I recently spent four days at the annual Progress Conference in Berkeley, California, organized by the Roots of Progress Institute — an organization whose mission is to create a new philosophy of progress for the 21^st century. 

I usually find conferences pretty soul-sucking: hotel conference rooms, fluorescent lighting, bad food. Trying to snatch a few moments of conversation with friends or colleagues while organizers remind you to clear the hallway and join the official sessions. Sitting in the back of a large ballroom, laptop out, sneaking in a little work while people disguise their own mini-talks as questions for the speaker.

Apparently, I’ve been going to the wrong sort of conferences. 

Progress Conference 2025 was held at Lighthaven, a quirky and very Berkeley space filled with overgrown gardens, conversation nooks, and oddly shaped rooms that felt more like part of an eccentric mansion than a traditional conference center.

But the biggest difference? The people. 

The conference was packed with talks, possibly too much so — compelling sessions sometimes ran concurrently. But the organizers encouraged what they called “the garden track,” blocking out time in the day to mingle in the garden and talk. 

It was hard to define the “type” of person who attended the conference. I connected with third-generation farmers trying to bring progress to agriculture, physicians rethinking health policy, old friends in the urbanism space, and more. There was even a professional conference organizer who wants to advance the way we convene. 

The plenary sessions were as diverse as the attendees. The first main stage event was an interview with Michael Kratsios, Trump’s science advisor and director of the Office of Science and Technology Policy (OSTP). The choice was controversial and emphasized the diversity of the crowd.

I found myself in frequent discussions about the “big tent” feel of the conference and the progress movement in general. Was it too diverse? Too open? Not clear enough on its aims or purpose? It did include a mixed group — and a very mixed bag of topics and viewpoints — but there was a vibe at the conference, a sense of life, a connection that made disagreements feel like opportunities. 

In a plenary session on the second day, Blake Scholl, founder of Boom Supersonic, began to imagine what a better, more comfortable, more convenient airport could look like. Why don’t our airports look like that already? “We live in a world,” he explained, “full of things that are radically improvable, and yet we’ve learned to live with most of the problems.” To this sentiment, the crowd seems uniformly aligned: the big tent, the differing opinions, the differing fields, coming together in the belief that life is radically improvable and that each of us can be a part of that improvement. That each of us can bring about progress. 

It is an inspiring ethos to live in, even just for a long weekend. 

The pursuit of longevity

In the sections of the conference dedicated to health and longevity, the speakers and perspectives were as diverse as the plenaries. Many of the speakers did ostensibly fall under the umbrella of longevity science, and I took the opportunity to explore the topic as an area I’m less familiar with.

Science fiction, of course, includes many examples of extended lifespans, from Heinlein’s Lazarus Long to the reincarnating Time Lords of Doctor Who. But novelists usually focus on the extremes: the eons-old travelers who are functionally immortal compared to our own mere span of decades. Longevity researchers, by and large, chase a more proximal goal. What would an extra year mean to you, if it were a functional and healthy year? What if you could have five more years, or 10? What would it mean for society if people worked an average of 1, 5, or 10 more productive years? 

But that’s still an incredibly broad target. Eradicating a specific childhood disease might have the same, or greater, impact on overall lifespan curves as finding a miracle drug to grant an extra year or two at the end of life to everyone who doesn’t succumb in childhood. The longevity crowd at Progress Conference 2025 played in both arenas: exploring the impact of specific technologies or treatments on longevity, and focusing on aging qua aging as its own disease.

Aging as a disease

Almost every speaker in the longevity group began their talk by sharing how underrepresented aging is in the science funding landscape, with only a small fraction of all science dollars going toward research in the field. 

One challenge with breaking off aging as its own area of inquiry, especially with longevity as an outcome, is that most people don’t die of old age. Most people die of diseases, and many diseases become increasingly common as we age. So the first hurdle for the longevity field is defining its terms. Some speakers imagined how better preventive measures against cardiovascular disease could lead to increased longevity. Is that disease-targeted research or aging-focused?

Although still muddled, the emergence of longevity science as a standalone discipline is an exciting moment in the history of medicine. Throughout most of human history, most people died from a specific injury or disease. Childhood mortality rates were 10% in Europe as recently as 1950. They’re now below 1%, and in the past 75 years, life expectancy has nearly doubled across the world. 

But these trends were not caused by eradicating “aging” — they came from curing or preventing diseases that cut life unnaturally short. The longevity talks, even those beginning with a plea for more focus on the field, oscillated between the potential impact of curing a specific disease and the potential impact of addressing the biological hallmarks of aging itself. Genomic instability, telomere shortening, mitochondrial dysfunction, cellular senescence — the new frontier is a challenge to find targeted interventions that impact these biological hallmarks. Not a cure for an illness, not a repair for an injury. Not the eradication of disease, but the pursuit of life. As the poet Alfred Tennyson wrote so many years ago, it is “…life, not death, for which we pant; More life, and fuller, that I want.” 

Longevity economics

Interspersed with discussions of longevity science were talks on the economics of longevity. How would society change if people, on average, lived even one additional year? Of course, this depends on the quality of that year. Experts estimate that up to 25% of all Medicare spending goes toward treating and supporting beneficiaries during their final year of life. But if we could extend the average number of productive years, with each person working one additional year, the resulting benefit to the global economy would be in the trillions.

Discussing the economics of longevity is a challenge in part because the biggest thieves of productive years of life are specific diseases or injuries. An economic model of all-cause mortality does, by its nature, include all causes of mortality. John Burn-Murdoch, a data analyst and reporter for the Financial Times, hosted a Progress Conference 2025 session focused on the impact of suicide and drug use on longevity in the 20^th century. He argued that the historical trend for longer lifespans is threatened today by social mechanisms that particularly impact young people. 

If longevity science includes funding toward addressing all threats to lifespan in its calculations, it is the most funded field in the world today. If it considers only funding that goes toward addressing biological markers of aging, it is a much smaller tent. But overall, the economists at the conference promoted one conclusion: More life, and fuller, is better for the economy. While the utilitarian argument is not the one that wins me over, it’s good to know that all of our interests are aligned in pursuit of longer, healthier lives.

Putting death on ice

Alongside the more general discussion of longevity science were fascinating deep dives into specific research areas. One of my favorites came from Laura Deming. Unlike most of us, who are only bothered by the idea of growing older when we start to experience the impacts of aging for ourselves, Deming became interested in the problem of aging when she was eight years old. She then began studying biogerontology at 12. Although she has a wide range of longevity interests and research projects, the focus of her talk at the conference was cryonics.

My prior knowledge of the topic consisted of liking Futurama and holding a vague certainty that Walt Disney’s head is frozen in a vault somewhere. (Fun fact: This is apparently an urban legend. Walt Disney was cremated, and it’s an example of the Mandela effect that so many of us think otherwise.) The actual father of cryonics was Robert Ettinger, born in 1918 and himself cryopreserved in 2011. Similar to Deming, he was smitten with the idea of longevity while still quite young. In his case, he fell in love with the stories published in the classic science fiction magazine Amazing Stories. 

Ettinger assumed that by the time he grew up, scientists would discover the secret of immortality. He was already frustrated by what he saw as a lack of progress when he stumbled on reports of a French research team exploring cryopreservation. He began to advocate for the idea that everyone should be cryopreserved for reanimation by a later generation with more advanced medical technology, writing long letters at random to individuals selected from Who’s Who in America. Eventually, he published a book (The Prospect of Immortality) that captured the attention of Isaac Asimov, among others, and rocketed him to media fame.

In her talk, Deming called Ettinger’s plan “an ambulance to the future.” Her case is a compelling one. “One year of medical progress,” she argued, “can increase patient survival from 6-9 months to 10+ years.” And in specific disease cases, like metastatic melanoma or cystic fibrosis, dramatic recent advances mean that people born a year or two apart have dramatically different life expectancies. An ambulance to the future could mean a cure. Her current work is focused on a more proximal goal: cryopreserving organs to extend their viability and enable more transplants. Researchers have already demonstrated that a rat kidney that had been frozen, thawed, and then transplanted into a rat can regain full function. Human trials seem likely.

What’s next?

Most of my writing focuses on the history of medicine and innovators who found cures and solutions to problems that we barely remember today. To sit for four days with people who are so focused on the future, so committed to the next frontier, was an exciting departure. To pursue longevity, not survival — to target aging itself, not a specific disease — is to shift the paradigm of medicine. A transition from less disease to more life. The science is still in its early days, and it’s happening largely along non-traditional paths and with non-traditional funding and support models. In that, it keeps company with many of the true medical breakthroughs in history.  

Coming out of the conference, I look forward to seeing frozen organ banks that enable more transplants, gene therapies that target cellular senescence, and pharmacological interventions that we can take like vitamins to extend the lives of our cells (and ourselves). But my main takeaway from wandering through gardens with longevity researchers? A reminder that human life is an unqualified good. More life is better, and the frontier of medical science is premised on that understanding.

This article Aging as a disease: The rise of longevity science is featured on Big Think.

Consider a gamer playing a game. Maybe one of them is in a room near you right now. You hear periodic outbursts of anger and joy. They’ve been at it for hours. These games might be easy to pick up, but they sure aren’t easy to win. As Atari founder Nolan Bushnell said, “The best games are easy to learn and difficult to master.”

What is it about humans that keeps us glued to a game console for hours on end? One answer is evolutionary: We’re natural problem solvers. This same drive continues to benefit us today. Scientists, for instance, spend years mastering their fields — writing tedious grant proposals, culturing cells for hours, and enduring decades of training. Their persistence leads to better medicine, better technology, a better world.

Games exploit this evolved tendency; they appeal to the ancient circuitry in us that strives to figure things out. Game designers create a virtual embodiment of some kind of problem-solving situation — escaping an enemy, defeating an opponent, making it to the next level, unlocking a skill — and they make it easy and intuitive to start playing. They lure you in with easy wins and progress. But over time, it gets harder and harder, and in the end, to win, you must thread a narrow path through action space, doing just the right things, in the right order, to achieve your goal.

These remarkable parallels can be put to good and surprising use, as I argue in my book, Gaming Cancer. Cancer remains an unsolved problem, and thousands of scientists worldwide are working diligently to make progress in its treatment. What sequence of actions will lead to a better way to block that channel? How can that cell type be detected in early stages? How can that tumor be targeted without harming healthy cells nearby? What treatment will work to eradicate the tumor without making it resistant to the treatment? Scientists, like game players, must thread an incredibly narrow path through action space, but the situation is far more difficult, and it’s not even known if there is any path at all.

This is precisely what games are designed to do: They present players with a situation and a set of possible actions, and then challenge them to find the right sequence to achieve a goal. By leveraging this parallel, we can develop citizen science games and design open challenges that enable everyday people to support scientists on their challenging path. This is the task of citizen science.

The games to be made are not like standard games, where the designers know how the game players’ goals can be achieved. But that’s okay. There have long been genres of games where players did things game designers did not dream of. In fact, that is almost always the case. The creators of chess could not have dreamed of all the innovations the game would inspire. The designers of Pac-Man and Donkey Kong didn’t even know what the highest possible scores were. In those cases, they at least knew the game could be completed; players simply surprised them with new strategies and record-breaking runs. But some puzzles might not even have known solutions, and that can make them even more motivating. No one has figured this out before; I can be the first! So long as the game has clear success conditions, everything else stays the same. We can create games where players attempt to solve problems that have never been solved, utilizing a defined set of tools to engineer something that has never been engineered before.

Consider the following challenge: Build a Lego bridge using a fixed set of pieces to support a large weight. A success condition has been defined, but it’s unclear whether success is achievable. Then open the problem to a crowd, to see if they can discover a solution, or perhaps several solutions. In this way, players can find solutions to a problem that the game designer — or in this case, the challenge designer — was not aware of. (This challenge has actually been done. In an episode of the TV show Lego Masters, teams were tasked with building bridges that could hold 1,000 pounds.)

The idea here, however, is to explicitly place an unsolved problem related to a common concern within the context of a challenge or a game. In fact, there is a long history of games and competitions for public good. Modern canning and jarring techniques originated in part from a reward offered during the French Revolutionary Wars to anyone who could devise a cheap way of preserving large quantities of food. In 1714, British Parliament passed “An Act for providing a Public Reward for such Person or Persons as shall discover the Longitude at Sea,” establishing prizes with payouts tied to improvements in accuracy. The rewards were paid out for over 100 years, and the results had a lasting impact on precision timekeeping.

In the 1970s, my old boss Bob Horn published a series of books describing hundreds of board games and simulations that schools and companies had used to gamify complicated topics, from freeway planning games with hex tile boards to math practice games where students compete to make it to a target location using arithmetic to open-ended games like “Urbanista” (intended for graduate students and urban planners) where different stakeholders representing different interests work to collectively achieve an urban space consistent with their values.

In our era, we have computers, and this has taken the old idea of a game for good or a “serious game” and completely transformed it. The entire domain of modern science is available in game-like interfaces within seconds to anyone interested. The games involve citizens solving problems related to almost every area of science, from identifying celestial bodies (there are only so many human astronomers, and AI has its limits) to transcribing ancient texts to finding new ways to engineer quantum computers.

In the book, I focus on three examples, all of which center on drug discovery: Eterna, Foldit, and Nanocrafter. All three gamify the process of engineering the kinds of molecules that run our bodies. Each game has slightly different mechanics. Foldit is a bonsai-like game where you pull and twist the folds of a protein and see your score rise and fall. EteRNA is a more Sudoku-like discrete game, where an RNA strand is shown as a colored string of beads. Players change the colors and again, watch a score go up and down as they try to create an RNA molecule that does specific things, like fold in one way in the presence of one molecule but in another way in its absence. Nanocrafter, now defunct, was more of an abstracted puzzle game, in which strands of DNA snapped together like puzzle pieces in a sequence of slowed-down chemical reactions, and the objective was to set up a pathway that terminated in a specific sequence of DNA.

EteRNA and Foldit are notable because they have led to actual scientific discoveries that are now in use. An EteRNA challenge (the “OpenVaccine Challenge”) from a few years ago asked game players to help design RNA molecules for COVID vaccines that do not require ultra-cold storage, allowing for easier storage and transport, which is especially crucial in developing parts of the world. Although attribution is tricky, the challenge was a success; vaccines today are more stable at room temperature than they were before.

There’s no reason we can’t take this further with any open problem, including cancer research. Think of it this way: Cancer isn’t just one problem, but a giant tree of interconnected problems. Many of these problems could, at least in principle, be turned into a gamified open challenge. There are thousands of problems relating to cancer, and there are thousands of approaches to game design and genres of game, so the potential is vast. In addition, we have all the powerful tools and techniques of game design at our disposal, tools that didn’t exist at this scale even a decade ago.

I should be clear: It’s not obvious that this strategy will generally allow gamers to solve problems that professional scientists have not (though that could happen, as in the example of cold-storing viruses). But there are additional reasons to pursue this strategy. These games teach players about biology and how the body works — knowledge that could help them make more informed decisions about their health or advocate more effectively for others. Why not slip a little education in? The unusual embodiment of scientific problems in games could also get scientists and others to think about existing problems in new ways.

It’s an empowering thought: Cancer is a terrible foe, but we can fight it in concrete ways. Even without a background in biology, you might have skills in art or design, or just be really good at games. That’s enough to contribute. You could build new games and get us a little closer to a cure, and make people a little smarter along the way.

This article Gaming cancer: How video games and citizen science could help cure disease is featured on Big Think.

Aging is a privilege — one not guaranteed to everyone. Old age and good health often appear to be mutually exclusive paradigms. In Greek mythology, Tithonus was granted immortality by Zeus, but not eternal youth. As he ages, Tithonus laments his progressively frail body and eventually craves his own death. What Tithonus shows us, aside from being careful what we wish for, is the disparity between lifespan and healthspan. That is, not just the number of years we live, but how many of those we are healthy for. The key is optimizing for both, and the power is in our hands more than we realize.

Mainstream medical advice, quite correctly, pulls our focus onto diet, exercise, and sleep as the central pillars of optimal health. However, as interest in the field of longevity grows, we’re learning more about other ways to enhance our health behaviors, some of which are surprisingly easy to incorporate into daily life.

Ultra-processed foods

Good health often lies in what we ingest daily. We all know fruit and vegetables — especially those free from pesticides — are nutritionally favorable, and that the archetypal healthy human likely follows a Mediterranean or plant-predominant diet.

It’s what we consume alongside these “healthy knowns” that might be more concerning. Over time, the ingredients in many supermarket foods have changed, with ultra-processed foods (UPFs) making up a growing share of our diets. Definitions and classifications of UPFs vary, but they are generally identifiable as products you couldn’t make from ingredients in your own kitchen. (Now’s a good time to get familiar with the back of food packets.)

Often, UPFs masquerade as health products — “high protein” or “low fat” items sold under the guise of assisting your journey to supreme health. Certainly, restricting your calories with these products may help you lose weight. But the key question is: “What’s the trade-off here?”

Whole foods reign supreme. Synthetic additives, artificial flavorings, and indecipherable configurations of numbers serving as filler ingredients very likely contribute to poor health outcomes. UPF intake is associated with several cancers, in addition to the known cardiovascular risks of consuming UPFs packed with hidden sugars and fats.

Even over time, not all products are the same. Forty years ago, tomato ketchup likely contained tomatoes, sugar, spices, and perhaps some malt vinegar. Now, you’ll likely find some of these components are subbed out in favor of “E” numbers and lab-created flavorings. So, when Grandma Pam tells you to “eat the Spam” because it’s “what she ate in her day and she’s lived to tell the tale,” you might want to talk to her about UPFs in 2025.

Xenoestrogens

It’s not just the ingredients in our food that we need to scrutinize. In many personal care products, you will find chemicals called xenoestrogens, such as parabens and phthalates. Few of us are immune to the old marketing ruse of displaying seductive models with luscious lips or soft, hairless armpits to flog their latest product. Counterintuitively, opting for renowned higher-end brands carrying heftier price tags does not assure healthier ingredients.

That might not be the fault of the companies. Paradoxically, chemicals that make your hair feel shinier, softer, or even cleaner may actually be harming your health. Xenoestrogens raise concern even at low doses, and they are found in many everyday products, including shampoo, deodorant, and make-up.

We know that oestrogenic overstimulation plays a role in breast carcinogenesis. A 2023 study demonstrated that substituting these products with items free of parabens and phthalates reversed pro-carcinogenic gene expression within 28 days, though whether this translates to long-term health benefits remains to be seen.

Choosing products without xenoestrogens may lower exposure to hormone-disrupting chemicals — a small step that could support long-term health.

Cold water

An area garnering considerable attention is “cold water exposure.” Proponents bask in the adrenaline rush, claiming improved mental clarity and emotional well-being after a cold plunge. Indeed, there is evidence to suggest that exposing yourself to cold water improves metabolic health, amplifies antioxidant defences, and reduces chronic inflammation.

Now, more than ever, the medical field is acknowledging the pivotal role of chronic inflammation in the etiology of disease. A recent study demonstrated that short-term cold acclimation enhanced autophagic responses in young males. Autophagy is the body’s in-house recycling process, removing waste and facilitating cell repair, mechanisms believed to help reduce the risk of age-related diseases.

Some patients with chronic pain report feeling therapeutic benefits, particularly where conventional neuropathic medications have fallen short, though robust clinical evidence remains limited. Anecdotally, some of my patients going through menopause have reported that cold water exposure improves their anxiety and overall well-being.

Cold water exposure can also be entirely exhilarating. There are now local cold water swimming clubs, providing the additional benefit of social connection.

Like many medical practices, cold water exposure is not a “one size fits all” recommendation. It would be prudent to obtain medical advice before embracing this glacial pastime, since many conditions preclude its safety.

The social connection

Humans crave connection. We’re hardwired for it. Historically, operating in groups increased our likelihood of survival. The proverb “it takes a village” is used primarily in relation to childrearing, but also holds true for our well-being and health.

Social connection and support have been shown to improve health outcomes across the board —  from decreasing cardiovascular mortality to improved blood glucose control and even cancer survival rates. Unsurprisingly, social integration is associated with overall improved mental health.

The reverse is also true. That is, social isolation correlates with adverse health outcomes, namely, poorer mental health and increased mortality. This is something to be particularly mindful of with the inescapable passage of time.

Aging leaves us more vulnerable to disease. But with retirement, lost contacts, and the passing of loved ones, our social circle diminishes. Rather than simply submitting to this fate, I often encourage my patients to view retirement as an opportunity to seek out new ventures and meaning (or what the Japanese call “Ikigai”). Whether it’s volunteering, joining a walking group, rediscovering a long-lost hobby, or trying something new, these activities often cover several pillars of health, be it exercise, cognitive stimulation, or social connection.

Stimulate your brain

The good news is that cognitive stimulation can be completely unintentional, yet still beneficial to your health — an inadvertent byproduct of your leisure choices.

Reading has an association with reduced depressive and chronic pain symptoms, as well as combating cognitive impairment. Your job can also prove important. Adjusting for confounding factors, a recent study found that higher cognitive stimulation at work resulted in lower levels of proteins known to be associated with an increased risk of dementia. What you do for a living might make you live longer.

Engaging with word or number games daily has been linked to increased energy and reduced depression, and some studies suggest that regular cognitive challenges may even be associated with lower overall mortality risk. Even if you can only bring yourself to do a Sudoku on the odd occasion, it is still prospectively associated with reduced cognitive impairment.

Social mind games, such as cards and chess, mitigate loneliness and depression, which is not unexpected. But they also support mobility, may help reduce pain, and are linked to a lower risk of cognitive decline — factors associated with Alzheimer’s prevention.

Sustainable change

I often tell my patients that any lifestyle change has to be acceptable, achievable, and sustainable for them. Patient autonomy is paramount, and there’s power in evaluating what merits change in your own life. Certainly, what we’ve discussed cannot usurp the strong evidence in favor of the well-established pillars of health, namely, a healthy diet, regular exercise, and adequate sleep. But perhaps the core insight here is that there are additional mindful choices we can make that are positively impactful to our health. By incorporating small, mindful changes, we can work toward not just a longer life — but a healthier, more fulfilling one.

This article 5 science-backed ways to extend your healthspan is featured on Big Think.

Anyone marginally familiar with psychedelics has heard of magic mushrooms, LSD, or even MDMA. But ibogaine, the psychoactive compound in the Central African shrub Tabernanthe iboga, may not be on many people’s radars. Researchers are beginning to test its efficacy in treating mental health disorders, much in the same way scientists are studying classic psychedelics, with one surprising discovery documented in 2024 by a Stanford research team: The psychedelic may also be able to help treat traumatic brain injury. 

Ibogaine remains a Schedule I substance in the U.S., despite showing promise in treating addiction and PTSD since the 1960s. Still, safety concerns persist, including reports of cardiac arrhythmia and deaths among retreat participants in recent years.

Traditions and treatments

Ibogaine has been used for centuries by indigenous peoples of Gabon, in Central Africa, for initiation rituals. Identified by Westerners in the late 19th century, it was taken to France and used as an ingredient in an anti-addiction tonic called Lambarène. Clinical researchers began to study it formally in the 1960s, and it spread into detox and retreat centers across Europe and the Americas in the 1990s, when research was halted due to health and safety concerns. 

Since the early 2000s, an increasing number of ibogaine retreats have cropped up around the world, while controlled clinical trials remain practically nonexistent. A considerable amount of controversy around the safe and effective use of ibogaine has been stirred up since the 2010 death of a retreat participant forced a clinic to close down in Mexico, where ibogaine remains unregulated. Since then, as reported by Matha Busby for Rolling Stone Magazine, a string of deaths have called into question how responsibly these retreats are operating, and whether clinical science can shed some light on best practice.  

Promise for traumatic brain injury

Existing research has positioned ibogaine as a promising treatment for opioid addiction, PTSD, and — as of last year — brain injuries. In the first study of its kind, a Stanford research team published results in January 2024 detailing the safety, tolerability, and efficacy of ibogaine for treating traumatic brain injury (TBI) in military veterans. 

Of the 30 special operations vets who received treatment, nearly all experienced some level of immediate symptom relief. One month after treatment, the vets reported on average an 88% reduction in PTSD symptoms, an 87% reduction in depression symptoms, and an 81% reduction in anxiety symptoms, compared to pre-treatment. Notably, they also experienced improvements in cognitive function, including concentration, information processing, memory, and impulsivity. 

The vets had traveled to a clinic in Mexico to receive treatment, and were evaluated before and after their sessions. 

“It was a reasonably risky decision,” Nolan Williams, MD, associate professor of psychiatry and behavioral sciences at Stanford Medical School, told Big Think. “Going after a study that a lot of people told me was not the most straightforward scenario for this — trying to evaluate people at Stanford, have them go down to Mexico, come back, get re-evaluated.”

But for Williams, who is in the final stages of sending off an application to the FDA, it’s a meaningful first step toward reviving scientific research on ibogaine. It may also be a giant step forward for TBI, a notoriously difficult disease to cure. Defined as any brain injury that results from an acute physical trauma, it can show up in any number of places in the brain, leading to any number of effects, depending on where the injury occurred. 

“If you had a TBI in your visual cortex, you’d have cortical blindness. If you had a trauma to your mood regulatory circuitry, you’d have depression. Blindness and depression are very different, but they’re both the result of a TBI in that case.” 

And that’s what makes TBI so tricky to treat.

“It’s very hard to design a treatment for a problem that has such a broad repertoire of presentations. But if you’ve got a compound that seems to restore or rewind the time on plasticity and restore function, then it doesn’t matter where the hit was.” 

That’s what his team is starting to see with ibogaine. “The neuroanatomically specific areas may be irrelevant to therapeutic effect, whereas something like local brain stimulation (which I’m a big fan of) is only going to be relevant for the spots you’re stimulating.” 

How does ibogaine treatment work?

Even in 2025, some ideas about psychedelics’ mechanisms of action are overly simplistic, such as the notion that one type of neurotransmitter needs to target one type of receptor. 

“It’s very unlikely that the brain works that way, that you just need to hit one system,” Williams told Big Think. “Ibogaine hits a lot of different systems at the same time. It’s the difference between playing a single instrument and having an orchestra. The orchestra is kind of a simultaneous activation of multiple neurotransmitter systems at the same time that are probably working in concert with each other.” 

Ibogaine affects several key brain chemicals, including serotonin, dopamine, and glutamate. It also seems to boost the brain’s ability to grow and adapt by increasing levels of something called BDNF, a protein that supports brain health. Beyond the biology, the drug can trigger intense, dream-like experiences that many users describe as deeply meaningful or transformative.

Williams says this may be part of the reason why ibogaine has shown promise for treating PTSD.

