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Perseverance, Persistence Key to CAR T Success, Say Ross Prize Winners Carl June and Michel Sadelain

NEW YORK CITY — Patients, colleagues and peers gathered in midtown Manhattan last week to celebrate Carl June, MD, and Michel Sadelain, MD, PhD, who shared the 13th annual Ross Prize in Molecular Medicine.

The prize, which is made possible by the generosity of Feinstein Institutes board vice chairman Jack Ross and his wife, Robin, assistant vice president of principal gifts at the Northwell Foundation, recognizes biomedical scientists whose discoveries have transformed how medicine is practiced. Established in 2013, it is awarded annually through the Feinstein Institutes’ peer-reviewed, open-access journal Molecular Medicine.

June and Sadelain are both well-known in immunotherapy circles but could not disguise their delight at being recognized for their pioneering work in developing CAR T-cell therapy for cancer treatment.

June is an immunologist and cancer researcher at the University of Pennsylvania’s Perelman School of Medicine. He serves as the director of both the Center for Cellular Immunotherapies and the Parker Institute for Cancer Immunotherapy at Penn. Sadelain, who holds dual French and Canadian citizenship, is a professor of medicine at Columbia University’s Vagelos College of Physicians and Surgeons, where he directs the Columbia Initiative in Cell Engineering and Therapy.

With so many people wanting a chance to congratulate and interact with June and Sadelain—some even requesting autographs—it was hard to get more than a few minutes of their time to chat. June told me the award was a “huge honor” personally as well as a great way to recognize the efforts of those who have worked with him over the past three decades. “It’s a great way for the public to learn more about the value of what was initially basic research and how it can actually affect lives,” June said.

Sadelain expressed similar sentiments. ”I’m so fortunate that somebody looked at our work and thought that it warranted such recognition,” he told me. Additionally, the presence of both patients and students “who are curious and have a sense that there is something that that would like to get involved with” at the award ceremony reinforced both the human impact and educational value of his work.

That kind of curiosity coupled with persistence certainly served Sadelain and June well in their careers. An important theme that both honorees acknowledged is that scientific breakthroughs often require decades of dedicated work despite repeated setbacks.

As June noted, prior to 2011, when the first checkpoint inhibitor therapy was approved, and then in 2017, when the first CAR T-cell therapy was approved “there were many decades when cancer immunotherapy was tried and failed.” Multiple disappointing results can make science review boards nervous and cause federal funding sources to dry up. For the CAR T field, things changed once regulators and scientists realized that immunotherapies could work but “that initial paradigm shift” was needed for acceptance, June said.

Sadelain concurred. Scientists entering the field today are far less likely to face the same challenges that he and June and their teams had to contend with. “When we opened the first clinical trials, we couldn’t find patients,” he told me. “Today, there are waiting lists.”

A brief history of CAR T

The first CAR T trial was not in cancer but in HIV. In the 1990s, June’s lab explored the possibility of using T cells to treat the disease which at the time lacked treatments. “My first clinical protocol began when I was in the Navy in Bethesda and it was called RV 100,” he said in his award lecture. The work was done as part of a joint navy/army effort and marked “the first time we gave T cells to patients.”

Carl June, MD, director of the Center for Cellular Immunotherapies and the Parker Institute for Cancer Immunotherapy at University of Pennsylvania, giving his lecture at the 13th annual Ross Prize Awards [Uduak Thomas]
Carl June, MD, director of the Center for Cellular Immunotherapies and the Parker Institute for Cancer Immunotherapy at University of Pennsylvania, giving his lecture at the 13th annual Ross Prize Awards [Uduak Thomas]

For that first protocol, June’s team took patients with late-stage AIDS and expanded their T cells in the lab, without making any genetic modifications. They then infused those cells back into the patients to determine whether they could restore their immune systems.

“We thought it would be pouring fuel on fire” in the sense that “adding T cells back to the patients would cause more HIV replication.” But that did not happen because the scientists expanded the cells in a way that made them resist reinfection by downregulating the HIV co-receptor. The first clinical trial, published in 2002, showed a dose-dependent increase in T-cell counts following the infusions without a corresponding increase in viral load. June and his colleagues conducted three additional trials, which showed that the infused cells survived on average more than 10 years in patients.

Following those trials, June and his team engineered T cells with a receptor composed of the CD4 molecule fused to the CD3 zeta signaling chain of the T-cell receptor. Over the next five years, June’s group ran trials using these first-generation CAR T cells, demonstrating that they were safe and persisted in the body. Those findings provided important safety data as CAR T technology began moving towards oncology applications.

There were of course disappointments along the way. Several studies using the first-generation CARs did not demonstrate clinical benefit in cancer patients (in contrast to HIV patients). Enthusiasm for the technology waned and skepticism about its potential grew. Still June and his collaborators persisted. The second-generation CAR design incorporated a co-stimulatory domain rather than relying solely on CD3 zeta signaling. Specifically, they used 4-1BB in combination with CD3 zeta to target CD19-positive leukemia cells.

And that’s when the tide turned. The first patient treated with this new generation of cells, a 67-year-old man with end-stage leukemia, achieved a complete response. In total, three of the first patients that were treated responded. “We didn’t know if we were really lucky at that time or not, but it was a striking result,” June said.

Today, there are seven FDA-approved CAR T-cell therapies, and more than 60,000 patients have been treated. Several additional products are in development with many different designs being tested in thousands of labs. June closed by presenting some new, unpublished studies including a program in glioblastoma. It’s clear that June’s work is far from done.

Sadelain’s milestones

Sadelain said there were four major milestones that marked efforts to bring CAR T cells to the clinic. First was the development of methods for introducing genes into primary T cells. Before these techniques were available, scientists largely studied genes in leukemia cell lines as a surrogate for normal T cells. As such, critical aspects of T-cell biology remained poorly understood, including how they respond to antigen, when they proliferate, and when they undergo cell death.

Michel Sadelain, MD, PhD. professor of medicine at Columbia University’s Vagelos College of Physicians and Surgeons and director of the Columbia Initiative in Cell Engineering and Therapy, giving his lecture at the 13th Ross Prize Awards [Uduak Thomas].
Michel Sadelain, MD, PhD. professor of medicine at Columbia University’s Vagelos College of Physicians and Surgeons and director of the Columbia Initiative in Cell Engineering and Therapy, giving his lecture at the 13th Ross Prize Awards [Uduak Thomas].

Sadelain’s second milestone was the identification of the gene encoding the CD3 zeta chain, which sparked efforts to engineer fusion receptors that enabled T cells to recognize and kill target cells in a sustained way. Third was identifying a target that could be studied in the lab. Sadelain’s lab settled on CD19, which was known to be expressed in lymphomas and leukemias.

The fourth milestone was less a scientific discovery and more of a realization. If scientists wanted to bring T cells into clinical use, “you had to do it yourself,” Sadelain said. “There was no industry interested in developing or manufacturing cells as medicines.”

While CAR T-cell therapies today are spreading beyond cancer to other disease areas, there are still challenges to solve in oncology. CAR T cells do not yet work well in solid tumors, Sadelain said. Despite some promising clinical results, “it’s clear that what had been designed for these blood cancers cannot be applied exactly as is to solid tumors,” Sadelain said. “They can be applied exactly as is to autoimmunity perhaps but not solid tumors.”

Sadelain said the first challenge is the T cell itself. Once the engineered cells are released into the patient’s bloodstream, they have to reach the tumor and penetrate its defenses, which is not easy. Even if they are able to penetrate the tumor, they may not work because tumors have evolved mechanisms to shut off the immune response in order to survive. “The good news is that many of these mechanisms are understood today,” so the next step is to figure out how to engineer T cells that can overcome these mechanisms.

