Description of subprojects and results, including major changes from the original proposal
The final Grant Report for this project is here: https://docs.google.com/document/d/1U8zgg3_QF9WxQrQvoj6l3qAoN7nY7R-zX0pY3a2Q2BU/edit
7
Optimizing clinical Metagenomics and Far-UVC implementation.
CompleteGrant
$41,800raised
Project summary
Metagenomic sequencing and Far-UVC are two promising technologies for dramatically decreasing the risks from future GCBRs. Convergent Research (CR) has laid the groundwork for accelerating both by incubating $30-50M focused research organizations (FROs). For both FROs, CR is looking for help from a medical doctor with safety and efficacy trial experience to increase the chances of funding for these FROs and their expected impact.
Concretely, in this 3-month project, I will
(a) conduct on-the-ground interviews with clinicians to help CR find the best scope and design for a UK-based FRO to accelerate the development of clinical metagenomic sequencing for pandemic early warning.
(b) explore what it would take for the same hospitals to become early adopters of Far-UVC air disinfection and whether hospital adoption should be incorporated in a Far-UVC FRO design.
(c) consult on the design of safety and efficacy trials for a CR Far-UVC FRO planned for 2025.
What are this project's goals and how will you achieve them?
1/ Metagenomic Sequencing (MGS)
The key goal of this project is to inform the design of a £30-50M focused research organization (FRO) in the UK focused on accelerating the development and adoption of point-of-care MGS. This FRO proposal will be submitted to two separate open calls in the UK: one co-funded by the government and Schmidt Futures, one announced by the Advanced Research and Invention Agency. CR has put together many of the building blocks for success (technology roadmap, contact with companies that can develop fit-for-purpose devices, leading UK clinicians) and estimates the chances of unlocking these resources at 20-40%.
A key goal for CR is to prioritize the workstreams to achieve maximum catalytic impact. To aid these decisions, I (Miti Saksena) will work closely with the Convergent Research team by visiting identified relevant hospitals and interviewing clinicians. In the case of MGS, a key question is whether to push primarily on technology development or clinical approval and adoption of existing MGS protocols. The outputs of this project will be
Target product profiles for metagenomic sequencing tests in the context of British ICUs and emergency departments. Key variables to determine include the necessary cost and time to answer and modalities of integration into the healthcare and pathogen surveillance systems.
Prioritized goals for data gathering for multi-site trials of MGS as a diagnostic.
A clear plan for integrating point-of-care MGS into an early warning system.
A “playbook” for clinicians interested in adopting clinical MGS as a diagnostic.
A CRM of clinicians that could join multi-site trials of MGS cost-effectiveness and clinical utility.
2/ Far-UVC
Jasper Gotting and Vivian Belenky at CR have spent the last 9 months researching Far-UVC and finding the best design for a Far-UVC FRO. They gradually shifted their focus from the development of efficient emitters and came to believe that high-quality safety and efficacy trials would have a greater catalytic impact on the field. They are currently engaging with top experts in the field (David Brenner, Kenneth Wood, Ewan Eadie) on designing a FRO to coordinate this safety and efficacy work. They are looking for consulting on their ideal scope and design and help in finding the right performers for this FRO. In collaboration with Jasper and Vivian, I will iteratively identify priority work streams in Far-UVC with the aim of maximizing the chances that $50M for this project is unlocked and that it maximally accelerates Far-UVC adoption.
How will this funding be used?
3 mo FT salary for myself + benefits
Travel costs
Who is on your team and what's your track record on similar projects?
To date, Convergent Research has officially launched 5 FROs [1] with total funding of $250M and reached approval for another 3.
CR has shown commitment to long-termism by hiring a Biosecurity Program Associate as employee number 5 and providing an institutional home for technical roadmaps on Far-UVC and metagenomics. Outputs include state-of-the-art analyses of Far-UVC hardware, as well as general bottlenecks and a roadmap towards ubiquitous metagenomic sequencing.
