If you’ve got some free time, here are a couple talks for your listening pleasure.
Radiolab presents a story I told about a fateful trip to Sudan on their latest podcast. I’ve embedded it here:
Last week, I also talked about viruses on Skeptically Speaking, and they’ve posted our conversation here. (If you have trouble at that link, try here.) Among other things, we talk about the unimaginably huge number of viruses on Earth, and I offer my vote for the Worst Virus Ever. Fortunately, if you’re not a catepillar, you don’t have anything to worry about.
Story Collider is a monthly performance where people tell stories about science. (Think The Moth in a lab coat.) The organizer, Ben Lillie, invited me to tell a personal story about the place of science writing in my life. I decided to talk about a memorable night in South Sudan, when I wondered what I was living for.
I told the story to a great crowd at Union Hall in Brooklyn last week. And you can hear the podcast at the Story Collider web site. Check it out.
Talk you on the other side of the maelstrom.
[Update: Part one linked now fixed]
It’s time to revisit that grand old parasite, the brain-infecting Toxoplasma. The more we learn about it, the more marvelously creepy it gets.
Toxoplasma is a single-celled relative of the parasites that cause malaria. It poses a serious risk to people with compromised immune systems (for example, people with AIDS) and fetuses (which is why pregnant women need to avoid getting Toxoplasma infections). If you’ve got a healthy immune system, it doesn’t cause any immediate harm. (Ed Yong has explained why a purported link to brain cancer is very weak.) All told, perhaps a quarter or a third of all people on Earth carry thousands of Toxoplasma cysts in their heads. Most never become aware of their living cargo.
The Toxoplasma life cycle normally takes the parasite from cats to the prey of cats and back again. In the guts of cats, the parasites have sex and produce egg-like offspring which are shed with cat droppings. They can survive in soil for weeks or months. Rats and other mammals ingest the eggs, which produce cysts mainly in the brain. When the cats eat infected prey, they get infected.
For a little over ten years, scientists have been investigating whether Toxoplasma raises its odds of getting back into cats by manipulating their prey hosts. Oxford researchers kicked thing off by releasing healthy and infected rats into large enclosures. They spritzed corners of the enclosure with various odors, including the urine of rats, rabbits, and cats. Normally rats become anxious the instant they sniff cat urine and explore much less. Wise move.
Not so wise is the response of infected rats: in the enclosure experiments they either became indifferent to the smell of cats, or spent some extra time checking out the feline corner. There was no difference in how the infected rats responded to other smells.
Robert Sapolsky, a neuroscientist at Stanford University, and his colleagues have carried the experimental torch foreward. In 2006, they demonstrated just how precise Toxoplasma’s effects are. They found that infected rats did not lose their fear across the board. Dog urine still spooked them, and they could be trained to get scared of new stimuli. Only their innate fear of cats changed. Sapolsky’s team then looked at where the parasite actually ended up in the rat brain. They found Toxoplasma cysts clumped around the amygdala, a region of the brain that’s heavily involved in fear and other emotions.
Now Sapolsky and his colleagues have looked even closer at the parasite’s effects. They had rats sniff various odors and then examined their brains to look for a telltale protein called c-Fos. When neurons fire, they produce c-Fos, and so the more active a region of the brain, the more c-Fos accumulates in it. The scientists found two big differences in infected rat brains when they sniffed cat urine, both of which occurred in the region around the amygadala. A circuit in the brain that helps produce defensive behaviors became less active.
Near that circuit is another circuit that triggers sexual arousal.
And the parasite also altered this sexual arousal circuit. It increased the activity of those neurons.
Really, it would have been mind-blowing enough for a parasite to surgically swoop into a host brain and knock out the fear it felt towards a particular animal. We admirers of our parasite overlords would have been satisfied. But the possibility that these hosts are actually attracted to their enemy, that they feel the deepest desire a rat can feel, a desire that could lead them to death, and lead the parasite to live on, to achieve their own deepest sexual desires–well, we can only be grateful.
Sexual reproduction requires splitting a species into two sexes, only one of which will be able to produce offspring. There are some species of animals that do without males; the females simply trigger their eggs to develop into embryos without any need for sperm. All the offspring of an asexual animal can produce offspring of their own, instead of just half. So it would make sense that genes that gave rise to asexual reproduction would win out in the evolutionary race.
Clearly that hasn’t happened. The world is rife with sex. Animals do it. Plants do it. Even mushrooms do it. So evolutionary biologists have carried out a number of studies to get an answer to the question, “Why sex?”
