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Yoshinobu Yamamoto shines in Dodgers’ shutout win
The Padres never had a chance against Yoshinobu Yamamoto at his best, dominating in this shutout win
Argentina 38-47 Scotland: Have your say
Scotland opened their Nations Championship campaign with an impressive seven-try win against Argentina in Cordoba. Read the full match report here Have your say on the game via this link
Kansas Citians clap back at Denver sports anchor over World Cup hosting diss
The 2026 FIFA World Cup has largely been a success so far, with one of the biggest positives being the ways that host cities have been highlighted and appreciated by international fans. Those not paying close attention beforehand fully expected to see cities like Los Angeles, Dallas, Atlanta, Miami, and Seattle among the U.S. hosts.…
Celebrations for America’s 250th begin amid heat and political division
Despite sweltering heat, heavy security and brewing protests, thousands were expected to descend on the nation’s capital for the historic anniversary.
Chicago Cubs news — Swanson, Conforto, Suzuki, PCA, Busch, Rea
Dansby Swanson’s reaction to his third home run of the day, a grand slam, to spark a remarkable 23-3 Cubs win Wednesday.
Today on Pinstripe Alley
Will the Yanks get a win as America turns 250?
New HHS agenda targeting antidepressants creates pushback
As the Department of Health and Human Services creates new efforts to limit the overprescription of SSRI drugs, psychiatrists are pushing back.
What Is The Point Of A Video Game Console Now?
"I’m just like ehhhh. That new Naughty Dog game will probably be good, but I don’t need to buy a now-$900 PS5 Pro to play it"
Peachtree Health & Fitness Expo; Peachtree Junior
Runners and walkers have been checking out the Peachtree Health & Fitness Expo before the big race tomorrow and little runners and walkers participated in the Peachtree Junior on Friday morning.
Game 88 Game Day Thread – Detroit Tigers @ Texas Rangers
Once more into the consecutive games breach
Democrats demand HHS reinstate cancelled teen pregnancy prevention grants
Democrats across both chambers of Congress are demanding the Trump administration reinstate tens of millions of dollars in teen pregnancy prevention (TPP) grants that were suddenly cancelled last w…
Court Stops USDA From Enforcing Funding Conditions Tied to DEI, Women’s Sports
The U.S. District Court for the District of Massachusetts recently blocked the U.S. Department of Agriculture’s (USDA) efforts to withhold funding from states and grant recipients that have not confirmed their compliance with Trump administration policies on diversity, equity, and inclusion (DEI), “gender ideology,” women’s and girls’ sports, and immigration.
HHSC Announces Upgraded WIC Cards for Families | Texas Health and Human Services
HHSC launched upgraded WIC EBT cards integrated with the myWIC app to help Texas families manage, track and secure their benefits more easily.
Marshall Health Network first in West Virginia to offer histotripsy treatment for liver tumors
HUNTINGTON, W.Va. – Marshall Health Network–Cabell Huntington Hospital (CHH) is the first hospital in West Virginia to treat liver tumors using the Edison® Histotripsy System, giving patients access to an advanced treatment that targets tumors with focused sound waves instead of surgery, chemotherapy or radiation. The Edison Histotripsy System uses image-guided sonic beam therapy to precisely target […]
The Supreme Court tackled race, history and the law in fraught and reflective major rulings
The Supreme Court has wrapped up a term with significant rulings on race and discrimination.
How Melat Kiros, a Colorado democratic socialist, unseated a 30-year incumbent
Kiros, 29, is poised to become one of the youngest women in Congress. Her political work was sparked by the war in Gaza and caught fire in an antiestablishment year.
Middle School Students Conduct Summer Science Experiments at USU STARS GEAR UP Biotechnology Camp
Utah middle school students from Sanpete County gained hands-on STEM experience during a two-day Biotech camp in June.
NYC Health + Hospitals/Queens Receives the PRISM Award from the Academy of Medical-Surgical Nurses
NYC Health + Hospitals/Queens today announced that its Medical-Surgical Unit, 5B East, has received the prestigious PRISM Award from the Academy of
With DeGette’s loss, Raul Ruiz eyes her job on a powerful health panel - Live Updates
The Energy and Commerce Health Subcommittee has jurisdiction over HHS, Obamacare, Medicare and Medicaid.
With DeGette’s loss, Raul Ruiz eyes her job on a powerful health panel - Live Updates
The Energy and Commerce Health Subcommittee has jurisdiction over HHS, Obamacare, Medicare and Medicaid.
Africa CDC: Uganda health ministry confirms isolated Marburg case
Africa's top public health agency said on Wednesday that Uganda's health ministry had confirmed an isolated case of Marburg virus disease.
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?
