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By Richard Karel
A U.S. District Court ruling now under appeal could threaten the future of animal research critical to advances in psychiatry and other medical specialties, according to the Washington, D.C.-based National Association for Biomedical Research (NABR).
The ruling last October by now deceased U.S. District Court Judge Charles R. Richey struck down a section of the U.S. Department of Agriculture's (USDA's) animal welfare regulations and ordered the USDA to publish new regulations. According to Judge Richey's ruling, the new regulations would "establish standards including minimum requirements for a physical environment adequate to promote the psychological well-being of primates, in accordance with the Animal Welfare Act (AWA) and the Administrative Procedure Act. . .without delay. . . ."
According to an NABR analysis, the ruling could end up costing more than $300 million nationwide to upgrade and monitor animal care facilities.
"Many members of APA have become concerned over what they see as threats to the use of animals for research on psychiatric illness and treatments," said Samuel Guze, M.D., chair of the APA Council on Research. The issue was one of the key topics slated for discussion at the council's meeting at APA's annual meeting in San Diego at press time.
When complaints about the state of animal research facilities were first aired three decades ago, they were largely legitimate, Guze said. "I think it is important to say that the housing, care, and treatment of laboratory animals have improved tremendously over the last generation. I think 25 or 30 years ago, when a lot of criticisms of animal care were first voiced, a lot of us agreed. But I think almost every reputable medical center has upgraded its facilities tremendously."
Not all physicians and scientists agree with Guze, however, and APA has lost some members who oppose the Association's outspoken support for animal research.
One of those who resigned is psychiatrist Murry Cohen, M.D., of Annandale, Va., cochair of the New York City-based Medical Research Modernization Committee (MRMC). Cohen left APA in the early 1990's.
"I resigned specifically because APA became a lobbying group for the National Association for Biomedical Research," said Cohen. "And it still continues. I will say [Psychiatric News] did publish some letters representing the other side."
Every drug, by law, must be tested on animals for toxicity, but there is little evidence that the testing helps protect humans from untoward drug effects, according to Cohen. There are many examples where drugs tested for safety in animals turned out to be unsafe in humans, he said, including thalidomide and the antidepressant nomifensin.
"The truth is the only time you really know the toxicity of a drug [in humans] is when it's used" by physicians in practice, Cohen said. The metabolisms of animals and humans are too different to be comparable, he added.
As an alternative to animal testing, he suggested that new drugs be developed through more in vitro testing, careful analysis of computerized data, examination of serendipitous drug effects, and intensive, careful testing and postmarketing surveillance in humans.
In contrast, NABR Executive Vice President Barbara Rich pointed out that testing drugs in humans without first evaluating the risks in animals would be a violation not only of federal and state laws, but of international accords. These accords include the Nuremberg Code and the Declaration of Helsinki, both established in the aftermath of World War II (United States v. Karl Brandt, et al. Trials of War Criminals Before Nuremberg Military Tribunals Under Control Council Law No. 10, October 1946-April 1949; and Declaration of Helsinki, 18th World Medical Assembly, 1964, revised at World Medical Assembly, Tokyo, 1975).
Monkeys, rodents, and other animals are similar enough physiologically to humans that they can provide valuable insight into how drugs are likely to affect humans, said Rich. Toxicological studies use at least two species, which may or may not include a primate, she added. That animals and humans differ metabolically does not invalidate the use of animals to guide drug development, said Rich. People, too, differ metabolically from one another, but that does not invalidate the rationale for determining drug efficacy compared with placebo, she observed.
Where it is possible to avoid animal testing, as is the case in the development of many cosmetic products, companies should do so, said Rich. Cosmetics only rarely involve the use of entirely novel ingredients, so it is possible to use computerized data to identify and evaluate ingredients that are "generally recognized as safe" (GRAS) by the Food and Drug Administration, Rich said.
But anti-vivisectionist Cohen believes that psychiatry, too, is a field in which animal testing is inappropriate. "Of all the fields in which animal research doesn't apply, psychiatry is first and foremost," Cohen asserted. He is not convinced that the long legacy of maternal deprivation and separation studies in primates, dating back to psychologist Harry Harlowe, for example, were "scientifically necessary" for advancing human psychiatry, and he is highly skeptical of animal models of addiction.
"Animal research can prove anything that you want to prove," said Cohen. "You can prove that smoking causes cancer; you can prove that smoking doesn't cause cancer." Before the surgeon general's report on smoking was issued in the 1960's, tobacco companies funded animal studies that failed to show a link between smoking and lung cancer, according to Cohen.
