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Yung Lie and Andy Rachleff are today’s guests on The Long Run.
Yung is the president and CEO of the Damon Runyon Cancer Research Foundation, based in New York. Andy is the board chair. Andy was one of the founding partners of Benchmark Capital, the prominent Silicon Valley VC firm, and today is the chairman of Wealthfront.
Yung Lie, president and CEO, Damon Runyon Cancer Research Foundation
This is a conversation about the many attacks on the scientific enterprise this year, and how scientists and nonprofit foundations can respond in a constructive way.
A lot has happened this year. The relationship between science and society is in a precarious state.
The Department of Government Efficiency started off the year by announcing plans to cut the indirect cost rate on federal grants to 15 percent. That has threatened billions of dollars in cuts to universities to run their labs and keep the lights on. That proposal was blocked by a federal judge, and is on hold pending court review.
About 1,200 staff jobs were cut at the National Institutes of Health, the largest and most important funding organization for biomedical research in the world. More than 2,500 NIH grants were canceled, although about 900 have been reinstated. Study sections that review grant proposals were canceled and rescheduled. Travel to conferences was disrupted. Anti-vaccine, and anti-science statements dominated public discourse. The cuts, and rhetoric about the cuts, sent shock wave after shock wave through US science in the first half of 2025.
Andy Rachleff, co-founder, Benchmark Capital; board chair, Damon Runyon Cancer Research Foundation
That’s not all. Immigration enforcement has stepped up, sending additional waves of fear and uncertainty through many young immigrants who come to study on visas at the US universities. Some countries are seeking to capitalize, rolling out the welcome mat for bright young talent in the US.
This show is about stamina and resilience to accomplish big things in biomedicine, and everyone is going to need it for what comes next. About one-third of all the federal government’s spending on basic research will be cut if the White House budget proposal for fiscal year 2026 is adopted, according to an analysis by the American Association for the Advancement of Science.
Philanthropy, of course, is nowhere near big enough to pick up the slack from the federal government. But there are things nonprofits and philanthropies can do.
There are creative long-term ideas in play. Andy in particular, with his Silicon Valley tech VC mindset, has championed a way to make small investments go a long way. Damon Runyon is setting aside $1 million to invest in its alumni fellows who have entrepreneurial ideas.
The foundation will make seed investments in these startups – $50,000 at a time. These scientific entrepreneurs can then hopefully leverage that initial cash to persuade other private investors to put more of their capital in. If even a few of these nascent companies pan out, they could plow large proceeds back into the Damon Runyon Foundation, allowing it to give more research grants.
I should say here that I am partial toward Damon Runyon, as I have led Timmerman Traverse campaigns that have raised $2 million for the organization since 2023. This work continues.
Yung and Andy are fighting the good fight on behalf of science. They are doing it in a positive way that others might be able to follow.
Please enjoy this episode of The Long Run.
Please subscribe and tell your friends why it’s worthwhile. Quality journalism costs money. When you subscribe to Timmerman Report at $199 per year, you reward quality independent biotech reporting, and encourage more.
Please subscribe and tell your friends why it’s worthwhile. Quality journalism costs money. When you subscribe to Timmerman Report at $199 per year, you reward quality independent biotech reporting, and encourage more.
Please subscribe and tell your friends why it’s worthwhile. Quality journalism costs money. When you subscribe to Timmerman Report at $199 per year, you reward quality independent biotech reporting, and encourage more.
Please subscribe and tell your friends why it’s worthwhile. Quality journalism costs money. When you subscribe to Timmerman Report at $199 per year, you reward quality independent biotech reporting, and encourage more.
David Shaywitz
I spoke recently at one of my favorite local conferences, an inspirational gathering that brings together remarkable health leaders (plus serendipitous invitees like me) to discuss difficult topics with the exceptional candor afforded by Chatham House rules.
While much of the focus was on broad health policy issues, the proceedings were enlivened by presentations from early-stage biopharma and healthcare investors describing how they saw the future of innovation in their areas of focus. (A biopharma venture capitalist, for example, shared his worry that the current market challenges might not represent a cyclic downturn but a symptom of a more serious and enduring concern.)
And then I showed up to talk to this Very Serious Audience about … what? Well, I originally had been invited, I think, to discuss the impact of AI on biopharma R&D — a worthy (and suitably serious) topic with which I remain deeply engaged.
Yet I couldn’t resist the opportunity to discuss instead “the expanding frontier of personal health” — sleep and exercise, wearables and chatbots, agency and flourishing — and share my excitement around the opportunities and exceptional promise I see here.
I assumed most people would listen politely and regard the session as an intellectual amuse-bouche, a chance to refresh their minds between the presumably weightier topics they’d come to discuss.
Yet to my surprise and delight, the topic seemed to capture the interest of the audience — not least because so many were engaged with this space on their own.
There were quite a few Oura Rings among the attendees, and a few Whoop straps as well. Some had experimented on their own with consumer continuous glucose monitors (CGMs), supplements, and different approaches to nutrition.
During the conference – between speakers, in the hallway, over dinner – I experienced some of the most enjoyable and impassioned conversations I can recall at any scientific gathering. I even met several attendees who were writing their own books on the topic (one of which was shared with me and is superb).
It’s clear that the world of personal health – approaches to health that exist largely outside the confines of traditional medicine – engages even the most discerning among us, very much including practitioners and leaders of traditional healthcare.
But even more gratifying – and far more significant, I think – was how resonant my central contention – a call for a view of health more capacious than relentless optimization – seemed to feel. This turned out to be a central theme of the book draft I previewed, and a recurrent theme in conversations both at the conference and, increasingly it seems, in the world beyond.
Today, I will first touch on a few highlights from my talk, then introduce several related and reinforcing examples from recent podcasts and discussions, and finally conclude with a poignant reminder of the need to keep ourselves firmly grounded in the struggles of the present even as we envision a healthier and more encouraging future.
Mention personal health and wellness, of course, and our minds immediately turn to some of the wild excesses – what Dr. Eric Topol has described aptly as the “longevity lifespan circus.”
But a key point I make in my talk is that personal health is increasingly driven by substantive advances in both measurement technology and geroscience, undergirded by advances in computation, particularly AI.
Our ability to measure ever-more parameters, from single cell multi-omics and whole slide imaging to wearables capable of credibly assessing physiological states, ideally longitudinally, and to examine the interrelationships – an ambition of “multimodal AI” – is both exciting and daunting. The brilliant Pfizer data scientist Subha Madhavan and I explored the promise and challenges of this explosion in measurable parameters in our recent perspective on AI and drug development, here.
The science of aging has also seen remarkable progress (see the latest instantiation of the ongoing “hallmarks of aging” report in the April 17, 2025 issue of Cell), and of course Dr. Topol’s Super Agers (my WSJ review here). Our increasing ability to relate measurable changes to rates of aging – so-called biological clocks – is remarkable, even if, as Open Evidence reminds us, “these tests remain research tools and are not yet validated for clinical decision making.”
