by Hal Herzog
Jackson researchers are particularly enthusiastic about the new field of personalized medicine. Genes play a role in your susceptibility to nearly every disorder, from tooth decay to AIDS. Genes also affect how your body responds to medications. Some people receive no benefit from a drug but suffer serious side effects (for example, those four-hour Viagra-induced penile erections that require an immediate trip to the emergency room). Other people, however, experience few side effects and have excellent treatment results from the same medication. The goal of personalized medicine is to tell who will and who will not benefit from a drug. Woychick believes that studies based on mouse genetics will eventually enable doctors to tailor the right drug and the right dose to meet each patient’s individual needs.
Carl Cohen, a University of Michigan philosopher, also believes that animal research is the key to the advancement of medicine. He is the author of a 1986 New England Journal of Medicine article regarded as the classic defense of animal testing. Cohen writes, “Every advance in medicine—every new drug, new operation, new therapy of any kind must sooner or later be tried on a living being for the first time…. The subject of that experiment, if it is not an animal, will be a human being. Prohibiting the use of live animals in biomedical research, therefore, or sharply restricting it, must result either in the blockage of much valuable research or in the replacement of animal subjects with human subjects. There are consequences—unacceptable to most reasonable persons—of not using animals in research.” That’s the party line, and I admit that I generally buy it—though I would like to see fewer mice killed for yet another minor variation of Claritin and instead used in the search for treatments for the neglected tropical diseases.
Opponents of animal research frame the debate differently. They throw thalidomide and Vioxx in your face as examples of the failures of tests on rodents to screen drugs that later turned out to be harmful to humans. (Mouse researchers dispute these claims.) They say scientists have exaggerated the contributions of animal research to improvements in our health. The anti-vivisectionists argue that 90% of the decline in the mortality rates for childhood killers such as scarlet fever and diphtheria came before the advent of vaccinations for these diseases. Animal research opponents argue that improvements to human well-being are really attributable to better nutrition and sanitation. They think studies on mice often lead down blind alleys and actually retard medical progress.
I support animal research and would like to dismiss the anti-vivisectionists as naïve and uninformed. However, they do have some legitimate points—including, for example, the problem of replication of research results. One reason researchers use inbred strains of mice is that they allow scientists in different labs to check each other’s findings by independently confirming their results. In 1999, the world of mouse researchers was shaken up by an article that appeared in the journal Science. Researchers in Portland, Oregon; Edmonton, Canada; and Albany, New York, ran eight strains of mice through a series of behavioral tests using exactly the same procedures. The animals in each lab were obtained from the same sources; they were born on the same day, fed the same food, reared on the same light-dark cycle, and put through identical procedures at exactly the same age. The experimenters even wore the same brand of surgical gloves when they handled the mice.
Despite the extreme lengths the researchers took to ensure that the animals were treated alike, in some tests the mice behaved remarkably differently. A dose of cocaine completely wired the animals in the Portland lab. Their coked-up brethren in Albany and Edmonton, however, showed little response to the drug. The authors concluded that subtle differences between laboratories mean that researchers can arrive at different conclusions even when studying genetically identical animals. I filed the article in my filing cabinet under “inconvenient truth.”
There is also the contentious issue of how much we can generalize from mice to humans. Biologically, there are some big differences between us and them. We live forty times longer than mice and weigh two thousand times as much. A mouse’s metabolism is seven times faster than a person’s. Our two species have not shared a common ancestor since the age of dinosaurs. Writing in the journal Immunology, Mark Davis, a professor of microbiology at the Howard Hughes Medical Institute, argued that while dozens of experimental treatments work on mice with immune system diseases, few of these have been successful on humans. He has concluded that rodents make poor models for immune disorders.
Ditto neuroscience. Amyotrophic lateral sclerosis (ALS) is a degenerative nerve disease for which there is no cure. The dead include Yankee slugger Lou Gehrig and Bob Waters, the late Western Carolina University football coach who, toward the end, was calling plays from a wheelchair, breathing through a respirator. Among its living victims are the Cambridge University theoretician Stephen Hawking. Disheartened that there are no effective treatments he could offer his ALS patients, Michael Benatar, a clinical neurologist from Emory University, read all the published mouse studies of ALS. He was surprised by the results. First, he concluded that most of the research was flawed. Often the samples were too small or the experiments poorly designed. Secondly, he found that nearly a dozen drugs that increased the life spans of mice with the rodent version of ALS had no effect when tested on humans. In fact, one drug that worked in four mouse studies made people with ALS sicker. Benatar says that using mice to study ALS is like searching for your missing keys at night under a street lamp because that’s where the light is.
The anti–animal research faction, however, should not take too much comfort in the fact that some scientists are questioning the usefulness of the mouse as a model for human neurological disorders. Some neurobiologists have forsaken mice and have turned to animals whose brains are more like ours—monkeys.
