UNIVERSITY OF CHICAGO PRESS

The Midwest’s largest literary event? Dispatch just in from our Department of All Things Reference and Regional about annual Chicago favorite, the Printers Row List Fest:

                       

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Come out and join us this weekend at the 2011 Printers Row Lit Fest, one of the most anticipated events of the year for authors, publishers, booksellers, and book lovers in Chicago. Among the bookstalls and reading stages occupying five city blocks in the South Loop, you’ll find the University of Chicago Press booth on Dearborn just south of Harrison. We’ll be selling some of our most popular regional and general interest titles at great prices, including The Thinking Student’s Guide to Collegeby Andrew Roberts for $10 and a table full of books such as theThe Rules of Golf in Plain English and The University of Chicago Spanish Dictionary for just $5. While you’re there, catch our distinguished authors speaking at the following events:

10:00 AM on Saturday at University Center/River Room

Hillary Chute, author of Graphic Women and Melissa Ann Pinney, author of Girl Ascending, in conversation with Mary Schmich of the Chicago Tribune

10:30 AM on Saturday at University Center/Loop Room

Adoption Nation with Jane Katch, author of Far Away from the Tigers: A Year in the Classroom with Internationally Adopted Children and novelist Gina Frangello, moderated by young-adult librarian Amy Alessio

11:00 AM on Saturday at the Central Stage

Bob Riesman, author of I Feel So Good: The Life and Times of Big Bill Broonzy, and Michael Charry, author of “George Szell: A Life of Music,” in conversation with Howard Reich of theChicago Tribune 

11:00 AM on Saturday at University Center/Lake Room

Carrie Pitzulo, author of Bachelors and Bunnies: The Sexual Politics of Playboy in conversation with Kimberly Yuracko, author of Perfectionism and Contemporary Feminist Values

2:15 PM on Saturday at University Center/Loop Room

John Vinci and Ward Miller, coauthors of The Complete Architecture of Adler and Sullivan, in conversation with writer and Northwestern professor Bill Savage

11:00 AM on Sunday at the University Center/River Room

Eric A. Posner, author of Law and Happiness and The Perils of Global Legalism, speaks to BookTV 

2:30 PM on Sunday at Hotel Blake

Larry Bennett, author of The Third City: Chicago and American Urbanism, and Kristina Ford, author of The Trouble with City Planning, in conversation with Donna Robertson, dean of the IIT College of Architecture

For more information and a full schedule of events visit the Fest’s official website. We’ll look forward to seeing you there!

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Welcome back to TRAFFIC, a Chicago Blog series featuring leading figures from across the humanities and sciences, whose prescient views on current events help us to interpret contemporary culture. We’re delighted to continue this month’s Friday TRAFFIC features, led by popular science writer Carl Zimmer. This week Zimmer welcomes MIT scientist Timothy Lu to talk about the quest to use viruses to cure infectious diseases.

Timothy Lu is assistant professor of electrical engineering at MIT, where he heads the Synthetic Biology Group. Carl wrote a profile of Lu last year in Technology Review.

All About Phage Therapy

**

Dear Carl:

Bacteriophages are the most abundant biological particles on earth, but due to their size, and perhaps ubiquity, most of us don’t think of them very often. Phages are essentially just bacterial viruses. When it comes to viruses, the popular notion is that they are bad entities that are responsible for disease and suffering. The truth is, however, that phages are very different from human viruses. Phages do not infect human cells and are not responsible for the viral diseases that plague mankind, such as AIDS, herpes, cervical cancer, and the common cold. Furthermore, phages have had a tremendous impact on modern biology and biotechnology.

Much of our early scientific efforts to understand genetic regulation were carried out in the humble phage. Phage proteins called recombinases are an integral component for the construction of “knockout animals,” which cannot express particular genes—an indispensable tool in modern biological research. Phage display, a technique for sticking a library of peptides on phage surfaces and panning for targets to which these peptides will bind, has been used to make nanowires for batteries, identify new antibodies to treat human diseases, and understand the basic science which underlie protein-protein interactions.

Despite their importance as major research tools in the biomedical community, however, research into the use of phages as human therapeutics has garnered a mixed reputation in the Western world. Soon after their discovery in the early twentieth century, phages were tried as novel antimicrobial agents. Indeed, one can imagine the excitement that the early phage researchers must have experienced when observing the lysis—or clearing of bacterial cultures—by the addition of a newly discovered biological agent!

