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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.
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.
Peyton Greenside is today’s guest on The Long Run.
Peyton Greenside, co-founder and CEO, BigHat Biosciences
Peyton is the co-founder and CEO of San Mateo, Calif.-based BigHat Biosciences. The company was started in 2019 to build on advances in synthetic biology and machine learning to design antibody drugs with a variety of different properties, faster.
The company has gone on to raise more than $100 million in venture capital and struck partnerships with a handful of large pharma companies, including AbbVie, Johnson & Johnson, Amgen, Merck, and most recently Eli Lilly.
BigHat’s drug candidates are all in preclinical development. Its focus is on cancer and inflammatory and immune disorders. Like anything else in biotech, the proof of the value of the technology platform will be determined by results from these medicines in clinical trials.
Now, please join me and Peyton Greenside on The Long Run.
David Shaywitz
Consumer health and wellness is experiencing a flurry of activity.
The lab testing company Function (motto: “It’s time to own your health”) acquired Ezra, a whole body MRI company promising “the world’s most advanced longevity scan.”
Oura, maker of the popular smart ring, recently added an integration for continuous glucose measurement as well as the ability to calculate meal nutrition based on a photo. Oura also hired Dr. Ricky Bloomfield as its first Chief Medical Officer; Dr. Bloomfield had previously served as Clinical and Health Informatics Lead at Apple, and is known for his expertise in health data interoperability.
Meanwhile, Oura competitor Whoop, maker of a smart band, just announced the latest versions of its device, with the ability to monitor blood pressure, ECG, and to assess what it describes as a measure of biological age, which it calls “Whoop Age.” Whoop now says it seeks to “unlock human performance and healthspan,” enticing users with the pitch, “Get a complete picture of your health.”
Notice a pattern yet?
What unites these approaches and so many others, as the industry newsletter Fitt Insider (FI) recently observed, is they reflect an attempt to generate a “personal health OS,” intended to “give individuals agency over their well-being,” and more generally, wrest control back from a health system that’s often perceived (especially by young adults) as somewhere between useless and obstructive.
Citing a recent Edelman survey, FI reports,
…nearly half of young adults believe well-informed people can be as knowledgeable as doctors, two-thirds see lived experience as expertise, and 61% view institutions as barriers to care.
Fed up with reactive care, many already collect data across wearables, lifestyle apps, DTC diagnostics, and more, but most are siloed. Rolling up, Function is architecting a unified platform capable of generating clinically relevant insights from raw inputs.
FI points to the proliferation of companies like Bright OS, Gyroscope, and Guava Health focused on “day-to-day data management,” as well as startups like Superpower (“Delivering concierge-level metrics minus the PCP”) and Mito Health (a “pocket-sized AI doctor” that “generates comprehensive digital health profiles by merging labs, medical records, family history, lifestyle info, and more.”)
AI seems poised to play an increasingly central role in many of these companies.
FI speculates,
A step further, end-to-end LLMs could close the loop, linking cause and effect, turning insights into actions, syncing with PCPs, and laying the foundation for an AI-powered medical future.
This is a good time to take a deep breath – as well as a closer, more critical look at this vision of consumer-empowered, data-fortified health.
Unquestionably, there’s a lot to embrace here, including in particular:
A tech-enabled approach to health where you have more abundant data about you, that are explicitly in your control, and which could lead to healthier behaviors represents the sort of progress that deserves to be celebrated.
At the same time, when I look at many of these approaches to health, I see two broad categories of concerns.
The first, perhaps more concrete worry, is that, to paraphrase comedian Dennis Miller, “two of [crap] is [crap],” and simply the collection of a lot of data, much of which may be fragile, isn’t sure to translate into brilliant insight, even if the magical power of AI is fervently invoked.
In an especially incisive “Ground Truths” blog post focused on “The business of promoting longevity and healthspan,” Dr. Eric Topol writes that “getting hundreds of biomarker results and imaging tests in an individual greatly increases the likelihood of false-positive results,” a concerning possibility.
