Metagenomic sequencing is a potentially game-changing technology to help defend society against emerging biological threats. It has the potential to identify new, unexpected pathogens in the first few infected cases, rather than months later. It can also help tell us how far and how quickly a pathogen has already spread. This would allow for a much earlier, targeted and effective response to an outbreak of an unknown pathogen.
Currently, the technology lacks an interface that is cost-effective and easy to use. A prize challenge structure to incentivise the development of metagenomics would help resolve this bottleneck.
Background to metagenomic sequencing:
Metagenomic sequencing takes a biological sample, reads the genetic material of all organisms in it, and compares these to a database of known pathogens, finding the closest matches. With effort and ingenuity, this could be affordable to the point where doctors can routinely sequence a sample from any patient who has an illness that they cannot diagnose with standard techniques.
It could cost less than £100 per sample to perform metagenomic sequencing and identify known and novel pathogens. This capability could be integrated into clinical settings, or take place in a central laboratory. These options would be extremely helpful for both regular patient care and detecting and controlling infectious disease outbreaks.
How this could have helped against Covid-19:
In the case of Covid-19, such technology would have immediately shown that the closest match was SARS, but that it was sufficiently different to be a novel SARS-like pathogen. If sequencing was cheaper and more widespread, then Covid-19 would also likely have been detected earlier.
Another major challenge very early in the epidemic was a lack of any data on 1) Covid-19’s rate of spread, 2) asymptomatic transmission, and 3) prevalence. Metagenomic sequencing would have provided this missing data and made clear that urgent political action was necessary to contain the pathogen.
If metagenomic sequencing had been widely available at the start of 2020, we would have had a greater chance of stopping Covid-19 from becoming a pandemic. And by making sequencing as routine as taking vital signs, we will have ensured sufficiently widespread coverage to provide for an effective early warning and response. Sequencing’s capability could be integrated into all laboratories, enabling doctors to use the insights gleaned from the samples in a timely manner, before eventually being available at pharmacies, workplaces and homes.
Benefits of a prize structure:
A prize challenge structure to incentivise the development of metagenomics would:
Increase the number of minds tackling this particular problem without having to predict which team or approach is most likely to succeed;
Provide publicity (and, thereby, funding) for those who make progress but do not ultimately win the prize;
Help identify talented individuals and teams who can be seconded for future programs;
Be about 10 times more cost-effective than traditional research projects; [1]
Prompt a higher degree of spending on research by the contestants; [2]
Support a wide variety of solutions to come into existence to address the challenge, creating an entire industry in the process.
Role of a prize in this area:
It is within our grasp to develop an interface that takes raw metagenomics data and turns out clinically relevant results. The current bottleneck is developing a complete package that automatically prepares a sample, sequences it, and performs the data analysis, all for £100 and by a standard lab technician. [3] This could be the focus of a prize. [4]
We can reduce the TRL (the ‘Technology Readiness Level’, or performance threshold which needs to be reached for the prize to be awarded), depending on the prize money available. Provided we are incentivising something that the market is not already producing, it can be useful to offer a prize to achieve a TRL that only constitutes a relatively small fraction (e.g. one tenth) of the technological readiness that is ultimately needed.
Next steps:
1. Identify a partner to design and run the prize
It would take an iterative process to design a specific prize that fills the relevant gap in the market, and sets the bar at the correct level to incentivise participation.
This process (and the process of running the prize) can be outsourced to a specialist organisation and trusted technical advisors such as Trinity Challenge or XPRIZE.
2. Ensure robust independent verification of the prize participants’ submissions
This is an area of risk for the project since independent verification of the relevant technology can be an area of market failure in and of itself. There is a risk of failing to come up with a sufficiently rigorous means of verifying the technology that the prize is incentivising.
3. Finalise a costed and timelined project plan for prospective philanthropists
The length of the competition and the prize amount should be tailored to the technical demands of the prize and decided in consultation with the project partner identified in (1) above. We estimate that a $3 to $5 million prize for a competition lasting 18 - 36 months would be appropriate for a project of this kind.
[2] This is both because competitors tend to overestimate the probability of winning, and because they tend to place a significant value on the reputational reward for winning or being shortlisted.
[3] A useful analogy is the GeneXpert for metagenomics. GeneXperts are boxes deployed globally for Tuberculosis diagnosis. They receive a sample in a small cartridge and then produce a report in one hour which specifies if a patient has Tuberculosis and if it's drug resistant. This technology has revolutionised Tuberculosis diagnostics with its accessibility, speed and ease. Metagenomics has the potential to do the same.
[4] Alternatively, the prize could focus on one aspect of this bottleneck (for instance, sample acquisition, preparation or analysis), to provide incentives for the market to come in and achieve the end goal.