Sunday, December 8, 2019

This Is Why Scientists Will Never Exactly Solve General Relativity

[[It is worth looking at the original for the excellent graphics.]]

Ethan Siegel 

[[Ah the wonder of the exact mathematical sciences!!]]

In theory, Einstein's equations are deterministic as well, so you can imagine something similar would occur: if you could only know the mass, position, and momentum of each particle in the Universe, you could compute anything as far into the future as you were willing to look. But whereas you can write down the equations that would govern how these particles would behave in a Newtonian Universe, we can't practically achieve even that step in a Universe governed by General Relativity. Here's why.

But in General Relativity, the challenge is much greater. Even if you knew those same pieces of information — positions, masses, and momenta of each particle — plus the particular relativistic reference frame in which they were valid, that wouldn't be enough to determine how things evolve. The structure of Einstein's greatest theory is too complex even for that.
In General Relativity, it isn't the net force acting on an object that determines how it moves and accelerates, but rather the curvature of space (and spacetime) itself. This immediately poses a problem, because the entity that determines the curvature of space is all of the matter and energy present within the Universe, which includes a lot more than merely the positions and momenta of the massive particles we have.
In General Relativity, unlike Newtonian gravity, the interaction of any mass you consider also plays a role: the fact that it also has energy means that it also deforms the fabric of spacetime. When you have any two massive objects moving and/or accelerating relative to one another in space, it causes the emission of gravitational radiation, too. That radiation isn't instantaneous, but only propagates outwards at the speed of light. This is an enormously difficult factor to account for.

Perhaps the most demonstrative example is to imagine the simplest Universe possible: one that was empty, with no matter or energy, and that never changed with time. That's completely plausible, and is the special case that gives us plain old special relativity and flat, euclidean space. It's the simplest, most uninteresting case possible.

Instead of flat, euclidean space, we find that space is curved, no matter how far away you get from the mass. We find that the closer you get, the faster the space beneath you "flows" towards the location of that point mass. We find that there's a specific distance at which you'll cross the event horizon: the point-of-no-return, where you cannot escape even if you were to move arbitrarily close to the speed of light.
This spacetime is much more complicated than empty space, and all we did was add one mass. This was the first exact, non-trivial solution ever discovered in General Relativity: the Schwarzschild solution, which corresponds to a non-rotating black hole.

·         perfect fluid solutions, where the energy, momentum, pressure, and shear stress of the fluid determine your spacetime,
·         electrovacuum solutions, where gravitational, electric and magnetic fields can exist (but not masses, electric charges or currents),
·         scalar field solutions, including a cosmological constant, dark energy, inflationary spacetimes, and quintessence models,
·         solutions with one point mass that rotates (Kerr), has charge (Reissner-Nordstrom), or rotates and has charge (Kerr-Newman),
·         or a fluid solution with a point mass (e.g., Schwarzschild-de Sitter space).
You might notice that these solutions are also extraordinarily simple, and don't include the most basic gravitational system we consider all the time: a Universe where two masses are gravitationally bound together.

Instead, all we can do is make assumptions and either tease out some higher-order approximate terms (the post-Newtonian expansion) or to examine the specific form of a problem and attempt to solve it numerically. Advances in the science of numerical relativity, particularly in the 1990s and later, are what enabled astrophysicists to calculate and determine templates for a variety of gravitational wave signatures in the Universe, including approximate solutions for two merging black holes. Whenever LIGO or Virgo make a detection, this is the theoretical work that makes it possible.

We can extract how the behavior of a solvable system differs from Newtonian gravity and then apply those corrections to a more complicated system that perhaps we cannot solve.
Or we can develop novel numerical methods for solving problems that are entirely intractable from a theoretical point of view; so long as the gravitational fields are relatively weak (i.e., we aren't too close to too large a mass), this is a plausible approach.

