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Deep divide over the merits of animal research
BY BRYN NELSON First of a series Long before the trouble started, Columbia University neurosurgeon Dr. E. Sander Connolly asked a question: How, he wondered, could the brain damage he often saw in stroke patients be reduced, if not prevented? The trouble began when veterinarian Catherine Dell'Orto asked a different question: How could Connolly's stroke experiments in baboons be justified? For many of his supporters, the neurosurgeon's baboon-based stroke research continued the climb of biomedicine toward its noble goal of preventing suffering and death for millions of humans. But for many of his critics, the experiments were but the latest outrage in a field blamed for the suffering and death of millions of animals along the way. For centuries, animals have served as human stand-ins for a broad range of experiments looking at how the body functions, or fails to function due to illness, injury and aging. Within the last century, such animal research has contributed to the development of insulin, kidney dialysis, vaccines for diseases like polio and diphtheria, and the coronary bypass surgery that New York surgeons performed last month on former President Bill Clinton. But all of the advances have come at a cost. Although no government agency keeps track of the number of mice and rats used for research, a nearly two-decade-old estimate suggested an annual tally of 16 million to 22 million. For the year ending Sept. 30, 2002, the last for which statistics are available, researchers used another 1.1 million rabbits, guinea pigs, hamsters, dogs, cats, primates and other warm-blooded animals overseen by the federal Animal Welfare Act . In a biomedical era of increasing demands and heightened tensions, is there a point at which the potential harm to animals outweighs the potential good to humans? No single experiment can encapsulate a sprawling debate over questions -- some shouted through bullhorns, some chewed over in silence. And virtually every major research university has had to contend with objections over its animal-based studies, including recent controversies in Massachusetts, North Carolina and Washington. But the story of a respected neurosurgeon, a disillusioned veterinarian, and the fight between a vocal animal rights group and a high-profile New York institution illustrate the deep divisions that persist over the limits of animal research. The story begins with a clot. Within a nasty cut, coagulated blood cells can act as the catalyst for a protective scab. But within a blood vessel delivering oxygen-rich blood to the brain, a clot can prove deadly. Connolly, a well-published 39-year-old assistant professor of neurosurgery at Columbia and a graduate of Louisiana State University's School of Medicine, has focused much of his research on ischemic strokes, or those in which blood flow to the brain suddenly stalls. Every year, these strokes afflict well over half a million Americans, with blood clot-jammed vessels blamed for most of them. Inducing a baboon stroke For these patients, death or long-term disability can result from a breakdown in the network of blood vessels beyond the blockage and an expanding zone of oxygen-starved brain cells -- akin to a perforated garden hose that develops a kink and leaves downstream plants with a mere trickle of water. In his research proposal -- officially titled Experimental Protocol 2860.02 -- Connolly sought to answer whether drugs might limit this downstream microvascular failure by protecting the brain's blood vessels and neurons from damage. Experiments in mice had suggested he was on the right track. And so Connolly turned to young adult male baboons, whose brain anatomy closely resembles that of humans. Experimentally inducing a stroke in a baboon is not for the faint of heart. According to Connolly's research protocol, it requires veterinary surgeons to clamp several major arteries that deliver blood-borne oxygen to the baboon's brain. To access those vessels, surgeons first anesthetize the baboon and remove its left eye, along with residual fat and muscles lining the eye socket. Then, using a high-speed drill, the surgeons remove bone segments forming the back of the socket. Finally, they remove two of the brain's outer coverings to reveal the inner arteries. Connolly asked permission to induce strokes in 60 baboons by clamping their arteries for an hour. Thirty would receive one of three experimental drugs intravenously, including a derivative of Vitamin C called dehydroascorbic acid, and 30 would instead receive a placebo. Each baboon would be euthanized either three or 10 days later, and its brain examined to gauge the drug's effect. In March of 2000, Columbia University's Institutional Animal Care and Use Committee signed off on the project -- just one of the dozens of animal experiments the review board would pore over that year. Some 41/2 years later, however, Experimental Protocol 2860.02 has become a flash point. After holding an initial press conference last fall, People for the Ethical Treatment of Animals (PETA) launched a publicity blitz earlier this