Yet another paper testing the current swine flu pandemic virus in animals appeared in Nature yesterday, covering much the same ground as two published July 2 in Science and with similar findings. All three of these papers show the pandemic virus more likely to infect tissues deeper in the lung than seasonal flu viruses used for comparison. But each of these papers had a slightly different author spin. This one is even being construed as suggesting that we may be confronting a virus much like the 1918 monster.
We discussed the first two, one from Holland and one from the US, in this post a couple of weeks ago. The Dutch paper used ferrets and showed efficient transmission of a virus from an uncomplicated case isolated from a 3 year old who recovered fully. The US team tested three isolates from patients with varying degrees of illness severity: one uncomplicated, like the Dutch case, one hospitalized, one fatal. Collaborators at MIT claimed that an analysis of receptor binding showed the new virus was not as capable in transmission as seasonal flu. A press release to that effect from the MIT media office came out at the same time that this very virus was obviously transmitting happily and efficiently in both the northern and southern hemispheres. It reminded me of Mrs. R. yelling at me when I would check the weather report on my computer before going out: "Just look out the window, you idiot. It's pouring!"
I have a little of that feeling with the new paper from a highly experienced Japanese team led by Yoshihiro Kawaoka (who is also spends time at the University of Wisconsin). The Dutch group used ferrets, the US group ferrets and mice and the Japanese went all out: mice, ferrets, monkeys and pigs, using five different isolates. Interestingly, one of the isolates was the same as the earlier paper from the US, A/California/04/2009 (CA/04). This virus was the first to be identified and came from an uncomplicated pediatric patient who recovered fully after a typical case of flu.
By several measures the swine flu viruses replicated better than the seasonal flu comparison virus and on pathologic examination of animal tissues seemed to be replicating in cells deeper in the lungs. This confirmed the findings in the earlier papers. Comparison of lethality in mice, however, did not suggest any of the swine flu viruses were more virulent, except for one isolate that came from a hospitalized patient (no statistical tests were documented and it isn't clear this single result of log 4.5 vs. log 6.5 could not have been sample variation). The same might be said of viral titers in monkeys given in Table 1 of the paper. The swine flu monkeys had slightly more fever than the seasonal flu monkeys but didn't lose any more weight. Since I'm an epidemiologist I tend to pay more attention to data in numbers, but examination of the photomicrographs showing the pathology in Figure 1 ferrets and the Supplementary materials for other animals does seem to show a more marked pathologic effect (assuming the photos are representative of the treatment groups). The swine flu viruses appeared to produce a different cytokine response, as well, although we don't know the significance of this. There was no apparent difference in transmission abilities. This agrees with the Dutch study (which used a different isolate) but not the US study (one of which isolates was the same).
What about the pigs? Not surprisingly the swine flu virus efficiently infected the pigs (these were a special kind of pathogen-free miniature pig) and like the other animals tissue pathology was more marked compared to the seasonal flu virus. But all the pigs were asymptomatic, so the differences were only visible with a microscope.
Regarding the animal experiments, then, we have data on five mammals: mice, ferrets, monkeys, pigs . . . and humans. And whatever these experiments say about how deep in the lung in mice or ferrets the virus appears to be, the clinical appearance doesn't seem to be very different from seasonal flu. Indeed the very viral isolate showing evidence of deeper penetration compared to seasonal flu came from a child without evidence of lower respiratory tract involvement. So these two pieces of information are discordant, suggesting that relying solely on experiments done under laboratory conditions with animals may not tell you everything you want to know. As Mrs. R. might say, "Look out the window." But we knew that, right? These data are pertinent observations. We just need to keep them in perspective.
There is one more puzzling result in this paper that is strangely glossed over without adequate discussion. We earlier posted on a CDC study showing that a third of US adults they studied who were over the age of 60 had antibodies cross reacting with the new swine pandemic virus. This was suggested as an explanation for why older adults seemed to be spared, just the reverse of the usual seasonal flu. H1N1 circulated from 1918 to 1957, then disappeared until 1977 when it once again began to co-circulate with H3N2 (see our post, here, for more details). Was there a difference between the pre-1957 H1N1 and the post 1977 virus? Karaoka et al. tried to resolve the question but instead deepened the mystery without even commenting on the lack of resolution.
