Part 1 Sequence data is being blocked
I have argued in several different threads that sequence data is being blocked. Why do I think this?
1. The American CDC’s official policy is to block the release of flu sequences. See this story CDC locks up flu data in the Atlanta Journal Constitution.
2. H5N1 was reported in children in Turkey on January 1 2006. The WHO had sequences on January 12 2006. “Studies on the genetic sequence of the viruses from tissue samples taken from the first two fatal human cases in Turkey indicated they were ‘very similar’ to H5N1 viruses found in birds in Turkey and China, the organization said.” Reference. These sequences are not yet deposited at GenBank. This can only mean the data is being blocked. The WHO has the data. Either they are blocking it or Turkey has prohibited them from releasing it. Which is true?
3. China has not deposited any sequences from humans in GenBank from 2005 or 2006.
4. Yesterday it was reported that H5N1 sequences from humans in Indoneisa do not match the avian sequences but instead match feline sequences (see discussion in this thread?). Human sequences from Indonesia have not been deposited in GenBank despite the fact that they people infected with H5N1 were identified in July 2005. Someone is blocking the Indonesian human sequences from being made public. Who?
What happens when sequence data is not blocked?
France discovered bird flu in a duck on February 18, 2006. Sequences from this duck were submited to GenBank on February 21, 2006 and available to the public on February 23, 2006.
Are they trying to keep the info out of the hands of terrorists, or are they incompetent, or are they just stoopid?
They want to be the one to make the ‘right’ vaccines.
Part 2 Blocking sequence data is harmful to our health
1. It is impossible to design reliable primers without accurate sequence information. Since PCR is one of the key techniques used to determine whether an individual is infected with H5N1 or not, blocking sequence data means that H5N1 could be spreading and infecting individuals without detection.
2. Blocking sequence deposits prevents us from knowing whether existing vaccines are likely to work.
3. Blocking sequence deposits prevents us from picking the most appropriate strain for vaccine development.
4. Blocking sequence deposits delays the use of new, rapid vaccine development technologies.
5. Blocking sequence deposits blinds us to the evolution of new strains of H5N1 which would cause us to raise our alert level if we knew about them.
These are not merely academic arguments. Blocking sequence data may result in the deaths of millions of people.
Monotreme, can you check whether it is only human sample sequences that are not appearing? For example, are they posting poultry sequences from Turkey for the same period?
Taubenberger published his 1918 sequences, so I guess the terrorists have all they need.
Information control is important to any governing group. And is important to us in the inverse.
We need these sequences that are obviously available. More eyes on the page will almost always solve a pattern faster and more accurately.
Monotreme-
Great aggregation of the quotes.
anon_22 may be right. If H5N1 goes pandemic with its existing virulence, the impact on the world will be similar to all out nuclear war between the major powers. Perhaps the hoarding of sequences are an attempt to turn a natural tragedy into an opportunity for national stategic advantage. Despicable, if true.
As an interesting aside, I spoke to a R&D guy from Aventis who told me that the part of the vaccine manufacturing process that is proprietary is the selection of the antigens. That is, the decision to choose a specific sequence or sequences to use would make a big enough difference to the efficacy of a vaccine, everything else being equal, to make this part of the process highly secretive and highly lucrative.
Anon-
They want to be the ones to make the right vaccine.
I wish it was as simple as a single ‘they’.
Let’s face it; we’ll be working with sparse data for the duration. We’ll do our work based on clinical reports and classify it as anecdotal until verified.
Mono, not ‘national’ advantage. Commercial advantage. The competition is not directly between nations, but between the vaccine manufacturers who have signed contracts to make vaccines for a particular country and therefore has to be protected.
Disclaimer: this is just my hypothesis, I have no insider knowledge.
anon_22: Avian sequences have been deposited from China and Indonesia, but not human sequences. Henry Niman pointed this out yesterday at Effect Measure. I’m not sure whether *any* sequences, avian or human, have been deposited from Turkey, but I’ll check.
It may not even be a the government’s choice to delay depositing the sequence. Suppose a government (without specifying which country) wants to get a major vaccine manufacturer to make vaccines on its soil instead of another country, so as to ensure that that country will have first go at the vaccine. What advantage would they have to give to the company? Money? Yes. Litigation protection? Yes. Help with securing viral sequence? Yes. An agreement to not disclose or to delay disclosing sequences for a period of time? Could be….
anon_22: I don’t doubt that there are commercial advantages to having the “right” sequence. However, the decision to block deposit of H5N1 sequences is being made by governmental and/or international agencies. For example, the decision to block sequences at the American CDC from being deposited was made by the director of the CDC. The only way companies could influence this process would be if they bribed these officials. Is this what your hypothesis?
anon_22: “An agreement to not disclose or to delay disclosing sequences for a period of time?”
Not sure this would be necessary in the US. We could just pay the company to make the vaccine or make it ourselves. Besides, my understanding that even if all the flu vaccine manufacturers in the world were to devote their entire capacity to making H5N1 vacccine, there still wouldn’t be enough for everyone for many years. An overabundance of competing vaccine is *not* going to be a problem for any company.
Mono, see my post 8:52.
Also, it could be argued that the ability to corral the ouput of a vaccine producing company gives some national security advantage, so your ‘national’ competition theme could come in, to justify this act.
Monotreme, whoever makes the vaccine first gets proprietary rights. Other companies cannot then make exactly the same thing without infringing those rights. That is the commercial advantage.
Anon and Mono-
Nationalism is on the rise around the world and especially in Asia. Mix that with a little xenophobia and you can see the move toward “national” advantage over assisting all people.
anon_22: Not sure if you saw my post at 08:59 reponses are going back and forth pretty fast.
My basic point is that no company *needs* a commercial advantage. They can only make so much vaccine. Every ounce of capacity will be used. Although I know companies are highly competitive, it seems unlikely that they simply want to be spoilers and let millions of people die so that their competitors don’t make any money off a vaccine.
In any case, the data blockage needs to be explained.
On the topic of national security, what is the relationship between the CDC and the USAMRIID these days? How do they carve their territories? Does anyone know?
MOno, “Although I know companies are highly competitive, it seems unlikely that they simply want to be spoilers and let millions of people die so that their competitors don’t make any money off a vaccine.”
No, the outcome is not to stop competitors from making vaccines. The outcome is to make them pay for the right to make the vaccine with that particular sequence.