“It’s sort of an early life emotional re-evaluator drug. You look at these emotionally salient memories, you relive them, you re-understand them. Like the Christmas Carol Scrooge movie, where he goes back and sees his childhood, you’re seeing it from a third-person perspective. That’s really what I think it’s doing.” 

That said, it’s up for debate how relevant the dream-like state is for treating TBI specifically.  

Since the study came out, Williams’ team has evaluated data showing that, at least preliminarily, ibogaine treatment might help to reverse aging in the brain to some extent, though these findings have yet to be peer-reviewed. These effects, which also include cortical thickening and alterations to the emotion regulation system, appear to be durable, lasting up to a year. 

To date, there has never been a prospective trial using a psychedelic to treat TBI. With several papers in review and grant applications in the works, Williams is “just trying to get this going.” So far, there hasn’t been a trial where the drug was administered in the US, he says, because of some of the cardiac risks associated with ibogaine. “They’re rare, but the FDA is aware of it.” 

Meanwhile, initiatives in other states are on the move, with the Texas Ibogaine Initiative advocating for $50 million in state funding to launch the first FDA-approved ibogaine clinical trials in the U.S. 

“My job, and our job, is to be able to educate the people about this psychoactive plant medicine that is absolutely showing a stunning ability to bring people back to normalcy,” former Texas governor Rick Perry said in an interview on the Joe Rogan Experience in January. “To literally give them their lives back.”

This article The overlooked psychedelic that may help treat traumatic brain injury is featured on Big Think.

Once upon a time, a flatworm’s head exploded in a Petri dish — not an especially uncommon occurrence in biological research. But what happened next mystified developmental biologist Michael Levin, who runs the Allen Discovery Lab at Tufts University in Medford, Massachusetts.  

The flatworms, called planaria, had been swimming in a solution of barium chloride, a nasty chemical they had never encountered before in their 500 million years of evolution. A few clogged potassium channels later and the planaria’s cells began to degenerate. 

“Their heads literally explode overnight,” Levin tells Big Think. Several weeks later, their heads had regrown, which isn’t itself unusual: Planaria have highly regenerative capacities, regrowing into fully intact organisms after being cut into hundreds of pieces. They are frequently studied by biologists for this reason. But what Levin’s team did not expect was that, after regrowing a new head, the planaria were no longer intolerant to barium chloride, suggesting they’d modified the expression of their genes to adapt to the new environment. 

“There is no reason why they should have a built-in mechanism for expressing certain genes when they encounter barium; this is a completely novel problem for them,” Levin says, noting that the worms somehow self-selected the right smattering of genes to modulate out of an entire genome. “We don’t know how this works. It’s very interesting to think about how this works.” 

The research hints at a larger idea: Biological systems don’t just passively follow genetic instructions — they adapt. Cells seem to “figure out” solutions to new problems, sometimes in ways scientists can’t yet explain. 

What if medicine could harness this innate healing ability with precision, using technology to direct the body to repair damaged tissues and organs, or even regenerate them entirely?

That’s the fundamental question driving regenerative medicine. About to enter its golden age, the field is coinciding with exciting developments in biology, computational neuroscience, and artificial intelligence to usher in what Tufts University Professor Michael Levin calls a kind of “somatic psychiatry” — and it may just be the future of medicine. 

Regenerative medicine

Regenerative medicine involves replacing or regenerating cells and tissues damaged by injury or disease, often by stimulating the body’s own reparative capacity. The poster child of regenerative medicine is arguably stem cell therapy, where self-renewing cells found naturally throughout the body are repurposed as other cell types to repair damaged tissue. These cells, which can be grown in a lab, can generate new specialized cell types. For example, stem cells found in bone marrow can be coaxed into becoming healthy blood cells. Other stem cells can become bone cells, heart muscle cells, or brain cells. When harnessed to maintain or repair tissue, both adult and embryonic stem cells can help scientists understand and treat disease. Stem cell therapies have already shown success in treating leukemia, lymphoma, neuroblastoma, and multiple myeloma in this way.   

But regenerative medicine is more than stem cell therapy. Technologies like 3D bioprinting, growth factor therapy, tissue engineering with biomaterials, and nanotechnology can help scientists stimulate the body’s healing capacity. 

The field has ventured into uncharted territory with the rise of bioelectric medicine, which focuses on signaling between cells rather than manipulating cells directly. Researchers have found that rather than focusing on the “hardware” of cells themselves, they can reach even greater regenerative goals by leveraging the “software” of how cells communicate, in some cases regenerating entire animal body parts through electrical signaling. Importantly, this works not because scientists tell the body how to regenerate, as is the case with stem cell therapy; they only tell it what to grow and where. The body takes care of the rest on its own. 

In Levin’s lab, research on planaria and other organisms has inspired the team to think differently about how biological systems find creative solutions to problems, and whether humans might have similar, but as of yet untapped, innate capacities. Although most of their work has been in animal models, they’ve made some tantalizing discoveries about regeneration that may someday apply to humans. 

Take the frog tadpole. In one study, after engineering a tadpole specimen without eyes in its head, the team inserted a series of eye precursor cells into its tail and the tadpole grew a functional eye on its tail, which connected to its spinal cord and supported the organism in navigating its environment despite not being connected to its brain. 

“You didn’t need thousands of generations for this to evolve,” Levin stresses, noting that it’s more about the innate plasticity of the organism. “Its architecture is already ready to be scrambled in this way and still have adaptive function, and that has huge implications for evolution.” 

Levin’s team is working on harnessing that innate plasticity to find solutions for a range of diseases, including birth defects, traumatic injury, cancer, and aging. 

“As workers in regenerative medicine, we’d like to know, if a part is missing, how do we recreate it?” Levin says. “As engineers, we want to go further and say, can we push these cells to do something other than what they normally do — can they build something completely different?”

Levin says biomedical science has been fixated on the “hardware” of life — gene editing, CRISPR, and molecular pathways — while largely overlooking the “software”: the bioelectric networks that govern how cells communicate, coordinate, and make decisions.

The endgame he envisions is a platform that interacts with these networks, sending signals that instruct cells to heal, regenerate, and adapt. Rather than manually rewiring genes or engineering tissues, users would input a desired outcome — regenerating a limb, reversing cancer, or prompting the body to form new biological structures — and the system would translate it into bioelectric cues that guide cells to achieve that goal.

Collective intelligence of the body

When or whether scientists will create such a platform remains an open question; scientists still don’t fully understand the complex bioelectric language that cells use to communicate, coordinate, and make decisions. But one reason that bioelectric networks hold promise for treating disease is because they are exactly that: networks. It is easy to overlook the fact that “everything is connected” within the human body, but that’s precisely the point — when things become disconnected, trouble tends to arise. 

In another experiment, Levin’s team showed that when human oncogenes (tumor genes) were injected into a tadpole, they produced tumors. However, when researchers changed the polarization of particular ion channels within the tadpole and those tumor-producing cells were guided into an electrical state of communication with neighboring cells, the chance of tumor development was significantly reduced despite the strong expression of the oncogene.   

Along these lines, Levin calls cancer “a disorder of collective intelligence,” meaning it occurs when cells disconnect from the goals of the larger electrical network of which they are a part. “When they disconnect, they can no longer remember this giant thing they’re working on.” The cells are not more “selfish” than normal cells — they just have smaller selves. This “dissociative identity disorder” leads them to pursue single-cell goals, which quickly get out of hand. Using diagnostics based on a bioelectric signature, future regenerative scientists may be able to detect cells that are about to disconnect from the network and intervene before it’s too late.

“What if we reconnected these cells with their neighbors — not killed them with toxic chemotherapy, just reconnected them?” 

In a way, the approach is more similar to behavior science than biology. Levin compares modern molecular medicine to a mechanical clock, where researchers are focused on “rewiring the hardware.” The assumption, he says, is that tissues and cells are like parts of a clock that need to be manually wired or rewired in a certain way. But what if medicine is more like classical conditioning, or even psychoanalysis? 

“You can change the goals and behaviors of a complex organism just by interacting with it, even once,” Levin says. “You can say to a human, ‘You really should go to grad school’ and they say, ‘Yeah, you’re right’ and then it’s ten years of effort because you said this one thing. You didn’t manually wire all of the possible outcomes of going or not going to grad school and manually set things into motion, or reward or punish them for it; their brains did all of the hypothetical work.”

The assumption that cells and tissues are low-agency things like mechanical clocks, Levin says, has been proven false. Instead, living tissues are what he calls “agential materials”: They have agendas, learning capacities, and memory. The real advances in regenerative medicine, he says, are going to be had by people who make use of this in a way that looks a little like what he calls somatic psychiatry. 

“They’ll need to ask, of cells, things like, ‘What did you learn in your last seven weeks of being a cell that is going to modify how you react to the drug I’m going to give you? Do you believe you’re in a safe environment? How do I get you to believe you’re in a safe environment, because you seem to be under stress all the time and you don’t need to be. You seem to be overthinking your lack of safety here.’”

Of course, researchers haven’t observed language or forward planning in cells, he says, but they have seen forms of memory, learning, decision-making, valence, preferences, and other traits that come from behavior science, not chemistry.

“If you go to any alternative healthcare practitioner, they’ll say to you [things like], ‘The body remembers’ and ‘the wisdom of your cells,’” Levin notes. “They’ve been saying that for thousands of years. What we’ve done — which is consistent with a lot of that stuff — is to take very specific ideas from cognitive and computational neuroscience and to pivot them to non-neural cells and to say, ‘It’s not just a metaphor. It’s not just a beautiful way of speaking. Look, we’ve taken perceptual bistability and active inference and we’re showing you how the cells are actually doing this.’” 

Neuroscientists know that the brain is more than a pile of neurons: Networks work together to support behavior and achieve the organism’s goals. It’s this kind of collective intelligence of the body that his lab is interested in studying.

That said, Levin warns against an overly poetic interpretation of “connectedness” being the answer to humanity’s problems.

“One interesting thing that happens in biology when these systems scale up is that these larger goals in no way guarantee the welfare of the parts.” He gives an example of leaving skin cells on a cliff after you’ve gone rock climbing. “Those cells did not ask to be left on that cliff to die.” When you provide an enforced collective, he explains, you will possibly meet certain large-scale goals at the expense of the welfare of most of the parts. “It works out very badly in practice.” 

Best to keep it in the lab for now.

The future of regenerative medicine

Levin sees regenerative medicine as “having complete control over growth and form” at some point in the not-too-distant future. 

“You should be able to sit in front of a computer and draw exactly what you want — the plant, animal, organ, biobot, whatever” whether it’s a normal heart or a frog with a propeller and wings. “After that, you compile those goals into a set of stimuli that gets the system to build what you want it to build. That’s the endgame.” 

Levin reiterated that this hypothetical “anatomical compiler” would not be a 3D printer for stem cells, molecular pathways, or proteins. Rather, the device would translate your goals into the goals of the tissues and cells.

A separate but not totally unrelated project Levin’s lab is working on is AI as a translation tool — a way to “talk” to cells and tissues, with language. “You should be able to say, ‘Hey liver, why do I feel like crap today?’ and for it to say, ‘Have you seen your potassium levels? And by the way, I’ve talked to the fridge and I know what you’ve been eating, so here’s what I suggest.’” There’s huge potential for using LLMs to interpret intelligence all around you. Just like how we didn’t know there was an electromagnetic spectrum around us. 

For Levin, the future of regenerative medicine is about learning to communicate and collaborate with — and exploit the intelligent capabilities of — the agential material of life. 

“When I put barriers in front of [an organism’s] goals, and they find ingenious ways of getting around what I’ve done and get their goals met anyway — that is intelligence.” 

This article The quest for a “communication device” that tells cells to regenerate the body is featured on Big Think.

When most people hear the name Kellogg, they think of breakfast ce­real. Corn Flakes, Rice Krispies, maybe even Eggo Waffles and Pop-Tarts. Misogynistically removing the clitoris as a punishment, masked as a treatment for female sexual promiscuity and masturbation, is not top of mind. Yet these kinds of moralizing ideas about health—embraced and perpetuated by a health authority of Kellogg’s significance—gave birth to the modern wellness industry and have become rooted in alternative medicine.

In 1878, John Harvey Kellogg and his brother, Will Keith, built some­thing called the Battle Creek Sanitarium. It was once a world-famous med­ical center, spa, and grand hotel, attracting the wealthy and preeminent celebrities of its day. While Will helped run the sanitarium before starting the now multi-billion-dollar Kellogg cereal company, John went on to be­come one of America’s most popular physicians and bestselling authors. The advice dispensed by John in his books, lectures, and Good Health magazine was followed by millions, and in 1921, his research on digestion and diet was nominated for a Nobel Prize.

But amid his brilliance was also folly. He was on a self-appointed, messiah-like mission from God to make the world healthier and was derided by colleagues for his grandiose personality. Many of his ideas blended medical concepts with Seventh-day Adventist Christian beliefs on health reform. The result was a philosophy that natural, wholesome living combined with faith in God made the best medicine.

The term wellness wasn’t even around yet. Instead, to obtain the lifestyle he idealized, John prescribed the precursor to wellness—what he called biologic living. It meant striving for health in mind, body, and spirit to prevent illness, but doing so with three panaceas: physical exercise, adequate sleep, and a diet replete with fruits, grains, vegetables, and milk. Literally every health condi­tion could be treated with that trifecta recipe.

He warned patients against sedentary lifestyles, meat, sugar, caffeine, to­bacco, alcohol, sex, and obesity—the latter of which was considered both a slight against physical attractiveness and a health hazard. He referred to mas­turbation as “self-abuse,” advising that it could lead to mental illness, cancer, and moral destitution. In boys, it was to be treated by circumcision if band­aging their hands didn’t work; in girls, he recommended pure carbolic acid to the clitoris, as well as its removal along with the labia minora of the vulva.

According to medical historian Howard Markel, John was obsessed with cleanliness and virtuous eating. He believed that digestion could be aided by chewing food to oblivion and would guide his dinner guests in a round of the “Chewing Song,” with the chorus beginning, “Chew, chew, chew, that is the thing to do.” He also told his patients they should have four or five odorless bowel movements a day. Occasionally, he would leave social gatherings, only to return with a container of his most recent fecal specimen, and then place it under the noses of his friends to brag about its sweet and odorless quality.

Quirks aside, John was developing and promoting his ideas at the dawn of modern medicine in North America. Something called the Flexner Report of 1910 ushered in this era. The book-length report written by Abraham Flexner embraced rigorous science and its advancement as the new ethos of health care. Although the report raised the quality of medical education, it simultaneously hurt disadvantaged communities by shutting down rural and historically Black medical schools and revising entrance requirements to medical schools that worked against those who were economically un­derprivileged by making them more arduous and expensive. Schools that offered training in alternative medicine—such as naturopathy, homeopathy, and chiropractic—were told to drop it from their curriculum or shut down as well.

By the time John died in 1943, modern medicine was an entrenched sci­entific enterprise. But the aftermath of the Flexner Report left something to be desired. As Thomas Duffy, a professor at the Yale School of Medicine, put it, the hyperfocus on excellence in science was not well balanced by a com­parable push for excellence in clinical care. In other words, some physicians became coldly distanced from patients in a way that allowed nurses and alter­native medicine practitioners to step in and fulfill the warm art of listening, comforting, and humanizing.

In parallel with John’s widespread promotion of biologic living, a man equally eccentric named Bernarr Macfadden was becoming the 20th century’s first celebrity health influencer. He made millions selling Americans a bill of health that consisted of fitness, fasting as a cure-all, and hostility to medical science. Staunchly opposed to vaccination, he would strut around New York barefoot so his soles could absorb the Earth’s energy, and he slept on the floor so his blood flow would align with its natural magnetic rhythm.

In 1899, Bernarr launched Physical Culture magazine, an assortment of articles about health advice alongside photos depicting scantily clad people (often him) showing off their physique. The magazine was a hit, leading to a New York-based publishing empire, and cementing Bernarr as an acclaimed health guru who sold the idea that “a person could exercise un­qualified control over virtually all types of disease” given the willpower to live righteously.

I spoke with family physician and adjunct assistant professor Michelle Cohen, who has written about the legacies of John and Bernarr. “They were two of the most important health promoters of the 20th century and their influence continues into our time,” she told me. “They brought 19th-century ideas of health moralism into a new era of mass marketing and celebrity cul­ture, championing the fantasy that your health could be controlled with a virtuous lifestyle.”

Eating nutritiously and exercising regularly certainly matter for all aspects of health, including mental health and illness. But as Cohen brilliantly articulates, “There’s a huge difference between lifestyle counseling and sel­ling a cure-all based on lifestyle change. The former makes you a healthcare provider, the latter makes you a grifter.”

Cohen also reminds us that “health is not a moral virtue.” It’s damaging when we hear disparaging comments about “lazy” people who “pop pills” and who use medication as a substitute for the hard work of eating “clean” and exercising.

These views especially apply to the nature and treatment of mental illness. Stigma festers and grows in the minds of those who unwittingly internalize the idea that mental illness is a sign of weakness or that taking medication is a personal failing.

The modern wellness industry inherited John’s and Bernarr’s moralizing attitudes toward health. Other historical and cultural threads too wove to­gether to create the juggernaut of an industry that we see today. The fallout from the Flexner Report lingered into the advent of the counterculture move­ment of the 1960s and 1970s. These two social forces synergized anti-medical establishment societal attitudes that propelled patients into the welcoming hands of alternative medicine. Simultaneously, in late-20th-century North America, people were increasingly identifying as consumers and demanding a wide range of choice whenever they spent money. This catalyzed a shop­ping cart approach to health care that magnified the role our own behaviors play in molding our health and led people to downplay the role of genetics and social factors, including plain old bad luck.

Sixteen years following John’s death and 4 years after Bernarr’s, the term wellness, as we use it today, was born. That’s when the so-called father of the wellness movement, biostatistician Halbert L. Dunn, first used the term in the Canadian Journal of Public Health, in 1959. Reminiscent of the distinc­tion between mental illness and mental health, Dunn distinguished between good health—freedom from illness—and high-level wellness, defined as “an integrated method of functioning which is oriented toward maximizing the potential of which the individual is capable, within the environment where he is functioning.”

Dunn’s thoughtful definition didn’t stick. “Wellness” quickly took on a life of its own.

Nowadays in many parts of North America, wellness has sprouted on every corner. Across from your local Starbucks, you’ll see yoga and medi­tation classes interspersed with spa, weight loss, massage, acupuncture, and chiropractic clinics. Employee wellness programs offering subsidized gym memberships for work-life balance and mental health are a click away.

In her book The Gospel of Wellness: Gyms, Gurus, and the False Promise of Self-Care, journalist Rina Raphael laments how there’s no agreed-upon definition of wellness, noting that it’s one reason the industry has grown so big: “Wellness has devolved into an ambiguous marketing term that can just as easily mean activated charcoal toothpaste as it does mindfulness.” It has seemingly ballooned to include anything and everything. Ask one guru what they mean by wellness and receive a different answer from the next.

Within its disorder, there’s paradoxical order. In her analysis of the way that wellness promoters use the rhetorical power of language, associate professor Colleen Derkatch has caught the industry red-handed. In Why Wellness Sells: Natural Health in a Pharmaceutical Culture, she beams a light on two opposing messages that bombard marketing materials and drive sales: On the one hand, we’re told that we need wellness to enhance, boost, and optimize our health; yet on the other, we’re sold products and services designed to treat health conditions and restore what we’re missing. We hear something like “maximize your mental health” by “treating your energy blockages and diet deficiencies.” The term wellness has drifted from Dunn’s definition and morphed into dollar signs, drawing us into a never-ending cycle of enhancing our health by treating problems we didn’t know we had.

The wellness industry is currently valued at a breathtaking $5.6 trillion worldwide, which includes earnings from bona fide resources for healthier living (e.g., sports and exercise classes) as well as alternative medicine products and services. It also includes what’s been dubbed the $181 billion global mental wellness economy, to capture money spent on sleep serv­ices and monitors, meditation and mindfulness resources, supplements for “brain health,” cannabis and psychedelics, and self-help delivered by gurus, coaches, organizations, and apps.

Most perniciously, wellness has come to represent a wonderland free from the constraints of scientific scrutiny. The beating heart of the industry flows with pseudoscience, and to say that it’s lucrative would be an understate­ment. It’s the commercial home to the alternative medicine industry itself, estimated to be worth nearly $200 billion worldwide in 2025. In the United States alone, Americans spend over $30 billion per year on alternative med­icine, and even the homeopathy industry is valued at $1.2 billion, used by an estimated 5 million adults and 1 million children.

The wellness industry owes a great debt to its forefathers. Celebrity doctors and wellness influencers of today resemble modern-era John Kelloggs and Bernarr Macfaddens, reincarnating many of the same tropes that moralize our health and berate mainstream medicine. Undue blame is laid at our feet if we don’t eat right, feel right, or live medication-free.

Both misplaced and well-earned distrust in modern medicine contribute to mental health misinformation and sustain the wellness market. People are willing to turn a blind eye to the pitfalls of alternative medicine in part because it offers the warmth and human comfort that they may not be getting from the health care system.

As personalized and attentive as alternative medicine might seem, the mechanics are faulty. The term lemon is used to describe a newly purchased car that turns out to be defective: It may look pretty and might even get you to your destination a few times, but it has manufacturing issues and malfunctions that make it unsafe to drive. Alternative medicine is a lemon composed of pseudoscientific parts that jeopardize your mental health.

This article The unsavory history of the wellness industry is featured on Big Think.

In February 2003, Carlo Urbani encountered a mysterious virus in Vietnam. A physician-epidemiologist well-regarded for his diagnostic skills, Urbani was asked to come to the French Hospital of Hanoi to see a patient named Jonny Chen, an American businessman who had grown seriously ill after a recent trip to Hong Kong. His doctors feared he may have contracted avian influenza — which, while rare in humans, has the potential to trigger the next flu pandemic — and they wanted Urbani’s expert opinion.

After examining Chen, Urbani grew worried. The patient’s decline had been rapid and severe for someone as young and, until then, healthy as him. Additionally, 12 healthcare workers who had contact with Chen fell ill. Given that healthcare workers take strict precautions to prevent contracting diseases from patients, Urbani feared the worst: a new disease that was not only deadly but also highly infectious. He contacted several colleagues and learned about an outbreak of pneumonia spreading through Guangdong, a Chinese province bordering Hong Kong to the north.

That proved enough for Urbani. He and his team alerted international public health officials over their concerns. 

Ultimately, it wasn’t an avian flu virus but a novel coronavirus that afflicted Chen — one known today as SARS-CoV-1, or simply SARS. Nor was Chen patient zero, as the first known case would eventually be traced back to Guangdong. It was, however, Urbani’s warning that triggered the World Health Organization (WHO) to forewarn public health officials worldwide to search for similar cases in their regions. Those early efforts to identify and isolate infected people allowed the world to restrain the virus’s spread, likely preventing the outbreak from blooming into an unruly pandemic.

As Caitlin Rivers, a senior scholar at the Johns Hopkins Center for Health Security who specializes in epidemic preparedness, writes, “When I think about the phase of an outbreak and the race to gain the upper hand, so much hinges on the skills of the experts rushing to respond. At each phase, there are skills both learned and intuited that spell the difference between success — bringing the outbreak under control — and failure.”

Rivers shares Urbani’s story, and the stories of many other researchers, in her new book Crisis Averted to shine a light on what she calls “the hidden science” of epidemiology. Why hidden? Because the more epidemiology succeeds, the less we have to think about. Unlike our ancestors, most people today don’t have to fret over whether their water is safe to drink, their hospitals are sanitized, or that case of flu going around will decimate their community. We simply accept these favorable conditions will persist and go about our lives.

That’s by design, but epidemiology’s hidden nature has a downside. It can inadvertently lead us to overlook the field’s importance in keeping us safe and healthy — which may undermine our preparedness for future outbreaks.

A cycle of panic and neglect

Epidemiology has come a long way since the ancient Greek beliefs that illnesses stem from an imbalance of bodily fluids or that contagions circulate on currents of poisonous air. In only the last few centuries has science managed to amass the empirical knowledge to capably contain outbreaks, thanks to forerunners like Antonie van Leeuwenhoek, John Snow, and Florence Nightingale. The “boots on the ground” techniques they helped establish — identifying microbes, isolating the sick, and sanitizing every surface in hospitals — remain vital in breaking the viral chains of transmission.

The tremendous efforts of public health workers ever since have allowed the modern world to bring to heel diseases that were historically perilous — even genocidal for some Indigenous peoples. Smallpox and rinderpest have been eradicated. Polio, mumps, measles, and rubella have been eliminated from many societies and may be eradicated one day. Vaccines alone have saved an estimated 150 million children’s lives in the last half-century, while diagnostic testing, treatments, and preventative medicine have saved countless more.

As this short history suggests, the story of epidemiology is a remarkable tale of human ingenuity and cooperation, but one largely untold and seldom uncelebrated. One reason is that epidemiology’s victories don’t make for the best photo ops. Viruses don’t surrender and sign treaties of non-infection. There are no parades on Main Street when the doctors come home. Instead, progress is made person by person, and day by day, the disease quietly retreats. And our minds turn to other, more immediate matters.

For reasons like this, Rivers refers to epidemiology as medicine’s “quiet cousin.”

“Historically, it’s been hard for us to make the case about why the work we do is so important and valuable,” Rivers told Big Think. “COVID-19 did elevate what can happen when things go wrong and when Mother Nature challenges us. But many success stories throughout history haven’t gotten the attention they deserve because epidemiologists pulled us back from a very scary situation.”

This invisibility leads to what Rivers calls the cycle of panic and neglect. An outbreak, pandemic, or other public health crisis rears up and jolts us out of complacency. Urgency builds, media outlets offer breathless coverage, and the pressure to respond pushes government officials to action. Downstream, public health officials receive a boost of attention, support, and funds to tackle the problem, which they often do.

“Progress, though, is not triumph,” Rivers writes. As case numbers fade and transmission rates fall, the urgency lapses in kind. Funding and support dim, and we return to complacency until the cycle starts again with the next crisis.

This cycle may even be playing out with the all-too-recent COVID-19 pandemic. While we are passed peak COVID, the disease hasn’t gone anywhere. Countries continue to report cases and deaths, and for the immunocompromised, the virus remains an ever-present danger. Yet, despite how fresh the memories of 2020 remain, the signs of complacency are present.

For instance, according to the CDC, only around 11% of children, 22% of adults, and 44% of the 65-plus crowd have reported receiving the most recent COVID-19 vaccine. While those numbers may climb as the winter season advances, they are well below the percentage of Americans who report getting the most up-to-date flu vaccine. And 40% of Americans report they likely won’t get this year’s COVID vaccine at all — despite evidence showing that vaccines, while not perfect, ease the severity of the illness and reduce the chance of passing it to others, thereby improving herd protection.

