Original thread closed for length.
Last post in that thread:
Monotreme – at 23:18 The Sarge
Production of a bioweapon is not the only possible source for an escapee. I’m also considering the possibility of a poorly thought out vaccine. China, and others, have created recombinant (in the artificial sense, not the Niman sense) live vaccines that are part flu virus, part fowlpox virus. I don’t know if it’s possible for the flu genes in this recombinate virus to reassort with naturally occuring flu virus. I need to do more research.
Some examples:
Trovac Aih5, An Avian Influenza Fowlpox Vector Vaccine, As An Alternative Vaccine for Hatcheries
Immunogenicity of Fowlpox Virus Expressing the Avian Influenza Virus H5 Gene (TROVAC AIV-H5) in Cats
and this one is especially interesting:
China: New bird flu vaccine capable of prevention
Chinese scientists claim to have developed a vaccine to prevent the spread of the killer bird flu. The Ministry of Agriculture (MOA) says its new vaccine can effectively “cut a key link in the transmission chain of highly pathogenic avian influenza among water fowl.” Using reverse genetics, scientists at the Key Laboratory of Animal Influenza, affiliated with Harbin Veterinary Research Institute, altered the genome sequence of the virus to construct a vaccine that is believed to be safe for both poultry and mammals. The MOA suggests that if necessary, the new vaccine could be used on waterfowl in the high-risk area, which contains many water bodies, namely lakes and rivers.
I plan to start a thread on this when I have more info.
Tom DVM, do you know anything about this vaccine?
bump
monotreme: I’m posting this ProMed email to head off any misunderstanding about the “new bird flu vaccine capable of prevention” article above in case anyone reads a different version (the one above seems clear}.
…”The vaccine is a muscular-injection formula — thus, it could not be applied by its introduction into “rivers and lakes” [as erroneously stated in the media]. The MOA statement was misinterpreted when it was translated into English by the media; therefore, I offer this statement to clear up any possible misunderstanding”…
Monotreme.
I do not know much about poultry vaccines and less about manipulations of viruses being done in China or anywhere else for that matter…
…but I do know that the last thing anyone with a rudimentary understanding of virology would want to do, would be to release any form of live, infectious influenza virus into the mutable soup that we normally find ourselves in with these viruses each year.
It is so obviously stupid that words could barely do it justice…when you consider the potential consequences of this one technological manipulation of nature.
“technological manipulation of nature.”
Word up, Tom.
Nightowl, thanks for the link.
Tom DVM, the virus above is not wholly flu. My understanding is that two of the flu genes, HA and N, have been spliced into a fowlpox virus. I’m not sure if this artificial virus is infectious. I assume it’s not supposed to be, but am not sure. Live H5N1 vaccine that is wholly flu is being tested both in China and the US. I believe it is not supposed to be infectious.
The concern I have is whether it is possible for a gene from one of these vaccines to reassort with normal virus. So, if you vaccinated someone with a live non-infectious H5N1 vaccine and they were infected with normal human flu, H3N2, could the H3N2 reassort with the H5N1 vaccine? I don’t think there is any evidence that this has happened. However, I wonder about pigs that are already infected with H1N1 being exposed to a recombinate H5N1 vaccine.
It might be useful to have the sequence of the H5N1 genes being used for vaccines in China.
Monotreme – at 21:12 —
Theresa42 – at 13:23 — Ok. How do they know this? I’m looking for any and all direct, experimental evidence to show that what we’re seeing are mutations and that, therefore, one can calculate mutation rates, etc., etc. As we all know, reconstructions based on phylogenetic analysis are fraught with all sorts of problems — basically, your phylogenetic tree is just as good as the data you base it on — so I’m not (so) interested in such indirect evidence.h
The references you and I have found describe exactly how mutation rates are measured. The in vitro experiments are as direct as is physically possible right now and do not depend on phylogenetic reconstructions.
Ok. Thanks. That’s all I wanted to know.
So, to sum up, as far as we’re aware — the fact that mutations (point mutations) occur in influenza viruses is inferred from the fact that changes are seen from one viral generation to another. There has been no absolute direct observation of mutations (a la what some other folks were mentioning in the previous thread about attaching radioactive isotopes to nucleotides or something like that — a discussion which zoomed far above my head!). No “machine” (as you put it) to watch nucleotides being mis-copied during viral reproduction.
That’s all I wanted to know. Scientists have inferred from the evidence that mutations occur in viruses and that mutations are the prime movers in viral evolution. Educated, informed inferences, but inferences nonetheless. I can live with inferences. I just wanted to know where, exactly, we stand on the matter.
Thanks!
Monotreme. Thanks. Considering all the information from all sides that has come to light in the last ten months including that from Taunenburgher et al, it is pretty clear that we don’t know very much about seasonal influenza and less about pandemic influenza and less about the twin titans…H1N1 and H5N1..
…so I am left to believe that they know how to manipulate live virus and remove all chance of transmission given this is the ‘falcon’ of all infectious viruses.
Obviously, this live virus is meant to replicate within the vaccinated person or there would be no reason to use live virus over killed virus vaccines.
If anyone on flu wiki had a ‘shadow of a doubt’ about the absolutes regarding H5N1 and a future pandemic, the information on this thread should settle the debate once and for all!!
Tom,
“If anyone on flu wiki had a ‘shadow of a doubt’ about the absolutes regarding H5N1 and a future pandemic, the information on this thread should settle the debate once and for all!!”
