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NBC Announces Plans For Special 'Star-Spangled Sunday'
NBC is having a special "Star-Spangled Sunday" broadcast next weekend. Next Sunday is July 5, 2026. It's a very special Fourth of July weekend this year. It's America's 250th birthday. NBC and Peacock will be airing all 15 MLB games on Sunday, July 5. Two games - Mets-Braves and Padres-Dodgers - ...
Master pianist Swann to perform Goldberg Variations
The Winter Harbor Music Festival will welcome internationally acclaimed pianist Jeffrey Swann for a special performance of J.S. Bach’s Goldberg Variations, BWV 988, on Saturday, July 11, at 7 p.m.
Health insurers are looking for MAHA wins
The companies are offering benefits aimed at appealing to Robert F. Kennedy Jr. and his Make America Healthy Again movement.
Efzimfotase alfa demonstrated improvements in bone health in treatment-naïve pediatric patients with hypophosphatasia achieving median difference of 1.67 vs placebo in RGI-C Score at week 25 in MULBERRY Phase III trial
Positive results from the MULBERRY Phase III trial showed that efzimfotase alfa (ALXN1850), an investigational enzyme replacement therapy, demonstrated a statistically significant and clinically meaningful improvement in bone health in children (2 to
Zohran Mamdani says he and allies he endorsed carry a ‘national message’
Mayor says progressive peers who swept primaries speak to Americans ‘coast to coast’ as moderates have reservations
American Airlines flight aborts takeoff at MIA after business jet enters runway
An American Airlines flight to Bermuda aborted its takeoff after a business jet entered the same runway at Miami International Airport on Saturday evening.
Trump’s Great American State Fair attendees say they haven’t noticed politics overshadowing the celebration
The gloomy, overcast weather on Saturday didn’t disturb visitors who attended the first weekend of President Donald Trump’s Great American State Fair, an event commemorating America’s 250th anniversar...
Trump’s Great American State Fair attendees say they haven’t noticed politics overshadowing the celebration
President Donald Trump kicked off the event with a headlining speech Wednesday after musical acts dropped out of the lineup citing concerns over partisanship.
Sarasota Business Awards honor innovation, entrepreneurship and the American spirit
The Greater Sarasota Chamber of Commerce recognized businesses in the community across 10 categories.
'All INdiana Politics'
U.S. Sen. Todd Young has said that a proposed $300 billion payment to Iran would not be funded by American taxpayers, and that any ceasefire with Iran must be contingent on the dismantlement of its nuclear program, while Indiana Senators Young and Banks have split on a housing bill now awaiting President Trump's signature.
Mamdani Says Primaries Show Voters Want a New Kind of Politics
New York City Mayor Zohran Mamdani said he believes Tuesday’s state primaries, where the slate of progressive candidates won, show that American voters are looking for a “new kind of politics.”
Poll: Everyone has a different idea of what counts as MAHA
The POLITICO Poll shows that the Make America Healthy Again umbrella includes people with opposing ideologies and different politics.
Americans find common ground on healthcare
Americans agree that healthcare needs to be better, cheaper, and less complicated. Good ideas toward those goals are bubbling up around the country.
America split from monarchy 250 years ago. Donald Trump’s presidency is testing how far it’s come
'The presidency today, even when colored by President Trump’s worst excesses, is not a monarchy.'
Jodi's Journal: The purple city prevails
No matter who emerges in this election, the purple city has prevailed. And I think that's a win.
Humor laurels for comedian Bill Maher as the Kennedy Center navigates Trump-era upheaval
Comedian Bill Maher is set to receive the Mark Twain Prize for American Humor at the Kennedy Center.
Humor laurels for comedian Bill Maher as the Kennedy Center navigates Trump-era upheaval
Comedian Bill Maher is set to receive the Mark Twain Prize for American Humor at the Kennedy Center.
Humor laurels for comedian Bill Maher as the Kennedy Center navigates Trump-era upheaval
Comedian Bill Maher is set to receive the Mark Twain Prize for American Humor at the Kennedy Center.