Other challenges include identifying suitable targets and developing ways to support the CAR T cells to ensure they persist. Lastly, scientists need a way to manufacture these cells at sufficient scale to make treatments more affordable and accessible. It may be possible to lower the cost to patients through better reimbursement or policy changes “but some of that can be improved through biology.”

Sadelain went on to describe three CAR designs that go beyond the foundation models and could be the treatments of the future. These designs aim to improve on some previous shortcomings, including a longer lifespan and requiring orders of magnitude lower doses than their predecessors. Sadelain closed by noting that it took nearly four decades for the field to get from “the very first ideas to where we are today,” but “it’s not static by any means.”

“These molecules keep getting better and better, and that’s why we are optimistic,” he said. Moving forward, “we need persistence combined with potency. We need greater sensitivity. I think many of these beautiful receptors are on the way to deliver these results.”

From discovery to deployment

Following the awards, I spoke with Kevin Tracey, MD, president and CEO of the Feinstein Institutes. He told me that the Ross Prize celebrates the complete scientific journey from discovery to deployment. “We live in a time where we benefit from all the work that came before us by brilliant people who used science and medicine and technology to eradicate diseases that some people have never even heard of and will never see,” he said. “But somehow, some of that of the importance and the optimism of that gets lost in the modern era we’re living in.”

Established in 2013, Tracey said the Ross Prize is unique because it celebrates that “rare individual who sets out to solve a problem, to cure a disease” and “stays with the entire process from discovery to development to deployment.” Sadelain and June “have lived that for decades,” Tracey said. Tens of thousands of people “are alive because of what these two men did and all of their colleagues.”

But the Ross Prize is also important at a time of rising anti-science sentiments, amplified by some news media and social media platforms. “What we’re losing is the tradition of storytelling and the creation of stories and themes that bind us all together for a common good. Stories have to be told or they are lost,” he said. The Ross Prize is “an opportunity to tell those stories and to celebrate that excellence.”

While the prize has always focused on rewarding excellence in science that forms the basis of new therapies, Tracey told me that over the past five years or so, the focus has expanded from basic research to include research that has made it into clinical use. There are many worthy science prizes that recognize “very elegant science,” Tracey said. But much of the downstream utility of that early science is “maybe decades in the making, and we decided to focus on the small number of times it actually does go the whole way. Those people deserve a prize too!”

Decisions about the awardees each year are made by committee, with representatives from multiple institutions. It has always been a tough decision selecting a few winners from the hundreds of nominations, Tracey acknowledged, “but we always come to a consensus.”

The next transformative therapy

The transformation from risky experimental therapy to standard of care for some cancers demonstrates how scientific consensus can completely reverse. These days, the future is certainly bright for immunotherapies far beyond its original oncology focus.

Both honorees expressed excitement about the possibilities while maintaining an awareness of practical limitations and reiterating the need for continued research. “I think basically all blood cancers will be treated with some kind of cell therapy,” June predicted. “That’s more of an engineering problem now.” Where advances are still needed, he said, is in similar therapies for solid cancers, something that both he and Sadelain are working on with their respective teams.

Asked whether in vivo CAR T-cell therapy could be the next transformative therapy, June said: “It’s very early. Just two months ago, the first in vivo CAR T cells were reported, and they had a mixture of toxicity and efficacy in myeloma, so that’s great.” But “it’s too early now to know how long [they] will last and how safe” they will prove. He also noted the cost savings that in vivo CAR T therapies could offer, not just for cancer. “There are 10 times more people that have autoimmune disease than cancer. If we have a way to make it cheaper and more readily available, that’s what we really need.”

Looking ahead, Sadelain said “there are many new potential directions that are really tantalizing.” There are, of course, many more cancers that need effective treatments, but researchers are starting to look to other areas as well including organ transplantation, neurodegenerative diseases, and infectious diseases.

Among the important questions left to answer is how to produce these cells? “If this starts working for some more common diseases… we’re going to hit a bottleneck,” Sadelain noted. Could allogeneic cells from healthy volunteers be adapted to work for some recipients? Or could we use T-cells made from pluripotent stem cells? “That’s a very interesting direction.” Another “exciting new frontier” is emerging from in vivo studies, although there is still much to learn about their efficacy and toxicity, especially in cases where multiple doses are required.

The Ross Prize committee is already thinking about next year’s honorees. In a few weeks, Tracey said a new batch of emails will be sent to solicit nominations for next year’s awards. The awardees for the 14th Ross Prize will be selected in January 2027.

The post Perseverance, Persistence Key to CAR T Success, Say Ross Prize Winners Carl June and Michel Sadelain appeared first on GEN – Genetic Engineering and Biotechnology News.

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The search for dark matter has been blown wide open

Underneath an Apennine massif, below the Jinping Mountains of Sichuan, and at the bottom of a South Dakota mine, there is a cosmic hunt afoot.

Isolated deep beneath these rocky shields, massive detectors filled with liquid xenon aim to make the first direct detections of dark matter, the long-sought invisible substance whose gravity has sculpted our universe.

The hope is that someday, a bit of dark matter called a weakly interacting massive particle (a WIMP, for short) will collide with a xenon atom, creating a burst of light and electric charge. After running for years, these experiments have recently begun seeing infrequent blips from a particle that glides ethereally through ordinary matter until it crashes into the detectors. Unfortunately, the new signal is not produced by dark matter. Instead, the detectors are picking up on something similarly insubstantial but much more mundane: neutrinos, the featherweight subatomic particles that the sun and other stars produce in massive quantities.

Physicists’ failure to find dark matter where they thought it was has led to a cornucopia of proposals for new ways to search: quantum sensors, liquid-helium-based detectors, searches in Jupiter’s atmosphere, and more.

Physicists have known for decades that this neutrino background was there; they were just hoping to discover WIMP dark matter first. Now the chance is looking slim. Some of today’s WIMP detectors are simply so large and sensitive that they are entering the so-called “neutrino fog,” in which the ordinary particles are likely to drown out any signal from the main target. There is no shielding these detectors from neutrinos, which easily slip through the Earth itself. That means the next experiment to use this long-standing approach for seeking WIMP dark matter may be the last. 

Hitting the neutrino fog does not, however, mean an end to the search for dark matter. Researchers just have to shift the focus of their hunt. “We haven’t seen WIMP dark matter,” says Kathryn Zurek, a theoretical particle physicist at the California Institute of Technology. Nor, she says, have scientists found new particles in the Large Hadron Collider (LHC), the powerful proton-smashing facility that straddles the border between France and Switzerland. “And so people naturally broaden their scope,” Zurek says. As they do, there are plenty more candidates waiting in the wings

In other words, the hunt is transforming from a narrow probe into a kind of free-for-all. It’s a big shift. Today, particle physicists are less sure about dark matter’s identity than when they began looking for it. They’ll freely admit that they cannot presume the basics—for example, if the stuff that makes up dark matter is heavier than the Earth or lighter than a radio wave, or if dark matter is one kind of particle or a dozen. 

The uncertainty can be frustrating, even humbling. “The potential range where the candidates could be is so enormous that the odds of any one small experiment finding it are very, very small,” says Hugh Lippincott, a dark matter experimentalist at the University of California, Santa Barbara. 

But physicists’ failure to find dark matter where they thought it was has also led to a cornucopia of proposals for new ways to search: quantum sensors, liquid-helium-based detectors, searches in Jupiter’s atmosphere, and more. “Now there’s a great deal of excitement. And finally, there’s technology there,” says Gray Rybka, a University of Washington physicist who co-leads an experiment looking for axions, an ultra-lightweight dark matter candidate. 

Still, with so many places to look, where does it make sense for physicists to begin again? 

