CHOLERA BEFORE ROBERT KOCH

         Cholera outbreaks today are confined to areas of famine, war, or other sites of public health disarray. Though an old disease in India, it is a relatively new disease from a global viewpoint. The first recorded pandemic, that of 1817, marched from India eastward through Asia and westward to Persia and the Caucasus, but spared Europe.

         In the next pandemic, beginning in 1829, cholera reached Russia, swept down through Europe, and traveled across the Atlantic to the United States, Canada, and South America, killing hundreds of thousands during its march. Western medical skills were powerless. Arguments raged over whether it was contagious or came from

French drawing, cholera (Wikipedia)

miasmas and/or foul air, and how to treat it. Quarantines of various types were debated and instituted irregularly. Galenic ideas, especially those involving corrupted humors to explain symptoms, still prevailed in medical thought. Accordingly, for treatment medical opinion favored measures to rid the body of corrupting material. 

The losses of fluid in cholera are dramatic. Liters can be passed in liquid stools in a few hours, exacerbated by vomiting. Records describe patients as cadaveric, with dry, cold, grayish skin, near-absent pulse, and inaudible heart sounds.  Blood from a vein or artery, if it came at all, resembled tar. Claude Bernard even suggested that survivors passed through a form of suspended animation similar to hibernation. It is obvious today that replacement of fluid is essential, but that was not so in the 1830s. Bleeding and purging were highly recommended treatments. Since blood was hard to extract, doctors often resorted to an artery to obtain small amounts of tarry material. Emetics, purgatives like calomel, cupping, and blistering were also part of regimens that did more harm than good.

Investigators in Moscow in 1830 were among the first to discover the high hematocrit and low water content of blood in cholera patients. Scattered reports of injecting water or saline solutions intravenously appeared, but results were disappointing. Inadequate amounts of fluid, injection of air bubbles, and bacterial contaminants all contributed to poor results, delaying intravenous fluid therapy until the twentieth century. Attempts to suppress bowel movements with opiates also met with little success.

A third pandemic lasted from 1845 to 1856. By then, contaminated water was under suspicion. John Snow’s surmise of a “cholera poison” in the water from a certain London water company and from a particular well resulted in removing the handle from the

John Snow (Wikipedia)

Broad Street pump in 1854. But the epidemic was already subsiding and the medical world paid relatively little attention. The “discovery” of the causative agent by an Italian microscopist also brought little reaction.

Filippo Pacini, son of a cobbler, received his medical education in Pisa. As a student, using a rudimentary microscope, he was the first to describe the tiny “Pacini” tactile dermal corpuscles, work later confirmed. His proficiency with the microscope catapulted him to the professorship of anatomy at the University of Florence. During the same pandemic that struck Snow’s London, Pacini studied cases in Florence using his microscope. He

Filippo Pacini (Wellcome Library)

noted disruptions of the intestinal mucosa and myriads of comma-shaped bacteria in the intestinal fluid. He published his findings in 1854 in an Italian journal, suggesting that the organisms caused the disease. He sent copies of his findings to the French Académie des Sciences, to Virchow, Henle, and Max von Pettenkofer in Germany. Reports also went to authorities in England, and to the Medical Society of London, where Snow was a member. Snow and Pacini never met, and it is not clear if Snow knew of Pacini’s work. Snow died in 1858 and a brief obituary in Lancet did not mention his work on cholera epidemiology.

Cholera struck Florence again in 1865. This time Pacini’s writings attracted the attention of William Farr, the British Registrar-General, who described Pacini’s findings in a report of 1868, including his insight that excess fluid loss was the cause of vascular collapse. Pacini recommended fluid replacement and developed complicated mathematical models to measure the fluid balance. Pacini’s writings, however, did not appreciably affect general medical opinion. It was too early. Lister’s first article on bacteria in wound infections appeared in 1867, was received skeptically, and Robert Koch first proved the bacterial cause of a disease (anthrax) only in 1874.

Max von Pettenkofer, the great German pioneer in public health

Max von Pettenkofer (Wikipedia)

science, explored cholera extensively. Having studied Snow’s work, he investigated water provisions in Munich and concluded that Munich’s water supply was not the problem. He went on to develop a cholera theory that required three factors to cause disease: the presence of live organisms (not yet discovered), proper soil conditions where the organisms can develop, and a susceptible host.