In 2009, I wrote an essay for Science about this research. If I had been writing that essay today, I’d have focused some attention on an elegant experiment on the sex life of a humble worm. It gives a big boost to the long-floated idea that evolution favors sex because it lets hosts fight better against parasites.
Allow me to explain by self-plagiarizing:
In the 1970s, several researchers built mathematical models of how parasites influenced the evolution of their hosts and vice versa. Their research suggested that both partners go through cycles of boom and bust. Natural selection favors parasites that can infect the most common strain of host. But as they kill off those hosts, another host strain rises to dominate the population. Then a new parasite strain better adapted to the new host strain begins to thrive, leaving the old parasite strain in the dust.
This model of host-parasite coevolution came to be known as the Red Queen hypothesis, after the Red Queen in Lewis Carroll’s book Through the Looking Glass, who takes Alice on a run that never seems to go anywhere. “Now here, you see, it takes all the running you can do to keep in the same place,” the Red Queen explains.
The Red Queen conundrum, some researchers have argued, may give an evolutionary edge to sex. Asexual strains can never beat out sexual strains, because whenever they get too successful, parasites build up and devastate the strain. Sexual organisms, meanwhile, can avoid these dramatic booms and busts because they can shuffle their genes into new combinations that are harder for parasites to adapt to.
Red Queen models for sexual reproduction are very elegant and compelling. But testing them in nature is fiendishly hard, because biologists need asexual and sexual organisms that share the same environment and parasites.
Scientists have found some mixed populations in the wild where they’ve made some important discoveries. But it’s also possible to test the Red Queen in laboratories. It’s not easy, because scientists need to bring together a host that can reproduce sexually and asexually with a parasite, and then they both have to be able to evolve in response to each other. But that’s what a team of scientists at Indiana University managed to do recently.
As they describe in a paper published today in Science, they reared populations of a tiny worm called Caenorhabditis elegans. C. elegans are born either as males or hermaphrodites. A hermaphrodite worm can fertilize its eggs with its own sperm, or it can seek out a male. The worms typically don’t have a lot of sex, and the rate at which they do is partly programmed into their genes. The Indiana team of scientists were able to engineer the worms so that they could have no sex at all, or could only reproduce through sex.
For their parasite, they chose a species of soil bacteria called Serratia marcescens. Soil bacteria are the regular prey of C. elegans, but if they slurp up S. marcescens by accident, they get sick and can die in under 24 hours. Previous studies had shown that the worm can evolve stronger resistance to the germ, and the germ can evolve to be deadlier for the worm. So the Indiana researchers set about combining their evolution into one big experiment.
They mixed together worms and germs in several different arrangements and let them duke it out for 30 worm generations. In each trial, the worms were either sexual or asexual. In some trials, the bacteria coexisted with the worms for the whole experiment, so that they could evolve along with the worms. In other trials, the worms were repeatedly presented with the same, fixed strain of S. marcescens. In other words, the bacteria could not evolve. And in control experiments, the worms enjoyed a Serratia-free life.
As this graph to the left shows, the asexual worms that faced co-evolving germs were annihilated in just 20 generations. (“Obligate selfing” means no sex.) If the germs couldn’t evolve, however, the asexual worms did fine. The scientists also tested the bacteria for deadliness after the experiments were over. They found that the bacteria that were allowed to co-evolve with the asexual became much deadlier. The co-evolving sexual worms, on the other hand, suffered far lower mortality rates from their germs.
In another experiment, the scientists started out with ordinary worms, which only had sex about 20 percent of the time they reproduced. Again, they exposed the worms to unchanging bacteria, or co-evolving ones, or no bacteria at all. The graph to the right says it all. The worms not exposed to the bacteria went on having infrequent sex. The worms that could evolve but faced fixed bacteria had more sex for a while, but eventually crashed back down to their original levels. The coevolving worms, on the other hand, became mostly sexual.
In each of these results, the Red Queen has left her mark. Far from being a waste of time, sex may save organisms from a swift oblivion.
(Update: paper link fixed)
Sometimes a blog must serve as a repository of regrets, a place to atone for not including some perfect fact in a book. While working on my book Parasite Rex, I came across many delicious examples of parasites manipulating the behavior of their hosts for their own benefit. After the book came out, I met scientists who enlightened me about other examples which would have been wonderful to include. A few years back, for example, a Johns Hopkins scientist pointed me to a parasitic wasp that turns cockroaches into zombies.