Enrollment in Affordable Care Act health plans drops by 3M, HHS data reveals
The Trump administration said the reduction can be attributed to a cleanup of fraud, waste and abuse, but the real reason extends back to enhanced subsidies put in place during the COVID-19 pandemic.
Multnomah County Just Fired a Key Health Leader. He Says He’s a Scapegoat in a Power Struggle.
Anirudh Padmala’s departure marks worsening tumult in the top leadership overseeing the network of 19 federally-funded Portland area clinics, which collectively serve tens of thousands patients annually.
North Dakota opens wellness equipment funding opportunity for rural hospitals | Health and Human Services North Dakota
From fitness and recovery equipment to mindfulness tools and wellness spaces that help reduce burnout, North Dakota Health and Human Services (HHS) is investing in the health and well-being of rural healthcare workers through a new funding opportunity for rural hospitals.Applications are now open for the Hospital Wellness Equipment funding opportunity through the North Dakota Rural Health Transformation Program (RHTP), providing resources to help rural North Dakota hospitals create healthier workplaces and support the physical, mental and emotional well-being of their workforce.
NYC Health + Hospitals/Metropolitan and MetroPlusHealth Support New Mother of Triplets
New York, NY – NYC Health + Hospitals/Metropolitan, in partnership with MetroPlusHealth, today shared the story of Doris A. Lucio Lucio, an immigrant
NC Gov. Stein tabs Treasurer Briner, Health Secretary Sangvai to lead probe of rising health costs
North Carolina has some of the fastest-rising healthcare costs in the country. Now, Treasurer Brad Briner, who oversees the State Health Plan, and DHHS Secretary Dev Sangvai will try to fix them.
Lionel Richie's ex-wife shares update on singer's condition after hospitalization
Lionel Richie's ex-wife, Brenda Harvey Richie, shared news on her former husband's health after a medical incident led to a concert stoppage and hospitalization.
'Supergirl' is a decent standalone movie — so why is everyone acting like it’s awful?
'Supergirl' has been in theaters for less than a week, and it seems everyone is quick to call it a failure after a disappointing opening weekend at the box office. But does it actually deserve the backlash it's receiving?
Pacers Sports & Entertainment hires Jas Bell to lead merch design
Pacers Sports & Entertainment's effort to appeal to global fans and cross into culture got a boost with its hiring of Jas Bell as global design and product director.
‘Paris & Pups’ Producer HappyNest Entertainment Expands Slate With New R.L. Stine Series, ‘Louie and Bear’ Adaptation and Space Camp Franchise (EXCLUSIVE)
HappyNest Entertainment, the producer behind Paris Hilton’s “Paris & Pups” YouTube show, is in early development on several new projects, including a series with “Goosebumps” author R.L. Stine, an ada...
Developer addresses community concerns around Franklin youth sports complex project
The project, proposed by developer BLVD Capital, would transform Brownland Farm, a 233-acre property on Hillsboro Road just outside downtown Franklin, into “The Banks at Brownland.”
Global financial firms pivot to South Korea, cautious on China and India, survey shows
Global financial firms are pivoting expansion plans towards South Korea while taking a more measured approach to China and India, according to an industry survey.
FDA panel on peptides will include experts who promote the unproven chemicals favored by RFK Jr.
The Food and Drug Administration is meeting next month to consider easing restrictions on several peptides, a group of unapproved drugs popular with followers of Robert F. Kennedy Jr.
CT health system reveals top CEO stepping down. Nationwide search to be done for replacement.
The CEO of Yale New Haven Health System is stepping down after 14 years in the post, according to the health system. CEO Christopher O’Connor joined YNHHS “after helping lead the Health System’s acquisition of the Hospital of Saint…
Nancy Guthrie demand letter’s authenticity questioned by sheriff
Pima County Sheriff Chris Nanos weighs in on a new demand letter in the Nancy Guthrie case, which claims to know who kidnapped the mother of 'Today' host Savannah Guthrie.
Connie Cepko: A Life in Science Mapping the Retina — and Working to Save It
Over a five-decade career, HHMI Investigator Connie Cepko has reshaped our understanding of how the retina develops and forged new paths toward treating blindness and inherited retinal disease. This story is part of a series exploring the careers of HHMI scientists.
TEFCA hits 1 billion as HHS invests $1.28M in network oversight
While marking TEFCA's milestone, ONC announces a new contract to enforce network compliance. Amid ongoing legal battles over alleged network misuses, Health Gorilla CEO Bob Watson emphasizes why federalizing governance is critical to trust.
Careers That Shaped Biology
Every great scientific career begins with a question no one has been able to answer — and a scientist stubborn enough to keep asking it. This series looks back at the careers of some of HHMI’s most distinguished scientists — people whose contributions have changed what we know about life itself, and whose stories reflect the best of what science, and scientists, can be.
