was a peaceful venue until you showed up again. You are incredibly divisive and that's the reason you have been banned at so many other places. You stir people up and get them arguing with each other. What is even more ridiculous, is that I said nothing in that post that disagrees with anything you said later, which leads me to believe you didn't read it any more than you proofread your own texts. You are manufacturing controversy, once again, for your own purposes. If you want to be taken seriously by scientists, then act like a scientist and publish your work and then everyone can talk about it. I've been hearing for years from you that papers are about to appear. Real peer review begins after publication, so then we can talk about your ideas.

We've discussed plenty of science here and in thousands of posts have not engaged in personal attacks and rarely in personal criticism (can you say the same? just look at your comment that started all this!). While this is as much a policy blog as a science blog we have also done quite a lot of science here, although you probably don't read it because it is out of your field of expertise.

I would say that the serology is more descriptive than gram staining. It is a relatively crude way to classify influenza strains, and is related to an immune repsonse. Sequences give more info, but different seroptypes are VERY different at the sequence level.

Artifacts in science are man-made and don't represent nature. Serotypes do represnt nature, so calling them "artifacts" is not really accurate.

Revere, Although I use my real name and it is quite easy to research my training and publications, you have posted that I wasn't a virologist, which would require that you have a very novel and restricted definition of a virologist. You have complained about publications, but as I noted some time ago, the data is avaiable in detail in public patents, and I have given you the URL (and they are linked on the "patents" page on the recombinomics site).

You latest post, seems to imply that there was some difficiency in a PhD from USC, which is why I thought it would be useful if you gave more than an "academic institution" for your appointment, which would put your comments on USC in proper perspective.

Similarly, I gave some of the peer reviewed journals where I have published, which is more descriptive that "peer reviewed publications."

I find personal attacks by anonylous posters particularly annoying, because the vast majority of anonymous posters use that approach because they can't argue the science. Such approaches are particularly prevalent on the internet, and greatly diminish the utility of the medium.

As far as this board is concerned, I generally focus on posts on science, although my dispapearing posts have certainly diminished my interest in those areas also.

I came back for a quick look at the outbreak in England, and my first post "disappeared", possibly because it had a link in it to a recent commentary on the outbreak, as well as recent pre-publication on H5N1 in a live teal in the Nile Delta in December, 2005, when every country in western Europe and Africa denied that there was are H5N1 circulating in their country.

Oooops, when I referred to 'Cat on a Hot Tin Roof' (1958), a classic film based on the play by Tennessee Williams, the character I identified with -- "chided" by Big Daddy -- was portrayed by Paul Newman and not Rock Hudson...

By Jon Singleton (not verified) on 28 May 2007 #permalink

As far as personal attacks on posters are concerned, my attacks are on the argument, not the poster, who is almost always anonymous. I have a few that follow me around, and sometimes I am fairly short with their arguments, because they are usually chronic copy and pasters of google searches and have no idea of what they are pasting.

That was quite prevelant on multiple boards and in some cases, was by moderators of boards such as the Flu Wiki, which was most annoying. In other cases, it was just the same set of poster(s) with multiple handles on multiple boards.


I for one will be quite relieved if the next flu pandemic is an H7N2 conjunctivitis outbreak.

Get a grip, people.

By Lisa the GP (not verified) on 28 May 2007 #permalink

Henry: You come highly recommended from the closest Friend I have in this world. Please don't allow yourself to become angry, just continue your work. I would ask that you, at times, come down to the level of the lay person in your explanations.

revere: No disrespect intended, you have your reasons for doing what you do and I'll accept that as many other's have also accepted it. Again, no disrespect however, you do tend to become argumentative when the commenter doesn't agree with you. Many times I've read very mean-spirited words from you if someone challenges you. And you also insult people by your silence.
I'd request that you not block Mr. Niman as what he has to share is valuable.

In closing, and no disrespect intended, I can hear you now revere, "don't come to EM if you don't like it Lea". That isn't the point and it would be yet another emotional remark from you. Your interpretation of me revere is misguided and hidden by your own agenda, I am someone you barely know, who has good intentions and a pure heart but doesn't meet your self-imposed requirements of intelligence. Therefore I'd request that you stretch your level of tolerance, as tolerance is a positive attribute and highly beneficial when dealing with people.

Jon, can you post the nucleotides of that "CaMV 35S"
and the H5N1 virus, where you think you can find
a similar one ?

niman, has anyone else but you ever mentioned or
acknowledged these single-nucleotide-recombinations
which you claim for ? And do you consider asking this
question "an attack"

"Artifacts" may not have been quite the word I was looking for.

