Ethics of Research involving animals
Study of polio and the development of polio vaccine
6.29 Animal disease models have been used in the study of poliomyelitis (polio), enabling an understanding of the disease process at the cellular level and facilitating the subsequent development of an effective vaccine. The polio virus enters the body through the mouth, from where it can travel to the digestive system and enter the bloodstream. The virus invades the CNS and destroys motor nerve cells, leading to paralysis and sometimes death. Before vaccines were introduced in developed countries in the late 1950s and early 1960s, polio was a common disease, estimated to be responsible for crippling more than half a million people around the world per year.28 Since the introduction of vaccines, polio has largely been eliminated from industrialised countries.29
6.30 It had long been thought that polio was infectious, and in 1908 two researchers aimed to induce polio in several animals by injecting them with extracts of spinal cord material from a boy who had died of the disease. While the extracts did not cause polio-like disease in rabbits, guinea pigs or mice, the disease manifested itself quickly in Old World monkeys. Later, researchers were able to transmit polio from monkey to monkey by the injection of extracts of diseased spinal cord. Thus the virus could be propagated and an animal model of the disease was created. Use of this animal model in further studies led to the identification of the polio virus. Welfare implications for animals used in this early research extended over a broad range, but could be expected to resemble some of the symptoms experienced by humans.
6.31 In 1939, researchers were able to adapt one of the strains of the polio virus to make it infectious to mice, thus creating a more convenient rodent model for the disease. In the 1940s, researchers who were subsequently awarded a Nobel Prize demonstrated that the polio virus could be grown in cultured human cells, a property essential for future research on the virus. It was still not possible to observe the virus under the microscope at that time. Therefore, in order to confirm that the virus did propagate in cultured tissue, fluid was injected from the cultures into animals to observe if the disease developed.30 In 1949, research on rodent models showed that there are in fact three types of polio virus.31 In the 1950s Dr Jonas Salk used cultured monkey kidney cells to grow the virus. He then used the virus particles to produce the first vaccine which was found to be very effective at preventing the disease in humans, although people could still carry and spread the virus if it invaded their intestinal tract. In the 1960s, a new oral vaccine against the disease was developed. This vaccine contained live virus which had been ‘attenuated’, or weakened, by repeatedly growing it in cultured monkey cells. The vaccine produced an adequate immune response without causing an infection. The live attenuated virus, however, can sometimes revert to a virulent form and cause infection. Animals are currently used to test the potential virulence of each batch of vaccine that is produced to overcome the problem of occasional vaccine-associated poliomyelitis (see Box 8.5).
6.32 Mice and monkeys were used during important stages of the study of polio and the subsequent development of the vaccine. However, the initial development of the polio vaccine is regarded by some as an example which shows that animal research is misleading.32 The early research was controversial because, in the first half of the 20th century, the dominant scientific theory was that the polio virus entered the body through the olfactory nerves of the nose, as indicated by experiments in monkeys. Scientists, particularly in the USA and Canada, inferred from these observations that it would be useful to develop prophylactic nasal sprays. The sprays were tested on animals and then on humans. In one large-scale trial in Toronto in 1937, the spray was tested on 5,000 children. The trial results soon revealed that the spray was ineffective as a preventative for infection by the virus and, furthermore, that the spray caused adverse reactions.33 It was then discovered that humans are in fact primarily infected via the digestive system and not through the nose. The researchers had not fully understood the pathogenesis of the disease and wrongly assumed that viral entry was via the nose. Thus, this error does not support the claim that polio is an example showing that, in principle, animals are unsuitable models for the disease. Rather, it indicates that failures in this case resulted from a false hypothesis made by the researchers.
Footnotes28 Eggers HJ (1999) Milestones in early poliomyelitis research (1840 to 1949) J Virol 73: 4533–5.
29 The World Health Organization has recently estimated that polio would be eliminated during 2004–5, although similar
statements have been made before. In 2003 there were 784 confirmed cases of the virus, mostly occurring in Africa and
south-east Asia, particularly in Nigeria, India and Pakistan. See World Health Organization Polio Eradication, available at:
http://www.polioeradication.org/; Polio Case Count, available at: http://www.who.int/vaccines/casecount/case_count.cfm.
Accessed on: 26 Apr 2005.
30 For a mini-review of early polio research see Eggers HJ (1999) Milestones in early poliomyelitis research (1840 to 1949) J
Virol 73: 4533–5.
31 Current vaccines contain a mixture of the three types which together confer immunity.
32 See Paul JR (1971) A history of poliomyelitis (New Haven and London: Yale University Press).