There is something that is weighing heavily on the minds of some infectious diseases scientists these days. It’s not the challenging Ebola outbreak in the Democratic Republic of the Congo, though that is deeply concerning. It’s not a new flu virus or slashed research budgets or laboratory safety violations.
It’s an international treaty. More specifically, it’s an agreement within a treaty that could, depending on how negotiations play out, make it extraordinarily difficult to conduct disease surveillance or forge research collaborations around the world.
The agreement — known as the Nagoya Protocol — could drown researchers in oceans of paperwork and hobble the world’s scientists when they must next race to combat a new disease disaster, some fear.
The protocol is part of the Convention on Biodiversity, an international treaty aimed at protecting each country’s control over its own biological resources. It lays out ways by which biological resources may be shared and the benefits of those resources be distributed.
But since the protocol came into force in October 2014, debate has raged about whether the genetic sequences of pathogens — the string of code that characterizes a flu bug making the rounds or an Ebola virus isolated from a stricken health worker — are subject to the agreement.
More than 100 countries have ratified the protocol. The United States, which is not a party to the Convention on Biodiversity, has not.
Some involved in the debate argue genetic sequences aren’t covered by Nagoya, and that the free sharing of digital genetic information is so entrenched in scientific practice — scientific journals require it of their authors — that there’s no going back. Plus, some argue, to subject genetic sequence data to further bureaucracy would be counterproductive to science and dangerous to public health.
But a large number of developing countries insist that the protocol gives them as much sovereignty over the genetic sequence data of viruses, bacteria, fungi, and other pathogens found within their borders as it does over plants that are crucial to drug production.
In an age of synthetic biology, when a virus can be made from scratch by following a genetic sequencing recipe plucked from a public database, to have the genetic information is to have the bug itself, these countries argue.
That’s not science fiction. At the start of the 2009 H1N1 pandemic, scientists at the J. Craig Venter Institute used the genetic sequence of the new virus to make the seed strain for flu vaccine. Until then, making the seed viruses for influenza vaccine production had always required an actual flu virus.
The dispute and the uncertainty generated by this debate are already rippling through academia and the pharmaceuticals industry. Some manufacturers, for instance, opted not to use a vaccine virus recommended by the World Health Organization for the 2019 Southern Hemisphere flu vaccine because it came from Switzerland, whose Nagoya-based access procedures were felt to be too onerous. Easier, they decided, to use a similar virus from elsewhere instead.
“I think it’s really worrying,” Dr. Jeremy Farrar, head of the Wellcome Trust, said of the debate and its implications. “This has to get resolved.”
Paradoxically, at least some of the scientists who are worried about the Nagoya Protocol’s impact on their work support the aims of the Convention on Biodiversity. The convention’s goal is to stop biopiracy — to ensure that any wealth that is derived from the vegetation and other genetic materials of a country is shared with that country.
If Company X uses material from a shrub found in the mountains of Nepal, for example, to make an expensive cancer drug, benefits should flow back to the Nepalese. Likewise, if the genes that make an important crop resistant to fungi can be identified in a hardy variety in Peru and genetically engineered into susceptible strains grown elsewhere, Peru should benefit when Company Y sells those enhanced seeds.
“That you put on the table, ‘Hey, we need to talk about who gets access [and] who benefits from that access,’ I think that’s fine. And I think it’s needed,” said Marion Koopmans, head of virology at Erasmus Medical Center in the Netherlands.
A lot of research, however, doesn’t generate products or profits. But it, too, could get caught up in this net, depending on how the ongoing negotiations over the scope of the protocol evolve.
As it stands, researchers in one country who want pathogen samples — actual viruses or bacteria — from another must obtain a certificate from the donor country, giving them permission to take possession of the material.
Often the government employee charged with issuing these certificates works in the department of the environment or agriculture, not the health department — a reflection of the fact that public health and health research were not top of mind when the protocol was being drafted, suggested George Haringhuizen, a public health lawyer responsible for infectious diseases issues for the government of the Netherlands.
Koopmans worries about the possibility of a crazy quilt of inconsistent rules, with countries around the world interpreting the protocol’s ramifications for sequence data differently; that, she warned, would be “a nightmare scenario for global collaboration.”
