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GTA 6 has no plans for a post-launch physical release, "not at launch, and not months later", insists new report
A new report has cast doubt on news that a physical version of Grand Theft Auto 6 will follow the digital release later this year after all.
Church pickles in dry storage, warm fish in restaurant inspections
See scores from local Lane County eateries in this week's write-up of restaurant inspections.
The war for Burnham’s ear: politicians and wonks fight for influence over a PM
There is high emotion, a deluge of policy papers and an ‘excruciating’ jostle for jobs as Labour’s probable next leader settles back into Westminster life
5 Hobbies You Can Turn Into Small Business Ideas
Looking to start your own business? These small business ideas let you monetize what you already love doing.
Scientists mull controversial plan to steer hurricanes
It might sound like science fiction, but some scientists say we have tools that could be used to disrupt natural disasters. Others are skeptical.
As America fights over food, this woman speaks for the unheard
Vanessa Rissetto, a dietician and \
Meet a scientist tracking invasive reptiles, and even their parasites
An insider's look at Florida’s war on invaders: the giant snakes, egg-eating predators and parasites spreading through the Everglades.
Nigel Farage’s anti-WHO campaign moves to US with allies added to board
Relocation of Action on World Health raises questions over why Reform UK leader is involved in a US pressure group
Nigel Farage’s anti-WHO campaign moves to US with allies added to board
Relocation of Action on World Health raises questions over why Reform UK leader is involved in a US pressure group
Trump-endorsed candidates hold nearly perfect record in GOP primaries
No modern president wields party influence the way Donald Trump does, experts say, but it could be costly to his party in the 2026 midterms.
Screen time can damage under-twos’ development, landmark study suggests
Exclusive: Researchers call for urgent investigation of risks to babies of tablets, smartphones and other digital devices
Trossard, De Bruyne score and Belgium defeats New Zealand 5-1 to advance at the World Cup
A flurry of late goals helped secure Belgium’s place in the knockout rounds, while New Zealand are heading home without a win.
From Supergirl to Muse: your complete entertainment guide to the week ahead
Milly Alcock’s Kryptonian hero bops baddies with a superdog in tow, while the Devon band return with another collection of all-caps rock
States seek to lower drug prices by targeting the companies that manage them for health plans
Legislators across the U.S. are trying to lower prescription costs by reining in big companies that handle drug coverage for health insurers.
Our Editors Found 401+ Best Amazon Prime Day Deals Worth Shopping Before the Sale Ends
You have less than 24 hours left to shop deals across categories, and some of them are so good that they’re already selling out.
Baylor teen health clinics provide free medical care, mental health services
According to the latest U.S. Census data, Texas leads the nation in the number of uninsured residents.
Will Cannon posts second-round 61, leads Memorial Health Championship presented by LRS
Will Cannon grabs a one-shot lead through 36 holes at the Memorial Health Championship presented by LRS after posting a 10-under 61 on Friday.
7 Best of the Best Prime Day TV Deals Under $1,000 I Recommend Looking at Before They Expire Tonight
From gaming-ready to budget-friendly, these TV discounts are worth grabbing before Prime Day ends.
Trump news at a glance: president tests out a new ‘red scare’ ahead of midterms
Republican strategists believe rise of Mamdani could present opportunity to tag Democrats with most extreme views of the left – key US politics stories from Friday 26 June
NY restaurant inspections: Search health code violations by restaurant
Search New York restaurant inspection reports to see if your favorite local dining spots are meeting safety standards.
Best Prime Day Tablet Deals From Apple, Samsung and TCL
Tons of Apple and Android models are still on sale, but these holdover bargains are selling out fast.
House Republican reacts to changing politics under Trump
Republican Rep. Dusty Johnson spoke to NBC News' Garrett Haake about his recent loss in the primary to become the governor of South Dakota, and how he feels about the current political environment under President Trump.
The Business of Grand Theft Auto VI, Explained: How a Billion Dollar Game Is Likely to Pay Off
Anthony Palomba on why the stakes are so high for the Grand Theft Auto VI launch and what it means for the gaming industry and the entertainment industry as a whole.
