The Quest to Cure Alzheimer’s | Sacha Schermerhorn, Babylon Bio

Summary

Sacha Schermerhorn, founder and CEO of Babylon Bio, joins Ti Morse to discuss his ambitious quest to find a cure for Alzheimer’s disease. Despite decades of research and billions of dollars spent with limited progress, Sacha argues that the history of failure has actually produced valuable knowledge by showing what doesn’t work, and that the information needed to cure the disease may already exist scattered across disparate fields of science. He describes how Babylon Bio is structured specifically to survive many failures through self-financing and a lean approach to drug discovery.

The conversation explores fascinating scientific connections, including the surprising finding that the shingles vaccine reduces Alzheimer’s risk by 20%, how Swanson linking can connect seemingly unrelated research findings, and why the most efficacious drugs for Alzheimer’s may already be sitting in plain sight. Sacha discusses his experience volunteering at memory clinics, which deeply informed his mission, and his unconventional approach to filtering for “missionaries vs mercenaries” when hiring. He also shares his radical practice of living without a phone to reduce distraction.

A significant portion of the interview dives into what actually causes cognitive impairment in Alzheimer’s, moving beyond the long-dominant amyloid hypothesis to explore axon degeneration and other mechanisms. Sacha makes the case that AI and large language models could be transformative for connecting scientific clues across disparate fields, potentially identifying the perfect target for Alzheimer’s treatment. His approach prioritizes impact-per-dollar and being scrappy over the traditional biotech model of burning through hundreds of millions in venture capital.

Highlights

”The Shingles Vaccine Reduces Alzheimer’s Risk by 20%”

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“There’s a group in Wales where if you were born after this cutoff date, you were eligible for the shingles vaccine. And if you were born just before, you were not. They found that people that had the shingles vaccine were 20% less likely to develop Alzheimer’s within 7 years. Why? We have no idea.” — Sacha Schermerhorn, 49:31

”Living Without a Phone”

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“I don’t carry a phone. I’ve found that the single biggest driver of my productivity and my ability to think deeply about hard problems is eliminating distractions. And the phone is the ultimate distraction machine.” — Sacha Schermerhorn, 46:02

”Filtering for Missionaries vs Mercenaries”

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“When you’re trying to solve something as hard as Alzheimer’s, you need people who are genuinely obsessed with the mission. Mercenaries will leave when things get hard. Missionaries will run through walls because they believe the problem must be solved.” — Sacha Schermerhorn, 36:24

”Lack of Agency Causes Burnout”

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“I don’t think burnout comes from working too hard. I think burnout comes from a lack of agency — when people feel like they can’t affect the outcome. Give people ownership and the ability to steer and they’ll work insane hours without burning out.” — Sacha Schermerhorn, 41:07

”Self-Financing Moonshots”

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“We structured Babylon to self-finance our Alzheimer’s moonshots. Most biotech companies raise hundreds of millions and bet it all on one drug candidate. We want to be able to take many shots on goal, and the only way to do that is to not be beholden to the typical VC model.” — Sacha Schermerhorn, 19:01