·         the curvature of space is continuously changing,
·         every mass has its own self-energy that also changes spacetime's curvature,
·         objects moving through curved space interact with it and emit gravitational radiation,
·         all the gravitational signals generated only move at the speed of light,
·         and the object's velocity relative to any other object results in a relativistic (length contraction and time dilation) transformation that must be accounted for.
When you take all of these into account, it all adds up to most spacetimes that you can imagine, even relatively simple ones, leading to equations that are so complex that we cannot find a solution to Einstein's equations.

We cannot even write down the Einstein field equations that describe most spacetimes or most Universes we can imagine. Most of the ones we can write down cannot be solved. And most of the ones that can be solved cannot be solved by me, you, or anyone. But still, we can make approximations that allow us to extract some meaningful predictions and descriptions. In the grand scheme of the cosmos, that's as close as anyone's ever gotten to figuring it all out, but there's still much farther to go. May we never give up until we get there.

Thursday, December 5, 2019

Small Wonders: Design in Tiny Creatures
December 2, 2019, 5:52 AM
[[Yes – everything is much much more complicated than we thought.]]
Miniature designs often require more foresight and delicate engineering than large designs. For example, think of how difficult it would be to design a nano air vehicle (NAV) that could flip over and land feet up on a glass ceiling. Yet we hardly notice when a fly does that. Scientists who look more closely at these things often stand in awe of what animals do. Here are some small wonders that deserve our admiration and respect.
The Fly
Scientists from the U.S. and India slowed down and magnified how flies could land on a ceiling. In their paper “Flies land upside down on a ceiling using rapid visually mediated rotational maneuvers,” published in the AAAS open-access journal Science Advances, they share what they learned.
Flies and other insects routinely land upside down on a ceiling. These inverted landing maneuvers are among the most remarkable aerobatic feats, yet the full range of these behaviors and their underlying sensorimotor processes remain largely unknown. Here, we report that successful inverted landing in flies involves a serial sequence of well-coordinated behavioral modules, consisting of an initial upward acceleration followed by rapid body rotation and leg extension, before terminating with a leg-assisted body swing pivoted around legs firmly attached to the ceiling. Statistical analyses suggest that rotational maneuvers are triggered when flies’ relative retinal expansion velocity reaches a threshold. Also, flies exhibit highly variable pitch and roll rates, which are strongly correlated to and likely mediated by multiple sensory cues. When flying with higher forward or lower upward velocities, flies decrease the pitch rate but increase the degree of leg-assisted swing, thereby leveraging the transfer of body linear momentum. [Emphasis added.]
Penn State researchers, who participated in the study, call this “arguably the most difficult and least-understood aerobatic maneuver conducted by flying insects.” Lead author Bo Cheng said, “Ultimately, we want to replicate that in engineering, but we have to understand it first.” The team was astonished to see how the fly could achieve four “perfectly timed maneuvers” to land upside down in the blink of an eye: acceleration, cartwheel, leg extension, and whole-body swing assisted by the legs.
The fly’s maneuvers “exhibited remarkably high angular velocity,” the scientists found, as they watched how the small insect “cartwheels” around its forelegs. Its body comes well equipped to handle the strain. “This process relies heavily on the adhesion from cushion-like pads on their feet (called pulvilli), which ensures a firm grip, and the viscoelasticity of the compliant leg joints, which damps out impact upon contact.” The research team was apparently too fascinated with the aerodynamics to speculate about evolution.
A fly is also well-equipped for stable flying. Michael Dickinson has been studying insect flight for years in his specialized lab at Caltech. His team published another “remarkable” paper in Current Biology, reporting that “Flies Regulate Wing Motion via Active Control of a Dual-Function Gyroscope.” Fruit flies are members of Diptera (two-wing), because their shriveled-up hind wings, called halteres, have been considered vestigial flight wings. Some have thought they function as gyroscopes. Dickinson decided to test that idea:
Flies execute their remarkable aerial maneuvers using a set of wing steering muscles, which are activated at specific phases of the stroke cycle. The activation phase of these muscles — which determines their biomechanical output — arises via feedback from mechanoreceptors at the base of the wings and structures unique to flies called halteresEvolved from the hindwings, the tiny halteres oscillate at the same frequency as the wings, although they serve no aerodynamic function and are thought to act as gyroscopes. Like the wings, halteres possess minute control muscles whose activity is modified by descending visual input, raising the possibility that flies control wing motion by adjusting the motor output of their halteres, although this hypothesis has never been directly tested.
Evolutionists who have treated halteres as useless vestigial organs are now going to have to explain even more function than previously thought.
