"What is man without the beasts? If the beasts were gone, man would die from a great loneliness of spirit. For whatever happens to the beasts soon happens to man."
~ Chief Seattle
Frederick Banting would never have begun his research without access to research animals. Before he had even spoken of his ideas, his first note to himself on the subject read: "Ligate the pancreatic ducts of dogs." The quiet Ontario doctor envisioned that severing the connection between the pancreas and the digestive system in a living animal would allow him to isolate the mysterious substance that would control diabetes.
During the first week in the laboratory, Banting and his assistant, Charles Best, operated on 10 dogs; all 10 died. Finally, in 1921, after months of experimentation, Banting and his colleagues isolated a material that kept a depancreatized dog named Marjorie alive for about 70 days. Exactly what information was gained from using dogs, and how many dogs were absolutely needed, is not clear. Work previous to Banting and Best's, some of it in humans, had indicated the presence and importance of a hormone involved in glucose transport. Many more experienced scientists in the diabetes-research community believed that Marjorie had never been fully depancreatized, and thus may have never been diabetic. More likely, they said, the dog died of infection caused by her pancreatectomy. It's possible that even the death of the famous Marjorie was unnecessary for the great discovery.
But the two Toronto researchers had isolated insulin, providing the first step toward producing it from pig and cow pancreas, available in bulk from slaughterhouses. The result--that Banting and Best "saw insulin"--appears to have justified all sacrifices. What's the life of a dog, 10 dogs, a hundred? Before Banting and Best operated on dogs, we had no insulin; afterwards, we did.
Stories such as these are the reason our society and the vast majority of societies in the world accept the use of animals as a vital component of medical research.
Deeply entrenched traditions support the notion that animal welfare must bow to the best interests of humans. Animal domestication was among the first labor-saving devices. Humans have experimented with animal breeding, feeding, and disease control for thousands of years--not to benefit the animals themselves, but to insure that the owners obtained a maximum yield.
"YOU COULD ALSO SAY THAT YOU COULDN'T HAVE SETTLED THE SOUTH WITHOUT SLAVERY. WOULD YOU STILL DO IT THAT WAY TODAY? JUST BECAUSE SOMETHING SEEMED ACCEPTABLE AT THE TIME IS NOT TO SAY THAT WE SHOULD DO IT IN OUR TIME." |
Today, those traditional practices have evolved into a scientific institution, the appropriateness of which is subject to perennial debate. In the United States alone, there are an estimated 17 million to 22 million animals in laboratory research facilities. To many people, animal research represents a doorway to the medical treatment of tomorrow. But to animal protectionists, and a growing number of other Americans, animal experimentation is a barbaric, outdated practice that--on the basis of a few notable past successes--has somehow retained its vestigial acceptability.
"Let's say that it's true, that animals were indispensable to the discovery of insulin," says Neal Barnard, M.D., of the Physicians Committee for Responsible Medicine, an animal-protection group. "That was a long time ago. I think to say, 'It was done this way and there's no other way it could have been done' is a bit of a leap of faith, but let's say that at the time there was no other way. You could also say that you couldn't have settled the South without slavery. Would you still do it that way today? Just because something seemed necessary or acceptable at the time is not to say that we should do it in our time."
|Arthur Lage makes sure that Harvard laboratories comply with animal-welfare laws.|
THE ANIMAL DEBATE
The legitimation of the animal-research debate challenges one of the most important and widely used scientific approaches to discovery about the human body and its diseases. Animal experimentation is often considered as much of a sine qua non to research as the Bunsen burner. But animal protectionists reply that the importance of animals to research is overrated, and that their pressure has exposed profligacy among experimenters.
In February 1997, a highly controversial collection of articles appeared in Scientific American on the subject of laboratory-animal research. The first, written by Barnard and Stephen Kaufman, M.D., of the Medical Research Modernization Committee, another protectionist group, advanced the view that data collected from animal experimentation are almost always redundant and unnecessary, frequently misleading, and by their very nature unlikely to provide reliable information about humans and their diseases. "Animal 'models' are, at best, analagous to human conditions," the authors wrote, "but no theory can be refuted or proved by analogy. Thus, it makes no logical sense to test a theory about humans using animals."
