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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.
13 things to do this weekend around the Seattle area
From the Seattle Pride Parade to new art gallery exhibitions, here are the latest local things to do around the Seattle area.
13 things to do this weekend around the Seattle area
From the Seattle Pride Parade to new art gallery exhibitions, here are the latest local things to do around the Seattle area.
Fulton County health officials notify Johns Creek High School community of possible tuberculosis exposure
Students and staff who may have had close contact with the individual will receive separate notifications and be offered free tuberculosis testing.
South Dakota mayoral candidates separated by just two votes in shockingly close race, recount expected
The Sioux Falls mayoral runoff contest shockingly resulted in just a two-vote margin separating the candidates out of more than 36,000 ballots cast.
CT AHEC Introduces New Public Health Programs and Partnerships
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How anti-LGBTQ policies can affect business
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Paranovus Entertainment Technology Limited Announces 1-For-100 Reverse Share Split
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Ball State Teacher Preparation Programs Earn Top Ratings in Science of Reading Reviews
Ball State University’s elementary education, early childhood education, and special education teacher preparation programs have earned top marks in two reviews focused on how well future educators are prepared to teach reading through evidence-based, scientifically grounded instruction.
Louisville doctor, nurse and nonprofit founder charged in federal health care fraud crackdown
Federal prosecutors in the Western District of Kentucky announced charges in four separate cases involving alleged schemes to defraud Medicare and Medicaid, misuse medical credentials and controlled substances, and submit
Felix Okpara selected by Orlando in NBA draft
Former Vol Felix Okpara selected by the Magic in the NBA draft.
NASA’s TESS Mission Reveals the “Puffiest” Planets Ever Found
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Will Smith, Jada Pinkett Smith make rare appearance in Paris outing
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Dave And Buster's Entertainment (PLAY) Stock Sees Fair Value Cut After Q1 Analyst Revisions
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Knicks Fan Who Stole Trash Can Identified, Fired From Job
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A review argues the family dog may become science’s unlikely ally against autism
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Arrests of immigrant parents create mental health crisis for children
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Health Beat: Parasitic fly outbreak prompts Pa. to restrict animal movement
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4 charged in separate health care fraud cases in Michigan, AG announces
Four people are facing charges in separate health care fraud cases, the Michigan Attorney General’s Office announced on Tuesday.
Why Paranoia About AI Is Healthy For Business Owners (and Panic Isn’t)
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"It's like lightning in a bottle" - Star Wars Galactic Racer devs spill the beans on why it's so hard to make a game as good as Burnout Paradise
Matt Webster and Kieran Crimmins recollect the creation of a racing classic, and how they're trying to strike gold twice.
Why Combat Sports Continue to Attract Global Audiences
No sports experience can beat the adrenaline rush of witnessing two opponents battle each other on equal footing, armed only with skills, preparation, and sheer willpower. Throughout the ages, boxing, MMA, wrestling, and judo have continued entertaining people all over the globe, uniting fans from many different backgrounds with a common language. Discover how fascinating […] The post Why Combat Sports Continue to Attract Global Audiences appeared first on Native News Online.
From soil to gut: why your gut health depends on the world around you
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Q&A: Why climate politics cannot be separated from Indigenous sovereignty and justice
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Business travel buyers look to AI for help managing disruption
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Justice Department charges two more in alleged plot to attack White House UFC event
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Zane’s Trace Commemoration Continues with Parade, Entertainment and Community Spirit - WHIZ - Fox 5 / Marquee Broadcasting
The second day of the Zane’s Trace Commemoration wrapped up with a full schedule of activities, entertainment and family-friendly fun in Putnam. The day began with a parade and a 5K before crowds gathered at Putnam Park to browse vendors and enjoy a variety of performances throughout the afternoon. What was once an event that had faded away has found...
“Voicemails for Isabelle ”writer-director Leah McKendrick reveals the true story that inspired the romcom
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‘The United States is showing troubling parallels’
Opinion, comment and editorials of the day
N.C. A&T College of Education Earns Top National Rating in Science of Reading Teacher Preparation
The undergraduate elementary teacher preparation program in the College of Education (CoEd) at North Carolina Agricultural and Technical State University has earned an A+ rating from the National Council on Teacher Quality (NCTQ) for how well it prepares future teachers to teach reading to elementary students.