I’ve recently been wondering about behavior-altering viruses, thanks to an online conversation I had with Ian Lipkin, a virus hunter at Columbia University, about my new book A Planet of Viruses. Lipkin wondered aloud if some viruses would turn out to manipulate their hosts for their own good. Did herpesviruses, for example, increase its transmission by boosting their host’s sexual desire?
Most of the examples I knew about came from parasitic animals and fungi. The only virus that could have this kind of effect that I knew of was rabies, which causes its hosts to become more aggressive. A rabid dog that bites anything that crosses its path may be able to spread the virus more. But I suspected that there were many other puppet master viruses out there.
Well, while I was at California State University Fresno last week to give a talk, I met an entomologist named Fred Schreiber. He asked me if I had ever heard of baculoviruses. They rang a bell in my head, but only faintly. So Schreiber told me an eldritch tale…
Baculoviruses infect invertebrates, with each species of virus typically infecting only one species of host. Caterpillars are a particularly favorite target; the insects swallow baculoviruses sprinkled on the leaves they munch. (“How did the viruses get there?” you may ask. Very good question–which we’ll get to in good time.)
Once inside the caterpillar, a baculovirus infects a host cell. The cell produces huge numbers of new baculoviruses. They come in two forms. Some of the viruses can slip out of the host cell on their own to infect new cells. Others stay in the cell, which makes huge quantities of a viral protein called polyhedrin. The viruses become embedded in massive polyhedrin blocks, like fruits in a fruitcake. A caterpillar may produce 10 million viruses from swallowing a single viral fruitcake. It even becomes visibly swollen with all its new viruses.
Soon the virus-packed host gets an uncontrollable urge to creep its way to the tops of plants, where it clamps on tight, hanging down as shown in the picture above. In fact, scientists noticed these strange death throes long before they knew that baculoviruses that caused it. They dubbed it tree-top disease.
After an infected caterpillar takes its position at the top of a plant, the virus releases an enzyme that literally makes the animal dissolve. The tough viral fruitcakes come tumbling out, landing on leaves below where they can infect a new host.
Hearing about tree-top disease gave me a deep sense of deja vu. A number of very different parasites have evolved the same strategy for getting to new hosts. Just a couple weeks ago, for example, I blogged about a fungus that sends its ant hosts to the undersides of leaves, whereupon the fungus sprouts branches out of the ant’s head and showers spores down on new victims. Lancet flukes send their hosts up to the tips of grass blades so that they can be eaten by grazing cows and sheep. It’s fascinating that even a virus–with just a few genes–can trigger this behavior as well.
Scientists have identified one of the genes in baculoviruses that is crucial for this manipulation. It causes insect hosts to start wandering in response to light. Strangely, the virus appears to have acquired this gene through a kind of evolutionary theft. The viral gene bears a striking resemblance to a gene in insects. In the insects, the gene is involved inforaging for food. It’s possible that an ancestral baculovirus picked up the host gene, which then evolved to take on a different behavior–one that sent insects to their doom, rather than to a meal.
All in all, this zombie strategy is terrifically successful for baculoviruses. They are everywhere, killing insects in staggering numbers. In 1973, scientists bought heads of cabbage around Washington DC and discovered that they were coated in baculoviruses. A single serving of cabbage contained up to 100 million of them.
Fortunately, baculoviruses are so finely adapted to invertebrate hosts that they pose no threat to humans. In fact, we can use baculoviruses to our advantage. Scientists can remove the polyhedrin gene from the viruses and replace it with another gene of their choice. If they infect an insect cell with the engineered virus, it will make dense blocks of the protein they desire. Thanks to the sophisticated biochemistry that baculoviruses use, they allow scientists to harvest high concentrations of the protein. As a result, baculoviruses have become a mainstay of the biotech industry, where they are engineered to make vaccines and other drugs.
Baculoviruses are also popular as a way to control pests in farm fields, and for years, scientists have been trying to engineer the viruses to become even nastier to their hosts. Ironically, this manipulation of the virus may get in the way of the virus’s own manipulation of insects. Scientists have found that engineered viruses end up paralyzing the caterpillars before they can get a good grip at the top of plants. They fall to the ground, and so they can’t showering more victims with the virus.
We shouldn’t be too disappointed at this sort of failure. After all, evolution has been fine-tuning these viruses for millions of years. Our imaginations may need a little more time to improve on the elegant horror that lurks in your salad.
