A Critical Analysis of Research at the Yerkes Regional Primate Research Center

Introduction
Because animal experimentation receives the largest share of federal biomedical research funding, the Committee on Animal Models in Biomedical Research (CAMBR) has attempted to determine animal experimentation's actual relevance and value to medical discovery. Previous research has indicated that the method has serious inherent limitations and often yields misleading results.
Animal research advocates claim that animal models can serve as reliable models of human conditions, permitting invasive studies in "controlled" laboratory environments. However this control is largely illusory, because interspecies differences in anatomy and physiology, differences in cause and course between natural human disease and artificially induced nonhuman pathology, and stress experienced by animals in laboratories invariably alter research results. Only human clinical investigation is inherently reliable. No theory about humans can be genuinely tested using nonhuman animals.
Interspecies differences preclude applying results derived in one animal species to another. In the area of behavior, for example, each species' behavior reflects social, physiological, and psychological factors unique to that species, and observations about one species' behavior cannot be reliably applied to another.
The same applies to interspecies differences of a biological nature. For example, toxicity and nutritional requirement experiments in rats cannot be applied to humans because, unlike humans, rats are physiologically unable to vomit toxins, have no gall bladders and therefore digest fats differently, manufacture their own vitamin C, obtain vitamin D by licking their fur, and absorb iron differently from humans.
Differences in cause and course between natural human disease and artificially induced nonhuman pathology also preclude accurately generalizing results. For example, the multiple, complex, and chronic pathologies that result in human stroke vary significantly from the experimental method of simply tying off an artery in nonhuman animals. Human colon cancer, which develops spontaneously and gradually, is very different from chemically induced experimental colon cancer of rats. Unlike human colon cancers, these rat colon cancers usually involve multiple primary lesions, arise from normal colon tissue, effect the small intestines, kill by bowel obstruction, and do not metastasize. Humans and nonhuman animals are not merely interchangeable machines.
Common experimental manipulations, such as food and water deprivation, prolonged immobilization, and invasive surgical procedures, profoundly alter metabolic, immunologic, and other parameters. Furthermore, there is also stress inherent in the laboratory environment, such as caging, social disruption, restraint, transport, and repeated handling, which undermines research results. These factors prevent applying results to free-living members of the same species, much less to humans.
Recognizing (but rarely openly acknowledging) the problems inherent in animal experimentation, animal researchers nevertheless claim that experimentation on monkeys and apes carries more validity because of our close kinship with other primates. But, is "close kinship" sufficient to overcome the many difficulties with animal research?
To help answer this question, the CAMBR evaluated the clinical relevance and impact of research at the Yerkes Regional Primate Research Center, an affiliate of Emory University, in Atlanta, Georgia. The nations's oldest of seven primate centers, Yerkes receives about $13 million per year in federal funding. The Center houses over three thousand primates, and, with about 200 chimpanzees, is the only center to conduct experiments on our closest relatives, the great apes.

Primate Research and Medical History
As depicted by animal research advocates, medical history is replete with major contributions from experimentation on monkeys and apes. A review of two "discoveries" often attributed to experimentation on nonhuman primates--the discovery of the polio vaccine and the importance of maternal affection in an infant's psychological and social development--reveals how medical history has been distorted.
The use of rhesus monkeys in polio research as "models" of the human disease immediately distorted the research. Although polio can paralyze both humans and monkeys, experimentally induced polio in monkeys differs in important respects from human polio. The monkey disease is primarily a neurological illness, whereas observations of humans prior to the monkey experiments suggested (correctly) that polio began as a gastrointestinal disease. The leading animal model, in which monkeys were infected via the nose, therefore contradicted this human finding. Nevertheless, researchers continued to trust the monkey "model," conceiving polio as a neurological disease. Because it was considered too unsafe to develop vaccines from neural tissue, vaccine development was retarded until John Enders and his colleagues, on the basis of human experimental data, grew polio virus in human intestinal tissue. Dr. Albert Sabin himself believed that "the work on prevention [of paralytic polio] was long delayed by an erroneous conception of the nature of the human disease based on misleading experimental models of the disease in monkeys."
Maternal deprivation experiments have involved separating infant monkeys from their mothers and rearing them with "surrogate" mothers made of wire and cloth or with "monster mothers" who abuse them. Other protocols have included partial isolation in wire cages or total isolation in "pits" or "wells of despair." While researchers repeatedly claim that these nonhuman primate experiments "prove" that maternal love and affection are necessary for healthy psychosocial development, this was well known from preceding studies of human infants who experienced maternal deprivation. Although researchers continue to manipulate nearly every conceivable variable, such as length of separation or caging parameters, Stephen Suomi, one of the major practitioners of this method, has acknowledged, "Most monkey data that readily generalize to humans have not uncovered new facts about human behavior; rather, they have only verified principles that have already been formulated from previous human data. . . To date the monkey data have added little to knowledge of human mother-infant interactions."
Those who experiment on nonhuman primates have grossly exaggerated the role of nonhuman-primate studies in medical progress and significantly minimized the misleading data that results.