Our results suggest that rather than acting solely as a gyroscope to detect body rotation, halteres also function as an adjustable clock to set the spike timing of wing motor neurons, a specialized capability that evolved from the generic flight circuitry of their four-winged ancestors. In addition to demonstrating how the efferent control loop of a sensory structure regulates wing motion, our results provide insight into the selective scenario that gave rise to the evolution of halteres.
But if the halteres serve useful timing and control functions now, who is to say they were not original equipment? After all, dipterans in general are among the most versatile flyers in the insect world. If something works, as Paul Nelson has pointed out, it’s not happening by accident. “Although the haltere is commonly described as a gyroscope,” Dickinson’s team says, “the structure is better interpreted as a multifunctional sensory organ.” Compared with other insects with four wings, flies have this advantage: “the wing mechanoreceptors can never provide as clean a clock signal as the mechanoreceptors on a haltere.” At best, the benefit can be seen as subfunctionalization of working hindwings. That would represent an example of devolution, not evolution of new functional traits. Like a driver low on gas, he eliminated the trunk to get better gas mileage.
Rapid Antics
A new land speed record has been discovered in ants. New Scientist writes, “Desert ant runs so fast it covers 100 times its body length per second.” Reporter Michael Marshall doesn’t say if the ant cries “Ouch!” at every footstep on the hot Sahara sand, but this ant looks like a blur as it runs, imitating the Road Runner of cartoon fame. The ant’s trick is to synchronize all six legs and take up to 47 steps per second. Hunting for heat-exhausted insects in the daytime, the Saharan silver ant has another adaptation: its body is coated with silvery hairs that beat the heat.
Nature’s coverage includes a video showing the ant’s running technique slowed down by a factor of 44 — and that is still almost too quick to concentrate on. Galloping at 85 centimeters per second, the ant practically flies with all its feet off the ground at some points in its gait. Touching down with three feet on the ground at a time also gives it stability, like a tripod, that helps keep the ant from sinking into the sand.
Burrow Masters
NASA’s engineers are trying to solve a problem with their newest lander on Mars, named Insight. Its “mole,” an instrument designed to burrow 16 feet into the Martian soil to measure Marsquakes, is stuck at 14 inches. It was equipped with an inertial hammer for digging, but the soil is proving harder than expected, JPL says. Perhaps they should have mimicked earthworms instead. How do soft, squishy animals manage to loosen the soil so effectively?
Helen Briggs of BBC News reports that “The first global atlas of earthworms has been compiled, based on surveys at 7,000 sites in 56 countries.” The atlas of global earthworm diversity, published by the AAAS in Science, begins by explaining why this is important. “Earthworms are key components of soil ecological communities, performing vital functions in decomposition and nutrient cycling through ecosystems.”
Separately, Liu et al. in Current Biology investigated how “Earthworms Coordinate Soil Biota to Improve Multiple Ecosystem Functions.” Their key concept was “multifunctionality” of soils, which refers to “aggregated measures of the ability of ecosystems to simultaneously provide multiple ecosystem functions.” Their experiments and observations showed that worms offer their vital contribution primarily by “shifting the functional composition toward a soil community favoring the bacterial energy channel and strengthening the biotic associations of soil microbial and microfaunal communities.” Less important were their effects on soil structure and pH. In other words, earthworms cooperate with the soil biota to promote the most possible ecosystem functions. 
One cubic meter of soil can contain 150 individual earthworms, the BBC says. How do soft, flexible earthworms squeeze through hard soils, then accomplish so much multifunctional good with small brains and no eyes? These papers don’t get into that, but suffice it to say, without them, Earth soil would likely be as inhospitable as that on Mars. 
A Dynamic Planet 
At many levels, our privileged planet was designed with the foresight to promote habitability. Environments on a dynamic planet are likely to change. When the habitat changes, organisms must be flexible enough to adapt. Intelligent design theory can support diversification, the “lawn” of life branching at the tips, instead of Darwin’s tree with a single root. The silver Sahara ant, for instance, could have diversified from other ants once the Sahara dried up from its former riparian habitat (as evidenced by river channels detectable under the sand). It would only require modifications or exaggerations of existing traits: body hairs, legs, and behaviors. 
There are some 6,000 species of earthworms, including species just a few centimeters in length to giants as long as 3 meters; these also could have diversified based on their local environments. A fly’s hind wings could shrink and degrade if the wings subfunctionalized, moving from multiple purposes to focus on the most important for its needs. This is not too different from blind cave fish that, having lost eyes, compensate with exaggerated senses of touch and smell.
None of these considerations affect the argument from design. Wings, legs, and the ability to burrow do not happen by accident. We can marvel at the foresight built into these creatures that become champions at particular traits in their respective family contests.

