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.”

Photo courtesy Eric Fortune and Melissa Coleman.
Video courtesy Science/AAAS

This image is an adult male plain-tailed wren.
Watch the video explaining how the bird-songs
study worked — with ultra-cool bird songs.

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

Poke deep inside an insect cell, and you may be in for a shock. At least we were startled to learn that bacteria live inside many insects, including the fruit fly, one of the workhorses of biology.

Photo: Biodiversity Institute of Ontario

The star of the study, Drosophila mauritiana.

Today, we hear how bacteria of the genus Wolbachia boost egg production in certain fruit flies. The mechanism, says Horacio Frydman, an assistant professor of biology at Boston University, involves a two-step: first the fly makes more egg cells, and then it blocks a process that would normally prune away extra eggs.

Insects, like other animals, are frequently “married” to bacteria in a relationship that benefits one or both parties. This is common: Bacteria in the cow’s rumen break down cellulose eaten by the cow. Bacteria in the human gut form vitamin K, necessary for blood clotting.

And bacteria in aphids synthesize essential amino acids that the aphids cannot make by themselves.
Wolbachia are not essential to the fruit flies, but their presence can quadruple egg production.

Speeding breeding

Producing four times as many offspring “is a powerful driver of infection,” Frydman says. “Wolbachia manipulate their host reproduction to favor their own spread in nature,” noting that in less than 20 years after Wolbachia was detected in fruit flies in southern California, the infection had spread as far as Canada. “It’s considered one of the largest pandemics in the recent evolution of life. Because Wolbachia influence their host reproduction, they also impact the evolutionary history of innumerable hosts.”

Wolbachia have been linked with a wide variety of effects in the insect realm. Wolbachia “lives in at least 20 percent of the world’s arthropods, including insects, spiders, mites, and crustaceans,” according to the Wolbachia project, making them an active area of investigation.

How could this symbiosis work to increase the number of offspring?

Using sophisticated microscopy, Frydman, Ph.D. student Eva Fast and colleagues tracked the location of Wolbachia in fruit flies. In D. mauritiana, a species native to the Mauritius Islands in the Indian Ocean, the bacteria congregate in the germline stem cell niche — a structure that supports stem cells that develop into eggs. In D. melanogaster, the bacteria accumulate in the niche that harbors a different type of stem cell, which produces the eggshell.

In the germline stem cell niche, the bacteria actually outnumber mitochondria, organelles involved in making energy for the fly.

Having the bacteria in the germline stem cell niche doubled the rate of division among those stem cells. Further investigation showed that the bacteria later also halved the rate of programmed cell death.
So the bottom line was a four-fold increase in egg production.

The virtue of pruning

“It’s remarkable that there are two mechanisms being manipulated by the bacteria, the rate of egg production and the rate of programmed cell death,” says Frydman.

Hitting both systems makes sense, Frydman adds, although the mechanisms remain unclear. “It is not surprising that Wolbachia would evolve to manipulate those two process, because they are key in controlling the rate of egg production, and therefore it has a profound impact in the reproductive success of the infected host and in spreading of bacteria in nature.”

Anything that increases the number of eggs and offspring is likely to be favored by natural selection, Frydman adds.

Photo: CDC, #373

Parasitic worms cause elephantiasis, which afflicts this man from the Philippines. Could killing Wolbachia prevent this disfiguring disease?

A healthy thing?

Beyond an insight into the fascinating biology of symbiosis, the finding could also have health implications. Parasitic worms that cause diseases like elephantiasis seem to benefit from Wolbachia infection.

And Wolbachia can affect insect immunity: Tests have shown that infected fruit flies are more resistant to some viruses, for example. And a recent paper in Nature found that mosquitoes in Australia could not transmit dengue fever if they carried a Wolbachia strain derived from Drosophila.

Mosquitoes also transmit malaria. Conceivably, better knowledge of the interaction between Wolbachia and insects might convert mosquitoes from a carrier of this ancient scourge into a defense against it.

– 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 “kill all the bacteria” crowd are loath to admit it, but we rely on bacteria for survival. Deep in the human gut, trillions of symbiotic bacteria make vitamins, help digest food and fight disease.

Symbiosis is the classic “you scratch my back and I’ll scratch yours” relationship, and it’s everywhere in biology: Coral is a mutual-benefit society between photosynthetic algae, which provide food, and the coral animals which eat that food and build a “home” for the algae. Plants feed fungi growing on their roots, because those fungi extract nutrients from the soil.

But how does a host plant or animal make sure its pet microbes don’t run amok? And how does the microbe avoid attack by the host’s immune system?