I am absolutely sure that we are absolutely sure about next to nothing.
Does that help?
:-)
Astronomy seems to have made great strides in knowledge and understanding in the last few decades. If Astronomy was at the same stage of development and understanding as Virology would it still be pre-Hubble, (the man)?
Theresa42, I don’t know if this makes you feel any better, but almost all of modern science is based on inferences, from particle physics to cosmological theory. Now, if only I could see protons…
Tom DVM, yes, I think viruses are supposed to replicate, but their infectiousness is supposed to be impaired. However, I can imagine that a mutation in the crippled virus could restore full infectiousness. I think the technical term is revertant.
anon_22, the most troubling thing for me is what Tom calls the phenotypic changes, ie, the progressive adaptation of H5N1 to mammals. There is zero doubt in my mind that this is happening. And I do think it worth trying to figure out why it’s happening.
Chimeric fowlpox/HPAI vaccine. Neat technical trick for sure - splicing together two completely different viruses, one with what, ~250k BP - >200 genes and the other ~12k BP - 8 genes, orthopox and orthomyxovirus - and getting it to amplify. I note that it is based on the work of Webster and Kawaoka, among others - and that the literature dates back at least 15 years. There are a number of references in PubMed to using pox viruses as vectors.
I wish I had time to look through all of the papers - my question is, if one can get the chimera to amplify for production, why couldn’t it be infective and transmissible? Furthermore, how does one vaccinate any appreciable portion of wild avia with IM injections? As a practical matter, this doesn’t sound like a workable strategy to decrease the viral load in nature.
Rabies control involves the use of oral vaccine in bait. How about a processed transgenic feed that expresses the HA and NA proteins, but doesn’t involve a live chimeric virus being loosed in the wild?
Naplespark -
Referencing your reply at 16:53 on the original thread - 2H20 - do I understand this to refer to dideuterium monoxide? Heavy water?
Thanks!
The Sarge, see Nightowl – at 02:25. The link there is a denial that China was delivering live vaccine directly into the water supply of the birds. The denial was necessary because some news sources initially said that is exactly what they were doing.
Sometimes what people deny is as interesting as what they admit to.
Monotreme – at 10:21 — Theresa42, I don’t know if this makes you feel any better, but almost all of modern science is based on inferences, from particle physics to cosmological theory. Now, if only I could see protons…
Yes, I am aware of that, thanks. But, since I wasn’t aware of what the knowledge base was regarding influenza viruses and mutations, etc., I thought I’d ask. Now I know. Thanks again!
Oh — I don’t need any cheering up or anything, btw (…if this makes you feel any better….). I’m perfectly happy living with uncertainty about the world in which we live. :) I just don’t like it when our uncertainty is passed off as some sort of certainty.
Monotreme -
Why is it that I don’t quite trust the statements of the MOA? Surely they have done all they can to gain our trust, being all forthcoming with their data and so on. Must be a personal failing on my part. <sarc>
If we take them at their word, let us imagine the process for vaccinating the wild avia of China. We round up a couple of hundred thousands of folks, train them, arm them with preloaded syringes. Then, we suspend a net a couple of hectares in size from helicopters, fly it over the lakes…
monotreme, who says it’s happening ? (adaption to mammals) The virus in humans is similar to the virus in birds, except maybe the Indonesian cleavage site and a few other examples. But in general there is little adaption. E.g. reassortment with human flu. Is the amount of adaption increasing compared with 2005,2004 ?
Theresa42 – at 10:33
I just don’t like it when our uncertainty is passed off as some sort of certainty.
That’s very fair, but it’s (alas) an argument used by intelligent design advocates to chip away at the ‘theory’ of evolution. I mention this not to start a debate on ID but to point out that science types are sensitized to the concept of ‘well, you don’t really know…
The fact is that inference backed by observation is as close to ‘knowing’ as you can get… until a better explanation of the facts (or better observation) comes along. You weren’t saying otherwise, and you’re right to ask for the facts as we know them to know where the inferences come from.
Sometimes you can find ‘graded’ recommendations from the experts. I got this from an emergency CPR class I took, for example. Something like:
Class I: Definitely recommended
Class II: Acceptable and useful
Class III: Not acceptable, may be harmful
Indeterminate: Preliminary evidence needs confirmation
Grading the observations and claims as to ‘strength of certainty’ is a useful tool for us to consider.
isn’t it funny, how people invent new phrases to describe probabilities, which they don’t want to name by numbers in order to be imprecise deliberately and being able to redefine the phrases later so to adapt the interpreted phrase-estimate to the then known outcome ?
anon: That was a mouthfull! : )
DemFromCT – at 10:44 — The fact is that inference backed by observation is as close to ‘knowing’ as you can get… until a better explanation of the facts (or better observation) comes along. You weren’t saying otherwise, and you’re right to ask for the facts as we know them to know where the inferences come from.
Yes. As I said in the previous thread:
Theresa42 – at 13:23 — I think Darwin’s ideas on evolution and the modern synthesis and all that are correct, so I’m not looking for anything more than a naturalistic explanation here.
As you say, inference backed by observation is as close to ‘knowing’ as you can get … until a better explanation of the facts (or better observation) comes along. I heartily agree. But, since genetics is a fairly young science (the double-helix structure of DNA was discovered in — what? — 1953) — and it was just in 1957 that Dr. Webster worked out the link between human and bird flu — I think it’s pretty safe to say that we’re probably not quite at the apogee of virology yet.