Astronomical ignorance

For starters: the birth of the universe. Dark matter has been with us since the beginning, and there’s much to learn from those early eons. Maps of the cosmic microwave background—the first light from the universe’s early years—are full of fluctuations caused by the clumpiness of under­lying matter. Reading these cosmic dregs, researchers can tell that only 17% of the matter in the universe is made of ordinary particles like protons and neutrons. The remaining 83% is dark matter, which has little to no interaction with light or ordinary matter other than through gravity.

We can tell quite a bit about dark matter from those gravitational effects. We know that the Milky Way contains a halo of the stuff. Our own solar system orbits the galactic center far too quickly to be bound by the tug of ordinary matter alone: without dark matter’s gravitational tether, we would be flung off into intergalactic space. We can also see how the heft of a galaxy’s dark matter bends the path of light as it makes its way to Earth’s telescopes. And on the grandest scale, we can see how superclusters of galaxies are distributed in space like dewdrops on a spiderweb. No cosmological theory without dark matter can explain all these phenomena. 

But all the astronomical and cosmological evidence has little to say about what dark matter is actually made of. “It does not tell you anything about the individual constituents. It just tells you the effect of a bunch of them together,” says Lippincott, who has led the LZ experiment, a WIMP dark matter detector currently in operation at the former Homestake Mine in South Dakota.

The idea of WIMPs emerged during the 1980s. At the time, theorists were exploring add-ons to the standard model, the overarching theory of particle physics that describes all the universe’s fundamental particles and their interactions. The standard model is powerful but doesn’t account for everything—notably, it omits gravity—so some adjustments seemed necessary. The most popular idea, a class of theories called supersymmetry (SUSY, informally), called for pairing each known particle type in the universe with an as-yet-unseen “super­partner.” To have avoided detection, superpartners would have to have a lot of mass (putting them outside the reach of existing colliders) and be weakly interacting, able to pass ghostlike through matter. That is to say, they would be WIMPs. It didn’t take too long for physicists to realize that the WIMP was also an excellent dark matter candidate: two problems, one particle. 

The appeal of SUSY was so strong that many particle physicists expected to see WIMPs as soon as the LHC turned on in 2008. Instead, as the data came in from the LHC, the most promising SUSY theories were largely ruled out. 

puzzle pieces showing image of detector
The PandaX-4T experiment in China’s Sichuan Province, which started up in 2020, is on the hunt for WIMP dark matter, using a detector filled with ultra-high purity liquid xenon.
ALAMY, GETTY IMAGES; IMAGING BY JANA HEIDENREICH

WIMPs, though, have lived on, no longer tied to the theory that birthed them. And the latest generation of dark matter detectors have kept the hunt alive. After all, Lippincott says, “the motivation to look for dark matter has not gotten any weaker, right?” 

Now it’s looking as if those WIMPs—if they exist—may be beyond our current powers of detection. There are a range of difficulties, but the most pervasive is that when you’re looking for a needle in a haystack, even a few other needle-shaped objects can cloud the search. Interactions between neutrinos and the xenon inside the detectors, while astronomically rare, do just that.

A future, final WIMP experiment would investigate the rest of the places WIMPs could be hiding, even peering into the neutrino fog. An effort called XLZD (a somewhat ungainly acronym reflecting a mashup of existing collaborations) would use 60 to 80 metric tons of liquid xenon, which is about the yearly global production of that rare element and at least six times more xenon than the biggest current detector contains. But it may already have been scuttled, for reasons unrelated to the neutrino fog: At a particle physics meeting in December 2025, the US Department of Energy announced that the US would neither host XLZD nor pay its share of the price tag, which could be well over $300 million. “It may be that the project doesn’t happen at all,” Lippincott says. “And then the US pulling out would have effectively killed it.” 

In the meantime, the hunting ground for dark matter has been expanding dramatically. In 2022, researchers developed an enormous plot showing various candidates for what dark matter is made of and their possible masses. The options fell mainly into two ranges that span about 50 orders of magnitude (that’s 1050, or 10 with 49 more zeroes). At the heavy end of the scale are primordial black holes, hypothetical asteroid-size objects that formed shortly after the Big Bang and might still be floating about the universe. 

But many physicists are most interested in the lightest option: the axion.

Listen closely

Like the WIMP, the axion first emerged as a solution to problems with the standard model. In the axion’s case, it was to address an outstanding question about the strong nuclear force, the fundamental force that holds atomic nuclei together. Axions were proposed by theorists in the 1970s as a mathematical tweak. By adding a particle with a trillionth to a millionth the mass of an electron, they could explain why the strong force seems to behave precisely the same way when it comes to both matter and antimatter even though it doesn’t need to—an unanswered question known as the strong CP problem. 

Axions would be abundant and interact infrequently with ordinary matter, two necessary features for dark matter. Detecting axions is no walk in the cosmic park, though. The delicate particles carry only a hint of energy—about as much as a radio wave. That makes them imperceptible to traditional particle detectors. (Proton collisions at the LHC, for example, pack about a quintillion times more energy.)

Physicists have developed strategies they hope will bear fruit. One of the most promising ideas is to use an ultracold chamber suffused with a strong magnetic field like a radio, tuning it to specific wavelengths. If an axion happens to be resonant, meaning it has the same wavelength as the chamber, it stands the chance of transforming into something far easier to detect: a particle of light. The first full-size detector, called a haloscope, was built at Lawrence Livermore National Laboratory in 1994; today there is a coterie of detectors around the world, with quirky acronymic names like MADMAX and ABRACADABRA.

Fiddling with a cosmic radio to listen for a rare invisible particle is tricky and requires quantum sensors cooled to millikelvin temperatures, a fraction of a degree above absolute zero. Even that doesn’t entirely negate background noise. “At one point, we detected a ‘message from God’ in our experiment,” Rybka tells me wryly. “We looked it up in the FCC allocation of spectrum. It was a religious programming station.” 

So far, particle physicists have combed somewhere between 10% and 20% of the parameter space—the area on a chart showing how massive and interactive dark matter might be—where an axion that solves the strong CP problem might exist. But the search for axions might not end there. Physicists are also looking for axions that don’t address the strong CP problem but could still be dark matter. “More and more people are thinking about models specifically for dark matter, even without connecting that to any other problem,” says Stefania Gori, a theorist at the University of California, Santa Cruz. “Of course,” she says, “if one can solve more than one problem at once, it’s even nicer.”

Quiet revolution

As dark matter has continued to go undetected, physicists have dropped some of their theoretical desiderata. Modern candidates don’t need the convenience of WIMPs or the clean simplicity of axions; they need only fulfill the requirements for dark matter.

The poster child for these unpretentious candidates is low-mass dark matter, so named because it is somewhere between an electron and a proton in weight. If a WIMP is a billiard ball, low-mass dark matter is a ping-pong ball, explains Rouven Essig, a theorist at Stony Brook University. Like a ping-pong ball hitting bowling pins, low-mass dark matter wouldn’t have enough heft to produce a clear signal from a collision with atomic nuclei. “One needed to really come up with new ideas for how one could detect the signals, and then, of course, also new technologies,” says Essig. 

Researchers have designed novel detectors and installed them in underground labs around the world—often right next to their WIMP-detecting forebears. Some of the new machines look for evidence that particles have collided with electrons and ionized them. Others peer into crystals whose lattices should jiggle subtly after a bump from such a particle. There are even proto­types that look for hints in liquid helium, a sensitive superfluid that should throw up a splash when hit by incident dark matter.

puzzle pieces with image of dots arranged to fill a circle
This array of light-sensing photomultiplier tubes was used in XENON1T, a dark matter detector at INFN Gran Sasso National Laboratory in Italy. Its successor, XENONnT, is now in operation and boasts more than eight metric tons of liquid xenon.
XENON COLLABORATION, GETTY IMAGES; IMAGING BY JANA HEIDENREICH

There is, however, a rub: noise. While all experiments in dark matter detection are hampered by noise from the outside world, low-mass searches also suffer from the intrinsic din of their detector mediums. Atomic lattices like those inside crystals are like a crowded subway car, naturally prone to shaking and jostling their electron passengers. It’s not the quiet space you want if you’re looking for dark matter. 