Sunday, November 24, 2019

What is Dark Energy?

What’s the difference between dark energy and dark matter? What does dark energy have to do with the cosmological constant and is the cosmological constant really the worst prediction ever?

First things first, what is dark energy? Dark energy is what causes the expansion of the universe to accelerate. It’s not only that astrophysicists think the universe expands, but that the expansion is actually getting faster. And, here’s the important thing, matter alone cannot do that. If there was only matter in the universe, the expansion would slow down. To make the expansion of the universe accelerate, it takes negative pressure, and neither normal matter nor dark matter has negative pressure – but dark energy has it.

We do not actually know that dark energy is really made of anything, so interpreting this pressure in the normal way as by particles bumping into each other may be misleading. This negative pressure is really just something that we write down mathematically and that fits to the observations. It is similarly misleading to call dark energy “dark”, because “dark” suggests that it swallows light like, say, black holes do. But neither dark matter nor dark energy is actually dark in this sense. Instead, light just passes through them, so they are really transparent and not dark.

What’s the difference between dark energy and dark matter? Dark energy is what makes the universe expand, dark matter is what makes galaxies rotate faster. Dark matter does not have the funny negative pressure that is characteristic of dark energy. Really the two things are different and have different effects. There are of course some physicists speculating that dark energy and dark matter might have a common origin, but we don’t know whether that really is the case.

What does dark energy have to do with the cosmological constant? The cosmological constant is the simplest type of dark energy. As the name says, it’s really just a constant, it doesn’t change in time. Most importantly this means that it doesn’t change when the universe expands. This sounds innocent, but it is a really weird property. Think about this for a moment. If you have any kind of matter or radiation in some volume of space and that volume expands, then the density of the energy and pressure will decrease just because the stuff dilutes. But dark energy doesn’t dilute! It just remains constant.

Doesn’t this violate energy conservation? I get this question a lot. The answer is yes, and no. Yes, it does violate energy conservation in the way that we normally use the term. That’s because if the volume of space increases but the density of dark energy remains constant, then it seems that there is more energy in that volume. But energy just is not a conserved quantity in general relativity, if the volume of space can change with time. So, no, it does not violate energy conservation because in general relativity we have to use a different conservation law, that is the local conservation of all kinds of energy densities. And this conservation law is fulfilled even by dark energy. So the mathematics is all fine, don’t worry.

The cosmological constant was famously already introduced by Einstein and then discarded again. But astrophysicists think today that is necessary to explain observations, and it has a small, positive value. But I often hear physicists claiming that if you try to calculate the value of the cosmological constant, then the result is 120 orders of magnitude larger than what we observe. This, so the story has it, is the supposedly worst prediction ever.

