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“Supergirl” is a decent standalone movie — so why is everyone acting like it’s awful?
Despite what the reviews and backlash may lead you to believe, the second film in the DC Universe is an enjoyable adventure.
Cavaliers have interest in second reunion with LeBron James
Cavaliers have interest in second reunion with LeBron James
Supreme Court agrees to review ban on AR-style semi-automatic rifles in major Second Amendment case
The Supreme Court announced Tuesday that it will decide whether cities and states may ban people from owning AR-15 rifles and similar semiautomatic weapons, taking up a major Second Amendment dispute that it had previously declined to address.
Jazz Under the Stars returns August 6
KCCK's Jazz Under The Stars celebrated the station's 50th anniversary last year by reuniting some of Iowa's best-known jazz, blues and R&B performers. Iowa's Jazz Station kicks off its second
Iowa Business Council projects positive six-month economic outlook
The Iowa Business Council has released its second-quarter Economic Outlook Survey for 2026, showing member expectations for sales, capital spending and employment remain positive for the next six months despite a slight overall decline from the previous quarter. The survey’s overall economic outlook index sits at 64.81 points for the second quarter, a decrease of […]
Press Release- Rowan County Sees Increase in Overdose Emergency Department Visits 2026
Rowan County Sees Increase in Overdose Emergency Department Visits; Ranks Second Highest in North Carolina for Fentanyl-Positive Death RateSalisbury, NC – Rowan County health officials are raisin
Want to Feel Less Stressed or Anxious? Science Says Just Fake a Smile
Research shows a 20-second fake smile 'improves physiology during acute stress, improves stress recover, and reduces illness over time.' Can't beat that.
Ivory Coast vs Norway – Match preview and team news
Ivory Coast and Norway meet in the Round of 32 fixture on Tuesday at the Dallas Stadium after both teams secured second place in their respective group table.Ivory Coast vs Norway – Match preview an...
Jazz Chisholm leaves with injury, Yankees lose odiously to Tigers
The Yankee second baseman entered concussion protocol; the Tigers dealt New York another nasty loss.
Jazz Chisholm injury update: Yankees star exits game after collision
Yankees second baseman Jazz Chisholm Jr. exited Monday's game after a collision with teammate Jasson Dominguez.
Terrion Arnold released: Where Lions go from here after secondary suffers loss, plus potential replacements
The Lions cut ties with their former first-round pick after his arrest on kidnapping and armed robbery charges, leaving a void in Detroit's secondary.
Netflix and Superheroes Are Having a Rough Stretch on Streaming....
(Welcome to my weekly streaming ratings report, the single best guide to what’s popular in streaming TV and what isn’t. I’m the Entertainment Strategy Guy, a former streaming executive who now analyzes business strategy in the entertainment industry. If you were forwarded this email, please subscribe to get these insights each week.) I have a quick prediction before we start today’s article: You might see this data in future news articles. Not my specific charts or analysis, but the core trend I’ve been monitoring—Netflix is having a lackluster Q2—will become inescapable. Often, folks want to know “What does the data say?” Well, that’s what it says. I haven’t seen this analysis hit the trades really yet, but I have a feeling some other outlets are going to start making this case soon. Remember, you read it here first. You probably have read about the problems facing superhero films at the box office this weekend. Well, this week, I explore whether superheroes are dying on TV as well! And the data says: definitely maybe! We have a lot to cover in today’s Streaming Ratings Report, which covers the two weeks of 18-May and 25-May. Today, I’m just looking at TV, like Netflix’s disappointing Q2, superhero shows underwhelming, a few TV shows dropping off the charts, The Pitt finally ending its epic run on the viewership charts (and whether “view counts” change its status as one of the biggest shows of all time), all the flops, bombs and misses, and a whole lot more. Tomorrow, I’ve got a great rundown of the film side of things. Let’s dive right in! (Reminder: The streaming ratings report focuses on the U.S. market and compiles data from Nielsen’s weekly top ten viewership ranks, Luminate’s Top Ten Data, Showlabs, TV Time trend data, Samba TV household viewership, company datecdotes, Netflix hours viewed data, Google Trends, and IMDb to determine the most popular content. While most data points are current, Nielsen’s data covers the