Carl Zimmer's Blog, page 27

Freeing Animals From Our Evolutionary Traps

James Snyder noticed one day that a frog had climbed onto a tree in his backyard in southern Florida and swallowed one of his Christmas lights. He snapped this eerie photo in which the light glows through the frog’s stomach, like a herpetological holiday ornament.

This frog’s behavior seems weirdly stupid. But there’s actually a wisdom of sorts in swallowing a Christmas light–if you’re a Cuban tree frog, that is. For thousands of years, the only glows  your ancestors ever saw on a tree came from luminescent insects. If they responded to a little glow by attacking, they got a meal. They were more likely to survive and have baby frogs. The frogs that didn’t respond? Some of them may have done just fine. But others may have gone hungry. The males might have struggled to attract a mate; the females might have laid small eggs that failed to develop.

Natural selection laid down this response in Cuban tree frogs, in other words. Christmas lights have only recently come into their lives, and natural selection has shown no sign yet of striking the “attack glowing light” behavior off the menu.

Snyder’s glowing frog is one of the prettiest examples of a surprisingly common thing that happens when animals come into contact with humans. We have altered the environment in a vast number of ways, both small and large. And when animals try to read the cues from our human environment, they can get tricked. They can end up doing something that kills them, loses them the opportunity to reproduce, or simply wastes their time. Scientists call these situations evolutionary traps.

In the journal Trends in Ecology and Evolution, Bruce Robertson of Bard College, Jennifer Rehage of Florida International University, and Andrew Sih of University of California, Davis, take a look at a lot of documented examples of evolutionary traps and try to come up with a theory for them. They would like to be able to predict when traps will occur, and find a strategy to prevent evolutionary traps from endangering species.

Some evolutionary traps, like the Christmas lights, play on the visual strategies animals use to find prey. Albatrosses will peck at brightly colored pieces of plastic floating in the water, for example. It’s a response that used to give them energy but now can fill their guts with trash. Some of the species we’ve moved around the planet are tricking native predators. A native North American wasp used to lay its eggs in a native ladybird insect species. We’ve now imported a new species, which the wasp now prefers. Unfortunately for the wasp, the defenses of the alien ladybird are so strong that it can kill the wasp’s eggs.

Evolutionary traps can even fool animals looking for a mate. In Australia, male beetles of the species Julodimorpha bakewelli, are attracted to the gleaming brown surface of female beetles. Beer bottles, it just so happens, look a lot like female Julodimorpha bakewelli, and so male beetles can often be found furiously trying to mate with them.

Artificial light can set evolutionary traps not just by creating the illusion of prey, but by throwing off an animal’s navigation. When caddis flies become adults and are ready to mate, they need to get to a body of water. Without Google Maps to help them, they do what their ancestors have done for countless generations: they take advantage of the fact that ponds and streams change the reflection of moonlight, altering its polarization. Unfortunately, large plate glass windows can polarize light in the same way, with the result that caddis flies will sometimes blanket the glass, mate, and lay their eggs there.

Sometimes, an evolutionary trap is fairly harmless. Cuban tree frogs don’t swallow Christmas lights that often, and Snyder found that his hapless visitor was actually still alive and eventually spat out its mistaken prey. But in other cases, a mistake can be catastrophic. Some beetles lay their eggs in fallen trees. If they make the mistake of laying their eggs in trees that people have cut down for lumber, their offspring will end up dead in a mill.

These evolutionary traps can be especially dangerous when they’re more attractive than their natural counterpart. Beer bottles, it turns out, throw male beetles into a mating frenzy, because they have exaggerated versions of the visual cues on female beetles. Super-attractive traps lure away a greater fraction of a species to their doom. Robertson and his colleagues surveyed 445 scientific studies of evolutionary traps and found that 86 percent of the severe ones involved this combination of danger and heightened attraction.

The scientists also ranked the ways in which we humans create traps. Invasive species top the list. Next comes agriculture and forestry. Some birds, for example, usually prefer to build their nests at the edges of forests, so that they can fly a short distance to find food in open spaces. These birds are attracted to thinned forests and the edges of cleared land. Unfortunately, so are mammal predators that eat them. Buildings and roads create traps, as well as artificial lighting that goes with it. Sea turtles that lay their eggs on beaches near hotels may head inland instead of going out to sea, fooled into thinking hotel lights are the moon over the ocean.

