James' World 2

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The passage of time often seems like the most malleable thing in the world. A minute may feel much longer when you’re asked to hold a plank position in a workout class, and an hour may fly by when you’re chatting with a friend. In these cases, your perception of time is altered. But real, physical time dilation also happens. According to Albert Einstein’s special theory of relativity, clocks that are closer to Earth’s centre of gravity, say at sea level, tick more slowly than those at the top of a mountain. A similar slowing happens when a clock is physically travelling extremely fast.

Undeniably, this sounds bizarre, but decades’ worth of experiments haven’t managed to disprove it. Yet in what exact sense time dilation is real – and what it means for a physical effect to be real at all – has inspired philosophical debates ever since Einstein first formulated his theory in 1905.

In fact, in June, at the Foundations of Physics conference in Irvine, California, I heard Marco Giovanelli discuss how time dilation is both real and apparent at once. It sounds paradoxical, but when I called Giovanelli, who is a historian of philosophy and science at the University of Turin in Italy, to talk through it, I started to understand that it reflects the facets of our physical world that Einstein’s work first uncovered.

For Einstein, it was all about rods and clocks, explains Giovanelli. Suppose that you and a friend each had an identical clock and a metre-long rod. You stand still, while your friend gets into an incredibly fast spaceship and sets off on a journey. Compared with yours, their clock will tick less quickly, and their rod will contract in size. If you want to know by how much, Einstein’s got your back: he worked out those calculations more than a century ago. If you happen to have a second friend who has a slightly slower spaceship and their own clock-and-rod set, the same trick will work again, except that their clock will slow and their rod contract a little less than your speedier friend. Finally, if you also acquire a spaceship and catch up with either of your friends, your clocks will start to tick at the same rate again, and your metre-long rods will again look the same length.

To discuss these effects, physicists use the language of “inertial frames”, similar to comparing a room at rest, or a rest frame, with a spaceship travelling at a constant speed, or a moving frame. In your individual frames, you and your friends can each establish a coordinate system, the familiar grid of width, depth and height. Your coordinate systems will match when you are all at rest or when your spaceships move side by side at the same speed.

When one of you moves more quickly, though, special relativity shows that their grid will deform, contracting in the direction of motion. It is this detail that bothered Einstein’s contemporaries. It seemed that the change in the rod length was uncomfortably intertwined with changes in the coordinate system used to situate it. But an effect that is a function of a coordinate system cannot possibly be real, critics argued. Ultimately, coordinate systems themselves are of dubious reality. They seem to simply be tools that we humans made up to help us organise our theories and observations of the physical world.

In 1911, physicist Vladimir Varićak argued that the rod’s length contraction “is only a psychological and not a physical fact, i.e., the body has not really undergone any change”. Giovanelli recounts another anecdote where, in the 1970s, physicist John Stewart Bell surveyed his colleagues at the CERN particle physics laboratory about whether length contraction could break a thread suspended between two spaceships accelerating at exactly the same rate. Most physicists said the thread wouldn’t break, endorsing the idea that nothing physically changes about the atoms in the thread. Could they have possibly been wrong? This made my head spin.

I will admit to having always been a rather terrible student of relativity, only learning it just well enough to pass my preliminary exams in graduate school. However, I’m certain I was previously taught that relativistic time dilation and length contraction are unquestionably real. We know they are, from experience in everyday life. The precise clocks on GPS satellites tick at different rates than those on Earth. This is partly because they move quickly and partly because of the gravitational effects explained by Einstein in his general theory of relativity. For GPS to be accurate, the difference in ticks must be corrected for. Failing to do so would have very real consequences, like ending up in someone’s backyard when I try to use my phone to visit a new café or bookstore. But here’s the crucial thing: the clocks on GPS satellites derive their precision from leveraging quantum control over atoms rather than some macroscopic clock gears, so it feels especially egregious to suggest that time dilation does, well, nothing to an atom.

