TRAFFIC: Carl Zimmer and W. Ian Lipkin

May 3, 2011
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Welcome to TRAFFIC, a series exclusive to the Chicago Blog presenting an exchange of thoughts between leading figures from across the humanities and sciences, whose prescient views on current events help us to interpret contemporary culture. We’re delighted to begin a month’s worth of Friday TRAFFIC posts helmed by popular science writer Carl Zimmer in collaboration with some of our most acclaimed virologists, immunologists, and scientifically minded journalists.
Please join us for the next four weeks in welcoming discussions on virology and immunology with W. Ian Lipkin, director of the Center for Infection and Immunity; small pox with Richard Preston, New Yorker writer and bestselling author; phage therapy with Timothy Lu, inventor and Novophage founder; and ocean viruses with Sallie Chisholm, biological oceanographer and marine science expert.
With that in mind, join us for our first TRAFFIC exchange with Zimmer and Lipkin below:
jacket imageThe New York Times calls Carl Zimmer “as fine a science essayist as we have.” In his widely admired books, essays, and blogs, Zimmer charts the frontiers of biology. Booklist acclaimed his most recent title A Planet of Viruses as “absolutely top-drawer popular science writing.” Zimmer is a lecturer at Yale University, where he teaches writing about science and the environment. He is also the first Visiting Scholar at the Science, Health, and Environment Reporting Program at New York University’s Arthur L. Carter Journalism Institute. W. Ian Lipkin, MD, is the director of the Center for Infection and Immunity, John Snow Professor of Epidemiology, and professor of neurology and pathology in the Mailman School of Public Health and the College of Physicians and Surgeons at Columbia University. His specialty is detecting new viruses and testing links between viruses and diseases. In A Planet of Viruses, Zimmer describes Lipkin’s discovery of West Nile Virus in the United States, as well as his work uncovering hidden strains of the common cold. Zimmer also profiled Lipkin in November 2010 for the New York Times.


Dear Carl,
I just finished A Planet of Viruses. It’s a compelling read that explores new frontiers in microbe hunting and the complex path from disease association to disease causation, a path we have not fully traveled. As with any book there are holes to be filled; nonetheless, this is an excellent roadmap!
We typically think of viruses as pathogens, but there is abundant and increasing evidence that they had an important and positive role in our evolution as mammals and the planet we live in. Retroviruses, a special kind of RNA virus of which HIV is the most famous, intercalate their genetic code into their host’s. When host cells replicate their DNA, the virus replicates with it. If the virus makes its way to a sperm or egg cell, the virus wins the (rare) opportunity to get passed on from parent to child, over and over again. These genetic infiltrators, known as endogenous retroviruses, have integrated themselves into mammalian genomes over millions of years. They activate genes during pregnancy to produce proteins that prevent rejection of a fetus as a foreign body, likely facilitating the evolution of the placenta and live birth. Marine viruses, known as bacteriophages, which are the most abundant viruses on earth, shape our ecosystem by infecting and lysing bacteria in deep-sea sediment, thus affecting how nutrients are recycled.