This noise has created challenges. In 2020, a surprising number of what physicists call “excess events” cropped up across a range of detectors looking for low-mass dark matter. Could they, some physicists wondered, be a signal of dark matter? Unfortunately, the noise causing most of these readings has been identified, and the answer is a pretty firm “no.” 

Background noise can come from anywhere: impurities in silicon-based detectors, materials that have spent too long on Earth’s surface (cosmic rays make them lightly radioactive). In one experiment, a crystalline detector was clamped too hard; the extra pressure caused vibrations that looked like evidence of dark matter. “It’s always been true that understanding those backgrounds has been difficult,” says Dan McKinsey, an experimentalist at Lawrence Berkeley National Laboratory. “But we’ve shifted our regime so quickly that suddenly we don’t understand, as a community, what the key backgrounds are.”

Getting a handle on that background noise is key, especially as experiments to detect low-mass dark matter get bigger. In a few years, for example, McKinsey and his colleagues plan to install a number of tabletop experiments in Modane, France, underneath 1,700 meters of solid rock on the Italian border. One of them is a vessel with about a tablespoon of ultracold liquid helium. If a particle of low-mass dark matter impacts the liquid, it will generate a vibration that sprays thousands of helium atoms upward, where silicon detectors will look for microscopic changes in voltage. Other setups will work with sapphire-silica crystals and gallium arsenide, a semiconductor. 

These experiments will help researchers identify the best approaches to use for bigger, more sensitive—and more expensive—detectors. “There’s still lots of ideas, and it’s still not quite clear what’s going to be the best one to really scale up,” Essig says. For now, if it fits on a table and can plausibly detect dark matter, physicists are willing to try it.

The utmost gravity 

The hunting ground for dark matter extends past the surface of any table, or even Earth itself. Some researchers have suggested we look for the stuff not in underground laboratories but on planets, stars, and moons. If dark matter particles occasionally annihilate when they encounter one another, they could ionize hydrogen in the atmosphere of a planet, creating an ultraviolet aurora visible from space. This self-annihilation could also be a strong source of heat—enough to melt a planet’s core. The fact that Earth’s core is solid provides limits for dark matter’s characteristics, and measuring the temperatures of planetary cores more precisely could set even more stringent constraints.

Searching for astrophysical signs of dark matter is not new, but in recent years physicists have become almost artistic with their proposals. One particularly evocative suggestion: looking at the icy ocean of Jupiter’s moon Ganymede. If dark matter is indeed really heavy—possibly a primordial black hole—it could punch through the surface and leave a crater that looks very different from one caused by an asteroid.

Some particle physicists think it would be better to drop all the existing assumptions and refocus. “Everything we know about dark matter has come from its interaction with gravity,” says Caltech’s Zurek. If you concentrate more specifically on that interaction, she says, at least “you’re guaranteed to learn something.” We know how dark matter behaves on the scale of the observable universe as far down as galaxies. “Below that, we really know very little about how dark matter collapses under the weight of gravity,” Zurek says. How, for example, does it clump up on the level of a solar system? 

In recent years physicists have become almost artistic with their proposals. One particularly evocative suggestion: looking at the icy ocean of Jupiter’s moon Ganymede.

This isn’t a “next year” or “next five years” project. The technologies physicists have now are simply not sensitive enough to search for these gravitational interactions. So Zurek is thinking long term. Really long term. “It’s going to take decades, like probably 100 years,” she acknowledges. “It may not be something that I see in my lifetime.” 

Someday—perhaps by monitoring the timing of distant pulsars (the spinning remnants of dead stars) or measuring slight perturbations in gravitational interaction between atoms suspended in lasers—physicists could learn more about dark matter’s true nature. 

For now, the scale of the problem seems daunting, especially compared with the ones particle physicists have tackled in the past. Before the LHC even turned on, for example, those hunting for the Higgs boson had hemmed their quarry in. They knew, from rigorous theoretical calculations and robust experimental measurements, that if the boson existed, it had to weigh between 120 times and 150 times the mass of a proton. Soon after the LHC began smashing protons, the Higgs popped out of the data, right at 133 times the mass of a proton.

Dark matter, by contrast, remains an almost total mystery. Rybka likens guessing about its mass or its interaction strength to “drawing numbers out of a hat.” “We literally don’t even know what the hat looks like,” he adds. 

With this many unknowns, success is far from certain, and the researchers have no illusions. “There’s no discovery guaranteed. You might be wasting your time completely,” Essig says. 

None of this has dissuaded him or others. “That’s just the nature of the problem. We have to search far and wide and explore lots of things,” Essig says. “If you don’t like it, do something else.” 

Dan Garisto is a freelance physics journalist based in Syracuse, New York. 

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Proactive Surveillance Pays Off for Patients with Li-Fraumeni Syndrome

Research presented at the annual conference of the European Society of Human Genetics shows that screening people with the rare, inherited cancer predisposition condition Li-Fraumeni syndrome (LFS) brings both medical benefits and substantial healthcare cost reductions.

The findings “could help inform future discussions about how surveillance protocols for LFS can be further optimized,” said Marion Rolain, a biomedical researcher and engineer in the genetics department at the Centre Hospitalier Universitaire Rouen in France, who presented the research.

“The goal is not necessarily to increase or decrease surveillance, but rather to ensure that screening strategies are as effective, evidence-based and personalized as possible,” she added.

Rolain explained that LFS is caused by pathogenic variants in the TP53 gene, which occur in approximately one in 5,000 to one in 20,000 individuals. It often presents as cancer, particularly rare adrenal or brain tumors, osteosarcoma, soft tissue sarcomas and/or breast cancer, that develops at an unusually young age. LFS is also suspected when a person has multiple primary cancers, including cases of childhood cancer within the same family, with diagnosis confirmed through genetic testing of the TP53 gene.

The high lifetime risk for multiple primary cancers among individuals with LFS means that their care is based on intensive multiorgan surveillance that includes annual whole-body and brain magnetic resonance imaging (MRI), regular clinical examinations of organs at risk, and age- and risk-adapted screening such as abdominal ultrasound, blood pressure measurements, breast MRI in women, and looking for signs of early puberty or virilization caused by potential adrenal tumors in children.

Carla Oliveira, PhD, from the Institute of Research and Innovation in Health at the University of Porto, in Portugal, who coordinated the study as part of the EU PREVENTABLE project, told Inside Precision Medicine that “although surveillance programs for LFS are increasingly implemented, there is still limited real-world evidence on their overall clinical, social, and economic impact.”

Her team wants to better understand and demonstrate the value of proactive prevention, early detection, and specialized care in individuals with hereditary cancer predisposition syndromes, including LFS.

“More broadly, the PREVENTABLE project aims to generate evidence to support a shift from a reactive healthcare model focused on treating advanced cancer to a more proactive approach centered on prevention and earlier diagnosis, when a genetic diagnosis is available,” Oliveira said.

The study included retrospective clinical data from 505 TP53 carriers and 361 non-carrier relatives from seven European countries.

The researchers used standardized French hospital fees to calculate the costs of each individual’s healthcare pathway then compared two groups; those without a prior cancer diagnosis who underwent proactive surveillance with regular screening, and those who received treatment after being diagnosed with cancer.

Among the 155 TP53 carriers (median age 28 years) without a prior cancer diagnosis included in the preventive arm, 18 (11.6%) developed one or more cancers during more than six years of follow-up. The mean cost of prevention was €6047 ($7007) per patient.