Einstein himself was thinking about this, too, Giovanelli tells me. In fact, an atomic effect was at the centre of a 1906 debate he had with Johannes Stark, a physicist who was awarded the Nobel prize for discovering how electromagnetic fields can affect the energy states of atoms. Stark was studying fast-moving charged atoms, and Einstein recognised that these experiments may display the transverse Doppler effect – in the same way that a siren changes pitch as it approaches you due to a shift in the frequency of its sound waves, a similar effect can happen due to time dilation. It is a distinct prediction of special relativity, an effect that doesn’t exist in other theories, says Giovanelli.

For the standard Doppler effect, you know that you could cancel it out by driving after the police car and that what is happening isn’t due to something changing inside the car’s speaker. The same question reared its head for the transverse Doppler effect. “Stark really thought, kind of naively but naturally, that something is going on in the atom,” says Giovanelli – in our analogy, the speaker in the car would be physically changing. Einstein rejected this. He posited that all the atoms remain the same and that their inner workings are unaffected by motion. Time dilation was the only explanation. Seemingly apparent, here it was confronted with a real, empirical test.

Ironically, when the transverse Doppler effect was experimentally verified in 1938, one of the two physicists involved was Herbert Ives, who never accepted special relativity. Ives thought that he had found signatures of the “luminiferous aether”, a hypothetical substance that some researchers thought permeated the universe and provided one preferred, true reference frame. A preponderance of other experimental evidence, much of it obtained even prior to Ives’s work, completely ruled out this option, and special relativity became the only game in town. For all the clamouring about the oddity of an effect related to an observer’s perspective, one that many physicists wanted to dismiss, time dilation withstood the test of time. Over the ensuing decades, ever-increasingly precise atomic clocks hav

e never uncovered any evidence that something more “real” could be happening.As far as Giovanelli is concerned, what happened was not so much a dispute over physics, but rather a run-in between physics and philosophy. Underneath the sticky question of whether time dilation is real hides another, even stickier philosophical one: what does it mean to be real?

“At a certain point, you cannot avoid it,” says Giovanelli. “And so, Einstein was forced to address the question philosophically. OK, really, let’s define: ‘apparent’ means disappears for the co-moving observer, ‘real’ means empirically testable.” In some sense, the situation ought to never have become that complicated, he says. Scientific theories provide testable hypotheses – it is what they are designed for – and special relativity has passed every test we’ve put it to. What more could you ask from a theory?

Well, it’s hard to understand from an intuitive point of view, says Giovanelli. Einstein even had his own questions, primarily about how certain he could really be that two clocks, or two atoms being used as clocks, could be reliably identical. The advent of quantum physics offered some assurances, but Einstein had his qualms with quantum theory and spent time worrying about it way beyond how it applies to rods and clocks. But he never questioned the empirical reality of time dilation and length contraction, says Giovanelli.

As we talked, I wondered whether for me, like Einstein’s critics, it was my notable lack of relativistic intuition that made time dilation so hard to grasp. It may have been easier to accept that when atoms within a clock or a rod move at a certain speed, some as-yet-unknown mechanism physically changes them, leading to time dilation and length contraction. Instead, I have to grapple with there really being no such thing as absolute time.

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When I’m tired of cooking, there’s truly nothing like going out to a restaurant and letting the professionals take the reins. There’s something about the atmosphere of dining out that makes the day feel special. And let’s face it: I’m almost always getting a tastier meal than I could make myself (unless, of course, I’m following a Delish recipe). The problem is that not every dish is worth your hard-earned cash.

Sometimes a restaurant is overcharging for a menu item. Sometimes the dish lacks flavor. And sometimes, the ingredients may even raise food safety concerns. We tapped chefs across the country to find out what they would never order at a restaurant, so you never have to overpay, leave unsatisfied, or worse, deal with food poisoning. You’re welcome.

This steak-loving gal was shocked to find one of her favorite cuts on the list. But Antimo DiMeo, co-owner and Executive Chef at Bardea Restaurant Group, says he would pass on filet mignon, especially when he isn’t dining at a steakhouse.

“There’s nothing wrong with filet when it’s sourced beautifully and executed with precision, but in a lot of restaurants, it becomes the ‘safe’ luxury order,” he says. “It’s tender, yes, but it’s also one of the least flavorful cuts on the animal because it doesn’t have the same fat, marbling, or character as a ribeye, strip, hanger, bavette, or even a great short rib.”

