by Sam Kean
Not until the completion of the Human Genome Project around 2000 did biologists grasp how extensively microbes can infiltrate even higher animals. The name Human Genome Project even became something of a misnomer, because it turned out that 8 percent of our genome isn’t human at all: a quarter billion of our base pairs are old virus genes. Human genes actually make up less than 2 percent of our total DNA, so by this measure, we’re four times more virus than human. One pioneer in studying viral DNA, Robin Weiss, put this evolutionary relationship in stark terms: “If Charles Darwin reappeared today,” Weiss mused, “he might be surprised to learn that humans are descended from viruses as well as from apes.”
How could this happen? From a virus’s point of view, colonizing animal DNA makes sense. For all their deviousness and duplicity, retroviruses that cause cancer or diseases like AIDS are pretty stupid in one respect: they kill their hosts too quickly and die with them. But not all viruses rip through their hosts like microscopic locusts. Less ambitious viruses learn to not disrupt too much, and by showing some restraint they can trick a cell into quietly making copies of themselves for decades. Even better, if viruses infiltrate sperm or egg cells, they can trick their host into passing on viral genes to a new generation, allowing a virus to “live” indefinitely in the host’s descendants. (This is happening right now in koalas, as scientists have caught retroviral DNA spreading through koala sperm.) That these viruses have adulterated so much DNA in so many animals hints that this infiltration happens all the time, on scales a little frightening to think about.
Of all the extinct retrovirus genes loaded into human DNA, the vast majority have accumulated a few fatal mutations and no longer function. But otherwise these genes sit intact in our cells and provide enough detail to study the original virus. In fact, in 2006 a virologist in France named Thierry Heidmann used human DNA to resurrect an extinct virus—Jurassic Park in a petri dish. It proved startlingly easy. Strings of some ancient viruses appear multiple times in the human genome (the number of copies ranges from dozens to tens of thousands). But the fatal mutations appear, by chance, at different points in each copy. So by comparing many strings, Heidmann could deduce what the original, healthy string must have been simply by counting which DNA letter was most common at each spot. The virus was benign, Heidmann says, but when he reconstituted it and injected it into various mammalian cells—cat, hamster, human—it infected them all.
Rather than wring his hands over this technology (not all ancient viruses are benign) or prophesy doom about it falling into the wrong hands, Heidmann celebrated the resurrection as a scientific triumph, naming his virus Phoenix after the mythological bird that rose from its own ashes. Other scientists have replicated Heidmann’s work with other viruses, and together they founded a new discipline called paleovirology. Soft, tiny viruses don’t leave behind rocky fossils, like the ones paleontologists dig up, but the paleovirologists have something just as informative in fossil DNA.
Close examination of this “wet” fossil record suggests that our genome might be even more than 8 percent virus. In 2009, scientists discovered in humans four stretches of DNA from something called the bornavirus, which has infected hoofed animals since time immemorial. (It’s named after a particularly nasty outbreak among horses in 1885, in a cavalry unit near Borna, Germany. Some of the army horses went stark mad and smashed their own skulls in.) About forty million years ago, a few stray bornaviruses jumped into our monkey ancestors and took refuge in their DNA. It had lurked undetected and unsuspected since then because bornavirus is not a retrovirus, so scientists didn’t think it had the molecular machinery to convert RNA to DNA and insert itself somewhere. But lab tests prove that bornavirus can indeed somehow weave itself into human DNA in as few as thirty days. And unlike the mute DNA we inherited from retroviruses, two of the four stretches of borna DNA work like bona fide genes.
Scientists haven’t pinned down what those genes do, but they might well make proteins we all need to live, perhaps by boosting our immune systems. Allowing a nonlethal virus to invade our DNA probably inhibits other, potentially worse viruses from doing the same. More important, cells can use benign virus proteins to fight off other infections. It’s a simple strategy, really: casinos hire card counters, computer security agencies hire hackers, and no one knows how to combat and neutralize viruses better than a reformed germ. Surveys of our genomes suggest that viruses gave us important regulatory DNA as well. For instance, we’ve long had enzymes in our digestive tracts to break down starches into simpler sugars. But viruses gave us switches to run those same enzymes in our saliva, too. As a result starchy foods taste sweet inside our mouths. We certainly wouldn’t have such a starch-tooth for breads, pastas, and grains without these switches.