Senators call for military healthcare program to cover autism therapy as a basic benefit
A letter to Defense Secretary Pete Hegseth follows an NBC News investigation into the military healthcare program’s restrictions on applied behavioral therapy.
Tired of long waits? Mochi Health offers virtual care starting at $39
Mochi Health now offers full-service virtual care with unlimited visits, flexible pharmacy options and plans starting as low as $39.
What if the economy gets better and it doesn’t help the GOP?: From the Politics Desk
Plus, Gavin Newsom’s next move in the billionaire tax fight.
Democratic candidate challenging Rep. Lawler on her bid to ‘tear down political silos’
New York U.S. House candidate and combat veteran Cait Conley (D) joins Meet the Press NOW following her primary win. She faces incumbent Republican Rep. Mike Lawler in one of November’s most closely watched races as Democrats try to flip the House.
‘It’s a bad time to be a normal’: House Republican on current political environment
Rep. Dusty Johnson (R-S.D.) reacts to President Trump's decision to cancel the signing of the bipartisan housing affordability bill. Rep. Johnson also discusses the president’s Iran strategy and the current political environment.
iPhone 18: Everything We Know About Apple's Biggest Updates
Rumors about Apple's next flagship phones point to a new foldable, a variable-aperture camera, improved battery life and, yes, higher prices.
White House mandates move away from overdose prevention in US health programs
Experts say move signals greater political interference into public health and will exacerbate opioid overdose crisis
Mel Brooks Is Turning 100! His 1 Tip for Longevity, a Healthy Life
The comedy legend and father of satire celebrates his big 100th birthday on June 28.
PlayStation hardware sales fall to their lowest May total since 2000
Price rises hit Sony's console sales, but 007 First Light and Switch 2 help US game spending to grow 3%
What your sleep schedule says about your health
From the time you naturally wake up to how long you actually sleep, your schedule holds clues about your heart, hormones, mental health, and longevity
Why the Amex Business Gold is my go-to card for business expenses
The Amex Business Gold makes earning rewards simple with automatic bonus categories, flexible Membership Rewards points and statement credits that help offset its annual fee.
An Incomplete History of Seattle Sports
Sonics, Seahawks, Sounders, Storm, Steelheads, Mariners, Kraken, and more.
Iran's Pride Match is about visibility, not politics
Iran’s World Cup match against Egypt has become a test not only of FIFA’s approach to inclusion but also of whether LGBTQ+ Iranians can claim visibility on one of the world’s biggest sporting stages.
Nintendo’s Summer Sale Is Now Live and Not Only Includes Discounts on Digital Titles, but Also the Switch 2 Upgrade Pack for Breath of the Wild
Nintendo has launched a new Summer Sale until July 8. Save on select digital titles across Nintendo Switch and Switch 2, alongside a Switch 2 upgrade pack for Zelda: Breath of the Wild.
Take an 8-Minute Gameplay Tour of the Remade Havana in Assassin's Creed Black Flag Resynced
Join Assassin's Creed Black Flag Resynced lead level designer Jean Strachen as she takes you on an eight-minute gameplay tour of Havana. See what it looks like now in the gorgeous new remake that will be released for PC, PS5, and Xbox Series X|S on July 9.
From The Sports Desk: The U.S. lost, but also saw return of star Christian Pulisic
The Americans may have lost their final group stage. But Pulisic, who had been nursing a calf injury, returned to action. He’s back just in time for the start of the knockout round.
Air-conditioning becomes political amid sweltering Europe heatwave
Much of western Europe baked under a “heat dome” as temperatures soar. Authorities warn that the extreme conditions could endanger lives across countries, many of which have limited air conditioning, a topic of which has left the people of Paris divided.
Who plays in the World Cup today, June 26?
Here's your daily rundown on Philadelphia's Fan Festival hours and entertainment.