Better observation and, possibly, a better explanation of the facts is sure to come. It’s the nature of science.
To think that what we know about influenza viruses now is all there is to know about influenza viruses is misguided. At this point, we have well-informed inferences about mutations in influenza viruses based on observations. There may be more to it than that or there may not. It’s important — essential — to keep that in mind though. In other words, to keep an open mind.
anonymous – at 10:52
Everyone finds humor in different places.
Theresa42 – at 11:04
I agree, no argument. It’s amazing how much we don’t know, and I think that category is growing faster than what we do know, alas (though we know more than we did a few years ago).
But I agree about keeping an open mind. the operative phrase is “that’s not supported by the evidence” rather than “that’s wrong”.
DemFromCT – at 11:09 — the operative phrase is “that’s not supported by the evidence”
Yes, indeed. Which is why I asked in the first place, what is the evidence for mutations in influenza viruses (and, therefore, for mutational rates and the idea that mutations are the driving force behind viral evolution). ;-)
anon_22 @ 10:07 “I am absolutely sure that we are absolutely sure about next to nothing.” Is this an original? If so, you need to have it published! May I borrow it on occasion?
Tom, I truly apologize if I was in any way responsible for for yesterday’s event. I had thoughts of leaving this forum, but decided not to give a certain someone the satisfaction.
I would like to know when I gave up my right to freedom of speech! gina
Monotreme,
Is this vaccine for just water fowl or is it a precursor for a human vacine? gina
Monotreme,
“anon_22, the most troubling thing for me is what Tom calls the phenotypic changes, ie, the progressive adaptation of H5N1 to mammals. There is zero doubt in my mind that this is happening. And I do think it worth trying to figure out why it’s happening.”
I’m completely with you on that. And I see that from 2 different directions:
1) new reassortants constantly being created out of the original parent A/Goose/Guangdong/96 and becoming more virulent to mammals, and
2) the increasing size and number of clusters of human cases from 2004 to now suggesting increasing transmissibility
Hurricane Alley RN – at 11:24 anon_22 @ 10:07 “I am absolutely sure that we are absolutely sure about next to nothing.” Is this an original? If so, you need to have it published! May I borrow it on occasion?
LOL.. of course, this is GNU, right?
But seriously, thought, the second half of that should read:
‘We are also absolutely sure that waiting till we are absolutely sure is suicidal and irresponsible.’
How’s that?
anon_22,
Absolutely correct in all standards. I love it!
Thanks for you post at 11:47. You must have been reading my mind. Sometimes it’s better to leave some things alone. This one looks to be straight out of “Frankenstien”. Feeding it to a volcano would be a better idea. gina
Hi gina. I honestly didn’t know there was an event yesterday.
I haven’t seen anything you have written ever on flu wiki that was a problem…and if someone else had a problem with something you wrote…it is there problem not yours.
You just keep doing what you’re doing and don’t worry about what others may think!!
Hi Tom. Thanks for the really big band-aid. It really does help. I think playing in the rain helped too. As a trucker might say, “Catch ya on the flip flop.” gina
anonymous at 10:52 -
WHO?
Theresa42 – at 11:04
‘’Better observation and, possibly, a better explanation of the facts is sure to come. It’s the nature of science.
To think that what we know about influenza viruses now is all there is to know about influenza viruses is misguided. At this point, we have well-informed inferences about mutations in influenza viruses based on observations. There may be more to it than that or there may not. It’s important — essential — to keep that in mind though. In other words, to keep an open mind.’‘
I agree completely. I think all the conventional flu scientists would as well.
Hurricane Alley RN – at 11:47
Is this vaccine for just water fowl or is it a precursor for a human vacine?
The vaccine I described was intended for birds. More about the many vaccines for H5N1 produced in China in another thread.
anon_22 – at 11:47
1) new reassortants constantly being created out of the original parent A/Goose/Guangdong/96 and becoming more virulent to mammals, and
I’m not sure that A/Goose/Guangdong/96 is the parent. But I agree the new assortments should be expected and should be watched carefully. However, this is only part of the story. In your second point, you suggest:
2) the increasing size and number of clusters of human cases from 2004 to now suggesting increasing transmissibility
which I agree with completely. The problem is: what is the selective pressure that is driving this? In my original tutorial, I should have distinguished between mutation rate and evolution rate - they aren’t the same. A gene may mutate at a high rate, but the protein it gives rise to may evolve at a slow rate. If the mutations are deletarious to the functioning of the protein, they won’t be maintained. Regardless of the mechanism for change, mutation, reassortment or recombination, changes will not be maintained unless they increase the fitness of the organism or are at least neutral. The progressive adaptation of the virus towards mammals suggest that this is increasing the fitness of at least one subset of the H5N1 swarm. This is why I suspect the human sequences don’t match the bird sequences - they are distinct sub-subtypes that are under different selective pressure - a bird H5N1 and an increasingly mammalian H5N1.
If I may be so bold, I’ll even suggest a new nomenclature: bH5N1 (bird H5N1) and mH5N1 (mammalian H5N1). My hypothesis is bH5N1 continues to evolve in birds,to infect birds whereas mH5N1 is evolving in mammals and is getting better at infecting them. This would explain why, in spite of massive exposure to infected birds (as graphically depicted in the PBS video linked to by Moeb the other day) infection of humans is relatively rare - bH5N1 just does not infect humans very easily. OTOH, mH5N1 may infect humans much more easily, but humans rarely come into contact with the mammalian reservoir. Just an idea.