Ironically, evolutionary restoration projects can also create evolutionary traps for the very species conservationists are trying to save. To increase the eggs laid by Coho salmon, conservation managers have attracted the fish to streams where farmers later draw down the water for their crops. The salmon that hatch from the eggs get stranded and die.

Any explanation of evolutionary traps has to account not just for why some species fall into them, but why so many don’t. Fortunately, there’s been a lot of research on how animals respond to different stimuli, and so Robertson and his colleagues have adapted these findings to the question of when evolutionary traps work. They predict that evolutionary traps are more likely to work the more they resemble a cue animals relied on in the past–especially if that cue was reliable. Some cues are especially important for animals to respond to, the scientists also point out. Rejecting them can have disastrous consequences. If an ecological trap resembles one of these essential cues, animals will be less likely to reject it.

Once animals fall into a trap, they may go in one of two directions: escape or doom. Some animals may be able to learn from experience that a cue they used to rely on now brings them grief. Of course, some lessons are easier to learn than others, and some animals are better at learning than others.

Evolution can also spring animals from an evolutionary trap. If an animal is born with genes that lower its preference for a cue, it may be less likely to die–and more likely to pass on its genes. Even if animals don’t evolve this new behavior, they may still persist. There may still be enough good habitat where they can reproduce, so that their entire population doesn’t get sucked into a trap. But if a trap is too potent and animals can’t lose their attraction to it, extinction is a real risk.

One way to reduce that risk is to get rid of the trap. Take away the beachfront lights that fool sea turtles, for example, or block them by restoring sand dunes. Move lumber out of forests before rare beetles try to lay their eggs in them.

It’s also possible to take away an evolutionary trap’s allure. Solar panels, for example, turn out to be very attractive for aquatic insects because their polarized dark surfaces resemble water. But scientists have discovered that all it takes is a thin white border around a solar panel to make it unappealing to the insects.

To save some species, in other words, we may need to learn how to break our spells.

The Devil’s Tumor: My Talk Next Week In San Francisco

Cancer may not seem to have much to do with evolution, but they’re actually intimately linked. Cancer cells evolve within tumors, becoming better at exploiting our bodies and resisting cancer drugs. We have evolved a number of adaptations to fight cancer–or at least to put it off until past our child-bearing years. The intersection of cancer and evolution has become so fruitful that there’s now a biennial international meeting on the subject. This year, the meeting organizers asked me to give a public lecture on cancer and evolution in San Francisco. My talk, “The Devil’s Tumor,” will take place on Friday, June 14, at 7 pm–followed by a performance by the one and only Baba Brinkman. Details here. I hope Bay Area folk can join us!

The Left and Right of Life

Not long ago, a friend of mine asked me if I had heard of a condition called situs inversus. He had learned about it when his grandson had been born with his internal organs flipped–heart on the right, liver on the left, and so on. Despite that remarkable reversal, the boy was fine. His story got me curious about how the condition happens–and how our bodies, for the most part, figure out which side is which. The result is a story in tomorrow’s New York Times. Check it out.

An Open Letter to Science Students and Science Teachers

One day a few years ago, I got an email from someone who called himself Davis.

hey carl,

i have 2 do a report on the book parasite rex. and i kind of need help on chapter 4 i dont really get it! can u please help me?

thank you alot

your pal,

Davis

__________

Dear Davis:

If you have some specific questions, maybe I can answer them.

Best wishes,

Carl

__________

i mean can u explain to me what chapter 4 is talking about??? cuz i really dont get please help me out

your pal,

davis

__________

I don’t have time to answer such a general question. I suggest you reread the chapter, and if you are still confused, look at a

biology textbook for some of the concepts you don’t understand. If you later find you have some specific questions, feel free to contact me.

Carl

__________

i did all that and i still need help. please help me i have a C in biology i need at least a B- please help me

D

__________

The point of the chapter is to show how parasites can control their hosts for their own benefit. They control how their hosts digest their food, how they behave, and so on. The chapter gives a series of examples how parasites do this, and the effects that they have on ecosystems as a result.

Carl

__________

thank you soooooooo much

__________

[The next day…]

now can u help w/ chapters 5-the last chapter?

please

__________

[A day later…]

well can u help me

__________

[Three days later…]

hey carl

can u please help me w/ chapter 5 can u just tell me that it is about?

please

you pal

Davis

__________

Dear Davis-

Describing one chapter for you is a favor. Describing two is

doing your homework for you. Sorry.