I’ve discussed the challenge of false positives here, and get into some of the details around Bayes Theorem (which informs the assessment) here. The OG reference in this space may be this 2006 paper by Zak Kohane and colleagues, in which they introduce the term “incidentalome.”
To be fair, at least some of the proponents of extensive testing recognize the challenge of false positives but feel that the opportunity to collect dense data on individuals over time enables important inflections to be observed, a point Dr. Peter Attia explicitly emphasizes in Outlive; I discuss his “risk-management” mindset here.
Similarly, Nathan Price, a professor at the Buck Institute and the CSO of Thorne, has argued that close inspection (assisted by AI) of rich individual data could identify (for example) opportunities for supplement intervention. These interventions may not make much of a difference on the population level (hence the paucity of persuasive clinical trial data for supplements, as Dr. Topol notes in his latest book, Super Agers – my WSJ review here), but could in selected individuals. (I also discuss Price here, here).
Proponents of the “personal health OS” also might emphasize the presence of tailwinds – the likelihood of improved predictions as measurement technologies continue to get better, denser data become available, and the AI tools become ever-more capable. Perhaps we’re not quite at the point of realizing the future we imagine, advocates might argue, but we’re close enough to start to see what it might look like.
What’s arguably a deeper concern about the model of health we seem to be moving towards is the degree to which it seems to be informed by a rigidly reductive mindset. In this limited, classically managerial (or consultant) view, health becomes simply metrics on a dashboard, an ever-expanding series of parameters that must constantly be measured, quantified, optimized.
A recent, beautiful essay about our evolving understanding of and approach to happiness in the New York Times Magazine by Kwame Anthony Appiah reminds us what we may be missing.
Around the start of the new Millenium, Appiah writes, we entered
the life-hacking, self-quantifying, habit-stacking era of optimization gurus like Tim Ferriss, whose first book, published in 2007, was “The 4-Hour Workweek” — “a toolkit,” in his words, “for maximizing per-hour output.”
Consequently, Appiah continues, the concept of flourishing was decomposed into “modular upgrades” as we refine our “personal operating system.”
Yet it’s essential to recognize, Appiah writes, that “happiness is not an optimization problem,” but something deeper and more substantial.
I reached for a similar point in 2018, in a piece entitled, “We Are Not a Dashboard.”
Observing that the “dashboard has become a potent symbol of our age,” I wrote that “the ideology of big data has taken on a life of its own, assuming a sense of both inevitability and self-justification.”
I continued, “From measurement in service of people, we increasingly seem to be measuring in service of data, setting up systems and organizations where constant measurement often appears to be an end in itself.”
I’m reminded of a favorite phrase from Kate Crawford’s Atlas of AI (my WSJ review here): “The affordances of the tools become the horizon of truth,” a reminder, in this context, that even if we’re awash in tools enabling the measurement and analysis of health data, we must ensure our understanding of health transcends the limits of these tools.
Of course, the point isn’t to go the other way, and reject metrics completely.
As Professor Jerry Muller, author of the brilliant book Tyranny of Metrics, explains, “I can’t see how competent experts could ignore metrics. The question is their ability to evaluate the significance of the metrics, and to recognize the role of the unmeasured.” (emphasis added).
I also spoke to this need in a 2011 piece entitled “What Silicon Valley Doesn’t Understand About Medicine,” writing, ”a novel technology platform that overlooks the integrated needs of patients or underestimates or fails to account for the complexity and messiness of illness as it actually occurs and is experienced by patients (and those closest to them) will inevitably fall short.”
To most effectively meet the needs of patients – including the vitally important goal of preventing or preempting disease so people don’t become patients – it’s essential to embrace the power and promise of emerging technologies, including those enabling the conceptualization of “personal health OS,” while not mistaking this map for the territory (as Alfred Korzybski famously instructed).
