An early (1753) clinical trial

Before there were pharmaceutical companies, CRO’s, or IRB’s, a Scottish physician named James Lind conducted what is probably the first documented clinical trial. He published his results as A Treatise of the Scurvy in 1753. As an educated man of his time, Lind would have no doubt been familiar with Francis Bacon’s ideas on experimentation, and he begins his treatise by describing the setup for his experiment:

On the 20th May, 1747, I took twelve patients in the scurvy on board the Salisbury at sea. Their cases were as similar as I could have them. They all in general had putrid gums, the spots and lassitude, with weakness of their knees. They lay together in one place, being a proper apartment for the sick in the fore-hold; and had one diet in common to all, viz., water gruel sweetened with sugar in the morning; fresh mutton broth often times for dinner; at other times puddings, boiled biscuit with sugar etc.; and for supper barley, raisins, rice and currants, sago and wine, or the like.

Lind divided his patients into six cohorts: two sailors were given a quart of cider per day, two were dosed with sulfuric acid, which he refers to as “vitriol.” Two were given vinegar, and two were put on “a course of sea water.” Two were given “…the bigness of a nutmeg three times a day of an electuray [a medicinal paste] recommended by an hospital surgeon made of garlic, mustard seed, rad. raphan. [dried radish root], balsam of Peru and gum myrrh…” And finally, two patients were each given two oranges and a lemon every day for six days, when they ran out.

The consequence was that the most sudden and visible good effects were perceived from the use of the oranges and lemons; one of those who had taken them being at the end of six days fit four duty. . . The other was the best recovered of any in his condition, and being now deemed pretty well was appointed nurse to the rest of the sick.

In spite of these results, Lind continued to recommend fresh air, dry conditions, and exercise to treat scurvy. Needless to say, none of these things were available on a ship at sea in the 18th century. It would be another 42 years before the British navy supplied its ships with lemon juice.

Dr. Michael Bartholomew argues that “our modern understanding of scurvy and vitamin C has hindered our understanding of Lind’s own conception of his work and of the place within it of his clinical trials.” Lind had no idea, before or after his experiment, that there was some essential substance in citrus fruits that worked against scurvy. By taking five paragraphs of Lind’s treatise out of context, and projecting our own knowledge, we can make Lind look very modern indeed. But the sad truth is that Lind never truly understood the disorder to which he devoted his career.