The University of Washington's vast animal-research program, including its troubled primate center near Spokane, is involved in one of the most unreconcilable disputes of our time: the needs of medical and scientific research versus the rights of animals. -----------------------------------------------------------------
The immensity of the University of Washington's animal-research program hits home when one stands at the end of the quarter-mile-long antiseptic brown-tile corridor that connects the animal rooms at the Magnuson Health Sciences complex.
Behind the corridor's doors are rooms in which rabbit cages are stacked in tiers like an apartment complex. In other rooms, rats lie sluggishly in clear plastic tubs. Collies bred to mimic a rare human immune deficiency wag their tails happily when scientists come into their room. Pigs painted with numbers lie in a clean pen.
The world's biggest monkey nursery, with 150 infants, is in the Health Sciences basement. Baboons that carry backpacks to monitor stress are among 450 primates on the seventh floor. Infected monkeys on that floor are used to test AIDS drugs.
The animals here and at UW's troubled Primate Field Station near Spokane are unaware that they are embroiled in one of the most irreconcilable disputes of our time, both locally and nationally: the needs of medical and scientific research vs. the rights of animals.
The controversy never fails to attract attention and incite heated feelings on both sides, as animal-rights activists protest use of the animals and researchers ardently defend their work. And the public, one national poll in 1994 showed, is split almost evenly on whether such testing is necessary.
The stakes are high: Animal research is a vast, quiet, uncomfortable underpinning of science and medicine. By the estimate of Congress' Office of Technology Assessment, American scientists use 17 million to 22 million vertebrate animals a year in research, including 15 million rats and mice, 60,000 primates, 180,000 dogs and 50,000 cats.
The controversy resonates at the UW, where animal researchers have been targets of vandalism; the Field Station is scheduled for closure and a student organization of animal-rights activists has urged the school to get out of animal testing altogether.
Each year in its research, the UW uses about 370,000 vertebrate animals - those high enough on the evolutionary ladder to have backbones. About 18 percent of that total are mammals, and 0.5 percent are primates.
Studies range from benign to unpleasant: from observations of bird intelligence in UW aviaries to using pistons to crack the skulls of rats so that Harborview Medical Center researchers can learn how to cope with human head traumas.
Hammered by government and public criticism - and about to apply to the federal government for renewal of its primate-center grant - the UW Health Sciences' Regional Primate Center announced Jan. 25 it is closing its troubled Primate Field Station at Medical Lake, near Spokane, by Oct. 1. It is moving more than 1,200 primates to Louisiana, Oregon and Seattle until a new facility can be built.
Housed in a grim former prison for the criminally insane behind Eastern Washington State Mental Hospital, the 27-year-old breeding colony has been wracked the past couple of years by primate deaths from cold and thirst, a $20,000 fine from U.S. Department of Agriculture (USDA) inspectors, and staff turnover and dissension.
The university decided not to sustain the hard-to-maintain facility until 1998 while a modern, $10 million to $12 million replacement is built on leased property at Fort Lewis - a plan announced last fall. Instead, UW officials think it would be more cost-effective to temporarily farm out their primates - mostly to Tulane University near New Orleans - and apply savings estimated at $1 million a year toward a new Primate Field Station. Some UW monkeys used in AIDS research will be moved to Seattle, and 100 more to a state-of-the-art AIDS lab at the Oregon Regional Primate Center in Beaverton.
The switch is designed to head off criticism that could jeopardize the 60 percent of UW medical research that uses vertebrate animals. For that research, the university receives funding of at least $120 million a year.
"We're going to have to be very, very visible," said William Morton, director of the Regional Primate Center. "We have to be very responsive to a number of concerns from a number of different directions."
If the UW cannot sustain confidence that animals are being handled properly, "the entire university's animal-research program comes down," he warned.
Research animals are used to test drugs and vaccines, pioneer medical procedures, determine poisonous doses, indicate which chemicals might cause cancer, test cosmetics, toiletries and household cleaners, and study behavior that ultimately influences human psychology.