Among the most important advances in the study of aging has been recognition of the role of chronic low-grade inflammation as common driver of many chronic diseases of aging. I even asked Open Evidence about the support for this hypothesis and was told that it’s “strongly supported by the medical literature as a central, causal process in aging and the development of multiple age-related diseases.” This mechanism helps explain how known deleterious factors like adiposity and ultraprocessed foods can be harmful, as well as how positive interventions like exercise and sleep can do good.
(Interestingly, a just-published Nature Aging paper suggests the association between chronic inflammation and diseases of aging may not hold true for “Indigenous participants living in non-industrialized or semi-industrialized communities,” as a Nature correspondent Miryam Naddaf explains.)
In my presentation, I reviewed some of the most compelling data around exercise (both physical activity and muscle strengthening), sleep, and nutrition, emphasizing the value of attending to each. I also discussed the motivation behind (and potential risks associated with) the drive for increased, presymptomatic testing, centered on the idea that because chronic diseases of aging develop over time, early identification of vulnerabilities seems appealing.
Existing health and wellness companies, like Tonal, Oura, and Peloton, I told the audience, now explicitly focus on healthy aging. Whoop even created a parameter, “Whoop Age” (and its derivative, “Pace of Aging”) that integrates multiple measurements of sleep and activity.
I told listeners that these platforms offer considerable promise – motivating the improvement of parameters like exercise where the health benefits are supported by strong scientific data. The concern, however, is that these approaches tend to reduce health into a game of metric optimization, distilling the pursuit of health and flourishing to a rank on a leaderboard. In fact, this is exactly the object of the “Rejuvenation Olympics,” which ranks users on the basis of an experimental rate-of-aging score, updated quarterly.
These metric-obsessed approaches to health, as regular TR readers will appreciate, lack two essential components.
Dr. Robert J. Waldinger, Director of the Harvard Study of Adult Development.
First, these platforms tend to overlook or underemphasize aspects of life that are vital for flourishing but difficult to capture on a wearable, such as meaningful relationships with others, time in nature, pursuit of meaning, and absorption in an activity. Multiple lines of investigation, including most famously the Harvard Study of Adult Development (often known as the Harvard Aging Study), have produced the “surprising finding is that our relationships and how happy we are in our relationships has a powerful influence on our health,” explained Robert Waldinger, director of the Harvard study.
As the Harvard Gazette nicely summarized in 2017, the Harvard study found:
Close relationships, more than money or fame, are what keep people happy throughout their lives, the study revealed. Those ties protect people from life’s discontents, help to delay mental and physical decline, and are better predictors of long and happy lives than social class, IQ, or even genes. That finding proved true across the board among both the Harvard men and the inner-city participants.
Health platforms focused on metric optimization also generally overlook the centrality and power of agency – your sense of conviction that you can change your life for the better. As I’ve discussed in TR, and also in Stat, agency is an incredibly powerful concept, representing the motivational currency of behavior change.
To be sure, it’s been challenging for researchers to demonstrate that agency-enhancing interventions can improve health at scale. I am encouraged by data suggesting that physical activity can enhance our sense of purpose, which in turn can motivate more physical activity, and also inspired by the remarkable sense of empowerment that durable weight loss mediated by GLP-1 medicines seems to deliver.
I can imagine several potential ways to move forward:
The key takeaway from my talk: aging appears to be more plastic and malleable than we have long assumed. By:
(1) leveraging measurement technology;
(2) following the rapidly developing science of aging;
(3) utilizing advances in computation (particularly AI); and, most importantly,
(4) embracing a more capacious, evidence-based vision of health and flourishing,
we can aspire realistically to improve health, in a meaningful and substantive fashion, through scalable personal health platforms.
Three recent podcasts – all intrinsically interesting and worth listening to on their individual merits – offer insights that collectively emphasize the importance and amplify the urgency of embracing a more expansive view of health and a more proactive approach to aging.
“Excellence, Actually” co-host Brad Stulberg.
The first, “Excellence, Actually” (originally launched as “Farewell” and recently renamed) comes from three distinguished performance coaches: Brad Stulberg, Steve Magness, and Clay Skipper. Their focus is on delivering the sort of grounded advice that leads to excellence and flourishing, rather than what they describe as “performative nonsense.” Consequently, their message aligns remarkably well with our emphasis on a deeper notion of flourishing, rather than a reductive focus on metric optimization.
Three key takeaways from their inaugural (rebranded) episode are:
A second resonant listen comes from “Freakonomics,” specifically an episode focused on the consequences of an aging population, a phenomenon they recognize is often viewed as burden but which might more appropriately be considered a privilege and an opportunity. Once again, this aligns with the positive and proactive vision of health and healthy aging we’ve discussed.
Key takeaways here include:
Economist Andrew Scott.
VC Katy Fike
Some of the most successful companies with aging … have done it so discreetly that it’s kind of hard to point out who they are. And the exact reason they’re having success is because they’re doing it discreetly, and not so overtly. I think Apple is actually a fantastic example of that, where Apple has really focused on, you know, good design, really good customer service. If you walk by an Apple store, you will often see who’s at the genius bar might skew a little bit older, but they haven’t made this, you know, the help bar for seniors. It’s just Apple. Frankly, even being able to walk into a store in the first place is a very ageless and age-friendly tactic.
A third relevant listen is the final episode of the “The World As You’ll Know It: The Future of Aging,” a short series hosted by New York Times science writer Carl Zimmer (my WSJ review of his recent book, Air-borne, here). The entire set is recommended, and the penultimate episode, featuring an extended conversation with Dr. Topol, offers a particularly useful summary of the current state of the science. But I wanted to call out the final episode, as it extends the message of the “Freakonomics” podcast, encouraging us to reexamine our view of life given the promise of a longer and healthier one.
Highlights include:
Psychologist Laura Carstensen, Director of the Stanford Center on Longevity.
Dr. Jim LaBelle.
Finally, I wanted to share what I thought was unusually insightful perspective offered by Dr. Jim LaBelle, who I happened to be sitting next to at a delightful recent group dinner overlooking the Pacific in Cardiff, California.
LaBelle, who trained as an emergency room physician and is the former Chief Medical Officer of Scripps, has thought with unusual depth about how to integrate the promise of technology with the humanistic essence of medicine.
So much of what LaBelle discussed resonated with me, including his emphasis on the importance of curiosity (for patients as well as physicians), of developing compassion for others and for yourself, and for seeking a greater sense of and awareness of consciousness, presence, and joy.
One reflection of his particularly connected with me, as it captured, with unusual elegance, a view of technology and health that I deeply share: “Can we use technology,” he asked, “to create moments of awakening, small openings where people can see themselves more clearly, become curious, and choose transformation and healing?” A worthy goal, especially for those of us – including me – who see technology not as an end in itself, but as a mechanism for enhanced self-awareness and insight, and a catalyst for healthy behavior change.
While I couldn’t resonate more with the ambitions, perspective, and optimism exuded by Carstensen and others, I also recognize the temptation to get out over our skis, and lose sight of the many very real challenges faced by those growing old today – in particular, the debilitating chronic diseases of aging that Dr. Peter Attia calls “The Four Horsemen” (as TR readers will recall, here).