A rebuttal in support of animal research followed, by Jack Botting, Ph.D., former scientific adviser to the Research Defense Society in London, and Adrian Morrison, Ph.D., D.V.M., of the University of Pennsylvania School of Veterinary Medicine. Their reply cited examples of scientists from Louis Pasteur to John Gibbon, a twentieth-century pioneer in open-heart surgery, who made important breakthroughs in the treatment of human disease through animal research.
Many scientists--both supporters of animal research and advocates for its diminution--simply refused to discuss the difficult topic, recalls Madhusree Mukerjee, the editor who proposed that Scientific American explore the controversy and who wrote a third article, reporting on the overall state of animal research in the sciences. (Similar difficulties were encountered in researching the present article.) Mukerjee suspects that possible interviewees feared the criticism of their colleagues.
Reader response, on the other hand, was overwhelming, both pro and con. "We got a huge amount of flak for dealing with the subject at all," recalls Mukerjee. "Some of it was fairly frightening." To many animal-research supporters, it was as though the floodgates had been opened. "I am simply stunned that Scientific American, a paragon of promotion of scientific research, would actually offer up for debate whether animal research should occur," wrote one reader. "Please leave this question of animal research to animal-rights activists, and stop yourselves from turning into scientific wimps." "A lot of the scientific community felt [Scientific American's editors] had overstepped their bounds and compromised their values by printing the Barnard-Kaufman article," says Joanne Zurlo, associate director of the Johns Hopkins School of Public Health Center for Alternatives to Animal Testing and a specialist in chemical carcinogenesis.
Those researchers who supported animal use and wrote in said the animal-protectionists' side of the Scientific American debate was fraught with misstatements and scientific errors, although Mukerjee maintains that all the articles were painstakingly fact-checked. "We annoyed a lot of influential scientists," she says. "Our publication has spent more than a century describing advances in medical research, including some by fairly controversial figures. We'd never addressed the question of research on animals before, and in a sense it was a necessary thing to do. We probably lost some subscriptions because of it. But we are a bridge between the researchers who write for us and the public who read us, and we decided to let our readers decide for themselves."
Animal protectionists date their movement back to the times of Leonardo da Vinci and even Pythagoras, who are alleged to have been vegetarians. Numerous essayists and animal lovers have detailed their objections to the misuse of animals. Yet not long ago, virtually anyone who wanted to could conduct experiments on animals. In the 1960s, it was not uncommon to walk into a laboratory and find mice, dogs, cats, even monkeys, housed on the premises in whatever conditions researchers saw fit to provide. Banting himself frequently bought pound dogs and may even have caught dogs on his own; his collaborators recalled that he once arrived at the lab with a dog he had leashed with his tie.
Only in the nineteenth century did animal research begin to draw explicit objections from protectionists. A pivotal event occurred in England in 1874, when a lecturer at the University of Norwich demonstrated how to induce epileptic symptoms in a dog through the administration of absinthe. Objections were raised by students in the audience, and the dog was set free. Later, charges were filed against the lecturer under Dick Martin's Act, an 1822 law that called for a fine of 10 shillings from anyone committing acts of cruelty against animals. Two years later, in 1876, Parliament passed the Cruelty to Animals Act, requiring a license for animal experimentation and placing restrictions on some painful forms of experimentation.
In the United States, minimal restrictions on animal experimentation prevailed until 1966, when the first federal Laboratory Animal Welfare Act (now known as the Animal Welfare Act, or AWA) was passed by Congress. In 1970 the AWA was broadened to require the use of appropriate pain-relieving drugs, and to include commercially bred and exhibited animals. Six years later, provisions were added covering animal transport and prohibiting animal-fighting contests. In 1985, Congress passed the Improved Standards for Laboratory Animals Act, which again strengthened the AWA by providing laboratory-animal-care standards, enforced by U.S. Department of Agriculture (USDA) inspectors, and also aimed to reduce unnecessarily duplicative animal-research experimentation.