[Image: Bill Tyne/Flickr]
It’s time to pay another visit to Cordyceps, the fungus that turns its hosts into spore-sprouting zombies.
The fungus, which can be found in many parts of the tropics, penetrates an insect’s exoskeleton and then work its way into its host’s body. At first the ant seems normal to the human eye, but eventually it makes its way to a leaf, where it clamps down with its mandibles. Cordyceps then sprouts out of the ant’s body, lashing it to the leaf’s underside, and producing a long stalk tipped with spores. The spores can then shower down on unfortunate insects below.
David Hughes of Penn State University has been publishing a string of fascinating papers in recent years about this science-fiction-topping parasite. In 2009, I wrote about one study of his on the exquisite precision of the fungus’s manipulations. He and his colleagues found that one species that lives in Thailand almost always causes infected ants to clamp onto a leaf vein about 25 centimeters off the ground–a spot where the humidity and other conditions may be ideal for a fungus to grow. When Hughes and his colleagues moved infected ants higher up into the canopy, the fungus ended up deformed. On the other hand, when the scientists moved the ants to the ground, the ants simply disappeared–devoured most likely by other animals or washed away by rain.
Now Hughes is looking more closely at how the fungus pulls the strings on its insect marionette. First off, how does it drive the ant to its climatic sweet spot? The species of fungus that Hughes studies, Ophiocordyceps unilateralis, infects a species of ant, Camponotus leonardi, that usually stays 60 feet off the ground, living in the canopy of the Thai rain forest. It sometimes drops to the ground, but promptly walks a short distance along an ant trail to the nearest tree.
Infected ants, by contrast, were beset by convulsions that caused them to fall out of trees. Instead of following a trail, they wandered the forest floor in random directions for hours, and then climbed up small plants instead of trees. Healthy ants are active from dawn to dusk, but Hughes and his colleagues could only find infected ants during midday. And they all became synchronized in their leaf-biting, typically clamping onto a leaf around noon.
Hughes then took a close look at the death grip itself. In the hours before the zombie ants clamped onto a leaf and died, their jaws were in good working order. The ants could use their mandibles to clean off their antenna and legs without chomping them off, for example. Once the ants clamped onto leaves, Hughes dissected their heads and peered inside. They were full of fungal cells. He also observed that the muscles controlling the mandibles were atrophied.
It’s a bizarre finding, given that zombie ants typically have enough strength to pierce through a leaf vein. One possibility Hughes offers is that the atrophy sets in after the ants bite down, and it attacks the muscles that the ant might use to let go of the leaf.
All in all, Hughes’s research supports the idea that the ant becomes what Richard Dawkins has dubbed the extended phenotype of the fungus. The behavior of the host is not just a side-effect of having a bad fungal infection. It’s a manipulation that lets the parasite reproduce more successfully.
Still, Hughes has much left to figure out. Why, for example, do the ants pick leaves that point north northwest, for example? It may seem eerie that a fungus can work its zombification like clockwork, but other parasites can, too. A fluke that infects ants causes them to clamp grass blades at dusk. That timing works out nicely for the fluke, because it needs to get into grazing mammals like cows or sheep to complete its life cycle, and those animals like to graze when it’s cool out. The fluke-infected ants even climb down at dawn so they don’t bake in the sun, returning to the tops of the grass the next evening.
Hughes doesn’t know what’s so special about noon for this fungus. But I’d bet that there’s some eldritch horror in the answer.
To mark the publication of A Planet of Viruses, the University of Chicago Press asked me to participate in a weekly series of conversations with experts on some of the themes I explore in the book. They’ll be coming out each Friday in May. First up is an exchange between me and Ian Lipkin, a virus hunter at Columbia University and the subject of this 2010 profile I wrote for the New York Times. As if waving a piece of red meat before me, Lipkin wonders if viruses can alter our behavior. I then take the bait. Check it out.
I’ll be speaking tomorrow at SUNY Plattsburgh on the occasion of the publication of the new edition of Parasite Rex. I’ll be talking about the many ways in which parasites have infiltrated my mind since the book first came out a decade ago. I hope some Loominaries will be able to attend, and be infiltrated as well.
Where: SUNY Plattburgh, Plattsburgh NY. Room 206, Yokum Hall. (Directions and campus map)
When: Friday, April 15, 12:15 pm.
More details here.