In the 273 patients who had already developed cancer prior to genetic testing, (median age 33 years), the mean treatment cost was €53,906 ($62,464) per patient. Within this group, 109 patients had early stage and 164 advanced stage disease.

Rolain noted that as well as a nine-fold lower cost among the patients who received screening before a cancer diagnosis, there were significant improvements in survival among the screened patients.

“From a clinical perspective, our results were not surprising, since intensive screening should enable earlier cancer detection, generally associated with better clinical outcomes. But what is particularly noteworthy is that we have been able to see this reflected in real-world data across several European countries. And we were also struck by the dramatic difference between prevention and treatment costs,” said Rolain.

She added: “While further large-scale prospective studies will be needed to confirm our findings, we believe that they are already sufficient to make the case for investing in early genetic testing in tumor risk syndromes. We have been able to show that catching cancer early or preventing it altogether is not only better for patients, but also for healthcare systems.”

The researchers hope that their study findings will contribute to future refinements of existing guidelines and help improve the balance between early cancer detection and the burden associated with intensive long-term screening for patients with LFS and other rare tumor risk syndromes.

Chair of the conference, Alexandre Reymond, PhD, who was not involved in the research, said: “With ever-increasing health system costs, it is time to change from a predominantly curative mantra and put more emphasis on prevention. This study is a beautiful example of the clinical and economic benefits of the implementation of personalized health care.”

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Philippe Pouletty: Turning Europe’s Life Science Startups Into World Leaders

Jonathan D. Grinstein, PhD, North American Editor of Inside Precision Medicine, hosts a new series called Behind the Breakthroughs that features the people shaping the future of medicine. With each episode, Jonathan gives listeners access to his guests’ motivational tales and visions for this emerging, game-changing field.

Philippe Pouletty, MD, is one of Europe’s most accomplished life sciences entrepreneurs, with a track record of creating category-leading companies in both biotechnology and medical technology. Over more than three decades, he has repeatedly identified breakthrough scientific innovations, assembled world-class teams, and scaled businesses from inception to global prominence.

His most celebrated success is Abivax, the biotechnology company he founded and led as chairman for a decade. Under his leadership, Abivax evolved into a global biotechnology powerhouse, achieving an approximately $10 billion market capitalization after positive Phase III results in 2025. In 2025, the company delivered the strongest stock market performance of any European company across all sectors.

Philippe Pouletty, MD, Co-founder and CEO of Truffle Capital and Co-founder of Abivax and Carvolix. [Truffle Capital]

Today, Philippe Pouletty is applying the same entrepreneurial playbook to Carvolix, a next-generation cardiovascular MedTech company focused on heart valve disease and stroke. Carvolix is built on the strategic combination of breakthrough implant technologies, AI-powered software, and autonomous mini-robotics. The vision follows the successful Abivax model: bring together differentiated technologies, speed up industrialization, build clinical leadership, and create a company that can transform patient outcomes while attracting significant strategic and public-market value.

A physician, scientist, inventor, and venture capitalist, Philippe has founded or co-founded numerous successful life sciences companies and holds dozens of patents, including one of Stanford University’s highest-revenue-generating life sciences inventions. With Abivax and now Carvolix, he has demonstrated a rare ability to build transformative healthcare companies that combine scientific innovation, commercial scale, and lasting impact for patients worldwide.

This interview has been edited for length and clarity.

 

IPM: Having spent time in both Silicon Valley and Europe, what cultural or structural differences have you discovered that have given Europe an advantage in deep tech and life sciences or that may be holding it back when compared to companies in the United States?

Pouletty: In California, financial resources are virtually limitless as long as you have a company with a great mission that addresses large medical needs and markets. Unfortunately, Europe is behind. France is an excellent place to begin, with companies to hire, good engineers, management, and so on. However, raising more than €50 or €60 million is often difficult when compared to the United States. So, things have improved over the last two decades, and there are some good grants and tax breaks available to help businesses raise capital.

However, the stock market in France and Europe is not as competitive as the Nasdaq. So, while I love the United States, many French and European companies must list on Nasdaq in order to grow, remain independent, and eventually reach the commercial stage. Then it becomes an American company, often a large pharmaceutical company or one with significant innovation. Wonderful small company. Let us buy it. So that’s great for the United States and big pharmaceutical companies. However, Europe’s prospects for the next 20 years do not look promising. The challenge for Europe is that competition will primarily come from the United States, China, and, most likely, India.

Europe faces a difficult task in catching up. But, because I’m still a crazy entrepreneur who is interested in European policies, it’s time for France and Europe to do the right thing and establish independent companies. I believe what is of interest is to do things that have an impact on patients. And if you have a positive impact on patients, you will increase shareholder value; however, you should not always focus on doing an IPO or selling the company as soon as possible. What matters is developing completely novel, radical innovation that will change or prolong the lives of patients while also benefiting the environment.

 

IPM: As one of Europe’s standout biotech success stories, what set Abivax apart from the many biotech companies that never scale beyond promising science in Europe before venturing out west?

Pouletty: What we like to do at Abivax and Carvolix is build businesses by merging two or three of our biotech companies when much of the R&D is completed in order to reach critical mass and have several product candidates available. So if one fails, the company is not doomed. To be able to attract extremely experienced management. There are too many very small businesses in Europe. For example, the president, Emmanuel Macron, likes to refer to France as the “startup nation.” The goal should not be to become the startup nation. The goal should be to develop world leaders similar to those in the United States, regardless of sector.

Abivax emerged in 2013. Three of our biotech companies were able to complete a Euronext IPO, which remains the largest biotech IPO on Euronext. We had raised €58 million at the time. Surprisingly, the most advanced product candidate, a drug candidate, failed following the IPO in phase two. So it was unpleasant but not disastrous because the second product candidate, which was only in phase one at the time, is now assembled, has a $7 to $10 billion valuation, and has had excellent results in phase three in treating ulcerative colitis patients.

So, it appears to be a straightforward business plan. It’s not correct. You must stay focused on your mission. Disappointment can occur during pre-clinical R&D and clinical development. Of course, this happens to the majority of biotech companies. And this is why, for example, when sailing across the Atlantic or Pacific, you must keep in mind that reaching the other side requires a strong team; sometimes we change the team and the CEO.

But we are very proud to say that the above acts would not exist without Truffle Capital, and I was chairman of the board for ten years and was very pleased. it looks like the drug should be approved. In the last few days the stock dropped because the long-term maintenance clinical results showed great efficacy and there were very few cancers, which is typical in this kind of patient population with a dysfunctional immune system.

So to me, it’s a little hiccup, but I’m very confident it will change and improve the lives of the patients with ulcerative colitis. Now, maybe the little drop in valuation will boost the M&A appetite of some big pharma companies. And I can send that because, well, not any more shareholders are involved in the epilogue. It’s my personal opinion, of course, about the future. I could be wrong.

 

IPM: How do emerging European companies like Carvolix or Abivax compete with American or Chinese companies? Do you try to establish a market in Europe first, then expand internationally, or do you try to do everything at once? What’s your strategy there?

Pouletty: When Carvolix first launched in the United States, the largest market was heart valve software. So, while launching in the United States with a very concentrated focus team, step by step with specialized centers and then with the market, research based on this successful launch will expand. We may later hire a partner for the United States, or agents or a single partner.

We want our products to be agnostic, regardless of whether the valve is Abivax, Medtronic, or Abbott, so that hospital clinicians can choose which valve system to use for their patients with our software and robot. We will continue to conduct direct sales in Europe, as we have in the past. If you have a highly innovative product, you will need a small, highly technical sales force that can visit clinics, hospitals, and clinicians to be successful in Asia.

 

IPM: How do you get clinicians and hospitals to buy into something like this, which isn’t really an upgrade of their system, but rather the introduction of a whole new line?

