A coworker of my wife loaned us his copy of the John Adams HBO series and we have recently watched the first two episodes.
Like many Americans, I’ve always been interested in the founding fathers, but I admit that I never thought much about Adams. Apparently, it was because I hadn’t known much about him. Being caught in history between two of the best remembered presidents, Washington and Jefferson, put Adams in a tight spot from the outset. Washington was a war hero and first political leader (ever?) to step down willingly from power; Jefferson was an intriguing philosopher, inventor and writer of the declaration of independence.
Apparently, I was missing out on a fascinating man. As the series tells it, Adams was a lawyer with a keen sense of justice and an agitator in the continental congress who actually managed to get action out of a legislative body.
Nevertheless, as immunologists, we were both immediately interested in the smallpox epidemic that was hitting Boston in episode 2 and wound up stopping the episode several times to explain smallpox to our son who was watching this with us – he’s seven years old and a budding immunologist himself.
Of prime importance is to put this time period into perspective with Jenner’s work developing and testing the first smallpox vaccine in 1796. Prior to the vaccine there was only a rudimentary understanding of the immune system, however it was recognized that once a person had the disease once, they did not contract it again. This led to a dangerous practice of inoculation (also called variolation). The idea was very similar to that of vaccination, except that where vaccination is defined as using a killed or weakened pathogen, inoculation used virus collected from sickened individuals to induce a ’controlled’ infection that would induce immunity without harming the patient. The practice was extremely risky though as there was little done to weaken the virus.
In the film, scrapings of a blister from a sick person was used directly as a inoculum given to the patients. However, it was more common to take blisters from less sick persons (who had the minor form of the disease), bottle these and allow them to dry out before administering to a healthy patient. This simple desiccation was probably vital to tempering the virus at least partially.
The threat from smallpox was not trivial. This disease was quite infectious and the major form had mortality rates around 20-60%.1 Those who did live through the illness might be blinded and were likely severely scarred – often on the face.
In 1721 an epidemic of smallpox hit Boston so hard that the entire city’s population fled.2 Although the epidemic in the 1770s was not as devastating as that of 1721, thousands died from the disease throughout the colonies.
Abigail Adams was certain to know how deadly the disease was and was balancing this against the terrible risk of inoculation. In the end, she was lucky and, despite a close call, all of her children survived the ordeal.
So, briefly… how does inoculation work?
In a very basic sense, the immune system is made up of two major parts. The first is the innate immune system. Innate means built in, and this is exactly what this system is, built in and ready to go without preparation. The innate immune system includes barriers such as skin and mucus membranes as well as cells that respond rapidly to any invasion of the body.
Innate immunity is a generic, non-specific response that can be called up quickly. The benefit is that this system works immediately to protect the host. The weakness is that the innate immune system has no memory.3 So even after a first infection is beaten by this ‘primary’ response, there is no improvement in the response of these cells the second time around.
The second part of the immune system is the adaptive (or acquired) system. This is the part of your immune system that ‘learns’ from what it sees and is stronger when the same pathogen is encountered multiple times. This immunological ‘memory’ works just as you would expect it to: There is a relatively weak response on first exposure to any given pathogen, but after the infection is beaten and most cells die away, a small population of these ‘memory’ cells remain and can be called up quickly in subsequent exposures. These repeated exposures leads to a much quicker, very specific immune ‘secondary response’ that often stops an infection in its tracks.
Vaccination (and inoculation) takes advantage of this adaptive response and is ideally elicited with a primary, safe exposure to the pathogen. Despite the weakening of the virus (or any other pathogen – it isn’t limited to only viruses), robust immunological memory can be induced and an individual can be protected for years – sometimes even for life.
Later, any exposure to the real pathogen should result in protection from disease as the memory cells are awakened and respond rapidly. Further, a subset of the cells that remain after the primary exposure (plasma cells) make proteins called antibodies4 that circulate throughout the body and will neutralize pathogens immediately. Together, circulating antibodies and memory cells can provide complete immunity.
- Stefan Riedel. “Edward Jenner and the history of smallpox and vaccination” Proc (Bayl Univ Med Cent). 2005 January; 18(1): 21–25.
- Oda Y. “Inoculation in Boston from 1721 to American Independence”. Nihon Ishigaku Zasshi. 1999 Mar;45(1):31-44.
- There is some recent evidence that cells of the innate immune system do have some ‘memory’, see Joseph C. Sun, Sandra Lopez-Verges, Charles C. Kim, Joseph L. DeRisi and Lewis L. Lanier. “NK Cells and Immune ‘Memory’” The Journal of Immunology February 15, 2011 vol. 186 no. 4 1891-1897
- Antibodies are proteins produced in direct response to immunological challenge and bind to foreign specifically. These are products of mature B Cells, called Plasma Cells, and are what physicians look for in a ‘titer’ to determine if someone needs a booster vaccine. Low titer means little circulating antibody and a booster vaccine is recommended.