Monotreme. How would things change if existing science had it wrong and birds were much more closely related physiologically to humans than previously thought?
I should have said that we are already susceptible to many diseases that are acclimatized to both species…why not a similar but not exactly same situation for influenza…it does seem that birds and humans are the two species most susceptible (phenotypically) to influenza.
Monotreme. One other thing to consider in this thread is that H1N1 and H5N1 are pretty much unanimously considered to be twin sisters…
…H1N1 jumped suposedly without much in the way of involvement of other animal species, although an intermediate host could have been there and was missed…
…The point is that if they are right H1N1 found a way to evolve without a mammalian host other than the end host.
It still seems to me that these ‘freak’ viruses may have the ability to ‘leap tall buildings’ while the rest of the influenza viruses have to ‘walk’.
Tom DVM, there are some species of birds with some similarities to humans, quail for example. But I’m not sure that there is one bird species that has all the traits necessary for it to go bird to human pandemic strain.
Pigs and seals are also susceptible to influenza. There was a huge die-off of seals from flu a few years back.
Monotreme. If there is an intermediate mammal host, which does seem most likely especially in this outbreak, I’ll bet you that they are shoreline mammals probably rodents…they would be in constant contact with waterfowl and more specificaly waterfowl faeces.
Monotreme. The thing is that I do not believe there is order in nature as we know it…more like disorganised order…and for that reason I believe H5N1 will be orderly for a while and then jump…all in…all required mutations at once.
For the first ten or twelve years in my veterinary practise, I had never seen a case of Blackleg ( same family as tetanus in humans). The last outbreak had occured in my area in the early 1950′s, had occured over a number of years and then disappeared for FORTY YEARS. One of my farmers phoned me to say he had a heifer with a sore foot. I had other calls to do first so we agreed to check her after lunch…when I arrived the heifer was down and died a few hours later. Within three weeks, similar cases occured in farms all over the county.
I observed the same thing with Leptospira abortion in cattle. You wouldn’t see anything for a few years and then bingo…all of a sudden you would see them all over the place…and then they would disappear again…It was orderly and disorderly at the same time…that’s why many vets have no hair…they either rub it off thinking or pull it out in frustration.
Monotreme,
On your last point, because of current evidence that H5N1’s virulence against both wild and domestic ducks are increasing, and breaking the previous notion of ‘evolutionary stasis’ between aquatic waterfowl and influenza viruses, we are entering uncharted territory of having pathogenic H5N1 passing repeatedly between mammalian and wild aquatic hosts. This last is likely to have different effects than passage into domestic poultry.
In addition, both domestic and wild ducks are now shedding more viruses through their respiratory tract than through the GI tract Are Ducks Contributing to the Endemicity of Highly Pathogenic H5N1 Influenza Virus in Asia? thus increasing the chance of human transmission via aerosol.
It seems to me that even this change in birds is geared towards adaptation to mammals, cos how would airborne rather than faecal-oral transmission be more advantageous to the virus for the purpose of adaptating to birds, seeing as the major receptor binding sites in birds are still in the GI tract?
And, of course, we don’t know the mechanism or the environmental conditions under which this was promoted. That is, we’ve been recording progressing genotypic and phenotypic changes of the virus in birds, humans and other species for the past few years with very little idea of how these changes were driven or arrived at. But we do know that airborne transmission from birds is much much worse news to humans than faecal-oral.
In other words, all bets are off.
anon_22,
I don’t scare so much anymore, but that post just raised the hair on the back of my neck.
Melanie-
I have had several similar unpleasant epiphanies. Some recent. Don’t like them at all, but when my little alarm goes off like that I listen to it.
“I see a bad moon arising, I see trouble on the way, I see barest winks of lightning, I see a bad time today.
Don’t go out tonight, It’s bound to take your life, There’s a bad moon on the rise.”
Credence Clearwater Revival
Tom DVM and anon_22 are both saying that strange things are occuring with H5N1. I agree. It also seems to be getting stranger and stranger.
I’d really like to know what’s driving this. I do think if we had more samples from more animals, especially mammals, the sequences were made public, we’d have a better idea what was going on.
Right now, the whole thing is like a horror movie. The monster is just a blur before it attacks, then goes back into the bushes. You’re never sure who’s going to be next, but it’s getting bolder and bolder.
Tom asked an intriguing question at 21:27. This information may be of interest:
Monotreme. Why don’t we go over to China, Russia and Indonesia and test those shore-line rodents. In Canada, they would be Beaver, Muskrat, Mink, Otter, Martin, Weasel etc.
Would the Civet cat be considered a rodent.
I wish I could give credit to the our one colleague who has been continually saying rats are involved…I can’t remember the name…maybe this virus has a propensity to rodents.
Nightowl Thanks!!
Your welcome, Tom
“the increasing size and number of clusters of human cases from 2004 to now suggesting increasing transmissibility”
I do not completely agree with this, and a lot of why I don’t is precisely that since a human host is still a dead-end for the virus, selection cannot be driving better transmissibility to humans. It does no good to leap tall buildings if you land like a heap of bricks on the other side. Selection may be driving something else that can have better H2H as a side-effect, but what continues to make the most sense to me is simply that as the virus becomes more widespread in birds, opportunities for human infections increase accordingly, the main concern still being that opportunities for re(whatever) increase along with that. I stand ready to change my view as soon as someone convincingly points to this mammalian reservoir.
