Sweeping New Global Biodiversity Deal Sets Out Plan for Sharing Gene Sequences
Global patterns of gene sequence data sharing, June-November 2022. The bigger the dot/higher the number, the more DSI data generated by the country was used by researchers elsewhere.

Along with a pledge to conserve 30% of the world’s biodiversity, the sweeping new deal reached in Montreal on Monday also etches a way forward to create an open-access platform for sharing gene sequences (digital sequence information) as part of new benefit-sharing arrangements. But some observers worry these policy advances still aren’t keeping up with the frenetic pace of technological advances.

The UN Convention on Biological Diversity’s (CBD) historic deal this week has been hailed for its ambitious aims to conserve at least 30% of the planet’s lands, freshwater and ocean resources by 2030, while mobilizing US$200 billion a year to help meet the targets.

Another significant, less understood part of the agreement, is a decision to establish “a multilateral mechanism for benefit-sharing from the use of digital sequence information (DSI) on genetic resources, including a global fund” to be finalized at the next UN Biodiversity Conference in two years.

The text outlines the need for this mechanism to “not hinder research and innovation,” and “be consistent with open access to data” on genetic sequences.  Ensuring open access to such data is something that health researchers and pharma developers have underlined as critical to rapidly responding to emerging threats from potentially dangerous pathogens. Such pathogens are also considered to be part of global biodiversity and fall under the mandate of the CBD. 

Ambitious roadmap, but implementation will be challenging

While the CBD deal, reached at the 15th Conference of Parties (COP15), is regarded as a signal of the direction countries aim to take, hammering out policies that embed open data sharing of biodiversity, particularly of pathogens, into practices, while also ensuring “benefit sharing” from such access will remain a formidable challenge, observers told Health Policy Watch in a series of interviews.

“Unfortunately, DSI technology is light years away from the policy governing it,” said Liz Willetts, an environmental health policy expert from the International Institute for Sustainable Development. “I’m not sure, in practice, the policy will be able to shape industry based on timeline alone.”

When the conference kicked off in Montreal, negotiations on the question of DSI benefits sharing were at a standstill. DSI refers to the digital mapping of DNA or RNA genomes, which enables new product development in areas ranging from cosmetics to vaccines without the physical exchange of biological samples. 

Hundreds of billions of sequences are stored in publicly accessible databases, which are a crucial base of scientific knowledge used extensively by private and public sector researchers alike.

Conservation efforts, medical research, ecosystem restoration, and sustainable agriculture are all heavily reliant on genomes published on public databases.

But the commercial value that genetic materials can generate raises key questions around DSI: who owns these digital sequences, and what constitutes fair compensation for their use in a product like a vaccine or cosmetic?  

In the run-up to the conference, African Union member states and Asia-Pacific countries like India and Bangladesh cited the inclusion of DSI benefits sharing as a non-negotiable part of any final agreement.

Their efforts were successful, making the Kunming-Montreal biodiversity agreement the first of its kind to include language on DSI benefits sharing.

No exception made for pathogens

Pharmaceutical companies argue pathogens should be treated differently from other DSI and genetic materials, highlighting the importance of swift and unhindered sharing of the information sequence of SARS-CoV-2.

However, the final text of the agreement does not have any explicit reference to excluding pathogens from the proposed multilateral DSI framework, a key ask by the pharma industry.

In a press statement following the conference, the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) expressed concern over the final CBD text on DSI sharing, despite the agreement’s reference to the preservation of open access platforms for such data sharing.

“While it might seem a small detail, the lack of consideration on the fundamental difference between the biodiversity of flora and fauna versus pathogens, including genomic sequence data (or “DSI”) derived from such pathogens, is a problem for all those involved in R&D of vaccines, treatments and diagnostics to fight future outbreaks,” said the IFPMA in a press statement.

IFPMA also emphasized that “ensuring immediate and unhindered pathogen sharing, through a public health exemption to access and benefit (ABS) rules, is critical for the future of public health.”

James Love, a UN advisor and Director of Knowledge Ecology International (KEI), agrees that pathogens should be treated differently – but not in the no strings attached manner advocated for by the pharmaceutical companies.

“The world needs people to share information on pathogens, that sharing is in the interest of everyone. The IFPMA members are keen on others sharing but are not willing to share knowledge assets themselves, so this creates a sense of unfairness,” said Love.

“KEI has recommended that an agreement addresses benefit-sharing more broadly, and not as a condition for sharing pathogens or their digital sequences, but to reward the sharing of anything useful in the response and development of countermeasures, including in addition to pathogens or their sequences, inventions, cell lines, manufacturing know-how, data, etc,” he added.