weeks of May 18th to May 31st, 2026. You can find a link to my terminology here.) Subscribe Television - Netflix’s Q2 Slump Continues Having analyzed streaming ratings for going on half a decade, I have learned to trust my gut, but I’m always relieved when I can find actual data to back it up. For example, after a string of very popular shows like Stranger Things, Bridgerton, The Lincoln Lawyer and The Night Agent came out, week after week, in January and February, my gut wondered if Netflix had enough new and returning TV shows to sustain them throughout the year. Since then, Netflix’s post-March slate of shows has not impressed me. This week seemed to feature a potential new hit, but then, like a classic Duffer Bros. TV show, there was a twist. I speak of The Boroughs, Netflix’s latest (and last) Duffer Bros. produced show. The pitch is “Stranger Things with older actors”. And it topped the Nielsen charts: With just two weeks of viewership, The Boroughs would have been a top 25 debut show last year: But here’s the twist: Netflix has already cancelled The Boroughs! What happened? Likely a few things. First, the show didn’t do as well globally as it did in the US. As What’s on Netflix showed, it lagged behind several other shows that got cancelled. Second, its completion rate was likely low; after an initial burst of interest, it quickly dropped off on the Samba TV and Luminate charts. Third, the Duffer Bros. left Netflix for Paramount, and that may have factored into Netflix’s decision here. (Though I tend to believe that if a show is doing well, Netflix would have kept greenlighting seasons.) Still, just because I can explain why Netflix may have cancelled this show doesn’t mean I’m justifying it. In particular, as I’ve noted before, Netflix is losing a lot of their bigger shows as they reach their natural ends, and they need to replace those shows. This show had the hallmarks of a big new genre show, and it’s their biggest hit of the last few months (in the US at least), but now it’s done. Netflix’s other show this week—The Four Seasons, the second season of the “hit” show from last year—definitely disappointed. Its sophomore season had about half the viewership of the first, only 12.7 million hours. It also only had a two week run on Samba TV, and its numbers were all down on Luminate too. In other words, even with two successes, the Q2 slump for Netflix looks real: I could add to the list of disappointments: Both Lord of the Files and Man on Fire had short runs on the Nielsen charts. Running Point’s sophomore season also opened to about half its viewership, similar to The Four Seasons. A Good Girl’s Guide to Murder’s second season—see below—didn’t even make any of the three viewership charts I track, unlike the first season. Netflix is absolutely having a dismal second three months of 2026. If this Nielsen data is any indication, and I think it is, I think this will show up in Netflix’s engagement report, and maybe even their financial outcomes. And the rest of June doesn’t look much better. We have two hit shows coming back—Sweet Magnolias, one of their quietest big shows, and Avatar: The Last Airbender, a big hit for them in 2024—but the other big swings are limited series crime thrillers i.e. no future season potential. Like I said above, sometimes when I uncover a juicy nugget like this, other outlets end up writing very similar articles mimicking the data without credit. We’ll see if that happens this time! Share Television - The State of Superhero Shows on Streaming When I first heard the pitch for Spider-Noir—a Sony TV show on Prime Video that binge-released eight episodes first on MGM+ then on Prime Video two days later—I had my doubts. It’s a live-action Spider-Man show set in the 1930s, starring Nicholas Cage, based on a cameo of a character in Spider-Man: Into the Spider-Verse. No, seriously, that’s the pitch. That could either go terrifically well or horribly wrong. Great because, Spider-Man. He’s the biggest superhero we have. I’ve seen tracking numbers that put the new _Spider-Man: Brand New Da_y as the blockbuster of the year and initial pre-sales back that up. And yet this Spider-Noir pitch feels very esoteric. (Also, the eight-episode binge release feels very “Amazon copying Netflix” again.) So what’s the data say? And what does this say about the future of superhero shows?
PENN Entertainment to Report Second Quarter Results and Host Conference Call and Webcast on August 6
PENN Entertainment, Inc. (Nasdaq: PENN) announced today that it will release its 2026 second quarter financial results at 7:00 a.m. ET on Thursday, August 6,...
Second 2026 Connecticut measles case reported
Connecticut’s second measles case of 2026 in Connecticut was confirmed by state health officials in Monday.
