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Weekend reads: Computer science conferences impose caps; Lancet strikes to continue; Is this the ‘mathocalypse’?
If your week flew by — we know ours did — catch up here with what you might have missed. The week at Retraction Watch featured: A company named Springer that isn’t the publisher is offering authors…
Doctors may be getting childhood obesity wrong, new research suggests
A Lancet Commission definition of clinical obesity cuts pediatric rates sharply by requiring evidence of health complications beyond body mass index.
Takeaways from an evaluation of Google's diagnostic chatbot, AMIE
In this edition of STAT Health Tech: A look at a study recently published in The Lancet about Google's diagnostic chatbot, AMIE.
Is The World Ending? A Lancet Commission Says Maybe
BERLIN – As candidates to become WHO director-general squabbled in the halls of the InterContinental, a three-year effort by the Lancet on future health
Lancet Commission identifies seventeen catastrophic threats to global health
Global experts warn that today's decisions across health, finance, climate, defense and security sectors will determine how many years of good health future generations gain - or lose - to preventable illness and early death by 2100.
Nuclear war, malicious AI pose extinction risk by 2100 among 17 health threats: Lancet
A Lancet commission ranks 17 major threats to health through 2100, with nuclear war and malicious AI carrying real risk of human extinction.
Nuclear war and malicious use of AI threaten end of humanity by 2100, says Lancet assessment
Newly established commission identifies 17 catastrophic threats to human health but says ‘realistic route to act’ on each exists
Global experts call for coordinated action on digital health risks
The way digital technologies are currently built and governed creates real risks to health worldwide, alongside genuine benefits, according to a new three paper Series authored by 13 global experts, published in The Lancet.
From nearsightedness to self-harm: Meta-review looks at how digital media impacts young people’s health
The authors of an expansive new series in ‘The Lancet’ argue that gaps in our understanding about digital harms shouldn’t delay urgent policy action.
Is 50 the new 60?
Subscribe TL;DR: Younger generations are showing signs of worse health compared to earlier-born cohorts at the same age This backward “drift” is showing up both in mortality risk and chronic disease Worsening trends in obesity and diabetes are the most consistent signals Taking the long view, we’ve made astonishing gains in health and life expectancy in the last century. Global average life expectancy has more than doubled from 32 years in 1900 to 73 years in 2024. (But don’t forget, there were still old people when life expectancy was 32). As people lived longer, they also generally lived healthier along the way. It turns out that avoiding things that can kill you early, like malnutrition and lots of childhood infections, also keeps you healthier later in life. In a classic 2004 paper, Finch and Crimmins proposed that cohorts of children who benefited from fewer early life infections had less lifetime exposure to inflammation and cardiovascular disease later in life, accelerating mortality improvements at older ages. Poor nutrition in the womb has also been linked to a higher risk of later chronic disease. The upshot is that improvements in childhood health can pay dividends many decades later. The combination of better living conditions (nutrition, sanitation) and medical advances (antibiotics, vaccines, blood pressure meds, etc) meant that people’s healthy lifespan generally expanded, even as they lived longer. Aging researchers call this best-case scenario “compression of morbidity”—meaning we delay the onset of disease and disability even faster than the years of life we are adding. During my 20+ year research career, we could generally bank on the idea that younger generations would not only live longer but also keep getting healthier along the way. “60 is the new 50” as they say… Enter “Generational Health Drift” Sadly, this expectation of steady progress may be changing. You’ve probably heard that US life expectancy gains have slowed to a crawl in the past couple of decades. Mortality improvements are also slowing (though less dramatically) in many other high-income countries (you can read more about that in a review paper I wrote here). Mortality is a very blunt health measure, but it is often a good barometer for the broader population health trends happening underneath. And we are now seeing that younger generations may be in worse health at similar ages compared to earlier born cohorts. My collaborator Prof. George Ploubidis at University College London coined this worsening health in more recently born cohorts “generational health drift.” “Generational health drift” is bad news on multiple fronts. Most obviously, we don’t want our health progress to go backward. But the timing is also bad, since our populations are aging. In demographic terms, “population aging” means that the proportion of the population at older ages (i.e >65 years) is increasing. Fun demography fact: Current population aging is not due to the recent declines in the birth rates making the news, but declines in fertility decades ago, after the “baby boom.” As baby boomers reach older ages, the smaller cohorts behind them mean the percentage of older adults will increase. For example, the share of the population age 65 and older in the US increased from 12.4% in 2004 to 18.0% in 2024. This story of population aging was written long ago. Many worry that population aging will put pressure on health care and pension systems. But if people reach older ages in better health than in years past, those fiscal pressures would be less dire than projected. Healthy older people can also continue to contribute to society in many valuable ways, including paid work, caregiving, community service….even high political office 🤷. On the flip side, if younger generations reach retirement age in worse health and with more disabling conditions, this could magnify the societal challenge of population aging. Evidence for worsening generational health A recent paper that I LOVED in the Proceedings of the National Academy of Sciences by Dr. Leah Abrams and colleagues