Humor laurels for comedian Bill Maher as the Kennedy Center navigates Trump-era upheaval
Comedian Bill Maher is set to receive the Mark Twain Prize for American Humor at the Kennedy Center.
America split from monarchy 250 years ago. Trump's presidency is testing how far it's come
America is getting ready to celebrate the 250th anniversary since it split from Britain's monarchy and embarked on its experiment in democracy.
America split from monarchy 250 years ago. Trump's presidency is testing how far it's come
America is getting ready to celebrate the 250th anniversary since it split from Britain's monarchy and embarked on its experiment in democracy.
Where Side Hustles Businesses Are Booming: The Top Cities in America Right Now
Miami and other hotspots are seeing a surge in side hustle businesses. Here’s how to choose one that matches your skills and schedule.
Americans now live longer in Democratic-held House districts. Here’s why
Even as health care issues rise in the 2026 campaign debate, new data show that far more House Republicans than Democrats represent districts where the most residents face major medical challenges — and lack health insurance.
Again, Trump said nobody left his speech. Again, that wasn’t true
President Donald Trump posted on social media on Thursday about the speech he gave the day prior to kick off the Great American State Fair in Washington, DC: “Everybody stayed right until the end of my Speech because they loved hearing about a truly successful America.”
Opinion | Trump’s Science Cuts Betray America’s Past Since Lewis and Clark
America has funded scientific research since 1804 — and remembers that first project as a national glory. Cutting similar funding today is a betrayal.
Costs of Iran war will linger despite conflict's end, experts say
The effects of the war and other factors driving inflation are likely to stick around for months, experts say, presenting an ongoing challenge to American households.
Kevin O'Leary's latest villain arc: data centers
Kevin O'Leary, the acerbic "Shark Tank" investor, is everywhere trying to sell a skeptical American public on the idea of a data center in their town.
Slate is betting Americans want less car for less money
Slate unveiled the starting price for its tiny, electric pickup truck this week. It's betting that today's overly techy cars created a white space.
SG Americas Securities LLC Has $8.39 Million Holdings in Flutter Entertainment PLC $FLUT
SG Americas Securities LLC lessened its holdings in Flutter Entertainment PLC (NYSE:FLUT - Free Report) by 85.8% during the first quarter, according to the company in its most recent Form 13F filing with the Securities & Exchange Commission. The fund owned 82,269 shares of the company's stock a
‘Photo I.D. should be at the core.’ Rep. Byron Donalds on polling that Americans favor requiring a photo I.D. to vote
American Airlines flight aborts takeoff in Miami after business jet enters the same runway
An American Airlines flight headed to Bermuda aborted its takeoff in Miami Saturday evening after a business jet entered the same runway, getting as close as a third of a mile apart at one point.
American Airlines flight aborts takeoff in Miami after business jet enters the same runway
An American Airlines flight headed to Bermuda aborted its takeoff in Miami Saturday evening after a business jet entered the same runway, getting as close as a third of a mile apart at one point.
14 unique ways to celebrate America’s 250th birthday
Fireworks, hotdogs and summer blockbuster movies are Independence Day staples. But this year brings a flurry of unique and alternative events where Americans can come together, put aside our differences,
Senators, Pennsylvania businesses to represent Commonwealth at Great American State Fair
WASHINGTON, D.C. (WHTM) — Pennsylvania will be represented at the Great American State Fair after all. The Commonwealth’s delegation to the U.S. Senate announced a planned “strong…
3 million Americans have dropped Obamacare health coverage over past year, after Republicans let federal subsidies expire
KFF expects the total number of people in the government healthcare program to continue to decline throughout the year, potentially to a low of about 17.5 million from 19.2 million now.
Dean Cain discusses stark contrast in patriotism among political parties
Actor Dean Cain joins 'Fox News Live' from the Great American State Fair in Washington, D.C., to share his take on patriotism and a tense border hearing with DHS Secretary Mullin.
The sky is not falling. Americans are getting healthier.
