A Critique of Animal Psychology Research at the University
of California at Berkeley
Brandon P. Reines, D.V.M.
Memory research: Dr. Mark R. Rosenzweig
Rosenzweig has received $648,656 from the NIMH. His early studies involved comparing the mental abilities of rats raised in empty lab cages to the mental abilities of rats raised in cages filled with toys. More recently, Rosenzweig's research has involved training mice to avoid entering a compartment in which electric shocks are delivered. He then injected various chemicals which are thought to influence memory formation through holes drilled in the skull. The purpose was to determine whether the chemicals caused the mice to. "forget" their training and enter the electrified compartment. During 1985, the last year for which Rosenzweig received NIH funding, he used 2,500 mice in his experiments.
Rosenzweig is one of the nation's best known physiological psychologists. For nearly three decades, Rosenzweig has attempted to illuminate human memory through animal experiments. In the introduction to Rosenzweig's well-known undergraduate text, Physiological Psychology, he claimed that physiological psychology research on animals has led to major improvements in public health. Later in his book, he stated that animal experiments on memory, including his own research, have led to major advances in the treatment of human memory disorders. Rosenzweig's two assertions will be analyzed in detail. First, in Physiological Psychology, Rosenzweig wrote:
Fortunately, many impairments and disorders may now be alleviated. For example:
1) It is now believed that by the year 2000 the incidence of mental retardation can be reduced by half through the application of principles learned in research. Factors contributing to this reduction will be genetic counseling, early diagnosis of certain metabolic disorders, better nutrition, and adequately stimulating environments.
2) Before the introduction of effective antipsychotic drugs in the 1950's, half the hospital beds in the United States were occupied by mental patients. Now the number of people who require hospitalization is dramatically lower. New drugs engender hopes of returning more psychiatric patients to full roles in the community.
3) Discoveries that reveal the mode of action of habit-forming drugs and their effect on the nervous system give hope that there will be effective cures of people addicted to drugs and prevention of damage to infants born of mothers who take drugs. (1982, p.5)
A point-by-point critique of Rosenzweig's three claims follows:
1) Rosenzweig's prediction that physiological psychology research on animals will lead to a 50% reduction in the incidence of mental retardation by the year 2000 is made without evidence. Undoubtedly, Rosenzweig's contention that "adequately stimulating environments" during early childhood development will decrease the incidence of mental retardation is based on his own animal research and other similar experiments. In the 1960's, Rosenzweig and his co-workers found that rats raised in a cage with a variety of running wheels and toys performed better at complex tasks such as maze running later in life (Rosenzweig et al., 1964). While Rosenzweig's findings were heralded in the popular science press, there was never any real evidence that the mouse data is consistent with observations of actual human children. In a 1973 critique of such animal research, Dr. J. P. Das explained that the human data is in fact opposite to the animal data:
In recent years there has been some re-examination of the animal data on restricted environment and their application or extension to humans. A good review is presented in Jensen ... For example, it is seen that even in animal studies when an animal is brought up in a lighted environment in contrast to a darkened one, and with all other conditions being constant, the animal typically does not show the ill effects of sensory deprivation. Secondly, animals which have been reared in a restricted environment do show initial disadvantages in discrimination learning, but such disadvantages gradually disappear with exposure to a normal environment. In other words, the gap between the sensory-deprived animals and those raised normally begins to narrow as the deprived animal is increasingly exposed to a normal environment following its early exposure to a restricted one. In the case of human children, however, the opposite is known to happen. The gap between a culturally disadvantaged child and a nondisadvantaged child begins to grow with age and exposure to normal classroom learning. The IQ tests reveal a wider and wider gap between, say, the black and middle-class white child as they progress in school years. Such considerations lead one to question the validity of extending findings from animal research to the culturally disadvantaged child" (p. 4).
2) As the debate over psychological experimentation on animals has heightened, several leading experimental psychologists have claimed that animal experimentation led to the major antipsychotic drugs (Miller, 1983). It is understandable that the discovery of the antipsychotics is the focus of attention, because such drugs represent some of the very few treatments for mental illness that have been shown effective in controlled human trials (Melmon and Morelli, 1985). In fact, it is well known among pharmacologists that the effects of the main drugs for the treatment of psychiatric disorders were found via clinical serendipity - from their side-effects in human patients McIlwain, 1957; Woolley, 1963; Baldessarini, 1977; Sitaram and Gershon, 1983). In the U. S. Public Health Service Study Establishing the Efficacy of Psychotropic Agents, the editors wrote, "During the brief history of treating depressed patients with drugs, therapeutic efficacy has almost always been developed from clinical experience - usually by accident" (1971, p. 101).