These cases may be only the beginning. Almost half of human DNA consists of (à la Barbara McClintock) mobile elements and jumping genes. One transposon alone, the 300-base-long alu, appears a million times in human chromosomes and forms fully 10 percent of our genome. The ability of this DNA to detach itself from one chromosome, crawl to another, and burrow into it like a tick looks awfully viruslike. You’re not supposed to interject feelings into science, but part of the reason it’s so fascinating that we’re 8 percent (or more) fossilized virus is that it’s so creepy that we’re 8 percent (or more) fossilized virus. We have an inborn repugnance for disease and impurity, and we see invading germs as something to shun or drive out, not as intimate parts of ourselves—but viruses and viruslike particles have been tinkering with animal DNA since forever. As one scientist who tracked down the human bornavirus genes said, highlighting the singular, “Our whole notion of ourselves as a species is slightly misconceived.”
It gets worse. Because of their ubiquity, microbes of all kinds—not just viruses but bacteria and protozoa—can’t help but steer animal evolution. Obviously microbes shape a population by killing some creatures through disease, but that’s only part of their power. Viruses, bacteria, and protozoa bequeath new genes to animals on occasion, genes that can alter how our bodies work. They can manipulate animal minds as well. One Machiavellian microbe has not only colonized huge numbers of animals without detection, it has stolen animal DNA—and might even use that DNA to brainwash our minds for its own ends.
Sometimes you acquire wisdom the hard way. “You can visualize a hundred cats,” Jack Wright once said. “Beyond that, you can’t. Two hundred, five hundred, it all looks the same.” This wasn’t just speculation. Jack learned this because he and his wife, Donna, once owned a Guinness-certified world record 689 housecats.
It started with Midnight. Wright, a housepainter in Ontario, fell in love with a waitress named Donna Belwa around 1970, and they moved in together with Donna’s black, long-haired cat. Midnight committed a peccadillo in the yard one night and became pregnant, and the Wrights didn’t have the heart to break up her litter. Having more cats around actually brightened the home, and soon after, they felt moved to adopt strays from the local shelter to save them from being put down. Their house became known locally as Cat Crossing, and people began dropping off more strays, two here, five there. When the National Enquirer held a contest in the 1980s to determine who had the most cats in one house, the Wrights won with 145. They soon appeared on The Phil Donahue Show, and after that, the “donations” really got bad. One person tied kittens to the Wrights’ picnic table and drove off; another shipped a cat via courier on a plane—and made the Wrights pay. But the Wrights turned no feline away, even as their brood swelled toward seven hundred.
Bills reportedly ran to $111,000 per year, including individually wrapped Christmas toys. Donna (who began working at home, managing Jack’s painting career) rose daily at 5:30 a.m. and spent the next fifteen hours washing soiled cat beds, emptying litter boxes, forcing pills down cats’ throats, and adding ice to kitty bowls (the friction of so many cats’ tongues made the water too warm to drink otherwise). But above all she spent her days feeding, feeding, feeding. The Wrights popped open 180 tins of
cat food each day and bought three extra freezers to fill with pork, ham, and sirloin for the more finicky felines. They eventually took out a second mortgage, and to keep their heavily leveraged bungalow clean, they tacked linoleum to the walls.
Jack and Donna eventually put their four feet down and by the late 1990s had reduced the population of Cat Crossing to just 359. Almost immediately it crept back up, because they couldn’t bear to go lower. In fact, if you read between the lines here, the Wrights seemed almost addicted to having cats around—addiction being that curious state of getting acute pleasure and acute anxiety from the same thing. Clearly they loved the cats. Jack defended his cat “family” to the newspapers and gave each cat an individual name,* even the few that refused to leave his closet. At the same time, Donna couldn’t hide the torment of being enslaved to cats. “I’ll tell you what’s hard to eat in here,” she once complained, “Kentucky Fried Chicken. Every time I eat it, I have to walk around the house with the plate under my chin.” (Partly to keep cats away, partly to deflect cat hair from her sticky drumsticks.) More poignantly, Donna once admitted, “I get a little depressed sometimes. Sometimes I just say, ‘Jack, give me a few bucks,’ and I go out and have a beer or two. I sit there for a few hours and it’s great. It’s peaceful—no cats anywhere.” Despite these moments of clarity, and despite their mounting distress,* she and Jack couldn’t embrace the obvious solution: ditch the damn cats.