Whether my hypothesis is accurate or not, and we may never know, as we get closer to a possible pandemic, such commercial interests will play a bigger and murkier role. We need to keep an eye out for them.
who cares about rights, when the pandemic is there. If they _do_ have a vaccine, do you think they won’t use it because of proprietary-rights ?
Suppose, I go to the beach, pick up a dead swan and send it to France,USA,China,Weybridge..Would that be illegal ? Would they even pay me for the swan ? What about the dead swans in international waters in the Baltic Sea ?
gs-
get all you can carry and report back here.
Oh yeah, do this exercise first . . .
What are the probabilities of infection of the bird thief? What are the probabilities of mortality of the bird thief? What are you thinking gs?
anon-
Now, you’re opening a whole can of germs (CDC/Detrick/Plum)? Official statements may display information control cycle.
I’m not sure it’s governments (could be) and it’s clearly not (just) WHO (see CDC comments) - but the bottom line is that these sequences should be available to everyone.
I do tend to comment when the ‘wrong’ people are blamed, but the bottom line is that we all want the same thing.
gs, Don’t forget to wear your goggles mask and gloves. Not sure a swan will make it through the x-ray screen at the airport…
;-)
Really need human samples. How many labs are even the right level of biosecurity to look at such samples?
The sequences should be being made public. (The people witholding them should be put on burial detail if pandemic occurs.)
“Modern advances” are not going to save us from a worse than 1918 pandemic, because the human nature/motivation/character has not improved.
“Whoever wishes to foresee the future must consult the past; for human events ever resemble those of preceding times. This arises from the fact that they are produced by men who ever have been, and ever shall be, animated by the same passions, and thus they necessarily have the same results.”~ Machiavelli
It’ll be a few hundred years after this pandemic before all the threads of the political/economic story are separated and told. I find this the most fascinating of all the threads because 1) BF is natural and science can eventually figure it out and 2) the human variables are what will truely determine the outcome. BF is a potential goldmine to those positioned to play on both the knowledge they hold/withhold and to those who are willing to prey on human fear.
anon_22 – at 09:13 “commercial interests will play a bigger and murkier role. We need to keep an eye out for them.” I agree, how do we push for accountability? What leverage do we use?
That’s where the press and media are invaluable.
DemFromCT – at 09:56 “That’s where the press and media are invaluable. “ And Fluwikie. :)
There is a similar conversation on the flu clinic http://www.curevents.com/vb/showthread.php?t=40506 about the prompt release of sequence data from Italy.
Niman mentioned some North American data has just recently been added to GenBank which is up to 30 years old. I think the H5N1 sequences from Canada have not been published. Conspicuous by omission. I believe that sequences can be looked up here http://flu.lanl.gov. Just use H5N1 in the refine field of the search.
http://www.fluwikie.com/index.php?n=Forum.H5N1InTheUnitedStates 22 February 2006 niman – at 05:12
A large number of sequences from North American isoaltes have been withheld for the past 25–30 years. Thsi month those sequences became available and they help track the path of portions of genes that are acquired via recombination.
Most importantly, notice how niman was able to immediately put that new, old data to work.
More data always equals a more reliable model.
Montanan, “how do we push for accountability? What leverage do we use?”
Public outcry? The indignation of the crowds?
But seriously, our most important leverage is our credibility. To praise where praise is due, to criticise or challenge where those are appropriate, but never losing sight of the purpose of the wikie, which is the seeking of truth for the benefit of all humanity. Not just truth for its own sake, the seeking of pieces of data or information to be collected and displayed in a museum. No, we want to put out truth that is useful, that is pragmatic, that takes into consideration all the imperfections and obstacles that others as well as ourselves face, and strive to turn those into positive outcomes. And at any time to be willing to acknowledge when one is wrong.
<Dem, you should take away those soap-boxes…>
NS1: “More data always equals a more reliable model.”
I think we’re all agreed on that.
The CDC was hoarding influenza sequences before H5N1. Further, this information was not used to develop a better vaccine for the flu. In fact, it wasn’t used for anything at all. The NIH finally got access to the sequence data and discovered that H3N2 had drifted, but too late to change the strain used for vaccine. The CDC had sat on the data too long. The result was that vaccine used was a bad match to the circulating virus. It it is highly possible that people died as a result.
I agree commercial interests may be at play, but I just don’t think the vaccine manufacturers have enough juice to blackmail the president of the United States. He can order Dr. Gerberding to release the sequences the American CDC has. Why doesn’t he?
No, I don’t think it’s all commercial interest either. It was just a hypothesis that I wanted to throw out. Probably a combination of many things including bureaucratic sclerosis.
“the president of the United States. He can order Dr. Gerberding to release the sequences the American CDC has. Why doesn’t he?”
Why should he? Do you know that there are people whose instinct is to hoard? Any information that I have over you may eventually give me an advantage even if that advantage is not obvious at the moment. (Here I am just speaking in general terms.) Each president must have only a certain amount of goodwill or political capital he can spend. Why should he spend that in ordering the head of the CDC to do something that has no immediate obvious benefit to himself but would very likely alienate a whole chunk of people that he cannot afford right now?
That’s a need to know question and . . . ---------------.
The remainder of that sentence was withheld for the purposes of biosecurity.
anon_22 – at 10:18
<Dem, you should take away those soap-boxes…>
why? you say it so well. ;-)
If commercial interests are involved, it is possible the POTUS will not order the release of anything. Part of the pandemic plan is to favor commercial interests. Some of that is needed, perhaps, but the liability protection issues are rather controversial, and favor the manufacturers. Just an example.
anon_22: Frankly, I wish POTUS would fire Gerberding. She has screwed up vaccine delivery year in, year out. If she continues to hoard data and screw up vaccine delivery many, many people will die.
Grieving family members are going to hold the President accountable for the perfomance of his Director of the CDC. Talk about alienating people.
Caveat emptor.
In the end, we are the experimental subjects and knowing that fact, we much accept the liability or remove ourselves from the lab table and take responsibility for our own individual health.
The databases (GenBank and Los Alamos) seem to be on a war footing. Usually it takes days or weeks for submitted sequences to appear amd then more days or weeks to actually enter the searchable database. Both GenBank and Loa Alamos already have the Nigerian and French sequences in the searchable databases.
Now is really the time to pressure the laggards who are holding the data.
There are no human sequences from China or Indonesia. There are no sequences from Turkey or Iraq. The European and Middle East sequences are limited to the French and Italian sequences just depositied. Canada has only deposited the one H5N2 from the duck farm in British Columbia.