year against the perceived cruelty of Connolly and two other Columbia scientists conducting separate experiments on baboons and rhesus macaque monkeys. PETA supporter and political humorist Bill Maher sent Columbia's faculty and staff a mass e-mail in May, urging them to oppose the research. Protesters disrupted the university's graduation ceremony in June. An elaborate Web site appeared, labeling the researchers "Columbia's Death Squad" and including a video of caged primates at the university. "This Columbia case is especially poignant because of the incredible suffering -- it's the suffering of those primates in these laboratories that has really compelled us to push hard on Columbia to clean up its act," said Mary Beth Sweetland, PETA's director of research and investigations. Strong allegations One of the organization's allies, 22-year-old pop singer Nellie McKay, even released a song about the controversy, called "Columbia is Bleeding." In its complaints to regulatory and law enforcement agencies, PETA alleged that Connolly's research was improperly conducted and the follow-up care inhumane. But a broader message emerged in statements from the organization and its supporters: The science itself was barbaric and shouldn't have been conducted at all. In fact, other surgery-based experiments have proven vital to biomedical progress. The successful quadruple bypass surgery of former President Bill Clinton at the Columbia-Presbyterian Center of New York-Presbyterian Hospital, for instance, relied on a heart-lung machine and coronary bypass techniques -- both developed from research on dogs and other animals. The victims of a rare human disorder known as moyamoya disease, in which the main blood vessels leading to the brain become narrowed or irreversibly blocked, have similarly benefited. For many of these patients, the chance of a stroke becomes all but certain without surgery. Dr. Connolly, one of the leading moyamoya neurosurgeons on the East Coast, specializes in bypass procedures that reroute the brain's blood supply past the blockage -- surgeries honed in past experiments with animals. The mother of a former patient referred to Connolly on an Internet message board as a "skilled brilliant doctor" with a "great" bedside manner, while another concurred in an e-mail sent to Newsday, in which he described the neurosurgeon as "a very kind and caring person as well." Columbia officials declined to make Connolly or his baboon research protocol available. Nor would the university confirm or deny the authenticity of a 15-page summary of Connolly's protocol that Newsday received from PETA, citing reasons of confidentiality. Dr. Catherine Dell'Orto, a former veterinary post-doctoral fellow at the university, said she could vouch for it, however. Objections are raised Dell'Orto, now 35, arrived at Columbia's Institute of Comparative Medicine in July of 2001 with her doctorate in veterinary medicine from Mississippi State University and a view that animal research was a necessary evil. By then, Connolly had finished the first phase of his research with 23 baboons and begun the second phase with a new contingent. Within weeks, Dell'Orto said, she had raised multiple objections with a senior veterinarian -- that the baboons were receiving inadequate pain medication given the severity of the surgery, that they were receiving poor post-surgical care and being left to die in their cages. And, she contended, dogs and pigs in the facility were being mistreated as well. But after a meeting with other veterinarians to address her concerns, she said, "I was told I was not allowed to go into the experimental surgery area, where they performed those surgeries. I was told that I should focus on rodents." Licensed veterinary technician Idalia Padilla-Weiss also began working at Columbia in the summer of 2001. With Dell'Orto, she shared an office and a belief that some of the lab animals were suffering needlessly. Some baboons and monkeys bit themselves repeatedly, Padilla-Weiss said. Others ate their feces or wouldn't eat at all. She blamed their behavior on stressful housing conditions and a lack of environmental enrichment, a view she said was not shared by her colleagues. "They just pooh-poohed me and told me I was new in the field and couldn't be too emotional about it," she said. But she couldn't help it. "Emotionally, you get involved. Some people can block it out. Other people can't," Padilla-Weiss said. "Just because someone gets emotional about what they've seen, doesn't mean they don't know what's going on." To improve what she considered a poor environment for the primates, Padilla-Weiss said she requested a television (some rhesus macaques are known to chatter angrily if they can't watch "Sesame Street" on a daily basis). None was forthcoming. So she began bringing her charges treats like popcorn, nuts and cut-up fruit. She brought in a lava lamp, a radio, cardboard boxes, even a plastic gun that released soap bubbles. Disputes over methods Over the next year, Dell'Orto said, Padilla-Weiss or another technician would ask her to examine particular animals, such as a male baboon recovering from a stroke, or a female rhesus