examined which birth cohorts (aka generations) were behind worsening US mortality. Behold the Lexis diagram (cue swooning demographers). Calendar time is on the x-axis, age on the y-axis. Birth cohorts can be followed over time as they age on the diagonal lines moving up and to the right. This figure plots the year-on-year % change in all-cause mortality at a given age. Green shading indicates mortality improvements over time, white is stagnation, and gray shading indicates worsening mortality. Following the diagonal line for those born in 1950, you can see a noticeable shift from green to gray that follows this cohort for most of their lives. This gray shading shows generally worsening mortality for the 1950 to 1959 birth cohorts compared to their predecessors across all ages. Concerningly for my GenX and elder millennial peeps, there was also a deterioration in mortality for birth cohorts born in the 1970s and 1980s, visible as dark gray areas at ages 30 to 45 during the 2010s. While some of these mortality changes reflect specific shocks such as the opioid epidemic, most deaths still occur from major causes of death such as cardiovascular disease and cancer. For cancer, the gray in the top left corner of the figure below reflects the legacies of smoking for older cohorts, followed by a period of green with improvements in cancer mortality as smoking rates declined. But the white/gray shading in the bottom right corner highlights a stagnation and reversal of the cancer trends, with cohorts born around 1970 to 1985 experiencing worsening cancer mortality. This deterioration was most noticeable for colon cancer mortality, possibly linked to obesity or dietary factors. Not just dying more, but less healthy along the way. A recent paper by Dr. Laura Gimeno of University College London (of which I am a co-author), found evidence that more recently born cohorts in Great Britain have stagnating or worsening health. A stylized picture of what“generational health drift” might look like: The review paper found: Rates of childhood overweight and obesity were highest among Gen Z. Rates of diabetes in the 40s almost doubled from 3.1% among the Baby Boomers to 5.9% in Generation X. Gen Z reported higher rates of poor mental health in adolescence compared to earlier-born groups. These UK results are consistent with studies showing worsening health across generations in the US as well. A 2021 US study found that more recently born cohorts had worse biological markers (like blood pressure and blood sugar) than earlier generations at the same age. A separate 2022 study of Americans aged 50 and over found that more recently born generations had a higher number of chronic diseases, with younger age of disease onset. A 2024 Lancet paper found that in the US, women born in 1945 had 33% obesity prevalence at age 50, rising to 48.2% for women born in 1970 turning 50. So what’s going on, and can we turn it around? We don’t have a definitive answer for what’s causing the deteriorating health of younger cohorts, but circumstantial evidence points to worsening trends in obesity and diabetes in both the US and UK. Remember that cohort trends reflect lagged effects of early environments, and younger generations have faced both earlier onset and more severe obesity across their lifetimes. Despite these very concerning trends, the future is not set in stone. We’ve reversed poor generational health trends before: drops in smoking are a major reason cancer and heart disease deaths fell so dramatically in recent decades. GLP-1 drugs may finally turn the tide against rising rates of obesity and diabetes, though it is still early days. But things could also get worse…for example from a return to higher levels of childhood infectious diseases that can have a lasting impact on health. See for example: [ ](https://jenndowd.substack.com/p/dont-you-forget-about-measles-the) [ Don’t You Forget About Me(asles): The Virus That Erases Immune Memory ](https://jenndowd.substack.com/p/dont-you-forget-about-measles-the) Jenn Dowd, PhD · March 24, 2025 [ Read full story ](https://jenndowd.substack.com/p/dont-you-forget-about-measles-the) Even as an optimist, emerging data on the “generational health drift” has my full attention. For most of my research career, we took it for granted that each generation would be healthier than the last. But if present trends continue, **50 could be the new 60….**and Gen Z celebrities will soon look older than Paul Rudd :). Stay well, Jenn Share the Health! If you found this post useful, please share it with a friend. Share
The Big Holes in Wearable Heart Rate Variability And Readiness Scores
On September 9th, Apple announced it was revamping its Apple Watch Health Sensing System, rolling out a Readiness score (0 to 10), and increasing the frequency of heart rate variability (HRV) outputs 24-fold. This can be viewed as upping its competition with various other consumer wearable sensors. These “readiness scores” as a composite of multiple metrics, with heart rate variability (HRV) being front and center for most. The majority of Americans are now using wearable sensors, which equates to well over 100 million adults. HRV and Readiness scores are increasingly being marketed as a measurement of autonomic nervous system health, a digital marker for future disease, a clock for biological age, and a holistic metric to promote healthspan and even longevity. (Apple also introduced a new longevity tab and “Health Age”.) None of this has been proven. In this edition of Ground Truths I am going to review what we know about heart rate variability and readiness scores. Heart Rate Variability HRV is the variation in normal heart cycle timing. The variability of the heart rate, the barely perceptible millisecond changes in time between consecutive heart beats (see R-R intervals in the Figure below, left panel), is due to interplay between the sympathetic and parasympathetic (vagal nerve) inputs. Distinct from heart rate, individuals with the same heart rate can have very different HRVs. It is a rough reflection of the autonomic nervous system (ANS) activity, inadequate to say whether a person’s ANS function is abnormal. For more than three decades, heart rate variability (HRV) has been measured and several studies have found an association of low HRV and clinical outcomes, particularly a link with higher all-cause and