Scientists have thought for a decade that iron-bearing structures in the homing pigeon’s beak help the bird find its location by “reading” Earth’s magnetic field. Now, it turns out that this iron occupies cells that battle infection, rather than nerve cells.

Oops!

The new results leave a chasm in our understanding of bird navigation, says Charles Walcott, an expert on the subject at Cornell University, who was not involved in the study. “It’s astonishing that we have what seems like a terribly simple-minded problem. Take a homing pigeon any direction, and after circling a couple of times, it heads for home … and we don’t understand how these animals do this?”

Study leader David Keays, of the Institute for Molecular Pathology in Vienna, did not set out to debunk a beautiful theory, but rather to explore the nerve cells in the beak that supposedly register magnetism. “My background is in molecular biology and genetics, and I thought there must be some incredible biology involved. I wanted to get a handle on the molecules and create an artificial receptor.”

Because the “magnetic neurons” in the beak contained iron, Keays applied a blue stain that gloms onto iron. Christoph Treiber and Marion Salzer generated one-quarter million slices for microscope slides, each one-hundredth of a millimeter thick.

(Makes us dizzy … Didn’t they outlaw slavery?)

A fly in the ointment!

Although the magnetic neurons were said to number just six, iron-rich cells showed up all over the beak. One beak had about 108,000 blue-stained cells while another had just 200, Keays says. “This did not make sense. If these were magnetoreceptors, we would expect a similar number in birds of the same age and sex.”

When the scientists treated the samples with stains that attach to neurons, there was almost no overlap with the iron-bearing areas.

As questions accumulated, the researchers got a lucky break. One bird’s infected beak attracted blue cells that resembled macrophages, immune cells that fight infection (and also process iron). “You could see the cells’ tentacles engulfing other cells,” Keays says.

Stains that attach to immune cells overlapped heavily with the iron stain, Keays says; further evidence that the iron was inside macrophages, not neurons.

The study is “quite interesting and convincing,” says Walcott, and it explains why scientists have found no connection between the iron crystals and the nervous system. “If this is going to be seen as a sense organ, I think the two ought to be connected.”

Paradigm paranoia

Although the new study overthrows the accepted explanation for the pigeon’s magnetic mastery, Walcott says magnetism isn’t the whole story in navigation; birds also use vision, memory and smell.

Looking at the sun can help the bird figure out direction, but magnetic methods are needed to find a location on the globe.

Confusingly, birds seem to have a mechanism in the eye that detects Earth’s magnetic field. But because this works only when the sun is shining, it’s unlikely to explain nighttime navigation.

Keays says attitudes have changed since he “released a cat among the pigeons” at a conference a year ago. “Half of the audience wanted to hug me, they had been very skeptical, but the other half wanted to kill me.”

Since then, however, “We were able to persuade some big players in the field that the original reports were wrong. I think the great thing about science is that it is a self-correcting enterprise. If we get it wrong, somebody is going to come along and work out what the truth is.”

At this point, though, mystery rules. “It’s absolutely clear that birds, pigeons, can detect magnetic fields,” Keays says, “but the way they do that is the mystery.”

Robots are great at what they do — if the job is dull and predictable. Throw in the unexpected, and robots can do the unpredictable.

The task of programming a robot’s brain for the real world can be gnarly, says Josh Bongard, an assistant professor in the University of Vermont College of Engineering and Mathematical Sciences. “It turns out that building a robot, and programming it to do something interesting is a very non-intuitive process, and it’s a difficult one for humans to do well.”

The real world, he says, “is quite messy.”

Robots, in the jargon, need “adaptive behavior” to accommodate changing circumstances, says Bongard. When programming a free-roaming robot, “We are not likely to factor in a lighting change or people moving in and out of the field of view.”

It’s not clear how animals or people make adaptations, Bongard says, “and so it’s difficult to program a robot to do them.”

Robots: Are they alive?

Bongard, like a number of roboticists, is turning to biology for answers. But he does not want to emulate living structures. Instead, he wants to use evolution to craft robot control.

The process is akin to the “artificial selection” that helped lay the foundation for the science of evolution. Darwin, after all, wrote about how animal breeders had changed their livestock by repeatedly breeding the best animals and eating the rest.

In January, 2011, Bongard reported that he had taught four-legged, digital robots to stand and run toward a light source, by grading their control software on its ability to meet those goals.

Adaptive behavior was necessary, he says, because the light source could appear anywhere, or even take evasive action, “so the robot can’t just move its legs blindly every time.”

The robots had five seconds to do or die, and their first movements were grotesque because the control software initially moved their body parts at random. After every attempt, the control programs were graded by their ability to walk, stay upright and approach the light.

It’s brutal. More than 100 million failed programs went to the virtual graveyard in the name of science, Bongard says. The programs that showed some promise were retained, randomly varied and re-tested.

The same process is found in nature, where successful genes that face random mutation are re-tested by tomorrow’s environment.

Like the average biological mutation, the mutated robot software usually failed. But over a year of supercomputer time — equivalent to 1,000 years on a desktop computer — the winning programs evolved the ability to walk toward the light.

Weird winners

Considering the amount of trial and error, that was a satisfying but not necessarily surprising result. But here’s something to chew on. Bongard found that robots “born” with four legs had a handicap. During repeated simulations, the robots that started as snakes and developed legs during the five-second experiment were much quicker to learn the task.

You might guess — we would have — that the quick learning would have occurred in robots with full-time four-leg drive, given their longer experience with legged locomotion, but Bongard says the leg-free starters benefited by chunking the challenge: a) learn to approach the light, and b) learn to walk.

These robots “could evolve the ability to go from point A to point B while they still look like a snake, they don’t have to worry about balance, because they are already on the ground,” Bongard says. “Once evolution has figured out how to move toward the light, the ability to move on four legs could evolve.”

