How Novel: Novelty Indicators

Humans crave novelty. Our visual cortex is stimulated by changes in our visual field. Even infants show more interest in new sights and sounds. Curiosity doesn’t entirely distinguish homo sapiens from other species, but we certainly would win the prize for maximizing its value. Science, art, and music wouldn’t exist without our drive for novelty. Science in particular thrives on some scientist thinking, “hmm, isn’t that interesting?” then turning it into something that helps us understand the universe we live in better, often with practical applications.

We don't always recognize important novelty when we see it

Depending on what source one believes, there are somewhere between 3 million and 7 million scientific papers published each year; whatever the number, it is growing rapidly, and impossible for a scientist in any particular field to keep up with, much less to look for insights from other fields. Most of these papers, of course, are likely to be incremental work, building on previous research and probably not reflecting true breakthroughs. How then, do researchers, and the people who fund them, spot the truly novel papers that may spark breakthroughs?

Enter the idea of a “novelty indicator” – and welcome to the Metascience Novelty Indicator Challenge.

The need for something to help identify scientific novelty has been recognized for some time. A 2016 paper by Wang, et. al warned that there was, in fact, a bias against such novelty. “Research which explores unchartered waters has a high potential for major impact but also carries a higher uncertainty of having impact,’ the authors warn. “These findings suggest that science policy, in particular funding decisions which rely on traditional bibliometric indicators based on short-term direct citation counts and Journal Impact Factors, may be biased against “high risk/high gain” novel research.”

Similarly, a 2019 paper by Veugelers and Wang emphasizes:

We find that the small proportion of scientific publications which score on novelty, particularly the 1% highly novel scientific publications in their field, are significantly and sizably more likely to have direct technological impact than comparable non-novel publications. In addition to this superior likelihood of direct impact, novel science also has a higher probability for indirect technological impact. being more likely to be cited by other scientific publications which have technological impact.

The issue is, how to best do such a score?

In Nature, Dr. Benjamin Steyn, co-head of the UK Metascience Unit, laments that he has “been stumped by the fact that there are no good ways to measure novelty,” and so: “Without good indicators, researchers can’t assess the prevalence of original papers or their value in scientific progress.”

He mentions work done by DeSci Labs and others on novelty scores, but believes “none of which are foolproof.” There has to be a better way:

That’s why the UK Metascience Unit has partnered with the non-profit organization RAND Europe; the Sussex Science Policy Research Unit; and the publisher Elsevier, to launch MetaNIC (see go.nature.com/3hhsdp3) — a competition to produce and validate indicators for scientific novelty in academic papers. Running until November, MetaNIC is open to researchers all around the world.

Participants will test their algorithm against 50,000 scientific papers that will have been ranked by 10,000 researchers on their novelty. The team whose indicator best matches the humans’ assessments will win £300,000 (US$407, 000). 

The Challenge website explains the importance:

If the global science system had responsibly used better and more timely indicators of research excellence, this could have a profound impact on the incentives of researchers, our understanding of the factors which make excellence more likely, and in turn, the pace of research progress. Better metascience indicators can help funders, governments, academic institutions, and individuals get more high-quality research out of limited resources.

As Dr. Steyn says: “Better indicators could improve our understanding of the factors that make research excellence more likely, the incentives of scientists and so the pace of scientific progress. That is worth exploring.”

Credit: MetaNIC

It’s worth pointing out exactly what the Metascience Unit that he is co-head of is for. It is a branch of the UK government, and the website explains: “Metascience typically examines the institutional structures, practices and incentives explaining how researchers spend their time and the speed, direction, nature and impact of their outputs.”

To put that in practice:

All our work starts from a simple idea: that the scientific method, so powerful in so many areas of life, should be systematically and routinely applied to how we practice, fund and support science itself.

Investing in research, development and innovation is vital to UK and international economic growth and prosperity. However, it is not just the quantity of that investment that matters, but also the quality. How research is funded and practiced is critical to accelerating scientific breakthroughs and innovations, nurturing talent, and shaping research culture.”

It makes me wish the U.S. had a Metascience Unit. Instead, we have DOGE, which is slashing federal scientific funding in the name of curbing “waste, fraud, and abuse,” crushing anything that can even remotely be considered “DEI,” and, while they are at it, punishing universities that President Trump is mad at. That’s no way to invest in science, to discover innovation, or to prepare for the future. If anything, it scorns novelty.

In JAMA Network, David Cutler and Edward Glaeser warn that the proposed NIH cuts are “the $8 trillion health care catastrophe.” In Forbes, John Drake, a professor at the University of Georgia, points out: “New macro-empirical research finds that every dollar invested in non-defense public R&D yields $1.40–$2.10 in economic output, and since World War II, government funding has driven roughly 20% of U.S. productivity.”  A paper from American University researchers concludes: “…budget cuts to public R&D would significantly hurt the economy in the long run, with large negative effects on GDP, investment, and government revenue. A 25 percent cut to public R&D spending would reduce GDP by an amount comparable to the decline in GDP during the Great Recession.”