Much of this data is being generated with government funds. It is time for the government funded agencies hoarding the data to make sequence deposits immediately.
to me the bigger picture is “world power”, may sound “over the top” but the goverment with the “healthy people” vaccinated public,, will be the strongest. They will have more then the upper hand on all aspects of this. It’s more then scary. Where did this start? Asia….. What country has the most to gain by the “rest” of the world dealing with a pandemic?
Sorry maybe I’ve been watching too many movies….
Perhaps not a surprise, but I agree completely with niman at 11:14.
Anonymous at 11:41: Friday there was a good front page article in the Wall Street Journal on China withholding this data. Even the reporters of the story had to admit that the original “academic flap” was an excuse not to release the data. They are still negotiating with China. Any day. Ha!
The WSJ story was by Nicholas Zamiska, an excellent reporter for the WSJ. Search for him on the site as he often writes about bird flu there.
Monotreme – at 11:56
here’s a rare scenario: Monotreme, niman and I all agree. In fact, it’d be hard to find someone on these pages who doesn’t. niman’s right in the sense that if governments wanted to get this done, it’d get done.
POTUS somehow pressures CDC to release blocked sequences. But China and Indonesia continue to withhold.
Are USA special interests harmed and Chinese special interests served? How important are withheld blocks of data? How similar to published data? Americans don’t know how similar, but Chinese do?
Someone should invent effective pressure.
anonymous: There will be no negative consequences to the US if the sequences are released. People in the US who are working on vaccine that would be used to treat American citizens first do not have access to the CDC sequences. US preparedness is being harmed by the Director of the CDC’s behaviour. Also, the more countries and agencies that release the data, the more pressure it puts on the holdouts. If the US comes clean, it can make a case for economic sanctions on those who don’t. Right now, POTUS is in no position to complain about what others are doing. The Director of the CDC is an embarassment to his administration. She has the potential to make Michael Brown look like a crack efficiency expert.
i wouldn’t go that far. No one could do that.
re “effective pressure” and “economic sanctions”, to be any more than a privately expressed threat, the latter “sanctions” would require some public announcement. Imagine some US government official threatening economic sanctions because China has withheld bird flu sequences when the US government is still low key about bird flu as a public health risk. That could be a curious thing, a case of one thing not being in accord with another. The discord problem is solved if the US threat could be delivered quietly, but it’s still of little or no consequence unless the threat is made public. To deliver the threat publically would be tantamount to public admission that bird flu sequences and bird flu in general is a big deal. Now China is able to ask, what’s it really worth to you?
So going public against China would come at some cost and increase the dissonance that comes of saying we should be prepared but still doing precious little to mobilize for it.
DemFromCT: I’m not so sure that Gerberding has any more going for her than Michael Brown. Until Katrina happened, how many people knew how incompetent he was? The full depth of Julie Gerberding’s incompetence may not be apparent until the pandemic has begun. Too late then to install competent leadership at the CDC.
dubina: Good analysis dubina. I think the threat posed by an influenza pandemic is only slowly being realized by politicians, especially in the West. More scientists need to support Osterholm in banging the drum for preparedness.
A dumb question here…the influenza sequences I’ve been reading about all this time refer to what exactly? Gene sequences, protein sequences…??? I need to know so I can start demanding some action from my government.
dubina,
We threaten sanctions against China constantly with no effect. Our economic power of using their prison and slave labor is becoming a basis of our economy. I’m not sure that our threats of economic sanction have recently been taken seriously?
The gene sequences are missing. Gene sequences are conceptually translated to get the protein sequneces. The flu sequences are deposited at GenBank or Los Alamos flu database , which are publicly available.
One more dumb question…Are flu sequences determined by the gene sequence?
…or should i ask are gene sequences and flu sequences one and the same?
BF: Both the gene sequences, which are RNA, and the protein sequences are “flu” sequences. Every organism, including the flu virus, has its own gene and protein sequences. Knowing the precise “spelling” of these sequences is critical to address the issues in my post at 08:39.
Thanks. So when I call my congressman, I take it I should complain about the “flu sequences” not being readily available to those needing them…thus possibly delaying any potential vaccination on the horizon and hindering the ability of tracking the current strains of the avian flu.
BF, sure, or call them H5N1 sequences.
House congress critters are here, Senate here. Phone calls mean more than email.
And faxes are better still. Congressional staffers actually weigh the stacks of paper.
Thanks. I feel like I’m back in school in science class, and you guys are the teachers.
If I had $20,000 to donate to their campign, that would work even better. They might even take my call.
if you live in their district, they’ll take your call.
If you are writing or phoning, add that you want FULL sequences published. The Astrakahn PB1 and PB2 sequences have picked up human polymorphisms
http://www.recombinomics.com/News/02260601/H5N1_Astrakhan_Human.html
The corresponding genes fro Nigeria, France, and Italy have not yet been deposited (and the US hasn’t found anything to deposit - although just seeing hwat’s in Canad would help).
can we be sure that the published sequences are correct ?
Is it even possible to control/verify that ?
In theory they could send a part of their sample to a reference
laboratory who does random controls.
Has it ever happened that a published sequence had been proven fake ?
How certain are they about the sequences, can errors occur
with small probability ?
I assume they get the data slowly, first partial sequences which
then are more and more completed, so they are often saying: “we are
not ready yet”. But they have the partial sequences in their
computers.They could just put it on their webpage
Dem:not only H5N1. And it’s not a good moment in USA, now that the St.Jude sequences finally were released, looks as if we wanted to complain about that. Maybe a party to celebrate this or lots of thanking letters were better ;-)
gs: GenBank is based on the honor system. Sequencing errors do occur. The best way to sort out fraudulant sequences, which I have never heard of, and sequencing mistakes, which occur quite frequently, is to have as large a database as possible from as many independent labs as possible. The data can be obtained very quickly - 24–48 hours. Depositing in GenBank is expected of honest scientists and is a simple procedure which takes very little time.
The CDC has NOT released their sequences of flu viruses that infected people. We can celebrate the sequences that were released from Webster et al., but the CDC is still hoarding tons of valuable flu sequence data.
If the information is considered vital to national security and is classified as Secret, Top Secret, etc., can the CDC release it? What rules prevent its release and who do we talk to about it?
may I also say, that IMO the databases are bad. The data isn’t easily computer-readable, someone should modify and edit the data, so it can easily be used by computer programs. It’s lots of wasted time, if everyone who works with the data has to write his own programs and convert the data into better formats.
