The time for sitting on flu data is over
Posted on March 18th, 2010 by wktd
http://declanbutler.info/blog/?p=44
Nature has a short but strong editorial (http://www.nature.com/nature/journal/v441/n7097/full/4411028b.html) today on the problem issue of access to flu data, which I’ve already blogged about here (http://declanbutler.info/blog/?p=41) and here (http://declanbutler.info/blog/?p=38). It follows up on our much longer March editorial on the issue — Dreams of Flu Data (http://www.nature.com/nature/journal/v440/n7082/full/440255b.html).
Here are a few excepts, from today’s:
Indonesia has become the hot spot of avian flu, with the virus spreading quickly in animal populations, and human cases occurring more often there than elsewhere. Yet from 51 reported human cases so far — 39 of them fatal — the genetic sequence of only one flu virus strain has been deposited in GenBank, the publicly accessible database for such information.
Yet scientists outside the WHO networks have no access to these data. The problem last year spurred the US National Institutes of Health (NIH) to create a consortium to sequence and make public thousands of flu strains from humans and birds. Very quickly, this more open approach led to the useful discovery that viruses swap genes with each other more frequently than had been previously thought.
Some political leaders are drawing the appropriate conclusions. Dennis Kucinich (Democrat, Ohio) and Wayne Gilchrest (Republican, Maryland) are circulating a letter in the House of Representatives that calls on Michael Levitt, the US health secretary, to require H5N1 sequences and other publicly funded research data “to be promptly deposited in a publicly accessible database, such as GenBank”.
To see a pdf copy of the Kucinich/Gilchrest letter click here (http://www.declanbutler.info/blog/Kucinich%20Gilchrest%20Avian%20Flu%20letter.pdf).
The time for sitting on flu data is over.
Concern about the accessibility of data on flu strains remains an acute issue, which research administrators and political leaders should step forward and address.
Indonesia has become the hot spot of avian flu, with the virus spreading quickly in animal populations, and human cases occurring more often there than elsewhere. Yet from 51 reported human cases so far — 39 of them fatal — the genetic sequence of only one flu virus strain has been deposited in GenBank, the publicly accessible database for such information.
And last week in China, researchers belatedly published details of a case that tested positive for the virulent H5N1 strain in 2003 — contradicting the government's official line that none had occurred before November 2005. The unnecessary delay reaffirms the critical importance of better dissemination of flu data.
Back in Indonesia, the World Health Organization (WHO) has just confirmed that a cluster of eight cases in an extended family in northern Sumatra was the first unequivocal occurrence of limited human-to-human transmission of the virus. Whereas the WHO initially stated that the virus in the cluster showed "no significant" mutations, it now says that genetic changes in the virus account for the appearance of human-to-human transmission. In the Sumatra event, the transmission did not spread beyond the family.
Yet scientists outside the WHO networks have no access to these data. The problem last year spurred the US National Institutes of Health (NIH) to create a consortium to sequence and make public thousands of flu strains from humans and birds. Very quickly, this more open approach led to the useful discovery that viruses swap genes with each other more frequently than had been previously thought.
Some political leaders are drawing the appropriate conclusions. Dennis Kucinich (Democrat, Ohio) and Wayne Gilchrest (Republican, Maryland) are circulating a letter in the House of Representatives that calls on Michael Levitt, the US health secretary, to require H5N1 sequences and other publicly funded research data "to be promptly deposited in a publicly accessible database, such as GenBank".
http://www.nature.com.proxy.library.vcu.edu/nature/images/quoteleft.gifH5N1 sequences should be promptly deposited in a publicly accessible database.http://www.nature.com.proxy.library.vcu.edu/nature/images/quoteright.gif
An appropriate model for better data access is at hand. Earlier this month, the Paris-based World Organisation for Animal Health and the United Nations Food and Agriculture Organization said that they would work with the NIH to sequence H5N1 samples from birds and deposit them in GenBank. The WHO and its member states urgently need to establish a similar mechanism to ensure that data on human cases are immediately put in the public domain.
Recombinomics Commentary
June 29, 2006
Indonesia has become the hot spot of avian flu, with the virus spreading quickly in animal populations, and human cases occurring more often there than elsewhere. Yet from 51 reported human cases so far - 39 of them fatal - the genetic sequence of only one flu virus strain has been deposited in GenBank, the publicly accessible database for such information.