In other words, filet may sound like the fancy choice, but it’s not always the most exciting one.

“A lot of times, people order filet because it feels like the premium choice, but premium doesn’t always mean most delicious,” he notes. “Unless the restaurant has a serious steak program, I’d rather order a cut with more personality.”

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As the leaders of China, Russia, India, Iran and other nations converged on Central Asia for a two-day summit beginning on Monday, one thing was clear from the outset. Even as President Trump tries to bend the world to revolve around Washington, President Xi Jinping of China has his own powerful orbit.

The Chinese leader’s arrival in Bishkek, the capital of Kyrgyzstan, for a meeting of the 10-nation political and security grouping known as the Shanghai Cooperation Organization underscored Mr. Xi’s broad ability to sustain Washington’s foes, both in peacetime and in war.

The talks come against the backdrop of two wars that have pushed the globe into a period of intense geopolitical instability, suppressing economic growth and driving up inflation. Those challenges were at the heart of discussions taking place simultaneously on the other side of the globe in Asheville, N.C., at a gathering of finance ministers from the Group of 20 countries.

The meeting in Bishkek, in contrast, was a showcase for the incredible leverage that the wars have given Mr. Xi.

No nation has been more critical to Russia and Iran in sustaining their economies and war efforts than China. Mr. Xi has undermined efforts by the United States and its allies to pressure Russia and Iran economically, employing Beijing’s vast geopolitical and economic clout as the world’s largest importer of crude oil and exporter of consumer goods.

Mr. Xi’s biggest rival, the United States, has been distracted by the war in Iran and has pulled some of its military forces from Asia and Europe. Last month, the Chinese leader was able to brush off threats by President Trump that the United States would inflict an “economic D-Day” on countries that provided Tehran with a lifeline. Mr. Trump once made similar threats about purchasers of Russian oil, but did not follow through with any actions against Beijing.

“After the past year, Trump has a fundamental credibility problem with Xi,” said Julian Gewirtz, who served as the senior director for China and Taiwan Affairs at the National Security Council during the Biden administration. “Both his threats and his assurances appear to Beijing, as another world leader put it, to be written in pencil.”

In Bishkek, Mr. Xi’s priority is to burnish his image as the leader of non-Western nations and to push back against what he calls U.S. hegemony. Despite that, he will most likely be cautious about how much support he publicly offers Iran.

The Chinese leader cannot afford to provoke Mr. Trump less than a month before he is scheduled to travel to Washington to attempt to extend a fragile economic truce between the United States and China. Before heading to the United States, Mr. Xi will travel to Egypt and India for state visits.

The series of trips leading up to his summit with Mr. Trump is aimed at casting Mr. Xi as a powerful statesman at a time when Mr. Trump has frayed U.S. relations globally, analysts said.

“Xi appears to see an opportunity to show that China has friends and options around the world at precisely the moment Washington is alienating many of its allies,” Mr. Gewirtz said.

This week’s summit in Bishkek is a reminder of the limits of U.S.-led economic warfare. President Vladimir V. Putin of Russia and President Masoud Pezeshkian of Iran, both critically reliant on China, arrived in the Kyrgyz capital on Monday as they work to defy Western efforts to isolate them and persevere with their own wartime goals.

Beijing has largely obliged, extending economic lifelines to both Moscow and Tehran and leveraging its economic clout to the frustration of Washington.

While Mr. Xi’s power is on the rise, there are limits to it. Though the Shanghai Cooperation Organization is partly a security grouping, Beijing has been unwilling to deploy its military to defend members such as Iran, which joined the organization in 2023, or Russia, instead formally calling for dialogue and an end to the conflicts.

Mr. Xi does not want to be entangled in foreign wars, analysts have said, viewing them as one of the primary reasons the United States has seen its power wane over the decades. But Beijing is willing to increase trade and provide technologies that can be used on the battlefield.

The Chinese leader met with Mr. Putin for bilateral talks in Bishkek on Monday, praising what he called ever-brighter prospects for relations between China and Russia.

