Immunocompetent

More Notes from the WHO PIP IGM

perezoso — Thu, 11 Dec 2008 08:13:29 -0500

Here we continue notes from the World Health Organization Pandemic Inflluenza Preparedness Intergovernmental Meeting. Refer to the previous post to read: Pretending You are In Charge (WHO), America Insults the Scientists of the Developing World - Or Is It About Patents?, and Japan's Big Bluffer.

US Shenanigans on Distributing Vaccine Seed Strain

Uncle Sam is up to something untoward when it comes to WHO's (pre)pandemic influenza vaccine seed strains. Immuncompetent doesn't know for sure what it is; but he's got a hunch. The issue is the language under discussion that would direct WHO Collaborating Centres to distribute influenza vaccine seed strain.

In addition to providing H5N1 vaccine seed strain to industry (which WHO CC's presently do), most countries want to make sure that the vaccine seed strain is also provided to national influenza centers around the globe or, at least, in the country of origin of the HA gene used in the seed strain.

Although the US professes to be in favor of this, it actually seems to have problems with sharing vaccine seed strains. To wit, it insists on inserting qualifying language into the paragraph saying, in a limiting fashion, that vaccine seed strain should only be distributed "as broadly as possible". (Key words: "as possible".)

Asked what the heck it means by this, the US response was frankly unintelligble. The closest thing to something coherent that it said was the qualification is necessary "because we know there may be some restrictions upon us". Whatever the hell that means.

The US also keeps emphasizing that the recipient lab must have acceptable biosafety facilities and practices. Making this point, the US reminded everyone that "these viruses are highly pathogenic and deadly", so the vaccine seed strain could not be so easily distributed.

What? This is factually incorrect. That's odd, because the US usually gets its technicalities right.

Vaccine seed strains produced by WHO are attenuated (i.e. weakened). They are typically handled at BSL-2 containment. They are not deadly nor highly pathogenic like viruses found in nature because of their lab-adapted genetic backbone and/or altered HA gene. Sadly, the WHO Secretariat did nothing to correct the US - despite WHO having stated less than an hour before that its seed strains are attenuated.

So some biosafety capability (BSL-2) is needed; but the safety requirements are not nearly as stiff as the US claims.

What's up with this American nonsense about "as possible" and "deadly" BSL-2 vaccine viruses?

Immunocompetent thinks the US is looking for a back door in the agreement to raise security and patent issues - to permit it to impose export controls on influenza vaccines (like it presently does for Cuba, North Korea, and some others) and/or patent protections on seed strain (an "additional procedure" that the US has contradictorily argued against). This may be why they don't want a clear obligation to share vaccine seed strain with developing countries. They may want to reserve the right to say no to some countries for political reasons (e.g. Cuba) and to make money for patent holders (an in, it's "not possible" to give you the seed strain because you won't pay royalties).

Immunocompetent could be wrong; but that's our guess...

Even if you don't buy this explanation for Uncle Sam's odd behavior, if you think about it, the US position is pretty retrograde nonetheless. There is really no valid reason to refuse to provide WHO vaccine seed strain to anybody who is able to use it to produce effective vaccines.

Notes from the WHO Pandemic Influenza Preparedness Intergovernmental Meeting

perezoso — Wed, 10 Dec 2008 07:05:04 -0500

Here are some notes, updated when I feel so moved, from the resumed WHO Pandemic Preparedness Intergovernmental Meeting (WHO PIP IGM). This is the continuation of previous WHO PIP IGM meetings on the topic that is commonly understood to the be the conflict between Indonesia and the US over virus sharing, but which in fact is broader and much more complicated. The meeting reopened on Monday, 8 December and will last until this Friday or Saturday.

This is not a comprehensive report. It's a collection of thoughts about issues, particularly when they are amenable to being dealt with discreetly. A more comprehensive piece will, hopefully, follow.

The mini blog posts here here are:

Pretending You are In Charge (WHO)
America Insults the Scientists of the Developing World - Or Is It About Patents?
Japan's Big Bluffer

Pretending You are In Charge (WHO)

To any careful observer of the WHO Global Influenza Surveillance Network it is clear that labs in the powerful countries - like the US, Japan, UK, and Australia - just do whatever they want with H5N1 samples and call it a WHO activity. They are "WHO labs" in name only. So, for example, the US "WHO" lab in Atlanta just starts some practice - say use of a particular diagnostic - and then the real WHO just acts like it planned this all along.

This "WHO Veneer" is subtly apparent all the time when looking at the GISN's operations (some of the WHO-endorsed labs don't even have the loosest terms of reference). But it must be particularly painful for the pride and credibility of the WHO when its ancillary status breaks out into the open. Like when the real WHO doesn't know the details of how its "own" system operates, which happened in public today.

A controversial class of laboratories "inside" the WHO system are the so-called "Essential Regulatory Laboratories" (ERLs), like the US FDA. These labs are essential for licensing vaccines; but their WHO status is ambiguous. WHO has long said that there are three "essential regulatory laboratories" that should get special global treatment - NIBSC in the UK, the FDA in the US, and TGA in Australia. Nevermind that these labs don't have standardized capabilities and nor uniform responsibilities in the WHO system, never mind that they don't have terms of reference. It shows you how loosey-goosey WHO has been in its so-called "oversight" of the GISN.

The system is supposed to be controlled by WHO. But today, in response to a question from Indonesia - and a year after it started declaring in official documents that there were three ERLS - WHO suddenly decided that there is a fourth ERL. This newly-discovered ERL is located in Japan. And what's more, WHO's influenza leaders aren't sure where it is and if it is separate or the same as the WHO Collaborating Center in Japan.

What an embarrasssment. The PIP IGM is supposed to be negotiating the roles and responsibilities of labs the constitute the WHO global influenza surveillance system, which allegedly is oveseen by a functional and vigilant WHO. But WHO doesn't even know its own system very well and, in this case, doesn't even know where one of its allegedly "essential" labs is!

After this embarrassing revelation, I shot the following e-mail to a senior WHO official from North America who was sitting on the dias across the room from me:

"The [Essential Regulatory Labs] and [WHO Collaborating Centers] obviously do whatever the hell they want to do and then you guys get up and pretend that WHO actually knows what is going on and approves of it. What an embarrassment. You guys don't even know where all your labs are nor do you have a clear idea of what they all do"

Sometimes he answers my e-mails. No reply yet; but I'll let you know if I get one.

America Insults the Scientists of the Developing World - Or Is It About Patents?

The American delegation in Geneva seems to take a dim view of the capabilities of developing country influenza scientists. Or is it up to something else when it insults their intelligence?

Although the US says "it is imperative that we have as many viruses from human cases as possible", itself not an unreasonable position (assuming "we" means WHO, and not the Pentagon), the United States of America does not think that the countries that provide those viruses should have a right to see the full characterization data that is generated from them.

Instead, the US just wants to give "summary information" about the virus characterization to the donor country, and it doesn't want to the WHO PIP IGM to try to define what that summary information is (thereby leaving it up to .... you guessed it .... the CDC in Atlanta - acting as a "WHO lab" - to decide what to send).

So, if you are a developing country with H5N1 cases, Uncle Sam insists that you must send all your virsues, but Uncle Sam is unwilling to commit to sending you back the full results of the characterization that is performed on those viruses. What a stinking double standard.

It's gets even "better". The reason why it has a double standard, said the US delegation this morning (Wednesday), is that developing country national influenza centers are too stupid or incapable to understand the output from the CDC's sophisticated science. The data would not, the US condescendingly noted in open working group, be useful for other labs. Chalk another one up for the Bush administration's efforts at international cooperation and understanding.

What's going on? Immunocompetent suspects that the Americans are actually up to something more than insulting other countries. We suspect that they are trying to keep intellectual property rights and even perhaps protecting rights to publish or possible proprietary diagnostic procedures and results. Or CRADAs, perhaps?

And seing that this would NOT be an acceptable reason to keep secrets in the WHO public health system, the rather politically-unpalatable excuse that they've come up with is to say that developing countries are too stupid to understand it anyway. (After all countries aren't sending viruses to CDC so they can be patented.)

The above is just a hunch; but Immunocompetent's hunches are often pretty good. The US is either obfuscating its attempts to acquire intellectual property rights with insults, or it just being insulting out of arrogance. Either way, it's bad.