Carl

__________

I never heard from Davis again. But I have continued to get a steady stream of emails from other students. Some are a pleasure to read. They are the products of young minds opening up to the rich rewards of science. These young correspondents are starting to understand something important about the natural world, and that understanding triggers a flood of questions that will take them even deeper.

But a lot of the emails follow in the tradition of Davis. Essentially: I have homework. I need information from you.

In the past couple years, I’ve noticed a shift in the tone of these requests. They’re not furtive acts of desperation. They seem to bear the seal of approval from adults–either from teachers or parents.

Here, for example, are three emails I received on the same day not long ago:

Hello. My name is —- and I am a 9th grader at —-. I am currently writing a research paper for my Honors Biology class on the topic of evolution. More specifically, my topic is on the evolution of dinosaurs over geologic time.

From my preliminary research, one thing I have learned is that dinosaurs are related to birds. I was hoping you could provide me with additional information about this topic. Some of the questions I will attempt to answer through my research include: What are some specific features of birds that prove they are related to dinosaurs? How are they related? How did dinosaurs change through each geologic period? What were some reasons for the evolution?

Thank you for your time and I look forward to hearing back from you soon.

__________

…I am a ninth grade honors biology student, and I am working on a research project regarding the evolution of dogs. I was wondering if there are any reference materials or websites you could suggest to add to my research, or if you or anyone else may be able to contribute any information. Thank you for your time. I look forward to hearing back from you.

__________

…For my biology honors final exam, I am doing a research paper on evolution and how evolution and the Galapagos and evolution are related. As part of the research paper I must contact specialist in this field. I would be so grateful if you could email me information about this topic. Also if you know anyone else who specializes in this topic please email me their contact information. Thank you so much.

__________

All three emails came from the same class at the same high school.

I got in touch with the chair of the science department at that school to find out what was happening. Here’s the reply I got:

Their final examination internet research project is to select an evolution topic which must be approved by the teacher. These students will be entering a world in which global communication is necessary. They will have to confer with fellow researchers and professionals in many countries. This assignment is to provide these youngsters opportunities to investigate their topics by reading current articles, etc. and then communicating with authors, scientists, professionals, etc. Students are supposed to have read the work, formulated questions, all in an effort to bring their topics up to the minute. Teachers were very specific about “bothering” people just for information.

I wondered if other writers and scientists were having the same experience as me. In a discussion that started on Twitter, I found that they are. Here’s one example, from Rebecca Skloot, the author of The Immortal Life of Henrietta Lacks:

@carlzimmer @JLVernonPhD Some have good questions, but vast majority just clearly haven’t done their homework & r asking us 2 do it for them

— Rebecca Skloot (@RebeccaSkloot) May 21, 2013

I want to emphasize that when a writer like Skloot says something like this, you should not take it to mean, “These awful kids! They’re interrupting my soap operas!” Skloot has dedicated a lot of her time to helping young students delve into the science in her book. In addition to speaking in person at schools, Skloot has posted a lot of resources on her web site specifically intended for students. And yet Skloot reports getting three or four desperate pleas for personalized help each week.

Over the past few days, I continued this conversation on Twitter and email and found other scientists and writers with the same experience. And we all felt the same consternation. We want to help students learn about science, but we don’t have time to handle floods of requests, and it doesn’t feel right to supply emails that students can simply cut and paste into their assignments, when they should be learning how to learn from reading.

So, here are a few thoughts I have about how to make this situation better.

First, to science teachers:

It’s great that you are looking for new ways for your students to do research and learn about science. But having them send emails to scientists and writers has failure stitched into its very concept. Writers are perpetually scrambling to meet deadlines and pitch new stories. Scientists have full plates as well, between their research, their eternal quest for the next grant, and their teaching. To answer a single email from a student–either in the form of a long list of questions or just an open-ended plea for help–takes a lot of time. We may respond to the first few emails we get, but as they keep pouring in, we tend to burn out. And the more popular this becomes as a pedagogical tool, the more emails students will be sending to scientists and writers. And that makes people burn out even faster. It doesn’t seem fair to the students for their grade to depend on whether they get a reply from their email. Even the most polite email may land in the inbox of someone who decided long ago never to respond to such requests.

And, frankly, we can’t help but wonder what good this exercise does. When we were young, it certainly was a thrill to get an email or a letter from someone we admired. A message like that can steer young people into a career and change their life. But the exchanges we get today are nothing of the sort. They are just requests for information. They’re sometimes courteous and they’re sometimes unintentionally rude. But it feels about as educational for the students as copying a Wikipedia page.

