Revolutionising Basic Nutrition and Hygiene

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As we celebrate International Clinical Trials Day today, we pay homage to one of the pioneers of early clinical trials research, James Lind (1716 – 1794). James Lind was a Scottish doctor and strong advocate for hygiene during his professional career, especially during his time in the Royal Navy. While accurate documents of the events of his scientific investigations are not so easy to obtain, through fact, fiction or good storytelling, the tale of "the very first clinical trial" conducted by James Lind has become a cornerstone of good clinical practice and fair testing principles for centuries.

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During his professional life, James Lind was able to grow on the strong connections observed between the consumption of citrus fruits and the prevention of scurvy. Scurvy presents itself through a variety of symptoms including gum bleeding and soreness, exhaustion, anaemia, limb pain and heart complications. The consequences of scurvy, while debilitating, we now know can be avoided with consumption of adequate amounts of Vitamin C (ascorbic acid) - 90% of which one can obtain from citrus fruits and vegetables including peppers, tomatoes, broccoli and cauliflower.

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This knowledge may be commonplace today, however, the direct link between - at the time - the unknown nutritional elixir, Vitamin C, and good health at sea was absent. Despite James Lind's legacy, it was still many years until another scientist, Albert Szent-Györgyi, successfully isolated Vitamin C, winning him the Nobel prize in 1937. James Lind had reported that scurvy was responsible for a large number of deaths in the British Fleet compared to the French and Spanish counterparts. While this finding on demographic susceptibility to such a disease was interesting in its own right, it also provided some significant clues to the aetiology of scurvy.

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The Mediterranean Diet

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When we think of continental countries within Europe such as France, Spain and Greece we often think of rich and diverse foods that are able to grow in more welcoming climates. It's certainly true that the so-called Mediterranean diet holds great health-promoting potential. Today, meta-analysis of a number of trials and research studies have demonstrated the health-promoting effects of this diet. Current research indicates that consumption of food types in this group can provide some protection against cardiovascular diseases, dementias and metabolic disorders. This narrative becomes incredibly relevant when we think of the era in which James Lind lived.

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Nutritional status at sea was poor and trade of more exotic fruits and vegetables to countries overseas, including Great Britain, was also poor. Crucial land-mass connections within Europe could support simpler trade of, quite literally, the fruits of agricultural labour in exotic Europe while Great Britain was left comparatively isolated from such farming innovations and delights. This very geographical and geopolitical relationship, and the emerging health benefits of citrus fruits was what James Lind was beginning to piece together during his time at the Royal Navy. As the story goes, what happened next was truly revolutionary.

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Trial and Error

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The health benefits of citrus fruits had previously been reported by the likes of John Woodall and John Fryer, but James Lind was the very first to have reportedly tested this systematically using the scientific method. While more mainstream double-blinded, randomised controlled trials (RCTs) certainly took centre-stage from the 1940's, Lind's study in 1747 is postulated to be the first reported controlled clinical trial in medical history. Grouping together participants in treatment groups with somewhat rudimentary control group comparators, Lind was able to identify a treatment effect from the consumption of oranges and lemons in crew members afflicted with the blight of scurvy. Other crewmen not receiving such a treatment did not recover, and so James Lind attributed the health-promoting effects of oranges and lemons to scurvy amelioration in a matter of days.

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"One of those who had taken them being at the end of six days fit for 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.", James Lind documenting his experimental findings in his historic work, Treatise of the Scurvy, 1753.

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"James Lind has been the means of saving innumerable lives and preventing an incalculable amount of suffering; yet even to the members of his own profession today his name is almost unknown. Of his life even less is known than that of Shakespeare.", (Anonymous 1896; Source: The James Lind Library).

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Despite this revolutionary finding, it is disappointing that it was a further 42 years until the Admiralty issued an order to distribute citrus fruit juice to sailors. Even so, historians and scientists still celebrate the efforts of James Lind in saving the lives of many men at sea to this day.