Turned up to eleven: Fair and Balanced

Friday, May 16, 2003

Introduction (fragment)

Our world is populated, as has been oft repeated, by creatures great and small, in diverse forms well beyond reckoning. J.B.S. Haldane famously quipped, when arguing over Evolution, that the Creator "must have an inordinate fondness for beetles." (ref) However, it is truly clear that even that fondness is dwarfed by the Creator's clear bias toward unicellular life. We often only pay attention to microbes when they cause us harm. The great scourges of history have been bacterial and viral plagues, from the Black Death (caused by Yersinia pestis), which claimed perhaps 1/3 of Europe's population in the 14th century (ref), to smallpox, which kills approximately 30% of those infected, and has been the predominant cause of human suffering throughout much of human history. The history of microbiology as a science can be seen as having two distinct tracks, one revolving around infectious disease, the other studying bacterial prevalence in the environment. In the popular imagination, the study of disease has clearly been predominant.

The sources of human suffering have clearly, and rightly, been a preoccupation of thinkers, philosophers, scientists, and historians since the time of Thucydides' account of the Peloponnesian War. His riveting description of the plague of Athens (History of the Peloponnesian War) is the first historical description of epidemic disease. It is not known clearly what the etiologic agent of this disease was, and possibilities proposed include Yersinia pestis (bubonic/pneumonic plague), Rickettsia prowazekii (typhus), Bacillus anthracis (anthrax), and even Ebola virus (TeethPlague PNAS)! Documentation of plagues throughout history has been quite substantial and thorough, even documenting the use of germ warfare by Cortes and company in their conquest of the Aztec empire in Central America, and more generally in the conquest of the Americas, first by the Spaniards and Portuguese, and later other European powers (as described in Jared Diamond’s book "Guns, Germs and Steel"). Controversy remains as to the intent of the conquerors to spread disease, but the outcome is beyond question. The decimation of Native American populations by diseases borne by European invaders was undoubtedly a major factor in the conquest of the new world.

Without question, the study of infectious disease has been a wildly successful endeavor. Beginning with the work of Edward Jenner, observation of disease susceptibility has led to the protection of people against these horrific plagues(here is a web source for Jenner's work ) . Dr. Jenner's observation of diseases in horses and cattle that bore very strong resemblance to smallpox in humans was the first step. His documentation of the transmission of disease from horse to cow to human was crucial to the eventual formulation, much later, of the general germ theory of disease. (although it was later shown that the horse disease he described was not caused by vaccinia virus) . In some respects, it should be noted, we would term Jenner's experiments barbaric, and his methods unethical, particularly his infection of human subjects with smallpox virus ("variolous particles"(ref)) to test if prior infection with cow-pox was protective. This criticism, however, is unjust in the sense that his work was entirely in keeping with the ethical sensibilities of his time, and his seminal work did result in the ability to protect people against a great and terrible scourge.

Other great innovations in the study of infectious disease involved tremendous insights by individuals such as Louis Pasteur, Robert Koch, Paul Ehrlich, and many others. The list of these great mens' accomplishments is truly daunting to a budding young microbiologist. The identification of Mycobacterium as the causative agent of tuberculosis (the "tubercle bacillus"); identification of Bacillus anthracis, the agent of anthrax in sheep and humans; the discovery of antibodies, proteins in the blood that protect us from foreign invaders; perhaps most importantly, in addition to these singular accomplishments as experimentalists, all three of these men were able to produce important ideas about how disease is caused, how it is spread, and how we fight it off, which still guide medical research. Koch's postulates, which describe a method for proving that a microbe isolated from a disease victim is the etiologic agent, are still taught in medical school and microbiology programs worldwide, and used by researchers to demonstrate the validity of the label "infectious agent." First, you must isolate the organism from the infected host (often no small task). Second, you must determine a model system (usually an animal host, such as mice or rabbits; TB, the model is guinea pigs), and show that the organism causes a similar disease in the animal. Third, when the organism is re-isolated from the diseased animal, it can be used to cause the disease in a healthy animal. Finally, it can again be reisolated from the diseased model animal (here's an online source ). As an aside, this method to determine the cause of infectious disease was recently used by the world health community to identify the cause of SARS. Pasteur's study of anthrax led him to formulate the "germ theory of disease" (often credited, justly, to Pasteur and Koch jointly, and the source of harsh disagreement between them), and his studies of heat inactivation and attenuation of virus particles sparked the revolution of the late 19th century in biomedicine, with the development of vaccines against a number of serious disease agents, such as diptheria and tetanus.

(note: I haven't done these pioneers justice by a longshot, but I am not sure how much to recount this important, but secondary to my purposes, history)