Perspectives On Medical Research

Volume 5, 1995

Aping Science

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

Primate Research’s Role in Medical History

Medical history as described by nonhuman primate researchers is replete with examples of major contributions from monkey and ape experimentation. Former Yerkes director Frederick King, for one, attributed significant advancements in virtually every major field of medical and behavioral research to nonhuman primate studies.¹ A look at three of the most celebrated “discoveries” from primate laboratories--the importance of affectionate maternal contact on psychological and social development, the discovery of the polio vaccine, and the discovery of the Rh blood antigen--is a revealing indication of just how questionable these claims are.

Maternal Contact

Primate researchers have generated voluminous literature on the effects of various kinds of maternal deprivation on both maternal and infant behavior. King has credited such research with major contributions:

Research on the effects of varying types and degrees of infant separation from mothers and mother surrogates have documented the importance of emotional care and stimulation for the short- and long-term psychological health of the offspring.¹

In fact, clinical studies, many of which preceded the nonhuman primate work, clearly demonstrated the deleterious effects of inadequate emotional care and stimulation on human infants.^2,3

Disregarding clinical data, animal researchers have separated infant primates from their mothers under myriad conditions, including different postnatal time periods, different durations of separation, and different opportunities to be re-united with or see mothers. The “finding” that has perhaps received the most attention from the popular press was Harry Harlow’ s observation that infants separated from their mothers shortly after birth would cling to a cloth “surrogate mother” rather than a monkey-like wire construction, even if the wire structure included an attached milk container.⁴ Harlow concluded, “The infant monkeys continually clasped and clung to the cloth mother, and thus the original research showed that body texture, the skin we love to touch, was a variable of completely overwhelming importance over all activities associated with the breast, including the ingestion of milk.”⁵ While such a study is dramatic in that infant monkeys chose to go hungry so as not to forgo a soft touch, it is unclear whether this observation has yielded knowledge about monkeys in their natural environment, let alone humans. Rather than any genuine insight into monkeys’ natural behavior or psychology, the findings may reflect the artificial laboratory situation, with its early maternal deprivation and human-constructed “mother.” Furthermore, infant monkey behavior reflects instincts derived from millions of years of jungle living. While an infant monkey must cling to the mother to survive as the mother climbs trees, human infants have no such need. Although baby monkeys have a strong instinctive desire for maternal contact, given different infantile needs, there is no reason to expect from Harlow’s experiments that human infants would necessarily share this desire. The fact that they do was learned from earlier clinical research, and it was this research that allowed Harlow to generalize his monkey results to humans.

Despite the obvious scientific limitations of Harlow’s experimental protocol with nonhuman primates, regarding one observation in which human and monkey data differed, he declared, “The data of the human theorists did not generalize to monkeys because the human theory was false. Monkey theories basically generalized to human infants because the monkey facts were true.”⁵ Harlow’s position as president of the American Psychological Association undoubtedly gave considerable weight to such confident, albeit unwarranted, preference for nonhuman primate laboratory data over human data. Harlow’s professional position likely helped convince the public, and perhaps fellow scientists, of the supposed value of nonhuman primate research.

Polio Vaccine

Animal research advocates repeatedly cite the polio story as an example of animal experimentation’s utility.^1,6,9 In truth, the principle monkey model of polio infection was fundamentally misleading, and, as a result, it misdirected preventive measures and delayed vaccine development.¹⁰ As Albert Sabin, who developed the oral polio vaccine, explained in 1984, “the work on [polio] prevention was long delayed by an erroneous conception of the nature of the human disease based on misleading experimental models of the disease in monkeys.”¹¹

In the 1800s, polio’s clinical presentation and natural history were deduced from bedside observations and post-mortem studies of human victims. Ivar Wickman’s detailed analyses of two Swedish epidemics in the early 1900s revealed that mild or even subclinical cases contributed to contagious spread of the disease. Most investigators had focused on polio’s Iife-threatemng paralysis and considered polio primarily a central nervous system disease, but Wickman found that polio affects the alimentary tract (throat, stomach, and intestines) and correctly suggested that the gastrointestinal system may be the initial site of infection.^12,13