“The last respiratory pandemic was in 1918, so we think of it as an every hundred years event, but Mother Nature’s not on a schedule,” Rivers says. “I worry that it’s going to be all too easy — or maybe we’re already starting — to fall back into the neglect cycle and move on without absorbing the lessons of what we all experienced.”

Can we break the cycle?

Breaking this cycle wouldn’t render our societies impervious to the next outbreak. Natural selection ensures novel viruses will continue to evolve and that we’ll be susceptible — if not to the next one then one further down the adaptation line. Doing so would, however, be an important step in helping us better prepare for that inevitable event and hopefully strengthen the safeguards that allow us to detect and respond to diseases quickly.

Unfortunately, several barriers stand in our way, one of which is simply our mental makeup. Evolution wired us to pay attention to the immediate and harmful. An outbreak happening right now in our neighborhood? That demands our attention. One that may occur decades from now halfway across the world? Worth considering, but life overcrowds with more pressing concerns. That’s not to say we never plan for the future — public health’s ability to respond to SARS proves otherwise — just that it’s not always our forte.

Consider your personal habits and behaviors. We understand that eating healthier, sticking with an exercise routine, and staying home when we’re sick today confer long-term benefits later, but we also know the difficulties of sticking with these habits. And even if we do stick with them, we all feel the ever-present draw of complacency. As life and family responsibilities pile up, it becomes easy to skip the morning run or head to the office with a barking cough. Immediate concerns take priority over our future health.

Public health officials deal with this problem at scale. They have to inform citizens of the science so they can make informed decisions about their behaviors while also steering entire communities to remedy potential health risks before they become tangible emergencies. Unfortunately, Rivers cites research in her book showing that such interventions typically produce modest returns.

The problem is compounded by the matter of communication. Science is nuanced. New evidence often complicates established research findings, experts disagree over what lessons to draw from the evidence, and news outlets favor eye-catching studies over rigorous methodology. Finding a message that is concise, accurate, and leads to the desired action is no easy task. Oversimply too much, like in the 1990s “Just Say No to Drugs” campaign, and people feel talked down to. Fail at offering a coherent message, and they get confused — as we saw during the early days of the COVID-19 pandemic when expert advice seemed to shift daily.

“[Today’s] fractured landscape has made it even more difficult to know how to reach different segments of the population,” Rivers points out. “The only thing we can do is accept that it’s going to require many more touch points to reach different segments of the population.”

That’s not to say public health hasn’t managed some landmark successes. The campaign to stop smoking, a leading cause of preventable diseases, proved a massive achievement. Today, only 12% of US adults have taken up the habit, compared to 42% of their 1965 peers. That trend line is even steeper among young people, and second-hand smoke has cleared out of public places such as restaurants and airplanes.

“Tobacco cessation is a strong example of sustained efforts to build the science and the evidence base for why a behavior is unhealthy,” Rivers says. “But that is one success story in a field of stories that are not quite as successful. It’s still an open question, I think, of how to do it successfully.”

Revealing the hidden science

One of Rivers’s projects — both in her book and her other writings — is to share the story of epidemiology. She wants to not only tell the incredible tales of people like Urbani, but also remind us to remember and share our own. After all, we lived through the COVID-19 pandemic and experienced it in different ways. While that year was certainly demanding, and for many tragic, being more open about those experiences and struggles may help us avoid another lapse into complacency.

“I believe in the power of stories to help us understand the world,” Rivers says. “Storytelling has been a major part of military history and even the medical field in ways that have not been true of public health. Part of what I wanted to do in the book is tell [those] stories to help readers understand how gripping the history of public health can be and, maybe through them, start to appreciate what public health has done for us.”

Rivers also thinks our news media needs to report on public health more like the weather. Meteorologists aren’t spotlighted only when they need to warn us to batten down the hatches. They provide daily updates to help us understand how the weather will affect our days and communities — whether that’s a warning about an incoming hurricane or a gentle reminder to carry an umbrella.

News media could do a better job of regularly informing citizens of what diseases are currently in their area and what precautions they should take. The goal is to normalize public health to become a small piece of everyday upkeep, so we’re better prepared when the larger events happen.

“I think another latent assumption about public health communications is that it always has to be alarming,” Rivers says. “It’s also okay to say things are looking great right now. That can be useful information, as well.”

Stories of triumph and tragedy

Urbani’s personal story sadly ended soon after his discovery. He contracted SARS and died on March 29, 2003. He was 46 years old.

Thanks to his selfless efforts, public health officials broke the SARS chain of transmission early and, in doing so, saved an untold number of lives. All told, the disease claimed the lives of 774 of the roughly 8,000 worldwide cases, but that number represents a fatality rate of 9.6%. For comparison, COVID’s fatality rate was about 1%.

“To stop it in its tracks, this virus had to be chased to the ends of the earth — person by person by person,” Rivers recounts. “If epidemiologists had lost control of that outbreak, it could have been horrifying. Even the situation as it played out was certainly a great tragedy, but the thing with outbreaks is that they grow until you stop them. We came very close to being in a much worse position.”

Urbani’s story reminds us what we gain from epidemiology and how people on the frontlines of this hidden science keep the modern world safe and healthy.

As Rivers writes: “We are never more than one laboratory accident, one virus spilled over from animals, one contaminated consumer product away from disaster. I offer that observation not to startle, but to reinforce that the work cannot be taken for granted for even one second. Only with great effort does public health maintain an invisible veil between us and a world I don’t want to see return.”

This article The dangers of keeping epidemiology the “hidden science” is featured on Big Think.

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It’s 2028, and for the first time in living memory, the US obesity rate is trending downward, and more and more Americans are achieving a healthy weight — potentially signaling the beginning of the end of the obesity epidemic.

The obesity epidemic

The US has a weight problem. According to the CDC, the percentage of Americans 20+ years old who classify as obese — meaning they have a body mass index (BMI) above 30 — has nearly tripled over the past 50 years, from 14.5% in the early 1970s to 40.3% in 2023.

However, that newest figure is slightly lower than the rate from 2020 (41.9%), causing some speculation that we have reached a turning point in the obesity epidemic. To find out whether that’s true — and, if so, what may be causing the trend — let’s explore the past, present, and future of obesity in America.

Where we’ve been

Obesity isn’t entirely a new phenomenon — archaeologists have uncovered sculptures depicting people with obesity dating back 30,000 years — and for much of human history, carrying excess weight was viewed as a sign of fertility and prosperity.

As far back as Ancient Greece, though, people were already connecting obesity to health problems, including early death, and their ideas for addressing excess weight focused on two things: diet and exercise.

“If we could give every individual the right amount of nourishment and exercise, not too little and not too much, we would have found the safest way to health,” reads the Hippocratic Corpus, written around 400 BC.

Fast forward about 2,400 years, and in many parts of the world, including the US, food has become both abundant and cheap, leading to unprecedented obesity rates. This, in turn, has led to higher rates of diseases and deaths linked to obesity.

Dropping excess pounds by moving more and eating less hasn’t gotten any easier over the centuries, either.

Despite countless diet and exercise programs designed to simplify the process, it still takes a lot of willpower to hit the gym consistently and eat the right number of calories. Our biology can actually work against us in the process, too — weight loss leads to lower levels of the hormone leptin, for example, and that reduction triggers feelings of hunger.

In the 20th century, the FDA approved a handful of medications designed to facilitate weight loss, but they haven’t been much help: many were later pulled, usually because they were deemed unsafe, and others had side effects that prevented them from becoming popular.

About 50 years ago, bariatric surgery emerged as an option for people with severe obesity or serious obesity-related health issues. It’s considered one of the most effective options, but adoption has remained low — only about 1% of Americans who qualify for the surgery get it, with cost, recovery time, and general fears of surgery contributing to the low rate.

Now, millennia after doctors first realized that obesity was a serious health issue, the number of people living with it is the highest it has ever been, and yet treatment options have remained basically the same: move more and eat less.

Where we are

After decades of increases in the obesity rate, the CDC survey showing a small decline is encouraging — 40% is still high (the CDC has set a modest goal of 36% by 2030), but perhaps we’ve hit “peak obesity” and will soon see rates of obesity-related diseases also start to fall.

Unfortunately, it’s too soon to celebrate. Obesity rates in the US have seemingly leveled off before, just to start increasing again soon after.

“I do not think we can make any predictions about obesity levels plateauing by comparing just two points in time,” Peter T. Katzmarzyk, associate executive director for population and public health sciences at the Pennington Biomedical Research Center, told Freethink. “We need to look at longer-term trends over several time points, which indicate that obesity has been increasing over several decades.”

“It appeared that obesity was plateauing between about 2007-2012, but then started to increase again,” he added.

If the decline is real, though, a leading theory as to why is the recent development and approval of the new blockbuster GLP-1 agonist drugs — medications that mimic the activity of the hormone GLP-1, which is produced after you eat and suppresses hunger.

GLP-1 agonists were initially approved to treat diabetes, with approvals for weight loss coming later. In recent trials, the latest formulations were found to help people lose as much as 10-20% of their body weight, as well as reduce their risk of weight-related health problems, such as heart attacks and deaths from cardiovascular disease. 

Between 2019 and 2023, the number of Americans taking a GLP-1 agonist for weight loss has increased by more than 700%, and as of May 2024, 6% of adults self-reported as taking one of the meds.

“Even if a notable minority is taking the drugs and losing weight, that’s going to alter the shape of the curve, the prevalence rates, and related statistics,” David Ludwig, an endocrinologist at Boston Children’s Hospital, told the Atlantic. “So it would be surprising, and very depressing, for us not to see any impact of these extremely costly drugs by this point.”

Where we’re going (maybe)

As Katzmarzyk noted, we won’t know for sure that obesity rates are actually leveling off or falling until we have longer-term data. We’ll then need to dig into it to figure out exactly what is behind the trend — new weight loss drugs seem like an obvious answer, but it’s possible other factors, like fewer people going out to eat, could be contributing, too. 

If GLP-1 agonists are having a notable impact on America’s collective waistline, though, it’s worth considering whether the medications could be a permanent solution to the problem, and if so, how we could get them into the hands of everyone who could benefit from them.

Losing weight is easier than keeping it off. Aside from our biological drive to regain lost weight, the motivation of seeing positive changes in the mirror, or in our bloodwork, while we’re losing weight can end once we hit our goal weight, making it easy to fall back into old habits.

Freethink spoke with three people currently using GLP-1 agonists for obesity, and all three reported feeling like they were in a much better position to maintain their weight loss on the drugs than they had been after losing weight through other methods in the past.

“Every diet that was available, I tried, and while I lost weight initially, it was really hard to sustain being on these diets for a long period of time,” a 38-year-old woman told Freethink. “Eventually, I got either bored of doing it or I wasn’t able to stick to it, and I ended up just gaining the weight back.”

Two years ago, she started taking a GLP-1 agonist and lost about 60 pounds in 10 months. Since then, she’d been focused on maintenance, which has been going better than it had in the past.

“I’ve been a little up and down with weight within 10 pounds,” she said. “Some of it has been due to an injury that I’ve had which prevented me from doing some of the physical activity I wanted. It also does get a little more tricky around the holiday season — I think that everybody struggles with that.”

This idea that the drugs alone aren’t enough to ensure permanent weight loss was another common thread in Freethink’s discussions with GLP-1 agonist users — all three emphasized that they also needed to (you guessed it) eat less and exercise more to reach their goals. The medications just made doing that easier.

“These are not miracle drugs,” the 38-year-old woman emphasized. “You don’t just give yourself an injection and poof, you lose weight. I started working out way heavier, doing a lot more cardio, and I started to change the foods that I ate.”

“The overwhelming majority [of patients] will need ongoing and chronic therapy.”

A Novo Nordisk spokesperson

Aside from sticking to a diet and exercise plan, people who lose weight with GLP-1 agonists typically need to stick with the drugs, too — patients tend to regain their lost weight if they stop taking their meds.

“Obesity is like other chronic cardiometabolic diseases which require ongoing treatment,” a spokesperson for Novo Nordisk, maker of the popular GLP-1 agonists Ozempic and Wegovy, told Freethink. “Just like hypertension, high blood pressure, or high cholesterol, you would never just stop your medicines.”

“There are always exceptions to the rule, as there are patients who lose weight with medication and then come off of it and keep the weight off, but the overwhelming majority will need ongoing and chronic therapy,” they continued.

Not only did the GLP-1 agonist users that Freethink talked to seem OK with the idea of being on the drugs indefinitely, two of them expressed trepidation at the thought of not taking them. 

A 36-year-old woman who has lost 84 pounds on one of the meds said she was “scared” at the thought of quitting the drugs because she didn’t think she’d be able to maintain the weight loss on her own. A 63-year-old man who has lost 80 pounds said he was “a bit worried” about what might happen if he stopped.

While the three patients Freethink spoke to might want to stay on their meds longterm, there’s no guarantee they’ll be able to.

Right now, they’re each paying between $25 and $50 per month for their prescriptions through their health insurance plans. If insurance doesn’t cover it, though, the out-of-pocket costs for the meds can be as high as $1,300 per month, and about 55 million Americans living with obesity don’t have insurance that covers anti-obesity drugs, according to Novo Nordisk.

While some companies are adding GLP-1 coverage to their health insurance plans, others are going in the opposite direction and dropping it due to the high cost of the meds, meaning some people are being forced to stop taking the drugs even when they don’t want to.

“If my insurance was to stop covering it, then I won’t be able to afford it every month,” the 36-year-old woman told Freethink.

The bottom line

GLP-1 agonists aren’t going to be the answer for everyone with obesity. An estimated 20% of users don’t respond to the medications, and many can’t tolerate them — 17% of people who received Wegovy in one large trial quit due to the medication’s unpleasant side effects, which can include vomiting and diarrhea.

However, they are the most effective weight-loss medications available today, and even if it’s too soon to note any impact they’re having on obesity rates in the US, millions more Americans could potentially benefit from the drugs if we can increase access to them, which means addressing the cost issue.

The most straightforward solution there would be for pharma companies to lower the price. Pressure from policy makers could encourage this in the US, as could competition from new GLP-1 agonists and other types of obesity treatments — many are now in clinical trials, and some are even oral meds, which could be preferred over the currently weekly shots. 

Further down the line, the patent for the drug in Ozempic and Wegovy will expire in 2032, after which cheaper generic versions will hit the market.

“Obesity is a complex disease that requires complex solutions.”

Peter T. Katzmarzyk

Pharmacological treatment alone might never be enough to lower America’s obesity rates, though — Katzmarzyk told Freethink he expects we’ll need to attack the problem from multiple angles.

“The reliance on individual-level treatment approaches is very time-consuming and expensive,” he said. “It is also questionable if we really can address the broader obesity epidemic by using approaches that affect one individual at a time.” 

“Obesity is a complex disease that requires complex solutions,” he added. “We will need coordinated obesity treatment and prevention programs at the community and at the individual level.”

These community-level initiatives could include things like the creation of more bike paths and parks or supermarkets in places that are currently food deserts — basically, anything that lowers barriers to eating healthier and moving more.

Regardless of what it takes to get there, if the US can lower its obesity rate, the benefits could be wide-ranging: a healthier military, higher fertility rates, and huge economic savings — right now, obesity is costing the US healthcare system $173 billion a year.

For now, though, all we know for sure is that at least one approach to treating obesity is having a major impact on the lives of millions of individuals, helping them make the changes needed to lose weight, keep it off, and improve their overall health.

“When you start to see your cholesterol come down, when you see your blood pressure is under control, when you’re able to cut back on your other medications … it really has been life-changing,” the 63-year-old man told us.

This article Has the US reached “peak obesity”? is featured on Big Think.

For a substantial part of human history, people thought smoking tobacco was perfectly healthy. Native American tribes, who introduced the tobacco plant to Europeans and — by extension, the rest of the world — used it for cultural and spiritual purposes, giving little thought to its long-term effect on the human body.

Meanwhile, vintage advertisements from the early 20th century claimed that smoking provided a variety of health benefits, from relieving stress and anxiety to helping with indigestion, weight gain, depression, and even respiratory infections. Plus, Big Tobacco frequently partnered with physicians and other health professionals to give such claims an extra air of credibility.

Interestingly, this unlikely partnership was itself a response to a growing body of research introducing the now universally known fact that smoking does – in fact – lead to serious, often life-threatening health complications, including throat, mouth, and lung cancer. Lung cancer alone killed more than 1.8 million people in 2020, making it the leading cause of cancer deaths worldwide.

Example of a vintage cigarette ad. (Credit: Theatre Magazine / Wikipedia)

Over the years, government agencies and activist groups have greatly restricted Big Tobacco’s power to drive down the number of smokers, providing resources for aspiring quitters, replacing those aforementioned, Norman Rockwell-style advertisements with disconcerting pictures and health warnings, driving up cigarette prices, and limiting tobacco sales to specialized shops.

Still, the number of lung cancer deaths remains astronomically high. Fortunately, new and improved treatments for smoking-related illnesses have been making tremendous progress, with fields like nanosurgery and immunotherapy injecting hope into what is otherwise an extremely upsetting subject. But no alternative treatment option has received quite the same level of attention as German biotechnology company BioNTech’s lung cancer vaccine.

Drawing on technologies used in the creation of COVID-19 immunizations, BioNTech launched its first clinical trials involving the new vaccine in August 2024. While media outlets praised the trials for their promise and potential, most of the coverage has focused on the company’s skyrocketing valuations, leaving many to wonder how the vaccine actually works on a scientific level, why it arrived at the time that it did, and when (if ever) it will become a widely available form of treatment.

An injection of a BioNTech mRNA cancer immunotherapy for non-small cell lung cancer (NSCLC) – known as BNT116 – at the University College London Hospital. Approximately 130 participants were enrolled in the study across 34 research sites in seven countries, with six UK sites selected. Picture date: Tuesday August 20, 2024. (Aaron Chown / PA Images / Getty Images)

How it works

To understand how BioNTech’s lung cancer vaccine works, you first have to understand why we’d need a vaccine in the first place. While a functioning immune system can fight against plenty of nasty, potentially dangerous ailments, cancer cells — abnormal, continuously growing tissue — are, regrettably, supremely adept at slipping under the system’s radar.

That’s because, in simple terms, cancer cells aren’t external invaders but malfunctioning cells from our own body, making them harder for the immune system to recognize as a threat. More specifically, small, newly formed cancer cells often lack strong antigens — or can suppress immune responses — allowing them to evade detection. By the time they do express recognizable antigens, the tumors may have grown too large for the immune system to effectively eliminate on its own.

This insight marks the jumping-off point for immunotherapy treatment, which — unlike chemotherapy or surgery — does not target cancer cells directly, but instead helps the immune system carry out its job more effectively.

BioNTech’s laboratory in Mainz. (Credit: Epizentrum / Wikipedia)

Some immunotherapies are injected directly into the veins. Others come in the form of pills or creams. BioNTech’s is a vaccine. Specifically, it’s a vaccine containing mRNA, or messenger-RNA, which can be loosely defined as a genetic blueprint for the production of proteins. In this case: proteins that improve the immune system’s ability to find and kill tumors.

“The role of mRNA is to carry protein information from the DNA in a cell’s nucleus to the cell’s cytoplasm (watery interior),” notes the National Human Genome Research Institute, “where the protein-making machinery reads the mRNA sequence and translates each three-base codon [sequences made up of the DNA molecules adenine (A), cytosine (C), guanine (G), and thymine (T)] into its corresponding amino acid in a growing protein chain.”

A BioNTech spokesperson tells Big Think that the vaccine “is designed to train the immune system to specifically recognize and attack cancer cells by delivering mRNA that encodes for cancer-specific antigens, prompting the immune system to target those proteins presented by tumor cells. This can help the body to detect and destroy cancer cells and potentially prevent them from returning.”

COVID lessons

BioNTech’s vaccine draws heavily from scientific advancements made during the pandemic, which led to the creation of vaccines that also use mRNA to assist the immune system in identifying a specific target. In this case: coronavirus.  

Although mRNA was first discovered in 1961 (earning the researchers involved a Nobel Prize), and Penn Medicine employees Katalin Karikó and Drew Weissman figured out how to use it in a vaccine as early as the 1990s, its primary application at the time — fighting infectious diseases in Africa — failed to garner sufficient funding from Western investors. Then, of course, came COVID.

BioNTech has a long history working with mRNA. During the pandemic, it co-developed the coronavirus vaccine distributed by New York-based pharmaceutical conglomerate Pfizer, Inc., discovering a mechanism capable of delivering genetic information to dendritic cells (a type of immune cell), vastly improving the vaccine’s efficacy and stability.

COVID vaccines use mRNA. (Credit: Spencerbdavis / Wikipedia)

As clinical trials continue, BioNTech stresses that its vaccine is currently not intended to replace existing treatments for late-stage lung cancer.

“In early-stage,” the company tells Big Think, “where the immune system might be more responsive to the approach since the tumor burden is lower, BNT116 [the vaccine’s official name] could potentially be evaluated as a standalone treatment. However, it’s generally designed to complement existing treatments, such as surgery, chemotherapy, or immunotherapy, to enhance the overall effectiveness of cancer treatment and reduce the risk of recurrence.”

When and whether BioNTech’s lung cancer vaccine will become a widely available form of treatment depends on the outcome of the company’s ongoing clinical trials, which are currently taking place at 34 research sites across 7 countries — including Germany and the UK — and involve around 130 test subjects who receive 1 vaccine per week for 6 consecutive weeks, followed by one vaccine every 3 weeks for 54 weeks.

The first person to receive BioNTech’s vaccine, a 67-year-old, Polish-born analyst named Janusz Racz, credits his profession for motivating him to join the trial. “As a scientist myself,” he said in an article published by University College London Hospitals, where he is being treated, “I know that science can only advance if people agree to participate in programmes like this.”

This article How BioNTech’s “revolutionary” lung cancer vaccine actually works is featured on Big Think.

The United States is a big country. Its size, just slightly smaller than Europe, leaves plenty of room for cultural differences. Cuisine, religious belief, and language all shift in disparate parts of the U.S. But despite the variations, Americans tend to unite around one flag, a shared identity, and a cherished ethos of liberty and opportunity. Though there are many united states, there is one America. But this idealized conception comes apart when considering life expectancy.

As a team of researchers at the University of Washington (UW) revealed in an analysis published in November to The Lancet:

“One’s life expectancy varies dramatically depending on where one lives, the economic conditions in that location, and one’s racial and ethnic identity.”

When it comes to how long Americans can expect to live, the authors made a stark conclusion: We do not live in one America but rather ten different Americas.

Ten Americas

The researchers mostly hail from the Institute For Health Metrics and Evaluation, a leading public health research institution based at UW. They pored through numerous large datasets covering mortality between 2000 and 2021 and paired this information with detailed demographic data. Through this exhaustive analysis, they divided the country into ten Americas based on how long Americans can expect to live at birth.

• America 1 comprises the roughly 21 million Asians and Native Hawaiian or Pacific Islanders (NHPI) living in counties where the NHPI population was less than 30% of the total Asian and NHPI population in 2020. In 2021, they could expect to live 84 years at birth, compared to 83.1 years in 2000.
• America 2 is made up of Latinos living outside of Arizona, Colorado, New Mexico, and Texas. Its population is about 46 million. In 2021, these Latinos’ life expectancy was 79.4 years, down slightly from 80.4 in 2000.
• America 3 is essentially a catch-all group and includes the vast majority of white people as well as a sliver of Asians and American Indians who live in predominantly white counties. This group’s life expectancy was 77.2 years in 2021, essentially unchanged from 77.5 years in 2000.
• America 4 is made up of low-income white inhabitants of non-metropolitan counties in Iowa, Minnesota, Montana, Nebraska, North Dakota, and South Dakota. These roughly 300,000 Americans could expect to live 76.7 years at birth in 2021, down from 77.6 in 2000.
• America 5 comprises the 16.5 million Latinos dwelling in Arizona, Colorado, New Mexico, and Texas. In 2021, they had a life expectancy of 76 years, a sizable decline from 77.8 years in 2000.
• America 6 is inhabited by black Americans living outside of large, segregated metropolitan areas and not in the rural parts of the Deep South. They number about 32 million and could expect to live 72.3 years in 2021, compared to 72 years in 2000.
• America 7 represents black Americans living in highly segregated, large metropolitan areas. Its population numbers a little over 10 million. People living here had a life expectancy of 71.5 years in 2021, up from 70.6 in 2000.
• America 8 is made up of whites living in poor parts of Appalachia and the Lower Mississippi Valley. Its 10.3 million residents could expect to live 71.1 years in 2021, sharply down from 74.8 years in 2000.
• America 9 comprises the 2.1 million black Americans living outside of big cities in low-income counties of the Lower Mississippi Valley or the Deep South. Their life expectancy was 68 years in 2021, versus 70.5 years in 2000.
• America 10 represents American Indians and Alaska Natives inhabiting the Midwest or western states not bordering the Pacific Ocean. These 1.3 million people had a shockingly low life expectancy of 63.6 years in 2021, cratering from 72.3 years in 200.

Tales of longevity inequality

Numerous narratives jump out when examining these ten Americas within the United States. First and foremost, there’s a 20.4-year gap in life expectancy between the Asians and Native Hawaiian or Pacific Islanders who make up America 1 and the American Indians and Alaska Natives dwelling in America 10. This gap between the longest-living and shortest-living Americas was 12.6 years just two decades prior.

“This gulf was large at the beginning of the century, only grew larger over the first two decades, and was dramatically exacerbated by the COVID-19 pandemic,” the authors commented.

Americans who live the shortest tend to dwell in lower-income and rural counties with reduced access to healthcare. They’ve succumbed in greater numbers to obesity and opioid addiction. This stagnated life expectancy gains in the 2010s and rendered these Americans uniquely susceptible to death from COVID-19 in the early 2020s.

Second, there is a serious health crisis in America 10. American Indians and Alaska Natives dwelling in mostly western states saw their life expectancy consistently decline throughout the century, even before the pandemic. Their life expectancy of 63.6 years in 2021 is similar to that of citizens of Mozambique, whose country is currently in a state of civil war. The researchers cited some statistics that could explain this tragic trend. For starters, roughly one in five of these individuals have health insurance, compared with about 92% of Americans overall. Moreover, they’re plagued by higher unemployment and lower rates of educational attainment, fueled by hundreds of years of systemic discrimination. These deficits of opportunity lead to excessive alcohol consumption, tobacco use, injuries, and poor dietary habits.