We also need to recognize that while a healthier lifestyle can meaningfully improve our odds of living longer and better, there remains a huge amount of chance involved, with many factors beyond our control.
I’ve recently emphasized this for TR readers in the context of a recent study demonstrating the potential benefit of exercise in the response of colon cancer patients to chemotherapy, sharing poignant observations from Jennifer Goldsack, a former Olympic athlete who had thoughtfully embraced preventive medicine yet still found herself diagnosed with stage 3 colon cancer.
Dr. Samir Qamar.
Today, I want to encourage you to read a similarly powerful post from Dr. Samir Qamar, a physician-entrepreneur, who shares the story of his late cousin, Aafi.
He writes,
In 2023 Aafi died of lung cancer.
She never smoked, never drank alcohol, and never had a family history of cancer. She exercised, maintained a healthy weight, and was always cheerful.
Her husband, brother, and father, all physicians, were shocked when the stubborn pain in her back ended up being metastatic lung cancer.
When we’re young, it’s easy to feel invincible when our labs are essentially normal. I don’t remember visiting a doctor once in my 20s.
Healthspan, however, isn’t roses and rainbows. Over time, our bodies are exposed to pollutants, chemicals, UV light, and a host of invisible threats.
With age, previously unknown genetic and structural changes begin to happen. Our bodies change. Accidents happen. Surprises happen. Life happens.
The entire thoughtful post is an essential read – and an important reminder.
Note: Useful references and links related to the promise of personal health technology pursuing a more expansive vision of health and flourishing can be found at kindwellhealth.com.
Claire Mazumdar is today’s guest on The Long Run.
She is the founding CEO of Boston-based Bicara Therapeutics.
Claire Mazumdar, CEO, Bicara Therapeutics
Bicara is developing a bifunctional antibody for head and neck cancer. It’s called ficerafusp alfa, and it’s designed to bind with a couple of well-known biological targets, EGFR and TGF-beta. The idea is to block a well-known cancer driver in EGFR, while also making the tumor microenvironment a little less hostile for cells of the immune system. By combining this Bicara medicine with Merck’s pembrolizumab, a drug that releases the brakes on the immune system, scientists hope to create the conditions for a long-lasting, vigorous immune system attack on the cancer.
The company released Phase I clinical trial data at the recent American Society of Clinical Oncology. Bicara looked a group of head and neck cancer patients who didn’t have cancer driven by the human papillomavirus. Researchers found that 15 of those first 28 patients (54 percent) had significant tumor shrinkage, and the median survival time was 21.3 months. That’s good news for cancer patients, and enough to justify Bicara’s plan to advance into a pivotal Phase II/III clinical trial to confirm the finding in a larger patient population.
Wall Street, however, was disappointed by the results, especially compared with a competing bispecific antibody for head and neck cancer from Netherlands-based Merus.
Bicara is fortunate that it hasn’t had to make cutbacks to weather the storm of bearish sentiment in the markets. It raised $362 million in an IPO in September 2024. The company said in its most recent quarterly report that it has enough cash to operate into the first half of 2029.
The biological rationale for the program, recent advances in antibody engineering, the entrepreneurial spirit of Claire and her colleagues, and a deep pool of investors with an appetite for risk are all part of the equation of what makes this sort of progress possible for patients with head and neck cancer.
Now, please join me and Claire Mazumdar on The Long Run.
Aaron Ring, associate profesor, Anderson Family Endowed Chair for Immunotherapy, Fred Hutch Cancer Center
AI won’t revolutionize drug discovery for Big Pharma. They don’t need it.
Pharma has been making remarkable biologic molecules for decades. Not just simple blockers, but a dizzying array of sophisticated therapeutics. Bispecific and multispecific antibodies. T cell engagers. “Masked” molecules that activate specifically in the tumor microenvironment. ATP- and pH-controlled antibodies. Binders to integral membrane proteins like GPCRs and ion channels.
These aren’t lucky accidents—they’re the result of massive long-term investments in research and development that would make most academic departments weep with envy. The global biopharmaceutical industry investment in R&D, across 4,191 public and private companies, was a staggering $276 billion in 2021, according to an analysis in Nature Reviews Drug Discovery.
By comparison, the National Institutes of Health, the biggest source of funding for basic and translational academic research in the US, had a $47 billion budget in 2024.
When a pharma team launches a new drug development program, they build on a basis of shared biological understanding from academic and industry colleagues, and they attack from every angle. The tools in their toolbox are remarkable. Transgenic mice churning out human antibodies. Vast phage and yeast display libraries. High-throughput screening robots testing millions of variants. Computational platforms are useful, sure, but biopharma companies also leverage good old-fashioned medicinal chemistry intuition backed by unlimited resources.
The message is clear: pharma can and will make a drug against any target. For them, AI drug discovery tools are just another arrow in an already overflowing quiver.
Breathless headlines promise that AI will slash drug development timelines and costs. As the legendary drug discovery blogger Derek Lowe has repeatedly pointed out, these claims consistently fall flat. Even if we could design perfect binders instantly (which we can’t do—yet), that barely moves the needle on what makes drug development expensive and slow.
Nearly 90% of drug candidates fail in clinical trials despite having preclinical data compelling enough to advance to the next steps in humans. AI doesn’t accelerate manufacturing scale-up. It doesn’t speed up the months of GLP toxicology studies. It doesn’t shortcut the regulatory maze between a promising molecule and a first-in-human trial. The most elegant AI-designed drug still needs to navigate the same treacherous path from bench to bedside.
So if AI won’t make drug development dramatically faster or cheaper for those who already have the tools, what’s the revolution?
The revolution isn’t about making Big Pharma more efficient. It’s about giving everyone else a seat at the table.
Academic labs and small biotechs are where the truly audacious ideas emerge—the moonshots targeting novel biology that pharma considers too risky. But these groups face a maddening catch-22. Want to work with a premium antibody discovery firm? Prepare to write a check for $200,000 just to start the conversation. Oh, and sign away a slice of your future success through milestone payments and royalty stacks. For most academic researchers living on shoestring budgets, this is a non-starter.
The scarcity mindset, the zero-sum thinking, is literally underpinning the business models for many platform biotechnology companies. They guard their capabilities behind prohibitive paywalls, knowing that academic labs and startups have no other options. The result? The most innovative therapeutic concepts—the ones that could transform how we treat disease—die on the vine because their champions can’t afford the tools to prove them.
AI changes this equation completely.
David Baker, professor of biochemistry, University of Washington; director, Institute for Protein Design
For over 15 years, I’ve watched computational protein design evolve from the sidelines as a wet-lab protein engineer. The field, pioneered by scientists like Nobel Laureate David Baker, has been laying crucial groundwork, developing the algorithms and principles that would eventually transform drug discovery. But for most of that time, these tools remained the domain of computational specialists. The methods were complex, computationally intensive, and required deep expertise to implement effectively.
That’s changed dramatically. Today’s AI-powered platforms have built on those foundational advances to generate designs with experimental success rates that make high-throughput screening unnecessary. We’ve reached the tipping point where computational design isn’t just theoretically powerful, it’s practically accessible.