I take it that since we presently cannot reliably predict cross-reactivity by detailed examination of either the hemagglutinin structure or the underlying sequences, the subtype distinction (like the LP/HP distinction) is a "proof of the pudding is in the eating" sort of thing; virus IS as virus DOES. It's a functionalist approach.

I guess I was picturing some biogeek peering through a microscope, going: "Aha, it has a short-necked twisted dangly, and that hooked loop-splitter; definitely H7". Such an approach might be valid, just as looking at the cleavage site might be a valid means of predicting pathogenicity -- but it's a "bottom-up" approach, whereas the conventional approach is "top-down".

I'd still like to know a little more about this "broad classes of HA" business. If cross reactivity between serotypes does occur for other kinds of immune reaction measures, then using those measures, we'd have fewer subtypes, whereas if we found something more precise than what we're using now, we'd have more. Right? Though perhaps not an "artifact" of the methodology, the naming convention emerges out of the methodology.

Also, I wonder if cross-reactivity to a given antibody might not represent a location in design-space which could be reached by different paths. Could two HA proteins react with the same antibody despite appearing quite different if you were looking at danglies and loops and things? Or is that just ridiculously unlikely?

Lea: Two replies. To the extent I have been mean spirited I deserve to be called on it. Please do so next time. I do not recall ever expressing opinions or interpretations of you that you allude to in your comment. Argumentation is allowed here, so I will continue to do that as do many others, including you. Indeed as you just did. I welcome it. You are no shrinking violet whom I have cowed into silence, as many of your comments prove. That's fine with me.

Regarding my silence. There is no way I can keep up with all the comments here. I often don't even have time to read them all, especially when they are very long. I make a place for people to talk together and my participation is not necessary. I try as hard as I can. I have a very busy life outside this blog, both personally and professionally and within the last two weeks welcomed into the world a new grandson, so my silence can be for many reasons. Never does it have to do with intentionally slighting a commenter, although there are times I deliberately choose not to comment. However people here seem to get on fine without my taking part for which I am grateful.

racter, I assume the serology with ferrets also depends on
some human posed level of reactivity - changing it
also changes the number of HAs.
See here for a pure mathematical classification:

12HAs looks more reasonable. Might also depend
on the alignment software

>>I assume the serology with ferrets also depends on
some human posed level of reactivity - changing it
also changes the number of HAs.

Yes, that occurred to me as well. I'm certainly no expert on double immunodiffusion, but it looks to me like a band of precipitation either forms, or it doesn't.

Looking at phylogenetic similarity is a "bottom-up" approach. The next rung on the ladder would be to look at structural similarity. Functional similarity is surely driven by both. The problem is that some differences in either phylogeny or structure might have little effect on function (reactivity) despite being relatively large, while others might have considerable effect despite being relatively small. You'd be hard pressed to predict which ones were which unless you knew how the effects of each change at the sequence level would propagate up to the functional level. We're not there yet. The current classification avoids this difficulty by going directly to the level of function.

Do you remember when I suggested that you investigate what is known as the "protein folding problem"?

anon, I think that single nucleotide acquisitions by recombination are quite novel, although conceptually quite straight forward. Such an approach was used to predict the appearance of S227N in the Middle East in 2005. I made the prediction in October, and when it was comfirmed in January, 2006 in Turkey, some called it a lucky guess! (I gave the nucleotide position, geographical location, and time frame).

I also did a commentary on the acquistion of NA G743A by 11 H5N1 genomes on 6 genetic backgrounds in 3 countries (Egypt, Russia, and Ghana). I would add a link, but when I do, the post manages to "disappear" and never gets posted.

I called it elegant evolution for a reason. As more sequences come out there will be more examples (like the 3 BP deletion in Egypt that EXACTLY matches the 3 BP delection in Hunan, China, but the deletions are at the same positions on VERY different H5N1 backbones.

The story is in the sequence, and as the sequence data base get filled, the recombination will be quite clear.

I have been working with NAMRU-3, who have generated a large number of H5N1 sequneces in Egypt and Ghana. As more sequences come out, the acquisitions of single nucleotide polymorphisms increase. I predicted that 2007 would be the year that the random mutation nonsense finds the circular file. I stand by that prediction.

"SOPMA correctly predicts 69.5% of amino acids for a three-state description of the secondary structure [ ] proteins."

That sounds fine. Now: how much further to reliable prediction of tertiary (or quaternary) structure, and thence to predicting function?

Bypassing the drama completely, I have a question about H7N2, or indeed any avian flu virus that occasionally causes mild disease in humans.

At one point, three of nine people tested were hospitalized. (I'm assuming they were also out of the four who tested positive, although that's not explicitly stated.) Were they admitted as a precautionary measure to monitor them, or were they seriously ill? None died; this is good, and in stark contrast to H5N1's behavior when it infects humans.