(The EU, meanwhile, is maintaining pretty much dead silence on this issue and many others, mainly because it really doesn't seem to much care. "We need their virus, they need our vaccine, nobody needs this framework", two EU delegates were heard to emphatically agree outside the room. The EU is on track to easily win the award for being the largest group of countries to make the smallest leadership contribution to these talks.

What can be positively said about the Americans is that if it weren't for Japan and sometimes Canada, the US would be the only rich country that at least has taken care and undertaken serious preparation for these talks. Not necessarily constructive preparations; but at least they've got a plan that they've thought about, which is more than it seems possible to say for many other developed countries.)

Japan's Big Bluffer

Japan has been unusually vocal at this PIP IGM, perhaps in response to its domestic influenza vaccine producers, like Biken. While Immunocompetent has no problem with the usually quiet Japanese talking up a storm, we're not so sure about the quality of their contributions.

The evidence is to be found in how Japan is swerving and dodging. Japan seems to have little purpose but to see what it can get away with in watering down the text. Japan weighs in, for example, to delete language on benefit sharing. Or to complain (inappropriately) about not wanting to see new text.

When confronted with opposition, however, Japan usually beats a hasty retreat. But this certainly doesn't seem to be because Japan is unsure of itself. It is quick to the mike when new items open up, with its watering down usually clearly thought through in advance.

At this PIP IGM, Japan has seemed like a heckler to the process, stirring up little problems where it can, but often with little serious constructive intent behind its proposals.

CDC Statutorily Prohibited from Being a WHO Collaborating Center?

perezoso — Sat, 06 Dec 2008 13:31:00 -0500

The Centers for Disease Control has a World Health Organization Collaborating Center (WHO CC) for influenza, but it may be unable to fulfill its duty to WHO because US domestic law prevents it from adequately sharing influenza viruses. The law is US export control legislation, and it requires that labs, including CDC, obtain a license from the Department of Commerce before sharing a number of disease agents.

This means that shipments of H5N1 to other countries require a license. For some countries, like Canada, obtaining a license is routine; but for many others, including many WHO Member States, tighter export controls apply. These countries are indicated in a list maintained by the US Department of Commerce called the Commerce Control List Country Chart.

(“CB” type controls generally govern H5 virus exports. These range from “CB1” to "CB3”, with “CB3” being the most restrictive. The exception are the extra "special" countries in the USG's eye, like North Korea or, much less probably, Cuba, who have country-specific - i.e. even more restrictive - export control regimes.)

Export controls have been sharply criticized by developing countries for being arbitrary and political, and for contradicting technology transfer obligations in international agreements.

The US Department of Commerce has authority to simply deny shipment of H5N1 virus to other countries, even if the virus was given to the WHO Collaborating Center at CDC by a National Influenza Center in another country. In other cases, the US Department of Commerce may insist that foreign labs comply with US-style security rules or that they even to try prove to the US government that they are not a security threat to the United States.

US domestically legislated procedures to obtain H5N1 are contained the Select Agent Rule. They include submitting the fingerprints and biographical data of researchers to the Federal Bureau of Investigation (FBI), periodic laboratory security inspections (ironically conducted by CDC itself), and a large number of mandatory physical security measures and procedures.

Other restrictions on H5N1 viruses under US law include a prohibition on foreign recipients of H5N1 viruses from US labs from transferring them to others. So, for example, if the WHO CC at the Centers for Disease Control is able to send an H5N1 virus to a foreign National Influenza Centre for research purposes, the CDC may require the NIC to not transfer that virus to anyone else, even another WHO network laboratory.

Such strict domestic legislation may be sensible in the US because of its severe domestic bioterrorism threat (for example, the 2001 anthrax letters that were produced at US government lab and sent by a US government scientist), however, they may interfere with the ability of the Centers for Disease Control to effectively function as a WHO Collaborating Center for Influenza and to abide by its WHO Terms of Reference, which require sharing H5 viruses internationally.

The WHO Pandemic Preparedness Intergovernmental Meeting (PIP IGM) should be careful to avoid allowing national legislation to stand in the way of WHO-approved virus sharing by WHO Collaborating Centers. Therefore the PIP IGM should ensure that WHO Collaborating Centers for influenza are not located in where domestic legislation conflicts with the Collaborating Center’s responsibilities to WHO Member States.

In the specific case of the United States, WHO Member States should seek a public assurance from the US government that the WHO CC at the Centers for Disease Control will provide H5N1 viruses and vaccine seed strains to all Member States with a WHO-recognized laboratory, without the imposition of any delays, denials, or additional requirements due to export controls or other national legislation.

WHO, NAMRU-2, and Indonesia According to the US Pacific Command

perezoso — Tue, 02 Dec 2008 09:41:35 -0500

Stashed away in a somewhat obscure corner of the .mil webzone are an interesting set of H5N1 reports. Prepared about every week by the US Pacific Command (PACOM) and the Australian Army's Land Headquarters (LHQ), the reports summarize recent developments with H5N1 with an interesting twist. Who they are prepared for isn't clear; but Immunocompetent thinks they look like a slide that goes into scheduled briefing for higher-ups somewhere on the military food chain, probably at the Office of the US Secretary of Defense, on whose website the files can be found.

We have some choice extracts below; but there's plenty more interesting reading that you can download. (And if the OSD "disappears" this information off its website, we have a complete archival copy.)

The reports, marked "unclassified", provide abbreviated updates H5N1 cases worldwide; but they are more interesting for what they select as newsworthy H5N1 politics.

Recently, PACOM has been very interested in the NAMRU-2 negotiation and the WHO PIP IGM, and the reports have included information not public elsewhere. For instance, details on conversations between WHO staff and US government representatives, and on the (apparently failed) bilaterals between Indonesia and the US. (These were facilitated by Australia.)

The reports, at least recent ones, appear to be prepared by Air Force Lt. Colonel Peter Breed, who was recently listed as the PACOM's Chief of Force Health Protection. PACOM is headquartered in Hawaii.

There is no direct publicly-accessible URL to see a listing of these reports (it appears to be only available to people in the .mil and .gov domains). Instead, if you have construct a Google search that will hit them. This search works pretty well.

In short, the reports offer an interesting view into Bird Flu According to The Pentagon. And they show just how closely the US (and Australian) military are following H5N1 issues. Here are some recent extracts:

31 October 2008:
CEO of Indonesia’s National Committee for Avian Influenza and Pandemic Control (KOMNAS), reportedly told French officials that the “successful” GOI-USG negotiations,” facilitated by Australia, could lead to an end of the sample-sharing impasse at December’s WHO Intergovernmental Meeting.

24 October 2008:
Indonesia: Legal proceedings against the USG and WHO brought in April 2008, alleging responsibility for the death of an Indonesian from H5N1 have again been postponed. As a result of internal debate, the court further postponed a decision regarding the proceedings until perhaps mid-December.

26 September 2008:
Indonesia: (1) NAMRU-2 laboratory will be temporarily shut down because it offers "little benefit" to Indonesia said the GOI’s MOH. Negotiations between the USG and GOI are ongoing. U.S. HHS Secretary said Indonesia's refusal to share its samples of the H5N1 virus with the rest of the world has spilled into the NAMRU talks. (2) USDEL in Manila reported in conference calls September 21 and 22 that the two delegations, in discussions facilitated by Australia, made progress in reviewing a U.S.-drafted notional materials transfer agreement (MTA) text, as well as a text on Terms of Reference (TORs) for the WHO influenza surveillance network provided by Indonesia

19 September 2008:
Indonesia: The next round of consultations involving Indonesia, the U.S., and the WHO Intergovernmental Meeting Chair (Australia) on sample and benefit sharing is scheduled for September 21-22 in Manila. USG will draft a human influenza virus model Materials Transfer Agreement for discussion in Manila.

12 September 2008:
(2) MOH recently claimed that developed countries are creating new viruses that are meant to infect people in poorer nations in order to help drug companies sell more vaccines.

...

WHO Assistant Director-General David Heymann spoke with Special Rep Lange today about the November Intergovernmental Meeting on Pandemic Influenza Preparedness. Based on his conversations, Heymann expects that developing countries will seek recognition of some kind of “viral sovereignty" and will agree to continue sharing human influenza virus samples only in return for “sustainable” benefits (i.e., some system by which developing country access to benefits, such as vaccine stockpiles, is guaranteed over the long term).