Don’t get us wrong. We enjoy communicating with students and we see it as a valuable thing to do. But we just want to do so in a better way. The Internet offers many other opportunities for students to make contact with scientists and writers. One way is to have a Skype video chat with a class. In 45 minutes, we can talk with dozens of students, who can pepper us with questions. Again, it’s not possible for any person to talk to a dozen classes a week. But there are a whole lot of writers and scientists out there.

If you decide that it’s still useful to have your students send out emails, please don’t just shoo them off into cyberspace. Spend time making sure that students are actually getting something from what they’re reading, so that their emails are thoughtful rather than boilerplate. I’d also suggest having them turn in draft emails to you as part of the assignment. Help them learn the fine art of letter writing. Don’t just send them off to write emails that start, “hey carl…”

And, to students:

You’re the first generation to grow up in the ocean of information that we call the Internet. In some ways, this makes you incredibly lucky. You can get hold of information in a matter of seconds that the students in the picture above would never be able to find.

But getting a string of words on your computer screen is not the same as learning, or as understanding. Once you find an article on, say, carnivorous plants, you need to read it deeply. Let the ideas sink in. The first time through, you may not appreciate how all the pieces of the story fit together into a whole. Read it again. Resist the urge to click away to Facebook after every sentence. Print the story out if you have to. Save it as a pdf if you have to. The more you focus on reading, the stronger your mind becomes.

As you read, questions will occur to you. Some of those questions may answer themselves as you come to understand the piece you’re reading. Others may require reading something else. You may find that something else through the Internet. But the Internet is not an Answer Machine, into which you type a vague question and out of which comes a paragraph you can drop into an assignment. Give yourself the chance to really understand the words that come flowing across your screen.

These are the years when you learn to think. When you send an email to an expert, hoping that the Answer Machine will spit out something you can show your teacher, don’t get angry when someone politely declines to do your thinking for you. Believe it or not, that’s actually a compliment.

__________

I would be grateful if science teachers and students leave comments below. It’s time we had a conversation.

The High Life: My New Column For the New York Times

Humans have spread across the planet, settling in deserts and marshes and deep forests. They’ve adapted to their new homes, not just culturally but genetically, as natural selection has favored certain genes over others. But nowhere has this adaptation been more intense than at high altitudes–in places like Tibet, the Andes, and the Ethiopian highlands. For my Matter column in the New York Times this week, I look at the latest research on mountain life, and at the lessons it can teach us about evolution in general.

The Girl Who Turned to Bone: My New Feature for the Atlantic

Skeleton of Harry Eastlack at the Mutter Museum. Courtesy: © A.B. Shafritz et al., New Eng. J. Med., 335 (8): 555-61, 1996, Source: http://www.uphs.upenn.edu/news/news_r...

Over the past year or so I’ve gotten to know some extraordinary people. They were born with a single mutation to a single gene that caused them to grow a second skeleton. Their condition, called fibrodysplasia ossificans progressiva, affects only one person out of every two million. If you traveled across the entire the United States and gathered everyone with the condition, you could fit them all comfortably on a single Greyhound bus.

I was inspired to meet them on a visit to Philadelphia last summer. The Mutter Museum, housed at the College of Physicians and Surgeons, is a collection of medical specimens of the sort you will see nowhere else in the United States. You feel an alternation of fear and exaltation at all the ways that the human body can be transformed. In one corner of the museum was the skeleton of a man named Harry Eastlack, who asked that his body be donated to science so that his disorder might someday be understood.

Looking at his skeleton, I wondered how on Earth something like this could happen, and what on Earth it was like to experience something like this. The result is the longest feature I’ve written in some time, which appears in the June issue of the Atlantic. You can read it here.

New on Matter: How Earth Escaped Becoming A Dead Sea Planet

My “Matter” column this week at the New York Times is a biography of the element chlorine. You may know it from roles in such classics as The Swimming Pool or Table Salt. But chlorine has had a long, weird history on Earth. Recent studies suggest that chlorine levels were ten times higher on our planet when it formed. If it still had that much chlorine today, we probably never would have existed. Check out my column for the full story.

Another Link Between Dog Brains And Our Brains

Last week I wrote in my “Matter” column at the New York Times about how wolves became dogs. I described two new studies on the genetic transformation that produced our canine pets, starting about 32,000 years ago. The scientists who did the research discovered that certain genes in the dog genome have experienced strong natural selection.