cardiovascular mortality. There have also been less well established links of low HRV to risk of early cognitive impairment, dementia, mental illness, Type 2 diabetes and substance abuse. An important reminder is that HRV is a surrogate marker without any established cause-and-effect relationship. If you increase your HRV, that doesn’t mean it will improve health outcomes. In fact, there is no hard evidence for that. All that work linking to health outcomes was done with electrocardiogram (ECG) derived HRV. Now, in the era of consumer wearables, this is getting assessed differently, by optical pulse (yes, the lights you see) plethysmography (PPG) or what is called pulse rate variability (PRV). They are not the same, as shown below (right panel) and only concordant when the delay between the ECG and pulse is kept constant, which basically means at rest. I should mention there’s also what I will call MPV, a mattress mechanical movement sensor, a derived heart rate variability, that companies like Eight Sleep use, even further away from directly measuring HRV. HRV has not one uniform measurement but many different types of quantification, such as RMSSD, the magnitude of difference between successive R-R intervals of normal sinus beats (N-N) or SDNN, the standard deviation of NN intervals, both in milliseconds. SDNN is one of the so-called frequency domain HRVs (others are LF, HF, LF/HF). Different wearable sensors use different metics; Apple has relied on SDNN and nearly all of the others use RMSSD, which is generally considered the more accurate metric. There’s also the different length of time measured, such as for a matter of minutes, all day, or an overnight’s sleep. Short measurements are especially problematic since they don’t capture enough of respiratory modulation and other factors that influence HRV. Share Ground Truths How well does HRV correlate with PRV? There are very limited studies, especially independently done. One that is commonly cited was conducted by Air Force researchers in only 13 healthy adults assessing Oura ring 3 and 4, Whoop 4.0, and Garmin Fenix 6 and showed a correlation coefficient of 0.88 to 0.97 and a mean absolute percentage error from 6 to 10%. The correlation is not a perfect 1.0, but there’s at least a fairly high level of correlation. HRV is supposed to increase during the night due to takeover of the parasympathetic nervous system, and higher during deep sleep. A recent example of my 1 week, all day “HRV,” and one during sleep is shown below. As you can see, the N of 1 data are inconsistent for the same days from different sensors (Oura, AppleWatch, Fitbit Air, and Eight Sleep) by patterns, absolute numbers, and comparison with prior days and weeks. The largest study in over 8 million Fitbit users (the old version, not Google Fitbit Air, introduced in May 2026) gives you a sense of the effect of age, sex, and the 2 different main HRV (here PRV) metrics, with RMSSD on the left and SDRR (=SDNN) on the right below. That study, from data collected in 2018, is a major outlier, since all the more recent ones are tiny with respect to sample size. Many of the companies have not had independent evaluation of their HRV, such as Eight Sleep, but have published a low standard error on their website. There are some other published studies on the correlation between HRV and PRV, but they are all small and only in healthy adults. A scoping review emphasized the lack of study in underrepresented individuals, including the aged, people of color (which affects the PPG signal), and individuals who are underweight or obese. Add the typical adult age 60 plus with one or more chronic diseases. For example, one study in over 900 adults found poor correlation of HRV and PRV, non-uniformly underestimated across many chronic diseases (cardiovascular, endocrine, neurological, respiratory, and others), concluding PRV is “an invalid surrogate for HRV.” A recent systematic review of 43 studies comparing HRV and PRV found reasonable pooled absolute standardized error (HRV as gold standard) but only 10 of the studies provided quantitative synthesis in ideal conditions. Their main conclusion was similarly cautious: “PPG-derived HRV [PRV] should not be regarded as universally interchangeable with ECG-derived HRV across all devices, populations, and recording contexts.” Factors Affecting HRV and PRV That gets me to the long list of factors that affect HRV (and PRV) besides the device, the type of measurement (RMSSD, SDNN or others), the person’s signal, the sensor site, the duration of data capture, if weighting by sleep stage is used, how artifact is processed and corrected. And this list is not complete!: Oura puts out data from their community of users (who input data) on what affects their overnight HRV. The factors currently provided are: no alcohol (increase 8%), melatonin (increase 2%, float tank (increase 2%), wine (decrease 4%), and party (decrease 14%) in overnight HRV. Must be some big parties! Subscribe What is a PRV measurement good for? It has been falsely characterized as an index of “autonomic balance” and a specific indicator of stress. A 2018 review of the studies available for HRV and its relationship to stress, not using any of the current wearables, found that stress can lower HRV. But so can many other factors. The non-specificity of the signal, indexed to the table above, is striking. Evidence from a UK Biobank study of over 46,000 participants with actual HRV looked at genetically predicted HRV, a genetic risk score, that failed to show the expected HRV-mortality link, indicating that _HRV is likely not causa_l, but rather a reflection of person’s physiologic state. A review of consumer wearable HRV data from 5 longitudinal studies showed that nighttime PRV was not associated with perceived stress, and surprisingly higher HRV, in the largest cohort (N=717 participants), was correlated with higher stress. An Oura ring cohort of 525 first-year college students found a link between overnight PRV and perceived stress, but that was also seen with resting heart rate, sleep, and respiratory rate. Several very small studies have examined the relationship of HRV and athletic injuries or guiding training with mixed, and predominantly negative results. HRV biofeedback training with paced breathing had no significant effect on reducing stress or raising HRV, as demonstrated