macaque in a separate project studying how stress alters the menstrual cycle. PETA has contended that the latter experiment, led by Columbia researcher Dr. Michel Ferin, induced physical stress by surgically anchoring a metal cap to the monkey's skull. Dr. Thomas Martin, director of the university's Institute of Comparative Medicine, disputed that allegation, instead describing the implant as a plastic tube "smaller than a toothpick," or a catheter, surrounded by a non-implanted flexible metal tether to prevent the catheter from being dislodged. The macaques, he said, received aspirin suppositories for pain relief after surgery. Dell'Orto, however, said that on at least three occasions, she found a macaque trying to remove the implant, bloodying itself and the cage in the process. "There should have been tranquilizers," she said. In October of 2002, Dell'Orto complained again -- this time to the administrator for the university's Institutional Animal Care and Use Committee, the panel that initially approved both experiments. The university set up a committee to investigate. But Dell'Orto said she became discouraged when a professor associated with Connolly's stroke research was named to that committee. So she took her concerns to the enforcement arm of the USDA, the agency that ensures compliance with the federal Animal Welfare Act. And then she told her story both to PETA and The Humane Society of the United States. Dell'Orto would testify before the Columbia committee. So would Padilla-Weiss. Both said they were allowed too little time to press their case or make their questions heard. "Everyone wants animal research," Dell'Orto said. "But if you are actually seeing these animals suffering and dying, you can't but help to say to yourself, 'There's something wrong here.' " Taunts and vulgarity Dell'Orto said she voluntarily left Columbia in February of 2003, after enduring ostracism and retaliation from colleagues. After a stint as a veterinarian in Westchester County, she moved to an animal clinic in Tuscon, Ariz. Padilla-Weiss, likewise, said co-workers began to treat her with derision after hearing of her role in the investigation. "I was known as the 'monkey lady' and the 'baboon lady,' " she said. More vulgar names were whispered anonymously over the work telephone. Padilla-Weiss voluntarily left Columbia in January, and now works as a veterinary technician with the ASPCA in Manhattan. "I could go back to that, I would make more money," she said. "But I won't." After repeated requests by Newsday, Dr. Martin and Dr. Mark Underwood, chairman of Columbia's Institutional Animal Care and Use Committee, agreed to discuss some of the more contentious aspects of Connolly's research. In a joint interview, Martin said he had reviewed all of the university's investigation-related documents. "And what that supports is that Columbia moved very quickly," he said. "I don't think that the investigation could have been any more thorough or any more open." According to a June 30, 2003, letter sent to Dell'Orto by Dr. Harvey Colten, vice president and senior associate dean for translational research at Columbia, the university's investigative committee discovered substandard record keeping. It confirmed "inadequate or questionable veterinary care to 11 of the 23 animals about which you expressed concerns, as well as to six puppies infected with scabies in an incident reported by another individual." And it found that many of the adverse events were not reported to the university's Institutional Animal Care and Use Committee. No violations found The investigation uncovered no evidence of significant violations in the conduct of the research, however. Nor did it find evidence of retaliation against Dell'Orto. Every institution that conducts research on animals protected under the Animal Welfare Act must establish a review committee to ensure that each proposed experiment passes muster. Are animals the best way to tackle the research question? If so, what animals? How many? Will they feel pain or distress? If so, can they be treated? And, when necessary, killed in a humane way? Even after permission is granted, researchers must report back on their findings and ask for permission before embarking on the next phase. In answering these questions, biomedical researchers say they are paying unprecedented attention to issues like pain management and environmental enrichment. At Columbia, Martin said, any scientist who proposes a procedure likely to cause pain must meet with a veterinary surgeon to devise an anesthetic and pain medication plan. Martin described the plan developed by Dr. Connolly, which also involved discussions with a hospital anesthesiologist, as "excellent." In addition to the mixture of drugs in the gas anesthesia administered during the surgery, he said, surgeons also used a local anesthetic at the surgical sites. For pain control, the surgeons used fentanyl, which Martin described as "a very powerful morphine." Changes are made He said the intravenous dose -- 10 times the amount normally given to animals in pain -- was continued at the same level for 20 hours after surgery. With regard to environmental enrichment