TimmermanReport.com - Your Edge In Biotech

30 Oct 2025

David Shaywitz

A lifestyle intervention delivered by AI was found to be as effective as validated traditional interventions delivered by trained experts in a carefully conducted implementation study conducted by Johns Hopkins researchers and just published in JAMA.

These results have broad significance and speak to the promise of AI to deliver promising behavior-change interventions at unprecedented scale.

Context: The DPP

The core of the study involved a striking and unexpected finding from a classic study, the Diabetes Prevention Program (DPP), conducted two decades ago, and led by Dr. David Nathan of the MGH Diabetes Center.

Dr. David M. Nathan

The DPP was designed to examine whether one of three potential interventions administered to patients at high risk for diabetes could prevent or delayed their progression to the full-blown disease, compared to placebo.

The interventions examined by the DPP originally included one of two medicines (metformin or troglitazone), although the troglitazone was soon dropped due to safety concerns. The third intervention evaluated was intensive lifestyle coaching.

In 2002, the DPP investigators reported that intensive lifestyle coaching reduced incidence of diabetes by a staggering 58% compared to placebo over three years; metformin reduced incidence by 31% compared to placebo over the same time.

This 58% reduction has become the benchmark – a consistently elusive benchmark – that researchers and companies have chased ever since.

As I discussed in Forbes in 2012, in piece about the (at the time, nascent) digital health company, Omada Health leveraging digital tools to try to emulate the DPP success, the secret sauce of the DPP is the intensity and dedication of the coaching provided.

I had particular visibility into the nature of this coaching since my endocrinology training was at MGH, where I was mentored in diabetes by Dr. Nathan and his colleagues at the MGH Diabetes Center, and learned about the nature of the DPP lifestyle interventions directly from some of the coaches who administered them.

My takeaway: these coaches were determined and relentless, deeply dedicated to connecting with their patients individually, understanding their challenges, and urging them onwards. From what I saw, there was nothing pro-forma or box-checking about any of it – the coaches (compassionately) pestered patients, exhorted them, humored them, listened to them, and believed in them – ultimately to great effect.

But duplicating these efforts – and this commitment – has been challenging.

Even when the same protocol has been followed, and coaches appropriately trained, the results have never been quite as impressive, and usually come in at about half the efficacy seen in the original DPP. This impact is still clinically meaningful, to be sure, but not at the level seen in the DPP.

Challenges include matching the original intensity (particularly when trying to deliver the program with less resources to larger populations) and maintaining participant engagement and retention.

AI- vs Human-Delivered DPP

The latest study randomized patients at high risk of diabetes into two groups: one received a DPP-style intervention administered by AI, while patients in the other group received an DPP-protocol intensive intervention delivered by human coaches. The initial intent was for these sessions to be in person, but this was changed to virtual sessions due to COVID, a change that may have actually helped the study, since as an excellent editorial by Dr. Leigh Perreault accompanying the JAMA publication observed, “the human-led DPP group saw higher-than-typical participation rates when delivered virtually compared with historical in-person rates.”

As the study authors note, “The AI used in the intervention consisted of a reinforcement learning algorithm that did not use large language models. It personalized messaging by continuously learning which prompts, timing, and content elicited greater user engagement.”

The result of the non-inferiority study, using a composite endpoint incorporating measures of glucose control, physical activity, and weight loss, was a tie: the two approaches delivered similar outcomes: about 32% of patients in each group achieved the pre-specified outcome, suggesting that for this population, the AI intervention did as well as the human coaches.

A closer look at the results highlights an important nuance: fewer patients randomized to the human coaches actually initiated the program (only about 83%), while more than 93% of patients allocated to AI coach started that intervention. Doing the math, this means that the human coaches were slightly more effective on the patients they actually reached – but the AI reached more people, and these effects netted out to the same impact.

Why This Matters

The ability of AI to achieve the same efficacy for a study population as human coaches using a well-validated approach has significance for at least three reasons that take us far beyond an encouraging proof of principle.

Scale: AI was built to scale; the cost for delivering an AI intervention to ten patients, 100 patients, or 10,000 patients almost certainly will be far less expensive than human coaches would be, coaches who must be individually trained, organized, supported, etc. The AI will also be far more consistent in its content delivery.
Constant learning and improvement: an AI system also will facilitate the rapid, continuous learning upon which medical progress often depends. Not only can new best practices be identified, but they can be incorporated immediately at scale. It is also much easier to set up comparisons between slightly different approaches, enabling ongoing refinement. Thus, whatever level of performance the AI achieves at the start is likely to improve significantly over time.
Supercharging promising local approaches: it is not uncommon in medicine (or in any other pursuit) for a motivated provider, craftsperson, or inventor somewhere to figure out a better way of doing something, such as caring for patients with a particular type of condition. Their solution might be highly effective in the provider’s hands, but hard to transmit outside their local practice. The promise of AI-delivered interventions is to enable these insights to be systematized (perhaps in partnerships with a motivated startup), deployed as a pilot, evaluated, iteratively improved, and if effective, rapidly scaled, potentially benefiting far more patients.

An important question I continue to have is whether this approach will plateau at a point that is still below the level of the most expert practitioners who deliver the intervention in person.

I think about the next-level DPP coaches at the MGH Diabetes Center, for example, or the late, next level cystic fibrosis doctor Warren Warwick at Fairview-University Children’s Hospital, in Minneapolis, so memorably profiled in The New Yorker by Atul Gawande.

In theory, it might be possible to capture and systematize much of what the MGH diabetes coaches and Dr. Warwick have done so well, and to use technology to deliver at scale, and iteratively improve the approach to a level that matches or even exceeds that of these exemplars.

I’m curious about this possibility, but skeptical.

Gawande writes about other medical centers trying to replicate Warwick’s CF success, and reflects,

“Yet you have to wonder whether it is possible to replicate people like Warwick, with their intense drive and constant experimenting. In the two years since the Cystic Fibrosis Foundation began bringing together centers willing to share their data, certain patterns have begun to emerge, according to Bruce Marshall, the head of quality improvement for the foundation. All the centers appear to have made significant progress. None, however, have progressed more than centers like Fairview.”

The ability of technology to scale means that reasonably effective interventions delivered consistently can benefit large swaths of patients.

But it feels comforting to know, or at least to believe, that there may be something special, powerful, ineffable and deeply human that lies beyond the reach of even the most impressive digital technologies.

Oct

2025

Innate Immune System Activators for Cancer: Art Krieg on The Long Run

The Long Run with Luke Timmerman · Ep188: Art Krieg on Innate Immune System Activators for Cancer

28 Oct 2025

Art Krieg is today’s guest on The Long Run.

Art is the founder and CEO of a Cambridge, Mass.-based startup called Zola Therapeutics.

Art Krieg, founder and CEO, Zola Therapeutics

Zola is developing an oligonucleotide drug candidate to activate a family of Toll-like receptors known as TLR7 TLR8 and TLR9. Activating these receptors is thought to spur the innate immune system to attack cancer cells.

Art designed the molecule himself and believes it could be the biggest thing he’s done in a long and distinguished career. He is a physician-scientist who’s considered one of the founders of the field of oligonucleotide therapies. These drugs consist of short strands of synthetic RNA or DNA to do some specific job.

Art became enthralled with this type of medicine when he was a rheumatologist, thinking about how oligos might modulate the immune system. When he was on the faculty at the University of Iowa in the 1990s, Art discovered the immune stimulatory CpG DNA motif, which led to a new approach to immunotherapy and vaccine adjuvants. He then moved over from academia to industry, living through a historic boom in cancer immunotherapy in the 2010s. His most recent company, Checkmate Pharmaceuticals, developed a TLR9 agonist for cancer which was acquired by Regeneron Pharmaceuticals for $250 million in 2022.

