This article was originally published by Endpoints
In a field full of eccentrics, Jacob Kimmel may stand out most for his normality.
Kimmel is a leading anti-aging researcher who isn’t trying to sell you a first full of pills or a life hack to cheat death. The 29-year-old, instead, is headsdown in the laboratory, working to unravel the biology behind how cells age and how to rewind that process. He joined our secret channel in the latest installment of our Endpoints Slack Interview series, where we chat with the fascinating characters shaping the industry’s future.
Make sure to check out our first Slack interview with Lux Capital’s Josh Wolfe as well. And if you’ve got an idea for somebody we should interview, get in touch. This conversation has been minimally edited for readability.
Andrew Dunn
I’m excited to fire up the channel again with Jacob Kimmel. Jacob has had quite the biotech career already, by the age of 29: a PhD from UCSF at 24, joining Alphabet’s Calico and becoming a principal investigator at 27, and most recently helping launch NewLimit, an anti-aging biotech, as head of research. Thanks for joining me today, Jacob!
To start, where are you chatting from?
Jacob Kimmel
Hey Andrew — appreciate the kind words. Slacking you today from NewLimit’s headquarters in South San Francisco — the birthplace of biotechnology
Andrew Dunn
Fantastic – we have the cross-country connection going with me in DC. There’s a ton of science I’m excited to dive into but there’s not many biotech conversations I can start by bringing up Kim Kardashian
Her recent Instagram post on Prenuvo’s full-body MRI scans has caught attention. ARCH’s Bob Nelsen is also a big fan and user. It’s not explicitly anti-aging, but it feels like it fits this broader trend of proactive health that includes longevity a lot of times
Both areas also seem to attack conventional wisdoms of what exactly is disease and when someone should get checked out. To start, what do you make of the trend of seemingly healthy people getting full-body MRIs?
Jacob Kimmel
I think it reflects a broader positive trend in passive monitoring of latent disease. We’ve seen this sort of proactive diagnostic approach blossoming in the liquid biopsy space as well with tests from Freenome, Grail and others. For MRIs specifically, I’m not aware of direct evidence that preventive screening is beneficial given the risk of false positives, but I do imagine there are patients for whom it’s an expected value-positive practice. Overall, I think we’re likely to see more passive monitoring of this type emerging as the observational technologies decrease in cost and our ability to interpret the high dimensional signals we’re collecting improves.
Not sure I’d go for it myself. What about you?
Andrew Dunn
Interesting – I think I’m with you on probably passing for today. The idea of worrying over something ambiguous, and maybe getting more tests, seems really challenging until there’s a lot more data. But also, if Bob Nelsen and Kim K are both into something, maybe I have to keep an open mind?
What do you make of these ideas and figures being the face of the field to the public, particularly considering the research that you’re doing — which we’ll get into next, I promise — that is deep in the weeds of human biology?
Jacob Kimmel
I’m of two minds here. I admire the work of science communicators like Johnson who have done much to raise the salience of longevity science in the popular conversation. This is one of the biggest unsolved problems in science, but it rarely gets discussed head-on. Johnson’s efforts have led to more conversations about longevity with my peers outside the field than I’ve had in years.
That said — I do think there is a risk of overhyping the current state of our understanding. It’s important that all of us in the field emphasize the fact that there are few interventions known today that are likely to have a meaningful effect on human lifespan, and even those have largely been studied in distant animals models. We should be striving as a community to both communicate the exciting potential of the science, while being forthright with the current limitations.
To your last point, I do think the extreme n=1 personal experiments get outsized coverage relative to the rigorous laboratory science that many in the field are performing. I wish the balance of coverage was shifted a little.
Andrew Dunn
gotcha, and do you practice any longevity ideas in your own life?
particularly in being steeped in the research, i imagine there’s a lot of fascinating ideas out there
Jacob Kimmel
I like to joke that my personal longevity recipe is something your grandmother could have written. I try to eat food, but not too much, and mostly vegetables. I try to sleep enough and exercise regularly. Diet, exercise, and sleep are still among the strongest longevity interventions we know.