Some of those evolving genes are especially intriguing, because they’re known to be important in the brain. One of these genes, for example, makes a protein that’s involved in controlling the level of a neurotransmitter called serotonin. Serotonin influences behaviors like aggression–not just in dogs, but in humans. And in humans, that same gene has experienced strong natural selection, too. For humans and dogs, alike, a key step in our recent evolution may have involved becoming more sociable.

I got a surprising email yesterday from Pat Levitt, the director of the Program in Developmental Neurogenetics of the Institute for the Developing Mind at the Keck School of Medicine of USC in Los Angeles. Although Levitt wasn’t involved in the dog research, it hit home for him. This table is the reason why. It lists a dozen genes that experienced strong selection in both dogs and humans. Two of those genes have been shown to be involved in the brain, four in digestion, and six in the cell cycle. (When those last six mutate, they can cause cancer.)

There’s a mistake on that list–but a mistake of the good kind. One of the six cancer genes is called MET. “However,” Levitt wrote to me, “in 2006, my laboratory published a paper in the Proceedings of the National Academy of Science on a mutation in the MET gene that increases risk for autism.” (Here’s the paper.) In fact, a variant of the MET gene is now recognized as one of the strongest genetic risks for autism.

Levitt and his colleagues have continued to study the gene to understand how it plays a role in autism. My fellow Phenomena blogger Virginia Hughes wrote last year about how Levitt and his colleagues discovered that it shapes the wiring connections between neurons. Not just any neurons, however. It’s most active in circuits in the brain that are involved in social and emotional behavior.

“I don’t believe it is a coincidence that both the serotonin transporter and MET are on the list,” says Levitt.

It’s not exceptional for a gene to be active in different parts of the body and to have different functions. Natural selection can spread a gene because one of those functions boosts survival and offspring, while the other function gets carried along for the ride. So scientists who want to know why MET evolved in both us and dogs will need to figure out how its protein changed in each species, and how that change affected its different incarnations. It’s conceivable that MET evolved as a defense against early cancers in both humans and dogs. It’s also conceivable that its transformation was crucial for the emergence of sociable people and dogs alike.

I contacted one of the dog gene scientists, Ya-Ping Zhang, to see what he thought of Levitt’s correction. Zhang is excited to discover MET is moonlighting in the brain. He and his colleagues are now studying MET, along with the other fast-evolving genes, to get a better sense of what they’re up to in dogs and wolves. It’ll take a few years, at least, before they get some answers. But I think it will be worth the wait.

 

 

Getting To Know Your Inner Mushroom

Leave a bagel on the counter for a few days, and you’ll probably notice purple splotches growing over it. At some point a mold spore wafted across the kitchen, landed on the bagel, and started to eat your food. Molds are a kind of fungus–just like toadstools, brewer’s yeast, and death cap mushrooms. They don’t just nosh on bagels. Fungi exist on all continents, and have been thriving for many hundreds of millions of years. Some break down the remains of animals and plants in the soil. Some provide nutrients to trees and crops through their roots, in exchange for a supply of carbon the plants make with sunlight. While fungi have evolved different shapes and sizes, they are all alike in some fundamental ways. When it comes to eating, for example, they are like inside-out animals. We animals swallow food and then break it down with enzymes. Fungi break their food down first by releasing enzymes, and then they absorb it.

In the abstract, fungi are impressive and fascinating. (Biggest organism on Earth? A fungus.) But as you get to know fungi in their full reality, there’s something disturbing about them that you have to learn to accept. You are loaded with them. Slathered. That bagel on the counter? That’s you.

So I understand if some readers at this point say, “You know what? I have some very important pots to scrub,” and switch off their iPhones. But for the rest of you–you hardy, curious few–let me give you a tour of your personal fungal garden.

This tour is based on decades of research carried out by many scientists. Originally, their research dealt almost exclusively in the fungi that make us sick. Fungal infections can range from bothersome to deadly. Athlete’s foot, caused by mold such as Trichophyton rubrum, typically does nothing more than makes the skin itch. But other fungi can explode in our bodies. In the 1980s, people whose immune systems had been decimated by HIV became overwhelmed with a fungus called Pneumocystis jiroveci. It took over their lungs and caused lethal pneumonia.

But we are hosts to fungi both in sickness and in health. Fungi are an important part of the microbiome, along with bacteria and viruses–the subject of my post on Monday. Like those other organisms, our fungi have made it tough to study them with their reluctance to grow in labs. So scientists are beginning to use a different strategy–dispensing with gardening fungi and just gathering fungal DNA from healthy people.

