Let nature take its course experiments

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In Boston around 1721 there was argument over variolation with churchmen on both sides "...within a year or two after the first experiment nearly three hundred persons had been inoculated by Boylston in Boston and neighbouring towns, and out of these only six had died; whereas, during the same period, out of nearly six thousand persons who had taken smallpox naturally, and had received only the usual medical treatment, nearly one thousand had died."[1]

Natural experiment around Boston
Total DiedMortality %
Variolated C 300 6C 2%
UnvariolatedC 6000C 1000C 14%*

[1]*
gives it as about 14% rather than 17%, likely with closer figures.

References