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Born to run and refusing to die: evolved robots

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For those who prefer to read about the science, a November 6, 2025 Northwestern University news release (received via email and on EurekAlert) by Amanda Morris describes the work, Note: Links have been removed,

AI-designed metamachines run in the wild, recover from damage and transform into new shapes

Northwestern University engineers have developed the first modular robots with athletic intelligence. They can be combined and recombined in the wild, recover from injury and keep moving no matter what’s thrown at them.

Called “legged metamachines,” the creations are made from autonomous, Lego-like modules that snap together into an endless number of configurations. Each module by itself is a complete robot with its own motor, battery and computer. Alone, a module can roll, turn and jump. But the real agility and indestructibility emerges when the modules combine.

The study was published today (March 6 [2026]) in the Proceedings of the National Academy of Sciences [PNAS].

To design the most effective combinations, the engineers used artificial intelligence (AI) to evolve novel body configurations. Instead of sticking with standard dog- or human-like designs, the AI churned out strange new “species” of machines that no human engineer would have conceived. When connected to other modules, the metamachines undulate like seals, bound like lizards or spring like kangaroos.

The robots also can flip themselves upright when turned over, hop over obstacles and perform acrobatics like spinning in air. Because a metamachine is essentially a robot made up of other robots, it can resist catastrophic damage. Broken parts don’t become dead weight; they keep rolling, crawling and rejoin the team.

By combining physical modularity with AI-driven design, the researchers have opened the door to a new class of robots that don’t just survive the real world — they adapt to it. These machines point toward a future where robots are less like fragile, pre-designed tools and more like resilient, evolving lifeforms.

“These are the first robots to set foot outdoors after evolving inside of a computer,” said Northwestern’s Sam Kriegman, who led the study. “They are rapidly assembled and then quite literally hit the ground running. They can move freely in the wild and easily recover from major injuries that would be fatal to every other wild robot. If flipped upside down, they instinctively bring themselves upright and continue their journey. They can survive being chopped in half or cut up into many pieces. When separated, every module within the metamachine can become an individual agent.”

An expert in biorobotics and AI, Kriegman is an assistant professor of computer science, mechanical engineering and chemical and biological engineering at Northwestern’s McCormick School of Engineering, where he is a member of the Center for Robotics and Biosystems (CRB). The study’s co-first authors are Chen Yu, David Matthews and Jingxian Wang, who are all Ph.D. students in the CRB. 

Evolution accelerated by computers

While today’s robots can be fast and agile, their body shapes are often fixed and rigid. Most robots cannot adapt to new tasks, environments or physical damage. If a robotic dog breaks a leg, for example, it’s basically useless. To escape those limitations, Kriegman’s team turned to AI — not to copy familiar designs but to evolve something entirely new.

Kriegman and his team started with an evolutionary algorithm that mimics natural selection. As a starting point, the team gave the algorithm the building blocks for the robot. These building blocks are half-meter-long modular legs, which look like a pair of sticks joined by a central sphere.

“Inside the sphere, the robot has everything it needs to survive: a ‘nervous system,’ a ‘metabolism’ and ‘muscle,’” Kriegman said. “By that, I mean a circuit board, a battery and a motor. The modules are mechanically simple. They can only rotate around a single axis, but they are surprisingly athletic and smart.”

Then, Kriegman and his team gave the algorithm a goal: Design a robot with efficient, versatile movement. By mixing and matching the modules in different combinations, the algorithm generated new body types. It then simulated each design, keeping the best performers and discarding the weak. It also iteratively “bred” new designs by combining or mutating them. Depending on the robot’s body, modular legs became legs, spines or tails. 

“We simulated the Darwinian process of mutation and selection within a virtual, physical environment,” Kriegman said. “This is survival of the fittest — accelerated by computers and made real by athletic modular building blocks.”

Traversing rugged terrain

To test the designs, Kriegman and his team assembled the best three-, four- and five-legged designs found by evolution. In outdoor tests, the metamachines ran across rough terrain, including gravel, grass, tree roots, leaves, sand, mud and uneven bricks. They jumped, spun and righted themselves when flipped — all without complicated setup or retraining.

Unlike traditional robots that fail when a single part breaks, these machines can adapt, recover and survive.Even when a leg breaks off, the metamachine remains resilient. The modules adapt to a missing leg and keep moving. The missing leg, too, can roll home and rejoin its team. 

“It can sense its surroundings, move from place to place, compute and learn,” Kriegman said. “Metamachines can be rapidly assembled, repaired, redesigned and recombined. Once assembled, they immediately move themselves across a wide array of unstructured environments.”

The new study builds off previous work from Kriegman’s lab, in which his team designed the first AI algorithm to intelligently design robots from scratch. By compressing billions of years of evolution into mere seconds, the algorithm successfully designed a small, flexible walking robot in mere seconds. While those robots could not do more than walk across a table, they proved that AI can instantly evolve working robots.

“Our previously evolved robots couldn’t sense their own bodies or coordinate themselves,” Kriegman said. “But they still taught us a lot about how evolution works and how to distill those lessons into useful technologies. Evolution can reveal new designs that are different from or even beyond what humans were previously capable of imagining. So, we really wanted to study how and why it works. The best way — or at least the most fun way — is to evolve structures in realistic conditions.”

The study, “Agile legged locomotion in reconfigurable modular robots,” was supported by Schmidt Sciences AI2050 (award number G-22-64506) and the National Science Foundation (award numbers FRR-2331581 and FRR-2440412).

Here’s a link to and a citation for the paper,

Agile legged locomotion in reconfigurable modular robots by Chen Yu, David Matthews, Jingxian Wang, Jing Gu, Douglas Blackiston, Michael Rubenstein, and Sam Kriegman. Proceedings of the National Academy of Sciences (PNAS) March 6, 2026 vol. 123 (10) e2519129123 DOI: https://doi.org/10.1073/pnas.2519129123

This paper is open access.

Kriegman was last mentioned here in a September 13, 2024 posting, “Moving past xenobots (living robots based on frog stem cells).”

No more plastic sorting for your recycle bin?

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This is a problem many of us can relate to, is the plastic recyclable and where do I put it for recycling? I have two stories about solutions to these recycling issues.

Northwestern University

A September 2, 2025 Northwestern University news release (also on EurekAlert) by Amanda Morris announces a new catalyst for plastic recycling, Note: Links have been removed,

The future of plastic recycling may soon get much less complicated, frustrating and tedious.

In a new study, Northwestern University chemists have introduced a new plastic upcycling process that can drastically reduce — or perhaps even fully bypass — the laborious chore of pre-sorting mixed plastic waste.

The process harnesses a new, inexpensive nickel-based catalyst that selectively breaks down polyolefin plastics consisting of polyethylenes and polypropylenes — the single-use kind that dominates nearly two-thirds of global plastic consumption. This means industrial users could apply the catalyst to large volumes of unsorted polyolefin waste.

When the catalyst breaks down polyolefins, the low-value solid plastics transform into liquid oils and waxes, which can be upcycled into higher-value products, including lubricants, fuels and candles. Not only can it be used multiple times, but the new catalyst can also break down plastics contaminated with polyvinyl chloride (PVC), a toxic polymer that notoriously makes plastics “unrecyclable.”

The study will be published on Tuesday (Sept. 2 [2025]) in the journal Nature Chemistry.

“One of the biggest hurdles in plastic recycling has always been the necessity of meticulously sorting plastic waste by type,” said Northwestern’s Tobin Marks, the study’s senior author. “Our new catalyst could bypass this costly and labor-intensive step for common polyolefin plastics, making recycling more efficient, practical and economically viable than current strategies.”

“When people think of plastic, they likely are thinking about polyolefins,” said Northwestern’s Yosi Kratish, a co-corresponding author on the paper. “Basically, almost everything in your refrigerator is polyolefin based — squeeze bottles for condiments and salad dressings, milk jugs, plastic wrap, trash bags, disposable utensils, juice cartons and much more. These plastics have a very short lifetime, so they are mostly single-use. If we don’t have an efficient way to recycle them, then they end up in landfills and in the environment, where they linger for decades before degrading into harmful microplastics.”

A world-renowned catalysis expert, Marks is the Vladimir N. Ipatieff Professor of Catalytic Chemistry at Northwestern’s Weinberg College of Arts and Sciences and a professor of chemical and biological engineering at Northwestern’s McCormick School of Engineering. He is also a faculty affiliate at the Paula M. Trienens Institute for Sustainability and Energy. Kratish is a research assistant professor in Marks’ group, and an affiliated faculty member at the Trienens Institute. Qingheng Lai, a research associate in Marks’ group, is the study’s first author. Marks, Kratish and Lai co-led the study with Jeffrey Miller, a professor of chemical engineering at Purdue University; Michael Wasielewski, Clare Hamilton Hall Professor of Chemistry at Weinberg; and Takeshi Kobayashi a research scientist at Ames National Laboratory.

The polyolefin predicament

From yogurt cups and snack wrappers to shampoo bottles and medical masks, most people interact with polyolefin plastics multiple times throughout the day. Because of its versatility, polyolefins are the most used plastic in the world. By some estimates, industry produces more than 220 million tons of polyolefin products globally each year. Yet, according to a 2023 report in the journal Nature, recycling rates for polyolefin plastics are alarmingly low, ranging from less than 1% to 10% worldwide.

The main reason for this disappointing recycling rate is polyolefin’s sturdy, stubborn composition. It contains small molecules linked together with carbon-carbon bonds, which are famously difficult to break.

“When we design catalysts, we target weak spots,” Kratish said. “But polyolefins don’t have any weak links. Every bond is incredibly strong and chemically unreactive.” 

Problems with current processes

Currently, only a few, less-than-ideal processes exist that can recycle polyolefin. It can be shredded into flakes, which are then melted and downcycled to form low-quality plastic pellets. But because different types of plastics have different properties and melting points, the process requires workers to scrupulously separate various types of plastics. Even small amounts of other plastics, food residue or non-plastic materials can compromise an entire batch. And those compromised batches go straight into the landfill.

Another option involves heating plastics to incredibly high temperatures, reaching 400 to 700 degrees Celsius. Although this process degrades polyolefin plastics into a useful mixture of gases and liquids, it’s extremely energy intensive.

“Everything can be burned, of course,” Kratish said. “If you apply enough energy, you can convert anything to carbon dioxide and water. But we wanted to find an elegant way to add the minimum amount of energy to derive the maximum value product.”

Precision engineering

To uncover that elegant solution, Marks, Kratish and their team looked to hydrogenolysis, a process that uses hydrogen gas and a catalyst to break down polyolefin plastics into smaller, useful hydrocarbons. While hydrogenolysis approaches already exist, they typically require extremely high temperatures and expensive catalysts made from noble metals like platinum and palladium.

“The polyolefin production scale is huge, but the global noble metal reserves are very limited,” Lai said. “We cannot use the entire metal supply for chemistry. And, even if we did, there still would not be enough to address the plastic problem. That’s why we’re interested in Earth-abundant metals.”

For its polyolefin recycling catalyst, the Northwestern team pinpointed cationic nickel, which is synthesized from an abundant, inexpensive and commercially available nickel compound. While other nickel nanoparticle-based catalysts have multiple reaction sites, the team designed a single-site molecular catalyst. 

The single-site design enables the catalyst to act like a highly specialized scalpel — preferentially cutting carbon-carbon bonds — rather than a less controlled blunt instrument that indiscriminately breaks down the plastic’s entire structure. As a result, the catalyst allows for the selective breakdown of branched polyolefins (such as isotactic polypropylene) when they are mixed with unbranched polyolefins — effectively separating them chemically.

“Compared to other nickel-based catalysts, our process uses a single-site catalyst that operates at a temperature 100 degrees lower and at half the hydrogen gas pressure,” Kratish said. “We also use 10 times less catalyst loading, and our activity is 10 times greater. So, we are winning across all categories.”

Accelerated by contamination

With its single, precisely defined and isolated active site, the nickel-based catalyst possesses unprecedented activity and stability. The catalyst is so thermally and chemically stable, in fact, that it maintains control even when exposed to contaminants like PVC. Used in pipes, flooring and medical devices, PVC is visually similar to other types of plastics but significantly less stable upon heating. Upon decomposition, PVC releases hydrogen chloride gas, a highly corrosive byproduct that typically deactivates catalysts and disrupts the recycling process.

