Good news for anyone who's 2 feet tall and bleeding out of his nipples: A new drug treatment has eliminated the Ebola virus from a monkey host. Last week, immunologists in Winnipeg, Canada, presented a cocktail of monoclonal antibodies that can rescue a macaque with hemorrhagic fever. As for humans, who knows? Ebola enthusiasts (they do exist) might point out that we've already stopped the virus in monkeys using RNA interference and experimental vaccines—two approaches that never panned out in people.
It's a problem that affects all animal research: Some non-human models of disease produce spectacular, world-changing results; others turn out to be a waste of time. How can we tell the difference? Scientists have struggled with this question for as long as they've been doing dissections, and anyone with the answer would soon have a seat in the Blue Hall. But the issue of when, exactly, data drawn from one species can (or should) be applied to another isn't confined to scholars. It has crept into everyday language and shaped the way the rest of us talk about science. Whenever we invoke the standard metaphor for experimental subjects, calling someone or something a guinea pig, we invoke a long-standing debate among scientists and natural philosophers over the question of what a lab mouse or a hemorrhagic monkey can tell us about a man.
Aspects of that debate are reflected in the ways we use the guinea pig as an emblem of science. To call someone or something a guinea pig may suggest a mere experiment ("Joe Biden was put out as a guinea pig for the White House"), or it can invoke the specter of exploitation (the U.S. Army wanted "to use young men as guinea pigs and throw them away"). The image either describes the scientific process or condemns it. It's a totem or a scarecrow.
What makes this wording more curious is the fact that guinea pigs, real ones, don't mean much to working scientists. For all their rhetorical importance, the animals scarcely register in the lab: According to the National Library of Medicine, researchers now publish around 50,000 studies per year using mice, another 36,000 using rats, and just 1,300 with guinea pigs. Even the macaque monkey—an animal that costs at least a thousand times more to buy and maintain than a guinea pig—shows up 50 percent more often in the published literature.
How did this laboratory oddball, a chubby and docile rodent that was domesticated 3,000 years ago in South America, become the icon of science and its excess?
The guinea pig's celebrity (and infamy) dates to the late 1800s and the sundry reputations of the early germ theorists. One by one, the major diseases of the time were reduced to their bacterial causes. Robert Koch, a country doctor working out of his cottage in Wollstein, Germany, identified the agents responsible for anthrax, cholera, and staphylococcus. He began by swapping sera from field mice, rabbits, monkeys, and guinea pigs, but the latter proved especially apt. Bred as a food source, guinea pigs were gentle, quiet, unperturbed by cages, and—by a fortunate coincidence, perhaps—prone to infectious disease. (You can give a Cavy full-blown tuberculosis with a single Mycobacterium tuberculosis, says TB researcher David McMurray.*) By the time he was named to a prestigious professorship in Berlin, Koch was using guinea pigs by the armful.
Meanwhile, the guinea pig had become a poster animal for the movement to ban, or at least temper, the practice of vivisection. An 1886 tract called "Some Fallacies of Science" bemoaned the "high priests" whose work amounted to determining "the length of time a new poison takes to kill a guinea-pig." Another described the experimental guinea pig as "a little creature, about the size of a half-grown kitten," prone to "piercing little squeaks" when placed under the knife. According to A Guinea Pig's History of Biology by Jim Endersby (from which both those examples are drawn), the importance of this animal among humane societies arose from the its long-standing popularity in the home. Queen Elizabeth I had kept one in her royal menagerie, and in the Victorian Age guinea pigs were bred and groomed for shows, as dogs are today.
The laboratory guinea pig's most dramatic moment came in 1890. It had been 8 years since Koch's greatest achievement, the discovery of the bacterium responsible for tuberculosis. The "Great White Plague" was the most pressing medical issue of the time, responsible for an estimated one-seventh of all deaths in Europe, rich and poor alike. Yet Koch’s cultures of the waxy-coated bug hadn't led to any progress toward a cure. Critics of microbiology noted that for all its success in naming organisms, this new science had done almost nothing to save human lives. Then, on Aug. 4, Koch stood before an international medical conference and made the declaration that everyone was waiting for. He'd found a cure for TB using guinea pigs.
Within a week, 1,500 doctors had arrived in Berlin, along with a horde of patients in search of treatment. Sickened throngs turned up at hotels and boarding houses, or slept outside in the hopes of getting a dose of "Koch's lymph," a precious liquid the color of East Indian sherry. Arthur Conan Doyle, having arrived from London to interview the scientist, reported that "his name is on every lip, his utterances are the constant subject of conversation, but, like the Veiled Prophet, he still remains unseen to any eyes save those of his own immediate coworkers and assistants." Doyle found Koch sitting amid a pile of written requests for the cure, "four feet across and as high as a man's knee … and that was a single post."