I’ve experienced this firsthand in my lab, where these tools have already accelerated our work beyond what I thought possible. The impact was so profound that I founded Ariax Bio to ensure every researcher could access this same power.
At Ariax, we started with BindCraft, a state-of-the-art AI-powered protein design tool developed by Martin Pacesa and Bruno Correia at EPFL. I previously described BindCraft as representing a ‘DeepSeek moment’ in drug discovery: an open-source tool that matches or beats proprietary platforms while remaining completely free to use. Through our web platform, protein design jobs with BindCraft take less than a minute to set up and are completed in hours. No permission needed. No royalties owed. No IP entanglements. Users only pay for compute time—less than AWS charges and orders of magnitude less than they would pay a CRO for conventional protein-discovery approaches.
This shift fundamentally rewrites the economics of early-stage drug development. One of the steepest value inflection points in any therapeutic program happens at pharmacologic proof of concept—that magical moment when you prove your hypothesis actually works in a living system.
Previously, reaching this milestone required either massive institutional resources or painful compromises. I’ve watched brilliant researchers shelve transformative ideas simply because they couldn’t access the tools to test them. The gap between “compelling hypothesis” and “testable compound” was too wide to bridge.
Now? An academic lab can go from target identification to designed binders in days. A startup can iterate through multiple approaches for the cost of a single traditional screening campaign. Most crucially, they can walk into investor meetings not with PowerPoint promises but with IND-ready molecules less than a year from the clinic.
This isn’t about competing with pharma on their terms. It’s about changing the terms entirely. As AI leaders like Sam Altman like to say, “You can just do things.”
Big Pharma has burned through hundreds of billions in R&D dollars by stampeding toward “de-risked” targets. The entire industry chases the same “validated” biology, competing to make incrementally better versions of existing drugs. It’s a rational strategy when you have shareholders to please and billion-dollar infrastructure to feed.
But breakthrough medicines rarely come from playing it safe. They emerge from researchers willing to challenge dogma, to pursue mechanisms others dismiss as too speculative. This is where the underdogs enter the picture. These are the academic labs and small biotech companies unencumbered by institutional inertia. They can move nimbly to seize upon a new technological shift.
AI-powered drug discovery hands these risk-takers the tools they need to prove their wild ideas actually work. We’re entering an era where the limiting factor isn’t the ability to make drugs, but the audacity to imagine new ones. Where a graduate student’s insight can become a clinical candidate without navigating a gauntlet of discovery platform companies and their lawyers.
In my introduction to Ariax, I asked: “What happens when anyone can make a drug?” Let me provide an answer. It means exponentially more attempts at genuine moonshots. A vast expansion of the therapeutic landscape. When barrier-to-entry collapses, conformity collapses with it. Drug discovery is about to get weirder. And that’s exactly what medicine needs.
AI won’t make drugs 10x cheaper or deliver them 10x faster. It will make our drug pipeline 10x more innovative.
At Ariax, we’re building the infrastructure for this future. Not because we think AI will make drug development easy—it won’t. But because we believe the best ideas for new medicines can come from anywhere. And now, finally, anyone can act on them.
Aaron Ring is an associate professor in the translational science and therapeutics division at Fred Hutch Cancer Center, and the Anderson Family Endowed Chair in Immunotherapy.
Luke Timmerman, founder & editor, Timmerman Report
Every thriving biotech hub can trace its origins to one or two outstanding scientific institutions. But every thriving region can also trace some of its success back to community leaders.
These are people who attend boring night meetings. They aren’t household names. They’re fine with that.
These people were especially common in America after World War II. They laid down the physical infrastructure and social norms for those of us who came next.
One of these people in Seattle, where I live, was named Jim Ellis.
Jim Ellis
Ellis died six years ago at age 98. He was a named partner at one of Seattle’s top law firms, Preston Gates & Ellis. He worked with William Gates Sr., Bill’s dad. The firm today is known as K&L Gates.
But that’s not why we remember Jim Ellis.
When he was a up-and-coming lawyer, Lake Washington, a freshwater jewel linked to Puget Sound and the Pacific, was full of sewage. People at the time said the water was like “split pea soup.” Various government fiefdoms and unrestrained private land developers contributed to it. It was a mess. Fingers were pointed.
Ellis got involved. Behind the scenes, he brought his energy and creativity to the task of herding the necessary cats to clean it up.
But there was more. The Seattle region was growing beyond its natural resource-based economy – logging, fishing, the seaport. Boeing was emerging. Newcomers were coming. The region needed to think about how to manage the growth intelligently.
Highways needed to be expanded. Parks, trails, public swimming pools and youth centers needed to be built and upgraded. It was going to cost money. Ellis mobilized community support for a series of bond initiatives in the 1950s and 1960s that were collectively known as “Forward Thrust.”
All of this was happening in tension with the natural splendor of the Cascades. Millions of acres of forest needed to be preserved for wildlife habitat, for outdoor recreation, for clean air and water, and to preserve natural beauty. The competing interests between economic growth and environmental preservation needed to be held in balance.
Ellis thought about common interests, the common good. By the early 1990s, he put it all together with his greatest achievement — the Mountains to Sound Greenway. It’s 1.5 million acres of preserved land between Ellensburg, on the east side of the Cascades, stretching to Seattle in the west.
I first saw it as a 21-year-old kid from Wisconsin. It was Memorial Day weekend of 1997. I was excited to start a summer reporting internship at one of the nation’s great regional newspapers – The Seattle Times. I had driven my rusty Pontiac 2,000 miles across the Great Plains, long stretches of Montana, and the arid Columbia River basin.
Then came the mountains. They were covered in Evergreen trees. Alpine lakes shimmered.
From Snoqualmie Pass to Seattle, for 50 miles, it kept going. No strip malls or tacky billboards. People lived in the suburbs east of Seattle, the foothills of the Cascades. But the trees were everywhere, swallowing you up. Nature felt big. Individual people felt small.
This seemed like a great place to live, to explore, to build a career.
For years, I knew nothing about the history of the Mountains to Sound Greenway. Maybe a decade ago, I learned for the first time about Jim Ellis. There was no statue to the man. When he died, I looked for more information, but there wasn’t much. Recently, I found this touching tribute published in 2021 by the Trust for Public Lands.
It’s hard to imagine what Ellis was up against in his day. Think of the vision and tenacity it must have taken with all the federal, state, and private landowning interests. A lot of people with different viewpoints needed to rally around a shared vision.
Ellis wasn’t in it for money or ego. He never ran for public office.
One secret to his success was his philosophy on how to spend his time. He spoke of a one-third/one-third/one-third way of life. One-third was for professional work, one-third for family, and one-third for community.
Where did this philosophy and drive come from? It’s hard to say for sure. But Ellis’ brother died in World War II in 1945. That, according to the Trust for Public Lands, lit a fire in him to honor his brother’s memory. I also have a hunch that the community work, and the family time, helped energize him and make him even more effective professionally. It could have been a virtuous cycle.
Ellis was on my mind last weekend, when I took a small group of biotech people on a hike up Mailbox Peak. It’s a 4,800-foot peak near North Bend, smack in the middle of the Mountains to Sound Greenway.
