October 30, 2023
A warming world could unleash dangerous new pathogens. Metagenomics early warning tools are vital for pandemic prevention.
The world is experiencing a rapid rise in average global temperatures and climate change is increasingly recognized as a health security threat multiplier. Climate-induced changes in land use and global ecosystems are increasing the risk of emergence of novel zoonotic pathogens that can spill over from animals to humans. In the Arctic, global warming is causing the thawing of permafrost reported to be releasing biogeochemical hazards such as viruses, bacteria, anthropogenic chemicals, and nuclear wastes into the environment. Globalization also increases the risk that “time-traveling pathogens” stored for thousands of years in permafrost could potentially survive, spread to other regions of the world, and evolve over time.
Amid these cascading global risk drivers, there is a need for policies that enable mainstream adoption and equitable scale-up of next-generation sequencing (NGS, or NextGen sequencing) technologies capable of rapid and comprehensive surveillance of emerging and reemerging biological threats. NGS technologies aid in the earlier identification and tracking of infectious disease pathogens by collecting samples containing pathogen genetic material from different sources and aggregating this data to make a microbial diagnosis. These technologies also provide valuable surveillance insights into the characteristics of the outbreak-causing pathogens, including disease transmission patterns and the presence of antimicrobial resistant (AMR) genes. Notably, metagenomics “shotgun” NGS technology can more quickly detect a diversity of known and unknown pathogens within a genetic sample simultaneously to better inform public health action. However, a lack of policies to ensure investments in its cost-effective scale-up and integration with traditional epidemiologic surveillance systems are hindering the widespread adoption of this critically important technology as an early warning tool for biological threat detection.
Learning the right lesson from COVID-19
Potentially catastrophic biological events, such as emerging and reemerging pathogens from permafrost thaw and with spillover potential, are often viewed as falling within the realm of science fiction. However, the emergence of SARS-CoV-2 (the coronavirus causing COVID-19) made clear that low-probability, high-consequence events, such as an outbreak of a pandemic-causing novel zoonotic virus, are increasing in likelihood and, thus, not confined to Hollywood screenwriting.
A major lesson emerging from the COVID-19 pandemic is the need for stronger partnerships on strengthening the global architecture to enable routine adoption of NextGen sequencing technologies for early detection of emerging pathogens and the utilization of sequencing data to rapidly initiate risk mitigation activities. During the pandemic, there was an increase in the use of “omics” technology to identify different strains of SARS-CoV-2 in circulation. This advanced pathogen surveillance and characterization method was highly instrumental in providing an effective response to the pandemic, including for developing targeted COVID-19 vaccines. In the United States, genomics sequencing combined with wastewater surveillance data was successfully used to keep track of new strains of SARS-CoV-2 and to provide an early warning about other pathogen types, including AMR pathogens, circulating in a community.
The early identification of the Omicron variant of SARS-CoV-2 by researchers in South Africa and Botswana in November 2021 highlighted the advanced genomics capacities in place in some countries in Africa, as part of the Africa Centres for Disease Control and Prevention Pathogen Genomics Initiative (PGI). In real-time, researchers from the region took appropriate measures to share sequenced data with the rest of the world as an early warning about the emergence of a new variant of the virus. The “rewards” of such proactivity, however, were travel bans and other punitive measures adopted by many countries, including the United States, to the detriment of southern African countries. This unfortunate turn of events highlights the need to strengthen policies to enable better cooperation of countries around rapid sharing of pathogen genomics data in real time and near real time as new pathogens emerge to better inform data-driven decision-making for pandemic prevention, preparedness, and response (PPPR).
Technology solutions
To ensure the effective monitoring and early detection of biological threats such as emerging AMR pathogens with the potential to spread across geographic regions, there is a need for mainstream adoption of a high throughput sequencing platform that can provide detailed genetic information about pathogens more rapidly and in the most cost-efficient manner. Amid the warming of the Arctic, there are ongoing research studies into the genomic diversity of permafrost pathogens using metagenomics sequencing. This pathogen-agnostic approach to pathogen surveillance enables the rapid identification of multiple pathogen types in a genetic sample and prediction of resistance emergence to inform public health decision making, policy formulation, and the implementation of appropriate biothreat risk mitigation interventions.
At present, metagenomics sequencing technology is yet to be routinely adopted and integrated into national surveillance systems such as the National Antimicrobial Resistance Monitoring System (NARMS). This problem may be due to the complex workflow protocols and computationally demanding procedures that drive up implementation costs, thus making the current approach to metagenomics sequencing hard to scale as a nationwide strategy for routine AMR pathogen surveillance and early detection of emerging pathogens. Identifying the problem provides an opportunity to also inform the development of policy solutions focused on reducing costs.
One cost-cutting approach is to implement a standardized process and automated workflow protocol for routinely collecting, sequencing, analyzing, and integrating metagenomics sequenced data and ensuring harmonization/integration of data with the NARMS and other epidemiologic surveillance systems. Similarly, adopting a portable metagenomics sequencing platform will help reduce the time and corresponding costs of metagenomics data synthesis and reporting by simplifying the workflow process and reducing the turnaround time of sequenced data results. Existing portable sequencing platforms that have been validated and may be adopted for real-time analysis of metagenomics sequencing data include Oxford Nanopore’s MinION and iGenomics app.