Meanwhile, the four-legged counterparts may still be flipping, flopping and floundering (Note to self: sell soul as political hit-man if science-writing gig crash-burns?) “The robots that had to stand upright would fall over, and it took evolution a long time to master balance,” Bongard says.

The approach — take the winners and vary them for a retest — resembles directed chemical evolution, which aims to create a better antibiotic by modifying and retesting molecules that show some ability to kill bacteria. “It’s basically the same idea,” says Bongard, “but instead of a candidate drug, we have virtual robots, and instead of selecting for … resistance to disease, they are selected for the ability to get to the light.”

Robots resemble rodents?

As a final exam for the digital robots, Bongard tested their balance with a blast of air. Although the leg-less robots “had evolved into legged robots that looked exactly like the other species, they were better able to run around under simulated windy conditions,” Bongard reports.

Bongard is first to acknowledge that he is “stealing from biology to help us build better robots,” but says, “the more interesting question is what this tells us about biological evolution. This recent work suggests that robots that change their bodies gain an adaptive advantage … and you see the same radical changes in body plan in nature: in insects, reptiles and in humans as they develop from infant to adult.”

If you’ve hung around a big-city park, you may think that pigeons are countless — or uncountable. But according to scientists from New Zealand, pigeons now join the short list of animals that can count — or at least, can places images containing two countable items in numerical order.

It’s blue news for those who think only humans deserve human capacities. From empathy and altruism to murder and war, animals seem to have caught on to some of our best — and worst — tricks.

Now Damian Scarf, a post-doctoral researcher at the University of Otago, with his colleagues, has taught three pigeons to order pairs of numbers in the range from one through nine.

This is not exactly counting, but it certainly is a sign of numerical awareness in birds.

More important, the researchers have taught these retired racing pigeons the concept of smaller-to-larger, Scarf says. “Previously, this number abstraction was only known in primates, and now we have shown that it is not unique to primates.”

Serious screen-time serves science

The experiment began with a year-long training period, during which the birds were shown pairs of images, each containing one, two or three countable items. If the birds pecked at both images, smaller number first, they were rewarded with some wheat. (Although the images never contained a numeral, we refer to the “number” they contain for brevity.)

To prevent the birds from focusing on color, shape or other non-numerical details, the images showed a range of items, so that the only correct answer would reflect their number rather than other distinctions.

“The training time reflects how difficult it is for them to abstract,” Scarf says. “It’s such a foreign situation, number is not the first port of call when presented with a stimulus to discriminate. That’s why we had so many shapes, colors, surface areas.”

Even if the birds originally made their judgments based on color, “we pushed them to use a different strategy, to break away from that. Number is not the default discrimination mechanism” for pigeons, says Scarf, who worked under advisor Michael Colombo of Otago.

A genius for abstraction?

This does not mean that the birds are counting, says Scarf. “It’s more a fuzzy representation in the brain of what ‘three’ is. We can apply this verbal label to three, but they cannot. Pigeons, and animals in general, don’t have a definite idea of a number, that’s why they don’t perform perfectly, and why we see the distance effect.”

When the numbers on the test pair are further apart, Scarf found, “the fuzziness overlaps a little less.”

A greater distance between the numbers produced a quicker response and greater accuracy. For adjacent numbers, like four and five, the birds scored about 66 percent accuracy, compared to more than 95 percent for numbers separated by at least six. Once the difference rose to at least three, the pigeons did as well as monkeys in a path-breaking 1998 study that opened the field of numerical “thinking” in animals.

Scarf stresses that the birds were not just regurgitating what they had learned, but were learning numerical rules. “The goal was to find out whether they could acquire an abstract rule. We were just training for one through three, but they learned some flexibility, an abstract, ascending rule for ordering numbers” that would apply to other numbers on the screen.

Rooted in evolution, but where?

Being able to recognize that one thing is more numerous than another could help an animal survive, Scarf says. “When food is available in multiple places, an animal has to develop an optimal strategy for figuring out where the most food is, and I think we have subverted that capacity for this task.”

Where this capacity arose is anybody’s guess at this point. The evolutionary lineage of mammals and birds divided about 300 million year ago, Scarf says. “If this derived from a common ancestor, it’s very old. It’s also possible that primates and birds have evolved this independently.”

“I do think it’s important, just as our study of mirror self-recognition in monkeys, from the fundamental standpoint of how these abilities come about,” says Luis Populin, a professor of anatomy at the University of Wisconsin-Madison, who has found that, under certain conditions, monkeys can recognize themselves in a mirror. “It’s very nice and is yet another step toward understanding how our cognitive functions develop.”

You have to hand it to these birds, which have set a new standard for avian aptitude. “The new part is the idea that this abstraction of numbers is not tied to training,” says Scarf. “Most numerical tests with animals involve training and testing with the same numbers, but we were training with a limited set of numbers and testing them with numbers outside the range. They learned an abstract rule, and that’s what makes this study unique.”

What causes your brain to switch from the quiet focus needed to read (or write) these words to the frantic, goggle-eyed arousal needed to confront a frothing dog or rabid boss?

That hyper condition, popularly called the fight-or-flight response, is a hormonally inflicted surge of stress that puts all systems on alert, raises the heart rate and blood pressure, and shifts blood from the gut to the muscles.

This is not when you want to be translating Latin or solving equations, but fight-or-flight certainly fulfills its evolutionary role of allowing the body and brain to survive threatening circumstances.

After the transition, the brain regulates attention differently: A person studying Japanese woodcuts is unlikely to notice someone prowling on the other side of the art library. A person cranked up on stress hormones is unlikely to miss the lurker.

Neuroscientists long ago fingered two “stress” hormones — cortisol and noradrenaline — as playing key roles in fight-or-flight and today, a study in Science helps confirm that noradrenaline, not cortisol, triggers the transition to a different level of attention. “Many people thought cortisol would have an effect on the attention process in the early phase, but our study shows cortisol probably is not as important” as noradrenaline, says first author Erno Hermans, of the Donders Institute for Brain, Cognition and Behaviour at Radboud University Nijmegen Medical Center in Holland.