Bridget and Mike Chiodo on Strong Bond, Health Struggles, Family
Influencer Bridget Bahl and her husband Dr. Mike Chiodo join TODAY’s Jenna Bush Hager and Sheinelle Jones to celebrate Bridget becoming cancer free, open up about their steadfast bond and share an update on their dream of starting a family.
The 5 Healthiest Fats You Can Eat
Fat has historically been demonized, but some types can be good for you.
How to Keep Your Skin Healthy and Hydrated in Summer Months
From sunburns to heat rashes, board-certified Dr. Angela Lamb joins TODAY with solutions for common summer skin problems.
Newsom urges a national 'billionaires' tax' while fighting one in California
California Gov. Gavin Newsom is calling for a national “billionaires' tax” and suggests the U.S. government should own a stake in AI companies.
Medical miracles that changed how we treat disease
We've come a long way since \
Sports quiz of the week: heat, animals, money and a big week at the World Cup
Have you followed the news in football, cricket, tennis, rugby, golf, athletics and cycling?
How to get free Windows 10 security patches until October 2027 - and avoid the $30 fee
Don't want to pay to keep Windows 10 security updates? Microsoft has several workarounds, with the best deal for European users.
Volkswagen reportedly planning to axe 100,000 jobs
Volkswagen, one of the world’s largest automakers, is reportedly planning to axe as many as 100,000 jobs over the next few years, representing 15% of its global workforce.
New study suggests health damage from exposure to Ohio toxic train spill
Research finds immune systems still ‘responding to toxic chemical exposures’ related to East Palestine derailment
Sweden and WHO launch new long-term initiative to transform Ukraine’s health system
WHO and the Swedish International Development Cooperation Agency (Sida) have launched a new multi-year cooperation project to support the long-term recovery and transformation of Ukraine’s health system. The new project, “Ukraine’s Health System Transformation Initiative: Strengthening Health Governance, Health Financing and Service Delivery for Long-Term Recovery”, was launched at the Ukraine Recovery Conference 2026 in Gdansk, Poland on 26 June, and will run from June 2026 to 2029. Sweden will contribute approximately US$ 26 million (240 million Swedish krona) to support this project. This contribution forms part of Sweden’s broader support to Ukraine through the Team Europe approach, which brings together the European Union, its Member States, and key partners such as the European Commission’s Directorate-General for Enlargement and Eastern Neighbourhood and Enabel, and WHO as lead health agency, to support Ukraine’s recovery, reform agenda and European integration.“Ukraine’s health recovery cannot be measured only by what is rebuilt, but by whether people can count on the health system when they need it most. The scale of the task is immense, with health reconstruction and modernization needs estimated at US$ 19.4 billion over the next decade. Sweden’s US$ 26 million contribution to Ukraine’s Health System Transformation Initiative is a timely investment in the institutions, financing and services that will support Ukraine’s long-term recovery and European integration. WHO remains a trusted partner of the Government of Ukraine in advancing this process. I am deeply grateful to Sweden for its consistent support and partnership,” said Dr Hans Henri P. Kluge, WHO Regional Director for Europe. More than 4 years of war have placed unprecedented pressure on Ukraine’s health system, creating 3 interconnected challenges. The first is responding to the immediate consequences of the war and the urgent health needs of the population. The second is recovering and modernizing health services today. The third is continuing reforms and aligning the health system with European standards in the context of Ukraine’s future accession to the European Union. The war has led to large-scale population displacement, an increasing need for trauma care and rehabilitation, and shortages of health workers. High out-of-pocket payments in Ukraine make access to health services more difficult. Around 46% of total health expenditure is paid directly by individuals, placing a significant financial burden on many households and underscoring the need for reforms in health financing. Older people, persons with disabilities, women, children and veterans continue to face the greatest difficulties in accessing health services. “Ukraine is demonstrating that health system transformation can continue even during war. Ukraine is also continuing to align its health system with European norms and standards. WHO is committed to supporting Ukraine on this journey. We provide technical support, help coordinate partners’ efforts and support the institutional changes needed to strengthen the system. We are grateful to Sweden for its support. Through this