Finally, in 1884, Robert Koch “discovered” again the offending

Robert Koch's Egyptian team. Koch is 3rd from right. (Wikipedia)

organism during a trip to Egypt. He does not seem to have known about Pacini’s work. As the leading bacteriologist of the time, Koch was able to culture the vibrio and study its properties, techniques unavailable to Pacini. Though Pettenkofer accepted Koch’s findings, he was so assured of his soil development theory that he swallowed a pure culture of cholera vibrio, sustaining only mild diarrhea. A couple of his students who tried it, though, suffered from severe cholera. 

In India, David D. Cunningham, an army doctor in charge of cholera research, was a follower of Pettenkofer and continued to

David Cunningham (Wikipedia)

resist Koch’s thesis of direct transmission for years. But accumulating evidence overcame the last doubters and solidified the modern view of cholera transmission, pathology, and treatment. Today the disease is primarily a feature of a breakdown in water supplies and hygiene.

 

SOURCES:

 

Isaacs, J D, “D D Cunningham and the Aetiology of Cholera in British India, 1869-1897.” Medical History 1998; 42: 279-305.

 

Carboni, G P, “The Enigma of Pacini’s Vibrio cholerae Discovery.” J Medical Microbiology 2021; 70 (11): 1-7.

 

Pettenkofer, M, “Nine Propositions Bearing on the Aetiology and Prophylaxis of Cholera, Deduced from the Official Reports of the Cholera Epidemic in East India and North America.” Indian Medical Gazette 1877; April 2, May 1, July 2, and  August 1.

 

Howard-Jones, N, “Cholera Therapy in the Nineteenth Century.” J History of Medicine 1972; 27: 373-95.

 

Pollitzer, R, Cholera 1959; WHO, Geneva.

 

Evans, A S, “Pettenkofer Revisited: The Life and Contributions of Max Pettenkofer (1818-1901).Yale J Biol Med 1973; 46: 161-76.

 

Vinten-Johansen, P, et al, Cholera, Chloroform, and the Science of Medicine: A Life of john Snow. 2003; Oxford Univ Press. 

A full index of past essays is available at: 

 https://museumofmedicalhistory.org/j-gordon-frierson%2C-md

 

 

 

 

 The “Autopsy” of St. Ignacius de Loyola and the 

Anatomists Who Performed It

 

       On July 31, 1556, Ignatius de Loyola limped into Rome to die. The limp stemmed from a cannonball injury to his right leg sustained during his youthful days as a soldier. During convalescence Ignatius, born Íñigo López de Oñaz y Loyola in the Basque village of Loyola, experienced a spiritual conversion. After a pilgrimage to Jerusalem

Saint Igantius of Loyola (Wikipedia)

followed by studies of theology in Spain and Paris, he and colleagues in Paris formed the Society of Jesus. He expired in Rome after a long illness.

 To avoid decomposition of the body in Rome’s July heat, embalming (the custom for important religious figures) was undertaken quickly. Realdo Colombo, a famous anatomist and at that time a physician in the papal household, was assigned to open the body. Juan Valverde, a prominent Spanish anatomist, assisted him (Valverde, like Ignatius, was Basque.) Who were these anatomists and did the future saint undergo an autopsy?

         Realdo Colombo, the son of an apothecary, was born in Cremona, Italy, around 1515. After an apprenticeship with a Venetian surgeon, he moved to Padua to study medicine. His anatomy professor, Andrés Vesalius, noticing his anatomical skills, appointed him as his assistant. After a dispute with Vesalius, Colombo taught at

Realdo Colombo (Wikipedia)

Pisa and then moved to Rome where he taught at the papal university, the Sapienza, and served as a physician in the papal court. He began work on his own anatomy text, De Re Anatomica, that saw publication shortly after his death in 1559. In it he corrected some of Vesalius’ anatomical statements and, more importantly, described the pulmonary circulation and the proper function of the heart valves. William Harvey studied the work intensely, crediting it with helping him unravel the scheme of circulation in 1626. Colombo had asked Michelangelo to illustrate his planned anatomy text, but the latter was too old and died soon after.

Juan Valverde de Amusco, after obtaining a university degree in Spain, studied medicine under Vesalius and Colombo in Padua and followed Colombo to Pisa, pursuing anatomy studies. Valverde, like Colombo, came to Rome where he studied under Bartolomeo

Juan Valverde (Wellcome Library)

Eustachi, professor of medicine at the Sapienza. Valverde later taught anatomy at the Hospital Espíritu Santo, which boasted an anatomical theater. Cardinal Juan Álvarez de Toledo chose him as his personal physician, and both Valverde and Colombo moved in prominent social and scientific circles in Rome. Valverde worked closely with Colombo while investigating the pulmonary circulation. 