Despite declining obesity and heart disease rates, increasing cancer survival rates, and a record high life expectancy, politicians from both parties are pushing costly and ineffective policies to …
Vanilla Ice: Music brings people together, transcends politics
Rapper Vanilla Ice explains his decision to perform at the America 250 event. He states music is universal and should bring people together, transcending political divides. He emphasizes celebrating the country's 250 years.
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 […]
GameThread: Detroit Tigers vs. Houston Astros, 6:40 p.m.
Detroit Tigers (35-46) vs. Houston Astros (40-44) Time/Place: 6:40 p.m., Comerica ParkSB Nation Site: The Crawfish BoxesMedia: Detroit SportsNet, MLB.TV, Tigers Radio NetworkPitching Matchup: LHP Framber Valdez (4-5, 3.91 ERA) vs. RHP Kai-Wei Teng (4-6, 4.03 ERA)
Five Million Americans Lost ACA Health Insurance—Here’s What That Could Mean For Public Health
New data shows 5 million Americans have lost health insurance through the ACA. A doctor breaks down the downstream consequences for public health in America.
Ranked: America’s Best-Selling Albums Ever
Michael Jackson may be the king of pop, but in the U.S. he's been outsold by a rock band from Los Angeles.
Israel’s Vance problem is bigger than JD Vance
Vice President JD Vance has become the face of a Washington that no longer treats Israel as the exception to "America First."
The NHL's Obsession With No-Trade Clauses: Why Hockey Is The Outlier In North American Sports
No-trade and no-move clauses have become so commonplace in the NHL that many fans assume they are simply part of the business of sports. They aren’t.
Some paid the ultimate price to enact voting rights. Their survivors see America turning backward
It’s been six decades since the Voting Rights Act was enacted
In Trump’s America, two very different views of Christianity in politics emerge
Adherence to organized religion is falling in the United States, but defenders of the religious right are ascendant in positions of power in the Trump administration.
How Trump’s takeover fractured America’s birthday party
When Next250 organizers began planning for America’s 250th birthday, they envisioned bringing together communities in a polarized country to celebrate democracy.
4 iconic American CEOs are making way for nuts-and-bolts leaders
Warren Buffett, Tim Cook, Bob Iger, and Doug McMillon are making way for nuts-and-bolts leaders, but success will require more than an eye for detail.
As America fights over food, this woman speaks for the unheard
Vanessa Rissetto, a dietician and \
Siekerka on Spadea: Climate Superfund Another Strike at NJ Business Climate
Appearing on Bill Spadea’s new show, Speak for America, on ONNJ, NJBIA President and CEO Michele Siekerka said it’s difficult to determine whether the
Chicago teacher visiting every FBS stadium while bridging gap between LGBTQ+ community, sports world
A Chicago teacher is hard at work on his quest to visit every NCAA Division I Football Bowl Subdivision stadium in America, while also strengthening bonds between the sports world and the LGBTQ+ community.
J. William Fulbright, proponent of cultural exchange, left complex legacy across politics, education
As the Vietnam War heated up, U.S. Sen. J. William Fulbright became uncomfortable with American involvement in the conflict.
J. William Fulbright, proponent of cultural exchange, left complex legacy across politics, education
As the Vietnam War heated up, U.S. Sen. J. William Fulbright became uncomfortable with American involvement in the conflict.
DNC plans weekend of local events to focus on affordability concerns under Trump
Two years ago, Democrats were the ones accused of being indifferent to Americans’ anger about rising prices. Now they're pointing the finger at Trump, who has downplayed the impact of lingering inflation.
Screens are virtually inescapable. What are they doing to our health?
They’re in our pockets, workplaces, homes and schools — screens are everywhere. Americans are spending more than seven hours a day looking at screens. What is this doing to our well being? And does all this screen time affect different generations differently? Horizons moderator William Brangham explores what we know and don’t know with researchers Kostadin Kushlev and Courtney K. Blackwell.
Politics Unusual: Co-chairs of NYC-DSA, Rep. Malliotakis
In this episode of Politics Unusual, FOX 5 NY's political reporter Morgan McKay sits down with the co-chairs of New York City's Democratic Socialists of America to discuss their success on primary night. Also, a conversation with Rep. Nicole Malliotakis about the rise of democratic socialism and the direction the Democratic Party could take in the coming years.