Amazingly, not only did Northwestern’s catalyst withstand PVC contamination, PVC actually accelerated its activity. Even when the total weight of the waste mixture is made up of 25% PVC, the scientists found their catalyst still worked with improved performance. This unexpected result suggests the team’s method might overcome one of the biggest hurdles in mixed plastic recycling — breaking down waste currently deemed “unrecyclable” due to PVC contamination. The catalyst also can be regenerated over multiple cycles through a simple treatment with inexpensive alkylaluminium.

“Adding PVC to a recycling mixture has always been forbidden,” Kratish said. “But apparently, it makes our process even better. That is crazy. It’s definitely not something anybody expected.”

Here’s a link to and a citation for the paper,

Stable single-site organonickel catalyst preferentially hydrogenolyses branched polyolefin C–C bonds by Qingheng Lai, Xinrui Zhang, Shan Jiang, Matthew D. Krzyaniak, Selim Alayoglu, Amol Agarwal, Yukun Liu, Wilson C. Edenfield, Takeshi Kobayashi, Yuyang Wang, Vinayak Dravid, Michael R. Wasielewski, Jeffery T. Miller, Yosi Kratish & Tobin J. Marks. Nature Chemistry volume 17, pages 1488–1496 (2025) DOI: https://doi.org/10.1038/s41557-025-01892-y Published: 02 September 2025 Version of record: 02 September 2025 Issue date: October 2025

This paper is behind a paywall.

Pink box

While British Columbia (Canada) can’t yer avail itself of the solution (that situation changed, in Vancouver anyway, as of February 2026) offered by Northwestern University (Chicago, US), there is the ‘pink box solution’ as described in a September 11, 2025 article by Chad Pawson for the Canadian Broadcasting Corporation’s (CBC) news online website,

The organization behind B.C.’s recycling system wants residents to do more to keep plastics from going to landfills or ending up as litter — as only 45 per cent of plastic packaging used by residents is recovered for recycling.

“There’s been a lot of hesitancy around recycling, but our model proves that you can have a system that responsibly manages and recycles these plastics,” said Sam Baker, executive director of Recycle B.C.

…

In 2024, residents either put into their blue boxes or took to depots 31,362 tonnes of plastic packaging — from Ziploc bags to yogurt containers — of which 98 per cent was recycled, according to Recycle B.C.’s latest annual report.

B.C.’s not-for-profit system, introduced 10 years ago, was the first in North America to require producers to pay for the packaging and paper they create to be recycled, lifting the burden from local governments.

…

In 2024, Recycle B.C. recovered 100 per cent of glass made by producers and used by residents, and 92 per cent of paper.

…

The recovery of plastic bags and wrapping trails far behind the recovery of things like plastic containers, even though in 2022 Merlin Plastics figured out for Recycle B.C. how to turn flexible plastics into pellets for new products, rather than be burned as fuel.

Baker said there are several reasons for this, ranging from a lack of understanding of how B.C.’s system works and possible distrust in it, to confusion over how to sort items and ultimately the need to take some items to special depots.

…

Recycle B.C.’s goal is to raise the recovery rate of all plastics to at least 50 per cent. One way to make gains will be to improve the recovery of flexible plastics, such as bags and wrappers.

Currently most residents need to collect and keep those items and then take them to one of 227 depots spread across the province or one of 53 London Drugs locations, which has recycling kiosks for items not accepted in curbside or multi-unit building pickup.

“London Drugs recognizes that we put a lot of material out into the market,” said Raman Johal, sustainability manager at the retail chain. “So we only feel right that we are responsible for taking some of that material back.”

But the corporate responsibility only works if residents are willing to make the effort to bring in the materials.

Recycle B.C. has a plan to overcome that barrier. In January it launched a pink box, to be used in communities alongside residents’ blue boxes.

…

Aubrey Smethurst, a West Vancouver resident who works in marketing, describes the pink box as a “game changer.”

The mother of two says she has long cared about recycling and would go out of her way [emphasis mine] to make sure things like the plastic bags her family used got to depots.

Now she diverts them to her pink box, which gets picked up once a month from her home.

…

I’m glad to learn of the pink boxes and hope to see one for my building in the near future. (That day arrived a few weeks ago) and I have a message for Mr. Baker,

Dear Mr. Baker,

I appreciate the ‘pink box’ option but could do without your scolding tone. Depots for recyclables in difficult to reach locations if you don’t have a car/truck. It’s especially difficult if the items in questions are awkwardly shaped.

As for the communication strategies used by organization, those could do with a bit or work. How did you get the message across about the change regarding soft plastics? Life is busy for most of us and putting out a notice on your website and a few notices at London Drugs stores and at your recycling depots is not enough. An article in a newspaper or on a media website is not enough.

Given how ‘media rich’ most people’s environments are, once or twice is not enough.

I suggest you abandon the scolding and simply work on getting the message out.

Sincerely

As much as was possible, Baker’s scolding was removed from Pawson’s article.

Tripling CRISPR efficiency with DNA-wrapped nanoparticles

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A September 7, 2025 news item announced a big step forward where gene-editing (CRISPR or clustered regularly interspaced short palindromic repeats) is concerned,

At a glance: 

  • CRISPR gene-editing machinery could transform medicine but is difficult to get into tissues and disease-relevant cells
  • New delivery system loads CRISPR machinery inside spherical nucleic acid (SNA) nanoparticles
  • Particles entered cells three times more effectively, tripled gene-editing efficiency, and decreased toxicity compared to current delivery methods

With the power to rewrite the genetic code underlying countless diseases, CRISPR holds immense promise to revolutionize medicine. But until scientists can deliver its gene-editing machinery safely and efficiently into relevant cells and tissues, that promise will remain out of reach.

Now, Northwestern University chemists have unveiled a new type of nanostructure that dramatically improves CRISPR delivery and potentially extends its scope of utility.

…

An artistic interpretation of a spherical nucleic acid (SNA) nanoparticle, carrying CRISPR cargo, entering a cell. When inside an SNA nanoparticle, CRISPR machinery enters cells three times more effectively. Image by the Mirkin Research Group

A September 5, 2025 Northwestern University news release by Amanda Morris (also on EurekAlert but published September 1, 2025), which originated the news item, provides more detail, Note: Links have been removed,

Called lipid nanoparticle spherical nucleic acids (LNP-SNAs), these tiny structures carry the full set of CRISPR editing tools — Cas9 enzymes, guide RNA [ribonucleic acid] and a DNA [deoxyribonucleic acid] repair template — wrapped in a dense, protective shell of DNA. Not only does this DNA coating shield its cargo, but it also dictates which organs and tissues the LNP-SNAs travel to and makes it easier for them to enter cells.

In lab tests across various human and animal cell types, the LNP-SNAs entered cells up to three times more effectively than the standard lipid particle delivery systems used for COVID-19 vaccines, caused far less toxicity and boosted gene-editing efficiency threefold. The new nanostructures also improved the success rate of precise DNA repairs by more than 60% compared to current methods.

The study will be published on Sept. 5 [2025] in the Proceedings of the National Academy of Sciences.

The study paves the way for safer, more reliable genetic medicines and underscores the importance of how a nanomaterial’s structure — rather than its ingredients alone — can determine its potency. This principle underlies structural nanomedicine, an emerging field pioneered by Northwestern’s Chad A. Mirkin and his colleagues and pursued by hundreds of researchers around the world.

“CRISPR is an incredibly powerful tool that could correct defects in genes to decrease susceptibility to disease and even eliminate disease itself,” said Mirkin, who led the new study. “But it’s difficult to get CRISPR into the cells and tissues that matter. Reaching and entering the right cells — and the right places within those cells — requires a minor miracle. By using SNAs to deliver the machinery required for gene editing, we aimed to maximize CRISPR’s efficiency and expand the number of cell and tissue types that we can deliver it to.”

A nanotechnology and nanomedicine pioneer, Mirkin is the George B. Rathmann Professor of Chemistry at Northwestern’s Weinberg College of Arts and Sciences; professor of chemical and biological engineering, biomedical engineering and materials science and engineering at the McCormick School of Engineering; professor of medicine at the Feinberg School of Medicine; executive director of the International Institute for Nanotechnology; and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

CRISPR needs a ride

When CRISPR machinery reaches its target inside a cell, it can disable genes, fix mutations, add new functions and more. But CRISPR machinery cannot enter cells by itself. It always needs a delivery vehicle. 

Currently, scientists typically use viral vectors and lipid nanoparticles (LNPs) to perform this function. Naturally good at sneaking into cells, viruses are efficient, but they can cause the human body to mount an immune response, leading to painful or even dangerous side effects. LNPs, on the other hand, are safer but inefficient. They tend to get stuck in endosomes, or compartments within the cell, where they cannot release their cargo.

“Only a fraction of the CRISPR machinery actually makes it into the cell and even a smaller fraction makes it all the way into the nucleus,” Mirkin said. “Another strategy is to remove cells from the body, inject the CRISPR components and then put the cells back in. As you can imagine, that’s extremely inefficient and impractical.”

A DNA-wrapped taxi

To overcome this barrier, Mirkin’s team turned to SNAs, which are globular — rather than linear — forms of DNA and RNA previously invented in Mirkin’s lab at Northwestern. The spherical genetic material surrounds a nanoparticle core, which can be packed with cargo. Roughly 50 nanometers in diameter, the tiny structures possess a proven ability to enter cells for targeted delivery. Seven SNA-based therapies are already in human clinical trials, including a Phase 2 clinical trial for Merkel cell carcinoma being developed by Flashpoint Therapeutics, a clinical-stage biotechnology startup.

In the new study, Mirkin’s team started with an LNP core carrying the CRISPR machinery inside. Then, they decorated the particle’s surface with a dense layer of short strands of DNA. Because the DNA can interact with a cell’s surface receptors, cells easily absorb SNAs. The DNA also can be engineered with sequences that target specific cell types, making delivery more selective.

“Simple changes to the particle’s structure can dramatically change how well a cell takes it up,” Mirkin said. “The SNA architecture is recognized by almost all cell types, so cells actively take up the SNAs and rapidly internalize them.”

Boosted performance across the board

After successfully synthesizing LNP-SNAs with CRISPR cargo, Mirkin and his team added them to cellular cultures, which included skin cells, white blood cells, human bone marrow stem cells and human kidney cells. 

Then, the team observed and measured several key factors: how efficiently the cells internalized the particles, whether the particles were toxic to cells and if the particles successfully delivered a gene. They also analyzed the cells’ DNA to determine if CRISPR had made the desired gene edits. In every category, the system demonstrated its ability to successfully deliver CRISPR machinery and enable complex genetic modifications.

Next, Mirkin plans to further validate the system in multiple in vivo disease models. Because the platform is modular, researchers can adapt it for a wide range of systems and therapeutic applications. Northwestern biotechnology spin-out Flashpoint Therapeutics is commercializing the technology with the goal of rapidly moving it toward clinical trials.

“CRISPR could change the whole field of medicine,” Mirkin said. “But how we design the delivery vehicle is just as important as the genetic tools themselves. By marrying two powerful biotechnologies — CRISPR and SNAs — we have created a strategy that could unlock CRISPR’s full therapeutic potential.”

…

Here’s a link to and a citation for the paper,

A general genome editing strategy using CRISPR lipid nanoparticle spherical nucleic acids by Zhenyu Han, Chi Huang, Taokun Luo, and Chad A. Mirkin. Proceedings of the National Academy of Sciences (PNAS) September 4, 2025 122 (36) e2426094122 DOI: https://doi.org/10.1073/pnas.2426094122

This paper is behind a paywall.

Scientific fraud: widespread and organized according to Northwestern University research + math fraud scandal

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I have three stories about issues with science and mathematics: the research, the reporting, and the fraud.

Northwestern University and widespread scientific fraud

An August 4, 2025 article by Cathleen O’Grady for science.org describes a study into global networks instigating scientific fraud, Note: A link has been removed,

For years, sleuths who study scientific fraud have been sounding the alarm about the sheer size and sophistication of the industry that churns out fake publications. Now, an extensive investigation finds evidence of a range of bad actors profiting from fraud. The study, based on an analysis of thousands of publications and their authors and editors, shows paper mills are just part of a complex, interconnected system that includes publishers, journals, and brokers.

The paper, published today in the Proceedings of the National Academy of Sciences, paints an alarming picture. Northwestern University metascientist Reese Richardson and his colleagues identify networks of editors and authors colluding to publish shoddy or fraudulent papers, report that large organizations are placing batches of fake papers in journals, suggest brokers may serve as intermediaries between paper mills and intercepted journals, and find that the number of fake papers—though still relatively small—seems to be increasing at a rate far greater than the scientific literature generally.

