Viruses From Structure to Biology


The disease of poliomyelitis has a long history. The first example may even have been more than 3000 years ago. An Egyptian stele dating from the 18th Egyptian dynasty (1580 - 1350 BCE) shows a priest with a deformity of his leg characteristic of the flaccid paralysis typical of poliomyelitis. But a very brief history of poliomyelitis as an infectious disease would start in 1908 when Karl Landsteiner - the same Landsteiner who subsequently won the Nobel Prize for the identification of the four blood groups - and his assistant Popper transmitted the disease of poliomyelitis from the spinal cord of a nine year old boy who had died after a brief illness to two Old World monkeys. They proposed that this was a viral disease.

It was almost 40 years later that it became clear that infection with poliovirus was common, that paralytic disease was a rare consequence of infection, and that the route to the spinal cord was through the blood stream. Much of the credit goes to the Yale Poliomyelitis Study Unit and in particular to John Paul (1893-1971) who was Professor of Preventive Medicine and Epidemiology at Yale. In addition to his work on the disease of polio, he is the author of a book that is a brilliant and detailed description of the history of the disease and the virus (A History of Poliomyelitis, Yale University Press, New Haven, 1971).

A significant step in understanding the disease was the realization that there are immunologically distinct strains. The clearest evidence for antigenic differences came from work in Australia by Burnet and Macnamara (Brit. J. Exp. Path. 12:57-61, 1931). Sir Macfarlane Burnet, like Landsteiner, made a major contribution to the understanding of poliomyelitis, but then won the Nobel Prize for his work in immunology. According to John Paul: "The report by Burnet and Macnamara was greeted with a certain amount of skepticism in the United States. Burnet was a comparatively unknown figure who had done little in the poliovirus field and Australia was remote; anything, it was argued, might come out of that far-off continent, including an exotic variety of poliovirus".

In the late 1940s, early 1950s the Yale group, in particular Dorothy Horstmann and John Paul, as well as David Bodian's group at Johns Hopkins demonstrated that oral infection by polio followed by viremia was how the virus could enter the spinal cord and cause paralysis. And if viremia were prerequisite for disease, it might be possible to stop the virus before it entered the central nervous system. But even before this was realized there was the groundbreaking discovery that poliovirus could be grown in culture and in cells that were not derived from the nervous system. This discovery, published in 1947 by John Enders (1897 - 1985), Thomas Weller and Frederick Robbins was a milestone in polio research and was recognized as such by the awarding of the Nobel Prize in 1954.

The work by the Yale group and by Enders and his colleagues paved the way for development of vaccines against poliomyelitis. Jonas Salk was responsible for the introduction and successful use of inactivated poliovirus as a vaccine. (Salk's accomplishments are well-documented on the Web. For example see Any mention of those very important and essential studies must also give credit to Thomas Francis who was the person responsible for carrying out the field trials of 1954 that showed just how effective the vaccine was. In the late 1950s, the possibility of using live virus - an attenuated vaccine - began to receive much more interest and attention. Field trials in the United States would have been difficult for many reasons including that the inactivated or Salk vaccine was being widely used. Albert Sabin developed the attenuated strains that are still in use today. He was able to collaborate with scientists and physicians in the former Soviet Union where extensive trials with that vaccine were done. The success of those studies led many, although not all, countries to switch to the attenuated virus for vaccination. The success of the live vaccine also led to the idea that the disease of poliomyelitis could be eradicated.

The eradication of an infectious disease proved to be a possible goal with the last reported case of smallpox in Somalia in 1977. The World Health Organization was responsible for this enormous achievement. One of the very few properties that poliovirus has in common with the virus that causes smallpox is that humans are the only host. Eradication of an infectious agent can only be contemplated if there is no animal reservoir.

The first steps in the eradication of poliomyelitis were taken by Ciro A. de Quadros and Carlyle Guerra de Macedo, who at the time were head of the Expanded Program on Immunization for the Americas and Director of the Pan American Health Organization (PAHO) respectively. They were responsible for leading the efforts to eliminate polio from the Americas under the auspices of PAHO. The eradication program for the Americas was begun in 1985; the last reported case of polio in the Americas due to the wild type virus was in August 1991 in Peru. This last case was in a two year old boy who fortunately did survive. Ciro de Quadros had also been part of the World Health Organization serving as chief epidemiologist for the Smallpox Eradication Program in Ethiopia. He is presently the Director of the Division of Vaccines and Immunization at PAHO.

One of the most effective means of vaccination was to have national immunization days. The strategy of setting aside several days during the year when all children under a certain age would be immunized had been used by Cuba in the 1960s and effectively interrupted transmission of polio in that country. A major problem in the general program for vaccination was what to do in those countries that were in the midst of civil wars, in particular El Salvador and Peru. Ciro de Quadros described making arrangements with a guerilla representative from El Salvador for a cease-fire period, referred to as "days of tranquility", during which the children of El Salvador could be vaccinated (in Polio, edited by T.M. Daniel and F.C. Robbins, University of Rochester Press, 1997). He also wrote that in Peru they took a chance. They attempted to inform everyone that vaccination in Peru could mean the end of polio in the Americas and were able to vaccinate almost two million children under the age of five years without any interference from the guerilla group, the Shining Path. Some months later, they discovered that members of the Shining Path had actually been involved in helping in the vaccination campaign.

The worldwide eradication of polio is now underway and the World Health Organization expects this goal to be reached within the next few years. The approach of this incredible achievement has raised some crucial issues. Perhaps the most immediately important one is: when and how to stop vaccinating. For more details about the eradication program and potential difficulties see

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| Introduction | Some historical highlights: structural virology and virology |
| Solving the Structure of Icosahedral Plant Viruses | Picornavirus Structure | Poliovirus | Polio
The Influenza Virus Hemagglutinin
| The Influenza Virus Neuraminidase |
Issues of Science and Society |contributors|
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