Those are “burning questions” for the biologists of symbiosis, says Margaret McFall-Ngai, a professor of medical microbiology and immunology at the University of Wisconsin-Madison.

Photo: University of Wisconsin-Madison

The Hawaiian bobtail squid maintains a unique symbiotic relationship with the bacteria that colonize its light organ.

For about 20 years, McFall-Ngai has been studying the bobtail squid, a small, defenseless critter that lives in warm water in the Pacific. The bobtail has a problem, and it’s not people interested in squid sushi: When it hunts near the ocean surface, its shadow would make it an easy target for predators lurking below.

This so-called “flashlight squid” solves this problem with a symbiotic relationship with a luminescent bacterium called Vibrio fischeri. This bug, a relative of the one that causes cholera, glows inside the squid in return for food and shelter. But that shelter is not forever: the squid only needs light at night, when it’s active. During the day, when the squid burrows in the sand, the light is unnecessary.

Fifteen years ago, McFall-Ngai and coworkers discovered that the squid were ejecting about 90 percent of their bacterial cargo each morning, about the time they sink to the ocean floor for protection.

Is this what passes for gratitude in the dog-eat-dog world of biology?

Anyway, the remaining bacteria multiply during the day, so by nightfall, the squid contain enough bacteria to switch on that protective flashlight as they head upward to feed.

Photo: AJC1

The bacterium Vibrio fischeri gets food and shelter from the Hawaiian bobtail squid in exchange for making light.

How does this happen?

In a new study, McFall-Ngai, Edward Ruby and colleagues studied the changing daily pattern of gene expression in the squid and the bacteria. The scientists took samples four times a day, including just before and after the squid “spat out” the bacteria, then put the samples on detectors capable of recognizing particular strands of RNA. Because RNA is patterned on DNA, that info told the researchers which genes were active at each sampling time.

“One fact that popped out right away, was that just before dawn, the vast majority of the genes associated with the squid’s cytoskeleton were activated,” says McFall-Ngai. The cytoskeleton is composed of microscopic strands that shape a cell, and also determine the location of its sub-structures, called organelles. “It looked as if the cells were preparing for something at 4 a.m., so we decided to look with a microscope at around that time, and we found that the squid tissue that normally houses the bacteria looked like dogmeat.”

More specifically, the tissue was missing tiny projections, called microvilli, that house bacteria and help them multiply. These structures, which resemble those found in the human intestines, “hug the bacterial symbionts,” McFall-Ngai says, “but after the squid expels the bacteria, the surface looks like it has been shaved; the microvilli are no longer present, and the surface of the cells is flat.”

No dumb bug…

Similarly, the bacteria had their own routine changes in genetic activity. As the squid sheds the microvilli, the un-evicted bacteria start making proteins that help them digest the microvilli, McFall-Ngai says. “The bacteria somehow sense that they are being presented with a huge pool of resource molecules in these animal membranes, and they turn on genes and pathways that let them digest those membranes.”

Later, after the membrane meal is masticated, the bacteria switch to a different set of enzymes that digest chitin, a structural molecule in the squid.

The symbiotic situation in the human gut is phenomenally more complicated, as we house hundreds of species of bacteria, rather than the loner living in the flashlight squid. But cycles of genetic activity have recently been recognized in mammalian intestines, McFall-Ngai says. “Biologists have shown a very significant 24-hour rhythm in the immune system of the gut, and also in the epithelial cells that line the gut, which have a close interaction with the countless gut microbes.”

Photo: NOAA

Reef-building corals like this get up to 90 percent of their energy from their symbiotic algae, but every now and then they find a tasty snack like this marine worm.

Too close for comfort?

The supreme simplicity of the squid is its benefit, she adds. “We can ask questions with incredible precision; it’s just one host and one microbe, but we hope that what we find will be more widely applicable. To our knowledge, this is one of the first attempts to ask questions about symbiosis at the level of gene expression. We found that persistence of the symbiosis involves a daily fluctuation between what appears to be very healthy interaction and what looks like a disrupted, almost pathogenic, situation.”

Both partners in a symbiosis must “let their guard down,” but that, like every other aspect of the relationship, requires moderation, McFall-Ngai says. “Once you get the symbiosis started, you have to keep it going through the life of the host. How do you make sure the immune system does not get rid of the bacteria, or the bacteria do not overgrow the host? There has to be a balancing mechanism so it persists in a healthy condition. It may look like an uneasy alliance. To keep the symbiosis going, the squid has to do something drastic. But it works…”

David J. Tenenbaum