Pouletty: At first, we assumed that top-tier cardiologists who treat hundreds or thousands of patients would not require our services. And it will primarily benefit younger, less-trained cardiologists. However, we conducted studies in France with data from the world’s leading cardiologist for aortic valve replacement, as well as in Australia with highly trained cardiologists. They said, “That’s great because I’m less stressed during the implantation.” I may not need a second cardiologist in the room, as is frequently required, and I may see more patients during the day.

It’s somewhat similar to cars. You could argue that autonomous cars will not meet the needs of taxi drivers. But yes, taxi drivers will say, “Great.” I can drive more miles, transport more passengers, and feel more relaxed at the end of the day. I have no doubt that it will become the norm in medium and small hospitals over the next few years. Place special patients in the care of an expert cardiologist. Now for given special patients in the hands of an expert cardiologist, we don’t pretend it will do better. But many more patients who have not the chance, whether it’s hardware replacement or brain stroke treatment to healthcare… will if we are successful.

It is critical to ensure that introducing AI and robotics does not prolong the procedure. It takes roughly the same amount of time or appears to be shorter. However, it is always under clinical supervision. We can take over and stop the procedure, just like on a plane, and carry it out manually. However, after some initial training with a few patients, the clinician will most likely allow the procedure to be completed autonomously while closely monitoring the screen to ensure that everything is running smoothly.

 

IPM: How do European healthcare systems differ in their ability to adopt new biotech and medtech innovations?

Pouletty: No system is perfect. I do a very simple comparison in France and Europe. even patients who do not work will be treated in the hospital at no cost. In the U.S., you’d better have a plan. You’re working in the company to be covered. There is no perfect system. Certainly, pricing of drugs and medical devices in the U.S. is higher, which means that there is an incentive for investors and companies to do high-cost R&D to recoup their investment through high pricing. In France and Europe, there is a tendency to have to push for low pricing and low reimbursement, which is why for oncology drugs more are available and reimbursed in the U.S. today than for non-college products.

But there is not enough emphasis on the long-term impact of innovation. And pioneers often looked at the shorter impact and said, oh, that’s two weeks, let’s say. I’ll give you one example. In oncology, pancreatic cancer is tough because the diagnosis is very often very late when you have big tumors.

It’s very clear that if it were up to me, we would do imaging every two years. We would catch very small, tiny tumors very early on because an anatomical change in our cells within two years could indicate that you need to go and see if you should remove this little tiny one. But that’s not common in practice because it would be expensive to do an MRI every two years on everyone after 50 years old.

So beyond drugs and medical devices and the practice of medicine, how do you do? Preventative medicine needs to be greatly improved, and governments are not very good at looking at these approaches to improve healthcare. So, I went into politics. I would turn on that. I decided 25 years ago I would not run for any elected office and focus more on starting companies.

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Organs-on-a-Chip Offer “Elegant Solution” to Quandary of Animal Models in Drug Design

To the untrained eye, the chip is a piece of clear silicone about the size of a AA battery. Crisscrossing chambers within house hot pink and electric blue liquids that neatly cascade toward the device’s beveled edges.

Yet inside, invisible without a microscope, is the replicated microenvironment of a human liver. The pink and blue rivulets, each a millimeter wide, are endothelial and epithelial channels, respectively. Between them dance immune, stellate, and endothelial cells, complete with extracellular matrices and a membrane, hepatocytes galore. Together, they comprise the quad-culture model of Emulate’s Liver-Chip S1.

Lorna Ewart
Lorna Ewart, PhD
CSO, Emulate

“When you first look at it, you’re like, ‘That does this?’” said Lorna Ewart, PhD, CSO at Emulate, a Boston-based biotechnology firm specializing in organs-on-a-chip. “The engineering behind it is fairly complex.”

The chip, a marvel of photolithography, is assembled in layers of polydimethylsiloxane. A porous membrane separates the blue upper channel, which has a height of 1 mm, from the pink lower channel, which stands a mere 0.2 mm tall. Emulate prepares the multicellular framework for purchase and from there, researchers are free to experiment on the tissue-tissue interface in three dimensions.

“It’s a very elegant solution,” Ewart said. “When you place the cells in this device, you are starting to create an environment that feels like home for those cells.”

In the world of drug development, the advantages of organs-on-a-chip over traditional Petri dish cultures go beyond their 3D design, Ewart stressed. Microfluidics are at play, with perfusion the “secret sauce” that mimics human physiology.

“All of your tissues in your body are perfused,” Ewart said. “Recreating that in vivo-like environment is what makes these cells function as if they’re in the body, and therefore gives greater or more predictive data to the user.”

Emulate, whose founders began their work at Harvard University’s Hansjörg Wyss Institute for Biologically Inspired Engineering, is a key player in the explosion of the organ-on-a-chip industry. Valued at $227 million last year, the global market size is projected to soar to $3.4 billion by 2034, according to market research firm Straits Research.

This growth, Ewart said, comes down to one driver: Animal models are poor predictors of drug safety and efficacy

in humans.

Ancient problem meets futuristic solution

The vast majority of drug candidates—90%—fail in clinical trials, according to a 2022 report in the journal Acta Pharmaceutica Sinica B. That doesn’t include those that don’t make it past preclinical testing. The few drugs that are successful typically take more than 10 to 15 years each, and upward of $1 billion to $2 billion to go from discovery to market.

One reason for drugs’ limited success in this costly, lengthy pursuit is the inability of animal models to adequately simulate drug responses in humans.

Since antiquity, humans have relied on animals to help them understand their own anatomy and physiology. Though French chemist Louis Pasteur famously tested the rabies vaccine on animals before successfully doing so in humans in the 1880s, it wasn’t until the passage of the Food, Drug, and Cosmetic Act in 1938 that animal testing became the gold standard in U.S. clinical drug trials.

More than 80 years later, in 2022, the bipartisan Food and Drug Administration (FDA) Modernization Act 2.0 made animal testing optional. The new law encourages drug developers to conduct testing “in vitro, in silico, or in chemico, or a nonhuman in vivo test.” Organs-on-a-chip, which the FDA considers a type of microphysiological system, were listed as one such technology.

The FDA has continued to move away from animal testing. In March 2026, the agency issued draft guidance highlighting new approach methodologies (NAMs)—including organs-on-a-chip—that may be used instead.

“This draft guidance advances our commitment to replace animal testing with human-relevant, scientifically rigorous methods,” Secretary of Health and Human Services Robert F. Kennedy Jr. said in a recent statement. “Clear validation expectations will help modern tools earn regulatory confidence and speed safer, more effective therapies to patients.”

It’s a global effort. The U.K.’s Medicines and Healthcare products Regulatory Agency announced a commitment to “replace, reduce, or refine animal use in medicinal product development.” In Japan, the Pharmaceuticals and Medical Devices Agency established a NAMs Working Group. The Indian government recognizes NAMs as a valid preclinical endeavor.

Donald Ingber, MD, PhD, the scientific founder at Emulate and founding director of the Wyss Institute, has been a step ahead for the better part of two decades. In 2010, he and Dan Dongeun Huh, PhD, now a professor of bioengineering at the University of Pennsylvania and the co-founder and CSO of biotech firm Vivodyne, developed a “breathing” lung-on-a-chip. Their research, published in Science that year, is considered a seminal work in the organ-on-a-chip space.

In a video accompanying a 2010 Harvard Medical School news release about the research, Ingber described the chip as a “little, flexible device” designed “hopefully, someday, to replace animal studies.” Someday has arrived.

The FDA launched the pilot program, Innovative Science and Technology Approaches for New Drugs (ISTAND) in 2020 and adopted it as a permanent initiative in 2025. Part of Ewart’s job is to steer Emulate through this regulatory pathway. In doing so, she confronts one of the biggest hurdles in organ-on-a-chip expansion: standardization.