29 August 2008
India/Bangladesh: The bird flu virus, that caused India's worst AI outbreak, has been found to be "a lot similar" to the one in that cause havoc in Bangladesh. However, we can't say that Bangladesh was the cause of the outbreak. Sources said India complained to FAO and OIE about Bangladesh's slack handling to contain the virus, putting at risk India's internal security.

Indonesia: GOI authorities are now reporting possible human AI cases to the WHO within 24 hours in compliance with the International Health Regulations. WHO does not report Indonesian cases until the GOI MOH announces them, on a monthly basis. However, if there are international public health risks, WHO will report it with or without GOI permission.

18 July 2008:
Indonesia: A WHO official confirmed to Embassy Jakarta on 16 July that the GOI had reported a new, confirmed human AI fatality: a 38-year old male resident of Tangerang municipality died on 10 July. A WHO representative told Embassy Jakarta that Health Minister Supari had assured him that Indonesia would comply with the Health Regulations by notifying WHO of fatalities.

11 July 2008:
Indonesia:(1) MOA “temporarily”bans import of U.S. poultry. Poultry “treated to inactivate the avian influenza virus”is exempt, if it can pass a “risk analysis”and is approved by MOA. (2) Australian Authorities have sought clarification of Indonesia’s policy on reporting human cases of avian influenza to the WHO. A senior Australian official has said that Indonesia’s management of avian influenza is severely deficient.

3 July 2008
Indonesia: GOI and USG plan to meet in Australia, 25-28 July 08, to discuss next steps toward resolving sample sharing issue.

20 June 2008:
Reporting of these 2 cases demonstrates that Minister Supari is somewhat cooperate with WHO, but reporting not done within 24hr International Health Regulation requirement agreed to by the 193 member states of WHO.

22 May 2008:
Indonesia:(1) Virus sequence (genome) sharing with pubic database but no actual virus isolate sharing & proposed pay-for-virus system unacceptable to WHO.

29 February 2008:
Indonesia:Clarification on last week’s sample shipping report: US CDC confirms 15 samples, all came from 2 cases, a mother/daughtboth still alive; samples received without MTA or other restriction

18 January 2008:
GoI has reached tentative deal with Iran to co-produce bird flu vaccines, MoH says Iran has an advanced pharmaceutical industry, capable of producing bird flu vaccines using Indonesian virus.

WHO, the Pentagon, and Influenza Collections

perezoso — Tue, 02 Dec 2008 09:19:50 -0500

A flu article recently written for SUNS...

US military flu virus collection parallels WHO virus system

Bogota, 26 Nov (Edward Hammond*) -- A large and rapidly growing global US military virus collection system parallels the World Health Organization's Global Influenza Surveillance Network (WHO GISN) but does not entirely share its public health purposes.

The US military system is a source of viruses for the WHO GISN; but it does not give most of its virus collections to WHO. It does keep all the lab specimens and viruses it collects for its own use.

Wider knowledge of the extent of the US military virus collection system and its ambiguous relationship to the WHO GISN system will raise important questions for the WHO Pandemic Influenza Preparedness Inter-Governmental Meeting (PIP IGM), which will convene in Geneva the second week of December.

The extent of the Pentagon's quiet but large virus collecting and its relationships with the WHO GISN will surprise many. For example, the Pentagon claims credit for having collected several important influenza viruses that were subsequently selected by WHO for use in seasonal and H5N1 pre-pandemic vaccines from 2000 through the present, including viruses from Panama, Peru, Nepal, Malaysia, and Indonesia.

Some developed countries, including the United States, have insisted that developing countries only share influenza viruses with the WHO GISN and not bilaterally with others. Yet, contradictorily, the United States has a
massive military influenza virus collection program, but only provides a very small percentage of the materials that it collects to the WHO.

It is unclear if and how viruses collected by the US military in other countries would be covered by a WHO GISN material transfer agreement because they are obtained and transferred outside what is now-understood to be the WHO system.

If one WHO Member State unilaterally amasses influenza viruses without full participation in the WHO access and benefit sharing system there is strong potential for the WHO system to be undermined.

Also undefined is the legal status of a virus received by the WHO system; but not from an approved lab of its country of origin - a situation that now frequently occurs due to the activities of the US military virus collection system.

The US military system is active globally, including at least 56 countries where it is collecting influenza viruses (as of 2007). The system pulls in clinical specimens and locally isolated viruses that are shipped to the
United States. It provides some of these viruses to the WHO GISN network, mainly through the US Centres for Disease Control (CDC), a WHO Collaborating Centre in Atlanta, Georgia (and part of the US health ministry), but keeps all specimens and viruses for its own purposes.

The size and capacity of the US military program is dramatically expanding and has more than doubled in recent years. In 2005, it was active in 30 countries and included three BSL-3 labs and a total sample processing capacity of 9,000 specimens per year. By 2007, the network was active in 65 countries and included eight BSL-3 labs and the capacity to process 18,000 samples annually.

The network is named the US Department of Defense Global Emerging Infections Surveillance & Response System ("DoD-GEIS"). A DoD-GEIS program called the US Department of Defense Worldwide Influenza Surveillance Program focuses specifically on flu viruses.

The military network has "sentinel" sites around the globe, reported by US military sources to include 128 or more locations. These are installations where US military personnel are based, as well as collaborating non-military sites that collect samples from US personnel and local civilian populations.

In 2006-2007, the system collected influenza viruses from developing countries including:

-- Americas: Belize, Guatemala, Honduras, El Salvador, Nicaragua, Venezuela, Colombia, Ecuador, Peru, Bolivia, Paraguay, and Argentina.

-- Africa: Morocco, Libya, Egypt, Eritrea, Djibouti, Sudan, Uganda, Kenya, Burundi, Gambia, Ghana, Nigeria, and Cameroon.

-- Middle East: Turkey, Jordan, Iraq, and Oman.

-- Central/South Asia: Azerbaijan, Kazakhstan, Uzbekistan, Mongolia, Afghanistan, Pakistan, India, Nepal, and Bangladesh.

-- Southeast Asia/Oceania: Myanmar, Thailand, Vietnam, Laos, Cambodia, Philippines, Indonesia, Papua New Guinea, and Solomon Islands.

A US Air Force lab at Brooks City Base in San Antonio, Texas coordinates the system. In 2006 and 2007, its systemwide budget was over $40 million per year. In the 2006-2007 flu year, the Texas lab alone processed 5,810 specimens from persons across the globe suspected to have respiratory infections. Of these, 2,444 tested positive for a respiratory virus, including 1121 positive for influenza virus. According to the US Department of Defense (DOD), "All original specimens are archived and kept for requests from [Department of Defense] partners or the CDC."

Another lab at a US Navy facility in San Diego, California processes an unknown number of additional samples. Of note, the Navy lab systematically isolates flu viruses from military personnel who become infected during port
visits. Using this unusual collection method, in 2007, it isolated seasonal influenza viruses from countries including Indonesia, Papua New Guinea, and the Solomon Islands after US Navy ships docked there and US sailors became infected while ashore.

Including the Navy lab and other facilities (see below), the military system handled an overall total of approximately 8,000 influenza and other viral cultures in 2007. Of these, only a small percentage are given to CDC. In 2006, this number was 120 viral isolates (about 1.5%), meaning that over 98% of the viruses collected by the US military program do not enter the WHO system.

In addition to the CDC, collected viruses (especially H5N1 viruses) are provided to US Army Medical Research Institute of Infectious Diseases (USAMRIID) at Fort Detrick in Frederick, Maryland. USAMRIID is the historical home of the US offensive biological weapons program (terminated in 1969), and is presently the headquarters of the US military's biological defense effort. Drawing on viruses collected by the US military and WHO sources, as of 2007, USAMRIID maintained a collection of thirty different H5N1 strains plus many other flu types that it uses in research and provides to other US military labs.

According to the program, the primary purpose of the virus collection system is to ensure US military readiness: "The principal objective is to enable the rapid discovery of novel strain mutations that could trigger a pandemic and to monitor these strains for their ability to transmit and to cause disease... the priority of the DoD is to maintain readiness and protect the health of service-members and beneficiaries, the contributions from the [San Antonio-based] surveillance program also benefit the greater global health community."

