Research Articles

A New Paradigm for Threat Agnostic Biodetection: Biological Intelligence (BIOINT)

by Thomas Knight and Swati Sureka

Health Security

To accelerate global health security amid a diverse and growing set of biological threats, BIOINT must be a core organizational paradigm for the biological century and a core component of the new wave of multilateral intelligence. Biotechnological advancements are giving us unprecedented access to information about the world’s biological environment. Gathering and making sense of that information is a vital and urgent task as we seek to build a world free from the looming specter of the next global pandemic and resilient to the destabilizing effects of a crowded and manipulable information landscape. Moreover, as with satellite imagery, a wide variety of important collateral applications exist, ranging from environmental monitoring to enhancing bioengineering, to help unleash a sustainable bioeconomy. This is an ambitious project that certainly will not be built all at once—but the tools to realize this vision are within our grasp. We need a collective commitment to laying the global foundations to collect, analyze, and share biological intelligence.

Estimated Future Mortality from Pathogens of Epidemic and Pandemic Potential

by Nita K. Madhav , Ben Oppenheim , Nicole Stephenson , Rinette Badker , Dean T. Jamison , Cathine Lam and Amanda Meadows

Center for Global Development

Epidemics and pandemics pose a sporadic and sometimes severe threat to human health. How should policymakers prioritize preventing and preparing for such events, relative to other needs? To answer this question, we used computational epidemiology and extreme events modeling simulations to estimate the risk of future mortality from low-frequency, high severity epidemics and pandemics in two important categories—respiratory diseases (in particular those caused by pandemic influenza viruses and novel coronaviruses) and viral hemorrhagic fevers (VHFs) such as Ebola and Marburg virus diseases. We estimate a global annual average of 2.5 million deaths, attributed to respiratory pandemics. We estimate an annual average of 26,000 VHF deaths globally, 72 percent of which would be in Africa. Annual averages conceal vast year by year variation, and the reported analyses convey that variation—as well as variation across regions and by age. Our estimates suggest that both the frequency and severity of such events is higher than previously believed—and this is likely to be a lower bound estimate given the focus of this chapter on deaths caused by a subset of pathogens. Our simulations suggest that an event having the mortality level of COVID-19 should not be considered a “once in a century” risk, but rather occurring with an annual probability of 2-3 percent (that is, a one in 33-50-year event). Despite the substantial uncertainty in heavy-tail distributions, policymakers can use these estimates to develop risk-informed financing, prevention, preparedness, and response plans.

Historical trends demonstrate a pattern of increasingly frequent and severe spillover events of high-consequence zoonotic viruses

Meadows, A.; Stephenson, N.; Madhav, N.; Oppenheim, B.

BMJ Global Health

The COVID-19 pandemic has focused attention on patterns of infectious disease spillover. Climate and land-use changes are predicted to increase the frequency of zoonotic spillover events, which have been the cause of most modern epidemics. Characterising historical trends in zoonotic spillover can provide insights into the expected frequency and severity of future epidemics, but historical epidemiological data remains largely fragmented and difficult to analyse. We utilised our extensive epidemiological database to analyse a specific subset of high-consequence zoonotic spillover events for trends in the annual frequency and severity of outbreaks. Our analysis, which excludes the ongoing SARS-CoV-2 pandemic, shows that the number of spillover events and reported deaths have been increasing by 4.98% (confidence interval [CI]95% [3.22%; 6.76%]) and 8.7% (CI 95% [4.06%; 13.62%]) annually, respectively. This trend can be altered by concerted global efforts to improve our capacity to prevent and contain outbreaks. Such efforts are needed to address this large and growing risk to global health.

Notes from the Field: Early Identification of the SARS-CoV-2 Omicron BA.2.86 Variant by the Traveler-Based Genomic Surveillance Program — Dulles International Airport, August 2023

Bart SM, Rothstein AP, Philipson CW, et al. Notes from the Field: Early Identification of the SARS-CoV-2 Omicron BA.2.86 Variant by the Traveler-Based Genomic Surveillance Program — Dulles International Airport, August 2023. MMWR Morb Mortal Wkly Rep 2023

During August 13–14, 2023, a new SARS-CoV-2 Omicron subvariant with a large number of mutations compared with previously circulating BA.2 variants (>30 amino acid differences in its spike protein) was identified by genomic sequencing in Denmark and Israel and subsequently designated BA.2.86 (1,2). Given near-simultaneous detections in multiple countries, including the United States, further information was needed regarding geographic spread of BA.2.86. Since January 2022, submissions to SARS-CoV-2 sequence repositories have declined by 95%,* substantially decreasing global capacity to monitor new variants. To fill gaps in global surveillance, CDC’s Traveler-based Genomic Surveillance (TGS) program was developed to provide early warning of new variants entering the United States by collecting samples from arriving international travelers (3).

