The deal values Apogee at $135.11 per share, a roughly 50% premium on its previous closing price. The Financial Times reported last week the deal was in the works.
Apogee’s lead drug, called zumilokibart, could be a long-lasting option for patients with a range of inflammatory diseases. It’s being tested in atopic dermatitis and, in combination with another experimental medicine, in asthma. The drug, which targets an inflammatory cytokine called IL-13 that drives a number of conditions, could be given to patients just two to four times a year after they start treatment.
U.S. researchers have identified several life factors identifiable at birth that impact on a person’s risk of being diagnosed with colorectal cancer (CRC) at a younger age.
Being a man or having Hispanic ethnicity were potential risk factors for colorectal cancer before the age of 50 years, according to the study in Cancer. Among women, being heavier at birth or having an older father also increased this risk.
Conversely, men and women with a foreign-born mother had a significantly decreased risk of having colorectal cancer at this younger age.
“Evaluating demographic, birth, and parental characteristics is important in understanding what’s causing the rising incidence of early-onset colorectal cancer,” said lead author Sunny Siddique, PhD, MPH, from the Yale School of Public Health.
“Our findings warrant future studies aimed to understand the mechanisms through which factors such as male sex, Hispanic ethnicity, birthweight, maternal birthplace, and paternal age may influence risk of early onset colorectal cancer.”
Colorectal cancer is the second most common cancer in the U.S and, while rates have declined among people 50 years of age in the past few decades, they have steadily increased in younger people.
Compared with colorectal cancer that occurs in later years, early-onset disease presents at an advanced stage, both because of its aggressiveness and delays in diagnosis. It is typically found in the rectum and distal colon, a location associated with Western diets.
Siddique and team compared the characteristics of 1221 people diagnosed with colorectal cancer before age 50 with 61,050 matched individuals without cancer, all living in California.
Multivariable analysis revealed that men had a 34% higher risk of early-onset colorectal cancer compared with women. Hispanic ethnicity was also linked with a 43% higher risk compared with being White.
Among women, every half-kilo increase in birthweight was associated with a 10% increase in early-onset disease, while having a father aged 35 years or older was linked with a 56% increase in risk.
Overall, having a mother born outside the U.S. was associated with a 15% lower risk of early-onset colorectal cancer.
Siddique and co-workers note that more than 60% of foreign-born mothers in their study were born in Mexico and they point to other research suggesting that first-generation, foreign-born Hispanic women tend to have healthier diet and less obesity during pregnancy than their U.S.-born counterparts.
The team speculates that the paternal-age finding may relate to increases in rate of de novo mutations among children born to older fathers.
Referring to the raised Hispanic risk, the researchers note that this ethnic group continues to experience barriers to accessing screening and care, including language and cultural competency, income, and a lack of health insurance.
“Per recent recommendations by the U.S. Preventive Services Task Force to initiate CRC screening among average-risk individuals aged 45 years or older, it is important to note that people younger than age 45 years are not eligible for routine screening,” they pointed out.
“Yet, our finding of Hispanic ethnicity being a risk factor for CRC is particularly relevant to this group of young individuals who are experiencing a high incidence of CRC.”
Analyses of population cohorts found that young adults exhibited earlier systemic and organ-specific aging, which was associated with increased risk of early-onset cancer compared with older adults born decades earlier.
Real‑world evidence from a nationwide cohort suggests that using electronic cigarettes after smoking cessation may attenuate the benefits of quitting in reducing lung cancer risk and mortality; more studies are urgently needed to inform evidence-based guidance.
A second positive Phase III data readout in two months is a major reason why Intellia Therapeutics (Nasdaq: NTLA) shares have soared more than 76% over the past six months—including a 29% surge this past week that followed the CRISPR gene editing therapy developer’s lead pipeline candidate lonvoguran ziclumeran (lonvo-z) meeting three key secondary endpoints in a pivotal study in patients with hereditary angioedema (HAE).
Lonvo-z met the Phase III HAELO trial’s (NCT06634420) primary endpoint, Intellia announced back in April, by showing an 87% reduction (p<0.0001) in mean monthly attacks in the lonvo-z arm vs. the placebo arm during the efficacy evaluation period (weeks 5-28). Lonvo-z also aced the trial’s key secondary endpoint by showing that 62% of the 52 patients in the lonvo-z arm were entirely attack-free and therapy-free for the six-month efficacy evaluation period, vs. just 11% of the 28 patients in the placebo arm (p<0.0001).
