Be Ye Wondering About How Clinical Trials First Hit the Salty Sea?

Ahoy ye mateys! Have you ever wondered which enemy was the most dangerous to sailors during the 1700s? James Lind, a Royal Navy surgeon, described a foe that “proved a more destructive enemy, and cut off more valuable lives, than the united efforts of the French and Spanish arms.” In order to conquer this threat, Lind employed a brand new weapon. This weapon was previously unknown to science and has now been used to defeat countless foes. The enemy was scurvy, and the weapon was a clinical trial.

May 20, 2022, marks the 275th anniversary of that first clinical trial. Scurvy could lead to muscle pain, gum disease, fatigue, jaundice, and death. Remedies at the time varied widely and only anecdotal, word-of-mouth evidence for them was available. Every sailor who was afflicted with scurvy sought a cure, but the overall disease was caught in the doldrums without a solution for 150 years. Lind had bigger ambitions. His big insight wasn’t trying to treat just a few individuals for scurvy, but instead trying to solve the problem of scurvy on the scale of public health. Though he only had 12 participants in that first trial, how Lind compared different remedies showed his big-picture thinking. He sought not to give relief to just those 12 patients, but to quantify and share his results to cure the whole of the Royal Navy.

In this effort, Lind laid the groundwork for the modern clinical research study. He started with a set of 12 patients with conditions “as similar as I could have them.” He controlled extraneous variables, giving all patients the same diet during the study and keeping them on the same boat. He split them into 6 random conditions:

• A quart of cider per day
• Elixir vitriol (sulfuric acid and alcohol), 3x daily 
• 2 spoonfuls of vinegar, 3x daily
• ½ pint of seawater per day
• 2 oranges and 1 lemon per day
• The bigness of nutmeg (a medicinal paste made of herbs and spices)

The results were clear; citrus gave quick and significant relief.  Importantly, Lind didn’t leave his findings high and dry. He recorded and reported what he saw. Probably the most important aspect of Lind’s clinical trial was that he looked at the results in an unbiased way. He wrote extensively on the need to remove personal and societal bias:

“it is no easy matter to root out old prejudices, or to overturn opinions which have acquired an establishment of the time, custom, and great authorities; it became therefore requisite for this purpose, to exhibit a full and impartial view of what has hitherto been published on scurvy.”

Today the same core ideas guide clinical trials, but there are many more safeguards for participants. A good clinical trial today is grounded in science, provides benefits to patients that should outweigh any risks, and treats patients with respect. Critically, clinical trials have informed consent; all participants join voluntarily and must have full knowledge of any risks before signing up. Trials also have oversight from Institutional Review Boards and have medical staff on-site to help with any adverse reactions. Following Lind’s example, clinical trials also target specific conditions, have randomized patients, control conditions (as much as possible), and dutifully record and report their findings.

Though his aim was to blow scurvy out of the water, Lind ended up making waves in how scientists solve medical problems in general. His quantitative, balanced approach gave the world a system to tackle medical problems. On this International Clinical Trials Day, we can help keep up the bounty of Lind’s legacy by volunteering as a clinical research trial participant and sending some diseases to Davy Jones’ Locker!

References:

Lind, J. (1753). A treatise of the scurvy: in three parts, containing an inquiry into the nature, causes, and cure, of that disease, together with a critical and chronological view of what has been published on the subject. Bulletin of the World Health Organization: the International Journal of Public Health 2004; 82 (10): 793-796.From https://www.jameslindlibrary.org/lind-j-1753/