In China, the world’s manufacturing powerhouse, a new industry is taking shape: the mass production of mutant mice. Peek into the 45,000 mouse cages at Shanghai’s Fudan University and you’ll see a growing collection of misfits. By randomly disabling the rodents’ genes, the scientists here are churning out hundreds of odd animals, assembly-line style. They have created mice studded with skin tumors and mice that grow tusks. There’s a mouse with male-pattern baldness, hair everywhere save for a lonely bare spot on its head.
Some of the mice have strange behavioral quirks—they endlessly bury marbles, for instance, or make only left turns. One strain ages at warp speed. Another can’t feel pain. While some of the rodents have obvious abnormalities, others reveal their secrets over time. One variety appears normal on the outside, with thick white fur and healthy pink ears and noses. But the animals are klutzes. They are clumsy and spectacularly uncoordinated. They fail miserably when researchers put them through their paces at a special rodent boot camp.
In one test, the mice are tasked with standing on top of a rotating rod for as long as they can manage, the rodent equivalent of a logrolling challenge. It’s not an easy undertaking, but normal mice eventually find their footing. The mutant mice never do. They also have trouble balancing on a narrow wooden beam and keeping their grip when suspended, upside down, from a wire screen. And they have strange gaits—taking abnormally wide steps and holding their tails at odd angles, curved up toward the ceiling, instead of letting them simply drag along the floor behind them, as mice usually do.
Even stranger, perhaps, are the Lonely Hearts Club mice. The males of this strain look like regular rodents, but the females consistently refuse to mate with them. The poor guys, lacking some certain je ne sais quoi, simply have no sex appeal, and they are rejected time and time again. These mice are just a small sample of the more than 500 different kinds of mutants the Fudan team has created. Ultimately, the researchers hope to create 100,000 strains of modified mice, each eccentric in its own way.
It would be enough to fill a carnival sideshow thousands of times over. * * * As long as we’re dreaming up animal sideshows, we needn’t stop with peculiar mice. Science has given us a whole new toolbox for tinkering with life, and we have the power to modify animals in profound new ways. We are editing their genetic codes, rebuilding their broken bodies, and supplementing their natural senses. Headlines frequently herald the birth of strange new creatures: Bionic beetles! Glowing cats! Spider goats! Roborats!
The breakthroughs are simultaneously astounding and puzzling. What are these creatures exactly? What do they look like? Who’s creating them, and why? And are these animals really so novel? Indeed, we have a long history of refashioning animal bodies. Take the varied members of the species Canis lupus familiaris—the modern dog—which are products of millennia of life with humans and bear little resemblance to their ancestors, gray wolves. Exactly how this dog domestication began is a subject of intense debate.
Some scientists suggest that we deliberately set out to acquire canine companions, adopting wild wolf pups. Others hypothesize that hungry wolves, attracted to the bones, trash, and scraps produced by early humans, approached our camps on their own terms, and that our tolerance of the least threatening interlopers gave rise to future generations of human-friendly canines. Either way, as wolves became part of human society, moving from cold ground to warm hearth, they lost many of the traits they needed to survive in the wild.
Their bodies and heads shrank, their faces and jaws grew more compact, and their teeth decreased in size. As our relationship with canines developed, we began to breed them more carefully, molding dogs that excelled at specific tasks. We created the bulky, barrel-chested mastiff to guard our homes, and the dachshund, a wiggly salami of a dog, to shimmy into badger burrows. The diversity among modern dogs is so astounding that the thirty thousand dogs that strut their canine stuff at Crufts, the largest dog show in the world, don’t even look like members of the same species.
One year, the “Best in Show” contenders included King, a hound with a deer’s build, all legs and lean muscle, and Ricky, a tiny black-and-white fluff ball who could stand easily underneath King’s smooth brown belly. They shared the ring with Donny—a standard poodle whose shaved gray haunches were set off by a thick white mane—and Cruella, an Old English sheepdog whose long, shaggy hair obscured all but the black dot that presumably served as her nose. Today, thanks to us, dogs are the most physically diverse species on Earth.