It will be essential to establish priorities – in partnership with each patient – and identify a handful of key health parameters on which to focus on; Drs. David Blumenthal and J. Michael McGinnis discuss the topic of “core metrics” thoughtfully in this 2015 JAMA “Viewpoint.”
At the same time, we must hold fast to a vision of health and wellness that expands far beyond the confinement of a dashboard and aspires to something beyond the recursive optimization of metrics (as I recently discussed here). Our approach must be capacious enough to include, authentically value, and meaningfully cultivate other components of a healthy, flourishing life, which might include intellectual captivation, the pursuit of purpose, and social engagement with family, friends, and community.
(Martin Seligman’s PERMA model — positive emotion/joy, engagement/flow, relationships/connection with others, meaning/purpose, and accomplishment — represents a potentially useful framework [see here, here] for expanding our thinking.)
Despite the difficulty, if not utter impossibility, of reducing some of the most important and profound components of health to an easily digested number, we must continue to value and pursue them.
Even as we diligently leverage emerging technology to construct and refine health dashboards, let’s resolve to work towards a more expansive, durable, and meaningful vision of health that exists beyond the sterile syntax of rows, columns, and digits.
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David Shaywitz
For at least a decade, nearly every tech company has promoted their product as facilitating the “democratization” of something – perhaps “data driven medicine,” or “genetic information” or “access to clinical trials” or “digital health” (all real examples).
Like “mission-driven,” “results-oriented,” and “disruptive,” the term “democratization” has become so overused by the tech community that it’s now more of an obligatory buzzword than a meaningful, resonant concept.
However, just when we may have been inclined to tune out, two prominent recent examples remind us of the extraordinary power of technology to empower individuals and drive bottom-up change – hopefully (but not inevitably) for the better.
While experts fretted about the accuracy of the medical information that might be proffered by genAI chatbots like ChatGPT, patients (as journalist and author Carey Goldberg presciently observed) had another thought: “Just give me access!”
As Goldberg wrote in The AI Revolution: ChatGPT-4 and Beyond, anticipating the initial release of an advanced ChatGPT model,
health-related web searches are second only to porn searches, by some counts. Surveys find roughly three-quarters of American adults look for health information online. It’s not hard to predict a massive migration from WebMD and old-style search to new large language models that let patients have a back-and forth for as long as they want with an AI that can analyze personal medical information and seems almost medically omniscient.
This was a savvy observation, applying not only to medicine but also to many other domains, where chatbots like ChatGPT are increasingly an essential source of critical information.
For instance, when I was struggling recently with a connectivity issue involving my exercise bike, the company’s tech support was less than helpful, and painfully slow. Yet ChatGPT provided immediate, insightful suggestions and ultimately an effective solution.
Similarly, when Dr. Benjamin Davis encountered difficulty with a kitchen appliance (an ice machine), he described the problem to ChatGPT. According to Davis, the chatbot “told me what to buy (some sort of thingy). How to fix. Boom I’m a refrigerator tech and we have ice.”
The rapid adoption of tech that’s both useful and ubiquitous, like AI, echoes our recent experience with the phone camera. When it was initially introduced, experts ridiculed the the camera’s (admittedly poor) quality, and confidently predicted it would never replace traditional photography. Yet, the extraordinary convenience of the techology, and its rapidly improving quality over time, resulted in the wholescale disruption of the photography industry, and turned everyone with a mobile phone (which is to say, essentially everyone) into a photographer and potential journalist.
One question, of course, is how this will change the practice of medicine; many doctors were irritated when patients started showing with information from “Dr. Google.” Now, patients can arrive with a far greater level of knowledge and specificity about what’s ailing them. Sure, this may be off base (especially if user prompts have led the AI down a rabbit hole infused with misinformation), but chances are that it’s reasonably well informed, in some cases (many cases?) perhaps even more informed that the treating physician.
Traditionally, the expertise and authority of physicians was based on their exceptional knowledge (as well as, of course, deep experience, and hopefully interpersonal skills supporting a beneficial therapeutic relationship). It’s difficult not to see physician authority challenged by the emergence of savvy AI, particularly as digitally native patients increasingly rely upon it.
