Tag: Academic research

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Inside interoception: The hidden sense of how you feel inside

MIT Technology Review Explains: Let our writers untangle the complex, messy world of science and technology to help you understand what’s coming next. You can read more from the series here.

Your brain lives in the dark space of your skull. Yet it knows when the wind lifts the hairs on your skin, when your heart is racing, when your gut tightens with fear.

It’s also, right now, predicting what you’ll read next as your eyes move across this page. It’s picking up signals that help it make sense of what’s happening around you and prepare you to act if you need to stay safe. You aren’t usually aware that your brain is doing all that.

Our senses take in information at a staggering rate—roughly 11 million bits flood in every second from our skin, eyes, ears, and more. That’s nearly three paperback novels’ worth of data every second. Only a sliver reaches our conscious awareness.  Researchers estimate that our conscious minds can process roughly 10 to 60 bits of information per second, about the rate at which you’re reading this sentence. That’s a ratio of about one conscious bit to hundreds of thousands of unconscious bits.

And that’s a mercy. As Moriah Thomason, a neuroscientist at NYU Langone, says, “Thank goodness we’re built like this. There’s a layer of what we have access to in conscious awareness. And then we have a right-under-the-surface amount. There is only a certain amount we are meant to ‘hold in mind’ in order to function successfully.” 

What you are aware of: Your stomach growling when you’re hungry. Your palms sweating before you speak in public. The breath you just took, if you pay attention to it. Even your heartbeat, which some people can sense from the inside without feeling their pulse in their wrist.

Scientists have a word for how we sense ourselves from the inside: interoception. 

The term was coined in 1906 by the British neurophysiologist Charles Sherrington. For most of the 20th century it remained largely confined to textbooks. Today, thanks to a 2021 Nobel Prize and new tools that can map the interoceptive system across the body, the study of this facility is suddenly quite hot. As researchers decode how signals move between body and brain, a clearer picture is starting to take shape—with implications for how we understand and treat conditions from obesity to chronic pain to anxiety.

The field began to take off in the 1990s. In 1994, the neurologist Antonio Damasio published a book with a pointed title: Descartes’ Error. He challenged the historical separation of thinking and feeling, arguing that our ability to choose and act is driven by feelings, and those feelings in turn are shaped by the body’s signals, such as your gut clenching or your skin going clammy. When we lose that connection between feeling and thinking, as one of Damasio’s patients did after surgery to treat a brain tumor, we may still be able to reason with perfect logic about the pros and cons of traveling on a Tuesday or a Wednesday. But without the emotional signals that help us predict what a choice will feel like, our reason spins and circles, and we cannot decide.

A contemporary of Damasio’s, the neuroscientist Bud Craig, spent his career asking one question: How do you feel? He charted how the brain builds an inner map of the body and updates it in real time every moment you are alive.

Think of the captain’s bridge on the USS Enterprise, where a live map displays the status of the ship’s critical systems: oxygen levels, energy availability, hull integrity, shield strength. Another set of indicators senses things outside the ship: asteroid belts, enemy ships, radiation, life signs, and spatial anomalies not yet understood.

Your brain, only about the size of your two fists pressed together, creates a map like this for your entire body, along with a map of the outside world, from data streaming in through your five senses. Together, they feed into your brain’s working model of you in the world, now and across time—where you are, who you are, your expectations for what’s about to happen (based on everything you know), and what all that means for you.

When someone asks “How are you doing?” we consult our maps and report back on our status. We might say we’re happy, depleted, anxious, or energetic. These feelings are always a braid of emotional and physical sensations. They’re what your interoceptive navigational system serves up to your awareness when you sense yourself from the inside.

As we grow up, we learn to interpret what these sensations mean—interpretations that, in turn, can alter our physiology, emotions, and behavior. Research by the psychologist Alia Crum shows that people who embrace a “stress is enhancing” mindset produce more growth hormones than people who have a “stress is debilitating” mindset. They also experience more positive emotions and greater cognitive flexibility.

Language also matters. We learn words for the textures of our feelings—words that then shape how we feel and act. People low in emotional “granularity”—as the psychologist Marc Brackett calls the ability to distinguish between closely related feelings—react more impulsively under stress and are less able to find meaning in difficult experiences. But mindsets and emotional intelligence are malleable. We can learn that “anxious” is different from “terrified,” and we can even reframe how we interpret our body’s sensations. Instead of thinking of the butterflies in our bellies as annoying, we can welcome them as our body’s way of preparing us for a peak performance.

Scientists have long understood that the interoceptive information informing these lived experiences travels via two major systems: nerves and humors (blood and lymph). Now they’re actively studying a third system—the “interstitium,” a network of fluid-filled spaces woven throughout the body’s connective fascia that may also play a role in communication.

But until recently, scientific understanding of this interoceptive system looked like a high-level schematic that left out vital details—how information travels from the outside environment in, how it moves from your body to your brain, and how it is integrated and interpreted within your brain. Researchers are now racing to explore what the neuroscientist Catherine Tallon-Baudry calls this “new continent of awareness.”

The wandering highway

One of the most active areas of research centers on the vagus nerve, the main component of the parasympathetic nervous system and an information highway carrying news from your organs up to your brain and back down to your body. The vagus has become a celebrity nerve, ubiquitous in wellness podcasts and trauma therapy. “Tone your vagus nerve.” “Activate your parasympathetic system.” The language suggests a single thing you can target, like a muscle. The reality, as Steve Liberles at Harvard Medical School is discovering, is far more interesting.