Fabian Rohden, a molecular biologist from Germany, has been monitoring the debate closely. A graduate student at the Technical University of Darmstadt, Rohden is on a steering committee of the German Association of Synthetic Biology.
The arguments over Nagoya’s impact on genetic sequence information or genetic sequence data — both terms are used — are complex, he acknowledged. And finding a way to ensure that a treaty that wasn’t designed with public health and science in mind doesn’t adversely affect them isn’t going to be easy, he predicted.
But Rohden warned it would be a mistake for scientists to assume the status quo — a belief that open sharing of sequence data is the norm and the goal — will ultimately prevail in this process. Too many of the stakeholders in the discussions see the inclusion of sequence data “as the hill they want to die on,” he said. “They are really making this the key issue.”
David Fidler, an expert on global health law at the Indiana University’s Maurer School of Law, argued the Nagoya Protocol does not apply to genetic sequence data; the wording isn’t in the document, he noted.
But he also believes the point is effectively moot. With so many parties arguing that the protocol does apply, if the dispute is not settled, some countries will treat sequences as protected while others will not.
That could lead to scenarios in which countries cut bilateral sharing agreements, with other countries or even companies. Such deals likely won’t be disclosed, Fidler suggested.
The ensuing situation could be a quagmire; some scientists envision a scenario in which access to data will be shared only with the highest bidder.
“We really don’t want to go down this road of a non-transparent patchwork approach because it’s going to take us in directions that are unhelpful and perhaps dangerous,” Fidler said.
Scientists who monitor the evolution of seasonal influenza viruses are worried about the debate’s potential to disrupt that work, which relies on contributions of mass numbers of viruses from around the world.
These are people who know well how a dispute like this can affect science; they’ve lived through an earlier fight.
About a decade ago, H5N1 bird flu was racing through Asia. The deadly virus decimated poultry flocks and occasionally infected people. Its high death toll in humans — about 60 percent of known cases died — alarmed health authorities, who feared the virus was mustering its might to trigger a catastrophic flu pandemic.
Indonesia was a hotspot for human infections. At the time, a vaccine manufacturer used an Indonesian H5N1 virus to make batches of flu vaccine for testing and stockpiling by wealthy countries.
The country’s then-health minister, Siti Fadilah Supari, learned of the experimental vaccine and, angered by the discovery, refused to give outside researchers access to sample viruses — even when the World Health Organization insisted the samples were needed to track the evolution of H5N1.
The standoff precipitated a WHO-led effort to create a system whereby countries that contributed to pandemic flu surveillance efforts would be assured help in shoring up their own pandemic planning efforts in return. The system, called the Pandemic Influenza Preparedness or PIP Framework, was adopted by WHO member countries in 2011.
Some see this type of a side deal as the best option for resolving the dispute over Nagoya and genetic sequence data.
In fact, the WHO has proposed a workaround it hopes will deal with the need to ensure quick access to sequence data during disease outbreaks. Vasee Moorthy, who co-leads a project to spur development of vaccines and drugs to counter dangerous diseases underserviced by the pharmaceutical industry, said the global health agency is hopeful the proposed code of conduct for sharing of this genetic sequence data will gain traction.
The code of conduct would ensure, among other things, that scientists could not publish findings based on genetic sequence data provided by others without crediting or collaborating with the researchers who generated and shared the data.
“We want everyone to agree to a set of behaviors,” Moorthy said. “If we can get everybody on the same page about how to ensure that the benefits are shared and everybody has access to the products [that are developed], we think that it should be possible — or we hope it’s possible — to make a case to the Nagoya processes that essentially this is being addressed in the human health sector.”
Rohden said the holy grail of solutions would be an agreement covering all genetic sequence information that would make clear non-commercial use of the material is permitted. If such use led to development of a drug or other product, the requirement that the company compensate the country for the use would kick in.
These kinds of side deals, if they can gain the support of the countries looking for benefit sharing under Nagoya, could stave off less helpful outcomes and would likely be quicker — though not quick — compromises to reach. The alternative makes some people shudder.
“If we’re talking about a change in the Nagoya Protocol, we could be having this debate for a decade,” said Farrar.