So, yeah, how one cuts research, and which research gets cut, makes a difference, not just to researchers and their institutions but to all of us and the future of our country. 

I understand that federal funding isn’t unlimited and perhaps could be spent more judiciously, but arbitrary cuts are perhaps the worst way to do it. It sure seems like focusing on novelty, with its bigger potential for large impacts, could be a much better way to direct funding.

Maybe you, or a researcher you know, should sign up for the Metascience Novelty Indicators Challenge! 

The Long Game Should Have Already Started

Two books I recently read reminded me that, when it comes to playing the long game, conservatives have it all over, well, let’s not call them liberals, since the conservatives have managed to make that a pejorative term. Let’s just say left/center-left/center or even -- dare I say it? – progressives. Whatever we call them, they better get in that game.

Andrew C. McKevitt’s Gun Country: Gun Capitalism, Culture, and Control in Cold War America details how over the past sixty years conservatives successfully fought against efforts to regulate the sale, ownership, and use of guns, with the Heller decision opening up the doors and gun advocates flooding through them ever since.

Cara Fitzpatrick’s The Death of Public School: How Conservatives Won the War Over Education in America shows how conservatives sought to divert funds from public schools to private schools, even religious ones, for over seventy years. Conservatives recently “lost” a Supreme Court ruling (St. Isidore of Seville Catholic Virtual School v. Drummond) that would have allowed the nation’s first religious charter school, but no one should think the war is over or that advocates of public education are even holding their own, much less winning. Voucher programs are in place in most states and are on their way in most others.  

And, of course, conservatives spent forty years trying to overturn Roe v. Wade (see The Fall of Roe: The Rise of a New America by Elizabeth Dias and Lisa Lerer), succeeding with Dobbs. That was the long game played masterfully.

Credit: Jacquelyn Martin/AP

Most Americans support some form of gun control, public schools, and abortion rights, so the conservatives’ long game required shrewd planning and unrelenting persistence. What I don’t see -- what I’m worried is not happening -- are the long games on issues that people who aren’t hard right conservatives care about. Maybe they’re happening and are too subtle for me to be aware of, but I fear conservatives are just better at the long game.

Here are some of the key issues I mean:

Campaign finance:  It is appalling that the world’s richest man – who is not even a U.S. citizen – can essentially buy a Presidential election and several other races (along with fellow billionaires). It’s appalling that Citizens United held that corporations had the same rights as citizens to political donations and allowed them to flood campaigns with money. It's appalling that there was over $1b in “dark money” contributed in the 2024 election.  

This is not a way to run a democracy. In fact, it is a way to ensure we don’t have a democracy. We need real, meaningful campaign finance reform that returns power to the voters.

Voting Rights: The 1960’s saw some apparent victories in achieving voting rights, but sixty years later those rights are under attack again – in more pernicious ways. The Supreme Court is considering a case that would “gut” the Voting Rights Act, and states continue to chip away. Gerrymandering is widespread, in both red and blue states. Our vote is being neutered.

Conservatives talk about ID and other requirements, but let’s remind ourselves: in many other countries, if you are a citizen, you’re eligible to vote. In some countries, you are expected to vote. In the U.S., less than 75% of eligible voters were registered to vote in 2024, and that was for a hotly contested Presidential race.  Citizens should have both a right and a duty to vote. “States rights” to oversee elections don’t supersede our right to vote.

Privacy: We say we value our privacy, but we don’t act as though it actually is important. We’ve given it away to Big Tech and other corporations, and that is only going to get worse. Roe was based on an inferred right to privacy, and we saw how easily the Supreme Court swept that away.

The founders did not foresee Facebook, Google, surveillance cameras, or big data, and so the Bill of Rights doesn’t mention a right to privacy. If there is one thing that conservatives, liberals, and everyone in between should be able to agree on, it is that we deserve a constitutionally guaranteed right to privacy.

Credit: Tor Project

Living Wage: the federal minimum wage hasn’t been increased since 2009. Take that in: 2009. Meanwhile, most workers have seen wage stagnation, our income and wealth inequalities are at record levels, and intergenerational social mobility – e.g., the American Dream that your kids will do better than you did – has crashed.

We cannot have a democracy where the vast majority of our wealth goes to a tiny minority. We cannot have a stable country that is clearly split into the have and have-nots. Workers need to be paid a living wage -- one that doesn’t require them to work multiple jobs, that gives their children the upbringing and opportunities they should have, and that lets them have suitable housing.

Health care: I am so sick of conservatives saying people on Medicaid who don’t work don’t deserve coverage.  I’m disgusted that ten states, including two of our largest, never felt that their poor deserved Medicaid expansion at all. I’m dismayed that it is considered a victory that, due to ACA, we “only” have 30 million people without insurance (not to mention the tens of millions who are underinsured).  