with sham controlled trials. When HRV for multiple days showed a decline in conjunction with body temperature, the Oura ring published data for prediction of Covid. The WHOOP company sponsored an observational study, published in 2026, of 30,000 users for 72 weeks, without a control group, that reported reduced alcohol intake (5.8 % points) by self-report. That doesn’t tell us much, and particularly about the merits of HRV for behavioral change. If you use the same device and conditions as longitudinal trends for multiple (at least 2-3) weeks that may be the one way to get something useful from the measurements. Data for overnight sleep with minimal motion and using RMSSD is the best proxy for real HRV. The reason to look at trends rather than any given night is that it more likely represents something, even though you won’t know with certainty what the “it” is. Keep in mind there are no data, no peer-reviewed evidence, to show that HRV fluctuation in-person has any correlation with health outcomes. Share Readiness Scores These are proprietary scores that integrate different metrics for each of the wearables: no algorithms have been disclosed. They are unvalidated against health outcomes. In a review of 14 composite health scores of readiness and recovery, HRV contributed 86% to the scores, followed by reading heart rate (79%), physical activity and sleep duration (both at 71%). That review noted the substantial variability in measurement protools and lack of standardization. Sleep staging is notoriously inconsistent and inaccurate by these sensors, which adds further to the HRV uncertainties for what the scores, which use sleep stage data, mean. Only resting heart rate has been shown consistently across devices to be extremely accurate. I’ve made a Table to summarize what we know about which metrics are included, the scores, any peer-reviewed studies that compared the readiness score with health outcomes, and the corresponding (if any, NA-not available) citation. You will note that some companies do not use the term “readiness," such as WHOOP for recovery, and Garmin, which has 2 different scores, one of which is Body Battery. Eight Sleep uses the term “Fitness Score.” They all include HRV; Apple includes a new metric they call “Recovery HRV” which among other components uses 7-days of sleep, but it is unclear what this means or how it is differentiated from other scores (there are clearly no data for outcomes). We have no knowledge of how the different components are weighted or whether any of these scores are better than resting heart rate, HRV alone, physical activity, or any other single metric. Since none of these are standardized, they are not interchangeable, so if you get a 90 for Oura that has no relationship to a 90 on a Google Fitbit Air. Notably, the company can update its algorithm for readiness score at any point without notification to device users. Without any useful evidence of actionability for these scores or established relationship with health outcomes, it is hard to make a case for their value. At the Apple recent announcement they showed their Readiness score (0-10) on the watch (Figure below) but there are no published data on this score, not even on their website. It’s available only on their new Watch Series 12 or Ultra 4 [of course, ;-)]. That exemplifies the problems with these scores, lack of data and evidence for being meaningful to promote health. Perhaps the best study (which isn’t saying much) is the WHOOP Recovery for golfer performance, because it did correlate with an objective outcome, even though there was no control group and the authors were all from the company. Among the 389 pro golfers, an absolute 10-per cent point increase in Recovery score was associated with about 0.5 fewer strokes per round. But that’s hardly a health outcome! WHOOP is also conducting a study in over 2,700 runners to see if their recovery score will be linked to less injuries and improved performance, but that is not yet published and has no control group or randomization. Putting This in Context For two decades I’ve been enthusiastic about the potential for digital health and particularly wearable biosensors. Over the years, we’ve seen some great progress for their ability to promote physical activity and accurately detect atrial fibrillation (the first FDA cleared deep learning AI for consumers). That work was the subject of rigorous research. But there are holes in the data and evidence for other metrics. One notable one is the “VO2 max” story that I wrote about earlier this year. At that time many subscribers asked me to cover heart rate variability, which I finally got to here. When I dived into the research and publication for HRV and readiness scores, I expected to find at least some that were of high quality and demonstrated their utility by linkage to health outcomes. To my surprise, I found none. The wearable sensor measurements for HRV (PRV) are, for the most part, accurate, but that validation work has only been done in small studies of healthy adults and does not take into account the long list of factors, from the device, software side, and the user side, that affect HRV measurements. Moreover, this metric chiefly relies on optical sensing and, as we have learned for heart rate PPG sensing, may be less accurate in people of color. Keep in mind that all of the health outcome association evidence comes from ECG-derived HRV; none are from wearable sensor data. I will repeat the key point: there's no peer-reviewed evidence to show that in-person HRV fluctuation—or efforts to raise your HRV— has any correlation with health outcomes. For those of you who look at your HRV on awakening, or even 2+ week trends of it being low, I hope this context helps to relieve any anxiety. Yes, low HRV (not PRV) has been shown to increase risk of some diseases as summarized above. But efforts to raise your HRV—a surrogate metric— has not been established for improving any health outcomes. HRV does not have any evidence of causality (the genetic evidence actually goes against this possibility). In this summary, I have not included data for other wearable sensors such as Polar, Samsung, Withings, Suunto, Amazfit, Coros, Ultrahuman, or additional mattress sensors. These are beyond my first-hand experience, and as far as I know from my in-depth review none have any peer-reviewed