New York City and Lake Placid explore joint bid to host 2042 Winter Olympics and Paralympics
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Howie Mandel: OCD like mine isn't a joke. It's paralyzing.
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Scientists Discover Strange Horn-Shaped 'Hyperparasite', a World First
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NASA’s Next Generation Telescope Arrives in Florida Ahead of Launch
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Paragould business offers CPR certification class to the public
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Puppets, performers and politics filled the streets at LACMA’s first-ever Art Parade
The first-ever Los Angeles Art Parade and LACMA block party drew an estimated 60,000 to Wilshire Boulevard.
Puppets, performers and politics filled the streets at LACMA’s first-ever Art Parade
The first-ever Los Angeles Art Parade and LACMA block party drew an estimated 60,000 to Wilshire Boulevard.
Chinese sodium battery surprised scientists by matching key Tesla benchmarks
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The surprising science of how fatherhood changes the brain
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Letter: Missouri teachers need education in the 'science of reading' for kids
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The Carolina Hurricanes Stanley Cup Parade Was Magnificently Unhinged
A Mikko Rantanen sweater was thrown into the parade path (and stomped on by fans), and three of the featured […]
1980's 'That's Entertainment' by The Jam: Written in Just 10 Minutes
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Nicolas Deslauriers got down to business.
Sports culture expert discuss impact of Knicks win for city identity
Watch the full interview here.
Hurricanes fans jam into downtown Raleigh for team's Stanley Cup parade
Thousands of fans arrived hours early to line sidewalks for the team’s victory parade or packed in near the rally stage.
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A victory parade Saturday morning celebrated the Carolina Hurricanes' Stanley Cup win.
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Colorado Politics Calendar June 22-28
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UNC Health seeks approval for new hospital in Asheville
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The secret language behind animal cooperation
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Slocomb Tomato Festival to feature parade, live entertainment and vendors
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Unpatchable 'usbliter8' Exploit Breaks Apple A12 and A13 SecureROM Boot Chain
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Researchers uncover an unpatchable security flaw affecting several iPhone generations
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ICC delivers Business and Industry closing statement at Bonn Climate Change Conference - ICC
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The first unpatchable iPhone exploit in six years targets chips still running Apple's latest iOS
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Politicians share the spotlight at Knicks parade, diehard fan or not
Mayor Mamdani rode on a float, handed out keys to the city and made a speech heavy on Knicks history.
NYPD mistakes Knicks player for a fan, tries to kick him out of championship parade
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Public health professor completes third Fulbright Scholarship
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New unpatchable exploit targets Apple devices with A12 and A13 chips
Researchers at Paradigm Shift have published the technical details of usbliter8, a new unpatchable iPhone BootROM vulnerability.
Stanley Cup cash flow: Downtown Raleigh businesses prepare for big crowds during Saturday's parade
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Türkiye’s Democratic Breakdown: Authoritarian Consolidation and the Sources of Resilience
Lessons from Global Democratic Resistance is a public panel series that brings together frontline activists, civic leaders, institutional actors, and field‑informed scholars to examine how democratic actors have resisted, responded to, and learned from democratic backsliding across countries. The series aims to identify practical lessons and comparative insights for those defending democracy today and is organized by the Carnegie Endowment for International Peace in collaboration with the Ash Center for Democratic Governance at the Harvard Kennedy School; the Cornell Center on Global Democracy; Perry World House at the University of Pennsylvania; the Kellogg Institute for International Studies at the University of Notre Dame; the Democratic Futures Project at the University of Virginia; Stanford’s Center on Democracy, Development and the Rule of Law.
AI optimizer beats Claude Code, Codex by 2.5x
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The Special Olympics are coming to Minneapolis. Here's what you need to know
Next week, the Special Olympics come to Minneapolis June 20-26. More than 3,000 athletes and 1,500 coaches will engage in 16 Special Olympics team and individual sports. The event is expected to bring in 75,000 fans.
The Special Olympics are coming to Minneapolis. Here's what you need to know
Next week, the Special Olympics come to Minneapolis June 20-26. More than 3,000 athletes and 1,500 coaches will engage in 16 Special Olympics team and individual sports. The event is expected to bring in 75,000 fans.