Karaoka and his team looked at nursing home residents and workers from 1999 and from workers and patients in a hospital from this year (2009). Almost all the sera with neutralizing antibodies came from people born before 1920, a fact they interpreted as meaning that the current swine flu is related to the original 1918 virus before it diverged. So these data are not consistent with the CDC data nor do they explain why those over the age of 60 continue to be a striking minority in the current crop of swine flu cases. After raising the question of the CDC data and the discordance between pre-1957 lack of susceptibility and post 1977 sensitivity, they find yet a different result but do not comment on it. Very strange.
These three papers, by three highly competent teams of scientists, provide us with new information and raise still more questions than they answer. Indeed they answer very few questions at all, nor do they reduce any uncertainty about how this virus is acting now or in the future. I'll confess that just reading this paper and the news reports about it I might feel increased anxiety.
Until, that is, I look out the window. Then I'm right back where I started.
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This paper raised my anxiety too. Any relief I'd gotten from the declining numbers in the U.S. is basically gone.
The part of the study about immunity was more alarming to me than anything else they'd written. Especially the strong immune reaction from those born before 1920. Honestly, and with no scientific knowledge, I'd been kind of counting on that 1977 H1N1 exposure as our "safety net." I had pneumonia -- the one and only time I've ever had it -- at six years old, the winter of 1978. I've been wondering if it wasn't actually the Russian flu and if that exposure isn't why some adults in that age range have milder cases.
This is off topic, but looking at the U.S. map, it seems like cases are dropping off. Do you think we're nearing the end of the first wave here? And is there any way to predict when the second wave will start?
One possible interpretation of the Kawaoka paper and the two previous ones involving ferrets is that there are multiple variants of the new H1N1 that cause disease of different levels of severity. The isolates that came from people with more severe disease caused more severe disease in animals. This implies that some property of the virus itself is causing at least some of the variability in patient outcomes.
Dr. Kawaoka also points out that the virus may be adapting to humans. Thus, we may be seeing an unstable virus that is gradually getting better at replicating in and causing severe disease in humans.
Mono: Yes, that's a possibility. But we need to keep in mind that virulence is not just a property of the virus but a combination of virus, host and environment. CA04 came from an uncomplicated case (as did the Dutch virus) but doesn't look very different in the animal models than the isolates that came from more severe cases. Thus the animal models of virulence are only controlling certain of the relevant variables.
I'm under the impression that scientists, at this point, are able to pretty well assay the genetic make-up of these influenza viruses. Yet it seems they are relying on similarities between the phenotypic (pathogenic) expression of this Pandemic H1N1-2009 strain and the 1918 strain, and drawing some worrisome conclusions about their similar abilities to invade the lower lungs.
I was also under the impression that isolates of the 1918 virus had been extracted from the DNA of victims of that pandemic. Are they not able to simply compare (directly) their respective genetic structures to measure (with a more definitive accuracy) just how similar they are?
My follow-up is a sincere question (not rhetorical, and not implying any heinous purposeful actions by a nut-case). Isn't it true that these 1918 isolates are being held in secured laboratories. Is there the possibility that this actual 1918 virus escaped (accidentally or however) and is the very same virus now circulating. This, of course, could be easily ruled out, if your answer to my first question is in the affirmative.
Thanks, Paul
I too have been 'looking out of the window' and wondered why, if the novel H1N1 is so significantly more
pathogenic in anmimals than the seasonal flu, then why does the empirical
evidence in the by-now very large sample of the 'real-world' human population
with its surprisingly low CFR suggest just the opposite ?
Even the most pessimistic estimates for the CFR are still very well in line
with 'regular influenza CFRs' and this seems to be the case even for the
younger-than-65 age group
One paper I read estimated the number of excess deaths attributable to a typical seasonal influenza epidemic in the US to about 500-1000 deaths in the less-than-65 age group alone .