Mr. Putin, in turn, highlighted the success of visa-free travel between the two nations and said he was ready to make the arrangement permanent. The Russian leader noted that the first scheduled voyage of a Chinese container ship passed through what is known as the Northern Sea Route in mid-August, presaging broader cooperation in the Arctic.

Whether Mr. Xi meets with the Iranian leader separately from the summit will indicate how much the Chinese leader is willing to push the line ahead of the scheduled visit to the United States.

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Chinese President Xi Jinping, center, and Kyrgyz President Sadyr Japarov, left, during a welcoming ceremony in Bishkek, Kyrgyzstan, on Monday. Credit…Pavel Mikheyev/Reuters

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“When a clown moves into a palace, he doesn’t become a king, the palace instead becomes a circus. — Turkish proverb,”

 

Hmmmmm…History is repeating itself yet again!

 

Isaiah 59:14

New Living Translation

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You might find these videos enlightening!

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A. R. Bernard: one of many

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For an experienced reader, recognising the words on this page feels effortless. Yet, evolutionarily speaking, your brain shouldn’t be able to read. Reading has existed for too short a time to have shaped a dedicated centre in the brain.

Therefore, the brain has to learn to read using systems that evolved for other purposes. But it has long been unclear exactly which systems it recruits to do so and how.

This is important, as differences in these pre-existing systems could shed light on why some of us find reading easier than others. It could also explain how people who are deaf, blind or have dyslexia learn to read in remarkably different ways. In my new paper, published in Cerebral Cortex, I have come up with some answers.

In my study, I investigated the relationship between individuals’ reading skills and their fine-grained brain structure. I also compared twins with different degrees of genetic overlap to see whether shared genetic factors contribute to the links between brain structure and reading skill.

These patterns offer clues about which parts of the distributed “reading network” might provide the initial conditions for reading, and which might respond more to experience.

Basic, neural hardware

I used high-resolution brain scans from the Human Connectome Project, a large study of healthy young adults. The participants did not read while their brains were being scanned. Instead, they completed a range of language tests separately. The most important of these tests for my study was an adaptive reading test in which participants pronounced written words aloud. I used their scores on this test as a measure of reading ability.

I discovered that several brain areas contribute to the skills needed for reading, and that some show heritable links with it. To be clear, heritability does not mean that we are born a certain way and cannot change. The brain is, in fact, constantly changing. Rather, we begin with a partly inherited lump of clay that we continuously shape and refine throughout our lives.

Let’s begin with auditory abilities. When we learn how to read in school, we typically begin with identifying sounds and putting them together in our minds. In fact, problems with perceiving the sound structure of language are commonly cited as an underlying factor in developmental dyslexia.

To read, children learn to map each letter to a sound and join strings of letters into words: the letter s to the “sss” sound, i to the short “i”, and t to the “t” sound, so that s-i-t is pronounced “sit”. Breaking spoken words into individual speech sounds starts at the syllable level, dividing sitting into sit|ting. This requires the skill to identify slowly developing changes in loudness. Most syllables start quiet with a consonant like s-, then grow louder at the vowel (-i-), with its singing character, before going down in intensity again (-t).

Before we’ve learnt how to read properly, the brain can use auditory cues like these to detect syllables and their internal structure in spoken language and begin its road to literacy.

Particularly suited for this task is a region next to the primary auditory cortex at the top of the left temporal lobe, which sits underneath the temple and upper ear. It is called the medial belt area and is tuned to slow, coarse changes in sound. Strikingly, I found that a well-organized structure of its nerve cells is linked with reading ability.

The relationship had a genetic component, suggesting that the organization of this perceptual system might affect how easy we find it to learn to read. Such differences could contribute to variation in literacy that does not simply separate people with and without dyslexia, but span the whole population.

We also need to understand what we read, however. A skilled reader can usually see words and directly connect them to meaning, in parallel with the activation of their sound. Recognizing the visual aspect of a word is thought to build on our capacity to distinguish faces through their defining features. We identify letters and words by their smaller parts—bows, dots and lines—just like we recognise faces by the eyes, noses and chins.

Face identification seems to depend on a brain area in the right anterior temporal lobe called the dorsal temporal pole. Interestingly, I found that the size of this area is linked with reading ability—and this combination is also passed down. A possible explanation is that it helps us identify written words in a way similar way to how we recognise a face.