Liberles has spent most of his career mapping what he calls “the great wide unknown” of one of our largest and longest nerves. He speaks the way he works—methodically, without overselling. But the questions driving him are huge. How do we sense our body’s inner state? What information flows through which channels? And how does the brain decide what to do with it?

“When I’m nervous giving a talk in front of a thousand people,” he says, “my heart might race. I might get butterflies in my stomach. I might get goosebumps on my skin.” We all know what he’s talking about.

“It’s bizarre,” he muses. “Your brain has to send a signal to the gut, and then the gut back to the brain, to tell you you’re nervous?” He pauses. “This just shows there is this intimate connectivity between the brain and the body that’s real.”

The vagus is often called the calming nerve, because it controls “rest and digest” functions that quiet our body after the sympathetic nervous system revs us up with “fight or flight” impulses to handle danger or stress. 

But it is also doing something else: It’s listening to us inside. Anatomists have known for over a century that roughly 80% of its fibers carry information upward, from body to brain. Think of it as a two-lane highway with far more traffic headed north. What scientists are just beginning to understand in detail is what those signals are saying. 

Liberles is decoding the vagus with molecular precision and finding that its messaging system is unexpectedly diverse. So far, his research has uncovered dozens of types of vagus nerve cells, each wired to a specific organ. Team Red relays information about the heart; Team Blue, the gut.

Within those teams, each courier has a unique job that’s different from those all its teammates perform. Liberles found 10 types in the lungs alone. Until then, only one lung reflex had ever been identified, in 1868. One nerve courier carries information about breathing rate; another the stretch of your lungs; yet another information about airway threats, like food going down the wrong pipe.

“It’s super exciting to think about what each of these neurons is doing,” he told me in a conversation last fall, a flash of intensity breaking through the calm. “Where does it go in the body? What is it sensing? What is it controlling?”

The doors of the cell

Liberles is mapping the vagus information highways. But highways need on-ramps for signals to enter. For years, one of neurobiology’s biggest mysteries was the molecular on-ramp for our sense of touch.

Somewhere, something in our bodies was converting physical force into an electrical signal that the nervous system could understand. But no one knew how. 

Solving that mystery required a scientist willing to trust a hunch when the data couldn’t show the way. 

Ardem Patapoutian grew up in Lebanon and fled the country’s civil war at 18, landing in Los Angeles, where he delivered pizzas and wrote horoscopes for a local newspaper before falling in love with science at UCLA.

In the 1990s, as a postdoc at the University of California, San Francisco, he became fascinated with our sense of touch—the last of the five major senses not yet understood at the molecular level. The lung stretch signal that Liberles’s vagus neurons carry to the brain? No one had ever figured out how that signal began.

“How do you feel the embrace of a loved one? How do your fingers distinguish one texture of hair from another?” Patapoutian invites us to wonder in his 2021 Nobel Prize lecture. The problem: Most cellular communication works through chemistry. But mechanical force offers no molecule to bind. How does the body translate physical pressure into the electrochemical language that neurons speak?

Scientists knew that the answer had to be an ion channel—a protein gate embedded in cell membranes that opens to let electrically charged particles into the cell. But tracking down the one responsible for touch turned out to be absurdly difficult. Ion channels are a hundred thousandth the size of a cell, invisible to ordinary microscopes. Worse, they don’t resemble each other. You can’t recognize one by its shape or its sequence of amino acids. Even with one right in front of you, nothing would tell you it was there.

At Scripps, where he works now, Patapoutian decided to try an unusual approach. He’d try to find cells that showed sensitivity to touch and destroy their internal genetic blueprint one gene at a time—hunting for the move that would make the cell go numb. It was tedious, expensive, and possibly a dead end. “A lot of people made fun of us,” he says.

Two years in, Patapoutian’s collaborator Bertrand Coste had burned through half his postdoctoral appointment with no results. Patapoutian said: Another 30 genes, and then we decide whether to continue.

What kept them going, Patapoutian told me, was informed intuition. “As you gain more experience, you have this sense of what’s going to work, what’s not going to work. Sometimes the data cannot answer the question of when to stop or when to continue. There has to be another process. If you start trusting it, it gives you an avenue to continue.”

Coste knocked out candidate gene 72. Flatline. The cell had gone numb.

They’d found it—the mechanism behind something you feel every day.

They named the protein they identified PIEZO, from the Greek piezi, meaning pressure. There are two variations, PIEZO1 and PIEZO2, each responsible for sensing different kinds of pressure in the body. They’re elegant in their design—over 2,500 amino acids folded into a three-bladed propeller-shaped gate embedded in cell membranes. When pressure stretches the membrane, the gate opens and electrically charged ions flood through, translating physical pressure into an electrical signal that the brain can understand—all within milliseconds.

Patapoutian calls scientific discovery a dream that survives reality. He won the Nobel Prize in medicine in 2021 for his discovery of PIEZO, sharing the award with David Julius of UCSF for his work on how cells sense temperature. Now researchers are finding PIEZO proteins everywhere—skin, organs, blood vessels, and even red blood cells, where they help the cells squeeze through narrow capillaries. They’re how your brain knows where your hand is in space without looking at it, a sense called proprioception. They’re in plants too, enabling roots to sense pressure as they push down into the earth.