Five overseas laboratories operated by the US Department of Defense act as regional coordination centres for the collection effort. The five labs are:

-- Naval Medical Research Unit No. 2 (NAMRU-2) in Jakarta, Indonesia.
-- Naval Medical Research Unit No. 3 (NAMRU-3) in Cairo, Egypt.
-- Naval Medical Research Centre Detachment (NMRCD) in Lima, Peru.
-- Armed Forces Research Institute of Medical Sciences (AFRIMS) in Bangkok, Thailand.
-- United States Army Medical Research Unit-Kenya (USAMRU-K) in Nairobi, Kenya.

With the exception of NAMRU-2, which was recently closed by the Indonesian government, each of the above labs works not only in the country in which it is located; but also in nearby countries, where laboratory and personnel
detachments are sometimes placed.

NMRCD operates a high containment (BSL-3) lab in Peru, and coordinates virus collections in several South and Central American countries and, for example, has staff in Guatemala. In 2007, it reported that it is seeking to
expand virus surveillance efforts in Ecuador, Bolivia, Paraguay, and Uruguay.

AFRIMS in Bangkok operates a BSL-3 lab and, in addition to work in Thailand, maintains a facility in Nepal and collects samples from other countries in the region. In total in 2007, AFRIMS collected over 1,000 respiratory
samples from seven countries in Southeast and South Asia.

NAMRU-3 in Cairo has at least BSL-3 capability and collects human and animal influenza viruses. It is a WHO GISN H5 reference lab, submitting viruses both to other US government labs as well as WHO labs. NAMRU-3 maintains
activities in many African, Middle Eastern, and Asian countries, from Ghana eastward all the way to Pakistan.

It states that in 2007, "From Egypt, 141 human specimens were received for influenza A/H5N1 reference testing, and 26 specimens tested positive for H5N1. H5 reference testing was performed on 459 animal specimens, with 92 positive for H5N1 from Afghanistan, Egypt, and Ghana." From these H5N1 isolates, MANRU-3 deposited HA gene sequence information for 74 strains in GenBank.

USAMRU-K in Nairobi collects virus samples from hospitals and Kenyan military facilities and says that it is developing collection capabilities through universities in Uganda and Cameroon and the Nigerian defense ministry. Flu viruses it collects are provided to the CDC and the US military.

Until the Indonesian government closed it, NAMRU-2 in Jakarta played a similar role, including coordinating US laboratory detachments in Indonesia, Cambodia and Laos. In 2007, it says that it collected and tested more than 4,500 respiratory samples in Indonesia alone. It is unclear what will happen to NAMRU-2's activities outside of Indonesia now that the Jakarta laboratory has been closed.

Other US military BSL-3 labs in the network are located in Germany and South Korea. The DoD-GEIS network also collaborates with the US Defense Threat Reduction Agency (DTRA), although the exact nature of the collaboration has
not been publicly described.

Despite the Pentagon's claims that it has frequently contributed to WHO vaccine strain selections, none of the negotiating texts or background documents made available by WHO in the course of the Pandemic Influenza
Preparedness Inter-Governmental Meeting have discussed the large US virus collection system that parallels the GISN, much less explained the relationships between the two.

Nevertheless, the purpose of the US military system does not wholly coincide with WHO's public health ends, and its activities at times do not appear to be compatible with most proposals for a revised WHO GISN virus and benefit
sharing system.

The massive US military virus collection system, which parallels the WHO system yet does not currently operate under the same rules, creates an additional complication for diplomats seeking an agreement on virus and
benefit sharing. Its extent and different purposes than the WHO system may also be of concern to some countries, particularly because WHO system virus sharing is for public health and not military purposes.

Efforts should be made to ensure that all virus collection and transfers take place within the WHO system, using a WHO material transfer agreement, and that virus collections for purposes other than public health not be permitted.

Chair's Text for the December WHO Virus Sharing Meeting: Comments and Link

perezoso — Sun, 16 Nov 2008 12:53:42 -0500

WHO has posted the Chair's Text to be considered in December at the next installment of the WHO Pandemic Influenza Preparedness Intergovernmental Meeting (WHO PIP IGM). The meeting name is a mouthful; but all you need to remember is that this is the group that is trying to resolve the virus sharing controversies.

The Chair's lengthy text is exactly that, a text drafted by the Chair of the meeting, and word on the street is that the Australia's Jane Halton actually did do much of the drafting. (Often "Chair's texts" are only nominally written by the Chair.)

Too bad the text doesn't do a better job of plugging gaps in the system and reflecting the proposals of developing countries. A complete listing of problems great and small would probably explode this blog's buffer; but, in short form, here are some of the key problems in Halton's text that will have to be resolved:

• The text's definition of "Pandemic Influenza Preparedness biological materials" (i.e. the viruses and other materials given to the WHO system) is way too narrow. As presently written, the main option has got a lot of verbiage; but it would only protect donor country sovereignty over the materials as submitted (e.g. a throat swab) and not after they'd been worked on. It would not cover, for example, synthesized copies of H5N1 genes. The restricted definition is a non-starter. It will have to be expanded.

• The Chair's system would only cover viruses isolated from human cases of potentially pandemic influenza. Another non-starter. H5N1 candidate human vaccine strains have incorporated not only genes fro humans; but from animals too, and this is likely to continue throughout the prepandemic phase. H5N1 viruses isolated in animals and elsewhere (i.e. environmental samples) will have to be covered, or else the benefit sharing system will not work.

• The text proposes to place the obligation to share benefits from use of the viruses on governments and not on vaccine and pharmaceutical manufacturers. No way, Jose Sanofi. Perhaps governments like the US and in the EU will provide some benefits to developing countries; but a binding obligation to share benefits - like vaccine technologies and an international fund - must be part of the Material Transfer Agreement that companies and other researchers sign when they access PIP materials (i.e. viruses and related materials and data). It's very simple: If companies want access to H5N1 viruses to make and sell vaccines, they're going to have to make contributions to promote access to H5N1 treatments for poorer countries.

• Thre are no major restrictions made on patenting H5N1 viruses and genes. The only restriction the Chair's text would impose would be patents on viral gene sequences. This falls well short of what is needed and will have to be improved. Stopping the patent ripoffs are a requirement for the new system.

• The Chair's system for acquiring and sharing viruses is very leaky and would not stop piracy. Through a variety of means that become apparent on close analysis, in the system proposed it would be possible for companies and other labs to acquire and utilize H5N1 viruses outside the WHO system, and without agreeing to share benefits. These holes, which are many, will need to plugged. If the viruse sharing system isn't airtight, then developing.

• At one point, the text seems to suggest that a "benefit" for developing countries would be for some of their citizens to be used as guinea pigs in vaccine trials. We hope this was a misunderstanding, because it will be patently offensive to many. Being an experimental subject is not a benefit.

• The Chair's text is schizophrenic about the role of the so-called "Essential Regulatory Laboratories" (i.e. the US FDA and its UK and Australian equivalents). It can't seem to decide if the regulatory labs are fully in the WHO system or not, and if they regulate vaccines or if they develop them. Part of the confusion is perhaps understandable. Although it is the function of the WHO Collaborating Centres to develop vaccines, in fact, the US, UK, and Australia seem to have assigned some of the these duties to their regulatory labs. This can no longer fly. The regulatory laboratories are going to have to stick to regulating, not developing vaccines, and if this means that changes have to made in the US/UK/Aus organizational structures, so be it. If the ERL's want to develop vaccines, they are going to have to be treated as vaccine manufacturer.

The text can be found here:

http://www.who.int/gb/pip/e/E_pip3.html

Stay tuned to Immunocompetent for more commentary on the text and issues for the upcoming meeting, which begins in Geneva on December 8th.

Draft H5N1 Virus Sharing Text Wikileaked

perezoso — Tue, 19 Aug 2008 06:57:22 -0500

A draft text of the WHO Intergovernmental Meeting on Pandemic Influenza Preparedness (PIP IGM) has cropped up on Wikileaks, and Geneva, we have got some problems. The 17 page negotiating document was issued on June 29th. It was written by Jane Halton, the PIP IGM Chair from Australia, in an effort to reconcile differing ideas put forward by countries for reform of the WHO Global Influenza Surveillance Network (GISN).