Key Points

• Decades of Alzheimer’s failure produced valuable knowledge (1:00) - Sacha argues that decades of research have shown what doesn’t work, and the lack of an existence proof that a cure is attainable makes the problem exciting rather than discouraging
• Axon degeneration as a key mechanism (12:22) - Beyond the amyloid hypothesis, axon degeneration represents a potentially more fundamental mechanism behind cognitive impairment in Alzheimer’s
• Structuring for survival across many failures (13:57) - Babylon Bio is specifically designed to withstand multiple drug candidate failures rather than betting everything on one approach
• Self-financing model (15:24) - Rather than raising massive VC rounds, Babylon self-finances to maintain independence and take multiple shots on goal
• Viagra as an accidental discovery (19:01) - The story of Viagra illustrates how successful drugs can emerge from unexpected research directions
• Swanson linking and Raynaud syndrome (19:59) - Don Swanson’s method of connecting disparate scientific findings across fields, linking fish oil research to Raynaud’s disease without any researcher in either field knowing about the other
• Most efficacious Alzheimer’s drugs already known (24:16) - The most promising drug candidates may already exist in published research but haven’t been connected to Alzheimer’s
• Attracting mission-aligned people (31:34) - Building a team of people genuinely passionate about curing Alzheimer’s rather than just career advancement
• Missionaries vs mercenaries (36:24) - Sacha’s framework for filtering hires: missionaries stay when things get hard, mercenaries leave
• Lack of agency causes burnout, not hard work (41:07) - Burnout comes from feeling unable to affect outcomes, not from working long hours
• Living without a phone (46:02) - Sacha doesn’t carry a phone to eliminate distractions and enable deep thinking about hard problems
• Shingles vaccine reduces Alzheimer’s risk (49:31) - A Welsh study found the shingles vaccine reduced Alzheimer’s risk by 20% within 7 years, a clue from a completely different field
• AI and LLMs for connecting scientific clues (54:19) - Training models on expert heuristics and deploying them on the knowledge graph of science to find connections across disparate fields
• Controversial science (55:36) - Some of the most promising Alzheimer’s research involves controversial or unpopular hypotheses that mainstream researchers avoid
• Volunteering at memory clinics (1:03:11) - Sacha’s firsthand experience with Alzheimer’s patients deeply informed his mission and urgency
• Impact-per-dollar and being scrappy (1:04:28) - Prioritizing the most impact for every dollar spent rather than the traditional biotech approach of burning through capital
• Time to last embarrassment (1:09:26) - Measuring personal growth by the time since your last embarrassing decision or action
• What causes cognitive impairment (1:12:57) - Deep dive into the mechanisms of cognitive decline beyond just amyloid plaques

Mentions

Companies

• Babylon Bio (0:00) - Sacha’s company working on curing Alzheimer’s disease
• OpenAI (54:19) - Referenced in context of AI models that could help connect scientific findings

Products & Technologies

• Large Language Models (LLMs) (54:19) - AI models that could be trained to approximate expert heuristics for connecting scientific clues
• Shingles Vaccine (49:31) - Unexpectedly found to reduce Alzheimer’s risk by 20% in a Welsh study
• Swanson Linking (19:59) - Method of connecting disparate scientific findings across unrelated fields
• SSRIs (38:00) - Discussed in context of how existing drugs might have unexpected applications

People

• Sacha Schermerhorn (0:00) - Founder and CEO of Babylon Bio
• Don Swanson (19:59) - Researcher who developed the method of connecting disparate scientific literature

Surprising Quotes

“There are a lot of clues about Alzheimer’s. I think there’s enough clues for us to understand what is actually causing the cognitive impairment. Often these clues come from very disparate fields.” — 49:31

“I would actually disagree with the premise that no progress has been made. I think a lot of progress has been made but by showing us things that don’t work more than things that do. There’s no existence proof that this is attainable, which to me is extremely exciting.” — 1:00

“With these LLMs taking off, can we basically get very smart scientists to train these models to approximate some heuristic that they use and then just deploy these on the knowledge graph of science to try and connect? That seems really tractable.” — 54:19

“I don’t think burnout comes from working too hard. I think burnout comes from a lack of agency — when people feel like they can’t affect the outcome.” — 41:07

Transcript

0:00 There are a lot of clues about Alzheimer’s. I think there’s enough clues for us to understand what is actually causing the cognitive impairment. Often these clues come from very disparate fields. The shingles vaccine — there’s a group in Wales where if you were born after this cutoff date, you were eligible for the vaccine. And if you were born just before, you were not. They basically stratified those patients and followed them over time. And they found that people that had the shingles vaccine were 20% less likely to develop Alzheimer’s or all-cause dementia within 7 years. Why? We have no idea.

0:45 And that’s because again these are very distinct fields of science that don’t interface with each other directly. So with these LLMs kind of taking off, can we basically get very smart scientists to train these models to approximate some heuristic that they use and then just deploy these on the knowledge graph of science to try and connect? That seems really tractable and like we have more than enough clues to figure out the perfect target for something like Alzheimer’s or other diseases.