So considering the current number of US deaths (200+) and assuming a further doubling of this number until the end of the first pandemic wave (further assuming that the first pandemic wave roughly equals the number of infections of one normal seasonal wave) then the observed number of deaths among the younger-than-65 group would still be perfectly consistent with the novel H1N1 pathogenicity at most equal to that of seasonal flu.
The same conclusion can be drawn by the numbers of the published 'pediatric flu deaths' statistics where we now see about 60 seasonal versus 25 pandemic flu deaths since oct 2008.
So how can this empirical evidence fit all those worrying results of the animal studies ?
Hi Revere-
Are you saying (that this study is saying) that our current swine flu is more closely related to the 1918 flu than to the flu that circulated in the 1957 pandemic? (And related so closely that those old enough to have been exposed to the 1918 flu are more immune to the current flu than those exposed only to the 1957 flu are immune to the current flu?)
And, to ask a real "flu for dummies" question, does an entire population of flu virus all eventually mutate until it is no longer lethal to its host population, or can a tiny segment of the virulent, pre-mutated flu virus hide in another host while its relatives are busy becoming less virulent--only to reappear several human generations later with its pre-mutated virulence in tact?
In other (incoherently-strung-together) words: could the current flu have been a lurking segment of the 1918 flu that recently re-emerged, or is it necessarily a mutated form that has just mutated back/ re-assorted into a very similar virus to the 1918 flu? (Or is lurking just a standard part of mutation and evolution?) I obviously don't know as much as I would like to know about the basic evolutionary process of flu virus.
(But in my own defense--I live in Georgia--evolution is still just a theory here. Like gravity.)
Lots of questions here and I don't have time to answer them all (as much as I can, that is), but here's a brief try.
Paul: This is not the same virus as 1918 but all H1N1 is in a sense a descendent of the H1N1s that circulated in that time period. Some were in pigs, some humans. They diverged from the original(s), mixed and matched, adapted, etc. But this is not anywhere near the "original" 1918 virus. It is mostly like the virus circulating in pigs over the last 80 years or so. And the few examples of the reconstructed (not isolated) 1918 virus are in very secure facilities. Our ability to go from the genetics to the biology is very limited. And even in a single patient, there are many differences between inidividual viruses. Flu is a sloppy reproducer. The question always is which of the many small differences have any biological significance.
h1_n1: I don't know how virulent the current virus is. But the animal tests reported in these three papers don't suggest a large difference in virulence. Many different measures are used in several different animals. It is totally avirulent in pigs, the same lethality in mice. There are differences in the pathology that are of concern -- possibly -- and warrant further examination. There are differences in how the innate immune system reacts, of unknown significance. And there is the puzzle of cross-reactivity and prior immune protection, which is not settled by this paper or even discussed adequately. It is discordant with the epidemiology and the CDC serosurvey we posted on a month ago and linked in the post.
melbren: No, the current virus is not more closely related to 1918 except by virtue of the single finding relating to neutralizing antibody (which only measures a very specific similarity). But as noted above, that finding is inconsistent with other data, so we'll have to look into it more. I think the relationship of the current virus to 1918 is addressed somewhat in my previous answers but we have a couple of posts (one on the "pre-history" of swine flu) that discuss its evolution. It is not a covert 1918 virus. But as Karaoka points out, it is not a seasonal flu virus, either. That's true both biologically (his paper) or epidemiologically (age shift to the left and different risk factors).
revere, I agree that host and environmental factors likely influence patient outcome. For example, people between the ages of 20 and 60 seem to be more likely to have worse outcomes than other age groups. It is also well known that higher initial loads of virus can cause more severe disease.
However, I disagree with your statement that there is no difference in how isolates from more severe cases behaved in animal models. You have to look at all three papers to sort this out, but there is clearly a correlation between the severity of the human case and the pathology observed in the animal models. In the Kawaoka paper, the isolate from a hospitalised patient killed mice at the lowest dose. In the CDC study, the a ferret that had been inoculated with an isolate from a child that had died had to be euthanised due to severe disease.
I discuss this in more detail here here
I think it would be useful to explicitly test this hypothesis by comparing isolates from a range of patient outcomes in an animal model.