To give the Wrights credit, Donna’s constant cleaning made their home seem rather livable, especially compared to the prehistoric filth of some hoarders’ homes. Animal welfare inspectors not infrequently find decaying cat corpses on the worst premises, even inside a home’s walls, where cats presumably burrow to escape. Nor is it uncommon for the floors and walls to rot and suffer structural damage from saturation with cat urine. Most striking of all, many hoarders deny that things are out of control—a classic sign of addiction.
Scientists have only recently begun laying out the chemical and genetic basis of addiction, but growing evidence suggests that cat hoarders cling to their herds at least partly because they’re hooked on a parasite, Toxoplasma gondii. Toxo is a one-celled protozoan, kin to algae and amoebas; it has eight thousand genes. And though originally a feline pathogen, Toxo has diversified its portfolio and can now infect monkeys, bats, whales, elephants, aardvarks, anteaters, sloths, armadillos, and marsupials, as well as chickens.
Wild bats or aardvarks or whatever ingest Toxo through infected prey or feces, and domesticated animals absorb it indirectly through the feces found in fertilizers. Humans can also absorb Toxo through their diet, and cat owners can contract it through their skin when they handle kitty litter. Overall it infects one-third of people worldwide. When Toxo invades mammals, it usually swims straight for the brain, where it forms tiny cysts, especially in the amygdala, an almond-shaped region in the mammal brain that guides the processing of emotions, including pleasure and anxiety. Scientists don’t know why, but the amygdala cysts can slow down reaction times and induce jealous or aggressive behavior in people. Toxo can alter people’s sense of smell, too. Some cat hoarders (those most vulnerable to Toxo) become immune to the pungent urine of cats—they stop smelling it. A few hoarders, usually to their great shame, reportedly even crave the odor.
Toxo does even stranger things to rodents, a common meal for cats. Rodents that have been raised in labs for hundreds of generations and have never seen a predator in their whole lives will still quake in fear and scamper to whatever cranny they can find if exposed to cat urine; it’s an instinctual, totally hardwired fear. Rats exposed to Toxo have the opposite reaction. They still fear other predators’ scents, and they otherwise sleep, mate, navigate mazes, nibble fine cheese, and do everything else normally. But these rats adore cat urine, especially male rats. In fact they more than adore it. At the first whiff of cat urine, their amygdalae throb, as if meeting females in heat, and their testicles swell. Cat urine gets them off.
Toxo toys with mouse desire like this to enrich its own sex life. When living inside the rodent brain, Toxo can split in two and clone itself, the same method by which most microbes reproduce. It reproduces this way in sloths, humans, and other species, too. Unlike most microbes, though, Toxo can also have sex (don’t ask) and reproduce sexually—but only in the intestines of cats. It’s a weirdly specific fetish, but there it is. Like most organisms, Toxo craves sex, so no matter how many times it has passed its genes on through cloning, it’s always scheming to get back inside those erotic cat guts. Urine is its opportunity. By making mice attracted to cat urine, Toxo can lure them toward cats. Cats happily play along, of course, and pounce, and the morsel of mouse ends up exactly where Toxo wanted to be all along, in the cat digestive tract. Scientists suspect that Toxo learned to work its mojo in other potential mammal meals for a similar reason, to ensure that felines of all sizes, from tabbies to tigers, would keep ingesting it.