“We also suggest the money to reward and induce such sharing come from a 1% open source dividend on the sale of vaccines, drugs and perhaps other countermeasures. Negotiators could start by modelling a 1% royalty, and see how that looks.”

Same debate likely to shadow negotiations over WHO Pandemic Treaty

The same debate is likely to shadow the negotiations over the World Health Organization (WHO) pandemic accord, where the linkage between access to pathogens’ genomic codes and benefit sharing is likely to be addressed more directly.  Low- and middle-income countries have already proposed texts that make an explicit link between DSI access and the sharing of “benefits” from medicines or vaccines that are developed as a result.

A “conceptual zero draft” of the proposed pandemic treaty that was circulated to WHO member states in late November outlined the importance of promoting “early, safe, transparent and rapid sharing of samples and genetic sequence data” of pathogens with pandemic potential, and “fair and equitable sharing of benefits arising therefrom.”

Under the draft text, pharmaceutical companies would still have open access to pathogen sequences. But they may also be liable to share financial gains or provide vaccines derived at lower prices depending on the shape of the final treaty. 

“Within a few hours of downloading DSI, COVID-19 candidate vaccines were developed. But in terms of coverage, even after two and a half years we are still lacking,” said Nithin Ramakrishnan, a research scholar at the Center for Public Policy Research, who attended the Montreal conference. 

“Also, many of the [COVID drug and vaccine] purchase agreements have put developing countries into certain kinds of debt traps, including unjustifiable indemnity clauses pledging sovereign assets,” he said. “This is a highly inequitable way of handling benefits generated.”

“Decoupling” DSI from benefits-sharing

Recent advances in technology have led to the exponential growth of gene sequence data stored in online libraries like INSDC.org

Despite the hesitations of pharma, the CBD text pledging open access to gene-sequence information was a relief to the scientific research community, which had voiced worries about losing access to genetic sequence libraries.

The speed at which DSI technology has evolved in parallel with big-data science and artificial intelligence means access to large datasets has become critical to cutting-edge synthetic biology, medical research, and the fields of conservation, ecosystem restoration, and sustainable agriculture, amongst others. 

Scientists have opposed any mechanism based on bilateral agreements between countries on the grounds it would hamstring research and medicine development by placing undue bureaucratic burdens on the process of genetic sequence sharing.

The text of the agreement appears to have heeded these concerns. Along with recognizing the “value of depositing data in public databases” and encouraging the “depositing of more digital sequence information on genetic resources, with appropriate information on geographical origin and other relevant metadata, in public databases,” the treaty makes no mention of bilateral arrangements, instead noting that the “multilateral mechanism” for DSI benefit sharing should be “efficient, feasible, and practical.”

Percentage of DSI on the International Nucleotide Sequence Database Collaboration by country, based on provided sequences.

Negotiations on the exact shape of the multilateral mechanism still have a long way to go. Technical questions remain over whether DSI should be included under the umbrella of “genetic resources” outlined in the Nagoya Protocol – the current treaty covering access and benefits sharing to biodiversity – and how those benefits should be shared without slowing down the speed of DSI sharing remain unanswered. They will be subject to negotiation in the coming months.  

One network of scientists has argued for a “decoupling” of access and benefit sharing – at the research stage – with a mechnaism for sharing benefits at the product commercialization stage only.

In an article published in Nature, the DSI Scientific Network emphasized the importance of creating new benefit-sharing mechanisms that do not limit open access to DSI. 

“This is a fundamental shift away from traditional control-oriented access and benefits-sharing (ABS) to a new idea of OA (open access) and BS (benefit-sharing). This is necessary to protect the many benefits of openness and recognize that benefit-sharing can be accomplished without dramatically altering real-world access,” argued the scientists, representing 33 scientific research organizations working across 55 countries.

“New monetary mechanisms can be put into place upstream of DSI generation (e.g., a micro-levy on DSI-generation reagents and disposables), downstream of DSI use (e.g., a user fee on bio-based products), and/or outside the DSI life cycle (e.g., payment from high-income nation international development funds).

This mechanism precludes the need to trace the country of origin of the genetic resource from where the DSI was extracted and can support biodiversity conservation and sustainable use without compromising on open access to the resources, DSI Scientific Network scientists said.

“Access to DSI from genetic resources is ‘decoupled’ from benefit-sharing from DSI because payment would not be triggered by access to the databases but rather downstream at the point of commercialization or retail,” study co-author and DSI Scientific Network member Amber Scholz, told the conservation science magazine Mongabay-India,  describing the proposed mechanism.

Low-and-middle-income countries (LMICs) that grant comparatively more access to genetic resources that result in DSI would receive comparatively more funds, said Scholz, of the German-based Leibniz-Institut.