                          a bacteriophage

However, early reports claiming impressive successes at treating bacterial infections with phages were later tempered by failures in other settings and repeated trials.

Looking back, it is likely that a lack of detailed understanding of phage biology was responsible for much of these failures. Unlike antibiotics, which act like broad-spectrum bombs that blast all bacteria, good or bad, in their paths, phages are targeted warriors, the biological equivalent of a sniper or laser-guided missile. This targeted behavior is beneficial because it avoids killing bacteria which are good for us, as opposed to antibiotics which cause collateral damage. However, this targeted behavior also has its flaws because to effectively treat a specific bacterial contamination with phages, one must understand the bacterial compositions in detail and know what mixture of phages to use against them. Such capabilities were not available or known during the early days of phage therapy.

Thus, the subsequent discovery of antibiotics, along with their simplicity and miracle successes, largely displaced phages from antimicrobial research in Western medicine in the latter half of the twentieth century. As a result, the notion of phage therapy often elicits justifiable skepticism when discussed as an alternative to antibiotics today, even though the antibiotics pipeline has dried up and we are in desperate need of new strategies to combat the rising tide of antibiotic-resistant superbugs.

Fortunately, in the past few decades, there has been a renaissance brewing in the phage world. Commercial, government, and academic labs have begun to tackle the fundamental issues that have held back phage therapy using rigorous molecular tools. To use phages to effectively treat bacterial contaminations, these labs have been developing technologies for classifying bacterial populations, identifying the right combination of phages to use, and optimizing phage properties using evolutionary or engineering approaches.

Instead of tackling the high hurdles that need to be crossed for direct human use, many labs and companies have chosen to apply phages to other applications in industrial, environmental, and diagnostic settings. For example, Intralytix makes phages to treat listeria contaminations of food, Omnilytix makes phages that control bacterial infections on tomatoes and peppers, and Microphage makes phages that can detect and report on the presence of harmful antibiotic-resistant superbugs, such as MRSA. A company called Novophage is advancing the use of phages for industrial applications, where they have the potential to enhance energy inefficiency and decrease biofouling (for full disclosure, I am a founder of this startup). Major advantages of phages compared with chemical biocides and pesticides include greater biocompatibility and decreased environmental toxicity. Using natural biological particles to combat biological problems is consistent with our society’s continuous drive to reduce the use of harmful chemicals and is, I believe, a great application for phages in the modern era of biotechnology.

The hurdle that has yet to be overcome is the use of phages for human therapeutics, the original application area for phage therapy. Nonetheless, given the great need for new antimicrobial therapies and the inroads that these laboratories have been making into optimizing phages for practical applications, the prospect of effective phage therapy being applied to human infectious diseases in Western medicine seems to be growing!

Tim

**

Dear Tm:

In all my work as a science writer, I can’t think of a story as strange as the history of phage therapy. It’s been nearly a century since the Canadian physician Felix d’Herelle discovered viruses that infect bacteria. And yet, despite great promise, phage therapy has yet to become a mainstay of medicine.

What makes the story even stranger is that Herelle could see the promise of phage therapy as soon as he discovered the viruses. He was soon using them to treat dysentery and cholera. When four passengers on a French ship in the Suez Canal came down with bubonic plague, Herelle gave them phages. All four victims recovered. He went on to conduct large-scale public health campaigns for the British government in colonial India. Phage therapy became so well-known that Herelle inspired the central character in Sinclair Lewis’s 1925 best-selling novel Arrowsmith. Phage therapy became big business: Herelle developed commercial drugs that were sold by the company that’s now known as L’Oreal, which were used to treat skin wounds and to cure intestinal infections.

      Felix d’Herelle

But by the time he died in 1949, Herelle had sunk into obscurity. Doctors had abandoned phage therapy for antibiotics. His dream did not vanish entirely, however. On his travels, Herelle met Soviet scientists who wanted to set up an entire institute for research on phage therapy. In 1923 Herelle helped establish the Eliava Institute of Bacteriophage, Microbiology, and Virology in Tbilisi, which is now the capital of the Republic of Georgia. At its peak, the institute employed 1200 people to produce tons of phages. In World War II, the Soviet Union shipped phage powders and pills to the front lines, where they were dispensed to infected soldiers.