Finally, another region in the left anterior temporal lobe (the anterior middle temporal gyrus) is thought to connect word form and meaning. The bigger it is, the better we are at deciphering meaning. And it makes sense that having an advantage in accessing the meaning of words might make it easier to learn to read. Indeed, its size was also genetically related to reading ability.

The role of nurture

Now that we have identified some possible initial conditions for the brain’s reading ability—the lump of clay—we can turn to how the clay might be shaped.

After detecting syllables, the speech-sound distinctions need to be refined. This requires the primary auditory cortex to perform fine-grained sound analysis. Here, a thicker cortex (the outermost layer of the brain) is associated with better reading skills.

But, as I discovered, this combination of reading skill and a thick cortex was not genetically driven. In fact, it might be that experience—including exposure to speech sounds, other forms of auditory analysis (such as picking up different individual sounds from a soundscape) and reading practice—contributes to greater cortical thickness.

The structure of the nerve fibre bundles connecting sound to meaning and visual form also correlates with reading ability. But these relationships do not appear to be heritable either. These bundles might develop when sound, meaning and visual word form are connected during literacy training and general language exposure. So the more we read, the better the brain gets at doing it.

What can we learn from all this? Some brains might have an easier time learning to sound out letters, identify written words or access the meaning of words. In the end, though, our reading and language activities substantially mould the brain’s reading network. In other words, devoted parents, teachers and speech therapists can actually help children develop their inner worlds.

Alternative ways of learning to read

But there is not only one way to learn to read or even only one way to read. I once talked to a physics professor with dyslexia. He was incapable of sounding out words readily and didn’t hear them in his head while reading. He did, however, understand text, describing it as if written words silently built up systems of meaning in his head. He even felt that his reading style was advantageous in his line of work. While listening, I couldn’t keep from wondering what his anterior temporal lobes (involved in identifying familiar forms and accessing meaning) might look like.

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AI has been expected to remove some of the bottom rungs on the corporate ladder. As software absorbs routine analysis, research, drafting, and administrative work, companies have had fewer reasons to hire large classes of junior employees. Recent evidence suggests that assumption may be changing. Some major employers are hiring again, and companies using AI extensively are reporting greater demand for entry-level workers.

KPMG (Klynveld Peat Marwick Goerdeler) offers an especially interesting example. The professional services company recently brought nearly 1,000 interns to its Lakehouse training center in Orlando for intensive development in critical thinking, judgment, communication, and interpersonal skills. KPMG’s own research found that interns ranked critical thinking and problem solving as the most important capabilities they wanted to demonstrate while working alongside AI.

KPMG may be responding to a problem that extends far beyond accounting and consulting. Entry-level jobs have always produced more than inexpensive labor. They provide the experiences through which organizations create their next generation of experts, managers, and decision makers.

AI can remove the work that teaches people how to work

Consider what traditionally happens during the first few years of a career. Junior employees research unfamiliar problems, prepare first drafts, make mistakes, receive corrections, observe customers, and explain their reasoning to people with greater expertise. Much of that work can look inefficient because learning itself is inefficient.

Generative AI changes the calculation. A senior employee who once delegated research or preliminary analysis to a junior colleague can now ask an AI system to produce it in seconds. The immediate productivity gain is obvious. The developmental cost is much harder to see.

A recent study of software engineers identified precisely this risk. Researchers interviewed junior and senior software engineers and found evidence that generative AI was absorbing some of the work through which novices traditionally developed expertise. They described the loss of “productive struggle,” the difficult process of working through problems that helps beginners construct the knowledge they later need to solve more complicated ones.

The study is small, involving 14 interviews in South Korea, so its findings should not be treated as proof of what is happening across every profession. It raises an important organizational question, however. If AI continually transfers entry-level work from beginners to experienced employees working with machines, where will future experienced employees come from?

Productivity today can create a capability problem tomorrow

Organizations naturally measure AI by what it saves. A task takes 20 minutes instead of two hours. One employee produces what previously required three. Projects move faster and staffing requirements decline.