for the university's primates, Martin said a program existed before the investigation, but a review process with input from outside veterinary experts found it needed to be formalized. Columbia now has an enrichment coordinator, he said, who oversees the use of enrichment items like a television, a water fountain, and a variety of toys and puzzles. In response to its own review, Martin said the university also extended the routine hours of animal care, established training sessions in record keeping and hired a coordinator to help veterinarians make sure animal research proposals comply with all guidelines and regulations. And the university has established a new process for veterinarians to discuss whether unexpected events -- such as infections or post-surgery complications -- should be reported. "Columbia didn't get to be a great institution by closing its mind and its door to ideas," Martin said. In an evolving field filled with hard questions, he said, "we're trying to do our best to lead the way." Martin and other researchers concede that animal experiments, even those that exceed every guideline, can still present unpleasant choices. "It's not easy to decide to use an animal," he said. If a research question could be answered another way, "there is not a researcher here who wouldn't jump at that. There isn't a researcher that is using animals because they want to." A growing dilemma With a lack of viable alternatives, other researchers say the dilemma extends beyond just scientists and activists. "It's terrible to use dogs in heart disease studies, but as soon as your older family member needs heart care, you want the best," said Dr. Alan Beck, Director of the Center for the Human-Animal Bond at Purdue University's School of Veterinary Medicine. And despite the objections of activists, he said, few people would forgo new cures in exchange for a total ban on animal research. In the absence of a complete ban, should some research be off limits -- a position adopted by some foreign countries? "In Europe to a degree, and especially in Great Britain, there's a point where animal concerns trump human needs," said University of New Mexico bioethicist John Gluck. "In theory, there is no experiment in the United States, no matter how invasive, no matter how excruciating it is to the animal, that could not be approved on some level, if the argument is that the benefits seem to be sufficiently valuable." Great Britain, whose review committees operate under some of the most stringent animal welfare regulations in the world, differs from the United States in another major respect: Unlike Americans, a majority of Britons believe medical testing on animals is morally wrong. In this country, animal research is governed by a complicated system of guidelines and regulations that some have likened to the federal tax code. University passes muster Martin said Columbia reported its findings to two federal agencies, each of which expressed satisfaction with the university's handling of its investigation. One of them, the USDA's Animal and Plant Health Inspection Service (APHIS), completed its own review in May and issued what's known as a stipulation, fining the university $2,000 in the process. Some of the agency's findings echoed those of Columbia's investigation, while others cited specific faults with animal housing and with the university's internal oversight. Of similar cases resolved in 2001, the last year for which detailed records were available, APHIS issued 130 stipulations in all and imposed fines totaling roughly $143,000. Separately, judges working on behalf of the agency delivered 83 legal decisions as a result of animal welfare violations, imposing fines totaling more than $365,000. APHIS spokesman Jim Rogers said the Columbia findings did not reach the level of violations that would spur legal action. "We're just essentially saying, 'Cut it out, pay this fine.' " Columbia did, and APHIS took no further action. But other questions remain. In a Feb. 28, 2001, letter to the university's Institutional Animal Care and Use Committee, Connolly wrote: "We completed a trial of a novel anti-oxidant compound (DHA) and were able to show that its efficacy in lower rodent models is not mirrored in primates." The effectiveness of the Vitamin C derivative in protecting mice from stroke-related brain damage had not extended to the 23 baboons he studied. And so he requested permission to use 30 baboons to test a separate drug. PETA provided the letter to Newsday. Columbia, citing reasons of confidentiality, would not confirm or deny its authenticity, but Dell'Orto again vouched for it. Yet Connolly, quoted in a press release 10 weeks later, touted the drug's effectiveness in a mouse study and its potential "to protect patients against the debilitating consequences of stroke," but never mentioned its less promising results in his own baboon study. Tarrytown, N.Y.