Putting the stress on stress

Image: Irréversible

According to some film critics, Irréversible was one of the most disturbing films of 2002. No wonder it stressed-out the study subjects!

To study the mental effects of stress, Hermans and colleagues put 80 subjects in a magnetic resonance imager and tracked the usage of oxygen in the brain to show which structures were active at any moment. Then the subjects watched parts of a French movie containing what Hermans calls “particularly horrific” scenes of violence.

The scans revealed changes in what’s called the salience network, which “is active in a general state of hyper-arousal, vigilance,” Hermans says. “It scans the environment for things that might be important, and allows you to redirect your attention.” The result is not just a change of focus, “but a switch to a state where a change of your focus becomes more likely.”

To confirm that the violent movie clip was triggering the stress response, the researchers measured heart rate and chemicals in the saliva.

Counting on cortisol

Long-term stress can lead to many problems, including the disabling post-traumatic stress disorder, and cortisol, which makes memories more vivid and plays a major role in the constant arousal and intrusive memories of PTSD, has long been considered a major player in stress in general.

“Stress research in humans has been very focused on cortisol for very good reason,” says Hermans, “as it’s linked to a number of very important features of stress in the body and also in the brain.”

In a second phase of the experiment, Hermans and his colleagues used drugs to block either cortisol or noradrenaline. Blocking cortisol did not prevent the changes in brain networks, but blocking noradrenaline did. “Because blocking noradrenaline results in a reduction in the salience network, this shows that noradrenaline is important for this reorganization of the brain,” Hermans says.

Stress or distress?

The new study helps explain our world, says Christopher Coe, a professor of psychology at the University of Wisconsin-Madison and an expert in cortisol and stress. “As we all have subjectively experienced, a fearful stimulus can exert a galvanizing influence on us. It can reorient our attention and, when sufficiently provocative, make us feel more alert, energized and focused. This change in state is facilitated by the type of coordinated brain reaction described in this Science paper. We and our brains are mobilized in order to better analyze the situation, to quickly interpret and utilize incoming information … and to respond adaptively.”

Coe adds that although “it is reasonable to conclude” that cortisol is not initiating the change in salience, “nevertheless, because of cortisol’s widespread effects and potency, if its release into the blood stream is sustained, it may ultimately exert a more protracted effect on both the brain and other physiological functions.”

Changes in the mode of attention are a fact of life, Hermans says. “We are really selective about accepting information while doing a focused task,” but a threat “requires a switch so your brain can respond to significant things in the surroundings. The brain becomes more responsive to stimuli, the eyes are wide open, the pupils become larger, everything is focused on having more sensory intake.”

– David J. Tenenbaum

She asks if she’s overweight, and you wait half-a-second before responding, “Of course not, dear! I’ve just been noticing how slim you look these days.”

Any well-schooled husband knows the pitfalls of faltering in this “marital duet.”

And now, we find a similar phenomenon among a singing duet by plain-tailed wrens, natives of the cloud forest in Ecuador.

Pairs of these wrens engage in a high-speed duet that relies on perfect timing: She utters a call, and if he chimes in on cue, she sings her part, and the duet continues.

If he’s late or silent, she is slow to resume the song.

This is cooperative behavior, but close examination also reveals a new mental phenomenon, says Eric Fortune, an associate professor of psychological and brain sciences at Johns Hopkins University. Fortune, first author of a study of the wrens that appears today, says his research “indicates that the full mental representation of the song exists in both birds, even though each one contributes only half of the song.”

The study looked at the interaction between the hearing and motor circuits in the brain via a concept called “mirror neurons.” Discovered in 1983 by Dan Margoliash of the University of Chicago, mirror neurons were “a key discovery that has profoundly shaped our thinking,” Fortune says. “He showed that an area of the brain used to control song responded only when the bird heard a playback of its own song, but not of any other bird’s song.”

Zina Deretsky,
National Science Foundation

Takes two to tango: The song of the plain-tailed
wren is a his-and-hers production.

These nerve cells, since seen in people, other primates and birds, are now called mirror neurons. In simple terms, mirror neurons allow a bird that hears its own song to “imagine” singing that song.

Brainiest birds?

In the new study, however, the mirror response occurs when an individual in a pair hears both birds singing — a sound that each bird cannot produce by itself.

In 2006, scientists identified the plain-tailed wren’s song as a two-part composition that required cues from both partners. “When we heard about these wrens, where one-half of the song is produced by the female, and the other half by the male, we thought, ‘This is amazing. Here’s a song this bird has learned completely in the sensory part of the brain, but it has only half of the motor program.’”

How could this work?

To unravel the sensory-motor linkage, Fortune, with Gregory Ball of Johns Hopkins and Melissa Coleman of Claremont McKenna College, recorded pairs of plain-tailed wrens, manipulated the songs in various ways, and then played them back.

They found that the birds not only sang in pairs, but sometimes also sang solo, making the same calls it would otherwise contribute to the duet, but with altered timing. They found that when a male flubbed his lines, the female might continue to sing, but with a measurable delay. “She’s waiting for him, then gives up and sings anyway,” Fortune says.

The birds were basing their behavior on what they heard — not very surprising. But the fascinating part emerged from the fact that they were engaged in a truly cooperative, back-and-forth behavior that was deeply embedded in the mirror neurons.

Both images courtesy Eric Fortune and Melissa Coleman

Like many field worker, Fortune had to make do with local material, as
shown in this laboratory. Rollover for a look at their solar and
hydro-powered neurophysiological rig, featuring a home-made version
of a $7,000 vibration damper.

Such cooperation, also evinced by dancers and musical ensembles, requires each party to know its own part, but the brain studies showed that they knew much more than that, says Fortune, who is also a visiting professor at Catholic University in Quito, Ecuador. “Both birds had very similar patterns of activity. The neurons responded most strongly to the combined song, not to their own part. The brain knows that they were trying to do this together.”