Animal data contradicted Wickman’s observations and delayed understanding of polio’s true pathogenesis and natural history. The first animal model of polio was developed by Simon Flexner, who induced polio-like paralysis in rhesus monkeys after placing infected human tissue into their noses. Convinced that his animal model precisely paralleled the human disease, he concluded that human polio was introduced to the brain via the nose and confined to the central nervous system. For decades, most scientists adhered to this erroneous theory, which spawned misguided measures. For example, the “Schultz-Peet prophylactic” nasal spray, based on Flexner’s model, did not protect children from polio infection. Clinical polio researcher John R. Paul observed, “It was another demonstration that the problem of preventing human poliomyelitis was not to be easily solved on the basis of evidence deduced from the experimental disease in the rhesus monkey.”¹⁰

While animal studies remained the principal focus of polio research in the United States, Swedish clinical investigators continued to make important contributions by studying infected humans. They tested for the presence of polio in tissues of human polio victims and family members by inoculating monkeys with test samples. If a test monkey contracted polio, the sample was determined to be infected. The investigators found that polio carriers could have polio virus present in their throats and intestines up to seven months after exposure. Importantly, these Swedish investigators did not use the monkeys as models of polio infection. The monkeys were used as bioassays, allowing researchers to determine whether virus was present in certain human tissues. Today, few animals are used as bioassays, because less expensive, more reliable non-animal bioassay techniques exist. Overwhelmingly, nonhuman primates are used as “models” of human conditions, not as bioassays.

Yet, Flexner and other animal researchers continued to study rhesus monkeys infected with viruses obtained from other rhesus monkeys. This process selected for more virulent polio strains that tended to infect nervous tissue. Consequently, the animal model increasingly diverged from human polio in pathogenesis and natural history.

In the 1940s researchers found that polio infection in chimpanzees accords more closely with the human disease. Chimpanzees, like humans, were found to harbor the polio virus in their alimentary tracts. In a convoluted regression, researchers were now willing to accept the clinically derived hypothesis from earlier years that polio involves the human alimentary tract.

While clinical studies showed that polio virus infects gastrointestinal tissue, decades of monkey experimentation suggested only neural tissue involvement, and, as a result, vaccine researchers mistakenly believed that polio virus would only grow in neural tissue. Vaccine development was therefore delayed because it was thought that vaccines derived from neural tissue culture were too dangerous. In 1948, however, John Enders, Thomas Weller, and Frederick Robbins, on the basis of human experimental data, grew polio virus on human intestinal tissue, which finally led to a safe vaccine.

Rh Blood Antigen

[An antigen is a cell surface protein that may initiate an immune system response. If a person who lacks a certain red blood cell antigen receives donor blood with that antigen, that person may have a transfusion reaction.]

In 1937, a woman bled severely after delivering a macerated fetus, requiring a blood transfusion. A transfusion with her husband’s blood, matched for the known blood groups at the time, resulted in a near-fatal transfusion reaction. Clinical researchers, after performing a series of clotting studies, surmised that there must be a yet-undefined major blood antigen.¹⁴ Karl Landsteiner and Alexander Wiener’s subsequent blood clotting studies indicated that this antigen was similar to one found in monkeys, and they named it Rh for the rhesus monkey.¹⁵ Subsequent research demonstrated that the two antigens were genetically different,¹⁶ but the term Rh had already been so widely used that it was impossible to change. R. Race and Ruth Sanger have observed:

Many years later it came to be realized that the rabbit anti-rhesus and the human anti-Rh antibodies are not the same. The vast literature which had accumulated made it impossible to change the name of the human antibody from anti-Rh, and the suggestion of Levine that the rabbit anti-rhesus antibody should be called anti-LW, in honour of Landsteiner and Wiener, has been widely adopted.⁷

