The journal
Capua was among the first scientists to call publicly for contemporaneous (immediate) release of flu sequences by researchers. These sequences are often held privately for a variety of reasons, some good, some not so good. Some governments want sequencing done but don't want it publicly known H5N1 is in unannounced regions. Some researchers want to keep sequences private while they or their students ready papers for publication. Proprietary issues involving vaccine seed strains have motivated some countries like China who has also had its national pride wounded when "its" viral isolates became the basis for scientific publications by non-Chinese scientists without acknowledgment of their origin. In order to facilitate limited sharing, WHO went so far as to set up a limited access database at Los Alamos National Laboratory in the US where 15 scientific groups could both deposit sequences and have access to the sequences of the others. This solved the problem of making the information available to a few other knowledgeable scientists, but certainly was not satisfactory. The arrangement has been widely condemned, but continues. Thousands of sequences are said to be deposited there.
Here is the Capua et al. letter:
Avian influenza infections caused by viruses of the Asian HPAI H5N1 subtype have spread from East and Southeast Asia to Europe, the Middle East, and Africa. The virus is occurring in new ecosystems and infecting new hosts, resulting in novel host-pathogen interactions and genetic modifications. There is a lack of information on how the virus spreads across and within continents, including the role of wild birds. This hampers research into avian influenza, which is causing significant food security issues in developing countries, in addition to its pandemic potential.
Veterinary virologists have been working on avian influenza viruses for many years, and our collections of influenza virus isolates could be of great value to the international scientific community.
Within the Scientific Committee of OFFLU (the World Organization of Animal Health/United Nations Food and Agriculture Organization Network of Expertise on Avian Influenza), we have initiated the FLU-ID project. We will make available for genome nucleotide sequencing H5N1 contemporary isolates from several countries and relevant historical strains. This will be achieved in collaboration with the NIH Influenza Genome Project, and the full genetic sequences will be available in GenBank
The Asian HPAI H5N1 virus is spreading very quickly. Real-time availability of genetic information is now possible and is essential for timely monitoring of viral evolution. These data will increase our knowledge of this pathogen and will help the appropriate selection of viral candidates for experimental studies, thus avoiding duplication of efforts and waste of resources.
We firmly believe that knowledge of the genetic profile of avian influenza viruses from animals is a prerequisite to understanding a complex disease that has already killed hundreds of millions of birds worldwide and that is threatening human lives. We are convinced that this initiative will contribute substantially to the efforts that are being carried out worldwide, and we invite other medical and veterinary virologists to join us.
Ilaria Capua
Istituto Zooprofilattico delle VenezieMichael Johnson
Australian Animal Health Laboratory
CSIRO Livestock IndustriesDennis Senne
National Veterinary Services Laboratories
Ames, Iowa, USADavid Swayne
Southeast Poultry Research Laboratory
USDA/ARS, Athens, Georgia, USA
This letter is from some of the most important veterinary pathology laboratories in the world, so it represents and important milestone. But none are from China, one country where transparency and availability has been in question. Nor is there a commitment from some of the important WHO reference laboratories that handle medical sequences. Nor from the US CDC who is said to have thousands of unreleased influenza sequences (see posts here, here, here and here). Nor from prominent flu scientists like Robert Webster, Richard Webby and their colleagues at St. Jude's in Tennessee, the Palese or Garcia-Sastre laboratories at Mt. Sinai, New York, or Malik Peiris's or Guan Li's laboratories in Hong Kong, among others.
It is time for US government policy to require all NIH and NSF grantees to deposit avian influenza sequences into GenBank immediately as they are obtained and certainly for CDC to do likewise. Intramural NIH researchers already do so. It is a scandal that CDC does not. In addition, flu researchers should now refuse to sequence isolates when there are restrictions on public availability from the source. If this means that some sequences will not be seen by some it is more than balanced by the many others that will be seen by all.