PIEZO was just the beginning. With a $14.5 million grant from the US National Institutes of Health, Patapoutian and his collaborators are now mapping the body’s entire interoceptive system—as many internal senses as he can find, he says.8

Patapoutian has translated his discovery into a unique form of public outreach. At scientific conferences, he sometimes rolls up his sleeve mid-lecture to reveal half his arm covered in ink—a gigantic PIEZO protein in exquisite anatomical detail, its blades spreading across his biceps. Then he flexes. The tattoo flexes with him, the structure bending exactly as the real protein does when pressure opens the gate.

“At a pub or a party,” he explains, smiling, “how else would I demonstrate this beautiful structure?”

Orchestrating the field

Steve Liberles is mapping a major interoception highway. Ardem Patapoutian discovered the gates of touch. Meanwhile, Wen Chen at the National Institutes of Health is pulling the field together, putting neuroscientists, immunologists, physiologists, and clinicians into the same room. The demand, she says, has been enormous.

She tested her pitch at a dinner party with NIH colleagues a few years ago. You’re hungry right now—that’s interoception. You’re thirsty—that’s interoception. Heads nodded as she pointed around the table.

“We can’t have just the brain or just the body,” she told me. “We need to look at the whole person.”

In 2018 she organized a symposium on interoception where Liberles was one of the invitees, along with researchers and practitioners of meditation and yoga. “It was not their thing,” she says, laughing as she recalls how uncomfortable some of the researchers looked. But the practitioners were excited to finally meet scientists who were studying the inner mechanisms of what they did.

That was followed by a series of NIH workshops on interoception that spanned topics from basic science to clinical practice. Patapoutian was the keynote speaker for the first one. 

The NIH began funding scientists to chart the neural circuits of interoception and bringing them together to talk about their findings. Partway through one of these meetings, the equipment failed for an hour. More than 1,000 people stayed online, waiting for it to come back.

“We were shocked at the turnout,” she says. “There was much bigger interest than we could have imagined.”

Chen is now building infrastructure to match the demand: a formal community, funding mechanisms, a venue where cardiologists and neuroscientists and clinicians can all find each other. And she’s redefining the field as she goes; interoception is not a one-way signal from body to brain but a continuous two-way communication system, each direction shaping the other in real time.10   

Liberles’s nervousness on stage is that two-way loop in action. Signals from his racing heart and belly butterflies travel up to the brain, which weaves them into an interpretation: This is anxiety, and this is what to do to handle it. His actions produce fresh signals that the brain reads in light of its ongoing predictions about what will happen next. In the body-brain communication loop, each player constantly updates the other.

I asked Wen what her work on interoception might mean for another inner sense: intuition. “People talk about ‘gut feelings,’” I said. “How does that relate to interoception?”

 “Intuition might be the bridge where interoception moves from unconscious processing to conscious awareness,” she answered. “If that’s true, then intuition is not magic. It’s physiology.”

But it depends on how we read the signals. Intuition is like pain. It tells you something, but it’s not always clear what. “Perhaps we can treat intuition as a source of data,” she says. “Meaningful, but probably not complete.”

“Maybe we can be grounded in both—in feeling and fact.”

Which raises a more personal question: What do you do with the signals your body is sending?

One avenue for exploration is therapeutic intervention—both pharmacological and neural stimulation. Vagal nerve stimulation has treated epilepsy and depression for four decades, but as Liberles puts it, it’s like pressing all the keys on the piano to hit one note. Weight-loss drugs like Ozempic act in part through vagal pathways but can cause nausea as a side effect, because the targeting isn’t precise enough. Map the body’s circuits with enough accuracy and you might hit the note you actually want.

Another area of active research is psychological and behavioral—teaching people how to detect and even shape interoceptive signals. Low interoceptive awareness is linked to mental-health disorders and stress-related physical conditions.11 But like emotional intelligence, it’s not fixed. Researchers are finding that people can boost their body awareness by, for example, learning to detect their heartbeats from the inside—now a common measure of interoceptive awareness.12 Other interventions focus on body-based therapies and conscious activation of the parasympathetic “rest and digest” system to improve emotional and physical well-being. The placebo effect is another example of the mind acting on the body through expectation alone.

The signals we once dismissed as vague feelings—when your gut tightens before you know why, when your body says yes or no before your mind catches up—those are real. How we interpret them and whether we act on them is another frontier.

It’s clear that gut feelings play a role in scientific research, especially when the path forward looks foggy. Patapoutian’s informed intuition kept him and his colleagues going long enough to find PIEZO, a reminder that major discoveries often start with a hunch that is later tested against evidence. Chen puts it well: Maybe we can be grounded in both feeling and fact.

Katherine W. Isaacs is a writer and senior lecturer at the MIT Sloan School of Management. Her teaching and research focus on the intersection of psychology, technology, and innovation. Originally trained as a biologist and later as a social psychologist, she is currently working on a book called Gut Feel, about intuition, interoception, and embodied decision-making.

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Why “reprogramming” is the buzziest approach to reversing aging right now

Earlier this week, Life Biosciences, a biotech company focused on reversing age-related diseases, announced that it had dosed its first volunteer. A person with glaucoma has had an experimental treatment injected straight into their eyeball.