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Oct

2025

Report from China: Setting Sight on New Modalities and Global Markets

David Li

27 Oct 2025

David Li, co-founder and CEO, Meliora Therapeutics

Chinese biotechs opened 2025 with a bang at JPM week, and the momentum has continued.

Much of the conversation early this year was about how the US could rise to the challenge, and hold onto its historic position as the world leader in biotech innovation (see my Jan. 8, 2025 editorial in TR).

The evidence of a China biotech renaissance was overwhelming and could no longer be downplayed. Recall a flurry of deals from January totaling billions in upfront and milestone payments, including Innovent / Roche, Kelun / Harbour – Windward Bio, Keymed / Innocare – Prolium, Duality Bio – Avenzo, KeyMed – Timberlyne, among others.

Six months later, a Jefferies report showed that one in three licensing deals for all new drug candidates — 32 percent — trace their origins to China. Even as US biotech has shown signs of recovery this fall, Chinese biotechs are maintaining a competitive pace.

Last month, I traveled to Beijing, Shanghai, and surrounding areas on a 10-day business trip to see with my own eyes. I wanted to explore opportunities for my company, San Francisco-based Meliora Therapeutics, and spot the latest trends. I met with local biotech startups, established pharmas, and Chinese VC funds.

Here are my top impressions:

First Came Antibodies and Bispecifics, Now Come Genetic Medicines

Chinese biotechs have burst on the scene the past five years to become a dominant force in antibody engineering and biologics development. This is mainly attributable to their advantages in cost, efficiency, and speed.

The deals speak for themselves: BioNTech’s $800 million upfront deal value with Biotheus for their PD-L1/VEGF bispecific, and Merck’s acquisition of a PD-1/VEGF bispecific from LaNova Medicines for $588 million upfront and up to $2.7 billion in milestone payments are a couple recent examples.

This year, we have seen Chinese biotechs pursue with in vivo CAR T-cell therapies and other genetic engineering technologies with a similar fervor.

This is exemplified by recent deals like Vitalgen licensing a lipid nanoparticle (LNP) construct from GRIT Biotechnology for in vivo CAR-T applications and Porton Advanced partnering with RongCan Biotech to develop ionizable LNPs aimed at mRNA, gene editing, and in vivo CAR-T payloads. This is just the tip of the spear. By latest count, there are over *150* China-based in vivo CAR-T companies now.

Most of these companies will not survive, but such is the market in China. The Darwinian selection pressure is intense, but it also drives breathtaking speed.

China’s advantages in cost and velocity are even more apparent in this modality, with some companies claiming timelines of nine months to development candidate for RNA and other genetic medicine programs. This is perhaps 3X+ faster than the norm in the US.

Novel Translational Biology Is In Sight

For many years, the critique of Chinese biotech has been they are fast followers, not innovators. This narrative is beginning to shift, albeit slowly.

On my trip in September 2025, I counted at least a dozen instances of startups genuinely pursuing novel biology, from novel rare disease targets identified through proprietary human genetic databases to first-in-class oncology programs that are not simply leveraging Western academic & industry publications as starting points for scaffolds and molecules.

The competition among biotechs inside China is intense. The CEOs leading these biopharma companies understand that novel biology is the one differentiator that can help them stand out in a field of many me-toos seeking investment dollars.

The larger pharmas in China all now have R&D groups that are exploring novel targets and mechanisms via small molecules, antibody-drug conjugates, bispecific T-cell engaging antibodies, and more. Most of Chinese biotech still operates in the validated target space. But the desire and capability to explore novel biology is evident. Green shoots are visible.

The constraint, as always, is talent. China has extraordinary depth in antibody engineering, chemistry, process development, formulation, and manufacturing science. It has growing – but still limited – talent depth in translational medicine and disease biology. The companies making the leap into novel biology are typically those that have successfully recruited native-born Chinese scientists who were educated in the US and Europe, and who are now returning to China to lead their R&D efforts.

Fewer Newcos, But Business Development Still Humming

In 2024, newco activities were all the rage. Windward Bio, Prolium Bioscience, and Timberlyne Therapeutics were a few of the startups that debuted, each raising substantial rounds of venture capital. At the time, Western VCs were looking for clinical stage assets that could reach clinical value inflection points quickly, and Chinese biotechs were willing sellers of assets given financing difficulties in their market.

Fewer new companies are being formed in China with assets to out-license to the US and Europe this year, but it’s still happening.

First, the financing environments in China have recovered faster than in the US, meaning existing biotechs in China are not desperate to do outlicensing deals to stay alive. Second, valuation expectations are higher after substantial deals like those mentioned earlier have set the high-water mark. Third, and perhaps most importantly, many of the obvious targets and clinic-ready assets are gone.

While newco activity as slowed, it hasn’t gone away completely. San Francisco-based Expedition Therapeutics recently raised a $165 million round, and Boston-based Bambusa Therapeutics raised a $90 million Series A. Both companies are built around assets from China.

Additionally, licensing activity remains robust as mentioned by the Jefferies report. The difference is that deals are increasingly happening at earlier stages and with more creative structures. For example, there are now meaningful examples of Western biotechs licensing Chinese platform technologies for speed and cost advantages in manufacturing and formulation, e.g. Kite / Gilead & Pregene, rather than licensing specific assets.

This is still early innings, but the trend is notable in that it demonstrates Western pharma’s interest in leveraging Chinese platform capabilities broadly.

Chinese Pharma Has a New Slogan: “Go Global”

During my visit, it became apparent there is a new slogan for the major Chinese biopharma companies today, whether Hengrui, Sino Biopharma, Simcere, or Innovent: “go global.”

Their model? Takeda, which over decades built a truly global R&D and commercial presence that transcended its Japanese origins.

The aspiration is clear and understandable. After spending the better part of two decades building innovative R&D capabilities and seeing those capabilities validated through licensing deals and promising clinical data, Chinese pharmas are asking the logical next question: why stop at outlicensing when we could capture the full value ourselves? The domestic market, while large, is hyper competitive and subject to aggressive volume-based procurement policies from the main buyer of its products – the Chinese central government. That squeezes profit margins. Global expansion is seen as both a growth opportunity and a strategic hedge.

While this aspiration is clear, there are still challenges that should not be underestimated. The capital intensity of global registrational trials is much higher than domestic or regional studies. Clinical development expertise for navigating FDA, EMA, and other global regulatory authorities has not been fully developed internally yet, and hiring clinical development organizations internationally represents a significant commitment in both cost and management attention.

Only the best financed and profitable of the Chinese biopharma are likely to make the jump successfully, but make no mistake, this is an industrywide goal that was uttered many times on this most recent trip.

As China’s home-grown pharma companies start generating meaningful cash flow domestically from innovative therapeutics, they have set their sights on commercializing that innovation in global markets. This will be a key theme to watch in the coming quarters and years. The first Chinese biopharma to successfully launch and commercialize a novel drug in the US or Europe without a partner will be a watershed moment.

The Relentless March Continues

The pace of China’s development continues to astound. Every quarter the Chinese biotech ecosystem has a new “feel,” and progress is relentless if uneven. Some areas surge ahead while others stumble, but the overall trajectory is unmistakable.

For observers in the West, particularly those making capital allocation or partnership decisions, the imperative is clear: the world would benefit from continuing to watch this market closely as Chinese biotech continues to make strides.