-based Progenics Pharmaceuticals, which developed the drug, issued the release. A Progenics spokesman did not return multiple calls and e-mail inquiries seeking comment. Critics have decried the omission of negative research results from human clinical trial press releases, and two ethicists contacted by Newsday similarly criticized the integrity of the Progenics release. Barbara Orlans and John Gluck, both affiliated with Georgetown University's Kennedy Institute of Ethics, stressed the importance of animal-based stroke studies to the medical field. But they also raised concerns about Connolly's experimental design -- citing as a "major failure" its lack of a proper post-surgery pain and distress assessment for the baboons. And they questioned the reliability of what they termed "crude" behavioral and physiological measurements to assess the drug's impact. As for the USDA's settlement agreement, Orlans and Gluck characterized it as "a serious indictment of a committee and some researcher(s) who failed to follow basic welfare commitments." Did Dell'Orto's complaint make a difference? Whether Columbia's own review would have occurred without it is debatable. But as Underwood, chairman of the university's Institutional Animal Care and Use Committee, said, "We are doing things differently now." So is PETA. Citing animal cruelty, the group asked the New York County District Attorney's office to investigate and prosecute Connolly and 19 other Columbia-affiliated individuals, including most of the university's internal review board. A spokeswoman for the district attorney confirmed the request but declined to comment further except to say, "We are looking into it." PETA is pushing the envelope in other ways. Sweetland portrayed the Columbia researchers as torturers and lowbrow "Joe Six-Pack" scientists who do "cutting up," not "cutting-edge," experiments. Martin said Connolly stopped his own baboon experiments -- not because of any complaint or threat, but because of an agreement to suspend the research during the university's investigation. "I and others believe that biomedical research is one of the most powerful forces for good that there is," Martin said. He confirmed that some Columbia scientists have received threats from those who believe otherwise, but he declined to elaborate. He vowed, though, that the university wouldn't halt its animal-based research in response to "terrorist tactics." For now, at least, one biomedical project has yet to resume. Tomorrow: Debating current animal protections Copyright (c) 2004, Newsday, Inc. - This article originally appeared at:
******************************************************************* Ethics as the argument BY BRYN NELSON September 27, 2004 Second of a series On Feb. 4, 1966, Life magazine published a photo essay, "Concentration Camps for Dogs," that detailed animal cruelty by a Maryland dealer suspected of stealing dogs from their owners and selling them to researchers. Six months later, the expose and public outcry had spurred the passage of the federal Laboratory Animal Welfare Act. In the nearly 40 years since then, the federal law and three major amendments have been widely credited with improving the lives of dogs and many other warm-blooded laboratory animals in the United States. Other questions have been brewing, not only of how research should be conducted, but also of whether some should be conducted at all. Questions of whether animals have rights precluding their use as guinea pigs. And despite the accords of the past, ethicists and welfare advocates say the scientific community is ill-prepared to deal with an evolving debate that is generating new questions and becoming increasingly inflammatory. "The polarization in this country is most regrettable," said Barbara Orlans, founder of the Scientists Center for Animal Welfare and an affiliate at the Kennedy Institute of Ethics at Georgetown University. At the extremes, "it's just a closed book," she said, citing the "ridiculous" allegation that all animal research is worthless, while also faulting the opposing view that "it's wonderful, and we're lily white." Bernie Rollin, a Colorado State University ethicist and architect of the Animal Welfare Act's 1985 amendment, said the regulations have "done wonders" for animal welfare in most institutions. Debating the merits Studies on the use of pain medication in animals have skyrocketed, and ever- more attention is being paid to living conditions - even for mice. The Journal of Animal Behavior has even established an ethics committee and welfare guidelines, and has rejected scientific papers not on their scientific merits but on their ethical merits. But as some old questions about animal research are finding resolution, new ones are starting to emerge. "And what I think is happening is people are beginning to ask, 'Should it be done at all?' " Rollin said. In 1976, a few protesters asked that very question in picketing the American Museum of Natural History in Manhattan over sexual behavior experiments on cats, helping to launch the early animal rights movement. More than a quarter-century later, the same question has figured prominently in a noisy dispute over baboon- based stroke studies and other primate experiments at Columbia University, and in other recent battles pitting activist groups like People for the Ethical Treatment of Animals against the research community. At the extreme ends of the debate, a 2003 Gallup poll found that only 3 percent of Americans believed "animals don't need much protection from harm and exploitation since they are just animals," while 25 percent thought they deserve "the exact same rights as people to be free from harm and exploitation," a view more likely to be held among women and Democrats. Mary Beth Sweetland, PETA's director of research and investigations, said her organization has grown every year as more people question animal-based experiments. For the fiscal year ending July 31, 2003, PETA reported raising $23.3 million in contributions and helping to organize 921 demonstrations. "I personally hear a lot of people
saying that we simply don't have the right to do this to animals,"