AB Science reports completion of the step 3 of phase 1, evaluating the combination of AB8939 with venetoclax for the treatment of refractory or relapsed AML
PRESS RELEASE AB SCIENCE REPORTS COMPLETION OF THE STEP 3 OF PHASE 1, EVALUATING THE COMBINATION OF AB8939 WITH VENETOCLAX FOR THE TREATMENT OF REFRACTORY OR RELAPSED ACUTE MYELOID LEUKEMIA THE COMBINATION OF AB8939 WITH VENETOCLAX GENERATED A 67% OVERALL RESPONSE RATE (ORR) AND A 100% DISEASE CONTROL RATE (DCR), WITH NO DOSE-LIMITING TOXICITIES (DLT) OBSERVED, IN A POOR-PROGNOSIS POPULATION WITH ADVERSE GENETICS TREATED IN THE SECOND - TO FOURTH-LINE RELAPSED OR REFRACTORY SETTING Paris, June 2
AHA/ACC/ESC/WHF Expert Consensus Document in Collaboration with HFSA, HFA and JHFS: Second Universal Definition of Heart Failure (2026)
In response to the rising global prevalence of heart failure (HF) and limitations in research, surveillance, and prevention, in 2021 multiple cardiac societies convened to issue the First Universal Definition of Heart Failure, establishing uniform terminology, including a designated Stage B (pre-HF) to identify at-risk individuals.
Student-athlete ECG law takes effect July 1; families share why it's needed
Florida is the first state to require electrocardiogram (ECG) screenings for high school athletes. It is called the Second Chance Act.
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
Apple iPhone 18 Pro Release Schedule: Why iOS 27 Signals September Date
The just-released second developer beta of the next iPhone software helps confirm what is likely to happen and when for the next iPhones’ release date.
Leo XIV’s second “business” consistory produced few headlines, but that’s by design
On Saturday, Pope Leo XIV brought an end to the second extraordinary consistory of his pontificate. The meeting of cardinals was not very exciting, which might have been the point.
Second Measles Case of 2026 Confirmed by Wyoming Department of Health
The Wyoming Department of Health (WDH) has confirmed a case of measles in an unvaccinated adult from Teton County. Measles is a highly contagious infection that can cause severe illness. The public may have been exposed to measles at the following locations and times: Cafe Court Pizzeria and Ranch House Restaurant, Colter Bay Village, Grand […]
Lyles to take charge of Ultimate Championship entertainment
Noah Lyles has been announced as an Ultimate Star for the World Athletics Ultimate Championship, taking place from September 11-13 in Budapest, Hungary.Lyles, the dominant US sprinter who has won consecutive 200m golds at the past four World Championships, is locked in to compete at the inaugural edition of the new global championship. Lyles has earned automatic qualification into both the 100m and 200m by virtue of his podium-topping performances in those disciplines at the Paris 2024 Olympic Games and the World Athletics Championships Tokyo 25, respectively.
On anniversary of disastrous debate, Biden rallies Democrats at a casino
President Joe Biden spent the second anniversary of his disastrous debate performance at a Maryland casino, giving the keynote speech at an annual fundraiser for Maryland Democrats.
Pokémon GO Events This Week: June 29
Pokémon GO’s June 29 – July 5 week sees us enter the second month of the season of Forever Forward! We end June and kick off July with 10th Anniversary celebrations and Sobble Community Day! Plus the weekly rotating Raid Hours, Spotlight Hour, Dynamax Battles and Mega Raids. ⭐Highlights Raid Boss Change (July 1): Articuno, Zapdos, Moltres and […]
Could Ennis Rakestraw Save the Lions’ Secondary?
Terrion Arnold’s arrest has left a major hole in Detroit’s secondary. Could this finally be Ennis Rakestraw’s chance to prove he belongs?
US Oilfield Business Activity Strengthens, Though Oil Price Uncertainty Remains
The Federal Reserve Bank of Dallas’ second-quarter energy survey reports improved business conditions, despite a mixed outlook on oil prices and input costs.
Q&A: Mike Rogers on the Iran deal, weaponization fund, bridge politics
As Democrats beat one another up in a primary, GOP's Mike Rogers says his second bid for Senate is "night and day" over where he stood two years ago
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.
Local business gathers donations for Venezuela earthquake victims
HARRISBURG, Pa. (WHTM) — A local business is stepping up to help earthquake victims in Venezuela. The Arepa House on Second Street in Harrisburg is accepting donations all day Sunday. They sa…
Esports means business for new generation of fans
Valhallan, a youth esports training organization, hosted a grand reopening of its second Long Island storefront in Wantagh on Saturday.
Eugenio Suárez rescues Reds in 9-7 win over Pirates
The Reds got a 9th inning homer from the slugger they hope can carry them through the season’s second half.
Hawaii is turning ocean plastic and fishing nets into roads
Hawaii researchers are giving old fishing nets and recycled plastic a second life by mixing them into asphalt roads. Early tests found these roads didn't release more plastic particles than standard pavement, with tire wear overwhelming any plastic signal from the recycled material. If future studies confirm the roads are durable, the technology could help tackle both marine pollution and overflowing landfills.