Andrew Dunn
oh man, that’s not much fun
Jacob Kimmel
There are lots of other ideas floating around, especially around dietary schedules and composition, but I don’t think the evidence is substantial enough today to warrant the trade-offs that would entail in my own life
Your mileage may vary — I really like ice cream, so the cost-benefit analysis is slanted toward the status quo
Andrew Dunn
it feels like the desires of the field, going back to like bryan johnson and sinclair, can get ahead of the science
talking to you feels like being pulled back to reality here
like, we still have a lot — a lot — to learn on the science front with aging
Jacob Kimmel
Agreed! those of us passionate about the science are always striving to be on the frontier. I admire those willing to test some of these less risky hypotheses (like dietary schedules) in their own lives and record it rigorously.
but it’s important to keep in front of us that the vast majority of questions we have about intervention X’s impact on healthspan metric Y are unanswered.
Andrew Dunn
does the field need to call that stuff out more? like, the goal is great but some of these practices are unproven + risky
Jacob Kimmel
100%. If ever someone is communicating something beyond the truth or doing something inadvisable, the field needs to draw a clear line and emphasize that it’s not actually supported by the science.
As an example, I don’t believe there are any supplements today that one could say have a rigorously validated impact on longevity/healthspan.
Andrew Dunn
the joe rogan advertisements may like to have a word with you on that point
Jacob Kimmel
And now time for our sponsor: …
Andrew Dunn
I appreciate the instinct haha … Let’s turn to Calico and your own career
what’s one thing that surprised you about working there and for Art Levinson, a legend in biotech?
Jacob Kimmel
The biggest surprise for me was that when you really looked at the accumulation of evidence in the longevity field up to Calico’s founding, the number of actionable drug targets was vanishingly small. There was a great deal more fundamental work to be done relative to other therapeutic areas. It’s easy in an academic setting to get excited about target X in this year’s coolest paper, but when you’re actually in a position to try and develop one of those therapeutic hypotheses, you begin to see the vast chasm between that initial discovery and a real therapeutic.
Another surprise on the upside — working for Art was even better than I imagined. He has a way of motivating everyone around him to find the best scientist within themselves, and I learned a great deal just watching how he ran the organization.
Andrew Dunn
going in, straight from your PhD, did you have the belief it’d all be quicker to get to big progress?
Jacob Kimmel
if I answer honestly, yes. Most academic settings don’t provide the drug development training necessary to see the gap between early results and therapies. I was privileged to learn how to see that gap from seasoned drug hunters at Calico.
Andrew Dunn
even with the science challenges, you’re running your own lab there at age 27! you got Alphabet money and, presumably, patience to see this out long term. That sounds like the dream job
Jacob Kimmel
Calico is an amazing place to work
Andrew Dunn
so why’d you leave? How’d NewLimit come about?
Jacob Kimmel
The NewLimit story on my end starts with a few experiments. Summarizing a great deal of work in the field into a one-liner: several groups reported that epigenetic reprogramming with Yamanaka Factors could reverse features of aging in old cells. I got excited about these results, but honestly wasn’t sure if they would replicate. I started to explore this approach as a way to restore youthful function in aged cells while I was at Calico, and we were excited to find that the phenomenon didn’t seem unique to the full Yamanaka Factor set, this was potentially a more general approach to restoring youthful function. This was particularly exciting to me because of some of the challenges we discussed above — it’s quite difficult to test longevity interventions in the general case, but epigenetic reprogramming is a cell-intrinsic mechanism, suggesting we could iterate quickly on possible interventions.
Around the same time, my cofounders Brian Armstrong and Blake Byers became interested in this biology and we got connected through mutual friends. We came to believe that we could increase the chances that reprogramming therapies would help patients in the near term by founding an organization solely focused on epigenetic reprogramming medicines, and so NewLimit was born.
