18 September 2019

What is pathogen sovereignty? … and why does it matter?

Global Health Research

In the book Sapiens, Yuval Noah theorises that humans are able to collaborate on vast scales because we can construct ‘fictions’ that almost everyone believes in. The sovereignty of pathogens is one such fiction. But will it help us collaborate, or will it be a liability?

In 2007, Indonesia was being overrun by a deadly strain of avian influenza when it decided, out of “protest against the established more-than-50-year-old WHO system”, to stop sharing samples of the H5N1 virus with the rest of the world.

For the past half-century, countries had been handing over pathogen samples to the WHO’s Global Influenza Surveillance Network with no strings attached.

Biological sample sharing had obvious advantages; it meant that countries could study the virus before it spread into their territory.

Cooperation had been the norm. Between 2005 and 2007, Indonesia dutifully sent more than 50 bird flu samples to WHO Collaborating Centres in the United States and Hong Kong.

But, in 2006, when Indonesia was experiencing the largest outbreak of H5N1 in the world, a series of events led the Indonesia government to take drastic action.   

While foreign research depended entirely on the Indonesian specimens, Indonesian scientists were left out of the manuscript-writing process and were only tacked on as co-authors at the end. 

The last straw was the revelation that an Australian company, CSL, had used Indonesia’s specimens to develop an H5N1 vaccine without asking permission. (Indonesia had been in talks with the pharmaceutical company, Baxter, about developing its own vaccine but the Australian company beat them to the punch.)

In January 2007, Indonesia finally put its foot down and ceased sharing samples.  This caused international panic. The H5N1 virus had an 81% mortality rate. It had only spread to 116 people in Indonesia, but if foreign scientists couldn’t get their hands on samples, they couldn’t protect their country against the spread of the disease.

In the ‘global north’ Indonesia was criticised as holding the world to ransom. Prominent commentators in the US called Indonesia’s decision ‘‘moral blackmail’’ and ‘‘morally reprehensible’’.

But in the ‘global south’, low-income countries backed Indonesia, affirming its policy of viral sovereignty.

“Indonesia, in effect, asserted that it had a right and duty as a sovereign state to use its biological resources to benefit its citizens,” one US-based analyst wrote in a 2017 paper on the subject. “Viral sovereignty itself threatened to go viral.”

From Indonesia’s perspective, wealthy, industrialised nations had been plundering the biological resources of poorer, agricultural-based countries for years.

The ‘stolen’ biological material was used by high-tech countries to create vaccines, diagnostics and drugs, which were then patented and sold for profit.

Often, the disease-affected countries that supplied the original biological samples could not afford to buy these life-saving products.

“Poor countries have no bargaining position because their participation in the production of these products is not valued,” Indonesia’s health minister Siti Fadilah Supari said.

Pathogens, of course, don’t give two hoots about national borders, so trying to claim national ownership over a virus is like trying to drive a flagpole into the wind. It’s a futile and logically incoherent exercise because the pathogens that infect humans tend to be contagious.

But, in practice, countries do have a temporary monopoly over pathogen strains that arise in their territories and, as Indonesia showed, this can be a valuable bargaining chip in international negotiations.

Indonesia’s actions in 2007 radically shifted the global mindset; in some countries, the climate of scientific openness gave way to nationalism.

In a private cable circulated around Brazilian government departments in 2009 (and later published on Wikileaks), the government of Brazil likened the colonial theft of plant species to the patenting of vaccines based on Brazilian samples.

“Government of Brazil officials … often point to the historic tragedy for Brazil when England smuggled rubber plants from the Amazon to Asia, which broke Brazil’s lucrative rubber monopoly.

“More recently, Government of Brazil officials expressed concern over sharing H1N1 virus samples, which could produce a profitable vaccine.”

Indonesia’s showdown with the WHO did more than just spur patriotic sentiment; it actually pushed the boundaries of international law.

Thanks to a legal argument made by the Indonesia’s minister for health, pathogens are now considered sovereign entities under the 1992 Convention on Biological Diversity, and its supplementary agreement, the 2014 Nagoya Protocol.

These treaties were originally designed to encourage conservation. But they also laid down some ground rules for how countries should share biological resources such as plants, animals and microbials.

There are 196 parties to the Convention on Biological Diversity, and 118 parties to the Nagoya Protocol, with the notable exception of the United States.

Parties are each allowed to enact their own laws governing the collection and removal of biological samples from their territory and must enter into bilateral negotiations if they want to take biological material out of a foreign country.

If any benefits arise from the use of that resource, the benefits have to flow back to the country of origin.

These benefits don’t necessarily have to be in the form of royalties. They could also be recognition in scientific publications, education, employment or discounted products or services.

The treaties also don’t specify the amount or type of benefits that need to return to the supplier country – this is left to individual nations to decide.

