Apr 20, 2014 8
Much of my current research involves randomized control trials (RCTs), in which participants or clusters of participants are randomized into a treatment group (or groups) and a control group. The treatment group gets some sort of intervention and the control group does not. If the sample size is large enough, randomization ensures that each group is ex ante identical and that therefore any difference in outcomes can be causally attributed to the intervention and not e.g. to selection bias or existing trends.
A couple of colleagues and I started talking about the historical origins of randomization in science. Most people associate this approach with clinical trials in medicine and epidemiology, which is indeed where they gained fame, but I was pretty sure that they had earlier and first been used in agriculture by the pioneering statistician and biologist Ronald Fisher. I was half right: Fisher did use them earlier, and his text on experimental design is a classic treatise laying out the principles of randomization, but he was not first.
Apparently the first reference to comparing treatment and control groups is in the Book of Daniel in the bible, where King Nebuchadnezzar orders his people to eat only meat and drink only wine (for their health). When some object, he allows them to eat only legumes and drink only water for 10 days, after which he compares their health to the “control” group of meat-eaters. They do better, so he allows them to continue their diet. Note, however, the lack of randomization and hence the possibility of a strong selection effect. The king appears to implicitly understand this, since he does not order everyone to switch to the new diet.
That story is told in this interesting medical history of clinical trials (as well as this follow-up article). It also discusses the famous streptomycin (for tuberculosis) trial of 1946 (published 1948), which is generally considered the first random trial in medicine. Indeed the wikipedia article on RCTs calls it the first published RCT, although as we shall see this is essentially incorrect. One of the medical histories bizarrely states, without citation, “The idea of randomization was introduced in 1923.” This is wrong by approximately three centuries.
A few years earlier, during the war, the british Medical Research Council performed a trial of patulin (related to penicillin) for the common cold. They didn’t explicitly randomize; instead they alternated patients to treatment vs control. That strikes me as a generally valid approach, and they also deserve a lot of credit for carefully double-blinding the study. Apparently there was also an early randomized experiment to test a potential immunization against whooping cough. But neither of these interventions proved efficacious, and the streptomycin trial was published first, so it takes the credit (within medicine).
Meanwhile the medical literature points back to Dr. James Lind, an 18th-century physician who decided to test various methods for treating scurvy while serving as a naval ship’s surgeon in 1747. He took 12 diseased sailors, split them into groups of two, and gave each of the six groups a different treatment (cider, sea water, nutmeg, etc). After 6 days one group showed marked improvement: those who had received oranges and lemons. Formally this wasn’t randomized, and the sample size was very small, but this is probably the first rigorous experiment along such lines.
However, the idea of randomization dates back to 17th-century belgian physician Van Helmont. As everyone knew at the time, bloodletting was a great cure for most ailments. Van Helmont agreed, but he thought that evacuation (i.e. inducing vomiting and defecation) was even better. To …