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This profile is tailored towards students studying engineering and biological sciences, however we expect there to be valuable open research questions that could be pursued by students in other disciplines.
Why is this a pressing problem?
Pandemics could pose an increasing threat to humanity’s flourishing in the future. ‘Spillover events’ where pathogens jump from animals to humans are increasing due to factors like habitat destruction and intensive farming; technological advances are increasing the number of people who can synthesise dangerous pathogens; and an increasing number of laboratories are working with pathogens that could cause pandemics if accidentally released. Early detection to limit the spread and allow countermeasures to be taken is key to limiting the harm when a pathogen with pandemic potential next emerges.
This is where biosurveillance – ‘the detection and monitoring of biological agents to prevent biological threats’ – is important. Metagenomic monitoring is a particularly promising approach because it’s pathogen agnostic; it allows the detection of all microorganisms in a sample without prior knowledge of their identities, meaning novel pathogens can be detected. There are three kinds of monitoring this can involve: environmental surveillance, which involves testing samples from the built environment, such as from wastewater or air filters that aggregate over many people; sentinel surveillance, which involves collecting samples from a pool of the population, potentially those at particularly high risk of exposure to pathogens; and clinical metagenomics, which involves sequencing samples from patients in clinics and hospitals.
In the video below, Dr Pardis Sabeti and Dr Christian Happi discuss their proposed metagenomic early warning system for detecting viral threats.
Explore existing research
- Ackerman, Cheri M., et al. (2020) Massively Multiplexed Nucleic Acid Detection with Cas13, Nature
- Gardy, Jennifer L. & Nicholas J. Loman (2017) Towards a Genomics-Informed, Real-Time, Global Pathogen Surveillance System, Nature Reviews Genetics
- Nieuwenhuijse, David F., et al. (2020) Setting a Baseline for Global Urban Virome Surveillance in Sewage, Scientific Reports
- Nucleic Acid Observatory Consortium (2021) A Global Nucleic Acid Observatory for Biodefense and Planetary Health
- The Apollo Program for Biodefense: Winning the Race Against Biological Threats (2021) Bipartisan Commission on Biodefense
Find a thesis topic
If you’re interested in working on this research direction, below are some ideas on what would be valuable to explore further. If you want help refining your research ideas, apply for our coaching!
This report from The Apollo Program for Biodefense Technology Priorities highlights the following as areas for further research:
- “To advance sequencing, we must increase investments in novel sequencing modalities, prioritizing methods enabling miniaturization and decreases in reagents or even reagent-free sequencing. Coupled with research and development focused on microfluidics and on-chip sample preparation, we can realize the vision of truly hand-held, affordable, easily operated sequencers.” – (The Apollo Program for Biodefense Technology Priorities)
- “While the ability to detect almost any known pathogen is a tremendous advantage, for wide deployment…[massively multiplexed assays] will need to become cheaper, more robust, simpler to operate, and faster. They must also achieve high sensitivity and specificity and ultimately be interpretable to clinicians…We should prioritize techniques enabling the tests to move out of centralized laboratories, and especially those that can operate in resource- constrained settings. The detection of viral pathogens for any host, including agricultural plants and animals, rapidly and with confidence would provide a capability to complement metagenomic sequencing and pathogen-specific point-of-person diagnostics. (The Apollo Program for Biodefense Technology Priorities)
Metagenomic sequencing isn’t yet a frontline diagnostic, in part due to prohibitive cost. Further research is needed to identify the key bottlenecks involved and make technological advancements to bring costs down. The author of Biosecurity needs engineers and materials scientists writes, “implementing metagenomic biomonitoring for early detection of outbreaks is going to need significant hardware advances in many domains, including for reliable and effective environmental sampling, easy point-of-care clinical sampling, automated sample processing, and sequencing technology.”
This report from The Apollo Program for Biodefense Technology Priorities highlights the following as necessary advancements to improve sequencing technology: “we must increase investments in novel sequencing modalities, prioritizing methods enabling miniaturization and decreases in reagents or even reagent- free sequencing. Coupled with research and development focused on microfluidics and on-chip sample preparation, we can realize the vision of truly hand-held, affordable, easily operated sequencers.” See SmidgION – a miniaturised DNA sequencer under development – for an example of research in this area.
Another area where further research is needed is in developing non-invasive and minimally invasive devices that can detect infection. The Apollo Program for Biodefense Technology Priorities report states, ‘We are on the verge of the ability to detect whether the body is currently infected with any pathogen…through the interrogation of host biomarkers. Increasingly, we can also detect infection indicators non-invasively through advances in wearables and volatolomics…non-invasive and minimally-invasive detection techniques could provide avenues to monitor high-risk, high-concern, and sentinel populations for infections, without disrupting daily life.’ See this podcast on a wearable device to monitor COVID symptoms.
To learn more about the general case for working on biosecurity and global catastrophic biological risks, see:
- Why experts are terrified of a human-made pandemic — and what we can do to stop it – Vox
- A Biosecurity and Biorisk Reading+ List – EA Forum
- Preventing catastrophic pandemics – 80,000 Hours
- This talk on Biosecurity as an EA cause area
Some podcasts relevant to this research direction include:
- Pardis Sabeti on the Sentinel system for detecting and stopping pandemics – 80,000 Hours
- Fin Moorhouse & Luca Righetti (2022) Ajay Karpur on metagenomic sequencing, Hear This Idea, June 13.
- Andy Weber on rendering bioweapons obsolete & ending the new nuclear arms race – 80000 Hours
Register your interest for the Biosecurity Fundamentals course, a course designed to help people develop the knowledge, community and network needed to pursue a high-impact career in biosecurity.
You could register interest for BlueDot Impact’s introductory course on the fundamentals of biosecurity. The Global Catastrophic Risk Institute suggests fellowships and other next steps here.
Apply for our coaching and we can connect you directly with researchers and potentially mentors who can help you refine your research ideas. You can also apply to join our community if you’re interested in connecting with other students specifically.
Apply for our database of potential supervisors if you’re looking for formal supervision and take a look at our advice on finding a great supervisor for further ideas.
Our funding database can help you find potential sources of funding if you’re a PhD student interested in this research direction.
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Explore our other profiles relating to biosecurity and pandemic preparedness:
This profile was last updated 5/12/2022. Thanks to Jeff Kaufman, Mike McLaren, Vivian Belenky for helpful feedback. All errors remain our own.
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