The idea is to try to treat the disease—which can cause vision loss—by regenerating healthy nerves in the eye. But David Sinclair, the chairman and cofounder of the company behind the trial, hopes to go further. If the treatment can reverse glaucoma, perhaps similar treatments can reverse other diseases of aging. Maybe, just maybe, they can reverse aging altogether.

The approach is designed to work by “reprogramming” cells to a younger state. It’s one of many strategies being explored by biotech companies looking to slow and reverse the process of aging. But of all of them, it seems to be the one that is truly taking off.

Aging is complicated. As we get older, we experience so many changes across pretty much all our biological systems. Scientists have tried to categorize these effects. In 2013, one team published a seminal paper describing nine “hallmarks of aging.” That list features many of the processes scientists have attempted to target. But some of those targets have fallen in and out of fashion over the years.

Take telomere attrition, for example. Telomeres are DNA sequences at the ends of our chromosomes, often likened to the plastic caps that stop the ends of our shoelaces from fraying. When cells divide, telomeres shorten until, eventually, the DNA is vulnerable to damage.

When I started reporting on aging, telomere shortening was all the rage. Shrinking telomeres had been linked to age-related diseases of the heart and brain. Shortened telomeres were considered a sign of premature aging. In 2017 Liz Parrish, CEO of the biotech company BioViva, injected herself with an experimental gene therapy that she hoped might lengthen her telomeres.

Then it suddenly seemed to go out of style. Research continued, but all the excitement within the aging and longevity community seemed to move on to another hallmark. (Parrish also continued with self-experimentation; she calls herself “the most genetically modified person on Earth.”)

That hallmark was cellular senescence. This happens when cells stop dividing but don’t die, instead entering a “zombie” state in which they churn out chemicals that can cause harmful inflammation.

Senescent cells gradually accumulate in pretty much every organ studied, where they are thought to contribute to age-related damage. Why not just periodically clear them out? When a team of scientists took that approach in mice in 2011, they found they could delay the onset of age-related conditions like cataracts and hunchback. The treated mice even looked younger.

But when scientists at Unity Biotechnology trialed a similar approach in people with osteoarthritis and an age-related eye condition in the late 2010s and early 2020s, the results were disappointing. The company laid off every employee in May last year and has since shuttered entirely.

Again, that doesn’t mean senolytic drugs that target “zombie cells” won’t work. But it feels as if many in the field have moved on. These days, the buzz is all about ✨reprogramming✨.

The idea here is to essentially return cells to a young state. It’s based on the Nobel Prize–winning discovery that four genetic factors can turn an adult cell into a stem cell, which can be encouraged to develop into pretty much any other cell type.

Some promising studies in mice suggest that this approach might help wind back the clock. It seems to improve tissue healing, restore vision, and even improve learning and memory.

Running parallel to all this research are repeated injections of hundreds of millions of dollars in funding. In 2021, my colleague Antonio Regalado reported on the founding of the biotech company Altos Labs to pursue reprogramming for rejuvenation.

Altos was funded by the billionaire Yuri Milner—reportedly along with Jeff Bezos, among others—to the tune of $3 billion, a previously unheard-of figure for a biotech startup. Other well-funded companies have since sprung up in this space.

There’s Retro Biosciences, for instance, which is pursuing reprogramming (among other approaches) in an effort to add 10 years of healthy life to human lifespans. Retro’s launch was supported by $180 million from OpenAI’s Sam Altman. Last month, the company announced a valuation of $1.8 billion.

NewLimit, another billionaire-backed biotech exploring reprogramming, says it has promising results from research in mice. It plans to trial a drug designed to rejuvenate the liver in people next year. Last week, the company announced it had raised $435 million toward reaching that goal, among others.

Life Biosciences, which was founded by the Harvard biologist David Sinclair, most recently secured $80 million to support its research. The eye trial is now officially underway, but Sinclair also has plans for whole-body rejuvenation. Earlier this week, he told my colleague Antonio that he plans to test a “highly, highly confidential” oral reprogramming drug as part of a $101 million competition organized by the XPrize Foundation. 

Reprogramming has certainly caught the attention of scientists, biotech companies, and investors. Studies in mice are hugely promising. Human trials are launching. And research in the field has billions of dollars’ worth of support.A lot of people in the field are really excited about reprogramming. But it comes with risks. And we still don’t know if it will work. The question now is: Do we finally have a rejuvenation drug within reach? And if not, what will the next research trend look like?

This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here.

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FEEL-GOOD: A Multicenter Trial of a Mindfulness-Based Group Therapy in Young Adults With Early Psychosis

Conditions: Early Onset Psychosis; First Psychotic Episode Within the Last 5 Years; First-episode Psychosis; Schizophrenia Spectrum Disorders (SSD); Psychosis; Psychosis NOS; Randomized Controlled Trial (RCT)

Interventions: Behavioral: FEEL GOOD; Other: Treatment as Usual (TAU)

Sponsors: Stephanie Mehl; German Research Foundation; Universitätsklinikum Hamburg-Eppendorf; Central Institute of Mental Health, Mannheim; University Hospital Augsburg; Ludwig-Maximilians – University of Munich; Charite University, Berlin, Germany; University Hospital of Cologne; Vivantes Klinikum am Urban; Philipps University Marburg

Recruiting
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An Investigator-Initiated, Randomized, Double-Blind, Double-Dummy Study to Evaluate the Adjunctive Effect of CreNeuroS™ CNS Fish Oil Plus Softgels in Patients With Major Depressive Disorder Receiving Escitalopram.

