For many of us working in clinical research or participating in the studies, the notion of testing new medications in statistically controlled, highly regulated trials is so natural that we, for the most part, take it for granted. Yet clinical trials have a long and fascinating history. Here are some of the early milestones.

It is often suggested that the world’s first clinical trial was conducted by King Nebuchadnezzar. According to The Bible (The Book of Daniel), the king, concerned about keeping his warriors in top physical condition, ordered his people to eat only meat and drink only wine. Yet several young men of royal blood, who liked to eat vegetables, objected. The king permitted the dissenters to follow the diet of veggies and water – but only for 10 days[1]. The history is vague as to whether the participants signed informed consent or were compensated for time and travel. What we know, however, is that when the experiment ended, the vegetarians appeared better nourished than carnivores, so the king permitted the group to continue with their diet. While the Babylonian ruler was not being able to decidedly resolve the question of which of the diets is preferable, we cannot fault him for this – the question has not been fully answered up to this day. Yet the king certainly deserves credit for introducing two major components of a clinical trial: (i) separate groups following different prescriptions and (ii) finite length of the trial, upon which the results are evaluated.

According to the FDA paper, the first mentioning of a subject being paid for participation in research dates back to 1667 England. According to a diary by a contemporary, the local college hired a “poor and debauched man” to have some sheep blood “let into his body”. It’s hard to imagine this Phase I trial happening today (particularly without drug screening…), yet although there had been plenty of trepidation before the test, the man reportedly suffered no ill effects[2].

The first “scientific” clinical trial is commonly credited to James Lind. Born in Edinburg, Scotland in 1716, he started his medical studies as an apprentice when he was just 15. Eight years later he entered the Royal Navy as a surgeon mate and in 1747 became surgeon of HMS Salisbury, patrolling the Bay of Biscay. As it was common in those days, in about two months into the voyage, a large number of sailors were down with scurvy.  Lind describes: “On the 20th of May 1747, I selected twelve patients in the scurvy, on board the Salisbury at sea. Their cases were as similar as I could have them. They all in general had putrid gums, the spots and lassitude, with weakness of the knees. They lay together in one place, being a proper apartment for the sick in the fore-hold; and had one diet common to all, viz. water gruel sweetened with sugar in the morning; fresh mutton-broth often times for dinner; at other times light puddings, boiled biscuit with sugar, etc., and for supper, barley and raisins, rice and currants, sago and wine or the like. Two were ordered each a quart of cyder a day. Two others took twenty-five drops of elixir vitriol three times a day … Two others took two spoonfuls of vinegar three times a day … Two of the worst patients were put on a course of sea-water … Two others had each two oranges and one lemon given them every day … The two remaining patients, took … an electary recommended by a hospital surgeon … The consequence was, that the most 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…” (Dr. James Lind’s “Treatise on Scurvy” published in Edinburgh in 1753)[3]

Remarkably, while the results were convincing, Lind hesitated to recommend the use of oranges and lemons because they were too expensive. It took the British Navy nearly 50 years to make lemon (later lime) juice a compulsory part of the sailors’ diet. Yet by the end of the 18th century, scurvy, commonly affecting up to 50% of men on warships, was no longer a threat to the Royal Navy. And who knows how the Battle of Trafalgar would have turned out if not for Dr. Lind’s clinical trial…

Since 1747, clinical trials made a long way. The studies are conducted under strict guidance and oversight by the FDA, Institutional Review Boards, and the medical community.   Yet the overarching goal of clinical trials is still the same: to find cures that do not yet exist today but will save lives tomorrow.

To find more about studies conducted by Boston Clinical Trials and to learn about benefits and risks of participation, please visit BCT’s website: www.bostontrials.com.

[1] Evolution of Clinical Research, by Arun Bhatti (www.ncbi.nlm.hih.gov, downloaded 07/27/14)

[2] FDA and Clinical Drug Trials, by Suzanne White Junod (www.fda.gov/aboutFDA, downloaded 07/27/14)

[3] Evolution of Clinical Research, by Arun Bhatti (www.ncbi.nlm.hih.gov, downloaded 07/27/14)