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Initiatives like the Human Microbiome Project, which surveys the human body’s resident microorganisms and how they interact with our genes to influence health and disease, have mostly focused on bacteria. However, scientists cannot continue to ignore viruses, fungi, and other bugs! Traditionally, we have focused on bacteria because they are easy to clone, allowing us to replicate parts of their genome that may shed light on our own evolution. With the advent of newer and “sexier” technologies like virus detection microchips and high throughput sequencing, we can turn our attention to studying our interactions with viruses in more detail. As we learn more about the viruses in our gastrointestinal and respiratory tracts, I will be very much surprised if there are no helpful inhabitants among them.
Stay tuned!
Carl, you also discuss zoonotic diseases like AIDS, influenza, SARS, and Ebola, but let’s not forget that how investigators decide where and when to sample for potential pathogens is also important. Hotspot modeling allows us to target surveillance efforts to ‘hot spots’ for human disease—the areas where human pathogens are most likely to emerge. The EcoHealth Alliance is a pioneer in this field and an advocate for the idea of One Health, which promotes collaboration among environmental scientists, vets, and clinicians.
And what about those curious about how microbe hunters do what we do? What are the platforms we use to find known and novel agents? How do we prove relationship to disease (or equally important, disprove a causative relationship)? Carl, let’s give them directions! The work we do the Center for Infection and Immunity helps to answer some of those queries. We provide links to papers and interviews that address these challenges as well as video demonstrations of some relevant technologies
Last (but not least), as this is not a peer reviewed publication, and I have been encouraged to let my imagination run free, I wonder whether you might consider a chapter in a potential sequel focused on how microbes may alter host behavior to enhance their growth and dissemination. For example, rabies is associated with the inability to swallow, leading to the accumulation of saliva that contains rabies virus, and with aggressive (rabid) behavior that facilitates its spread. It is possible, though I have no experimental proof, that when herpes simplex virus infects the sacral ganglia, it may (in)advertently stimulate nerve endings in the pelvic area , promoting sexual activity and increasing the likelihood it will move into another host.
Carl, thanks again for sending me a preview copy of your book. I look forward to many spirited discussions!
Best,
W. Ian Lipkin


Dear Ian:
Thanks for your reflections. There’s a lot to ponder in them, but I’m most intrigued by your most speculative ideas—namely, whether viruses manipulate their hosts for their own benefit. As we discover more and more viruses, I suspect that scientists will indeed find good evidence that at least some viruses act like puppet masters.
I first became familiar with this sort of strategy while writing my previous book, Parasite Rex. Some of the most spectacular examples of parasite manipulation come from animal parasites. The lancet fluke—a parasitic flatworm—has a life cycle that takes it from snails to ants to grazing mammals like cows or sheep. Getting from one species to another is no simple feat. The lancet fluke has ways of manipulating one host after another to make its way through life. Mammals release the fluke eggs in their droppings, which are then eaten by snails. The snails defend themselves by coating the eggs in slime and then “coughing” them up. Ants passing by find the slime delicious, and devour it, along with the eggs inside.
Once inside the ant, the fluke eggs hatch, and the parasites develop. When they’re ready for their next host, they begin to alter the ant’s behavior. At twilight, the ant crawls up a blade of grass and clamps onto the tip. That’s when grazing mammals are likely to pass by and devour the grass, and the ant, and the parasites inside. If the ant does not get eaten by dawn, the parasite causes it to release its grip and crawl down to the ground, where it can enjoy the shade until the end of the next day—when it feels the urge to climb again.
There are many such examples, and for some reason most of them come from parasitic animals—tapeworms, parasitoid wasps, thorny-headed worms, and the like. I don’t think that this bias reflects the superior sophistication of parasitic animals over non-animal parasites like viruses. I think it’s just another case of the drunk looking for his keys under a lamp post—not because the keys are there, but because that’s where it’s easier to look.