We’ve reshaped other species, too, turning scrawny chickens into plump broiler birds and bristlyhaired wild sheep into producers of soft wool. The list goes on and on. We learned to breed animals that suited our every need, creating hunters, herders, guardians, food sources, and companions. Over the course of generations, the members of many species diverged from their wild ancestors and took their place in a human world. But selective breeding was a blunt instrument, one that required us to transform animals using educated guesswork, breeding desirable hounds together, over and over again, until a puppy we liked squirmed into the world.
It took thousands of years to turn wolves into dogs. Now we can create novel organisms in years, months, even days. Today, the tools of molecular biology allow us to target one specific gene, to instantly turn it on or off, to silence or amplify its effects. For instance, the researchers at Fudan University are creating their stunning array of strange mice simply by knocking out a single gene at a time. To do so, they’re relying on a special genetic tool called a transposon or a “jumping gene,” a segment of DNA capable of hopping around the genome.
When the scientists inject a transposon into a mouse embryo, this foreign piece of DNA inserts itself into a random place in the rodent’s genome, disabling whatever gene it finds there. But the real beauty of the system is that when this mouse grows up and mates, the transposon jumps to a different location in the genome of its pups, sabotaging a new gene. With each mating, researchers have no idea where the transposon will end up, what gene it will disrupt, or what the ultimate effects will be. It’s like throwing darts at a genetic dartboard. Blindfolded.
Only when the pups are born, and start exhibiting various abnormalities, do the scientists learn what part of the genome has gone haywire. The approach is allowing the researchers to create cages upon cages of novel mutants, simply by playing matchmaker between their amorous rodents. In some cases, the scientists are making furry freaks faster than they can figure out what’s wrong with them. We can also recombine genes in ways that nature never would—just consider a very curious cat skulking about New Orleans. With downy orange fur and a soft pink nose, the feline looks like your average tabby.
But flick on a black light, and the cat becomes Mr. Green Genes, his nose turning from soft pink to electric lime, due to a bit of jellyfish DNA tucked into each of his cells. The insides of his ears and the whites of his eyes glow brightly, his face emerging from the dark like a modern-day Cheshire cat. (His son, Kermit, also glows green. ) Meanwhile, nearly two thousand miles away, a barn in Logan, Utah, is home to a strange herd of goats. Thanks to a pair of genes borrowed from a spider, each female goat produces milk that’s chockfull of silk proteins.
When the milk is processed in the lab, scientists can extract the spider proteins and spin them into silk. Genetics isn’t the only field providing us with the power to reengineer other species. Advances in electronics and computing make it possible to merge animal bodies with machines, to use tiny electrodes to hijack a rat’s brain and guide the rodent, like a remote-controlled toy, through a complicated obstacle course. Breakthroughs in materials science and veterinary surgery are helping us build bionic limbs for injured animals, and we can train monkeys to control robotic arms with their thoughts.
Today, our grandest science fiction fantasies are becoming reality. * * * Some of us may find our growing control over living, breathing beings to be unsettling. After all, biotechnology is the stuff of dystopian nightmares, and many an apocalyptic scenario has been constructed around crazy chimeras or world-conquering cyborgs. Ethicists and activists worry about whether we should be altering other species when we can’t possibly get their consent. Some say that manipulating the planet’s wild things—whether we’re inserting genes or electrodes—is profoundly unnatural, causes animal suffering, and turns other life-forms into commodities.
Critics worry that our effort to remake the world’s fauna is the worst example of human hubris, the expression of an arrogant desire to play God. It’s true that remaking other species according to our own wants and needs doesn’t necessarily put animal welfare first. Selective breeding hasn’t always turned out well for animals—we’ve saddled dog breeds with all sorts of hereditary diseases and created turkeys with such gigantic breasts that they can barely walk. And of course, biotechnology gives us new ways to do damage.
The Fudan University scientists have created mouse embryos with defects so severe that they die in the womb. Some of their mutant mice are prone to tumors, or kidney disease, or neurological problems. One strain, unable to absorb nutrients from food, essentially starves to death. In fact, a whole industry has sprung up to sell diseased lab animals to scientists, with numerous biotech companies hawking their unique creations. In October 2011, many of these companies converged on St. Pete Beach, Florida, for an international meeting of scientists who work with genetically modified organisms.