I’m wondering a bit, whether this is intentional so to discourage others on working with the data. I offered to work on unifying the data without payment, but apparantly they are not interested.
The St Jude sequnces were released in part due to the NIAID flu blueprint program, which will sequence flu isolates for free (but the data has to be made public). TIGR has been doing the human sequences and St Jude is doing animal. The goal is to get full sequences on all eight genes and to include details such as collection date and in the case of human isolates, age and gender (and the large number of NY isolates included the county where the patient lived).
Russia may be paying attention. They just released the data on the 7th mute swan (and released PB1 and PB2 sequences first). The data indicate that the acquisition of the polymorphisms have been RECENT because this latest isolate matches the consensus but is missibng one of the PB2 polymorphisms from Hunan.
Do all the countries have the equipment to isolate the sequences? Many european countries are able only to determine the presence of H5, for the additional research the samples are being sent to UK (I think name of lab is Waybridge). Who is then responsible to publish the sequence? Owner of the sample or the lab?
gs-
what are your ideas in unifying the data. How much data is there? How complex is it? which part should be unified first for maximum effect? I’d be happy to be a sounding board.
Niman-
Is there a better sequence format / delivery mechanism that would make your life easier or allow you a faster interrogation / interpretation of the data once it’s published? Are you using a standard software or does your model include some sort of front-end that re-formats, cleans and typifies the data?
No, I can use the standard software that is freely available to extract and analyze sequences and though I am in discussion regarding more fine tuned analysis and better outputs using the standard databases like GenBank.
Niman-
Do you think they have the resources to be responsive to the features that you are requesting?
Do you work with any software developers in honing your model?
How much data do you personally store? If you could store more and manipulate it more freely, would it be useful?
at the rate of human sequence aquisition, not to be morbid, but how much time do we have?
Yes,please, just a guess as to how much time we have????
2.3 hours.
NS1, :(
Did anyone else think 2.3 hours is funny?
No one can say with certainty. The latest isolates have a strong set of genes for H2H. The bug is traveling very widely and very well and is still changing.
Be prepared as soon as possible. Make your body perform properly. Be sensible and be aware.
Your local news station may not be the ones to break it to you if PF51 comes; if you pay attention, you’ll already know.
I think you are awesome, NS1 : )
jskol-
is that a sad face?
A smile just for you! You work so hard for all of us!!!
I appreciate the work that so many do on this site.
Thanks for the smile. It’s already been a long year.
I’m just trying to get my brain around all this H5 stuff and look at the larger picture of where we are going, individually and as a people.
NS1:
Which isolates? from swans? So this doesn’t matter IMO… and again, if it’s more and more adapted to humans, for the facts that now it’s widespread, why we see LESS human cases than before? (apart from Indonesia, which IMO is the great unknown now)
NS1, some thousand records (5000?) for H5N1, the names are nonunified, e.g. hemagglutinin or Haemagglutinin, many orthographic errors, some sequence errors . The sequences should be aligned so they can be compared. The genes are not easily linked to the viruses. I’m new to this, I don’t know about the software Niman is talking about. I couldn’t find another forum, where this is being discussed.
gs-
I noticed all the same things when I undertook analysis.
I study trending as an art and a science. So I frequently architect the underlying data designs for inquisition on massively parallel supercomputers. I wonder if these guys have already solved the problems that we see?
H5N2 sequence from Bavaria shows what Canada is hiding
http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?db=nucleotide&val=88656455
A/mallard/Bavaria/1/2005(H5N2)
Although the above sequence is H5N2, it has aquired a number of H5N1 and H7 polymorphisms.
H5N1 knows what it is doing. It has silently taken over Canada, which is why the LPAI H5N1, H5N2, H5N3, H5N9 sequences have not been put into GenBank.
The sequences show H5N1 and recombination in action and is cause for concern.
Henry,
Any fix on the H7 polymorph likely donors? species? location?
Where is the cleavage on this Bavarian mallard strain?
The cleavage site is LPAI. Here are the isolates that share one of the polymorphisms
DQ340848 A/chicken/Crimea/1/2005 2005 H5N1
DQ320910 A/chicken/Hunan/999/2005 2005 H5N1
DQ095630 A/Duck/Hunan/114/05 2005 H5N1
DQ320902 A/duck/Hunan/127/2005 2005 H5N1
DQ320903 A/duck/Hunan/139/2005 2005 H5N1
DQ320904 A/duck/Hunan/149/2005 2005 H5N1
DQ320905 A/duck/Hunan/152/2005 2005 H5N1
DQ320906 A/duck/Hunan/157/2005 2005 H5N1
DQ320907 A/duck/Hunan/160/2005 2005 H5N1
DQ320908 A/duck/Hunan/166/2005 2005 H5N1
DQ320909 A/duck/Hunan/182/2005 2005 H5N1
DQ095631 A/Duck/Hunan/191/05 2005 H5N1
AY651365 A/Dk/HN/101/2004 2004 H5N1
AY651364 A/Dk/HN/303/2004 2004 H5N1
AY651363 A/Dk/HN/5806/2003 2003 H5N1
The above shows why the polymorphsism being aquired are NOT random mutations. the polymorphism in the “novel” 2005 H5N2 isolate from Bavaria is clearly recombining with H5N1 and picking up “novel’ polymorphisms. In this case the polymorphism is limit to a Qinghai sequence from Crimea isolated in the fall of 2005 as well as a long list of Hunan isolates from 2003 to 2005.
This is how influenza evolves and why H5 is so dominant in Canada (and those sequences have been described - LPAI H5N1, H5N2, H5N3, H5N9 - but have NOT been deposited at GenBank).
Sequences at GenBank and Los Alamos are submitted by the researchers. so there will be spelling errors and not all descriptions or names follow all of the rules..
BLAST searches are used to find the closest matches and sequences are aligned. The uses interface at Los Alamos is the most friendly, but now requires a fee to use. There is a similar alignment set up at NIH, but it is slow and the output is not as easily read. Other software like Clustal W are widly avaiable an line up selected sequences (protein or nucleic acid).
HA cleavage site of Bavaria mallard is PQRETRGLF.
Significance of this polymorph besides tracking and proof of recombination? Where is the change? What does it do?
Is there a deletion near the cleavage site?