The apparent increase in cluster size I see as an example of Gould’s “left wall hypothesis”; they can’t decrease in size, so they vary in the only direction available.
Tom DVM, I think most of the critters you list are actually mustelids rather than rodents. Mutelids do have a tendency to eat birds.
I’d think twice about going over to China, even reporting on bad news is now a crime there. Indonesia, yeah, a quick trip over there. Problem is, I don’t think we’re going to need to leave North America to get our samples
Theresa42 – at 11:04 — At this point, we have well-informed inferences about mutations in influenza viruses based on observations. There may be more to it than that or there may not. It’s important — essential — to keep that in mind though. In other words, to keep an open mind.
Monotreme – at 21:02 — I agree completely.
Hey Monotreme,
I don’t mean this to sound rude, but I don’t think that you do. Not really.
In the previous thread you said:
Monotreme – at 21:12 — “…but when two Theories conflict, we must decide which one is better at explaining the available data. No contest, IMO.”
To me that sounds like you’ve made up your mind as to how viruses evolve — i.e. that you’ve picked one theory over all others. In that case, I would say you’re no longer open-minded about the issue.
Similarly, I have stated that I think Darwinism and evolution and naturalistic explanations provide the best explanations of life — and I admit that I am not open-minded about religious or other non-naturalistic explanations about the world. To be honest, I’d have to have some pretty earth-shattering evidence presented to me before I would change my opinion on this matter.
If you were truly open-minded about the issue of viral evolution, you would be questioning mutations equally as much as other theories on the matter — you would probably even be demanding better evidence for mutations.
Again, I really don’t mean to be rude about this — this is not meant to be a personal attack — and I’d be more than happy to agree to disagree on this matter. I just would prefer an open and honest discussion about this issue since it is so critical to us all.
Thanks again for answering all my questions!
Racter, I don’t buy the bird hypothesis unless genetic susceptibility was involved. Many, many people have been exposed to birds and not been infected. Even in the same village where some got it. Also, the sequences don’t match.
The best way not to find a mammalian reservoir is to not take samples from mammals. Seems to be the current strategy.
Theresa42, I should have been more clear. I think it is true to say that there is alot about influenza that we don’t understand. No theory is ever complete. However, the evidence that random mutations occur frequently in flu viruses is overwhelming, IMO. There are multiple lines of evidence that all point in the same direction. I don’t think the scale between conventional science and Recombinomics ends up at an equal weight. If, after reading all the papers on the subject, you don’t think the evidence is sufficient, well, nothing I can say to convince you.
I hope you’re not waiting for a machine that can see into live cells and watch mutations occur, because if so, it’s going to be a long wait. Also, do you believe in protons? No-one can see them. All evidence of their existence is based on inference.
btw, I don’t mind if you disagree with me. I’m not really trying to convince anyone. My main goal has been to present the view of conventional science, which, strangely, is almost never represented on flu boards, and to indicate why I agree with it.
Mono: “I don’t buy the bird hypothesis unless genetic susceptibility was involved.”
I, of course, DO believe that genetic susceptibility was involved, but I absolutely think we should be testing everything we can get our hands on.
We continue to discount the question of genetic acquisition speed differences in the wild versus in the lab.
If the so-called mutation rate truly is as repeatedly stated between 3 in 10,000 and 5 or 6 per 100,000 replications, then with only 12,000 nucleotides in Influenza, you can see that we’d quickly no longer have Influenza?
Ergo, some rules or templates or guides do exist for genetic acquisition and we have yet to discover, quantify, correlate and causate them.
Monotreme. I agree some some of these animals produce scent or must…but according to Webster’s dictionary:
Rodent.- any of an order of gnawing mammals , as rats, mice beavers etc.
- common varieties of rodents include the following: rat, mouse, squirrel, chipmunk, beaver, porcupine, rabbit, muskrat, prairie dog, gopher, marmot, groundhog, woodchuck, ground squirrel, chinchilla, mole hare, guinea pig…I believe the rest of the my list are also rodents.
I think we need to remember that if H1N1 jumped with all mutations required directly from chickens to pandemic potential…then we must assume that H5N1 hypothetically can do the same thing.
I think we have to get away from an orderly nature in the same sense as an orderly universe…nature is not orderly.
Racter – at 23:24
Can’t really disagree with the genentic susceptibility hypothesis, but doesn’t explain increasing virulence of H5N1 in mammals. Never bought Gould’s left end analogy. Think was wrong about many things. Actually, I know he was blowing smoke in some of his old Natural History articles. He never let the facts get in the way of a good story.
NS1, what is commonly missing from these discussions is the role of selection in evolution. As I tried to explain above, rates of evolution are different than rates of mutation. Most mutants never see the light of day because they are incompatible with existence. This is true, not only of viruses, but of people as well. The spontaneuous abortion rate in humans is over 50%, mostly because of genetic defects in the embryo. What do you think the defect rate is in viruses? High, very high. But so what, they make so many it doesn’t matter than most don’t make it to another host. Survival of the fittest.
The question is: Why are the fittest increasingly the ones that can make mammals sick?
Tom DVM, now you’ve gone an done it. You’ve awakened my inner zoologist :-)
Mustelids are a family in the order Carnivora.
Rodents have their own order, Rodentia.
Never the twain shall meet, except in Webster’s apparently.
Monotreme. I think that possibly some of the difference of opinion is because I think nature is sometimes ordered and often disordered…which means I think that the most likely scenario in 1918 was that it pretty much simultaneously produced several mutations at once and instantly became more or less a pandemic virus.