Representatives from various biotech firms held court from booths ringing a hotel ballroom, advertising animals that had been engineered to suffer from all sorts of medical afflictions. One company was selling pigs with cystic fibrosis and cancer; a brochure from another outlined eleven available strains of rodents, from the NSE-p25 mouse, designed to display Alzheimer’s-like symptoms, to the 11BHSD2 mouse, which has a tendency to drop dead of heart failure. (And just in case nothing there caught your fancy, one company’s poster promised, “You design the experiment, we’ll design the mice.
”) These companies aren’t making sickly animals purely to be cruel, of course; studying these creatures yields valuable insight into human disease. That’s good news for us, but little consolation for a tumor-riddled rodent. If there is peril here, there is also great promise. Biotechnology could do more for animals than it’s given credit for. Sure, we can make animals sick, but we can also choose to deploy our speciesshaping powers to help other species survive and thrive, to create healthier, happier, fitter critters, and some scientists are doing just that.
With the sophisticated techniques at our fingertips, we may even be able to undo some of the damage we’ve done to other species, alleviating genetic disorders in dogs, for instance, or bringing wild animal populations back from the brink of extinction. Some forwardthinking philosophers are dreaming of more extreme interventions, such as boosting the brainpower of apes, and using genetic modification and electronic enhancement to help animals transcend the limits of their own bodies. Right now all the options are open.
Though biotechnology’s strange new creatures are being created in the world’s labs, they don’t tend to stay there very long, and there are already cutting-edge animals living in fields, homes, and nature preserves across America. Before long, we may all be able to shop for animals the same way that scientists in Florida shopped for carefully engineered mice. Imagine a future in which we can each pick out the perfect animal from a catalogue of endless options. We could create something for everyone. Avid nighttime reader? How about your own Mr. Green Genes so you can stay up late, reading by the light of the cat?
For the twelve-year-old who has everything, skip the toy cars and planes at Christmas and wrap up a remote-controlled rodent. Equestrians could order up a foal with the same genes as the winner of last year’s Kentucky Derby, while sprinters could get themselves a golden retriever whose artificial carbon-fiber legs would allow it to run as fast as a greyhound. The tools of biotechnology are becoming increasingly accessible to the public; future generations of animal lovers may be able to design their own creatures without fancy lab equipment or advanced scientific training.
* * * In the pages that follow, we’ll go on a journey from petri dish to pet store, seeking out the revolutionary breeds of beasts that are taking their places in the world. We’ll venture from the rocky shores of California to the dusty fields of Texas, from the canine clones that live in Korean labs to the pets that sleep in our homes. We’ll delve into genes and brains, into work that seems frivolous and projects that are anything but. We’ll meet an engineer who is turning beetles into stunt planes and a biologist who believes cloning just might save endangered species.
And, of course, we’ll come to know the animals themselves—from Jonathan, a sad sack of a seal with hundreds of online friends, to Artemis, a potentially life-saving goat whose descendants could one day take over Brazil. Along the way, we’ll puzzle through some larger questions. We’ll probe how our contemporary scientific techniques are different from what’s come before and whether they represent a fundamental change in our relationship with other species. We’ll consider the relationship we have with animals and the one we’d like to have.
Most of us care deeply about some form of animal life, whether it’s the cat or dog curled up on the couch—60 percent of Americans share their homes with pets of one species or another—the chickens laying our eggs, or some exotic predator fighting to survive as its habitat disappears. Now that we can sculpt life into an endless parade of forms, what we choose to create reveals what it is we want from other species—and what we want for them. But even if you feel no special affection for the creatures with whom we share this planet, our reinvention of animals matters for us, too.
It provides a peek into our own future, at the ways we may start to enhance and alter ourselves. Most of all, our grand experiments reveal how entangled the lives of human and nonhuman animals have become, how intertwined our fates are. Enterprising scientists, entrepreneurs, and philosophers are dreaming up all sorts of projects that could alter the course of our collective future. So what does biotechnology really mean for the world’s wild things? And what do our brave new beasts say about us? Our search for answers begins with a tank of glowing fish. 1. Go Fish To an aspiring animal owner, Petco presents an embarrassment of riches.
Here, in the basement of a New York City store—where the air carries the sharp tang of hay and the dull musk of rodent dander —is a squeaking, squealing, almost endless menagerie of potential pets. There are the spindly-legged lizards scuttling across their sand-filled tanks; the preening cockatiels, a spray of golden feathers atop their heads; and, of course, the cages of pink-nosed white mice training for a wheel-running marathon. There are chinchillas and canaries, dwarf hamsters, tree frogs, bearded dragons, red-footed tortoises, red-bellied parrots, and African fat-tailed geckoes.
