Editing Serial passage (section)

==History==
The technique of serial passage has been around since the 1800s.  In particular, [[Louis Pasteur]]'s work with the [[rabies vaccine]] in the late 1800s exemplifies this method.<ref name="smith">{{Cite journal |vauthors=Smith KA |date=2012 |title=Louis pasteur, the father of immunology? |journal=Frontiers in Immunology |volume=3 |pages=68 |doi=10.3389/fimmu.2012.00068 |pmc=3342039 |pmid=22566949 |doi-access=free}}</ref>

Pasteur created several vaccines over the course of his lifetime.  His work prior to rabies involved attenuation of pathogens, but not through serial passage. In particular, Pasteur worked with [[cholera]] and found that if he cultured bacteria for long periods of time, he could create an effective vaccine.<ref name="smith" /><ref name="schwartz">{{Cite journal |last=Schwartz |first=M. |date=2001 |title=The life and works of Louis Pasteur |journal=Journal of Applied Microbiology |volume=91 |issue=4 |pages=597–601 |doi=10.1046/j.1365-2672.2001.01495.x |pmid=11576293 |issn=1364-5072}}</ref> Pasteur thought that there was something special about oxygen and this was why he was able to attenuate (create a less virulent version of) the bacteria. Pasteur also tried to apply this method to create a vaccine for [[anthrax]], although with less success.<ref name="smith" />

Next, Pasteur wanted to apply this method to create a vaccine for rabies. However, rabies was, unbeknownst to him, caused by a virus, not a bacterial pathogen like cholera and anthrax, and for that reason rabies could not be cultured in the same way that cholera and anthrax could be.<ref name="schwartz" />  Methods for serial passage for viruses in vitro were not developed until the 1940s, when [[John Enders]], [[Thomas Huckle Weller]], and [[Frederick Robbins]] developed a technique for this.  These three scientists subsequently won the [[Nobel Prize]] for their major advancement.<ref>{{Cite journal |vauthors=McCullers JA |date=September 2007 |title=Evolution, benefits, and shortcomings of vaccine management |journal=Journal of Managed Care Pharmacy |volume=13 |issue=7 Suppl B |pages=S2–6 |doi=10.18553/jmcp.2007.13.s7-b.2a |pmc=10438138 |pmid=17874877 |doi-access=free}}</ref>

To solve this problem, Pasteur worked with the rabies virus in vivo.<ref name="smith" /><ref name="schwartz" /> In particular, he took brain tissue from an infected dog and transplanted it into another dog, repeating this process multiple times, and thus performing serial passage in dogs.<ref name="smith" /> These attempts increased the virulence of the virus.<ref name="smith" /> Then, he realized that he could put dog tissue into a monkey to infect it and then perform serial passage in monkeys.<ref name="smith" /> After completing this process and infecting a dog with the resulting virus, Pasteur realized that the virus was less virulent.<ref name="smith" /> Mostly, Pasteur worked with the rabies virus in rabbits.<ref name="schwartz" /> Ultimately, to create his vaccine for rabies, Pasteur used a simple method that involved drying out tissue. As is described in his notebook:

<blockquote>In a series of flasks in which air is maintained in a dry state…each day one suspends a thickness of fresh rabbit spinal tissue taken from a rabbit dead of rabies. Each day as well, one inoculates under the skin of a dog 1 mL of sterilized bouillion, in which has dispersed a small fragment of one of these desiccated spinal pieces, beginning with a piece most distant in time from when it was worked upon, in order to be sure that it is not at all virulent.<ref name="smith" /></blockquote>

Pasteur mostly used other techniques besides serial passage to create his vaccines. However, the idea of attenuating a virus through serial passage still holds.