The paper shows that misconduct “has become an industry,” says Anna Abalkina of the Free University of Berlin, who studies corruption in science and was not involved with the research. Richardson and colleagues hope their sweeping case will attract attention and spur change.

…

O’Grady’s August 4, 2025 article provides some fascinating detail, Note: Links have been removed,

…

They began their analysis by pinpointing corrupt editors. They focused their investigation on PLOS ONE, because the megajournal allows easy access to bulk metadata and publishes the names of the editors who have handled the thousands of papers it publishes each year, making it possible to detect anomalies without behind-the-scenes information. The researchers identified all the papers from the journal that had been retracted or received comments on PubPeer—a website that allows researchers to critique published work—and then identified each paper’s editors.

All told, 33 editors stood out as more frequently handling work that was later retracted or criticized than would be expected by chance. “Some of these were immense outliers,” Richardson says. For instance, of the 79 papers that one editor had handled at PLOS ONE, 49 have been retracted. Flagged editors handled 1.3% of papers published in the journal by 2024, but nearly one-third of all retracted papers.

The team also spotted that these editors worked on certain authors’ papers at a suspiciously high rate. These authors were often editors at PLOS [Public Library of Science] ONE themselves, and they often handled each other’s papers. It’s possible that some editors are being paid bribes, Richardson says, but “also possible that these are informal arrangements that are being made among colleagues.” The researchers detected similarly questionable editor behavior in 10 journals published by Hindawi, an open-access publisher that was shuttered because of rampant paper mill activity after Wiley acquired it. A spokesperson for Wiley told Science the publisher has made “significant investments to address research integrity issues.”

Renee Hoch, head of publication ethics at PLOS, said in an email to Science that the publisher has long been aware of networks like these, and will assess whether any of the editors implicated are still on the journal’s editorial board, opening investigations if they are. She emphasizes that the study focused on PLOS because of its readily accessible data: “Paper mills are truly an industry-wide problem.”

Researchers working on paper mills have long assumed that editors and authors have been colluding. The new findings are “killer evidence” for these suspicions, says Domingo Docampo, a bibliometrician at the University of Vigo (Spain). He adds that although the findings only show collusion at a limited number of journals, others are probably affected. Just last week, Retraction Watch reported that the publisher Frontiers had begun to retract 122 papers after discovering a network of editors and authors “who conducted peer review with undisclosed conflicts of interest,” according to a company statement. The network of 35 individuals has also published more than 4000 papers in journals from seven other publishers, the company said, which require further scrutiny. A Frontiers spokesperson said they planned to share information with the other affected publishers.

Richardson and his colleagues found that the problem goes far beyond networks of unscrupulous editors and authors scratching each other’s backs. They identified what appear to be coordinated efforts to arrange the publication of batches of dubious papers in multiple journals.

…

For the curious, there’s more in O’Grady’s August 4, 2025 article. An August 4, 2025 Northwestern University news release by Amanda Morris (received via email and available on EurekAlert) focuses on other aspects of the research,

From fabricated research to paid authorships and citations, organized scientific fraud is on the rise, according to a new Northwestern University study.

By combining large-scale data analysis of scientific literature with case studies, the researchers led a deep investigation into scientific fraud. Although concerns around scientific misconduct typically focus on lone individuals, the Northwestern study instead uncovered sophisticated global networks of individuals and entities, which systematically work together to undermine the integrity of academic publishing.

The problem is so widespread that the publication of fraudulent science is outpacing the growth rate of legitimate scientific publications. The authors argue these findings should serve as a wake-up call to the scientific community, which needs to act before the public loses confidence in the scientific process.

The study will be published during the week of August 4 the Proceedings of the National Academy of Sciences.

“Science must police itself better in order to preserve its integrity,” said Northwestern’s Luís A. N. Amaral, the study’s senior author. “If we do not create awareness around this problem, worse and worse behavior will become normalized. At some point, it will be too late, and scientific literature will become completely poisoned. Some people worry that talking about this issue is attacking science. But I strongly believe we are defending science from bad actors. We need to be aware of the seriousness of this problem and take measures to address it.”

An expert in complex social systems, Amaral is the Erastus Otis Haven Professor and professor of engineering sciences and applied mathematics at Northwestern’s McCormick School of Engineering. Reese Richardson, a postdoctoral fellow in Amaral’s laboratory, is the paper’s first author.

Extensive analysis

When people think about scientific fraud, they might remember news reports of retracted papers, falsified data or plagiarism. These reports typically center around the isolated actions of one individual, who takes shortcuts to get ahead in an increasingly competitive industry. But Amaral and his team uncovered a widespread underground network operating within the shadows and outside of the public’s awareness.

“These networks are essentially criminal organizations, acting together to fake the process of science,” Amaral said. “Millions of dollars are involved in these processes.”

To conduct the study, the researchers analyzed extensive datasets of retracted publications, editorial records and instances of image duplication. Most of the data came from major aggregators of scientific literature, including Web of Science (WoS), Elsevier’s Scopus, National Library of Medicine’s PubMed/MEDLINE and OpenAlex, which includes data from Microsoft Academic Graph, Crossref, ORCID, Unpaywall and other institutional repositories.

Richardson and his colleagues also collected lists of de-indexed journals, which are scholarly journals that have been removed from databases for failing to meet certain quality or ethical standards. The researchers also included data on retracted articles from Retraction Watch, article comments from PubPeer and metadata — such as editor names, submission dates and acceptance dates — from articles published in specific journals.

Buying a reputation

After analyzing the data, the team uncovered coordinated efforts involving “paper mills,” brokers and infiltrated journals. Functioning much like factories, paper mills churn out large numbers of manuscripts, which they then sell to academics who want to quickly publish new work. These manuscripts are mostly low quality — featuring fabricated data, manipulated or even stolen images, plagiarized content and sometimes nonsensical or physically impossible claims.

“More and more scientists are being caught up in paper mills,” Amaral said. “Not only can they buy papers, but they can buy citations. Then, they can appear like well-reputed scientists when they have barely conducted their own research at all.”

“Paper mills operate by a variety of different models,” Richardson added. “So, we have only just been able to scratch the surface of how they operate. But they sell basically anything that can be used to launder a reputation. They often sell authorship slots for hundreds or even thousands of dollars. A person might pay more money for the first author position or less money for a fourth author position. People also can pay to get papers they have written automatically accepted in a journal through a sham peer-review process.”

To identify more articles originating from paper mills, the Amaral group launched a parallel project that automatically scans published materials science and engineering papers. The team specifically looked for authors who misidentified instruments they used in their research. A paper with those results was accepted by the journal PLOS ONE.

Brokers, hijacking and collusion

Amaral, Richardson and their collaborators found fraudulent networks use several key strategies: (1) Groups of researchers collude to publish papers across multiple journals. When their activities are discovered, the papers are subsequently retracted; (2) brokers serve as intermediaries to enable mass publication of fraudulent papers in compromised journals; (3) fraudulent activities are concentrated in specific, vulnerable subfields; and (4) organized entities evade quality-control measures, such as journal de-indexing.

“Brokers connect all the different people behind the scenes,” Amaral said. “You need to find someone to write the paper. You need to find people willing to pay to be the authors. You need to find a journal where you can get it all published. And you need editors in that journal who will accept that paper.”

Sometimes these organizations go around established journals altogether, searching instead for defunct journals to hijack. When a legitimate journal stops publishing, for example, bad actors can take over its name or website. These actors surreptitiously assume the journal’s identity, lending credibility to its fraudulent publications, despite the actual publication being defunct.

“This happened to the journal HIV Nursing,” Richardson said. “It was formerly the journal of a professional nursing organization in the U.K., then it stopped publishing, and its online domain lapsed. An organization bought the domain name and started publishing thousands of papers on subjects completely unrelated to nursing, all indexed in Scopus.”

Fighting for science

To combat this growing threat to legitimate scientific publishing, Amaral and Richardson emphasize the need for a multi-prong approach. This approach includes enhanced scrutiny of editorial processes, improved methods for detecting fabricated research, a greater understanding of the networks facilitating this misconduct and a radical restructuring of the system of incentives in science.

Amaral and Richardson also underscore the importance of addressing these issues before artificial intelligence (AI) infiltrates scientific literature more than it already has.

“If we’re not prepared to deal with the fraud that’s already occurring, then we’re certainly not prepared to deal with what generative AI can do to scientific literature,” Richardson said. “We have no clue what’s going to end up in the literature, what’s going to be regarded as scientific fact and what’s going to be used to train future AI models, which then will be used to write more papers.”

“This study is probably the most depressing project I’ve been involved with in my entire life,” Amaral said. “Since I was a kid, I was excited about science. It’s distressing to see others engage in fraud and in misleading others. But if you believe that science is useful and important for humanity, then you have to fight for it.”

Here’s a link to and a citation for the paper,

The entities enabling scientific fraud at scale are large, resilient, and growing rapidly by Reese A. K. Richardson, Spencer S. Hong, Jennifer A. Byrne, Thomas Stoeger, and Luís A. Nunes Amaral. Proceedings of the National Academy of Sciences August 4, 2025 122 (32) e2420092122 DOI: https://doi.org/10.1073/pnas.2420092122

This paper is open access.

And now—math fraud

A September 19, 2025 news item on ScienceDaily features an investigation into fraudulent math research, Note: A link has been removed,

An international team of authors led by Ilka Agricola, professor of mathematics at the University of Marburg, Germany, has investigated fraudulent practices in the publication of research results in mathematics on behalf of the German Mathematical Society (DMV) and the International Mathematical Union (IMU), documenting systematic fraud over many years. The results of the study were recently published on the preprint server arxiv.org and in the Notices of the American Mathematical Society (AMS) and have since caused a stir among mathematicians.

…

Sanjana Gajbhiye’s September ??, 2025 article for earth.com delves further into the topic, Note: Links have been removed,

…

Quality lost to quantity

The findings show how the definition of research quality has shifted. Instead of focusing on content, originality, and insight, institutions and individuals are increasingly evaluated by commercial metrics. These include the number of publications, total citations, and the so-called impact factor of journals.

Such measures, calculated by private companies with little transparency, have gained outsized influence. Providers promote their databases globally, and universities use them to enhance prestige and compete internationally.

This environment rewards quantity over quality, pushing academics to publish more, even when contributions are marginal or flawed.

Fraudulent companies have seized this opportunity. They sell services that manipulate rankings, offering ghostwritten articles, fake peer reviews, and even bundles of citations. For individuals, this can mean better career prospects.

For universities, it can result in higher rankings, increased funding, and greater appeal to international students. The collateral damage is a growing pool of unread publications that add nothing to scientific understanding.

Fake mathematics success

The report documents striking examples that reveal how metrics can produce absurd outcomes. In 2019, Clarivate Inc., the market leader for citation data, ranked a Taiwanese university as having the most world-class mathematicians. The catch was startling: mathematics was not even offered at the institution.

…

Mathematic trust under threat

“‘Fake science‘ is not only annoying, it is a danger to science and society,” said IMU Secretary General Professor Christoph Sorger.

“Because you don’t know what is valid and what is not. Targeted disinformation undermines trust in science and also makes it difficult for us mathematicians to decide which results can be used as a basis for further research.”

This erosion of trust strikes at the heart of mathematics. Proofs rely on certainty, yet when fraudulent or hollow work appears in respected outlets, that certainty weakens.

…

Fixing trust in mathematics publishing

The commission’s work does not end with exposing the problem. It also outlines possible solutions for a healthier publication system. These recommendations emphasize the need to strengthen peer review, encourage collaboration among journals, and recenter the evaluation of research on quality rather than raw numbers.

…

Metrics are deeply tied to funding and prestige, so the shift won’t be simple, but it could reshape the landscape for future generations.

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A September 20, 2025 Castle Journal blog posting provides more information,

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The “Culture of Numbers” and its Consequences

The study, led by Professor Ilka Agricola of the University of Marburg, argues that the root cause of the problem is a “culture of numbers” that prioritizes commercial metrics over scientific content. Universities and research institutions have become increasingly reliant on commercial databases like Clarivate’s Journal Citation Reports (JCR) to evaluate researchers. These metrics, which are not transparent and are not vetted by the scientific community, have become the main currency for career progression, grants, and prestige.

 * “Megajournals”: The study highlights the rise of “megajournals,” which publish anything as long as the authors pay a fee. These journals now publish more articles per year than all reputable mathematics journals combined. The report cites a shocking example where a commercial database ranked a university in Taiwan as having the most world-class researchers in mathematics, despite the fact that the university does not even offer mathematics as a subject.