HOW LABELS AFFECT OUR ATTITUDES TOWARD
ANIMALS: GOOD MICE, BAD MICE, PET MICE
A recurring theme in anthrozoology is that the ways humans think about animals are mired in an uncomfortable mix of logic and emotion. Some of our decisions about the use of animals in science are perfectly reasonable. For example, an individual’s attitudes about animal research depend, in part, on their perception of the potential payoff of the experiments, the degree of suffering they think the animals will experience, and the species used in the research. A survey conducted in England found that two-thirds of people approved of painful studies on mice aimed at developing a cure for childhood leukemia, but only 5% supported using monkeys to test the safety of cosmetics.
At other times our views on the moral status of animals are more convoluted. Consider the effect of labels and categories on how we think about mice. I once spent a year as a visiting scholar in the University of Tennessee Reptile Ethology Laboratory. The lab is located in the Walters Life Sciences Building, home to hyperactive marmosets, cooing White Carneau pigeons, beady-eyed albino rats, spiky green tobacco worms, and 15,000 mice. The mice were housed in spotless cedar-smelling rooms in the building’s basement, where they were cared for by a competent and fully certified staff. But while all mice in the building belonged to the same species, they were not afforded the same level of moral consideration.
The vast majority of these animals were good mice—the subjects in the hundreds of biomedical and behavioral experiments that were conducted by faculty, post-doctoral fellows, and graduate students. Most of these projects were directly or indirectly related to the search for treatments for the various afflictions that affect our species. Though they did not have any say in the matter, these animals lived and died for our benefit. Because the university received grants from the National Institutes of Health, these mice were treated according to the Public Health Service Guide for the Care and Use of Laboratory Animals. Each research project involving the good mice was approved by the university animal care committee charged with weighing the costs and benefits of the experiments.
There was, however, another category of mice that inhabited the building, the bad mice. The bad mice were pests—free-ranging creatures
you would occasionally glimpse scurrying down the long, fluorescent-lit corridors. These animals were potential threats in an environment where a premium was placed on cleanliness and in which great care was taken to prevent cross-contamination between rooms. The little outlaws had to be eliminated.
The staff of the animal facility had tried several techniques to eradicate bad mice. Snap-traps were ineffective and the staff was reluctant to use poison for fear of contaminating research animals. Thus they settled on sticky traps. Sticky traps are rodent flypaper. Each trap consists of a sheet of cardboard about a foot square, covered with a tenacious adhesive and embedded with a chemical mouse attractant—hence their other name, glue boards. In the evening, animal care technicians would place glue boards in areas where pest mice traveled, and check them the next morning. When a mouse stepped on a sticky trap, it would become profoundly stuck. As it struggled, the animal’s fur would become increasingly mired in the glue. Though the traps did not contain toxins, about half of the animals were dead when they were found the next day. Mice that were still alive in the morning were immediately gassed.
Animals caught in sticky traps suffer a horrible death. I doubt that any animal care committee would approve an experiment in which a researcher requested permission to glue mice to cardboard and leave them overnight. Thus a procedure that was clearly unacceptable for a mouse labeled “subject” was permitted for a mouse labeled “pest.”
This paradox was magnified when I discovered where the pest mice came from. The building, it seemed, did not have a problem with wild rodents, but in a facility housing thousands of small creatures, leakage is inevitable. Thus virtually all the bad mice were good mice that had escaped. The animal colony manager told me, “Once an animal hits the floor, it is a pest.” And poof—its moral status evaporates.
In the Walters building, the moral status of a mouse depended on whether a creature was labeled a subject or a pest. I was quick to criticize this seemingly arbitrary distinction until I realized that the same theme was playing out in my home. For our son’s seventh birthday, I kidnapped a mouse who was destined to become a meal for IM, the two-headed snake, from our lab and gave him to Adam as a birthday present. Adam named the mouse Willie and set up a home for his new pet in a cage in his bedroom. We liked Willie. He was quiet and affectionate. But mice have short life spans, and one morning Adam woke up and found Willie dead on the bottom of his cage. We held a family discussion, and the children decided a funeral ceremony would be appropriate. We put Willie in a little box and buried him in the flower garden with a piece of slate for a headstone. We stood around his grave and said a few nice things about him. Betsy and Katie cried a little; it was their first encounter with death.
A couple of days later, Mary Jean, a neatnik, discovered mouse droppings on the kitchen floor. She looked at me and said, “Kill it.” That night, I put a dab of peanut butter in a snap trap on the floor between the refrigerator and the stove. I found the mouse the next morning. It was a clean kill. This time, there was no funeral. As I tossed the little guy’s body into the bushes not far from Willie’s grave, it struck me that the labels we assign to the animals in our lives—pest, pet, experimental subject—affect how we treat them more than the size of their brain or whether they experience happiness.
THE WASTED MICE
A woman named Susan who worked in a rodent breeding facility recently convinced me that I needed to add a new category to my typology of lab mice. In addition to good mice, bad mice, and pet mice, there are “surplus mice” that are never used in experiments. Lots of them. Some of them will be fed to snakes and owls at a zoo; most will be incinerated. Susan said that in the animal colony where she worked, surplus mouse babies were euthanized nearly every day. One of the senior techs would put handfuls of them in a clear plastic bag, insert the end of a hose that was connected to a tank of carbon dioxide, and turn on the gas. How many mice would be killed in a typical day? Susan said that it varied, but usually about fifty.