The Lancet Commission on peaceful societies through health equity and gender equality

Valerie Percival, DrPH; Oskar T Thoms, PhD; Ben Oppenheim, PhD; et al.

The world is experiencing a polycrisis—ie, an interaction of multiple crises that dramatically intensifies suffering, harm, and turmoil, and overwhelms societies’ ability to develop effective policy responses. Bold approaches are needed to enable communities and countries to transition out of harmful cycles of inequity and violence into beneficial cycles of equity and peace. The Lancet Commission on peaceful societies through health equity and gender equality provides such an approach. The Commission, which had its inaugural meeting in May, 2019, examines the interlinkages between Sustainable Development Goal 3 (SDG3) on health; SDG5 on gender equality; and SDG16 on peace, justice, and strong institutions. Our research suggests that improvements to health equity and gender equality are transformative, placing societies on pathways towards peace and wellbeing.

Scaling Smart Solutions with AI in Health: Unlocking Impact on High potential use cases

1.2 Use case for acceleration #2: infectious disease intelligence

World Economic Forum

The healthcare sector is grappling with critical challenges, such as a shortage of frontline workers, health disparities and escalating spending. Artificial intelligence (AI) promises transformative potential to tackle these issues through public-private collaboration. The potential of AI to serve as an early warning system for infectious disease can complement and enhance the outcomes of traditional mathematical modelling and algorithmic forecasting. Moreover, a cutting-edge AI-based computational platform (known as ENDAR) has been developed that can detect and characterize genetic engineering in biological samples, representing a critical piece of biosecurity infrastructure.

The Lavatory Lens: Tracking the Global Movement of Pathogens via Aircraft Wastewater

Bivins, A.; Morfino, R.; Franklin, A.; Simpson, S.; Ahmed, W. 

The Lavatory Lens: Tracking the Global Movement of Pathogens via Aircraft Wastewater. 2023, 2023050587.

During the COVID-19 pandemic, public health agencies used multi-layered control strategies including pre-departure testing and vaccination requirements, masking, post-arrival testing, and quarantine to manage the risk of COVID-19 transmission associated with air travel. Simultaneously, the surveillance of aircraft wastewater emerged as a promising new data source to screen for SARS-CoV-2 infections, including newly emergent lineages, among international air travelers. Herein, we review the potential of aircraft wastewater for public health surveillance. The known contributing population and flight itinerary combined with the highly concentrated waste stream and convenient sampling during routine lavatory servicing make aircraft wastewater a strategic opportunity for unintrusive surveillance of the global fluxes of human pathogens.

Notes from the Field: Aircraft Wastewater Surveillance for Early Detection of SARS-CoV-2 Variants — John F. Kennedy International Airport, New York City, August–September 2022

Morfino RC, Bart SM, Franklin A, et al. Notes from the Field: Aircraft Wastewater Surveillance for Early Detection of SARS-CoV-2 Variants — John F. Kennedy International Airport, New York City, August–September 2022. MMWR Morb Mortal Wkly Rep 2023;72:210–211. 

During August 1–September 9, 2022, the biotech company Ginkgo Bioworks, in collaboration with CDC, evaluated the feasibility of SARS-CoV-2 variant detection in aircraft wastewater from incoming international flights. Aircraft wastewater samples were collected from selected flights from the United Kingdom, Netherlands, and France arriving at John F. Kennedy International Airport in New York City. Wastewater (approximately 0.25 gal [1 L]) was collected from each plane during normal maintenance using a device that attaches to the lavatory service panel port and the lavatory service truck hose.