Valverde’s move to Rome from Spain was not unusual. The Spanish population in Rome had been growing, partly due to the election of two Spanish popes (Callixtus III, 1455-58 and Alexander VI, 1492-1503). The educational reforms of Pope Julius III (1550-55) had enhanced Roman medical education,

Bartolomeo Eustachio (Wikipedia)

reformed medical licensing, and encouraged the formation of new hospitals. In Spain, medicine was less advanced and bodies for dissection were harder to obtain. Additionally, the majority of physicians in Spain had been Jewish and the Spanish expulsion of the Jews in 1492 had driven many to Rome and elsewhere. Whether Valverde had Jewish origins is uncertain. 

Valverde published an anatomy text, Historia de la Composición del Cuerpo Humano in 1556, three years before Colombo’s work. It was well illustrated but most of the illustrations, attributed to Gaspar Becerra, who trained in Michelangelo’s workshop, are copies of those in Vesalius’ text, though smaller in size. The book includes corrections from Vesalius’ original Fabrica (which angered Vesalius), and some original findings that include a correct rendition of the pulmonary circulation, though still with Galenic overtones. The main advantage of

Striking illustration from Valverde's Historia
(Wellcome Library)

Valverde’s book is the readability and clarity of text, making it popular with medical students and physicians. The book was published in Spanish (many Spanish surgeons did not know Latin) but eventually appeared in Italian, Dutch, and Latin translations during some sixteen editions. It was one of the most widely used anatomy texts in Europe at the time. 

Colombo recorded in De Re Anatomica that inside Ignatius he found stones in the kidneys, lungs, liver, and portal vein and that the stomach and intestines were empty, the latter finding attributed to Ignatius’ frequent fasting. The dissection has often been characterized as an autopsy of Ignatius, but Colombo was there to embalm him and did not speculate on a cause of death. The nature of the “stones” is uncertain and may have alluded to gallstones, urinary tract stones, phleboliths, or some combination.

Actual autopsies were, however, not so rare at the time. Leonardo da Vinci had written in the latter 1400s, “…and I did an autopsy on him to see the cause of such a quiet death.” Antonio

Antonio Benivieni (Wikipedia)

Benivieni, a Florentine physician and contemporary of da Vinci, penned the first known book of autopsies, published posthumously in 1507. In it Benivieni describes 110 cases with postmortem findings. Normal anatomy was not fully understood at the time, not to mention abnormal anatomy, and Benivieni was steeped in Galenic medicine, a doctrine that explained health and disease in terms of the balance of humors. Thus, Benivieni did not always relate autopsy findings with the clinical picture. By Colombo’s time autopsies, still brief by modern standards, were more common. 

St. Ignatius’ death occurred at an important moment when post-Vesalian objective anatomy investigations were eroding the ancient Galenic framework of medical thought. The work by the Spanish anatomist, Valverde, was an important and often overlooked contribution. And findings at autopsy gradually reshaped concepts of disease though it was not until the great work of Morgagni in 1761, De sedibus et Causis Morborum, correlating the clinical picture with autopsy findings, that modern pathology began to take shape.

 

Sources:

King, L S and Meehan, M C, “A History of the Autopsy.” Amer J Pathol 1973; 73 (2): 513-44.

 

Andretta, E, “Juan Valverde, or Building a ‘Spanish Anatomy’ in 16^th Century Rome.” Working paper, European University Institute, Max Weber Programme, 2009. https://cadmus.eui.eu/bitstream/handle/1814/12094/MWP_2009_20.pdf?sequence=1

 

Rosenman, L D, “Facts and Fiction: The Death of Saint Ignatius of Loyola.” Surgery, 1996; 119 (1): 56-60.

 

Hernandez-Mansilla, J M, “Autopsia, embalsamamiento y signos de santidad en el Cuerpo de Ignacio de Loyola.” Rev de Ciencias de las Religiones 2016; 21: 79-91.

 

Fye, W B, “Realdo Colombo.” Clin Cardiol 2002; 25: 135-37.