Exclusive: Rama Duwaji Sports Cult NYC Label at New York Knicks Championship Parade
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Apple's A12 and A13 Chips Facing New Unpatchable Exploit
Security research firm Paradigm Shift today published details of a new BootROM vulnerability affecting Apple's A12 and A13 chips, along with a working proof-of-concept exploit named "usbliter8". The BootROM, or SecureROM, is the first code an iPhone runs when it powers on. Because it is baked directly into the chip at manufacture, any vulnerability found there cannot be fixed with a software update, meaning affected devices will remain vulnerable for the rest of their lives.
This Spirited New Puzzle Platformer Puts A Clever Spin On Celeste
Tethergeist is a clever spin on a familiar genre, with a parade of new and interesting ideas giving it a soul all its own
Ted Cruz bill to regulate college sports in NIL era advances
The Texan said he hopes the proposed changes, written with a Democratic senator, can save athletics from a stark separation between the haves and have-nots.
Sports is driving a large part of the entertainment economy, says Activate CEO Michael Wolf
Michael Wolf, Activate Consulting CEO and co-founder, joins 'Squawk Box' to discuss Versant's media rights agreement with the WNBA, appetite for live sports, Fox's $22B acquisition of Roku, Paramount-WBD merger, and more.
Sports is driving a large part of the entertainment economy, says Activate CEO Michael Wolf
Michael Wolf, Activate Consulting CEO and co-founder, joins 'Squawk Box' to discuss Versant's media rights agreement with the WNBA, appetite for live sports, Fox's $22B acquisition of Roku, Paramount-WBD merger, and more.
Legislation overhauling college sports faces major test in Senate
The bill has support from several athletic conferences and the NFL, the NFL Players Association and the U.S. Olympic & Paralympic Committee, but the SEC and the Big Ten have not endorsed it
Legislation overhauling college sports faces major test in Senate
The bill has support from several athletic conferences and the NFL, the NFL Players Association and the U.S. Olympic & Paralympic Committee, but the SEC and the Big Ten have not endorsed it
Corey Feldman Reveals 'Misdiagnosis' After Medical Emergency on Flight, Says He Actually Had Food Poisoning
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The surprising science history behind New York City’s ticker-tape parades
On Thursday Knicks fans are flocking to Manhattan for a ticker-tape parade. But where did ticker tape even come from?
The surprising science of how fatherhood changes the brain
Studies suggest that, like mothers, fathers may undergo a shift in their biology in preparation for and in response to the responsibilities of parenthood.
Average US gas price drops below $4
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Here's how to watch New York Knicks parade, championship celebration
Yankees’ power parade flattens White Sox once again
With the Knicks’ parade on the horizon, the Bomber bats kept the good times rolling in the Bronx.
A Mamdani-backed progressive’s challenge to a veteran Democrat highlights party fractures
The divides between the Democratic old guard and a new class of progressive challenger were on sharp display on Tuesday night as a congressional candidate in New York’s 13th District apologized for past disparaging remarks about Kamala Harris.
Valve Steam Machine Benchmarks Show Near Twice The Uplift Over Steam Deck & Comparable To Ryzen 5 5600X at 30W
New benchmarks of Valve's Steam Machine show performance comparable to a 6-core AMD Ryzen CPU from 2020, but could be decent if priced right.
Essentia Health-Casselton Clinic to offer sports physical and immunization blitzes
Essentia Health will offer sports physical and immunization blitzes to area students in preparation for the 2026-27 school year.
Essentia Health-Casselton Clinic to offer sports physical and immunization blitzes
Essentia Health will offer sports physical and immunization blitzes to area students in preparation for the 2026-27 school year.
Scientists stunned by the world’s largest whale “graveyard” millions of years old - Futura-Sciences
The Hidden Depths of the Diamantina Zone Deep beneath the Indian Ocean, researchers from China, Italy, and New Zealand got more than they bargained for during their recent expedition. Exploring the remote Diamantina Fracture Zone—which formed during the separation of Australia and Antarctica—the team operated the Fendouzhe submersible, a machine...
Far-right general upends Italian politics
Ahead of next year’s election, Meloni has to decide whether to embrace firebrand ex-paratrooper Roberto Vannacci.
Nuanced differences on business issues separate Democratic gubernatorial hopefuls
Both Democratic gubernatorial candidates vow to boost Colorado's business atmosphere, but they offer different approaches to doing so.