Caldwell University Professors Join Nationwide "Phage Hunters" Science Alliance
Caldwell, NJ – Three professors of Caldwell University’s Department of Natural Sciences, Dr. Maria Agapito, Dr. Darryl Aucoin, and Dr. Hector Loyola Irizarry, attended the Howard Hughes Medical Institute (HHMI) […]
Kadyn Proctor Can Solidify Dolphins Offensive Line in Big Way
The Miami Dolphins' offensive line may be good, but it can reach a strong height if rookie Kadyn Proctor can live up to expectations.
GOP Sen. Cassidy seeks to explains RFK Jr. confirmation vote for Health and Human Services
Sen. Bill Cassidy (R-La.) in a Sunday inteview sought to explain his controversial vote to confirm Health and Human Services (HHS) Secretary Robert F. Kennedy Jr., as he said Kennedy is dug in on h…
Pharr grocery store to close after nearly 100 years in business
After nearly 100 years in business, the historic M Rivas Supermarket in Pharr is closing its doors, marking the end of a multi-generational Rio Grande Valley legacy.
Politics: Sand speaks with TH on launch of “Rob-publicans” campaign
Ahead of the unveiling of his “Rob-publicans” campaign, Democratic Iowa gubernatorial candidate Rob Sand sat down with the Telegraph Herald to discuss his stance on excess partisanship and what it
Florence community rallies for local business owner diagnosed with brain tumor, here’s how you can help
The Florence community held a fundraising event for a local business owner who was diagnosed with a brain tumor for the second time.
Egor Shilov Drafted 43rd Overall By Colorado Avalanche
Penn State hockey commit Egor Shilov was drafted 43rd overall by the Colorado Avalanche in the 2026 NHL Entry Draft: Shilov quickly flew up the NHL Draft radar after an outstanding 2025-26 season with the Victoriaville Tigers of the QMJHL. He had 82 points (32 goals, 50 assists) in the regular season, good for 7th […]
Prediction market Kalshi sues Illinois over its push to regulate sports bets
Prediction market Kalshi — which offers trades on everything from the World Cup top goalscorers to the winners of the reality show Love Island and the 2028 Democratic primary — sued Illinois on Tuesday over its latest push to regulate sports bets on the platform.
LVMH and Accor's Orient Express sets its sights on new tech billionaire class
Shuttling across the French and Italian Riviera, Orient Express's first giant yacht aims to attract a new class of billionaire.
Health Brief: Inside the CDC nominee’s finances
Plus: Supreme Court ruling sparks health worker deportation fears
Registration open for 2026 Behavioral Health & Children and Family Services Conference | Health and Human Services North Dakota
Registration is now open for the sixth annual Behavioral Health & Children and Family Services Conference, scheduled for Sept. 14-17 at the Bismarck Event Center and online through a livestream option.The main conference will take place Sept. 15-17, with optional pre- and post-conference sessions offered Sept. 14 and Sept. 17.More than 1,400 in-person attendees and hundreds of virtual participants are expected to take part in keynote presentations, breakout sessions and networking opportunities focused on behavioral health, child welfare, suicide prevention and youth development.
Trump tries out midterms message that focuses on ‘communists’
Trump warned an audience of religious conservatives that communism is spreading in the U.S., a new theme for his midterm campaign.
HHS Expands Secure Access to Health Records Through the TEFCA® Network, Announces Milestone of One Billion Health Records Exchanged
The Office of the National Coordinator for Health IT at HHS announced new steps to strengthen the Trusted Exchange Framework and Common Agreement™ TEFCA®
NYC Health + Hospitals/Queens NICU Awarded Gold Beacon Award for Excellence
The Neonatal Intensive Care Unit (NICU) at NYC Health + Hospitals/Queens has been honored with the prestigious Gold Beacon Award for Excellence from the
Lionel Richie is 'heartbroken' to postpones concerts after reported hospitalization
Lionel Richie is postponing two shows after cutting his St. Paul, Minn., concert short and a reported hospitalization.
Massachusetts marijuana legalization repeal question battle heats up
Cannabis industry leaders are urging businesses to take the initiative seriously after many previously dismissed its chances.
Trump nominates Chris Klomp as HHS second-in-command
President Donald Trump on Thursday named Medicare director and former health care executive Chris Klomp to be deputy secretary of the US Department of Health and Human Services.
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.
President Trump Signs Executive Order Advancing Regenerative Agriculture as Part of Make America Healthy Again Agenda
President Trump Signs Executive Order Advancing Regenerative Agriculture as Part of Make America Healthy Again Agenda
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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