Today in Nature, Julie Segre of the National Human Genome Research Institute and her colleagues present the first comprehensive atlas of the fungi growing on our skin. They collected fungal DNA from 14 sites on the bodies of 10 healthy volunteers. They found fungi everywhere: not just on the soles of people’s feet, but on the palms of their hands, on their backs, and in their ear canals.

Most of the skin is dominated by a single genus of fungi, called Malassezia. Malassezia‘s closest relatives include corn smut, a fungus that brings misery to corn farmers. At some point in the past, however, the ancestors of Malassezia shifted from plants to humans, where they now feed on the fatty secretions released by our skin. Malassezia has evolved into at least 14 different species; Segre and her colleagues found 11 of them among the participants in their study.

In some places, like the nostrils or the back of the head, Malassezia rules supreme. But in other places, the diversity goes far beyond that genus. The heel proved to be the big fungal jungle, hosting around 80 different genera. Second and third place were won by the webbing between the toes and toenails. Fungi do love our feet. Intriguingly, the diversity of fungi and bacteria travel in opposite directions around our body. Feet have a low diversity of bacteria, while arms–dominated by the single genus Malassezia–have a rich variety of bacterial species. Fungi may have become especially adapted to feet because we can pick up spores on our soles. Our shoes then create wonderfully humid, airless habitats for them to grow.

Segre’s survey is, by design, only skin deep, and so it’s hardly the full fungal story. Writing this week in Trends in Microbiology, Gary Huffnagle of the University of Michigan and Mairi Noverr of Louisiana State University catalog the more preliminary expeditions inside our bodies. Our mouths cradle many species of fungi, although many of them are probably transients that wind up there riding on food or breaths. On the other hand, there are a number of species–in the mouth and elsewhere–that are specialized for life in various parts of our bodies. Some species can survive in the acid-drenched depths of our stomachs, for example.

Even Pneumocystis, Huffnagle and Noverr suggest, may actually be very well-adapted to life in humans. It has become so dependent on humans that it has lost the genes for building some essential compounds. Instead of being self-suffcient, it takes these compounds from us. As strange as it may sound, Pneumocystis may actually be a quiet lodger in our lungs most of the time. It goes unnoticed in healthy people because of its rarity, a rarity enforced by our immune system. Our immune system tolerates a few of the fungi, but if their numbers grow to large, it culls the herd. Only when HIV or some other disruption weakens the immune system does the balance collapse. Unchecked, Pneumocystis turns the lungs into a mushroom colony.

A similar disruption may explain other fungal disorders. Malassezia obviously can exist peacefully with our immune systems, given that it’s all over us. But in some cases, our immune system begins to look upon some of the proteins made by the fungus as a danger and responds with inflammation. Fungi can thus help give rise to allergies and immune disorders like eczema. (Dandruff is another result of a bad relationship with Malassezia, it turns out.)

Our resident bacteria may also help keep fungi in check. Scientists have found that a microbe-destroying course of antibiotics can raise the risk of a bloom of Candida fungi. It’s possible that the bacteria work against fungi simply by grabbing most of the good attachment points in our bodies. They may even spray their own anti-fungal drugs around their vicinity.

A big question for future generations of fungus surveyors will be whether the hundreds of species of fungi in our bodies do us any good at all. “There is no strong evidence for a mutualistic or beneficial relationship with the fungal microbiome,” Huffnagle and Noverr write. But this might just be the result of how little research scientists have done on the question. And there are some good reasons to explore the possibility. Some species of yeast show promise as probiotics against bacterial infections, for example. And we’re all intimately familiar with the alchemy of fungi–from bread to beer. Synthetic biologists are now using yeast’s versatility to make malaria drugs and biofuel. Long before biologists discovered fungal alchemy, cows were taking advantage of it to break down the plants they eat. Perhaps our own fungal garden is helping us out in ways we don’t yet understand.

Photo by Dallas75, via Creative Commons. http://www.flickr.com/photos/dallas75...

Meet Your New Symbionts: Trillions of Viruses

With deadly new viruses emerging these days in Saudi Arabia and China, it can be hard to imagine that viruses can be good for anything. It’s easy to forget that we are home to trillions–perhaps quadrillions–of viruses on our healthiest days. And, according to a team of California scientists, those viruses are our symbiotic partners, creating a second immune system. These viruses serve as a defensive front-line, keeping bacteria from invading our gut lining and causing deadly infections.