People in America should have a right to health care (just as they should have a right to clean air and water, safe and sufficient food, and adequate housing). These should not have to be “earned” or given on the whims of the legislators. And don’t talk to me about “Medicare for All,” a meaningless phrase; if we ever get universal coverage, it shouldn’t look, or be financed, anything like Medicare. We can do much, much better.

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You may have your own list of priorities. I could probably come up with a few more. But that’s the thing about priorities: if too many things are a priority, then nothing is.  Those five are big, big asks, but I’m hard pressed to see what I’d take away.

So, where’s the long game for these? Not just looking ahead to the next election cycle or the next Presidential race, but knowing what the end game is and plotting out the gritty detail about how to get there, no matter how long it takes or what setbacks are encountered. Who is doing that work, what are they doing – and how can we help?

There’s famous saying that applies here: the best time to plant a tree is twenty years ago. The second best is now. Let’s start planting. 

The Future Is Here - and We're Not Ready

The war in Ukraine started out pretty much like you’d expect a 20^th century war might: aerial and artillery bombardment, followed by massed troops behind tanks and armed vehicles. It devolved into an early 20^th century war, complete with trenches and suicidal frontal attacks. Somewhere along the line, though, it turned into an actual 21^st century war, with cyberattacks and, most of all, drones dictating the battles.

That's the future knocking. Credit: Microsoft Designer

The latest surprise was Ukraine hitting Russian airbases as far as 3,000 miles away, using trucks with camouflaged drones to get near the bases, deployed remotely to great effect. Russia didn’t see it coming; neither did NATO or the U.S.

We think about the future, we try to prepare for it, but somehow it still manages to surprise us.

W.J. Hennigan writes in The New York Times:

The mission, called Operation Spider’s Web, was a fresh reminder to leaders of the world’s most advanced militaries that the toughest threats they face today are not limited to their regular rivals with expensive gear. Instead, swarms of small, off-the-shelf drones that can evade ground defenses can also knock out billions of dollars of military hardware in an instant.

What happened in Russia can happen in the United States — or anywhere else. The risk facing military bases, ports and command headquarters peppered across the globe is now undeniably clear.

The Editorial Board of The Wall Street Journal (with whom I seldom agree!) felt similarly: “ One urgent lesson beyond that conflict is that the U.S. homeland is far more vulnerable than most Americans realize.” 

“The Pentagon should be very worried about this,” Stacie Pettyjohn, a senior fellow at the Center for a New American Security who focuses on drone warfare and nuclear deterrence, told The Washington Post. Jason Matheny, CEO of the Rand Corporation, added: “Any country that has strategic bombers, strategic missiles and silos, or strategic nuclear submarines at port is looking at the attack and thinking the risk to our arsenal from a containerized set of drones disguised as a semitrailer poses a real risk.”

“If I think asymmetrically, if you’re Russia or China or another actor, what they’d likely do is try to infiltrate the United States and build their weapon from within the country,” retired General Glen VanHerck told WaPo. “Or if they put a container ship carrying drones into the Port of Long Beach or somewhere in close proximity to our critical infrastructure, including nuclear ports, that would be really hard to detect.”

The WaPo article also quotes Army Gen. Bryan Fenton, commander of U.S. Special Operations Command, in an April Congressional hearing: The “character of warfare is changing at a ratio faster than we’ve ever seen. Our adversaries use $10,000 one-way drones that we shoot down with $2 million missiles. That cost-benefit curve is upside down.”

Mr. Hennigan warns: “The U.S. military has globe-spanning technology to detect, track and shoot down ballistic missiles, but — so far — its multimillion-dollar systems remain helpless against the drone threat. The Pentagon has tried to develop technologies and defensive tactics, but results have been spotty at best.” 

One only also has to think about how Ukraine had previously used cheap drones to sink expensive Russian ships last year, how the ragtag Houthis have rattled the mighty U.S. Navy in the Red Sea using drone attacks, or how the Israelis snuck explosives in the pagers and cell phones using by Hezbollah in a devastating “red button” attack last fall. This is war in a new age.

Rep. Jason Crow (D-Colorado) told WaPo: “This conflict has already fundamentally changed the nature of warfare,” with the Pentagon still spending “exorbitant amounts of money” on military programs for conflicts “that would be relevant decades ago.”

Billion dollar warships are impressive, multi-million dollar warplanes are the norm, pricy ballistic missiles are assumed, and who doesn’t like a fancy tank? But we’re learning that enough drones in the right places handled by the right people (or an AI) can negate all those investments in the past.

We’re seeing the future of war right now, and our slow moving military-industrial complex is too focused on what it has been doing -- and the trillions of dollars it brings them -- to react quickly enough. And guess what: its evolution won’t stop with drones.

