FEATURE
spectacular public experiment . He and his assistants vaccinated sheep , goats and cattle with live attenuated anthrax microbes and left an equal number of animals unvaccinated as controls . Later the whole group was challenged with virulent anthrax . The vaccinated animals did not develop anthrax and it is reported that Pasteur himself characterized his success as “ one of the greatest and most fruitful discoveries .”
Pasteur ’ s most important contribution to mankind is undoubtedly the development of the rabies vaccine . He and his assistants , after years of trials and failures figured out that the rabies virus can be progressively attenuated by desiccating the spinal cords of rabbits infected with saliva from rabid dogs . July 6 , 1885 is a memorable day in medical history , as it marks the day on which a human being was inoculated with the rabies vaccine for the first time . Nine-year-old Joseph Meister was bitten by a rabid dog and was expected to die from rabies . The boy was given daily injection of the material from desiccated spinal cord of rabid rabbits for 13 days ( each successive injection had less and less attenuated virus ). 2 This first trial of post-exposure prophylaxis for rabies turned out to be an impressive success . Pasteur ’ s technique was widely adopted and modified to reduce the amount of neural tissue in the vaccine to prevent complications like encephalomyelitis . With the development of cell culture for viruses , new vaccines derived from human diploid or purified chick embryo cells have replaced the original CNS-derived rabies vaccine .
The technique of exposing one to an inactivated or attenuated microbe to prevent occurrence of disease on subsequent exposure to the virulent microbe was adopted for many decades to develop vaccines for numerous diseases . Several vaccine-seekers adopted Pasteur ’ s technique of attenuating the pathogen by different techniques . A phenomenal success was the invention of the vaccine for yellow fever culminating in the award of the Nobel Prize to Max Theiler in 1951 . Another spectacular success story is that of the polio vaccine ( Salk vaccine with inactivated virus and Sabin ’ s vaccine with an attenuated virus ) which has made the planet free of polio , except for a few countries . 3 Other common infections that have been controlled with vaccines include measles , mumps and rubella , to name a few . However , developing new vaccines using attenuated or inactivated viruses take considerable time and expense . The need for new technology to make the process faster and more efficient has been gradually gaining momentum . The premise is if the antigenic component can be isolated or even better , synthesized in the lab , one could avoid use of the whole organism in the vaccine .
Like many stories of medical discovery , the development of the hepatitis B vaccine is also one of non-targeted research serendipitously leading to a phenomenal achievement . In the 1960s , Baruch Blumberg was obsessed with the question of genetic polymorphism : why some people are more susceptible to certain diseases , while others are resistant . He chose to study serum protein variations to unlock the secrets of disease susceptibility . He collected human blood samples from all over the world to include a wide variety of ethnic population resulting in the detection of a mysterious protein , named Australia antigen or Aa as it was first detected in the blood sample of an Australian aborigine . Further studies by several scientists finally confirmed the notion that Aa ( later called hepatitis surface antigen , HBsAg ) is part of the hepatitis virus B ( HBV ) and has the potential for transmission by blood transfusion . This led to the development of a rapid test to detect Aa and was extensively utilized to exclude blood donors with hepatitis . Rapid decline in transfusion-related hepatitis B was the result and Blumberg was honored with the award of the Nobel Prize in Medicine and Physiology in 1976 .
Blumberg played an important role in the production of the hepatitis B vaccine as well . The first HBV vaccine used the traditional technology of inactivated virus ; the source of the virus was plasma collected from HBV infected donors , who unfortunately were in short supply and sometimes HIV positive . The next step was production of the recombinant vaccine ; in principle , such vaccines are made using bacterial or yeast cells to manufacture the antigenic component . A small piece of DNA from the virus is inserted into the DNA of yeast cells , leading to the production of one of the surface proteins of the virus , the main constituent of the vaccine . 4 This led to large scale production of HBV vaccine and the technology also helped to produce vaccines against human papilloma virus , meningococcus B and recently , malaria .
The remarkable feat of producing an effective vaccine against COVID-19 in a matter of months may have triggered a smile ( perhaps with some envy ) in the bearded face of Louis Pasteur , considering the years of difficult and often frustrating time he and his associates endured to invent the rabies vaccine . It is certain that he will be more than gratified that those scientists who followed in his footsteps heeded his advice : “ These three things , Work , Will , Success fill human existence . Will opens the door to Success both brilliant and happy ; Work passes these doors and at the end of the journey Success comes to crown one ’ s efforts .” 1
References :
1
Kruif P . Louis Pasteur in Microbe Hunters . 1926 . Harcourt , Brace & World , New York
2
Smith KA . Louis Pasteur , the father of immunology ? Front in Immunology . 2012 . 3 ( 68 ): 1-10
3
Aylward B , Tangermann R . The global polio eradication initiative : lessons learned and prospects for success . Vaccine . 2011.10.005 . PMID : 22486981
4
Valenzuela P et al . Synthesis and assembly of hepatitis B virus surface antigen particles in yeast . Nature . 1982 . 298 : 347-350
5
Pieracci E . et al , Vital Signs : Trends in Human Rabies Deaths and Exposures — United States , 1938 – 2018 . Weekly / June 14 , 2019 / 68 ( 23 ); 524 – 528 . On June 12 , 2019 , this report was posted online as an MMWR Early Release . Emily G . Pieracci , DVM1 ; Christine M . Pearson1 ; Ryan M . Wallace , DVM1 ; Jesse D . Blanton , DrPH1 ; Erin R . Whitehouse , PhD1,2 ; Xiaoyue Ma , MPH1 ; Kendra Stauffer , DVM3 ; Richard B . Chipman , MS , MBA4 ; Victoria Olson , PhD1 .
Dr . Iyer practices at the Neurodiagnostic Center of Louisville and is a retired professor of neurology at the University of Louisville School of Medicine .
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