But one of these animals is not like the others. The discerning pet owner in search of something new and different merely has to head to the aquatic display and keep walking past the speckled koi and fantail bettas, the crowds of goldfish and minnows. And there they are, cruising around a small tank hidden beneath the stairs: inch-long candy-colored fish in shades of cherry, lime, and tangerine. Technically, they are zebrafish ( Danio rerio), which are native to South Asian lakes and rivers and usually covered with black and white stripes. But these swimmers are adulterated with a smidgen of something extra.
The Starfire Red fish contain a dash of DNA from the sea anemone; the Electric Green, Sunburst Orange, Cosmic Blue, and Galactic Purple strains all have a nip of sea coral. These borrowed genes turn the zebrafish fluorescent, so under black or blue lights they glow. These are GloFish, America’s first genetically engineered pets. Though we’ve meddled with many species through selective breeding, these fish mark the beginning of a new era, one in which we have the power to directly manipulate the biological codes of our animal friends. Our new molecular techniques change the game.
They allow us to modify species quickly, rather than over the course of generations; doctor a single gene instead of worrying about the whole animal; and create beings that would never exist in nature, mixing and matching DNA from multiple species into one great living mash-up. We have long desired creature companions tailored to our exact specifications. Science is finally making that precision possible. * * * Though our ancestors knew enough about heredity to breed better working animals, our ability to tinker with genes directly is relatively new.
After all, it wasn’t until 1944 that scientists identified DNA as the molecule of biological inheritance, and 1953 that Watson and Crick deduced DNA’s double helical structure. Further experiments through the ’50s and ’60s revealed how genes work inside a cell. For all its seeming mystery, DNA has a straightforward job: It tells the body to make proteins. A strand of DNA is composed of individual units called nucleotides, strung together like pearls on a necklace. There are four distinct types of nucleotides, each containing a different chemical base.
Technically, the bases are called adenine, thymine, guanine, and cytosine, but they usually go by their initials: A, T, C, and G. What we call a “gene” is merely a long sequence of these As, Ts, Cs, and Gs. The order in which these letters appear tells the body which proteins to make—and where and when to make them. Change some of the letters and you can alter protein manufacturing and the ultimate characteristics of an organism. Once we cracked the genetic code, it wasn’t long before we figured out how to manipulate it.
In the 1970s, scientists set out to determine whether it was possible to transfer genes from one species into another. They isolated small stretches of DNA from Staphylococcus—the bacteria that cause staph infections—and the African clawed frog. Then they inserted these bits of biological code into E. coli. The staph and frog genes were fully functional in their new cellular homes, making E. coli the world’s first genetically engineered organism. Mice were up next, and in the early 1980s, two labs reported that they’d created rodents carrying genes from viruses and rabbits.
Animals such as these mice, which contain a foreign piece of DNA in their genomes, are known as transgenic, and the added genetic sequence is called a transgene. Encouraged and inspired by these successes, scientists started moving DNA all around the animal kingdom, swapping genes among all sorts of swimming, slithering, and scurrying creatures. Researchers embarking on these experiments had multiple goals in mind. For starters, they simply wanted to see what was possible. How far could they push these genetic exchanges? What could they do with these bits and pieces of DNA?
There was also immense potential for basic research; taking a gene from one animal and putting it into another could help researchers learn more about how it worked and the role it played in development or disease. Finally, there were promising commercial applications, an opportunity to engineer animals whose bodies produced highly desired proteins or creatures with economically valuable traits. (In one early project, for instance, researchers set out to make a leaner, faster-growing pig. ) Along the way, geneticists developed some neat tricks, including figuring out how to engineer animals that glowed.
They knew that some species, such as the crystal jellyfish, had evolved this talent on their own. One moment, the jellyfish is an unremarkable transparent blob; the next it’s a neon-green orb floating in a dark sea. The secret to this light show is a compound called green fluorescent protein (GFP), naturally produced by the jellyfish, which takes in blue light and reemits it in a kiwi-colored hue. Hit the jelly with a beam of blue light, and a ring of green dots will suddenly appear around its bell-shaped body, not unlike a string of Christmas lights wrapped around a tree.