But it’s not just physicians whose lives are likely to be changed by ever more sophisticated AI chatbots. Many individuals are finding themselves drawn into extended conversations and interactions with chatbots – exactly as both Harvard’s Zak Kohane and even more so, Microsoft’s Peter Lee both described in The AI Revolution.
The chatbots, for their part, have deliberately encouraged this, not least by a mode of engagement that can be so solicitous that ChatGPT recently had to dial it back, and essentially issue an apology for the degree of “sycophancy.”
It’s fascinating to contemplate that in the not too distant future, we may reflect back fondly, and wistfully to the time we were all immersed in texting and social media, rather than individually absorbed in chats with exceptionally attentive AIs.
But (to borrow Commentary Executive Editor Abe Greenwald’s already iconic phrase), it’s worse than that.
Some companies, including Meta, are taking digital companionship to the next level, developing chatbots that Mark Zuckerberg believes will be “the future of social media,” according to a recent Wall Street Journal article, and which have been endowed with “the capacity for fantasy sex.” (Because TR is a family publication, I’ve omitted disturbing details included in the Journal article.)
To avoid this dystopian future, Kohane says we’ll need “align AI to make us want more interactions with fellow humans.” He acknowledges that it’s “all too easy to align [AI’s] with atomized, consumerized society,” a phenomenon he describes as “inceleration” (a portmanteau of “incel” and “acceleration”), and which traces its intellectual origins, he notes, to Asimov’s The Naked Sun.
Today’s Wall Street Journal features a fascinating example of a bottom-up approach driving meaningful change. The story, by Jesse Newman, describes how the remarkable popular adoption of the “healthy food” evaluation app, Yuka, is apparently driving change from food companies, a degree of responsiveness (or at least awareness) that had previously seemed elusive.
Yuka, Newman writes, enables users to scan the bar codes of food items, and reports back “a score from one to 100 based on nutritional quality, additives and whether it is organic.”
Health and Human Services Secretary Robert F. Kennedy Jr., Newman reports, is a fan of the app, saying that both he and his wife use it.
Large food companies like Conagra have taken notice:
Conagra Chief Executive Sean Connolly said that no one app is the authority over nutrition. “There are a lot of opinions out there,” he said, adding that the opinions that matter most to Conagra are those of its consumers.
But Conagra’s consumers use Yuka, too. Thousands have complained about additives found in the company’s products, using a feature on the app that enables shoppers to shoot off a predrafted message via email or social media asking food makers to remove additives.
Startups and smaller companies have been impacted directly as well:
Jack McNamara, CEO of seltzer maker Tru, said he first learned about Yuka while handing out samples at a Los Angeles Costco. Shoppers began pulling out their phones and scanning Tru’s bar code.
Yuka gives Tru drinks a score of 43 or 48 out of 100—“poor”—in part because they contain stevia and erythritol, sweeteners that Yuka says carry risks. McNamara said he doesn’t fully agree with Yuka’s methodology, which deducts points for drinks that aren’t water, but he takes the app’s input seriously.
“Platforms like [Yuka] are going to have massive repercussions,” McNamara said.
Tru, which he said rates better than many competitors, is trialing new versions of its drinks that would fetch higher scores, using less or none of the sweeteners.
The power of apps like Yuka – like so many other technologies– is a double-edged sword, positive to the extent its evaluation scheme aligns with your own priorities, but worrisome to the extent it might drive substantial change based on popular vibes (demonization of non-organic food, say) rather than rigorous scientific evidence.
David Shaywitz
A recent piece by Nathan Price captures our collective hope for AI in health with unusual clarity, even as there remains impassioned disagreement regarding how close these ambitions are to meaningful realization.