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Consider, for example, the fungus Cordyceps. This little mushroom has no animal nervous system. It’s just a mass of fungal cells. Yet Cordyceps manages to manipulate ants as well as lancet flukes. Ants pick up its spores on the ground, whereupon the fungus penetrates its host exoskeleton and starts to grow inside. It doesn’t kill its host, however. Instead, it feeds on the ant’s internal fluids until it’s ready for its next stage of life. The ant then starts to climb—not to the tip of a blade of grass, but to the underside of a leaf a few feet off the ground. The ant clamps onto a vein in the leaf, whereupon the fungus sprouts a flower-like stalk out of its head, which showers spores on the ants below.
While Cordyceps may not have the complexity of the animal nervous system, however, it’s not simple. Fungi have big genomes. Yeast, for example, has about 6,500 genes. There’s a lot of storage capacity in such a genome to encode lots of sophisticated strategies. A parasitic fungus might be able to use some of its many genes to make proteins that interacted with its host’s nervous system to direct it to just the right spot on a leaf. Viruses, on the other hand, typically only have a handful of genes.
Are ten genes enough for a virus to manipulate a host? I suspect they may well be. After all, scientists have already shown how viruses can manipulate us in other ways, such as the way that human papillomaviruses can speed up the growth and division of their host cells. There’s nothing particularly special about behavior that would make it beyond the reach of viruses. They’d just need to make proteins that could shut down certain genes in neurons or switch other ones on to produce big changes. And as I mention in A Planet of Viruses, scientists are now finding giant viruses that contain over a thousand genes. Perhaps they have unappreciated powers of manipulation, too.
Parasitologists have one big piece of advice for anyone who wants to investigate whether viruses manipulate their hosts: don’t be fooled by mirages. It is very tempting to see any change in a host as the product of a fine-tuned adaptation in its parasite. But it’s also possible that a strange host behavior is merely a byproduct of being infected. It’s not easy to distinguish between these alternatives. One way is to measure just how big of a difference these “manipulations” make to parasites. Robert Poulin of the University of Otago has studied a parasitic fluke that infects cockles on the beaches of New Zealand. It then needs to get into the shore birds that eat the cockles to move to the next stage of its life cycle. And it just so happens that the infected cockles lose the ability to burrow. So if you walk around on the beach in New Zealand, a lot of the cockles you see may be infected and unable to dig back down into the sand.
Seems like a great way for the parasite to boost its odds of getting into a bird, right? Well, Poulin worked through a detailed model of the parasite life cycle and discovered that it actually makes little difference. For one thing, the cockles also get eaten by other predators in which the parasite can’t survive. So Poulin concludes that this case of “manipulation” could not have evolved because it benefited the parasites. Instead, it’s just a side-effect. If someone wants to see if the aggression caused by rabies is a manipulation, they could try to carry out a similar test. It wouldn’t be easy, but it would be interesting.
Still, it would be a mistake to look only for the most fine-tuned adaptations in viruses. Just consider a single-celled protozoan called Toxoplasma, which normally has a life cycle that takes it from cats to rats and other mammal prey and back to cats again. Toxoplasma does not make rats sick. Instead, it forms harmless cysts in rat brains. And there it seems to manipulate rats in a very precise way: it causes them to lose their fear of cat odor. This change may make them easier prey for cats, boosting the reproductive success of the parasite.
Toxoplasma is a serious health problem for humans. Pregnant women need to avoid contact with cat litter or garden soil, because they may pick up the parasite and accidentally ingest it. While healthy adults can keep Toxoplasma in check, fetuses with immature immune systems cannot. Toxoplasmosis can thus cause serious brain damage, as the parasite grows unchecked. Toxoplasmosis is also a serious concern for adults with compromised immune systems—due to AIDS or immune-suppressing drugs taken after organ transplants.
In human adults, the parasite may be benign, but it does appear to cause some shifts in personality. Some studies suggest that people with Toxoplasma are more likely to get into car accidents, for example. It would be a mistake to see these personality shifts as the parasite’s strategy for getting us eaten by cats. For one thing, Toxoplasma was probably not a common disease in humans until the domestication of house cats—when we came into close contact with their parasite-laden droppings. For another, I doubt my pet cats would ever consider me a potential breakfast.
Still, the fact that these personality shifts are not fine-tuned adaptations does not make them unimportant. Could some psychological disorders, like depression, be the result of viruses that alter the behavior of their regular animal hosts? And as virologists like you discover new viruses moving into our species from other animal hosts, I wonder if they’ll bring their puppetmaster tricks with them.
Best,
Carl


Stay tuned for next Friday’s installment of TRAFFIC, featuring Zimmer in conversation with Richard Preston. And for more info on A Planet of Viruses, please visit the book’s UCP page here.
This blog and the book A Planet of Viruses are part of the World of Viruses project, funded by the National Center for Research Resources at the National Institutes of Health through the Science Education Partnership Award (SEPA), Grant No. R25 RR024267.

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