On June 13, Intellia presented and published additional data showing lonvo-z to have achieved positive results on three other key secondary endpoints:
Monthly rate of attacks requiring on-demand treatment, Weeks 5–28, mean (0.19 vs. 1.79, 95% CI).
Monthly rate of moderate/severe attacks, Weeks 5–28, mean (0.11 vs. 1.23, 95% CI).
Change from baseline to Week 28 in AE-QoL total score, mean ( — 23.51 vs. — 6.47, 95% CI).
Intellia presented the data at the European Academy of Allergy & Clinical Immunology (EAACI) Annual Congress 2026 in Istanbul, Türkiye, and published the results in TheNew England Journal of Medicine.
The data was strong enough for Intellia to continue the rolling Biologics License Application (BLA) submission that it began in April. The company expects to complete the BLA filing by year’s end and hopes to gain FDA approval and launch lonvo-z in the first half of 2027.
“Super pleased”
“We were super pleased with the results that we saw,” John Leonard, MD, Intellia’s president and CEO, told GEN. “We’re essentially replicating what we’ve seen throughout the program, where most of the patients reached a status of no attacks, no therapies over the course of this extended observation period. For those patients who didn’t, they appeared to be on their way to reaching that kind of a state. And critically important was that every single patient who got the drug was off long-term prophylaxis.”
“Across the board, and across all subgroups, the drug performed extremely well. So, we think it speaks to physicians, it’s going to speak to payers in terms of how they think about the drug and its ultimate, excellent utility,” Leonard said.
Investors and analysts appeared to share that enthusiasm this past week, as Intellia’s stock price rose over three of the four trading sessions following the release of data on the secondary endpoints. Intellia shares jumped 23% on June 15, the first trading day since the news, rising from $12.11 to $14.92. After a day of profit-taking that saw shares dip 2.5%, to $14.55, Intellia’s stock resumed its upward trajectory, rising nearly 4.5% to $15.20 on Wednesday, then another 3% Thursday, closing the week at $15.67. Markets were closed on Friday for the Juneteenth holiday.
Since December 18, 2025, when Intellia shares closed at $8.88, the stock has soared nearly 76.5%, accounting for most of its one-year gain of 62%. Lonvo-z accounted for three of Intellia’s four stock price peaks in 2026: The dosing of the first patient in HAELO, announced January 22, led the stock to climb 13%, from $14.03 to $15.90.
Shares surged 12% March 2, from $13.78 to $15.44, when the FDA lifted a clinical hold on the company’s Phase III MAGNITUDE trial (NCT06128629) assessing nexiguran ziclumeran (nex-z) in transthyretin amyloidosis with cardiomyopathy (ATTR-CM). The FDA imposed the hold after an elderly patient died during a study of Nex-z, an in vivo CRISPR-based therapy developed in partnership with Regeneron Pharmaceuticals (Nasdaq: REGN) to treat ATTR-CM by inactivating the TTR gene.
The third peak, an 8% gain from $15.31 to $16.57 on April 22, followed Intellia reporting positive data for lonvo-z, showing that it met HAELO’s primary endpoint, while the fourth peak followed the secondary endpoint announcement.
Misperceived market
“Hereditary angioedema has, in the last 10 to 15 years, had a variety of therapies arrive that are better than the ones that were there 20 years ago. Twenty years ago, circumstances were pretty grim for patients with HAE,” Leonard recalled. “I think some investors have looked at this incorrectly as a satisfied market, only because there are other therapies available.”
Among those therapies are three that won FDA approval last year. Last August, the agency approved Dawnzera® (donidalorsen), a prekallikrein-directed antisense oligonucleotide designed to prevent HAE attacks in patients ages 12+, marketed by Ionis Pharmaceuticals (Nasdaq: IONS). A month earlier, the FDA authorized Ekterly® (sebetralstat), a plasma kallikrein inhibitor indicated for the treatment of acute attacks of HAE in patients ages 12+, marketed in the United States by KalVista Pharmaceuticals (Nasdaq: KALV).