I wanted confirmation so I called John, a veterinarian I had met at a conference on the care of laboratory animals. He runs the animal colony at a major research university where many scientists use mice to figure out how genes work.
“John, I just found out that that in some animal colonies, mice are killed without ever being used for research. Is that true?”
“Sure.”
“Do you guys cull surplus mice?”
“Yeah. We have a carbon dioxide chamber.”
“How many animals?”
“Well, four thousand litters are born here every month. There are usually five pups per litter, so that would be a quarter of a million mice a year. We euthanize about half of them. I’d guess about 10,000 mice a month.”
“Holy shit.”
There are several reasons for the proliferation of surplus mice. According to Joe Bielitski, former chief veterinarian for NASA, most males are euthanized because they are prone to fight. Besides, you only need a couple of males to keep a genetic line going. He estimates that 70% of male lab mice are never used in experiments. But the most important reason for the large numbers of wasted mice is the explosion of research on genetically modified (GM) animals that began in the 1990s. Ninety percent of animal GM studies use mice. These experiments have led to important scientific breakthroughs. (A gene that affects the part of the human brain responsible for language was recently inserted into a line of GM mice. The mice did not talk, but they did squeak at a lower pitch and the gene changed the structure of their brains.) From a mouse’s point of view, GM studies are terribly inefficient. It is not easy to slip a piece of DNA into the chromosome of a different species and have it be successfully incorporated into the genome. The efficiency rates of attempts to create a strain of transgenic mice range from 1% to 30%. In other words, sometimes only one animal in a hundred can be used for research. The other ninety-nine will be killed when they are a few weeks old. They are the junk mice, collateral damage.
According to calculations by Andrew Rowan, executive vice president of the Humane Society of the United States and an expert on the use of animals in research, more genetically modified mice are gassed each year in rodent production facilities than are actually used in experiments. But we actually don’t know the exact number for sure because according to Congress, lab mice in the United States are not animals.
ARE MICE ANIMALS?
In 1876, the British Parliament enacted the world’s first law governing the use of animals in research. The United States caught up ninety years later. The events that precipitated congressional action were a pair of articles on dogs. The first was a 1965 Sports Illustrated story about Pepper, a Dalmatian who disappeared from her yard one afternoon, apparently abducted by a dealer who provided animals to laboratories. Pepper’s distraught owners finally located their dog, but only after she had been euthanized at the end of an experiment in a New York hospital. A year later, an article appeared in Life magazine titled “Concentration Camp for Dogs.” Again, the story focused on the treatment of family pets who wound up as laboratory subjects. Members of the House and the Senate were bombarded with letters from constituents worried that their cats and dogs might suffer a similar fate. For a couple of months, Congress received more mail about animal research than about the two great moral issues of the time, the war in Vietnam and civil rights. The House and Senate quickly enacted the Animal Welfare Act of 1966. (It was not until 1974 that the government took steps to ensure that human research subjects were treated ethically.)
The bureaucratic gyrations of the Animal Welfare Act exemplify the convoluted ways humans think about other species. Perhaps the strangest aspect of the legislation concerns an apparently straightforward question—what is an animal? The Act’s definition of the term animal starts reasonably enough: “Animal means any live or dead dog, cat, nonhuman primate, guinea pig, hamster, rabbit, or other such warm-blooded animal, which is being used, or is intended for use for research, teaching, testing, experimentation, or exhibition
purposes, or as a pet.” The smoking gun is in the next sentence. “This term excludes: birds, rats of the genus Rattus and mice of the genus Mus bred for use in research…”
That’s right, according to Congress, mice are not animals. Nor are rats or birds. This means that 90 to 95% of the animals used in research in the United States are not covered under the main federal animal protection legislation. (Mice and other vertebrates used in research at institutions that receive grants from the National Institutes of Health are covered under a separate set of guidelines.) Federal Judge Charles Richey called the mouse/rat/bird exclusion in the Animal Welfare Act arbitrary and capricious. He was right. For instance, the congressional definition of the word animal means that a researcher who unobtrusively videotapes the sexual behavior of white-footed mice (genus Peromyscus) has to jump through all the federal legal hoops. His friend down the hall who delivers electric shocks to brain-damaged lab mice (genus Mus), however, is exempt from the regulations.
It is instructive to compare how the Animal Welfare Act treats mice, a species most people do not like, with our best friend, the dog. Because mice are not animals, they have no standing under the law. End of story. Dogs, in contrast, are singled out for special treatment. They are entitled to a daily dose of “positive physical contact with humans” (I think this means play). Ironically, because the act applies to dead as well as living animals, dead dogs have more legal protection than live mice. (A footnote in the Animal Welfare Act, however, exempts dead dogs from the husbandry and cage-size requirements.)