All this came home to me in a New York Times opinion piece by Thomas Friedman:

[Trump’s] ridiculous right-wing woke obsession with destroying the U.S. electric vehicle industry that President Joe Biden was trying to build up undermines U.S. efforts to compete with China in electric batteries. Batteries are the new oil; they will power the new industrial ecosystem of A.I.-infused self-driving cars, robots, drones and clean tech.

The consequence of this, the economics writer Noah Smith observed, is the weakening of America’s capacity to build the kind of cheap, battery-powered drones that Ukraine just used to destroy part of Russia’s air fleet — and that China could use the same way against our aircraft carriers. “Trump and the G.O.P.,” Smith noted, “have decided to think of batteries as a culture-war issue instead of one of national security. They think they’re attacking hippie-dippy green energy, sticking it to the socialist environmentalist kids and standing up for good old red-blooded American oil and gas. Instead, what they’re actually doing is unilaterally disarming America’s future drone force and ceding the key weapon of the modern battlefield to China.

Add to that Trump’s war on science, especially on health care, makes this all so much worse. Mr. Friedman continued:

What has distinguished and enriched the United States for so many years — and kept it the dominant global economic and military power — has been the ability to consistently attract that extra scientist or ambitious immigrant, that extra dollar of investment and that extra dollop of trust from allies. As the biggest economy in the world, we benefited disproportionately from a stable, global free market.

“Any conventional understanding of U.S. power would say that we would be crazy to put all three at risk, but that is exactly what we are doing today,” Nader Mousavizadeh, a founder of the geopolitical consulting firm Macro Advisory Partners, told me.

The lowest level in 35 years. Source: NYT/NSF

The future is happening now. All the money we’ve been spending, on so many things in so many ways, are sunk costs. They may or may not be the best things to be spending money on in the 21^st century. Chances are, many of them are not. Where’s our UBI? Where is our 21^st century healthcare financing and delivery system? Where is our robotics industry, our EV industry, our alternative energy industries? Where is our AI strategy?

Meanwhile, we’re driving away the people who are inventing the future, and that future is happening now. We have a geriatric President bent on personal vengeance and a geriatric Congress busy fighting pointless cultural wars. They are not equipped to lead us into the future. But it is coming nonetheless.

Waste, Fraud and Abuse - Oh, My!

So the House has passed their “big, beautiful bill,” by the narrowest of margins. Crucial to the bill are large savings from Medicaid, which in past years Republicans would have taken some glee from but now they are careful to explain away as just cutting “waste, fraud and abuse,” having finally realized that many MAGA voters depend on Medicaid.

Much of those savings come from proposed work requirements for Medicaid recipients, long a favored Republican tactic that the Biden Administration kept rejecting. Speaker Mike Johnson is very vocal about their importance. The people impacted by the work requirements, he insisted on Face the Nation:

If you are able to work and you refuse to do so, you are defrauding the system. You're cheating the system. And no one in the country believes that that's right. So there's a moral component to what we're doing. And when you make young men work, it's good for them, it's good for their dignity, it's good for their self-worth, and it's good for the community that they live in.

He's convinced that, instead of working, too many of them – especially young men – “playing video games all day.” He and other Republicans want to return Medicaid to what they see as its original purpose: “It’s intended for young, you know, single, pregnant women and the disabled and the elderly,” Speaker Johnson said. “But what’s happening right now is you have a lot of people, for example, young men, able-bodied workers, who are on Medicaid. They’re not working when they can.”

Maybe he should be working, but does this mean he shouldn't have Medicaid? Credit: Microsoft Designer

He’s generally right that, for most of its existence, Medicaid was not truly a program for the poor so much as for certain kinds of poor people, especially low income pregnant women and children, and the medically impoverished. It took Obamacare to widen coverage to all people under the poverty line, although the Supreme Court allowed states to decide if they wanted to do so, and ten states still have not.

It is, indeed, a moral question, just not the kind that Speaker Johnson likes, about whether there is a moral imperative to give more people, especially poor people, health coverage.  

The issue of these non-working Medicaid recipients is something of a shibboleth. Kaiser Family Foundation, for example, found “that 92% of Medicaid adults are either working (64%) or have circumstances that may qualify them for an exemption.” A 2023 CBO analysis cast doubt that such work requirements wouldn’t have much impact on the number of Medicaid recipients working. Work requirements are a solution in search of a problem.

Credit: Kaiser Family Foundation

What we do know about work requirements, from waiver programs in Arkansas and Georgia, is that they do, indeed, reduce the number of people on Medicaid, but largely by making it more difficult to verify eligibility. The requirements are confusing, the processes the recipients/potential recipients have to follow are cumbersome, and the mechanisms required to oversee them are expensive (or, depending on your perspective, lucrative for some vendors).

It's not about getting able-bodied people on Medicaid to work, and it is not about “waste, fraud and abuse;” it’s about getting fewer people enrolled in Medicaid.