For context, Price is Professor and Co-Director of the Center for Human Healthspan at the Buck Institute for Research on Aging and CSO of Thorne, a company best known for its supplements, and which is now expanding into testing. He’s also the co-author, with Lee Hood, of the 2023 book, Age of Scientific Wellness.
Writing in MedCityNews, Price argues that AI represents a key enabler of “precision wellness.”
AI now makes true biological personalization possible by analyzing an individual’s unique genetic variants, microbiome composition, and blood markers to create lifestyle and nutrition recommendations that traditional one-size-fits-all approaches cannot match. Where conventional wisdom offers standardized solutions, your biology demands precision….
The complexity of the vast number of biological interactions creates a virtually impossible puzzle for individuals to track independently. This is precisely where AI excels — processing vast amounts of personalized data to identify which natural product combinations could work with your unique biological system.
AI enables personalization at scale, delivering both cost-effectiveness and depth of analysis….
The result transforms overwhelming complexity into simple, actionable recommendations tailored to your body’s specific needs, limitations, and opportunities.
These three conceptualizations of AI – its promise as a (1) critical complexity-management tool; (2) vital integrator of ever-larger datasets available through improved measurements techniques including digital/wearables; and (3) personalization machine — are manifesting as key themes across many health domains.
Besides wellness, recent examples include:
Nutrition: “Precision nutrition for cardiometabolic disease,” by Guasch-Ferre et al, in a recent issue of Nature Medicine.
Geromedicine: “From geroscience to precision geromedicine: Understanding and managing aging,” by Kroemer et al, in a recent issue of Cell.
Clinical Development in Biopharma: “AI: An essential tool for managing the burgeoning complexity of clinical development in pharmaceutical R&D,” which Pfizer’s Subha Madhavan and I published in Drug Discovery Today.
As Madhavan and I write,
Profound advances in biomedical science have created abundant opportunities for drug developers, who are now privileged with the responsibility of sifting through an ever-increasing number of therapeutic targets, treatment modalities, and measurement techniques in effort to deliver transformative medicines to patients. Digital technologies, particularly AI, represent a promising approach to managing the burgeoning complexity of clinical development.
There are remarkably similar themes articulated in each of these papers – namely that today, we tend to make consequential decisions in each of these domains based on heuristics, instinct, and our ability to process some fraction of the available data (which represents a tiny fraction of the theoretically obtainable data). The expectation is that we could make better decisions if we could responsibly access and thoughtfully analyze a far greater volume of every type of data, ideally collected longitudinally. The hope is that AI can profoundly enable this analysis and perhaps is already starting to do so.
Many tech optimists believe success in health is inevitable, and even on our doorstep. Deep Mind CEO Demis Hassabis recently told reporter Scott Pelley on 60 Minutes that the end of disease may be “within reach. Maybe within the next decade or so, I don’t see why not.”
In contrast, biopharma veterans tend to be more skeptical. This comes through in chemist and blogger Derek Lowe’s thoughtful response to the Hassabis interview. Our knowledge of biology’s interlocking systems is “completely inadequate to cure disease within ten years,” he writes. “And unfortunately, it’s going to be inadequate at the end of that ten years, too – I will put that marker down, although it doesn’t make me happy to do it.”
Lowe continues,
That’s because we don’t have enough pieces on the table to solve this puzzle. We don’t even have enough in most of these areas to know quite what kind of puzzle we’re even working on. Nowhere near. And AI/ML can be really, really good at rearranging the pieces we do have, in the limited little areas where we have some ground-truth knowledge about the real-world effects when you do that. But it will not just start filling in all those blank spots. That’s up to us humans. My most optimistic take on these technologies is that if things go really, really well they might be able to help guide us towards more productive research than we might otherwise have been doing, but we are going to have a lot of data to gather, a lot of answers to run down, and a lot of twists and turns and utter surprises to deal with along the way. We’re going to need a terrifying amount of new knowledge before we can actually turn to any AI/ML systems and ask them the kinds of big questions I mention above.