Around Noon, there were about 20 people on the summit when my small group arrived. Most were in their 20s and 30s. The skies were sunny and clear. You could see snow-capped peaks more than 100 miles away.
Two young people we met on the hike happened to be from the biotech community. A postdoc on my team, Aleena Arakaki, wasn’t surprised. It’s part of what draws young scientists to the Fred Hutchinson Cancer Research Center – the chance to occasionally get away, to clear the head, get a little exercise, maybe get a beer afterwards with lab friends and colleagues.
Seattle’s biotech community exists because of decades of public investment in science at the University of Washington and Fred Hutch. But it also thrives today because we have such amazing quality of life in the Northwest that continually attracts people from around the world.
For that, we can thank unsung heroes like Jim Ellis.
This also makes me wonder: Who are the people doing similar things in Boston, San Francisco, San Diego, Philadelphia, Los Angeles, Chicago, Raleigh-Durham, New York, New Jersey and elsewhere?
Who laid down the critical scaffolding that made it possible for those regions to thrive?
Who’s continuing this work today?
There are people out there doing this hard and thankless work to strengthen our communities. Let’s show a little respect. Maybe get involved personally. It’s meaningful work, and it can be lasting work.
Please subscribe and tell your friends why it’s worthwhile. Quality journalism costs money. When you subscribe to Timmerman Report at $199 per year, you reward quality independent biotech reporting, and encourage more.
David Shaywitz
While medical advances have afforded us the luxury of longer lives, we now spend many of our later years coping with the ravages of chronic illnesses of aging — cardiovascular disease, type 2 diabetes, neurodegenerative conditions like Alzheimer’s, and cancer. Many of these conditions seem linked to long-term exposure to low grade systemic inflammation, a pathological process known as “inflammaging.”
Because these diseases often take decades to emerge, there’s a conspicuous opportunity to prevent them (to various degrees) by addressing the inciting chronic inflammation early on, ideally before it even develops.
Because the U.S. medical system concentrates most of its efforts on (and draw most of its revenue from) caring for the sick, rather than on keeping us healthy, many consumers are looking outside the traditional medical system for resources to support their health – particularly as evidence mounts for the utility of so-called “lifestyle” approaches such as exercise, diet, and sleep.
Interest in more aggressive monitoring of aging, as well as the development of more and often better measurement tools has also led to a proliferation of testing companies like Functional Health and Lifeforce, even as the clinical utility of such testing has not yet been well-established.
Consequently, a remarkable number of consumer-focused companies, ranging from wearable manufacturers like WHOOP and Oura to fitness platforms like Peloton and Tonal, have positioned themselves in the personal health space. Many focus explicitly on enabling consumers to optimize meticulously a range of parameters thought to be associated with health. Even physician-prescribed medicines like GLP-1s are often embedded in programs that offer customized behavioral support and designed to maximize long-term results.
The dominant model – illustrated in the figure below – treats health as a quantitative function of measurable metrics and encourages users to optimize relentlessly.
The canonical example here may well be longevity guru Brian Johnson’s “Rejuvenation Olympics,” where participants are scored every three months based on their DunedinPACE score, an experimental measure of the rate of biological aging, and then ranked publicly on a leaderboard (with Johnson proudly in first place).
There’s much to admire in this approach, which borrows from familiar methods for continuous improvement. And many companies in this space are genuinely impressive. Peloton, for example, motivates users to move. WHOOP encourages attention to not just activity but also to recovery.
Still, this vision of health tends to fall short in two critical ways.
First, it often overlooks critical human experiences – like connection – that are difficult to quantify but vital for flourishing. A more expansive conception of health is needed.
Second, and even more fundamentally, it tends to ignore the foundational, catalytic role of agency in improving health.
Agency, as described by Martin Seligman, the father of positive psychology, is the belief that you can shape the world for the better. I’ve described agency as the “motivational currency of health, the ATP of successful behavior change.”
Critically, enhanced agency developed in one domain – which I’ve called the “agentic dividend” – can energize progress in other areas, creating a virtuous cycle of health. See figure below.
Seligman and colleagues have found strong correlations between agency (or optimism – he often uses the terms interchangeably) and improved health. As he explained to Yale Professor Laurie Santos on her “Happiness Lab” podcast, “Pessimism is probably between smoking two and three packs of cigarettes a day as a risk factor. And optimism seems to give between six and eight years of extra life, probably about twice as important as exercise.”
Encouragingly, Seligman also argues that optimism is teachable, through techniques known as positive psychology interventions (PPIs), such as cognitive reframing.
Yet despite compelling associations, we’ve seen limited evidence that these interventions meaningfully move the health needle at scale. That’s the gap we now have an opportunity to address.
Our current moment offers important opportunities to deliver at last on this promise.
Companies that already operate at scale and support meaningful achievements – like strength gain or improved recovery – can do more to highlight the agentic component of these wins. The opportunity is to infuse these achievements with a sense of agency – helping users recognize success as self-driven progress, not just score attainment. GLP-1 programs offer a compelling case study here: the success they unlock often catalyzes broader life changes, not because of weight the weight loss alone, but because they restore belief in what’s possible.
A focus on agency also creates on-ramps for those alienated by a hyper-quantified wellness culture. For many, the relentless emphasis on metrics and dashboard feels off-putting or exclusionary. By recognize the health impact of connection, intellectual engagement, and time in nature, for example, we can reach people where they are – and help build reservoirs of agency that power other, health-promoting behaviors.
Advances in generative AI may offer a scalable way to deliver effective PPIs, such as cognitive reframing, in short, supportive, bursts. Startups like Lore Health and Slingshot_AI already seem to be exploring this space. The goal isn’t ethereal new insights – it’s palpable, pragmatic real-world behavior change.
Consumers – motivated to live well, empowered by better information about aging, and supported by improving measurement technologies and compelling platforms — are increasingly looking beyond the traditional healthcare system for ways to support their health. To meet this moment, consumer health platforms must embrace a vision of health that goes beyond metric optimization. By cultivating agency, the motivational engine of behavior change, these platforms can help improve not only the length of our lives but also the quality of our days.
To continue this discussion, I’ve set up a workspace (kindwellhealth.com) and a dedicated account on X (@KindWellHealth) that focus on the opportunities and challenges of centering health around agency, and the role emerging technologies might play in enabling these efforts at scale. Links to key readings can be found here as well.
Please subscribe and tell your friends why it’s worthwhile. Quality journalism costs money. When you subscribe to Timmerman Report at $199 per year, you reward quality independent biotech reporting, and encourage more.
John Rinn is today’s guest on The Long Run.
John is the Leslie Orgel and Marvin Caruthers professor of RNA science at the University of Colorado in Boulder. His research is focused on long non-coding RNAs.
John Rinn, professor of RNA science, University of Colorado; co-founder, Lincswitch Therapeutics
This is the vast expanse of the genome that doesn’t contain genes with code for making proteins. Researchers once dismissed this area of the genome as “junk DNA.” Now it’s sometimes filed under the broad header of the “dark genome” — a place with a lot of potential to discover basic underpinnings of health and disease. They are often involved in gene expression, especially during early development, and increasingly seen as regulators in basic cell processes.