Conditions: Adjunct in the Treatment of Depressive Disorder

Interventions: Combination Product: Escitalopram (as escitalopram oxalate) tablet +CreNeuroSTM CNS Fish Oil Plus Softgels; Combination Product: Escitalopram (as escitalopram oxalate) tablet +Placebo softgels

Sponsors: Sichuan Credit Pharmaceutical Co., Ltd.; Vivotech Research Lab Pvt Ltd

Not yet recruiting
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Advancing Clinical Translational Research for Profound Autism

Autism Spectrum Disorder (ASD) has emerged as a key battleground in the federal assault on science. US government leaders have systematically ignored expert advice, reanimated baseless claims about the causal role of vaccines, forwarded thinly supported hypotheses blaming ASD on parental behavior, and promoted unsubstantiated treatments. This barrage comes at a time when the prospects for dramatic near-term advances in clinical translation, particularly for the severe end of the ASD spectrum, have never been greater.

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Digital Health Monitoring and Intervention Suite for Stress in Frontline Nurses: Prospective Cohort Trial

Background: Stress among health care workers (HCWs) contributes to burnout, workforce attrition, and adverse patient outcomes. Although virtual reality (VR), psychoeducation, ecological momentary assessments (EMAs), and wearables have independently shown promise in stress research, no integrated digital suite has combined controlled stress induction, intervention delivery, and longitudinal real-world monitoring in HCWs. Objective: This study aimed to evaluate the feasibility, engagement, and preliminary effectiveness of a multimodal Digital Health Monitoring and Intervention suite for Stress framework integrating VR simulation, psychoeducation, EMAs, and wearable biometrics. We examined (1) the impact of VR simulation and psychoeducation on stress outcomes and (2) associations between physiological and self-reported mental health outcomes. Methods: Ninety-nine nurses (mean age 33.7, SD 8.9 yr, 87% female) were enrolled in 2023. We conducted a single-arm prospective cohort study (NCT05923398). Using convenience sampling, participants were recruited from social media advertisements, flyers, and email notices distributed through professional listservs. Participants completed ≥2-week baseline monitoring, a single VR session (2 runs separated by a brief psychoeducation intervention), and 12-week follow-up. In-VR stress was assessed using the Subjective Units of Distress Scale (SUDS) and 4-item Moral Injury Outcome Scale (MIOS-4), with synchronous heart rate variability. Longitudinal outcomes included weekly and biweekly EMAs alongside 70 wearable-derived features. Paired tests, aligned rank transform ANOVA, and Pearson correlations informed study objectives, with P values adjusted for multiple comparisons. Qualitative content analysis classified emotional responses during and after VR. Results: VR significantly increased subjective stress across checkpoints in both runs, with attenuation in Run B relative to Run A (all <.001). No significant heart rate variability differences were observed between runs (.15). During VR, 92% (91/99) of participants felt stressed, 36% (36/99) reported anxiety or nervousness, and 51% (50/99)‐78% (77/99) endorsed anger, guilt, shame, and/or betrayal. Most (59/99, 60%) HCWs returned to an emotional baseline post-VR, although 12% (12/99) reported lingering distress. Immediate reliable improvements in anger, guilt, shame, and/or betrayal occurred for 50% (50/99)‐75% (74/99) of participants post intervention. Anxiety (mean −0.53, SD 2.34; .03) and stress (mean −3.05, SD 11.35; .01) decreased 2 weeks post intervention, but were not sustained at 12 weeks. Increased sleep restlessness was the only wearable feature showing significant changes (mean 2.46%, SD 5.43; <.001). In-VR stress correlated with 12-week real-world stress (SUDS: =0.57‐0.58; MIOS-4: =0.58‐0.61; all .01). Data completion exceeded 90%, with 71% achieving full compliance. Conclusions: This study moves beyond single-tool interventions to demonstrate the feasibility and preliminary effectiveness of an integrated, multimodal stress platform within a single coordinated framework. This trial demonstrates high engagement, short-term symptom responsiveness, ecological validity, and emotional safety. The framework provides a scalable model for proactive stress identification, skills training, and implementation in high-risk occupational settings. Randomized controlled trials are needed to establish sustained efficacy and optimize deployment for real-world implementation. Trial Registration: ClinicalTrials.gov NCT05923398; https://clinicaltrials.gov/study/NCT05923398 International Registered Report Identifier (IRRID): RR2-10.2196/54180
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Examining the Social and Mental Health Benefits of Virtual and In-Person Physical Activity Intervention Among Postsecondary Students: Quasi-Experimental Study