Soccer meets nature at Vancouver mountaintop watch party
The match between England and Panama was shown on a big screen atop Grouse Mountain, a 4,100-foot mountain that's part of the Pacific Ranges with a sweeping view of British Columbia. When Jude Bellingham scored England's breakthrough goal in the second half, the fans roared. Both Toronto and Vancouver are hosting matches during the tournament.
Usha Vance pokes fun at ‘political significance’ of maternity dress
Second lady Usha Vance poked fun at a New York Times article examining the public image of pregnant women in President Trump’s orbit, joking that she did not realize her maternity dress carried so …
Bruins draft goalie Yuri Ivanov with second-round pick
The Bruins went with a goalie with their first pick of the 2026 NHL Draft.
Flyers continue to add on defense with first of two second-round picks
With their first of two second-round picks in the 2026 NHL draft, the Flyers selected Brek Liske.
FISU reinforces its commitment to the World University Sports Movement
On the second day of the meeting, the Executive Committee focused on the upcoming Universiades and the future of the FISU Forum. After a first day concentrating on updating statutes and strategies for a simpler, more innovative and effective future, FISU’s Executive Committee focused on upcoming events on this second and last day of their […]
Malachi Moreno: “Next year is my year”
Big expectations surrounds Kentucky’s second-year, homegrown center.
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.
Nia Long explains why she turned down Prince's advances
The "Michael" actress said that she later met Prince a second time: "He was lovely, but we talked about my hair the whole time."
First Bend Block Party draws crowds to Central District
Live music, art, food and fun are taking over Bend’s Central District for the first Bend Block Party. Come down to Second Street near Open Space and check it out before 9 p.m. today!
Barker reclaims title at National Road Championships
Megan Barker reclaims her British elite women's circuit race title as the second day of the National Road Championships produces its second Welsh winner.
France's Ousmane Dembélé records second-fastest hat trick in World Cup history in 4-1 win over Norway
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...
Biggest offseason question for every East team: Will Knicks duck second apron? What's next for Celtics, Heat?
Can New York keep its championship roster together? What will Boston do with Jaylen Brown?
Thunder reportedly trade Isaiah Joe to Pistons for two second-round draft picks
Isaiah Joe still has two years left on his contract.
Scientists Turn Wet Coffee Grounds Into Coal-Like Fuel in Just 90 Seconds
A new process skips energy-intensive drying for recycling coffee waste.
Nintendo Switch 2 ends first full year in the U.S. at nearly 6 million units sold, second fastest-selling video game system
Following the latest U.S. sales report from Circana, we have information about the first full-year sales of Nintendo Switch 2. The console ended its first twelve months at 5.9 million units sold. According to Circana, it’s the second fastest-selling video game system in the U.S. with tracked history dating back to 1995. The only other platform to outdo it was...
Four bad habits tournament golf exposed within my game
What one writer learned from his second tournament round of the year.
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.
World Cup brings a boost to bar and restaurant businesses across the Piedmont-Triad
Bars and taprooms across the Piedmont-Triad are extending their hours and providing the ultimate experience as the World Cup enters its second week.
4 Takeaways From USA's Last-Second World Cup Loss To Türkiye
So much for a perfect group stage. But the USA can now turn its attention toward the knockout stages.
Shohei Ohtani Earns Three Nominations for 2026 ESPYS
Shohei Ohtani of the Los Angeles Dodgers has redefined what a two-way player can look like in the modern era of baseball. Ohtani is coming off a 2025 season in which he won his fourth MVP and second straight World Series championship. On Thursday, ESPN announced the nominations for the 2026 ESPYS awards.
Sharonville mom raising money for UC Health's ICU patient program after she nearly died
It's been a year since a Sharonville mom suffered a medical emergency days after giving birth to her second child.
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.
21ALIVE SPORTS DIGITAL EXCLUSIVE: Loyer to the Clippers, TinCaps find second half success
21Alive Sports Director Andy Newman and Weekend Sports Anchor Nia Hinson catch you up on this week’s sports news.
Man Utd's Onana set for Trabzonspor loan
Manchester United goalkeeper Andre Onana is close to securing a second loan spell at Turkish club Trabzonspor.
The Business of Beauty Global Forum: Inside the Industry
Jane Hertzmark Hudis, Simone Dominici and Vicky Tsai were among the speakers unpacking the most pressing topics for the industry in the second session of The Business of Beauty Global Forum 2026.
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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