partnership, we can help Ukraine build a more resilient, accessible and people-centred health system,” said Dr Jarno Habicht, WHO Representative in Ukraine. About the Health System Transformation InitiativeThe new initiative will support Ukraine through 3 interconnected areas: strengthening governance and coordination of health sector reforms through more inclusive coordination platforms and structured policy dialogue; transforming service delivery by reinforcing a primary health care-centred model that integrates family medicine, nursing and midwifery; and improving financial sustainability by supporting reforms that ensure the long-term viability of the national health system and reduce out-of-pocket payments for households. Overall, these reforms are expected to make the health system more coherent and easier to navigate, improve the quality and continuity of care, and ensure more equitable access to services, particularly for those who need them most. They will also support Ukraine’s progress towards a more modern health system aligned with European standards. “We are convinced that long-term recovery is not possible without strong, high-quality, person-centred health services that are accessible to everyone. Our partnership with WHO is designed to support deep and lasting systemic changes. Investments in human capital especially autonomous midwives, whose role for maternal, newborn and adolescent sexual and reproductive health cannot be understated, stronger governance, digital transformation and the financial sustainability of the health system are investments in Ukraine’s future. We are proud to support this process,” said Malin Perhult, the Head of the Ukraine Unit at Sida. Focus throughout implementation will be given to the most vulnerable population groups, including older people, women and children, and persons with disabilities, who have been affected by the war and face greater health-care needs. The initiative will be implemented in close cooperation with the Ministry of Health of Ukraine, the National Health Service of Ukraine, the Public Health Centre of Ukraine, regional authorities and international partners. This project will help Ukraine move towards a system where everyone can access the health care they need. It will strengthen primary care, make the health finance system more stable and predictable, and reduce the out-of-pocket costs that Ukrainians face when using health services. As a result, the Ukrainian health system will become more aligned with European standards and more sustainable in the long run.
OHSU advances massive leap in medical science with cellular therapies
Patients are benefiting from CAR-T to treat neurodegenerative diseases, cancer, lupus and other autoimmune conditions.
Amazon Brazil GTA 6 description mentions unannounced features
New Grand Theft Auto 6 details are seemingly leaked by an Amazon Brazil product description.
Gambling disorder diagnoses spike after states legalized sports betting
Researchers analyzed millions of electronic health records and found a major difference between states that greenlit sports gambling and those that didn’t.
Gambling disorder diagnoses spike after states legalized sports betting
Researchers analyzed millions of electronic health records and found a major difference between states that greenlit sports gambling and those that didn’t.
Trump forced to drain the reflecting pool swamp
Jonathan Freedland speaks to Arwa Mahdawi about why this project is proving to be such an embarrassing failure for the president
KXNO layoffs leave Iowa sports community too quiet
This week's layoffs of local sports radio talkers leaves our sports community worse off, columnist Travis Hines writes.
Battlefield 6 is altering its long-range gunplay to feel more like Battlefield 4
In just a few short days, Battlefield 6's combat encounters could potentially play out a lot differently from the way they do today.
Gemini begins rolling out for existing Android Automotive vehicles
Some months after its confirmation, Gemini for Android Automotive appears to be finally rolling out to existing vehicles.
PlayStation Boss Says New Console Experiences Will Involve 'Leveraging Technologies That Can Be Used in Various Forms and Locations' — and I'm Convinced He's Teasing a PS6 Handheld
Recent comments from Sony Interactive Entertainment CEO Hideaki Nishino have suggested PlayStation may move towards more hybrid, Switch-like consoles in the future to match modern on-the-go players.
St. Norbert, FVTC partner to make business degree transfer 'seamless'
St. Norbert and Fox Valley Technical College are joining forces to make getting a bachelor's in business at SNC easier.
Elroy Air to Become Publicly Traded Company via Business Combination with Inflection Point-led SPAC
Elroy Air, Inc., a leading U.S.-based technology developer of autonomous heavy-cargo drones for defense, rapid response and commercial logistics, and Columbu...