For some basic terms and an overview, I’d encourage listeners to go read a paper in Nature Reviews Molecular Cell Biology from January 2023.
There is a lot of basic science here – the curiosity-driven, how-stuff-works line of research that sometimes takes us in unexpected directions. But some of this work already has clear industrial application.
John is a co-founder of a startup called Lincswitch Therapeutics which seeks to “switch” a problematic long non-coding RNA or lnc-RNA, into a healthier state. Triatomic Capital, SALT, BlueSpruce and Mossrock are among the company’s early investors.
John got access to a lot of the early-generation tools, and people who knew how to use them, thanks to support during his postdoc days from the Damon Runyon Cancer Research Foundation. As a big supporter of Damon Runyon through my Timmerman Traverse expeditions, I’m always curious to hear what alumni are working on to push the frontiers of medicine.
Now, please join me and John Rinn on The Long Run.
Please subscribe and tell your friends why it’s worthwhile. Quality journalism costs money. When you subscribe to Timmerman Report at $199 per year, you reward quality independent biotech reporting, and encourage more.
Timmerman Traverse is looking for a few good men and women.
Opportunities are here for people who are physically fit, enjoy nature, thrive in community, and who want to roll up the sleeves for worthy causes — including cancer research, sickle cell disease and fighting poverty.
Here’s how to get involved.
This 2-day expedition will be in the North Cascades of Washington state Aug. 17-20, 2025. Back-to-back day hikes that will add up to 7,000 vertical feet of gain over about 20 miles. Marvel at 360 degree views of the American Alps. Each participant has committed to raise a minimum of $35,000 for Life Science Cares. This team has already raised $600,000 toward its $1 million goal. 1-2 spots remain. If you’d prefer to donate and cheer these bold hikers from the sidelines, click here.
Timmerman Traverse for Life Science Cares 2024. Pacific Northwest.
An extraordinary single-day hike on Aug. 21, 2025 for people with intermediate to advanced-level fitness and outdoor experience. 20 miles of hiking, 4,700 vertical feet gain. $10,000 donation to Life Science Cares required. Join this trip and enjoy some of the most spectacular scenery in North America. 1-2 spots available.
Dave Melville, CEO of The Bowdoin Group, coming up Aasgard Pass in The Enchantments of Central Washington.
A new single-day program on Oct. 4, 2025 for Damon Runyon Cancer Research Foundation. 13 miles of hiking, 4,700 vertical feet of gain on the Katahdin North Loop. Hike up to the terminus of the Appalachian Trail and enjoy fall colors. $10,500 donation required. Intermediate to advanced-level fitness and outdoor experience required. 6-8 spots available.
The standard 7-day Kilimanjaro expedition. Feb. 7-18, 2026 with door-to-door international travel. Peak elevation: 19,300 feet. A once-in-a-lifetime experience on the most iconic peak in Africa. $50,000 fundraising minimum. Team goal: $1 million for high-risk / high-reward cancer research. Physically fit beginners eligible. 10-15 spots available. Companies may nominate a delegate sponsored in full.
L to R: Henry Kilgore, Luke Timmerman, and Will Chen on Kilimanjaro, Feb. 2024. Henry and Will are Damon Runyon Fellows who participated in the inaugural Timmerman Traverse for Damon Runyon on Kilimanjaro, Feb. 2024.
This isn’t a Timmerman Traverse program, but I’m serving as a volunteer guide in Colorado Sept. 24-28, 2025 to support Sickle Forward. It’s an excellent organization devoted to improved screening and treatment for sickle cell disease around the world. For more information on how to support this program, click here.
Timmerman Traverse for Sickle Forward on the summit of Kilimanjaro, Sept. 16, 2024.
Timmerman Traverse has raised more than $13.5 million since 2017 to alleviate suffering from cancer, sickle cell disease, and poverty. More than 180 people have participated all over the world — experiencing natural beauty, physical challenges, camaraderie, and the joy of giving.
Interested?
Send me a brief note with the following:
Let’s get out there together.
David Shaywitz
This week featured a rare crossing of the streams, as the buttoned-down world of cancer research met the buzzy world of exercise and wellness. One result: a randomized controlled study of exercise in 889 cancer patients published in the New England Journal of Medicine (NEJM), and accompanied by a torrent of enthusiastic coverage in the popular press. Another: the publication of two important and thoughtful commentaries about this study, analyses that are the focus of today’s column.
The study, which ran from 2009-2024, examined the impact of a structured exercise program (compared to a health information pamphlet, essentially) on patients with colon cancer, following surgery and adjuvant chemotherapy. The patients were randomly assigned to one of the two groups and followed for a median of 7.9 years.
The headline result was that the exercise group demonstrated significantly better overall survival (90.3% vs 83.2%) after 8 years), as well as significantly better 5-year disease-free survival (80.3% vs 73.9%). Phrased differently, the exercise group demonstrated a 28% reduction in the relative risk of disease recurrence, and a whopping 37% reduction in the relative risk of death.
As the authors point out, the apparent magnitude of effect of exercise on cancer, in this context, is “similar to that of many currently approved standard drug treatments.”
This extremely encouraging result reinforces an emerging view of exercise as a remarkably powerful medical intervention. As I discussed in my recent WSJ review of Super Agers, by Dr. Eric Topol,
“Nothing surpasses regular exercise for promotion of healthy aging,” Dr. Topol writes, calling it “the single most effective medical intervention that we know.” If you came up with a drug that delivered all the health benefits of exercise, he says, “it would be considered a miracle breakthrough.”
I’ve also examined in TR the unreasonable benefit of a modicum of exercise, particularly going from none to some, in projected years of additional life.
Not surprisingly, on both social media and traditional media, the response (which I shared) was generally one of delight, a sense that a compelling hypothesis has now been validated in a rigorously conducted RCT published in the august New England Journal of Medicine.
Not so fast, says Dr. John Mandrola, a cardiologist, exercise enthusiast, and thoughtful, occasionally contrarian healthcare commentator.
Writing in his “Sensible Medicine” blog on Substack, Dr. Mandrola essentially presents what might be called the “Reviewer 2” rebuttal (if Reviewer 2 was an extremely savvy clinical trialist), offering a list of the ways in which the study seems to fall short of its ambitious claims. His commentary offers a valuable read for anyone interested in the critical assessment of clinical trials.
Dr. John Mandrola
Among his objections: the effect size (37% reduction in all-cause mortality) lacks face validity – it’s unreasonably large, he argues, suggesting that something is amiss. (While it seems a tad circular to argue a result can’t be true because it’s excessively different from what you expected, it’s also a pragmatic sense check, and one he argues the study fails.)
He was also underwhelmed by the impact on fitness-associated parameters; if the exercise program was so impactful, he asks, why didn’t the subjects in that group demonstrate a lower Body Mass Index and a lower waist circumference that the control group? He was unimpressed by the slight differences between the groups observed in the six-minute walk test.