And in June 2025, the FDA approved Andembry® (garadacimab-gxii), an activated Factor XII (FXIIa) inhibitor (monoclonal antibody) and the first long-term prophylactic HAE treatment designed to target Factor XIIa, administered as a once-monthly subcutaneous injection for patients ages 12+, marketed by CSL Behring, the largest business unit of Australian-owned CSL (ASX: CSL).
“What we’re showing is that a lot of efficacy and a lot of utility has been left on the table, and that it’s possible for patients to get pretty close to something resembling a normal person who does not have HAE and all of the things, benefits that come with that,” Leonard said. “As people have looked at the data more completely, I think they’re seeing more and more that that’s the case, and maybe some of those original premises that they had are not quite correct.”
In research notes, three analysts said Intellia’s latest data strengthened the company’s future case to regulators for pursuing approval of lonvo-z as a one-time HAE treatment.
“We view these data as furthering Intellia’s case for regulatory approval following its expected completion of a rolling BLA,” Myles R. Minter, PhD, a partner and biotechnology analyst with William Blair, wrote June 15.
A day earlier, Jefferies equity analyst Maury Raycroft, PhD, commented that Intellia’s latest data will help lonvo-z gain more than a foothold in the HAE market.
“Positive implications”
“Big picture, we believe total HAE data have positive implications for commercial positioning” of lonvo-z, Raycroft wrote. “Editing is expected to be durable (we have seen longer term ph.I/II data out to 3-yrs); therefore, NTLA’s approach could eliminate need for lifelong chronic tx [therapy], justifying the value proposition of a 1X tx, despite competition in a crowded HAE space.”
Raycroft cited market research from Intellia showing that 64% of surveyed patients on LTPs [long-term prophylaxis drugs] are extremely likely to transition to a one-time therapy, while 54% surveyed docs expressed intent to prescribe such a treatment.
Mani Foroohar, MD, senior managing director, genetic medicines, and a senior research analyst with Leerink Partners, said Intellia’s latest results “again demonstrate lonvo-z’s clean safety and best-in-class efficacy and convenience.”
Writing in NEJM, the team of HAELO investigators reported no serious adverse events in patients treated with lonvo-z: “The most common adverse reactions were infusion-related reactions, which were generally transient and resolved without intervention. Elevated levels of serum aspartate aminotransferase and alanine aminotransferase, which occurred in approximately 10 to 15% of patients treated with lonvo-z, were transient, asymptomatic, and resolved without intervention.”
Foroohar sided with optimistic investors over their pessimistic counterparts in arguing that patients will warm up to a one-time treatment, though it will likely be costlier than current therapies.
Bears and bulls
“Bears argue limited patient demand to move up the innovation curve in a market with several approved treatments. We take the other side of this and see onetime therapy (vs lifetime chronic dosing) and patient desire to be attack-free as potent tailwinds to adoption,” Foroohar wrote. “Longer follow-up and crossover data (caveat – small n [number of patients studied]) provide an early glimpse at the improving profile of lonvo-z over time. We look to more data ahead of 1H27 launch to further educate physicians/patients.
“Subgroup analyses demonstrate clear benefit across all patient populations (prior LTP use, historical attack severity/frequency, etc.), supporting broad uptake as SoC [standard of care] across HAE—recognizing this will take time to play out as physicians gain comfort with this (likely) first approved in vivo gene editing therapy,” Foroohar added.
Intellia has not set a price for lonvo-z.
“We have said publicly we’re not going to set any new records beyond prices that have been precedented,” Leonard said.
HAE patients, he continued, “are some of the most costly patients that payers have. They’re small in number, but high in cost, with the therapies they take and their healthcare resource utilization exceeding $1 million a year.
“When you consider that these are patients that are oftentimes treated, or first diagnosed in adolescence or young adulthood, the lifetime costs are frighteningly high,” Leonard explained. “We are confident that, and we have this as an intended outcome, that we will save lifetime health, resources in very, very substantial terms, in a way that payers see and can recognize. We want to make it easy for patients to get onto the therapy, and we want to make it very competitive, cost-competitive for physicians taking care of them.”