The viruses in question are far less familiar than, say, influenza viruses or Ebola viruses. They are known as bacteriophages, which means “eater of bacteria.” And yet bacteriophages (or phages for short) are vastly more common than viruses that infect humans. They’re more common than all the viruses that infect every animal on Earth. The reason is simple arithmetic: there are far more hosts for phages to multiply in than there are for viruses that infect our own cells. They’re in the ground, in the oceans, under ice, and in the air. By some estimates, there are 1031 phages on Earth. That makes phages the most abundant life form, period.

Despite the fact that phages are just about everywhere, it was inside of humans that scientists first discovered them. Felix d’Herelle, one of the co-discoverers, came across them while treating French soldiers in World War I. He filtered the stool of soldiers sick with dysentery and isolated microscopic particles that could kill the dysentery-causing bacteria. The idea that bacteria had viruses seemed far-fetched to d’Herelle’s fellow scientists, and it wasn’t until the 1930s that engineers developed microscopes powerful enough to see them, to document their attacks on bacteria. d’Herrelle spent the rest of his life trying to transform phages into a medical weapon against bacterial infections. “Phage therapy,” as his method came to be known, continues to attract curious scientists over sixty years after his death. While it’s not ready to replace antibiotics, phage therapy is starting to be used to disinfect food.

For scientists who pursue phage therapy, phages are simply weapons to be deployed in a medical battle. By comparison, we don’t know much about these phages in nature–in other words, on what phages do in our inner ecosystem. It has been, frankly, too hard of a problem. If you’re an ecologist studying how lions control their prey’s populations, you can go out to a savanna and watch lions. You can tag lions. You can scoop up lion scat. Viruses that live inside our bodies–that don’t even make us sick–are practically invisible to science.

That’s starting to change. In recent years, our inner world of microbes has become the subject of massive scientific research. (Michael Pollan has a long feature on the so-called microbiome in this week’s New York Times Magazine; here’s an article of mine from last year’s New York Times.)

Scientists who study the microbiome have focused most of their efforts on mapping the diversity of the 100 trillion bacteria in our bodies. Part of the reason is practical. To conduct these surveys, scientists take samples–skin scrapings, saliva, stool, and so on–and strip away everything except the fragments of DNA in them. Then the scientists sequence those fragments and identify their origins. Bacteria, which generally have much larger genomes than viruses, are much easier to recognize this way.

This research has revealed a world of vast complexity–and a world on which our own well-being depends. Our resident bacteria break down tough plant matter, synthesize vitamins, and keep invading pathogens from taking over our bodies.

But that doesn’t mean that our bodies embrace the microbiome without reserve. As we get to know the microbiome better, we shouldn’t fool ourselves into thinking of it as some wise guardian angel. It’s a horde of several hundred species of microbes, a horde that can do some stupid things.

Consider the bacteria that line the delicate walls of our large intestines. If they multiplied with abandon, they would end up pushing down into the intestinal wall, pressing against our cells and wedging between them. If they broke through, they’d get swept away into the bloodstream where they could cause dangerous infections.

Our intestinal walls are also loaded with immune cells, and they can make this kind of a breach even more damaging. They may overreact, causing dangerous levels of inflammation in the intestines–creating a new environment that can foster the growth of disease-causing bacteria.

To avoid this disaster, our bodies hold back the microbiome. One strategy that intestinal cells use for their defense is secreting a dense layer of mucus.  While the surface of the mucus provides lots of tasty food for bacteria, the lower levels are so dense they’re hard for the microbes to invade. Our intestines also defense themselves from the microbiome by secreting microbe-killing molecules to knock off any bacteria that get too close to breaching the wall. And when pathogens invade, our intestines can ramp up these defenses–making more antimicrobials and even thicker layers of mucus.

But these defenses are no guarantee of safety. Indeed, some pathogens have actually evolved the ability to hack our defenses for their own benefit. Salmonella, for example, goes out of its way to trigger inflammation in the gut. In the toxic environment created by the immune system, Salmonella outcompetes other bacteria. And as immune cells move into the intestinal lining to attack, Salmonella performs its greatest humiliation: it invades the very immune cells that are supposed to protect us.

If we focus only on the relationship between human cells and bacteria, however, we miss a third major player in our intestinal ecosystem. Phages thrive in our guts, attacking bacteria and using them to make more copies of themselves.