Trouble is, that’s not true! It just isn’t a prediction. If it was a prediction, I ask you, what theory was ruled out by it being so terribly wrong? None, of course. The reason is that this constant which you can calculate – the one that is 120 orders of magnitude too large – is not observable. It doesn’t correspond to anything we can measure. The actually measureable cosmological constant is a free parameter of Einstein’s theory of general relativity that cannot be calculated by the theories we currently have.

Dark energy now is a generalization of the cosmological constant. This generalization allows that the energy density and pressure of dark energy can change with time and maybe also with space. In this case, dark energy is really some kind of field that fills the whole universe.

What observations speak for dark energy? Dark energy in the form of a cosmological constant is one of the parameters in the concordance model of cosmology. This model is also sometimes called ΛCDM. The Λ (Lambda) in this name is the cosmological constant and CDM stands for cold dark matter.

The cosmological constant in this model is not extracted from one observation in particular, but from a combination of observations. Notably that is the distribution of matter in the universe, the properties of the cosmic microwave background, and supernovae redshifts. Dark energy is necessary to make the concordance model fit to the data.

At least that’s what most physicists say. But some of them are claiming that really the data has been wrongly analyzed and the expansion of the universe doesn’t speed up after all. Isn’t science fun? If I come around to do it, I’ll tell you something about this new paper next week, so stay tuned.

Sunday, November 17, 2019

Cells That ‘Taste’ Danger Set Off Immune Responses
Taste and smell receptors in unexpected organs monitor the state of the body’s natural microbial health and raise an alarm over invading parasites.

[[Everything is much more complicated that we thought.]]

Cells with taste receptors sometimes develop inside the lungs of animals infected with influenza. By “tasting” the presence of certain pathogens, these cells may act as sentinels for the immune system.

November 15, 2019

When the immunologist De’Broski Herbert at the University of Pennsylvania looked deep inside the lungs of mice infected with influenza, he thought he was seeing things. He had found a strange-looking cell with a distinctive thatch of projections like dreadlocks atop a pear-shaped body, and it was studded with taste receptors. He recalled that it looked just like a tuft cell — a cell type most often associated with the lining of the intestines.
But what would a cell covered with taste receptors be doing in the lungs? And why did it only appear there in response to a severe bout of influenza?
Herbert wasn’t alone in his puzzlement over this mysterious and little-studied group of cells that keep turning up in unexpected places, from the thymus (a small gland in the chest where pathogen-fighting T cells mature) to the pancreas. Scientists are only just beginning to understand them, but it is gradually becoming clear that tuft cells are an important hub for the body’s defenses precisely because they can communicate with the immune system and other sets of tissues, and because their taste receptors allow them to identify threats that are still invisible to other immune cells.