When scientists discovered GFP, they began to wonder what would happen if they took this jellyfish gene and popped it into another animal. Researchers isolated and copied the jellyfish’s GFP gene in the lab in the 1990s, and then the real fun began. When they transferred the gene into roundworms, rats, and rabbits, these animals also started producing the protein, and if you blasted them with blue light, they also gave off a green glow. For that reason alone, GFP became a valuable tool for geneticists. Researchers testing a new method of genetic modification can practice with GFP, splicing the gene into an organism’s genome.
If the animal lights up, it’s obvious that the procedure worked. GFP can also be coupled with another gene, allowing scientists to determine whether the gene in question is active. (A green glow means the paired gene is on. ) Scientists discovered other potential uses, too. Zhiyuan Gong, a biologist at the National University of Singapore, wanted to use GFP to turn fish into living pollution detectors, swimming canaries in underwater coal mines. He hoped to create transgenic fish that would blink on and off in the presence of toxins, turning bright green when they were swimming in contaminated water.
The first step was simply to make fish that glowed. His team accomplished that feat in 1999 with the help of a common genetic procedure called microinjection. Using a tiny needle, he squirted the GFP gene directly into some zebrafish embryos. In some of the embryos, this foreign bit of biological code managed to sneak into the genome, and the fish gave off that telltale green light. In subsequent research, the biologists also made strains in red—thanks to a fluorescent protein from a relative of the sea anemone—and yellow, and experimented with adding these proteins in combination.
One of their published papers showcases a neon rainbow of fish that would do Crayola proud. * To Richard Crockett, the co-founder of the company that sells GloFish, such creatures have more than mere scientific value—they have an obvious aesthetic beauty. Crockett vividly remembers learning about GFP in a biology class. He was captivated by an image of brain cells glowing green and red, thanks to the addition of the genes for GFP and a red fluorescent protein. Crockett was a premed student, but he was also an entrepreneur. In 1998, at the age of twenty-one, he and a childhood friend, Alan Blake, launched an online education company.
By 2000, the company had become a casualty of the dot-com crash. As the two young men cast about for new business ideas, Crockett thought back to the luminescent brain cells and put a proposal to Blake: What if they brought the beauty of fluorescence genes to the public by selling glowing, genetically modified fish? At first, Blake, who had no background in science, thought his friend was joking. But when he discovered that Gong and other scientists were already fiddling with fish, he realized that the idea wasn’t far-fetched at all.
Blake and Crockett wouldn’t even need to invent a new organism—they’d just need to take the shimmering schools of transgenic fish out of the lab and into our home tanks. The pair founded Yorktown Technologies to do just that, and Blake took the lead during the firm’s early years, setting up shop in Austin, Texas. He licensed the rights to produce the fish from Gong’s lab and hired two commercial fish farms to breed the pets. (Since the animals pass their fluorescence genes on to their offspring, all Blake needed to create an entire line of neon pets was a few starter adults.
) He and his partner dubbed them GloFish, though the animals aren’t technically glow-in-thedark—at least, not the same way that a set of solar system stickers in a child’s bedroom might be. Those stickers, and most other glow-in-the-dark toys, work through a scientific property known as phosphorescence. They absorb and store light, reemitting it gradually over time, as a soft glow that’s visible when you turn out all the lights. GloFish, on the other hand, are fluorescent, which means that they absorb light from the environment and beam it back out into the world immediately.
The fish appear to glow in a dark room if they’re under a blue or black light, but they can’t store light for later —turn the artificial light off, and the fish stop shining. Blake was optimistic about their prospects. As he explains, “The ornamental fish industry is about new and different and exciting varieties of fish. ” And if new, different, and exciting is what you’re after, what more could you ask for than an animal engineered to glow electric red, orange, green, blue, or purple thanks to a dab of foreign DNA?
Pets are products, after all, subject to the same marketplace forces as toys or clothes. Whether it’s a puppy or a pair of heels, we’re constantly searching for the next big thing. Consider the recent enthusiasm for “teacup pigs”—tiny swine cute enough to make you swear off pork chops forever. Harold Herzog, a psychologist at Western Carolina University who specializes in human-animal interactions, has studied the way our taste in animals changes over time.