Soviet scientists continued to investigate phage therapy after World War II. They conducted the best trial of the viruses in 1963. They enrolled 30,769 children in Tbilisi. Once a week, about half the children swallowed a pill that contained phages against dysentery. The other half of the children got a pill made of sugar. To minimize the influence of the environment as much as possible, the Eliava scientists gave the phage pill only to children who lived on one side of each street, and the sugar pill to the children who lived on the other side. The Eliava scientists followed the children for 109 days. Among the children who took the sugar pill, 6.7 out of every 1,000 got dysentery. Among the children who took the phage pill, that figure dropped to 1.8 per 1,000. In other words, taking phages caused a 3.8-fold decrease in a child’s chance of getting dysentery.

Phage therapy only began to attract interest in the West after the fall of the Soviet Union, when Soviet scientists could communicate more freely with the rest of the world. And yet, as you point out, the U.S. government has been leery of approving viruses for medical treatments. Gone are the days when a physician like Herelle could pretty much do as he pleased. As a result, many companies and investors are reluctant to embrace his phages.

If phage therapy can leap over these hurdles, I think that there are a vast number of potential applications. Treating a skin infection is just the start. Phages, after all, are part and parcel of every person’s inner ecology. Our bodies are home to 100 trillion bacteria and other microbes. Recent surveys estimate that these microbes play host to about four trillion phages, which come in about 1,500 different species. In some cases, our phages kill their hosts, and thus maintain an ecological balance in our mouths, noses, guts, and other nooks and crannies. In other cases, phages insert genes into their microbial hosts, giving them new powers.

The human microbiome is not merely an infestation we tolerate. It plays many different roles in our bodies. Microbes synthesize vitamins for us, regulate how much energy we get from our food, fight off invading pathogens, nurture our immune system, and potentially even influence our behavior. It may be possible to manipulate the microbiome through the phages that have coevolved with it for millions of years.

Carl

**

Stay tuned for next Friday’s installment of TRAFFIC, featuring a conversation between Zimmer and Sallie Chisholm on the nature of ocean viruses. 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. Additional materials, including those directed at a K-12 audience, can be found on the World of Viruses website.

TRAFFIC: Carl Zimmer and Richard Preston

Welcome back to TRAFFIC, a Chicago Blog series featuring leading figures from across the humanities and sciences, whose prescient views on current events help us to interpret contemporary culture. We’re delighted to continue this month’s Friday TRAFFIC features, led by popular science writer Carl Zimmer. This week Zimmer welcomes Richard Preston, New Yorker contributor and bestselling author, for a conversation on smallpox and the possible eradication of other viruses.

Richard Preston is the author of seven books, including The Hot Zone, The Cobra Event, and The Demon in the Freezer. He is a regular contributor to the New Yorker, and his awards include the American Institute of Physics Award and the National Magazine Award. Preston also the only person who isn’t a medical doctor ever to receive the Centers for Disease Control’s Champion of Prevention Award for public health.

Should Smallpox Be Put To Death?

Dear Carl:

There’s a debate in the scientific community about what to do with the remaining stocks of smallpox virus on the planet. Should the virus be preserved so that it can be studied? Or should the virus be destroyed, so that—in theory at least—it would become extinct and would not threaten the human species again?

Smallpox virus, or Variola major, is the cause of probably the worst infectious disease in human history. During the nineteenth and twentieth centuries, experts believe that smallpox killed half a billion people, accounting for far more deaths than all the wars of the time. Smallpox is a grisly and supremely painful disease. The disease has around a 33 percent case-fatality rate in unvaccinated patients. That is, a third of the disease’s victims who haven’t been vaccinated die. The victims suffer from an incredibly painful rash—blisters known as pustules stud the body. The survivors are typically left with scars for life. About ten percent of fatal smallpox cases consist of hemorrhagic smallpox, a manifestation of the disease in which the victim dies with hemorrhagic symptoms, including bleeding from the orifices. Smallpox virus spreads in the air from person to person, traveling in tiny droplets spewed when an infected person speaks or coughs. The vast majority of the world’s population today has little or no immunity to smallpox, because vaccination ceased during the 1970s.

Smallpox was declared eradicated globally in 1980 by the World Health Organization (WHO), after a remarkable and heroic WHO-led effort to eradicate the virus worldwide. Today, the only remaining samples of live smallpox virus are stored in just two locations: a high-security lab at the Centers for Disease Control in Atlanta, Georgia, USA, and in the Vector State Research Center in Siberia, Russia. For a number of years, now, various member nations of the WHO have been pressing the WHO to order those stocks destroyed.