The above comments from an editorial in today's Nature are welcome. Declan Butler offered some additional comments in his blog (http://declanbutler.info/blog/?p=44) and provided a link (http://www.declanbutler.info/blog/Kucinich%20Gilchrest%20Avian%20Flu%20letter.pdf) to letter by Dennis J Kuchinich and Wayne T Gilcrest to appealing to colleagues to support a request to secretary Michael Levitt to make deposit of H5N1 sequences to a public data within 24 hours of verification as a condition for NIH support. The letter also supports transparency of these and related H5N1 bird flu issues.
The situation in Indonesia is particularly acute. It is now almost one year (http://www.recombinomics.com/News/07150502/H5N1_H2H_Indonesia.html) since the first confirmed human case in Indonesia was reported, yet sequences from that index case are the only human H5N1 sequences publicly available. The sequences were deposited in the WHO private database on August 1, 2005 but were not made public until March 25, 2006 (http://www.recombinomics.com/PR/051906.html) and sequences from six of the eight gene segments have still not been released. Malik Peiris (http://www.recombinomics.com/News/05310602/H5N1_Sumatra_Sequestered.html) declined comment (http://www.recombinomics.com/News/06010601/H5N1_Indonesia_Release.html) on direct questions on mutations in the sequences because the sequences were done under contract with WHO. WHO said they couldn't release the sequences without approval from the Indonesian government, and the Indonesian government said that no one had requested release (http://www.recombinomics.com/News/06010602/H5N1_Indonesia_Progress.html).
The sequences are at Los Alamos and can be released to the public by simply removing the password protect, as was done with the index case. Data released at the Jakarta meeting also raised significant questions about what data is being hidden in the database
WHO's statement (http://www.who.int/csr/don/2006_05_23/en/print.html) on the sequences in the Karo cluster indicated there were no "significant mutations" and no reassortment with human and avian genes. They also indicated that the sequences indicated sensitivity to Tamiflu. However, data presented (http://www.recombinomics.com/News/06250601/H5N1_Karo_Amantadine.html) at the closed door meeting indicated the sequences in the cluster had the S31N polymorphism in the M2 protein, which indicated the H5N1 was amantadine resistant (http://www.recombinomics.com/News/05230604/H5N1_Sumatra_Sequences.html).
Similarly, media was told that the nephew of the index case and his father shared a "minor mutation" indicating the son infected his father. However, data at the closed door meeting indicated the father had 13 additional differences (http://www.recombinomics.com/News/06250602/H5N1_Instability_Karo.html) with his son's H5N1 sequence strongly suggesting that the father had been infected by two H5N1 viruses, one from his son and one from an unknown source. The sequence of the H5N1 from the father had evidence for both reassortment and recombination.
WHO consultants have indicated the recombination in H5N1 was rare. However, analysis by WHO fails to detect recombination, which is common in H5N1. Obvious recombination is present in H5N1 generated by the very WHO consultants who say that can't find homologous recombination. These obvious cases were in sequences from Hong Kong in 2003 and 2003 and the sequences were generated via a collaboration between Hong Kong and St Jude labs. The recombination was not described in the peer reviewed publication (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&query_hl=1&list_uids=15241415) of these sequences. Obvious recombination was also present in 2003 H9N2 sequences from Korea. These sequences were also generated by St Jude, yet they were also not reported in the peer reviewed paper (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=15680418&query_hl=53&itool=pubmed_DocSum),
H5N1 bird sequences from Indonesia have acquired Qinghai sequences (http://www.recombinomics.com/News/06170601/H5N1_Bali_Qinghai.html), including the Qinghai HA cleavage site in at least one isolate from Bali. Similarly, Qinghai sequences are in the H5N1 from the father (http://www.recombinomics.com/News/06260601/H5N1_Qinghai_Karo.html) who was infected by his son. These Qinghai sequences on an Indonesian genetic background are additional evidence fro recombination in H5N1 sequences in Indonesia.
The sequence data is not being shared. The human sequences from Turkey (http://www.recombinomics.com/News/06230603/H5N1_S227N_Turkey_Cases.html) were finally released. However, a request for identification of the WHO confirmed cases was not answered. Nor was a simple question about the cell line or chicken eggs used to isolate the H5N1 from Turkey because the pattern of S227N sequences was unusual.
The time for secrecy regarding these sequences has passed. Release of the sequences and providing minimal information on the source of the sequences should be made immediately. Many of the Indonesian human sequences have bee held for almost a year. The sequences from Turkey were held for six months.
H5N1 is rapidly evolving and this evolution should be matched by researchers who are hoarding sequences for publication. The time for release of the sequences has long since passed.
http://www.recombinomics.com/News/06290601/H5N1_Sitting.html
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