1:00 Today I have the pleasure of sitting down with Sacha Schermerhorn and he is the founder and CEO of Babylon Bio. They are currently trying to find a cure for Alzheimer’s. I think over the last many decades, tens of thousands of people have been basically working on a cure for Alzheimer’s. Billions and millions of dollars have been spent and almost no progress has been made. What about that got you excited?

1:30 I would actually disagree with the premise that no progress has been made. I think a lot of progress has been made but by showing us things that don’t work more than things that do. There’s no existence proof that this is attainable, which to me is extremely exciting. And I think the past several decades of failure have given the perception of intractability but have also created an enormous body of knowledge about what the disease is not and what doesn’t work against it.

2:30 The history of Alzheimer’s research is fascinating because for decades, almost the entire field was focused on the amyloid hypothesis — the idea that amyloid plaques in the brain are the primary cause of the disease. Billions were spent on drugs targeting amyloid, and they almost all failed. Some reduced amyloid but didn’t improve cognition. This told us something really important: amyloid may be a symptom, not the cause.

4:00 What’s really compelling about the current moment is that we’re in a post-amyloid world where researchers are finally exploring other hypotheses. There’s the infectious hypothesis, the metabolic hypothesis, the neuroinflammation hypothesis, and the axon degeneration theory that we’re particularly interested in. Each of these has supporting evidence from different corners of science.

8:09 What about this problem specifically got me excited was the combination of massive unmet need — there are 50 million people worldwide with Alzheimer’s and that number is growing — and the fact that the existing approach clearly wasn’t working. When an entire field has been running in one direction and failing, there’s often a massive opportunity to come at the problem from a different angle.

12:22 Axon degeneration is really interesting because it happens before the neurons die. The axons, which are the long projections that neurons use to communicate with each other, start to degrade. This happens years before clinical symptoms appear. If you could intervene at this stage, you might be able to prevent the disease from progressing to the point where neurons are dying and cognition is impaired.

13:57 We structured Babylon specifically to survive many failures. Most biotech companies raise a round of funding, bet it all on one drug candidate, and if that fails, the company is essentially done. We wanted to build something that could take 10, 20, 30 shots on goal. The way to do that is to be incredibly efficient with capital and to have multiple programs running simultaneously at different stages.

15:24 The self-financing model is critical to our approach. When you take VC money in biotech, you’re on a clock. You have to show progress within a certain timeframe or the funding dries up. That creates perverse incentives — you end up optimizing for the next fundraise rather than for actually solving the problem. By self-financing our moonshots, we can take the time to do it right.

19:01 Viagra is actually one of the best examples of accidental drug discovery. It was originally being developed as a heart medication. During clinical trials, the researchers noticed an unexpected side effect. The drug didn’t work well for the heart, but the side effect turned out to be worth billions. This happens more often than people think in drug development.

19:59 Don Swanson was a library scientist in the 1980s who developed this incredible method of connecting scientific findings across unrelated fields. His most famous example was linking research on fish oil with Raynaud’s disease. No researcher in either field was aware of the connection, but by systematically analyzing the published literature, he identified that fish oil could be an effective treatment. This was later validated experimentally. This idea of Swanson linking is central to how we think about finding new treatments.

24:16 When you look at the most efficacious interventions that have been shown to reduce Alzheimer’s risk, many of them are things that already exist. Exercise reduces risk by about 30%. Certain anti-inflammatory drugs show promise. The shingles vaccine reduces risk by 20%. These clues from disparate fields suggest that the information to cure Alzheimer’s might already be out there, just scattered across thousands of papers in unrelated journals.

27:29 Starting Babylon was an intense experience. I had this deep conviction that the problem was solvable but that the existing approaches were wrong. The hardest part was convincing people to join a company that was essentially saying, “Everyone else in this field has been wrong for 30 years, and we think we can do better.” That’s a hard pitch.

31:34 Attracting mission-aligned people has been one of the most important things we’ve done. When you’re working on something as hard as curing Alzheimer’s, you need people who genuinely care about the outcome. We’ve been fortunate to attract scientists and researchers who have personal connections to the disease — people whose parents or grandparents had Alzheimer’s.

