Ancient DNA Isn't Just History

I knew what DNA was. I knew what synthetic DNA was. I knew what mirror DNA was. I even knew what eDNA was. But I didn’t know about aDNA, or that the field of study for it is called genomic paleoepidemiology. A new study by one of the pioneers of the field illustrates its power.

Those cows are going to have some surprises for prehistoric humans. Credit: Microsoft Designers

The study was led by Eske Willerslev, who is both Professor of Ecology & Evolution, Department of Zoology at Cambridge University and Director/ Professor, Centre of Excellence in GeoGenetics at the University of Copenhagen. He studies ancient DNA, aka “aDNA.” The new study traces 37,000 years of human disease history by examining the DNA from 214 known human pathogens, coming from the remains of some 1,300 prehistoric humans.

Our recent experience with COVID-19 and, currently, with bird flu, should have made everyone aware that one of the dangers of living with large populations of animals (like livestock) creates opportunities for diseases to cross over from those animals to us, often with devastating effect. These are called zoonotic diseases, and they still kill millions of people each year.

 When humans transitioned from hunter/gatherers to a more pastoral lifestyle, and then to farming, the pathogens had their chance.

Humans are thought to have started domesticating animals around 11,000 years ago. “This is the time when you’re in close proximity to animals, and you get these jumps,” Dr. Willerslev told Carl Zimmer of The New York Times. “That was the expectation.” So the researchers were surprised to find that the earliest evidence of zoonotic diseases didn’t appear until around 6,500 years ago, and didn’t become widespread until about 5,000 years ago.

Not surprisingly, they found evidence of the plague bacterium, Yersinia pestis, in a 5,500-year-old sample. They also found traces of Malaria (Plasmodium vivax) -- 4,200 years ago; Leprosy (Mycobacterium leprae) -- 1,400 years ago; Hepatitis B virus -- 9,800 years ago; Diphtheria  (Corynebacterium diphtheriae) -- 11,100 years ago.   

Credit: Sikora, et. al.

In all, the researchers identified 5,486 DNA sequences that came from bacteria, viruses and parasites. Not bad for DNA from tens of thousands of years ago.

The authors note:

Although zoonotic cases probably existed before 6,500 years ago, the risk and extent of zoonotic transmission probably increased with the widespread adoption of husbandry practices and pastoralism. Today, zoonoses account for more than 60% of newly emerging infectious diseases.

“It’s not a new idea, but they’ve actually shown it with the data,” says Edward Holmes, a virologist at the University of Sydney, Australia. “The scale of the work is really pretty breathtaking. It’s a technical tour de force.”

“We’ve long suspected that the transition to farming and animal husbandry opened the door to a new era of disease – now DNA shows us that it happened at least 6,500 years ago,” said Professor Willerslev. “These infections didn’t just cause illness – they may have contributed to population collapse, migration, and genetic adaptation.”

The researchers speculate that populations in the Steppe region were among the first to tame horse and domesticate livestock at scale, and it was their migration west that caused the appearance of the zoonotic diseases in the wider population. Moreover, it seems likely that the Steppe populations had acquired better immunity for them, unlike the existing populations they encountered. That would have led to massive population losses and made the Steppe migration much easier.

Think of what happened to the indigenous populations of the Americas or Australia when European settlers first came to their shores, only this time it was the then-Europeans who were the victims, dying off in huge numbers. Those of “European” background may need to think further east for their actual heritage.

“It has played a really big role in genetically creating the world we know of today,” Dr. Willerslev told Mr. Zimmer.

This isn’t just of academic interest. Zoonotic diseases are still very much with us. “If we understand what happened in the past, it can help us prepare for the future. Many of the newly emerging infectious diseases are predicted to originate from animals,” said Associate Professor Martin Sikora at the University of Copenhagen, and first author of the report.

Professor Willerslev added: “Mutations that were successful in the past are likely to reappear. This knowledge is important for future vaccines, as it allows us to test whether current vaccines provide sufficient coverage or whether new ones need to be developed due to mutations.”

The study has several limitations. The samples are all from Eurasia. “Africa would of course be super exciting, but we don’t have enough data,” Dr. Sikora told Mr. Zimmer. The researchers were only able to identify pathogens present in high doses in the bloodstream. “I’m sure there’s more in there,” says Professor Sikora. Last but not least, it only looked at DNA-based pathogens, not ones that use RNA, such as the viruses that cause influenza or polio.

Nonetheless, as Hendrik Poinar, an expert on ancient DNA at McMaster University in Canada who was not involved in the study, told Mr. Zimmer: “The paper is large and sweeping and overall pretty cool.”