Review of Yerkes Primate Experiments

Behavior
Yerkes researchers claim that their studies of monkey and ape behavior provide insights into human mental development and behavior. For example, having found that captive chimpanzees do not teach gestures acquired in adulthood to their offspring, Yerkes researchers extrapolated this finding to both free-living chimpanzees and humans. Free-living chimpanzees, however, often do teach gestures to their offspring--including behaviors regarding food preferences and tool making and use. Captive chimpanzees might not do so because unnatural laboratory conditions impose intellectual and social deprivation.
Yerkes researchers also hypothesize that the ability to learn and use communicative symbols is genetically based in humans, but not chimpanzees. They suggest that human children with learning disabilities might, like chimpanzees, lack the necessary genetic material. This conclusion is totally unwarranted. Chimpanzees did not stop evolving millions of years ago; rather, they have continued to evolve physical and social attributes to serve particular survival needs in particular environments. Gleanings from captive chimpanzees cannot elucidate human learning disabilities.

AIDS
A large proportion of available AIDS research funds has supported experimentation on nonhuman primates, yet the approach is replete with shortcomings. The most widely used "models" of AIDS at Yerkes and other primate centers are monkeys infected with different strains of simian immunodeficiency virus (SIV). However, all SIVs differ markedly from the principle AIDS-related immunodeficiency virus (HIV-1). Also, monkey immunoregulatory responses to SIVs fundamentally differ from human response to HIV-1. Finally, clinical features of AIDS and SIV-induced illness differ.
Contrary to claims by Yerkes officials, Yerkes researchers cannot determine whether HIV can be transmitted via breast milk by studying SIV transmission in monkeys. Major differences exist between SIV and HIV transmission. For example, in utero transmission occurs only rarely with SIV but frequently with HIV, making application of SIV transmission findings to humans problematic.
Yerkes researchers have also infected chimpanzees with HIV in an attempt to study "AIDS" in nonhumans. However, it has been exceedingly difficult to make chimpanzees sick from HIV infection. Although many HIV researchers concede that HIV-infected chimpanzees cannot serve as reliably "models" for humans with AIDS, Yerkes researchers continue to study HIV resistance in chimpanzees in an attempt to uncover methods of inducing HIV resistance in humans. Studies of people who have remained AIDS-free despite chronic HIV infection are far more relevant.
Moreover, experimentation on chimpanzees is poorly equipped to test potential AIDS vaccines. Federal regulators have sometimes waived animal-testing requirements when a potential vaccine or drug has appeared particularly useful. To effectively combat AIDS, we must better understand the mechanisms of HIV transmission in humans, the disease's natural history, and humans' immunological response to HIV. Improved understanding requires studies of humans who develop and resist illness after exposure to HIV.

Vision
Most Yerkes vision research involves disrupting normal visual development in nonhuman primates during a critical period of their youth, causing permanent vision loss. Much of the information sought in such research could be safely and accurately obtained with non-invasive imaging technologies and autopsy studies of humans.
Yerkes researchers induce vision loss by sewing animals' eyelids shut, removing their natural lenses, or surgically misaligning their eyes. Yerkes officials claim that studies of artificially induced vision loss have uncovered therapies for reversing vision loss, but these therapies have actually derived from clinical studies involving human children.