In 1976, however, the AWA was amended in a rather curious way: rats, mice, birds, horses, and farm animals were specifically excluded from its purview for reasons that are not fully clear, although the USDA's limited resources--along with political pressure from interested parties--are likely to be among them. Since rats and mice make up more than 95 percent of all research animals in this country, the amendment effectively put the vast majority of laboratory animals outside the reach of the USDA. Since then, at least one court has ruled the 1976 amendment "arbitrary and capricious."
THE MOUSE WAREHOUSE
As associate professor of surgery Arthur Lage, D.V.M., walks through the doors of Harvard Medical School's Alpert Building, people recognize him, smile, and let us pass without showing identification. He is director of the Center for Animal Resources and Comparative Medicine and the Center for Minimally Invasive Surgery at the medical school and director of the Office of Animal Resources for the Faculty of Arts and Sciences as well. We take an elevator down to a basement, where Lage swipes a card through a reader, unlocking a door to a hallway, where he speaks into a phone. A minute later, a young man clad in blue scrubs opens the door. Lage explains that he's bringing a reporter in for a tour and that we'll need keys to see certain rooms. The young man hands over the keys and closes the door.
At the other end of the short hallway are two doors, each leading to a sanitary changing room. When you turn the lights on in the changing rooms, the doors at either end lock automatically. After we've pulled blue scrubs over our clothes, Lage douses the lights and we step out of the room into another brightly lit hallway.
We're in one of Harvard's 16 animal facilities now, a moderately "clean" facility--meaning that it requires only minimal preparations for entry. Some laboratories would require us to remove our clothes and shower before entering; others don't even stock scrubs. But this facility is full of mice--transgenic mice. A stray pathogen in one of the animal rooms could wipe out millions of dollars' worth of experiments or, just as disastrous, infect a colony of mice with viruses or bacteria that might confound the results of a study.
|Regulator Julie Medley reviews animal experiments in Cambridge to ensure they meet standards for pain control.|
Of course, the security isn't intended only to repel microbes. Perhaps in frustration with perceived shortcomings in the oversight of animal experimentation, some animal-protection groups have gained a reputation for tactics that are rash and often destructive. On several occasions, animals have been "liberated" from laboratories, erasing potential results and sometimes careers. In 1989, the Animal Liberation Front took credit for the release of more than 1,200 laboratory animals, some of them infected with cryptosporidium, which can be harmful to infants and immunocompromised people. The total damage was estimated at $250,000. In 1987, a laboratory under construction at the University of California at Davis was burned; the loss was estimated at $3 million.
Although there is little evidence of violence toward animal researchers here in the United States, in Europe, where the animal- protection movement is more firmly entrenched, activists have taken aim at individuals, sometimes with disastrous results. In 1990, the infant daughter of a researcher was injured by a car bomb believed to have been set by animal protectionists. In separate, related incidents, a furrier and a breeder of cats used in experimentation were injured by letter bombs. Responsibility for the mail bombs was assumed by "The Justice Department," a militant, underground, animal-protection organization.
Even today, animal-protection groups find ways to gain access to research and testing facilities. In 1997, Michelle Rokke of People for the Ethical Treatment of Animals (PETA) infiltrated Huntingdon Life Sciences, a drug- and cosmetic-testing firm in East Millstone, New Jersey. Using a surveillance camera embedded in her eyeglasses, Rokke took hours of films that PETA claimed showed animals being slammed into cages and roughly handled. PETA president and co-founder Ingrid Newkirk said their investigation also revealed that young beagles' legs were broken for another study at Huntingdon. Movie star Kim Basinger gave a press conference on Huntingdon's lawn. In April 1998, the USDA fined Huntingdon $50,000 for AWA violations.
In the basement of the Alpert building, there is no evidence of such fury. Each room holds literally hundreds of mice in shoebox-sized cages, and there are so many of them it looks like a shoe warehouse. There are about 55,000 mice involved in research at Harvard at any one time, but that number is growing constantly. In 1997 it was closer to 50,000; by the end of 1998 it approached 58,000. By comparison, the numbers of other animals are almost negligible: about 1,300 rats, 145 rabbits, 115 hamsters, 70 guinea pigs, 67 primates, 35 pigs, 30 gerbils, 25 chicks, 20 dogs, 18 sheep, 6 cats, and 1 ferret. In addition, the New England Regional Primate Research Center in Southborough, Massachusetts, houses another 1,500 monkeys and other primates. Established at Harvard in 1966 with a grant from the National Institutes of Health, the NERPRC is one of seven such centers created by Congress in the early 1960s to serve as regional resources for scientists.