The smallpox virus stock at the CDC occupies a volume about the size of a basketball; the virus samples are frozen in small plastic tubes the size of pencil stubs. The Russian stock is probably similar. It would be very easy to destroy the virus: just heat it up.

But should it be destroyed? A series of defectors from the old Soviet Union have revealed that the Soviet Union weaponized smallpox; that the virus was a mainstay of the clandestine Soviet biowarfare program. Illicit stocks of smallpox may have been taken out of Russia; nobody knows where the virus might exist on earth today in the form of undisclosed, secret stocks of the virus.

Researchers using live smallpox virus at the CDC have been studying the virus in an effort to develop antiviral drugs that would be effective against a smallpox infection. The drugs might also be effective against genetically engineered smallpox.

The genome sequence of smallpox virus is publicly available and can be downloaded from the Internet. Some day it will probably be technically feasible to recreate live smallpox from its genome sequence. Even if all the living smallpox were destroyed, it might be brought back to life in a lab somewhere, some day.

D. A. Henderson, who led the WHO eradication of smallpox, argues that the virus should be destroyed, regardless of whether it can be recreated. He argues that if the WHO makes smallpox extinct, then anyone who later had the live virus would be committing a crime against humanity and could be prosecuted in international courts.

On the other hand, researchers who are developing defenses against smallpox argue that the disease is simply too dangerous to destroy; they argue that we must continue to study it under the principle of Sun Tzu, “Know thy enemy.”

What do you think?

Richard

**

Dear Richard:

Your question is a timely one. On May 16, the World Health Organization will be having their annual meeting, and one of the items on their agenda is a global consensus about what to do with the world’s remaining smallpox stocks.

If WHO does decide on eradication, it will be an historical moment. We humans have only eliminated two viruses from the wild. Smallpox was the first. The second, as of last October, is rinderpest, a devastating scourge of cattle. For now, both smallpox and rinderpest remain in laboratory stocks. But if WHO decides to get rid of the smallpox lab stocks, too, the virus may be eliminated from the planet.

The prospect of such a milestone raises the question of why we haven’t been able to wipe out any of the other viruses that plague us. In some cases, it’s because viruses have escape routes. In 2004, for example, SARS burst on the scene, killing 774 people in total before quarantines and other public health measures beat it back. There have been no reported cases of SARS since then in humans, but SARS is probably thriving. It spread from animal hosts—bats and civets—to humans, and it doubtless retreated back to them.

Some viruses are hard to eradicate because they’re lurkers. HIV takes years to produce symptoms, making it hard to recognize and treat infected people. By the time it makes itself known, people may have spread it to many other victims. And doctors still lack vaccines for HIV and many other viruses.

SARS virus

In all these respects, smallpox is a peculiar virus. Unlike SARS, smallpox only infects humans. Unlike HIV, smallpox makes itself known in a matter of days. It’s also unusual in that there’s a cheap, effective smallpox vaccine. Combined, these three factors made it possible to effectively break the transmission cycle of smallpox and thereby drive it towards extinction.

Whenever a species goes extinct, we lose the opportunity to get to know it better. I’m sure no one would shed a tear at the extinction of smallpox, but, as you note, there’s a lot we still don’t understand about the virus. I don’t think getting the opportunity to try people for crimes against humanity is worth giving up the chance to learn more about smallpox.

Even if smallpox never rears its ugly head again, that knowledge could still be valuable. Studies on smallpox DNA suggest that it evolved just a few thousand years ago from a pox that infected African rodents. Many closely related pox strains infect animals today, and they have plenty of chances to evolve into a new human pox. In 2003, for example, people in the Midwest came down with monkeypox, an African virus that is closely related to smallpox. It was baffling at first that an African pox could infect American victims. Eventually public health workers determined that the victims got the virus from prairie dogs they all bought at the same Missouri pet store.

If smallpox can help us prepare for the next pox, we should resist the urge to annihilate it.

Carl

Stay tuned for next Friday’s installment of TRAFFIC, featuring a conversation between Zimmer and Timothy Lu on phage therapy. 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. Additional materials, including those directed at a K-12 audience, can be found on the World of Viruses website.

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 withSallie Chisholm, biological oceanographer and marine science expert.

With that in mind, join us for our first TRAFFIC exchange with Zimmer and Lipkin below:

The 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.

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.

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.