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Cowboys countdown to kickoff: Top 100 iconic games
We countdown 100 days until kickoff with a series of the most iconic games in Cowboys history. Today is Day 74
There’s already a history with both Miami and …
There’s already a history with both Miami and …
Sony will cease production of discs for new PlayStation games in 2028
New games sold for PlayStation consoles will only be available digitally and won’t be sold on discs effective January 2028, Sony has announced. The move applies to all PlayStation games released from that point on, including those made by Sony and those released by third parties. The PlayStation group calls the change “a natural direction for Sony Interactive Entertainment to adapt to consumer trends as the general preference for digital media significantly outpaces physical discs,” according to a PlayStation blog post reviewed by Game File in advance of its publication. As movies, TV and music have shifted from physical media to an age of downloads and streaming, Sony’s move could speed the demise of physical media in a gaming. The industry has offered consumers games via cartridges, cassettes, floppy discs, CDs, DVDs and Blu-Rays across a 50-year stretch. Sony has been reporting to investors in recent years that PlayStation games have been increasingly purchased as downloads, not as discs. The most recent figures show nearly four in five purchases of full games for PlayStation 4 and PlayStation 5 were purchased digitally in the past year. Stats like that may cause today’s news to carry an air of the inevitable. But Sony’s declaration for 2028 is still likely to produce a shock, as the biggest gaming platform on the planet that uses game discs leaves them behind. Discs going away, but the fate of game boxes is unknown Sony is committing to still selling games in physical retailers even after they drop discs in 2028. Just how those games will be sold—in boxes with codes inside, as cards marked with digital redemption codes—is unclear. Digital games will also continue to be sold in the online PlayStation Store. New games released for PlayStation consoles prior to January 2028 will be unaffected by the policy change, Sony says. That means the PS5 games of 2027, be they a new Madden, a new God of War, a new Call of Duty, a new Sly Cooper (one can dream?), would still potentially be offered on disc. PlayStation 6 implications Sony’s timeline for a transition to a no-disc era will also spin up more speculation about the timing and configuration of Sony’s next-generation console, the probable PlayStation 6. “This pretty much guarantees that PS6 won’t arrive until 2028 at the earliest,” Piers Harding-Rolls, senior games research analyst at Ampere Analysis tells Game File. Harding-Rolls also concludes from today’s news that “the base version of a PS6 will not include a physical media drive,” as Sony looks to keep costs down on the device. Sony itself is saying nothing about the PS6 today: not its timing, nor how it might or might not support internal or external disc drives in order to run disc-based PS4 and PS5 games, should the console be backwards compatible. The many signs this was coming Industry support for games being released on physical media has been waning. As has consumer interest in them. PC games effectively went all-digital years ago, thanks to the popularity of playing games through Steam and other digital storefronts. The Covid-19 pandemic and the lockdowns that kept much of the global population home helped shift shopping patterns toward downloads. Sony’s own data shows PlayStation game downloads being an uncommon consumer choice a decade ago and now becoming the norm. On consoles, physical media has been in such decline that Sony and Microsoft both launched their current gen Xbox Series and PS5 consoles in 2020 with cheaper versions that lacked disc drives. In early 2024, Phil Spencer, then head of Xbox, told me that ““[w]e ship games physically and digitally, and we’re really just following what the customers are doing.” He added that the game industry had become an outlier in still supporting disc-based entertainment, even as movies and TV have bailed on discs in favor of downloads and steaming: “Gaming consoles themselves have kind of become the last consumer electronic device that has a drive. And this is a real issue, just in terms of the number of manufacturers that are actually building drives and the cost associated with those. And when you think about cogs that we’re going to go put in a console—and as you have fewer suppliers and fewer buyers—the cost of the drive does have an impact.” Last year, the Nintendo’s Switch 2, which uses cartridges rather than discs, introduced the concept of game-key cards, which are physical media that contain no game, just a prompt for a download. Even disc-based games aren’t what they once were, now frequently containing just stubs of games rather than the whole thing. The website Does It Play has tested over 3000 games and found that, for example, that the disc version of this year’s hit 007: