What with your enemies鈥� cannonballs and your own bosun鈥檚 cat-o鈥�-nine-tails, life at sea in the 18th century was no joke. But worse than death and injury at the hands of others were the effects of disease-and one disease in particular, scurvy. After witnessing scurvy鈥檚 dire effects, naval surgeon James Lind decided to do something about it. He proved that fresh oranges and limes could prevent the disorder-a finding which eventually persuaded the Navy to provide all its ships with citrus fruit. It also led, of course, to the nickname 鈥淟imey鈥�.
Scientifically speaking, though, this potted history neglects the best part of the story: not what Lind discovered, but how. He knew nothing about vitamin C. But in demonstrating the effects of citrus fruit, Lind had carried out what was probably medicine鈥檚 first properly controlled trial.
SCURVY was a horrible disease. After making a three-month voyage to the East Indies in 1738, naval architect William Hutchinson could write from experience. He recalled pining away to 鈥渁 weak, helpless condition, with my teeth all loose, and my upper and lower gums swelled and clotted together like a jelly, and they bled to that degree that I was obliged to lie with my mouth hanging over the side of my hammock to let the blood run out, and to keep it from clotting so as to cloak me.鈥�
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The man who ultimately prevented all this misery, James Lind, trained as a doctor in Edinburgh and signed on as a ship鈥檚 surgeon in 1739. Like any sailor, he became familiar with scurvy鈥檚 grisly symptoms and all too predictable outcome. 鈥淭he scurvy alone, during the last war, proved a more destructive enemy and cut off more lives, than the united effects of the French and Spanish arms,鈥� he wrote. Lind was also familiar with the numerous, mostly ineffective remedies for preventing it. But unlike his shipmates, Lind鈥檚 streak of practical common sense prompted him to try an experiment.
He began it aboard HMS Salisbury on 20 May 1747. He chose 12 scurvy patients with spots, lassitude and putrid gums. 鈥淭heir cases were as similar as I could have them,鈥� he notes in his book A Treatise of the Scurvy. This was important. So too was the fact that the men stayed together in one place, and all ate the same diet: 鈥淲ater 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.鈥�
Lind picked a selection of the various remedies then touted as good for scurvy, and divided his dozen patients into six pairs. 鈥淭wo of these were ordered each a quart of cyder a day,鈥� he writes. 鈥淭wo others took 25 gutts of elixir of vitriol three times a day upon an empty stomach using a gargle strongly acidulated with it for their mouths.鈥� Elixir of vitriol is sulphuric acid, so this pair clearly drew the short straw. Happily they didn鈥檛 have to swallow too much of the stuff, a gutt being an old pharmacists鈥� term for a drop.
The next two got off more lightly: two spoonfuls of vinegar three times a day, also on an empty stomach. Two more (the most severely afflicted, says Lind) had to drink half a pint of sea water every day. A fifth pair 鈥渢ook the bigness of a nutmeg three times a day of an electuary recommended by an hospital surgeon鈥�. An electuary is simply a medicinal paste. The ingredients of this particular concoction included garlic, mustard seed, tamarind and cream of tartar. Maybe the elixir of vitriol pair didn鈥檛 do so badly after all.
The remaining two sailors, the true beneficiaries of this chancy drama, each received a couple of oranges and a lemon. 鈥淭hese they eat with greediness at different times upon an empty stomach,鈥� Lind observed. 鈥淭hey continued but six days under this course, having consumed the quantity that could be spared.鈥� Note that he doesn鈥檛 say they had run out of oranges and lemons, but that no more 鈥渃ould be spared鈥�. Maybe the captain鈥檚 fruit bowl took precedence.
The outcome of the experiment was clear: although cider brought some improvement, it was the fruit which did the trick. In Lind鈥檚 own words: 鈥淭he sudden and visible good effects were perceived from the use of oranges and lemons, one of those who had taken them being at the end of six days fit for duty.鈥� Some of his spots remained, and his gums were not fully healed; but by the time the Salisbury sailed into Plymouth on 16 June, this sailor was otherwise back to full health.
As claimant to be the inventor of the controlled trial Lind does have one or two competitors. The great French army surgeon Ambroise Par茅, for example. Two hundred years earlier he had investigated the benefits of crushed onion as a wound dressing. He applied onion to some parts of the wound, and more conventional remedies to others. But Lind鈥檚 claim to the prize, relying on the more onerous task of comparing different individuals, remains the stronger.
Lind鈥檚 experiments had their limitations. Nowadays you wouldn鈥檛 rush to The Lancet to report on just 12 patients taking no fewer than six different remedies. But, in its time, the simple idea of comparing one treatment with another was little short of revolutionary. You might imagine that the findings would have had a dramatic effect on how doctors evaluated remedies, new and old. Lind鈥檚 simple and logical process should have swept through medicine, brushing aside the accumulated hocus-pocus of centuries. It did not. Medicine was ever a conservative profession, and not much happened for another 100 years.
It wasn鈥檛 until the late 1800s that Louis Pasteur demonstrated the benefits of his anthrax vaccine by inoculating alternate animals before exposing them to the microbe. But even this alternation in comparing treatments did not become common until the early decades of the 20th century, and truly random allocation-now routine in medical research-emerged only in the 1930s. It was Britain鈥檚 Medical Research Council that established the last great landmark in the development of trials. In its 1948 study of streptomycin as a treatment for pulmonary TB, even the doctors didn鈥檛 know which patients would receive which therapy, so minimising bias. The randomised controlled trial had arrived.
As for scurvy, you鈥檇 think the Admiralty would have embraced Lind鈥檚 discovery as a cheap and effective way of keeping sailors fighting fit. Not so. For years his work was derided. One of the few converts was Captain James Cook. It wasn鈥檛 until he returned from his great voyage that the Admiralty could be persuaded to take an interest. A general order to carry citrus fruit was finally issued in 1795, a year after Lind鈥檚 death.
As Lind himself mused: 鈥淚t is no easy matter to root out old prejudices, or to overturn opinions which have acquired an establishment by time, custom and great authorities.鈥