Oct

2025

The Biology of Belonging: Social Connection Meets Geroscience

24 Oct 2025

David Shaywitz

Digital health, fitness, and longevity platforms have focused on the constant measurement and relentless optimization of biometric parameters, an often-valuable effort but one that has systematically left behind vital components of health and flourishing – such as social connection — that are more difficult to measure.

The Health Value of Social Connection

Robust longitudinal studies, including the Harvard Study of Adult Development, and Northwestern’s Super Agers study, have demonstrated that a critical determinant of longevity is warm human relationships. The Harvard research, for example, “found that the people who stayed healthiest and lived longest were the people who had the strongest connections to others,” according to a Harvard School of Public Health summary of the work.

Moreover, a 2021 review by Jaime Vila of 23 meta-analyses of studies conducted over the last sixty years, involving over a billion subjects, found a “significant association of functional and structural measures of social support with health and longevity.”

Vila continues, “The strength of this association is equivalent to that documented for other well-documented risk factors such as smoking or obesity.”

The health importance of social connection is also a key theme of Why Brains Need Friends, a new book by neurobiologist (and social media phenomenon) Ben Rein that I recently reviewed for the Wall Street Journal.

Rein’s bottom line: “I really think you should spend more time socializing.” He adds, “Your brain is counting on you.”

Geroscience pioneer Steve Horvath

This message is reinforced by a pair of just-published papers that used “aging clocks” to explore the impact of social connection. One of these papers was highlighted by geroscience researcher Steve Horvath at the 2025 Biomarkers of Aging conference held this week at Harvard Medical School.

Before we get to these papers, I thought it might be useful to share a few thoughts from this meeting with TR readers.

Biomarkers of Aging Conference: Reflections

As a first-time attendee (and I only was able to make it to some of the sessions), I was struck by the remarkable (and welcome!) degree of energy, hope, and optimism among so many of the speakers, including many (like Horvath) who were toiling in the field long before it became so trendy.

Much of the work presented involved various measures of aging, so-called “aging clocks” that relate specific patterns of biological or structural measurements to estimates of age and health. For example, patterns of DNA methylation accumulate as individuals age, and seem to build up faster in less healthy people; thus, this measurement can reveal someone is “older” or “younger” than their chronological age would otherwise suggest.

The first multi-tissue aging clock, based on DNA methylation, was developed by Horvath back when he was a geneticist at UCLA; today, he works at Altos Labs. (This 2024 interview of Horvath by Dr. Eric Topol on the Ground Truths podcast explores the fascinating origin story, rich in serendipity, of aging clocks, and is highly recommended.) Perhaps not surprisingly, a colleague referred to Horvath as the “King of Clocks” in a discussion at the conference.

The attraction of ever more researchers to geroscience is easy to understand. As Nobel Laureate Venki Ramakrishnan writes in Why We Die, “aging is connected intimately with so many biological processes,” and captures the attention of scientists in so many disciplines.

These connections weren’t always so apparent. Ramakrishnan, an RNA biologist (see his wonderful first book, Gene Machine), explains “when I started my career, I had no idea that anything I did would be connect with the problem of why we age and die.”

But more recently, Ramakrishnan says, he’s learned that his life’s research on “the problems of how proteins are made” is highly relevant to aging, since “much of aging has to do with how our body regulates the production and destruction of proteins.”

As palpable as the attendees’ excitement, however, was a frustration, perhaps even impatience, with a nagging sense that their work is still not quite taken seriously by the biomedical “establishment” – even as they appreciate that many patients (or more precisely, individuals who are hoping to forestall becoming patients) are drawn to the field looking for answers.

Among the promising initiatives to integrate longevity into medicine were:

Professor Andrea Maier, National University of Singapore

“Healthy Longevity Medicine Society,” discussed by professor Andrea Meier of the National University of Singapore. Meier was the founding President of the organization, which was established in 2022 “to build a clinically credible framework and platform for longevity medicine that promotes the highest standards of interdisciplinary collaboration in the field.”
Dr. Evelyne Bischof
“Sheba Longevity Center,” discussed by medical director Evelyne Bischof. Sheba, located in the Tel Aviv metropolitan area in Israel, describes itself as “the first longevity center within an academic medical institution,” and is focused on “integrating the latest research and innovations in longevity into patient care.”

Other prominent centers in geroscience include the Buck Institute in Novato, California, “an independent biomedical research institute that researches aging and age-related disease,” and was founded in 1999; and the Abu Dhabi-based Institute for Healthier Living, which characterizes itself as “the world’s first specialized healthy longevity medicine center.”

Professor Terrie Moffitt, Duke University

On many levels, I especially appreciated the presentation from Duke’s Terrie Moffitt, a psychologist who first pursued the roots of antisocial behavior, and who — by following the Dunedin birth cohort across five decades — has helped redefine how we understand biological aging.

Her group’s DunedinPACE clock, now widely regarded as one of the most rigorous measures of biological aging, is even featured in the Rejuvenation Olympics (although, as Open Evidence reminds us, Dunedin aging measures “are not yet established for routine clinical practice”).

In her talk, Moffitt described a range of new clocks the team is developing, including one based on neuroimaging (the DunedInPACENI) that aims to predict overall aging rate (not the aging rate of the brain, specifically).

The conference presenters included several leaders from several emerging biotechs focused on aging, and with established pharma partnerships. These include:

Kristen Fortney, CEO BioAge

BioAge, represented by CEO and co-founder Kristen Fortney. The company has ongoing relationships with Lilly (focused on therapeutic antibody discovery) and Novartis (focused on target discovery, with an eye towards therapeutics that can mimic some of the benefits of exercise).
Alex Zhavoronkov, CEO Insilico Medicine
Insilico Medicine, represented by founder and CEO Alex Zhavoronkov. The company’s active partnerships include a target discovery relationship with Sanofi, earning a milestone payment in 2024.

The only speaker from an established and comparatively large biopharma was David Glass, a world expert in muscle biology who is now Vice President, Research, Aging/Age-Related Disorders, at Regeneron. Glass thoughtfully discussed important (and easily-overlooked) nuances of the molecular study of sarcopenia in rats vs mice.

David Glass, VP Research, Aging/Age-Related Disorders, Regeneron

A final observation from this conference is simply that as I considered the ever-increasing number of biological clocks available, their remarkable ease of use, and the tendency to use multiple clocks in single studies, I found it all too easy to imagine p-hacking efforts (whether deliberate or just self-deception) where, if you test enough clocks in enough conditions, eventually you find some association, and then can persuade yourself (or others) that you’ve found a way to reverse aging – or have discovered a factor that accelerates it. If most everything can be tied to alterations in some biomarker of aging, then it will be increasingly challenging to identify meaningful signal beneath the volume of noise.

Fortunately, while one of studies we’re about to discuss does consider multiple measures of aging, it was performed rigorously, and accounts for multiple comparisons in their statistical analysis.

Social Connection and Biological Aging

Social connection, as we’ve discussed, is good for your health. Two research groups have recently published findings reflecting their efforts to relate measures of biological aging to social connection and dissect the most impactful components. Interesting, the teams both analyzed the same basic dataset — a well-characterized cohort, the Midlife in the United States (MIDUS) project that includes extensive self-report data as well as biobanked samples — but approached their analyses in slightly different, fairly complementary fashions.

One team — Anthony Ong of Cornell, Frank Mann of Stony Brook, and senior author Laura Kubzansky of Harvard – analyzed data from over 2000 MIDUS subjects, with an average age of about 55.