The calls to return Medicaid to its original purpose seem very self-serving. Medicare, for example, did not original cover people with ESRD or disabled people under 65. Social Security did not originally cover farm workers or self-employed workers, and didn’t include benefits for disabled people or survivors of retired persons (spouses and children). We could save lots of money by returning those programs to their original purposes, but those are bridges that Republicans are not ready to cross…yet.

If we think Medicaid is not the right program for many poor people, well, that’s a fair discussion. Medicaid has more than its share of problems, not the least of which are low reimbursement rates in most states and a resulting lack of participating health care providers. Many poor people might, indeed, be better served by just letting them enroll in an ACA plan.

Unfortunately, though, ACA wasn’t designed for poor people, Its premium subsidies and cost sharing reductions do not apply to people with incomes under the federal poverty level. It was assumed that such people would all be covered by Medicaid expansion. Sure, low income people could get an ACA plan, but it is hard to see how they could afford the premiums or to pay deductibles/coinsurance amounts for care they might receive.

Maybe those low income, videogame playing young men could get jobs, but there’s a good chance their employers wouldn’t offer health insurance, or, even if they did, the required employee premium contribution would be unaffordable, or they could try to get an even more unaffordable ACA plan. For better or for worse, in the convoluted system we have Medicaid is the best place for them.

The moral component that Speaker Johnson and others – many of whom profess to be devout Christians – seem to miss is that in the richest country in the world no one should not get the health care they should have due to its cost. The best way the U.S. has found to try to achieve that – and it is a wildly imperfect solution -- is to get more people covered by some form of health insurance. ACA cut the number of those without insurance almost in half, but that still leaves almost 30 million people without coverage.  

The ”big, beautiful bill” is estimated to add another 10+ million people to the ranks of the uninsured, most but not all of whom would come from people losing Medicaid coverage. It could also, oh-by-the-way, further cripple safety net hospitals and professionals, further exacerbating the impact.

So when you hear Republicans talk about “waste, fraud and abuse” in Medicaid, what they’re saying is that some people do not deserve to get health care (similar SNAP cuts mean some people don’t deserve to eat). I have a hard time with that, and I don’t even need to check my Bible to be pretty sure it’s morally wrong.

Whether or not those people are playing videogames.

If they want to go after fraudulent billing, overtreatment, kickbacks, and so on, yeah, I’m all onboard for targeting those kinds of waste, fraud and abuse. But kicking poor people when they’re already down, no.

I'm Sensing Some Future

One of my frequent laments is that here we are, a quarter of the way into the 21^st century, yet too much of our health care system still looks like the 20^th century, and not enough like the 22^nd century. It’s too slow, too reactive, too imprecise, and uses too much brute force. I want a health care system that seems more futuristic, that does things more elegantly.

We're not there yet - but we're getting closer. Credit: Microsoft Designer

So here are three examples of the kinds of things that give me hope, in rough order of when they might be ready for prime time:

Floss sensor: You know you’re supposed to floss every day, right? And you know that your oral health is connected to your overall health, in a number of ways, right? So some smart people at Tufts University thought, hmm, perhaps we can help connect those dots.

 “It started in a collaboration with several departments across Tufts, examining how stress and other cognitive states affect problem solving and learning,” said Sameer Sonkusale, professor of electrical and computer engineering. “We didn’t want measurement to create an additional source of stress, so we thought, can we make a sensing device that becomes part of your day-to-day routine? Cortisol is a stress marker found in saliva, so flossing seemed like a natural fit to take a daily sample.”

The result: “a saliva-sensing dental floss looks just like a common floss pick, with the string stretched across two prongs extending from a flat plastic handle, all about the size of your index finger.”

The floss sensor that can assess your stress level. Photo: Atul Sharma and Nafize Ishtiaque Hossain

It uses a technology called electropolymerized molecularly imprinted polymers (eMIPs) to detect the cortisol. “The eMIP approach is a game changer,” said Professor Sonkusale. “Biosensors have typically been developed using antibodies or other receptors that pick up the molecule of interest. Once a marker is found, a lot of work has to go into bioengineering the receiving molecule attached to the sensor. eMIP does not rely on a lot of investment in making antibodies or receptors. If you discover a new marker for stress or any other disease or condition, you can just create a polymer cast in a very short period of time.”

The sensor is designed to track rather to diagnose, but the scientists are optimistic that the approach can be used to track other conditions, such as oestrogen for fertility tracking, glucose for diabetes monitoring, or markers for cancer. They also hope to have a sensor that can track multiple conditions, “for more accurate monitoring of stress, cardiovascular disease, cancer, and other conditions.” 

They believe that their sensor has comparable accuracy to the best performing sensors currently available, and are working n a start-up to commercialize their approach.

Nano-scale biosensor: Flossing is all well and good, but many of us are not as diligent about it as we should be, so, hey, what about sensors inside us that do the tracking without us having to do anything? That’s what a team at Stanford are suggesting in A biochemical sensor with continuous extended stability in vivo, published in Nature.