This might sound like a just-so story so far—a tale that sounds clever but lacks real evidence. Except for one thing. Scientists have discovered that two of Toxo’s eight thousand genes help make a chemical called dopamine. And if you know anything about brain chemistry, you’re probably sitting up in your chair about now. Dopamine helps activate the brain’s reward circuits, flooding us with good feelings, natural highs. Cocaine, Ecstasy, and other drugs also play with dopamine levels, inducing artificial highs. Toxo has the gene for this potent, habit-forming chemical in its repertoire—twice—and whenever an infected brain senses cat urine, consciously or not, Toxo starts pumping it out. As a result, Toxo gains influence over mammalian behavior, and the dopamine hook might provide a plausible biological basis for hoarding cats.*
Toxo isn’t the only parasite that can manipulate animals. Much like Toxo, a certain microscopic worm prefers paddling around in the guts of birds but often gets ejected, forcefully, in bird droppings. So the ejected worm wriggles into ants, turns them cherry red, puffs them up like Violet Beauregarde, and convinces other birds they’re delicious berries. Carpenter ants also fall victim to a rain-forest fungus that turns them into mindless zombies. First the fungus hijacks an ant’s brain, then pilots it toward moist locations, like the undersides of leaves. Upon arriving, the zombified ant bites down, and its jaws lock into place. The fungus turns the ant’s guts into a sugary, nutritious goo, shoots a stalk out of its brain, and sends out spores to infect more ants. There’s also the so-called Herod bug—the Wolbachia bacteria, which infects wasps, mosquitoes, moths, flies, and beetles. Wolbachia can reproduce only inside female insects’ eggs, so like Herod in the Bible, it often slaughters infant males wholesale, by releasing genetically produced toxins. (In certain lucky insects, Wolbachia has mercy and merely fiddles with the genes that determine sex in insects, converting male grubs into females ones—in which case a better nickname might be the Tiresias bug.) Beyond creepy-crawlies, a lab-tweaked version of one virus can turn polygamous male voles—rodents who normally have, as one scientist put it, a “country song… love ’em and leave ’em” attitude toward vole women—into utterly faithful stay-at-home husbands, simply by injecting some repetitive DNA “stutters” into a gene that adjusts brain chemistry. Exposure to the virus arguably even made the voles smarter. Instead of blindly having sex with whatever female wandered near, the males began associating sex with one individual, a trait called “associative learning” that was previously beyond them.
The vole and Toxo cases edge over into uncomfortable territory for a species like us that prizes autonomy and smarts. It’s one thing to find broken leftover virus genes in our DNA, quite another to admit that microbes might manipulate our emotions and inner mental life. But Toxo can. Somehow in its long coevolution with mammals, Toxo stole the gene for dopamine production, and the gene has proved pretty successful in influencing animal behavior ever since—both by ramping up pleasure around cats and by damping any natural fear of cats. There’s also anecdotal evidence that Toxo can alter other fear signals in the brain, ones unrelated to ca
ts, and convert those impulses into ecstatic pleasure as well. Some emergency room doctors report that motorcycle crash victims often have unusually high numbers of Toxo cysts in their brains. These are the hotshots flying along highways and cutting the S-turns as sharp as possible—the people who get off on risking their lives. And it just so happens that their brains are riddled with Toxo.
It’s hard to argue with Toxo scientists who—while thrilled about what Toxo has uncovered about the biology of emotions and the interconnections between fear, attraction, and addiction—also feel creeped out by what their work implies. One Stanford University neuroscientist who studies Toxo says, “It’s slightly frightening in some ways. We take fear to be basic and natural. But something can not only eliminate it but turn it into this esteemed thing, attraction. Attraction can be manipulated so as to make us attracted to our worst enemy.” That’s why Toxo deserves the title of the Machiavellian microbe. Not only can it manipulate us, it can make what’s evil seem good.
Peyton Rous’s life had a happy if complicated ending. During World War I, he helped establish some of the first blood banks by developing a method to store red blood cells with gelatin and sugar—a sort of blood Jell-O. Rous also bolstered his early work on chickens by studying another obscure but contagious tumor, the giant papilloma warts that once plagued cottontail rabbits in the United States. Rous even had the honor, as editor of a scientific journal, of publishing the first work to firmly link genes and DNA.