published data that differ from the 6 sensors I’ve reviewed here. From the points I’ve gone over above, we’re not ready for readiness scores. Besides being proprietary, they are predominantly based on metrics that have their own issues. It’s compounding the problem, like building a house without a solid foundation that has never undergone a rigorous inspection, and then selling it. Like I mentioned for PRV, you can look at trends over weeks rather than any single day, to get a handle, but even that may not be helpful. There’s simply no evidence that these scores meaningfully relate to health outcomes. I’d emphasize they might, but that requires doing prospective or randomized studies to prove it. None exist. There’s great promise for HRV/PRV utility_. For example**,**_ Prof Maiken Nedergaard, who discovered the brain glymphatics that are essential in eliminating metabolic waste products from the brain during sleep, has posited that HRV could be a non-invasive marker for neuromodulator oscillations, brain-body regulatory circuits, and brain clearance. That would be extremely useful, but like everything else on HRV and readiness scores it requires solid research and validation. The lay media isn’t helping much to get the story straight. Earlier this year The Economist published a piece entitled “The most useful indicator of your overall health” which ordained HRV as an “accumulated stress score.” That’s akin to the false assertion about VO2max: “V02 max is the singular most powerful marker for longevity.” As I’ve summarized here, that is not established. The fact is that so many things can lower HRV, including physical exercise (especially an intense workout), reduced sleep quality, stress, the list above, no less the device, signal, and software. Whatever fluctuations observed have not been correlated with any health outcome. Sadly, “datamaxxers” are widely using HRV and readiness scores that have never been validated to mean anything. We already know that for some people using the sensors for sleep metrics, it can induce “orthosomnia,” an obsession to get high sleep quality, with associated high levels of anxiety. In an experiment done by a company to promote sleep quality for its employees, “For those employees who did use the trackers, many reported feeling perfectly rested until their tracker told them they had had a terrible night. Others were told that they had slept like a baby when they had actually been lying awake worrying about the quality of their sleep. “ The same problem can result from preoccupation with HRV or readiness scores, with anxiety that would lead to further reduction in both. It you are using a wearable like >100 million American adults, it’s OK to look at these data, but contextualized with the major caveats reviewed here. If you are one to require evidence that HRV or readiness scores are linked to health outcomes, you may not even want to look. The companies make it hard to turn them off! Let me end with the companies that make and sell wearables. Apple’s doubling down on HRV (24-fold more reporting and heart rate very 5 seconds) and introduction of a Readiness score tells us that consumers have bought into these metrics and they are joining the club. However, all of this is occurring with a backdrop of tens millions of users, claims about the data that are not backed up by adequate evidence, marketing way out in front of whatever limited data exists, and not being transparent about their readiness score algorithms. The companies can well afford to do the research that is needed to connect these metrics with health outcomes show, once and for all, that increasing HRV or using readiness scores promotes our health. If they believed and invested in the products they are selling, we’d not be in this position of not knowing. That’s essentially where we are with HRV and readiness scores. Perhaps someday this will change and we’ll have good reason to embrace them. NB: I wrote this post. No AI. I have no conflicts of interest with any of its content. Loading... Ground Truths has 215,000 subscribers from every US state and 214 countries. There are over 300,000 followers of Ground Truths so more than 90,000 folks who can easily convert to be free subscribers. Your subscription to these free essays and podcasts makes my work in putting them together worthwhile. If you’re not a subscriber, please join! If you found this interesting PLEASE share it! Share Ground Truths The proceeds from all voluntary paid subscriptions go to support our summer internship program. It enabled us to accept and support a record number of 62 summer interns that joined us in 2026! These are high school, college and medical students selected from thousands of applicants. We couldn’t do this expanded program without the funds coming in through Ground Truths. Thank you!
Nearly 1.7 million deaths linked to second-hand smoke in 2023, study finds
More than 2.7 billion people worldwide, including 767 million children, were exposed to second-hand smoke in 2023, contributing to nearly 1.7 million deaths, a Lancet study said on Tuesday. Researchers…
Women dominate health workforce but gaps remain, study finds
Women have driven the expansion of the global health workforce over the past three decades, yet substantial workforce shortages remain, according to a new study published in The Lancet Public Health.
The Lancet Regional Health – Europe: Europe’s failure to deliver on drug-resistant TB
The Europe's TB paradox: some of the world's wealthiest and most advanced health systems are failing to implement known tools to tackle drug-resistant TB.
SDSU leads international research collaboration to broaden understandi
The series was published in The Lancet Public Health and expands the evidence on sex workers' well-being and occupational safety.
Four-paper series broadens sex workers' health focus beyond HIV prevention
A new four-paper series in The Lancet Public Health reflects a two-year collaboration among researchers at San Diego State University and the Johns Hopkins Bloomberg School of Public Health, the Global ...
[AIDS 2026] Johns Hopkins Bloomberg School of Public Health: Lancet report recommends paradigm shift in care for older adults with HIV
The report recommends health systems caring for older individuals with HIV should move beyond the standard ART to a more comprehensive, healthy-aging approach.