Those measures capture current output. They rarely capture the expertise the organization would have developed while producing that output. A junior analyst struggling through an assignment may be slower than AI, but that assignment is simultaneously producing an analysis and a more capable analyst.

KPMG appears to recognize that distinction. Its Lakehouse is explicitly designed as a learning and development environment, and the company says it is expanding immersive, in-person experiences as AI increases the importance of human judgment and other skills. KPMG has also emphasized mentorship, hands-on work, feedback, and real-world application as part of preparing employees to work alongside AI.

Redesign entry-level work around learning

Companies do not need to preserve routine work simply because generations of employees learned from doing it. They do need to identify what developmental function that work performed before automating it away.

That means designing early-career roles around experiences AI cannot easily provide by itself. Junior employees can frame problems before prompting an AI system, verify its work, explain why they accepted or rejected its recommendations, interact directly with customers, observe experienced colleagues making consequential decisions, and assume progressively greater responsibility for outcomes.

This also changes what leaders should measure. The fastest junior employee may be the person who delegates the most thinking to AI. A more useful question is whether that employee is becoming capable of handling increasingly difficult work with less supervision.

AI can make an organization more productive while simultaneously weakening its ability to reproduce expertise. Those outcomes will not appear on the same dashboard or on the same timetable. KPMG’s investment in interns offers a useful reminder that organizations still need beginners, because somewhere inside today’s entry-level workforce are the seasoned experts they will depend on tomorrow.

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Only a fraction of the over 2,500 missing are turning up among the dead, underscoring a bleak reality: The death toll is likely to keep rising for days to come.

Five days after an angry deluge tore through the mountain passes of Nepal, family members arriving after long journeys looked for something — anything — that could identify their loved ones amid the hundreds of mangled bodies.

In one hall in the downstream city of Bharatpur, men and women stared at a small television screen, watching a slide show of recovered remains in complete silence.

Next door, another government hall turned makeshift morgue housed the 270 sets of remains whose photos had been flashing on that screen. Nearly all remained unidentified.

Bharatpur, over 100 miles from where the floods first hit, had no capacity to preserve the corpses that washed up to its riverbanks, and could not keep them any longer. They were being transported to a forest for a mass burial before darkness took over the city.

At the burial spot, security forces in protective gear offloaded the bodies one by one onto stretchers, as cameras documented each step. Nearby, rows of metal numbered signs stuck into concrete-filled pots — the markers for each grave — awaited.

Only a fraction of the missing are turning up among the dead, underscoring a bleak reality: The death toll is likely to keep rising.

As of Sunday night local time, nearly 800 bodies had been found. More than 2,500 people were still missing, with hopes dimming they would be found alive. The initial 72 hours after a disaster are usually seen as critical to a rescue operation.

The devastating flood swept through northern Nepal and Tibet on Wednesday after part of a glacier sheared off a mountain face, and its fall created such seismic force that officials initially believed it was an earthquake. The massive wall of water and mud it created swept up villagers, hydropower workers and hundreds of tourists and travelers from nearly three dozen countries on religious pilgrimages. Tens of thousands of people remain in need of relief, with entire towns wiped out, and roads, bridges and communication lines destroyed.

The bulk of the ongoing rescue effort has focused on the tunnels of several major hydropower projects in Rasuwa, which saw some of the earliest and fiercest damage in Nepal, and in Nuwakot, just downstream.

Through a night of rain, the army had tried to drill its way to tunnels buried under debris and mud. By Sunday afternoon, with support from Indian rescue teams, they had managed to find an opening to one tunnel, which they found brimming with water, according to Brig. Gen. Raja Ram Basnet, the army spokesman. A second tunnel has proved more difficult to locate an opening to, he said.

“The Nepali Army has been using thermal drones to search for signs of life,” he said. “But there have been no indications of survivors so far.”

The force of the deluge was such that nearly a dozen bodies were swept hundreds of miles away and found in India.

When the remains started washing up on the riverbanks of the Chitwan district, dozens of miles downstream from where the floods first hit, the officials were immediately overwhelmed.

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Officers at a mass burial of unidentified victims in the Devghat forest area of Bharatpur, Nepal, on Sunday.