NTT DATA | Transforming Data Into Exceptional Fan Experience
We worked with Penske Automotive Group to create a mobile application to amplify the fan experience and make the iconic Indianapolis Motor Speedway a smart venue through NTT Smart Solutions.
Grand Theft Auto 6 demand may be so high it will "likely outstrip supply" this holiday season, a video game retailer warns
Speaking to The Game Business, a major senior games buyer has warned that stocks might not survive the spending frenzy this fall.
These 15+ award-winning gadgets are on sale for Prime Day - but we'd pay full price
Editor-approved tech is still on sale during Amazon's Prime Day sale - but don't wait much longer to shop.
Louisville coaches can't afford to stay sidelined amid NCAA changes
The NCAA has brought college sports into instability, which is why coaches like Louisville's Jeff Brohm and Pat Kelsey have to be activists.
Cabo Verde Is a Breakout Star of the World Cup. So Is the Family-Owned Business That Designed Its Jerseys
After more than three decades manufacturing apparel, Capelli Sport co-founder and CEO George Altirs found his company’s biggest billboard yet—3,500 miles away from his midtown Manhattan office.
Remembering Victory Stadium: How Roanoke’s lost landmark changed sports and civil rights
It’s been 20 years since Victory Stadium was demolished, but the memories and legacy remain alive in Roanoke.
Introducing: Breguet Celebrates the 225th Anniversary of the Tourbillon with Four New Releases, And the Return of a Collector Favorite (Live Pics)
A revived and revised version of the Roth-designed caliber 558.1 movement (significantly improved) headlines four watches to celebrate the patent date of one of Abraham-Louis Breguet's most notable achievements.
Amazon Reveals New GTA 6 Features on Product Page
In a product listing for Grand Theft Auto 6, Amazon has revealed some interesting new details about the game.
Rain stopped play? Biggest worry now in British sport is extreme heat
Climate crisis is on show every day when sportspeople do their thing and the rest of us sweat on the sofa
Hollywood gets into the microdrama race as mobile-first storytelling draws stars and major studios
Mobile-first serialized storytelling is rapidly becoming one of entertainment's fastest-growing businesses.
TravelTech Show, Business Travel Show Europe name 2026 innovation award winners
Arcube, ImpersonAlly, Acai and Nowadays were recognized in separate competitions for travel technology innovations spanning airline retailing, brand protection, contact center automation and meetings management.
Kenny Klein, former longtime Louisville Athletics administrator, dies
Kenny Klein, a former Louisville Athletics administrator of 39 years who worked more than 1,300 straight men's basketball games, has died at age 65.
It's Summer Sale Season, So I Tracked Down 25 Actually Good Gaming Deals Under $20
There's a million sales happening right now, so I sifted through them all to find 25 genuinely solid gaming deals that are each under $20.