At least it's supposed to have reconciled ideas. Sadly, the text looks far more like what ~~certain developed countries~~ the pharmaceutical industry wants than a good faith effort to bridge gaps and present options. I guess some pigs are more equal than others at WHO. Egregiously, the text moves full-bore ahead with the insidious securitization of public health, making multiple references to "public health security", a national security / defense concept, that screws up WHO left and right.

Your bloghost will offer more commentary soon, but in the interim here's a detailed news article about the text written by Sangeeta Shashikant of Third World Network:

TWN Info Service on Intellectual Property Issues
15 August 2008
Third World Network
www.twnside.org.sg

WHO: Concerns over Chair's text on sharing of flu viruses and benefits

Published in SUNS #6539 dated 15 August 2008

Geneva, 14 Aug (Sangeeta Shashikant) -- The issue of the balance between the sharing of the influenza virus and the sharing of the benefits from the use of the virus (especially vaccines and other medical products to counter the deadly avian flu) is being handled by a process in the World Health Organisation, in which developed and developing countries are negotiating the terms of a decision that covers rights and obligations in the sharing of virus, the research and commercial use of the virus, and the access to the vaccines and other products.

A step in the process has been the issuing at the end of June of a draft text on virus sharing and benefit sharing by the Chair of the Intergovernmental Meeting (IGM) on Pandemic Influenza Preparedness. The Chair is Jane Halton, Secretary of the Department of Health and Ageing, Australia.

The text is giving rise to concerns among officials of some developing countries as well as independent experts, who feel that the Chair's text does not adequately reflect, even as alternative options, many of the ideas and suggestions put forward by developing countries. In particular, Indonesia, the African Group and Thailand had submitted comprehensive proposals as inputs to the drafting of the text.

The IGM on Pandemic Influenza Preparedness was set up by the 2007 World Health Assembly through Resolution 60.28, to undertake reform of the WHO Global Influenza Surveillance Network (GISN) and in particular to formulate Standard terms and conditions for virus sharing and benefit sharing as well as to review the terms of reference of the WHO Collaborating Centres dealing with influenza.

A Working Group of the Intergovernmental Meeting held on April 3-4, 2008 in Geneva, agreed that the various proposals contained in the consolidated text of EB 122/5 would contribute towards preparation of a Chair's text, which is to be the basis for discussion at the next WHO meeting on virus and benefit sharing on 9-15 November 2008.

The Chair's draft takes the form of a "streamlined" text, as if there is agreement on almost all aspects of the document, although to date very little discussion has actually taken place on the proposals. In some areas, it summarises proposals put forward to the extent it misrepresents the original proposal.

It also excludes several issues that could hurt the sensitivities of major industrialized countries such as the US and EU, whose businesses are major beneficiaries of the present virus sharing system. This is most obvious in the way the Chair's text treats intellectual property (IP) issues.

The paper excludes any provision that the recipients of viruses should not have IP claims over the products derived from viruses donated. Such a provision is supported by Indonesia, the Africa Group and by Thailand, but heavily contested by industrialized countries.

According to sources, during the Working Group meeting, in reply to a query by a Member state, it was confirmed that if there is dissatisfaction with the Chair's text, member states at the forthcoming November meeting could rely on the consolidated text of EB 122/5, which contains all the proposals of member states.

According to some diplomats, although it is not expressly mentioned in the outcome document of the Working Group, the understanding is that the Chair would prepare a text that would merge similar proposals and present as options proposals which diverge.

However, the present Chair's text disregards many of the proposals put forward, and where it puts forward options, it does so selectively. The Chair also presents what she believes to be "compromise text" in areas that have not been the subject of an in-depth discussion nor any agreement on the compromise.

Halton explains her actions in an email to delegations. She says that "some have expressed a preference to retain all of the original language and alternative concepts as proposed in submissions to the IGM in November 2007, while others have expressed a preference for a streamlined text with a minimal number of areas of disagreement".

She adds that an attempt has been made to balance the various comments, with two key guiding principles: (1) where a compromise position seems feasible, this has been put forward as streamlined text (adding that this approach has chiefly been used with regard to virus sharing, which has had more lengthy discussion); (2) where positions cannot be reconciled, or where issues have not been debated, an attempt has been made to retain all of the competing concepts and ideas, though not in full detail or in the original terminology (this approach has chiefly been used in benefit sharing, which has not yet been discussed in the working group).

She asked countries to comment on: (I) concepts or issues which are included in EB122/5 and which do not appear in the draft Chair's text; (ii) concepts or issues which have been paraphrased in the draft Chair's text but which do not adequately capture the proposals as they appear in EB122/5; (iii) textual suggestions to improve the technical correctness of the draft Chair's text; and (iv) Member States' views on issues in the draft Chair's text, particularly where they have not been debated to date and also where there may be room for compromise.

Some developing countries have privately indicated that the Chair's text in its present form is unacceptable.

Further, unlike the relatively open debate of the WHO's Intergovernmental Working Group on IP, Innovation and Health (whose negotiating document and comments on the document by countries as well as by NGOs were made available on a public website), secrecy shrouds the Chair's text and the comments on the Chair's text, all of which are not publicly available.

According to an email message sent by Halton and received by some delegations, "contributions received from Member States will be considered by the Chair in preparing a final version of the text" and "that on 28 July, all contributions will also be posted in the original language of submission, on a password-protected website", adding further that "information on accessing the website will be sent to Bureau Members before that time".

A WHO official informed SUNS that "a password-protected web community" has been set up for Member States to access contributions received from Member States on the Draft Chair's text, and this has been communicated to the Bureau Members (which should in turn inform other countries that they represent).

Some delegates contacted by SUNS were however unaware of this website, while others who were aware of this could not use the password.

Concerns on the Chair's text, some of which are mentioned in some developing country submissions, include the following:

(1) The Chair's text presents a mostly streamlined text on virus and benefit sharing, on the assumption that much of the content has already been agreed to by member states, although the actual situation is to the contrary.

(2) The text does not adequately reflect even as alternative options, many of the proposals put forward by developing countries, i. e. Indonesia, the African Group and Thailand. For example, termination clauses proposed in the Africa Group and in Thai papers have been left out of the Chair's text.

Another example is that Indonesia, Thailand and the Africa Group have stated that there should be no IP claim by WHO-designated laboratories and other entities that receive biological materials, over the substances, processes and products derived from the use of the biological material. However, no mention of this is made in the Chair's text.

(3) The Chair's text also drops crucial details from original proposals and sometimes even narrows proposals put forward to the extent it misrepresents the original proposals. For example, para 6.11 of the Chair's text states that "Vaccine manufacturers shall set aside x% of each production cycle of vaccines for H5N1 and other influenza viruses of human pandemic potential for the provision to the WHO stockpile free of charge," while para 6.12 of the Chair's text states "Vaccine manufacturers shall also set aside x% of each production cycle of pandemic vaccine for provision through the WHO on the basis of public health need".

These paragraphs seem to be taken from the Africa Group proposal, but it inadequately captures what the African paper states. While the Chair's text only speaks of providing vaccines to the WHO, the Africa paper also advocates prioritizing the needs of developing and least developed countries and that X% should be reserved for developing countries and provided at an affordable price. It also proposes a method of calculating the affordable price. (Para 6 (b) (I) & (ii) of the Africa Group paper A/PIP/IGM/7).

Another example is para 6.16 of the Chair's text, which narrows the scope of the proposal in the Africa Group paper to vaccine manufacturers providing royalty free licence to any influenza vaccine manufacturer based in the member states from where the relevant clinical specimen was collected from. The African proposal was broader; it required third parties to grant on request, a non-exclusive, royalty free license to any domestic influenza vaccine manufacturer from developing and least developed countries and in particular to the country providing the specimen.

Para 6.16 also does not make any reference to the proposal in the Africa Group paper, which talks about access to and transfer of technology and know-how in vaccine development as well as capacity building for domestic influenza manufacturers from developing and least developed countries. (The proposals are in the African paper, para 6 (a) (I) (ii) of Section H).

(4) A positive element in the Chair's text is that it refers to "Standard Material Transfer Agreement" (SMTA), thus accepting the concept in principle. However, there is concern that the SMTA in the Chair's text shows no characteristics of being legally binding on the recipient of the specimens and viruses provided through the WHO virus and benefit sharing system.