Reproduction
Investigations into reproductive physiology have been a Yerkes mainstay, although the "models" are often obviously inapplicable to understanding human sexuality. Consider, for example, Yerkes research involving the effects of oral contraceptives (OCs) on chimpanzee sexuality. Unlike human females, chimpanzee females do not pair monogamously with males, are not sexually receptive throughout their estrous cycle, have external genitalia much more responsive to changes in sex hormone levels, becomes more sexually attractive to chimpanzee males due to genital swelling, and, through their nakedness and quadrupedal position, exhibit their genitalia for male inspection.
A similarly unsound research program involves creating experimental endometriosis in nonhuman primates through surgical interventions, a mechanism that differs considerably from the spontaneous endometriosis found in women. The results of hormonal treatment of the artificially induced "endometriosis" in monkeys cannot guide treatment of human endometriosis. In fact, prior to Yerkes' experiments, clinicians had already recognized the effectiveness of hormone treatment of human endometriosis. Because the Yerkes findings cannot be reliably extrapolated to natural disease processes in humans, they have at times duplicated and at times contradicted clinical findings in humans.
Yerkes research with experimental "osteoporosis" illustrates how expediency often takes priority over good science. While aged female monkeys do spontaneously develop osteoporosis, there has been little research to determine whether this is a valid model for human bone loss. To avoid the cost of raising monkeys to old age, Yerkes researchers used drugs to suppress ovarian function in young females, which promoted bone loss. Given that osteoporosis reflects chronic bone use, posture, and a wide range of hormonal effects, using young human women with ovarian suppression as a model for osteoporosis in the elderly would be unsound. It makes even less sense to extrapolate findings in young monkeys to old women.

Parkinson's Disease (PD)
Yerkes' claim that its research has been central to PD treatment is unwarranted. Yerkes' monkey "model" of PD, which involves acute exposure of a young monkey to a chemical that damages specific brain areas, cannot be compared with the enigmatic spontaneous and gradual deterioration of the substantia nigra found in the brains of older humans with PD. Despite the superficial similarity between the two conditions, there are significant differences in location of brain damage and microscopic features of damaged cells.

Atherosclerosis
Another Yerkes research focus is studying atherosclerotic vessel pathology, such as coronary artery disease, in baboons. However, the artificial thrombus (clot) produced in the baboon differs from the naturally occurring human atherosclerotic plaque in that the baboon disease:

1. develops over the course of one hour rather than years

2. forms in normal blood-vessel walls rather than the damaged arterial walls found in humans

3. involves clots comprised of only blood components

Evidently recognizing the obvious incongruity between their model and human arterial plaques, Yerkes researchers have, at times, claimed that their model is analogous to a "venous-type thrombus." But, the baboon thrombus develops much more rapidly than human ones and forms in an artery-vein shunt that resembles an artery more than a vein. Use of such shunts is not a reliable way to discover agents that prevent blood clots in human veins.

Periodontitis
Prostaglandins are chemicals produced by the body that incite pain and inflammation. Observations in humans have linked local increases in prostaglandin concentration with periodontitis and loss of tooth attachment. In accord with these findings, Yerkes researchers found that drugs blocking prostaglandin formation reduced experimentally induced periodontitis in monkeys. However, the experimental periodontitis was caused by placing a tie around the tooth base. In contrast, human periodontitis typically develops slowly, is promoted by such factors as inadequate dental care and poor dietary habits (such as excessive sugar intake), and does not involve foreign bodies. The animal model does not, therefore, mirror human periodontal disease and is unlikely to generate new, clinically useful hypotheses.