First Light, only contained the game’s first mission, with the rest needing to be downloaded. Beyond all that, last week brought the news that Grand Theft Auto VI, likely the biggest game launch this decade, will debut for PS5 and Xbox Series without a disc-based version. Today’s big news comes to you for free. Game File is a reader-supported publication. To receive new posts and ensure more of my work is possible, please consider becoming a free or paid subscriber. Subscribe Discs helped define PlayStation However the trends in entertainment may be going, it is still remarkable to see PlayStation ditch discs given their importance in PlayStation history: In the late 1990s, the first PlayStation’s support for games on relatively cheap CD-ROMs instead of traditional game cartridges allowed the upstart console to outmaneuver cartridge-based systems from Nintendo and Sega, as it drove down game prices down in the process. (The cheaper disc format even prompted Final Fantasy VII maker Square to taunt Nintendo in a magazine ad, saying that if the game was “available on cartridge, it’d retail for around $1200.”) PlayStation devices often doubled as machines for watching movies and TV on the latest disc-based formats. In the late 2000s, for example, Sony’s pricy PS3 gained traction as a go-to device for playing then-novel Blu-Ray discs. In 2013, Sony effectively roasted the digital game-sharing restrictions proposed by rival Microsoft for its upcoming Xbox One console by showing how games could be shared for the then-upcoming PS4. In a 21-second clip that has over 20 million views on YouTube, one PlayStation executive simply handed a game box—presumably with disc inside—to another, who said “thanks.” Sony’s possible motivations The PlayStation announcement today cites “consumer preferences” and a shift away from discs among “the broader entertainment industry,” but does not delve into the decision-making process that brought Sony to this point. Sony is not discussing the economics of this move (I asked!), but there are a number of potential factors: Abandoning discs will spare Sony the cost of manufacturing and shipping them, which analysts and industry veterans I spoke to said could account for $1 or so of a game’s retail price. For first-party games, that’s direct savings for Sony, though the amount is limited by the winnowing percentage of people who were even buying the disc-based versions. For third-party games, Sony could pass the savings on to partners or just retain the better profit margin for themselves. As the 2024 comments from Phil Spencer alluded to, leaving discs behind could mean leaving disc-drives behind, allowing Sony to produce consoles more cheaply. Switching to digital-only for games could diminish the risks of copies of new games leaking. It would also seemingly make second-hand sales of used games impossible, pushing more people to buy their own copies of games. These economic benefits for Sony could be boons for the games industry overall, Ampere analyst Piers Harding-Rolls tells Game File. Among other things, it could free publishers and retailers from having to worry about securing an inventory of game discs when trying to sell games, he noted. “If there is a way to streamline the business of games retail, I generally think it’s a good thing for the industry as it removes unnecessary costs,” Harding-Rolls said. “This will help offset pressure on margins from other directions – development and staffing costs for example.” Should the industry shift from game boxes that contain discs to smaller, cheaper game cards, Harding-Rolls said, that reduces pressure on publishers and retailers. “The advantage of everything going digital for the industry is that sales can be tracked much more easily and there is less commercial risk for publishers wanting to continue selling via retail,” he said. The shift to no discs will also likely impact game development timelines, as developers will no longer face the same urgency to have a build ready to submit to PlayStation for the production of a disc, as industry experts noted around GTA VI’s no-disc news last week. Instead, projects may gain weeks of development time, in the event delivery deadlines for platform approval move closer to release date. Preservationists’ likely worries While millions of gamers have shifted to digital, there are still people who associate game discs—and only game discs—with actual ownership of PlayStation games. That portion of the gaming community spoke up last week about wanting to buy a version of GTA VI that they could hold in their hands, could lend to a friend and could potentially pop into a well-preserved PS5 console three decades from now and still see it run. Such gamers didn’t want to worry that they’d merely purchased a digital copy that could lose access to the game if, say, the company behind the game someday turns of the servers that transmit downloadable copies. Digital copies of games are inherently less long-lasting, because consumers aren’t actually buying a game (on a disc), just buying access to the game. The fine print in