But-For Causation and the Essential Business Hurdle: Analyzing the Summary Judgment in RAAM Construction
RAAM Construction Inc v. United States of America, Case No. 2:25-cv-04681-SPG-AJR, 2026 WL 18391 (C.D. Cal. June 23, 2026). The Employee Retention Credit (ERC) codified under Internal Revenue Code Section 3134 remains a significant source of controversy, audits, and high-stakes federal litigation.
Confederate flag displayed at N.C. exhibit at America's State Fair
A flag featured in the North Carolina exhibit at America’s State Fair on Washington’s National Mall is drawing some unwanted attention.
Trump posts new passport rendering — featuring a memorable photo of himself
President Donald Trump unveiled a new rendering of a special commemorative US passport bearing his likeness Friday, debuting a limited-edition passport to mark America’s 250th anniversary this year.
Americans keep poisoning themselves with semaglutide, other weight loss drugs
These incidents became much more common after the FDA started approving GLP-1 drugs for chronic weight management in 2021.
Trump warns ‘godless communists’ will turn cities into slums as Dems fail to fight socialist surge
Trump calls Democratic socialist primary winners "godless communists" at Faith & Freedom Coalition, warning of threats to America's founding principles.
Honda Strengthens Power Sports & Products Business With More Unified Structure
American Honda announced a restructuring of its Power Sports & Products center, aligning its Powersports, Power Equipment and Marine divisions under a unified structure.
Faculty voice: The creative tension of America’s founding documents
Eric Gonzalez Juenke, an associate professor at MSU's Department of Political Science, reflects on the founding documents of America and what it means 250 years later.
Axios Live: "Health care costs are scaring people," Rep. Dingell says
Americans are not just thinking about the high prices of health care — they're afraid of them
Trump threatens 100% tax on European imports if countries impose tax on digital services
“Please let this statement serve to represent that any Country that imposes such a Tax will immediately be met with a 100% TARIFF on any and all Goods sent to the United States of America,” Trump wrote in a post on social media.
Celebrate America 250 with Renfro Valley Entertainment Center!
Lexington and Central KY News, Weather, and Sports | WDKY
Your Social Security benefits could be cut by a quarter in 2032. Here’s what to know
Americans’ Social Security benefits will have to be cut by roughly a quarter in six years due to depleted funds, according to a June 9 report from the Social Security Board of Trustees. That’s months sooner than the group had estimated in 2025.
DAVID MARCUS: In rural Maryland, petty politics takes back seat to World Cup fever
The World Cup and America 250 celebrations unite Americans beyond politics, as the Save America Act and Trump debates fade in small-town gatherings.
Scientists Baffled by Discovery of Rare “Pink Floyd” Spider Hidden in Home Walls - Futura-Sciences
The Birth of a “Pink Floyd” Spider Tiny, discreet, and quietly settled on urban walls, a new species of spider was recently discovered in Colombia—and christened as a tribute to the iconic rock band Pink Floyd. As part of a study published in the journal Zoosystematics and Evolution, South American...
Evoke Entertainment Signs Tribeca-Honored Filmmaker Elisee Junior St. Preux
EXCLUSIVE: Evoke Entertainment has signed Haitian American filmmaker Elisee Junior St. Preux, whose debut feature The Tropic Sun and His Eyes world premiered in Tribeca’s Viewpoints section and earned...
We cut MBA prices because America needs more professionals, not fewer
America is running short on educated workers at the exact moment when they matter the most.
Walton Arts Center to host blood drive with free entertainment July 1
The Walton Arts Center will host a blood drive in partnership with the American Red Cross from 10 a.m. until 4 p.m. on Wednesday, July 1. The center will provide live entertainment for blood donors in attendance that day, including performances by cellist Carrington Truehart, and guitarists Ben Harris and William Reyes. SUBSCRIBE: Get our
PepsiCo Q2 earnings expected to reflect weakness in North American snack business, delayed recovery
PepsiCo Inc (NASDAQ:PEP, XETRA:PEP) earnings outlook was trimmed by Bank of America analysts ahead of the company’s second quarter results, with softer-than-expected performance in its North American snacks business offsetting steadier international trends. The analysts lowered their fiscal...