The researchers say:

The development of biosensors that can detect specific analytes continuously, in vivo, in real time has proven difficult due to biofouling, probe degradation and signal drift that often occur in vivo. By drawing inspiration from intestinal mucosa that can protect host cell receptors in the presence of the gut microbiome, we develop a synthetic biosensor that can continuously detect specific target molecules in vivo.

“We needed a material system that could sense the target while protecting the molecular switches, and that’s when I thought, wait, how does biology solve this problem?” said Yihang Chen, the first author of the paper. Their modular biosensor, called the Stable Electrochemical Nanostructured Sensor for Blood In situ Tracking (SENSBIT) system, can survive more than a week in live rats and a month in human serum.

A figure showing how SENSBIT mimics intestinal mucosa. Credit: Yihang Chen using BioRender

“This work began more than a dozen years ago and we have been steadily advancing this technology,” said Tom Soh, senior author of the paper. “This order-of-magnitude improvement in whole-blood sensor longevity over existing technologies is a huge advancement toward next-generation biosensors.”

The researchers believe their approach can lead to a new medical paradigm – “one where we can not only detect disease earlier but also potentially tailor treatments in real time.” Amen to that!

In vivo CAR-T therapies: If you follow cancer treatments, you’re familiar with CAR-T therapies, which engineer immune cells to fight cancer cells. They’re very promising, but very expensive, and time-consuming to make. “This whole process, it’s just inefficient,” Saar Gill, a haematologist and oncologist also at the Perelman School of Medicine, told Cassandra Willyard in Nature. “If I’ve got a patient with cancer, I can prescribe chemotherapy and they’ll get it tomorrow.”

Ms. Willyard profiles the approach of engineering the CAR-T cells in vivo. The potential, she reports, is enormous: “Treatments that deliver a gene for the CAR protein to cells in the blood could be mass produced and available on demand — theoretically, at a much lower price than current CAR-T therapies. A single dose of commercial CAR-T therapy costs around $500,000. A vial of in vivo treatment might cost an order of magnitude less.”

“If it’s efficacious and safe, it could really challenge the current paradigm,” Joseph McGuirk, a haematologist and oncologist who studies cellular therapies at the University of Kansas Medical Center, told her. And “we need to challenge the current paradigm”.

Obviously, this is not simple. “The stumbling block is, how do you get it to the right cell, the right place, right time?” said Michel Sadelain, a genetic engineer and director of the Columbia Initiative in Cell Engineering and Therapy at Columbia University. Ms. Willard describes different approaches that different companies are trying to accomplish this. Some companies, for example, are using viral vectors, while others use nanoparticles to deliver RNA into T cells. Other companies are skipping T cells and inserting the RNA into macrophages and other immune cells.

Human trials are underway, although with small numbers of participants. “I think 2025 and 2026 are going to be two very busy years in this area,” one CEO told Ms. Willyard.  Let’s hope so.

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Each of these is promising, and certainly in the right direction. Add these to, say, 3D printing in vivo using sound or programming smart cells, and forgive me if I get excited. We’re seeing glimpses of the future.

So next time someone wants to stick a needle in you for a blood test, put you through a colonoscopy, or start you on a grueling chemotherapy regime, ask yourself: would I be doing this in the 22^nd century?  

Innovation Must Be Cultivated

I’ve been thinking a lot about how the current Administration is waging war on U.S. science/scientists, and how other countries are hoping to benefit from a U.S. brain drain.  But two articles in today’s Wall Street Journal reminded me that attracting talent is only part of what must happen for science, technology, and innovation to flourish. Getting the talent is, in some ways, the easy part; getting the most out of that talent is the tricky part.   

If only creating innovation hubs was that easy. Credit: Microsoft Designer

The first article, by Tom Fairless and David Luhnow, is about the European tech industry, and they pull no punches in their opening sentence: “The world’s technology revolution is leaving Europe behind.”

Europe, they point out, actually has more people than the U.S., a large economy, and a well educated work force. It is home to some of the best universities in the world. It even has some strong history in tech, including Nokia, ASML, Spotify, and Klarna.

But, they point out, only 4 of the world’s top tech companies are European, and they cite calculations from Andrew McAfee, a principal research scientist at the MIT Sloan School of Management: “Over the past 50 years, the U.S. has created, from scratch, 241 companies with a market capitalization of more than $10 billion, while Europe has created just 14.”

Umm…

The authors say:

Europe lacks any homegrown alternatives to the likes of Google, Amazon or Meta. Apple’s market value is bigger than the entire German stock market. The continent’s inability to create more big technology firms is seen as one of its biggest challenges and is a major reason why its economies are stagnating. The issue is even more urgent with the prospect of higher tariffs threatening to further curb economic growth. 

Investors and entrepreneurs say obstacles to tech growth are deeply entrenched: a timid and risk-averse business culture, strict labor laws, suffocating regulations, a smaller pool of venture capital and lackluster economic and demographic growth. 