Pretty. Cool. Indeed.

The paper concludes:

Our findings demonstrate how the nascent field of genomic paleoepidemiology can create a map of the spatial and temporal distribution of diverse human pathogens over millennia. This map will develop as more ancient specimens are investigated, as will our abilities to match their distribution with genetic, archaeological and environmental data. Our current map shows clear evidence that lifestyle changes in the Holocene led to an epidemiological transition, resulting in a greater burden of zoonotic infectious diseases. This transition profoundly affected human health and history throughout the millennia and continues to do so today.

As Dr. Poinar told Mr. Zimmer: “It’s a great start, but we all have miles to go before we sleep.”

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 I’ve long been amazed at what archaeologists and paleontologists have been able to tell us about our past, based on a few fossils, bones, or artifacts. I’m even more impressed that we’re recovering ancient DNA and using it to tell us even more of the story about how we got here.

It should be sobering to us all that, as much as we worry about weapons and invasions, the biggest risk to a population remains infectious diseases, especially zoonotic ones. The “winner” is the one who happens to have the best immunity.

We're Gonna Need a Bigger Boat

My friends, we are like explorers of yore standing at the edge of a known continent, looking out at the vast ocean in hopes of finding new, unspoiled, better lands across it. True, we may have despoiled the continent behind us, but certainly things will be better in the new lands.

When it comes to getting to the 22nd century healthcare system, we're going to need a bigger boat

In the metaphor I’m thinking of, the known continent is our shambles of a healthcare system. For all the protestations about the U.S. having the best health care in the world, that’s manifestly untrue. We don’t live as long, we have more chronic diseases, we kill each other and ourselves at alarming rates, we pay way more, we have too many people that can’t afford care and/or can’t obtain care, we have too much care that is ineffective, inappropriate, or even harmful, and we spend much too much on administration.

We don’t trust the healthcare system, we don’t think its quality of care is good, we have an unfavorable opinion of it, we think it fails us. The vast majority of us think it should be fundamentally changed or completely rebuilt. That’s what we want to flee, and its no wonder why.

Across that metaphorical ocean, in the distance, over the horizon, lies the 22^nd century healthcare system. It will, we hope, be like magic. It will be more equitable, more effective, more efficient, more proactive, less invasive, more affordable. We don’t know exactly what it will look like or how it will work, but we’ve seen what we have, and we know it can be better – much better. We just need to get there.

This leads me to the next part of the metaphor. I recently read a great quote from the late nature writer Barry Lopez, from his posthumous book of essays Embrace Fearlessly the Burning World. Mr. Lopez laments: “We are searching for the boats we never built.”

The boats aren’t coming to save us, to transport us to that idealized 22^nd century healthcare system. Because we never built them. Because we still don’t have the courage to build them.

We’ve never built a system to ensure universal coverage. We rely on a hodgepodge of coverage mechanisms, each of which is struggling with its own problems and still leaving some 25 million people without insurance – and that’s before the 10-20 million who are predicted to lose coverage due to the “Big, Beautiful Bill” – plus the tens of millions who are “underinsured.

We’ve never built a system that was remotely equitable, just as we never did for housing, education, or employment. Money matters, ethnicity matters, geography matters. Discrepancies in availability of care and in outcomes show up clearly for each of those, and more.

We’ve never built a system that prizes patients above all. We deferred to doctors and hospitals, not calling them out when they gave us substandard care or when they charged us too much. Now health care has gone from a “noble calling” to a jobs and wealth creator. A recent New York Times analysis found (among other things):

• Health care is the nation’s largest employer;
• In 1990, health care wasn’t the largest employer in any state; now it is in 38 states;
• We spend more on health care than on groceries or housing.

Pick your favorite target: private equity firms buying up health care entities, for-profit companies extracting profits from our care (or nominal “non-profits” doing the same), the steady corporatization of health care. Thrown in favorite boogeymen like health insurers, PBMs, or Big Pharma. One way or another, it’s about the money, not us.

The adage about Big Tech comes to mind: we’re not the customer, we’re the product (or, as I’ve written before, we’re simply the NPCs.).

We’ve never built the systems to make administration easier. So many codes, so many rules, so many types of insurance, so many silos, so many administrators. By now you’ve no doubt seen the chart of the growth of administers versus clinicians in our health care system, and are aware that around a quarter of our healthcare dollar goes to administration. It doesn’t have to be this way, it shouldn’t be this way, but administrative bloat is getting worse, not better.  