I, too, am a layperson on this, but what I have read leads to the following answer to the "flu for dummies" question. Because influenza and H1N1 in particular can inhabiot a vast number of different species, it can leave the human realm for years of decades and live in ferrets, mice, pigeons or pintail ducks and re-assert itself into the human population when events allow. The new studies on pre-1918 mixing in various species prior to the huge 1918 outbreak in humans indicates that what we are seeign now could just be the progeny of 1918 or 1957 or 1977 H1N1 coming back home to humans from a vacation in another species or realm. What we have to worry about is the potential re-mix of H1N1 and other cousins (say H5N1) whilst it is re-introducing itself to humans. Pray for us when H1N1 gets a foothold in someplace like Egypt that cannot keep H5N1 from killing their rural toddlers.
(But in my own defense--I live in Georgia--evolution is still just a theory here. Like gravity.)
melbren: I resemble that remark (malapropism intended). I, too, live in GA. And just like revere, I too, had to be instructed by my wife to just look out the window, while I feverishly conjured with my techno-meteorologic delphic gismos. So you see, even whereever revere lives, science pulls little more weight than it does in GA, when it comes to the ever-vigilant, common-sensically skeptical Wife.
This was a very strained attempt at relevance to revere's remark about his incident with his wife - what a hoot! A true everyman experience!
I live in central CA where we have moved beyond simple evolution and survival of the fittest, to enlightened evolution and survival of the cutest. From my window I can see an entire beach where humans are forbidden to tred as it is snowy plover sex and nest season. We actually had a front page story bemoaning the fact that the Canadian pig herd was the "victim" of infection from the humans of "swine" flu. They missed the important message of that story and what it means to humanity.
Source of my earlier post:
http://www.pnas.org/content/early/2009/07/10/0904991106.full.pdf+html
Revere-Thanks for referencing that earlier (June 12) post--I must have been absent that day!
Paul & Revere-Just tell your wives that if God had intended for us to look out the window to check on the weather, She wouldn't have invented Doppler Radar.
Educated guessing is about it.
My guess. The second and much larger wave will be early. This flu seems to be persisting through the summer in the northern hemisphere.
So it could rise up again as soon as conditions become more conducive to the flu. Looking for it to start around October and November, colder weather and the kids are back at school.
The game changer could be the vaccine. Projections are for the first batches to be ready in mid- September to mid-October. That might be too optimistic.
The timelines for flu resurgence and vaccine readiness are rather close. Got to wait and see.
I noticed that there have been a few pictures out there of that this little demon looks like. I know squat about viruses, but I noticed that on some LA newspaper's site today they had a TEM of H1N1, and commented that it is rod shaped, as opposed to normal seasonal flu that is spherical. Elsewhere I noticed that H5N1 is rod shaped.
Creepy. Does shape denote anything beyond shape? Or does it imply something else that I should start stocking up for the apocalypse for?
And just to re-emphasize the inadequacy of MSM coverage of H1N1, the following:
"Other tests showed the virus could be controlled by the antiviral drugs Relenza, made by GlaxoSmithKline, and Tamiflu, made by Roche AG, the researchers said."
I especially like the "could be controlled" assertion. What a relief! (not)
New flu resembles feared 1918 virus: study
http://www.reuters.com/article/healthNews/idUSTRE56C3K120090713
Mono: What I said was that lethality wasn't different in mice. I acknowledged that the pathology looks different and this is signficant. But the pigs are asymptomatic and while CA04 was more virulent in animals it wasn't in humans. You need to be careful when going from bench to bedside in situations like this. We are still learning how to make the translation and I do believe the animal tests are informative. The problem is what the information means. There are also no statistical evaluations done on some key data here, which I noted. The bottom line here is that there is room for disagreement on how to interpret these papers (and the authors all interpreted them slightly differently). That's what science is like, as you know.
raven: I think the whole wave issue is an unknown at this point. I will tell you the honest truth, which is I could believe almost any outcome at this point. As for the vaccine, it has to be made in sufficient quantities and it has to work. We can't be sure of either at this point.