Are you offloading and norming the data names and then aligning the sequences in a standardized way for your own storage and analysis?
The polymorphsism is one of many to show that the H5N2 has H5N1 sequences. These homologies increase the frequency of recombination and provide another mechanism for the H5N1 takeover. Clearly LPAI H5 is all over Canada and it is probably also all over western Europe.
The cleavage site is a typical LPAI.
http://www.recombinomics.com/News/11250502/H5_H7_Maritimes.html
http://www.recombinomics.com/News/11190504/H5_LPAI_Quebec_British_Columbia.html
http://www.recombinomics.com/News/11190503/H5N1_LPAI_Manitoba.html
24% of bird tested in British Columibia were H5
Is it likely that the H5N2 could carry take some important H5N1 H2H polymorphisms and conserve them long enough to pass them to another developing LPAI isolate of H5N1?
What rules of recombination apply here? Can H5N2 be a taker and then a giver later?
Niman,
Weren’t some species close to 50%?
The sequences are aligned using the standard BLAST program at NIH and then the flu database is screened for interesting polymorphisms using proprietary techniques (for identification and screening).
For those interested in running BLAST on their own clusters, mpiBLAST works quite well. You can get it here. Here is GenBank’s ftp site. You can download what you want and run mpiBLAST or BLAST on your cluster. BLAST is not necessarily the best algorithm for aligments. Its main advantage is that its fast. Here’s a page with information on various types of alignment algorithms.
For some regions 50% of the tested birds had avian flu. If believe the 24% in BC was the highest group testing positive for H5.
NONE of these H5 sequences in wild birds in Canada are available at Genbank or Los Alamos.
Is your method rules based or data-matching based?
Or are you the hueristic engine?
My approach identifies EXACT matches which will fa=cilitate recombination. Here is some additional detail on hoarding of sequences
Niman-
Are you using a database of rules or a database of sequence combinations?
Or do you just have all this info in your head?
I use a BLAST program for a quick alignment and them search sequence databases for identification of isolates with donor sequences. These approaches leave little doubt that the newly acquired polymorphisms are NOT “random mutations” and are acquired via recombination.
The analysis requires a robust and complete database and I expect WHO and consults hoarding of data or sharing it in a small group who all think alike and put out the same old phylogentic trees in an effort to find reassortment, will soon come to an end.
It is becoming increasingly obvious that the two pillars of of influenza genetics, reassortment and “random mutation”, will soon come tumbling down because they can’t hold the sequences forever (although holding the North American sequences for 20–30 years certainly comes close to forever).
well sounds to me (I’m a software developper in a big german company, i.e. SAP, with brackground in computer science and optimisation) that you don’t have a program that use mathematical applied (heuristics) or expert engine or artificial intelligence or constraint programming… and I can conclude that you have everything in your head, nothing else…
It’s called “Elegant Evolution” because it is quite straight forward and easy to analyze. Here is another example of the “novel” 2005 H5N2 duck from Bavaria. Many of its polymorphisms are found in H5N1 isolates. This polymorphism is most telling and is clearly NOT a “random mutation”.
Of the 4 isolates at Los Alamos that share the “mutation” three are H5N1 and the other one is H5N3 from a duck at Chany Lake (first Nature Reserve where Qinghai strain was found after Qinghai Lake outbreak). One of the H5N1 has the same HA cleavage site (GERRRKKR) found in all Qinghai isolates in Europe, Middle East, and Africa.
This “random mutation” has a few too many coincidences.
AY830774 A/chicken/Macheng/2004 2004 H5N1
AY639405 A/goose/China/F3/2004 2004 H5N1
DQ007623 A/Anas platyrhynchos/Chany Lake/9/03 2003 H5N3
ISDN111352 A/Chicken/Indonesia/11/2003 2003 H5N1
NS1 – at 20:48 (26 Feb)
“We threaten sanctions against China constantly with no effect. Our economic power of using their prison and slave labor is becoming a basis of our economy. I’m not sure that our threats of economic sanction have recently been taken seriously?”
I’m sure that true, but think of horsetrading. Whenever these people want something (short of going to war to get it) they have to decide what it’s worth. What do they have that we want, and what do we have that they want? Negotiation, formal or otherwise, creates an array of possibilities. More negotiation narrows those possibilities to a few. In any case, it seems to me that the side wanting sequences doesn’t want them enough for a public display of affection, partly as said display would betray the higher value / greater cost to have said sequences in trade.
This conjecture is predicated on the notion that elements in China could have much to gain at the possible expense of global biosecurity. That may be; it’s not such an unbelievable thing.
Anon-
Agree with possibility of your conjecture.
An advantage is an advantage. An advantage used without moral underpinning loses all opportunity of community and tends toward selfish directions.
China has more people “to burn” than anybodyelse in the world, proles and specialists alike. Could be a sort of “germ warfare by default” that won’t trigger a retaliation because it is too subtle. And they get hurt, too, but just not as badly.
It is the old making “lemonade out of lemons” concept. Sorry if I offended anyone, but as the above posts show, many are starting to wonder.
Dr. Niman,
Is it possible that an H5N2 or H5N3 strain would become a pandemic virus? Would there be any human immunity with an N2 or N3 infection?
Thanks for all your research and info!
Med Mavin,
I’m a student of Sun Tzu and know he is studied in China very carefully. What you say is consistent with “The Art of War.”
niman: if it’s so clear and evident, then why can’t we see an article
or a small paper ? Why can’t we get any independent expert-confirmation
or expert-review ?
melanie,who is “he” ? What’s Sun Tzu ? You’re not a Chinese student, posting here uncensored ? ;-)
BLAST is a search tool on a gen database, nothing else… nothing to play with in order to simulate what mutation could happen based on rules and constraintes.
NS1,
As indicated above, another thing to wonder about is the value of withheld Chinese sequences to vaccine designers. Niman wants to see them, and others too, no doubt, but what does Condi Rice know and think of their need? Are withheld Chinese virus sequences an urgent issue at HHS, DHS and the State Department or is it a peripheral issue? You can be sure it’s an issue that’s being followed, but how is it being weighted? Might someone somewhere have knowledge of vaccine development that renders the missing Chinese sequences less useful when their value isn’t certain anyway? (More to that in a bit.)
My point is that the pandemic vaccine problem is complex, important and relatively secretive. It’s unlikely that anybody knows all there is to know, and it’s probably rare that anybody encounters the full spectrum, weighs it and sorts it out. If someone does, who are they, and what are they saying? Many people are saying these days; who of them to heed?