36:24 I think about this as filtering for missionaries versus mercenaries. Missionaries are people who believe deeply in the mission and will persist through adversity. Mercenaries are there for the paycheck or the resume line. When you’re trying to solve something as hard as Alzheimer’s, mercenaries will leave when things get hard. Missionaries will run through walls because they believe the problem must be solved.

41:07 I don’t think burnout comes from working too hard. I think burnout comes from a lack of agency. When people feel like they can’t affect the outcome, that’s when they burn out. If you give people ownership and the ability to steer, they will work insane hours without burning out because they feel like their effort matters. The opposite is true too — you can work 40 hours a week and burn out completely if you feel like nothing you do changes anything.

46:02 I don’t carry a phone. I’ve been living without a personal phone for about two years now. I have a phone at the office that I use for essential calls, but I don’t carry one with me. I found that the single biggest driver of my productivity and ability to think deeply about hard problems is eliminating distractions. The phone is the ultimate distraction machine. Without it, I have hours of uninterrupted thinking time every day.

49:31 The information to cure Alzheimer’s might already be out there. There’s this group in Wales where if you were born after a certain cutoff date, you were eligible for the shingles vaccine. If you were born just before, you were not. They stratified those patients and followed them over time. People who had the shingles vaccine were 20% less likely to develop Alzheimer’s within 7 years. Why? We have no idea. These are very distinct fields of science that don’t interface with each other directly.

54:19 With LLMs taking off, can we get very smart scientists to train these models to approximate some heuristic that they use and then deploy these on the knowledge graph of science to try and connect disparate findings? That seems really tractable. We have more than enough clues to figure out the perfect target for something like Alzheimer’s. The challenge has always been connecting dots across fields, and AI might finally make that possible at scale.

55:36 Some of the most promising research is controversial. In science, there’s a strong herding effect where researchers follow the dominant paradigm. If you propose something that contradicts the mainstream view, you risk your career, your funding, your reputation. This means that some of the most important ideas get suppressed or ignored. We specifically look for controversial hypotheses that have strong supporting evidence.

1:03:11 Volunteering at memory clinics was one of the most formative experiences of my life. You sit with people who are losing themselves. You see the fear in their eyes when they realize they can’t remember their children’s names. You see families torn apart. It’s devastating. And it gave me an urgency that I don’t think I would have had otherwise.

1:04:28 We think about everything in terms of impact-per-dollar. In traditional biotech, the first instinct is to raise more money. Our instinct is to figure out how to get the same result for less money. Being scrappy isn’t just about saving money — it forces you to be creative and to prioritize ruthlessly. Every dollar we spend has to move us closer to a cure.

1:07:55 When you make a bad decision, you have to internalize the pain of it. You can’t externalize blame. If I hire the wrong person, that’s on me. If we pursue the wrong drug target, that’s on me. Internalizing that pain is what drives you to make better decisions next time. It’s uncomfortable, but it’s essential.

1:09:26 I measure personal growth by what I call “time to last embarrassment.” How long ago was the last time I did something that makes me cringe? If it’s been a long time, I’m probably not taking enough risks. If it was yesterday, I’m probably learning a lot. The goal is to always be slightly embarrassed by your past self.

1:10:51 Risk-taking in drug development is fundamentally different from risk-taking in software. In software, you can iterate quickly and the cost of failure is low. In drug development, each experiment can take years and cost millions. So you have to be much more thoughtful about which risks to take. But you still have to take risks — playing it safe in drug development means you’ll never find a cure.

1:12:57 What causes cognitive impairment in Alzheimer’s is still not fully understood. The amyloid plaques are there, yes, but drugs that remove amyloid often don’t improve cognition. Tau tangles are there too, and they correlate better with cognitive decline. But there’s also neuroinflammation, vascular dysfunction, and axon degeneration. The disease is almost certainly multifactorial, which is part of why it’s been so hard to treat.

1:22:11 What keeps me up at night is the fear that we’re too slow. Every day that goes by without a cure, thousands more people develop Alzheimer’s. The urgency is real. And the challenge is balancing that urgency with the scientific rigor needed to actually find something that works. You can’t rush drug development, but you also can’t accept the current pace. We have to find a way to be both rigorous and fast.