Phages tend to specialize on certain strains of bacteria. To invade a host microbe, they act like a thief using a key to slip into a locked house. Proteins on a phage’s surface bind to proteins on a host cell, creating a passageway through which the phage can inject its genes. This video below shows what it looks like when a phage called T4 invades E. coli:

This intimate relationship between phages and their victims turns them into coevolutionary partners. A mutation that alters a microbe’s lock will be favored by natural selection, because it makes the phage’s key less effective. (The  mutation has to be able to bring about this change without harming the microbe itself.) The phages, in turn, benefit from mutations that adapt their keys to the new locks.

These arms races may also help explain the tremendous diversity of microbes in our guts. When one strain of bacteria has a population boom, it creates lots of new opportunities for its phages to multiply as well. Eventually, the phages may become so abundant that they decimate their host population. That crash may let another strain of bacteria rise up and become dominant–only to be driven down by its phages.

But what if there was a hidden partnership between phages and us? What if the enemy of our frenemy was our friend?

Jeremy Barr of San Diego State University and his colleagues recently explored this possibility in a study they’re publishing this week in the Proceeding of the National Academies of Sciences. They started their investigation with a simple but profound observation: compared to other parts of the intestines, the mucus layer is packed with phages.

This might simply be a matter of predators going to where their prey are. But when Barr and his colleagues took a closer look, they found evidence that our own bodies make the mucus layer an inviting home for the phages.

Some of this evidence comes in the form of hooks that grow on the phages. To understand what their function was, the scientists engineered phages that didn’t make the hooks. They did no worse at invading bacteria in a Petri dish. So the hooks are not involved in infection, like their keys. The hooks must therefore have another function.

Barr and his colleagues carried out a series of experiments to find out what that function was. The answer lies not with bacteria, but with us. The hooks are exquisitely adapted to latching on to certain molecules that make up our mucus, known as mucin glycoproteins. Thanks to their hooks, phages drifting through our intestines can snag onto the mucus, forming a viral carpet.

To see what sort of effect that carpet had, Barr and his colleagues ran another set of experiments. They created two cultures of human cells. In one culture, the cell grew in a layer and produced a covering of mucus. In the other culture, the cells produced no mucus.

Then the scientists sowed phages on all the cell cultures. They gave the phages some time to anchor themselves, and then washed away any phages that were still floating free. Finally, the scientists added bacteria on top of the cultures and let them grow for four hours.

The differences between the two cultures were stark.The normal cells snagged an abundance of phages in their mucus layer, and the viruses killed off most of the bacteria. The cells that couldn’t make mucus, on the other hand, ended up with no phages to defend them. The bacterial population exploded, killing off some of the human cells underneath.

What makes this discovery all the more fascinating is how the phages hook onto mucin glycoproteins. At first glance, those would seem like the worst target a virus could go after. There is no single kind of mucin glycoprotein in your body. Scientists have identified 19 kinds, and there may be many more. The variety comes from how we make them. First, our cells make a protein; then they decorate it with sugars in many different patterns. A hook that lets a phage grab onto one glycoprotein will be useless for another.

Phages seem to be equipped to handle this variety. It turns out that the gene for the phage hook is far more prone to mutating than its other genes. Each time a phage produces new viruses, they generate new shapes to fit different mucin glycoproteins.

All this suggests that the phages in our guts have evolved a sophisticated strategy for taking hold in the mucus layer of the gut. It allows them to find an abundant supply of victims to kill. It may be a winning strategy for us to, because the phages become an extra immune system for our own bodies. Bacteria settle onto the top of the mucus layer, feed, and grow. But as they spread down towards the wall of the intestines, they encounter a dense barrier of phages. The phages kill them off and increase their numbers even more, creating an even more powerful barrier of defense.

Scientists have found viruses in other species, such as fungi, plants, and insects, that help out their hosts. It’s possible that we can add ourselves to the list of hosts that depend on their own virome. If this new research holds up, it will be fascinating to see how far evolution has taken this partnership. Many species that host symbiotic microbes go to great lengths to care for their residents. Some insects even grow special organs to house them. Do we tailor our intestines to grow as many phages as possible?

Answers to these questions might eventually provide us with a new way to approach the enduring dream of phage therapy. Rather than unleashing an invasion of shock troops on infections, maybe we should learn how to help our phages keep up their quiet defenses.

(For more on bacteriophages, see my book A Planet of Viruses.)