Indeed, Philip Levine himself, who discovered the new human blood antigen, has noted that Landsteiner and Wiener’s report, “contains nothing of clinical significance.”¹⁶ While the name Rh suggests a close link between nonhuman primate research and human medicine, we now know it to be a misnomer. Nevertheless, animal research advocates often point to “the Rh factor” to emphasize the supposed value of nonhuman primate research. For example, the Department of Health and Human Services produced a brochure that includes discovery of the Rh antigen as one of many purported contributions of animal experimentation.⁸


Conclusion

Primate researchers have grossly exaggerated the role of nonhuman primate studies in medical progress and significantly downplayed the misleading data such research has spawned.^18-21 Several such researchers have attained leadership positions within the scientilic community, adding credibility to their historical interpretations and enhancing nonhuman primate research’s prestige.

1 King FA, Yarbrough CI. Medical and behavioral benefits from primate research, in Gay WI (ed). Health Benefits of Animal Research. Washington DC, Foundation for Biomedical Research, 1986, pp 65-79.

2. Bowlby J. Grief and mourning in infancy and early childhood. Psychoanalytic Study of the Child 1960;15:9-52.

3. Spitz RA. Anaclitic depression: An inquiry into the genesis of psychiatric conditions in early childhood, II. Psychoanalytic Study of the Child 1946:2;313-342.

4. Harlow HF, Zimmerman RR. The development of affectional responses in infant monkeys. Proceedings of the American Philosophical Society 1958;3: 1017-1023.

5. Harlow HF, Gluck JP, Suomi SJ. Generalization of behavioral data between nonhuman and human animals. American Psychologist Aug 1972, pp 709-716.

6. Nuland SB. Animal-rights activists waging struggle against medical science and humanity. Los Angeles Times Sept 7, 1989, p 7.

7. Landers A. Advice to readers. Baton Rouge Morning Advocate Mar 1, 1990.

8. Department of Health and Human Services. Animal Research: The Search for Life-Saving Answers. Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, circa 1991.

9. Committee on the Use of Laboratory Animals in Biomedical and Behavioral Research. Use of Laboratory Animals in Biomedical and Behavioral Research. Washington, DC, National Academy Press, 1988.

10. Paul JR. History of Poliomyelitis. New Haven, Yale University Press, 1971.

11. Sabin AB. Statement of Albert B. Sabin, M.D. [before the Subcommittee on Hospitals and Health Care of the Committee on Veterans’ Affairs, House of Representatives]. Serial no. 98-48, April 26, 1984.

12. Wickman I. Studien über Poliomyelitis acuta; zugleich em Beitrag zur Kenntnis der Myelitis acuta. Berlin, Karger, 1905.

13. Wickman I. Beitrage zur Kenntnis der Heine-Medinschen Krankheit. Berlin, Karger,1907.

14. Levine P, Stetson RE. An unusual case of intra-group agglutination. Journal of the American Medical Association 1939; 113:126-127.

15. Landsteiner K, Wiener AS. An agglutinable factor in human blood recognized by immune sera for rhesus blood. Proceedings of the Society for Experimental Biology and Medicine 1940;43:223.

16. Levine P. The discovery of Rh hemolytic disease. Vox Sanguinis 1984;47: 187-190.

17. Race RR, Sanger R. Blood Groups in Man. Oxford, Blackwell Scientific, 1975.

18. Reines BP. On the locus of medical discovery. Journal of Medicine and Philosophy 1991; 116:183-209.

19. Reines BP. On the role of clinical anomaly in Harvey’s discovery of the mechanism of the pulse. Perspectives in Biology and Medicine 1990;34: 128-133.

20. Cohen MJ. The irrelevance of animal experimentation in modern psychiatry and psychology, in Cohen MJ, Nadelson N (eds) Proceedings of the Conftrence “Future Me4ical Research Without the Use of Animals: Facing the Challenge”. Alexandria VA, Concerned Helping Animals in Israel, 1991, pp 91-107.

21. Kaufman SR. Does vivisection pass the utilitarian test? Public Affairs Quarterly 1995;9: 127-137.