 * Paper Mills and Citation Cartels: The investigation found evidence of “paper mills,” which sell fabricated papers to researchers, and “citation cartels,” where academics agree to cite each other’s work to artificially inflate their metrics. These services are offered anonymously online, with prices for articles and citations ranging from hundreds to thousands of dollars. The report describes these networks as “criminal organizations” that have invaded the “ecosystem” of scientific publishing.

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Ilka Agricola gave an interview to Retraction Watch, from the undated article, Note: Links have been removed,

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A pair of papers posted to the arXiv addresses the issue of fraudulent publishing in math, particularly metrics gaming, and offers a list of recommendations to help detect and deal with that problem and other fraudulent activities. (The former was also published in the October AMS Notices; the latter will appear in the November issue.) “Fraudulent publishing undermines trust in science and scientific results and therefore fuels antiscience movements,” mathematician Ilka Agricola, lead author of both papers, told Retraction Watch. 

A professor of mathematics at Marburg University in Germany, Agricola was president of the German Mathematical Society in 2021-2022 and is chair of the Committee on Publishing of the International Mathematical Union. The new articles are the products of a working group of the IMU and the International Council of Industrial and Applied Mathematics. 

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Retraction Watch: As you note in the new papers, Clarivate announced in 2023 it had excluded the entire field of math from its list of “Highly Cited Researchers,” or HCRs. What’s going on?

Agricola: The publication culture in math differs a bit from, say, experimental and life sciences. On average, mathematicians publish fewer papers with fewer authors than scientists in other fields. So, with the same absolute number of papers and citations, one can become a “highly-cited researcher” in math, but not in other fields. Thus, gaming the system is easier. 

The list of HCRs for mathematics became so screwed that Clarivate couldn’t pretend anymore that it had any value. This being said, Clarivate announced that they would look into new measuring tools, but didn’t come up with any alternative ideas in the meantime, nor did they contact any representatives of the international mathematical community. 

Retraction Watch:  Few people talk about fraudulent publishing in math. Why is that?

Agricola: For a long time, mathematicians thought that as long as they keep away from predatory journals or paper mills, the problem does not affect them. This turned out to be wrong. 

Retraction Watch: If you look at the number of papers that tripped Clear Skies’ Papermill Alarm in 2022 (we included a histogram in this article we wrote for The Conversation [link and excerpts follow]), math is pretty far down the list. Are there a lot of fake papers in math?

Agricola: It is probably fair to say that the problem is not as severe as in other fields like cancer research, but the community is smaller and the number of fake papers is growing at alarming speed. Predatory and low-quality mega-journals are trying hard to lure respected scientists into their parallel universe of fake science, thus trying to give themselves the impression of respectability. Thus, one of our goals is to raise awareness for the issue in the mathematical community!

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Retraction Watch: You and your coauthors are mathematicians, and yet you argue against focusing on numbers like journal impact factors and publication and citation counts. Is that what’s driving all of this bad behavior?

Agricola: “When a measure becomes a target, it ceases to be a good measure.” This quote is from the British economist Charles Goodhart, and it also applies to bibliometrics measures. Of course, gaming these metrics has always existed, but some of us liked to believe that they would be roughly OK, with some error bar due to some cheating. Now, we realize the error bar is larger than the number one wants to measure. Perhaps one advantage of mathematicians is that they are not easily impressed by numbers, and we have the means to understand and analyze them — this is our job. And so, the conclusion is very clear: The correlation between bibliometrics and research quality is so low that we should not use bibliometrics. And I urge all colleagues to say so openly!

Retraction Watch: So how do we judge research quality if we shouldn’t use publication metrics?

Agricola: Read the actual publications instead of relying on bibliometrics! Plus, in mathematics, we are lucky to have two extremely well curated databases for math papers and journals, zbMath Open and MathReviews. If a journal is not included there, it’s either very interdisciplinary or one should get suspicious.

Retraction Watch: Is it possible for individual researchers to jump off the bibiometrics bandwagon without jeopardizing their careers?

Agricola: We need to fight for a change in culture, that’s for sure, and the path will be rash and hard. To young researchers, we should give the warning that being involved in predatory publishing can also just as well put their scientific integrity at risk. Remember the people who had to resign because of data falsification? 

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I am providing citations (of a sort) to both papers and links to all three sites where both papers can be found and PDFs for both papers: Everything is open access.

Fraudulent Publishing in the Mathematical Sciences by Ilka Agricola, Lynn Heller, Wil Schilders, Moritz Schubotz, Peter Taylor, Luis Vega.

arXiv: https://arxiv.org/abs/2509.07257

AMS (American Mathematical Society) Notices October 2025: https://www.ams.org/journals/notices/202509/noti3217/noti3217.html?adat=October%202025&trk=3217&pdfissue=202509&pdffile=rnoti-p1038.pdf&cat=none&type=.html

Ilke Agricola’s Research Gate website: https://www.researchgate.net/profile/Ilka-Agricola (scroll down to see the listed papers)

PDF: https://www.ams.org/journals/notices/202509/rnoti-p1038.pdf

How to Fight Fraudulent Publishing in the Mathematical Sciences: Joint Recommendations of the IMU [International Mathematical Union] and the ICIAM [International Council for Industrial and Applied Mathematics] by Ilka Agricola, Lynn Heller, Wil Schilders, Moritz Schubotz, Peter Taylor, Luis Vega.

arXiv: https://arxiv.org/abs/2509.09877

AMS (American Mathematical Society) Notices November 2025: https://www.ams.org/journals/notices/202510/noti3266/noti3266.html?adat=November%202025&trk=3266&pdfissue=202510&pdffile=rnoti-p1179.pdf&cat=none&type=.html

Ilke Agricola’s Research Gate website: https://www.researchgate.net/profile/Ilka-Agricola (scroll down to see the listed papers)

PDF: https://www.ams.org/journals/notices/202510/rnoti-p1179.pdf

Fraud slows down research

Mentioned in the Retraction Watch/Agricola interview, this January 29, 2025 article by Frederik Joelving (contributing editor, Retraction Watch), Cyril Labbé, (professor of computer science, Université Grenoble Alpes [UGA]), Guillaume Cabanac, (professor of computer Science, Institut de Recherche en Informatique de Toulouse) is chilling, Note: Links have been removed,

Over the past decade, furtive commercial entities around the world have industrialized the production, sale and dissemination of bogus scholarly research, undermining the literature that everyone from doctors to engineers rely on to make decisions about human lives.

It is exceedingly difficult to get a handle on exactly how big the problem is. Around 55,000 scholarly papers have been retracted to date, for a variety of reasons, but scientists and companies who screen the scientific literature for telltale signs of fraud estimate that there are many more fake papers circulating – possibly as many as several hundred thousand. This fake research can confound legitimate researchers who must wade through dense equations, evidence, images and methodologies only to find that they were made up.

Even when the bogus papers are spotted – usually by amateur sleuths on their own time – academic journals are often slow to retract the papers, allowing the articles to taint what many consider sacrosanct: the vast global library of scholarly work that introduces new ideas, reviews other research and discusses findings.

These fake papers are slowing down research that has helped millions of people with lifesaving medicine and therapies from cancer to COVID-19. Analysts’ data shows that fields related to cancer and medicine are particularly hard hit, while areas like philosophy and art are less affected. Some scientists have abandoned their life’s work because they cannot keep pace given the number of fake papers they must bat down.

The problem reflects a worldwide commodification of science. Universities, and their research funders, have long used regular publication in academic journals as requirements for promotions and job security, spawning the mantra “publish or perish.”

But now, fraudsters have infiltrated the academic publishing industry to prioritize profits over scholarship. Equipped with technological prowess, agility and vast networks of corrupt researchers, they are churning out papers on everything from obscure genes to artificial intelligence in medicine.

These papers are absorbed into the worldwide library of research faster than they can be weeded out. About 119,000 scholarly journal articles and conference papers are published globally every week, or more than 6 million a year. Publishers estimate that, at most journals, about 2% of the papers submitted – but not necessarily published – are likely fake, although this number can be much higher at some publications.

… there is a bustling online underground economy for all things scholarly publishing. Authorship, citations, even academic journal editors, are up for sale. This fraud is so prevalent that it has its own name: paper mills, a phrase that harks back to “term-paper mills,” where students cheat by getting someone else to write a class paper for them.

The impact on publishers is profound. In high-profile cases, fake articles can hurt a journal’s bottom line. Important scientific indexes – databases of academic publications that many researchers rely on to do their work – may delist journals that publish too many compromised papers. There is growing criticism that legitimate publishers could do more to track and blacklist journals and authors who regularly publish fake papers that are sometimes little more than artificial intelligence-generated phrases strung together.

To better understand the scope, ramifications and potential solutions of this metastasizing assault on science, we – a contributing editor at Retraction Watch, a website that reports on retractions of scientific papers and related topics, and two computer scientists at France’s Université Toulouse III–Paul Sabatier and Université Grenoble Alpes who specialize in detecting bogus publications – spent six months investigating paper mills.

This included, by some of us at different times, trawling websites and social media posts, interviewing publishers, editors, research-integrity experts, scientists, doctors, sociologists and scientific sleuths engaged in the Sisyphean task of cleaning up the literature. It also involved, by some of us, screening scientific articles looking for signs of fakery.

What emerged is a deep-rooted crisis that has many researchers and policymakers calling for a new way for universities and many governments to evaluate and reward academics and health professionals across the globe.

Just as highly biased websites dressed up to look like objective reporting are gnawing away at evidence-based journalism and threatening elections, fake science is grinding down the knowledge base on which modern society rests.

…

The January 29, 2025 article highlights a number of problems including these,

To expedite the publication of one another’s work, some corrupt scientists form peer review rings. Paper mills may even create fake peer reviewers impersonating real scientists to ensure their manuscripts make it through to publication. Others bribe editors or plant agents on journal editorial boards.

María de los Ángeles Oviedo-García, a professor of marketing at the University of Seville in Spain, spends her spare time hunting for suspect peer reviews from all areas of science, hundreds of which she has flagged on PubPeer. ……

“One of the demanding fights for me is to keep faith in science,” says Oviedo-García, who tells her students to look up papers on PubPeer before relying on them too heavily. Her research has been slowed down, she adds, because she now feels compelled to look for peer review reports for studies she uses in her work. Often there aren’t any, because “very few journals publish those review reports,” Oviedo-García says.

An ‘absolutely huge’ problem

It is unclear when paper mills began to operate at scale. The earliest article retracted due to suspected involvement of such agencies was published in 2004, according to the Retraction Watch Database, which contains details about tens of thousands of retractions. (The database is operated by The Center for Scientific Integrity, the parent nonprofit of Retraction Watch.) Nor is it clear exactly how many low-quality, plagiarized or made-up articles paper mills have spawned.

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“The threat of paper mills to scientific publishing and integrity has no parallel over my 30-year scientific career …. In the field of human gene science alone, the number of potentially fraudulent articles could exceed 100,000 original papers,” she [Jennifer Byrne, an Australian scientist] wrote to lawmakers, adding, “This estimate may seem shocking but is likely to be conservative.”

In one area of genetics research – the study of noncoding RNA in different types of cancer – “We’re talking about more than 50% of papers published are from mills,” Byrne said. “It’s like swimming in garbage.”

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… in the global south, the publish-or-perish edict runs up against underdeveloped research infrastructures and education systems, leaving scientists in a bind. For a Ph.D., the Cairo physician who requested anonymity conducted an entire clinical trial single-handedly – from purchasing study medication to randomizing patients, collecting and analyzing data and paying article-processing fees. In wealthier nations, entire teams work on such studies, with the tab easily running into the hundreds of thousands of dollars.

“Research is quite challenging here,” the physician said. That’s why scientists “try to manipulate and find easier ways so they get the job done.”

Institutions, too, have gamed the system with an eye to international rankings. In 2011, the journal Science described how prolific researchers in the United States and Europe were offered hefty payments for listing Saudi universities as secondary affiliations on papers. And in 2023, the magazine, in collaboration with Retraction Watch, uncovered a massive self-citation ploy by a top-ranked dental school in India that forced undergraduate students to publish papers referencing faculty work.

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According to the January 29, 2025 article, there is a root cause, Note: Links have been removed,

… unsavory schemes can be traced back to the introduction of performance-based metrics in academia, a development driven by the New Public Management movement that swept across the Western world in the 1980s, according to Canadian sociologist of science Yves Gingras of the Université du Québec à Montréal. When universities and public institutions adopted corporate management, scientific papers became “accounting units” used to evaluate and reward scientific productivity rather than “knowledge units” advancing our insight into the world around us, Gingras wrote.