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In the 17th century, physician Samuel Collins observed a mesh around each organ, which he called a “common Vest” made of “curious well-spun Threads… wonderfully interwoven with each other”. The “remanent spaces”, he noted, were filled with a “concreted Animal Liquor”.

Over the following centuries, the purpose of these structures was thought to be purely architectural. The vest, known today as fascia, offers a kind of girding that holds our organs in place; the gaps filled with that “animal liquor” – called interstitial fluid – provide a kind of shock absorber that allows our organs to slide freely as we move, without bruising.

We now know that those pockets of fluid are far more important than this. Emerging research suggests they form an interconnected network called the interstitium that provides an important channel of communication between and inside our tissues. And that is set to cause a quiet revolution in medicine, changing how we think about everything from muscle pain and the microbiome to the spread of cancerous tumours across the body.

According to some scientists, it may even offer a modern explanation for concepts in traditional Chinese medicine, including the fundamental life force “qi”.

The discovery of body-wide channels

The interstitium’s basic anatomy certainly suggests some structural role. The extracellular matrix within it provides structural support for pockets of fluid, with threads made of collagen, which create a strong scaffold, and elastin, which act like tiny bungee cords and offer flexibility. The interstitial fluid coursing through gaps in this matrix comprises around 12 per cent of our body weight and contains hyaluronic acid, a large molecule that forms a gel in water, perfect for cushioning delicate tissue.

The mainstream view was that each organ and muscle is sealed off in its own compartment, with its own, isolated interstitium. While a few researchers, such as molecular engineer Melody Swartz at the University of Chicago, have long been interested in how the fluid flows within the different compartments, there was little evidence that they were interconnected.

That was partly due to a serious practical limitation: when you take tissue samples to study under a microscope, the interstitial fluid drains away and the collagen fibres that give the cavities their structure collapse in on themselves. This made it very hard to characterise the space.

That changed with a groundbreaking study in 2018, using a new procedure that combines a laser with an endoscope to build microscopic images of tissue in a living body. This enabled Neil Theise, professor of pathology at the New York University Grossman School of Medicine, and his colleagues to follow the movement of a fluorescent dye injected during pancreatic surgery. This revealed a series of channels and cavities where they had expected to find dense connective tissue, suggesting that the interstitium was larger and more intricate than previously recognised. Widening their search to other organs, their detailed images provided the strongest evidence yet that it comprised a network spanning the whole body.

“If this organ is present in every tissue and other organ the way the cardiovascular and lymphatic systems are, then we have an incomplete understanding of the entire body,” Theise said at the time. “I don’t think there’s anything that doesn’t get changed by this.”

Building on these results, Theise and his colleagues later examined biopsies of people with tattooed skin. They found that some of the ink had crept from the skin into the interstitial spaces around other organs, proving that the interstitial compartments are interconnected.

Such discoveries paint the interstitium as a tidal marsh, streaming in nutrients and washing out waste. The main drift comes from high-pressure arteries, which supply much of the interstitial fluid, to low-pressure lymphatic vessels where the trash is deposited. But the motion of the fluid is also strongly affected by body movement, with every muscle in the body contributing a squeeze. Even in repose, there is flow from the peristaltic motion of the digestive tract, overlaid with the tremolo of arterial pulsing throughout the body.

This may have immediate implications for fast-moving infections like necrotising fasciitis, which destroys the tissue beneath the skin, including fascia and muscles, and cellulitis, a deep infection that leaves the skin red and swollen. “Appreciating the interstitial location of these infections may give us important information about their spread,” says Rebecca Wells, professor of gastroenterology at the University of Pennsylvania and part of the team behind the 2018 study. “On the flip side, the patterns of spread in fasciitis and cellulitis may tell us about interstitial structure and flow.”

Rewriting biology

More profoundly, a closer study of the interstitium could offer new insights into basic biological systems.

We know, for instance, that immune cells called T-cells pursue pathogens throughout the extracellular matrix. Peter Friedl, director of the Microscopic Imaging Centre at Radboud University in the Netherlands, who has studied cellular transport through the interstitium since 2007, compares them to “little monkeys” swinging through the “jungle” of collagen. Investigations into the interstitium might therefore reveal overlooked but essential elements of the immune response. 