It's Xbox's turn (again), as console prices keep going up
Microsoft announced a price hike for the Xbox Series consoles today, the third in little over a year. Effective August 1, the Xbox Series S, which launched in 2020 for $300, will cost $500 in the U.S. The Xbox Series X, which launched in 2020 at $500, will go for $800. This follows a round of PlayStation 5 price increases from Sony this spring, and a slow-motion increase for Nintendo’s Switch 2, which will kick in in the U.S. in September. (Mind you, there were also eight video game industry price hikes in six months of 2025). The chart up top shows the sudden ascent of console prices over the past year, a sudden surge in an already unusual hardware generation. Prices had been flat for years, now “up” is the new “flat.” Game console prices used to go down across the length of a console generation, but not this time around. Microsoft’s explanation for the new price hike today: We hoped another price increase would not be necessary, and we have spent the last several months working with suppliers on options. Unfortunately, console storage and memory prices have increased by more than 2.5x and we expect another doubling by the fall of 2027. The entire consumer electronics industry is struggling with the current components crisis, but the effects are particularly hard on consoles. Unlike phones, computers, speakers, and other consumer devices, consoles are typically not sold at a profit, but instead for less than they cost to make. This is an issue well beyond game consoles. Apple announced price hikes on its computers and tablets today as well. Game File is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber. Subscribe Item 2: Brutal Bungie cuts Bungie laid off “most” of its Destiny development team and some developers who worked on Marathon, the newest game from the struggling Sony-owned studio. A WARN notice issued by Sony to Washington State, where Bungie is based, tallied cuts impacting 292 workers, effective next month. That’s strictly for Bungie/Sony jobs in Washington and wouldn’t account for any elsewhere. The video I clipped below shows the redacted list of Bungie cuts filed to Washington State officials. As you’ll see, I had to scroll for a while… In a note emailed to PlayStation workers and published online, PlayStation game studios chief Hermen Hulst offered the following explanation for these latest cuts at Bungie: This is painful news, especially for talented colleagues whose roles have been eliminated. This decision was made only after extensive discussion and careful consideration, and I want to provide some context on how we arrived here. Over the past several months, together with Bungie leadership, we reviewed the studio’s long-term direction, development priorities, resource needs, and role within our broader portfolio strategy. We explored multiple alternatives before concluding that a reduction was necessary to align the studio’s resources with its current priorities and long-term goals. In 2022, Sony bought Bungie for $3.7 billion. The studio’s marquee game, the multiplayer live service shooter Destiny 2 was losing popularity at the time. Its next game Marathon, released earlier this year, has been well-reviewed but had a slow start. Bungie is renowned for making great shooter games, and Destiny fans have mourned the wind-down of Destiny 2. They’ve also expressed bewilderment over reports that Destiny 3 is not, per Bloomberg, immediately in the cards.
JD Vance says Nixon’s Watergate scandal would be ‘12-hour news story’ today
Vice-president declares admiration for 37th president and claims Nixon and Trump targeted by ‘deep state’ forces
Politics Chat, June 25, 2026
A newsletter about the history behind today's politics.
Caitlin Clark made the WNBA bigger. It’s still playing small
The league’s paltry one-game suspension of Alyssa Thomas after her fist to Caitlin Clark's throat barely begins to address the problem.
Serious statin side effects on muscles are extremely rare, new research confirms
Scientists created a new tool to help doctors predict a patient’s risk of severe muscle problems from taking a statin.
Digital-Only 'Grand Theft Auto VI' Is a Car Crash for Physical Media
Not all progress is progress.
MLB All-Star 2026: Shohei Ohtani and Ernie Clement receive automatic spots after winning Phase 1 of fan vote
Monkey Business: Wild rhesus macaque spotted at Mount Dora hotel
A wild rhesus macaque was spotted at the historic Lakeside Inn in Mount Dora, Florida, spending about 45 minutes roaming the property and attracting attention from guests and staff. The hotel and local businesses responded with humorous, monkey-themed social media content, engaging the community. Wildlife officials cautioned the public not to approach or feed wild monkeys due to potential health risks and encouraged reporting sightings to authorities. The monkey has not returned to the hotel but has been seen elsewhere in downtown Mount Dora.
This autism therapy is covered by many insurers. Why does the military’s plan restrict it?
Logan Cabiao started applied behavior analysis therapy for autism when he was 2. Several years later, TRICARE, the military’s healthcare program, imposed major coverage restrictions.
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.
Tennessee court temporarily blocks state health officials from sharing undocumented ill children’s information
The “state cannot go forward with the policy” until the judge makes a final decision, said the head of the Tennessee Justice Center.
Michigan president has strong words for college sports after Dusty May exit
Michigan president Domenico Grasso spoke with Dusty May and said he cited the transfer portal and uncertainty about NIL as reasons for his departure.
Brand New, Retail Boxed Nintendo Switch 2 Gaming Consoles Are Going for as Low as $399 for Amazon Prime Day
Brand new.
Democratic socialists’ battleground test: From the Politics Desk
Plus, Pete Buttigieg is back on the campaign trail. And digging into Michael Whatley’s bio in the North Carolina Senate race.
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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