The path of infection taken by polio (poliomyelitis) long remained a puzzle for researchers. It was not discovered until 1948 by John Enders and his colleagues.

The experimental method, in other words exploration of a disease using a "model organism", proved to be misleading in polio research. At the beginning of the twentieth century Simon Flexner was the director of the Rockefeller Institute for Medical Research (New York, USA) and a leading authority on polio research. He was also a proponent of the animal experimentation method. Flexner studied the path of infection for poliomyelitis in rhesus monkeys and concluded that the virus was transmitted via the nasal mucosa and then migrated via the olfactory nerve to the brain and spinal cord. He believed that the results of his research with rhesus monkeys could be applied to humans. Yet in fact the path of infection in humans is not the same as it is in rhesus monkeys: in the case of humans the polio virus enters the body through the mouth and then multiplies in the intestine before attacking the nerve cells of the spinal cord.

Various authors maintained that the path of infection would have been discovered significantly earlier if research had not been concentrated one-sidedly on the results of animal experiments, but had instead taken greater account of research conducted on human patients (tissue samples etc.). With this in mind the history of polio research is sometimes used as an argument to support shifting research away from animal experiments towards methods that do not use animal experiments.