When Herzog consulted the registry of the American Kennel Club, he found that dog breed choices fade in and out of fashion the same way that baby names do. One minute, everyone is buying Irish setters, naming their daughters Heather, and listening to “Bennie and the Jets”—welcome to 1974! —and then it’s on to the next great trend. Herzog discovered that between 1946 and 2003, eight breeds—Afghan hounds, chow chows, Dalmatians, Dobermans, Great Danes, Old English sheepdogs, rottweilers, and Irish setters—went through particularly pronounced boom and bust cycles.
Registrations for these canines would skyrocket, and then, as soon as they reached a certain threshold of popularity, people would begin searching for the next fur-covered fad. Herzog identified a modern manifestation of our long-standing interest in new and unusual animals. In antiquity, explorers hunted for far-flung exotic species, which royal households often imported and displayed. Even the humble goldfish began as a luxury for the privileged classes. Native to Central and East Asia, the wild fish are usually covered in silvery gray scales.
But ancient Chinese mariners had noticed the occasional yellow or orange variant wriggling in the water. Rich and powerful Chinese families collected these mutants in private ponds, and by the thirteenth century, fish keepers were breeding these dazzlers together. Goldfish domestication was born, and the once-peculiar golden fish gradually spread to the homes of less-fortunate Chinese families—and households elsewhere in Asia, Europe, and beyond. As goldfish grew in popularity, breeders stepped up their game, creating ever more unusual varieties.
Using artificial selection, they created goldfish with freakish and fantastical features, and the world’s aquariums now contain the fantail, the veiltail, the butterfly tail, the lionhead, the goosehead, the golden helmet, the golden saddle, the bubble eye, the telescope eye, the seven stars, the stork’s pearl, the pearlscale, the black moor, the panda moor, the celestial, and the comet goldfish, among others. This explosion of types was driven by the desire for the exotic and exquisite—urges that we can now satisfy with genetically modified pets.
We can also use genetic engineering to create animals that appeal to our aesthetic sensibilities, such as our preference for brightly colored creatures. For instance, a 2007 study revealed that we prefer penguin species that have a splash of yellow or red on their bodies to those that are simply black and white. We’ve bred canaries, which are naturally a dull yellow, to exhibit fifty different color patterns. And before GloFish were even a neon glint in Blake’s eye, pet stores were selling “painted” fish that had been injected with simple fluorescent dyes. With fluorescence genes, we can make a true rainbow of bright and beautiful pets.
* Engineered pets also fit right into our era of personalization. We can have perfume, granola, and Nikes customized to our individual specifications—why not design our own pets? Consider the recent rise of designer dogs, which began with the Labradoodle, a cross between a Labrador retriever and a standard poodle. Though there’s no telling when the first Lab found himself fancying the wellgroomed poodle down the street, most accounts trace the origin of the modern Labradoodle to Wally Conron, the breeding director of the Royal Guide Dog Association of Australia.
In the 1980s, Conron heard from a blind woman in Hawaii, who wanted a guide dog that wouldn’t aggravate her husband’s allergies. Conron’s solution was to breed a Lab, a traditional seeing-eye dog, with a poodle, which has hypoallergenic hair. Other breeders followed Conron’s lead, arranging their own mixed-breed marriages. The dogs were advertised as providing families with the best of both worlds—the playful eagerness of a Lab with the smarts and hypoallergenic coat of the poodle. The rest, as they say, is history.
The streets are now chock-full of newfangled canine concoctions: puggles (a pug-beagle cross), dorgis (dachshund plus corgi), and cockapoos (a cocker spaniel–miniature poodle mix). There’s even a mini Labradoodle for doodle lovers without lots of space. Tweaking the genomes of our companions allows us to create a pet that fulfills virtually any desire —some practical, some decidedly not. When I set out to get a dog, I thought I had settled on the Cavalier King Charles spaniel: small, soft, and bred for companionship.
Then I discovered a breeder who was crossing Cavaliers with miniature poodles, yielding the so-called Cavapoo. I was sold. I loved the scruffier, shaggier hair of the Cavapoo, and given what I knew about biology, I figured that a hybrid was less likely to inherit one of the diseases that plague perilously inbred canines. A dog that didn’t shed would be an added bonus. Plus, poodles have a reputation for being brainy, and I’m an overachiever; if I was going to get a dog, I wanted to be damn sure he’d be the valedictorian of his puppy kindergarten class.