Sweetland said. Notoriety led to reform Several ethicists and researchers said the often theatrical actions of PETA and other animal rights groups have helped uncover ethical abuses and advance regulations - often in spite of the initial objections of researchers. But animal research advocates contend that the well-reasoned objections of some activists are being lost amid the edgier statements of others who liken the research to torture. "If the question is, 'Are you for or against animal suffering,' what are you going to say?" said Frankie Trull, president of the Foundation for Biomedical Research. In response, the foundation and other pro-research groups have launched ad campaigns describing how animal-based medical advances have alleviated death and suffering not only in humans, but also in pet dogs and cats. Trull said she's pleaded with animal researchers to speak openly about why their work matters and how they're pursuing humane animal care, only to have the approach backfire. "The minute the scientists raise their hands to say what they do, they're [verbally] attacked," she said. "And what's happened is that there's this tremendous bunker mentality that has developed, unfortunately for a legitimate reason." Perceptions are created Some ethicists say the "circling of the wagons" approach adopted by scientists who feel beleaguered may create the perception that they have something to hide, furthering the cycle of mutual distrust. Beyond an increase in the intimidation of researchers, the FBI has documented another trend. Phil Celestini, a supervisory special agent for the FBI's domestic terrorism unit, said cumulative property damage attributed to environmental and animal rights extremists has roughly doubled within the last three years. Groups like the Animal Liberation Front and Stop Huntingdon Animal Cruelty are at the top of the FBI's watch list. Both are active in the New York region and Celestini said both are adopting "European tactics," a euphemism for targeting individuals instead of institutions. "You have university professors, either getting out of certain animal-based research, or losing very highly qualified people because, frankly, they don't want to deal with the possibility of being hassled," he said, noting that he has heard anecdotes from "a great many people" in the biological and pharmacological fields. "There is a definite chilling effect." Industry feels the impact The biomedical industry has likewise felt the impact, especially Huntingdon Life Sciences, a British-based animal testing company with a lab in East Millstone, N.J. In February of 2001, three masked men wielding pickax handles attacked Huntingdon Managing Director Brian Cass outside his home in England, leaving him with a head wound. A neighbor who came to his aid was sprayed with CS gas. Five months later, animal rights activists on Long Island claimed responsibility for drilling holes into a Sands Point yacht owned by a Bank of New York executive to protest the bank's ties to Huntingdon. Since then, activists have vandalized homes in Long Island and New York City belonging to executives from at least three other companies tied to the animal research company. Trull's Foundation for Biomedical Research is so worried by the trend that it has begun distributing an ad picturing three ski mask-clad activists, one of them wielding an ax. "Some people think the best way to protect animal life is to make scientists fear for theirs," reads the ad copy. Eric Kandel, a Nobel Prize- winning neurologist at Columbia University whose early studies on memory and learning processes relied on sea slugs, cited two main failures of animal researchers in winning over their detractors. "I think that there was a period in which certain laboratories were not terribly sensitive to the needs of certain animals, and they did not take proper assurances to make sure that animals were taken care of in humane ways," he said. "It occurred occasionally, and it should occur never." "Two: the scientific community is not good at getting out its message," he said. A big part of that message is explaining why animal research is "key to biological science," he said. Of his own field, he added, "it is the key, at the moment, of understanding neurological and psychiatry research. It is not the only key, but it is a key. There's no reason why it cannot be sensitive to animal care and beneficial to mankind." But several ethicists have pointed to a third