TEM-tech: Flu virus in cell culture is often nice and spherical, but in tissues it is frequently polymorphous and the elongated form is often seen. We don't know whaqt the different morphologies mean (if anything), unfortunately.
Valerie: That Reuters piece was the one I linked to in the post. I don't know if that was the fault of the headline writer, something Kawaoka or someone else interviewed said or Maggie Fox giving it a little spin, but I don't think it was the best way to put what the paper actually showed. The 1918 connection was mainly through the serology, which, as I've noted, was not discussed in any depth and doesn't seem to agree with other data. It seemed like one of those pieces that didn't quite fit, wasn't enough for a whole paper and piggybacked on the other more substantial work.
we should also not forget the fact that antigenic similarity is not the same as genetic similarity i.e. gentically different viruses can still look the same to the immune system response ... So the observed antigenic match to the 1918 virus does not necessarily mean a very close match of the viruses itself.
Besides, this issue could be easily setteled by simply comparing the gene sequences of the (reconstructed)1918 and the 2009 viruses itself rather than indirectly comparing their antigenic response similarity.
I'd suspect that the mainstream media spin on the Kawaoka article came directly from the press release issued by the University of Wisconsin.
"The ability to infect the lungs, notes Kawaoka, is a quality frighteningly similar to those of other pandemic viruses, notably the 1918 virus, which killed tens of millions of people at the tail end of World War I. There are likely other similarities to the 1918 virus, says Kawaoka, as the study also showed that people born before 1918 harbor antibodies that protect against the new H1N1 virus.
And it is possible, he adds, that the virus could become even more pathogenic as the current pandemic runs its course and the virus evolves to acquire new features. It is now flu season in the worldâs southern hemisphere, and the virus is expected to return in force to the northern hemisphere during the fall and winter flu season."
http://www.newswise.com/articles/view/554196/?sc=dwhn
revere, the lethality *was* different in mice. Specifically,the mouse 50% lethal dose was 106.6, p.f.u. for seasonal H1N1 and 104.5 p.f.u. for the isolate from the individual that had been hospitalised. This is at the end of page 1 and beginning of page 2 of the paper.
Ferrets and monkeys are the animals flu scientists use to model influenza, not pigs. Pigs were looked at in this study because the virus is supposed to have originated in this species.
I agree that greater numbers of animals and isolates should be examined so that appropriate statistics can be done. However, the relatively greater effects of isolates from severe cases in humans in the work done thus far is striking, imo. It is certainly worthy of note and, I hope, of further experimentation.
I do agree that more human work should be done.
Can you tell me why on earth the CDC is not doing a seroprevalence study to get a real estimate of CFR?
Can the CFR of hospitalized swine flu cases be compared with the CFR of hospitalized seasonal flu cases? Would that tell us anything useful?
I assume we don't keep good track of all seasonal flu cases, but it should be possible to get data for the hospitalized ones. And we're certainly not keeping up with all swine flu numbers, but I assume someone is keeping count of the hospitalized ones.
And yes, I can belive this summer's ILI is cooking lungs, among other organs. Even the ones that (fortunately) don't end up in the hospital. Just a heads up for the preppers. Stick to rehydration flavors that don't include red dye. You do NOT want to wonder if what's coming out is dye...or blood!
Mono: If you read the post, you will see those figures quoted and the observation that the data presented don't allow us to know if sample variation is a possible explanation. As for what work is or is not being done now, I don't have an accounting, but I would not that CDC has had to divert many of its personnel to swine flu and there still aren't enough hands to answer all the pertinent questions that come up. We have so underinvested in public health that we will have to live with the consequences: we don't have enough scientists to do the work that needs to be done.
ipmat: One can make all sorts of comparisons. The question is, what do they mean? Because these are not cases that are representative of all cases, there can be severe and very misleading biases in making comparisons like that. Worse, we don't have an easy way to know the direction and extent of those biases. It really requires systematically planned studies and there is too much work and not enough hands available to do them all. Some are no doubt being done, but not as many as could be done if we hadn't been cutting CDC and NIH in real dollars year on year.
revere, sorry, at this point I'm not sure what you are saying about the animal studies. In any case, I think we have both made our points on this subject.