There is no excuse for anyone to block release of H5N1 sequences. Witholding them is crime against humanity. Period.
Hi Dubina!
Here she is again, Selfish Vaccine Mama! I think that some of the novel vaccines,such as Purdue’s and maybe Pitts,may already have what they need,the H5. Purdue’s, should cover the different variatons and this is a question I’ll try and have answered the next time I contact them. I have spoken to Generex and they are sending me some of their data, so I will see what theirs may cover. These scientists are brilliant and they are caring! They are also very approachable to those, spoiled, selfish people such as nobody me, who would like not to see any child die of this scourge, even the hungrey ones. Think of the donations we could leave at the food banks if we could just settle this, worldwide, with a vaccine.
gs,
Sun Tzu is the 6th C BCE author of the strategic classic “The Art of War,” which is used by both the military and businesses for strategy in adversarial situations. Sun Tzu is the “he” to whom I was referring.
H5N2 and H5N3 in Asia are LPAI.
Dubina and Melanie-
Recent movement in China suggests a return to Confucian values in a small but somewhat influential portion of the population.
Dr. Niman-
I understand the current LPAI status of H5N2/H5N3 in Canada; have you ever seen LPAI goes HPAI via recombination of the entire cleavage site at once.
According to your latest commentary, I have to conclude that we have a significant piece of evidence for recombination.
With the Mallard from Bavaria, you seem to have found one match of 12 contiguous nucleotides in the H5N1 HPAI isolates and have matched 11 contiguous nucleotides in a total of 51 distinct H5N1 HPAI isolates?
Do I have my numbers correct? This finding would seem to open the eyes of the ReAssortment afficiandos?
NS1 – at 18:27
inscrutible, but perhaps optimistic? ;-)
Dem-
Perhaps not Confucianism may oblige a leaning toward hegemony and nationalism leading to xenophobic policies at worst and very China-centered, world-unfriendly policies at best.
Dem-
Perhaps not, Confucianism may oblige a leaning toward hegemony and nationalism leading to xenophobic policies at worst and very China-centered, world-unfriendly policies at best.
Niman-
I’m still trying to track the commentary.
Is it . . .
Using the Mallard from Bavaria, you seem to have matched a 13 contiguous position polymorphism from the concensus H5N2 strain to the H5N1 HPAI isolate A/chicken/Crimea/1/2005 (ACCESSION DQ340848)
Additionally, probing that same area of nucleotides, you substituted new endpoints in two separate searches and have matched a 12 contiguous position polymorphism from the concensus H5N2 strain to a total of 51 distinct H5N1 HPAI isolates?
Summation:
H5N2 Mallard matching to H5N1 GenBank
51 isolates(H5N1 HA) match 12 positions in 2 searches varying 1 endpoint EACH.
1 isolates(H5N1 HA) match 13 positions
Of this 13 position match, the start and the end single positions have ONLY been found in HPAI H5N1 (G496A and C508T) from Qinghai.
Is this correct?
It’s the dead cat on the beach which is real problem.
The match is with H5N1 from the Crimea (which is the Qinhai strain, but is from the Crimea peninsula). It is the only sequence at Genbank that matches the full probe (other than the H5N2 Bavaria isolate).
http://www.recombinomics.com/News/02280605/H5N1_H5N2_Bavaria.html
Domestic cats killed by H5N1 is not new
http://www.recombinomics.com/News/02280602/H5N1_Germany_Cat.html
This is the first confimation of a H5N1 positive mammal in Europe, but dogs dying after eating sick birds is also not new and stray dogs were being rounded up in Romania last fall.
As far as missing H5 data from Canada is concerned, the HA of the H5N2 from the farm duck in British Columbia does have a polymorphism shared with the H5N1 Astrakhan sequences (and it also has many N2 sequences from H9N2 in Asia).
The H5 sequneces from Canada have not been made public, but there is little doubt that they have H5N1 polymorphisms.
Niman-
Can H5N2 go High Pathogenic?
Yes, both H5 and H7 have acquired poly-basic cleavage sites in the past, including H5N2 in Mexico.
Science story on WHO hoarding sequence data is out. Time to write your represntatives. WHO’s policies are hazardous to your health.
WHO agrees that in an ideal world, scientists would share their data widely and voluntarily, says Wenqing Zhang of the agency’s Global Influenza Programme. But because that’s not happening, the agency created a special secured section at the Influenza Sequence Database at Los Alamos National Laboratory in New Mexico in 2004. Currently, some 15 labs have passwords to access these data, says Zhang, including WHO’s eight reference labs. The system is invaluable for WHO, she adds, as it helps the agency track the virus and adjust risk assessments if necessary.
More details on WHO hoarding of sequences
http://www.recombinomics.com/News/03020602/WHO_Sequence_Hoarding.html
Niman-
Are you hoarding any sequences?
Future sequences? Potential targets or outputs of your recombination models / studies?
Give us a peek at a few?
Here is the Science link.
Science 3 March 2006: Vol. 311. no. 5765, p. 1224 DOI: 10.1126/science.311.5765.1224
News of the Week AVIAN INFLUENZA: As H5N1 Keeps Spreading, a Call to Release More Data Martin Enserink
Another Science link:
With the H5N1 avian influenza virus racing across the globe, scientists are debating new evidence on the role of migratory birds. As Science went to press, the virus had just been confirmed in a third African nation, Niger, one of the world’s poorest countries. It had spread further in Europe and Asia, with 13 countries confirming outbreaks in just the past 2 months. And France reported the European Union’s first outbreak in domestic poultry.
Increasingly, scientists are attributing this remarkably fast spread to migratory birds, but dissenters remain. One set of data that points to a role for wild birds comes from recent, unpublished analyses of influenza viruses recovered from outbreaks stretching from Russia and Kazakhstan to Nigeria, Iraq, and Turkey. A World Health Organization report issued last week,* which drew upon these analyses, concluded that all of the viruses involved in these outbreaks appear to be related to the strain identified from Qinghai Lake in northwestern China, where an outbreak killed 6000 wild birds last spring. And instead of the constant evolution typical of avian viruses, the Qinghai variant appears to have remained unusually stable for nearly a year. “This finding raises the possibility that the virus—in its highly pathogenic form—has now adapted to at least some species of migratory waterfowl and is … traveling with these birds along their migratory routes,” the WHO report concludes.
more from Science:
The article goes on to say that although swans in Europe have it, which species gives it to swans is unknown (a point made by several of us a while back).