Andrew Dunn
and tying that back to Calico, do you view the for-profit biotech setting as the right place for pursuing these big goals? even with real resources, i’m curious if you think that’s still underappreciated for the field: that gap between early results and therapies you mentioned
especially tying in the leading role of tech entrepreneurs here, who don’t come from a biopharma background, be it larry page at google or brian armstrong at coinbase
Jacob Kimmel
Historically, for-profit biotechs have been one of the best vehicles for addressing challenging scientific problems that stand between us and therapeutic interventions. Longevity interventions may represent an extreme case of the usual drug development challenges, but I think it’s a difference of degree rather than a difference in kind. If we think through some of the most dramatic successes in therapeutic development over the past decades — take say Herceptin, Trifakta, and Zolgensma as examples — it’s challenging to imagine these problems being solved to the same degree elsewhere.
My hot take is that I actually think most drug hunters and company builders in the longevity space appreciate the challenges fairly well. If you look at the ecosystem of companies working on longevity therapies, you’ll find that the capital structures are distinct from biotechs in other therapeutic areas. I think those differences in construction commensurately reflect the challenges of this field.
Andrew Dunn
quickly, is the “bits to bio” idea overused? this idea that tech people see genetic code just like computer code that they can hack or optimize … is that idea pretty much shattered the second you start briefing BA and BB on the latest experiment
i think it may be time to just retire that type of comparison altogether in computer and genetic code
Jacob Kimmel
I definitely agree that the cell = computer and DNA = software analogies are overused and more detrimental than helpful.
My cofounders were never under that illusion either (to my knowledge )
Andrew Dunn
that’s good! i imagine they couldn’t have been after even a single dinner with you!
Jacob Kimmel
that said, I do think many ideas from software development and computer science do have utility in the life sciences. Concepts like and unit and integration testing, free parameters and absolute constants are all useful cognitive tools. We frequently compare our experimental platform to a software application at NewLimit and have derived a lot of value from that shared language.
Andrew Dunn
okay wanted to wrap up with rapid fire: fragmented sentence, acceptable, if not even encouraged here! the goal to learn a bit more about your personal side
let’s start with: snapshot of your typical workweek – how many hours, where you at, split of lab bench, computer, remote?
Jacob Kimmel
50-60 hours at NewLimit HQ, some additional hours I don’t track at home on the couch
Most of it spent writing code, reviewing data, working with the team to plan experiments
I keep begging for the team to let me help with experiments, but they’re smart enough to rarely take me up on it anymore
Andrew Dunn
when you get stuck with those experiments, ideal research setting? what’s it look like?
time of day, any particular music (or silence)?
Jacob Kimmel
lab with windows
late night, after 1900
late period Bright Eyes record, turned up loud
Andrew Dunn
love it, will have to check out Bright Eyes. see if it applies to writing too.
outside the lab: what do you do for fun?
Jacob Kimmel
I’m personally convinced California is the most beautiful place in the world, so I try to spend as much time as possible exploring it.
Lots of hiking in the northern part of the state
Attempting to become a better surfer down in Santa Cruz
Andrew Dunn
one book you’re forcing everyone to read right now?
Jacob Kimmel
True for a long time: Invisible Frontiers by Stephen S Hall. Long out of print, but the best history of early biotech I’ve read. We keep copies at the office.
Andrew Dunn
You can host 3 people, dead or alive, for a private dinner to give NewLimit advice. Who you got?
Jacob Kimmel
John Maraganore
Conrad Waddington
Aviv Regev
Andrew Dunn
awesome – although sorry Ponce de León, but those may be more helpful
Jacob Kimmel
I grew up in Florida. I can promise you that the sulfur water he found did not prevent me from aging
Andrew Dunn
final Q: this has been a ton of fun. Who should we invite next to join us here?
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