Got my eye (and ear) on you, mister!

Although Fortune says the songs are probably used to defend territory, he suspects she is also checking him out, gauging his evolutionary fitness, much as female birds rate a fellow’s feathers. “The female is testing the male’s ability to cooperate,” Fortune says. “She produces a long song, and the male has to work hard to insert his syllables at exactly the right time.”

Louis Vest

People also learn cooperatively. Do these
tango dancers hold a representation of the
complete dance in their heads, or is this just
another example of sexual selection at work?

These wrens, he says, “are wired to cooperate. There is a set of rules and the male’s job is to respond rapidly and accurately to the female’s challenge.”

It’s not just feathery guys that fail to respond on cue, and the evolutionary significance could extend far beyond birds. “This happens a lot in people,” Fortune speculates. “Why do women get annoyed when you forget their birthday? They are challenging your neural circuitry. It’s not like flexing your muscles; they are probing your brain. That’s a stronger cue for sexual selection.”

Bringing it back to birds, Fortune says, “It’s most surprising that these animals have a memory of their cooperative behavior in the brain, which includes the performance of another animal; this had not been shown before on a neurological basis. You can take their own half of the song, and play it back, and the motor neurons fire,” but the response is much more powerful when the bird hears the full, two-part song.

— David J. Tenenbaum

If you think slavery has been abolished, consider the case of the gypsy moth and the virus. For more than 100 years, people have noticed that some gypsy moth caterpillars climb to the top of trees before they die and decompose, or “melt.”

Melting releases more virus particles and is the normal fate of these caterpillars, but why did only some caterpillars perform this ascending death march?

Gypsy moths are voracious insects that have been spreading across the United States for a more than a century, so nobody is feeling too sorry for them, especially people who have seen them strip forests bare.

Still, it’s nice to read a good explanation for this peculiar “climb, croak, melt” behavior.

All the better to infect you with, my dear!

A study published today identifies a viral gene that blocks one stage of maturation in gypsy moth caterpillars, which normally hide during the day. But when Kelli Hoover, a professor of entomology at Penn State, and her colleagues infected bottled caterpillars with the virus of doom, the caterpillars showed the same climbing ‘n’ dying behavior that appears in the field.

In nature, those caterpillars would melt and then rain virus down to infect other gypsy moths.

The moth misbegotten

Gypsy moths were introduced to Massachusetts in the late 1800s by a bumbler who wanted to raise silk by crossbreeding them with silkworms — a different species, says Hoover. “It was crazy; this guy did not know anything about species, apparently.”

Still, the gypsy moths did bring fecundity and a ferocious appetite to the table — or forest. “They eat so many different kinds of trees and plants … in a bad outbreak, the insect frass dropping down sounds like rain, so you need a hat,” Hoover says.

We had to look it up to be sure, but frass is basically insect poop.

Gypsy moths are such effective defoliators that authorities try to control them with Bt, a bacterial spray that unfortunately kills beneficial insects, not just harmful ones.

Hoover’s study focused on a viral gene called egt, which inactivates a hormone that starts molting – a process that ends each stage, or “instar,” of the caterpillar’s development. “When they stop molting, they keep feeding, and that’s why we looked at egt,” Hoover says.

Photo: USDA APHIS Pest Survey Detection and Exclusion Laboratory

The battle against gypsy moths was joined before 1900, when an unknown chemical was sprayed against the invader.

ENLARGE

A dangerous meal

In every case, Hoover says, “if the gene was active, the moth died at the top of the bottle. If the gene was inactivated, it died at the bottom.”

It’s not clear, Hoover says, exactly why the gene changes behavior, but this is the first time it was traced to a single gene.

Because LdMNPV (the Lymantria dispar nucleopolyhedrovirus) infects only gypsy moths, and kill them at a young age, it might work as a biocontrol agent against a disastrous insect invasion. However, Hoover says, “the experiment’s goal was more basic – to understand how the virus enslaves its host.”

Certainly there is evolutionary logic behind changing your host’s behavior for your own benefit, assuming you are a pathogen or parasite, and “body-snatching” is well-known. For example, a fungus forces ants to climb, zombie-like, and die where they can easily spread fungal spores.

And it’s not just insects. The rabies virus, Hoover adds, “causes dogs, raccoons and bats to become more aggressive, to be out during the day, where they approach people and try to bite them,” which spreads the virus even though it endangers the animal.

And toxoplasmosis, a parasite, can make mice less fearful of cats, Hoover says, “so they are more likely to get eaten and infect the cat.”

There is even speculation that toxoplasmosis may cause men to behave with greater jealousy, Hoover says, “but the only thing that’s really been looked at is that mice with toxoplasmosis have a higher level of dopamine,” a feel-good neurotransmitter.

Is slavery therefore not all drudgery?

— David J. Tenenbaum

Image: M.J. Grimson & R.L. Blanton

The single-celled amoeba Dictyostelium discoideum has no brain, but its complicated social cycle enables farming.

Amoeba, single-cell, shape-shifters that eat bacteria and live in the dirt, don’t get much respect. When they run out of food, they gang up and move their sorry selves to greener pastures.

Pastures with edible bacteria, that is.

If ever a creature needed re-branding, this is it.

Could labeling amoeba as farmers boost their brand? In the human realm, farming gave rise to cities, writing, metallurgy and the computer in front of your face.

Amoeba don’t use the Internet. And although they do have a cell nucleus, nobody claims they have an ounce of smarts.

But now we know that some amoeba move “seeds” of bacteria to a new location and plant them as a food source. In other words, they farm.

Ants grow fungus. Termites and some saltwater snails do ditto. Damselfish grow algae. But until now, nobody has identified any life form that “farms” bacteria, and nobody has identified any single-celled farmers, says Debra Brock, a graduate student in ecology and evolutionary biology at Rice University.