Background: Physical activity (PA) is a promising prevention approach for supporting mental health and enhancing social inclusion among postsecondary students. However, it is unclear whether similar outcomes are realized when PA programming is delivered in-person versus virtually. Objective: Using data from a multiphase research project, the purpose of the study was to examine the influence of on-campus PA programming (virtual and in-person delivery) on mental ill health symptoms (ie, anxiety and depression), social inclusion indices (ie, social connectedness, emotional ties, and social relationship quality), and well-being. Three objectives were addressed: (1) to assess pre-post change in symptoms, social inclusion indices, and well-being for virtual and in-person delivery; (2) to evaluate whether outcome change over time differed by delivery mode; and (3) to examine whether change in symptoms and social inclusion indices predicted change in well-being for both delivery modes. Methods: Physically inactive postsecondary students experiencing mental ill health participated in a 6-week structured and supervised PA program. Pre-post intervention data were collected across 3 phases, and the analytical samples included: 1. In-person delivery (n=87; 82%, 69/84 young adults; 86%, 74/86 women; 38%, 33/86 White; 20%, 17/86 Chinese; 86%, 75/87 with mental illness; 2. Virtual delivery (n=62; 69%, 42/61 young adults; 95%, 59/62 women; 34%, 21/62 White; 21%, 13/62 South Asian; 55%, 34/62 with mental illness), and 3. Data from students who received in-person or virtual delivery: (n=92; 67%, 61/91 young adults; 90%, 83/92 women; 32%, 29/92 White; 20%, 18/92 South Asian; 59%, 54/92 with mental illness). Data were analyzed using 2-tailed paired samples tests to address objective 1, a 2 (delivery mode) × 2 (time: pre-post) repeated-measures ANOVA to address objective 2, and hierarchical regression analyses to address objective 3. Results: Both virtual and in-person PA delivery were effective for symptom reduction and social inclusion improvements across all outcomes (<.001), with moderate-to-large effects. There was no significant time × delivery mode (=0.72, ²=0.04, =.60) interaction effect. Change in social inclusion indices explained unique variance in well-being, beyond covariates (gender, mental illness, and ethno-racial identity), and symptom reduction for virtual ( = 0.75, 008001) and in-person ( = 0.72, =0.16, <.001) PA delivery. Conclusions: Online distance learning is increasing across postsecondary settings worldwide, underscoring the need for accessible, technology-enabled mental health prevention interventions. The results provide support for the effectiveness of virtual and in-person PA programming for reducing symptoms of anxiety and depression, while also enhancing social inclusion indices and overall well-being. Social inclusion indices were also a key contributor to improved well-being, emphasizing the relevance of social factors in both virtual and in-person PA-based mental health prevention strategies for postsecondary students.
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Cyclana Bio Is Exploring the Extracellular Matrix to Treat Endometriosis

Despite an estimated 190 million women and girls around the world living with endometriosis, a chronic and painful gynecological condition, no disease-modifying therapy has yet been approved to treat it. Léa Wenger, PhD, and her colleagues at Cyclana Bio are aiming to fix this.

Endometriosis occurs when endometrial tissue grows outside the uterus, causing inflammation, pain, and sometimes scarring and fertility problems. Although this condition was historically neglected in terms of research and development, Cyclana is now one of a small but growing group of companies trying to develop more effective endometriosis treatments. After completing a veterinary degree, Wenger shifted away from clinical practice when she discovered a passion for biomedical research during her PhD at the University of Cambridge. During this time, Wenger was diagnosed with endometriosis, which led her to co-found Cyclana Bio in 2024 with Kevin Chalut, PhD, who was her colleague at Altos Labs at the time.

The company joined the Babraham accelerator program last year and has already raised an oversubscribed £5 million ($6.8 million) pre-seed round. Wenger spoke to Inside Precision Medicine’s senior editor, Helen Albert, about her inspirations, career, and what she and her colleagues are hoping to achieve at Cyclana.

 

Q: What inspired you to become a scientist?

Léa Wenger, PhD
Léa Wenger, PhD

Léa Wenger: I was always very curious as a child. What drove me directly to science, rather than going for any other subjects, was my desire to be a vet. I wanted to be a vet and knew vets needed to know about science, so I decided to learn all the science I could. The irony of that was that I didn’t end up practicing a single day of veterinary medicine, but it got me into the doors of institutions where they teach you veterinary medicine in a way that was very scientific and research-driven. I really discovered a passion for science at that point, a passion for actually understanding things that we don’t know. I was exposed to this idea of driving knowledge where it isn’t present, and that was really what got me excited about research. That’s when I effectively shifted from the veterinary medicine career to the more traditional biomedical research route.

 

Q: What made you decide to go into biotech rather than staying in academia?

Wenger: I think the frustration I had in academia was that the system was set up to do a one-person, one-project type of research. That can be fun in some ways, but for me, it didn’t really address impact in the way that I really wanted it to. I wanted to feel like I was working towards creating discovery, translating it, and being able to improve patient lives. I just felt that biotech was a better conduit for that because it was based on faster-moving collaborative teamwork.

I was working in neurodegeneration at the time and on organoid models made of 3D stem cell-derived complex architectures. Organoid models are incredibly good at reproducing human development. But when you’re looking at neurodegenerative diseases that happen with age, it’s a lot harder. Aging in a dish is really hard to reproduce.

Cyclana Bio scientists
Cyclana Bio scientists working in the LiveLabs laboratory, from left to right, Kevin Chalut, PhD, cso and co-founder, Léa Wenger, PhD, ceo and co-founder,
Siiri Salooma, PhD, founding scientist, and Tom Wyatt, PhD, founding scientist.

It was at exactly then that I wanted to go down this research route in more detail that Altos Labs opened in Cambridge. The company had a thesis of “Let’s try and do real discovery science, deep, groundbreaking science,” but in a biotech environment where you’re much more collaborative. That really attracted me at the time, and so I applied to work there after my PhD. Luckily enough, they took a chance on me and believed in me.