We’ve never built the systems to properly track our health or risks to it. From wastewater monitoring to tracking of diseases/outbreaks to adverse impacts from prescriptions drugs, medical devices, we’re relying on haphazard methods that leave us with no effective warning systems. The various public health mechanisms we had in place were woefully unfunded prior to COVID, crashed (and were burned) during COVID, and now are gleefully being defunded.

Worst of all, we’ve never built a system to track what care actually works. Sure, there are gold standard controlled studies that are supposed to do that, but much care that is delivered is not based on such studies, the impacts of such studies take years to permeate actual practice patterns, and practitioners aren’t really monitored to ensure they are delivering the “right” care or in the “right” way. We submit to care, we pay for that care, without really knowing if it is the care we should be getting or from the person/institution who should be giving it to us. 

Shame on us, and the system that allows all this.

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Without building all those boats, we’re not getting to the 22^nd century healthcare system that we want, and deserve.

Sure, there’s lots of exciting technology that will help make things look more like a 22^nd century healthcare system. AI, robots, genetic editing, nanobots, smart cells, synthetic biology, and more – these are all exciting, and will all be useful in that 22^nd century healthcare. But they won’t get us to the 22^nd century healthcare system we should get. They’ll just take us to a slicker, more expensive version of the one we have.

You may have seen that a couple weeks ago was the 50^th anniversary of the initial release of Jaws. One of its most iconic lines was the Chief Brody’s reaction when he first glimpsed the size of the shark he and two companions were foolishly hunting: “You’re gonna need a bigger boat.”

When it comes to getting us to the 22^nd century healthcare system we should want, we’re gonna need a bigger boat too – and we better start building it now.  

A New Future for DNA

As a DNA-based creature myself, I’m always fascinated by DNA’s remarkable capabilities. Not just all the ways that life has found to use it, but our ability to find new ways to take advantage of them. I’ve written about DNA as a storage medium, as a neural network, as a computer, in a robot, even mirror DNA. So when I read about the Synthetic Human Genome (SynHG) project, last week, I was thrilled.   

Welcome to the Synthetic Human Genome Project, Credit: SynHG

The project was announced, and is being funded, by the Wellcome Trust, to the tune of £10 million pounds over five years. Its goal is “to develop the foundational tools, technology and methods to enable researchers to one day synthesise genomes.”

The project’s website elaborates:

Through programmable synthesis of genetic material we will unlock a deeper understanding of life, leading to profound impacts on biotechnology, potentially accelerating the development of safe, targeted, cell-based therapies, and opening entire new fields of research in human health. Achieving reliable genome design and synthesis – i.e. engineering cells to have specific functions – will be a major milestone in modern biology.

The goal of the current project isn’t to build a full synthetic genome, which they believe may take decades, but “to provide proof of concept for large genome synthesis by creating a fully synthetic human chromosome.”

That’s a bigger deal than you might realize.

“Our DNA determines who we are and how our bodies work,” says Michael Dunn, Director of Discovery Research at Wellcome. “With recent technological advances, the SynHG project is at the forefront of one of the most exciting areas of scientific research.” 

The project is led by Professor Jason Chin from the Generative Biology Institute at Ellison Institute of Technology and the University of Oxford, who says: “The ability to synthesize large genomes, including genomes for human cells, may transform our understanding of genome biology and profoundly alter the horizons of biotechnology and medicine.”

He further told The Guardian: “The information gained from synthesising human genomes may be directly useful in generating treatments for almost any disease.”

Project lead Professor Jason Chin. Credit: Magdalen College, Oxford

Professor Patrick Yizhi Cai, Chair of Synthetic Genomics at the University of Manchester boasted: “We are leveraging cutting-edge generative AI and advanced robotic assembly technologies to revolutionize synthetic mammalian chromosome engineering. Our innovative approach aims to develop transformative solutions for the pressing societal challenges of our time, creating a more sustainable and healthier future for all.”

Project member Dr Julian Sale, of the MRC Laboratory of Molecular Biology in Cambridge, told BBC News the research was the next giant leap in biology: "The sky is the limit. We are looking at therapies that will improve people's lives as they age, that will lead to healthier aging with less disease as they get older. We are looking to use this approach to generate disease-resistant cells we can use to repopulate damaged organs, for example in the liver and the heart, even the immune system.”

Consider me impressed.

Professor Matthew Hurles, director of the Wellcome Sanger Institute, explained to BBC News the advantage of synthesizing DNA: “Building DNA from scratch allows us to test out how DNA really works and test out new theories, because currently we can only really do that by tweaking DNA in DNA that already exists in living systems."