Presiding over the interstitial tissues are multi-tentacled cells called telocytes, first named in 2010 by Laurentiu Popescu at the Carol Davila University of Medicine and Pharmacy in Romania and Maria-Simonetta Faussone-Pellegrini at the University of Florence in Italy. Using electron microscopy, they found that the arms of these cells have an impressive reach, which they use to create junctions with distant cells. The junctions are similar to neural synapses, except they connect with all types of body cells, including blood vessels, nerve fibres, muscle cells, glands, stem cells and other telocytes.

Like neurons, telocytes have electric properties that allow them to stimulate those neighbouring cells. In this way, the interstitium complements the nervous system as a body-wide sensory tissue, responding to stretching, tension, pressure, vibration and movement. The resulting input provides us with proprioception – the sense of where our body is – and much of what we feel as muscle pain and stiffness may originate in the interstitium.

Telocytes also play a crucial role in healing. Popescu and Faussone-Pellegrini observed them controlling the release of heart stem cells in the myocardial interstitium, for instance.

Stemming the spread of cancer

The interstitial fluid is also awash with extracellular vesicles, tiny packets filled with bits of RNA, proteins and lipids. These interstitial messengers bud off from sender cells and drift to a recipient. Extracellular vesicles include potent regulatory microRNAs that can make epigenetic changes to the receiving cell, altering its behaviour or even changing its identity.

This may have particularly important implications for the treatment of cancer. In 2015, David Lyden at Weill Cornell Medical College in New York and his colleagues discovered that tumour cells continuously launch extracellular vesicles into the interstitium, complete with a chemical “address” directing them to specific target tissues.

Because they are tiny, they can easily sail through the interstitium, leaving a trail of chemical breadcrumbs behind them. When they hit their target, they promote the growth of new blood vessels, preparing the ground for the metastatic cells to follow.

To make that journey, the cancer cell reaches out a sticky appendage and attaches to a fibre in the matrix of collagen. It isn’t an easy trek; it must pull its cell body along until its chunky nucleus gets jammed in the webbing. At that point, the cell releases chemicals that break down the collagen around the nucleus, freeing the cell to continue hacking its way through the interstitial undergrowth.

In this way, rogue cancer cells create tunnels throughout the interstitium, making it easier for subsequent metastatic cells to slide through.

With time, researchers may find ways to interfere with interstitial metastasis before the tumours embed. Because the tumour extracellular vesicles are addressed to specific organs, Lyden’s goal is to create personalised treatments that direct therapeutic payloads to specific tissues, avoiding damage to healthy organs.

Swartz, meanwhile, has been developing a vaccine that induces the growth of lymphatic vessels in the interstitium around melanomas. The idea is that these would attract cancer-killing T-cells. The research is still in its early stages, but her tests on mice suggest it can limit the spread of the disease.

Beyond cancer, the interstitium and its contents may shed light on endometriosis, in which tissue similar to the lining of the womb starts to grow outside the uterus, leading to pain, fatigue and fertility problems. Some experts have therefore proposed that malfunctioning telocytes may support the growth of new blood vessels that help the endometrial tissue to implant and survive.

A back door to the brain

The all-encompassing continuity of the interstitium, including organs, blood, lymph cells and nerves, is astonishing. But there is an exception: the brain, which has its own private interstitium.

This is largely to avoid friendly fire from our immune system, which could take out memories, cognitive function and motor control. The brain is therefore separated from the rest of the body by the blood-brain barrier. It keeps out most microbes most of the time, but if they do manage to sneak in, they alert the brain’s more delicate immune cells, the microglia, that must avoid too much collateral damage.

In the brain, the interstitial liquid is called cerebrospinal fluid (CSF). It provides the fuel for brain tissue and picks up the waste afterwards. The flow of CSF runs through the glymphatic system, first discovered by Maiken Nedergaard, a neuroscientist at the University of Rochester Medical Center in New York state. Arteries and veins normally run alongside lymphatic vessels, but in the brain, they run inside the glymphatic vessels. The pulsing of arteries drives the surrounding CSF into the brain interstitium, pushing its fluid towards returning veins, helping to flush out detritus.

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