Third, black Americans as a whole do not dwell in the top five longest-living Americas. The researchers noted that they did make strong gains in life expectancy in the 2000s, significantly narrowing the gap with white Americans. Improvements in education, falling HIV/AIDS deaths, and lower homicide rates contributed. But these gains evaporated in the latter half of the 2010s, owing to rising obesity, a pick-up in homicides, and outsized harm from COVID-19.

Lastly, Asians and Native Hawaiian or Pacific Islanders definitively outlive other Americans. Is there anything we can learn from them? A confluence of factors may be at play. They tend to have relatively higher socioeconomic status, lower rates of obesity, and the lowest smoking rates of any racial group in the U.S. Healthier traditional cooking may also contribute to their longevity.

Closing health disparities

Overall, the study reveals that a shocking life expectancy divide in the United States has widened to a chasm.

“The extent and magnitude of health disparities in the USA are truly alarming,” the authors wrote. “In a country with the wealth and resources of the USA, it is intolerable that so many are living in conditions and with health outcomes akin to those of an entirely different country.”

America, the richest country on Earth, has a middling average life expectancy, ranking 48th out of 200 countries. Yet tens of millions of people living in some parts of the country live just as long as the healthiest people in the world. Observing them, we have a good idea of how to boost the life expectancy of everyone else: Access to healthcare, opportunity, and quality education is paramount. This simply takes resources, of which the U.S. has plenty.

The researchers call for a massive effort to raise the life expectancy of ailing Americans, thus reunifying the country from ten Americas back into one.

“It is time for us to take collective action; to invest in equitable health care, education, and employment opportunities; and to challenge the systemic barriers that create and perpetuate these disparities.”

This article When it comes to life expectancy, there are 10 Americas is featured on Big Think.

The transformative potential of digital connectivity became a global game changer more than two decades ago. Mobile phones reshaped telecommunications, enabling connectivity even in homes without landlines. Digital health quickly leveraged these innovations, making remote patient-doctor communication, digital payments, care coordination, and online peer support networks possible.

Artificial intelligence (AI) has undoubtedly sparked another phase of digital innovation. Although the field’s origins date to the mid-twentieth century, recent advancements in large language models (LLMs) have thrust it into the spotlight. Reflecting this growing relevance, the World Health Organization (WHO) dedicated a session at its World Health Assembly (WHA) in early 2024 to AI’s implications for global health, convening regional, national, academic, and international health organizations and actors to examine this matter.

AI applications in global health

The literature generally presents four key use cases for artificial intelligence in health in low- and middle-income countries: disease diagnosis, risk assessment, outbreak preparation and response, and planning and policy-making. As the 2021 WHO report on AI in healthcare indicates, several AI applications are already in use or in development for diagnosis and assessment, such as in India for rapidly creating encephalograms in six minutes; in Rwanda and Pakistan for patient navigation; in Uganda, for malaria diagnosis; and in Nigeria for monitoring vital signs in mothers and children, and detecting infant asphyxia. On a broader scale, the advancement of DeepMind’s AlphaFold system in predicting the three-dimensional shape of proteins holds promise for enhancing our understanding of diseases and accelerating treatments.

Use cases in outbreak surveillance and response are also prominent. Google Flu Trends used search engine queries to predict influenza activity, but its overestimation of flu prevalence demonstrated the need for continuous algorithm updates. Tools like HealthMap have also proven valuable, detecting early signs of vaping-related lung disease and issuing an early bulletin about the novel coronavirus in Wuhan.

AI is also being used in planning and policy making, such as in South Africa where machine-learning (ML) models were used to predict how long recruited health workers’ would commit to their placements in rural communities; and in Brazil where artificial neural networks were used to create a method to geographically optimize resources based on population health needs.

Could AI represent a sea-change in global health?

The integration of AI in public health is still evolving and being cautiously assessed in some cases, but it’s poised to transform key health functions. Evidence generation, the foundation of health policies and practices, is undergoing significant change. Traditionally, systematic reviews, a cornerstone of evidence synthesis, may take months or even years to complete. Now tools like Eppi-Reviewer use ML for more efficient screening, while platforms like Open Evidence are able to summarize existing studies rapidly. As AI becomes capable of handling technical aspects such as quality appraisal, meta-analysis, and synthesis with high rigor and fidelity, its role in evidence generation will expand. This advancement will enable more cost-effective and timely production of health guidelines, with leading bodies already creating guidelines for AI use in evidence synthesis.

Data collection and analysis are also experiencing transformative changes. AI-powered tools enable rapid analysis of both structured and unstructured data, marking a significant shift from traditional paper-based methods and conventional fieldwork. This capability has a remarkable impact on public health strategies centered on behavior change. AI can allow for the creation of highly targeted health promotion campaigns with unprecedented speed and precision. Moreover, sentiment analysis tools can assess public perceptions in real-time, enabling agile adjustments to ongoing health campaigns.

The healthcare workforce is also expected to evolve as AI-human partnerships are normalized. For instance, Hippocratic AI’s generative models can perform certain care management functions, while Google’s Med-Gemini provides real-time feedback on medical procedures, including surgeries. As they improve and are adopted by practitioners, these tools will have the potential to enhance the cost-effectiveness and precision of healthcare delivery.

As of May 2024, the FDA had authorized 882 AI- and ML-enabled medical devices. The rising volume of such AI-enabled devices as well as the rise in registered clinical trials related to their use underscores how much the field has embraced such tools.

A changing actor landscape

The integration of AI in healthcare is not only transforming practices but also reshaping the landscape of global health actors. Historically, global health was a multilateral activity, dominated by international non-governmental organizations and national governments alike. The early twenty-first century saw the emergence of influential philanthropic actors like the Gates Foundation. Now, we are entering a phase where private-sector AI companies are poised to become increasingly influential in this arena.

While open-source models and government-developed AI systems exist, the predominance of private-sector AI models, such as OpenAI’s ChatGPT and Google’s Gemini, raises critical questions about data governance in global health. Unlike existing cross-national commercial influences on health such as the fast food or tobacco industries, AI systems present more nuanced concerns. For instance, if private models become integrated into existing multilateral health initiatives, how can we ensure their compliance with global health objectives? How do we address potential conflicts of interest when companies hold influence over health data and decision-making?

Regional and national guidelines are emerging to govern this evolving landscape. The European Health Data Space, discussed at the World Health Assembly, offers one such example. This initiative aims to create a single data space across the twenty-seven EU member states, empowering patients to control their health data while establishing a framework for safe data reuse and AI deployment. It also includes provisions for rigorous evaluation of high-risk AI systems in healthcare.

Similarly, the African Union recently launched its Continental AI Strategy, with a stated aim “to harness artificial intelligence to meet Africa’s development aspirations and the well-being of its people, while promoting ethical use, minimizing potential risks, and leveraging opportunities.” Monitoring measures like this as they develop will be instructive for the future deployment of AI in global health initiatives.

Building foundational infrastructure

Another factor to consider is that advances in AI mean little for health systems at an insufficient level of maturity. Progress in AI depends heavily on a strong foundation of digital health architecture, which encompasses secure data management, interoperability between health information systems, and comprehensive digital strategies. While most countries have digital health strategies, their implementation varies widely, with progress in resource-limited settings often lagging. Several countries have neither sufficient health workers to regularly input data nor dependable electricity and Wi-Fi to support a transition from paper to digital records. The lack of foundational infrastructure presents a significant barrier to AI implementation.

Initiatives like the Precision Public Health Initiative, led by the Rockefeller Foundation in collaboration with the WHO, UNICEF, global health funding agencies, ministries of health, and technology companies aim to strengthen AI use in low- and middle-income countries (LMICs). With initial funding of US$100 million, it aims to extend the use of AI and data science in LMICs, providing the latest technology to under-resourced parts of the world. Initiatives like this will need to concentrate resources on foundational health system strengthening functions such as the training and supportive supervision of staff and resource management.

Ethical Implications

As AI advances, ethical considerations must keep pace. These challenges can be broadly categorized into privacy and surveillance concerns, data misuse, algorithmic biases, and issues of transparency and liability. Recent cases highlight the urgency of addressing these matters proactively.

As the research report Ethics and Governance of Artificial Intelligence for Health: WHO Guidance explains, during the COVID-19 pandemic, China’s Alipay introduced a “Health Code” that used collected data to determine exposure risks. This system, which determined individuals’ mobility based on their assigned color codes, raised concerns about privacy, rights, and the potential for mass surveillance. Another case discussed in the WHO guidance report is Dinerstein vs. Google, in which the University of Chicago shared patient records stripped of identifying information with Google to develop machine-learning tools for predicting medical events. A class action complaint was filed, alleging that records could be re-identified, threatening patient privacy.

Several cases other cases in the WHO guidance report highlight the critical issue of bias in AI systems. In Argentina, an AI system designed to predict adolescent pregnancy faced criticism when it was found to have flawed methodology and to violate the privacy of adolescents. Similarly, a study in the US revealed racial biases in an algorithm that resulted in Black patients receiving less medical attention than equally sick white patients.

Additionally, an AI technology designed to detect potentially cancerous skin lesions was trained primarily on data from lighter-toned individuals in Australia, Europe, and the US, highlighting its inadequacy for darker-skinned populations.

The “black box” nature of many AI algorithms also raises critical questions about informed consent and liability. If an AI system recommends a specific drug dosage, but the underlying algorithm is opaque to the physician, who bears responsibility for adverse outcomes?

A case study

To illustrate how the various considerations of AI in global health converge, the WHO’s Smart AI Resource Assistant for Health (S.A.R.A.H.) project provides a recent and relevant case study. Launched in April 2024, S.A.R.A.H. is a video-based generative AI assistant designed to address gaps in health information accessibility. Developed in partnership with Soul Machines Biological AI, this initiative represents, in the words of WHO Director-General Dr. Tedros Adhanom Ghebreyesus, “how artificial intelligence could be used in future to improve access to health information in a more interactive way.”

The potential for LLMs in health promotion must be viewed against the backdrop of the burden placed on health systems. For example, Sub-Saharan Africa and South Asia have an estimated 0.2 and 0.8 doctors per 1000 people, respectively, compared to 4.3 in the European Union and 3.4 in North America. A map of travel time to health facilities reveals that it’s not uncommon to spend a day traveling to see a doctor in several regions such as North Africa. Even when they can see a doctor, more than a billion people are driven into poverty each year because of exorbitant health care costs. In such contexts, LLMs can complement the health promotion efforts currently being provided by community health workers. They can also enhance supervision and training.

S.A.R.A.H. stands out for its efforts to tailor recommendations to local contexts. For example, it offers meal recommendations based on regional dietary habits. It also uses visual emotional cues to display empathy. Like its WhatsApp-based chatbot predecessor for sharing COVID-19 information, S.A.R.A.H.’s reach will probably expand through partnerships with telecommunications providers and social networks, supporting its broad dissemination.

However, S.A.R.A.H. faces some challenges that mirror broader issues in AI for global health. Users have noticed errors in the information S.A.R.A.H. has provided; it incorrectly stated, for example, that a drug for Alzheimer’s was still in clinical trials when the drug had been approved in 2023. This highlights the critical need for AI systems to keep pace with rapidly evolving medical knowledge.

While S.A.R.A.H. offers a wider range of languages than many existing tools (including French, Russian, English, Spanish, Hindi, Portuguese, Arabic, and Chinese), this still represents only a fraction of global languages, potentially limiting its reach. Also, the success of video-based tools like S.A.R.A.H. depends on robust digital infrastructure and access to smartphones with video capabilities, which are hardly universally available.

The processing of users’ video data also raises important privacy considerations. While not yet available, the WHO has committed to making the training materials and the evidence base for S.A.R.A.H. publicly accessible, aligning with its principles on LLM use. Transparency in how S.A.R.A.H. processes and uses data will be crucial in maintaining trust and offering insights for this emerging space.

Conclusion

As noted by WHO Director-General Dr. Tedros at the WHA, AI represents a transformative advancement in global health akin to past innovations such as the introduction of vaccines, penicillin, MRI machines, and human genome mapping, all of which revolutionized the field. As reported in the above-linked 2021 WHO report on AI in healthcare, the integration of AI into health systems presents immense potential with projections noting that the top ten AI applications in health could result in an estimated US$150 billion in savings by 2026.

While the potential of AI is undeniable, the critical question remains: can it fulfill the promise of improving health outcomes worldwide? This hinges on several factors, including building foundational infrastructure, addressing ethical considerations, and effectively governing the evolving landscape of actors, which are no small feats.

This article Dr. AI will see you now is featured on Big Think.

In 2022, scientists found microplastics — pieces of plastic less than five millimeters long — in human blood. Since then, they’ve been discovered throughout the human body, including in our lungs, kidneys, livers, hearts, and brains.

So, why do we have all this plastic in us, what does it mean for our health, and what can we do about it?

Living in a plastic world

Plastics are a wonder material. They’re tough, lightweight, flexible, sterile, and cheap, which has made them hugely popular — since the 1950s, production levels for plastic have increased faster than for any other material. We’re now producing 440 million tons of plastic every year, with the total still trending upward.

Unfortunately, there’s a major tradeoff for all the benefits of plastic. Not only is the production of it bad for the environment, contributing to global warming, but so is the way we treat the material after we’re done using it: only about 9% of the world’s plastic waste is recycled, while 19% is incinerated. The rest goes into landfills (50%) or becomes litter (22%).

Researchers have known since the 1960s that plastic waste was an issue, but the problem took a new shape in 2004 when marine biologist Richard Thompson published a paper in the journal Science in which his team reported the discovery of microscopic plastic fragments and fibers in the ocean environment.

They dubbed these pollutants “microplastics.”

“The fragments appear to have resulted from degradation of larger items,” the researchers wrote. “Plastics of this size are ingested by marine organisms, but the environmental consequences of this contamination are still unknown.”

In 2024, Thompson led a new study, also published in Science. This time, his team looked back at the 7,000 microplastics studies that followed their 2004 discovery to see what we now know about the pollutants — and the answer wasn’t great.

In 2004, @ProfRThompson led the first ever study – published in @ScienceMagazine – to use the term #microplastics to describe the tiny plastic particles being found in the marine environment. pic.twitter.com/izRUXzgoNn

— University of Plymouth (@PlymUni) September 20, 2024

Not only had the amount of microplastics in the ocean increased over the past two decades, scientists had also found the particles in tons of other places — they’re in the air we breathe, the water we drink, and the animals we eat, as well as hundreds of species outside our food chain. They’ve also been found in other foods that we consume, from vegetables to ice cream.

As for where all these microplastics were coming from, Thompson’s team was right that many were once a part of larger pieces of plastic — polyester clothing and synthetic rubber tires proved to be particularly large sources of microplastics in the environment. The tiny plastic pellets which are used to create larger plastic products are a big contributor, too — at various points in the supply chain, they can slip into the environment.

Identifying microplastics and their sources was just the start, though. A major focus of research has been on determining the impact of these particles, and that’s led to more bad news.

“After 20 years of research, there is clear evidence of harmful effects from microplastic pollution on a global scale,” said Thompson in a press release about the new study. “That includes physical harm to wildlife, harm to societies and cultures, and a growing evidence base of harm to humans.”

Mitigating microplastics

That evidence has been enough to inspire officials in some places to take action to try to reduce the amount of microplastics in the environment.

In 2015, for example, Congress passed the Microbead-Free Waters Act, which banned the inclusion of plastic microbeads in toothpaste, face wash, and other products. Some states and cities have also banned some single-use plastics, which can break down into microplastics once discarded.

These policies aren’t enough to significantly reduce the amount of microplastics in the environment, though — the most straightforward way to make that happen would be for the textile industry and tire manufacturers to stop creating products with so much plastic.

“[W]e can not dramatically reduce microplastic pollution without leadership from the textile industry and tire manufacturers to produce consumer products that don’t add to the growing problem,” said Mark Gold, executive director of the California Ocean Protection Council.

These are massive, global industries, though, and convincing them to change en masse how they operate (or getting governments around the world to force them to change) won’t be easy, especially since we still don’t know for sure just how bad microplastics are for human health.

There’s no straightforward path to figuring it out, either.

Because microplastics are everywhere, we can’t exactly compare the health of people who are exposed to them to people who aren’t to determine their possible effects, so our real world studies have no controls — already a big strike against them.

“Plastic” is also not just one thing. There are more than 13,000 different chemicals used in plastic production, which complicates matters even further — how do we know which ones are causing which health effects and therefore need to be regulated or banned? There isn’t any systematic testing of these chemicals in humans, much less the countless potential combinations of them that are used in plastic products. 

Scientists can — and have — exposed human cell cultures to certain kinds of plastic chemicals and microplastics and recorded how often the cells experienced inflammation, DNA damage, or death. They’ve also performed controlled studies on animals and recorded their effects, noting how exposure to certain levels of microplastics can cause mice to experience organ failure, develop immune disorders, demonstrate signs of dementia, and more.

Even though these studies (and common sense) suggest that having microplastics in our bodies is probably harming us in some way, they don’t prove it, though. 

“Are the plastics just simply there and inert or are they going to lead to an immune response by the body that will lead to scarring, fibrosis, or cancer?” Albert Rizzo, chief medical officer for the American Lung Association, told National Geographic in 2022. “We know these microplastics are all over the place. We don’t know whether the presence in the body leads to a problem.”

Looking ahead

Proving a link between microplastics and health issues may be a huge challenge, but as Thompson noted, the evidence base of harm to humans is growing. 

A study published in March 2024, for example, analyzed plaques removed from the clogged heart arteries of about 300 people with heart problems and found microplastics in about 60% of the samples. People with microplastics were 4.5 times more likely to have a heart attack, stroke, or die within 34 months of the plaque removal surgery, compared to those without. 

That correlation does not prove causation — it could be that people who are sicker for other reasons are also ingesting or retaining more microplastics, and that’s what the study is picking up on. But the result is certainly consistent with microplastics worsening health problems.

We don’t have to wait as researchers work to unravel the connection between microplastics and human health to start mitigating the problem, though. 

We already know that plastic waste in the environment, big and small, is killing wildlife, degrading ecosystems, and generally just making the world a worse place, and tire wear particles, which include plastics as well as a range of other unpleasant substances, have long been known as a major source of pollution. 

To combat this, some people are developing better plastic recycling tech and sustainable plastic alternatives. Others are collecting and recycling the plastic waste that’s already in the environment and taking steps to prevent new waste from reaching it.

These are still relatively small-scale solutions, but in 2022, the members of the United Nations committed to establishing a legally-binding agreement designed to end plastic pollution. This agreement is expected to include concrete plans for reducing plastic production, phasing out particularly problematic plastics, redesigning products that create significant microplastics, and more. A UN committee will meet in South Korea the week of November 25 to finalize a draft of the agreement.

“Nobody’s saying there’s no safe way to use plastics,” Thompson told Yale Environment 360. “It’s just that we need to start making them to be safer and more sustainable than we have done so far, and that’s what the treaty needs to help us do.”

This article Are microplastics really destroying our health? is featured on Big Think.

If a 175 pound-man drank five one-liter handles of vodka in a day, he would die. But when a tiny Oriental hornet weighing half a gram consumes the equivalent amount of alcohol relative to its body size, it carries on like nothing happened.

Many animals, humans among them, imbibe alcohol. Pen-tailed tree shrews enjoy a boozy nectar produced by the bertam palm. African warthogs sometimes sup on fermented marula fruit. Humans down a couple IPAs at the local brew hall. But no matter how an animal chooses to consume alcohol, we all fall prey to its intoxicating effects.

Except for the Oriental hornet, it seems. In experiments recently described in the Proceedings of the National Academy of Sciences, researchers from Tel Aviv University in Israel plied these insects with enormous amounts of alcohol and watched as…nothing happened. They fed worker hornets solutions containing up to 80% ethanol for a week straight — a lengthy time for insects whose lifespan lasts only three months. The alcoholic hornets survived just as long as their abstaining counterparts and showed no signs of intoxication.

In another experiment, the scientists housed hornets with water, a sugar solution, and varying concentrated ethanol solutions, and let the insects choose what to drink. The insects consumed exorbitant amounts of the alcohol mixture over 24 hours — enough to kill a human many times over — yet were behaviorally and physically unaffected.

The researchers also fed bees similar amounts. Unlike their hornet cousins, bees became overtly inebriated, and many died the same day.

An alcohol-tolerating “superpower”

An explanation for Oriental hornets’ alcohol-tolerating superpower can be found in their genes. These insects have multiple copies of the alcohol dehydrogenase gene, the researchers found. This produces the enzyme that breaks down alcohol. The hornets likely evolved the extra copies over their long history of living with ethanol-producing yeasts. Many species of hornets and wasps harbor yeasts in their digestive systems. (Some brewers have even sampled these yeasts to craft new beers.) When they bite into fruits, they spread these single-celled fungi. The yeasts then ferment the fruit, creating alcohol.

What do hornets and wasps get for lugging yeasts around in their guts and delivering them to food sources? Access to extra energy, it seems. A gram of alcohol contains seven calories while a gram of sugar holds four. This makes alcohol a more efficient food source, provided consumers can handle the intoxicating effects. Encouraged by the yeast in their bodies, Oriental hornets apparently have evolved to do just that.

“To the best of our knowledge, Oriental hornets are the only animal in nature adapted to consuming alcohol as a metabolic fuel,” senior author Eran Levin of Tel Aviv University’s School of Zoology said in a statement.

Another benefit to the hornets: Alcohol kills potentially harmful bacteria. This comes in handy for hornet workers and larvae. Workers frequently collect carrion to nourish developing larvae.

Can the discovery come in handy for humans?

“With 5.3 percent of deaths in the world linked to alcohol consumption, we believe that, following our research, Oriental hornets could potentially be used to develop new models for studying alcoholism and the metabolism of alcohol,” Levin said.

In a commentary published in the wake of the study’s release, Prof. Dr. Rainer Spanagel at the University of Heidelberg agreed. Spanagel specializes in animal research on alcohol and drug addiction and translating the results to benefit humans.

“The study […] should serve as a wake-up call to develop new small molecules or repurpose drugs to specifically target alcohol metabolism genes, with the aim of reducing alcohol consumption or the harms associated with alcohol use disorder.”

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There’s no doubt that exercise does a body good. Regular activity not only strengthens muscles but can bolster our bones, blood vessels, and immune system.

Now, MIT engineers have found that exercise can also have benefits at the level of individual neurons. They observed that when muscles contract during exercise, they release a soup of biochemical signals called myokines. In the presence of these muscle-generated signals, neurons grew four times farther compared to neurons that were not exposed to myokines. These cellular-level experiments suggest that exercise can have a significant biochemical effect on nerve growth.

Surprisingly, the researchers also found that neurons respond not only to the biochemical signals of exercise but also to its physical impacts. The team observed that when neurons are repeatedly pulled back and forth, similarly to how muscles contract and expand during exercise, the neurons grow just as much as when they are exposed to a muscle’s myokines.

While previous studies have indicated a potential biochemical link between muscle activity and nerve growth, this study is the first to show that physical effects can be just as important, the researchers say. The results, which are published today in the journal Advanced Healthcare Materials, shed light on the connection between muscles and nerves during exercise, and could inform exercise-related therapies for repairing damaged and deteriorating nerves.

“Now that we know this muscle-nerve crosstalk exists, it can be useful for treating things like nerve injury, where communication between nerve and muscle is cut off,” says Ritu Raman, the Eugene Bell Career Development Assistant Professor of Mechanical Engineering at MIT. “Maybe if we stimulate the muscle, we could encourage the nerve to heal, and restore mobility to those who have lost it due to traumatic injury or neurodegenerative diseases.”

Raman is the senior author of the new study, which includes Angel Bu, Ferdows Afghah, Nicolas Castro, Maheera Bawa, Sonika Kohli, Karina Shah, and Brandon Rios of MIT’s Department of Mechanical Engineering, and Vincent Butty of MIT’s Koch Institute for Integrative Cancer Research.

Muscle talk

In 2023, Raman and her colleagues reported that they could restore mobility in mice that had experienced a traumatic muscle injury, by first implanting muscle tissue at the site of injury, then exercising the new tissue by stimulating it repeatedly with light. Over time, they found that the exercised graft helped mice to regain their motor function, reaching activity levels comparable to those of healthy mice.

When the researchers analyzed the graft itself, it appeared that regular exercise stimulated the grafted muscle to produce certain biochemical signals that are known to promote nerve and blood vessel growth.

“That was interesting because we always think that nerves control muscle, but we don’t think of muscles talking back to nerves,” Raman says. “So, we started to think stimulating muscle was encouraging nerve growth. And people replied that maybe that’s the case, but there’s hundreds of other cell types in an animal, and it’s really hard to prove that the nerve is growing more because of the muscle, rather than the immune system or something else playing a role.”

In their new study, the team set out to determine whether exercising muscles has any direct effect on how nerves grow, by focusing solely on muscle and nerve tissue. The researchers grew mouse muscle cells into long fibers that then fused to form a small sheet of mature muscle tissue about the size of a quarter.

The team genetically modified the muscle to contract in response to light. With this modification, the team could flash a light repeatedly, causing the muscle to squeeze in response, in a way that mimicked the act of exercise. Raman previously developed a novel gel mat on which to grow and exercise muscle tissue. The gel’s properties are such that it can support muscle tissue and prevent it from peeling away as the researchers stimulated the muscle to exercise.

The team then collected samples of the surrounding solution in which the muscle tissue was exercised, thinking that the solution should hold myokines, including growth factors, RNA, and a mix of other proteins.

“I would think of myokines as a biochemical soup of things that muscles secrete, some of which could be good for nerves and others that might have nothing to do with nerves,” Raman says. “Muscles are pretty much always secreting myokines, but when you exercise them, they make more.”

“Exercise as medicine”

The team transferred the myokine solution to a separate dish containing motor neurons — nerves found in the spinal cord that control muscles involved in voluntary movement. The researchers grew the neurons from stem cells derived from mice. As with the muscle tissue, the neurons were grown on a similar gel mat. After the neurons were exposed to the myokine mixture, the team observed that they quickly began to grow, four times faster than neurons that did not receive the biochemical solution.

“They grow much farther and faster, and the effect is pretty immediate,” Raman notes.

For a closer look at how neurons changed in response to the exercise-induced myokines, the team ran a genetic analysis, extracting RNA from the neurons to see whether the myokines induced any change in the expression of certain neuronal genes.

“We saw that many of the genes up-regulated in the exercise-stimulated neurons was not only related to neuron growth, but also neuron maturation, how well they talk to muscles and other nerves, and how mature the axons are,” Raman says. “Exercise seems to impact not just neuron growth but also how mature and well-functioning they are.”

The results suggest that biochemical effects of exercise can promote neuron growth. Then the group wondered: Could exercise’s purely physical impacts have a similar benefit?

