I intended to move away from the flu after 3 weeks, but decided I left some things unsaid. Long, long ago, when I was applying for college, I wanted to study either history or chemical engineering. That may sound like and odd mix, but if you have been reading this blog you will have seen that the “overlapping” interests remain. In Parts I, II, and III of this series I reviewed viruses, the immune system, and the flu.  I hope you enjoyed them. Now that I’ve covered all of the basic science, I thought I’d add this epilogue on the broader implications of infectious disease.
Recall that in order for a virus to enter a cell, the cell must have the proper receptors on its surface. For example, there are some people who don’t have the particular receptor on their T-cells which lets the HIV virus latch on and infect them. Therefore, these people are immune to HIV.   Before humans understood the origin and method of spread of diseases, epidemics would routinely decimate large portions of the population. Those with susceptible cells would die, along with any other genetic features they possessed, and those who were immune would become the new Adams and Eves. Through this mechanism, viruses have been major drivers in both human evolution and world history.
To my point of view, the most dramatic example of the impact of infectious diseases on world history is the colonization of the Americas by Europeans. This story, like so many in human history, includes a pivotal moment in the vicinity of Jerusalem. Homo Sapiens Sapiens, us, evolved in the African Rift Valley and out-competed all other hominids. Approximately 100,000 to 200,000 years ago, early humans began to migrate out of Africa passing near Jerusalem on the way.  Some stayed in the general area and colonized southern Europe and the Middle East – the Indo-Europeans –  and an intrepid few continued on walking all the way across Asia across the Bering Strait and into the Americas. At the end of the last ice age, approximately 10,000 to 14,000 years ago, the seas rose, filling the Bering Strait with water and isolating these early Americans from the rest of humanity both geographically and genetically.
The humans who remained in Europe and the Middle East, in the area stretching from the Straits of Gibraltar to foothills of the Himalayas, built all of the great empires of Indo-European history;  the Babylonians, Egyptians, Assyrians, Persians, Hindu, Carthaginians, Greeks, and Romans. The humans who walked to the Americas built the Incan, Aztec and Mayan Empires and complex societies like the Iroquois League.   Around 7,000 to 12,000 years ago these isolated groups of humans independently developed agriculture, with one important difference. The Indo-European humans domesticated pigs and chickens and the Americans did not.
In Part III of this series I explained that birds and pigs share similar types of receptors with humans on some of their cells allowing them to swap viruses with us. By living in close proximity with their livestock ,the Indo-Europeans created a living bioreactor which spawned wave after wave of infectious disease. In Part II of the series I explained how you have both an innate immune system which fends off all invasions of things that are “not you” and an adaptive immune system which responds in a targeted way to viral infections.
So if you grew up in a placed like Carthage, Nineveh, Petra, or Athens you were exposed to a barrage of pathogens from the day you were born. If you had a weak innate immune system you died as an infant. If you were strong enough to survive infancy you then had to endure wave after wave of epidemics. Each time you survived one your adaptive immune system was better prepared for the next challenge. This environment allowed the Indo-Europeans to evolve very strong immune systems. In the Americas, societies did not co-develop with livestock, so their immune systems were less challenged. You could have a fairly unsophisticated immune system and still live to know your grandchildren.
In the 12th Century the two groups of humans who parted ways in Jerusalem 200,000 years earlier had a reunion when travelers from Iceland met the Americans of Greenland and Northern Canada. Contact continued periodically through the centuries and began to pick up the pace in the late 15th Century. (I am quite tempted to go on a long tangent about pre-Columbia European contacts with the Americas but this is a science blog, not a history blog.) The reunion was not a happy one for the Americans.
The Americans’  innate immune systems were not nearly as strong as the Europeans’ and their adaptive immune systems had never seen anything like small pox , typhus, measles, influenza, bubonic plague, cholera, malaria, tuberculosis, mumps, yellow fever, or pertussis that the Europeans brought with them. Population estimates for the Americas in 1491, the year before Columbus’ most famous journey, range from 70 to 120 million people.   It is estimated that approximately 90% of those people died in the waves of epidemics which spread inland following European contact. Some early European settlers, including the Pilgrims, considered this depopulation of the Americas as evidence of divine providence. 
Though one cannot really quantify such things, the extermination of Native American peoples by Indo-European diseases may be the biggest catastrophe in human history. Take a moment and try to imagine the physical and emotional devastation of having 90% of our population die off. We, like the Native Americans, would be reduced to abject desperation and scraping out our existence with basic hunting and gathering.  
The impact of infectious disease was, overwhelmingly, the leveraging factor for the transformation of the Americas to European colonies with majority European populations. Other parts of the world where the residents had more similar immune systems to the arriving Europeans, such as India, Algeria, and Vietnam while enduring subjugation for a period of time, were never fully converted to European societies due to the continued presence of the local population. The implications are clear; the scourge of disease was a much more influential factor in the founding of the United States than the piety of the
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