Making Our Own Luck
We are cross-posting a piece that former NIH official Kris Willis wrote for Macroscience. Kris is now the President and Founder of the Woodley Park Institute, for which I’m a board member. Picking winners or hedging bets? Federal science agencies have long wrestled with the question of how to ensure their billions of dollars of grants and contracts result in maximum benefits for Americans. On the surface, it might seem that a goal-oriented, interventionist style of management would be the best policy: prioritize our most pressing problems and distribute funding accordingly.This top-down strategy creates a unique hazard, though: bad choices can send resources in the wrong direction, resulting in slow progress that impedes the delivery of tangible benefits to citizens. Moreover, if decision makers pursue an applied advance when the underlying scientific principles remain poorly understood, they risk costly failures and a loss of support for the research enterprise at large. Examples include Nixon’s 1971 War on Cancer, undertaken on the premise that a cure could be achieved in less than a decade, the drive to build an operational commercial fusion plant by the mid-1990s, and the National Plan to Address Alzheimer’s Disease, which failed to produce the effective treatments and prevention strategies promised by 2025. The contrasting laissez-faire approach is to hedge your bets. If the path to an advance is impossible to predict, then the wisest choice might be to distribute funding to as widely as possible. The main risk of this strategy is that spreading funding thinly may limit the resources available to the most promising research, resulting in the same negative outcomes as the interventionist approach: limited support for the most promising topics, slow progress, and delayed returns. In reality, at science agencies like the National Science Foundation and National Institutes of Health, program managers navigate between these two extremes, setting some funds aside to target high-priority areas and using the rest to cover the widest possible range of meritorious proposals. This middle path seems like the most rational way to proceed, but it still requires making choices. How much should be set aside for high priority topics? What should those topics be? How should we define merit? Expert opinion can provide a helpful guide, but leading experts can have remarkably different opinions about what matters and what should be prioritized. Moreover, experts and administrators alike can be risk averse, giving an edge to high-profile, well-established concepts. What’s really needed is a data-driven framework to help guide decision-making, one that doesn’t simply repackage prestige or incumbency. Recognizing breakthroughs years in advance Many breakthroughs fail to attract funding or recognition at the earliest stages of development. Katalin Karikó, for example, spent years struggling to win grants for work on mRNA that would eventually win her and Drew Weissman a Nobel Prize. Similar stories can be told about Jim Allison’s groundbreaking studies leading to the development of cancer immunotherapy, Stan Pruisner’s demonstration that prions can self-replicate without DNA, or Robin Warren and Barry Marshall’s proof that Helicobacter pylori, not stress, causes ulcers. Yet at some point, the scientific community recognizes and responds to transformative breakthroughs like these. How does that change happen? And what if science funders could identify the areas that are on the cusp of a breakthrough? Those questions led my collaborators and me to study how scientists responded to past breakthroughs. Based on patterns in that data, we developed a means of predicting future breakthroughs, using biomedicine as a proof of concept. It’s worth taking a moment to describe how our approach works. Briefly, our prediction process begins by grouping the 18 million or so peer-reviewed papers in PubMed, the authoritative database of biomedical research, into roughly 50,000 unique topics. A small subset of these topics are so widely acclaimed as breakthroughs that they have been recognized with a major prize like a Nobel or a Lasker Award. We theorized that studying the development of these outliers over time, especially before they gained acclaim, was the key to identifying future instances of them. After defining topics, we chose 21 representative breakthroughs and asked what they looked like before they won prestigious prizes. To answer that question, we re-ran our topic-mapping algorithm repeatedly, winding back the clock one year each time, stringing together the years to follow the progress of each field as it grew and advanced. We found that in each case, the years leading up to a discovery followed a pattern: a burst of papers on a new, rapidly evolving topic, many of which quickly became influential. These characteristics—the percent of papers that are new, the percentage of papers that are brought in from other topics, and the influence of each individual paper—can all be measured separately for any given topic. Together, they act as a predictive signal that is detectable an average of five years before a transformative discovery is made, and up to thirty years before the discovery receives a major prize. Scanning the current research landscape for topics that display this signal allows us to predict what work will likely produce a future breakthrough. Each year we analyzed includes four or five signals, a number that appears to have remained constant across a twenty year time frame. In their classic work on the sociology of science, Bruno Latour and Steve Woolgar established that the desire to participate in a major discovery is an important motivator for scientists as they consider whether they should take up (or abandon) a research problem. Although further work is needed, the simplest explanation for our results is that this behavior is widespread enough to detect at scale. A foundational advance, or something like it, draws the attention of scientists and causes them to change the direction of their research. They vote with their feet, staking their own reputation and careers by publishing on and citing the new idea. That upswell of interest is the foundation of our breakthrough signal. What kind of research does our model identify as a breakthrough? After building a model based on the patterns in our 21 preselected breakthroughs, we tested it by identifying all early signals of discovery from 1994 through 1997. Of the 18 signals we found in that time period, 17 can be traced forward in time to a breakthrough. Examples include super-resolution fluorescence microscopy (see the image above), the directed evolution of proteins and enzymes (Chemistry Nobel, 2018), and sequencing the human genome (National Medal of Science, 2008). The discovery of the role of leptin signaling in obesity is a particularly interesting case study. Around 1950, scientists noticed the existence of a type of lab mouse that suffered from a unique inherited form of obesity. When given the freedom to choose their own diet, these mice ate more than normal and preferred food that was high in fat. Researchers had few clues as to why the animals overate; early experiments pointed to the existence of a soluble ob factor found circulating in the bloodstream that regulated appetite, but its identity was unknown. In 1994, Jeffrey Friedman and colleagues identified and sequenced the ob gene, noting that the protein it encoded appeared to fit the profile of a circulating factor. A year later, a trio of high-profile publications demonstrated that ob was a hormone that regulated body weight and fat deposition by regulating appetite. One of these was co-authored by Friedman, who christened it leptin from the ancient Greek word