“Neurons are physically attached to muscles, so they are also stretching and moving with the muscle,” Raman says. “We also wanted to see, even in the absence of biochemical cues from muscle, could we stretch the neurons back and forth, mimicking the mechanical forces (of exercise), and could that have an impact on growth as well?”

To answer this, the researchers grew a different set of motor neurons on a gel mat that they embedded with tiny magnets. They then used an external magnet to jiggle the mat — and the neurons — back and forth. In this way, they “exercised” the neurons, for 30 minutes a day. To their surprise, they found that this mechanical exercise stimulated the neurons to grow just as much as the myokine-induced neurons, growing significantly farther than neurons that received no form of exercise.

“That’s a good sign because it tells us both biochemical and physical effects of exercise are equally important,” Raman says.

Now that the group has shown that exercising muscle can promote nerve growth at the cellular level, they plan to study how targeted muscle stimulation can be used to grow and heal damaged nerves, and restore mobility for people who are living with a neurodegenerative disease such as ALS.

“This is just our first step toward understanding and controlling exercise as medicine,” Raman says. 

This article When muscles work out, they help neurons to grow is featured on Big Think.

In the summer of 2016, 100 teenage girls living in California’s Salinas Valley slipped silicone bracelets onto their wrists and committed to keep them there for a week. Around the same time, 92 preschoolers in Oregon accessorized the same way. The bands found their way onto the wrists of farmworkers in Peru and Houston residents working to rebuild after Hurricane Harvey. Aside from color, the wristbands looked much the same as the yellow Livestrong bracelets popularized by cyclist Lance Armstrong in the early 2000s.

But this was not some fashion trend shared by teenage girls, farmworkers and preschoolers. These bands were research tools, whose porous silicone made them ideal for soaking up chemicals in their surroundings. All were worn as part of a growing effort to understand just what is present in different environments and how those “exposures” — be they pesticides, smoke, floodwater contaminants or just the day-to-day contents of a preschool classroom — can affect health.

In homes, on buildings, from satellites and even in apps on the phone in your pocket, tools to monitor the environment are on the rise. At the intersection of public health and toxicology, these tools are fueling a new movement in exposure science. It’s called the exposome and it represents the sum of all environmental exposures over a lifetime. As explored in a trio of papers in the Annual Review of Public Health, scientists think that if we knew every substance that a person was exposed to at every moment ever, it could give rise to dramatic improvements in the understanding of the causes and risk factors for disease.

That goal, its architects will readily admit, is absurdly ambitious — even impossible. But even imperfectly realized, the approach may be what’s needed to finally understand why one person develops a disease and another doesn’t, which environmental exposures are the most worrying and if there are windows of vulnerability — times of life when exposures may be especially harmful.

“We think about all health and illness as a combination of genes and the environment, and now it really is time to fill out the environment side of that equation,” says Julia Brody, a toxicologist affiliated with Brown University and the leader of the Silent Spring Institute, which studies environmental links to breast cancer. “We’ve made an enormous investment in understanding the genome and almost nothing comparatively to focus on the exposome.”

Impossible or not, researchers are forging ahead, breaking off bits and pieces of a lifetime’s exposure to put under the microscope. Still, discussions continue about how to make real progress and how to collect and examine information in a meaningful way.

Some scientists are advocating for more air monitors in cities and homes. Others are developing wearable monitors that soak up pieces of the environment as people move through their day. Some are trying to match tracking data from cell phones to satellite indicators of air quality, helping to assess individual exposures based on a person’s locale and movements. Still other researchers are looking inside the body, hoping to identify chemical footprints that distinct exposures may have left behind.

Bracelets made of porous silicone passively soak up chemicals from the environment. The material can trap thousands of airborne substances, including pesticides, pharmaceuticals and flame retardants. Researchers are taking advantage of the lightweight bracelets to detect chemicals that study participants encounter in their day-to-day lives. (CREDIT: KNOWABLE MAGAZINE. SOURCE: OREGON STATE UNIVERSITY EHSC)

Though varied, the approaches share the goal of adding breadth to traditional exposure science studies, which have historically focused on linking a single disease to one or more suspicious exposures, often as cases build up over time. A history of poisoned lead workers dating back to the time of the Romans led modern researchers to demonstrate that even low levels of lead from automobile exhaust posed a serious public health risk. And a startling spike in lung cancer cases alongside increased smoking popularity drove researchers to perform focused studies on the dangers of cigarettes in the mid-twentieth century.

But many potentially harmful exposures could be far less obvious. The air you breathe, the food you eat, the products you use, the medicines you take, the surfaces you touch — all may contain multitudes of invisible chemicals (many naturally occurring, others not) and microbes you never know you’ve contacted. Thus, exposure science remains far from what it would ideally be: a guide to avoiding disease risk. Exposome scientists want to change that by capturing as broad a picture as possible. They want to ask not only if certain chemicals or microbes can harm health, but also if certain substances are dangerous in particular combinations, during particular times — such as during pregnancy — or to particular groups of people.

An “ome” of one’s own

It was a concern for unexplained diseases that led cancer researcher Christopher Wild to first come up with the term “exposome” in 2005. Wild had closely followed the race to sequence the human genome, which had successfully concluded two years prior, and worried that, in its eagerness to advance genetics, the world had forgotten the importance of environmental exposures in health. It’s a sentiment that has only grown stronger in recent years as genetics has failed to yield clear links to many cancers and other diseases. A recent study looked at the prevalence of 28 chronic conditions in twins and found that genetics explained less than 20 percent of the risk in most of the illnesses examined. Even in asthma — which ranked highest in terms of genetic contribution — genetics explained less than 50 percent of the risk. For leukemia — on the other end of the rankings — genetics explained only 3 percent.

“I was excited about the genetics,” says Wild, who formerly directed the World Health Organization’s International Agency for Research on Cancer. “But I felt it was an imbalance in the tools and the investment that we had available, and that was going to lead to problems. If we can’t measure this other component, we’re not going to get to the bottom of the problem.”

To remind the world that the genome was only half the equation, Wild coined an “ome” of his own. He hoped that if the two factors had mirroring names it would push other scientists to think of them as having equal importance. It took some time, but slowly his colleagues have begun to rally around the idea. Efforts to develop sophisticated devices that sample the world around us are on the rise. And new research groups are forming around the world to bring together the technology and expertise needed to process the vast amounts of data that will come from emerging exposomics projects.

One example is the Children’s Health Exposure Analysis Resource, a network of US laboratories and other resources established by the National Institute of Environmental Health Sciences to support researchers who want to add a stronger environmental component to their studies. CHEAR will allow scientists to test for more chemicals that children may be exposed to — hundreds to thousands at once — and will develop standardized testing to allow for data comparison across studies. The importance of such a resource is to help researchers break away from looking at a small number of potential threats at a time and start moving toward a way to take into account the entire realm of exposures, says Susan Teitelbaum, a member of CHEAR’s executive committee and a public health researcher at the Icahn School of Medicine at Mount Sinai in New York City.

Efforts so far have focused largely on establishing the technology, methods and collaborations needed to move forward, but early studies have already yielded some small insights. A preliminary study that used wristbands to examine chemical exposure in preschoolers found that, as they go about their daily lives, children are exposed to many flame retardants — even some that have been phased out due to concerns about toxicity.

Pilot studies to test new devices have led to a few, more personal realizations as well. Katherine Sward, a biomedical informatics researcher at the University of Utah, reported that a family trying out an in-home air monitor realized that vacuuming right before a visit from their child’s asthmatic friend might actually lead to more, not less, risk after the cleaning launched dust particles into the air. In another pilot, a researcher using a portable monitor to track exposure to airborne particles concluded that he was allergic to eucalyptus, not pine, as he previously believed, when he noted that his worst symptoms seemed to correlate with high levels of eucalyptus pollen detected by his device.

Looking inward

Researchers are still a long way from tracking even a fraction of the potential threats that surround us. Some think it might be more practical to tackle the problem by focusing on what’s inside the body, hunting for traces of past exposures. Signatures left over in blood, urine, teeth and even toenails can hint at previous exposures. Blood in particular holds clues that can let researchers work backwards to match biological changes to triggering exposures, says Dean Jones, a biochemist at Emory University in Atlanta and coauthor of a 2019 article about the promise of the exposome paradigm in the Annual Review of Pharmacology and Toxicology. The dream, he says, is to someday be able to create a readout of how the body is being affected by the environment and then determine the substances an individual should avoid, based on how they respond to each one.

“All people are pre-disease,” Jones says. “The vision is that we will have tools good enough to put data together into predictive programs and the predictive programs will say: You are likely to develop renal disease when you are in your 50s and if you do a, b, c, you’ll reduce that risk.”

In blood, Jones can look for metabolites, small molecules broken down or created by body processes. With tens of thousands of detectable components that hint at what the body is doing chemically, metabolites may be one possible alphabet scientists could use to read back what’s happened internally following various exposures.

At the UC Berkeley School of Public Health, Stephen Rappaport is exploring a different language found in blood. By examining human serum albumin — a protein that vacuums up damaging compounds circulating in blood — Rappaport can look for the residues those compounds have left behind. Both Jones and Rappaport think they can link these internal signs to external exposures. Eventually they aim to identify the ones that pose harm.

Blood can provide a snapshot of the goings-on inside the body, says Rappaport. “Most of the things we think about as being toxic or protective from disease are things that are actively transported by the blood.”

A data problem

Even if scientists can count on the body to point to harmful chemicals, other challenges remain. Once scientists have found something in the blood, they must try to trace it back to a known chemical in a database. But they often won’t find a match. The vast majority of the world’s chemicals (both natural and human-made) have never been characterized and new chemicals are created all the time.

Simply getting a handle on how many chemicals are out there is harder than it sounds. A recent study attempted this in 100 consumer products. Toothpaste contained 85 chemicals, while one plastic children’s toy contained about 300. Across all the products, the study detected 4,270 unique chemical signatures and tentatively identified 1,602 of those. But only 30 percent of those 1,602 chemicals could be matched to public lists of known ingredients in consumer products or compounds of toxicological interest.

“There’s got to be tens of millions — hundreds of millions, if not more,” says Jon Sobus, an environmental health scientist at the US Environmental Protection Agency and coauthor on the consumer products study. “Where does the number of chemicals end?”

With so many unknowns, scientists are left with a huge number-crunching issue, making the exposome, like so many fields today, a big data problem. That’s forcing scientists to devise new ways to analyze the information they collect. One approach gaining popularity borrows from a common, if sometimes controversial, method in genetics. Dubbed the genome-wide association study, or GWAS, the method looks to see which of thousands of genes vary in conjunction with a particular disease or symptom.

In 2010, Harvard bioinformatician Chirag Patel adapted the GWAS into an environment-wide association study to see how 266 environmental factors varied in step with the risk of developing type II diabetes. The study rediscovered certain factors already linked to diabetes risk, but also pointed researchers to other potential risks, including a dietary component of vitamin E and heptachlor, a pesticide previously linked to type II diabetes in workers who applied it, but not known to have an effect at smaller levels in the general population.

After this, other researchers adopted the EWAS method to look for substances that might confer risk and should be studied further. In a 2011 study examining metabolites in human plasma, researchers found three small molecules that correlated with increased risk of cardiovascular disease later on. One of these was trimethylamine N-oxide, or TMAO. TMAO is a byproduct of choline, which is found in certain foods, including meat and eggs. Researchers realized that certain gut microbes converted choline to an intermediate compound, which was then broken down to TMAO in the liver. In mice, high TMAO levels corresponded to thickened artery walls. The researchers proposed that manipulating a patient’s microbiome might be able to protect people from this type of dietary exposure.

The study was applauded by researchers like Rappaport, who sees it as a validation of the EWAS method. Still GWAS itself is far from perfect and the EWAS faces many additional challenges when compared to its genetic predecessor. A genome-wide study is contained in a way that an environment-wide search is not. Humans have a lot of genes — about 20,000 that code for proteins. But that number pales in comparison to the number of things people might encounter in the environment. And unlike the genome — which is packaged together in a place we know how to find — our “exposures” can be anywhere at any time in any quantity.

The sheer scope of the problem is daunting to researchers just hearing about the exposome. But for Sobus, it’s not unlike the early days of genomics, when many wondered if mapping the human genome was an unfeasible goal. As more tools and resources are created, more scientists are finding ways to incorporate the idea into their studies, he says. And each researcher who decides to tackle even a small chunk helps move the field forward.

“I think everyone kind of goes through that growth period of a little bit of disbelief,” he says. “Then you start warming up to it and you want to get on the band wagon.”

This article The next omics? Tracking a lifetime of exposures to better understand disease is featured on Big Think.

Parkinson’s disease is on the rise. According to the World Health Organization (WHO), the prevalence of the neurodegenerative disease has doubled worldwide since the turn of the century. This has been linked to a constellation of factors, though the most prominent risks are age and genetics. As the world population grows older, we’re likely to see Parkinson’s cases, and deaths, grow in tandem.

Parkinson’s disease caused 329,000 deaths in 2019, according to the WHO, a 100% increase since 2000. Each data point represents the heartbreaking struggles of people and families living with the diseases. And those realities can be devastating.

Mart Saarma, a neurobiologist and professor at the University of Helsinki, has witnessed it firsthand. His uncle was stricken with the disease, and Saarma watched as it slowly degraded his uncle’s quality of life and transformed his personality. Once, Saarma went to help his uncle, and his uncle called the police. Unable to recognize his nephew, he feared a stranger had come to rob him.

“People have understood how important it is to fight cancer, and thanks to that, we have started to get the first efficient cancer drugs. Unfortunately, this has not been the case with neurodegenerative diseases,” Saarma says. “The field still suffers from [a lack of] funding, and this is becoming a significant problem in Western societies. We now have about 10-12 million Parkinson’s patients, which will double in 20 years. We need to take this very seriously.”

The message is starting to get out. Last year, GeneCode, a pharmaceutical company where Saarma serves as the chief science officer, won a record-breaking €16 million funding option from the European Innovation Council Accelerator. The reward was to support the development of a novel drug designed to combat neurodegeneration in Parkinson’s patients.

Freethink recently spoke with Saarma to discuss how their treatment promises to help Parkinson’s patients. According to him, preliminary evidence suggests the drug may not only alleviate symptoms, it may also protect the neurons from further damage and help to restore them for a healthier, longer life.

On the path to neuron death

Another reason that treatments for Parkinson’s and other neurodegenerative diseases are lagging behind those for other ailments is that the brain is a fiendishly complex organ. The human brain houses 100 billion neurons. That’s roughly the same number of stars in our Milky Way galaxy. But as Saarma points out, it’s hardly a perfect comparison because neurons don’t exist in interstellar isolation. Instead, they form thousands of intimate, unique connections with other neurons — connections that are vital to their health and function.

“So, the Milky Way galaxy is a piece of cake compared to our brain,” he jokes.

The brain is exceptional in another way, too. Unlike skin cells, the vast majority of neurons don’t go forth and multiply — or, in this case, divide. They are among the few cell types in your body that don’t regenerate through mitosis, leaving the brain with limited opportunities to self-repair. Once a neuron matures, it either lives or dies; if it dies, that’s that. To stay alive, neurons need energy and protection. Without them, neurodegenerative diseases begin.

In the case of Parkinson’s disease, the epicenter of this die-off is the substantia nigra, a structure located in the midbrain. It houses clusters of dopamine-producing neurons that are necessary for proper brain and, by extension, bodily function.

Although dopamine is famous for being one of the “happy hormones,” its role in the body and brain is manifold. In our brains, it serves as a neurotransmitter that neurons use for communication and coordination. It signals rewarding feelings for experiences we find pleasurable. It helps regulate sleep, mood, motivation, and blood flow. In the substantia nigra, it is especially important for aligning movement.

Because of this diversity, Saarma likens dopamine to a symphony conductor. When dopamine production is normal, these bodily activities act in harmonious rhythm. But when production is disrupted, these same activities grow discordant. And Parkinson’s robs the brain of its conductor.

As disease sets in, these midbrain neurons become impaired and lose the ability to produce dopamine. Their synaptic connections break down, and unable to coordinate with the millions of other neurons they rely on, they begin to die. This creates a cascading effect — as the neurons die, the disease progresses, leading to more neural death and further progression.

Their loss is experienced as inhibited movement. Parkinson’s patients endure tremors, spasms, and muscle stiffness. These alienate them from their bodies in ways that make even prosaic activities like getting out of bed a painful endeavor.

But as dopamine’s conductor role suggests, patients may also experience a gamut of other debilitating symptoms. These include insomnia, constipation, vertigo, tooth decay, and a variety of aches and pains. There’s also the possibility of dementia. Some, though not all, patients develop apathy, impulse-control problems, or wild mood swings. They can lose their attention, motivation, and even memories.

Whatever set of symptoms ultimately develop, they all harm a patient’s quality of life, and the mere presence of this symptomatic lottery weighs heavily on them and their loved ones from the first diagnosis.

The challenge of curing Parkinson’s

To prevent this die-off, researchers like Saarma have been looking for a way to reinvigorate neurons. While that’s proven challenging, there have been some successes in managing the symptoms of the disease — though the ultimate goal of treating it remains out of reach.

Today, a standard treatment for Parkinson’s patients is levodopa. It’s a dopamine-replacement agent often taken as a pill. Once absorbed into the blood through the gut, the drug enters the brain where it converts into dopamine that neurons can use. Unfortunately, levodopa only helps manage symptoms. It also has some downsides, such as inducing nausea.

It’s nonetheless essential for Parkinson’s patients because this drug, unlike most, can pass through the blood-brain barrier. Think of the barrier like a biochemical wall that keeps foreign pathogens from entering the brain. It’s a necessary defense for our health; however, that very protection also makes it difficult for life-saving drugs to reach their neural destination.

“None of the available drugs can slow down or stop the degeneration and death of these neurons,” Saarma says. “So, the major goal of companies is to develop drugs that would slow down or even stop disease progression. If that were to be successful, it would be a fundamental change in the treatment of neurodegenerative diseases.”

Other treatments have focused on neurotrophic factors — proteins that support the maintenance of neurons by activating “neuroprotective mechanisms.” In our interview, Saarma cited animal research showing that a specific protein — called a GDNF — actually cured the disease in mice and non-human primates. 

Human clinical trials, he notes, have also shown positive results in rescuing and regenerating neurons.

But there’s a catch: These proteins are hefty in molecular terms. They weigh roughly 32,000 daltons, a unit of mass used by chemists and physicists. That’s far too large to pass the blood-brain barrier — which imposes a limit of around just 400-600 daltons — meaning GDNF can’t be taken as a pill or through an injection. To get these proteins to the degenerating neurons, the researchers in these trials needed to put them there directly through brain surgery. 

Such a surgery is obviously invasive and risky. Because of this, Saarma explains, ethics committees won’t approve it for early-stage patients — even though the sooner one starts treatment after a diagnosis, the better the outcome will likely be.

“In these clinical trials, GDNF has been given to patients 10 years after their diagnosis,” Saarma says. “[By then], only 20–25% of dopamine neurons are still alive.”

Harmonizing the mind-body connection

GeneCode’s own novel drugs exist in the middle ground. They developed what is commonly known as a “GDNF mimetic,” composed of molecules that imitate how neurotrophic factors act in the brain. Like the large proteins, they bind to the GDNF receptors on the neuron’s axons and send chemical signals that stimulate dopamine production. This helps the neurons with axons stay active and maintain synaptic connections with other neurons.

Unlike the proteins, these molecules are small, weighing roughly 500 daltons. This means GeneCode’s drug can pass the blood-brain barrier as a potential pill or injection. This would allow treatment during earlier stages, when more neurons are still alive and higher quality of life can be potentially maintained much longer.

“The production, the transportation, the storage of small molecules is much, much, much cheaper,” Saarma says. “This means that the whole treatment will potentially be available for people all over the world, which I think is quite important.”

The preliminary results have been promising. Saarma and his team in Helsinki tested both GDNF proteins and their mimetic compound on model Parkinson’s dopamine neurons in the lab. They found that both not only protected these neurons from further degeneration, they also stimulated the growth of axons and neural regeneration.

“If we are lucky, we will have a wonderful drug that slows down or stops neurodegeneration in the brain and also stops it in the periphery to alleviate non-motor symptoms like constipation, pain, sleep disorders, and depression, which significantly reduce the quality of life of Parkinson’s patients,” Saarma says.

The path ahead 

Drug development is a long and arduous process, and GeneCode still has much to do. The company is about to finish animal experiments. After that, they must certify that the drug can be consistently and safely produced to ensure future quality assurance. They then have to perform toxicology studies — all before the drug can begin clinical trials in humans.

“Although I think we have a very good drug candidate, there is, of course, always room for improvement,” Saarma says. “We have great preliminary data and a model of Parkinson’s disease, [but] the situation is different when you get into humans. A reminder: The rat brain is three grams. Our brain is one-and-a-half kilos. That’s a 500 times difference.”

But while Saarma is pragmatic, he’s also optimistic. During our conversation, he mentioned how GeneCode’s efforts have been supported by an international community of researchers and medical professionals. Among them are the French start-up ArgoBio, which GeneCode partnered with to develop their drug, and a collection of labs across Europe and the United States, including the Neil McDonald Lab at the Francis Crick Institute in London.

Even if GeneCode’s drug doesn’t work out, it’s that kind of collaboration and knowledge sharing that ultimately leads to the progress necessary to give Parkinson’s patients and their loved ones more hope than they had yesterday.

As Saarma notes, “The field is endless, but my life is limited, as are all of ours. But you do what you can with your time.”

This article The exciting research that may cure Parkinson’s  is featured on Big Think.

Billions of cells die in your body every day. Some go out with a bang, others with a whimper.

They can die by accident if they’re injured or infected. Alternatively, should they outlive their natural lifespan or start to fail, they can carefully arrange for a desirable demise, with their remains neatly tidied away.

Originally, scientists thought those were the only two ways an animal cell could die, by accident or by that neat-and-tidy version. But over the past couple of decades, researchers have racked up many more novel cellular death scenarios, some specific to certain cell types or situations. Understanding this panoply of death modes could help scientists save good cells and kill bad ones, leading to treatments for infections, autoimmune diseases and cancer.

“There’s lots and lots of different flavors here,” says Michael Overholtzer, a cell biologist at Memorial Sloan Kettering Cancer Center in New York. He estimates that there are now more than 20 different names to describe cell death varieties.

Here, Knowable Magazine profiles a handful of classic and new modes by which cells kick the bucket.

The identification of new forms of cell death has sped up in recent years.

Unplanned cell death: Necrosis

Lots of bad things can happen to cells: They get injured or burned, poisoned or starved of oxygen, infected by microbes or otherwise diseased. When a cell dies by accident, it’s called necrosis.

There are several necrosis types, none of them pretty: In the case of gangrene, when cells are starved for blood, cells rot away. In other instances, dying cells liquefy, sometimes turning into yellow goop. Lung cells damaged by tuberculosis turn smushy and white — the technical name for this type, “caseous” necrosis, literally means “cheese-like.”

Any form of death other than necrosis is considered “programmed,” meaning it’s carried out intentionally by the cell because it’s damaged or has outlived its usefulness.

A good, clean death: Apoptosis

The two main categories of programmed cell death are “silent and violent,” says Thirumala-Devi Kanneganti, an immunologist at St. Jude Children’s Research Hospital in Memphis, Tennessee. Apoptosis, first named in 1972, is the original silent type: It’s a neat, clean form of cell death that doesn’t wake the immune system.

That’s handy when cells are damaged or have served out their purpose. Apoptosis allows tadpoles to discard tail cells when they become frogs, for example, or human embryos to dispose of the webbing between developing fingers.

The cell shrinks and detaches from its neighbors. Genetic material in the nucleus breaks into pieces that scrunch together, and the nucleus itself fragments. The membrane bubbles and blisters, and the cell disintegrates. Other cells gobble up the bits, keeping the tissue tidy.

In necrosis, a cell dies by accident, releasing its contents and drawing immune cells to the site of damage by creating inflammation. In apoptosis, the cell collapses in on itself and the bits are cleared away without causing damaging inflammation.

Red flags: Necroptosis and pyroptosis

These are the violent kinds, and they helped expand the cell death repertoire beyond apoptosis and necrosis. They’re often engaged when cells have been hijacked by viruses or other infectious agents. Rather than be reduced to virus factories, they kill themselves. These cells go down waving big red flags, in the form of chemicals they release to alert the immune system to come in and save their neighbors.

In a 1998 study, a team disabled the ability of cells grown in dishes to undergo apoptosis, and the cells still died. But they did it in a messy way that came to be called necroptosis for its mix of apoptosis and necrosis features. As with necrosis, the cells and their organelles swell up and then the outer membrane ruptures. Necroptosis is a handy backup mechanism because some infectious agents can disable apoptosis.

Then there’s pyroptosis, first observed in 1992 among white blood cells infected with dysentery bacteria and christened in 2001. This is “the screaming, alarm-ringing pro-inflammatory death of a potentially dangerous cell,” the namers wrote. As with necroptosis, cells swell up. They activate enzymes that poke holes in the cell membrane, so their contents leak out, calling up an immune response.

Whether from pyroptosis or necroptosis, that immune response is needed to activate the body’s defenses against infection, such as the fever that cooks invaders, says Kanneganti, who coauthored an article about molecules involved in cell death in the 2020 Annual Review of Immunology. But if too many cells die or the immune system gets stuck in the “on” position, that can lead to ongoing inflammation or autoimmune disease.

Mix and match: PANoptosis

Immune cells, too, may need to die in the case of infection, inflammation or even cancer. As Kanneganti’s group investigated this process, they noticed an alternate mode of death that incorporated elements of apoptosis, necroptosis and pyroptosis. Using the first letter of each classic type, they dubbed it PANoptosis. Since then, researchers have found this hybrid death method in other kinds of cells, too.

In PANoptosis, the cell assembles a big protein machine called the PANoptosome. This activates enzymes to puncture the cell’s membranes. As it dies, the cell releases red-flag molecules that tell other immune cells there’s a problem.

Why do cells need so many ways to achieve the same fatal end? Cells probably evolved these different options during an arms race with disease-causing microbes, Kanneganti surmises. The microbes, aiming to survive, may try to turn off cell death. But if the cell has a wide menu of death mechanisms, it can commit suicide in another manner, sacrificing itself to thwart the pathogen.

Kamikaze killing: NETosis

Immune cells may sacrifice themselves even more dramatically, in a kamikaze action that takes out surrounding pathogens too. This sensational act is the purview of white blood cells called neutrophils, which patrol areas of infection and swallow invaders.