I loved it and I learned a huge amount. Not just in terms of how you build discovery programs from the ground up, but also how you work in a team, how you focus, and how you align incentives in biotech. I think it completely shifted my mindset away from simple academic curiosity to, “How do we drive that curiosity towards impact as quickly as possible?” The bar, in my opinion, is somewhat higher than in academia because you’re not just saying, “Is this good enough to publish?” You’re saying, “Is this a therapy? Is this actually good enough to put into a human and help them and not harm them?”

 

Q: What made you decide to found Cyclana Bio?

Wenger: I was in an epigenetics lab within Altos, and my co-founder was actually one of the group leaders there working on the extracellular matrix. The more I worked with him, the more I realized how massively important it is in guiding how cells behave. You can get completely different responses from a cell depending on what environment it’s in. I got really interested in that interface between the epigenetics, the gene level regulation, and the [extracellular] matrix.

I was doing a lot of discovery science there, but during that time, I also developed endometriosis. I was in my mid-to-late 20s when my symptoms started, and they got worse very quickly. Like every scientist who gets diagnosed with a condition, I nerded out on the disease. In my spare time, I downloaded all the data and looked into what research was there, and very quickly realized that there wasn’t much information available.

There’s not much that we know about the disease and how it happens. People are still debating the causes and drivers of endometriosis. That was interesting and another area of unknown, which has always been what I was attracted to. I’d always been passionate about women’s health, but never really had the opportunity to do something about it.

There’s an easy, non-invasive way of getting access to cells to study endometriosis because menstrual fluid is built and shed every month from your endometrium. It’s built and shed in healthy women, in women with endometriosis, and in women with other conditions. On top of that, biopsies are actually way more common in gynecology than in a lot of other conditions. So I realized this was a huge opportunity to do this tissue-level discovery that we were so passionate about, but for a cause that I really believed in, in a field that was unknown.

I spoke to the CEO at Altos at the time and explained what I wanted to do. He was supportive and thought it was an interesting idea, but ultimately, the indication didn’t align with the priorities of Altos—of looking into age-related diseases. So that’s when we left and started Cyclana Bio.

 

Q: How easy was it to start the company?

Wenger: We were very lucky in that we got into the Babraham accelerator program very quickly, last May. That was important because not only did it give us validation that someone had actually picked us and said this is a good idea, but it also gave us lab space and access.

We did take quite a bit of a risk. Both my co-founder and I left without having raised funding or grants to start the company. For a short while, we were living off our savings and also paying for some very preliminary science and our first scientist to try and get some data going. That was in May [2025], but quite quickly, we got a bit of traction. By July, we had our first investment term sheet because we started fundraising immediately. Then by September, we were oversubscribed. We finalized the closing in October–November for a £5 million pre-seed round.

I think along the way, we basically just had to assume it was going to happen. We were building the company as if we had the money already, although we were always very open with Tom [Wyatt], the scientist who joined us first, about how much funding we had when he joined.

We’re nine people now and have some amazing scientists who have joined the team, including a great CTO who was also at Altos beforehand. We are still growing as we speak. It’s funny how science brings so much more science.

 

Q: What are you trying to achieve at Cyclana?

Wenger: Our main aim is to get at least one therapy that’s truly disease-reversing to the clinic. Based on a lot of research, we know that the extracellular matrix can guide how cells respond. It can act as a sink for particular signal factors. Sometimes it can sequester or deliver things like growth factors or inflammatory signals, but it also massively changes how the cell is interacting with its neighbors.

It’s a key component of a positive runaway effect that happens in lots of chronic inflammatory diseases and in some cancers. A lot of the time, when trying to develop treatments, we focus on the cells and whether we can stop that inflammation. What we think is, if you don’t address problems with the matrix, you are not going to cure the disease. You’re effectively just going to mitigate the side effects, and this matrix is going to act like a memory of the disease. This means that if you stop the treatment, it comes back because the matrix issue hasn’t been solved.

We think that that’s a big element of what’s going wrong with endometriosis. Lesions are removed surgically and then they come back. We really think the diseased extracellular matrix is very much driving the pro-inflammatory phenotype, and that if we don’t address that, we don’t actually get to the point where we are curing the disease. We want to see if we can effectively reverse the phenotypes and if we can effectively get to a cure by stopping this recurrent feedback loop.

We haven’t settled on an exact target or modality yet. We’re exploring a few different targets, and I think based on exactly what mechanism we want to go after, we will determine what the best modality is. We want to be sure about the science, very sure about the target, and then make that target work.

 

Q: Where does precision medicine come into your strategy?

Wenger: Our overall strategy is based on how we see endometriosis as a whole, but I think endometriosis hopefully won’t be viewed like that much longer. We hope that there’s going to be much better stratification and classification of the disease, because it manifests very differently in different women.

Although we think the extracellular matrix might be a common mechanism, we’re building a research platform where we will hopefully find out for sure because we’re collecting data. We’ve got an ongoing observational clinical study where we’re collecting biopsy tissue, menstrual fluids, clinical data, and blood from women, either with or without endometriosis.

We’re collecting that data, looking at the tissue, the proteins, and the architecture, but also isolating cells to test in our models. Then, when we start perturbing with particular interventions that we think might reverse the disease’s impact on the matrix or have different effects on the cells, we might start seeing patterns as to which types of women with endometriosis respond well to different treatments.

It’s going pretty well so far, thanks to our clinical collaborators and participants who have donated samples. Menstrual fluid is a very good way of getting samples from seemingly healthy women, because they don’t need to go to the doctor, [they] just send us a sample. We are also collecting tissue biopsies during routine gynecological procedures to minimize invasiveness and inconvenience.