Leaders and laggards
Elicio Therapeutics (Nasdaq: ELTX) shares plunged 72.5%from $14.85 to $4.08 on June 15 after the developer of immunotherapies to treat high-prevalence cancers said it was evaluating multiple strategic financing and partnership opportunities to advance its planned Phase III adjuvant pancreatic cancer immunotherapies program and broader AMP platform. The action came after ELI-002 7P, a 7-peptide formulation of its lead candidate ELI-002, failed the Phase II AMPLIFY-7P trial (NCT05726864) in patients with mKRAS-driven pancreatic ductal adenocarcinoma (PDAC). ELI-002 7P missed the pre-specified primary endpoint of disease-free survival (DFS) in the intent-to-treat population. Elicio said the ELI-002 7P arm had a higher proportion of R1 resected (higher residual disease) patients vs. the observation arm (19% vs. 10%), and that post-hoc analyses showed significant DFS improvement (R0: HR 0.65, p=0.048) in the 121 lower residual disease (R0 completely resected) patients, a subgroup representing approximately 84% of enrolled patients. Elicio said the trial results will shape a Phase III strategy focused on a defined R0 resected population and additional ELI-002 7P dosing.
Neumora Therapeutics (Nasdaq: NMRA) shares plummeted 49% from $1.78 to 91 cents on June 15 after the brain disease drug developer said it was chopping its workforce by approximately 35% or about 34 jobs, ending development of its major depressive disorder (MDD) candidate navacaprant, and refocusing on advancing the rest of its pipeline. The actions came after navacaprant missed statistical significance on the primary and key secondary endpoints of the Phase III KOASTAL-2 trial (NCT06058013) and KOASTAL-3 trial (NCT06058039) in MDD. The primary endpoint was the change from baseline to week 6 on the Montgomery-Åsberg Depression Rating Scale (MADRS). Neumora projected the job cuts would save it approximately $10 million annually, to be partially offset this year by approximately $2 million in one-time restructuring costs. Neumora said current cash and cash equivalents are expected to provide runway into Q3 2027, including multiple expected key clinical milestones. Neumora’s pipeline includes NMRA-511 in Alzheimer’s disease agitation, NMRA-898 in schizophrenia, and NMRA-215 in cardiometabolic disease.
uniQure (Nasdaq: QURE) shares zoomed 78% from $26.99 to $48.16 Wednesday after the gene therapy developer announced the FDA’s revised position that a three-year analysis from its two-trial, Phase I/II study (United States, NCT04120493, and Europe (NCT05243017) of AMT-130 in Huntington’s disease was now acceptable as the primary basis of a Biologics License Application (BLA) for accelerated approval of the gene therapy. Researchers hailed “game-changing” data last year showing significant slowing of Huntington’s disease (HD) progression, but the FDA disagreed while its Center for Biologics Evaluation and Research (CBER) was headed by Vinayak (Vinay) Prasad, MD, who resigned in April. uniQure said the FDA seeks to align on the confirmatory study design prior to the BLA submission, including considering allowing concurrent control on standard-of-care therapy instead of a sham procedure. “FDA communicated that they would work as expeditiously as possible with uniQure on this effort. The company is committed to conducting the confirmatory study without delay and expects to further align with the FDA on the details of such a study prior to BLA submission,” uniQure stated.
Developing a vaccine against infectious disease isn’t always straightforward. While many injectable vaccinations are highly effective, growing research has identified that targeted vaccination to the primary affected tissues may be both more effective and longer lasting.
Genital herpes, caused by herpes simplex virus 2 (HSV-2), is notoriously difficult to effectively vaccinate against due to the immunosuppressive nature of the vaginal mucosal lining, which reduces the effectiveness of vaccines through reduced immune priming.
Previous research shows that CpG oligodeoxynucleotides (ODNs), a synthetic DNA molecule, is effective at stimulating the immune system and reduce viral loads when delivered intravaginally. While effective, this method often results in significant inflammation of the mucosa.
Researchers at Yale University published a study in Science Immunology in which they explain a new strategy to improving the protective ability of an HSV-2 vaccine while reducing the inflammatory side effects. Their approach combines a vaccine adjuvant to stimulate the immune system by recruiting T cells with ODNs.