As a result, they speculate: “Having largely missed out on the first digital revolution, Europe seems poised to miss out on the next wave, too.” They mention how Mario Draghi, the former European Central Bank president, wrote in a report last fall: “The EU is weak in the emerging technologies that will drive future growth.”  As evidence, they note: “None of the top 10 companies investing in quantum computing are in Europe.”

Their diagnosis of the problem: “A big reason why Europe is now behind can be summed up as a lack of speed. Entrepreneurs complain that everything takes longer in Europe: raising money, complying with local regulations, and hiring and firing workers.”

“What is different in America is the speed of almost everything,” Fabrizio Capobianco, a tech entrepreneur from Italy, told them. “Americans make decisions very fast. Europeans need to talk to everybody—it takes months.”

The EU has been more proactive than the U.S. on important 21^st century issues like privacy and AI regulation, but this is both a blessing and a curse. Protecting the public and workers fits the European social contract, but can have adverse impacts on businesses’ abilities to take chances. U.S. companies complain about our federal and state regulation, but often find that doing business in Europe is even harder.

The authors mention Bird, a messaging start-up from the Netherlands, that is moving its main operations out of Europe. “Stop regulating, Europe. We might be the first, but we won’t be the last (to leave),” Robert Vis, the company’s founder, wrote.

The authors close with another quote from Professor McAfee about the Dragi report, which called for more government investment in tech, not for finding more ways to attract private capital. “That’s when I went from nodding my head in agreement to banging it on the table.” 

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The second article was on, of all places, Austin. Austin, the darling of so many people, for so many reasons. Its slogan is “Keep Austin Weird!” It has a very non-Texas laid-back vibe. Such a distinct music scene! And it’s not Dallas or Houston!

A few years ago, especially at the worst of the pandemic, Austin seemed fated to be a new tech center. People were fleeing Silicon Valley and San Francisco in particular: too expensive, the quality of life had suffered, and remote work was in. Austin seemed like a great alternative.

That, according to WSJ reporter Isabelle Bousquette, may be ending. She reports:

A new report from venture-capital firm SignalFire shows that in 2024 Big Tech employment declined 1.6% in Austin, and startup employment fell 4.9%. Tech employment in Dallas and Houston also declined, along with cities like Denver and Toronto. Tech employment grew, on the other hand, in New York and San Francisco. 

“I think that promise was never realized,” said Asher Bantock, SignalFire’s head of research. “This idea that it would become a new startup hub didn’t materialize.” The SignalFire report also showed that Big Tech employment in San Francisco rose 1.8% during the same time period, and start-up employment went up 0.8%.

Credit: SignalFire State of Tech Talent Report 2025

Ms. Bousquette quotes one tech worker, who broke his lease in Austin after six months, tried Boston and D.C., then moved to San Francisco. “They [his employer] gave me a list of cities and asked me about Austin, and I said, ‘No, not Austin. It’s kind of dead.” 

That’s not what we’re used to hearing about Austin.

You may remember – I did not – that part of the 2022 CHIPS Act was for Regional Tech Hubs. The Biden Administration designated 31 such hubs in 2023, although current Commerce Secretary Lutnick recently vowed to put the Administration’s own spin on the program (and just yanked funding from Spokane’s would-be aerospace hub). It’s nice to give grants and try to spur the kind of innovation ecosystem Silicon Valley has long enjoyed, but it’s not so simple.  

“People are putting down roots in these regional tech cities all across the country and I think that’s frankly good for America,” Julie Samuels, president and CEO of Tech:NYC, told Ms. Bousquette. “But people who want to ride the AI wave, people who are really ambitious, who are trying to build big companies, those people are really attracted to the coasts right now.” 

That’s the lesson that Austin is learning, and that Europe hasn’t quite learned.

Innovation hubs may be things that one can’t really create, but they are things one can easily ruin. Making them flourish, ah: that’s the hard part.

And Now for Some Fun Future

I feel like I’ve been writing a lot about futures I was pretty worried about, so I’m pleased to have a couple developments to talk about that help remind me that technology is cool and that healthcare can surely use more of it.

Technology can still give us hope for the future. Credit: Microsoft Designer

First up is a new AI algorithm called FaceAge, as published last week in The Lancet Digital Health by researchers at Mass General Brigham. What it does is to use photographs to determine biological age – as opposed to chronological age. We all know that different people seem to age at different rates – I mean, honestly, how old is Paul Rudd??? – but until now the link between how people look and their health status was intuitive at best.

Moreover, the algorithm can help determine survival outcomes for various types of cancer.

The researchers trained the algorithm on almost 59,000 photos from public databases, then tested against the photos of 6,200 cancer patients taken prior to the start of radiotherapy. Cancer patients appeared to FaceAge some five years older than their chronological age. "We can use artificial intelligence (AI) to estimate a person’s biological age from face pictures, and our study shows that information can be clinically meaningful,” said co-senior and corresponding author Hugo Aerts, PhD, director of the Artificial Intelligence in Medicine (AIM) program at Mass General Brigham.

