The Siege of Breda is one of the most graphic events of the Eighty Years War (also known as the Dutch War of Independence). Under the orders of Spanish general Ambrogio Spinola, the walled city of Breda in what is now the Netherlands was besieged by the Spanish army for more than eleven months. So extreme were conditions inside the town for the 7,000 soldiers defending the town that they soldiers began dying of scurvy due to the lack of fresh fruit and vegetables. Though curable through simple nutrition, scurvy is potentially deadly for anyone whose diet is low in Vitamin C and the Dutch soldiers were no exception. Along with problems stemming from malnutrition, the long siege also led to a critical shortage in various medications, including medications for relieving pain (primarily opium and laudanum). To solve this problem, the garrison commander Justin of Nassau (a son of William of Orange), hit on a cunning plan.
Working with the city's doctors, Justin had the doctors provide their patients with a powerful new medicine that he reportedly managed to smuggle in from the mysterious East. The medicine was so strong that only a few drops in a gallon of water would clear up their symptoms. The soldiers were impressed that their commander had managed to get them this medicine despite the risks and expense involved. Except that the "medicine" in this case was nothing more than a mixture of wormwood, camomile, and camphor, carefully placed into small phials which Justin provided to the doctors. While available reports stated that "they took the medicine eagerly and grew well rapidly", there are likely limits to how well the power of suggestion could work in preventing the symptoms of scurvy. Certainly men continued to die and only 3,500 Dutch soldiers were still alive by the time Justin surrendered the town.
Though medical doctors had long observed that patient belief had a powerful effect on the body and how they responded to medical treatment, the first formal investigation into what would be called "the placebo effect" would not begin until the early 19th century. The word "placebo" is Latin for "I will please" and actually comes from a Latin translation of the Bible. British physician John Haygarth published what would be the first treatise on the placebo effect when he investigated that medical effectiveness of a popular cure of the time known as "Perkins tractors." Invented by American physician Elisha Perkins, these "tractors" consisted of two 3-inch metal rods made of steel and brass. By using the tractors to "draw off the noxious electrical fluid that lay at the root of suffering", Perkins claimed to be able to cure a wide variety of illnesses including rheumatism and arthritis.
Even though conventional medical doctors were quick to denounce Perkins' invention as sheer quackery, many patients reported getting significant pain relief from the treatments and John Haygarth decided to investigate further. Alarmed at the growing popularity of Perkins tractors among his patients in Bath, Haygarth dem0nstrated that patients could get the same pain relief from rods made of virtually any substance and that they were unable to tell the difference between fake tractors and the "real" ones. He also noted that some patients actually got worse instead of better which suggested that imagination could cause as well as cure disease. What mattered most was the credibility of the doctor (famous doctors were more likely to get positive results than obscure ones) as well as how credulous the patients were. The best results appeared to come from both the doctor and the patient believing in the power of the medical treatment. He prophetically commented that: "medical practitioners of good understanding, but of various dispositions of mind, feel different degrees of scepticism in the remedies they employ. One who possesses, with discernment, the largest portion of medical faith, will be undoubtedly of greatest benefit to his patients."
As Haygarth concluded in his 1800 paper Of the Imagination as a Cause and as a Cure of Disorders of the Body, what really caused pain relief was the belief that patients were getting an apparently effective treatment. Haygarth concluded in his paper that his results showed "to a degree which has never been suspected, what powerful influence upon diseases is produced by mere imagination". While his research into the power of belief would be largely overlooked by medical historians (he is mainly remembered as a pioneer in smallpox inoculation), he is still the first physician to raise questions about the placebo effect which have haunted discussions of alternative medical treatments ever since.
At the same time that John Haygarth was making his groundbreaking observations on the power of positive belief in relieving pain, the influence of Franz Mesmer and his disciples was also being felt across Europe and North America. Despite attempts by skeptics such as Benjamin Franklin and Antoine Lavoisier to debunk Mesmer's work, mesmerists would ply their trade for decades afterward and physicians were slowly beginning to understand how they were accomplishing their apparently miraculous cures.
Along with mesmerism, the early 19th century was also seeing a rise of interest in homeopathy. Based on the "like cures like" doctrine of Samuel Hahnemann, homeopathic practitioners began offering their treatments for various illnesses with only anecdotal evidence from satisfied patients to prove that it even worked. The first formal clinical trial to test the effectiveness of homeopathic medicine was carried out in Russia in 1832. Not coincidentally, it was also the first clinical trial to use a placebo in medical research. Tests comparing homeopathic medicine with placebo pills made of flour paste showed no real difference was found in medical effectiveness. After publishing these results, the term "placebo effect" became well-known to medical researchers across Europe and North America (though homeopathic medicine seems not to have been seriously derailed by the findings).
In another informal test of the placebo effect, French physician Albert Matthieu informed many of his tuberculosis patients at the Hopital Andral in Paris of a powerful new treatment for tuberculosis that had recently been discovered in Germany. This new treatment, which he dubbed "antiphymose" was supposed to yield wonderful results in people suffering from tuberculosis and the news quickly spread with patients demanding that the drug be tested on them. After a time, Matthieu began conducting clinical trials which the drug he had supposedly received from Germany. All patients receiving antiphymose injections were carefully tested on a regular basis to see if their weight and temperature changed as a result of the new treatment.
According to the results, antiphymose had a powerful effect on tuberculosis patients receiving the injections. Not only did the patients gain weight but their chronic fever was reduced as well. Some gained as much as three kilogrammes of weight while other symptoms such as persistent coughing and insomnia improved as well. When the antiphymose injections stopped, the old symptoms returned as well and patients quickly lost the weight they had gained before. Only afterward did Matthieu reveal that there was no such treatment as antiphymose. What they had received was simply sterilized water and saline. The record fails to state how the patients responded to being deceived, even in a good cause.