online gaming shops notes this, as does a recent law that went on the books in California in 2025. That lasw requires game publishers doing business in the state to refrain from words like “sell” when offering digital copies of games, unless they explicitly tell consumers that what’s being sold isn’t the game itself but a potentially revocable license to access it. A Sony spokesperson noted to Game File that “[w]ith all digital content, including games, movies, and music, players are purchasing a personal license for non-commercial use.” Regarding the fears of PlayStation games being lost to time in an all-digital era, the rep also noted that Sony remains “committed to delivering experiences from past generations to the new platforms our players are using.” They noted that PlayStation has used emulation and remasters to keep offering its classic games to modern gamers. It’s true that many consumers have become accustomed to not having physical copies of new music albums or movies, but the relative precariousness of digital copies of games is in fact being highlighted today by…. Sony’s other big announcement: the upcoming closure of the PS3 and PS Vita online stores Sony said today that it will be closing the online marketplaces for its PlayStation 3 console and PS Vita handheld in most countries in July 2027 (sooner elsewhere: August 2026 for the PS3 store Mexico, Honduras and Nicaragua; late 2026 for PS3 in other Latin American countries and the Middle East). “We know this news may be disappointing to PS3 and PS Vita players who hold a special place in their hearts for this generation of gaming,” Sony said in its announcement, saying the move “was not an easy decision for us to make.” Sony said that PS3 and Vita marketplaces “are no longer able” to support modern commerce systems, prompting a “need” to close the shops and focus on more modern PlayStation platform stores. The news may spark some deja vu. Sony announced back in March 2021 that it planned to take the PS3, Vita and PlayStation Portable marketplaces offline that summer. The move would have caused some 2,000 digital-only games to become unavailable for new purchasers, according to a VGC analysis at the time. Fans complained loudly. By April 2021, Sony walked back the PS3 and Vita shop closures, with then PlayStation boss Jim Ryan saying “it’s clear that we made the wrong decision here.” This time around, Sony is giving a longer notice period in most regions. The closure of those stores is still likely to cut off access to new purchases of digital-only PS3 and Vita games. The current PlayStation 5 marketplace sells PS5 and PS4 games, as well as a selection of PS1 and PS2 games. It does not sell PS3 games, because games for that platform can’t run on the system (some are offered via a PlayStation Plus streaming option). Vita games also aren’t sold via PS5. Sony says digitally purchased PS3 and Vita games will be downloadable after the stores’ shutdowns “for the foreseeable future.” Sony’s move contrasts with Microsoft’s Xbox platform, which continues to sell and support games from all four Xbox console generations. But it puts it in line with Nintendo, which disabled purchases in the marketplace for its Wii console (a contemporary of the PS3) in 2019. Nintendo discontinued purchases in the online shop for its 3DS portable (a contemporary of the Vita) in 2023. The big questions about Sony’s 2028 post-disc era Will Microsoft follow suit, ending support for new disc-based games on Xbox platforms and therefore all game consoles, too? Whether Microsoft does or not, will third-parties that can no longer release games on discs for PlayStation, simply ditch the disc options across the board? Given the GTA VI no-disc experiment launching this November, will more game publishers decide to forgo disc-based offerings even in 2027? How will no-disc PS5/6 games be packaged and sold in brick-and-mortar retail stores? What becomes of game sharing in an all-digital era? Will Sony modify its current set-up, which currently allows some sharing of digital games across a pair of consoles, to allow more casual lending? (See for example, Nintendo’s year-old system of letting players lend a digital game to another player in a “family group” for up to 14 days.) Will there be a version of a PS6 with a disc drive? Or will a drive be offered as an add-on? And how will gamers who want to retain access to PS4/PS5 disc-based games react to whichever configurations Sony chooses to offer? What will the final disc-based PlayStation game be?
Mexico Teenager Gilberto Mora Makes History With Start vs. Ecuador
Gilberto Mora will make history just by stepping on the pitch for Mexico's round of 32 match against Ecuador on Tuesday at Mexico City Stadium.
Lakers, Luka Dončić react to LeBron James leaving team in free agency: 'One of the greatest athletes in history'
Push to add limits on school sports participation to Nebraska Constitution gathers 211k signatures
The push comes after the U.S. Supreme Court upheld two similar state laws; the group said it collected the most signatures in state history.