“Effective local immunity, mediated in part by tissue-resident memory T cells (TRM cells) and luminal antibodies, provides immediate viral control,” wrote the authors. They tested the ability of chemokines bound to ODNs to improve vaccine specificity and efficiency in vaginal mucosa. Their technique is celled bioactive enhanced adjuvant chemokine oligonucleotide nanoparticles (BEACONs).
“Systemically primed immunity can be leveraged to generate appropriate mucosal responses,” the authors reasoned. “For example, intramuscular priming [can] establish a pool of antigen-specific T and B cells, followed by a mucosal boost to drive their recruitment to and activation at the site of infection.”
Using a mouse model, the team tested the adjuvant which combined the CpG ODNs with CXCL9. The mice were initially dosed with an intramuscular injection of HSV-2 glycoprotein-encoding messenger RNA–lipid nanoparticles, followed by an intravaginal booster containing the cognate recombinant glycoprotein and BEACONs.
While additional chemokines were tested, including CXCL10 and a truncated version of CXCL9, neither was effective. “These data emphasize the structural features of the chemokine component that directly influence particle formation and immunological function,” wrote the authors.
BEACONs were shown to improve uptake of ODNs by antigen presenting cells and promoted the recruitment and retention of HSV-specific CD8 T cells in the vaginal mucosa. However, this effect was only seen in the combination treatment. “This response was not induced by CXCL9 or CpG ODNs alone, nor was it observed after intramuscular boosting, indicating that both local antigen and adjuvant signals are required to establish durable CD8 TRM cell populations,” they wrote.
“Our data support a model in which mucosal boosting primarily leads to recruitment and local reprogramming of systemically primed effectors rather than driving a second systemic expansion.”
These data suggest that not only is this technique effective in vaccinating against HSV-2, but there are broader implications to this technique. They explored the concept of delivering a vaccination dose for systemic priming followed by localized delivery of the vaccine components combined with an adjuvant to amplify relevant effectors at infection sites. Further, they highlighted how use of nanoparticle formulations can help to fine-tune reactogenicity of CpG ODNs to reduce inflammation responses, which would be helpful for clinical translation.
“Our findings offer a generalizable strategy for targeting other sexually transmitted pathogens, including HIV-1, human papillomavirus, and chlamydia, in which mucosal immunity is essential but poorly induced by [other types of] vaccines,” the authors wrote.
While these results are promising, more work is needed to establish the long-term efficacy of the strategy by testing viral shedding and testing in alternate models, and multiple delivery methods to adapt for self-administration or clinical options for dose delivery.
There are plenty of useful things a metric can reveal. There are even more it can obscure or corrupt. It took me well over a decade of tracking my own life in ever greater detail to fully appreciate this duality, which probably reveals something about both me and the nature of measurement.
Like a lot of people bitten by the self-quantifying bug, I initially started gathering personal data to pursue a nebulous collection of goals and desires. As a sedentary technology journalist, I wanted to feel better physically and emotionally, to get outside more, and—where possible—to bring order to some of the messiness and uncertainty of my daily existence. These all seemed to be things that could be improved with the cool clarity of numbers.
Self-quantifiers often get stereotyped as obsessive self-optimizers (and many of them are), but my reasons for producing and collecting personal data were less about life-maxxing and more about life meaning—at least at first. As most people who know me will attest, I do not have now, nor have I ever possessed, a “productivity mindset.” I’m also not all that interested in life hacks, shortcuts, or new ways to compare myself with other people. Instead, what I wanted out of metrics—what I hoped I could divine from a never-ending stream of numbers about my health, work, and social life—was something more elusive: self-knowledge. This was my first mistake.
The idea that the more we know, the better is so profoundly embedded in our culture that it feels weird to even point it out. Since at least as far back as the Enlightenment, the primary way we’ve all agreed to go about knowing more has been through measurement and quantification. After all, more knowledge—more data—leads to better decisions, which leads to happier, more fulfilled people. Or so we’re told, and with increasing frequency in the era of AI.