Surprisingly, there is no hint of animal smell within the basement facility. Temple Grandin of Colorado State University, a specialist in the behavior of captive animals, says that what mice really crave is some form of bedding--wood chips, paper, or shavings--which not all these animals have. Still, these laboratory animals, born and bred under fluorescent lights, are comfortable enough to live out lifespans they would never approach in the wild and, of course, to reproduce. And since almost all of them are involved in genetic studies, making sure they're happy and healthy enough to reproduce is of vital importance. Keeping these buildings clean and free of infection is a triumph of research design. All the soiled animal cages are shuttled to one end of the laboratory where, before they re-enter, they pass through an enormous autoclaving machine that sanitizes the cages as well as the carts they sit on.
Amid the towers and technology of the medical area, animals one normally associates with a farm are a jarring sight. But Lage (pronounced lah-gee) led me through animal laboratories in the basement of the Seeley Mudd Building where we saw pigs, sheep, and rabbits held in small, clean pens. At one point, we watched eight sheep slated for experimental surgery frisk around a room that looked almost exactly like an office. If the straw were swept away, one could easily have moved in a desk and gone to work.
"We care for all these animals just as though they were covered by the [Animal Welfare] Act," Lage says proudly. "I think most of us believe that the act should cover rats and mice."
Although the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC), like the USDA, inspects laboratory-animal facilities, including those of rats and mice, AAALAC accreditation isn't legally required to conduct animal research. "AAALAC conducts something like a 'peer review' assessment," Lage says. "It's a voluntary process, subscribed to by many, many research organizations. If you decide not to go through accreditation, you have to describe your entire program every time you apply to the government for funding for animal research."
"I'M SURE SOME OF THE PRINCIPAL INVESTIGATORS RESENT THESE REGULATIONS. IT DOESN'T HAPPEN THAT OFTEN, BUT THERE ARE RARE OCCASIONS WHEN I RUN INTO RESISTANCE FROM AN INVESTIGATOR."
Many laboratories and commercial drug-testing companies that receive no funding from federal sources and use only rats and mice proceed with only minimal oversight from their own institutional animal care and use committees (IACUCs). But restrictions on animal research are, if anything, increasing, not abating. Not content with the level of state and federal regulation, for example, the city of Cambridge in 1989 passed its own law creating an inspector's office with the power to make USDA-type inspections of all research facilities housing vertebrate animals, including rats and mice.
Cambridge's current commissioner of laboratory animals, Julie Medley, D.V.M., annually inspects 34 laboratories, makes follow-up visits to some facilities (sometimes unannounced), and reviews "hundreds and hundreds" of research protocols to ensure that all experiments meet federal standards for pain control. Investigators readily comply with Medley's suggestions for better animal care and pain control, she says, but she perceives an undercurrent among some researchers who chafe under what they perceive as excessive government intervention in their work. "I'm sure some of the principal investigators resent these regulations," she says. "It doesn't happen that often, but there are rare occasions when I run into resistance from an investigator."
Still, for animal protectionists, the intentions of the Animal Welfare Act, AAALAC, and state inspectors are not enough. Sandi Larson, a scientific adviser to the New England Anti-Vivisection Society, who has a master's degree in microbiology, concedes that "not all researchers are Dr. Frankensteins. But," she adds, "they have been trained to look at animals as tools. It's ingrained in them to shut off their compassion and act like scientists. They think there's no room for emotions." A significant portion of the animal-protection movement believes that most experimentation on animals is without merit. If animals are different enough from humans that we can dismiss their suffering as inconsequential, isn't it just a little too convenient that they resemble us enough to be considered a source of reliable information about human physiology?
[ Continued... ]