Comcast to Spin Off NBCUniversal Into Standalone Entertainment Company
Comcast announced today that it plans to separate NBCUniversal into its own publicly traded entertainment company, marking one of the biggest corporate restructurings in the company's history. Under the proposed split, NBCUniversal will become an independent entertainment company, separating from C
Free exhibition at the Science History Institute breaks down the flash, bang and boom of fireworks
"Flash! Bang! Boom! A History of Fireworks" at the Science History Institute is a blast. The free exhibition, in celebration of America's 250th, explores the history and science behind the spectacular Fourth of July tradition.
Wings' Azzi Fudd achieves 29-year WNBA history
Fudd was the No. 1 overall pick and is trying to prove it was worthy.
South Bay History: Del Amo Financial Center spotlighted Torrance’s thriving 1960s business community
The Del Amo Financial Center had its official grand opening on Sept. 20, 1967.
Git 2.55 Released With Rust Support Enabled By Default, <em>git history fixup</em>
Git 2.55 is out today as the latest stable update to this distributed version control system.
LDI and American Healthcare
A news feature from the Pennsylvania Gazette reflects on LDI’s history and leaders, and how they are currently meeting the federal health policy moment.
Lauryn Hill honored, Janet Jackson stuns and Druski makes history at BET Awards
Hill performed “Ex-Factor” Sunday
Meet the worst L.A. free-agent signing ever
There have been a lot of bad free-agent signing in L.A. sports history, but this one rises, or sinks among all the others.
Americans' pride in US history and democracy drops, and fewer are proud to be American, polls find
A new AP-NORC poll finds that Americans have grown less proud of the country’s history or the way its democracy works over the past several years
Experts bet World Cup wagers will bring Mass. big tax revenue
Experts say the tournament is on pace to be the biggest sports betting event in history, bringing new revenue to the state. But some fear it carries public health costs, too.
Experts bet World Cup wagers will bring Mass. big tax revenue
Experts say the tournament is on pace to be the biggest sports betting event in history, bringing new revenue to the state. But some fear it carries public health costs, too.
First ever dinosaur found in Antarctica described for science
Dinosaur backbone is the first found on the icy continent, and belongs to a titanosaur around 6–7 meters in length.
Kings’ Acuff Jr., Nets’ Brown Jr. Rivalry Continues in NBA
From high school shootouts to collegiate clashes, these elite lottery picks bring a storied history to the pros as they prepare to ignite a cross-conference professional feud.
A brief history of same-named political candidates, election hijinks and Dan Sullivans in Alaska
The kerfuffle surrounding the Alaska Senate race isn’t the first time two Dan Sullivan candidates have wound up on the same ballot.
Gretchen Walsh breaks Kate Douglass' 50 meter freestyle World Record
Gretchen Walsh has broken the 50 meter freestyle world record, becoming the fastest female sprinter in the history of swimming.
Saints great Joe Horn takes his place in Louisiana Sports Hall of Fame
Joe Horn, one of the best receivers and most charismatic players in New Orleans Saints history, officially joined the Louisiana Sports Hall of Fame.
Iran Might Be The Unluckiest Sports Team Ever
After two late goals in another game sealed Iran’s fate, Team Melli was left to rue one of the most brutal exits in World Cup history.
Nest’s quest to fix your thermostat
On Version History: What “the iPod of thermostats” really means.
Popular 9-season sitcom losing its streaming home at end of the summer
The Emmy-award winning series is regarded as as one of the most iconic shows in television history.
🥜 Still nutty after 50 years
Center City snack shop Nuts To You marks 50 years in business and looks to TikTok for sustained growth. Plus: Olney update here TK, and we compare Revolutionary history in Philly vs Boston.
Carman: Tuesday’s election is more than just a primary. It’s a colossal opportunity to change history.
The template for tyrants goes back at least to Ancient Rome and, as Nero discovered, generally ends badly.
BET Awards: Druski to make history as youngest host as show honors Lauryn Hill and Teyana Taylor
Druski will make history as the youngest host of the BET Awards on Sunday.