This transformation led many researchers to compete on numbers instead of content, which made publication metrics poor measures of academic prowess. As Gingras has shown, the controversial French microbiologist Didier Raoult, who now has more than a dozen retractions to his name, has an h-index – a measure combining publication and citation numbers – that is twice as high as that of Albert Einstein – “proof that the index is absurd,” Gingras said.

Worse, a sort of scientific inflation, or “scientometric bubble,” has ensued, with each new publication representing an increasingly small increment in knowledge. “We publish more and more superficial papers, we publish papers that have to be corrected, and we push people to do fraud,” said Gingras.

In terms of career prospects of individual academics, too, the average value of a publication has plummeted, triggering a rise in the number of hyperprolific authors. One of the most notorious cases is Spanish chemist Rafael Luque, who in 2023 reportedly published a study every 37 hours.

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There is some hope according to the January 29, 2025 article, Note: Links have been removed,

Stern [Bodo Stern, a former editor of the journal Cell and chief of Strategic Initiatives at Howard Hughes Medical Institute] isn’t the first scientist to bemoan the excessive focus on bibliometrics. “We need less research, better research, and research done for the right reasons,” wrote the late statistician Douglas G. Altman in a much-cited editorial from 1994. “Abandoning using the number of publications as a measure of ability would be a start.”

Nearly two decades later, a group of some 150 scientists and 75 science organizations released the San Francisco Declaration on Research Assessment, or DORA, discouraging the use of the journal impact factor and other measures as proxies for quality. The 2013 declaration has since been signed by more than 25,000 individuals and organizations in 165 countries.

Despite the declaration, metrics remain in wide use today, and scientists say there is a new sense of urgency.

…

Stern and his colleagues have tried to make improvements at their institution. Researchers who wish to renew their seven-year contract have long been required to write a short paragraph describing the importance of their major results. Since the end of 2023, they also have been asked to remove journal names from their applications.

That way, “you can never do what all reviewers do – I’ve done it – look at the bibliography and in just one second decide, ‘Oh, this person has been productive because they have published many papers and they’re published in the right journals,’” says Stern. “What matters is, did it really make a difference?”

Shifting the focus away from convenient performance metrics seems possible not just for wealthy private institutions like Howard Hughes Medical Institute, but also for large government funders. In Australia, for example, the National Health and Medical Research Council in 2022 launched the “top 10 in 10” policy, aiming, in part, to “value research quality rather than quantity of publications.”

Rather than providing their entire bibliography, the agency, which assesses thousands of grant applications every year, asked researchers to list no more than 10 publications from the past decade and explain the contribution each had made to science. …

Gingras, the Canadian sociologist, advocates giving scientists the time they need to produce work that matters, rather than a gushing stream of publications. He is a signatory to the Slow Science Manifesto: “Once you get slow science, I can predict that the number of corrigenda, the number of retractions, will go down,” he says.

At one point, Gingras was involved in evaluating a research organization whose mission was to improve workplace security. An employee presented his work. “He had a sentence I will never forget,” Gingras recalls. The employee began by saying, “‘You know, I’m proud of one thing: My h-index is zero.’ And it was brilliant.” The scientist had developed a technology that prevented fatal falls among construction workers. “He said, ‘That’s useful, and that’s my job.’ I said, ‘Bravo!’”

Sometimes, there’s a science reporting problem

A September 3, 2025 Universiteit van Amsterdam press release (also on EurekAlert) highlights a problem with science reporting and over confidence,

Science journalists aren’t particularly concerned about so-called “predatory journals”, confident that they have the skills and intuition needed to avoid reporting on problematic research. For many, a journal’s reputation and name-recognition are decisive factors in assessing the quality of scientific research – but this could be exacerbating existing imbalances in science and journalism. This perspective emerges from a new study, led by Dr Alice Fleerackers of the University of Amsterdam (UvA), and published on 2 September [2025] in Journalism Practice.

Predatory journals prioritise profit over editorial and publication standards. They often charge researchers publication fees but offer little to no real quality control, such as peer review. As a result, some journals publish almost everything submitted. ‘Predatory journals are not a harmless side effect of the academic publishing industry,’ says Fleerackers. ‘They are becoming increasingly common, raising concerns about the integrity of scientific publishing. They not only undermine the reliability of science but also jeopardise science journalism, as journalists can unknowingly report on weak or even flawed research.’

In the new study, Fleerackers – along with colleagues from Simon Fraser University (Canada) and San Francisco State University (US) – investigated how science journalists view predatory journals and what strategies they employ to ensure the reliability of the journals they report on. The researchers present a qualitative analysis of interviews with 23 health, science, and environmental journalists in Europe and North America.

Problematic, but only in theory

Some of the journalists interviewed were familiar with the phenomenon of predatory journals and acknowledged that they are theoretically problematic. However, most weren’t concerned that they might be using them in their own work. They acknowledged that these journals might be a problem for colleagues, but not for them.

Well-known, therefore reliable

Journalists in the study were confident they wouldn’t fall for a predatory journal because of their strong intuition, which they said allowed them to immediately distinguish high-quality from problematic research. Besides their intuition, they also relied on strategies for verifying the reliability of research that they had developed through years of experience. These strategies often centred on trust proxies – like the journal’s prestige, impact factor, and selectivity – as well as whether the journal claimed to conduct peer review.

Proofreading also played a role for some journalists: if an article contained grammatical or spelling errors, it could be a sign of low-quality research. Open access journals were also considered less reliable by several journalists. ‘But by far the most commonly used benchmark for reliability was the journal’s reputation,’ Fleerackers explains. ‘Some journalists avoid all journals they’re not familiar with and report only on research published in top journals like Science and Nature.’

Distortion in science news

According to Fleerackers, journalists’ focus on the reputation and prestige of journals has major consequences for the diversity of research in the news media. ‘Research from newer, lesser-known journals, and from journals in the Global South, for example, remains hidden from the public. Most journalists in our study didn’t realise that their selection strategies could perpetuate the existing imbalance in science news. I hope that our study can raise awareness of this among journalists.’

Here’s a link to and a citation for the paper.

“I’d Like to Think I’d Be Able to Spot One”: How Journalists Navigate Predatory Journals by Alice Fleerackers, Laura L. Moorhead & Juan Pablo Alperin. Journalism Practice 1–19. DOI: https://doi.org/10.1080/17512786.2025.2551984 Published online: 02 Sep 2025

Final comments

This has been a good wake up call for me. Bad apples, yes, but criminal networks? I had no idea. I will probably write more about this in my 2025 year post. In the meantime, This is a good reminder to exercise caution.

Neuron survival in Alzheimer’s model dramatically improved with sugar-coated nanotherapy

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A May 14, 2025 news item on ScienceDaily announces research from Northwestern University (Chicago, Illinois) that could delay the progress of diseases like Alzheimer’s and amyotrophic lateral sclerosis (ALS),

Scientists at Northwestern University have developed a new approach that directly combats the progression of neurodegenerative diseases like Alzheimer’s disease and amyotrophic lateral sclerosis (ALS).

In these devastating illnesses, proteins misfold and clump together around brain cells, which ultimately leads to cell death. The innovative new treatment effectively traps the proteins before they can aggregate into the toxic structures capable of penetrating neurons. The trapped proteins then harmlessly degrade in the body.

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Caption: Labeled micrographs of human neurons exposed to amyloid-beta proteins and either left untreated (left) or treated with the new nanotherapy developed at Northwestern (right). Dead neurons are stained in red; live neurons are green. Credit: Samuel Stupp Laboratory/Northwestern University

A May 14, 2025 Northwestern University news release (also on EurekAlert) by Amanda Morris, which originated the news item, provides more detail about the work, Note: Links have been removed,

The “clean-up” strategy significantly boosted the survival of lab-grown human neurons under stress from disease-causing proteins.

Designated as an ACS [American Chemical Society] Editor’s Choice article, the study will be published on May 14 [2025] in the Journal of the American Chemical Society [JACS].

“Our study highlights the exciting potential of molecularly engineered nanomaterials to address the root causes of neurodegenerative diseases,” said Northwestern’s Samuel I. Stupp, the study’s senior author. “In many of these diseases, proteins lose their functional folded structure and aggregate to make destructive fibers that enter neurons and are highly toxic to them. 

“By trapping the misfolded proteins, our treatment inhibits the formation of those fibers at an early stage. Early stage, short amyloid fibers, which penetrate neurons, are believed to be the most toxic structures. With further work, we think this could significantly delay progression of the disease.”

A pioneer in regenerative medicine, Stupp is the Board of Trustees Professor of Materials Science and Engineering, Chemistry, Medicine and Biomedical Engineering at Northwestern, where he has appointments in the McCormick School of Engineering, Weinberg College of Arts and Sciences and Feinberg School of Medicine. He also is the founding director of the Center for Regenerative Nanomedicine (CRN). Zijun Gao, a Ph.D. candidate in Stupp’s laboratory, is the paper’s first author.

The Stupp group led the development and characterization of the new therapeutic materials. Co-corresponding author Zaida Alvarez — a researcher at the Institute for Bioengineering of Catalonia (IBEC) in Spain, former postdoctoral fellow in Stupp’s laboratory and current visiting scholar at CRN — led testing of the therapies in human neurons.

A sugar-coated solution

According to the World Health Organization, as many as 50 million people worldwide might have a neurodegenerative disorder. Most of these diseases are characterized by the accumulation of misfolded proteins in the brain, leading to the progressive loss of neurons. While current treatments offer limited relief, a dire need for new therapies remains.

To tackle this challenge, the researchers turned to a class of peptide amphiphiles, pioneered by the Stupp laboratory, that contain modified chains of amino acids. Peptide amphiphiles are already used in well-known pharmaceuticals including semaglutide, or Ozempic. In fact, the Northwestern investigators developed a similar molecule in 2012 that boosted insulin production.

“The advantage of peptide-based drugs is that they degrade into nutrients,” Stupp said. “The molecules in this novel therapeutic concept break down into harmless lipids, amino acids and sugars. That means there are fewer adverse side effects.”

Over the years, Stupp’s research group has designed many peptide-based materials for different therapeutic purposes. To develop a peptide amphiphile to treat neurodegenerative diseases, his team added an extra ingredient: a natural sugar called trehalose.

“Trehalose is naturally occurring in plants, fungi and insects,” Gao said. “It protects them from changing temperatures, especially dehydration and freezing. Others have discovered trehalose can protect many biological macromolecules, including proteins. So, we wanted to see if we could use it to stabilize misfolded proteins.”

Instability is key

When added to water, the peptide amphiphiles self-assembled into nanofibers coated with trehalose. Surprisingly, the trehalose destabilized the nanofibers. Although it seems counterintuitive, this decreased stability exhibited a beneficial effect.

By themselves, the nanofibers are strong and well-ordered — and resistant to rearranging their structure. That makes it more difficult for other molecules, like misfolded proteins, to integrate into the fibers. Less stable fibers, on the other hand, became more dynamic — and more likely to find and interact with toxic proteins.

“Unstable assemblies of molecules are very reactive,” Stupp said. “They want to interact with and bond to other molecules. If the nanofibers were stable, they would happily ignore everything around them.”

Searching for stability, the nanofibers bonded to amyloid-beta proteins, a key culprit implicated in Alzheimer’s disease. But the nanofibers didn’t just stop the amyloid-beta proteins from clumping together. The nanofibers fully incorporated the proteins into their own fibrous structures — permanently trapping them into stable filaments. 

“Then, it’s no longer a peptide amphiphile fiber anymore,” Stupp said. “But a new hybrid structure comprising both the peptide amphiphile and the amyloid-beta protein. That means the nasty amyloid-beta proteins, which would have formed amyloid fibers, are trapped. They can no longer penetrate the neurons and kill them. It’s like a clean-up crew for misfolded proteins.

“This is a novel mechanism to tackle progression of neurodegenerative diseases, such as Alzheimer’s, at an earlier stage. Current therapies rely on the production of antibodies for well-formed amyloid fibers.”

Improving neuron survival

To assess the therapeutic potential of the new approach, the scientists conducted laboratory tests using human neurons derived from stem cells. The results showed the trehalose-coated nanofibers significantly improved the survival of both motor and cortical neurons when exposed to the toxic amyloid-beta protein.