The National Institutes of Health (NIH) spends more than $12 billion yearly, of which 40 percent is animal research, according to Cohen. But "all the major breakthroughs [at NIH] have nothing to do" with animal testing, he contended. Eventually the major pharmaceutical companies will realize that it is "in their scientific self-interest, their ethical self-interest, and their financial self-interest" to focus on research not based on animals, Cohen predicted.
If the goal of activists such as Cohen is to end animal research, it is pointless for supporters of animal research to seek common ground, said APA Council on Research Chair Guze.
"I think there can be a meeting of minds for the appropriate care of animals in research. But there can't be a meeting of minds when there is an ulterior motive of trying to prevent any use of laboratory animals by raising the cost prohibitively," Guze said.
"We're not talking about legitimate differences of scientific opinion," said Rich. "I don't think that's at all what's going on in the general animal research topic. Every institution that uses animals covered under the Animal Welfare Act is asking, 'Could we do it another way? Could we use fewer animals? Could we reduce the suffering? Can we eliminate the pain?' These are questions that are asked over and over again."
Although not all animal studies are worthwhile, said Rich, "I would not want to pick out the one we can do without. If we knew in advance, we wouldn't be doing research. Murry Cohen may be a master of hindsight, but in many ways I think he rewrites history."
APA Past President Herbert Pardes, M.D., dean of the College of Physicians and Surgeons at Columbia University, spoke with Psychiatric News about the research controversy.
Psychiatry has made "extraordinary advances in psychiatric research and development of new treatments," he said, and animal research has been "absolutely central" to this progress. "Psychiatry as a field will be stronger and will be able to do more for its patients the better the treatments it has. So to the extent that anything undercuts the strength of the research, it's a risk for patients with psychiatric disorders, most importantly, and in turn, for psychiatry."
There have been "dramatic improvements in animal research facilities over the last decade or so," Pardes said. Columbia University, for example, has spent approximately $20 million over the last 10 years upgrading animal facilities, he noted. The animal facilities there are now "phenomenal," he said.
"I think that the danger of the people who seem to be promoting animal rights to the detriment of medical research is that they will try to find sophisticated ways of doing that," Pardes said. They are turning to legislation, the courts, and attacks on the reputations of individual researchers, he noted. "That's a formidable fight to take on."
APA should do more to fight irrational constraints on animal research, said Pardes. "There are a million things APA can do. [The publications] can do stories. APA could hold a special session at its annual meeting on the value of animal research in developing psychiatric medications. APA can send out educational information to the membership [and] have educational forums with key Congressional people and the media. APA should support [NABR Executive Director] Frankie Trull. APA should call on psychiatrists to support state organizations that support animal research. But at the same time APA should stress that it supports humane care of animals. APA is on the side of the angels for [supporting] the proper care of animals but recognizes the critical need for animals in research."
Charles Chesanow, D.O., is the chief clinical officer of the Alcohol, Drug Addiction, and Mental Health Services Board in Franklin County, Ohio. Like Cohen, he resigned from APA to protest what he saw as the Association's uncritical support for animal research. Unlike Cohen, however, he sees a place for animal research, but believes it should be much more carefully regulated. Moreover, "the aspect of suffering and cruelty to animals should be factored in, in terms of the merits of project design, which is not currently being done."
He continued, "I am pro-progress. But I am against exploitation and needless cruelty. I don't view most people who work in animal research as sadistic or getting their kicks out of maiming and mutilating. I think it's much more insidious. I think there is callous disregard of suffering for the furtherance of personal goals such as tenure, doctoral degrees, and simply research dollars."
Chesanow would like APA to take an active role in evaluating the merit of various animal research protocols and take into account the potential suffering of the animals. APA should "determine if these projects are worth it, and not simply rubberstamp the projects of scientists, and factor into the equation whether the suffering justifies the perceived knowledge to be gained."
Chesanow told the story of a chimpanzee infected with hepatitis virus and then "left to rot in horrible conditions" for more than a decade.
"We've all known of tremendous progress that has been made thanks to the use of animals in research," he told Psychiatric News. "What we don't hear about are the multitude of other projects in which animals are cruelly treated, suffer needlessly, and for which there is nothing of value gained. And these projects are probably in the overwhelming majority."
At the least, said Chesanow, APA should try to distinguish the meritorious from the nonmeritorious animal research protocols. As a side effect, research might become more effective, he said.
(Psychiatric News, June 6, 1997)