Adds Brock, whose report on farming amoeba appears in Nature tomorrow, “Certainly there has never been an amoeba that’s known to farm.”

Bring on the rebranding!

Working with the well-studied amoeba Dictyostelium discoideum (“dicty” to you and me) Brock noticed that the fruiting bodies — reproductive structures that distribute the amoeba in new habitat — seemed to contain bacteria. That was odd, Brock admits. “To get anybody to believe me, I had to prove that the little spots were bacteria, and not an infection.”

When she spotted the sorus (mass of spores) on growth medium, colonies of bacteria grew on some of the plates — showing that about one dicty in three transports bacteria. The bacteria didn’t seem to be a harmful infection, since amoebas with and without bacteria grew similarly, she says.

She fed the shape-shifters antibiotic to kill their bacterial cargo, but when the amoebas resumed eating bacteria, some bacteria showed up in the sorus. Since this only happened with amoebas that had originally carried bacteria, Brock concluded that this was normal, healthy behavior for those amoeba, although she’s can’t yet say whether the bacteria are inside or alongside the amoeba spores.

Photo: Scott Solomon

Fruiting bodies of the amoeba Dictyostelium discoideum contain bacteria and spores of amoebas. Each sorus is attached to a single slug, comprised of about 100,000 individual amoebas.

Wild about amoeba

The project began when Brock was studying wild amoeba rather than a strain that had been living in labs since the 1930s, and she noticed that some clones consistently carried bacteria.

Brock says dictys are “social amoeba” because “they have a structured society, and can exist in two states.” Individual amoebas in the soil eat bacteria, divide and eat some more. So long as edible bacteria are available, “they are perfectly happy to do this,” says Brock. “But if they use up all the food, they start talking to each other with chemical signals: ‘Wow! There’s not enough food!’ And then approximately 100,000 come together to form a slug.”

The slug serves as a truck to haul amoeba to new territory, Brock says. “During the multi-cellular part of the life cycle, they are starving, and they want to go somewhere else.”

The slug eventually shoots up a stalk containing amoeba spores, and among the farmers, bacteria. When the sorus opens, the bacteria can plant themselves as amoeba food.

Reminds us of Johnny Appleseed…

The Darwinian decision

Why does the same species of dicty use two survival strategies? Why do some farm while others don’t? “It’s a smart evolutionary strategy,” says Brock. “It’s bet-hedging. If you happen to land in a patch without bacteria, farmers have a great advantage because they bring their food with them, which allows them to grow and divide and bear a huge number of progeny while the poor non-farmers have nothing to eat.”

But while the farmers quit eating before they remove all bacteria from their old location, non-farmers can eat all those bacteria, so non-farmers do benefit if the new home already contains edible bacteria.

Apparently, both strategies work, because both have survived the evolutionary gauntlet. Brock is exploring whether a “farmer gene” causes some amoeba to hoard bacteria…

It’s enough to give a person a new respect for protozoans, which offers a firm basis for rebranding. “From quite a long time ago, we’ve thought we are so special,” says Brock, “but you can’t imagine the number of genes the amoeba has that are just like human genes. It’s scary; it takes you down a notch or two.”

– David J. Tenenbaum

Talk about going to extremes: In 2004, an anonymous American man with ulcerative colitis chose to eat parasitic worms instead of having his diseased colon removed. He hoped that whipworms would provide a last-ditch biological balm for painful, bloody and frequent diarrhea, and more serious complications of colitis.

If his symptoms had not improved, you would not be reading about his sojourn through planet parasite. “It did work with this individual, he seemed to get better, not just once but twice,” says P’ng Loke, a parasite immunologist at New York University who studied the case.

Photo: Delorieux for Johann Gottfried Bremser

Imagine swallowing 2000 of these guys. You just might, if you were plagued with an inflammatory bowel disease.

In the same year that Mr. A swallowed those worm eggs, two other biological treatments gained Food and Drug Administration blessing as “medical devices”: leeches for removing excess blood after surgery, and maggots for cleaning difficult wounds.

Live organisms once played a bigger role in medicine, observes Ronald Sherman, a California doctor and maggot maven. “Before we had a good method for controlling syphilis, the bacterium was killed by inducing a fever, and one of the best methods was through malaria, carried by mosquitoes.”

Ready for some greatest hits from the ancient-but-modern realm of medicinal vermin?

Wondrous whipworms

Ulcerative colitis is a chronic bowel disease that afflicts up to one American in a thousand, apparently caused by some combination of inflammation and heredity. There is no cure. To prevent holes in the colon and other nasty outcomes, the bowel is often removed — a treatment that is also used for Crohn’s, the other major inflammatory bowel disease.

Photo: Uma Mahadevan, UCSF

Mr. Anonymous’s colon has a heavy infestation with whipworms, which are damaging the intestinal walls. Could that bleeding be a good thing?

In 2003, Mr. Anonymous was diagnosed with ulcerative colitis, and in 2004, he went to Thailand and ate 500 eggs of Trichuris trichiura, a parasitic helminth worm, and then 1,000 more.

The symptoms abated, and when they returned in 2008, Mr. A, who’s now 35, slurped 2,000 more whipworm eggs, and again his symptoms receded.

There is some support for the idea that parasitic worms can help with ulcerative colitis. Whipworms infest almost a billion people around the world, and colitis is scarce in infected regions. Animal tests, and one human trial¹ suggest that parasitic worms can help with ulcerative colitis.

This story of salvation courtesy of planet parasite might be dismissed as another tall tale told over a tall goblet of organic wheat-grass at the Health-4-All-Spa, except that Mr. A came under the scrutiny of medical experts² eager to explore the effect of parasites on one ulcerated colon.