So far, there’s lots of variability, which was what we expected and which is why we want to collect [samples from] a high number of donors. Not because we think that variability is noise, but because variability is signal. It can tell us more about the nuances of the disease in these different manifestations.

 

Q: What has the experience of being a CEO and biotech founder been like so far?

Wenger: It’s definitely been a steep learning curve. I think that’s also why it’s been so fulfilling, because I do love being in an environment where I’m not complacent, where I’m always learning.

To some extent, because we had so much freedom at Altos to drive our own projects, I had exposure already to the pure project management side of science, so that didn’t seem quite as much of a step up.

Obviously, there’s a huge business, commercial, and legal dimension that I never had thought about before. But I have been trying to learn as much as I can, as quickly as I can, from others. One thing that the biotech field is quite good at is volunteering information. You go to any sort of networking event, or you meet someone from the industry, and they are often very willing to talk to you about what they’re interested in, but also about what you’re doing, and give any advice they might have.

I’ve met many people who have helped me along the way and who have shared their opinions with me. I walked in expecting academia to be way more collaborative than the biotech industry, but actually, I’ve been very pleasantly surprised with my experience.

 

Q: Can you share any key learning experiences from the last year?

Wenger: If you have scientific training or you can think in a scientific way, going into the field of business or building a company is somewhat similar. There’s lots of information and lots of alternative paths that you can take, just like in scientific discovery, and there is differently weighted evidence as to which paths are the best ones to take. Once you have a certain amount of information, you can then take the best educated guess. That’s how I’ve gone about building the company. For example, when I started, I was told by a friend, “If you’re starting a biotech, you’re going to need to raise venture capital.” They gave me a book called Venture Deals, which is a very good book that explains how funds work. I read that book and felt I was better equipped to talk to people at the fundraisers. I think the first thing I’d say is, when going into any sort of field, try to really understand how and why that field exists and what are the structures that define its environment. Then you can put context into how people work. As a first-time founder, you might think, “I’m going to find investors, and if they believe in me, they’ll invest.” But there’s so much more to running a venture capital fund. Those things are important to know when framing your discussion.

Something I would do differently is not do everything at once. I left my job, started the company, started the science, started building the network, and started fundraising at the same time. There was always this pressure when I was meeting people that I also had to get them to invest. I think looking back on it, if I could start over, I probably would have spent a few more months trying to build my network and understanding the field better before I started having those investment conversations. It still worked out for us, we still raised funds, but it was stressful. Networking events were very high stakes!

 

Q: How has the endometriosis space changed in recent years?

Wenger: Gedeon Richter purchasing the Celmatix portfolio and backing FimmCyte are very good signs that people are trying again. I think endometriosis has been plagued by failures in clinical trials, and I think now we’re finally seeing some non-hormonal options being tested, which makes me hopeful. Some will fail, some will succeed, and the successes will drive more interest and availability of funding and hopefully, more successes in the future. I’m really looking forward to seeing the results from some of those clinical trials because I think the more solutions we have for women, the better.

 

Q: Is funding in the overall field of women’s health changing for the better?

Wenger: Absolutely. I think the funding environment is more open to women’s health. I think that’s been helped by the World Economic Forum and McKinsey Health Institute driving the message of value there. There is excitement, I think, and more funding, especially privately.

I’m not sure about public funding. I do think that on the public funding side, we have a trend of saying, “We should fund women’s health, let’s look for quick wins.” I think that’s a bit of a problem with any field that’s been somewhat left behind, once we realize that we need to bring it back. The risk will be funding the wrong things or putting too much of the money into solutions that may not be revolutionary because they don’t have the foundational science to back them up.

It can also be easy to get stuck in the valley of death between seed and late-stage funding. But I do think that there are incredible scientists moving into the field, and there are some great companies starting up. So even if there is this bias towards pre-seed or seed funding, you only need a couple of those companies to have some really promising data, and they will be funded. The bar might be higher than in other fields, but if you produce groundbreaking discoveries, there will be money.

 

Q: What advice would you give other new founders starting to build their companies?

Wenger: Just follow your gut and your dream. That’s the most important thing. I started Cyclana because I thought this needed to happen and we needed to look into endometriosis. I thought it was a bit hypocritical of me to think we needed to do something and not do it, despite having the training and the skills to try and find a solution. If you really believe something needs to happen in the world, startups are the best way to feel like you are driving that change and contributing to seeing the change that you want to happen. Whether it succeeds or not, you won’t wake up thinking, “What am I doing this for?” You’ll just be thinking, “I really hope that we don’t fail!”

 

Helen Albert is senior editor at Inside Precision Medicine and a freelance science journalist. Prior to going freelance, she was editor-in-chief at Labiotech, an English-language, digital publication based in Berlin focusing on the European biotech industry. Before moving to Germany, she worked at a range of different science and health-focused publications in London. She was editor of The Biochemist magazine and blog, but also worked as a senior reporter at Springer Nature’s medwireNews for a number of years, as well as freelancing for various international publications. She has written for New Scientist, Chemistry World, Biodesigned, The BMJ, Forbes, Science Business, Cosmos magazine, and GEN. Helen has academic degrees in genetics and anthropology, and also spent some time early in her career working at the Sanger Institute in Cambridge before deciding to move into journalism.

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