The dimension of the challenges we’re wistfully hoping AI can somehow solve is perhaps most easily appreciated in the domain of wellness, with its goal of staying healthy and preempting illness.
On the one hand, we all recognize the limitations of the familiar heuristics – eat healthily, exercise, engage with others. These can feel superficial and non-specific, the guidance not particularly customized.
Yet if you decide to make the relentless optimization of health your personal “objective function,” with every life choice adjudicated based on whether it’s likely to maximally enhance your health, you can easily lose your mind as you disappear down the rabbit hole of endless ramifications and never-ending tradeoffs.
In this context, the appeal of an algorithm that can effortlessly manage this optimization for you, personalizing and prioritizing your endless choices in an evidence-driven fashion seems enormously attractive. If only data existed to enable such assessments; at the moment, like Lowe, I’m skeptical.
Realistically, in all of the health domains we’ve discussed, the critical question isn’t so much whether we will “cure all disease” (or not), or “optimize personal wellness” (or not), but rather what are the “pockets of reducibility” (to borrow Stephen Wolfram’s term). Where will we have the requisite data – and, as Andreas Bender has discussed, a problem posed with suitable constraints — to fully leverage the power and promise of AI to move the needle in a domain of health.
Legendary Harvard physician-anthropologist Arthur Kleinman, who delivered his Last Lecture at Harvard this past week, introduced the concept of the “explanatory model” in medicine.
As I described it a few years back, the “basic idea is that different people have different views of illness and disease, and the physician or healer needs to understand and acknowledge the patient’s model to optimize the therapeutic relationship.”
At the time, I was writing about how legendary geneticist Francis Collins was famously motivated to change his diet and exercise routine after a genetic test reportedly suggested he might be at increased risk for diabetes.
This seemed striking to me, because, as I noted,
from a medical perspective, the logic is lacking, or at least soft; most people would presumably benefit from a healthier lifestyle, whether genetic testing reveals a particular predisposition or not. Collins, a physician-scientist, shouldn’t have needed genetic testing to motivate lifestyle changes. Yet apparently, it took genetic testing because that deeply resonated with his explanatory model of illness.
The notion of explanatory models applies to our discussion of AI in health in at least two ways.
First, in the same way that Collins was motivated to adopt healthier behavior on the basis of genetic data, I can easily imagine others who might be similarly motivated because an algorithm supposedly powered by a superintelligence spits out a very specific, ostensibly precisely customized lifestyle plan.
The second application of explanatory models to AI may apply not to patients but to investors. Many tech investors are convinced that biology is poised to be disrupted by technology and technologists.
Consider these comments from noted investor (and contrarian) Peter Thiel, in the context of a 2019 interview:
Biology, I continue to think we could be doing a lot more, we could be making a lot more progress. And you know, the pessimistic version is that no, biology is just, is much harder than physics, and therefore it’s been slower going.
The more optimistic one is that the culture is just broken. We’ve had very talented people go into physics. You go into biology if you’re less talented. You can sort of think of it in Darwinian terms. You can think of biology as a selection for people with bad math genes. You know, if you’re good at math, go to math, or physics, or at least chemistry, and biology we sort of selected for all of these people who are somewhat less talented. So, that might be a cultural explanation for why it’s been been slower progress.
In other words, biology, and biomedical research has apparently been slowed by the comparatively inferior minds who’ve been attracted to it, versus the prodigies drawn to more quantitative disciplines.
The corresponding hope among many tech investors is that with the arrival of quants and their technology, including in particular AI, biomedical science can be rescued from the plodders.
Not surprisingly, many companies promoting revolutionary AI solutions to biopharma R&D have raised significant capital, especially impressive — not to mention useful — in this otherwise dour biotech market.
Recently, I saw a representative deck from one of these companies; what was striking was how the entire process of drug development had been completely reframed in a way that seemed likely to align perfectly with a tech-first view of the world.
This marketing strategy was apparently successful, since the company in question has raised considerable capital.