If I read you properly, I believe that you may consider nature in terms of the evolution of viruses as an orderly affair with significant road-blocks and rules that must be followed for the virus to successfully become pandemic. Am I wrong in this perception?
Tom DVM, I won’t pretend that I know what the rules are, but yes I do get the sense of a slow progression towards a pandemic strain.
I also agree with the idea of order and disorder, except that sometimes apparent disorder really is a type of order. I’m thinking of chaos theory, complexity and strange attractors. I have absolutely no idea how any of those ideas could be used to explain what’s going on with H5N1 but your post reminded of some books I’ve read on the subject.
Monotreme. When I was a little kid I used to spend a couple days each winter with a trapper friend of the family…it was very interesting…but just because I am a veterinarian does not mean I am an expert on the thousands of animals around the world…although I wish I was…maybe not…my head would hurt or worse SWELL!! /:0)
Where I come from, we call them rodents. By the way, I believe that the gnawing means that most are neither carnivores or omnivores…but I will bet you that they are your intermediary mammals.
I think it would be interesting to see what the Chinese Government would do with us scientists…who thought they might need a little help!!
Monotreme. Maybe what sets H1N1 and H5N1 apart…subtle unseen abilities to mutate in completely unique ways…and maybe that is what you are observing…
…but I still bet shore-line mammals are the intermediaries.
Tom DVM – at 00:32
…but I still bet shore-line mammals are the intermediaries.
Not a bad bet, IMO.
Monotreme. I should read your resources when you post them instead of making myself look like a fool first.
Okay. The beaver and muskrat are rodents who are not carnivores or omnivores. By the way, a Native friend told me that if you are walking down a path and meet a beaver…get off the path…I guess if they go after you it is not a pretty sight. I haven’t run into a beaver on a path yet so I haven’t had a chance to test his hypothesis.
The others mink, fisher, martin, weasel etc. are meat eaters and are not rodents but are mustelids. So you are right and I and Websters Dictionary are wrong and thanks…I learned something new today!!
Monotreme at 0015:
Excellent example using spontaneous abortion, almost as good as a picture. I sincerely hope squirrels aren’t involved in the stew pot. Although it is a mammal that’s found on the dinner table while I doubt beavers are. All the speculation seems sound and I appreciate all the fine tuning I’m working out as I read this thread. One thing I’m not clear about—when the virus enters this suspected (shoreline host)could there be within the host some type of sickness that it may carry asymptomactically that increases the rate of mutation or the rate of virulence as its exchanged constantly back and forth. Perhaps that would explain the increasing virulence to humans. I’m wondering if the baseline temperature in this host would account for sporadic jumps as well.
Leo7. I think that is what Monotreme is thinking…an largely asymptomatic intermediary host that greatly accelerates acclimatization or evolution to humans.
By the way, beavers and muskrats, at least in the past, were eaten by native peoples. I haven’t tried them but it would probably be interesting.
One interesting aspect of the spontaneous abortion theory is that it appears that each virus may give birth to millions of little viri…so if 50% of those spontaneously abort that still leaves a lot in the pot…so to speak.
Leo7. I saw a news report I think yesterday about an influenza outbreak in pigs in India. The one place I do not want to see asymptomatic infections or widespread lethal outbreaks would be in pigs.
Tom:
Monotreme stands pat mostly with his cards, while you play the hand you’re given! Yes, I felt he was heading that way, and I remember months ago you stating you would be concerned if lethal outbreaks occurred in pigs. Your prediction timeline is right on course-sadly. Let me ask you this—would the temperature of this host be what makes it so special to the mutations and do the body temps vary widly among these shoreline mammals? Even if this suppossed host is located—I fear it’s too late to change the action of the virus. My sense is that countries, governments and Aid organizations are getting much better at controlling the news now—even the Wicki won’t have much time to scream “Duck!”
The pig fever outbreaks seem to be very lethal in India and with the population-whew-I hope we’re wrong. When you reported you felt a live virus was used in a vaccine for pigs and chickens which were housed closely together—it gave a real sense of how things might have taken off. I just wish all the missing sequences could all be entered by date, that would clear up the noise quite a bit. By the by, I could never eat muskrat or beaver, or squirrel. I’d eat grass first. I hope you will let that experience fall off your things to do list.(please?).
NS1:
Even if we assume one or more mutations per whole genome copy on average, random distribution of that rate would easily insure an adequate number of functional virions to prevent descent into chaos.
Rule 1: If it works, it gets replicated.
What more rules do you think are required? Perhaps more importantly, how do you imagine that they might be implemented?
Monotreme:
Increased virulence is scary, and therefore seems to get all the attention, but increased transmissibility is the thing I worry most about. Finding widespread infections among any mammal population would be deeply disturbing even if massive die-offs weren’t involved.
I definitely agree about Gould in a broad sense, but the left wall hypothesis is pretty straightforward. The thing that amazed me was that he managed to get a whole book out of such a simple concept as a skewed distribution curve.
Tom DVM, the reason why I emphasized that mustilids are carnivores and not rodents is because almost all of the mammals that have been shown to be infected in Nature are carnivores. The exceptions are pigs and humans. You can find a list here. Rats and mice can be infected in the laboratory, but no-one has shown that any have been infected naturally, yet.
I suspect the mammals most at risk are the ones that eat birds - and possibly the ones given poorly thought out live vaccines.