But sometimes the infectious agents are too large, or too numerous, to devour. The neutrophils switch tactics and vomit their own DNA over the pathogen, ensnaring the invaders in a kind of genomic net. It’s called NETosis (for neutrophil extracellular traps). Other cells then dispose of the entangled pathogens.

On occasion, the net-throwing cell is already dying or dead as this takes place, making it a zombie cell committing one final, altruistic act, says immunologist Ben Croker, who studies the phenomenon at the University of California San Diego School of Medicine.

Death metal: Cuproptosis and ferroptosis

While cancer cells seem ominous, they are, in fact, quite vulnerable to death, says Todd Golub, a cancer biologist at the Broad Institute in Cambridge, Massachusetts. “The key,” he adds, “is to find the right triggers.”

Golub’s group found a trigger in drugs that ferry copper into cells. The team is still working out how that makes the cells croak in a process they christened cuproptosis in 2022.

Iron, too, can be deadly to cancer cells, as chemical biologist Brent Stockwell at Columbia University in New York discovered. In addition to tumors, normal cells in the brain, liver and kidneys appear to be particularly susceptible to this form of cell death, which he named ferroptosis in 2012. Researchers have also observed ferroptosis in a wide range of organisms, even yeast and plants, says Stockwell, who cowrote a description of the key features of ferroptosis in the 2019 Annual Review of Cancer Biology.

Stockwell and other researchers are working to identify drugs or special diets that would activate ferroptosis to combat cancer, or block it to protect cells from dying in diseases such as Alzheimer’s.

Eat me: Entosis

Overholtzer, while studying breast cancer cells in the early 2000s, noticed something weird: cancer cells burrowing into other cells. He and his lab supervisor dubbed the phenomenon entosis in 2007.

The invading cell winds up enclosed in a big, membranous bubble. It may starve and undergo apoptosis, or be killed by the surrounding cell. Then the outer cell digests its remains.

But sometimes, weirdly, it survives and pops out of the cell to live independently again. Noting this, some researchers have proposed that entosis gives cancer cells a way to temporarily hide out from the immune system or cancer drugs.

There’s still plenty to learn about cell deaths, and there are probably death modes still awaiting discovery, Golub speculates.

Ultimately, the study of life requires the investigation of cell death. As the Japanese author Haruki Murakami wrote, “Death exists, not as the opposite but as a part of life.”

This article Your cells are dying. All the time. is featured on Big Think.

A highly contagious bird flu epidemic has spread from continent to continent since 2020. It has killed hundreds of millions of wild birds and caused sporadic outbreaks among poultry. In recent months, the avian influenza strain that causes the disease (H5N1) has jumped to dairy cows, domestic cats, and even humans.

In one case this year, a Missouri patient contracted the disease seemingly without exposure to an infected animal. It’s currently unknown how the patient contracted the virus. Some experts have suggested it may have been from consuming raw milk, but while traces of the virus have been found in unpasteurized milk samples, the limited information available makes it challenging to determine if raw milk is a potential source (though, it should be noted, pasteurized milk is perfectly safe to drink).

While bird flu in humans is a cause for concern, transmission remains fortunately rare. According to the World Health Organization (WHO), only 896 cases have been reported worldwide between January 2003 and July 2024. That said, if cases of bird flu in humans continue to rise, it could mean the virus is getting better at infecting people. In a recent study published in Nature Communications, researchers at the European Molecular Biology Laboratory (EMBL) discovered mutations in the bird flu genome that could give the virus this ability by allowing it to better exploit mammalian ANP32 proteins.

Viruses of a feather (don’t always stick together)

Viruses are incapable of reproducing outside a host. To make more of themselves, they must first invade a host cell and take over its cellular machinery. In the case of the bird flu virus, its polymerases — enzymes that make new copies of the virus genome — interact with ANP32 proteins to form a structure called the replication complex. As the name suggests, this complex is necessary for the virus to replicate. (In fact, in a different study, scientists used CRISPR gene-editing technology to engineer chickens resistant to bird flu. They did so by targeting the genes coding for ANP32 proteins.)

However, differences in avian and mammalian versions of this protein explain why avian influenza doesn’t typically infect mammals. Specifically, the avian ANP32 has an amino acid tail that is missing in human ANP32. Researchers have previously observed that virus particles could hold on to the avian ANP32 as they move from birds to mammals, possibly explaining some of the cases of avian flu in mammals. Even so, for the virus to be more successful in mammals, it must be able to use the mammalian ANP32 as effectively as the avian version.

In the recent study, the EMBL researchers used cryo-electron microscopy (cryo-EM), an advanced imaging technique with near-atomic resolution, to look at the structures of the viral polymerases of human-adapted bird flu strains as they interacted with human ANP32.

They found that the ANP32’s amino acid tail steadies the viral polymerases. Besides replicating the viral genome, the polymerases encapsulate the genome into virus particles that subsequently infect other cells. When carrying out the two functions, the polymerases take on two conformations, termed replicases and encapsidases. The study revealed that ANP32 creates a bridge between the two conformations, and this bridge facilitates the assembly of the replication complex.

The extremely detailed cryo-EM structures of the replication complex revealed which individual amino acids participated in the assembly of the replication complex. In other words, the researchers could figure out which amino acids in the replication complex were essential to the replication of the virus. Mutations in these regions of the viral polymerase could make it bind more tightly to human ANP32, potentially improving the virus’s ability to replicate inside human cells.

Keeping better tabs on avian influenza

To monitor the spread of avian influenza, the Centers for Disease Control and Prevention sequences viruses from samples obtained from infected animals in addition to tracking reports of illnesses and deaths. This is to trace mutations in the virus populations. The EMBL study establishes a link between the structure of the replication complex and adaptive mutations in the viral polymerases. Researchers could use this insight to determine if a particular bird flu virus strain is close to gaining the ability to infect people.

As bird flu continues to spread among birds and cattle, there will be more opportunities for the virus to jump to the humans who contact them. This is why experts suggest that more animals, and people around them, be checked for bird flu even in the absence of symptoms. Bird flu becoming the next pandemic is still an unlikely scenario as there is no evidence of human-to-human transmission of the virus. 

But while human cases of bird flu may not be widespread, they are highly deadly. Of those 896 cases reported between 2003-2024, 463 were fatal. The high lethality could arguably be attributed, in part, to the fact that many human cases lack obvious symptoms and go under-diagnosed. Regardless, there is a pressing need for therapies to treat human cases of avian influenza as well as stem the spread of avian influenza outbreaks among poultry and cattle.

While there are many influenza virus strains, and new ones keep emerging, the replication complex is central to how they infect and replicate in host cells. Future studies will need to investigate the dynamics of replication in more detail to make the replication complex a key target for anti-influenza drugs.

This article Decoding bird flu: New research reveals potential route for human infection is featured on Big Think.

Low-calorie diets and intermittent fasting have been shown to have numerous health benefits: They can delay the onset of some age-related diseases and lengthen lifespan, not only in humans but many other organisms.

Many complex mechanisms underlie this phenomenon. Previous work from MIT has shown that one way fasting exerts its beneficial effects is by boosting the regenerative abilities of intestinal stem cells, which helps the intestine recover from injuries or inflammation.

In a study of mice, MIT researchers have now identified the pathway that enables this enhanced regeneration, which is activated once the mice begin “refeeding” after the fast. They also found a downside to this regeneration: When cancerous mutations occurred during the regenerative period, the mice were more likely to develop early-stage intestinal tumors.

“Having more stem cell activity is good for regeneration, but too much of a good thing over time can have less favorable consequences,” says Omer Yilmaz, an MIT associate professor of biology, a member of MIT’s Koch Institute for Integrative Cancer Research, and the senior author of the new study.

Yilmaz adds that further studies are needed before forming any conclusion as to whether fasting has a similar effect in humans.

“We still have a lot to learn, but it is interesting that being in either the state of fasting or refeeding when exposure to mutagen occurs can have a profound impact on the likelihood of developing a cancer in these well-defined mouse models,” he says.

MIT postdocs Shinya Imada and Saleh Khawaled are the lead authors of the paper, which appears today in Nature.

Driving regeneration

For several years, Yilmaz’s lab has been investigating how fasting and low-calorie diets affect intestinal health. In a 2018 study, his team reported that during a fast, intestinal stem cells begin to use lipids as an energy source, instead of carbohydrates. They also showed that fasting led to a significant boost in stem cells’ regenerative ability.

However, unanswered questions remained: How does fasting trigger this boost in regenerative ability, and when does the regeneration begin?

“Since that paper, we’ve really been focused on understanding what is it about fasting that drives regeneration,” Yilmaz says. “Is it fasting itself that’s driving regeneration, or eating after the fast?”

In their new study, the researchers found that stem cell regeneration is suppressed during fasting but then surges during the refeeding period. The researchers followed three groups of mice — one that fasted for 24 hours, another one that fasted for 24 hours and then was allowed to eat whatever they wanted during a 24-hour refeeding period, and a control group that ate whatever they wanted throughout the experiment.

The researchers analyzed intestinal stem cells’ ability to proliferate at different time points and found that the stem cells showed the highest levels of proliferation at the end of the 24-hour refeeding period. These cells were also more proliferative than intestinal stem cells from mice that had not fasted at all.

“We think that fasting and refeeding represent two distinct states,” Imada says. “In the fasted state, the ability of cells to use lipids and fatty acids as an energy source enables them to survive when nutrients are low. And then it’s the postfast refeeding state that really drives the regeneration. When nutrients become available, these stem cells and progenitor cells activate programs that enable them to build cellular mass and repopulate the intestinal lining.”

Further studies revealed that these cells activate a cellular signaling pathway known as mTOR, which is involved in cell growth and metabolism. One of mTOR’s roles is to regulate the translation of messenger RNA into protein, so when it’s activated, cells produce more protein. This protein synthesis is essential for stem cells to proliferate.

The researchers showed that mTOR activation in these stem cells also led to production of large quantities of polyamines — small molecules that help cells to grow and divide.

“In the refed state, you’ve got more proliferation, and you need to build cellular mass. That requires more protein, to build new cells, and those stem cells go on to build more differentiated cells or specialized intestinal cell types that line the intestine,” Khawaled says.

Too much of a good thing

The researchers also found that when stem cells are in this highly regenerative state, they are more prone to become cancerous. Intestinal stem cells are among the most actively dividing cells in the body, as they help the lining of the intestine completely turn over every five to 10 days. Because they divide so frequently, these stem cells are the most common source of precancerous cells in the intestine.

In this study, the researchers discovered that if they turned on a cancer-causing gene in the mice during the refeeding stage, they were much more likely to develop precancerous polyps than if the gene was turned on during the fasting state. Cancer-linked mutations that occurred during the refeeding state were also much more likely to produce polyps than mutations that occurred in mice that did not undergo the cycle of fasting and refeeding.

“I want to emphasize that this was all done in mice, using very well-defined cancer mutations. In humans it’s going to be a much more complex state,” Yilmaz says. “But it does lead us to the following notion: Fasting is very healthy, but if you’re unlucky and you’re refeeding after a fasting, and you get exposed to a mutagen, like a charred steak or something, you might actually be increasing your chances of developing a lesion that can go on to give rise to cancer.”

Yilmaz also noted that the regenerative benefits of fasting could be significant for people who undergo radiation treatment, which can damage the intestinal lining, or other types of intestinal injury. His lab is now studying whether polyamine supplements could help to stimulate this kind of regeneration, without the need to fast.

“This fascinating study provides insights into the complex interplay between food consumption, stem cell biology, and cancer risk,” says Ophir Klein, a professor of medicine at the University of California at San Francisco and Cedars-Sinai Medical Center, who was not involved in the study. “Their work lays a foundation for testing polyamines as compounds that may augment intestinal repair after injuries, and it suggests that careful consideration is needed when planning diet-based strategies for regeneration to avoid increasing cancer risk.”

The research was funded, in part, by Pew-Stewart Scholars Program for Cancer Research award, the MIT Stem Cell Initiative, the Koch Institute Frontier Research Program via the Kathy and Curt Marble Cancer Research Fund, and the Bridge Project, a partnership between the Koch Institute for Integrative Cancer Research at MIT and the Dana-Farber/Harvard Cancer Center.

This article Study reveals the benefits and downside of fasting is featured on Big Think.

In a year-long study carried out between June 2016 and October 2021, 296 previously sedentary older adults with mild cognitive impairment, a disorder that often precedes Alzheimer’s disease, were assigned to undergo one of two treatments for 12 months. Their disease progression was compared to a matched group of subjects undergoing usual care. Over the trial, participants receiving the treatments experienced no change in their cognitive function, while the matched group continued to decline.

Maria Carrillo, PhD, chief science officer of the Alzheimer’s Association, called the results “remarkable and encouraging.” So what were these “remarkable” treatments? One was aerobic exercise and the other was stretching. Each was administered four times per week for 45 minutes per session, including warm-up and cool-down.

Over the past year, Eisai and Biogen’s Leqembi and Eli Lilly’s just-approved Kisluna have received heaps of attention as the first disease-modifying drugs to slow the progression of early-stage Alzheimer’s disease. But considering their onerous treatment regimens, hefty costs (approaching or exceeding $100,000 per year), and scarcely noticeable benefits, many health professionals are skeptical that these drugs will be worth it for patients. Is it possible that exercise could be a far less costly but equally effective remedy?

Research has already made clear that regular exercise is one of the top tools to prevent Alzheimer’s in the first place. A meta-analysis of 16 studies analyzing 160,000 subjects showed that physically active people are 45% less likely to develop the debilitating disease. But historically, scientists have been less certain that exercise can meaningfully stall Alzheimer’s once it takes hold.

Slowing Alzheimer’s

The Phase III EXERT trial referenced at the beginning provided one of the strongest recent examples that it can stall the disease. The participants’ cognitive decline effectively stalled during the year-long trial, despite the average subject being in their seventies. Another shorter trial featuring fewer participants with actual Alzheimer’s disease had similar findings. Both of these results are more glowing than what was found in the pivotal Leqembi or Kisluna trials: In these, subjects’ disease simply progressed more slowly relative to controls. It must be noted, however, that patients in these trials were slightly further along in their disorders at the experiments’ outset. So it’s possible that exercise would make less of a dent in more advanced Alzheimer’s.

Still, the tandem findings — coupled with the fact that physical activity is salubrious at any age — indicate that exercise is a must for any Alzheimer’s patient capable of doing so.

Studies suggest that aerobic exercise, which elevates heart rate, tends to be most effective at boosting cognition. Resistance training, while still beneficial, is less so. A 2022 systematic review found that three to four bouts of aerobic exercise per week lasting roughly 45 minutes each seems to produce the best results.

Alzheimer’s and exercise

Various mechanisms could explain exercise’s apparent ability to slow Alzheimer’s disease. One is increasing blood flow to the brain. Aerobic exercise in particular stimulates hemoglobin proteins in red blood cells to release nitric oxide. In turn, this compound causes small blood vessels to dilate, thus accepting more blood and oxygen. Another mechanism is reducing markers of inflammation in the central nervous system. A third is boosting brain size. Numerous trials have shown exercise to enlarge the anterior cingulate cortex and the hippocampus in older adults. (The hippocampus in particular shrinks with Alzheimer’s.) These changes were accompanied by improvements in reaction time, motor function, spatial memory, and cognitive processing speed. Fourth, exercise greatly boosts the production of BDNF, one of a group of compounds called neurotrophins. Collectively, they regulate various functions that help the brain grow and work smoothly. BDNF is one of the most important. In Alzheimer’s patients, it’s often depleted.

By 2050, close to 100 million people could suffer from Alzheimer’s disease as the world’s elderly population over 65 balloons to nearly 1.5 billion. Considering the social, human, and economic costs of this devastating disease, cost-effective solutions must be deployed. For treatment and especially prevention, exercise is indispensable.

This article Aerobic exercise is surprisingly good at slowing, preventing Alzheimer’s is featured on Big Think.

There are many drugs that anesthesiologists can use to induce unconsciousness in patients. Exactly how these drugs cause the brain to lose consciousness has been a longstanding question, but MIT neuroscientists have now answered that question for one commonly used anesthesia drug.

Using a novel technique for analyzing neuron activity, the researchers discovered that the drug propofol induces unconsciousness by disrupting the brain’s normal balance between stability and excitability. The drug causes brain activity to become increasingly unstable, until the brain loses consciousness.

“The brain has to operate on this knife’s edge between excitability and chaos. It’s got to be excitable enough for its neurons to influence one another, but if it gets too excitable, it spins off into chaos. Propofol seems to disrupt the mechanisms that keep the brain in that narrow operating range,” says Earl K. Miller, the Picower Professor of Neuroscience and a member of MIT’s Picower Institute for Learning and Memory.

The new findings, reported today in Neuron, could help researchers develop better tools for monitoring patients as they undergo general anesthesia.

Miller and Ila Fiete, a professor of brain and cognitive sciences, the director of the K. Lisa Yang Integrative Computational Neuroscience Center (ICoN), and a member of MIT’s McGovern Institute for Brain Research, are the senior authors of the new study. MIT graduate student Adam Eisen and MIT postdoc Leo Kozachkov are the lead authors of the paper.

Losing consciousness

Propofol is a drug that binds to GABA receptors in the brain, inhibiting neurons that have those receptors. Other anesthesia drugs act on different types of receptors, and the mechanism for how all of these drugs produce unconsciousness is not fully understood.

Miller, Fiete, and their students hypothesized that propofol, and possibly other anesthesia drugs, interfere with a brain state known as “dynamic stability.” In this state, neurons have enough excitability to respond to new input, but the brain is able to quickly regain control and prevent them from becoming overly excited.

Previous studies of how anesthesia drugs affect this balance have found conflicting results: Some suggested that during anesthesia, the brain shifts toward becoming too stable and unresponsive, which leads to loss of consciousness. Others found that the brain becomes too excitable, leading to a chaotic state that results in unconsciousness.

Part of the reason for these conflicting results is that it has been difficult to accurately measure dynamic stability in the brain. Measuring dynamic stability as consciousness is lost would help researchers determine if unconsciousness results from too much stability or too little stability.

In this study, the researchers analyzed electrical recordings made in the brains of animals that received propofol over an hour-long period, during which they gradually lost consciousness. The recordings were made in four areas of the brain that are involved in vision, sound processing, spatial awareness, and executive function.

These recordings covered only a tiny fraction of the brain’s overall activity, so to overcome that, the researchers used a technique called delay embedding. This technique allows researchers to characterize dynamical systems from limited measurements by augmenting each measurement with measurements that were recorded previously.

Using this method, the researchers were able to quantify how the brain responds to sensory inputs, such as sounds, or to spontaneous perturbations of neural activity.

In the normal, awake state, neural activity spikes after any input, then returns to its baseline activity level. However, once propofol dosing began, the brain started taking longer to return to its baseline after these inputs, remaining in an overly excited state. This effect became more and more pronounced until the animals lost consciousness.

This suggests that propofol’s inhibition of neuron activity leads to escalating instability, which causes the brain to lose consciousness, the researchers say.

Better anesthesia control

To see if they could replicate this effect in a computational model, the researchers created a simple neural network. When they increased the inhibition of certain nodes in the network, as propofol does in the brain, network activity became destabilized, similar to the unstable activity the researchers saw in the brains of animals that received propofol.

“We looked at a simple circuit model of interconnected neurons, and when we turned up inhibition in that, we saw a destabilization. So, one of the things we’re suggesting is that an increase in inhibition can generate instability, and that is subsequently tied to loss of consciousness,” Eisen says.

As Fiete explains, “This paradoxical effect, in which boosting inhibition destabilizes the network rather than silencing or stabilizing it, occurs because of disinhibition. When propofol boosts the inhibitory drive, this drive inhibits other inhibitory neurons, and the result is an overall increase in brain activity.”

The researchers suspect that other anesthetic drugs, which act on different types of neurons and receptors, may converge on the same effect through different mechanisms — a possibility that they are now exploring.

If this turns out to be true, it could be helpful to the researchers’ ongoing efforts to develop ways to more precisely control the level of anesthesia that a patient is experiencing. These systems, which Miller is working on with Emery Brown, the Edward Hood Taplin Professor of Medical Engineering at MIT, work by measuring the brain’s dynamics and then adjusting drug dosages accordingly, in real-time.

“If you find common mechanisms at work across different anesthetics, you can make them all safer by tweaking a few knobs, instead of having to develop safety protocols for all the different anesthetics one at a time,” Miller says. “You don’t want a different system for every anesthetic they’re going to use in the operating room. You want one that’ll do it all.”

The researchers also plan to apply their technique for measuring dynamic stability to other brain states, including neuropsychiatric disorders.

“This method is pretty powerful, and I think it’s going to be very exciting to apply it to different brain states, different types of anesthetics, and also other neuropsychiatric conditions like depression and schizophrenia,” Fiete says.

The research was funded by the Office of Naval Research, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the National Science Foundation Directorate for Computer and Information Science and Engineering, the Simons Center for the Social Brain, the Simons Collaboration on the Global Brain, the JPB Foundation, the McGovern Institute, and the Picower Institute.

This article Study reveals how an anesthesia drug induces unconsciousness is featured on Big Think.

Fad diets come and go, but one appears to have staying power: intermittent fasting. Roughly one in 10 Americans were estimated to have practiced it in 2023. Interest in the eating strategy, as indicated by Google searches, picked up in 2011 and has remained elevated since. One could say that intermittent fasting is no longer a fad — it’s simply a diet.

The eating strategy’s enduring popularity can likely be attributed to a key distinction: It doesn’t tell you what to eat but merely when to eat. There are no pricey supplements, bland meals, complicated recipes, or maddening dietary restrictions. You simply eat what you want at certain times, and at other times, you don’t eat at all. It’s clean, simple, and effective.

Studies suggest that intermittent fasting reduces body weight, body fat, LDL cholesterol, triglycerides, and blood insulin. It also optimizes cellular use of fuel sources, improves mitochondrial function, and suppresses inflammation.

These benefits primarily arise because people practicing intermittent fasting tend to unwittingly reduce the calories they consume by between 200 and 550 per day on average. But unlike calorie counters, fasters are better at adhering to their diet plan, research suggests. It’s easier to fast for a time than to restrict food intake.

As a team of scientists from the University of Illinois-Chicago (UIC) described in a recent paper published in Nature Reviews Endocrinology, there are two main approaches to intermittent fasting: alternate-day fasting and time-restricted eating. With alternate-day fasting, dieters eat freely one day and then don’t eat at all or consume just one small meal the next. For time-restricted eating, practitioners eat all their meals during a window of four to 10 hours and drink only drink zero-calorie fluids the rest of the time.

Many could benefit from intermittent fasting, yet some avoid it out of fear that it could endanger their health. In their review, the UIC researchers avowed that the strategy is safe and effective, and dispelled four common myths.

Myths about intermittent fasting

First, they noted a widespread belief that intermittent fasting can negatively affect sex hormones. Women worry that the diet could lower estrogen levels, leading to irregular menstruation and fertility problems. Meanwhile, men fret that fasting could reduce testosterone, thus lowering libido and muscle mass. Intermittent fasting doesn’t appear to diminish estrogen in women, the researchers report, though young male athletes could experience minor drops in testosterone. The studies that turned up this effect didn’t find any accompanying reductions in strength or muscle, however.

Second, there’s a myth that intermittent fasting leads to greater muscle loss compared to other weight-loss diets. Calorie-reducing diets do cause followers to shed a little muscle along with all the fat. Intermittent fasting is no different, but it isn’t any worse, the authors say. In fact, combining the strategy with weightlifting and boosted protein intake can attenuate most of any muscle loss.

Third, there’s a notion that people practicing intermittent fasting make poorer dietary choices. The idea is that, when freed of their fast, people will opt for ultra-palatable foods higher in salt, sugar, and fat. Randomized clinical trials don’t bear this out, however.

“Evidence suggests that people don’t typically change the types of food they eat during intermittent fasting, they just eat less of those foods,” the researchers write.

Fourth, some clinicians worry that the structure of intermittent fasting could make individuals prone to eating disorders. Again, trials don’t support this concern. On the contrary, “adults participating in intermittent fasting report fewer food cravings, weight concerns, mood issues, binge-eating behaviors and less anxiety about their appearance, relative to control individuals,” the authors write.

In summary, despite intermittent fasting’s extreme reputation, it’s as safe as a reduced-calorie diet and often easier to stick to, the authors say.

“Intermittent fasting is just another tool that can be used to help individuals eat less food to manage their weight and metabolic health. Fasting is no more advantageous or disadvantageous compared to other diets and should not be demonized for simply suggesting that we take a break from eating once in a while.”

This article Debunking 4 popular myths about intermittent fasting is featured on Big Think.

Imagine that you just had a terrible day at work. On the commute home, you turn on some music. It’s an old song, one you haven’t heard in years but once bookmarked a meaningful chapter in your life. You turn up the volume and the hassles of the day fade away. The song crescendos. On your arms, you feel goosebumps (also called “frisson” or “aesthetic chills”), a phenomenon that, despite being a common reaction to music and other stimuli, has no immediately obvious evolutionary explanation. And as the next song starts, you’re already in a better mood.

Music can move us deeply. But besides nudging us to move to the beat or sparking emotional reactions, how exactly does music affect us? What does science have to say about the prospect of using music as a therapy, and what insights can musicians themselves offer when it comes to designing good studies? 

The science of sound 

Long considered alternative medicine, research suggests that music and sound may help ease symptoms of mental health conditions. On a broad note, music interventions have been shown to boost mood and well-being. A 2022 systematic review and meta-analysis of 26 studies found that music interventions were associated with statistically and clinically significant improvements in mental health-related quality of life. The review found evidence that these interventions may have positive physical effects, too, but these benefits were less pronounced. 

An earlier review of over 400 scientific papers also highlighted the mental and physical benefits of music, especially in improving mood and reducing stress. Sound meditations (sound healing sessions) appear to have similar effects, relieving tension, improving mental health, and even decreasing physical pain. 

One concept in understanding how music affects us is “brainwave entrainment,” a process where our brain activity naturally synchronizes with the rhythm of periodic external stimuli, like the beat of a song. In the 1990s, researchers showed for the first time that entrainment via music can yield therapeutic benefits: Patients with movement disorders were able to improve their motor control and coordination by following rhythmic auditory cues, demonstrating enhanced timing, spatial accuracy, and force in their movements.

Through neuroimaging techniques, it’s possible to observe brainwave entrainment as someone listens to music. The synchronization can be seen by measuring the hertz (Hz) of the sound waves, which correspond to different brain frequencies that we experience throughout the day. 