Primate Research Risks

Viral Epidemics
Inadvertent human exposure to lethal nonhuman-primate viruses during experimental procedures could initiate devastating epidemics. For example, hundreds of millions of people were innoculated with a polio vaccine contaminated with the simian virus SV40, and this population has experienced a higher than normal rate of certain tumors. Similarly, HIV and hepatitis B likely came from human exposure to chimpanzees, perhaps in their capture or use for research.
There is no way to test for unknown viruses, and viruses hidden in nonhuman-primate DNA could have fatal consequences for humans. Already the virulent herpes-family "B" monkey viruses have infected at least twenty-five people associated with nonhuman-primate research, killing 16 of them. There is also reason to fear Ebola viruses, which have been responsible for two outbreaks in central Africa that have killed hundreds.

Social Risks
Because many people see monkeys and apes as "almost human" but lacking human social conventions, researchers often assert that nonhuman primates can model "human nature." Repeatedly, distorted notions and caricatures of nonhuman primate "behavior" have been perniciously used to defend racism and sexism as "natural." For example, a top government research official recently drew parallels between violent behavior of captive monkeys and violent inner city youths. Of course, such flippant application of laboratory data to humans is unwarranted. Furthermore, the data do not even reveal anything about innate monkey behavior. Their violence is unnatural--caused by the researchers themselves--and reflects the pain and suffering provoked by laboratory confinement.

Biomedical Research Risks
Findings in many areas of research, such as polio, bypass surgery, organ transplantation, were distorted by use of nonhuman primates as models for human diseases. Nevertheless, few scientists openly question animal experimentation's reliability, because powerful research bureaucrats and academicians regard any serious challenge to this multi-billion dollar institution with vitriol, effectively silencing most criticism. The Medical Research Modernization Committee has documented cases of those ignoring the implicit warnings suffering professional harassment, ranging from ridicule and contempt to loss of funding or dismissal.

Public Health Research for the Future
Over the last several decades, federal funding priorities have shifted from learning about human diseases through direct observation of human patients to performing non-clinical experiments, particularly on animals and cells. In 1987 only 7.4 percent of new National Institutes of Health (NIH) grants were directed for patient-oriented research; only 4.5 percent of 1990-1991 NIH grants funded basic research involving human subjects. Animal experiments involve manipulating different variables to create a condition that mimics--in some of its aspects--a naturally occurring disease in humans. This approach cannot enlighten us about human diseases, which invariably differ from experimentally induced conditions in cause, course, and symptoms. Only human clinical inves tigation can definitely reveal the cause of human disease.
In order to uncover the causes of cancer, heart disease, stroke, and other major killers, researchers should seek to identify the biochemical, physiological, andcal, and environmental characteristics of individuals with these diseases. American health officials would do well to consider Sweden's system, which assigns newborn infants tracking numbers and records medically relevant events throughout their lives. Theories derived from human clinical material--including medical histories, biochemical analyses of cells, tissues, and organs, and autopsies--are directly relevant to human anatomy, physiology, and pathology.

Recommendations
Experimentation on nonhuman primates should be sharply curtailed.
To accomplish this, we recommend that the federal government take these actions:

• Close the primate center system of the National Center for Research Resources.
• Reallocate freed base-grant funding to research on the environmental causes of human diseases.
• Mandate that nonhuman primates currently at primate research centers be transferred to environments--such as suitable animal sanctuaries--that best serves their needs.
• Eliminate EPA regulations that mandate animal testing.
• Expand the funding to develop in-vitro tests using human cells and tissues.
• Expand epidemiological and public health research and add additional clinical investigators as NIH officials.
• Include at least one sociologist, anthropologist, or social psychologist to the study section memberships of the National Institute on Drug Abuse, National Institute on Aging, National Institute of Mental Health, and National Institute on Child and Human Development.
• Include at least one public-health biostatistician and one human pathologist on the study sections of the National Cancer Institute, National Institute of Allergy and Infectious Disease, National Heart Institute, Lung and Blood Institute, and General Medical Sciences Institute.

To order a copy of the full report, Aping Science, send a check in the amount of $12.00 to the

Medical Research Modernization Committee
20145 Van Aken Blvd #24
Shaker Heights, OH 44122
(216) 283-6702 (phone and fax)