Stupp says the novel approach of using unstable nanofibers to trap proteins offers a promising avenue for developing new and effective therapies for Alzheimer’s, ALS and other neurodegenerative conditions. Much like cancer treatments combine multiple therapies — like chemotherapy and surgery or hormone therapy and radiation — Stupp said the nanotherapy might be most effective when combined with other treatments.

“Our therapy might work best when targeting diseases at an earlier stage — before aggregated proteins enter cells,” Stupp said. “But it’s challenging to diagnose these diseases at early stages. So, it could be combined with therapies that target later-stage symptoms of the disease. Then, it could be a double whammy.”

Here’s a link to and a citation for the paper,

Supramolecular Copolymerization of Glycopeptide Amphiphiles and Amyloid Peptides Improves Neuron Survival by Zijun Gao, Ruomeng Qiu, Dhwanit R. Dave, Palash Chandravanshi, Gisele P. Soares, Cara S. Smith, J. Alberto Ortega, Liam C. Palmer, Zaida Álvarez, Samuel I. Stupp. Journal of the American Chemical Society 2025, 147, 21, 17710–17724 DOI: https://doi.org/10.1021/jacs.5c00105 Published May 14, 2025 Copyright © 2025 American Chemical Society

This paper is open access.

Dwarfed by a grain of rice—the world’s smallest pacemaker

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OMG,

A jaw-dropping moment (for me anyway). An April 2, 2025 news item on Nanowerk announced the research,

Northwestern University engineers have developed a pacemaker so tiny that it can fit inside the tip of a syringe — and be non-invasively injected into the body.

Although it can work with hearts of all sizes, the pacemaker is particularly well-suited to the tiny, fragile hearts of newborn babies with congenital heart defects.

Smaller than a single grain of rice, the pacemaker is paired with a small, soft, flexible, wireless, wearable device that mounts onto a patient’s chest to control pacing. When the wearable device detects an irregular heartbeat, it automatically shines a light pulse to activate the pacemaker. These short pulses— which penetrate through the patient’s skin, breastbone and muscles — control the pacing.

…

An April 2, 2025 Northwestern University news release by Amanda Morris (also received via email and on EurekAlert), which originated the news item, provides more detail about the work, Note: Links have been removed,

Designed for patients who only need temporary pacing, the pacemaker simply dissolves after it’s no longer needed. All the pacemaker’s components are biocompatible, so they naturally dissolve into the body’s biofluids, bypassing the need for surgical extraction.

The study will be published on April 2 [2025] in the journal Nature. The paper demonstrates the device’s efficacy across a series of large and small animal models as well as human hearts from deceased organ donors.

“We have developed what is, to our knowledge, the world’s smallest pacemaker,” said Northwestern bioelectronics pioneer John A. Rogers, who led the device development. “There’s a crucial need for temporary pacemakers in the context of pediatric heart surgeries, and that’s a use case where size miniaturization is incredibly important. In terms of the device load on the body — the smaller, the better.”

“Our major motivation was children,” said Northwestern experimental cardiologist Igor Efimov, who co-led the study. “About 1% of children are born with congenital heart defects — regardless of whether they live in a low-resource or high-resource country. The good news is that these children only need temporary pacing after a surgery. In about seven days or so, most patients’ hearts will self-repair. But those seven days are absolutely critical. Now, we can place this tiny pacemaker on a child’s heart and stimulate it with a soft, gentle, wearable device. And no additional surgery is necessary to remove it.”

Rogers is the Louis Simpson and Kimberly Querrey Professor of Materials Science and Engineering, Biomedical Engineering and Neurological Surgery at Northwestern — where he has appointments in the McCormick School of Engineering and Feinberg School of Medicine — and the director of the Querrey Simpson Institute of Bioelectronics. Efimov is a professor of biomedical engineering at McCormick and professor of medicine (cardiology) at Feinberg. Rogers and Efimov co-led the study with Yonggang Huang, the Jan and Marcia Achenbach Professor of Mechanical Engineering and Civil and Environmental Engineering at McCormick; Wei Ouyang, an assistant professor of engineering at Dartmouth College; and Rishi Arora, the Harold H. Hines Jr. Professor of Medicine at the University of Chicago.

Meeting an unmet clinical need

This work builds on a previous collaboration between Rogers and Efimov, in which they developed the first dissolvable device for temporary pacing. Many patients require temporary pacemakers after heart surgery — either while waiting for a permanent pacemaker or to help restore a normal heart rate during recovery.

For the current standard of care, surgeons sew the electrodes onto the heart muscle during surgery. Wires from the electrodes exit the front of a patient’s chest, where they connect to an external pacing box that delivers a current to control the heart’s rhythm.

When the temporary pacemaker is no longer needed, physicians remove the pacemaker electrodes. Potential complications include infection, dislodgement, torn or damaged tissues, bleeding and blood clots.

“Wires literally protrude from the body, attached to a pacemaker outside the body,” Efimov said. “When the pacemaker is no longer needed, a physician pulls it out. The wires can become enveloped in scar tissue. So, when the wires are pulled out, that can potentially damage the heart muscle. That’s actually how Neil Armstrong died. He had a temporary pacemaker after a bypass surgery. When the wires were removed, he experienced internal bleeding.”

In response to this clinical need, Rogers, Efimov and their teams developed their dissolvable pacemaker, which was introduced in Nature Biotechnology in 2021. The thin, flexible, lightweight device eliminated the need for bulky batteries and rigid hardware, including wires. Rogers’ lab had previously invented the concept of bioresorbable electronic medicine — electronics that provide a therapeutic benefit to the patient and then harmlessly dissolve in the body like absorbable sutures. By varying the composition and thickness of the materials in these devices, Rogers’ team can control the precise number of days they remain functional before dissolving.

Body fluid-powered battery

While the original quarter-size dissolvable pacemaker worked well in pre-clinical animal studies, cardiac surgeons asked if it was possible to make the device smaller. Then it would be better suited to non-invasive implantation and for use in the smallest patients. But the device was powered by near-field communication protocols — the same technology used in smartphones for electronic payments and in RFID tags — which required a built-in antenna.

“Our original pacemaker worked well,” Rogers said. “It was thin, flexible and fully resorbable. But the size of its receiver antenna limited our ability to miniaturize it. Instead of using the radio frequency scheme for wireless control, we developed a light-based scheme for turning the pacemaker on and delivering stimulation pulses to the surface of the heart. This is one feature that allowed us to dramatically reduce the size.”

To help further reduce the device’s size, the researchers also reimagined its power source. Instead of using near-field communication to supply power, the new, tiny pacemaker operates through the action of a galvanic cell, a type of simple battery that transforms chemical energy into electrical energy. Specifically, the pacemaker uses two different metals as electrodes to deliver electrical pulses to the heart. When in contact with surrounding biofluids, the electrodes form a battery. The resulting chemical reactions cause the electrical current to flow to stimulate the heart.

“When the pacemaker is implanted into the body, the surrounding biofluids act as the conducting electrolyte that electrically joins those two metal pads to form the battery,” Rogers said. “A very tiny light-activated switch on the opposite side from the battery allows us to turn the device from its ‘off’ state to an ‘on’ state upon delivery of light that passes through the patient’s body from the skin-mounted patch.”

Pulsing with light

The team used an infrared wavelength of light that penetrates deeply and safely into the body. If the patient’s heart rate drops below a certain rate, the wearable device detects the event and automatically activates a light-emitting diode. The light then flashes on and off at a rate that corresponds to the normal heart rate.

“Infrared light penetrates very well through the body,” Efimov said. “If you put a flashlight against your palm, you will see the light glow through the other side of your hand. It turns out that our bodies are great conductors of light.”

Even though the pacemaker is so tiny — measuring just 1.8 millimeters in width, 3.5 millimeters in length and 1 millimeter in thickness — it still delivers as much stimulation as a full-sized pacemaker.

“The heart requires a tiny amount of electrical stimulation,” Rogers said. “By minimizing the size, we dramatically simplify the implantation procedures, we reduce trauma and risk to the patient, and, with the dissolvable nature of the device, we eliminate any need for secondary surgical extraction procedures.”

More sophisticated synchronization

Because the devices are so tiny, physicians could distribute collections of them across the heart. A difficult color of light could illuminate to independently control a specific pacemaker. Use of multiple pacemakers in this manner enables more sophisticated synchronization compared to traditional pacing. In special cases, different areas of the heart can be paced at different rhythms, for example, to terminate arrhythmias. 

“We can deploy a number of such small pacemakers onto the outside of the heart and control each one,” Efimov said. “Then we can achieve improved synchronized functional care. We also could incorporate our pacemakers into other medical devices like heart valve replacements, which can cause heart block.”

“Because it’s so small, this pacemaker can be integrated with almost any kind of implantable device,” Rogers said. “We also demonstrated integration of collections of these devices across the frameworks that serve as transcatheter aortic valve replacements. Here, the tiny pacemakers can be activated as necessary to address complications that can occur during a patient’s recovery process. So that’s just one example of how we can enhance traditional implants by providing more functional stimulation.”

The technology’s versatility opens a broad range of other possibilities for use in bioelectronic medicines, including helping nerves and bones heal, treating wounds and blocking pain.

…

Caption: The tiny pacemaker sits next to a single grain of rice on a fingertip. The device is so small that it can be non-invasively injected into the body via a syringe. Credit: John A. Rogers/Northwestern University

Here’s a link to and a citation for the paper,

Millimetre-scale bioresorbable optoelectronic systems for electrotherapy by Yamin Zhang, Eric Rytkin, Liangsong Zeng, Jong Uk Kim, Lichao Tang, Haohui Zhang, Aleksei Mikhailov, Kaiyu Zhao, Yue Wang, Li Ding, Xinyue Lu, Anastasia Lantsova, Elena Aprea, Gengming Jiang, Shupeng Li, Seung Gi Seo, Tong Wang, Jin Wang, Jiayang Liu, Jianyu Gu, Fei Liu, Keith Bailey, Yat Fung Larry Li, Amy Burrell, Anna Pfenniger, Andrey Ardashev, Tianyu Yang, Naijia Liu, Zengyao Lv, Nathan S. Purwanto, Yue Ying, Yinsheng Lu, Claire Hoepfner, Altynai Melisova, Jiarui Gong, Jinheon Jeong, Junhwan Choi, Alex Hou, Rachel Nolander, Wubin Bai, Sung Hun Jin, Zhenqiang Ma, John M. Torkelson, Yonggang Huang, Wei Ouyang, Rishi K. Arora, Igor R. Efimov & John A. Rogers. Nature volume 640, pages 77–86 (2025) DOI https://doi.org/10.1038/s41586-025-08726-4 Published online: 02 April 2025 Issue Date: 03 April 2025

This paper is behind a paywall.

With some 50 researchers involved in this work, I have not tagged each one as is my usual practice and I apologize for not tagging each and every one.

Harvesting water from air

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You can watch the nano-sized water droplet form in following video,

A September 30, 2024 Northwestern University news release (received via email and on EurekAlert) by Amanda Morris describes a first, Note: Links have been removed,

For the first time ever, researchers have witnessed — in real time and at the molecular-scale — hydrogen and oxygen atoms merge to form tiny, nano-sized bubbles of water.

The event occurred as part of a new Northwestern University study, during which scientists sought to understand how palladium, a rare metallic element, catalyzes the gaseous reaction to generate water. By witnessing the reaction at the nanoscale, the Northwestern team unraveled how the process occurs and even uncovered new strategies to accelerate it.

Because the reaction does not require extreme conditions, the researchers say it could be harnessed as a practical solution for rapidly generating water in arid environments, including on other planets.

The research will be published on Friday (Sept. 27 [2024]) in the Proceedings of the National Academy of Sciences [PNAS].

“By directly visualizing nanoscale water generation, we were able to identify the optimal conditions for rapid water generation under ambient conditions,” said Northwestern’s Vinayak Dravid, senior author of the study. “These findings have significant implications for practical applications, such as enabling rapid water generation in deep space environments using gases and metal catalysts, without requiring extreme reaction conditions. 

“Think of Matt Damon’s character, Mark Watney, in the movie ‘The Martian.’ He burned rocket fuel to extract hydrogen and then added oxygen from his oxygenator. Our process is analogous, except we bypass the need for fire and other extreme conditions. We simply mixed palladium and gases together.”

Dravid is the Abraham Harris Professor of Materials Science and Engineering at Northwestern’s McCormick School of Engineering and founding director of the Northwestern University Atomic and Nanoscale Characterization Experimental (NUANCE) Center, where the study was conducted. He also is director of global initiatives at the International Institute for Nanotechnology.