According to a developing country's submission in response to the text, the Chair's text is not clear on who are the signatories to the SMTA; the format of the SMTA; how the SMTA will be executed; or the dispute settlement mechanism if a party to the agreement fails to comply with the terms and conditions in the SMTA.

The Chair's text thus appears to pay "lip-service" to the concept of "SMTA". The Africa Group has presented a paper which allows implementation of the SMTA through "Implementing Letters", which are signed by the provider and the recipient as relevant, but these also do not feature in the Chair's text.

(5) The Chair's text places benefit-sharing obligations of the recipientsand dispute settlement in a section separate from the terms of the SMTA with the result that the recipients of biological materials need not commit to benefit sharing through an agreement. In addition, if there is non-compliance with the terms of the SMTA, there is no mechanism for the provider of materials to take action against the recipient (e. g. the manufacturer). The dispute resolution provided in the Chair's text is only between Members.

The resulting effect is that countries that fail to comply with sharing the viruses (Chair's text states that Members agree to routinely provide clinical specimens) may be brought to the Health Assembly but no action may be brought against the recipients that do not fulfill their benefit sharing obligations or do not comply with the terms of the SMTA. For an effective virus and benefit sharing mechanism, benefit-sharing obligations have to be a part of the SMTA. The papers of Indonesia, Thailand and Africa Group require recipients of the virus to be bound to sharing of benefits through a written agreement. The Africa paper further proposes a dispute settlement mechanism between the provider of biological materials and the recipient.

(6) The section on benefit sharing in the Chair's text presents tasks and routine obligations of WHO as the primary benefit to be obtained by developing countries in "benefit sharing" arising from the use of the viruses. This detracts attention from the real issue at hand, i. e. what are the benefit sharing obligations of recipients of biological materials such as the vaccine manufacturers, etc.

(7) Para 5.1.1 (a) and (b) of the Chair's text are about entities that would be allowed to receive the "clinical specimens or viruses". Basically, it requires countries to share viruses with a WHO Collaborating Centre for Influenza or a H5 Reference Laboratory (H5RL) of their choice.

But through these laboratories, the materials can be shared with: (I) laboratories in the WHO Network, which according to the definition, is comprised of National Influenza Centres; WHO Collaborating Centres On Influenza; H5 Reference Laboratories (H5RL), and essential regulatory laboratories; (ii) vaccine manufacturers; (iii) diagnostic manufacturers; (iv) pharmaceutical manufacturers; and (v) public health researchers. In

effect, the Chair's text allows free flow of "clinical specimens and viruses" once the materials are given to the WHO Collaborating Centre/H5RL.

There are at least two issues that arise. First is the wide authority given to the WHO designated centres (although the mandate for H5RLs is only to diagnose H5 infection) to decide to whom to give the biological materials to, bypassing the WHO Secretariat.

Second is the fact that the Chair's text not only requires the transfer of the vaccine virus (i. e. the modified virus used for vaccine development) but also the clinical specimens (e. g. throat swabs), and the isolated viruses to third parties (i. e. entities other than the WHO designated centres).

This is in total disregard of proposals put forward in particular by the Africa Group, which wants to limit the number of parties that receive the clinical specimens and the vaccine viruses and limiting the type of materials transferred to third parties to vaccine virus.

(8) The lack of clarity as to whether the definition of "biological materials" extends to parts of the biological material such as genes, sequences etc, since it is not explicitly mentioned. According to Edward Hammond, an expert on virus and benefit sharing: "With current technology, vaccine companies and other biotechnology enterprises do not necessarily need to receive specimens, viruses, or other biological materials from WHO collaborating centres in order to obtain viruses (and viral genes) that are submitted to the WHO system. The copying of viruses and their parts from sequence data only takes a few days at present, and will get easier and faster in the near future."

Therefore, he adds, it is imperative that the same benefit sharing mechanisms should apply to the sequence data itself and to the biological material generated (i. e. synthesized) from that data through the application of computational and laboratory techniques.

(9) The Chair's text repeatedly uses the phrase "global public health security" although the concept of "security" in WHO documents has been objected to by several developing countries even in the context of virus and benefit sharing.

(10) The text proposes that the review of the Terms of Reference of the WHO-designated centres be done by the Advisory Committee and not by the IGM. However, the concern here is that there will likely be little coherence between the Standard Material Transfer Agreement and the Terms of Reference, if the review of the latter is left to the Advisory Committee.

(11) The overall effect of paragraphs 5.2.1 and 5.3.2 is that laboratories that share clinical specimens will have to register those specimens in the traceability mechanism as pandemic influenza preparedness biological materials (PIP biological materials). Those who receive the PIP biological materials will have to register receipt of the materials and comply with any other data requirements of the traceability and associated reporting mechanisms.

However, the proposed traceability mechanism in the Chair's text should also track movement of the vaccine virus; parts of the virus (e. g. genetic and other components, genes, sequences and polynucleotides as well as the polypeptides they encode); report on the "use" of the materials by laboratories that may be part of the WHO network (e. g whether the lab did isolation, developed vaccines virus, developed diagnostic kit etc.) and by the vaccine, diagnostic, and pharmaceutical manufacturers and public health researchers; track the benefits shared by recipients of biological materials with the WHO system and member states; and documents executed (e. g. MTAs signed) in the process of virus and benefit sharing.

Some submissions by countries also suggest that consideration should be given to the recently concluded "Global strategy and plan of action on public health, innovation and intellectual property" (WHA Resolution WHA 61.21).

The Strategy mentions concepts such as "appropriate licensing policies, including but not limited to open licensing", "patent pools", open-source approaches and it would be interesting to see how these concepts may be applied in the context of virus and benefit sharing particularly in resolving tensions surrounding IP.

Synthetic Influenza and In Silico Collections

perezoso — Fri, 15 Aug 2008 09:24:43 -0500

This post is really about synthetic biology and influenza; but I want to start by clarifying one thing: If I were free to decide, I'm pretty sure that I would not enshrine into law sovereign rights over creatures great and small.

But I don't get to make the rules, nor do virologists (and not even The Imperial Laurie Garrett, heretofore "TILG", no matter how intolerably super-sized her ego gets). Maybe in another post, on another day, I'll explore how the present legal and treaty situation came to be; but that's not the point now. Instead, let's make the best of the hand we've been dealt. Hint: Folks searching for a gene sovereignty bogeyman can blame, in significant measure, the large mainline environmental organizations.

Today's ugly bellyaching about sovereignty and microbes in the flu science crowd is pretty much identical to the whining I heard over a decade ago from agricultural researchers and other kinds of biologists. The latter groups have mostly stopped complaining and are instead learning to live with reality. Live productively and happily even. Unfortunately, the flu science crowd (with ample corporate encouragement) is stuck in some retrograde 1980s intellectual trickle-down time warp.

The issue I want to point out today is that of in silico collections. If you know the Biodiversity Convention, you probably get my reference. An issue that has bedeviled that treaty are questions about sharing the benefits from use of plants and other types of life found in "ex situ collections". These are your botanic gardens, seed banks, microbial repositories, etc. Questions like this: Say Kew Gardens in the UK has mounds of Malaysian rainforest trees and, hypothetically, one of them turns out to hold the permanent cure for 'erectile dysfunction'. Say Kew (and its corporate collaborators) make a fortune selling it to rich old men that can't get it up.

Is anything owed to Malaysia? It often is even more complicated: What if some Malaysian indigenous people used the plant as an aphrodisiac, helping Kew identify the drug. They're getting their homeland bulldozed while some pharma exec is buying a new yacht AND entertaining his girlfriend.

There certainly are ex situ collections of influenza - mounds of frozen vials in Memphis, Atlanta, and many other places. Who they belong to is a good question. Some labs seem to consider them personal property. This is undoubtedly wrong. Another topic for another day. I still haven't gotten to today's point...

Interestingly, with advances in synthetic biology, the most important ex situ collections of influenza may be in silico collections. I mean computer data. That's because with reverse genetics and advances in gene synthesis, it is becoming increasingly easy - a matter of a few days now, if in a hurry - to download a flu virus sequences and create the actual living bug. Of course, keeping the original isolate in the freezer somewhere will remain prudent; but for many functions, viruses (and genes and their parts) assembled from internet sequence data will come to replace sharing of actual physical viruses. For example, reverse genetics-produced H5N1 is already used as a challenge agent in vaccine trials (with animals, obviously), indicating the high level of confidence that some researchers have in the ability of the technology to faithfully reproduce the natural bug.