Scaling up metagenomics sequencing
Enhancing pathogen genomic surveillance capacities for informing public health action would require equitable scale-up of metagenomics sequencing nationally, regionally, and globally and having in place the right policies to enable its effective implementation across health systems. At the national level, there is a need to harmonize and ensure interoperability of metagenomics-enabled surveillance data with other existing data systems using a One Health approach. This approach would also require enhancing capacities of countries in environmental surveillance and climate forecasting. In the United States, the White House has put forward a new executive order on enhancing the biotechnology and biomanufacturing sector, in close partnership with other countries, and pledges to invest eighty-eight billion dollars in PPPR activities over a five-year period.
In line with efforts to leverage emerging technologies, the newly launched US Office of Pandemic Preparedness and Response Policy should prioritize policies that enable widespread use of metagenomics sequencing for early detection of biological threats including AMR pathogens. It will be important to ensure these policies align with the Pioneering Antimicrobial Subscriptions to End Upsurging Resistance (PASTEUR) Act reintroduced to the Senate in April 2023. The PASTEUR Act aims to address existing gaps in antimicrobial development by incentivizing private sector providers to discover and develop new antimicrobials and to increase public health preparedness. Improving the utility and scale-up of metagenomics sequencing for early warning of emerging biological threats and for resistant pathogen monitoring would help ensure the availability of more sensitive data to promote innovations for the development of novel broad spectrum antimicrobial drugs to fight the silent pandemic of AMR. Similarly, the recently proposed Emerging Pathogens Preparedness Program under the US Food and Drug Administration could help promote regulatory reforms needed to speed up the development of medical countermeasures.
As the Africa Centres for Disease Control and Prevention progresses with strengthening the capacities of all fifty-five African Union member countries in metagenomics-enabled microbial surveillance via the PGI, there is also an opportunity to enhance coalitions with the United States on PPPR to ensure better preparedness for the next biological threat that may potentially emerge from the Artic and other “hotspot” regions. In addition to existing partnerships across technical institutions, new coalition building opportunities should be explored with agencies such as the newly formed Bureau of Global Health Security and Diplomacy under the US Department of State, to set joint standards to enable the use of metagenomics sequencing more effectively for biological threat detection. Enhancing and scaling up pathogen genomics surveillance capacities across geographic regions also requires identifying opportunities for public-private sector partnerships, such as existing partnerships with Illumina, Inc. on the PGI; and the collaborative efforts of the Gates Foundation and Chan Zuckerberg Biohub initiative established during the COVID-19 pandemic.
Globally, a way to ensure harmonized standards setting and interoperability of genomics data across geographic regions is to align national and regional policies with global frameworks such as the World Health Organization (WHO) Global Genomic Surveillance Strategy for Pathogens with Pandemic and Epidemic Potential. The WHO Strategy aims to achieve a set target of ensuring access to timely and reliable genomic sequencing data for identified pathogens with epidemic and pandemic potential by 2032.
“Canary in the coal mine”
The ongoing thawing permafrost in the Arctic is just one of many ecosystem changes caused by climate change. This process of permafrost degradation and subsequent discoveries of emerging pathogens, such as resistant pathogen strains with the potential to spread to other regions, serve as a “canary in the coal mine” signaling the imminent risk of occurrence of a global catastrophic biological event, if left unaddressed.
Although there are no easy solutions to addressing the global climate crisis and its impact on infectious disease pathogen emergence and reemergence, there is a need to move away from the approach of adopting quick fixes in a fragmented and uncoordinated manner. It is also well-acknowledged that calling attention to the increasing global health security threat posed by climate change driven invisible “superbugs” is not as attention-grabbing as the threat of extinction of “charismatic megafaunas” driving many ecosystem conservation efforts. Nevertheless, there remains an urgent need to link PPPR initiatives to climate action goals of reducing carbon emissions to help reverse global warming and stop further degradation of the Arctic. Such initiatives might include adopting national and global policies that enable partnership building and investments in emerging technologies including metagenomics “shotgun” NextGen sequencing for environmental monitoring and early detection of emerging and reemerging pathogens. This sequencing approach could inform the development of antimicrobials and other medical countermeasures as a critical aspect of biological risk mitigation.
Robust policy solutions are required to enable the cost-efficient scale-up and interoperability of metagenomics sequencing data platforms with other complementary pathogen monitoring systems using a One Health approach. There is also a need to strengthen international cooperation on pathogen genomics surveillance. Such cooperation can be strengthened via the harmonization of data sharing platforms and adoption of joint policy frameworks to improve early warning and detection of environmentally driven emerging biological threats and looming threats such as Disease X, a term used to indicate an unknown pathogen with the potential to infect humans.
The gathering of various interest groups, including policymakers, international organizations, multisectoral experts, technology providers, and industry players at the upcoming United Nations Climate Change Conference, known as COP28, provides the right convening platform to strengthen existing partnerships and form new coalitions as a call to action during the COP28 Health Day and Climate-Health Ministerial. In advance of future global gatherings, ensuring an effective response to this clarion call requires setting data-driven, cross-sectoral policy agendas and implementing measurable joint action plans to track progress with achieving health security and climate change goals with known ancillary benefits across all relevant sectors.
Oluwayemisi (Yemisi) Ajumobi is a resident senior fellow at the Atlantic Council’s GeoTech Center who focuses on the adoption of NextGen sequencing technologies to enhance global health security.
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