After the Indonesia scare, the WHO had to concede that viruses also fell within this convention and quickly got to work establishing an international treaty to allow for the free flow of influenza samples.

It took four years to nut out the details, but the Pandemic Influenza Preparedness (PIP) Framework was finally agreed upon in 2011.

Basically, it’s a subscription model where manufacturers collectively pay the WHO around $US28 million each year to access the specimens in the network.

In the case of a pandemic, the framework guarantees access to free or discounted vaccines to all nations on the basis of need – even to those countries that don’t actively contribute samples.

Importantly, the PIP Framework only covers pandemic influenza. When it comes to gaining access to seasonal influenza or any other pathogen species, nation states are on their own.

There is growing concern that scientists might have to wade through an enormous amount of red tape to get pathogen specimens out of a foreign country, or be denied access entirely, which would slow down the global response to emerging infectious diseases. 

“I think we’ve woken up a bit late now and realised that if a particular virus shows up in a particular country, it becomes their sovereign property and then it’s up to them whether they want to share it or not,”  WHO chief scientist Dr Soumya Swaminathan told The World Conference of Science Journalists in July.

“Now, this can be potentially very serious when we’re talking about disease outbreaks … where you want specimens to be shared as quickly as possible.”

The WHO missed the opportunity after Indonesia’s sovereignty claim in 2007 and was now having to deal with the implications, Dr Michelle Rourke, a legal academic at Griffith University in Queensland, said.

“Even though the issue’s been on the table since 2007, it’s taken them this long to go, ‘Well, hang on. What does this mean for other viruses?’”, Dr Rourke said.

The WHO is now trying to salvage the situation by folding seasonal flu into the PIP Framework.

In May this year, WHO member states formally asked the WHO director-general to investigate how the Nagoya Protocol was affecting public health.

Claims to sovereignty can make pathogen-sharing more tense and politically complex, but there are only a few examples (that we know about) where this appears to have slowed science down.

For example, in June 2012 a major diplomatic incident occurred between Saudi Arabia and The Netherlands when an Egyptian scientist working at a Saudi hospital mailed a sample of the MERS coronavirus to a Dutch lab to confirm his discovery of a new disease.

Professor Ali Mohamed Zaki got full credit for the breakthrough, securing first authorship on the NEJM paper.

But the Dutch lab filed a patent application claiming ownership over the genetic sequence and the prophylactic and therapeutic methods. This infuriated the Saudi government, which contested the claims.

“Scientists reported halting research on MERS coronavirus altogether after the legal terrain became fraught from competing legal claims,” legal academics reported.

By September, Professor Zaki had resigned from the hospital and flown back to Cairo.

Oddly enough, the grounds for the Saudi government’s claims to pathogen sovereignty were shaky, at best. The coronavirus “was detected in camels in many countries so, it is not a Saudi virus,” Professor Zaki told The Medical Republic in an email.

The Dutch laboratory is now requiring foreign researchers to sign a material-transfer agreement before they can acquire the MERS coranavirus.

Legal expert Dr Rourke has heard similar anecdotes at conferences. But people who are in-the-know, such as microbiologists and aid workers, refused to go on the record because it was such a politically sensitive area, she said.

Dr Rourke and her co-authors from the US did manage to conduct a few anonymous interviews with people who worked on the MERS and ebola outbreaks, however.

Their study, published in the Journal of Health Care Law & Policy in August, concluded that the concept of pathogen ownership was a major barrier to scientific collaboration as it produced a climate of mistrust, confusion, secrecy and data hoarding.

But according to Dr Gary Kobinger (PhD), a Canadian virologist who led the development of the ebola treatment, ZMapp, getting your hands on foreign pathogen samples without causing a diplomatic incident is relatively easy if you just follow the spirit of international law.

In his contractual agreements with foreign nations, Dr Kobinger agrees to give the country of origin 100% ownership over any of the drugs, vaccines and diagnostics that are derived from the foreign pathogen sample.

The university gains zero intellectual property from this kind of research. Fortunately, Dr Kobinger’s university is amenable to these kinds of deals. Other researchers might not be so lucky, he said.

Dr Kobinger’s success in negotiating pathogen-sharing deals saw him become the ebola supplier to many labs across northern America during the 2014-16 outbreak.

Other countries were also taking blood samples containing ebola out of West Africa at the time, but they were not interested in signing away their IP rights.

More than 10,000 blood samples were shipped to the UK. Samples were probably also sent to laboratories in South Africa, France, Germany and the United States.

But West African scientists are trying to discover what happened to these blood samples, which they consider to be their countries’ sovereign property.

The ebola virus has continued to evolve, and a new strain emerged in the Democratic Republic of the Congo (DRC) last year, killing around 1,800 people. But no-one outside the country has access to the new strains of ebola because the DRC has completely blocked access.

