First Clinical Research Milestones
- ~1740: Albrecht von Haller, Swiss physician and botanist, writes (in Latin) "Of course, firstly the remedy must be proved on a healthy body, without being mixed with anything foreign; and when its odour and flavour have been ascertained, a tiny dose of it should be given and attention paid to all the changes of state that take place, what the pulse is, what heat there is, what sort of breathing and what exertions there are. Then in relation to the form of the phenomena in a healthy person from those exposed to it, you should move on to trials on a sick body..."
- 1747: James Lind of Scotland conducts a study of the treatment of scurvy, assigning 12 sailors, in pairs, to citrus and five other potential treatments.
- ~1750: Voltaire states: "The art of medicine consists of amusing the patient while nature cures the disease."
- 1759: Francis Home of Scotland tests measles “vaccine” (blood from a measles patient) in 12 children.
- 1760: Anton Storck of Vienna tests the effect of hemlock in increasing doses on himself.
- 1764: Thomas Bayes of England publishes Baye’s Theorem for calculating conditional probabilities, establishing the statistical basis for adaptive trials.
- 1767: English court rules in Slater v. Baker & Stapleton that informed consent is required prior to experimental medical treatment. Baker and Stapleton set and then rebroke Slater’s fractured but healing leg to test a new device.
- 1767: Prior to inoculating all the children at the Foundling Hospital in London, England for smallpox, Dr. William Watson conducts a vaccination trial with three groups of 10 children each. Two of the groups receive pre-and post-treatments; one does not.
- 1770: English physician William Stark dies after eight months of dietary self-experimentation intended to find the cause of scurvy.
- 1770: John Gregory, Scottish physician, writes "Observations on the Duties and Offices of a Physician and on the Method of Prosecuting Enquiries in Philosophy", the first English-language book on bioethics.
- 1775: British physician William Withering identifies leaves from the foxglove plant as an ingredient in herbal remedies for dropsy (the accumulation of fluid in the lower extremities due to cardiac insufficiency). He later proves its effectiveness in experiments on numerous patients. The active ingredient is digoxin, a current treatment for congestive heart failure.
- 1784: Under appointment by Louis XVI of France, a commission led by Benjamin Franklin conducts placebo-controlled and single-blinded (literally, by blindfolding the subjects) studies of the use of magnetism to treat various ailments.
- 1796: Edward Jenner of England demonstrates that cowpox vaccination protects against smallpox by vaccinating and then exposing 12-year-old James Phipps to someone with smallpox.
- 1796: First patent on a medical device is issued, for Perkins Metallic Tractors, consisting of two pointed metal rods about three inches long, one iron and one brass, used as levers to draw toxic electricity from the body in the treatment of headache, rheumatism, deformities, etc.
- 1799: John Haygarth conducts placebo-controlled and single-blinded (with sham wooden “medical devices”) studies of the use of Perkins Metallic Tractors, consisting of iron and brass rods, to relieve pain.
- 1800: Benjamin Waterhouse, one of three full-time professors at Harvard Medical School, successfully tests Edward Jenner’s cowpox vaccine on his son, then on six members of his household, and then on 19 children in a Boston hospital. He then creates a commercial monopoly on the vaccine in the United States. Partially as a result, he is expelled from the Harvard faculty in 1812.
- 1803: Thomas Percival of England publishes “Code of Ethics”, advising physicians to consult with colleagues before trying new remedies and treatments. Percival separately advises physicians not to inform the patient if the information would adversely affect the patient, the patient’s family, or the community.
- 1809: Scottish physician Alexander Lesassier Hamilton and two other army physicians conduct a clinical trial in which 366 sequentially-admitted sick soldiers are assigned in rotation to three physicians. One physician uses bloodletting; the other two do not. Mortality rate is 29% with bloodletting and 2% without.
- 1813: Vaccine Act regulates vaccines.
- 1818: The English author, Mary Shelley, publishes the novel, "Frankenstein, or The Modern Prometheus," about Victor Frankenstein's reanimation experiment.
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