We still have a long way to go before knowledge of the sequences translates into sure knowledge of the biology of these dangerous viruses. We don't believe the lack of sequence data will make the difference between life and death. We already know enough to understand that preparing for a pandemic should be a high priority in every community. Openness and transparency about the sequences is a matter of high principle, however. The sequences are the raw data for understanding a disease of global significance in a time of threatened peril. There can be no excuse for keeping them private at this juncture. The practice has been called hoarding, and the term is appropriately pejorative.
Once again Dr. Capua is leading by example. She has some followers. Time for the others to follow suit or risk the justifiable censure of their scientific colleagues and the world.
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Why isn't the medical community looking at ways to temper the deadly immune response this virus causes? It would seem that if they can do this for tissue rejection in transplant patients wouldn't a similar approach in avian flu patients help save lives? Even if we get a vaccine for the flu from what I've read it will take months to produce and will need to be given twice to be effective. Something that will stop the body from essentially killing itself in defense seems a more rational approach in the short term.
The simple, glib answer is that if it were easy, it'd be done by now. An ill patient has to balance fighting the original infection with any auto-immune questions, so spuuression of anything is tricky. And the immune response isn;t well enough understood yet to simply go in and intervene. Things have been tried, mind you (i.e steroids, interferon), but they do not always work.
I am delighted by this news and - as a Brit - am even happier to see Ian Brown on the list but am not clear which sequences are covered. Weybridge is also one of the WHO H5N1 referance labs are these sequences covered?
JJ: Yes, the inclusion of Weybridge is important. The letter implies it is the veterinary sequences at least. It is a WHO reference lab (which is why I said "some").
You know, in general the real breakthroughs in technology do not come from the large companies but from small start-ups. Even Tamiflu was created by then-small Gilead. By hoarding the sequence data to a few 'approved' labs, the NIH and CDC are effectively allowing only 'big science' to see them, and denying access to the very kind of 'start up' scientists who might see things just skewed enough to recognize what the mainstream is missing.
For all we know the key insight that will help us figure out how to combat this virus is lurking in some graduate or undergraduate student at a second or third tier school who decides to poke through the database on a lark to try out what they learned about blast last semester. We really don't know where the next good idea will come from and to limit access to those with a wet lab seems foolish.
The arguments I've heard for limiting access seem specious to me. Here are a few and why I disagree with them:
1. 'Bad guys' or 'terrorists' might get the sequences.
Well, I don't think bad guys are sophisticated or patient enough to care about sequences. If they want to cause trouble, all they need do is buy a sick chicken in the vicinity of Jakarta and feed it to a few amplification animals to brew themselves a big supply. The virus already kills 50% of those it infects, there's no need to mess with its genes to make it frightening for terrorist purposes, hence no need for sequences.
2. 'Intellectual property' and protection of financial rights for any vaccine produced.
The demand for any vaccine or drug produced from these sequences is going to be so high that sales will be manufacturing-limited, not demand limited. This is not a common situation in business and actually invalidates a lot of business assumptions. In this environment, intellectual property rights are not as important as manufacturing capacity and efficiency. You will sell everything you make. There is little point in keeping your IP from other's use since you are guaranteed to sell all that you make at whatever price you want, because demand so exceeds supply even when your competitors are making an identical product. If competitors undercut your price, you don't even need to match it because they'll sell out and people will still be forced to come to you at the price you name.
In the environment of pandemic flu it is actually to your advantage to have as much cure or vaccine available as possible anyway, to protect the economy; if too many people are out sick and the economy fails, then their ability to buy your product disappears. So having multiple (yet still inadequate) sources works to the advantage of all the producers.
3. National Embarassment.
Countries should be embarassed to hide their outbreaks, not to have had outbreaks. It isn't like people don't know that parts of China are still backward. Parts of the US are still backward too, though to a different degree. Having an outbreak is mostly a matter of bad luck, which the West does not regard as a character flaw.
4. Scientific prestige.
I think Revere has argued on this point better than I ever could.
This is important. Full credit to Ilaria Capuria. As an Australian it is great to see the AAHL on the list. I too support the release of sequences and only hope the people I have worked with in Indonesia who in principle have stated they agree, can join this movement. I think there is important information in the human and animal sequences from Indonesia that should be public knowledge.