Professor Laura Kubzansky, Harvard School of Public Health

The authors utilized a measure – “cumulative social advantage” (CSA) – they previous developed, intended to capture and integrate social resources across four broad domains:

Religious and faith-based support
Parent-child relationship quality
Community Engagement
Extended emotional support.

These were assessed by self-report, using several questions for each domain.

Then, the researchers analyzed samples by using a range of stress and aging, including several biological clocks, serum measures of inflammation, and urine measures of neuroendocrine function. The numbers were then crunched, comparing the singular, composite assessment of connection (CSA) to each of these measures of stress and aging, explicitly correcting for the multiple comparisons.

The result: higher CSA scores were linked in statistically significant manner to slower biological aging, and also with lower levels of IL-6 (a marker of inflammation), even after accounting for a comprehensive set of sociodemographic (eg socioeconomic status) and health-related (eg smoking history) confounders.

Within the CSA construct, the component of social integration–measured by the self-reported response to ‘I feel close to other people in my community’–accounted for much of the variability in CSA scores. The contribution of perceived community closeness to the observed association between CSA and slower biological aging and lower inflammation was inferred from its central role within the CSA composite.

The second team of scientists – Holly Prigerson and Paul Maciejewski of Cornell, together David Russell of Appalachian State University – examined data from 1309 MIDUS subjects, average age about 51.

Professor Holly Prigerson, Cornell University

This team explored the relationship between (presumptive) positive social experiences (such as volunteering for organizations) and negative social experiences (eg dropping out of school), on the one hand and two measures of biological aging on the others. The intention was to determine, after adjusting for known confounders (critical!), which experiences most impact aging, and also to explore whether there was a relationship between the net ratio of positive/negative experiences and aging.

The key findings: engaging in social meetings had the strongest (and highly significant) positive effect on aging; also scoring well: marriage and giving assistance to others. On the negative side, a strikingly deleterious effect on aging was associated with dropping out of school and with the subject’s parents experiencing drug problems.

Perhaps not surprisingly, a respondent’s total number of positive experiences were associated with slower aging, and total number of negative experiences were associated with accelerated aging. Comparison of subjects with “net positive” ratio of experiences to those with “net negative” revealed a profound difference between these two groups, with the “net negative” group aging much faster.

Interestingly, perceived social support was not found to be associated with aging in this publication.

While both studies link aspects of social connection with aging, they don’t speak directly either to causation (the social factors measured may reflect a deeper underlying driver of stress and aging, say) or to the biological mechanisms by which social connectivity exerts its putative effect on the biology.

Also not addressed: the potential impact on aging of interventions focused on enhancing social connectivity – a critical question for those seeking to improve health rather than just measure it.

Bottom Line

Social connection exerts a powerful effect on health and aging, with robust evidence linking greater social engagement and support to reduced morbidity, mortality, and slower biological aging. These relationships deserve greater attention in longevity-promoting efforts, including digital health and wellness platforms. Geroscience research is experiencing a remarkable intensification of interest, partly due to the availability of biological aging measures, though consumer enthusiasm for these tools often exceeds their current scientific validation. The ability to connect social connection to biological aging, and to use these measures to dissect and optimize social interventions, represents an exciting but still nascent approach to developing meaningful, targeted strategies for healthy aging.

Oct

2025

Takeda Bets on Innovent, NewLimit Lures Lilly, & Merck Makes in America

23 Oct 2025

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Oct

2025

Novo Buys Akero, BMS Bets on Orbital In Vivo CAR-T, & a Biotech Industry Nobel

Oct

2025

Creating a New Class of Medicines: Eric Fischer on The Long Run

The Long Run with Luke Timmerman · Ep187: Eric Fischer on Creating a New Class of Medicines

14 Oct 2025

Today’s guest on The Long Run is Eric Fischer.

Eric is a professor at Dana Farber Cancer Institute in Boston. His structural biology and chemical biology expertise has led him down a path to become one of the world’s experts in an emerging category of medicine that includes targeted protein degraders and molecular glues.

Eric Fischer, professor, Dana-Farber Cancer Institute

These novel chemical entities can be made to interact with disease targets inside cells that traditional drugs – small molecule compounds and genetically engineered biologics – haven’t been effective against.

This is an exciting new frontier emerging at the nexus of structural biology, chemical biology, and drug discovery.

Eric was one of the key scientists, along with Nathanael Gray, who were tapped to lead a Center for Protein Degradation at Dana-Farber supported with $80 million from Deerfield Management, an investment firm, in 2018.

Some of this research has led to startup activity. Civetta Therapeutics and Neomorph are a couple of the companies Fischer has co-founded.

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High-quality data across major assay types including ELISA/MSD, LC-MS, and PCR, supporting all modalities and therapeutic areas
Customer-first policies, like guaranteed outcomes and transparent pricing.

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Oct

2025

US Biotech Has an IRR Problem, Not a China Problem

Oct

2025

Too Many Life Sciences Boards Are Shirking Responsibilities

John Archer

09 Oct 2025

John Archer, partner, Catalyst Advisors

There is a persistent myth in life sciences that once a company transitions from a scrappy startup into a more mature company, its board will naturally evolve to meet those new, more complex challenges.

The reality is that these boards all too often fail to keep pace with their organizations. Those gaps leave management teams without the strategic guidance and governance needed for sustainable growth and enterprise value creation.

It doesn’t have to be that way.

Board evolution is typically a gradual process. Early-stage companies assemble boards composed of initial investors, past or current business colleagues, scientific or clinical luminaries or collaborators, and trusted allies. As companies approach commercialization or a strategic exit, they add functional experts to their boards: financial, commercial, R&D, and regulatory specialists.

While these moves are logical, they are often reactive and piecemeal—not part of a comprehensive plan for board effectiveness. These new board members may bring impressive credentials and deep subject-matter knowledge, but they remain focused on narrow functional silos rather than enterprise-wide stewardship. They become “financial guardians” rather than proactive advisors who can help the CEO and leadership team navigate the complexities of a maturing organization and think more strategically about the long-term future.

In short, they may be better suited to be consultants to the companies, not board members.

The Cost of Ineffective Boards

For companies otherwise poised for growth—that is, they may be developing differentiated clinical assets and a diversified portfolio; they have strong leadership and ample capital—the drag from an ineffectual board can be significant.

Those companies are more vulnerable to missed opportunities and value destruction. They struggle to raise capital in challenging markets and fail to commercialize products optimally. In the most extreme scenarios, these factors can collectively trigger a downward spiral that can be hard to bounce back from—a decline that can even gain the unwelcome attention of an activist shareholder. In these scenarios, the blame for that collapse typically goes to the leadership teams, while the board’s role in allowing that unraveling often escapes scrutiny.

Recent events with Dynavax Technologies illustrate how a sleepy board can fuel an activist challenge. Earlier this year, investor Deep Track Capital challenged the company’s strategic direction, arguing that it should focus on the products that drove its core value, not diversifying its vaccine portfolio. Deep Track wasn’t able to make any headway in conversations with the company leadership, and eventually launched a proxy fight, nominating four new directors to run against those chosen by the board. While Deep Track’s slate was ultimately unsuccessful, its challenge to the Dynavax leadership underscored valid concerns about the company’s spend rate, capital returns to shareholders, and M&A expertise.

Over three decades, I’ve helped recruit hundreds of board members. I’ve seen the good, the bad, and everything in between. What stands out for me is how many boards are stuck with a sub-optimal makeup for their needs and how slow boards are to move on from ineffective members, even when they correctly diagnose the gap. I’m not saying that it is quick or easy to swap out board members. But it’s important that board chairs start that process sooner rather than later.