Leo7, I’m going to work on organizing all the available sequences, one of these days. I suspect alot more are going to be available soon.
Racter, the left wall idea is correct as a mathematical statement. It is incorrect as an explanation of evolution. When Gould presented that hypothesis, very little sequence data was available. Now, we have much more. It has become increasingly clear that Darwin’s emphasis on the important of selection was correct and Gould’s emphasis on chance in Evolution was wrong.
Assignments of relationship among species based on morphology have turned out to be wrong, again and again. The reason? Convergent evolution. There are a growing number cases of strong positive selection at work. My sense is that H5N1 is being shaped, perhaps literally, by the same forces that shaped the 1918 virus. Doesn’t mean they come from the same source or that the sequences will be the same. Convergent evolution.
Monotreme. After I made my comment at 1:11 last night, I re-read your post at 00:15 and realized you had made the exact same point. Sorry.
As you said, it makes more sense that the omnivores or carnivores would be more likely intermediaries then the beaver or muskrat although if I could, I would test them as well. When there’s trouble…beaver always seem to be involved and in the middle of it somehow.
Leo7. Thanks. In my wildest dreams, I would not have considered the Chinese Government to be using live or modified live vaccines…Monotreme brought it up first and I was absolutelly flabbergasted!! That one fact explains a lot of what’s been going on in China for the past ten years…don’t forget they are seeding and re-seeding border countries continually with this virus.
I think you bring up another unseen evolutionary tool of the virus when you talk about body temperature. Generally, smaller mammals require higher internal metabolism and therefore have higher relative body temperatures.
Also, in adapting to previously unaffected animal species, if H5N1 selects for persons only with higher body temperatures then it is automatically affecting either those with an immune system involved in fighting another disease (perfect conditions to be a carrier and shedder) or on the other hand, a human that may be co-infected with another influenza for reassortment..recombination etc.
It just doesn’t seem to matter from what angle we look at this situation, H5N1 is winning the game and we haven’t scored yet!!
I honestly don’t see a ‘bright spot’ yet.
Monotreme at 9:07: “convergent evolution”-Another chilling concept, you do have a knack for insight.
Historically, we don’t really know of any other avian flu viruses quite like H1N1 (back in 1918) or H5N1. Correct? Could there be an inevitability to panflu once viruses such as these have reached some unknown critical mass in their evolution? And that clearly H5N1 has long since passed that critical mass? And that H5N1 is being pushed along by far more potent external forces than H1N1 was ever subjected to?
Medial Maven I agree with everything you said as usual…
…but how do we know that H5N1 is not being subjected to identical external forces (pressures) as H1N1 a hundred years ago?
Tom DVM: Those factors that both you and I have agreed upon such as increased solar radiance, solar flares, global warming, environmental stress, more animal and human hosts, etc. is creating more potent external forces for the evolution of this virus.
What I got from Monotreme’s idea of convergent evolution as applied to this situation is that it is a blend of internal and external forces. The internal mechanisms should not have changed since 1918, but those mechanisms could be accelerated by the the more potent external environment.
Medical Maven. Yep, you’re right. You and I have spent a lot of time discussing environmental conditions that could not have been there a hundred years ago but sometimes ‘the more things change…the more they stay the same’. In otherwords there may be factors that we do not have the ability to see or comprehend.
Could you explain this convergent evolution concept a little more. I’m not sure I quite understand the term. Thanks.
Tom DVM: Off of the top of my head a good example of convergent evolution would be flight by animals. The lineage of bats and birds are totally different, but they both arrived at the same solution: wing-like structures. That is why Monotreme was talking about how morphology can fool you when assigning species.
So with animals or viruses there are problems with the environment “to be solved”, but those solutions can be arrived at by remarkably different avenues.
H1N1 attained “flight” in or about 1918. H5N1 will most likely attain “flight” in the next few years, but it may attain that flight in an obscure, novel way that is distinctly and totally different than what H1N1 did. But the result will be the same.
Does the fact that many of these “shore-line” mammals eat fish as well as birds have any impact on the line of inquiry? Or are fish entirely out of the equation? (I know there has been some discussion of water contamination by feces and other waste being a possible vector). Muskrats, beavers, etc., etc. are big fish eaters, correct?
And weasels favorite food, according to my mom who used to raise ducks, seems to be the eggs of chickens or ducks…
BTW, I would not want to be the one injecting a muskrat, weasel, beaver or the like with anything — they can be incredibly vicious.
Monotreme – at 08:59 — Tom DVM, the reason why I emphasized that mustilids are carnivores and not rodents is because almost all of the mammals that have been shown to be infected in Nature are carnivores. The exceptions are pigs and humans. You can find a list here. Rats and mice can be infected in the laboratory, but no-one has shown that any have been infected naturally, yet.
Apparently, there were reports of dead mice at the recent outbreak at Uvs Nuur Lake, Russia/Mongolia:
Theresa42 – at 05:34 — Alertness of specialists caused communications about the detection in the lake of the small carcasses of mice, what, in their opinion, is unprecedented fact.
http://www.fluwikie2.com/pmwiki.php?n=Forum.NewsReportsJune29
No idea if any of these mice are being tested, though. Would be great if they were ‘cause obviously it would be a good opportunity to try to find out if non-carnivorous rodents are/can be infected in the wild.
Theresa Someone on flu wiki has been pushing the ‘rat’ argument for months. I would like to give credit where credit is due but I cannot remember their name.
Anyway, separate from shore-line animals, wherever you find humans you also find bats, mice and rats.