Not only do internet databases form a set of in silico collections from which the original biological article can be reproduced; but they also provide the grist for increasingly sophisticated sequence analysis tools. Remember that very small, even single nucleotide, mutations can make a world of difference in flu strain pathogenicity for chickens, cats, or even humans. Applying predictive analytical methods to the sequence data, therefore, may eventually produce genetic "riffs" on H5N1 particularly useful for vaccines (or to produce so-called "virus-like particles"). There are products in development that use this approach.

So, in a few years, it is entirely plausible that we will have influenza research labs that don't generally receive strains in biological form. They download them. Or point their gene synthesizer (or gene synthesis company) to a URL and, from there, the process is more-or-less automated. Make the genes in the lab, or have them synthesized, put them into well-known and standardized DNA plasmids, and let the strains assemble themselves in culture. Granted that doing it is not as easy as saying it; but it's not going to stay hard for long. Flu isn't a big organism. It has about as many letters in its entire genetic code as there are on the front page of each day's New York Times (~12,500). There are parallels here with the "biological parts" concept that the eager-beaver synthetic biologists are promoting, some of whom are also tied up in questions about intellectual property.

This presents a lot of problems when it comes figuring out how to make the virus sharing system more equitable. If labs and companies are only required to share benefits when they receive the virus in biological form, it will only propel them to develop their synthesis capabilities more quickly. Why "pay" for the virus, by receiving a physical specimen, when you can make it with no strings attached? Clearly, if it has any hope of success, the WHO system is going to have to confront the in silico collection issue head-on.

It's one of trickiest aspects of reforming the WHO system. Excluding a few problematic sequence hoarding labs, almost everyone agrees that influenza sequence data should be available to all. So, how do you make it available without encouraging proprietary claims and piracy? More inquiring minds than mine are thinking about this issue. It may prove that other areas, particularly writing and computer science, will offer adaptable models for how one can 'get things out there' without getting ripped off.

Richard Holbrooke and Laurie Garrett are Full of Sh*t

perezoso — Tue, 12 Aug 2008 21:17:46 -0500

Update: 6 September 2008

An Important Note About This Blog Entry

The short essay below was originally written as a Letter to the Editor of the Washington Post, because I believed that it was very important to publicly correct the numerous errors and misperceptions contained in the Holbrooke / Garrett editorial.

When the Washington Post did not publish the letter, I sent it to a number people and urgently asked them if they would be so kind as to put forward the ideas contained in the letter, given the important international humanitarian interest in reforming the GISN.

I was therefore very grateful when Ambassador Wibisono of Indonesia adapted the essay below and was able to have it published in the Jakarta Post on my behalf. An utmost priority in the debate over influenza virus sharing is widely circulating the powerful arguments for changing the current system, therefore, I again thank Ambassador Wibisono for his willingness to carry this message to a broader public.

------

... and it's time for America to wake up to that fact.

In their badly informed Washington Post op-ed "'Sovereignty' That Risks Global Health" (10 August), Richard Holbrooke and Laurie Garrett make a number of factual mistakes and misleading statements, some of which I will enumerate here.

The existing World Health Organization (WHO) system of sharing influenza viruses, called the Global Influenza Surveillance Network, is radically unjust in that it takes resources from developing countries and provides little in return, and leaves us all more vulnerable to an influenza pandemic. Indonesia and other countries that have taken the initiative to reform the WHO system are taking a laudable and overdue step to improve public health for all.

There is no constituency seeking to create "viral sovereignty". De facto, such sovereignty already exists in international law. Inexplicably, the authors mislead by simply ignoring that fact and, in particular, 20 years of development of the Convention on Biological Diversity which, among other international instruments, recognizes national sovereignty over genetic resources, including microbes. Viruses are, unequivocally, genetic resources subject to national sovereignty, whether Holbrooke and Garrett want to admit it or not.

Holbrooke and Garrett claim that it is "ludicrous" to apply sovereignty to genetic resources that easily cross borders. Their position belies ignorance of both biodiversity and related law and policy. As any farmer, biologist, or duck hunter can tell you, most genetic resources cross borders: birds, plants, insects, microbes, crops, and practically everything else made of DNA (or, as in the case of flu, RNA). This simple biological truth has not stopped sovereignty or international cooperation in biodiversity use and protection. Transboundary biodiversity issues have been discussed and addressed for over two decades by the UN. Holbrooke and Garrett have no apparently clue about this, otherwise they would not have made such an off-base assertion.

They further state that "The WHO has elicited pledges from the world's major drug companies not to exploit international repositories of genetic data for commercial benefit". Such pledges, even if they existed in the form claimed, are contradicted by fact. First of all, a number of companies have lodged US and international patent claims over hundreds of H5N1 genetic sequences - resources that were freely given to WHO by Indonesia and other countries. These resources come from the gene repositories.

Secondly, major pharmaceutical companies have advanced clinical trials underway utilizing Indonesian, Vietnamese, and other viruses in vaccines. One vaccine using a Vietnamese strain is licensed. The companies intend to profit from sales of these vaccines, and Indonesia (and other countries) will receive nothing of the proceeds. The fact of the matter is that industry - large and small - massively benefits from resources of the WHO system, and no commeasurate benefit accrues to Indonesia and other countries who, ironically, are facing the gravest immediate threat from H5N1.

Further, contrary to Holbrooke and Garrett's erroneous suggestion, the revised International Health Regulations do not require viruses to be sent to WHO, and Indonesia has not defied them. The revised regulations mandate sharing of information on disease outbreaks of international importance, and such information continues to be shared. The authors further - and unaccountably - allege that Indonesia has violated "a host of other WHO agreements". What agreements? I have participated in the WHO negotiations on influenza virus sharing, where I have not seen either Holbrooke or Garrett, and I am unaware of any such allegations.

In reality, Indonesia has repeatedly offered to provide more viruses to WHO. Neither Indonesia, nor its Health Minister, are intrinsically opposed to providing viruses. Rather, the stumbling block is an unwillingness of some countries to implement a just Material Transfer Agreement (MTA) to define the rights of parties when viruses are transferred.

The underlying proposition that Garrett and Holbrooke rail against in their callous editorial is that Indonesia and other countries are asking for a reasonable MTA for influenza viruses - one that doesn't rob them - and for an unbiased WHO. The hypocrisy of the US and some other countries is especially palpable when one looks at the typical agreements signed by US institutions for transfer of viruses between themselves. Those agreements are far more restrictive than anything that Indonesia or its allies have proposed for sharing their viruses.

The move to reform the WHO Global Influenza Surveillance Network is neither self-destructive nor anti-Western. Holbrooke and Garrett's lashing out against Indonesia is uninformed about the pertinent policy and law related to genes and sovereignty, and callous toward the concerns of developing countries trying to better protect their own citizens from a pandemic. In their blindness to the obvious injustices of the WHO system, Garrett and Holbrooke recklessly dismiss a very important, and potentially very positive - but delicate - negotiation underway to make the multilateral system more fair and equitable.

It's time for the US and its allies to stop hurling abuse at Indonesia and to acknowledge the need to reform the virus sharing system so that developing countries receive tangible benefits for their participation. Indonesia and other developing countries have put concrete and detailed proposals on the table for negotiation in Geneva. The real danger to public health is not sovereignty that is already a reality; but that these proposals are not discussed and implemented, leaving us with a dysfunctional global influenza surveillance system.

Quick Sketch of a New Global Virus Sharing System

perezoso — Mon, 11 Aug 2008 16:36:23 -0500

Back when I ran the Sunshine Project, and with the help of Third World Network, I wrote a brief item describing how the WHO Global Influenza Surveillance Network could be reformed. We distributed this at a meeting of the WHO Pandemic Influenza Preparedness Intergovernmental Meeting (WHO PIP IGM). (Yes, it's a mouthful.)

The jist of the following nearly year-old article is still about right. I should have given more attention to sequence data, with the rapid rise of synthetic biology; but it's there in rudimentary form. Take a gander at this short piece if you want to know what some of us are thinking about for a New Global System.