“Music certainly can both entrain networks in the brain at specific frequencies, such as 40Hz, in addition to synchronizing individuals’ brains with one another,” AZA Allsop, assistant professor of the Neuroscience Research Training Program at Yale School of Medicine, told Big Think. “We think this ability to bring groups of individuals together and physiologically synchronize their brains and bodies is an important mechanism for how music facilitates social connection and behavior and likely contributes to its therapeutic impact.”

Allsop’s lab is currently testing the hypothesis that brainwave entrainment contributes to the therapeutic effects of music. As one of several popular theories that have been put forward, it will need to stand the test of more rigorous research.  

Other studies have examined music’s impact on heartbeat. A 2023 observational study published in the European Journal of Cardiovascular Medicine noted that music therapy significantly increased heart rate variability (HRV), a measure of the variation in time between heartbeats. (Higher HRV is important because it indicates better autonomic nervous system function and a greater ability to adapt to stress, promoting overall cardiovascular health.) 

HRV especially increased when the therapy involved music that was calming or pleasantly stimulating. The study’s control group, which underwent relaxation exercises without music intervention, showed no changes in HRV. 

Music as medicine

Music and sound therapies seem to hold promise for treating, or at least alleviating, the symptoms of various conditions, though the mechanisms at play are not fully understood. Like music itself, the therapies can be more art than science. While scientists focus on the effects on the listener, artists provide valuable insights into how these effects come into existence, potentially influencing clinical studies and therapeutic approaches.

When it comes to music interventions, there are four broad approaches used for therapy, each carefully designed by the therapist/artist: 

• receptive, where the client simply listens to or “receives” music; 
• re-creational, where the client recreates music played by the therapist; 
• compositional, where the client and therapist work together to compose music; and 
• improvisational, where the therapist interprets the client’s mood based on spontaneous song creation 

Designing studies around specific creative elements of interventions — such as comparing the effects of different soundscapes or foregrounding physical feelings evoked by music — is something artists can weigh in on.

In a recent preprint examining the psychophysiological benefits of nature-based soundscapes, researchers found that participants who listened to 10-minute immersive recordings of natural sounds integrated with elements of music experienced a boost in HRV alongside reduced heart and respiratory rates, compared to a calm coffee shop soundscape. They also reported diminished feelings of anxiety and depression and enhanced feelings of comfort, enthusiasm, creativity, and belonging. 

Markus Pesonen and Catarina Brazao, who led the research along with their colleague Susanne Kumpulainen at the Active Life Lab at South-Eastern Finland University of Applied Sciences, believe sound journeys can be healing in part because of their somatic effects. Their app, Olo, is designed with this in mind.

Pesonen, who spent 20 years as a composer, musician, and sound designer, told Big Think: 

“When I started to look at the [sound journey] space 15 years ago, I was always baffled at why most of the ‘wellness music’ was so static. It’s all one thing, whether it’s nature sounds or singing bowls or gongs. I always thought, ‘This could be so much more interesting and diverse. Life is diverse. If we instead have an experience that is like taking your nervous system to the gym, things should happen. The biggest thing about music is not how it sounds now, but how it sounded before and where it is going. It happens in time. That whole journey of different sceneries and textures and sounds creates a ‘nervous system gym’ that moves us to think about ‘how do I respond to this change from A to B to C, how do I cope with it?’” 

Since “naturescapes” feature a wide spectrum of frequencies — the textures of the wind, rain, and animals, for example — Pesonen and Brazao travel to high-biodiversity locations and record in 3D in very high fidelity. 

“Then we compose sound journeys in such a way that nature is the soloist and the music is just enhancing that magic,” he says. “We want to create a habit where people close their eyes and feel themselves.” 

That’s where Brazao, a somatic therapist, comes in. Her role is to understand how sound modulates the nervous system, including how people’s bodies respond during a session. 

“The sound journey can be the thing we need before we connect with our bodies, even,” she says, noting that it may be the most accessible starting point for healing. “Healing happens when there’s enough safety for it to happen. You don’t make it happen. You create the conditions.”

Brazao’s philosophy dovetails with a recent study from the University of Turku showing that people tend to perceive music-induced emotions in specific parts of the body — happiness in the arms and legs, for instance, and sadness in the chest — across cultures, suggesting a universal component to some of those somatic effects.  

Our musical preferences are subjective, so there’s no single silver bullet when it comes to designing effective interventions. But what does seem universal is that music, in the right setting and context, can spark within us a sense of connection and transcendence — the kinds of experiences that science might never be able to fully capture. 

“Music has the power to resonate with your feelings or state of being in a way that’s ineffable,” Tornike Margvelashvili, a Berlin-based composer from Tbilisi, told Big Think. “It can provide a sense of connection, or being understood, or provide a space for introspection, which is a healing process in itself.”

For Margvelashvili and Ayumi Paul — a violinist, composer, and artist — creating the right conditions for healing can look just as much like doing science as creating art.

“As a composer, you can play with psychophysics (psychoacoustics) in many ways, like how sound propagates, how it behaves in space, how humans perceive it and use it as a kind of compositional tool,” Margvelashvili says. 

“For me, a simple example would be using beating frequency in the way I produce tones or timbers when I synthesize sounds. When I create a timber, I can pair together two pure tones (sine waves detuned from each other slightly) and the difference in frequency creates this phenomenon called beating, which is a very specific sound. So I can use this physical phenomenon as an aesthetic tool in my compositions.” 

Music has been a part of healing and spiritual traditions for centuries, though only in recent decades has it been the subject of serious scientific inquiry. Future research may show that sound packs outsized healing potential, especially when combined with insights from both scientists and artists. It’s also worth keeping in mind the simple fact that, when you’re in a slump, hitting “play” on your favorite record might be the easiest way to boost your mood.

This article Music as medicine: The therapeutic potential of sound is featured on Big Think.

In a study recently published in Annals of Internal Medicine, researchers reported that female Medicare patients seen by female physicians had a lower risk of readmission and death than those seen by male physicians. The roughly quarter-percentage-point difference in mortality rate was small but significant. It translates into 5,000 potentially unnecessary deaths per year. Male patients also fared slightly better under the care of women, though the 0.08% difference in mortality was not statistically significant.

While this result may surprise members of the general public, it did not surprise scientists who have studied differences in patient outcomes.

Ashish Jha, dean of the Brown University School of Public Health, is one of those researchers. As he told NBC News, women “tend to be better at communication, listening to patients, and speaking openly. Patients report that communication is better. You put these things together, and you can understand why there are small but important differences.”

In 2016, Jha was part of a study exploring differences in health outcomes by physician gender. Looking at 1,583,028 hospital visits among Medicare patients, he and his team found that mortality and readmission rates were 0.42% and 0.55% lower, respectively. In other words, if male doctors were as proficient as their female colleagues, 32,000 lives would be saved per year among Medicare patients alone.

Another study, this one from 2018, looked at more than 580,000 patients admitted to Florida emergency rooms with heart problems. It found that both male and female patients were less likely to die when treated by a female physician.

Women also appear to outperform men in the operating room, according to two studies published side-by-side last year. Researchers reviewed the medical records of more than one million patients in Canada and Sweden. They found that patients operated on by female surgeons suffered from fewer “adverse post-operative events” both 90 days and one year later. Such events included death, infections, and other complications. The differences were noticeable. Just under 21% of patients seen by female physicians had an adverse event within a year. The rate was 25% under male surgeons. More glaringly, patients treated by male surgeons were 25% more likely to die after one year.

Comparing male and female physicians

What could explain women’s apparent superiority? Studies have found that female surgeons operate more slowly than male surgeons and take fewer risks. Female physicians are more likely to follow established guidelines, better cooperate with their teams, and listen to their patients. Their appointments with patients also tend to run longer.

In short, it seems that women practice medicine as it should be practiced: with care and compassion. This approach could be one reason women are less likely than men to face malpractice claims.

Despite these findings, a sizable pay gap persists. Even when controlling for specialty, hours worked, experience, and the number of patients seen, women earn $2 million less than men during their medical careers — about 76 cents on the dollar.

To be clear, none of the studies suggests that male doctors are inherently inferior to female doctors. They do, however, suggest that men have a lot to learn from their female colleagues if they seek to achieve the best possible outcomes for their patients.

This article Women tend to be better physicians than men. Here’s why. is featured on Big Think.

Anti-obesity drugs cause people to lose more than just fat.

More than 73% of American adults are overweight, according to the CDC. This puts them at increased risk of death and many serious health issues, but losing weight and keeping it off through diet changes and exercise — the standard approach — is notoriously difficult.

That made the FDA’s 2021 approval of Novo Nordisk’s semaglutide (Wegovy) as an obesity treatment seem like something of a miracle.

The drug is in a class known as GLP-1 agonists, which were created to treat type 2 diabetes. Because they reduce appetite and trigger the release of insulin, they also have a proven ability to help people shed pounds, reduce blood pressure and cholesterol, and even reduce the risk of death. 

The problem is that all pounds are not created equal. 

Generally speaking, weight loss only occurs when your body needs more calories than you are eating. To make up the difference, your body taps into the energy stored in your fat cells. This causes the fat cells to shrink, and you lose weight.

Your body doesn’t just pull energy from fat, though — it also pulls it from “lean mass,” such as muscle tissue. All ways of losing weight, including dieting, typically involve losing muscle mass as well as body fat. But if you lose too much muscle, you can experience fatigue and a slower metabolism.

In older people, who are already experiencing normal muscle loss due to aging, losing too much muscle mass could potentially reduce mobility and increase the risk of falls.

“Just because we’re losing weight doesn’t always mean we’re getting healthier,” Michelle Hauser, obesity medicine director of the Stanford Lifestyle and Weight Management Center, told The New York Times.

Strength training and eating a high-protein diet can combat muscle loss if you’re losing weight using traditional methods — in those instances, a person can expect the weight they lose to be about 25% lean mass and 75% fat mass.

People just taking GLP-1 agonists may simply be eating less, though, and in studies, 20-40% of the weight they’re losing is muscle mass. This is inspiring drug developers to hunt for another kind of miracle cure: a medication that can prevent muscle loss while you lose weight. 

Especially for older adults — who have the most to gain from a drug that lowers the risk of heart disease but also need to preserve muscle strength — combining a muscle-preserving drug with GLP-1 agonists could be a big deal. 

Here are four of the most promising candidates:

The anti-aging med

The drug: BioAge Labs’ azelaprag is a drug that mimics the activity of apelin, a natural hormone secreted during exercise that helps regulate metabolism and promotes muscle regeneration.

The details: BioAge began developing azelaprag as an anti-aging medication, because the expression of apelin tends to decrease as we get older — one possible reason we lose muscle as we age. In a trial of 21 healthy seniors confined to bed rest for 10 days, it was well-tolerated and demonstrated an ability to reduce muscle atrophy compared to a placebo.

In studies on obese mice, combining azelaprag with Eli Lilly’s weight-loss drug, tirzepatide, actually resulted in more weight loss than tirzepatide alone. It also improved muscle function and body composition.

In October 2023, BioAge announced plans to collaborate with Eli Lilly on a phase 2 trial of azelaprag and tirzepatide in people with obesity. In February 2024, it closed a $170 million fundraising round to help support the trial, which is expected to kick off in mid-2024.

The advantage: Azelaprag is administered orally, so taking it alongside a GLP-1 agonist wouldn’t be much of a burden for patients.

The limitation: Though the bed rest trial and animal experiment results are promising, we won’t actually know whether azelaprag can prevent muscle loss due to medication (and not inactivity) until we start seeing the results of this new trial.

What they’re saying: “Our oral drug azelaprag, combined with an incretin drug, has the potential to improve weight loss quantity and quality. Tackling obesity can help cut the population burden of age-related disease.” – BioAge Lab’s CEO Kristen Fortney

Eli Lilly’s other bet

The drug: Versanis Bio’s bimagrumab is a monoclonal antibody, which is a kind of lab-made protein that seeks out and binds to specific receptors. Bimagrumab binds to “activin type II receptors,” which both encourages fat loss and prevents metabolic activity that typically leads to muscle loss.

The details: As of June 2023, bimagrumab had been administered to more than 1,000 people. In one phase 2 trial of people with obesity, some of whom also had type 2 diabetes, participants lost 20.5% of their fat mass while increasing their lean muscle mass by 3.6% over 48 weeks of treatment.

In animal experiments, administering bimagrumab along with a GLP-1 agonist preserved muscle mass while increasing the amount of fat lost. In January 2023, Versanis launched a phase 2b human trial of bimagrumab as an obesity treatment, either alone or co-administered with semaglutide, Novo Nordisk’s GLP-1 agonist. The first results are expected in mid-2024.

In July 2023, Eli Lilly acquired Versanis. If the phase 2b trial goes well, it’s possible the company could trial the combination of bimagrumab and tirzepatide — or another one of the GLP-1 agonists in its pipeline.

The advantage: While people on GLP-1 agonists tend to gain back any weight lost if they stop taking the meds, that might not be the case for bimagrumab — 12 weeks after their last dose, the people in the 1,000-person phase 2 trial had yet to regain any weight.

The limitation: Monoclonal antibodies are expensive to produce, and while bimagrumab only needs to be taken once every four weeks, it needs to be administered intravenously, which has to happen in a medical facility. Most GLP-1 agonists come in injector pens that can be used by patients at home. 

What they’re saying: “While the new generation of incretin therapies have been revolutionary for patients living with obesity, bimagrumab addresses a critical unmet need as a therapeutic that targets fat loss while building muscle mass.” – Versanis CEO Mark Pruzanski

The solo act

The drug: Altimmune’s pemvidutide is a combination GLP-1 agonist and glucagon agonist. While the GLP-1 agonist suppresses appetite, the glucagon agonist increases energy expenditure. Together, they are meant to mimic the effects of diet and exercise.

The details: In March 2024, Altimmune announced the results of MOMENTUM, a phase 2 trial in which people received weekly injections of pemvidutide as an obesity treatment. 

After 48 weeks, participants lost an average of 15.6% of their weight, and about 75% of the lost weight was fat — a favorable ratio comparable to what’s seen in people who manage to lose weight through improved diet and exercise.

The company plans to present a more detailed analysis of the MOMENTUM trial data at a TBD scientific conference.

The advantage: A single medication that helps people lose weight while also mostly preserving their muscle mass could be preferred over two separate drugs.

The limitation: During the MOMENTUM trial, participants also exercised more, so isolating the drug’s impact is difficult.

What they’re saying: “There is a growing appreciation that the quality of weight loss is as important as the quantity of weight loss … we believe that pemvidutide, if approved, could stand out as an attractive option for weight loss and weight maintenance.” – Altimmune’s CMO Scott Harris

The team effort

The drugs: Regeneron’s trevogrumab and garetosmab are monoclonal antibodies. While trevogrumab binds to and inhibits myostatin, a protein that limits skeletal muscle growth, garetosmab neutralizes a protein called activin A, which is linked to muscle atrophy. 

The details: Trevogrumab was developed to treat muscle loss linked to immobility or aging, while garetosmab was created as a treatment for a rare disease where muscle tissue is replaced by bone (called “fibrodysplasia ossificans progressiva”).

In February 2024, Regeneron announced plans to launch a phase 2 trial in mid-2024 that will test combining semaglutide for obesity with either trevogrumab or trevogrumab and garetosmab.

The hope is that the meds will not only prevent excess muscle loss, but potentially help people keep weight off even after they stop taking the GLP-1 agonist.

The advantage: Because Regeneron is targeting two different pathways linked to muscle preservation, its approach could be more impactful than those that target just one. 

The limitation: More meds means more opportunities for side effects, and because trevogrumab and garetosmab are monoclonal antibodies, they could be costly and complicated to administer. As is the case with azelaprag, we currently have no idea how these medications will perform in people taking weight-loss drugs, either.

What they’re saying: “We believe that inhibiting new pathways on top of GLP-1 receptor agonism has the potential to achieve comparable overall reductions in body weight, but with improved quality of a weight loss, resulting in more fat loss while preserving or actually increasing muscle mass.” – Regeneron’s CSO George Yancopoulos

The big picture

If any of these medications (or combinations of medications) can actually enable people to lose weight while preserving muscle mass, the impact on public health could be huge — but it’ll likely be years before they reach the market.

In the meantime, people taking GLP-1 agonists for weight loss may need to lean on old fashioned methods for retaining muscle — exercise and a healthy diet — and there are groups trying to make this easier.

Fitness company Equinox has launched the GLP-1 protocol, a coaching program specifically designed to help people on the meds retain and even build muscle. Country club operator Life Time, meanwhile, has launched a new membership program that can help people get prescribed the meds and then build workout routines to accompany them.

Healthcare company Abbott has unveiled a line of high-protein shakes designed to help prevent muscle loss in people taking GLP-1 agonists, and food delivery service Daily Harvest now has a GLP-1 Companion Food collection tailored to people on the meds.

Even if we get to the point that medications alone can help people with obesity lose weight while preserving muscle, being in the “normal” weight range with a good muscle-to-fat ratio doesn’t guarantee good health — as much as we might wish it weren’t true, a better diet and more exercise might still be necessary.

“The fundamentals of obesity management will always be changes to diet and exercise,” said Vijaya Surampudi, assistant director of the UCLA Weight Management Program. “But having anti-obesity medications is another tool in the toolbox.” 

This article Revolutionary weight-loss drugs like Wegovy come with a catch is featured on Big Think.

A team of scientists has created a hydrogel that breaks down alcohol in the stomach and intestines. When ingested, it prevents alcohol from entering the blood and stops the compound acetaldehyde from accumulating. A toxic byproduct of alcohol degradation, acetaldehyde is linked to liver cirrhosis and cancer. The hydrogel’s net result is to lessen the harms of alcohol, including the dreaded hangover. So, is this the hangover remedy we’ve been waiting for?

Have your booze and drink it too?

Companies, consumers, and scientists have sought one for years, with limited success. Although many supplements are claimed to prevent or alleviate the headache, nausea, fatigue, and other uncomfortable symptoms that can accompany heavy drinking, none are backed by convincing evidence.

The novel hydrogel appears to be different. Researchers primarily based out of ETH Zürich crafted it from whey protein, a common supplement and food ingredient derived from milk. They also added iron atoms, sugar molecules, and gold nanoparticles to the gel. Together, these additives produce reactions that convert alcohol into innocuous acetic acid within the gastrointestinal tract.

So, the gel doesn’t only remedy a hangover — it also limits alcohol intoxication itself.

Normally, alcohol enters the gastrointestinal tract and then seeps into the bloodstream, where it exerts its intoxicating influence. Alcohol eventually travels to the liver and is broken down to noxious acetaldehyde and then to harmless acetic acid.

In experiments recently detailed in the journal Nature Nanotechnology, the researchers fed mice control liquids or a liquid containing the hydrogel. Twenty minutes later, they dosed the rodents with large amounts of alcohol. Over the next five hours, the scientists monitored the animals’ behavior and collected blood, stool, and tissue samples.

An hour after the alcohol binge, blood alcohol concentrations in the mice fed the hydrogel were 40% lower than in control mice. After five hours, the difference was 56%. The difference in blood alcohol levels was apparent in the animals’ behavior. Mice given the hydrogel easily bested their counterparts at navigating mazes.

The hydrogel also prevented the animals from alcohol-related health problems. In additional tests, mice that chronically binge drank suffered liver damage, weight loss, and gut problems. Mice that binged on booze and consumed the gel were almost entirely spared from these issues. Preventing the buildup of acetaldehyde appeared to be key to preventing organ damage.

Crucially, throughout the tests, mice given the gel showed few to no signs of gastrointestinal distress or any other side effects.

From mice to humans

So when will this exciting hangover remedy be tested in humans?

“We hope and plan to move to clinical studies as soon as possible,” Professor Raffaele Mezzenga, a lead author on the study, told Big Think. “The exact timing is not clear yet and will depend on a number of factors, including ethical clearance and financial support of clinical trials.”

Mezzenga and his co-authors are confident these trials will demonstrate similar effectiveness in humans. They’ve already applied to patent the hydrogel. When commercially available, Mezzenga envisions that the gel will likely be consumed from a tube as an edible paste.

“It could be used for example in a recreational context before starting drinking to diminish the effect of alcohol socially (for example, allowing driving back home), or to reduce the side effects of hangovers,” he said.

But Mezzenga thinks the real benefits of the gel will be in therapeutic settings — perhaps in rehabilitation facilities to help wean patients off chronic alcohol use or in hospitals to help heavily inebriated individuals sober up.

“We believe this can and should also be used for people affected by chronic diseases related to alcohol abuse,” he told Big Think.

Alcohol abuse claims millions of lives each year. This novel gel could greatly reduce its harm.

This article Is this the hangover cure we’ve been waiting for? is featured on Big Think.

If the COVID-19 vaccines were the most significant FDA approvals of the 2020s so far, GLP-1 agonists to treat obesity are a strong runner up.

Though these drugs have been used to treat type 2 diabetes for nearly two decades, it wasn’t until 2021 that the FDA approved one of them — Novo Nordisk’s Wegovy (semaglutide) — as a treatment for obesity. Clinical trials showed that people lost 10-20% of their body weight.

This was huge. An estimated 42% of adults in America are classified as obese, which puts them at increased risk of many serious health issues, including heart disease and some cancers, and death. The standard prescriptions prior to this — diet changes and exercise — are notoriously hard for many people to implement and stick to.

GLP-1 agonists make it easier to lose weight by mimicking a hormone our bodies release naturally about 15 minutes after we start eating — this reduces our appetite and triggers the release of insulin, which helps take sugar out of our blood and convert it into energy.

In addition to helping people shed pounds, some GLP-1 agonists also have a proven ability to reduce weight-related health issues, such as heart attacks and deaths from cardiovascular disease. In clinical trials, people on the drugs ended up with lower blood pressure, blood sugar, and cholesterol, and some studies suggest the meds could treat fatty liver disease, too.

But evidence is mounting that they could treat other health issues — including ones that aren’t obviously related to weight. Researchers are now taking a closer look at these other potential indications for GLP-1 agonists. Here’s what they’re finding out.

Parkinson’s disease

Parkinson’s is a neurodegenerative disorder caused by the death of specific neurons in the brain. This causes problems with movement, mental and behavioral changes, and often premature death. While existing treatments can help control symptoms, none can stop the disease from progressing.

For a recent phase 2 trial, French researchers gave 156 people in the early stages of Parkinson’s a GLP-1 agonist (lixisenatide) or placebo every day for 1 year. Compared to at the start of the trial, the motor symptoms of people in the placebo group were slightly worse by the end of the year, while the treatment group’s motor symptoms remained essentially the same.

It’s not clear why this is happening — it may have something to do with the known but not well-understood connection between Parkinson’s and diabetes. This was a fairly small study and a lot of questions remain to be answered, including whether GLP-1 agonists could help people with more advanced Parkinson’s, halt the progression of Parkinson’s motor symptoms over a longer period, or prevent other types of symptoms, such as ones related to cognition, from worsening.

Still, with up to one million Americans affected by Parkinson’s, these results are highly encouraging, and the results of a larger phase 3 trial testing another GLP-1 agonist (exenatide) as a Parkinson’s treatment are expected in 2024.

Drug and alcohol addiction

Some people taking GLP-1 agonists for weight loss or diabetes have reported an unexpected, but often welcome side effect: decreased cravings for drugs, alcohol, and tobacco.

“GLP-1 receptors are located in the areas of the brain associated with both food and drug reinforcement,” Dr. Luba Yammine, associate professor of psychiatry at UTHealth Houston, told Freethink. “Additionally, brain mechanisms that contribute to overeating overlap with those that facilitate drug seeking behaviors. It is plausible that GLP-1 agonists could decrease reward (i.e., pleasure) and cravings for addictive substances.”

Plausible, but not confirmed. Several animals studies have found that GLP-1 agonists can reduce drug and alcohol seeking behavior, but there isn’t strong data from human trials: one small trial found that GLP-1 agonists could reduce opioid cravings, for example, while another found they could reduce cravings for alcohol, but only in people who were living with obesity.

Trials are ongoing, though. The National Institute on Drug Abuse is sponsoring one focused on alcohol addiction, and Yammine is leading two trials in people who are addicted to nicotine.

“In both of our trials, we incorporate measures to assess not only whether GLP-1 agonists ‘work,’ but also examine how they work via interrogating the hypothesized mechanisms,” she told Freethink, adding that they anticipate having trial results in about 2-3 years.

Because drug and alcohol addiction are, like obesity, unfortunately common in the U.S., if GLP-1 agonists prove to be effective treatments for any of these substances, this is another area where the medications could have a huge impact.

Sleep apnea

People with sleep apnea stop and start breathing again repeatedly while sleeping, usually because something is blocking their airway. This can prevent them from getting restful sleep, leading to daytime fatigue.

Obesity is one of the top risk factors for sleep apnea, which suggests that GLP-1 agonists could treat the condition by helping people lose weight. To get the FDA to approve the meds as sleep apnea treatments — and encourage insurance companies to cover them as such — drug makers need to prove the connection, though.

Eli Lilly is now doing just that.

In April 2024, the pharma company reported the topline results of a trial that found that people with obesity and sleep apnea who took tirzepatide (brand name Zepbound) for a year lost an average of 20% of their body weight — and experienced a far larger reduction in apnea-related events at night than people taking a placebo.

Based on these results, Eli Lilly plans to submit an application to the FDA in mid-2024 to get tirzepatide approved as a sleep apnea treatment.

“While there are pharmaceutical treatments for the excessive sleepiness associated with [obstructive sleep apnea], tirzepatide has the potential to be the first pharmaceutical treatment for the underlying disease,” said Jeff Emmick, senior VP of product development at Eli Lilly.

Infertility

In the U.S., about 10% of people of reproductive age have problems getting pregnant. Carrying excess weight is a risk factor for infertility, as is being diagnosed with polycystic ovary syndrome (PCOS), a hormonal condition that can also lead to weight gain.

Based on the promising results of small trials, doctors have been prescribing GLP-1 agonists off-label to people with PCOS for several years, and in addition to helping them lose weight, it also seems to be making it easier for them to get pregnant. Some people who started taking GLP-1 agonists to treat obesity or diabetes have also reported improved fertility.

Why this is happening isn’t clear — losing weight might simply increase fertility in both men and women, or perhaps the meds are interfering with birth control (although this wouldn’t apply to those trying to get pregnant). But researchers are looking closer at the connection, not only in the hope that GLP-1 agonists could be a new fertility treatment, but also to make sure it’s safe to be on the drugs during early pregnancy.

“The ‘oops’ babies on Ozempic and Wegovy are happening all over the place,” Melanie Cree, director of the PCOS clinic at Children’s Hospital Colorado in Aurora, told Bloomberg. “It’s very exciting, but it’s a bit scary because we’re moving forward without all the data.”