It’s mind-blowing to think about the potential benefits that could come of this work, but the potential risks are equally consequential. Designer babies, enhanced humans, hybrids with other animals – synthetic DNA might accommodate all those and more. The sky is the limit indeed.

The project leaders are aware that there are important ethical considerations in such work, and so are including a companion social science program, called Care-full Synthesis, that is being led by Professor Joy Zhang from the Centre for Global Science and Epistemic Justice at the University of Kent. It plans to undertake a “transdisciplinary and transcultural investigation into the socio-ethical, economic, and policy implications of synthesising human genomes,” placing particular emphasis on “fostering inclusivity within and across nation-states, while engaging emerging public–private partnerships and new interest groups.” 

“With Care-full Synthesis, through empirical studies across Europe, Asia-Pacific, Africa, and the Americas, we aim to establish a new paradigm for accountable scientific and innovative practices in the global age,” says Professor Zhang. “One that explores the full potential of synthesising technical possibilities and diverse socio-ethical perspectives with care.”

That may prove to be a harder task that synthesizing a human chromosome.

Working out the socio-ethical perspectives is going to be harder than this, Credit: Microsoft Designer

SynHG is not the only project looking at synthetic DNA; it is a technology whose time is coming. Does anyone think that researchers in China aren’t working on this? Does anyone think they’re equally looking at the ethical considerations? Or maybe the next breakthrough will be some U.S start-up, that is gambling big on a use for synthetic DNA and would be expecting a unicorn-level return.

Professor Bill Earnshaw, a genetic scientist at Edinburgh University, warned BBC News: “The genie is out of the bottle. We could have a set of restrictions now, but if an organisation who has access to appropriate machinery decided to start synthesising anything, I don't think we could stop them."

But Wellcome’s Dr. Tom Collins, who greenlit the funding, told BBC News: “We asked ourselves what was the cost of inaction. This technology is going to be developed one day, so by doing it now we are at least trying to do it in as responsible a way as possible and to confront the ethical and moral questions in as upfront way as possible."

Kudos to Wellcome for building these considerations into the project. They’d be considered too woke in the U.S. And kudos for acknowledging the costs of inaction, which many policymakers in the U.S. and elsewhere fail to recognize.

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We’ve made remarkable progress on DNA in my lifetime. When I was born, it had just been discovered. The Human Genome Project launched in 1990 and the first sequence of the human genome by 2003. The CRISPR revolution – allowing gene editing -- started in 2012, and we’re now doing personalized gene editing therapy.  “Remarkable” is too mild a word.

But there’s still so much we don’t know. We don’t always know when/why genes turn on/off. We still have a very imperfect understanding of which diseases are genetic and which genes cause them, under what circumstances. And, for heaven’s sake, what is all that “junk DNA” doing? Is it just left over from evolution doing its long kludge towards survival, or does it carry some importance we haven’t learned yet?   

Those are the kinds of things SynHG might help us better understand, and I can’t wait to see what it finds out.

Microplastics Are Here, There, Everywhere

Vaccine experts are going rogue in response to RFK Jr’s attacks on vaccine safety. Health insurers promise – honest…this time – to make prior authorizations less burdensome (although not, of course, to eliminate them). ChatGPT and other LLMs may be making us worse at learning. So many things to write about, but I find myself wanting to return to a now-familiar topic: microplastics.

You may not realize it, but you're eating (and drinking) microplastics. Credit: Microsoft Designer

I first wrote about microplastics in 2020, and subsequent findings caused me to write again about their dangers at least once a year since. Now there are, yet again, new findings, and, nope, the news is still not good.

A new study, from researchers at the Food Packaging Forum, Swiss Federal Institute of Aquatic Science and Technology (Eawag) and the Norwegian University of Science and Technology, and published in npj Science of Food reviewed 103 previous studies about the impact food packaging and “food contact articles (FCAs)” can have on micro- and nanoplastics (MNPs) in our food. They found that even normal use -- such as opening a plastic bottle, steeping a plastic tea bag, or chopping on a plastic cutting board – can contaminate foodstuffs.

“This is the first systematic evidence map to investigate the role of the normal and intended use of food contact articles in the contamination of foodstuffs with MNPs,” explains Dr. Lisa Zimmermann, lead author and Scientific Communication Officer at the Food Packaging Forum. “Food contact articles are a relevant source of MNPs in foodstuffs; however, their contribution to human MNP exposure is underappreciated.” 