BET Awards: Druski to make history as youngest host as show honors Lauryn Hill and Teyana Taylor
Druski will make history as the youngest host of the BET Awards on Sunday.
BET Awards: Druski to make history as youngest host as show honors Lauryn Hill and Teyana Taylor
Druski will make history as the youngest host of the BET Awards on Sunday
BET Awards: Druski to make history as youngest host as show honors Lauryn Hill and Teyana Taylor
Druski will make history as the youngest host of the BET Awards on Sunday.
San Antonio Pride festival celebrates LGBTQ+ community, raises money for local nonprofits
Thousands of people were expected at Crockett Park on Saturday for the Pride Bigger Than Texas Festival, an eight-hour celebration of LGBTQ+ history, resilience and community support.
Scientists finally explain why these wild boars stay more radioactive than Chernobyl's wolves - Futura-Sciences
What explains this surprising finding? The answer appears to be a complex mix of history, ecology, and diet. Bavaria’s wild boars mainly feed on underground fungi that absorbed radioactive fallout from both the notorious Chernobyl disaster and Cold War-era nuclear testing. Unlike wolves, which sit higher on the food chain...
HISTORY IN THE MAKING: A RECORD-BREAKING OPENING DAY AT THE PAN AMERICAN ATHLETICS CHAMPIONSHIP MEDELLÍN 2026
The Pan American Athletics Championship delivered everything the Americas had been waiting […]
Your health insurer shouldn’t decide your treatment plan. That’s what your doctor (and possibly AI) should be doing.
With a digital health record, clinicians and AI-driven diagnostic tools would be able to see your full health history — and then make better decisions.
My Boyfriend Said His Family Friend Is Like a “Sister” to Him. Uh, That’s Not What His Computer History Says.
He violated everyone's trust with this.
Rank the Derek Hill catch in Phillies history
It’s got to be up there
Cowboys Weekend Headlines: History's brink, Quinnen, Parker dilemmas
The Cowboys are looking to avoid an inglorious feat in 2026, while there are close eyes on two key components in the fight.
France's Ousmane Dembélé records second-fastest hat trick in World Cup history in 4-1 win over Norway
The Year 536 AD Was So Bad It May Have Been the Worst Time in Human History to Be Alive
Volcanoes, famine and plague made 536 a leading candidate for history’s worst year.
An Incomplete History of Seattle Sports
Sonics, Seahawks, Sounders, Storm, Steelheads, Mariners, Kraken, and more.
Nintendo Switch 2 ends first full year in the U.S. at nearly 6 million units sold, second fastest-selling video game system
Following the latest U.S. sales report from Circana, we have information about the first full-year sales of Nintendo Switch 2. The console ended its first twelve months at 5.9 million units sold. According to Circana, it’s the second fastest-selling video game system in the U.S. with tracked history dating back to 1995. The only other platform to outdo it was...
Who are Texas A&M's All-Time Quarterback recruits?
According to 247Sports, here are the top 10 ranked Texas A&M quarterbacks recruits in program history.
Politics Chat, June 25, 2026
A newsletter about the history behind today's politics.
UCLA comparative literature department to offer health humanities minor in fall
UCLA will offer a minor in health humanities starting this fall. The minor, housed under the comparative literature department, is an interdisciplinary program that examines how health and medicine are shaped by literature, culture, history and social experience, according to the department’s website.
Larry David and Barack Obama's American history show is deeply cringe
For Larry David and Barack Obama, history is a laughing matter. And they've got the sketch comedy show to prove it.
Golden State Valkyries employee named in Sports Business Journal's Forty under 40 list
The Golden State Valkyries have created a winning culture on and off the court. After making WNBA history last season becoming the first expansion team to reach the playoffs, the success is also extending throughout the organization.
Granger family pledges largest gift in history of UM-Health Sparrow
The Granger family has pledged the largest gift in University of Michigan Health-Sparrow history for a new behavioral health hospital.
Cowboys countdown to kickoff: Top 100 iconic games
We countdown 100 days until kickoff with a series of the most iconic games in Cowboys history. Today is Day 80
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.
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