Although eating worm eggs twice reduced the symptoms, one person does not constitute scientific proof, says Loke, a parasite expert. “The question is whether it would work for everyone, and for whom it would do more harm than good; that’s what we worry about.”

Image: Kimberley Evason, UCSF

Stained Trichuris trichiura eggs inside a worm from the ulcerative colitis patient who infected himself with these whipworms.

Whipped into shape?

The study did pinpoint a mechanism of help, and surprisingly, it was not, as expected, via a dampening the immune system. “When we analyzed this patient, we started thinking that the protection may be more related to restoring mucus production,” Loke says.

Mucus protects the intestinal lining from bacteria and other dangers, and Loke and his colleagues think the worms accelerated activity in genes involved in producing mucus, through a stimulating chemical called IL 22.

A second benefit probably came from faster growth of cells lining the intestine, Loke added. “We know from mouse studies of Trichuris that the mechanism of expelling the parasite from the gut involves a combination of turning over epithelial cells so worms will get sloughed off, and an increase in mucus production.”

Immunology still matters, he says, but it may be that the worms are triggering a protective immune response rather than immune suppression.

Before worms could be considered a treatment for ulcerative colitis, “we hope to understand the mechanism a bit better,” says Loke. “In the ideal situation, we’d like to activate this response without using the worms themselves.”

Amen.

Photo: Professor David B. Fankhauser, University of Cincinnati Clermont College.

Goblet cells (arrow) in the intestinal lining create protective mucus. Increased mucus production could explain how whipworms treat ulcerative colitis.

Worms v. asthma

There’s been some hope that regulating the immune system could help with asthma, but the improvements in patients in a clinical trial³ of hookworms were, disappointingly, not statistically significant.

But 13 of the 16 patients who swallowed hookworms decided not to get de-wormed afterwards, which suggests some perceived benefit, admits study author John Britton, in the division of epidemiology and public health at the University of Nottingham (United Kingdom). “We weren’t able to measure anything objective; hence the implication that larger, longer (and simpler) trials are needed.”

If you are tempted by do-it-yourself worm treatment for asthma, Britton has simple advice: “Don’t. There’s no evidence that it works.”

Both the benefits and the risk remain to be documented, says Loke, who tracked Mr. Anonymous, “and we don’t understand that fully. Worms can cause symptoms of colitis” and in the case of Mr. A, “are causing damage to the gut. But we think the gut is activating a healing response against the worms, and one benefit of that is the side effect of helping colitis.”

Marvelous maggots

While people have long used live organisms for medical purposes, many trace the scientific foundations of maggot therapy to World War I, when surgeon William Baer observed that maggot-infested wounds were often the cleanest and quickest to heal.

Photo: Alvesgaspar

Baby animals usually are cuter than the adults, but nobody told the green bottle fly!

In 1929, Baer reported complete success after treating 21 bone infections with maggots, and fly larvae quickly gained acceptance for wound treatment. But when antibiotics became widespread in the 1940s, healing became simply a matter of sprinkling a magic powder, and maggots were forgotten.

With diabetes becoming epidemic, and with so many bacteria immune to antibiotics, maggot use is again on the upswing. One key use is treating foot ulcers: slow-healing sores that affect about 15 percent of people with diabetes, and force 70,000 amputations each year in the United States.

Since Baer’s time, the common green-bottle fly, Phaenicia sericata, has been the preferred medical maggot, because it devours dead tissue, but not living flesh. Flies must be sterilized before use, and because the eggs quickly hatch into larvae (maggots), air-shipment is necessary, says Ronald Sherman, laboratory director of maggot-maker Monarch Labs.

The healing never stops

Sherman says he became interested in blending entomology and medicine when he read about Baer during medical school. “I was always interested in medical entomology, the intersection of health and insects, but usually that was in the context of insects that cause disease. I was also interested in the beneficial uses of insects.”

As investigations in maggot therapy started to ramp up the 1980s, he recalls a “huge wave of resistance [that] was not all due to revulsion” at the thought of hosting insects.

Part of the problem was resistance to change, he says, especially “When that change is associated with these negative, emotional connotations: death, flies, an unhygienic environment.”

Some resistance, he says, came from doctors “who saw that patients were lining up for [maggot] treatment. People … were canceling amputation surgeries … just to give maggot therapy a try!” According to Sherman⁷, some studies show that maggots can “salvage” 40 to 50 percent of limbs and digits scheduled for amputation.

One study⁸ found that although 43 percent of patients had flies escaping from their wounds, and 19 percent eventually needed amputation, 89 percent would use maggots again.

Courtesy Ronald Sherman

A bottle of chemically sterilized maggots costs about $100, plus shipping. Because the adult flies can be infectious, they must be restrained with cheesecloth or a special-purpose dressing.

Flies on trial

Other studies are less definitive. For example, in a randomized trial⁹ of wounds published in 2009, larvae-infested leg wounds were more painful, and while maggots were better at cleaning, they did not hasten healing or reduce bacterial infections.

A review¹⁰ of randomized treatments for diabetic foot ulcers found that “one small trial suggested that larvae resulted in a more than 50 percent reduction in wound area compared with hydrogel.” (Hydrogels are new dressings that keep wounds moist.)

Why only “one small trial” for the common diabetic foot ulcers? Because the gold standard for selecting therapies requires that neither doctor nor patient know which treatment was used — but this “double-blind” is doubly difficult when the medical device is a mess of growing flies!

Sherman, who is a maggot entrepreneur as well as medical doctor, says maggot therapy ought no longer be considered a last resort. “Most clinicians come to it either because their patients, or they themselves, are at a dead end. Facing amputation, they’ve run out of options. Once they see what maggots can do, and recognize how simple, inexpensive, and relatively safe they are, they recognize that they don’t have to wait so long, and in the future will think about maggot therapy … before the wound has progressed, before the infection has progressed.”

Image: Rsabbatini

Leeching was standard practice until the mid-1800s. Leech saliva contains anesthetics, which could also explain why this lady is so cool, calm and collected with her slithery pals!