Small Business Central to American Prosperity Celebration
House Small Business Committee celebrates small businesses as key to American prosperity ahead of nation's 250th anniversary. Learn why Main Street matters.
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.
NASA’s PACE Mission Studies Smoke, Fires
With the North American fire season underway, and a record number of acres already burned nationwide, NASA’s Plankton, Aerosol, Cloud, and ocean Ecosystem
New York’s primaries signal a new force in US politics
Progressive, Muslim and Arab American candidates are challenging old limits on debate over Israel and Palestine.
Whole Hog Politics: It was voters, not Senate Republicans, who forced Trump’s hand on Iran
The early returns are in, and we can pretty safely say that Americans like the peace with Iran but strongly dislike the war that it ended. The truce is shaky, with hour-by-hour challenges that seem...
Gavin Newsom opposes a California wealth tax. He’s proposing a national billionaire tax instead
California Gov. Gavin Newsom on Friday proposed a national tax on billionaires that he says is the first part of an “economic reset for America” agenda, which aides explicitly say is part of his considering to launch a presidential campaign.
North Dakota State Fair 2026: Food, Entertainment, Pride of Dakota Festival, Contests, and More
MINOT, ND (KXNET) — There are now three weeks until this year’s North Dakota State Fair kicks off, and the Fair is including America’s 250th birthday. The fair is an official partner of…
Williams to begin Wimbledon comeback against Joint
American superstar Serena Williams will make her highly-anticipated singles comeback at Wimbledon against Australia's Maya Joint in the first round.
Bank of America community roundtable highlights sales tax increase, small business struggles
Business and government leaders also discussed hiring trends and the importance of the Charlotte Douglas International Airport.
Salpointe flag football QB named MaxPreps Freshman of the Year
It is the first year that MaxPreps is putting together an All-American team as the sport continues to gain popularity.
WATCH: Stephen Miller says 'America's doors are closed fully to asylum seekers' after Supreme Court rulings
The Supreme Court voted 6-3 on Thursday to allow the Trump administration to end legal protections for migrants fleeing violence and natural disaster in Haiti and Syria, exposing hundreds of thousands more people to potential deportation.
Dems put on blast over poll that shows record-low patriotism in US: 'Tear our society apart'
Rep. Harriet Hageman raises alarm over Gallup poll showing just 17% of Americans were "very proud" of their country, a record low in 25 years.
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.
2026 World Cup Is Putting FIFA’s Rules on Political Neutrality to the Test
The World Cup is in full swing across North America, and the U.S. men’s team faces Turkey in its final group round appearance on Thursday. But behind the cheering fans and nail biting matches, FIFA's commitment to political neutrality is put to the test. Marisa sits down with Tariq Panja, global sports correspondent at The New York Times. They dig into the politics behind the games, from restrictions on Iran’s team and President Trump’s unusually close relationship with FIFA president Giann
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
Justices Clash on Whether Race Played a Role in Trump’s Bid to Deport Haitians
The split mirrored one that has long divided Americans: how seriously to take the president’s loose, provocative and sometimes ugly remarks.
PAHO mobilizes emergency health response following earthquakes in Venezuela
Caracas, Venezuela/Washington, D.C., 25 June 2026 (PAHO) – The Pan American Health Organization (PAHO) has activated its emergency response mechanisms to support the health response in Venezuela following two magnitude 7.5 earthquakes that struck the country on June 24.
Project manager says America’s Time Capsule is a ‘gift to the future’
The vessel will move from Washington to Philadelphia starting Friday.
WATCH: Kellyanne Conway insists socialist primary victories don't reflect American values nationwide
Kellyanne Conway says Democratic primary wins reflect only a handful of specific districts and do not signal a broader political shift nationwide.
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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