New technology enabled discovery

Since the early 1900s, researchers have known that palladium can act as a catalyst to rapidly generate water. But how, exactly, this reaction occurs has remained a mystery.

“It’s a known phenomenon, but it was never fully understood,” said Yukun Liu, the study’s first author and a Ph.D. candidate in Dravid’s laboratory. “Because you really need to be able to combine the direct visualization of water generation and the structure analysis at the atomic scale in order to figure out what’s happening with the reaction and how to optimize it.”

But viewing the process with atomic precision was simply impossible — until nine months ago. In January 2024, Dravid’s team unveiled a novel method to analyze gas molecules in real time. Dravid and his team developed an ultra-thin glassy membrane that holds gas molecules within honeycomb-shaped nanoreactors, so they can be viewed within high-vacuum transmission electron microscopes.

With the new technique, previously published in Science Advances, researchers can examine samples in atmospheric pressure gas at a resolution of just 0.102 nanometers, compared to a 0.236-nanometer resolution using other state-of-the-art tools. The technique also enabled, for the first time, concurrent spectral and reciprocal information analysis.

“Using the ultrathin membrane, we are getting more information from the sample itself,” said Kunmo Koo, first author of the Science Advances paper and a research associate at the NUANCE Center, where he is mentored by research associate professor Xiaobing Hu. “Otherwise, information from the thick container interferes with the analysis.”

Smallest bubble ever seen

Using the new technology, Dravid, Liu and Koo examined the palladium reaction. First, they saw the hydrogen atoms enter the palladium, expanding its square lattice. But when they saw tiny water bubbles form at the palladium surface, the researchers couldn’t believe their eyes.

“We think it might be the smallest bubble ever formed that has been viewed directly,” Liu said. “It’s not what we were expecting. Luckily, we were recording it, so we could prove to other people that we weren’t crazy.”

“We were skeptical,” Koo added. “We needed to investigate it further to prove that it was actually water that formed.”

The team implemented a technique, called electron energy loss spectroscopy, to analyze the bubbles. By examining the energy loss of scattered electrons, researchers identified oxygen-bonding characteristics unique to water, confirming the bubbles were, indeed, water. The researchers then cross-checked this result by heating the bubble to evaluate the boiling point.

“It’s a nanoscale analog of the Chandrayaan-1 moon rover experiment, which searched for evidence of water in lunar soil,” Koo said. “While surveying the moon, it used spectroscopy to analyze and identify molecules within the atmosphere and on the surface. We took a similar spectroscopic approach to determine if the generated product was, indeed, water.”

Recipe for optimization

After confirming the palladium reaction generated water, the researchers next sought to optimize the process. They added hydrogen and oxygen separately at different times or mixed together to determine which sequence of events generated water at the fastest rate.

Dravid, Liu and Koo discovered that adding hydrogen first, followed by oxygen, led to the fastest reaction rate. Because hydrogen atoms are so small, they can squeeze between palladium’s atoms — causing the metal to expand. After filling the palladium with hydrogen, the researchers added oxygen gas.

“Oxygen atoms are energetically favorable to adsorb onto palladium surfaces, but they are too large to enter the lattice,” Liu said. “When we flowed in oxygen first, its dissociated atoms covered the entire surface of the palladium, so hydrogen could not adsorb onto surface to trigger the reaction. But when we stored hydrogen in the palladium first, and then added oxygen, the reaction started. Hydrogen comes out of the palladium to react with the oxygen, and the palladium shrinks and returns to its initial state.”

Sustainable system for deep space

The Northwestern team imagines that others, in the future, potentially could prepare hydrogen-filled palladium before traveling into space. Then, to generate water for drinking or for watering plants, travelers will only need to add oxygen. Although the study focused on studying bubble generation at nanoscale, larger sheets of palladium would generate much larger quantities of water.

“Palladium might seem expensive, but it’s recyclable,” Liu said. “Our process doesn’t consume it. The only thing consumed is gas, and hydrogen is the most abundant gas in the universe. After the reaction, we can reuse the palladium platform over and over.”

The study, “Unraveling the adsorption-limited hydrogen oxidation reaction at palladium surface via in situ electron microscopy,” was supported by the Air Force Office of Scientific Research (grant number AFOSR FA9550-22-1-0300) and hydrogen-related work by the Center for Hydrogen in Energy and Information Sciences, an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science(grant number DE-SC0023450).

Here’s a link to and a citation for the latest paper,

Unraveling the adsorption-limited hydrogen oxidation reaction at palladium surface via in situ electron microscopy by Yukun Liu, Kunmo Koo, Zugang Mao, Xianbiao Fu, Xiaobing Hu, and Vinayak P. Dravid. PNAS September 27, 2024 121 (40) e2408277121 DOI: https://doi.org/10.1073/pnas.2408277121

This paper is behind a paywall.

Here’s a link to and a citation for the earlier work on the technique that made it possible to create the nano-sized water droplets out of thin air,

Ultrathin silicon nitride microchip for in situ/operando microscopy with high spatial resolution and spectral visibility by Kunmo Koo, Zhiwei Li, Yukun Liu, Stephanie M. Ribet, Xianbiao Fu, Ying Jia, Xinqi Chen, Gajendra Shekhawat, Paul J. M. Smeets, Roberto dos Reis, Jungjae Park, Jong Min Yuk, Xiaobing Hu, and Vinayak P. Dravid. Science Advances 17 Jan 2024 Vol 10, Issue 3 DOI: 10.1126/sciadv.adj641

This paper is open access.

New approach to cartilage regeneration

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Not long after announcing their new work on cartilage and ‘dancing molecules’, Samuel I. Stupp and his team at Northwestern University (Chicago, Illinois) have announced work with a new material that does not have dancing molecules in a study using animal models. It’s here in an August 5, 02024 Northwestern University news release (also on EurekAlert and on SciTechDaily and received by email) by Amanda Morris, Note: Links have been removed,

Northwestern University scientists have developed a new bioactive material that successfully regenerated high-quality cartilage in the knee joints of a large-animal model.

Although it looks like a rubbery goo, the material is actually a complex network of molecular components, which work together to mimic cartilage’s natural environment in the body. 

In the new study, the researchers applied the material to damaged cartilage in the animals’ knee joints. Within just six months, the researchers observed evidence of enhanced repair, including the growth of new cartilage containing the natural biopolymers (collagen II and proteoglycans), which enable pain-free mechanical resilience in joints.

With more work, the researchers say the new material someday could potentially be used to prevent full knee replacement surgeries, treat degenerative diseases like osteoarthritis and repair sports-related injuries like ACL [anterior cruciate ligament] tears.

The study will be published during the week of August 5 [2024] in the Proceedings of the National Academy of Sciences.

“Cartilage is a critical component in our joints,” said Northwestern’s Samuel I. Stupp, who led the study. “When cartilage becomes damaged or breaks down over time, it can have a great impact on people’s overall health and mobility. The problem is that, in adult humans, cartilage does not have an inherent ability to heal. Our new therapy can induce repair in a tissue that does not naturally regenerate. We think our treatment could help address a serious, unmet clinical need.”

A pioneer of regenerative nanomedicine, Stupp is Board of Trustees Professor of Materials Science and Engineering, Chemistry, Medicine and Biomedical Engineering at Northwestern, where he is founding director of the Simpson Querrey Institute for BioNanotechnology and its affiliated center, the Center for Regenerative Nanomedicine. Stupp has appointments in the McCormick School of Engineering, Weinberg College of Arts and Sciences and Feinberg School of Medicine. Jacob Lewis, a former Ph.D. student in Stupp’s laboratory, is the paper’s first author.

What’s in the material?

The new study follows recently published work from the Stupp laboratory, in which the team used “dancing molecules” to activate human cartilage cells to boost the production of proteins that build the tissue matrix. Instead of using dancing molecules, the new study evaluates a hybrid biomaterial also developed in Stupp’s lab. The new biomaterial comprises two components: a bioactive peptide that binds to transforming growth factor beta-1 (TGFb-1) — an essential protein for cartilage growth and maintenance — and modified hyaluronic acid, a natural polysaccharide present in cartilage and the lubricating synovial fluid in joints. 

“Many people are familiar with hyaluronic acid because it’s a popular ingredient in skincare products,” Stupp said. “It’s also naturally found in many tissues throughout the human body, including the joints and brain. We chose it because it resembles the natural polymers found in cartilage.”

Stupp’s team integrated the bioactive peptide and chemically modified hyaluronic acid particles to drive the self-organization of nanoscale fibers into bundles that mimic the natural architecture of cartilage. The goal was to create an attractive scaffold for the body’s own cells to regenerate cartilage tissue. Using bioactive signals in the nanoscale fibers, the material encourages cartilage repair by the cells, which populate the scaffold.

Clinically relevant to humans

To evaluate the material’s effectiveness in promoting cartilage growth, the researchers tested it in sheep with cartilage defects in the stifle joint, a complex joint in the hind limbs similar to the human knee. This work was carried out in the laboratory of Mark Markel in the School of Veterinary Medicine at the University of Wisconsin–Madison. 

According to Stupp, testing in a sheep model was vital. Much like humans, sheep cartilage is stubborn and incredibly difficult to regenerate. Sheep stifles and human knees also have similarities in weight bearing, size and mechanical loads.

“A study on a sheep model is more predictive of how the treatment will work in humans,” Stupp said. “In other smaller animals, cartilage regeneration occurs much more readily.”

In the study, researchers injected the thick, paste-like material into cartilage defects, where it transformed into a rubbery matrix. Not only did new cartilage grow to fill the defect as the scaffold degraded, but the repaired tissue was consistently higher quality compared to the control.

A lasting solution

In the future, Stupp imagines the new material could be applied to joints during open-joint or arthroscopic surgeries. The current standard of care is microfracture surgery, during which surgeons create tiny fractures in the underlying bone to induce new cartilage growth.

“The main issue with the microfracture approach is that it often results in the formation of fibrocartilage — the same cartilage in our ears — as opposed to hyaline cartilage, which is the one we need to have functional joints,” Stupp said. “By regenerating hyaline cartilage, our approach should be more resistant to wear and tear, fixing the problem of poor mobility and joint pain for the long term while also avoiding the need for joint reconstruction with large pieces of hardware.”

The study, “A bioactive supramolecular and covalent polymer scaffold for cartilage repair in a sheep model,” was supported by the Mike and Mary Sue Shannon Family Fund for Bio-Inspired and Bioactive Materials Systems for Musculoskeletal Regeneration.

Here’s a link to and a citation for the paper,

A bioactive supramolecular and covalent polymer scaffold for cartilage repair in a sheep model by Jacob A. Lewis, Brett Nemke, Yan Lu, Nicholas A. Sather, Mark T. McClendon, Michael Mullen, Shelby C. Yuan, Sudheer K. Ravuri, Jason A. Bleedorn, Marc J. Philippon, Johnny Huard, Mark D. Markel, and Samuel I. Stupp. Proceedings ot the National Academy of Sciences (PNAS) 121 (33) e2405454121 DOI: https://doi.org/10.1073/pnas.2405454121 August 6, 2024

This paper is behind a paywall.

Healing cartilage damage with ‘dancing molecules’

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A July 26, 2024 Northwestern University (Chicago, Illinois) news release (also on EurekAlert) by Amanda Morris describes a new application for ‘dancing molecules’, Note 1: Links have been removed; Note 2: These are ‘in vitro’ (petri dish) experiments ,

In November 2021, Northwestern University researchers introduced an injectable new therapy, which harnessed fast-moving “dancing molecules,” to repair tissues and reverse paralysis after severe spinal cord injuries.

Now, the same research group has applied the therapeutic strategy to damaged human cartilage cells. In the new study, the treatment activated the gene expression necessary to regenerate cartilage within just four hours. And, after only three days, the human cells produced protein components needed for cartilage regeneration.

The researchers also found that, as the molecular motion increased, the treatment’s effectiveness also increased. In other words, the molecules’ “dancing” motions were crucial for triggering the cartilage growth process.

…

“When we first observed therapeutic effects of dancing molecules, we did not see any reason why it should only apply to the spinal cord,” said Northwestern’s Samuel I. Stupp, who led the study. “Now, we observe the effects in two cell types that are completely disconnected from one another — cartilage cells in our joints and neurons in our brain and spinal cord. This makes me more confident that we might have discovered a universal phenomenon. It could apply to many other tissues.”