Even the philosophical foundation of the animal-rights movement - that animals can think, and have feelings - is an outgrowth of animal research.
Much of this human benefit comes at a price to animals. An estimated 1 million to 5 million monkeys, for example, died in the hunt for a polio vaccine. And, in decades past, there has been no shortage of horror stories about laboratory cruelties with dubious benefit, resulting today in a complex thicket of laws, regulations and oversight committees.
Their own worst enemies
It was different three decades ago, said UW psychologist Gene Sackett, who began his career working in Wisconsin with a controversial researcher named Harry Harlow, now deceased.
In the 1960s, Harlow isolated monkeys in cone-shaped enclosures he theatrically called "pits of despair," driving the primates insane. The scientist's public glee at his ability to break his monkeys psychologically is an example of how animal scientists became their own worst enemies.
As a result of such miscalculation, there are more than 400 animal-advocacy groups in the United States today, claiming a membership of 10 million and a lobbying budget of $50 million. They range from welfare groups seeking to minimize animal discomfort to rights groups seeking to shut down animal research altogether.
One of the biggest groups, People for the Ethical Treatment of Animals (PETA), says that in 1995 it held 356 demonstrations, gave 1,075 radio and television interviews, wrote 1,551 letters to the editor, sent out 225,049 pieces of mail and "reached" 9.3 million school children.
UW scientists periodically become the targets of outrage.
Veterinarian Doug Bowden, former director of the Primate Center, has seen his house picketed, his car spray-painted and his neighbor's house sprayed with an arrow pointing to his home with a sign proclaiming, "Animal Killer."
UW pediatrician Hans Ochs was pilloried in public meetings and bombarded with hate calls after he proposed infecting monkeys to study transmission of AIDS from mothers to fetuses, and whether it could be blocked with the drug AZT. "This is something you cannot start studying in humans," he said.
Sackett's house has been spattered with garbage. "All it has done is made me angry," said Sackett, "especially when you look at all the lives that have been saved by monkey research here and elsewhere."
Even Harlow's seeming cruelties have had human benefits, Sackett argued, proving to doctors how debilitating isolation and separation can be. One result, he suggested, has been a change in the birth procedures of Americans. Fathers are now allowed in delivery rooms and mothers immediately cuddle with their infants. What Harlow was trying to understand, Sackett argued, was "the nature of love."
But, animal advocates retort, such a goal does not justify scientific overkill. You don't need to take 2,000 monkeys from their mothers and spend $60 million - estimates cited in Pulitzer Prize-winner Deborah Blum's book, "The Monkey Wars" - to prove it creates stress, they contend.
They argue that animal research can be replaced by test-tube or computer techniques, and that lab conditions are often inhumane. "Nothing justifies confining these animals," said Wayne Johnson, a longtime Seattle animal-rights activist. "These animals feel pain and suffering like humans do."
Scientists disagree. "There is less good primate research than there should be," countered Bowden. The dilemma is that the animals closest to humans are often the most useful in medical research, he said. Monkeys are favorites because their brain, eyes, ears, uterus and other systems are so similar to ours.
Which helps explain what happened at Medical Lake.
Breeding their own monkeys
Eastern Washington State Mental Hospital is an ugly complex on a lovely hill, looking down toward Medical Lake and the rolling terrain of pine, pasture and wheat fields west of Spokane.
In 1955, a prison for the criminally insane was built behind the main facility, featuring concrete and steel 11-by-7-foot enclosures made obsolete a decade later by psychiatric drug treatments and mental-institution reform.
But, 27 years ago, what was no longer acceptable for people looked perfectly adequate for primates. The cells today are filled primarily with monkeys called pigtailed macaques.
The federal government's primate research did not explode until after a 1956 visit to the Soviet Union's centralized primate center by Dr. James Watt, director of the National Heart Institute.
After Watt proposed something similar in the United States for heart research, a scientific committee including Theodore Ruch, who was then chairman of the UW's physiology department, pushed for primates to be used for research on other diseases as well. Seven regional primate-research centers were set up in the United States, including the one in Seattle in 1963. Today, all the centers combined house about 18,000 primates.
