Recently, I caught up with Martin Borch Jensen, the Chief Science Officer of the biotech company Gordian Biotechnology. Gordian is a therapeutics company focused on the diseases of aging.
Martin did his Ph.D. in the biology of aging, received a prestigious NIH award to jumpstart an academic career, but decided to return the grant to launch Gordian. Recently, he designed and launched a $26 million competition called Longevity Impetus Grants. This program has already funded 98 grants to help scientists address what they consider to be the most important problems in aging biology (also known as geroscience). There is a growing body of research which suggests that there are underlying biological mechanisms of aging, and that it may be possible to delay the onset of multiple chronic diseases of aging, allowing people to live longer, healthier lives.
I interviewed Martin not only because I think that the field of geroscience is important, but also because I think the role that Martin is playing has significant benefits for science and society, and should be replicated in other fields. With this work, essentially, you could say that Martin is serving as a strategist for the field of geroscience as a whole, and designing a process for the competitive, merit-based allocation of funding that philanthropists such as Juan Benet, James Fickel, Jed McCaleb, Karl Pfleger, Fred Ehrsam, and Vitalik Buterin have confidence in, and have been willing to support. Martin’s role has a number of potential benefits:
- Many philanthropists are interested in supporting scientific research, but don’t have the professional staff capable of identifying areas of research that we are under-investing in. If more leading researchers were willing to identify areas where there is a strong case for additional philanthropic support, and design a process for the allocation of funding that inspires confidence, philanthropists would find it easier to support scientific research. Currently, there are almost 2,000 families in the U.S. alone that have $500 million in assets, and their current level of philanthropy is only 1.2 percent of their assets.
- Researchers could propose funding mechanisms that are designed to address shortcomings associated with the status quo. For example, at the beginning of the pandemic, Tyler Cowen and Patrick Collison launched Fast Grants, which provided grants for COVID-19 related projects in under 14 days. Other philanthropists have designed funding mechanisms that are specifically designed to support high-risk, high-return ideas by empowering reviewers to back non-consensus ideas. Schmidt Futures and the Astera Institute are supporting Focused Research Organizations, projects that address key bottlenecks in a given field, and are difficult to address using traditional funding mechanisms.
- Early philanthropic support can catalyze additional support from federal science agencies such as NIH. For example, peer reviewers in NIH study sections often want to see “preliminary data” before they recommend funding for a particular project. Philanthropic support could generate evidence not only for specific scientific projections, but for novel approaches to funding and organizing scientific research.
- Physicist Max Planck observed that science progresses one funeral at a time. Early career scientists are likely to have new ideas, and philanthropic support for these ideas could accelerate scientific progress.
Below is a copy of the Q&A conducted over email between me and Martin Borch Jensen.
Tom Kalil: What motivated you to launch Impetus grants?
Martin Borch Jensen: Hearing Patrick Collison describe the outcomes of the COVID-19 Fast Grants. Coming from the world of NIH funding, it seemed to me that the results of this super-fast program were very similar to the year-ish cycle of applying for and receiving a grant from the NIH. If the paperwork and delays could be greatly reduced, while supporting an underfunded field, that seemed unambiguously good.
My time in academia had also taught me that a number of ideas exist, with great potential impact but that fall outside of the most common topics or viewpoints and thus have trouble getting funding. And within aging biology, several ‘unfundable’ ideas turned out to shape the field (for example, DNA methylation ‘clocks’, rejuvenating factors in young blood, and the recent focus on partial epigenetic reprogramming). So what if we focused funding on ideas with the potential to shape thinking in the field, even if there’s a big risk that the idea is wrong? Averaged across a lot of projects, it seemed like that could result in more progress overall.
TK: What enabled you to do this, given that you also have a full-time job as CSO of Gordian?
MBJ: I was lucky (or prescient?) in having recently started a mentoring program for talented individuals who want to enter the field of aging biology. This Longevity Apprenticeship program is centered on contributing to real-life projects, so Impetus was a perfect fit. The first apprentices, mainly Lada Nuzhna and Kush Sharma, with some help from Edmar Ferreira and Tara Mei, helped set up a non-profit to host the program, designed the website and user interface for reviewers, communicated with universities, and did a ton of operational work.
TK: What are some of the most important design decisions you made with respect to the competition, and how did it shape the outcome of the competition?