CEOs can also hinder the development of the board. They sometimes simply accept (or even opt for) a board relationship that is frictionless. A rubber stamp might be what the CEO wants, but it isn’t what the CEO needs. Change demands work, and it’s vital that CEOs are active members in the board succession process.

Even when a board has the perfect makeup, the culture can be problematic. Whether board members engage with each other constructively determines the body’s overall value. It’s important that boards have ways to encourage the less extroverted to comment. There is sometimes an inverse relationship between how long a board has been place and its effectiveness. Boards, like anything else, can get stale over time.

Beyond that, it goes without saying that with any bad behavior among members, boards need to nip it in the bud quickly.

Given all that, what distinguishes an effective board from an ineffective one? In my experience, there are three key areas:

–Enterprise-Wide Stewardship: Effective board members bring not only deep functional expertise but also the ability to think across the enterprise.

–Proactive Recruitment: Boards recruit new members based on a clear, forward-looking plan rather than reacting to immediate needs.

–Constructive Engagement: Effective boards are hands-on advisors, not passive observers or harsh critics.

How Boards Can Be More Effective

To set themselves up for success, the boards of companies that haven’t yet developed commercially and clinically viable products must take the following steps:

–Elevate Board Succession Planning: Boards should make succession planning a strategic priority rather than an afterthought triggered by immediate vacancies or crises. This means establishing a formal, ongoing process for reviewing the board’s composition; identifying gaps in expertise; and forecasting future requirements based on the company’s direction. Tapping external advisors or governance consultants can help the company avoid insular thinking.

It’s critical to cultivate relationships with potential candidates well before seats open up—so there is a steady pipeline of qualified directors. This approach allows boards to anticipate shifts in market dynamics, technology, or business models, and to refresh their membership accordingly.

–Prioritize Enterprise-Wide Thinking: Boards should seek out individuals with a demonstrated ability to connect the dots across the business and who are known for challenging assumptions when necessary. Candidates with experience in major transformations, enterprise risk management, or leading initiatives that span multiple disciplines bring valuable perspective to the boardroom. Diversity in professional background and industry experience is also crucial. I was looking at the board roster of one company the other day where five of the seven board members are either current or former CEOs. While this may sound like a dream team board, it’s akin to an NBA team sending out a starting lineup of five power forwards. The best boards, like the best teams, have players with clearly defined roles – point guard, shooting guard, forward, center, etc.

Once they are brought on, directors should be oriented toward the company’s overall strategy and value drivers, not just their own specialties. Comprehensive onboarding and ongoing education sessions should focus on emerging trends and enterprise-wide challenges.

–Stay Ahead of Activism: Boards must remain vigilant about the risk of activist investors, but they cannot allow fear to drive decision-making. Staying ahead of activism requires a deft and delicate level of engagement with major shareholders. Some shareholders bring a natural balance of short- and long-term vision, while others can be quick to want change just because things aren’t going well in the moment. One big (and often overlooked) role of the chair is well-organized interaction with these disparate shareholders.

BioMarin Pharmaceutical provides an example of a board that deftly handled a potential activist. In that case, outside shareholder Elliott Investment Management was advocating for more discipline with operating expenses and faster performance improvements. After initial resistance from the leadership, Elliott raised its concerns with the board, which negotiated a resolution that temporarily expanded the board and installed Elliott’s nominees. This coincided with a CEO transition, giving Elliott significant influence over the leadership change and prompting the formation of a new committee to review BioMarin’s operations, capital allocation, and long-term planning. The skillful negotiation led by the board—particularly the lead outside director—helped address shareholder demands and headed off a potentially more disruptive activist scenario.

More often than you might think, boards of mature life sciences companies are failing to live up to their responsibilities, and in the process, they are causing long-term shareholder-value destruction. The solution is to build boards that are proactive and enterprise-minded. Only then will they be true partners with the leadership team and make sure the company doesn’t backslide into irrelevance.

Oct

2025

Silicon Valley: Yes, AI Does Enhances Productivity — In The Right Hands & Context

NYT on Eliezer Yudkowsky, AI’s “Prophet of Doom”

06 Oct 2025

David Shaywitz

Outside the glare of hyperbolic headlines, organizations of all sizes – including most in healthcare – are urgently trying to figure out how AI will fit into their workflows and business plans.

Perhaps the most interesting recent discussion I’ve heard on this subject involved a trio of Andreessen-Horowitz (a16z) partners — Erik Torenberg, Martin Casado, and Steven Sinofsky — who were joined by Aaron Levie, the CEO and co-founder of Box.

Torenberg, Casado, Levie, and Sinofsky

The entire conversation is an essential listen (or view, since it can be difficult on audio to distinguish the voices of the four men).

The most important takeaway: the greatest productivity gains (albeit self-reported) seem to be achieved by users, generally software developers, who are impassioned, engaged, curious, and forgiving – and who start off with a fair amount of expertise.

As Levie describes it,

“…the biggest gains of AI go to people who have some degree of expertise in an area to know what is actually true, what is not going to work, what should I integrate from the output of this AI … If you don’t have a deep understanding of your particular space or field or domain, you aren’t able to then have the right judgment to make all of those decisions. So I think the experts just get more powerful in this world.”

Or, as Casado says,

“The more senior small teams that use AI are superhuman. It’s like they woke up and they were all f–king Tony Stark and it’s unbelievable. And like, their productivity is insane. But they’re all they’re all super senior [i.e. experienced/expert].”

Levie notes that the most successful adopters of AI can also be really young engineers who are AI native and super engaged with the technology. He explains,

“They would have been maybe 10x engineers in a prior world, but now they’re like 100x engineers. And so, senior in terms of in their own kind of relative cohort, but like the way that they are building their startups are just like completely different.”

These pioneers – I’ve favored the term “lead users” — are able to guide the AI thoughtfully and constructively, in an intrinsically bottom-up approach. This is exactly what I’ve advocated (see below, reproduced from a recent TR column), but not necessarily how many biopharmas are tackling the problem.

Flashback to TR column from 11 September 2025.

As Casado notes, a recipe for failure, and what might account for the astonishingly high (95%) observed in AI pilots, is precisely this top-down approach favored by large companies. As he describes it,

“If you actually look at the reports on ‘enterprise things fail’ and look at what they were measuring, it’s clearly some internal project pushed down by the board where they hired some consultant to do it – it’s going fail.”

Sinofsky adds that AI is the latest example of “bottom-up adoption…really changing the productivity equation,” noting, “Big companies do not know how to deal with that because they need to control it. They worry about safety and security and privacy and all of their corporate rules.”

AI Implementation in Healthcare

The distinction between AI adoption in established organizations and startups can also be observed in healthcare.

Dr. Karandeep Singh

For example, in a recent (and resonant) NEJM-AI podcast, Dr. Karandeep Singh, the Chief Health AI Officer at UC San Diego Health, emphasized the lived complexities of AI adoption he’s experienced in an established healthcare system.

A key learning, offered by the NEJM-AI episode blurb: “the best AI is guided by patient care, deep expertise, and humility about the limits of technology.”

Contrast this cautious, thoughtful incrementalism with the disruption emphasized by a16z healthcare partner Julie Yoo in this post – not to mention a16z co-founder Marc Andreessen’s declaration, on the “Cheeky Pint” podcast, that “ChatGPT is in fact a better doctor than your doctor today with almost 100% certainty.”