But 4 is not a sample size large enough to learn much of anything about CFR, is it? We know for sure it's not 100%, and 0% is not out of the question. But if my dim recollection of statistics serves me correctly, if four people contract an illness with a 50% CFR, there is a 6.15% chance that all of them will live.

So how "mild" is the illness, really? How can we know? One assumes that if an H7N2 pandemic began now, it would be less lethal than an H5N1 pandemic. But H7N2 could have a "real" CFR of 10% (Category 5+, horrible social repercussions), and with 4 cases, there'd still be a better than even (~65%) chance that we'd see what we're seeing now: 4 survivors.

Obviously the uncertainty shrinks as the number of cases goes up, but I suppose I'm wondering whether an H7N2 pandemic couldn't turn out to be just as bad as 1918.

P.S. I am aware that there are probably any number of previous human cases of H7N2, which provide a sounder basis for stating that it's not a particularly deadly virus. However, if it's spreading human-to-human now, and hasn't in the past, then it's clearly changed somewhat from its previous iterations.

To me, this is the worst of all possible outcomes. H7 is not endemic yet...but it is certainly sporadic. Like H5N1, it just will not go away.

I don't think HPAI or LPAI really matters here because LPAI can become HPAI in an instant.

The bottom line is that H5N1 has a huge template of influenza subtypes with which to reassort-recombine etc.

Having H5 and H7 loose in China would not be all.

You can only dodge so many bullets.

Henry I have had electronic conversations with the son of the veterinarian who died in the prior H7N2 outbreak. I am not belittling his loss, merely stating that if what we *get* for the next pandemic is a widespread conjunctivitis outbreak with a death rate comparable to our usual seasonal flu, then we should be ecstatic compared to the dire possibilities H5N1 has implied.

Any flu epidemic is going to have casualties. Given that one *will* eventually hit us, I think we should be relieved if that casualty level is low.

As I said before, get a grip, people.

Of course, it would really suck to have H7N2 take off and then H5N1 right on its heels. Now *that* would be a real mess, just when you thought it couldn't get any worse...

By Lisa the GP (not verified) on 28 May 2007 #permalink

Lisa, As I said, this isn't Kansas. I have looked at the sequence of the H7N7 from the vet and it had MANY more changes than the sequences available from birds. I suspect the vet was infected by several H7N7's, which recombined to produce the deadly result.

H7 in humans is a bad idea, and in the Netherlands, over 1000 PEOPLE were infected. H7 has also been found in horses and seals. It likes mamamls and likes to change. Not a good combination.

In fact since it is mild, it is also easier to spread, because the hosts are walking around, wiping their eyes, and the touching door knobs.

A certain Chinese doctor/researcher type in Hong Kong told me today on a long winded email that took some deciphering as he doesnt finish words, or they are mispelled, or out of context that we should be very concerned about this H7 gig. He said in a two page long one that the why was co-circulation of two viruses that have suddenly taken a liking to humans. Not massively so just yet he said but that 11 sure cases in a week and possibly 36 would raise just about anyones eyebrows that took tenth grade science, much less the WHO.

He also went on to say that while he isnt panicked, he is concerned because DEFRA and the UK HS is in charge of this. DEFRA was the one that hired basically the local Audubon Society over there to do their surveillance for the last two years. Results? They found less bird flu and other diseases than any other baseline year. Kind of like putting PETA in charge of the hen house.

So I said to him, "whats your read on it? " His response was," Nothing conclusive as of yet. Nothing supports going to Pan 4" He started in with this technical stuff that Henry, Revere, Lisa might understand but I certainly didnt. So while he was IM'ming me I told him to stop and give me the bottom line... Is it coming? Talk about silence... it took about an hour for him to respond. He said in his opinion we have something less than 3 years simply because H5N1 hasnt gone away, H7 is saying hello (remember the assertion was H1N1 got into pigs reassorted/recombined and then kicked back out). This all was of course his opinion. I dont know. All I can say is that lets keep all the communications lines open regardless of personal issues or beliefs. I think this is going to humble everyone on this planet, every government and right down to their knickers. The guy on the other end of the blog might be the last voice you hear for quite some time.

Lisa, Webster asserted in his town hall meeting here two months ago that it might not be H5 that gets us...only a flu. His bent was more that it would be a hybrid with something else that is very H5 in nature. His point and I took it was that H5 just flat kills people too quickly and that the strain that comes for us has to be a little more sneaking than becoming symptomatic inside of 3 days or less. When it started most people took about a week to ten...sneaky and shedding virus after about a day post of the infection.

