Eat your oranges!

Warning: the following article contains brief graphic descriptions of medical symptoms.

What do you envision when you hear the word ‘experiment’? Bespectacled researchers with white coats and pristine microscope slides working into the wee hours of the night? Lab mice injected with this, that, and the other, scurrying around a maze?

What if I told you that the first documented clinical experiment occurred on the HMS Salisbury, a British 50-gun warship navigating the Bay of Biscay in 1746? The subjects: around-the-clock-drunk male sailors afflicted by scurvy, causing a “lazy inactive disposition”, “extremely putrid and fungous” gums, “black and livid spots” on the skin, and ulcers caked with “coagulated gore”. The researcher: one James Lind, the ship’s Scottish surgeon, who rose up Navy ranks after only an apprenticeship and no medical degree. The background: only a handful of military personnel were dying from battle wounds, but hordes were falling victim to scurvy. The research question: whether a change in diet would cure the sailors of their horrific symptoms.

Lind selected 12 sailors from the 30-40 on the ship that were already scorbutic (suffering from scurvy), making sure that his subjects had similar symptom severities, living quarters, and diets (featuring delicacies such as “water-gruel sweetened with sugar” and “fresh mutton-broth”). He assigned two sailors each to six daily treatments over two weeks: a quart of cider, twenty-five drops of dilute sulphuric acid, two spoonfuls of vinegar, half a pint of sea-water, a medicinal paste containing herbs and myrrh, and two oranges and a lemon (this last treatment was discontinued after six days because the citrus fruits ran out). All these were to be taken on an empty stomach.

As you might expect, the sailors who received oranges and lemons quickly recovered and were able to care for the other subjects within a week. Next in effectiveness were the cider and sulphuric acid, which eased dental symptoms (but may have created their own problems). The other treatments had little effect on the patients’ conditions, although one vinegar-drinker did improve after the experiment (Lind was able to attribute this to the natural course of the disease rather than the vinegar itself).

One glaring critique of Lind’s design is its sample size; how do we know that the various treatment outcomes were not due to chance if only two sailors were assigned to each one? Also, did Lind introduce his own biases in selecting sailors to participate in the study, and were the subjects he chose representative of the seafaring scorbutic population? Did the subjects always comply with the treatment assigned to them? Was there something apart from the treatment variable that caused a difference in disease outcomes of the subjects (heterogeneity)?

Nevertheless, the amount of experimental control Lind achieved is admirable, and his methods were a revelation to his contemporaries. More inspiring was the extent to which he doubted his own conclusions; unlike some headstrong scientists, he gathered that his results were almost meaningless and sought further research, even admitting defeat after the observations he made repeatedly contradicted the citrus fruit hypothesis. Given that Navy policies relied on reputation more than scientific evidence, citrus rations were only provided to sailors from 1795 onwards. Some could say that the British defeated Napoleon with lemon juice.

But was this trial ethical? Researchers use the term equipoise to describe the uncertainty that justifies a randomised control trial. Since Lind was the first to experiment on scurvy patients, he was hardly expected to recognise which treatment would be most successful. However, the treatments he enforced, such as the ingestion of sulphuric acid on an empty stomach, are hardly excusable to the modern reader. No publication, contemporary or otherwise, has mentioned Lind asking the sailors for informed consent. Such an experiment, especially one involving a potentially fatal disease, would never have been authorised today.

So this holiday season, be thankful that clinical trials have consent forms, ethics review boards, and medical professionals on hand. And be glad that attrition is due to participants who no longer want to give you their time, not those who happen to fall from your ship and drown every other week.

To read Lind’s 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 (1753), go to: https://babel.hathitrust.org/cgi/pt?id=ucm.5320216015&view=1up&seq=2

Sources:

Milne, Iain. “Who Was James Lind, and What Exactly Did He Achieve?” The James Lind Library, 2012, https://www.jameslindlibrary.org/articles/who-was-james-lind-and-what-exactly-did-he-achieve/.

Sutton, G. “Putrid Gums and Dead Mens Cloaths: James Lind Aboard the Salisbury.” Journal of the Royal Society of Medicine, vol. 96, no. 12, 1 Dec. 2003, pp. 605–608., doi:10.1258/jrsm.96.12.605.

*If you are interested in research design and using experiments and data analysis to solve our biggest challenges in the health and social sciences, consider a course in UCL’s Q-step Centre, a pioneering programme to introduce more quantitative skills to social studies degrees across the university’s diverse departments. Geography, Social Sciences, Political Science, and Population Health can all be studied with a Q-step pathway.