Andreessen added that a key limitation in the speed with which AI can transform medicine are pesky regulatory and licensure requirements, adding that the fields that will move the fastest, and attract the best and most ambitious talent, are those like many areas of software development that aren’t so encumbered.

A reinforcing example of Silicon Valley’s belief in the inevitability of AI transformation in healthcare comes from a recent job posting from chip maker NVIDIA, a company now worth about $4.5T (yes, that’s a “T”). Keen to expand AI adoption in healthcare and life sciences, they are hiring a “Director, Healthcare AI startups.”

In particular, they “are seeking a passionate Global Healthcare Life Science (HCLS) Startup Director to scale NVIDIA’s developer ecosystem worldwide…This role centers on building programs that drive adoption of NVIDIA technology by the HCLS startup community.”

So far, very reasonable.

Yet it turns out that in this role centered on enabling technology for drug developers and healthcare providers, actual experience in drug development or healthcare is apparently not required (other than industry/ecosystem contacts).

In contrast, helpful attributes for candidates to possess include “prior experience with AI, machine learning, or high-performance computing” and “background in venture capital, startup acceleration, or developer advocacy.”

In so many words: “AI is all you need.”

—

Additional recommended AI-related content:

Human Values Project that Zak Kohane is spearheading.

“Click Here” podcast episode (“AI’s giant pool of hype”) featuring AI skeptic Gary Marcus

With access to two leaked a16z LP decks, Leslie Feinzaig explains in Fast Company why a16z is “moving upstream,” pursuing bigger and bigger funds (you probably don’t need AI, just a rudimentary understanding of management fee math, to figure out the reason).

Incredibly captivating new “Acquired” podcast episode on Google and AI.

Oct

2025

An Outstanding ‘Mini’ Traverse of Katahdin for Damon Runyon Cancer Research

06 Oct 2025

The Timmerman Traverse for Damon Runyon Cancer Research Foundation had a spectacular experience on Mt. Katahdin in Maine on Saturday.

Weather was glorious. Fall colors were vibrant. The team was fit and mentally ready for rocky, rugged terrain. They got a rich outdoor experience with a steep rock scramble on Cathedral Path, then crossing Katahdin’s famous Knife Edge ridge.

This trip represents an iteration of the Timmerman Traverse. Expect more of this type of outing in 2026. Many are expressing interest in shorter trips closer to home, but that still combine giving and community building. I’m listening.

My vision is to explore trails for the Timmerman Traverse in naturally beautiful places in Washington, Colorado, Wyoming, Maine, New Hampshire, British Columbia and the Eastern Sierras of California.

These trips are about getting out in nature. Doing hard things. Making friends. Supporting good causes.

This work strengthens community.

Please enjoy a few photos from a memorable day on Mt. Katahdin, Oct. 4, 2025.

Want to participate or sponsor in 2026? luke@timmermanreport.com.

Participants on Katahdin 2025:

Luke Timmerman, founder & editor, Timmerman Report
Doug Fambrough, founder, portfolio manager, KCap Biotech Fund; former CEO, Dicerna Pharmaceuticals
John Keilty, venture partner, Third Rock Ventures
Anna French, managing partner, Qiming Venture Partners USA
Judith Hasko, partner, co-chair of life sciences, WilmerHale
Art Krieg, founder & CEO, Zola Therapeutics
Lalo Flores, venture partner, Scion Life Sciences
Vineeta Agarwala, general partner, A16Z Bio & Health Fund
Expery Omollo, postdoctoral researcher, MIT; Robert A. Swanson Family Fellow, Damon Runyon Cancer Research Foundation
Henry Kilgore, postdoctoral researcher, Whitehead Institute; Damon Runyon Cancer Research Foundation Fellow
Antonio LaPorte, postdoctoral researcher, Harvard University; Damon Runyon Research Foundation Fellow.

Oct

2025

“Food Intelligence”: Make Healthy the Default — In Public Spaces and Private Kitchens

06 Oct 2025

David Shaywitz

While “nutrition science” often seems to cry out for air quotes around “science,” we are fortunate now to have a new book on the topic written by one of the most thoughtful and deliberate nutrition researchers of the modern age: Kevin Hall.

Hall has consistently steered a course of thoughtful rigor, leading a succession of highly impactful studies at the NIH before departing earlier this year, citing concerns about censorship from the Robert F. Kennedy Jr regime.

Kevin Hall

In September, Hall, together with journalist Julia Belluz, published Food Intelligence, a much-anticipated, highly engaging book reviewing the current state of nutrition science, including Hall’s critical contributions to our current understanding.

Key takeaways include:

For those confused by nutrition science, there’s a good reason, the authors suggest: “Nutrition isn’t rocket science; it’s harder.” There are many variables (and physiological processes) involved, and definitive experiments seem to be as challenging as they as are rare.
Despite the many strongly-held views on both sides of the debate, there’s little evidence to suggest either “low carb” or “low fat” diets are better or worse than the other; some have enjoyed considerable success with each of these approaches. Moreover, the authors argue that this impassioned debate largely represents a distraction from more important considerations.
The real enemy, in the view of the authors: “hyperpalatable,” “calorie-dense” foods, which they view as a clear and present danger that overwhelms our ability to resist them. Consequently, much of the book emphasizes broad structural changes — inspired by our approach to tobacco — to shift the defaults in our environment.
Hall and Belluz’s bottom line advice for individuals:

“The evidence on optimal nutrition has been clear and consistent over decades; it’s boring by this point: Eat more vegetables, along with fiber, legumes, whole grains, and fruits. Limit sodium, sugar, saturated fat, and junk foods.”

Julia Belluz

“Imprecision Nutrition”

The authors are deeply skeptical of platforms offering “cutting-edge” putatively precise approaches to healthy eating, and suggest the term “imprecision nutrition” might be more apt. In particular, they report:

There’s scant solid evidence supporting “precision nutrition” approaches, beyond standard guidance: more plants and whole foods, fewer ultraprocessed items.
While consumer-grade continuous glucose monitors (CGMs) may be the flavor of the moment, Hall and Beluz write that the data they produce is remarkably noisy and inconsistent, noting that the “lack of reliable responses to the same repeated meal suggest[s] a good deal biological variability and technical imprecision.”
The authors observe that the microbiome is the “new frontier in health science, but assert that, like CGMs for precision nutrition, it’s “not quite ready for primetime.” They note that while we’ve gathered considerable associational data around the microbiome, the idea we know how to manipulate it to improve health is “massively overhyped.”

Beyond their robust summary of nutritional science, Hall and Belluz offer recommendations that are mostly focused on broad, structural changes to alter the way we encounter food in our environment.

As Hall explained to me,

“…we did not want to write a book filled with diet advice for individuals… Rather, we wanted to focus on explaining the fascinating world of nutrition & metabolism science, including how food intake is biologically controlled and the influence of our food environment in likely driving the increased prevalence of diet-related chronic disease.”

Their emphasis on the impact of environmental factors that influence health aging reminded me of the work of UK researcher Michael Kelly, in particular the paper “Why Is Changing Health-Related Behavior So Difficult,” as I’ve discussed with TR readers.

A key conclusion Kelly and Baker reach is the importance of deeply understanding the specific context in which behaviors occur; abstract away these pesky details, they write, and you miss critical insights.

Improve Eating By Focusing on Individuals or our Food Environment?

When pursuing change – including health-promoting behavior change, such as reducing smoking or improving how we eat — there’s an enduring tension between whether to focus on individuals (bottom up) or on structural obstacles (top down).