Maggot therapy is occurring “throughout the world,” Sherman says. “Twenty-four labs are producing medical grade maggots and providing them in 40 countries. In the United States alone, about 2,000 centers are regularly using maggot therapy. The treatments are included in textbooks, review articles on wound care and conferences.”

Leapin’ Leeches!

Leeches — bloodsucking aquatic worms — have been a part of medicine for at least 2,000 years. The Encyclopedia Britannica tells us that “Throughout most of Western history, leeching-or leechcraft-became such a common practice that a physician was commonly referred to as a ‘leech.’”

Modern-day “leeches” use leeches to drain excess blood after surgery. “The classic use is when a finger is reattached surgically,” says Kosta Mumcuoglu, a parasitologist at Hebrew University in Jerusalem. “Even if the surgeon succeeds nicely in reattaching the arteries, they often have problems with the veins, so blood can enter the finger but not return to the body. Then it’s a short time until the blood in the finger coagulates and the patient loses the finger.”

Surgeons may try to improve circulation with further surgery or anti-coagulants like heparin, says Mumcuoglu, president of the International Biotherapy Society. But if circulation is still stuck, “The skin may start to turn brown or violet, and any time now, the finger is going to be lost.”

Courtesy Kosta Mumcuoglu, Hebrew University¹¹

After finger-reattachment surgery, leeches excess blood that would otherwise clot and kill the finger. Those white objects are holding the surgery tight. Children whose fingers have been caught in doors are major beneficiaries of this surgery, but snowblowers can also amputate fingers.

Evolution plays two contrasting roles in our story: To avoid bleeding to death, mammals have evolved a powerful “coagulation cascade” that clots blood outside blood vessels. Because clotting could be deadly to leeches, they, like their bloodsucking brethren the ticks, mosquitoes and vampire bats, have evolved anti-coagulants.

One chemical in leech saliva, for example, blocks thrombin, which helps platelets clump to start a blood clot.

Not only do leeches produce prodigious amounts of clot-blockers, but they also have chemicals that relax blood vessels, which contributes to their utility in surgery. In 2004, leeches garnered FDA approval as a “medical device.”

The chemicals in leech saliva, aided by some manual clot removal, ensure that the skin around a surgery will bleed for hours or days after leeching. Even though the patient may need a blood transfusion, after a few days, “new blood vessels are growing in the area, and the circulation becomes normal, and we have a good feeling that we have saved the finger,” Mumcuoglu says.

Leeches also secrete anti-inflammatory compounds that are being tested against diseases linked to inflammation. In a randomized trial¹³ in Germany, four to six leeches, which attached for an average of 70 minutes, led to a significant decrease in pain of osteoarthritis of the knee after seven days, compared to the anti-inflammatory drug diclofenac. Leech treatment also significantly improved stiffness, function and general arthritis symptoms, for the entire 91-day study.

In 2008, the same researchers¹⁴ found that leeches. when compared to diclofenac, produced significant benefits in pain, mobility and quality of life for osteoarthritis of the thumb.

Solution: Outsourcing?

Still, leeches may never regain their former medical prominence. In London, in 1846, “at least tens of millions of leeches” were imported each year. A reservoir in Norwich, one author¹⁵ wrote, “might at least aid in supplying the quantity needed for our own consumption, instead of being almost entirely dependant, as we at present are, on a foreign supply.”

However, this last finding may be key to further progress, says Mark Siddall of the American Museum of Natural History, who led the group that identified three species. “This raises the tantalizing prospect of three times the number of anti-coagulants, and three times as many [other] biomedically important developments…”

Did we forget what parasitologists call the “Yuck! factor”? Do patients squirm at the thought of attaching primitive bloodsuckers to their wounds? Generally not, says Mumcuoglu. “We have less problem with leeches than with maggots. We explain, ‘This is your last chance, if you don’t want to lose the finger, we have to try this.’ … Nobody has rejected the treatment.”

The endocrine system is a marvel of subtlety and complexity. Through the life of the animal (human or otherwise), waves of hormones control reproduction, development, behavior, even other hormones. What happens when this natural system gets bollixed up?

We’ve known for decades that endocrine disruptors sourced in pesticides and plastics can operate at the parts-per-billion level. Disruptors in common body-care products ranging from birth-control pills to shampoo are washing down toilets and drains, then causing deformations in the animals that live downstream.

In 2006, for example, David Norris of the University of Colorado caged fathead minnows in the outflow from Boulder’s wastewater treatment plant. Within seven days, adult males were “feminized,” showing female anatomy and behavior.

Water leaving the treatment plant contained a regular toiletful of hormonally active crud, including ethinylestradiol, a chemical used in most contraceptives, and natural estrogens made and excreted by people. Other endocrine disruptors in the water included two common plastic compounds, bisphenyl A and phthalates. Detergents and pesticides had contributed (is that the right word?) a further group of endocrine suspects called nonylphenols.

Diagram courtesy Renewable Water Resources

Hormones run amok

To compare their ability to trigger the estrogen receptor on cells, estrogen disruptors are measured in units called estradiol equivalents per liter. In 2006, Boulder Creek contained 30 to 40 units, most of it artificial, Norris says.

A few trillionths of a gram in a liter of water may not sound like much, Norris realizes. “At first, people thought, ‘That’s such a small quantity, it can’t be meaningful,’ but biological systems can see it and respond to it. In lab studies, as little as 1 estradiol unit is enough to feminize a fish, so there was plenty of stuff there.”

All the estrogens, artificial and natural, work through same receptor, he says, “so the effects are additive. Even if any single one is not high enough, they add up.”

Ending the endocrine monster?

After the 2006 study (and for reasons unrelated to hormone disruption), Boulder’s treatment plant was upgraded. The newly installed “activated sludge process” transfers most of the estrogen disruptors from the liquid to the solid material, called sludge or biosolid, that remains after treatment.