When it became apparent it would be easier to breed monkeys than capture them in the jungle, the UW seized on the Medical Lake prison - cheap, solid and with ready-made cells - to hold breeding monkeys. Started in 1969, the Field Station eventually expanded to include macaques in the old cells and baboons in a shed and 2.5-acre outdoor enclosure.
Things started small, and the facility operated quietly for two decades. Then came AIDS.
When the federal government began to pour billions of dollars into researching the disease, scientists recognized they needed an animal that would react to the human immunodeficiency virus (HIV) the same way people do. This would allow vaccines and drugs to be tested to combat HIV, which causes AIDS.
Primates were obvious candidates. Unfortunately, our closest relatives genetically, chimpanzees, could be infected with HIV-1, the deadliest variant, and not develop symptoms. (One chimp, infected in 1985, recently developed AIDS after the virus mutated, but the long wait, the expense of chimps and the fact they are endangered in the wild argues against them as a model.)
Medical Lake's pigtailed macaques, cousins of the familiar rhesus monkey, could also be infected with HIV-1 and developed AIDS-like symptoms when infected with HIV-2.
Money drives science, and the UW had hit the jackpot. The university had the biggest colony of what suddenly had the potential of becoming the best vaccine-research subjects for the world's worst plague. Beating AIDS would be the ultimate medical coup.
In an audit of the UW Primate Center early in 1995, the accounting firm Peat Marwick calculated that the center's funding soared from $6.9 million in 1989 to $19 million by 1994, of which $12.5 million was tied to AIDS research. (The center uses a different accounting that excludes some research grants to come up with a 1995 budget of about $10.5 million for the Seattle and Medical Lake primate labs.)
Just one veterinarian at Medical Lake, pathologist Che-Chung Tsai, with no background in drug research, attracted what he estimated as $4 million in federal and drug-company money over five years to investigate AIDS drugs in pigtailed macaques.
As money climbed, so did the number of primates in UW's Seattle and Medical Lake facilities; the population peaked at nearly 2,500 in 1993.
So excited was the UW at the potential of macaques that it joined forces with an Indonesian university to turn Tinjil, an uninhabited, four-mile-long island near Jakarta, into a natural breeding colony. There are 2,000 monkeys on the island now, and 100 to 150 are imported into the United States for research each year.
Initial excitement cooled a bit when it became apparent macaques did not quickly develop AIDS-like illnesses from HIV-1. Meanwhile, the flood of research dollars was not matched by money to upgrade the primate facilities. Crowding grew. Staffing became short. Tensions developed. People quit. And by the fall of 1994, it was evident that the Field Station at Medical Lake was in trouble.
Field Station's problems
Medical Lake has the familiar atmosphere of the kind of out-of-sight, out-of-mind institutions set up by government in remote areas of Washington - the same as prisons, mental hospitals or group homes. It is functioning but threadbare, reasonably clean but cramped, and above all, a world unto itself. Its staff of approximately 60 people sometimes develops the personality conflicts of an isolated, extended family.
"Seattle gets what it wants and we're put on hold," one animal scientist at Medical Lake complained.
Problems at the Field Station included:
-- Breeding animals subsisted on a bland Purina "monkey chow," and there was a running fight among employees over whether this diet needed to be supplemented more frequently by nuts, grain and fruit. Proponents said too many monkey deaths could be tied to poor nutrition; opponents said the treats could spark primate fights and add to litter in cells cleaned just once a week.
-- Death rates from nonexperimental causes averaged about 8.5 percent a year from 1990 through 1994, more than twice the rate expected from simple aging. The difference came from fights, injuries and disease.
-- "Non-viable" or stillborn infants resulted from 12 percent of primate pregnancies in 1993. That rate rose to 18 percent in 1994, well above the 14 percent the UW, in 1994, told USDA inspector Harvey McKelvey was the acceptable limit.
-- Staff changes left only a single working veterinarian for as many as 1,500 primates. Monkey diarrhea became a persistent problem.