While Hall and Beluz acknowledge that there’s some individual responsibility in healthy eating, they predominantly direct their attention to what they see as powerful external dynamics that have rendered resistance to unhealthy deliciousness virtually futile.

A useful discussion of exactly this type of tension can be found in the latest episode of the (always worthwhile) “Excellence, Actually” podcast – in particular the insights offered by co-host Brad Stulberg

Stulberg cites a September “Excellence, Actually” episode featuring sports psychologist George Mumford, who has famously helped athletes such as Michael Jordan and Kobe Bryant stay mentally fit and resilient.

George Mumford

On the September podcast, Mumford poignantly described examples of racial discrimination he endured earlier in his career, but to Stulberg’s surprise, Mumford emphasized the importance of focusing on individual agency.

In the latest episode, Stulberg describes what happened when he pressed Mumford on the point:

“And he’s like, damn right there are structural issues, but you got agency and you can’t control the structure. What you can control is your agency. And if you want to sit and complain about the structure, see how that’s working for you. What’s that getting you? And you can’t go fix a broken world if you yourself are broken, if you, yourself aren’t working on self-improvement.”

Stulberg adds that if you “actually look at people who have reason to … complain about structures, they’re the ones that are like, ‘I need agency. Because if I don’t have agency, I got no one there to help me.’”

Brad Stulberg

That said, Stulberg also emphasizes that in deciding whether to focus your energy on changing individuals or structures, it should be “both/and” rather than “either/or”:

“If you want to be a badass performer and a badass person in the world, you need to realize that you have agency and you have responsibility and you need to get your sh-t together and you want to commit to getting better and taking on big goals and striving for them… You also want to make sure that you’re checking in on your neighbors and your community and you don’t want to bury your head in your sand and turn a blind eye to structural problems.”

Hall and Belluz, explicitly inspired by the long, difficult, and ultimately successful effort to depopularize smoking in the United States through top-down changes (Sid Mukherjee’s discussion of this effort in Emperor of All Maladies is a great read on the topic), believe a similar approach will be required to improve our eating.

I would have appreciated a deeper look at what individuals might do, particularly enabled by technology. Such approaches, if widely adopted, can also drive broader change, from the bottom up; the Yuka app, as I’ve highlighted for TR readers, may represent an example of how technology can help drive broader change by integrating the voices of many individuals.

Of course, the same bottom-up approach can also lead to scientifically questionable outcomes, such as the stigmatization of GMOs (to say nothing of essential childhood vaccines).

I appreciate – deeply, viscerally appreciate – the challenges of healthy eating, and the difficulty of resisting temptation in a world where you are constantly surrounded by meticulously engineered, hyperpalatable, calorie-dense highly processed deliciousness.

It’s a constant struggle at so many levels, from the social to the subcellular – a complex challenge Hall and Belluz help us more completely understand.

Oct

2025

Arbor Takes Next-Gen Gene Editing into the Clinic, Secures Chiesi Partnership

Oct

2025

Consumer Health’s Digital Convergence – And What’s Still Missing

05 Oct 2025

David Shaywitz

Consumers are taking increased ownership of their health.

As Laura Landro recently described in the Wall Street Journal, this trend is driven in part by necessity — specifically by “a shortage of doctors, long wait times for appointments and an increasing prevalence of chronic diseases such as diabetes earlier in adulthood.”

But our push to manage our own health is also motivated by a number of interrelated, encouraging factors as well, including:

Increased sense that our healthspan, and perhaps even our lifespan, is malleable, and that through our actions – our agency – together with some good luck, we can realistically hope to inflect it for the better (teaser: I discuss this topic in depth in a forthcoming commentary – stay tuned!).
Compelling new digital technologies, including increasingly powerful wearables and apps, that may provide greater insight into our physiology.
Continued advances in molecular characterization of human biology including the biology of aging, offering the promise of improved risk identification, and more precise mitigation approaches. A prosing example here is the use of polygenic risk scores, as Dr. Eric Topol emphasizes in Super Agers (my WSJ review here), and as Dr. Pradeep Natarajan and colleagues have recently implemented at Mass General Brigham.
Increased recognition that many diseases of aging are exacerbated by a shared mechanism — chronic low-grade inflammation – which typically takes years to exert its baneful effect, offering the opportunity, as Dr. Peter Attia and others emphasize – to identify this risk earlier and potentially take preemptive action.
Dramatically enhanced appreciation of the importance of so-called “lifestyle” factors – like movement, nutrition, and sleep – in impacting health.
Meteoric rise of AI that offers the promise of both integrating a range of lab and behavioral data, and then delivering relevant, customized health and coaching insights in an infinitely scalable fashion. I’ve recently discussed Google’s just-published work around an AI health coach, including the exciting hopes, and very real limitations, as well the over-the-top promises often associated with many supposed “precision” interventions.

Towards a “Personal Health OS”

The result of this convergence – or collision – of increased patient need and science-and-tech enabled opportunity has led a range of digital platforms to pursue what’s seen as the Holy Grail of consumer health, a “personal health operating system” (personal health OS) — a single dashboard you turn to that continuously integrates and helps you optimize multiple health parameters.

The current model, first discussed with TR readers in June, is summarized in the figure below.

Once we recognize that a personal OS is the goal, we can understand why wearable manufacturers Oura and WHOOP have each recently announced partnerships with Quest enabling members to obtain a battery of clinical labs, with results that read out in the associated app; these wearables already capture and leverage physiological data; now they want to add lab data to approach what they would view as the complete picture.

WHOOP CEO Will Ahmed has elegantly described the company’s ambitious vision for a “health operating system” that leverages technology and AI to monitor relevant health parameters.

WHOOP CEO Will Ahmed

This platform of the future, he writes,

“…will track how sleep fuels recovery, how recovery shapes performance, how performance generates stress, and how stress cycles back into sleep. But the technology won’t stop at observation: it will intervene, nudging behaviors, adapting routines, and even initiating care when risk rises. In this way, new technology will transform hidden feedback loops into an intelligent, always-on system for extending vitality and preventing crisis.”

He anticipates that in the near future, “Care will no longer be episodic and institution-centric, but literally centered and personalized within each person and driven by the continuous biometric signals their own body produces.”

Ahmed acknowledges many companies are working towards this goal, and anticipates,

“Success will belong to the few that can fuse massive, continuous health data with cutting-edge AI and deliver daily, trusted engagement that becomes inseparable from people’s lives. It is easier to envision the Health OS than actually build it, but there is no question this will exist in just a few years time.”

He concludes, “At WHOOP, we believe we have the ingredients and the team to tackle this opportunity.”

A few reactions.

First, I emphatically share Ahmed’s enthusiasm for the moment we’re in, for the promise of technology, and the believe in the promise of digital health – as Denny Ausiello and I envisioned back in 2013, when we wrote:

“Digital health [enabled by sensors and other mHealth tools] provides a way for medicine to break out of its traditional constraints of time and place and understand patients in a way that’s continuous rather than episodic, and that strives to offer care in a fashion that’s anticipatory or timely rather than reactive or delayed.”

I’m also thrilled that so many consumers find themselves inspired to improve their own health. As Harvard professor and primary care doctor Tom Delbanco tells Landro, “The evidence shows that the more a patient gets involved in their own care, the better the outcomes” – a sentiment that aligns with the focus on agency this column has been emphatically championing, as well as a piece I wrote for the New York Times in 2006 embracing the engagement of patient families as well.