for thin. Using our model, the data from 1996 make it clear this advance would become a breakthrough. Scientists had flocked to study the biology of the new hormone, generating the flurry of new papers and citations required to produce a signal. One of these demonstrated that serum leptin concentrations reflected the amount of adipose tissue in the human body, providing clinical validation of the earlier mouse studies. Before the identification of leptin, scientists were unable to point to a specific molecule that controlled appetite and adiposity, so that it was impossible to rule out non-physiological causes of obesity; its characterization fundamentally changed our concept of weight gain. In 2010, Friedman and fellow pioneer Douglas Coleman were awarded a Lasker for the discovery. Our work also identifies breakthroughs in clinical practice and behavioral and social sciences, even though these areas are less likely to draw the attention of major prize committees. One example that falls into this category is the introduction of endovascular aneurysm repair, a minimally invasive surgical procedure for the treatment of abdominal aortic aneurysm, a leading cause of death among Americans over the age of 65. Relative to the previous standard of care, it reduces in-hospital mortality by almost four-fold. In 2017, Timothy Chuter received the American College of Surgeons’ prestigious Jacobsen Innovation award for his multiple refinements to the technique. Another under-recognized breakthrough identified by our model is the development of standardized survey instruments to assess the quality of life for HIV+ patients. The antiretroviral cocktails introduced in the mid-1990s reduced AIDS mortality, but treatment came with serious side effects. The new evaluations showed that patients whose disease progressed had worse physical functioning than Americans with other chronic diseases, while those who were asymptomatic maintained a health-related quality of life on par with the overall US population. This evidence made it possible for patients and activists to argue that even in the absence of a total cure, and in spite of the side effects, alleviation of symptoms was a worthwhile priority for clinicians. My colleagues and I have failed to identify any significant recognition for the physicians and health policy experts who pioneered this advance, although in 2016, researchers called for the World Health Organization to set targets for good health-related quality of life as part of its framework to end the AIDS pandemic. From forecasting to funding How should science funders use our predictions? Any serious discussion of what we should do with this new capability needs to begin with an understanding of its limitations. We can’t (and shouldn’t) invest all of our resources in the small number of topics predicted to produce breakthroughs. Innovative new fields are born from existing ones; they rarely arise de novo. If funders don’t maintain a diverse portfolio, the breakthroughs of tomorrow will have no antecedents. Think of this as eating the seed corn, or killing the goose that lays the golden egg. There are also multiple goals of funding beyond basic scientific discovery, including translating discoveries into clinical practice, developing new technologies, supporting economic development, and training new scientists. The investments needed to accomplish these goals are likely different from those required to support emerging breakthroughs. Finally, we must be aware that we may not capture every instance of a breakthrough. The concept is fuzzy, and not every significant discovery is recognized with a major award. Further, breakthroughs are rare, meaning that our dataset is, by necessity, small. This makes formal estimates of accuracy challenging. Although our overall success rate appears to be high, any one signal may turn out to be a false positive. We found one apparent example: the development of the third generation COX-2 inhibitors, Vioxx and Celebrex, which were much celebrated in the early 2000s as effective but non-addictive pain relievers, meets all the algorithmic criteria of a breakthrough. Five years after it received FDA approval, researchers demonstrated that Vioxx was associated with serious cardiovascular complications, and the manufacturer voluntarily pulled the drug from the market. Celebrex remains available, although like other NSAIDs, it carries an FDA warning for increased cardiovascular risk. Decision makers who were overly focused on the breakthrough potential of this research might have wasted substantial resources nurturing an area that ultimately proved to be a failure—but so would those who relied on expert opinion at the time. That said, the potential benefits of funding the next mRNA vaccine or cancer immunotherapy years earlier than we might have are large. When we can’t assume the outcome of an action, it’s worth conducting an experiment. Can targeted support for areas that are poised to produce a breakthrough increase the return on scientific investment without cannibalizing future advances? With the necessary administrative infrastructure in place, conducting this experiment would be straightforward. First, identify all the breakthrough signals between 2018 and 2023, select half at random, and commit to a decade of investment. For biomedicine, a six year window should yield about 30 topics with the potential to produce a breakthrough. Providing strong support to half of these might be accomplished for $300 million a year. That’s roughly half of the recent annual budget of the NIH Common Fund or around 20% of the fiscal year 2025 budget for ARPA-H. After five years, then again at ten, compare to see which group — the one that was actively managed, or the control — produced more breakthroughs, and on what timescale. Although we used biomedicine as an example, the same experiment could just as well be run for physics, materials science, or any other discipline. Any attempt to undertake such an experiment should keep three points top of mind. First, we can predict the topic of future breakthroughs, but the people and vision for how to move the work forward are still important. In practice, this means success requires active program managers with the expertise to develop the science and the authority to do so, including by recruiting investigators. Second, we would be wise to learn from the failures of past attempts to fund transformative research. High among these are funding modestly repackaged work, confusing the genuinely novel with the merely unfamiliar, and relying too much on incumbent investigators. All of these risks can be mitigated by thoroughly and intelligently integrating high quality data into portfolio management. Finally, we need to have patience. Even with strong funding support, producing a breakthrough takes time. If supporting breakthroughs is the best way to nurture the birth of new fields, we also need to accurately describe and properly manage the other two stages, so that we invest wisely throughout the productive lifetime of ideas and divest once they reach the point of diminishing returns. We would benefit from more study of all of these phases, especially the transition from one to another. More research could answer questions like: When does a breakthrough become an established field? How do the availability of funding, the size and characteristics of the available workforce, and the accumulation of evidence that disagrees with prevailing models affect a field’s decline? Exactly how do old ideas give birth to new ones, and can we speed up the process? The more we understand about the dynamics of scientific progress, the better we can maximize the odds that our curiosity leads to results. I’d call that finding a way to make our own luck.