“This mechanism is seen by some as an attractive compromise because it does not require tracking the country of origin of the genetic resource from where the DSI was extracted throughout the value chain but only relies on the entry point of the DSI into the databases,” Scholz said.

Relationship between Nagoya Protocol and new DSI mechanism is not yet known

Even some developing country officials have said that the Nagoya Protocol, which covers the access and benefit sharing of physical and biological samples, doesn’t have to be interpreted to cover DSI. Whether the new mechanism will be its own instrument or an amendment to the protocol will be decided at COP16.

“The access and benefits sharing mechanism implemented in the Nagoya Protocol of the Convention on Biological Diversity is focused on genetic resources, ie, physical material. But DSI is the information obtained through the sequencing of the genome,” KC Bansal, former director of India’s National Bureau of Plant Genetic Resources, told  Indian environment and conservation news site Mongabay 

“Because of advanced technologies, especially omics (the branch of science aimed at the detection of genes), we have been able to convert our physical form genetic resources into DSI. And these DSI are housed in open databases,” said Bansal. Sources with knowledge of Indian negotiations on DSI at COP15 said Bansal’s comments were intended to provide an example of the complexities of defining DSI, rather than reflect India’s official position. 

In this interpretation, DSI does not exist until gene sequencing process happens. This means it would not fall under the language of “genetic materials” outlined in the Nagoya Protocol, and would not be covered by its access and benefit provisions. 

But some access advocates see this as hair-splitting.

“The Convention on Biological Diversity and Nagoya Protocol regulate access to genetic resources. Providing DSI is providing digital access to genetic resources, so whichever way one tries to limit the definition of DSI, the Convention would trigger,” said Ramakrishnan said. “For example, let’s imagine a 3D structure model of some genetic resource is shared, and not sequence info, according to me, the Convention and Nagoya Protocol would kick in.”

The existing ambiguity, though, may serve the interests of some countries by allowing them the freedom to make their own judgements about what genetic resources qualify, or don’t, he noted. 

What is open access, and what will benefit sharing look like? 

The question around open access also looks primed to dominate discussions leading up to the finalization of the DSI mechanism in two years.

Other proposals range from a 1% levy on commercial sales of any product derived from a DSI sequence, to the explicit inclusion of non-monetary benefits such as access to a proportion of vaccines or medicines generated from the DSI, or in the case of beneficial microbes, funding for biodiversity preservation.

“Open access does not mean unregulated or free. Principles of data governance are going to be studied further,” Ramakrishna said. “Without disciplining the way databases behave, it’s very difficult to ensure legal guarantees for benefit sharing.”

Inequalities in the DSI space 

The number of countries to which a country provides DSI is correlated to the number of countries from which it uses DSI, suggesting that there is a positive relationship between providing and using DSI, according to WiLDSI. There are no countries that only provide or only use DSI.

At first glance, discussions around DSI benefits sharing appear to reflect the same goal as recent international agreements on the loss-and-damage fund to offset the impacts of climate change in developing nations made at COP27, and increases in biodiversity funding pledges in the Kunming-Montreal agreement.

But the inequalities relating to DSI are more complex. 

A 2021 study on the use of DSI sequences found that the majority of published sequences do not come from low- and middle-income countries, but from the United States, United Kingdom, China and Canada, who collectively account for 52% of DSI data on the International Nucleotide Sequence Database Collaboration (INSDC), a key set of three global databases. 

But this data is far from complete. Only 16% of sequences in the INSDC have country-of-origin information associated with them. Another 44% of sequences without country data could and should have had country information provided by the submitting scientists, according to a UN Biodiversity document

“Practical issues ranging from more expensive access to molecular biological reagents, slower internet bandwidth that limits high-throughput analyses, financial limitations for research funding, limited bioinformatics training and career development opportunities, as well as brain drain, routinely limit those of us working in LMICs,” the DSI Scientific Network article in Nature Communications noted.

“Any DSI benefit-sharing framework must support technical capacity building focused on genomics and bioinformatics,” the scientists said. Based on experiences with the Nagoya Protocol, the sharing of financial proceeds from DSI also cannot be expected to generate transformational financial benefits, they added.

But to date, benefits shared from the commercial development of genetic resources have been effectively limited than the access side of the equation.

“Inequalities in using sequencing technology as well as fairness and equity in benefits sharing from both should be treated with equal importance,” Ramakrishnan said. “The agreement in the DSI is a solution to this. It agrees to share benefits fairly and equitably.”

Edited to correct the date the mechanism will be established. The initial article had confused the dates of COP.16 in Basel, with COP16, the next UN Biodiversity Convention. 

Image Credits: WiLDSI, NIAID-RML , WiLDSI.

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