I want to salute Ilaria Capua for her courageous and principled stand. She was offered access to the WHO’s secret database in exchange for locking her sequenced up in the same database. She refused this “arrangement” and instead has made her sequences publicly available by depositing them in GenBank.
You can read more here.
First Carlo Urbani, now Ilaria Capua. Italy is producing more than its share of Heros of Science.
Ilaria Capua will go down in history for her act of bravery. What she has begun may save millions of lives. May we all follow her example.
Now, as to the worms masquerading as human beings who dare to hide their H5N1 sequences for even one day. Its time to expose their dirty backroom deals. No negotiations with any government over sequences! Either the goverments agree to immediate deposit of H5N1 sequences as soon as they are done, or travel advisories are immediately imposed as they will have shown themselves to be untrustworthy.
There is no reason for Weybridge to delay deposit of any their sequences. All reputable journals require deposit of sequences in GenBank before acceptance. The fact that Ian Brown is prepared to endanger the lives of millions of people because he is afraid that someone else will analyze his sequences before he can get a paper out turns my stomach. People in the UK should raise bloody hell.
Every scientist hoarding H5N1 data needs to be identified and publicly shamed.
And that includes the Director of the American CDC, Julie Gerberding. Time to start writing our representatives.
Monotreme, you exaggerate…
although - I might suggest her as general director of WHO2 !
Sad, that they can’t solve these organization-problems.
The worls would benefit from public data and those who submit
should be given credit and reward, but apparantly they somehow
can’t agree on the details. And maybe we have not enough time
for long negotiations.
gs: I do not exaggerate. Please read my post at 08:39. If you think that anything there is in error, say what it is. Dr. Capua did a very brave thing. Read the article that my link points to. WHO1 is fine. Just fire the worm who has the job of Director-General now and replace him with someone like Dr. Capua. Problem solved.
The sequence credit/issue was resolved a long time ago (1996). When the human genome was being sequenced similar issues of credit versus accessibility were encountered. The top sequencers in the world came together and decided that the only ethical thing to do with data of such importance was to release the sequences to the public, in GenBank within 24 hours. These are called the Bermuda Rules. The release of H5N1 sequences is even more important. The scientists who refuse to release their sequences as soon as they are available are guilty of crimes against humanity, IMO.
Revere had an interesting post that included a discussion of the Indonesian cat and human sequences here. Dr. Jeremijenko confirms the news reports, and, in his comment here, indicates that he does not know why the sequences have not been deposited in GenBank. I wish him luck in his search for the truth.
Monotreme and Niman-
Anyone venture a proposition on the cleavage site difference in the hpai human versus the hpai bird isolates?
this: Ilaria Capua will go down in history for her act of bravery.
was exaggerated.
the problem is too big/important for one WHO and we need control
Jeremijenko: you can always put sequences on some webpage,forum,newsgroup,
email,..No need to send them to WHO alone.
e.g. www.fli.bund.de could just gather the German sequences,species,locations
but apparantly they don’t want to.
GS-
We need some civil disobedience here from these scientists. I wonder if they have the courage to bite the hand that feeds them?
This bug is changing quickly and is potent; we must have the sequences.
Ilaria Capua has the courage. I stand by my statement. She will go down in history for her bravery. Others will go down in history for their cowardice.
LARIA CAPUA URGES FELLOW RESEARCHERS TO PUBLISH H5N1 DATA
AGI) - Rome, Mar. 3 - Ilaria Capua, the director of the Veterinary Institute which serves as Italy’s reference centre on bird flu (as well as Italy’s reference centre of the World Organization for Animal Health) and one of Europe’s best-known experts on the bird flu virus has launched an appeal to fellow researchers and the World Health Organization calling for all the results of bird flu tests performed so far to be made available to the public. The prestigious scientific journal ‘Science’ reported the initiative in its latest edition. As soon as the information regarding the virus which hit Italy and Nigeria was known, Ilaria Capuanella posted it on a specialised website, GenBank. “WE must do so if we want to understand what is really going on and take all necessary measures in time. It’s unacceptable that all those data be kept closed in some laboratory, thus preventing us from taking stock of the current situation”
[snip]
…the information collected by these laboratories would be extremely important to the other researchers who have to deal with the infection also in remote areas of Nigeria. In order to promote access to this information and monitor any possible mutation comparing data as soon as they are available, that is 72 hours after the samples arrive in the laboratories, Capua decided to start this initiative.
Dr. Capua is absolutely correct. The supression of H5N1 sequence data is unacceptable.
Monotreme-
Do you see Dr. Capua moving toward recombination? She’s obviously courageous and brilliant and alarmed. Very Motivated in fact. Is she motivated possibly because she sees the speed of change / improvement of the virus fitness and transmissibility? Do this awareness possibly translate into an acceptance that recombination is far more common than we’ve believed in the past?
Where is Niman and NS1? I find the conversations between Niman and NS1 so very interesting.
jskol-
Sorry about being MIA for 24 hours?
Laying a fallen friend and his wife to rest makes for a low fitness recombinant of NS1, morose, in fact.
Be back later.
monotreme and gs are tracking the niman items with accuracy and great verve. with some help from dennis, we can stay on track.
gather and solve.
everyone face north… together.
NS1: Sorry I missed your question at 00:15. I think Ilaria Capua’s just an honest woman. I don’t know whether she thinks recombination is likely or not. I think she simply doesn’t think its right to hoard data that could be used to help people.
NS1- my condolences. Take good care of yourself and come back when you can.
NS1, Very sorry about your loss. Hope to see you back in the wikie soon. We miss you. Take care, JSkol
thx all for your patience in our drive for answers.
niman is progressingly sharing new patterns with us on the h5n1 recombination thread. recent key item- clustered single nucleotide polymorphs are frequently third-base, the ‘silent’ codon.
watch this trail. big surprises sometimes come in small packages.
The following was published on ProMed today
AVIAN INFLUENZA VIRUS: SEQUENCE DATABASE PROPOSAL
A Proposal from Dr. Ilaria Capua
Avian Influenza infections caused by viruses of the H5N1 subtype are causing concerns about public and animal health, food security for developing countries and financial losses to the poultry industry. Evidence of infection in the African continent and in the Mediterranean open an unprecedented scenario with reference to virus adaptation mechanisms to different hosts within the animal kingdom.