Appropriately, digital health platforms have come in for their fair share of (generally deserved) criticism because of their approach to comprehensive evaluation, in particular their promise these evaluations will lead to meaningfully personalized health guidance.

As University of Pennsylvannia researcher Anna Wexler tells Landro, lab tests “often don’t meet validated clinical standards and may mislead consumers or lead them to buy products that they don’t need.”

This echoes a frequent warning about many of these comprehensive lab testing and/or imaging approaches, reviewed by Eric Topol in his “Ground Truths” blog highlighting the perils of false positives, and the associated evaluations they can gratuitously trigger.

The problem of comprehensive genetic testing leading to potentially abnormal findings of uncertain significance – the so-called “incidentalome” – has been classically described in JAMA by Kohane, Masys, and Altman in 2006.

Unfortunately, far less attention has been devoted to what I suspect may be an even greater limitations of these platforms: their reflexive embrace of a remarkably reductionist view – it might be uncharitably characterized (or more accurately, caricatured) as an engineering mindset, a technologist mindset, or a managerial mindset — that essential treats us as if we’re merely pieces of factory machinery that can last longer if constantly mechanically surveilled, with performance scrutinized and parameters tweaked by AI algorithms.

The word “merely” is important here, since rigorously monitoring health parameters of course can be valuable, especially when enabling potential problems to be headed off before they cause real damage. To the extent digital platforms integrate useful metrics, help us stay on top of our health, and motivate us to engage in health-promoting activities, digital platforms can be enormously beneficial.

But what platforms like WHOOP, Peloton, Oura, Tonal, and others seem to have astonishingly overlooked – as I’ve discussed with TR readers and in the Boston Globe – is a more capacious vision that recognizes the difference between metric optimization and true flourishing, a pursuit that involves connection and purpose, meaning and engagement. The substantive stuff that matters to most people.

This deeper vision of consumer health, shared with TR readers in June, is summarized in the figure below.

The apparent inability of digital platforms to embrace attributes that they can’t measure almost certainly has a negative impact on the metrics they’re so keen to quantify and optimize.

For example, major studies of longevity — such as the Harvard Study of Adult Development, as well as Northwestern’s “Super Agers” study– find that the quality most strongly associated with longer life is warm relationships with others. Yet most digital platforms remain strangely indifferent here – as if the topic too soft, too woo-woo, or (most likely) not easily quantifiable with a watch, strap, or ring.

In overlooking what truly matters, digital platforms are missing out on meaningful opportunities to significantly expand their user base and improve the health of more people.

I’m not sure most of us want to be relentlessly optimized, but I think most of us would embrace the opportunity to flourish and would welcome a platform with the vision and insight to appreciate the synergy between improving health metrics and deliberately cultivating connection, purpose, and agency.

Expanding from counting steps to cultivating agency (which I’ve described as “the motivational currency of behavior change) and enhancing our sense of connection and purpose feels like an important and, frankly, obvious opportunity that just happens to sit in a real blind spot for many metric-obsessed digital entrepreneurs and investors.

Purpose

The health impact of purpose has been nicely highlighted by the work of Victor Strecher, who has spent his career studying the subject.

University of Michigan Professor Victor Strecher

A professor at the University of Michigan School of Public Health, author of Life on Purpose, and the founder and CEO of Kumanu, a digital tool focused on “purpose-powered wellbeing,” he recently spoke at The Harvard School of Public Health, in a lecture series organized by the Lee Kum Sheung Center for Health and Happiness; you can find the video here.

Key health-related takeaways include:

In a study of 1,666 adults Strecher did with University of Michigan colleague Ethan Kross (author of Shift), a stronger sense of purpose was linked to more adaptive coping (e.g., seeing the big picture, finding a silver lining) and less maladaptive coping (notably, drinking alcohol when stressed). These coping patterns tracked closely with better emotional self-regulation — the ability to “change your own emotional weather.”
In other research, Strecher found that about 68% of people can write a purpose statement, and those who do report higher happiness and lower depression (PHQ-9) in his analyses.
Moreover, the content of purpose matters: purposes centered on success/wealth/hedonic aims are associated with lower well-being and willpower, whereas multi-theme or relational/transcendent purposes show higher well-being across studies he cites.

When Purpose Meet Analytics: Boston College’s Inspiring Example

On a more personal note, I’ve been struck recently by the impact a sense of purpose can have on an organization, in this case an institution of higher learning. One our children recently started attending Boston College (BC), which describes itself as a “Jesuit, Catholic University…rooted in a world view that calls us to learn, to search for truth, and to live in service to others.” (The school conspicuously welcomes a range of faith traditions, including ours.)

What’s been most striking in our early interactions with BC is how deeply this commitment — and clear mission — permeates campus life. Purpose seems to infuse everything they do, and belief, along with values like service and gratitude, isn’t trotted out as a buzzword but lived in a personal, palpable way.

Boston College

Consequently, BC has a markedly different feel from many campuses, and its authentic, purpose-driven approach seems especially well-suited to the fractious, often divisive moment in which we live.

Bart Giamatti

Many universities today seem both rudderless and reactive, existing (like a number of companies) merely to continue to exist. They feel more managed than visionary, and (as I’ve argued) could use a dose of the inspirational leadership Bart Giamatti brought to the university president role.

Particularly against this backdrop, a learning environment like BC’s, guided by a powerful, positive, and substantive sense of purpose and mission is a palpably powerful thing.

Moreover, by thoughtfully integrating a lived sense of mission with an admission and financial aid policy guided by strategic intentionality and informed by data, Boston College, the New York Times recently reported, transformed itself from a “struggling commuter school running a deficit” to an ascendant institution with “a $4.1 billion endowment [that] rejects 87.5 percent of applicants.”

It’s an integrated approach to attracting and inspiring college students– combing a true sense of purpose with deep analytics – that could and should serve as a model for digital health platforms seeking a similarly profound impact.

Note: Readers seeking additional reading and resources on health and agency might find this site I’ve created useful.

Oct

2025

Pfizer Buys Metsera GLP-1s, Genmab Nabs Merus for $8B, & Sanofi Commits to VC

Oct

2025

Cartography Secures $67M for T-cell Engager for Colorectal Cancer (and a Platform, Too)

Sep

2025

A Song of Science and Hope: Bruce Levine & Mags McCarthy on The Long Run

The Long Run with Luke Timmerman · Ep186: Bruce Levine & Mags McCarthy on a Song About Science and Hope

29 Sep 2025

Today’s guests on The Long Run are Bruce Levine and Mags McCarthy.

Bruce is a scientist at the University of Pennsylvania Perelman School of Medicine. He’s one of the world leaders in engineering CAR-T cell therapies for cancer.

Bruce Levine, scientist, University of Pennsylvania

Mags McCarthy is a country music star.

What do these two have in common? A shared desire to sing from the rooftops about genuine hope for cancer patients.

These two have formed an unusual creative collaboration. They co-wrote a country song called “Ring That Bell.” It’s a testament to the power of engineered T-cell immunotherapies to save lives. When these treatments work, they do a beautiful thing. They enable people to “Ring That Bell,” free of cancer and free of fear, when they leave the hospital and get on with their lives.

Mags McCarthy, country musician

It’s a song about science and how, at its best, it can offer hope.

This episode digs into how scientists can build bridges to the arts and humanities to tell stories that resonate. Watch the video at ringthatbellsong.com and on YouTube and Spotify.

Please enjoy this conversation with Bruce Levine and Mags McCarthy on The Long Run.

Sep

2025

Roche Buys 89Bio, Novartis Doubles Down on Monte Rosa, & aTyr Flames Out

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