“Bacteria are eating the estrogen disruptors to some extent, but the vast majority of the chemicals that come into the sewage are trapped in the biosolids,” says Norris. “It’s not a mechanism that was planned to deal with these chemicals at these concentrations, but the procedures are pretty efficient at getting the endocrine disruptors out of the water.”

For the study he just presented at the Endocrine Society, Norris repeated his 2006 study, and found no feminization in fish after 28 days, even among fish that lived in pure treated wastewater.

That finding accords with tests performed at the Wisconsin State Laboratory of Hygiene, says Jocelyn Hemming, a research environmental toxicologist at the lab. “Activated sludge really helps a lot,” she says. In tests using both ultra-sensitive chemical analysis and living cells, “there was definitely good removal of endocrine disruptors, although it wasn’t complete at all facilities.”

The activated sludge process did transfer some unwanted hormone to the sludge, but Hemming says the bacteria likely ate some of the troublesome compounds. “I think there is a pretty good chance of destruction from the microbial community in the activated sludge; it would not all go into the solids.”

In Boulder, the chemists are not ready to release the numbers, but “preliminary chemistry shows that the levels of endocrine disruptors in the effluent have gone way down,” Norris says. “When you are dealing with nanograms per liter [parts per trillion, by weight], you have to be really careful.”

Most of the endocrine disruptors in the Boulder sewer system are artificial, Norris says, coming from plastics, solvents and drugs. About 5 percent comes from birth control pills, and about 10 percent is natural, human estrogen.

– David J. Tenenbaum

Learning is about connections: when the pathways between neurons get stronger, information flow is faster and smoother. We get better at triple toe-loops on the ice, or crooning a romantic ballad for “American Idyll.”

Nice notion, but what, exactly, is changing? Here, we get help from a singing bird that may never get beyond YouTube: the zebra finch.

In a study in Nature, Richard Mooney, a professor of neurobiology at Duke University, used a laser-powered microscope to peer into the brains of male zebra finches 60 days after hatching. Mooney and colleagues studied the birds’ first exposure to the song of their species, and correlated the amount of learning with changes in tiny spines on the dendrites of nerve cells, or neurons, in a motor circuit for singing in the bird’s brain.

Dendrites are branch-like structures on neurons that detect chemical signals, known as neurotransmitters, released from other neurons. When a neurotransmitter diffuses across a tiny gap, called a synapse, it is often received on tiny “dendritic spines” that, in their billions, define the neural wiring and thus the computational properties of the brain.

More and larger dendritic spines make stronger synapses, and that makes stronger and more reliable brain circuits.

Learning: All a matter of spines

In the study, Mooney, Todd Roberts, Katherine Tschida and Marguerita Klein labeled certain neurons so they would glow when viewed under a microscope; they then watched these neurons in living finches and measured what percentage of the dendritic spines appeared or disappeared over a two-hour interval.

The next day, these juvenile birds were allowed to hear the song of an adult male “tutor” of their species. Afterwards, the researchers looked at the spines again, noting that some had appeared, disappeared or changed size. In the following weeks, these birds never again heard their characteristic song, although some went on to learn it.

The birds with the highest spine turnover before hearing the tutor had a significant increase in spine size and stability immediately after tutoring. Eventually, these birds also did the best job of copying the tutor’s song.

Image: Todd Roberts

These tiny structures, called dendritic spines, receive inputs from neighboring neurons, and are an essential part of the brain’s wiring. A new study showed that these spines got stronger and larger as a bird learned to sing.

“We made an average measure of the turnover rate, and found some juveniles with high turnover and others with low turnover, and asked what their learning outcomes were, many weeks later,” says Mooney. “Those with high turnover before hearing a tutor song eventually learned more, and those with low turnover essentially learned nothing from their tutor. Apparently, if you have more dynamic spines, you are better equipped to encode and learn from experience. That’s a pretty important message, and this is the first time that relationship has been established in the context of learning a new behavior.”

Spinal tapestry

The pre-test differences in spines proved to have long-lasting influence, Mooney told us. “We are seeing changes in the brain that occur really quickly, within hours, even though the process of learning that is unfolding will take many weeks to complete. It’s not like the animal hears the tutor, and has mastered the song by the time we see the change.”

Image: Todd Roberts

After this zebra finch was “tutored” in singing by an adult finch, dendritic spines (the tiny white branches) emerged from the dendrite (green arrows) or enlarged (blue arrow). Both changes helped the birds remember the song.

And what makes a dumb bird? A fixity in the number of dendritic spines, Mooney says. The fact that spines tend to become fixed in mature birds could explain why birds cannot learn to sing if they wait too long to hear another bird’s song.

The same phenomenon could explain why it’s difficult or impossible for adult people to become fluent in a new language.

The study not only provides support for the notion that certain neural pathways grow stronger during learning, but it also explains how this could happen. A better distribution of dendritic spines eases the flow of nerve signals across synapses, which helps the bird remember how to sing like another zebra finch.

In essence, the mechanism that Mooney was watching comes down to a neural hybrid of use-it-or-lose-it and trial and error. “The spines are asking, ‘Am I needed? If no, I go. If yes, I stay,’” says Mooney. “They are waiting for a signal, and when it comes through, they are almost like a piece of photographic film. They respond and the synapse is permanently altered.”

Watching – and learning

Humans have many forms of learning, Mooney admits, “But bird song is imitative learning, and imitation is not only the sincerest form of flattery; it’s also basis of much of our culture,” such as speech, art and music. “Finding an animal model in which you can study cultural transmission of behavior is a really powerful way to explore how the brain responds to modeling of behavior by another animal.”

Smart brains are flexible brains, Mooney found. “We were able to see differences in juvenile brains in animals that were the same age, but some could learn and some could not. This suggests that if the brain is in a highly stable condition, you can get stuck.”

David J. Tenenbaum