failure, contending that scientists have been unwilling or unable to engage the growing philosophical debate over whether animals deserve rights, and therefore, greater protections. Although condemning the violence of animal rights extremists, Rollins contended that anyone who raises questions is likewise dismissed as a radical. Debate fueled by studies Ironically, part of the ammunition for the debate has come from scientific studies themselves. Research on whether animals feel pain has moved from human newborns in the early 1980s (they do) to, in the past few years, fish (a split decision). And with every new story suggesting that monkeys excel at certain video games, or that a gorilla has mastered sign language, or that a border collie understands an unusually large "vocabulary," researchers are discovering that some animals may be able to think in ways once considered the sole territory of the human mind. "It's hard to argue that bacteria have rights, but it's not too hard these days to argue that chimps or bonobos have rights," said Kenneth Pimple, an ethicist at Indiana University in Bloomington. "If you discovered that a cockroach thinks about the Buddha, you'd probably be a little bit reluctant to step on it," said John Gluck, a bioethicist at the University of New Mexico. Trull and other research advocates have taken pains to distinguish between traditional animal welfare advocates - those with whom they believe they can reason - and animal rights activists, or those who they consider on the fringes. But as the old labels begin to blur, the common ground once shared by bargaining partners is proving hostile territory. "The old animal welfarists, who I always distinguish from animals rights, are gone," Trull said. In fact, she said, "We view ourselves as animal welfarists. Frankly, I think the research community has seized the middle ground." Tomorrow: Using mice in research Copyright (c) 2004, Newsday, Inc. This article originally appeared at:
******************************************************** In the quest for knowledge BY BRYN NELSON September 27, 2004 In 1726, English physiologist Stephen Hales first measured blood pressure in a horse by inserting a tube into one of its arteries. Half a century later, in 1775, Danish veterinarian Peter Abildgaard tested the effects of electrical shock and countershock on chickens - essentially the first successful attempt at electrical defibrillation. Within the past 100 years, cardiovascular researchers have continued to call upon an array of animals in the quest for knowledge, using everything from cows to mice. But what have researchers learned, and how has it benefited their human patients? That question, after all, is a key component in the debate over the use of animals in biomedical research and whether the benefits outweigh the costs. A look at the procedures and medications involved in one patient's heart attack offers a snapshot of medicine's reliance on animal testing: Medical procedures considered CARDIAC CATHETERIZATION (1) What it is: Doctors insert a long, narrow tube into a blood vessel - usually in the patient's groin, arm or wrist - and guide it toward the heart. With the catheter in place, doctors can measure an artery's blood flow and pressure, diagnose coronary artery disease, and treat blocked or narrowed passages. How it was developed: Using dogs and rabbits, researchers pioneered the procedure in the 1900s. In 1929, German surgical resident Werner Forssmann performed the first recorded cardiac catheterization in a human - using himself as the research subject. BALLOON ANGIOPLASTY What it is: After catheterization, doctors guide a separate balloon-tipped catheter through the blood vessel to the site of a clogged or narrowed artery. Then surgeons repeatedly inflate and deflate the balloon portion, compressing accumulated plaque against the sides of the artery to improve blood flow. How it was developed: Researchers in Oregon developed the technique in the 1960s to open blocked arteries in the leg, but it was a Swiss researcher who pioneered the balloon catheter. In 1976, he presented the results of balloon angioplasty experiments on dogs to skeptical researchers. By the end of the next year, he had demonstrated the technique's value in humans. ATHERECTOMY What it is: An alternative to balloon angioplasty. Doctors guide a separate laser or rotating blade-equipped catheter through a blood vessel to the site of a clogged or narrowed artery, then vaporize or shave plaque into tiny pieces that disperse through the bloodstream. How it was developed: Building on earlier techniques, Dr. John Simpson introduced the first coronary atherectomy device in the mid-1980s. Such devices were tested in pigs and other animals. STENT What it is: After the preceding procedures, doctors may implant a mesh tube or metal coil into a patient's unclogged artery to prevent the artery from becoming narrowed or clogged again. How it was developed: Charles Dotter is credited with inventing the stent, which he implanted in a dog in 1969. In 1986, French surgeons inserted the .rst stent into a human. Pigs and baboons also have been used, with the former becoming the most popular