Third World Network
The Sunshine Project

INFORMATIONAL HANDOUT

November 2007

Intergovernmental Meeting on Pandemic Influenza Preparedness: Sharing of influenza viruses and access to vaccines and other benefits

A Quick Sketch of a New Global System for Sharing of Influenza Viruses

In the interest of public health and access to affordable medicines, a new international system is needed for the sharing of influenza viruses. The purpose of this short paper is to describe, in simple terms, the basic principles and methods of operation of such a system, without delving into great detail about problems with the present system. Here some important underlying concepts for the new Global System are presented, followed by a practical description of how it would operate.

In this document, viruses are understood to include sequences, virus genes and proteins (and subunits of both), as well as materials specifically derived therefrom, such as antibodies and complementary DNAs (and genetic constructs encoding the same).

The Global System must not allow patenting of influenza viruses. A fundamental problem currently is that transfer of viruses into the system is resulting in piracy of influenza viruses by companies and other labs, and even by some WHO Collaborating Centres themselves. These patents are ethically unacceptable and ignore the rights of donor countries and influenza victims. They will result in economic and social injustices including more expensive and less accessible treatments. Therefore, all transfers of biological materials and data into and out of the WHO system, including publication of sequence data, shall be with the legal stipulation that these items shall not be subjected to intellectual property claims.

The Global System must respect national sovereignty over influenza viruses. Sovereignty over genetic resources found within a country’s borders is established in international law and most prominently enshrined in the Convention on Biological Diversity.(1) Sovereignty should not be confused with ownership. Respecting sovereignty does not mean that a government owns influenza viruses occurring within its borders, rather, it means that the government has rights in determining how they are used. These rights must be preserved and applied when the viruses are transferred into and out of the Global System.

Specifically, in the new Global System, sovereignty means that governments must grant their prior informed consent to uses of the viruses that they contribute. For key functions such as surveillance and development of vaccine seed strains, this prior informed consent can be pre-negotiated and applied in the form of an agreement like those already routinely used for transfer of biological research materials. For other purposes, including commercial ones, it may be necessary to specifically request consent from the donating country.

The Global System must require the commitment of all participants to the fair and equitable sharing of benefits that arise from influenza virus research. The Global System must provide real, tangible benefits to participating countries, particularly developing countries, who receive next to nothing in return of participating in the current system. This would be the best way to avoid frustration with the system, which in turn could lead instead to mainly bilateral arrangements. The precise benefits will vary depending upon the situation, however, under the umbrella of the New Global System, for developing countries they may include: (1) free access to and assistance with vaccine production such as equipment and know-how (e.g. cell culture systems and adjuvants), (2) vaccine stockpiles under WHO physical control which would be distributed on the basis of public health needs, (3) free or discounted set-asides of a percentage of prepandemic and pandemic vaccine production lots; (4) free or discounted access to other influenza medicines, and (5) commitments of non-enforcement of influenza-related intellectual property rights. How would a New Global System operate? As a practical matter, there would be a number of major changes from the current system for sharing influenza viruses. These include:

Rewriting the terms of reference between WHO and the Collaborating Centres and enforcing them. Current WHO Collaborating Centres are governed by loose and unenforced arrangements. Because of intense commercial interest in influenza viruses and actual and potential conflicts of interest at some Centres, the terms of reference must be radically revamped. In particular, WHO itself will assume responsibility for virus use and transfers, meaning that in these areas, the Centres will no longer have any latitude to do as they see fit. In those matters, they will act only on behalf of WHO and only as specifically authorized in the new Terms of Reference. This means that transfers of virus into and out of the Centres will effectively be governed by the terms of agreement between donor countries and WHO and not ad hoc or peculiar arrangements, or lack of arrangements, between the Centres and donor countries.

In general, movements of viruses will be covered by Material Transfer Agreements.Presently, no such agreements are executed between donor countries and WHO Collaborating Centres meaning that, in effect, the viruses are a no-strings-attached gift from developing countries to the Centres, for the Centres to treat as they see fit. As benefits have not been shared and this practice has led to piracy, this unacceptable situation must be changed, and WHO must no longer tolerate, endorse or encourage it.

Material Transfer Agreements under the New Global System could be of three general types – 1) those from a country of origin to a WHO Collaborating Centre, 2) those of virus seed stock from a WHO Collaborating Centre to a vaccine manufacturer, and 3) all other transfers. The first two transfer types can largely or even completely be governed by pre-negotiated terms elaborated in a standard form.

Such Material Transfer Agreements are not onerous and are by no means unprecedented. In fact, similar MTAs are already the norm for transfers of biological research materials in developed countries. In many cases, MTAs already commonly used for influenza virus transfers between Northern institutions are more restrictive than those likely to emerge under a New Global System.

In the case of a standard MTA between the country of origin to a WHO Collaborating Centre (acting on behalf of WHO), the main purpose is to authorize the Collaborating Centre to perform its important responsibilities (such as identification and characterization of the strain) set forth in the Centre’s Terms of Reference and to preserve national sovereignty over the virus. /Such MTAs will make stipulations and preserve sovereignty in the event of transfers to third parties beyond the Centre that, in most cases, will require execution of a new MTA between the third party and the country of origin. In some cases, for example transfers between Centres and reference labs, or for research by a third party contracted to a Collaborating Centre for research in accordance with the Centre’s WHO Terms of Reference, there may be latitude for transfer for those purposes under the first MTA.

In the case of a standard MTA between WHO and a vaccine manufacturer for transfer of vaccine seed strain, the main purpose is for the vaccine manufacturer to obtain authorization from the country / countries of origin of the seed strain virus and for the manufacturer to make commitments for benefit sharing as pre-negotiated under the umbrella of the New Global System (as described at the top of page 2). This MTA will enable the manufacturer to use the seed strain for vaccine production or further development for vaccine production and will bind the manufacturer to fair and equitable sharing of benefits.

In the case of other transfers, prior informed consent of the donor country will be required, and execution of a new MTA with the country of origin will be necessary if requested by the donor. These include transfers of viruses that are not vaccine seed strain to companies, and use of virus by the Centres in ways not specifically authorized by the Terms of Reference. Because these transfers may be to very different kinds of institutions for widely varying purposes, no complete single set of terms may be applicable. WHO, governments, scientists, and NGOs should discuss these transfers with a view to establishing standard procedures and boilerplate MTA language, which perhaps may evolve into standard MTAs in the future. Importantly, setting final definition of terms of some of these types of transfers aside for the time being will not prevent establishment of a New Global System.

WHO Collaborating Centres and other entities will renounce influenza-related intellectual property claims as a condition of their participation in the New Global System. These include claims on viruses, genes, sequences, proteins, and their use in human and animal vaccines and diagnostics. This will ensure the availability of the system’s resources and outputs for public health uses. In the current system, some Collaborating Centres have made patent claims or argue that they should be made "defensively". "Defensive" patenting is not a solution, it is a symptom of the problem of privatization. Instead of worsening the condition by increasing the amount of patenting, the New Global System should renounce it, and seek to inoculate its resources and products from such claims.

Access to New Global System sequence data will not be impeded, and subject to the first MTA can be made available online. Important conditions will include that all data be available to all persons, and that all who access it must agree not to sell or make any type of proprietary claim to it or for its use. Models of these types of systems can be found for software and other media and these can be adapted for use with New Global System sequence information.

Virus transfers will be comprehensively tracked by WHO, which will maintain a database of them as it will be advised of all such transfers by virtue of its revised relationships with the Collaborating Centres. This data should be available to Member States and the public.
Donor countries will have certain other research-related rights, including those of immediate material return and provision of characterization data, other research results and publications.

Footnote: (1) It has been suggested by some that influenza viruses do not fall under the Biodiversity Convention because they are a potentially harmful type of genetic resource that humans seek to control. This is not only an incorrect assessment of the language of that treaty, in fact, the operations of the Global System and influenza research are very clearly aligned with the intent of the CBD. The collection, obtaining, distribution, and preservation of influenza diversity is a core purpose of the Global System, as that diversity is critical to treating influenza. The fact that governments value such diversity and its preservation is illustrated by the extreme lengths that have been resorted to in order to recreate the 1918 influenza virus.