When two Wired magazine editors, Gary Wolf and Kevin Kelly, coined the term “quantified self” in 2007 and helped launch the movement we are all now helplessly a part of, they were essentially selling this very idea. “Unless something can be measured, it cannot be improved,” wrote Kelly in an early blog post, doing his best impression of Lord Kelvin. “So we are on a quest to collect as many personal tools that will assist us in quantifiable measurement of ourselves.” Almost 20 years later, that quest is easier than ever thanks to a flood of devices, apps, and websites all designed to help us build our self-knowledge through numbers.
My first tool was a small, plastic clip-on Fitbit I started using in 2011. It did one thing: count the number of steps I took in a day. As a lifelong video game player, I was already well acquainted with the motivational power of simple scoring systems, and I hoped my new gadget would offer the gentle numerical nudge I thought I needed to step away from my Twitter feed and, if not touch grass, at least walk next to some. Walking also seemed to be one of the few times I had what could charitably be called intelligent ideas, which seemed like another promising by-product of doing more of it.
Alas, that was short-lived. I can’t tell you precisely when “getting out into nature more” or “thinking smarter thoughts” stopped mattering to me as goals, but I suspect it took no more than a few weeks. What I can say with certainty is that my initial goal of 6,000 daily steps quickly turned into 10,000, which then jumped to 15,000 and eventually settled at 20,000 for years. Stories about becoming a “steps guy” are clichéd at this point, and they’ve earned that status for a reason.
It didn’t take long for me to trade in pedometers for heart-rate monitors (I also started running), smartwatches, sleep-tracking rings, and an embarrassing number of macronutrient-tabulating apps. Outside the health and fitness realm, my early career as a journalist also happened to coincide with the rise of social media and web analytics tools like Chartbeat, which promised to further quantify difficult-to-measure aspects of my life, like “job success” and “impact,” by tracking things like page views, followers, retweets, likes, and all sorts of other attentional metrics that now carry great weight.
Metrics inevitably redefine your core sense of what’s important, whether you’re aware of the trap or not.
Ultimately, during the 10-plus years I diligently tracked my heart rate, steps, active calories, sleep, story engagement time, stress levels, and other metrics, I gained virtually nothing in terms of greater self-knowledge. (I suppose I did learn that I liked to make numbers go up and down, but who doesn’t?) The swirl of data that followed me everywhere did not lend additional meaning or insight to the way I relate to myself, my work, or the important people in my life. In fact, the more I used numerical proxies, the worse I felt about pretty much everything.
What I did learn were two important lessons about what happens when you try to quantify the minutiae of your life. First and foremost, whatever the amount of data you’re currently collecting about yourself, it will never feel sufficient. There’s always a new metric around the corner, a better way for a tracker to remix its readings and more accurately measure what’s “important”: heart rate variability, daily stress, exercise “readiness,” cardiovascular or “fitness” ages. Measurement begets more measurement. You can count on it.
The Score: How to Stop Playing Somebody Else’s Game C. Thi Nguyen
PENGUIN PRESS, 2026
The second lesson was less obvious but no less significant. The more personal or nuanced your goals are when you set off on your self-quantifying journey, the more likely it is you will ultimately replace them with some simplified metric or ranking. Want to become a better journalist? Why not use page views and leaderboards as a proxy for success? Enjoy cooking and want to improve? Foodie metrics dictate that more complicated recipes with longer ingredient lists are the answer. Even when we know that the value of good journalism isn’t reflected in how many people read a given story or that the joys of cooking are as much about improvisation and experimentation as about successfully following some complex recipe, it’s hard to resist the allure of a simple score or stat. Metrics inevitably redefine your core sense of what’s important, whether you’re aware of the trap or not.
Over the years, people have invented various terms to describe this phenomenon. In his recent book The Score: How to Stop Playing Somebody Else’s Game, the philosopher C. Thi Nguyen calls it “value capture.” Value capture happens, he says, when you adopt external sources of measurement and then let them rule you without adapting them to suit your life. “In value capture, you’re essentially outsourcing your values,” Nguyen writes. “You’re letting an external metric or ranking set what’s important for you.” Crucially, you’re also outsourcing the process of figuring out your own sense of meaning. It’s why my walks quickly shifted from feeling meditative to prioritizing miles.