An expert in regenerative nanomedicine, Stupp is Board of Trustees Professor of Materials Science and Engineering, Chemistry, Medicine and Biomedical Engineering at Northwestern, where he is founding director of the Simpson Querrey Institute for BioNanotechnology and its affiliated center, the Center for Regenerative Nanomedicine. Stupp has appointments in the McCormick School of Engineering, Weinberg College of Arts and Sciences and Feinberg School of Medicine. Shelby Yuan, a graduate student in the Stupp laboratory, was primary author of the study.

Big problem, few solutions

As of 2019, nearly 530 million people around the globe were living with osteoarthritis, according to the World Health Organization. A degenerative disease in which tissues in joints break down over time, osteoarthritis is a common health problem and leading cause of disability.

In patients with severe osteoarthritis, cartilage can wear so thin that joints essentially transform into bone on bone — without a cushion between. Not only is this incredibly painful, patients’ joints also can no longer properly function. At that point, the only effective treatment is a joint replacement surgery, which is expensive and invasive.

“Current treatments aim to slow disease progression or postpone inevitable joint replacement,” Stupp said. “There are no regenerative options because humans do not have an inherent capacity to regenerate cartilage in adulthood.”

What are ‘dancing molecules’?

Stupp and his team posited that “dancing molecules” might encourage the stubborn tissue to regenerate. Previously invented in Stupp’s laboratory, dancing molecules are assemblies that form synthetic nanofibers comprising tens to hundreds of thousands of molecules with potent signals for cells. By tuning their collective motions through their chemical structure, Stupp discovered the moving molecules could rapidly find and properly engage with cellular receptors, which also are in constant motion and extremely crowded on cell membranes.

“We are beginning to see the tremendous breadth of conditions that this fundamental discovery on ‘dancing molecules’ could apply to.” — Samuel I. Stupp, materials scientist

Once inside the body, the nanofibers mimic the extracellular matrix of the surrounding tissue. By matching the matrix’s structure, mimicking the motion of biological molecules and incorporating bioactive signals for the receptors, the synthetic materials are able to communicate with cells.

“Cellular receptors constantly move around,” Stupp said. “By making our molecules move, ‘dance’ or even leap temporarily out of these structures, known as supramolecular polymers, they are able to connect more effectively with receptors.”

Motion matters

In the new study, Stupp and his team looked to the receptors for a specific protein critical for cartilage formation and maintenance. To target this receptor, the team developed a new circular peptide that mimics the bioactive signal of the protein, which is called transforming growth factor beta-1 (TGFb-1).

Then, the researchers incorporated this peptide into two different molecules that interact to form supramolecular polymers in water, each with the same ability to mimic TGFb-1. The researchers designed one supramolecular polymer with a special structure that enabled its molecules to move more freely within the large assemblies. The other supramolecular polymer, however, restricted molecular movement.

“We wanted to modify the structure in order to compare two systems that differ in the extent of their motion,” Stupp said. “The intensity of supramolecular motion in one is much greater than the motion in the other one.”

Although both polymers mimicked the signal to activate the TGFb-1 receptor, the polymer with rapidly moving molecules was much more effective. In some ways, they were even more effective than the protein that activates the TGFb-1 receptor in nature.

“After three days, the human cells exposed to the long assemblies of more mobile molecules produced greater amounts of the protein components necessary for cartilage regeneration,” Stupp said. “For the production of one of the components in cartilage matrix, known as collagen II, the dancing molecules containing the cyclic peptide that activates the TGF-beta1 receptor were even more effective than the natural protein that has this function in biological systems.”

What’s next?

Stupp’s team is currently testing these systems in animal studies and adding additional signals to create highly bioactive therapies.

“With the success of the study in human cartilage cells, we predict that cartilage regeneration will be greatly enhanced when used in highly translational pre-clinical models,” Stupp said. “It should develop into a novel bioactive material for regeneration of cartilage tissue in joints.”

Stupp’s lab is also testing the ability of dancing molecules to regenerate bone — and already has promising early results, which likely will be published later this year. Simultaneously, he is testing the molecules in human organoids to accelerate the process of discovering and optimizing therapeutic materials.  

Stupp’s team also continues to build its case to the Food and Drug Administration, aiming to gain approval for clinical trials to test the therapy for spinal cord repair.

“We are beginning to see the tremendous breadth of conditions that this fundamental discovery on ‘dancing molecules’ could apply to,” Stupp said. “Controlling supramolecular motion through chemical design appears to be a powerful tool to increase efficacy for a range of regenerative therapies.”

The study, “Supramolecular motion enables chondrogenic bioactivity of a cyclic peptide mimetic of transforming growth factor-β1,” was supported by a gift from Mike and Mary Sue Shannon to Northwestern University for research on musculoskeletal regeneration at the Center for Regenerative Nanomedicine of the Simpson Querrey Institute for BioNanotechnology.

Here’s a link to and a citation for the paper,

Supramolecular Motion Enables Chondrogenic Bioactivity of a Cyclic Peptide Mimetic of Transforming Growth Factor-β1 by Shelby C. Yuan, Zaida Álvarez, Sieun Ruth Lee, Radoslav Z. Pavlović, Chunhua Yuan, Ethan Singer, Steven J. Weigand, Liam C. Palmer, Samuel I. Stupp. Journal of the American Chemical Society Vol 146/Issue 31 (or J. Am. Chem. Soc. 2024, 146, 31, 21555–21567) DOI: https://doi.org/10.1021/jacs.4c05170 Published July 25, 2024 Copyright © 2024 American Chemical Society

This paper is behind a paywall.

Electricity (electrodeposition) could help fight coastal (beach) erosion

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I live in a coastal region and a few months ago our local municipal voted down an initiative that included some mitigation for beach erosion. So, this research caught my eye.

Caption: An artistic impression of how electricity could be used to strengthen coastlines. Credit: Northwestern University

An August 22, 2024 news item on phys.org announces an unexpected approach to dealing with coastal erosion,

New research from Northwestern University has systematically proven that a mild zap of electricity can strengthen a marine coastline for generations—greatly reducing the threat of erosion in the face of climate change and rising sea levels.

…

An August 22, 2024 Northwestern University news release (received via email and also found on EurekAlert) by Amanda Morris, which originated the news item, delves further into the topic, Note: Links have been removed,

In the new study, researchers took inspiration from clams, mussels and other shell-dwelling sea life, which use dissolved minerals in seawater to build their shells.

Similarly, the researchers leveraged the same naturally occurring, dissolved minerals to form a natural cement between sea-soaked grains of sand. But, instead of using metabolic energy like mollusks do, the researchers used electrical energy to spur the chemical reaction.

In laboratory experiments, a mild electrical current instantaneously changed the structure of marine sand, transforming it into a rock-like, immoveable solid. The researchers are hopeful this strategy could offer a lasting, inexpensive and sustainable solution for strengthening global coastlines.

The study will be published on Thursday (Aug. 22 [2024]) in the journal Communications Earth and the Environment, a journal published by Nature Portfolio.

“Over 40% of the world’s population lives in coastal areas,” said Northwestern’s Alessandro Rotta Loria, who led the study. “Because of climate change and sea-level rise, erosion is an enormous threat to these communities. Through the disintegration of infrastructure and loss of land, erosion causes billions of dollars in damage per year worldwide. Current approaches to mitigate erosion involve building protection structures or injecting external binders into the subsurface.

“My aim was to develop an approach capable of changing the status quo in coastal protection — one that didn’t require the construction of protection structures and could cement marine substrates without using actual cement. By applying a mild electric stimulation to marine soils, we systematically and mechanistically proved that it is possible to cement them by turning naturally dissolved minerals in seawater into solid mineral binders — a natural cement.”

Rotta Loria is the Louis Berger Assistant Professor of Civil and Environmental Engineering at Northwestern’s McCormick School of Engineering. Andony Landivar Macias, a former Ph.D. candidate in Rotta Loria’s laboratory, is the paper’s first author. Steven Jacobsen, a mineralogist and professor of Earth and planetary sciences in Northwestern’s Weinberg College of Arts and Sciences, also co-authored the study.

Sea walls, too, erode

From intensifying rainstorms to rising sea levels, climate change has created conditions that are gradually eroding coastlines. According to a 2020 study by the European commission’s Joint Research Centre, nearly 26% of the Earth’s beaches will be washed away by the end of this century.

To mitigate this issue, communities have implemented two main approaches: building protection structures and barriers, such as sea walls, or injecting cement into the ground to strengthen marine substrates, widely consisting of sand. But multiple problems accompany these strategies. Not only are these conventional methods extremely expensive, they also do not last.

“Sea walls, too, suffer from erosion,” Rotta Loria said. “So, over time, the sand beneath these walls erodes, and the walls can eventually collapse. Oftentimes, protection structures are made of big stones, which cost millions of dollars per mile. However, the sand beneath them can essentially liquify because of a number of environmental stressors, and these big rocks are swallowed by the ground beneath them.

“Injecting cement and other binders into the ground has a number of irreversible environmental drawbacks. It also typically requires high pressures and significant interconnected amounts of energy.”

Turning ions into glue

To bypass these issues, Rotta Loria and his team developed a simpler technique, inspired by coral and mollusks. Seawater naturally contains a myriad of ions and dissolved minerals. When a mild electrical current (2 to 3 volts) is applied to the water, it triggers chemical reactions. This converts some of these constituents into solid calcium carbonate — the same mineral mollusks use to build their shells. Likewise, with a slightly higher voltage (4 volts), these constituents can be predominantly converted into magnesium hydroxide and hydromagnesite, a ubiquitous mineral found in various stones.

When these minerals coalesce in the presence of sand, they act like a glue, binding the sand particles together. In the laboratory, the process also worked with all types of sands — from common silica and calcareous sands to iron sands, which are often found near volcanoes.

“After being treated, the sand looks like a rock,” Rotta Loria said. “It is still and solid, instead of granular and incohesive. The minerals themselves are much stronger than concrete, so the resulting sand could become as strong and solid as a sea wall.”

While the minerals form instantaneously after the current is applied, longer electric stimulations garner more substantial results. “We have noticed remarkable outcomes from just a few days of stimulations,” Rotta Loria said. “Then, the treated sand should stay in place, without needing further interventions.”

Ecofriendly and reversible

Rotta Loria predicts the treated sand should keep its durability, protecting coastlines and property for decades.

Rotta Loria also says there is no need to worry negative effects on sea life. The voltages used in the process are too mild to feel. Other researchers have used similar processes to strengthen undersea structures or even restore coral reefs. In those scenarios, no sea critters were harmed.

And, if communities decide they no longer want the solidified sand, Rotta Loria has a solution for that, too, as the process is completely reversible. When the battery’s anode and cathode electrodes are switched, the electricity dissolves the minerals — effectively undoing the process.

“The minerals form because we are locally raising the pH of the seawater around cathodic interfaces,” Rotta Loria said. “If you switch the anode with the cathode, then localized reductions in pH are involved, which dissolve the previously precipitated minerals.”

Competitive cost, countless applications

The process offers an inexpensive alternative to conventional methods. After crunching the numbers, Rotta Loria’s team estimates that his process costs just $3 to $6 per cubic meter of electrically cemented ground. More established, comparable methods, which use binders to adhere and strengthen sand, cost up to $70 for the same unit volume.

Research in Rotta Loria’s lab shows this approach also can heal cracked structures made of reinforced concrete. Much of the existing shoreside infrastructure is made of reinforced concrete, which disintegrates due to complex effects caused by sea-level rise, erosion and extreme weather. And if these structures crack, the new approach bypasses the need to fully rebuild the infrastructure. Instead, one pulse of electricity can heal potentially destructive cracks.

“The applications of this approach are countless,” Rotta Loria said. “We can use it to strengthen the seabed beneath sea walls or stabilize sand dunes and retain unstable soil slopes. We could also use it to strengthen protection structures, marine foundations and so many other things. There are many ways to apply this to protect coastal areas.”

Next, Rotta Loria’s team plans to test the technique outside of the laboratory and on the beach.

The study, “Electrodeposition of calcareous cement from seawater in marine silica sands,” was supported by the Army Research Office (grant number W911NF2210291) and Northwestern’s Center for Engineering Sustainability and Resilience.

Here’s a link to and a citation for the paper,

Electrodeposition of calcareous cement from seawater in marine silica sands by Andony Landivar Macias, Steven D. Jacobsen & Alessandro F. Rotta Loria. Communications Earth & Environment volume 5, Article number: 442 (2024) DOI: https://doi.org/10.1038/s43247-024-01604-3 Published: 22 August 2024

This paper is open access.