Curiously, the algorithm doesn’t seem to care about whether someone is bald or has grey hair, and may be using more subtle clues, such as muscle tone. It is unclear what difference makeup, lighting, or plastic surgery makes. “So this is something that we are actively investigating and researching,” Dr. Aerts told The Washington Post. “We’re now testing in various datasets [to see] how we can make the algorithm robust against this.”

Moreover, it was trained primarily on white faces, which the researchers acknowledge as a deficiency. “I’d be very worried about whether this tool works equally well for all populations, for example women, older adults, racial and ethnic minorities, those with various disabilities, pregnant women and the like,” Jennifer E. Miller, the co-director of the program for biomedical ethics at Yale University, told The New York Times.  

The researchers believe FaceAge can be used to better estimate survival rates for cancer patients. It turns out that when physicians try to gauge them simply by looking, their guess is essentially like tossing a coin. When paired with FaceAge’s insights, the accuracy can go up to about 80%.

Dr. Aerts says: “This work demonstrates that a photo like a simple selfie contains important information that could help to inform clinical decision-making and care plans for patients and clinicians. How old someone looks compared to their chronological age really matters—individuals with FaceAges that are younger than their chronological ages do significantly better after cancer therapy.”

I’m especially thrilled about this because ten years ago I speculated about using selfies and facial recognition AI to determine if we had conditions that were prematurely aging us, or even we were just getting sick. It appears the Mass General Brigham researchers agree. “This opens the door to a whole new realm of biomarker discovery from photographs, and its potential goes far beyond cancer care or predicting age,” said co-senior author Ray Mak, MD, a faculty member in the AIM program at Mass General Brigham. “As we increasingly think of different chronic diseases as diseases of aging, it becomes even more important to be able to accurately predict an individual’s aging trajectory. I hope we can ultimately use this technology as an early detection system in a variety of applications, within a strong regulatory and ethical framework, to help save lives.”

The researchers acknowledge that much has to be accomplished before it is introduced for commercial purposes, and that strong oversight will be needed to ensure, as Dr. Aerts told WaPo, “these AI technologies are being used in the right way, really only for the benefit of the patients.” As Daniel Belsky, a Columbia University epidemiologist, told The New York Times: “There’s a long way between where we are today and actually using these tools in a clinical setting.”

The second development is even more out there. Let me break down the CalTech News headline: “3D Printing.” OK, you’ve got my attention. “In Vivo.” Color me highly intrigued. “Using Sound.” Mind. Blown.

That’s right. This team of researchers have “developed a method for 3D printing polymers at specific locations deep within living animals.” Apparently, 3D printing has been done in vivo previously, but using infrared light. “But infrared penetration is very limited. It only reaches right below the skin," says Wei Gao, professor of medical engineering at Caltech and corresponding author. "Our new technique reaches the deep tissue and can print a variety of materials for a broad range of applications, all while maintaining excellent biocompatibility."

They call the technique the deep tissue in vivo sound printing (DISP) platform.

“The DISP technology offers a versatile platform for printing a wide range of functional biomaterials, unlocking applications in bioelectronics, drug delivery, tissue engineering, wound sealing, and beyond,” the team stated. “By enabling precise control over material properties and spatial resolution, DISP is ideal for creating functional structures and patterns directly within living tissues.”

The authors concluded: “DISP’s ability to print conductive, drug-loaded, cell-laden, and bioadhesive biomaterials demonstrates its versatility for diverse biomedical applications.”

I’ll spare you the details, which involve, among other things, ultrasound and low temperature sensitive liposomes. The key takeaway is this: "We have already shown in a small animal that we can print drug-loaded hydrogels for tumor treatment," Dr. Gao says. "Our next stage is to try to print in a larger animal model, and hopefully, in the near future, we can evaluate this in humans... "In the future, with the help of AI, we would like to be able to autonomously trigger high-precision printing within a moving organ such as a beating heart,"

Dr. Gao also points out that not only can they add bio-ink where desired, but they could remove it if needed. Minimally invasive surgery seems crude by comparison.

Yeah, DISP can do all that. Credit:  Elham Davoodi and Wei Gao             

“It’s quite exciting,”  Yu Shrike Zhang, a biomedical engineer at Harvard Medical School and Brigham and Women’s Hospital, who was not involved in the research, told IEEE Spectrum. “This work has really expanded the scope of ultrasound-based printing and shown its translational capacity.”

First author Elham Davoodi has high hopes. “It’s quite versatile…It’s a new research direction in the field of bioprinting.”

“Quite exciting” doesn’t do it justice.

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In these topsy-turvy days, we must find our solace where we can, and these are the kinds of things that make me hopeful about the future.