As regards the CDC and the seroprevalence studies, sorry, I don't think they have been done because they are "too busy" or because they don't have the funds. They squandered huge amounts of money on office furniture, a fancy gymnasium, mood rooms, zero gravity chairs, useless flat screen monitors and more. To be fair, this occurred under the previous director. However, the new Director has plenty of money and personnel to do the necessary seroprevalence studies. It is choice not to do them, and instead, to do stupid phone surveys and "modeling".
Senator's report: CDC wastes millions on perks
Mono: No one was harder on CDC management then we were. But the idea that the money was wasted on furniture, etc., is utter nonsense. Those sums aren't at all comparable to what we are talking about. The problem was two fold. One was mismanagement, not of the fiscal of but the managerial type where a CDC Director sucked up to political bosses; and she also failed to fight for her agency and for public health. Those are both political issues traceable to a mandate given an administration by voters who didn't care it was happening and now are seeing the consequences. We are talking about a field you have no information about and I do. There has been a decimation of resources in public health over the last 30 years (since Reagan) and the result is we can't do things we need to do. I see it daily and I know how big the community is and what it has on its plate. You don't. And CDC did seroprevalence studies. Their personnel are working (to my certain knowledge) long hours and many are away from their families, sent from one place to another. There is no reserve capacity. You need to pick your targets more constructively. There are plenty. Like everyone who voted for lower taxes to start with.
As for Tom Coburn, he's not exactly pro science. But he is anti taxes and part of the problem. Yes, there was some stupid stuff done, but that kind of stuff was symptomatic of CDC Direcdtor sucking up to Coburn's party. He doesn't mention that because he's an opportunist ideologue who would like to see government go away and will attack it any way he can. His points are proper as far as they go but he doesn't want to go all the way because he'll wind up looking in the mirror.
revere, I don't endorse Senator Coburn's politics or his spending priorities. However, AFAIK, his accounting of how the CDC squandered money is accurate. I have seen many posts on CDCchatter also suggesting that Gerberding wasted money.
I support money for public health. However, I think the need for more funds is primarily at the State and Local level, not at the CDC. However, I won't claim to be an expert on this, as you apparently are.
I am an expert on PCR. So, believe me when I tell you that the CDC's capacity to do high-throughput PCR to determine whether or not people were infected with the new H1N1 was pathetic. The cost to set up an automated system to do this is minor compared to their budget. The need to do this before a pandemic started was obvious. Only incompetence can explain why it wasn't done.
If seroprevalence studies have been done, why haven't they been published?
Mono: If you can't think of any reason beyond incompetence, I can't help you. But what they did is provide the capacity for the states to do it, something they lacked before CDC gave them assistance. As for the serology studies, they appeared as a Dispatch in MMWR a month ago or more. They continue to do such studies as far as I know. They are not done with a snap of the finger. As for PCR, the surveillance system uses a network of laboratories (150), not one lab. CDC's lab developed the primers. It is not a high throughput lab.
revere, sorry, the CDC did not provide the States with any capacity whatsoever. What they did do was provide primers. Not exactly rocket science. The CDC was insisting that the samples be sent to them in the beginning to be confirmed. They should have had a high-throughput lab.
What is needed are seroprevalence studies, ie, systematic studies of who was infected and who was not so that a proper CFR can be calculated. AFAIK, these have not been published. Once an assay is ready, collecting the data should go pretty fast. In the meantime, it's a good thing we have animal studies (to bring us full circle).
Mono: According to CDC, the ability to do seasonal subtyping was a direct result of training and capacity building related to avian flu pandemic preparedness. When swine flu came along, provision of the primer then allowed the state lab network to do it at their sites. The quick development of the primer was also a result of work already being done at CDC on swine flu viruses. If you have information that says what CDC has said is incorrect, by al means I'm open to hear it.
revere,
The primary credit for discovering the new H1N1 virus should go to the US Navy. It was the Naval Health Research Center that spotted the anomalous result. It was DoD funding that made this possible. The CDC does have a collaborative relationship this group and did the final confirmation, but it is wrong to give them sole credit for this important achievement.
