Virology: from Jenner to HIV

December 05, 2016

Viruses have probably been around as long as life has existed and human history is full of references to them. In a tomb that dates from the ancient Egypt it was found a body with clear signs of smallpox. Yellow Fever and other exotic viruses have affected European explorers in many parts of the world for many centuries. Not only humans suffer from viral infections, as these agents infect every living being on earth, that is, animals, plants, bacterium, protozoa and yeast. They are still the major cause of most human diseases. With all this, it could be interesting to know a bit of how we discovered them.

Infectious diseases have been present in human history long before we knew the causative agents
Homer already talked about “rabid dogs” in his essays. Rabid dogs were also known in Mesopotamia, and drawings in the ancient Egypt show people suffering from withered legs, probably the result of polio. Moreover, there is evidence that smallpox was already known in South and Central America. It is also said that the legend of the “Flying Dutchman” began with a yellow fever outbreak. And curiously, when the tulip market began to prosper in Holland, the most valuable tulips were those variegated, which was the result of virus infection.

The history of virology as a scientific discipline is actually very short. The first bacteriologists already knew about invisible agents capable of causing disease, but they were not able to recognize what they were. 1798 is considered the birth of experimental virology thanks to the works in vaccination of Edward Jenner. The process of vaccination was already known by the Turks, and it is known that the Chinese practiced vaccination, or variolation, by inoculating material from smallpox pustules into healthy people to prevent the disease in them. Nevertheless, the first scientific process in variolation was performed by Jenner. He observed that many cow workers that had been exposed to cowpox did not suffer from smallpox. He inoculated material from cowpox pustules into a child that was later challenged with smallpox, and they surprisingly observed that he did not suffer from the disease. The term was coined vaccination after ‘vaccina’, latin for ‘pertaining to a cow’. I need to say such unsafe procedure is totally banned today, and that the virus used nowadays to vaccinate people against small pox is not the same as that used by Jenner, but a variant that arose during the last few hundred years, and may be of horse origin.




Jenner noticed that milk-maids occasionally had skin blisters (cowpox). He inoculated material from these blisters into a boy and observed that a later challenge with smallpox did not affect severely the boy (picture taken from http://www.blatner.com/adam/consctransf/historyofmedicine/3-immunology/3-lecture.html)

In 1884 Koch and Henle presented a series of criteria to identify the causative agent of an infectious disease. They were known as the Koch’s postulates and they were soon accepted by the scientific community. Although they revolutionized the world of microbiology, as they came to put a bit of order in this sometimes chaotic field at that time, they were difficult to apply to viruses. Even today they are difficult to apply to some animal viruses, such as HIV. Nevertheless, they are currently one of the central dogmas in general microbiology.

Pasteur (1822-1895) was the first person in proving that spontaneous generation of organisms does not occur. He also developed techniques to use animals as models for growing and studying viruses. Although Pasteur never knew what the causative agent of the rabid was, he discovered that passage of rabies virus recovered from infected dogs through cells of other species produced an attenuated rabies virus. When infected into dogs again, they produced milder infection with an increased latent period. He used the vaccine to prevent the disease in a child that had been bitten by a rabid animal, and this was the beginning of the vaccine against the deadly rabies virus.

In 1898, Beijerink demonstrated the filterable characteristic of viruses. At that time microbiologists knew that bacteria could not pass through certain types of filters, characteristic that was used to assume that an infectious agent should be stopped by filters. Using extracts from plants infected, Beijerink showed that the liquid obtained after filtration was still infectious and could only be neutralized by boiling or treating with formaldehyde. The term was then coined virus, Latin from Greek toxin. Loeffler and Frosh reported similar conclusions when they studied filterability of extracts from animals infected with foot and mouth disease virus.

1900’s, the fast development in virology
Bacteriophages (viruses that infect bacteria) have played an important role in the development of microbiology. Delbruck is considered the father of the modern molecular biology thanks to his discoveries when working with bacteriophages. These viruses were also crucial for Hershey and Chase to discover in 1952 that at least several viruses contain genetic material that can be infectious by itself.

Tissue culture techniques have been developing all over the century. Carel showed in 1910 that it is possible to grow chick embryo fibroblasts in culture, a kind of specialized cells. Thanks to this advance, by 1930 chick embryos were already being used to grow viruses and this allowed the emergence of new studies that ended up with the development of new vaccines. After the important demonstration by Enders that poliovirus could be grown in cell cultures of non-neuronal tissue, intense research was performed to obtain a vaccine. It was in 1953 when Sabin introduced the attenuated polio vaccine that helped years later in the eradication of the illness.

The 1980’s were of special importance in the advancements in virology. Complete viral genomes were sequenced, and the discovery of monoclonal antibodies and the development of PCR techniques, together with more advances in immunology, have led the virology to be one of the most active fields within biological sciences.
HIV, the threat of 1980’s

In the early 1980’s HIV (human immunodeficiency virus) was found to be the cause of AIDS (acquired immunodeficiency syndrome). It was spread mainly in west countries between homosexuals and intravenous drug users (IDU’s) with low repercussion in heterosexual people. The real epidemic, however, was and remains in Africa. Only the more increasing evidence that it could also spread between heterosexuals led the world to focus on this pathological disease. The only good thing for virology in relation to HIV is that the identification of AIDS and the discovery of HIV as the virus causing it, a new virus that was not known to have been in contact with humans before, finally put virology in the front line of pathology specialities.


References
http://courses.bio.indiana.edu/M430-Taylor/history.html
https://www.ibms.org/go/nm:history-virology
http://www.blatner.com/adam/consctransf/historyofmedicine/3-immunology/3-lecture.html