Science in the cultural context
Origins of Pharmacology
in the 16th Century
In a broad sense it can be argued that pharmacology is the oldest discipline in the health sciences: humans well before the historical record presumably concocted remedies for various illnesses. For example, plants may have been used to cure ailments for over 60,000 years, if the evidence from the graves of Homo neanderthalensis is accepted. Lietava has argued that the analyses of pollen from six plants found on Neanderthal graves indicate that the plants did not grow there, that none of them had attractive flowers, and that all have been used since that time for their remedial qualities (1). More certainly, cuneiform tablets from the library of Ashurbanipal, dated about 2000 BCE, contain detailed descriptions of the preparation of remedies (2). The word “pharmacology” was not used in print until the 17th century; however, as far back as the 4th century, the word “pharmacum” was used to denote a medicine or drug (3). In the late 1600s, Walter Harris in his Course of Chymistry adapted this late Latin term to “pharmacologia” (4). Coincident with its use in language, the study of pharmacology developed three basic principles that are used today. These concepts were formulated in the 16th century––and serve as a signpost for the origin of modern pharmacology– –when the traditional beliefs of Hippocrates (460–357 BCE) and Galen (131–200 AD) were overthrown by the modern ideas of drug action. These three principles are: 1. Each disease has a unique cause for which there is a specific remedy.
The Medieval Origins Of Pharmacology
2. The “doctrine of signatures” states that each remedy has an identifiable nature or essence that is obtained from the natural product by chemical extraction. 3. The administration of a remedy is based on dose-response by which the appropriate dose is determined. Although these guiding principles are obvious to a modern pharmacologist, the recognition of their fundamental nature in the use of drugs was a hard-fought battle. To Hippocrates, when the four humors of the body (i.e., black bile, yellow bile, phlegm, and blood) were not in balance, sickness or disease arose and the role of remedies was to restore balance. These four humors were reflected in the temperament of individuals (i.e., melancholic, choleric, phlegmatic, and sanguine) and also in Aristotle’s four elements (i.e., earth, fire, water, and air) out of which all substances were composed. Because earth was said to be cold, fire hot, water wet, and air dry, a useful drug would be classified according to the amount of the elements from which it was composed. For example, in his great herbal, John Gerard (1545–1612) gave the effect of each plant in degrees, stating that the seeds of the flea-wort (Plantago psyllium) were cold in the second degree and that bitter almonds were hot and dry in the second degree (5). The first significant challenge to the selection of remedies that subscribed to the doctrines of Galen came in the 16th century from those apothecaries who were seeking the active ingredients in plants, minerals, and animal products. Although alchemists have achieved recognition (or notoriety) for the pursuit of the Philosopher’s Stone that was expected to transmute base metals to gold [Ed.: See also the Beyond the Bench article in this issue], a large number of “medical alchemists” (6) were not trying to make gold but rather were trying to find better remedies for diseases. In contrast to information on the uses of specific plant parts as described in the herbals of Gerard and of Turner (5, 7), the medical
alchemists emphasized distillation as the most useful method to extract the active ingredient from the inactive dross. One of the most popular books on remedies in the 16th century was by Hieronymus Brunschwig whose first printed edition was published in 1500 as Kleines Destillierbuch (Little Book on...
References: 1. 2. 3. 4. 5. 6. 7. 8. 9. Lietava, Jan. Medicinal Plants in a Middle Paleolithic Grave Shanidar IV? J. Ethnopharm. 35:263-266, 1992. Thompson, R. Campbell. The Assyrian Herbal. Luzac and Co., London. 1924. Souter, Alexander. A Glossary of Later Latin. Clarendon Press, Oxford. 1996. Oxford English Dictionary. 12 Vol. Clarendon Press, Oxford. 1933. p. 768 Gerard, John. The Herbal. (1597). Revised edition by Thomas Johnson, 1633. Reprintof 1633 edition, Dover Publications, Inc., New York. 1975. Debus, Allen G. The Chemical Philosophy. (1977). Reprint, Dover Publications, Inc.Mineola, N.Y. 2002. Turner, William. A New Herball. 3 Vol. (1551). G.T.L. Chapman, M.N. Tweddle, editors. Cambridge University Press, Cambridge. 1995. Brunschwig, Hieronymus. Kleines Destillierbuch. Johann Gruninger, Publisher. Strassburg. 1500. Andrea, Giovanni. Libro de i Secretti con Ricette. (1562). The Jesuatti Manuscript. Unpublished manuscript at the Kenneth Spencer Research Library, the University of Kansas, Lawrence, KS. Folios 141–146.
10. Major, Ralph H. Classic Descriptions of Disease. 3rd edition. Charles C. Thomas, Publisher, Springfield, Ill. 1945. p. 7 11. Major, Ralph H. Classic Descriptions of Disease. 3rd edition. Charles C. Thomas,Publisher, Springfield, Ill. 1945. p. 37 12. Major, Ralph H. Classic Descriptions of Disease. 3rd edition. Charles C. Thomas, Publisher, Springfield, Ill. 1945. p. 163 13. D’Espagnet, Jean. Enchyridion Physicae Restitutae. (1623) (Summary of Physics Restored). John Everard, translator. T. Willard, editor. Garland Publishing, Inc.Taylor and Francis, New York. 1999. 14. Boyle, Robert. The Sceptical Chymist. (1661). Reprinted, Dover Publications, Inc. Mineola, N. Y. 2003. Figure 3. Dose-response relationship where the nature of the response changes with increasing doses. With increasing doses the response increases from the initial conditions up to dose X1. As the dose is increased further, the response decreases. Starting at dose X2 the response is below the initial conditions. 15. Strathern, Paul. Mendeleyev’s Dream. St. Martin’s Press, New York. 2000. p. 84 16. Scheindlin, Stanley. Transdermal Drug Delivery: Past, Present, Future. Mol. Interv. 4, 308-312, 2004. 17. Andrea, Giovanni. Libro de i Secretti con Ricette. (1562). The Jesuatti Manuscript. Unpublished manuscript at the Kenneth Spencer Research
The Medieval Origins Of Pharmacology
Library, the University of Kansas, Lawrence, KS. Folio 118v. 18. Andrea, Giovanni. Libro de i Secretti con Ricette. (1562). The Jesuatti Manuscript. (Translated by S. Norton).Unpublished manuscript at the Kenneth Spencer Research Library, the University of Kansas, Lawrence, KS. Folio 160v. 19. Paracelsus: Four Treatises. (Seven Defensiones, translated by C.L. Temkin). Henry E. Sigerist, editor. Johns Hopkins University Rress, Baltimore, MD. 1996. 20. Snedecor, George W. Statistical Methods. 5th Edition. Iowa State College Press, Ames,Iowa. 1956. 21. Govindarajulu, Zakkula. Statistical Techniques in Bioassay. S. Karger, Basel. 1988. 22. Bliss, C. I. Method of Probits. Science 79: 38-39, 1934. 23. Calabrese, Edward J. Hormetic Dose-Response Relationships in Immunology. Critical Reviews in Toxicology 35: (2-3) 89-295, 2005. 24. Krieger, William C. Forward on Paracelsus—Dose Response. In, Handbook of Pesticide Toxicity. Robert Krieger, editor. Academic Press, New York. 2002.
Stata Norton, PhD, is an Emeritus Professor in the Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS. SN has published over 120 research articles, reviews, and book chapters on neuropharmacology and neurotoxicology, especially on the effects of drugs and radiation on the developing central nervous system. E-mail firstname.lastname@example.org; fax: (913) 5887501.
June 2005 Volume 5, Issue 3
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