“When a tool is qualified, it can be used in a regulatory document without the FDA needing to reconsider or reconfirm its suitability,” Ewart said. “It saves the sponsor a lot of time, and it’s an acknowledgement that these tools perform very well. … The data that comes from them, they will use in their risk assessment of a drug as it moves into the clinic.”

Emulate was the first organ-on-a-chip company granted acceptance to ISTAND, Ewart said. The FDA noted its Liver-Chip S1 is designed to predict drug-induced liver injury, a major reason why drugs fail safety testing in trials and are withdrawn from the market.

“We’re in the final phase now of the program,” Ewart said. “Looking forward to trying to obtain qualification in 2027.”

Faster results for patients in need

As they continue their metamorphosis from futuristic concept to laboratory standard, organs-on-a-chip offer researchers and patients an unprecedented bench-to-bedside timeline.

Weiqiang Chen
Weiqiang Chen, PhD
Professor
NYU Tandon School of Engineering

While drugmakers and the general public alike stand to benefit from accelerated drug discovery, Weiqiang Chen, PhD, designs chips for patients who lack the luxury of time. Chen, a professor of biomedical, mechanical, and aerospace engineering at NYU’s Tandon School of Engineering in Brooklyn, helped develop the first immunocompetent leukemia-on-a-chip.

“It’s quite a different type of cancer,” Chen said. Most cancers form solid tumors, but leukemia, a liquid cancer, develops in the bone marrow. “It’s more challenging to generate the microenvironment for leukemia. … It involves a lot of immune cells, immune functions, and immune interactions.”

The leukemia-on-a-chip, commissioned by NYU Langone Health, is circular, roughly the size of a quarter. Green and vermilion pools surround a blue ring at the center. Within that lies a red liquid dot.

“Outside, we have one layer of osteoblasts, the bone cells, and inside are the central sinus and the vasculature and some mesenchymal stem cells,” Chen said. “All the immune cells are located within the vascularized niche, similar to real bone marrow.”

The technology allows Chen and his team at NYU’s Applied Micro-Bioengineering Laboratory to interrogate single cells. They can also observe how the cancer responds to chimeric antigen receptor T-cell therapy in real time—within a patient’s unique immune system.

The chips are constructed using a leukemia patient’s own cells. Meaning, Chen said, the observed therapeutic response is not only more accurate than it would be in an animal model but also patient-specific.

“We can help to identify responders, non-responders, or we can help screen out more efficient combination therapy for the specific patient for precision medicine purposes,” Chen said.

He acknowledged that the process is imperfect, yet strong enough to swiftly guide treatment. The chips take just half a day to build and yield results within weeks.

“We can fill the gap, providing a high throughput and also accelerated screening in three weeks,” Chen said. “We can screen many drugs at the same time.”

Chen pointed out that some patients have a weeks-long window in between chemotherapy and immunotherapy—a time crunch the leukemia-on-a-chip can accommodate.

The lab is also exploring other immunologic uses for organs-on-a-chip, including a lymph node-on-a-chip that can help validate new vaccines. In addition, in March, the NYU Grossman School of Medicine and Sage Bionetworks received a $25-million grant to launch the data hub and coordinating center for the National Institutes of Health’s (NIH) Complement-Animal Research in Experimentation program.

Though Chen will leave NYU in June to become the dean of the new School of Biomedical Engineering at Nanjing University in China, the work continues.

“It’s exciting for us to expand our research in the future to make a real impact,” Chen said.

Bone-deep discoveries, millimeters thin

Nearly 3,000 miles to the west, Avathamsa Athirasala, PhD, an assistant staff scientist at the Oregon Health and Science University (OHSU) in Portland, is studying other aspects of the bone in miniature.

“The bone is different from other tissues in how it feels and what it’s made up of,” she said. “It’s highly mineralized, it’s mechanically stiff, and it’s constantly being remodeled. It has a lot more forces being put on it.”

Avathamsa Athirasala
Avathamsa Athirasala, PhD
Assistant Staff Scientist
Oregon Health and Science University

Athirasala works in the Precision Biofabrication Hub, part of the OHSU Knight Cancer Institute, under founding director Luiz Bertassoni, DDS, PhD. Through their bone-on-a-chip, hub researchers are studying cancer metastasis.

For example, more than 80% of people with advanced prostate cancer experience bone tumors. A $2.5-million NIH grant awarded in April will help Athirasala’s team discover how.

“Some of these tumor cells—why are they attracted to bone? And why do they thrive in bone?” she asked. “Because they have never experienced an environment like bone.”

She added, “Using this model, we are able to try and maybe even understand how cancer progresses, or how it changes as it goes to a new environment.”

Athirasala is also investigating potential uses for the bone-on-a-chip in regenerative therapies. Soldiers, for instance, may have debilitating bone injuries that heal differently from fractures. A scaffold designed to regenerate bone may be a better treatment than a metal implant, and the chip could help evaluate patient reaction.

“What are the first things that the body starts doing in response to a foreign object? There will be inflammatory signals, there will be host stem cells that want to infiltrate in there and start remodeling it,” Athirasala said. “You can actually recreate the temporal aspects of this—what comes first, what comes later—in a chip.”

Problem and promise of precision

Athirasala delights in seeing solutions to biological problems play out before her. Within organs-on-a-chip, cells hold answers. Still, the devices’ possibilities aren’t endless—yet.

Precision medicine applications, in particular, face logistical roadblocks, she said.

“You have to get all the pipelines in place to be able to get patient cells, preserve them long enough, and get them to where the engineers are making these chips and incorporate them in the devices,” Athirasala said.

Preclinical drug testing that replaces animals with organs-on-a-chip is projected to curtail costs in the long run. Emulate, for example, expects its Liver-Chip alone to increase annual research and development productivity in the small-molecule drug development industry by $3 billion. But as with any new technology, for now, the chips themselves and the infrastructure required to sustain them aren’t cheap.

Market intelligence platform IndexBox estimates that in the U.S., single-chip readers cost about $10,000 each, while comprehensive systems that manage microfluidics run as high as $200,000. Chips are priced between $50 and $2,000, with assay kits and reagents hovering around $100 to $500.

Ewart, of Emulate, said the company doesn’t typically publish costs, which vary depending on customer needs.

What’s more, with each institution that builds its own organ-on-a-chip, standardization becomes harder to attain.

“Each one may have their own advantages, but no one can convince each other which one’s better,” said Chen, of NYU. “Without standards, we cannot really push this technology into practical use.”

Andrei Georgescu
Andrei Georgescu, PhD
CEO and Co-founder
Vivodyne

In the absence of device uniformity, Vivodyne, the Penn Engineering spinoff with offices in Philadelphia and outside San Francisco, is tackling the issue of reproducibility. CEO and co-founder Andrei Georgescu, PhD, saw a solution in end-to-end automation.

“If it is possible to scale up the production of these lab-grown tissues, then we have ourselves a substrate for solving what is the most challenging problem now in medicine,” he said, “which is, we don’t know how human biology responds very well to the perturbations that we make on it.”

The result not only eliminates human variation in lab technique but also allows Vivodyne to test more than 10,000 lab-grown tissues at once.

“We shrink what is like a state-of-the-art biotech lab into the footprint of a large desk,” Georgescu said. “Within each of these systems, we have complex confocal microscopy and a fridge and freezer and a robot arm with multiple tools for liquid handling, dispensing, and dosing these tissues, and we grow them within this platform.”

Vivodyne pairs its automated labs with artificial intelligence to create a feedback loop in experimental design, Georgescu said. The idea is to quickly identify druggable targets and pinpoint which drug candidates are most likely to succeed.