Arráez-Aybar, L, et al, “Juan Valverde de Amusco: Pioneering the Transfer of Post-Vesalian Anatomy.” Anatomia 2023; 2: 450-71. 

Burgos Lázaro, R, et al, “Juan valverde de Amusco en la Medicina del Renacimiento Español.” Anales RANM 2021; 138 (1): 82-91.

Singer, C.(translator), de Abditis Nonnullis ac Mirandis Morborum

et Sanationum Causis by Antonio Benivieni. 1954; Charles C Thomas.

 

Coppola, E D, “The Discovery of the Pulmonary Circulation: A New Approach.” Bull Hist Med1957; 31 (1): 44-77.

 

A full index of past essays is available at: https://museumofmedicalhistory.org/j-gordon-frierson%2C-md

 

 

 

 

 

 

                            THE DISEASE OF THE DEPOSED CHILD                                                                 

         In 1929, a 36-year-old Jamaican-born British physician, Cicely Williams, arrived by ship at the African “Gold Coast,” now known as Ghana. The inspiration for this assignment to a faraway place came from a Croatian professor of public health, Andrija Stampar, whom Williams had met on the way to work in a refugee camp near Salonika. He had shown her how to deal with with epidemics and nutritional problems at the community level using limited resources. Cicely determined to take up medicine in underserved communities as a way to confront these challenges. 

Gold Coast (Wikipedia) Click on 
image to enlarge.

 Dr. Williams, after her inspiring experience with Stampar, earned a Diploma at the London School of Hygiene and Tropical Medicine and was assigned by the British Colonial Medical Service to the town of Kumasi, in the Gold Coast. The area, formerly the land of the Ashanti empire, was now a center of cocoa production and extensive mining. 

While working in Kumasi and nearby stations, Dr. Williams encountered a clinical syndrome in young children that baffled her and did not appear in her medical texts. The afflicted children were edematous (puffed up with extra fluid), had orange hair, scaly and somewhat dry skin that was darkened in the creases, frequent diarrhea, and were mentally sluggish. Most of them died. Williams tried to obtain autopsies but was frustrated by mothers who whisked their children away before dying. After learning that the bus driver charged extra to transport a dead person, she paid the extra charge and autopsied several children. She found only an enlarged fatty liver, pallor, and edematous changes. Her first report of the disorder was in Gold Coast medical reports 1932. The local people called it “kwashiorkor.” 

Photos of kwashiorkor from Williams' first article (Wellcome Library)

Kwashiorkor was a tainted “ju-ju” word of the Ga language that locals were reluctant to pronounce. It referred to the sickness affecting a child after it is “deposed” from its privileged breastfeeding site to make way for a newborn child. The deposed child was put on a diet close or equal to an adult diet of ground maize, often laced with hot spices. The infants ate less and the reduced intake and lack of protein, sometimes mixed with parental neglect, led to what Williams determined to be a deficiency disease. She found that feeding the needy child with Nestlé’s canned, condensed milk produced a quick recovery, suggesting that protein deficiency was the main problem. Williams wrote a second report,
this one in a widely read pediatric journal, that brought the syndrome to broader attention.

Beginning of first article on kwashiorkor (Wellcome Library)

 Her second article caught the attention of the London physician, Hugh Stannus, who was an expert on pellagra, a disease due to niacin deficiency. Stannus felt that kwashiorkor was really pellagra, not a new disease. His authority held sway for a while, but eventually new evidence proved Stannus wrong. The work of Joseph Goldberger in the United States showing that pellagra was a dietary deficiency disease and the demonstration in 1937-8 that niacin alone, without a change in diet, could cure pellagra, established the difference between kwashiorkor and pellagra. 

Another champion of William’s ideas was Dr. Hugh Trowell, who worked in Uganda while Williams was in Ghana. Trowell found that medical missionaries in his area, back in the 1920s, had noticed a similar syndrome and described it in the first issue of the Kenya Medical Journal. They too had considered it a protein deficiency disease. Trowell had bowed before Stannus’ opinion but eventually joined Williams in considering it a new disease. The word “kwashiorkor” did not appear in textbooks of tropical medicine, however, until the 1950s.

Through the use of condensed milk and the encouragement of prolonged breast feeding many more children survived after abrupt weaning (though later findings showed that hypoglycemia could be a problem with condensed milk). Cicely’s work with children, mothers, and within the local communities lowered the child mortality rate, and resulted in women having fewer children. 