Similarly, the development of chlorpromazine for the treatment of schizophrenia (Caldwell, 1970) was based on clinical observations. Astute clinicians noted that the antihistamine promethazine made patients drowsy and less concerned about their environment (ataraxic). The potential to calm surgical patients encouraged investigators to search for a more potent drug. There was no good animal test to screen for the ataraxic effects, because the antihistamines made laboratory animals hyperexcitable, not calm. Chlorpromazine was ultimately chosen for clinical trials because it, like promethazine, reduced rat rope climbing performance. The rope climbing test was initially used to test muscular strength of experimental animals, and its relevance to ataraxia is questionable. Later, its antipsychotic effects in the treatment of schizophrenia were discovered entirely by clinical observations. It appears that the animal test served more as a justification for clinical trials than as an effective screen for clinically useful drugs. While J. Swazey (1979) maintained that the animal test led to the discovery of chlorpromazine, there is no scientific evidence that this was the case. Since phenothiazines that were ineffective in animal experiments were not tested clinically, it is not possible to show statistically that rope climbing performance was superior to random selection. Other antipsychotics have been "tested" first on animals by similar screens. All such screens have questionable relevance to schizophrenia, because it is unlikely that any animal besides man can suffer from schizophrenia. Even if nonhuman animals did develop schizophrenia, we would have no way to make the diagnosis, because the animals cannot verbalize to humans delusions or other hallmarks of this mental illness. Thus, researchers have relied on crude animal tests, such as rope climbing performance, which may have no bearing on future efficacy for human psychiatric effect.
3) Regarding drug addiction, the only new drug that has shown promise in treating drug addiction is the well known antidepressant imipramine. Dr. Jeffrey Rosecan, director of the Cocaine Abuse Treatment Program at Columbia-Presbyterian Medical Center in New York discovered imipramine's anti-addiction effect by clinical serendipity. While treating depressed cocaine addicts with imipramine, Rosecan found that the patients could no longer "get high" from cocaine. Based on this clinical observation, he began to treat cocaine addicts with the drug, and he has reported this effect in nearly 75% of his patients. Ironically, while the drug's effects were clearly discovered by clinical studies, scientists are now testing imipramine on animals. A July 6, 1986 report in the L.A. Times said: "And now the unforeseen uses of such drugs have sent neuroscientists back to their laboratories to conduct animal studies ... This is an unusual sequence of events because new drugs are tested in animals before they are given to humans." effects of methadone on narcotic addicts were also discovered by clinical serendipity, which led to its wide use in heroin detoxification (Dole and Nyswander 1965).
In his text, Rosenzweig maintained that animal research has led to the discovery of memory-restoring drugs:
Some drugs that have been shown to modulate memory formation and/or to affect memory retrieval in laboratory animals have now been found to be effective in human beings. For example, arecoline, a cholinergic agonist, and choline, a precursor of acetylcholine, improve serial verbal learning in normal human subjects; scopolamine, a cholinergic antagonist, impairs it. Those subjects who were more affected by both drugs were the ones who showed the poorer learning scores under control conditions. In other words, these drugs may be useful in bringing individuals toward an optimal level of cholinergic activity but may not be able to improve those who are already at that level ... Physostigmine improved both storage and retrieval of verbal material in normal human subjects ... Vasopressin (antidiuretic hormone) has recently been shown to occur in the brain, where it may be a synaptic transmitter. Administering vasopressin to rodents has been shown to aid memory formation ... Following up this lead, a pilot study with four cases of amnesia found that administering vasopressin over a few days brought about recovery of memory in each case ... (1982, pp. 634-5)
To understand fully the inaccuracy of Rosenzweig's statements, it is necessary to explain how a few of the major drugs for the treatment of brain disorders were really discovered. One of the most important advances in the treatment of any such disorder in recent decades is the discovery of L-dopa's efficacy against parkinsonism. L-dopa was tested on Parkinson's disease patients because the brains of such patients contain too little dopamine (Ehringer and Hornykeiwicz, 1960). In a like manner, researchers became interested in testing choline and related substances on Alzheimer's patients and other presenile dementia patients because the brains of such patients are low in the enzyme that produces acetylcholine (Spillane et al., 1977). While such drugs have failed to prove effective in restoring memory in controlled human trials, Rosenzweig's statement attempts to make the animal research "look good" by making several "positive-sounding" but totally irrelevant points. It makes little difference if acetylcholine improves "memory" in animals and perhaps in a few normal human volunteers (though uncontrolled human observations are not generalizable).
While the idea for using acetylcholine analogues to treat Alzheimer's disease came from clinical observations, the drug has failed to improve the functioning of Alzheimer's patients. The discussion of vasopressin is also superfluous. No drugs, including vasopressin, have thus far proved effective against any of the amnesic syndromes (Crook et al., 1986). Ironically, the animal researcher who did the original animal studies with vasopressin did not actually believe that it improved "memory" per se, but he was convinced by his colleagues to use the word "memory" to gain publicity for his research (Parnham and Bruinvels, 1983, p. 328). The fact is that virtually every major drug for the treatment of brain disorders, including mental illness, has been discovered through clinical serendipity.
1. Hormones and Behaviour Research
3. Mother-Infant Separation Research
4. Memory Research