The study authors, in contrast, argue that the difference between the groups – in the range of 5.2-7.4 MET-hours per week is meaningful, “equivalent to about 1.5-2.25 hours per week more of walking at 3 mph (approximately 3.3 METs).” They note that the subjects in the control group also increased their physical activity, although not as much, which suggests the benefits of exercise might be even greater if comparison was made to patients who remained sedentary.
Dr. Mandrola also pointed out that while we think we’re looking at exercise, we may instead be looking at attention, observing that the “structured exercise group received an incredible amount of intervention in both behavioral modification and exercise.” In other words, we may just be observing a manifestation of the Hawthorne effect, in which subjects change their behavior when they are being observed.
Again, the authors anticipate this objection and try to diffuse it by pointing to examples of cancer studies in which subjects also received considerable attention, in the context of nutrition or lifestyle interventions, yet these researchers “did not report a survival benefit.”
However, I’m not sure these examples – involving different types of cancer – effectively refute Dr. Mandrola’s point.
A related thought going through my mind when reading the paper was whether at least some of the beneficial effect might be attributable to an enhanced sense of agency experienced by the subjects in intervention group. I’ve previously discussed in TR the concept of the agentic dividend, in the context of GLP-1 treatment.
In the case of the present NEJM study, the benefit might accrue not just from the enhanced attention, but also from the positive effects of constructively engaging in exercise itself, which can set up a virtuous cycle — a pattern discussed in this 2021 paper, and nicely covered by Gretchen Reynolds in the New York Times.
Dr. Mandrola raises several other objections as well.
Yet his most valuable point may be the importance of criticism itself, even – especially! – when, as a reader, you desperately want to believe the argument the paper is making.
“The story is delightful,” Dr. Mandrola acknowledges. “But liking the conclusion is not a reason to stop thinking.”
Amen.
While Dr. Mandrola focused his attention on the possibility the conclusions may be wrong, Jennifer Goldsack worries about the consequences if the conclusions are right – in particular, the implications of the study for cancer patients like her.
Jennifer Goldsack is the CEO of the Digital Medicine Society (DiMe) and a former Olympic rower who has publicly discussed her journey with Stage 3 colorectal cancer.
Goldsack poignantly explains that when she first heard about the NEJM study, her reaction was “let’s celebrate. Anything that helps improve lives and reduce deaths is unequivocally good news.”
Jennifer Goldsack
But she writes that upon further reflection, her “thinking shifted… because I started to feel overwhelmed by the implied link between my behaviors and my survival.”
She continues,
One of the first questions I asked my oncologist after my late-stage colorectal cancer diagnosis was, “Is this my fault?”
I’ve had every genetic test you can run, and they all came back negative. As in, I should’ve made my millions selling my eggs in my 20s… bloody good breeding stock over here! 🐎
I’ve eaten clean my whole life. I’ve been active my whole life… as in, former world-record-holder active. I sleep like a champ. I’ve rarely been stressed beyond what can be well managed using the winning strategy of fruity language and regular dance breaks. I don’t even have a cavity (sidebar… shoutout to fluoride in drinking water!).
And yet, here I am.
She continues,
If my cancer comes back, will it be because I didn’t exercise enough? Didn’t eat well enough? Didn’t rest hard enough during chemo? Didn’t do something I was *supposed* to do?
There’s a specific kind of shame that comes with a diagnosis that gets lumped into the “lifestyle” category. When there’s no clear external cause, the only place left to look is inward.
And I know I’m not alone.
As we enter this MAHA era, where the administration is (rightly!) focused on nutrition, movement, and prevention, we have to be mindful. These are incredibly important strategies, but how are we making sure that we’re not creating a culture where getting sick means you’ve failed?
As she bluntly explains, “sometimes, shit just happens. Sometimes we do everything right, and it still goes wrong. We control what we can, but the reality is that it’s impossible to control everything.”
Goldsack powerfully speaks to the fine line between empowerment and blame, between the promise of marshalling all your physical and cognitive resources to fight a disease and the fear that if the illness triumphs it reflects a personal failing, a sense that in some way, you didn’t try hard enough.
A remarkably similar tension developed in the field of positive psychology, as the discipline’s founder, University of Pennsylvania professor Martin Seligman, describes in Flourish.
He explains that a number of studies “converge on the conclusion that optimism is strongly related to protection from cardiovascular disease,” even after “correcting for all the traditional risk factors.” He adds that “high optimism” protects people compared to average levels of optimism and pessimism, while highly pessimistic people fare worse than average.”
A similar result was observed in an experiment in which the optimism of healthy volunteers was assessed, then they were exposed to a standardized amount of cold virus via a rhinovirus injection squirted up the nose. The remarkable result: optimistic people were the least likely to come down with a cold, while pessimistic people were the most likely, and those in the middle fell in between.
While Seligman says he was always cautious about overly generalizing from these studies – particularly to conditions such as severe cancer — the idea that you can overcome disease with positive thinking began to spread in popular culture. It also prompted a profound backlash.
Leading the charge was Barbara Ehrenreich and her book, Bright Sided: How the Relentless Promotion of Positive Thinking Has Undermined America. (In case the point was missed, the British version of her book was entitled, Smile or Die.)
This takedown was motivated by Ehrenreich’s experience as a cancer patient, where (as Seligman describes it) “well-meaning healthcare workers” told her “that her breast cancer could be relieved if only she were a more positive person.”
As Seligman subsequently wrote to Ehrenreich,
[C]ardiovascular disease, all-cause mortality, and quite possibly cancer are not a function of fake smiling, but rather of PERMA [note: I’ve discussed for TR readers here, here], some configuration of positive emotion, plus meaning, plus positive relationships, plus positive accomplishment.
He noted in his letter to her that her “book – as uncongenial as I find it – is surely a meaningful and positive accomplishment.”
It’s instructive to appreciate that while Seligman may focus on the connection between a set of positive characteristics and a patient’s ability to respond to some diseases, it’s easy for much of the nuance to get lost in popularization.
While the NEJM study authors likely wouldn’t suggest that the cancer patients who experienced recurrence simply didn’t try hard enough, it’s easy to imagine how a more nuanced message might easily get distorted. By the time headlines or social media posts proclaim exercise as a “cancer drug,” the concern raised by Goldsack — that cancer will be seen as preventable if only you had done more burpees — can land as a heavy burden on patients.
Before we despair, let’s turn once more Goldsack, who concludes her piece with this wise and kind advice:
As we design policies, platforms, and headlines around “taking control of our health”, let’s not forget
1) Knowledge must be paired with compassion
2) Empowerment must come with grace
3) Health outcomes should never be weaponized into shame
Once again: amen.
Please subscribe and tell your friends why it’s worthwhile. Quality journalism costs money. When you subscribe to Timmerman Report at $199 per year, you reward quality independent biotech reporting, and encourage more.
They called it Gold Mountain.
For Chinese in the 19th century, the “gold mountains” of California and North America represented the promise of success and upward mobility. It was their name for the American Dream.
And at a time when America’s appeal to dreamers and strivers around the world is under strain, it’s worthwhile to reflect on the incredible paths of people within our industry.