Infolady, I believe muskrats and beaver do not eat meat. As far as fish go, nothing would surprise me anymore with this virus…unless it decided one day to just go away permanently.
The shore-line mammal could be the intermediary host and the rats and mice and bats could be the vector that brings the human and the shore=line mammals together.
Medical Maven. Thanks. I think I’m starting understand it now.
Leo7 at 01:37 -
OT but…As a child, I ate squirrel and rabbit many times. They’re really quite delicious. My dad and brothers enjoyed hunting and I never thought anything of it. I did grow up on a farm so maybe I’m just not the squeamish type. I do know that if times got desperate and my DH would go hunting, I could prepare and dine on them today with no problem. Thanks to my dear mother for teaching me something I thought I’d never need to know. Squirel and dumplings…yummm…
Monotreme: “It has become increasingly clear that Darwin’s emphasis on the important of selection was correct and Gould’s emphasis on chance in Evolution was wrong.”
Oh boy, you’ve pushed one of my buttons there. If I start raving, somebody slap me.
The importance of chance in evolution can never be dismissed. Life is a casino. Sharp claws, keen eyes, cast-iron stomachs, hard shells — none of these guarantee success; all they do is change the odds a little. “Survival of the fittest” is a 19th-century concept which remains well entrenched in common folklore despite having been long abandoned by modern theorists. It’s about probabilities. Life is a cacophony of micro-events, each of which is subject to influences so numerous and so subtle that they may be regarded as random from the perspective of any given point (such as an individual genome).
During a storm, a pregnant female of some species is washed out to sea on a floating log, and carried to a distant island where her progeny thrive, eventually evolving into a new species. In competition with each other, certain traits are selected more heavily than others, without a doubt. But they may all share other traits simply by virtue of having descended from the same individual female, traits having virtually nothing to do with her having ended up on a floating log (and absolutely nothing to do with her floating log happening to be the one to wash up on an island). We could drive ourselves nuts trying to explain those traits solely from a standpoint of selection, especially if the selective pressures that originally crafted them were absent in the environment defined by the new island home.
It’s the luck of the draw as much as anything, and sometimes more than anything.
I know I haven’t been asked for my opinion but I am going to give it to you two anyway.
Nature doesn’t care about rules, nature doesn’t have any rules.
Humans are preoccupied with the rules of nature because they like an ordered universe…and if they figure out the rules of nature then, in a sense, they are smarter than nature…
…problem is, from my experience, there is no one smarter than Mother Nature.
I don’t think we need all the rules or any of the rules for that matter…we just have to keep our eyes open and observe what she has or chooses to show us.
nature doesn’t have any rules
Tom, please. What do you think is physics about ?
Tao Te Ching “The ten thousand things rise and fall while the Self watches their return”.
We maybe know the “one thousand things” of the basic rules of nature in this universe of infinite multiverses. And viruses are so tricky and “spooky” I wouldn’t put it past them to be able to do quantum leaps of space, time, and dimension.
anonymous. Physics is disgusting. It doesn’t deserve to be in the same sentence with the beautiful science of organic and biochemistry and calculus. Actually I differ between the rules of science and the rules of nature.
Mother Nature sometimes gives us the impression she operates by a strict set of rules but I am convinced from a life-time of frustration that the only rule she has is to have no rules… but that doesn’t stop her from teasing us all the time about the rules she keeps breaking.
If you had watched a Blackleg outbreak in cattle after a perfect record for forty years, you would know what I mean.
Medical Maven. Took me a few minutes but I get his/ her point…good one!! and I agree with you on the rest. It is sometimes like there’s another dimension that we don’t get to look at or understand…it is very frustrating because I like to put things in nice neat boxes too.
Tom:
For my part, I’m always interested to hear what you have to say, and I’d be very surprised if that were’t true of the majority of the regulars here.
“Nature doesn’t care about rules, nature doesn’t have any rules. ”
We’re sailing into mighty deep waters here. I believe that where we observe regularities in our universe, we may confidently assume that these are the products of rules, but because the most fundamental of these rules are not known to us, our theories regarding them must remain provisional. Where our observations are made at levels well above the fundamental (as many of the most interesting indeed are), we may posit the existence of rules — but we should always keep in mind that this practice is for our convenience, and nature is in no way obligated to adhere to our rules; you are quite correct to differentiate between the rules of science and the rules of nature.
I currently find myself most interested in the rules of Niman.
TomDVM at 13:25
you are no physicist or philosopher, so what is your opinion worth ?
The experts disagree with you.
anonymous – at 15:05
What are the experts’ opinions worth? Something, surely. So’s Tom’s. So are yours. in the end, however, following the data is more important than following the opinions.
anonymous. You are right about the physicist part. I am no physicist but I did take and love philosophy…speaking of another pure science. My opinion? It is worth what you are paying for it.
As far as the experts go, we should keep in mind that so little is actually known about the virulence and transmissibility factors for influenza, there really aren’t any experts and the only one who does know, Mother Nature ain’t talking.
I welcome any disagreement you have…science would be pretty boring if everyone agreed all the time…and in fact there wouldn’t be any science without disagreement and ethical debate…
…so why don’t you choose a name so you can differentiate yourself from the other thousand anonymouses on flu wiki and we will ethically debate the issues…how about that?
Racter
A pleasure as always…and I mean it.
If we agree that sometimes things happen randomly in nature than by definition there can’t be rules?
This thread is getting long, so I’ve continued it here.