Individuals, institutions, and indeed entire societies can fall prey to value capture. In fact, once you start noticing it, you start seeing it everywhere—in journalism, education, and business, but also in our food, our hobbies, and, yes, the way we measure our health and happiness. Here’s how Nguyen puts it:
Value capture happens when a restaurant stops caring about making good food and starts caring about maximizing its Yelp ratings. It happens when students stop caring about education and start caring about their GPA. It happens when scientists stop caring about finding truth and start caring about getting the biggest grants. It even happens in religion. A pastor recently told me that his church had become completely obsessed with baptism rates. The higher-ups had established an internal leaderboard in which the pastors competed on monthly baptism rates, and it was starting to dominate everybody’s attention. He’d found himself caring less about the long-term spiritual development of his flock and focusing more on trying to deliver popular sermons that would up his baptism rates and move him up that leaderboard.
At its core, The Score is trying to untangle a mystery that Nguyen, a specialist in the philosophy of games at the University of Utah, has been thinking about for a long time: Why is it that numbers and scoring systems in games can be the source of so much joy and fluidity and play, but public measures and institutional metrics (i.e., scores that apply to the real world) seem to drain the life out of everything and thrust us all into a bleak mindset of grinding optimization?
Porter, a historian of science who specializes in the social power of numbers, has spent his career looking at why quantification has become so dominant, not just in political and bureaucratic life but everywhere. One of his key insights about the inherent attractiveness of quantification, which he calls “a technology of distance,” is that it “minimizes the need for intimate knowledge and personal trust.” Put another way, metrics travel extremely well between different contexts and are easy to grasp and aggregate.
Whether it’s a student’s GPA or a country’s GDP, these measures are understood by pretty much everyone. But that understanding comes at a price, Porter reminds us: To arrive at a clear metric, you inevitably need to simplify what you’re attempting to measure, often jettisoning heaps of nuanced, qualitative, or open-ended information so that others can find the resulting number legible.
No one (hopefully) believes that a GPA captures in any meaningful way a student’s entire educational experience or aptitude for learning, but we’ve agreed to use it because more qualitative assessments are onerous to wade through and require expertise to decipher and compare. Ditto for the economic metric of GDP, which politicians and societies are now compelled to drive higher and higher because a group of economists once concluded that this figure correlates with general economic well-being.
This is the essential tension at the heart of all data, argues Nguyen. Any institutional quantification, he says, requires that the evaluation procedure and its product be comprehensible across contexts. That profoundly limits what the metric can actually measure. “In value capture, you’re ultimately taking that decontextualized nugget and internalizing it,” he writes. “You’re guiding your life using an evaluative technology that has been engineered to travel between contexts, by stripping it of nuance.”
Every so often I’ll find myself in friendly debate with a “numbers person”—a statistician, an economist, or a friend who’s still a committed self-quantifier. After patiently listening to my measurement-gone-awry examples—the disastrous attempt to quantify pain as “the fifth vital sign” in the mid-1990s (which exacerbated the opioid epidemic), or any of the countless examples of the McNamara fallacy, where decisions in academia, medicine, and politics are based solely on what’s easily measured—many will insist that I’m misunderstanding or misinterpreting the whole point of measuring. Metrics, they’ll say, are simply a means, and the important questions concern the ends for which they are used. In other words, these unfortunate outcomes amount to user error, not something inherently dangerous or misleading about the nature of measurement.
At some point during these conversations, Goodhart’s Law will invariably come up, usually as an explanation the metrics-minded deploy for why the ends get all mucked up. The principle, which is attributed to the British economist Charles Goodhart, is often expressed as the following: “When a measure becomes a target, it ceases to be a good measure.” I have a profound dislike for Goodhart’s Law, not because I think it’s untrue, but rather for the way it gets interpreted.
As Nguyen notes, Goodhart’s Law says very little about why metrics fail to capture what’s important—or what to do about it. Find better measures, some will conclude. Don’t let metrics become targets, others will insist. These are not helpful takeaways. All measurements, I would argue, are in fact targets, whether you intend them to be or not. Metrics inevitably present one direction or option as better, Nguyen writes in The Score—“longer lifespans, faster student graduation rates, more page views, higher customer satisfaction scores.” What people are talking about when they bring up Goodhart’s Law isn’t human error; it’s actually a fundamental problem with measurement itself.