MBJ: A big one was to remain blind to the applicant while evaluating the impact of the idea. The reviewer discussion was very much focused on ‘will this change things, if true’. We don’t have a counterfactual, but based on the number of awards that went to grad students and postdocs (almost a quarter) I think we made decisions differently than most funders.
Another innovation was to team up with one of the top geroscience journals to organize a special issue where Impetus awardees would be able to publish negative results – the experiments showing that their hypothesis is incorrect. In doing so, we both wanted to empower researchers to take risks and go for their boldest ideas (since you’re expected to publish steadily, risky projects are disincentivized for career reasons), and at the same time take a step towards more sharing of negative results so that the whole field can learn from every project.
TK: What are some possible future directions for Impetus? What advice do you have for philanthropists that are interested in supporting geroscience?
MBJ: I’m excited that Lada (one of the Apprentices) will be taking over to run the Impetus Grants as a recurring funding source. She’s already started fundraising, and we have a lot of ideas for focused topics to support (for example, biomarkers of aging that could be used in clinical trials). We’re also planning a symposium where the awardees can meet, to foster a community of people with bold ideas and different areas of expertise.
One thing that I think could greatly benefit the geroscience field, is to fund more tools and methods development, including and especially by people who aren’t pureblooded ‘aging biologists’. Our field is very limited in what we’re able to measure within aging organisms, as well as measuring the relationships between different areas of aging biology. Determining causal relationships between two mechanisms, e.g. DNA damage and senescence, requires an extensive study when we can’t simultaneously measure both with high time resolution. And tool-building is not a common focus within geroscience. So I think there’d be great benefit to steering talented researchers who are focused on that towards applications in geroscience. If done early in their careers, this could also serve to pull people into a long-term focus on geroscience, which would be a terrific return on investment. The main challenges to this approach are to make sure the people are sincerely interested in aging biology (or at least properly incentivized to solve important problems there), and that they’re solving real problems for the field. The latter might be accomplished by pairing them up with geroscience labs.
TK: If you were going to try to find other people who could play a similar role for another scientific field, what would you look for?
MBJ: I think the hardest part of making Impetus go well was finding the right reviewers. You want people who are knowledgeable, but open to embracing new ideas. Optimistic, but also critical. And not biased towards their own, or their friends’, research topics. So first, look for a ringleader who possesses these traits, and who has spent a long time in the field so that they know the tendencies and reputations of other researchers. In my case, I spent a long time in academia but have now jumped to startups, so I no longer have a dog in the fight. I think this might well be a benefit for avoiding bias.
TK: What have you learned from the process that you think is important for both philanthropists considering this model and scientists that might want to lead an initiative in their field?
MBJ: One thing is that there’s room to improve the basic user interface of how reviews are done. We designed a UI based on what I would have wanted while reviewing papers and grants. Multiple reviewers wrote to us unprompted that this was the smoothest experience they’d had. And we only spent a few weeks building this. So I’d say, it’s working putting a bit of effort into making things work smoothly at each step.
As noted above, getting the right reviewers is key. Our process ran smoothly in large part because the reviewers were all aligned on wanting projects that move the needle, and not biased towards specific topics.
But the most important thing we learned, or validated, is that this rapid model works just fine. We’ll see how things work out, but I think that it is highly likely that Impetus will support more breakthroughs than the same amount of money distributed through a traditional mechanism, although there may be more failures. I think that’s a tradeoff that philanthropists should be willing to embrace.
TK: What other novel approaches to funding and organizing research should we be considering?
MBJ: Hmmm, that’s a tough one. So many interesting experiments are happening already.
One idea we’ve been throwing around in the Longevity Apprenticeship is ‘Impetus for clinical trials’. Fast Grants funded several trials of off-patent drugs, and at least one (fluvoxamine) now looks very promising. Impetus funded some trials as well, but within geroscience in particular, there are several compounds with enough evidence that human trials are warranted, but which are off-patent and thus unlikely to be pursued by biopharma.
One challenge for ‘alternative funding sources’ is that most work is still funded by the NIH. So there has to be a possibility of continuity of research funded by the two mechanisms. Given the amount of funding we had for Impetus (4-7% of the NIA’s budget for basic aging biology), what we had in mind was funding bold ideas to the point where sufficient proof of concept data could be collected so that the NIH would be willing to provide additional funding. Whatever you do, keeping in mind how the projects will garner continued support is important.