[1] https://www.convergentresearch.org/fro-portfolio
Self (Miti Saksena)
I currently work as an independent contractor for Securebio. I work on biosecurity policy papers and have assisted them in submitting a proposal to conduct a far-UVC efficacy clinical trial to the CDC.
I was previously employed at Alvea, an EA-aligned for-profit biotech startup dedicated to the accelerated development of shelf-stable COVID vaccines. I was a physician on their clinical trials team and was responsible for their products' safety (Pharmacovigilance). This involved technical and operational setup and strategizing for the company.
I was a Postdoctoral fellow in Microbiology at Mt Sinai Hospital, NYC. I worked with a virology lab, closely collaborating with renowned immunologists on crucial, early COVID vaccine research. This work resulted in influential recommendations for vaccine distribution efforts and informed clinical vaccination standards for different immunological profiles of patients. My lab operated its own clinical pathogen surveillance system across its hospital system in NYC, tracking the changes in the SARS CoV2 virus since the beginning of the NY outbreak. Although I did not contribute directly to this, I participated in operational and technical discussions.
I led a team of healthcare personnel while managing a level-2 ICU in rural India while providing and coordinating comprehensive critical care to admitted patients with ad hoc interactions with other acute care areas at a resource-strapped tertiary hospital for a year. This is part of ~3 yrs of clinical experience as a Medical Officer in India.
What are the most likely causes and outcomes if this project fails? (premortem)
Failure mode 1: No funding is received in time for me to commit FT to the project. This would result in :
CR continuing with the FRO proposal without incorporating the data I would collect or with an extreme MVP version aggregated by the existing staff. Ales Flidr estimates that this project could increase the chances of unlocking funding by 10-20 percentage points; we risk missing out on that.
OR,I look for alternate funding sources from other sources; this would come at a substantial cost to the projected timeline for the timely incubation of the FRO.
OR,I volunteer my time to work on this which comes with added personal financial stress, while being able only to contribute less than the ideal (ie. very little) amount of time.
Failure mode 2: The research is completed timely after funding, but the FRO incubation is unsuccessful (for any reason). The project output is generally valuable in this field, even outside the immediate utility for CR FROs. Making the results publicly accessible will still positively impact future projects.
What other funding are you or your project getting?
None atm. This was submitted for a 14-day decision with Lightspeed grants but was rejected after three weeks from submission.
Miti Saksena
over 1 year ago
Final report
Miti Saksena
over 1 year ago
The final Grant Report for this project is here: https://docs.google.com/document/d/1U8zgg3_QF9WxQrQvoj6l3qAoN7nY7R-zX0pY3a2Q2BU/edit
Miti Saksena
almost 2 years ago
Project Update: The FRO proposal submitted to the Research Ventures Catalyst open call in the UK, the one co-funded by the government and Schmidt Futures, has been selected as one of 12 out of over 250 high-quality applications to receive seed-corn funding. Public announcement here. (Project number 2 on the list) !!
Austin Chen
over 2 years ago
Approving this! Excited for Manifund's role here in accelerating the concrete research towards mitigating global catastrophic biorisks.
Austin Chen
over 2 years ago
Hi Miti! In general I'm excited for biosecurity work on these topics and excited that Gavriel likes this grant, and expect to approve this. I just wanted to check in on a (maybe dumb) question: given that Convergent Research seems to be both well-funded and also the primary beneficiaries of Miti's work, why aren't they able to fund this themselves?
From CR's website, they don't have a vast pool of funding themselves, and instead seek to incubate FROs that then get follow-on funding. This seems reasonable; I'd be happy to work out other financial arrangements that make sense here such as via a loan or equity.
For example, Ales estimates this work to raise the chance of unlocking funding by 10%+. In that case, assuming a conservative $10m raise for the FRO, that would make Miti's project worth $1m; and assuming a funder's credit portion of 10% for this, that would indicate a $100k value of the grant made. So eg would Ales/CR/the resulting FRO be willing to commit $100k back to Gavriel's regrantor budget, conditional on the FRO successfully raising money?