I want to be clear here: Measurement can and does serve a number of vital functions. It has in a very literal sense made the modern world possible, with all its life-saving, suffering-reducing, and awe- inspiring scientific breakthroughs. When used with care and diligence, metrics can make our progress (or lack of it) clearer and more transparent. Are we decreasing carbon dioxide emissions or not? They can also introduce accountability into formerly opaque systems, such as by measuring whether a company is complying with state and federal regulations. They can even make us more objective, reduce biases, and galvanize us to act.
But as Nguyen points out throughout The Score, the fundamental weakness of metrics comes when we use them to pursue subtler, more personal goals. What I think many of us miss—what I know I certainly missed—is that there are always trade-offs when you try to distill something important down to a data point. When we turn to metrics to understand ourselves, our social world, and culture as a whole, they will never come close to capturing what matters. Even worse, they’ll often actively obscure it.
Today, I find that numbers have very little to offer when it comes to my daily work, my physical or mental fitness, my relationships, or any other part of my life I consider important. Granted, I’m lucky enough to be in relatively good health at the moment. I don’t have to track my glucose levels or monitor my blood pressure. As a freelance writer, I also have the luxury of not having numbers foisted on me in the form of key performance indicators (KPIs), objectives and key results (OKRs), or any of the endless quantitative evaluations that come baked into pretty much every corporate and gig economy job.
Still, in a very real sense, there is no escaping metrics or, especially, the logic that accompanies them. Knowing has become numeric, and we all live in a world that increasingly sees us as a collection of numbers—as “data subjects.” The first and most urgent challenge, I’d suggest, is finding a way to keep us from seeing ourselves and each other that way.
This won’t be easy. As Porter, Nguyen, and countless other philosophers, anthropologists, and historians have already observed, the language of numbers is largely how we ascribe value today—as well as how we digest and metabolize our relationships to ourselves, to others, and to the world around us. Indeed, many of us have accepted not only that metrics have a natural existence in human affairs but that there are in fact no aspects of human life that cannot be somehow translated into data.
Knowing has become numeric, and we all live in a world that increasingly sees us as a collection of numbers— as “data subjects.”
So how do we push back? Nguyen’s book offers a useful first step. As he notes again and again in The Score, believing that numbers say something real or useful about human needs and desires gives them power. We can, at the very least, start to seriously question that belief, to ask what meaning and pleasure we might be giving up in pursuit of a metric.
Doing so will hopefully lead to another realization: that playing the numbers game is ultimately a losing proposition for humans. If we insist on expressing our worth through attentional metrics and productivity scores, if we continue to turn intelligence and creativity into a series of benchmarks for AI to surpass, we’ve already lost. Of course machines will surpass us in a world built around metrics. That is literally what we create them to do. The answer is not to turn ourselves into machines too.
If there’s one thing that keeps me up at night, it is that we’ve become so accustomed to seeing and understanding the larger world and ourselves through numbers that it has deprived us of the language to express what’s fundamental and valuable about our own humanity. We need this ability now more than ever, especially if we’re going to adequately answer two of the most important questions of our era: What are humans for? And what is AI for?
As part of my own attempts to disentangle myself from a life of numbers—efforts that started shortly before covid—I’ve abandoned most of the tools of measurement I spent a decade collecting. I’ve largely given up on social media. I stopped using apps to track my health and well-being. The watch I currently wear tells me the time and the date and nothing else.
In fact, the only holdover from my days of obsessive self-quantification is a dogmatic devotion to walking—without all the step counting, of course. These days, I walk when I’m feeling disillusioned or overwhelmed; I walk when I can’t figure out how to finish an essay; I also walk because I enjoy spending time outdoors with my dog and catching up on the details of my neighbors’ lives. The benefits of pursuing this daily activity are as clear and obvious to me as anything could be in life. I just can’t express them in a number.
Bryan Gardiner is a writer based in Oakland, California.
Cao et al. identify tryptamine as a sleep signal in mice. Wake-active monoaminergic neurons release tryptamine, which binds to GPR139 in POA neurons that suppress wake-promoting neurons. GPR139 agonists could be a new class of sleep medication.
