Poliomyelitis, shortened to Polio, is a disabling and life-threatening disease caused by the poliovirus.
Poliomyelitis has existed for thousands of years, with depictions of the disease in ancient art. Major outbreaks started to occur in the late 19th century in Europe and the United States, and in the 20th century, it became one of the most worrying childhood diseases. One of the triumphs of medical research is that most people today in developed countries are unaware of the horror of polio. Following the introduction of polio vaccines in the 1950s polio incidence declined rapidly.
Most people who get infected by the virus don’t develop any visible symptoms. 1 out of 4 people with poliovirus infection will experience flu-like symptoms that last 2 to 5 days and usually go away on their own. However, for a small portion of the population, the virus infects the spinal cord and the brain causing meningitis (1 to 5% of infections) and paralysis (0.05% to 0.5% of infections) which can lead to permanent disability and death (for 2-10% of patients affected by paralysis).
Polio is known to mainly affect children under the age of five. Children who seem to fully recover can develop new muscle pain, weakness, or paralysis as adults, 15 to 40 years later. This is called post-polio syndrome.
Once infected, there is no specific treatment. Today, the disease can be prevented by the polio vaccine, with multiple doses required for lifelong protection. This advance alone has saved millions of lives, and the World Health Organisation is close to eradicating polio completely through its worldwide vaccination programme. Incidence of wild polio has decreased by over 99% since 1988, from an estimated 350,000 cases to 416 reported cases worldwide in 2013 and 6 confirmed cases in 2021, confined to just three countries. Forty years of research using monkeys and mice led to the discovery of the virus and the introduction of the vaccines in the 1950s.
Discovery of the virus
The disease was first recognized as a distinct condition by the English physician Michael Underwood in 1789, but the virus that causes it, was only identified in 1909 by the Austrian immunologist Karl Landsteiner.
By the early twentieth century, bacterial diseases had been extensively studied. Viral diseases, however, remained difficult to study. Unlike bacteria, viruses are unable to reproduce in culture media – they are only active inside cells. Most medical professionals suspected polio was an infectious disease but had little proof.
In 1908, Dr Karl Landsteiner and Dr Erwin Popper used extracts from the spinal cord of a boy who had died from polio to replicate the disease in monkeys. The disease could then be transmitted from monkey to monkey, providing an invaluable model of the disease. Eventually, it was possible to transfer a strain of the virus to rats and mice, which could be used in sufficient numbers to establish the existence and virulence of the polio virus.
It is unfortunate that Landsteiner, at that time working in Vienna, was not able to continue in this field, since the enormous expense of maintaining a sufficient monkey colony to pursue this study was beyond his available funds. Incidentally, Landsteiner was awarded the Nobel Prize in 1930 for his work on the classification of blood groups.
From 1908 until the 1940s the induction of polio in monkeys was the only means of study of the disease. With this model it was established that three strains of the virus existed, that the route of infection was via the nose and mouth, and that the virus stayed and multiplied in the gut before, in more serious cases, migrating via the blood stream to the motor neurones of the spinal cord, where the destruction resulted in permanent paralysis.
The observation that nasal washings from patients with a relatively trivial infection caused severe paralysis when administered to experimental monkeys, indicated that individuals could, in some circumstances become immune. This undoubtedly encouraged those searching for a vaccine.
Polio vaccine development
Today polio is all but eliminated worldwide because of a highly effective vaccine, originally tested in monkeys. In the 1950s, after 40 years of research using mice, rats and monkeys, polio vaccines were developed and used to treat the disease.
Progress was initially held up because few groups could afford to maintain a monkey colony - and by the difficulty of growing Poliomyelitis in cell-culture. This problem was eased when, after much effort, a strain of poliovirus was transferred to the Cotton rat, and subsequently to the mouse. The maintenance of the poliovirus in mice was significant because it meant that it was now possible to use a sufficient number of animals to provide clear evidence for the existence and virulence of the poliovirus. Thus the way was paved for intensive efforts to grow the virus in culture.
