Classic Experiments Series—The First Clinical Trial?

It is common knowledge these days that severe Vitamin C deficiency causes scurvy, which is often accompanied by symptoms such as swollen, bleeding gums, bruises on the skin, severe joint pain etc. But how exactly was the link between Vitamin C and scurvy discovered? It turns out that the findings initially published on this topic by James Lind represent a landmark moment in biology; which some regard as the first ever clinical trial.

The National Institutes of Health (NIH) define a clinical trial as “A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes." The importance of such controlled trials in evaluating the performance of different drugs/therapeutic options cannot be overstated, and hence tracing them back to their supposed origin is quite an interesting task.

The hero of the story is James Lind, who was a Scottish doctor of the 18th century (1716-1794). Before his pioneering work, sailors lived in fear of the mysterious disease (scurvy), which caused their gums to rot and skin to sore, leading to countless deaths. In fact, no one really had any idea of its cause, and people were left to place the blame on the poor conditions and dirty drinking water customary of the voyages. In 1947, James Lind was appointed as the surgeon of the HMS Salisbury (an English patrol ship). Little did he know that his experiments were going to be etched forever in medical history.

Just like with all the other voyages of the time, scurvy began to affect the crew. Lind was ready. He took 12 sick patients and divided them into 6 groups of two. Each group was provided with a specific dietary supplement; among those used were vinegar, sea-water, oranges and lemons etc. Lind ensured that all the other variables were controlled; the patients all exhibited consistent symptoms, lived in similar conditions, and had identical diets except for the supplement.

Eventually, the two sailors given oranges and lemons improved, and a cure for scurvy was found! These results were formally published in his famous book “A Treatise of the Scurvy”. The work assumes historic importance because of the way in which Lind controlled the various variables in his experiment, setting a precedent for future scientists to follow. However, it is not without controversy. Some people point out that citrus fruits as a cure for scurvy were known well before the work of Lind, although this does not take much away from his visionary scientific methodology. Others claim that similar clinical trials were conducted as early as the 9th century. Perhaps most interestingly, some people believe that Lind never actually performed the trials, since records from the HMS Salisbury didn’t indicate much incidence of scurvy among the crewmates at all! However, in one way or another, the “work” of James Lind played a pivotal role in shaping the medical trials we see today.