I apologize if this seems like a money-grubbing ask; I'm coming into this a bit from a "fairness between funders" perspective and a bit of "sanity checking that the work really is as valuable to CR as purported". Manifund just doesn't have that much money at the moment, so being able to extend our capital is important; and also, I'm excited about using good financial mechanisms to make charitable fundraising much much better (ask me about impact certs sometime!).
donated $41,700
Gavriel Kleinwaks
over 2 years ago
One quick part of the response from something Joel posted in Discord a while back: "It isn't funded by Convergent already because : 1. Time, they need the data asap and time asap. 2. Logistics, CR is not incorporated in the UK and the intermediary employers cost a lot of overhead for them vs me applying for independent grants that will let me work here." Otherwise will let Miti respond.
Miti Saksena
over 2 years ago
Hi Austin! Thanks for the questions. I appreciate you looking out for the best use of Manifund's resources!
1. As Gavriel mentioned, there are a few logistical reasons why Convergent can't directly fund this work right now:
Time - They need the data as soon as possible to meet the research venture catalyst application deadline of Oct 23 for the MGS project. So applying for grants like Manifund promising quick turnaround is more feasible than navigating internal funding. (Note, the only other grant we were counting on being helpful was the 14-day Lightspeed grant)
Logistics - Convergent is not incorporated in the UK, so employing me directly would involve substantial overhead versus me applying for grants tailored to individual researchers.
Also, I should strongly emphasize that as an independent researcher, I have the freedom to make the results of this project public, rather than the work being siloed solely for CRs incubation efforts at risk of being lost when the purpose is served. We discussed making this a formal deliverable and adjusting the timeline/funding to account for this with Gavriel, but the grant write-up does not reflect that.
I'm satisfied these reasons make an independent grant the right mechanism for funding this work. CR needs the insights in a timely manner, and this gives me a solid reason to work on this in a sprint mode, avoiding undue bureaucratic delays. And outside of CR’s needs, this work should have been happening anyways, I serendipitously happen to be in the right place with the capacity to work on this to make it happen.
2. I understand CR can't legally commit FRO funds for this purpose. As a non-profit, CR has restrictions on how it can allocate funds. Their budgets are tightly earmarked for specific research/road mapping goals, making it difficult to flexibly commit money to adjacent projects, even if valuable. If Convergent were a for-profit company, it would be easier for them to invest in supportive initiatives like this that might not fit neatly into a pre-defined budget for exploring and pursuing incubation. The FRO budget they unlock will also be very specifically allocated to the research goals thereafter. From my understanding, those funds are allocated to whatever new entity/org the FRO will be, not to CR as such. Specifically for this project, the ‘seed-corn budget’ received at the end of a successful round 1 has strict requirements to be committed to developing the full technical plan for stage 2. I recognize why Convergent can't directly back this themselves at this time. I'm optimistic that my independent work here can provide data to accelerate their roadmaps in a timely way.
Please let me know if this addresses your concerns. I'm happy to discuss further.
Austin Chen
over 2 years ago
@MSaksena Thanks for the explanation! I understand that nonprofit funders have their hands tied in a variety of ways and appreciate you outlining why it's in Manifund's comparative advantage to fund this as an independent grant.
Someday down the line, I'd love to chat with the Convergent Research team or related funders (like Schmidt Ventures?) about solving the problem of how to "flexibly commit money to adjacent projects". In the meantime, best of luck with your research and thank you for your service!
donated $41,700
Gavriel Kleinwaks
over 2 years ago
I had a great conversation with Miti and Convergent’s Aleš Flidr about this grant, and will be fully funding it.
General:
I am explicitly looking for projects aimed at biosecurity/pandemic prevention, since I feel better equipped to understand what is valuable in that field than in AI. I also worry that biosecurity is underserved by the current quick-grants structure, relative to AI.