“I don’t have any ebola samples from this outbreak. Nobody has,” Dr Kobinger said. “A lot of work that could be done is not being done.”

The Centers for Disease Control and Prevention (CDC) in the US claims that the lack of access to recent ebola strains is due to a “logistical issue”.

But Dr Kobinger said it was common knowledge that all the ebola samples were sitting in a lab in the DRC capital, Kinshasa, where they could be easily sent overseas.

Nature recently reported that the DRC government was refusing to send ebola specimens out of the country because they didn’t want to fall victim to the same kind of asset stripping that was seen elsewhere in west Africa.

(The Medical Republic contacted the DRC’s National Institute for Biomedical Research in Kinshasa, which is managing the ebola outbreak, but did not receive a response for this story. The CDC also did not provide a comment.)

Professor Pamela Andanda, a legal academic and the chair of the Data and Governance Committee of The African Academy of Sciences, told The Medical Republic she was not aware of any country that had delayed sharing a pathogen sample due to sovereignty claims.

“However, the reverse situation tends to be the case: pathogen samples have been taken from African countries and not shared with African researchers,” she said in an email.

TAKING THE HIGH ROAD

The CDC has responded to this block in the pathogen supply chain with a high-tech solution. 

This year, the CDC announced that it had reverse engineered the most recent ebola strain using genetic sequence data that was publicly available on GenBank.

This work-around might not last for long, however. Some countries in Africa and Scandinavia are now pushing for genetic sequence data to be bound by the same international treaties that govern specimens.

Some scientists are concerned that free sharing would become illegal if genetic data falls under the Nagoya Protocol.

Allowing countries to block access to genetic data during a disease outbreak was not in anyone’s interest, Professor Andrew Rambaut, an evolutionary biologist at the University of Edinburgh who did much of the phylogenetic analysis of ebola samples during the 2014 outbreak, said.

When ebola spread between Sierra Leone and Guinea, scientists on the ground were sequencing the virus within 24 hours and using the tiny changes in the genome to track the spread of the disease, he said.

“They could sequence new cases and determine that they’d come in from over the border or whether they were local transmission and they shared that information between those two countries.”

If either country had tried to claim sovereignty over the first genetic sequence in the hope of monopolising a future vaccine, none of that vital epidemiological research could have been done.

Many countries that have signed the Nagoya Protocol have not yet laid down national regulations, leaving scientists in the dark about their obligations.

In countries that do have clear regulations, scientists often have to wade through a sea of documentation.

For an example of just how onerous this paper trail can become, look no further than Queensland’s sample biodiscovery agreement, which is 32-pages long and mandates that researchers apply for a licence, individually track every sample collected using a unique code, and file reports with the government every quarter.

This “old fashioned” form of bureaucracy was completely at odds with the way that science was actually done today, Professor Charles Lawson, a legal academic at Griffith University in Queensland, said.

While companies might have stumbled across a herb or plant and transformed it straight into a product in the 1980s, today the path to commercialisation was much more indirect, Professor Lawson said.

Research findings go into a global pool of knowledge and the intellectual assets that get extracted might be a pastiche of hundreds of different individual research projects published over a number of decades.

There was very little evidence that the Convention on Biological Resources had ever delivered monetary benefits back to communities, which made all this paperwork somewhat pointless, Professor Lawson said.

IS THIS REALLY HAPPENING?

While there’s hardly any published data that demonstrates the Nagoya Protocol has actually reduced pathogen-sharing worldwide, there’s another field where the effects are very well-documented.

The number of biocontrol agents being shared between countries has dropped by 80% since the Nagoya agreement was signed.

Biocontrol agents are plants and insect species used to control invasive species.

It took CABI, an international not-for-profit, three years to negotiate access to biocontrol agents in India after Nagoya Protocol laws were enacted.

CABI also found it impossible to work within Turkey, where foreign entomologists were arrested for collecting insects, and laws were passed banning specimen exports altogether in 2016.

Unfortunately, as Dr Rourke admits, there is no way to wind back the clock now; pathogen sovereignty is here to stay.

But that hasn’t stopped some groups with vested interests from trying to re-write international law.

In its 2018 position paper, pharmaceutical company GSK argued that pathogens should be excluded from the scope of the Convention on Biological Diversity and the Nagoya Protocol.

These treaties were all about protecting genetic resources with value to humanity and therefore “do not apply to genetic resources which cause disease and illness, as society is actively dedicated to their eradication”, GSK argued.

So, will the concept of pathogen sovereignty help humans collaborate on a global scale?

Probably not. 

For poorer nations, exercising state power over pathogen samples was quite often their only point of leverage, Dr Rourke said.

“And the scariest bit is that the more dangerous the pathogen, the more value they can leverage out of access to it.

“[The Nagoya Protocol] introduces a perverse set of incentives to limit the response to an emergency situation.”