FEVERISHLY EVOLVING ANTIGENS
CASE STUDY IN MOLECULAR EVOLUTION NO. 4
Written by Harold B. White 8/93, most recently revised 10/00
C-647 BIOCHEMICAL EVOLUTION, FALL 2002

Page 1
The Black Death

"Infectious disease is one of the great tragedies of living things – the struggle for existence between different forms of life. Man sees it from his own prejudiced point of view; but clams, oysters, insects, fish, flowers, tobacco, potatoes, tomatoes, fruit, shrubs, trees, have their own varieties of smallpox, measles, cancer, or tuberculosis. Incessantly, the war goes on, without quarter or armistice – a nationalism of species against species."(1)
A week before, Justin Middens had lain near death with bubonic plague in an Albuquerque hospital. He had developed a high fever and painfully swollen lymph nodes that required an emergency evacuation from his desert campsite where he was conducting field research on packrat behavior. A local doctor fortunately recognized his symptoms and treated him immediately with tetracycline. The quick action probably saved his life. According to the Center for Disease Control, 10 to 20 cases of bubonic plague occur in the United States each year, mostly in northern Arizona and New Mexico. It is still a life threatening disease, as was evident in Justin’s case. Now, with the crisis over, he was recovering and reading passages from the classic book on infectious disease, Rats, Lice, and History by Hans Zinsser (1), loaned to him by a doctor. He was puzzled by the following passage, which he read aloud to his research advisor, Perry Daugs, who had come to see how he was doing. "Resistance to infectious disease, an acquired characteristic, is not hereditary except in the evolutionary sense of selective survival of the more resistant...." Justin asked, "Why wasn’t I resistant to the plague? All my ancestors came from Europe. Certainly those living in medieval times, when about 25% of the people in Europe died, must have survived because they were resistant."

Dr. Daugs, launched into mini lecture. "Like snowflakes, no two humans are identical. The frequency of mutations is such that even identical twins are unlikely to be absolutely identical genetically. Heterogeneity in the gene pool of Homo sapiens, as with other species, provides the raw material for rapid evolution when natural selection is strong. As you noted, during the Middle Ages at least 25 million people, a quarter of the population of Europe at the time, died of the Black Death, bubonic plague (2). This is an example of strong selection for both resistance and for an effective response. One would not be able to detect that an evolutionary event had occurred by comparing the physical appearance of the survivors with that of the general population before the plague; however, selection certainly altered the gene pool and the population was more fit with respect to plague resistance. But, over generations in the absence of selection, independent assortment and genetic recombination of resistance genes can lead to individuals with increased or decreased resistance. Your experience suggests that you are lucky we have antibiotics."
 

For initial group discussion: Everyone gets sick from time to time. Consider the causative agents of the various human infectious diseases you know and classify them. Does the human body respond to all in the same way? How and why do the medical treatments for each differ?

For next time: Assume you had a time machine and were able to return to the Middle Ages with the tools of modern molecular genetics that in principle can assay for the presence of every allele of every gene in the human genome. If you wished to monitor the changes in allele frequency resulting from Bubonic Plague, what differences would you expect? Why?

Page 2: A World of Different People
Page 3: Warfare at the Molecular Level

References
1. Zinsser, H. (1933) Rats, Lice and History, Little, Brown and Co., Boston.
2. Burnet, M. and White, D. O. (1972) Natural History of Infectious Disease, 4th edition, Cambridge University Press, Cambridge, U.K.
Note: Refs. 1 and 2 are classics and are highly recommended reading for anyone aspiring to be a physician. In particular, they show the importance of an evolutionary perspective on disease.


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Created 3 October 2000. Last updated 11 October 2002 by Hal White
Copyright 2002, Harold B. White, Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716