Yet, when I cut through all the jargon, what I saw was essentially a tried-and-true strategy – in-license, develop through value inflection, sell. Sure, maybe AI is improving this process somehow, but my suspicion is that the main function of AI in this company is serving as an attractant for a huge amount of money, which talented and seasoned drug developers (including a very experienced drug picker) can then serially deploy, with multiple shots on goal.
It’s arguably similar (as I’ve described here) to Millenium Pharmaceutical’s experience of raising lots of money through the promise of genetics and molecular profiling, and then succeeding largely on the strength of using this money to acquire LeukoSite, including (unbeknownst to them at the time of the transaction) the compound that would ultimately become the blockbuster Velcade.
In short: the idea of cleverly applying AI to pharma R&D resonates with many deep-pocketed tech investors, articulating in effect their own “explanatory model” of where the next big breakthrough may come from. Savvy biotech startups have leveraged their understanding of this investor mindset to raise significant capital and pursue what (sans AI) might be considered reasonable if fairly prosaic approaches – only now with considerable resources to put behind these efforts.
I’ve previously highlighted the Acquired podcast (what “the smartest people in the world are all listening to,” according to a 2024 Wall Street Journal “Science of Success” column by the wonderful Ben Cohen) in the context of GLP-1 and an episode they did on Novo Nordisk.
Now, the Acquired team applies their exceptional talents to unpack the story of Epic, the electronic medical records behemoth physicians love to hate (my own contributions to this dialog here, here, both co-authored with Tory Wolff of Recon Strategy). I remembered how surprised I was in 2018 when the New York Times published an adoring account of the company, and thinking, “gosh, were they taken in.”
Yet it turns out the Times may have been prescient. The Acquired episode on Epic – focusing in particular on founder and CEO Judy Faulkner as a (phenomenally successful) tech entrepreneur – was even more effusive. While the dissatisfaction among providers was noted in passing, the clear emphasis was on how brilliantly and relentlessly the company delivers for its customers.
As the hosts explicitly emphasize, Epic’s customers are manifestly not the providers whose souls (some have said) are drained by Epic, but rather by the top executives — specifically the CEO, CIO, and CFO — of academic medical centers and other healthcare companies who choose to deploy Epic.
The episode – inspiring at times, maddening at others – is nevertheless an essential listen.
Luke Timmerman, founder & editor, Timmerman Report
We did it together.
The Timmerman Traverse for Damon Runyon Cancer Research Foundation completed a splendid expedition to Everest Base Camp on Apr. 23, 2025.
This trip succeeded on every count.
All 17 members of the team made it to the mountaineering camp at 17,600 feet / 5,364 meters.
We exceeded our $700,000 fundraising goal for high-risk / high-reward cancer research with $734,508 as of May 2. More gifts are in the pipeline, so our final tally should eclipse $800,000.
The experience was magnificent from beginning to end.
The views of the Himalayas were awe-inspiring, up close and far away.
The physical and emotional challenge was no small thing. We covered a little more than 40 miles over rugged, uneven, uphill and downhill terrain. When individuals struggled with altitude symptoms, our group rallied in support with anything that mattered in the moment — a sip of water or a hug.
The camaraderie was delightful. There’s something innately human about getting outside, with a group, with a shared goal, and pushing ourselves hard mentally and physically. We relaxed after these efforts by telling stories, playing cards, cracking jokes.
We shared the simple joys. A cup of ginger lemon tea. A handmade souvenir. A hot shower at 14,000 feet. The nourishing slurp of warm garlic soup.
We paid attention, and gave respect, to our wonderful Nepalese hosts.
The bonds formed were strong. At the end of an immersive experience like this, these are the people who will show up at your wedding or your memorial service.
Please enjoy a few photos from this transcendent experience.
Thanks to the 2025 Timmerman Traverse for Damon Runyon team.
Special thanks to lead guide Eric Murphy of Murphy Expeditions and our Nepalese support team led by Jiban Ghimire of Shangri-La Nepal Trek.