By M. Randolph Kruger (not verified) on 28 May 2007 #permalink


A recent Pubmed Search Inquiry sees emails sent to my inbox but, other than postings here at EM, nobody is writing bout the subject matter -- the pantry appears empty @ PubMed:

This message contains My NCBI what's new results from the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM). Monday, 2007 May 28. Range operation produced no results, check low/high limits.

The following term was not found: H7N2 and H5N1 recombination and transmission in and between humans[TIAB]. See Details. No items found.…

Posting excerpt: As mentioned in a previous posting, the Recombinomics Commentary (May 25), "Efficient H7N2 Transmission To Bird Flu Patients in England" highlights the pandemic trigger dangers posed by a geographic co-circulation of H7 and H5 -- Henry Niman: "The co-circulation of H7 and Qinghai H5N1 is cause for concern because of the ability of H5N1 to acquire sequences [eg. M230I] that increase the efficiency of human to human transmission..."

By Jon Singleton (not verified) on 28 May 2007 #permalink

Some of you may actually run into this Dr.Nicoll, but I won't; please buy him a pint of whatever he wants if you see him, for saying this to a reporter: ...
"The pandemic risk from low pathogenic avian viruses
is almost as bad as that from highly pathogenic avian viruses,"

said Dr. Angus Nicoll, an influenza expert at
the European Centre of Disease Prevention and Control.
"When people say low pathogenic or highly pathogenic,
that only refers to how unpleasant the disease is for birds," Nicoll explained.
"That's almost irrelevant for humans."

By crfullmoon (not verified) on 29 May 2007 #permalink


You Science Walas can really have a go at each other:)

In the mean time:

The National Public Health Service for Wales (NPHS) has identified 221 people, who may have had contact with the avian flu!!!

In fact DEFRA has requested any one who was recently at the Chelford Market in Cheshire to contact them.

Our associated blog, birdflunewsflash, has the full announcement and links here:

crfullmoon, or to put it the other way round:

the pandemic risk from H5N1 is as low as that from H7N2 ?
Now, what's the actual WHO-pandemic-phase for H7N2 ?

> I predicted that 2007 would be the year that the
> random mutation nonsense finds the circular file.
> I stand by that prediction.
> Posted by: Henry Niman | May 28, 2007 05:05 PM

would you accept a bet on this, say $1000 paid in advance
by each of us now to revere (or suggest another referee),
who then transfers $2000 to the winner on 1.Jan.2008 ?

Did anyone ever figure out how the 1918 flu really originated? Sounds like a bonehead question, but I read through everything I can find on the Web and seems that this is still a mystery to the experts. Wading through a long paper on the subject produced a conclusion something like "it appears H1N1 was circulating in an as yet unidentified host before it became a pandemic". I'm very, very curious what happened exactly in the period from 1915-1918. At some point, H1N1 was circulating and then changed and became a killer, what's to stop H7 doing the same thing?

I think it's ironic that everyone has been boresited on H5N1, who knows what other types have the potential but no coverage.

stu: Yep. You are right. Except that a number of people (e.g., Webster) have been warning for years about other subtypes, espec. H9 and H7.

and he thinks(thought?) H5N1 could go pandemic with 50%
and half of mankind could die. Now add H7 and H9 to this...

What level has WHO actually for a H7- or H9-pandemic ???
Should be at least level 3 then too ?!?

Dr. Osterhaus has consistently said...I believe...that he is more worried about an H7 pandemic than an H5 pandemic.

"would you accept a bet on this, say $1000 paid in advance
by each of us now to revere (or suggest another referee),
who then transfers $2000 to the winner on 1.Jan.2008?"

It would be the easiest $1K you could ever make, and Nimaturd the Great knows it.

I'll vager on this: before the end of summer 2008.

Could the single nucleotide acquisitions by recombination be calculated and predicted by calculating the fractal scaling exponents and/or approximate entropy of the H5N1 strains?

Thin: What is being scaled here? And the entropy of H5N1? For that you need the probability of . . . what? Each spot in the sequence, calculated how? Note that Chen has used an entropy method for some applications but I am not sure what you are referring to.

Approximate entropy of each spot in the sequence, and the fractal scaling exponents of the different sequences. Ask sleep and heart physiologists for more accurate explanation.

Further to a remark by caia, and speaking non-technically, isn't it the case that they haven't found lots of Welsh people with H7N2, they've found lots of Welsh people in contact with birds and not feeling very well? That is to say, have they trawled for cases of risk and found people who were sick, but not necessarily with bird flu? Even an unrelated eye infection? That isn't uncommon. I've had one.

By Robert Carnegie (not verified) on 05 Jun 2007 #permalink