due to the physiological similarities between the porcine and human cardiovascular systems and their availability. Medications prescribed HEPARIN What it does: Reduces blood's clotting ability, thereby reducing the risk that lifethreatening clots will form. How it was developed: First isolated from dog liver in 1916, it was one of the first drugs used to prevent blood clots. Researchers were able to extract it in large quantities from cow liver and lung, and by the late 1930s, purified extracts were proven safe and effective in dogs, rabbits, guinea pigs and mice. IMDUR (isosorbide mononitrate) What it does: Dilates blood vessels, making it easier for the heart to pump and allowing more oxygen-borne blood to .ow to the heart. How it was developed: Before FDA approval (1993), Imdur was tested in mice, rats, and rabbits. ZOCOR (simvastatin) What it does: Blocks the production of LDL cholesterol (the bad cholesterol). How it was developed: Two researchers won the 1964 Nobel Prize for research on rats showing how cholesterol is produced in the body. Before FDA approval (1991), Zocor was tested in dogs, rabbits, mice, and rats. TOPROL (metoprolol succinate) What it does: Reduces high blood pressure, treats heart failure and reduces the risk of another heart attack. Considered a type of betablocker. How it was developed: Rat and mouse-based research led to the first beta-blockers (1960s), used in the treatment of angina and cardiac arrhythmia. Later, beta-blockers were shown to reduce blood pressure and the risk of heart attack. Before FDA approval (1992), Toprol was tested in rats and mice. PLAVIX (clopidogrel bisulfate) What it does: Prevents blood platelets from sticking together, reducing the risk of blood clot formation. How it was developed: Before FDA approval (1997), Plavix was tested in baboons, rabbits, mice, rats, and Chinese hamster cells. ZESTRIL (lisinopril) What it does: Treats high blood pressure; can increase survival after a heart attack. Known as an angiotensin converting enzyme (or ACE) inhibitor. How it was developed: In the 1970s, synthetic versions of an ACE inhibitor found in snake venom and research in rats helped to develop similar drugs. Before FDA approval (1988), Zestril was tested in rats, mice, and rabbits. Timeline of animal-based cardiovascular research 1913 Nikolai Anichkov demonstrates the link between cholesterol and atherosclerosis, using cholesterol-fed rabbits. 1930s Researchers use cats to develop a range of early anti-blood clotting drugs. 1935 Dr. John Heysham Gibbon uses a heart-lung bypass machine, which takes over the process of circulating and oxygenating blood, in an operation on a cat. The cat survives for 26 minutes. 1950s Using IBM-built heart-lung machines and refined techniques, Gibbon conducts heart operations on dogs and succeeds in keeping 12 alive for more than an hour. Experiments in a variety of animals lead to the development of drugs for controlling high blood pressure, dissolving blood clots and for reducing stroke and heart disease risks. These experiments also help to develop arti.cial heart valves for patients with congenital defects or heart disease. 1953 Surgeons use a heart-lung machine in the first successful open-heart bypass surgery on a human. 1957 A dog at the Cleveland Clinic gets an artificial heart - and survives for 90 minutes. 1960s Animal experiments, mainly in dogs, lead to the .rst successful coronary bypass operation in a human. Transplants of hearts and other organs in dogs led to the first successful human heart transplant (South Africa, 1967). The recipient survived for 18 days. 1970s A variety of advances, such as improved heart bypass procedures, a way to measure coronary blood flow, and a myocardial preservation technique, rely on experiments with dogs. Replacement valves from pigs become ubiquitous. 1980s In the 1980s, a battery of surgical advances and new drugs that suppress the immune system from rejecting transplanted tissues pave the way for successes in heart and other organ transplant procedures. 1982 Doctors in Utah implant a permanent arti.cial heart, the Jarvik-7, into a human patient. The recipient survived for 112 days. 1984 California surgeons transplant a baboon heart into infant Baby Fae, who survives for 20 days. To date, she is the longest surviving recipient of an animal heart. 1994 Building on research in animals, researchers win approval from the Food and Drug Administration for a left ventricular assist device, which pumps blood for the heart's left ventricle. Intended as a temporary bridge for heart transplant patients, the device later is approved as a permanent implant. SOURCES: American Heart Association; Food and Drug Administration; Drugs.com; Columbia Encyclopedia; angioplasty.com; "Cardiology's 10 Greatest Discoveries of the 20th Century,'' Dr. Nirav J. Mehta and Dr. Ijaz A. Khan, Texas Heart Institute Journal. 2002. vol. 29 (3): pp. 164-171; National Library of Medicine; Foundation for Biomedical Research; Research Defence Society; Americans for Medical Progress; staff reporting. Copyright (c) 2004, Newsday, Inc. This article originally appeared at:
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