While Koch's fame grew in Berlin and around the world, precious vials of his lymph were smuggled across the continent and then to New York City, where rumors spread, patients mobbed anew, and charlatans hawked knockoff versions under private labels. In Germany, Koch's discovery earned him a personal audience with the emperor, the nation's highest medal, and a payout of 1 million marks from a pharmaceutical firm. And as tumult over the discovery raged in the streets of Berlin, the 46-year-old celebrity scientist left his wife for a beautiful, teenaged actress.
But supplies of the serum never matched demand, and the doses that were administered seemed to have little effect. Desperation turned into suspicion. "Too much has been expected of the lymph," the New York Times declared in December, and by the following summer the miracle drug had been declared a bust. Koch's son-in-law failed to replicate the finding, even in animals. As one physician told the Times: "The effect of the lymph treatment on the patients was often largely the result of their imagination. They believed they felt better because the lymph was heralded as a great cure."
Koch had announced his findings prematurely. The data he'd collected from guinea pigs failed to translate to the clinic. Animal research, which had been developing throughout the 19th century, was all at once made suspect. One of the best-known scientists of his day, the father of germ theory, had created a frenzy of false hope on the basis of a treatment that worked only in a lab cage.
Microbiology was not itself a bust, of course: Also in 1890, two of Koch's former trainees, Emil von Behring and Kitasato Shibasaburo, published their discovery of "antitoxins" (antibodies) against diphtheria and tetanus, a finding that would lead to the production of commercial vaccines a few years later. After these came many others, and the animal work that began in Koch's cottage eventually led to our mastery of infectious disease. But among Anglophones, Koch's favorite animal came to stand in for scientific failure and the perils of medical research.
In 1906, George Bernard Shaw published a play called The Doctor's Dilemma, about a scientist who had discovered a cure for tuberculosis. Its fervid introduction referred to bacteriology as a "superstition," inveighed against "the perils of inoculation," and impugned the value of animal research. A few years later, Shaw described in an essay the "folly which sees in the child nothing more than the vivisector sees in a guinea pig: something to experiment on with a view to rearranging the world to suit his own little ideas." Through one of England's greatest playwrights, the anger over vaccination and animal research turned the guinea pig into an unflattering metaphor for science.
The phrase guinea pig began as an insult, but its meaning shifted in the decades that followed. In the early 20th century, scientists used guinea pigs to find the cause of scurvy. (Like humans, guinea pigs can't make their own vitamin C.) And as the research establishment grew in size and significance during World War II, the expression human guinea pig gained in popularity, as did the idea of serving (voluntarily) as a guinea pig. While some military scientists experimented on humans in awful, secret ways, others had nobler projects. When Kenneth Mellanby published Human Guinea Pigs in 1945, he used the metaphor to describe the willing test-subjects who helped discover the source of scabies transmission in the military—and thus keep two divisions' worth of British soldiers out of the hospital.
By the late 1960s, attitudes toward government-funded animal research had begun to shift back toward skepticism. The passage of the Laboratory Animal Welfare Act in 1966 marked the transition to a more sensitive era, and the guinea pig metaphor, now half a century old, served once again as a warning. When bioethicist Maurice Pappworth published another book called Human Guinea Pigs in 1967, his title was meant to be taken in Shaw’s original sense: Doctors were using other people to suit their own little ideas.
Meanwhile, the few uses guinea pigs had in science were almost gone. The rapid growth of rat and mouse research between the 1930s and 1960s pushed the guinea pig to the margins of biomedicine. Not many people study the Cavia porcellus anymore, but it remains at the center of the debate over the value and ethics of animal work.
Update, June 25, 2012: Among English-speakers, the lab animal that stands for all other lab animals—and for our ambivalence about animal research—is the guinea pig. Other languages have their own iconic species, however. I mentioned last week that the equivalent phrase in German is Versuchskaninchen, or "research rabbit." Readers sent in a few more versions:
In Swedish, the word is försökskanin, or "experimental rabbit"—just like the German. Same goes for the Dutch proefkonijn, meaning "trial rabbit."
The French say cobaye, "guinea pig," perhaps influenced by Koch's archrival Louis Pasteur (who also tested on Cavia porcellus.)
In Spain, they use raton de laboratorio, or "lab rat."
In China, the metaphor for test-subjects is bai lao shu, meaning "white rat" or "white mouse."
Correction, June 20, 2012: This article originally described a single Mycobacterium tuberculosis as a “spore.” That word refers to a dormant stage in the life cycle of certain bacteria, fungi and plants. The microbe that causes TB does not produce spores. (Return to the corrected sentence.)