Behind the Scenes: Navy Researchers Helped Spot Swine Flu in the United States
re: designing primers for PCR. High school kids can, and do, learn how to do this in an afternoon. The CDC designed the primers because they controlled the sequences. Designing primers didn't require any kind of technology development. Anyone with access to the sequences could have done it. Well, except perhaps Peter Bogner. Now, if I want to learn how to ski, I'll ask the CDC. They could probably point me to the right person for that. And if I'm extra nice to the ski king, perhaps he will let me see some of the secret CDC sequences.
Mono: Please no more straw men, here. Don't put words in my mouth. We have covered the Navy lab contribution several times, in detail and on the first day. The BIDS surveillance found an untypable flu A. Sequencing was done at CDC and primers were already mostly prepared there for other reasons. If the reagents are so easy to make, why not make them and give them away yourself. The analysis is costing everyone else up to a couple hundred bucks.
All you seem to want to do is crap on CDC. My advice: do it when they deserve it and give them credit when they don't. No charge for the advice.
revere, I'm really not trying to put words in your mouth. If you gave credit to the Navy in an earlier blog, great. I didn't see that one. I was simply responding to your post above which did not mention them.
As regards designing the primers myself, I do think it would be great if all the States had access to all the sequences in a timely fashion so they could design their own primers. Although the sequences from the J. Craig Venter Institute are being deposited at NCBI, apparently some of the sequences the CDC has are being given to GISAID, Peter "the Ski king" Bogner's private reserve. This is disgraceful imo and deserves to be crapped on.
The relevance here is that in order to design primers, you need sequence data. Because this virus is constantly mutating, and possibly reassorting, a constant stream of sequences are necessary. It is beyond infuriating that a ski instructor should control any of these sequences. They should all be in Genbank. I'm pretty sure I'm not alone in this belief.
Mono: I agree completely about sequence, data, although I don't think the primers can possibly be a secret. They are available all over the world now. And do you really want everyone to be using different primers, whichever ones they want? As for GISAID, it's a bad compromise. I blame some of the world's leading flu scientists for this. No one should be allowed to even SUBMIT a manuscript unless the sequences are already public. There should be no review of manuscripts with non public sequences as data. Period. That's a scientific journal issue, too. CDC, St. Jude, Mr. Sinai and the whole crew (but not NIH, as I understand it) are guilty and deserve condemnation, which I have done here multiple times. The ski king thing is a red herring and not the issue. The ethics of scientific publication in a pandemic is the issue.
I'm glad that we agree that all sequences should be deposited in Genbank. I know that the CDC is guilty of not depositing all their sequence data in Genbank. I don't know about the institutions you list. I also think the NIH does support open access for flu sequences.
It's not the primer sequences that are secret, it's the flu sequences that they are based on that are under control of the ski king. To design primers, you need the sequence of your target before you start. Because flu sequences are constantly changing, you may need to design new primers. If you don't have access to the new flu sequences, you can't design new primers.
Let's take one example. Suppose a new variant of the new H1N1 arises which has a mismatch between its sequence and one of the primers. The PCR may fail as a result. This will result in two negative outcomes: 1. You will get a false negative result. 2. You will miss the spread of a new, and possibly more dangerous, variant.
Only by constantly sequencing new flu viruses as quickly as possible and comparing them with your primer sequences can you avoid this outcome.
Just one more question before slipping off to 7.48 hours of cell rebuilding slumber: having gotten a quick education of ARDS courtesy of wiki, is it possible that some of the deaths might be attributable to less than perfect medical response? Those being ventilated getting too much of a tidal surge, so to speak? I think also of the initial report of the 20 year-old woman in San Diego who walked into an ER and quickly succumbed. One article alluded to the possibility of her receiving too many fluids? Just a layman asking, not positing, or, as my teenage son might say, blowing out my ....
downeast: People who die while infected with flu virus die of all sorts of things -- including flu virus, but not always from flu virus. It's an unpredicdtable pathogen and much depends on the way your body handles it. Mostly we don't know why some people go sour and others go home.