The current H5N1 epidemic is characterized by spillover of infection to a variety of birds and mammals, and the range of hosts will increase as the virus affects new ecosystems.
[snip]
It is important to closely monitor the occurrence of adaptive mutations and compare genetic sequences of viruses obtained in other parts of the world. The OIE/ FAO Reference Laboratory for Avian Influenza at the Istituto Zooprofilattico Sperimentale delle Venezie in Padova, Italy invites other scientists to follow the line of conduct of Italian, UK, French, Croatian and Slovenian veterinary virologists to deposit H5N1 sequences into public databases as soon as they are available and expresses its gratitude to governments that grant permission to deposit sequences.
This increased availability of information in a timely manner appears to be the only tool available to attempt to understand the genetic implications of interspecies transmission and mechanisms of viral evolution in a rapidly changing scenario. Links to HA sequences of A/chicken/Nigeria/06 and A/swan/Italy/06 are currently available, and HA sequences of A/swan/Iran/754/06, A/duck/Niger/06 and A/swan/Slovenia/06 will be available shortly at the OFFLU website: <http://www.offlu.net>.
— Ilaria Capua OIE/FAO and National Reference Laboratory for Newcastle Disease and Avian Influenza Virology Department Istituto Zooprofilattico Sperimentale delle Venezie Viale dell’Universita’ 10 35020 Legnaro Padova, Italy <icapua@izsvenezie.it>
[ProMED-mail welcomes the opportunity to support Dr. Capua’s proposal.]
I went to the offlu website (could not get the link to work, but the cite is correct) and there I see a position open for Deputy Director, VLA (UK). Do you suppose that means there is some shakeup going on??
petperson: the offlu URL was embedded in the promed post, so it doesn’t have the right format for pm wiki. The link to the job opportunity for Deputy Director at VLA (Weybridge?) didn’t work for me. Anyone know anything about this?
Monotreme-
Are you planning a move to the exurbs of London?
NS1 and Monotreme:
You both do great work. I like to think I’m a smart layman. You speak to me.
Thank you.
Keep posting your ideas, Timber and we’ll keep honing solutions for everyone.
Gather and solve.
I’d like to see Monotreme at VLA, but the weather can be atrocious, I hear?
so they heard us and OFFLU is WHO2 !
I don’t like their webpage, though, with the bird-pictures and .pdf files :-(
(I don’t like the new fluwiki logo either, BTW.)
And 1treme’s worm is one of the members ?? And now his old position is vacant ?
Iran submits to OFFLU ?
surprise,surprise.
gs-
WHO2-God forbid!
Let’s pray that Dr. Capua’s involvement will accelerate a change in policy toward knowledge democracy and information freedom. This is only a first step, but a very large one.
did you notice ? Ian Brown , monotreme called him “worm” :
http://www.fluwikie.com/index.php?n=Forum.TheWormOfWeybridgeSpeaks
he’s one of the members of Offlu:
http://www.offlu.net/Organization/tabid/53/Default.aspx
and the job offer is maybe nothing but a proud announcement of this ?!
NS1, I deny your God and your prayers. Offlu is in competition to WHO
wrt. H5N1-sequences, that’s what we wanted. OK, WBFO2, if you want -
since they are limited to bird flu. But that’s fine.
I’m wondering, can/will they provide the Genbank-sequences in computer-readable format on their webpage or are they copyright ?
The Offlu-derived sequences are published at GenBank, so I’m not sure that Offlu wants to duplicate storage just for a new storage format. Don’t you think that GenBank may comply and allow an easy bulk offload. If not, then we’ll just have to look two places and build our own superbase of sequences in queryable form.
We really need a single, front-end software that takes a file of assession numbers as input, aligns the sequences, compares and scores them into an output file. Most of this is available in ClustalW except for the automatic tie to the GenBank and Los Alamos assession codes.
Ian is one of many giving guidance to Offlu; as long as he sticks to the real work and avoids the politics, I think he’ll be more successful. I believe that Dr. Capua will compel the group into ethical territory.
Niman-
Is there a simple solution to study bulk sequence comparisons soup to nuts?
Niman-
Have you had a look at Dr. Capua’s entry (A/swan/Italy/179/06(H5N1))?
What do you make of the transposition?
LANL has software that allows for choice of sequences from a large searcg list and the aligns nucleotide or aminio acid sequence. Used to be free, but now requires a fee. NIH has similar set-up that is free but slow.
Niman-
Do you have a roomful of post-docs downloading sequences into some powerful server to do local probes?
No, the databases are searchable without downloading.
NS1: I’m not qualified for the Weybridge position, I’m neither a virologist nor a Vet, but thanks for the vote of confidence. It would be nice if someone with some integrity would be put in charge there. Pressure needs to be applied to the UK government to compel Ian Brown to release the Turkish sequences he’s hoarding. I’m now starting to wonder what’s going on at Mill Hill. Apparently, they did the sequencing of the viruses from human cases which are even more important to have than sequences from viruses isolated from animals. Someone needs to ask them whether they are prohibited from releasing them or whether they are hoarding them.
Expect to hear, “Prohibited”, or “What sequences?”
I’m wondering whether and how much the military is envolved. I was reading the recent Helen Branswell article about this. We need international treaties to regulate this. We need a system such that noone should expect any harm or disadvantage by releasing sequences. There could be a special organization capable and allowed to pick up dead swans and blood-samples wherever they want.
GS-
That’s called the WHO and FAO under the guidance of the UN. They just aren’t completing the task properly.
We either must understand and act on the spirit of the law or mavericks will arise who collect the data and dispense it, like Dr. Capua. Others will become interested as the data takes on more value (PF51).
I assume, WHO and FAO have treaties with the submitting countries not to release the data to public. I assume, this was a condition of the submitting countries to provide the sequences in the first place.
BTW. what about the scientific articles published in papers and maybe
(? I don’t know. Someone please tell us how it works) available only
to some people on registering or only available in written form and
not on the internet.
Considering the magnitude and _global_ importance of the threat, shouldn’t
they make these papers freely available now to students, hobby-biologists
and everyone ? This is too important to subordinate on publishing companie’s
interests for fees or such. People who are willing to work on the
problem should be welcome and not hindered.
gs: There is a move towards open access publication. There are a wide range of journals dedicated to this proposition. You can find some of them here. NIH grant holders are strongly encouraged to publish in open access journals. I agree completely with this policy.
see the editorials collected here
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