Early Detection of Severe Acute Respiratory Syndrome Coronavirus 2 Variants Using Traveler-based Genomic Surveillance at 4 US Airports, September 2021–January 2022

Renee D Wegrzyn, Grace D Appiah, Robert Morfino, Scott R Milford, Allison Taylor Walker, Ezra T Ernst, William W Darrow, Siyao Lisa Li, Keith Robison, Duncan MacCannell, Dongjuan Dai, Brintha P Girinathan, Allison L Hicks, Bryan Cosca, Gabrielle Woronoff, Alex M Plocik, Birgitte B Simen, Leah Moriarty, Sarah Anne J Guagliardo, Martin S Cetron, Cindy R Friedman

Clinical Infectious Diseases, Volume 76, Issue 3, 1 February 2023, Pages e540–e543.

We enrolled arriving international air travelers in a SARS-CoV-2 genomic surveillance program. We used molecular testing of pooled nasal swabs and sequenced positive samples for sublineage. Traveler-based surveillance provided early-warning variant detection, reporting the first US Omicron BA.2 and BA.3 in North America.

Wastewater monitoring of SARS-CoV-2 RNA at K-12 schools: Comparison to pooled clinical testing data

Sooyeol Kim and Alexandria B. Boehm. 2023. PeerJ 11:e15079

The Concentric by Ginkgo team collaborated with researchers at Stanford university to investigate whether wastewater surveillance can be an attractive supplement to clinical testing in K-12 schools where individuals only spend a portion of their time but interact with others in close proximity, increasing risk of potential transmission of disease. Wastewater samples were collected from two K-12 schools in California and divided into solid and liquid fractions to be processed for detection of SARS-CoV-2. The resulting detection rate in each wastewater fraction was compared to each other and the detection rate in pooled clinical specimens.

Effect of Predeparture Testing on Postarrival SARS-CoV-2–Positive Test Results Among International Travelers — CDC Traveler-Based Genomic Surveillance Program, Four U.S. Airports, March–September 2022

Stephen M. Bart, PhD; Teresa C. Smith, MPH; Sarah Anne J. Guagliardo, PhD; Allison Taylor Walker, PhD; Benjamin H. Rome, MBA; Siyao Lisa Li; Thomas W. S. Aichele, MBA; Rob Stein; Ezra T. Ernst; Robert C. Morfino, MBA; Martin S. Cetron, MD; Cindy R. Friedman, MD. MMWR Morb Mortal Wkly Rep 2023;72:206–209.

During December 6, 2021–June 11, 2022, SARS-CoV-2 testing before departure or proof of recent COVID-19 recovery were required for passengers boarding U.S.-bound flights. CDC’s Traveler-based Genomic Surveillance Program collects postarrival nasal swabs for SARS-CoV-2 testing from volunteering international air travelers. Among 3,049 pooled (28,056 individual) samples collected during March 20–September 3, 2022, the predeparture testing requirement was associated with 52% lower postarrival SARS-CoV-2 positivity. We found that predeparture testing can reduce SARS-CoV-2 transmission risk during or after travel by reducing the number of infectious travelers. These results can help guide decisions for future outbreaks.

Building a Biological Radar for Monitoring Harmful Biology

Casandra Philipson

Chemical Engineering Progress, May 2023

The scientific and policy toolkit must evolve in lockstep with the biological risk landscape. Specifically, the biosurveillance ecosystem needs to layer in solutions that: focus on monitoring trends over time to inform intermediate-term planning and readily identify anomalies, provide early indicators that can help authorities mount timely responses to outbreaks or disruptive events, survey a broad landscape of ongoing and emerging threats, are more cost-effective and less time-consuming than mass testing, can scale rapidly and efficiently during periods of elevated risk or acute transmission. Two sets of tools, in particular, will be critical to building biological radar: genomic surveillance and passive environ-mental monitoring.

A new paradigm for threat-agnostic biodetection: biological intelligence (BIOINT)

Tom Knight and Swati Sureka (Under review)

As we face increasing risks of biological threats—whether from spillover, misuse, or other sources—current syndromic surveillance approaches are inadequate to provide early warning. We have an unprecedented opportunity and urgent need to understand our biological environment in a comprehensive way, through the new discipline of biological intelligence (BIOINT). BIOINT is persistent and pervasive within and beyond crises, pushes surveillance closer to sites of emergence rather than illness, takes a layered approach, integrating sequencing of environmental nucleic acids with other sources of data. Technological progress is reducing barriers to implementation and resourcing, but collective action is needed to create the infrastructure for not only collecting and analyzing, but also integrating, sharing, and operationalizing BIOINT data.