The non-profit ElevAAte, which supports East Asian American leadership in biopharma, gathered these stories for Asian Pacific Heritage Month. These narratives told in each person’s own words have been edited for clarity and length.
Angela Hwang, CEO-Partner, Flagship Pioneering, and CEO, Metaphore Biotechnologies
Cambridge, Mass.
Angela came to the US for graduate school from apartheid South Africa. She described the turning point that led to her decision to emigrate.
Early in my career I worked at a beer brewery as a microbiologist.
As is customary in many places in South Africa at that time, colleagues would meet up around mid-morning and take a “tea break.” It was a familiar and welcomed part of the day to meet and socialize with your colleagues, one-on-one or in a large group. Generally it was always filled with lively chatter and humorous storytelling.
One day, during a regular tea time, one of my white colleagues proceeded to tell a joke and make fun of my black colleagues.
Silence fell upon the tea room. I remember looking around at everyone, and it was clear that a line had been crossed.
Yet what was shocking was everyone’s reaction—or more accurately, lack of reaction.
My black colleagues tried to make light of the situation and responded back with polite humor even though they had clearly just been insulted. And everyone else just continued the banter, like nothing had happened.
At that moment I asked myself, “Has this been going on all this time and I didn’t notice or is this building up, and I have now reached my breaking point?” I was 24 at the time. And that’s when I decided that I needed to find a new home in a new country.
Connie Batlevi, Senior medical director, Genentech
Short Hills, NJ
Connie was born in Hong Kong, but after the death of her father, her mother moved them to Boston and worked at restaurants. Her mother’s chance encounter on a train changed their lives.
It’s a very beautiful love story actually. My mom was taking the MBTA subway in Boston. It was very slow, a little bit clunky, and there were some hooligans on a late-night train.
There was a uniformed officer who was taking the train home, and she’s smart, she’s savvy so she goes to stand next to him.
And he started a conversation with her broken English–because she didn’t really learn a lot of English. But he was trying to teach her English. He wanted to protect her.
He was smitten, and he missed his train exit and took her all the way home.
They exchanged numbers, and a short while later, he became our stepfather and gave us a childhood filled with memories like riding on the lawn mower or the back of his red F-150.
David Chang, CEO, Allogene Therapeutics
Los Angeles
David was 12 years old when his parents brought them from Korea to Los Angeles. After being inspired by professors like Tam RajBhandary at MIT, he got an MD-PhD and went into oncology.
I was at UCLA for about eight years. I was tenured, and in terms of grants and things like that, I was doing very well.
But when I turned 40, that’s when I said, “I can just continue doing what I’m doing, or I want to try something different.”
I chose the latter.
I didn’t want to have this feeling of not having at least explored what it was like outside the academic environment.
And as it happened, at that time, academic discovery translating into drug development, as well as people moving from academia to industry–although it was relatively uncommon–it was happening.
So that really gave me an opportunity to explore. That first job that I took – technically I was on sabbatical from UCLA. And after the sabbatical was done, I decided to stay with a company that I joined, which was Amgen back in 2003.
If you had asked high-school-me about biotech, I would have said, “What? What are you talking about?”
At that time, the focus was to be a good student and either pursue medicine–I mean, those are the common sort of professions that a lot of Asians pursue–or go more in the science and technology-related areas.
Business and all those things weren’t really what my parents were talking about.
Aileen Pangan, VP and Therapeutic Area Head, Immunology Clinical Research, Merck
Boston
Aileen moved to the US from the Philippines for residency and fellowship. Though she had intended to return to Manila, events during her training led her in a different direction.
When I was a medical resident at Rush University Medical Center, I represented the hospital at the American College of Physicians Illinois Chapter Clinical Vignette competition.
The year before, the person who won first place presented her case in a poetic type of way. The presentation could be creative.
I had an interesting case of amyloidosis, and I decided to sing it to the blues.
One of my chief residents was a musician and gave me a cassette tape of background blues rhythm.
I won the competition and was asked to present the case at Grand Rounds at Rush.
I thought to myself, how wonderful that I can combine my love of medicine with my love of music. That was when I got the sense that in this country, I have the opportunity to do something unique. Doing something different—and doing it well—can be a rewarding experience.
It was also when I presented the winning case at Grand Rounds that my future husband first saw me.
Leo Qian, Co-Founder, VP of Discovery Research, Entrada Therapeutics
Boston
Born in China, Leo was the first in his family to go to college and went on to Ohio to pursue a PhD. When he was wrapping up his graduate work, he grappled with whether to turn his academic work into a company.
At that time, the other option was to become a senior scientist at a pharma company. So I could have gone to a job where I would get paid every single month no matter what I was doing or I could take a leap of faith and do this.
The specific thing I remember was on a road trip to visit friends in Cleveland with my wife. We were driving in my 1997 Pontiac GT—I don’t know why I bought that car! I spent so much money fixing it.
On the way back to Columbus, I was just debating whether I really should do it or I should just take a safer approach and become a senior scientist where I will get a paycheck.
So my wife told me, “You should just do it. Even if you fail, you’ll learn something. You can afford it, you are so early in your life. You can always get a job any time you want.”
She said, “You know in the worst case, I will make a living for the three of us.” At that time, my older daughter had been born. “I make a living”–which was $55,000–“we can survive.”
That kind of pushed me to do it.
I really believe the immigrant experience shapes your ability to become an entrepreneur. Starting a company is hard and sometimes scary, but it’s still easier than figuring out how to build a life in a completely new country. If you can do that, you can do anything.
Ethan Weiss and Josh Lehrer are today’s guests on The Long Run.
Ethan is the co-founder and chief scientific officer of South San Francisco-based Marea Biosciences. Josh is the CEO.
Ethan Weiss, co-founder and chief scientific officer, Marea Therapeutics
They are seeking to blaze a new trail with a drug to reduce the risk of cardiovascular disease and type 2 diabetes. It’s a monoclonal antibody aimed at ANGPTL4. There are people with a mutation of the gene who have considerably lower levels of triglycerides and remnant cholesterol. The idea is for the drug to accomplish a similar task – hit ANGPTL4, lower a person’s triglycerides and remnant cholesterol, and reduce the risk of heart attack, stroke, and death. That’s the big idea.
Marea was founded by Third Rock Ventures and has raised $190 million in a couple of venture rounds. The company recently presented clinical trial data, and published the results in The Lancet, showing it can reduce triglycerides and remnant cholesterol by more than 50 percent. It’s now being prepared for a bigger randomized, placebo-controlled Phase 2b study designed to answer whether this really has potential to be the next big thing in cardiovascular disease.
Josh Lehrer, CEO, Marea Therapeutics
Ethan and Josh are both physicians and have a freewheeling conversational banter that comes from knowing each other for a long time. They both happened to participate in the Timmerman Traverse for Life Science Cares in 2024, in which they cracked jokes, bantered, and had a fun time in the outdoors with fellow biotech executives.
I remember mumbling a note to myself – after their sore legs feel better, be sure to invite those guys on The Long Run.
Here it is. I hope you enjoy this conversation about the future of cardiovascular medicine.