De’Broski Herbert, an immunology researcher at the University of Pennsylvania, was the first to notice the emergence of tuft cells, which are rich in “taste” receptors, developing in the infected lungs of sick mice.
Researchers around the world are tracing the ancient evolutionary roots that olfactory and taste receptors (collectively called chemosensory receptors or nutrient receptors) share with the immune system. A flurry of work in recent years shows that their paths cross far more often than anyone anticipated, and that this chemosensory-immunological network plays a role not just in infection, but in cancer and at least a handful of other diseases.
This system, says Richard Locksley, an immunologist at the University of California, San Francisco, helps direct a systematic response to potential dangers throughout the body. Research focusing on the interactions of the tuft cell could offer a glimpse of how organ systems work together. He describes the prospects of what could come from the studies of these receptors and cells as “exciting,” but cautions that “we’re still in the very early days” of figuring it out.
Not Merely Taste and Smell Receptors
One of life’s fundamental challenges is to find food that’s good to eat and avoid food that isn’t. Outside of our modern world of prepackaged food on grocery store shelves, it’s a perilous task. Taking advantage of a new type of food could mean the difference between starvation and survival, or it could mean an early death from accidental self-poisoning. Chemosensory receptors help us make this distinction. They’re so essential that even single-celled bacteria such as Escherichia coli carry a type of this receptor.
Despite the near universality of these receptors and their centrality to survival, scientists didn’t discover the big family of genes that encode for olfactory receptors until 1991, with the ones for taste receptors following in 2000. (The olfactory receptor discovery brought the researchers Richard Axel and Linda Buck a Nobel Prize in 2004.) Olfactory receptors and taste receptors for bitter, sweet and umami (savory) are all part of a large family of proteins called G protein-coupled receptors (GPCRs) that are embedded in cell membranes. Although the precise details vary from receptor to receptor, when a GPCR binds to the proper molecule, it sets off a signaling cascade within the cell. For taste and olfactory receptors in the mouth and nose, this cascade causes neurons to fire and enables us to recognize everything from the rich sweetness of a chocolate chip cookie to the nose-wrinkling stench of a passing skunk.
The discoveries of these receptors were momentous, groundbreaking advances, says Jennifer Pluznick, a physiologist at Johns Hopkins University. But in her view, labeling them as olfactory and taste receptors rather than as chemosensory receptors entrenched the idea that they function specifically and exclusively in smell and taste. If scientists found signs of these receptors in cells outside the nose and mouth, it was easy to write them off as mistakes or anomalies. [[Why was it easy? Because we  already know everything so this can’t change that.]] She herself was shocked to find an olfactory receptor called Olfr78 in kidney cells, a finding that she reported in 2009.
“I think I even famously said something to my postdoc adviser, like, ‘I don’t even know that I can trust this data, you know?’” Pluznick recalled. “Olfactory receptors in the kidney? Come on.”
This wasn’t the first time these receptors had shown up in unexpected tissues. For example, in 2005, the University of Liverpool biochemist Soraya Shirazi-Beechey showed in a paper published in Biochemical Society Transactions that taste receptors could be found in the small intestine as well as the mouth. Their presence was surprising, but it made a certain sense that the intestine might use a taste receptor to monitor the food it was digesting.
But then in 2010, the laboratory of Stephen Liggett, who was then at the University of Maryland School of Medicine, reported that smooth muscle in the airways of the lungs expresses receptors for bitter taste. Moreover, they showed that these receptors were involved in a dilation response of the airways that helped to clear out obstructions.
They were these really intriguing, weird cells that didn’t really have a clear function in terms of the normal physiology.
Michael Howitt, Stanford University
Receptors for sweetness also turned up on the cells lining the airways. In 2012, a research group led by Herbert’s colleague Noam Cohen at the University of Pennsylvania found that the sugars coating the respiratory pathogen Pseudomonas aeruginosa activated those receptors and caused the cells to beat their hairlike cilia more rapidly, a process that can sweep away invading bacteria and prevent infections.
Meanwhile, Pluznick and her colleagues had continued to study the role of the Olfr78 receptor in the kidneys. They demonstrated in 2013 that it responded to molecules secreted by intestinal microorganisms, and that signals from that response helped to direct the kidney’s secretion of the hormone renin, which regulates blood pressure. “Other labs finding similar things in other tissues was both very encouraging and very exciting,” Pluznick said.
These studies and a torrent of others from labs around the world drove home the message that these seemingly misplaced olfactory and taste receptors serve important and often vital functions. And a theme common to many of those functions was that the chemosensory receptors often seemed to be alerting tissues to the presence and condition of microbes in the body. In hindsight, that application for the receptors made a lot of sense. For example, as Herbert notes, being able to “taste” and “smell” minute traces of pathogens gives the body more chances to respond to infections before microbes overwhelm the host’s defenses.
A Job for Tuft Cells
In researchers’ assays for chemosensory receptors in tissues throughout the body, a cell type that kept popping up was a relatively rare, largely unstudied one called a tuft cell. Tuft cells had been known to science since the mid-1950s, when microscopy studies found them in the lining of practically every organ in the body, including the gut, the lungs, the nasal passages, the pancreas and the gallbladder. The passage of a half-century, however, hadn’t led to any greater understanding of what tuft cells do. The further discovery of taste receptors on many tuft cells only deepened the mystery: Given their locations in the body, they certainly weren’t contributing to our sense of taste.
As a postdoc at Harvard University in the lab of Wendy Garrett in 2011, Michael Howitt became fascinated with tuft cells, especially those found in the intestines. “They were these really intriguing, weird cells that didn’t really have a clear function in terms of the normal physiology,” said Howitt, who is now an immunologist at Stanford University. He set out to learn the enigmatic cells’ function, and he eventually got his answer — through an unexpected discovery involving the mouse microbiome.
Howitt’s findings were significant because they pointed to a possible role for tuft cells in the body’s defenses — one that would fill a conspicuous hole in immunologists’ understanding.
Because some studies had hinted at a link between taste receptors and immune function, Howitt wondered whether the receptor-studded tuft cells in the intestines might respond to the microbiome population of bacteria living in the gut. To find out, he turned to a strain of mice that other Harvard researchers had bred to lack a wide variety of bacterial pathogens.
But surprisingly, when he inspected a small sample of intestinal tissue from the mice, Howitt found that they had 18 times the number of tuft cells previously reported. When he looked more closely, he found that the mice carried more protozoa in their guts than expected — specifically, a common single-celled parasite called Tritrichomonas muris.
Howitt realized that T. muris wasn’t an accidental infection but rather a normal part of the microbiome in mice — something that neither he nor Garrett had thought much about. “We weren’t looking for protozoa,” Howitt said. “We were focused on bacteria.”
To confirm the relationship between the presence of the protozoa and the elevated numbers of tuft cells, Howitt ordered another set of similarly pathogen-free mice from a different breeding facility and fed them some of the protozoan-rich intestinal contents of the Harvard mice. The number of tuft cells in the new mice soared as the parasites colonized their intestines, too.