While complete bodies-on-a-chip remain a pipe dream, Vivodyne is among the companies investigating how different organs-on-a-chip interact with one another. Orlando-based Hesperos, for one, manufactures a Human-on-a-Chip® that can replicate several organs on a single device. TissUse, of Berlin, is developing multi-organ chips to mirror male and female environments: the HUMIMIC ChipXY and HUMIMIC ChipXX.

The burgeoning field of organ-on-a-chip drug testing lies at the intersection of bioengineering, pharmaceutical regulation, and data science. To Georgescu, at its heart, it’s also reassuringly straightforward.

“Just because biology is complex,” he said, “does not mean it is not already as simple as can be.”

 

Lindsey Leake is an award-winning, independent health reporter based outside Washington, D.C. She spent 15 years as a staff journalist at outlets including Fortune, the USA TODAY Network and Sinclair Broadcast Group. She holds an MA in Science Writing from Johns Hopkins University, an MA in Journalism and Digital Storytelling from American University, and a BA from Princeton University.

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Educational Intervention on Environmentally Responsible Inhaler Prescribing Among French General Practitioners: Pilot Pre-Post Study

<strong>Background:</strong> Climate change is expected to cause more than 250,000 deaths annually by 2050 and could increase the prevalence of asthma and chronic obstructive pulmonary disease (COPD) by up to 30%. Pressurized metered-dose inhalers (pMDIs), primarily delivering short-acting beta-2 agonists, generate 15 to 30 times more greenhouse gas emissions than dry powder or soft mist inhalers. In France, short-acting beta-2 agonist pMDIs account for 95% of reliever therapy prescriptions, despite their limited effectiveness in controlling disease symptoms. <strong>Objective:</strong> This study aimed to evaluate the preliminary educational impact of a single educational session on French general practitioners’ awareness and intended prescribing of lower-carbon inhaler alternatives. <strong>Methods:</strong> We conducted a multicenter, single-group pre-post pilot study among 34 general practitioners from 10 multiprofessional health centers in Eastern Occitanie, France, between March and October 2023. Participants were recruited through convenience sampling. The intervention consisted of a one-time 25-minute face-to-face educational session on environmentally responsible inhaler prescribing, aligned with Global Initiative for Asthma (GINA) and Global Initiative for Chronic Obstructive Lung Disease guidelines. Data were collected using self-administered online questionnaires before the intervention and approximately 3 months later. The questionnaires included 2 clinical vignettes, one on asthma and one on COPD, with 3 prescribing questions each. Responses were categorized according to whether they included a pMDI. Changes in responses between baseline and follow-up were analyzed using the Fisher exact test or chi-square test, as appropriate. <strong>Results:</strong> A total of 34 participants completed the baseline questionnaire. Responses including a pMDI decreased from 70.6% (48/68) to 4% (3/68) for reliever therapy (<i>P</i>&lt;.001) and from 21.3% (29/136) to 4.4% (6/136) for maintenance therapy (<i>P</i>=.003). In asthma scenarios, adherence to GINA recommendations improved, with increased responses including inhaled corticosteroid-formoterol for reliever therapy (6%, 2/34 to 38%, 13/34; <i>P</i>=.001) and maintenance therapy (35%, 24/68 to 56%, 38/68; <i>P</i>=.02). No significant improvements were observed for COPD-related prescribing scenarios. The proportion of participants reporting environmental impact as a factor influencing inhaler choice increased from 3% (1/34) to 51% (18/34). Satisfaction was high, with 93% of participants reporting being very satisfied with the intervention. <strong>Conclusions:</strong> This pilot study suggests that a brief educational intervention may improve general practitioners’ knowledge and intended prescribing of lower-carbon inhaler alternatives, particularly in asthma scenarios. However, the outcomes were based on theoretical clinical vignettes rather than real-world prescribing data, and the study was not designed to assess the safety or clinical effectiveness of changing inhaler prescriptions. Future studies should evaluate sustained changes in real-world prescribing while ensuring individualized, clinically appropriate, and safe inhaler choices.
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Why China is betting on big nuclear reactors

It’s a tale of two nuclear industries.

In China, large reactors are coming together at a stunning pace. The country has nearly doubled its nuclear fleet since 2016, reaching nearly 60 gigawatts of total power capacity. The new facilities are nearly all gigawatt-scale pressurized-water reactors.

Meanwhile, the US has built just two reactors in that time—Unit 3 and Unit 4 at Plant Vogtle in Georgia. Smaller reactors are attracting a lot of excitement and investment, though. A microreactor developer just saw its reactor reach criticality in a new Department of Energy pilot program.

The world is racing to meet rising electricity demand, and many countries are interested in energy sources, like nuclear power, that don’t come with greenhouse-gas emissions. The key question: Which of these strategies will really pay off in terms of getting electrons on the grid quickly?  

Today, the US and France are known as leaders in the nuclear industry. The US has the world’s largest fleet, with France coming in second. France is heavily dependent on nuclear for its grid—about two-thirds of the country’s power comes from nuclear reactors.

But they have hardly added any new reactors to their fleets in recent years. The US can point only to Vogtle, and France connected its latest reactor to the grid in December 2024—the first in over 20 years. 

It’s incredibly difficult to build the massive projects that dominate the nuclear industry today. Up-front investment can run well into the billions, so investors need to wait decades to break even. Designs are complex and can often change during the regulatory process, tacking on cost and time. 

Many are hoping that the key to turning things around in these countries could be smaller reactors.

The idea is that shrinking the footprint of a reactor cuts down the initial investment needed to prove out the new technology. The reactors could even be put together in a factory rather than being built on-site, allowing for a lower price over time.

These smaller reactors are the target of tons of interest and investment in the US, including a new Department of Energy pilot program. The department set a goal last year of having three test reactors reach criticality by July 4, 2026, the nation’s 250th anniversary. (Criticality is the point at which a reactor achieves a self-sustaining chain reaction that can release energy.)

Last week, California-based Antares hit the milestone with its Mark-0 reactor. 

The company plans to eventually build microreactors, designed to produce between 100 kilowatts and 1 megawatt of electricity (large reactors on the grid today are at least 1,000 times that size). The core design is a sodium-cooled reactor, and it uses TRISO fuel, self-contained graphite-coated spheres of a more concentrated fuel than what most reactors use today. 

But there is still a long way to go before it can actually produce power—the Mark-0 doesn’t have any power conversion or heat removal systems. The company plans to produce electricity in late 2027 and deploy in the field by 2028, CEO Jordan Bramble told the Associated Press.

The private sector is interested—and invested—too. Big Tech companies are throwing money at new reactors they hope can help power data centers. 

But look to the other side of the globe, and others are sticking with the established blueprint: China is absolutely churning out large nuclear reactors. Construction started on six new reactors there in 2025, and two more got underway in the first five months of 2026. The country is on course to overtake both the US and the European Union in installed nuclear capacity by 2030.

The speed here is staggering. As of 2024, the average time to build a new reactor in China came in at between five and seven years. The global average is about nine years, and the two most recent reactors in the US took about 15 years.

One key to this speed is standardization: China has set up a uniform project management system to design, license, and build new reactors. They’re built in batches of six or more to take advantage of economies of scale.

It’s one of the ideas meant to give the edge to smaller reactors, but China is working to realize the same benefits for larger projects. A huge amount of government investment is certainly helping.

Larger reactors generally provide more electricity to the grid for a lower price, a key consideration in view of China’s steeply increasing electricity demand. While smaller reactors require less up-front investment than larger ones because of their size, they’ll actually be more expensive per unit of electricity produced. 

That’s not to say China is exclusively focused on big reactors: the country is also expected to see its first operational small modular reactor, the Linglong-1, start sending power to the grid this year.

But looking ahead, it’ll be interesting to see if smaller reactors can help the West keep building new nuclear power. At the moment, with China’s quick progress, it’s looking as if bigger might just be better. 

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