Their collected data are freely accessible through the FCMiNo dashboard, which allows users to filter included data by the type of FCA, the main food contact material, the medium analyzed, and whether MNPs were detected, and if so, for their size and polymer type.

Removing the plastic from items you purchase at the grocery store may contaminate it with microplastics, as might steeping a tea bag. Simply opening jars or bottles of milk can as well, and repeated opening and closing of either glass or plastic bottles sheds “untold amounts” of micro- and nanoplastics into the beverage, according to Dr. Zimmerman, who further noted: “The research shows the number of microplastics increases with each bottle opening, so therefore we can say it’s the usage of the food contact article which leads to micro- and nanoplastic release."  

Dr. Zimmerman told The Washington Post: “Plastic is present everywhere. We need to know what we can do.” Examples of what she suggests we can try to do include avoiding storing food in plastic whenever possible and avoiding heating plastic containers. She admitted, though: “We have not really understood all the factors that can lead to the release of micro and nanoplastics.”

One of her co-authors, Dr. Jane Muncke, Managing Director and Chief Scientific Officer at the Food Packaging Forum, warns that ultraprocessed foods carry more risk of contamination: “There’s a higher number of manufacturing steps with ultraprocessed foods, which can increase the contact time with plastic food processing equipment, thus increasing the chance of micro- and nanoplastic migration.”

Dr. Muncke believes their research is a step in the right direction:  

This systematic evidence map helps fill gaps in knowledge on the source of MNPs in foodstuffs. However, it also shows that additional research is needed to better characterize MNP migration related to FCA materials and uses. Importantly, implementing a harmonized testing and reporting framework is key to ensuring reliable and comparable data, which can inform future policy decisions.

David Andrews, acting chief science officer at the Environmental Working Group, told CNN: “This new study highlights food packaging and processing equipment as potentially significant sources of microplastic contamination in the food we eat, and ultimately in our bodies. This study should raise alarm bells.”

It should indeed.

Here’s another study which illustrates that our expectations about microplastics risks aren’t always valid. Researchers from France’s state food agency ANSES found that drinks sold in glass bottles actually have more microplastics in them than do ones in plastic bottles. Glass bottles of cola, lemonade, iced tea and beer had at least five times the amount of particles than plastic bottles or cans.

"We were expecting the opposite result when we compared the level of microplastics in different drinks sold in France," said PhD student Iseline Chaib, who conducted the research. It turns out that the caps on the bottles are the issue. Ms. Chaib explained: “We then noticed that in the glass, the particles emerging from the samples were the same shape, colour and polymer composition – so therefore the same plastic – as the paint on the outside of the caps that seal the glass bottles.”

Remember what Dr. Zimmerman warned about the dangers of repeated opening and closing of bottles?

The team suggested manufacturers use a cleaning method of blowing air in the caps, and rising with water and alcohol, which could reduce contamination by 60 percent. Consumers were also advised to rinse caps before putting them back on.   

Variation of average contamination levels (MPs/L) by polymer clusters. Credit: Chaid, et. al.

Last but not least, a paper by West Virginia University biology undergraduate student Isabella Tuzzio tested the presence of microplastics in fish from central Appalachian streams -- and found them in every fish sampled. Each fish averaged 40 pieces of microplastics.

The paper concludes: “Overall, we conclude that microplastic contamination is present and widespread in freshwater ecosystems in North Central and surrounding Appalachian regions throughout three major watersheds (the Monongahela, Cheat, and Ohio watersheds)…Potential sources of microplastic pollution point to agricultural activity, wastewater treatment, and atmospheric deposition.”

"Microplastics are coming from everyday sources like synthetic fibers from laundry and plastic beads in exfoliating face washes," Ms. Tuzzio said. "They're now everywhere, from our streams to remote deserts and even the human body."

She thinks we should be worried:

These plastics are small, but their impact is massive. They carry pollutants, heavy metals and antibiotics. And while the microplastics are spread out in smaller fish, the bigger fish eat those smaller fish. As you work your way up the food chain, there are heavily concentrated levels of these plastics. It's a problem for them and for us, too.

I’m plenty worried. We know that microplastics are everywhere, from the bottom of the ocean to the top of atmosphere, and everywhere in between. We know that they’re throughout our food system, and throughout our bodies. We don’t have enough data yet on exactly what the health risks of all this exposure are, but we have enough evidence that it is not good.  

I’ll grant that microplastics are on RFK Jr’s radar, but I sure wish he’d move it ahead of undermining trust in vaccines or removing food dyes.

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.