Mental illness

Obesity correlates with an increased risk of developing many mental health issues, including depression, anxiety, and bipolar disorder. At the same time, the meds to treat those issues often lead to weight gain, which can discourage patients from staying on them.

So far, early research and anecdotal reports from patients suggest that GLP-1 agonists may positively affect some mental health issues. The meds have been shown to reduce depression symptoms in studies of people with diabetes, and preclinical research suggests they might be able to reduce metabolic dysfunction and cognitive impairments linked to schizophrenia, too.

One report found that people with diabetes who took GLP-1 agonists were less likely to be diagnosed with depression or anxiety later — however, this is observational research, which can’t prove cause and effect.

More research is needed to confirm any potential connection between GLP-1 agonists and mental health, but several trials are ongoing. If the drugs can treat or prevent psychiatric problems, the impact could be huge, given that 20% of Americans live with a mental illness and many don’t have an effective treatment. 

“There is evidence that GLP-1 agonists have direct effects on the brain, including an ability to restore dopamine imbalance,” Roger McIntyre, a professor of psychiatry and pharmacology at the University of Toronto, told Psychiatric News in December 2023. “What if these agents are psychiatric drugs that are masquerading as weight-loss drugs?” 

Alzheimer’s disease

Alzheimer’s is a progressive neurodegenerative disorder characterized primarily by problems with memory and cognition. The exact cause is unknown, but the most common genetic risk factor for Alzheimer’s is a gene involved in cholesterol transport in the brain, and diabetes appears to be a risk factor, too.

Suggestive but not conclusive evidence — preclinical studies, small clinical trials, and anecdotal reports — has found that GLP-1 agonists might improve memory, reduce rates of dementia, and more, suggesting they may be effective Alzheimer’s treatments. 

“GLP-1 agonists are known to affect inflammation, and so my hypothesis would be that they are helpful through a modulation of the brain’s inflammatory response to the Alzheimer’s disease proteins,” Ivan Koychev, a clinical academic psychiatrist, told Freethink. “Alternatively, we know that these medications reduce the risk of strokes and so it could be that they help by preventing vascular events that contribute to dementia.”

To explore the possible connection between Alzheimer’s and GLP-1 agonists, Novo Nordisk launched two phase 3 trials — EVOKE and EVOKE plus — in 2021. Those trials will see a total of 3,700 people with early stage Alzheimer’s given semaglutide or a placebo for up to 3.3 years to test if the med has a positive impact on cognitive decline. A Novo Nordisk spokesperson told Freethink they expect both trials to wrap up in 2025.

Meanwhile, Koychev is leading a trial at Oxford University that’s studying the impact of semaglutide on the buildup of tau in the brains of people at elevated risk of developing Alzheimer’s because they already have high levels of amyloid in their brains. Those results are expected next year, as well.

The bottom line

Based on the evidence so far, it seems likely that GLP-1 agonists will eventually be approved to treat some conditions beyond diabetes and obesity, even if they don’t deliver on every potential benefit. However, the “wonder drugs” aren’t without their downsides.

People taking GLP-1 agonists often experience gastrointestinal problems, such as nausea and diarrhea, and some data suggests that the meds may increase the risk of rare but serious gastrointestinal issues, including stomach paralysis.

In 2023, the FDA launched an investigation after GLP-1 agonist users started reporting thoughts of suicide — as of January 2024, it hadn’t found anything to confirm the connection, but it also said it couldn’t yet rule it out, meaning its possible the drugs could cause mental health issues for some people, rather than treating or preventing them.

GLP-1 agonists also have to be taken indefinitely for weight loss to last — most people who stop taking them gain back the lost weight. It’s possible the same would be true for other benefits, and some people might not want to get on the drugs knowing they’d have to take them forever.

Ultimately, we’re still in the early stages of understanding what GLP-1 agonists are capable of, but with countless research teams all taking a closer look at the meds, it won’t be long before we have answers — and potentially a new way to treat everything from addiction to Alzheimer’s.

This article Are weight-loss meds the next wonder drugs? is featured on Big Think.

“Some scientists refer to the immune system as the seventh sense,” says Dr. Hao Jin, a neuroimmunologist at the National Institute of Allergy and Infectious Diseases (NIAID).

It’s a comparison that anyone who’s ever had a common cold can appreciate. Much like our traditional senses help us perceive and interact with our external world, our immune system — a complex network of cells, tissues, and organs — helps us sense and respond to threats in our internal environment.

And, as we all know, it’s not always a pleasant experience. When bacteria or viruses invade our body, our immune system springs into action, releasing pro-inflammatory molecules that recruit immune cells to fight. This triggers familiar inflammatory symptoms like fever or swelling — all aimed at creating an inhospitable environment for the invaders. It’s a delicate balancing act: Too much inflammation can damage healthy tissues and lead to chronic autoimmune disorders, while too little can leave us vulnerable to infection and disease.

Scientists have made significant strides in understanding the immune cells and bodily responses that govern immunity. Yet, whether and how the brain regulates inflammation is unclear, even though there is robust evidence that inflammation does impact the brain. Now, Dr. Jin and his colleagues, including Dr. Charles Zuker, an eminent neurobiologist at Columbia University, ask, “How does the brain impact immunity?”

In May, they reported identifying groups of neurons in the brainstem they called the “rheostat” of the body-brain immune response: Turn it one way and inflammation goes up; turn it another and it goes down. This research, published in Nature, has huge implications for treating diseases that create an over-the-top inflammatory response, from diabetes to arthritis. The findings also reshape our understanding of the immune response: Instead of being a localized call to action, it seems a more distant governor is calling the shots.

Diving into the brain-body connection

Dr. Jin says that he and Dr. Zuker started by studying the neurobiology of mammalian taste, or how the chemicals that create a taste also activate specific neurons that drive behavior: keep eating or don’t keep eating. For example, the Zuker lab discovered that the neurons responsible for sour tastes also make mammals react negatively to these acidic flavors — a handy way to ensure you don’t ingest something like car acid. They began to see similarities between how the brain processes taste signals and how it responds to threats to the body’s immune system.

“We are obsessed with how different tastes communicate with the brain through specialized pathways,” says Dr. Jin. “We’ve spent years researching how the brain detects taste and nutrient signals — which are chemicals — and transforms them into behaviors and actions. Since the immune system also relies on chemicals, we wondered if we could use the same methods from studying taste to understand the brain’s role in regulating the immune response.”

The inflammation “rheostat” 

The researchers began by infecting mice with bacteria that induced an immune response. Then they compared the brain activity of these infected mice with a control group that received only a saline solution. They noticed a significant increase in neural activity within the brainstem, along the vagus nerve, a long nerve pathway connecting the brainstem to organs like the heart, lungs, stomach, and intestines.

Using a mix of chemical and genetic methods, they directly influenced this neural pathway. Blocking it led to uncontrolled inflammation, with pro-inflammatory molecules spiking over 300% compared to control mice that received the same bacterial injection but still had an intact connection to the vagus neurons. In contrast, artificially activating the neurons reduced pro-inflammatory chemicals by 70% compared to infected mice that didn’t receive the same intervention.

These experiments clearly showed that brainstem neurons could directly regulate the inflammatory response. Then, the researchers discovered there are two distinct groups of neurons within the vagus nerve: one responding to pro-inflammatory signals and the other to anti-inflammatory cues. Acting as a kind of balance, these neurons communicate with the brain, forming what researchers called a “biological rheostat,” like a finely tuned dial that controls the level of inflammation.

“The brain quickly understands the inflammatory response’s status by reading these two neural signal lines,” explains Dr. Jin. “Then, it guides the body towards the appropriate immune response.” 

For Dr. Jin, the findings make perfect sense in retrospect. “The brain regulates a wide range of our bodily functions, including metabolism, respiration, and more. There is no reason why the immune response would be the exception.”

Restoring the immune balance

A huge number of diseases trigger an overly active and prolonged inflammatory response, like diabetes, autoimmune disorders, arthritis, and even long COVID.

As part of the research, they tested whether manipulating the groups of vagus neurons could slow down a wild immune response. They used a drug to activate the neural circuit in mice with ulcerative colitis, an autoimmune disorder that causes chronic inflammation in the colon lining. Activating the anti-inflammatory vagal neurons significantly reduced the concentration of inflammatory cells and protected the mice from impacts like colon damage, a finding that Dr. Luke O’Neill, a biochemist at the School of Biochemistry and Immunology in Trinity College, Dublin describes as “very impressive.” 

“This research is potentially very important,” says Dr. O’Neill. “We already know that the vagus nerve had a role in limiting inflammation, but this study provided far more specific insights into which neurons are specifically at play.”

Dr. O’Neill notes that activating the circuit increased the bacterial load when the researchers infected mice with salmonella but not in the control animals. This result indicates that there is far more left to learn about the logic of how this body-brain link works.

Ongoing exploration

One limitation of this study is common to much of immunology and medicinal research: The subjects are mice, not humans. The mouse inflammatory response parallels ours in fundamental ways. But Dr. Jin points out that there are differences in the specific types of inflammatory cells and the potential speed of the response.

“The brainstem neurons we identified have analogous counterparts in humans,” he says. “But we need to study whether the human versions of these cells play similar roles when it comes to regulating inflammation.” 

While they work on finding evidence in humans, there is plenty more to learn about this circuit in mice and people. 

“We’d love to learn more about the descending branch of this body-brain circuit,” adds Dr. Jin. “How do these brainstem neurons exert their control over the distant inflammatory response?” 

Dr. O’Neill agrees, adding that we need more research to understand how to precisely activate this brain-body connection. 

If we could target those circuits very precisely, then there’s great potential to block the inflammation response for many diseases.

Along with the obvious practical implications, Dr. Jin highlights other aspects of the study that are particularly satisfying.

“It is very rewarding to see that the brain responds to inflammatory signals of opposing meaning (pro- and anti-inflammatory chemicals), with different ‘lines’ of neurons — just like one line of neurons responds to tastes that are bitter, and another responds to tastes that are sweet.” 

This article Discovered: A “brain-body circuit” that turns inflammation up and down is featured on Big Think.

Few drugs have achieved the stardom that semaglutide, marketed in the United States as Ozempic or Wegovy, has today. A synthetic, injectable version of an intestinal hormone, it is the flagship of a new category of drugs initially developed for diabetes that rose to fame in the medical and public arena as an effective weapon against obesity. Semaglutide has proved so successful that its manufacturer, the Danish company Novo Nordisk, is unable to keep up with demand.

The US Food and Drug Administration approved semaglutide in 2017 to improve the control of blood sugar levels in adults with type 2 diabetes — and then, in June 2021, for chronic weight management in adults who are obese or overweight and have related risk factors, such as high blood pressure or diabetes.

Social networks boosted the drug’s fame: In mid-2022, a viral TikTok clip claimed Kim Kardashian had used semaglutide to lose 15 pounds so that she could wear an iconic Marilyn Monroe dress to the Met Gala in New York. In the months that followed, everyone from former British Prime Minister Boris Johnson to billionaire entrepreneur Elon Musk acknowledged resorting to the medication to tamp down their appetites and slim down. Today, three out of four Americans say they have heard of this type of drug — and of those, more than half consider it a good option for weight loss, according to a Pew Research survey.

Last November, however, the ones with their eyes on the drug were cardiologists. At the opening of the 2023 annual meeting of the American Heart Association in Philadelphia, results of a clinical trial generated tremendous interest: Semaglutide, it appeared, was a new tool to treat heart disease.

The trial, called SELECT, was conducted in 41 countries with more than 17,000 people who were overweight or obese and at high cardiovascular risk but who didn’t have diabetes. It found that a weekly subcutaneous injection of 2.4 milligrams of semaglutide can, in addition to helping people lose an average of 15 percent of their original weight, reduce the risk of heart attack, stroke or death by 20 percent. It’s a magnitude of effect that puts it in the same category as other drugs that prevent cardiovascular events, such as low-dose aspirin, antihypertensives and statins to lower cholesterol.

From the study, scientists could calculate the total number of people who would need to be treated to produce the desired benefit in one of them. They found that treating 67 diabetes-free overweight or obese patients at high risk of a cardiovascular event for 40 months would prevent one major cardiovascular event, such as heart attack or stroke, or death due to heart disease. By way of comparison, this is the same number of patients with a cardiovascular history who must take aspirin or hypertension drugs for 60 months to avoid one stroke.

Based on the study results, in early March the FDA approved the use of injectable semaglutide to reduce the risk of cardiovascular death, myocardial infarction and stroke in adults with cardiovascular disease who are obese or overweight.

“It’s a milestone. For the first time, we have a drug, semaglutide, that not only causes weight loss, but also reduces the formation of atherosclerotic plaque and prevents deaths and cardiovascular events,” says Paola Harwicz, a cardiologist and obesity specialist in Buenos Aires who headed the Cardiometabolism Council of the Argentine Society of Cardiology and participated in the meeting in Philadelphia.

Several studies suggest that the drug reduces the buildup of plaque in the arteries; in one of them, in patients with type 2 diabetes, four months of treatment with semaglutide reduced carotid artery thickness, a clinical marker of atherosclerosis, by 13 percent.

A role for semaglutide and related drugs in staving off cardiovascular disease — the cause of one in three deaths worldwide — further boosts the drug’s prospects in the market by vastly expanding the universe of specialists who can prescribe it. It also repositions being overweight as one of the main truly modifiable risk factors for cardiovascular disease.

Dealing with extra pounds

According to the classic medical approach, to lose weight there must be an imbalance between calories taken in and calories burned: You either eat fewer or expend more. But in the last 30 years, new evidence has shown it is far more complicated than that, says Julio César Montero, a medical nutritionist and president of the Argentine Society of Obesity and Eating Disorders.

The emerging thinking among those working in this field, and reflected in a statement by the Endocrine Society, is that obesity is due to two related but distinct processes: the already mentioned energy imbalance (eating more calories than the body expends) and the resetting of the body weight “set point” — the weight that the body determines as its goal — to a higher value.

People with obesity have a disorder of the energy homeostasis system, the biological process that maintains weight stability by actively matching energy intake to energy expenditure over time. Thus, the body responds to weight loss by tenaciously trying to regain the lost pounds and return to its (higher value) target weight.

All current FDA-approved anti-obesity medications contribute to weight loss, although the results vary from one to another. Most of these compounds act at the brain level, to reduce appetite and increase satiety, and at the gastrointestinal level, to slow gastric emptying, promote insulin release or block fat absorption.

The mechanism behind the body’s quest to return to its body weight set point is not yet fully understood, but it explains why it is so difficult to achieve an effective treatment to manage obesity. It is estimated that only one in five people who lose between 5 and 10 percent of their initial weight through diet and exercise in six months manage to keep off the weight for more than a year. Losing and sustaining weight loss isn’t made easier by modernity’s sedentary way of life and the wide range of readily available ultraprocessed foods. By 2035, it’s projected that more than half of the world’s population will be overweight or obese.

Until now, traditional anti-obesity drugs have had limited effectiveness. Most act on brain-signaling chemicals — neurotransmitters — to reduce appetite, an approach pioneered in the 1960s with the use of amphetamines that has continued to today with safer derivatives and some other, nonamphetamine, drugs. Another often-used drug is orlistat (marketed as Alli or Xenical), which reduces fat absorption from food.

But for all of these, the effects over the short and medium term are relatively modest, achieving a reduction of 6 percent to 10 percent of a person’s starting weight. Moreover, adverse effects, ranging from insomnia, nervousness and increased blood pressure to diarrhea and fecal incontinence, limit their widespread use.

The role of hormones

In search of new ways to understand and treat obesity, in recent decades scientists have turned their gaze to the hormones secreted by the intestine.

Specifically, research has focused on a group of 10 hormones that have roles in optimizing the process of digestion and absorption of nutrients from the food we eat. They are also how the gastrointestinal tract sends signals to the brain about the body’s energy status, in many cases influencing metabolism and contributing to the regulation of our appetites.

The new strategy “has changed the therapeutic landscape of obesity to target underlying mechanisms” and spurred “an auspicious new era of highly effective drugs,” write endocrinologist Ania Jastreboff of Yale School of Medicine and her colleague Robert Kushner of Northwestern University in a 2023 article in the Annual Review of Medicine.

One such hormone is glucagon-like peptide type 1, or GLP-1, discovered in the 1980s. Semaglutide, the active molecule in Ozempic and Wegovy, is a lab-made lookalike that mimics the action of GLP-1. Like GLP-1 itself, and like an earlier drug, liraglutide, that was approved in 2010, it suppresses the release of glucagon — a hormone secreted by the pancreas to raise blood sugar levels. It also promotes the growth and function of pancreatic beta cells, which are responsible for producing insulin, the hormone that ensures that sugar from food enters the body’s cells to give them energy.

Both of these actions regulate blood sugar levels, which is why these drugs were initially intended to tackle diabetes. A series of clinical trials called SUSTAIN, which evaluated the drug in about 8,000 patients with type 2 diabetes, showed that semaglutide is more effective than other available drugs (sitagliptin, marketed as Januvia; exenatide, or Byetta; dulaglutide, or Trulicity; and insulin glargine, or Lantus) in reducing glycosylated hemoglobin scores — a test that measures average blood glucose levels over the prior three months. Maintaining blood sugar levels within the target range is a goal in the treatment of diabetes to avoid complications.

But it was soon realized that these drugs came with a bonus, since GLP-1 doesn’t act only on the pancreas. It also acts on centers in the brain that control appetite. And it decreases stomach movements and emptying, so people feel full for longer. These two mechanisms contribute to reducing food intake, but, unlike older anti-obesity drugs, “they do so in a more physiological way, with few adverse effects,” says Montero. One of the best effects, he adds, is that they take away suffering, because they assuage food cravings. Patients report a reduced desire to eat highly seasoned and salty foods, or foods rich in carbohydrates, as well as a better ability to resist urges.

Semaglutide, the active molecule of Ozempic and Wegovy, is a synthetic version of glucagon-like peptide type 1 or GLP-1. The functions of GLP-1 in the body are numerous, acting on the pancreas, stomach, gastrointestinal tract, kidneys, bones, heart, liver, muscle and adipose tissues, the energy-regulating center of the brain, and the rest of the neural system.

For Harwicz, semaglutide can be a facilitator that helps people make better decisions. One of her patients, a man weighing more than 160 kilograms (over 350 pounds) with a history of diabetes who had failed multiple previous attempts to lose weight, was able to lose 35 kilos (77 pounds) — more than 20 percent of his body weight — with weekly injections of the drug, along with dietary education and a tailored physical activity plan. “He really feels like he’s succeeding because the medication is helping him,” she says. “It’s important to modify lifestyle; medication isn’t magic. But people can make better food choices and reduce the amount they eat with a lot more peace of mind.”

Of course, like any drug, semaglutide does not work in all patients, nor is it tolerated by all. In the SELECT study, for example, 16.6 percent of participants receiving semaglutide dropped out of the trial because of adverse effects, mainly digestive problems such as nausea, vomiting and diarrhea.

More in the pipeline

Everything indicates that the injections of semaglutide are just the beginning in this new era of weight loss drugs. In addition to a high-dose oral version of semaglutide that showed promising effects in trials and is on the horizon for approval, a tsunami of clinical trial results is anticipated for new drugs that also operate on the gut-brain axis and re-create the action of other intestinal and pancreatic hormones.

One of these is glucose-dependent insulinotropic polypeptide (GIP), which promotes insulin release after meals and reduces appetite. Another hormone is glucagon, which counterbalances the action of insulin by raising blood sugar, helps eliminate fat from the liver and increases satiety. And a third is amylin, which delays stomach emptying, accelerates satiety and decreases the desire to eat.

Collectively, such therapies have been dubbed “nutrient-stimulated hormone-based treatments” because they mimic the action of hormones that are released or function when specialized sensor cells in the digestive tract detect food intake. And they promise to enhance slimming effects, alone or in combination, partly through a physiological reset that prevents the body from stubbornly returning to a weight range that seems predetermined. In other words, it reduces the body’s tendency to regain the lost pounds.

One of the newer drugs, tirzepatide from Eli Lilly (marketed as Mounjaro or Zepbound), acts both on GLP-1 and GIP receptors. It obtained FDA approval November 2023 for the treatment of obesity. One of the clinical studies of this drug reported an average decrease of 25.3 percent of initial weight in those who received a weekly injection for 88 weeks.

Another experimental drug from Eli Lilly, retatrutide — dubbed “triple G” because it acts on GLP-1, GIP and glucagon receptors — could be next on the list. Last June, a study led by Jastreboff reported weight declines never before seen with a single drug. Patients without diabetes averaged a 24 percent body weight loss in just 48 weeks (11 months). And in the group receiving the highest dose, one-fourth of the patients dropped more than 30 percent of their weight. That’s close to the results of highly effective, but more drastic, bariatric surgery.

“I never imagined that physicians would have to worry about our patients losing too much weight when taking an anti-obesity drug,” Kushner says. “This is really an interesting turning point in obesity science and practice, an important paradigm shift in how we think about and manage people living with obesity.”

Kushner and Jastreboff suggest in their article that combining various members of these hormone-based drugs could target the many intertwined mechanisms of obesity. Montero agrees: “There is a swarm of hormones that form a spider web. And touching more than one thread at a time may move the web better, potentiating the effect and making interventions more comfortable, with fewer adverse events,” he says.

A number of gut hormones have attracted scientific attention as potential therapeutic targets for the management of obesity.

What is more, semaglutide and tirzepatide could also have benefits in other diseases, such as alcohol abuse disorder and other compulsive or addictive behaviors, such as smoking, excessive shopping and nail-biting. The drugs also reduce inflammation, which could help to limit damage to various organs and structures, such as the kidneys and joints. There are also preliminary studies of the effects of the drug in preventing cancer, and for the treatment of Parkinson’s and Alzheimer’s, although further studies are still needed to confirm their results. Writing in 2023, the editors of the journal Science declared that no scientific breakthrough in that year had been so transformative in so many fields, affecting everything from financial markets to popular culture.

But, as with any medical innovation, unavoidable challenges also loom on the horizon. Although the visible adverse effects of GLP-1 receptor agonists — nausea, vomiting, constipation and diarrhea — are usually mild and limited to the gastrointestinal tract, other more unusual but serious complications have raised concerns, such as a possible increased risk of pancreatitis. In addition, animal studies (not yet demonstrated in humans) suggest that there is a link to thyroid cancer risk.

Another barrier is the cost of these drugs. In the United States, a monthly treatment with semaglutide costs almost $1,000; the price drops almost 10-fold in countries such as Japan, the United Kingdom and Australia. In Latin America, where obesity rates have grown faster than in other parts of the world, the drug remains unaffordable for the bulk of the population. In Argentina, for example, in March an Ozempic pen with four doses of 1 mg cost 409,000 pesos, which is equivalent to more than twice the monthly minimum wage. More than two pens per month would be required to reach the 2.4 mg per week dose used in the SELECT cardiovascular prevention study.

To make matters worse, studies show that the benefits on weight fade or diminish sharply when the treatment is stopped, so it would have to be continued long-term. Research published in 2022, for example, found that patients regained two-thirds of their lost weight within a year of stopping medication.

“Our enthusiasm as clinicians with these drugs wanes if you think about it from a public health point of view,” says Patricio López Jaramillo, an endocrinologist, researcher and rector of the University of Santander in Bucaramanga, Colombia. He thinks that the use of the drugs should be placed within a broader societal package that extends beyond “the rational, linear and disciplinary vision” of medical specialists.

“New anti-obesity drugs should be considered as a useful tool, if financial access is improved,” he says. “And [use] must be framed within global actions and programs that allow populations to have real possibilities to practice healthy lifestyle habits, such as exercising, following a balanced diet and staying away from smoking.”

Kushner says physicians need to reexamine the kind of lifestyle advice given to people receiving these new drugs, de-emphasizing calorie counting and daily weigh-ins. More focus should be placed on health impacts rather than weight loss, high-quality protein intake should be encouraged, and the importance of physical activity and resistance exercise to preserve muscle mass should be emphasized.

One option could be to use tests to predict which patients will have better results with the various medications and who, perhaps, should think about surgery or other approaches. “Not all patients respond to treatment,” says Andrés Acosta, an Ecuadorian physician and researcher who heads the Precision Obesity Medicine Laboratory at the Mayo Clinic in Rochester, Minnesota. It is important to identify those who would benefit most, he adds.

Acosta cofounded a company that last year launched a test that identifies patients with a feature called “hungry gut” — those who move food quickly from their stomachs and, consequently, lose satiety faster. This could be a subgroup that particularly benefits from these new anti-obesity drugs, he hypothesizes. For a drug market that could be worth $100 billion by 2030, it wouldn’t hurt to ensure that resources are invested in the patients who will get the most from them.

Article translated by Debbie Ponchner

This article What’s next in the Ozempic era? is featured on Big Think.

French researchers say they have discovered that genetic mutations aren’t necessary for cancer to develop, challenging a long-held assumption about the disease.

The cause of cancer: Cancer cells start out as normal, healthy cells, but then something goes wrong — instead of doing their job or dying when they’re supposed to, they start multiplying uncontrollably, potentially forming tumors and spreading to other parts of the body.

That “something” that goes wrong is usually genetic mutations in our DNA. They might have developed spontaneously as our cells divided, been triggered by something in our environment (like tobacco smoke), or inherited from our parents, but whatever their cause, anomalies in our genes are to blame for our cells going rogue, according to most cancer researchers.

That is clearly true for many cancers — but maybe not all of them. A team led by scientists at the French National Centre for Scientific Research (CNRS) is challenging the assumption by demonstrating how cancer can develop even in the absence of any genetic mutations.

How it works: Most genes tell cells how to make proteins, and while pretty much every cell in your body contains a complete collection of your genes (your genome), you don’t need every cell to be making every protein all the time. To flag which genes in a particular cell should be on or off, your body tags them with chemical compounds — collectively, these tags are your epigenome.

Your epigenome can change over time in response to age, diet, lifestyle, and more, and disruptions to it are a known hallmark of cancer. For a new study, published in Nature, the CNRS team demonstrated in fruit flies that epigenetic changes alone can cause cells to become cancerous — a genetic mutation to the DNA code itself isn’t necessary.

Even after the team restored the flies’ epigenomes to their original state, quieting the “signal” that caused the cells to become cancerous, parts of their genomes remained dysfunctional and the tumors kept growing.

The big picture: Now that we know that cancer can develop in the absence of genetic mutations, at least in some animals, the next step will be figuring out the relevance of this new information about the epigenome to treating or preventing the disease.

“This discovery forces us to reconsider the theory that, for more than 30 years, has assumed that cancers are predominantly genetic diseases caused necessarily by DNA mutations that accumulate at the genome level,” writes CNRS.

This article New study challenges long-held assumption about cancer is featured on Big Think.