Commission to examine how precision approaches improve healthcare effectiveness, cost-efficiency, equity, and scalability worldwide.
Prof. Michèle Ramsay at the Sydney Brenner Institute for Molecular Bioscience is one of four co-chairs of the Lancet Commission on Precision Health.
Barcelona Institute for Global Health: Chronic liver disease in Europe: A preventable crisis going undetected
A new Lancet Regional Health – Europe Series calls for liver disease to be embedded in broader national and EU-level policies on diet, alcohol, obesity, public health and non-communicable diseases.
Global Health Experts Urge Urgent Action to Prevent Future Pandemics Where They Begin
BRONX, NY, April 27, 2026—A new paper published in The Lancet calls on governments to prioritize preventing zoonotic disease spillover—the transmission of pathogens from animals to humans—as a central pillar of global pandemic preparedness, The authors argue that w
The Lancet Global Health: Untangling the complex relationship between HIV-exposure and TB in children: A narrative review
A review examined existing literature on TB prevention, prevalence, and outcomes in CHEU, identifying key knowledge gaps to guide future research.
Selwyn Rogers: Bearing Witness to Violence
Howie and Harlan are joined by trauma surgeon Selwyn Rogers, who reflects on caring for victims of gun violence and speaking with families in their darkest moments—and explains why the problem must be understood as a shared societal responsibility. Harlan examines new evidence suggesting U.S. healthcare spending has grown more slowly than expected; Howie discusses a retracted Lancet article that highlights the risks of undisclosed conflicts of interest.
The Lancet retracts half-century-old unsigned commentary on talc for undisclosed industry ties
SewcreamStudio/iStock The Lancet has retracted a 49-year-old unsigned commentary on the safety of cosmetic talc after two researchers discovered the author was a paid consultant to Johnson & Jo…
New York approves cannabis for anxiety. Science says it may not help
A Lancet Psychiatry study found no evidence cannabinoids treat anxiety, PTSD. In NY, any practitioner can certify a patient for medical cannabis for any condition they deem appropriate.
Pregnant women in ERs took less Tylenol after Trump autism warning
A study in The Lancet finds that pregnant women in emergency rooms used less Tylenol after President Trump said it could raise their babies' risk of autism. Scientists say there is no proven link.
Medical journal The Lancet blasts RFK Jr.’s health work as a failure
Kennedy's destruction "might take generations to repair," The Lancet said.
'One year of failure.' The Lancet slams RFK Jr.'s first year as health chief
In a scathing review, the top US medical journal's editorial board warned that the "destruction that Kennedy has wrought in 1 in office might take generations to repair."
The war on science: resisting and rebuilding at a crucial juncture
Peter Staley’s talk at the opening session of the Conference on Retroviruses and Opportunistic Infections (CROI 2026) in Denver was a grim post-mortem of one of the most challenging years in recent HIV history – an ‘annus horribilis’ – a phrase Queen Elizabeth II used to describe 1992 and The Lancet applied to 2025.
Weekend reads: CDC’s ‘unethical’ vaccine trial; The Lancet ‘refuses to retract’ letter; on the methods used to correct science
If your week flew by — we know ours did — catch up here with what you might have missed. The week at Retraction Watch featured: Journal tags ‘impossible’ case report with short erratum Guest post: …
Youth Mental Health Spotlighted at U.S. Launch of the Second Lancet Commission on Adolescent Health and Wellbeing | Johns Hopkins Center for Global Mental Health
In October 2025, global health leaders, policymakers, youth advocates, and researchers convened in the nation’s capital for a two-day A Call to Action for Youth Mental Health. The event served as the U.S. launch of the report of the Second Lancet Commission on Adolescent Health and Wellbeing, an international effort to address the urgent and escalating challenges facing adolescents worldwide. Hosted by the Johns Hopkins Center for Global Mental Health, the convening followed the World Health Assembly launch in May 2025. The next steps will be to continue collaborating with partners across the U.S. and the world to support the actions responsive to youth needs, including, Integrate youth lived experience expertise into mental health research, policy, and practiceApply data-driven accountability for equitable access to quality careShape urban environments to promote youth mental healthUnderstand gendered drivers and tailored responses to support youth mental healthCatalyze intersectoral engagement for youth mental health: health, education, and social support systems
The Lancet HIV & The Lancet Global Health joint Series on Sustainable HIV Prevention in Africa
African experts and global partners launch the joint Series on Sustainable HIV Prevention in Africa, calling for a new era in HIV response.
New Lancet series blends social science with medicine to tackle global health inequities
Can doctors in California learn from a patient who was bounced from one specialist to another in Japan? Can clinicians in London take lessons from a patient seeking asylum while suffering a medical emergency at the U.S.-Mexico border? Can doctors treating refugees in Africa inform health policy around the world?