In the 1940s Dr John Enders and his colleagues developed a culture technique which allowed the polio virus to be grown in human tissue. They discovered that the virus not only grew in brain tissue as expected, but also in other humans cells. This breakthrough was awarded the Nobel Prize in Physiology or Medicine in 1954.
However, the virus was too small to be seen with any available imaging technique at the time. There was only one way that Dr Enders could check that he had in fact extracted the virus from mouse brain tissue and grown it in culture. This was by injecting the culture fluid into mice and rhesus monkeys, where it produced paralysis typical of polio.
The ability to grow the virus in cell culture ensured the rapid development of a vaccine. An inactivated (killed) polio vaccine (IPV) developed by Dr. Jonas Salk was first licensed for use in the US in 1955. A few years later a live attenuated (weakened) oral polio vaccine (OPV) was developed by Dr. Albert Sabin and became available in 1961.
The essential role of animal research in creating these vaccines was underlined by Professor Albert Sabin's 1956 paper in the Journal of the American Medical Association where he stated: “approximately 9,000 monkeys, 150 chimpanzees and 133 human volunteers have been used thus far in the quantitative studies of various characteristics of different strains of polio virus. [These studies] were necessary to solve many problems before an oral polio vaccine could become a reality.”
Originally the vaccine virus was grown in cells taken from minced monkey kidneys. The vaccines were then safety-tested on rhesus monkeys, young mice, guinea pigs and rabbits, before being used on people. Since the 1990s, however, immortal cell-lines have replaced rhesus monkey kidney cells and a genetically modified strain of mouse that is susceptible to polio is now used to replace monkeys in safety testing.
Interestingly, humans are not the only mammals to have benefited from the development of a polio vaccine - it has also been used to protect a wild colony of East African colony of chimpanzees from a potential epidemic.
Two different vaccines
Both vaccines are highly effective against all three types of poliovirus. There are, however, significant differences in the way each vaccine works. The Salk vaccine has to be injected while the Sabin (oral) vaccine is taken as a drop on a sugar-cube.
Because the oral polio vaccine is inexpensive, easy to administer, and produces excellent immunity in the intestine (which helps prevent infection with wild virus in areas where it is endemic), it has been the vaccine of choice for controlling poliomyelitis in many countries. As such, the oral polio vaccine (OPV) was the main vaccine used from 1960 to 2000 to vanquish polio.
On very rare occasions however, about one case per 750,000 vaccine recipients, the attenuated virus in OPV reverts into a form that can paralyse. Consequently, as the incidence of wild polio diminishes, most industrialised countries have switched to injected polio vaccines, which cannot revert.
More than 10 million people are walking today, who would otherwise have been paralysed and an estimated 1.5 million childhood deaths have been prevented, through polio immunisation.
Albert Sabin, who developed the oral polio vaccine, said in 1991: “"My own experience of over 60 years in biomedical research amply demonstrated that without the use of animals and of human beings, it would have been impossible to acquire the important knowledge needed to prevent much suffering and premature death not only among humans but also among animals."
Unfortunately, endemic transmission still continues in Nigeria, Pakistan and Afghanistan. Failure to stop polio in these last remaining areas could result in the re-emergence of the disease in other countries with as many as 200 000 new cases every year, within 10 years, all over the world. The breakdown of vaccination services in war zones such as Syria show additional risks of polio, and other diseases, breaking out.
As more and more countries switch to injected vaccines, scientists continue to improve vaccines using inactivated virus, to make vaccines cheaper and more effective. Primates were and continue to be essential for the development and testing of the oral polio virus vaccine.
Research has already allowed mice to take the place of monkeys in safety-testing of polio vaccines. In the last couple of years the WHO has approved and recommended that a transgenic mouse test for OPV be implemented as an alternative to the monkey neurovirulence test. However, the hope is that a non-animal assay can be developed. But until then, and for as long as polio persists, it is likely that animals will be used to test the safety of polio vaccines.
Last edited: 24 October 2022 09:58