-- Five baboons were ostracized by the main troop in November 1994 after frequent animal transfers upset normal social hierarchies. Huddling together away from protective heat lamps, they froze to death.
-- In June 1994, at least four primates died of thirst. Three others suffered severe dehydration two months later. Another died in November last year. Records show two primates dying of thirst in February 1991, four in November 1991, three in November 1992 and one in September 1993.
The accidents occurred when a water line that feeds a cage water tube called a Lixit (animals lick or suck the tube to get water) was disconnected, mistakenly turned off or clogged by debris.
UW officials are not happy about the deaths but argue that some mistakes are inevitable when handling such a large number of animals.
"We are accountable; we do need to take the heat for things," said Field Station director Robert Letscher, brought in last year to correct the problems. "But doing right does not mean doing perfect. We don't live in a perfect world. Mistakes are made."
The Medical Lake staff, however, were split on whether something was fundamentally wrong.
Two employees, pathology assistant Terry Thompson and records keeper Linda Harrison, quit but filed a lawsuit saying they were forced out as whistle-blowers.
Although their most serious allegation - that Medical Lake pathologist Tsai falsified the results of AIDS drug tests to satisfy the hopes of drug companies - was rejected by a three-scientist investigative team from the UW's Office of Scholarly Integrity, Thompson and Harrison said they were trying to call attention to an institution they saw drifting out of control.
"As the population kept growing, they didn't increase the animal-technician staff," said Harrison, who had worked at the Field Station since 1971. "Tension was really high."
Meanwhile, USDA inspector McKelvey began turning up a growing list of problems. "We don't often see things to this extent, so many deficiencies for such a long time," he said of the 2 1/2 years, from 1993 to mid-1995, in which he wrote negative reports with little discernible improvement.
The UW's Regional Primate Center in Seattle was also rattled by a 1994 audit that showed one employee had embezzled $38,352, some $6,305 appeared to have been stolen, and money was used improperly to cover moving expenses, graduate-student tuition and other items. Accounting reforms have since been put in place.
Doug Bowden, director of the Primate Center, stepped down in August 1994, and Darrell Williams stepped down as head of the Field Station a month later.
In trying to improve monkey health, the UW added bedding in the Field Station cells at a cost of $250,000 a year. But that is $250,000 that cannot be used for direct medical research, of course, and veterinarians' thinking about the benefits of such additions tends to shift. It began to look cheaper just to shut the place down.
Making moral judgments
There is no question the UW's Primate Center has been plagued by problems stemming from rapid growth. More difficult is making a judgment about those problems.
Do animal-research benefits justify its costs? Do animals have rights?
French philosopher Rene Descartes said they don't because they can't think, but animal-rights advocates assert animals do think. They argue we have a moral obligation to leave them alone, that anything less is "species-ism."
Questions about the human relationship to animals quickly spills from science to philosophy, religion and politics. It jumps from research to pets, whales and endangered species.
In the broad scope of human affairs, animal research is small potatoes. There are probably more abandoned cats and dogs killed in animal shelters each year - 17 million to 29 million, by one estimate - than all the vertebrates used in research. The National Academy of Sciences says Americans eat 5 billion animals each year as food.
Complicating the argument is that most of the animals on which humans depend, from research primates to cows and chickens, are bred for the purpose and would not exist in such numbers without human intervention.
Given this moral swamp, the response of scientists has been to improve animal conditions while making clear the benefit of the research to people.
For example, Mel Dennis, a UW comparative-medicine professor, used sheep to develop a catheter used for human kidney dialysis.
Seattle heart surgeon Margaret Allen uses rabbits and monkeys to study rejection of heart and lung transplants. In some cases, she manages to connect organs to blood vessels in primate necks so that their chest cavity does not have to be opened.
Ochs, the UW pediatrician, credits his experiments using monkeys with halving the mother-to-infant HIV infection rate in humans.
Every time we get a shot, take a pill, read a warning label, ban a carcinogen or label a poison, we are relying on tests that were first done on animals.
