Detection and identification of dangerous pathogens
Using metagenomic surveillance and broad-spectrum diagnostics detect dangerous pathogens

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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

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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.

Further resources

To learn more about the general case for working on biosecurity and global catastrophic biological risks, see:

Some podcasts relevant to this research direction include:

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.

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.

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Contributors

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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