This is exactly the type of project Manifund is best poised to serve: the turnaround needs to be really fast, since Miti is targeting an October deadline, and it’s for a small enough amount that at my $50k regranting budget I can fully fund it.
Specific:
From my conversation with Miti and Aleš, it sounded as though there was a pretty good chance to unlock UK government buy-in for an important biosecurity apparatus, through the relatively inexpensive/short-term investment of a proposal submitted to the government. Biosecurity doesn’t have a lot of opportunities for cheap wins as far as I normally see, so this is really exciting.
Even if this project doesn’t unlock that buy-in, the project deliverables look really useful, and I would like for them to exist and be accessible to others.
Miti has worked at several different points in the chain of biosecurity-relevant roles, so seems especially well-positioned to come up with the listed deliverables and write a proposal to the UK government.
Reason for amount: The project is on a very tight timeline and Miti is assuming a very reasonable 3-month salary for herself in her budget. I don’t want to cut into it and cause financial pressure to take attention away from the project or for her to need to seek additional contract work.
Key uncertainties: The list of deliverables is a lot for one person for three months. It would be amazing if Miti actually got through the whole thing, but she and Aleš were forthright about the possibility that not all of the deliverables would come through, and that they were uncertain about how the project would be able to move forward after the October deadline. They did agree that there was value in the project beyond the deadline, and it would be ideal to continue it if circumstances allowed, so we were on the same page about that. I still consider the project to be well worth pursuing, as whatever information is gained will still be useful and accessible after the deadline.
donated $41,700
Gavriel Kleinwaks
over 2 years ago
(Would appreciate feedback on the clarity/usefulness of this writeup if others happen to have notes!)
Joel Becker
over 2 years ago
@GavrielK (Note to others: I have a major COI with Miti.)
I think your write-up is very clear. But I am somewhat surprised that you have ~nothing negative to say, which makes me think that it could be more useful if you said more (true, salient, and) negative things.
Even if you are totally positive about the project, could you say something about how other bio opportunities you've looked at feel below this bar? I am imagining things like "cost too much relative to Manifund pool," "seem better-suited to larger funders with more context on their project," and other stuff that I think you imply in the write-up but don't say outright.
donated $41,700
Gavriel Kleinwaks
over 2 years ago
@joel_bkr Makes sense, thanks for the feedback!
1) ~nothing negative to say: I think I instinctively made this sound a little too "nice" and also once I made up my mind, had a bias toward sounding confident, both of which probably disguise how negatively I weighed that key uncertainty referenced at the end of my writeup. Reading it back, it doesn't convey my real level of concern--it gave me serious pause that there's basically one person tackling this whole list, for an October deadline, who's also trying to handle immigration, and no clear person to pick up the ball. I think of this project as falling very much into the philosophy of hits-based giving, which makes that particular timeline problem more acceptable to me as a risk...but probably if I didn't already have some level of trust toward the people involved, I would have been harsher toward that aspect of the project. Even then, I think it would have been a stronger application if CR were able to say they had another person who could help Miti, or had a handoff process as backup, or some other method to ensure the ball isn't dropped.
2) other bio opportunities: For starters, there's very little else I've seen so far in the category of biosecurity specifically; almost all biosecurity/pandemic preparedness projects I know of are beyond my funding capacity, including the one other explicitly biosecurity-focused project posted on Manifund. Although I am not absolutely locked into funding biosecurity projects, I did want to start there, and I wanted to make sure I could fully fund at least one thing in case nobody else was interested in biosecurity. This project is also much more urgent than others, with a faster feedback loop--we'll know how it went within a few months. (Another project I was interested in isn't even ready to go yet, although I'd love to help that person find funding in the future). Beyond biosec, without getting too into the weeds of each individual project I looked at, most projects posted to Manifund just strike me as a) much more speculative or b) less valuable or c) not within my capacity to both evaluate and fund.