At the same time, there have been arguable cruelties. Pigs were exposed to the searing heat of test nuclear blasts because their skin is so similar to that of humans. Monkeys were exposed to radiation and fallout. Dogs were exposed to microwave blasts. Rabbits' eyes are still used to test the toxicity of cosmetics and cleansers, though that method is giving way to tests using cell cultures. Animals have been shot and had limbs broken to study war injuries.
Critics complain that sometimes experiments seem not just to replicate the results of other labs - necessary in science - but become redundant, driven more by the need to justify grants and keep researchers employed than advance human knowledge.
As a result, UW scientists proposing animal research are required to search scientific literature to make sure someone elsewhere has not already done their proposed experiment.
And Congress, federal agencies and universities encourage animal research while steadily tightening its regulation. Animal researchers must adhere to 11 primary laws or amendments to laws and obey several overlapping regulators.
The UW, for example, established its Animal Care Committee in 1964, a dozen years before such oversight was required nationally. This is a group of faculty and outside veterinarians who review animal-research proposals.
The Primate Center is inspected by that committee, by the USDA and the American Association for Accreditation of Laboratory Animals Care. It has answered questions from the Office of Protection of Research Risk of the National Institutes of Health, and sometimes from the Food and Drug Administration.
The system, though, is far from foolproof. USDA inspector McKelvey complained the Animal Care Committee never saw his critical reports on Medical Lake and never was told of specific incidents such as the five baboons freezing to death.
The Seattle Times received cooperation when we asked to visit various animal labs, but scientists also knew we were coming.
This reporter saw animals that had been operated on, animals infected with HIV, animals in tight cages and animals with wires coming out of their heads. None seemed in obvious pain, depressed or bored to the point of dullness, though such things are difficult to judge. All looked clean and well-fed. None shrank from the scientists, though some were made nervous by any appearance of strangers. Conditions seemed better than a factory farm, worse than a zoo.
The university limited the photographer's access to certain animals that were subjects of experiments.
Policing animal research
A perennial question is whether we can rely on scientists policing fellow scientists.
"The University of Washington is scared . . . to have a real animal rightist on their (animal care) committee," said Mitzi Liebst, an activist joining a recent protest at the Primate Center. "I think that's an outrage - it shows they're intellectual wimps."
Murray Robinovitch, a UW School of Dentistry oral biologist who heads the committee, said the membership draws a distinction between policing animal research and prohibiting it. Animal-rights proponents have a 15-minute comment period at committee meetings. "They choose to make it a forum to debate the use of animals. That's not our job," he said.
The committee reviews 1,300 proposed research projects yearly and requests changes in about 40 percent of them, Robinovitch said. Usually questioned is whether the proposed animal is needed or a simpler one could be used (substituting rats for dogs, for example), whether fewer animals could yield the same result, and how painful the experiment will be.
Are there other improvements that could be made?
UW officials complained they were being squeezed between stiffer federal regulation and a health-research-grant system reluctant to pay to comply with those regulations when there is so much competition for scarce research dollars.
Can we get away from animal-use altogether? Animal-rights activists argue substitutes, such as computers and cell cultures, are already being found. But scientists say many animals are still needed.
Ochs said one reason many gene-therapy attempts failed in 1995 is that researchers tried to move too quickly from test-tube theory to human application.
"You can't do this without intermediaries between the test tube and humans," he said. "You can't do this without animals." ----------------------------------------------------------------- Animals and medical advances
Here are some examples of how animals have been used in medical research:
-- Smallpox vaccine was developed from cowpox in cows.
-- Dogs were used in the development of insulin.
-- Cats tested drugs used to reduce blood clotting.
-- Rats were used to determine how cocaine becomes addictive.
-- Horses were used to develop inoculations against diphtheria.
-- Chimpanzees have been used to develop ways to teach language to the mentally retarded.
-- Baboons were used to see if it was feasible to use orthodontic braces to move and straighten adult teeth.
-- Rats and mice are used to determine whether chemicals or foods are carcinogenic.
-- Chickens and guinea pigs were used to develop the antibiotic streptomycin.
-- Rabbits were fed cholesterol-rich diets to show it could lead to atherosclerosis.