First Clinical Research Milestones
- 2737 BCE: Shen-nung pen ts'ao ching (Divine Husbandman's Medical Materials) describes 365 medicines derived from minerals, plants and animals; believed to be authored by Shen Nung, the "father of Chinese medicine."
- ~600 BCE: Daniel designs and participates in a controlled nutritional study in the court of Nebuchadnezzar II, King of Babylon. Study is reported in the Old Testament sometime later.
- 400-200 BCE: Charaka Samhita, a textbook in verse of Ayurvedic medicine, is written in India.
- ~400 BCE: Hippocratic Oath defines responsibilities of physicians to their patients (with no mention of experimentation). Hippocrates, who lived in Greece probably sometime between 460 and 380 BCE, probably did not write the oath.
- 280 BCE: City of Alexandria gives Greek physician Herophilus and his colleague Erasistratus permission to cut into and look inside a prisoner condemned to death, for purposes of scientific investigation.
- ~200 BCE: Sushruta Samhita, a textbook in verse of Ayurvedic surgery, is written in India.
- 137 BCE: Attalus III (Philometer), King of Pergamum, tests the effects of extracts from poisonous plants by offering them in beverages to his guests.
- 162: Galen moves to Rome, where he develops the science of experimental physiology.
- ~550: Babylonian Talmud (Niddah (30b)) tells story about Cleopatra, who, to settle an argument between two rabbis about how long it takes for male and female fetuses to develop, had slave girls impregnated and operated on at specified times to examine the development of the fetuses. The investigators reported that boys developed in 40 days and girls took 80 days.
- ~930: Rhazes (Bakr Muhammad ibn Zakariyya al-Razi) publishes Kitab al-Hawi fi al-tibb (The Comprehensive Book of Medicine), in which he describes treating one group of patients with early symptoms of meningitis with bloodletting and another without, thereby determining that bloodletting prevents development of the disease.
- ~1030: Avicenna (Abū ‘Alī al-Husayn ibn ‘Abd Allāh ibn Sīnā), a Persian physician, publishes The Book of the Canon of Medicine (Qanun fi al-Tibb), setting forth seven rules for systematically evaluating the effect of drugs on diseases.
- 1061: Chinese government administrator Song Su publishes Ben Cao Tu Jing (Atlas of Materia Medica), a pharmacopeia.
- ~1175: Moses Maimonides, physician, writes prayer, including the line: "Inspire me with love for my art and for Thy creatures. Do not allow thirst for profit, ambition for renown and admiration, to interfere with my profession, for these are the enemies of truth and of love for mankind and they can lead astray in the great task of attending to the welfare of Thy creatures."
- ~1260: Roger Bacon, English scientist, philosopher, and Franciscan monk, writes that, "it is more difficult [for a physician] to [experiment] in [medical] science than in any other...because of the nobility of the material in which he works; for that body demands that no error be made in operating upon it…."
- ~1296: Bernard de Gordon, French physician and professor of medicine, suggests "a hierarchy of drug testing, from birds, to brute animals, to 'those in the hospital,' to the 'lesser brethren,' and then on to others 'in order, because if it [the drug] should be poisonous it would kill.'"
- 1500s: Paracelsus (Theophrastus Bombastus von Hohenheim), who traveled widely in Europe, teaches to investigate nature “not by following that which those of old taught, but by our own observation of nature, confirmed by… experiment and by reasoning thereon.”
- 1537: In the middle of a siege battle, physician Ambroise Paré of France runs out of boiling oil, the usual remedy for treating open wounds at the time, and discovers that treatment with a tincture of egg yolk, oil of rose, and turpentine reduces pain, swelling and mortality.
- 1662: Jan Baptist van Helmont, a Flemish medicinal chemist and disciple of Paracelsus, proposes a randomized test of blood-letting with 200 to 500 fever and pleurisy patients, backed by his wager of 300 florins against blood-letting, which is not accepted.
- 1667: Samuel Pepys records in his diary an experiment in which the Royal Society of London pays Arthur Coga 20 shillings to allow 12 ounces of sheep blood to be "let into his body," with no apparent ill effects.
- 1721: With the support of Princess Caroline (who was persuaded by Lady Mary Wortley Montague, wife of the British ambassador to Turkey) and at the direction of Sir Hans Sloane, physician to the King of England, Dr. Terry of Enfield, who had practiced in Turkey, inoculates six prisoners with smallpox. All were infected and survived to gain the reward of release from Newgate prison. Dr. Charles Maitland subsequently demonstrated immunity for one of them.
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