The numbers of tuft cells also climbed when Howitt infected mice with parasitic worms. But the increase didn’t happen in mice with defects in the biochemical pathways underpinning their taste receptors, including those on the tuft cells.
Howitt’s findings were significant because they pointed to a possible role for tuft cells in the body’s defenses — one that would fill a conspicuous hole in immunologists’ understanding. Scientists understood quite a bit about how the immune system detects bacteria and viruses in tissues. But they knew far less about how the body recognizes invasive worms, parasitic protozoa and allergens, all of which trigger so-called type 2 immune responses. Howitt and Garett’s work suggested that tuft cells might act as sentinels, using their abundant chemosensory receptors to sniff out the presence of these intruders. If something seems wrong, the tuft cells could send signals to the immune system and other tissues to help coordinate a response.
At the same time that Howitt was working, Locksley and his postdoc Jakob von Moltke (who now runs his own lab at the University of Washington) were homing in on that finding from another direction by studying some of the chemical signals (cytokines) involved in allergies. Locksley had discovered a group of cells called group 2 innate lymphoid cells (ILC2s) that secrete these cytokines. ILC2s, he found, release cytokines after receiving a signal from a chemical called IL-25. Locksley and von Moltke used a fluorescent tag to mark intestinal cells that produced IL-25. The only cells that gave off a red glow in their experiments were tuft cells. Locksley had barely even heard of them.
“Even textbooks of [gastrointestinal] medicine had no idea what these cells did,” he said.

Andrew Vaughan, a lung researcher at the University of Pennsylvania, notes that even if the sudden emergence of tuft cells in infected tissues is part of the body’s defenses, it could still cause its own pathologies.
Courtesy of University of Pennsylvania School of Veterinary Medicine
The Howitt-Garrett and Locksley-von Moltke papers were prominently featured in Science and Nature, respectively. Together with a third paper in Nature by Philippe Jay of the Institute for Functional Genomics at the National Center for Scientific Research in France and his colleagues, these studies provided the first explanation for what tuft cells do: They recognize parasites by means of a small molecule called succinate, an end product of parasite metabolism. Once succinate binds to a tuft cell, it triggers the release of IL-25, which alerts the immune system to the problem. As part of the defensive cascade, the IL-25 also helps to initiate the production of mucus by nearby goblet cells and triggers muscle contractions to remove the parasites from the gut.
For the first time, biologists had found at least one explanation for what tuft cells do. Before this, “people just kind of ignored them or didn’t even realize that they were there,” said Megan Baldridge, a molecular microbiologist at Washington University in St. Louis.
As groundbreaking as this trio of studies was, the work focused on intestinal cells. No one knew at first whether the tuft cells appearing elsewhere throughout the body play the same anti-parasitic role. Answers soon began to roll in, and it became clear that tuft cells respond to more than succinate and do more than help repel the body’s invaders. In the thymus (a small globular outpost of the immune system nestled behind the breastbone), tuft cells help teach the immune system’s maturing T cells the difference between self proteins and non-self proteins. Kathleen DelGiorno, now a staff scientist at the Salk Institute for Biological Studies, helped to show that tuft cells can help protect against pancreatic cancer by detecting cellular injury. And in Cohen’s studies of chronic nasal and sinus infection, he discovered that recognition of bacterial pathogens such as Pseudomonas aeruginosa by receptors for bitterness on tuft cells causes neighboring cells to pump out microbe-killing chemicals.
As a lung biologist and a colleague of Herbert’s at the University of Pennsylvania, Andrew Vaughan followed these tuft-cell discoveries with interest. In many cases, tuft cells appeared to be intimately involved with the part of the immune response known as inflammation. Vaughan was studying how tissue deep in the lungs repairs itself after inflammation caused by the flu virus. After reading about some of the new findings, Vaughan began to wonder whether tuft cells might be involved in the lungs’ recovery from influenza. He and Herbert infected mice with the influenza virus and searched the lungs of those with severe symptoms for signs of tuft cells.

“Sure enough, they were all over the place,” Vaughan said. But the tuft cells only appeared after influenza infection, which made Vaughan believe that he and Herbert were “basically seeing a cell type where [it’s] not supposed to be.” Although he’s unsure exactly why this proliferation of tuft cells happens after the flu, Vaughan speculates that it might be an aspect of the body’s attempt to repair damage from the virus as part of the broader type 2 immune response.
The researchers don’t yet know what the tuft cells are doing in the lungs or what they are sensing, but Herbert believes that their ability to continually “taste” the environment for different compounds provides a key opportunity for the body to respond to even minute threats.
The tuft cell, Herbert said, is constantly sensing the metabolic products present in microenvironments within the body. “Once some of those metabolic products go out of whack … bam! Tuft cells can recognize it and make a response if something is wrong.”
Newly discovered connections between tuft cells and the immune and nervous systems provide further evidence that chemosensory receptors are multipurpose tools like Swiss Army knives, with evolved functions beyond taste and smell. It isn’t clear which function evolved first, though, or whether they all evolved in tandem, Howitt says. Just because scientists became aware of “taste” receptors on the tongue first, “that doesn’t mean that’s the order in which it evolved

In fact, a preliminary study in rats hints that the receptors’ immune functions may have evolved first. Two groups of immune cells known as monocytes and macrophages use formyl peptide receptors on their membranes to detect chemical cues from pathogens, and a group of Swiss scientists showed that rats use these same receptors to detect pheromone odors. Those facts suggest that at some point in history, the ancestors of rats made scent receptors out of the immunological molecules. The evolutionary history of other groups of olfactory and taste receptors has yet to be deciphered.
Whatever their history, scientists now say that a major role of these receptors is to monitor the molecules in our body, tasting and smelling them for any sign that they might be from a pathogen. Then, with help from tuft cells and other parts of the immune system, the body can fight off the invaders before they’ve gotten a foothold. But Vaughan cautioned that the sudden emergence of tuft cells in tissues like the lungs, where they are not always present, might also cause its own pathologies.
“You may not always want to have the ability to [defensively] overreact,” he said. That could be part of what goes wrong in conditions like allergies and asthma: There could be dangers “if you have too many of these cells and they’re too poised to respond to the external environment.”