 A dispute between Williams and her chief led to an abrupt transfer to Malaya in 1936. Infant malnutrition in Malaya turned out to be generally due to insufficient breastfeeding from birth. Mothers, responding to European advertising and culture, had curtailed breastfeeding, feeding their infants condensed milk instead. Williams aroused controversy by campaigning to restrict the use of condensed milk and encourage milk from the breast. World War II, however, curtailed her efforts while she was incarcerated by the Japanese in the infamous Changi Prison in Singapore. After the war, still energetic, Cicely worked as head of a new Maternal and Child Health Division at WHO and was regarded as a specialist in child nutrition. After

Dr. Cicerly Williams (Wikipedia)

another stint in Malaya, she settled as a lecturer at the London School of Hygiene and Tropical Medicine. Her lectures and writings emphasized that to combat malnutrition it was necessary to investigate the social and behavioral causes, such as she had seen in Malaya, in addition to correcting the diet. She died in 1992, at the age of 98. 

Andrija Stampar, the public health physician who inspired Williams, was active in the League of Nations, and later presided over the conference convened to draft the constitution of the World Health Organization, where he served for many years.

The word kwashiorkor in textbooks now appears as part of a spectrum of nutritional disorders under the category of “Protein-calorie-deficiency” or “protein-energy-deficiency” disorders. They include kwashiorkor and marasmus, the latter characterized by severe wasting, absence of fat, and loose skin. Research work continues, as evidenced by finding distinct intestinal microbiomes in healthy and kwashiorkor-affected children. Cicely Williams’ work on nutrition lives on, as does her decades-long devotion to community maternal-child care.

A full index of past essays is available at: https://museumofmedicalhistory.org/j-gordon-frierson%2C-md

SOURCES:

 

     Williams, C, “Deficiency Disease in Infants: A Report by Miss C.D. Williams, Woman Medical Officer, Princess Marie Louise Hospital, Accra. Report of Medical Department, Gold Coast Colony, 1931-32. 1932; pp 93-99. 

     Williams, C D, “A Nutritional Disease of Childhood Associated with a Maize Diet.” Arch Dis Childhood. 1933; 8: 423-33.

     Craddock, S, Retired Except on Demand: The Life of Dr. Cicely Williams. 1983; Green College, Oxford.

     Trowell, H. “The Beginning of the Kwashiorkor Story inn Africa.” Central African Journal of Medicine 1975; 21(1): 1-5.

     Stanton, J, “Listening to Ga: Cicely Williams’ Discovery of Kwashiorkor on the Gold Coast.” Clio Med. 2001; 61: 149-71.

     Goodall, J, “Malnutrition and the Family: Deprivation in Kwashiorkor.”  Proc Nutrit Science. 1979; 38: 17-27. 

     Trowell, H, “Kwashiorkor, 1. Nutritional Background, History, Distribution, and Incidence.” Brit Med J.  Oct 11, 1952, 796-8. 

 

                               THE ORIGIN OF BLOOD BANKS

 

         For hundreds of years physicians and surgeons drew blood from sick patients to improve their health. Today’s doctors still remove blood, though now from healthy individuals, and transfuse it back to the sick. Sporadic attempts at transfusion go back at least to the 17^th century, but with little success. Transfusion service as we know it had to await further knowledge of the physiology of shock, the discovery of blood groups, the development of sterilization techniques, and the prevention of blood clotting.

         By the 1920s blood clotting was the primary unsolved problem. Clotting often frustrated the transfer of blood by syringe from donor to recipient. Devices to connect an artery of the donor directly to a vein of the patient prevented clotting but required a surgical

Kit for citrated transfusion, early WWII, used by Geoffrey Keynes,
surgeon, British Army, and brother of John Maynard Keynes. See diagram 
below (Courtesy National Archives, U.K.)

procedure. In 1914, Albert Hustin, in Belgium, announced the use of sodium citrate as an anticoagulant. In the U.S., Richard Lewisohn, working on the same problem, published on the use of a 0.2% solution of citrate in Surgery, Gynecology, and Obstetrics in 1915, a time when WWI was raging. Oswald Robertson, from the Rockefeller Institute, joined Harvard’s Base Station Hospital in France with the assignment to study shock. He noted the favorable results in shock of direct person-to-person transfusions by the British. He devised an apparatus to collect blood in a citrate and glucose

Robertson's apparatus for citrated 
transfusion (From History of the Great War
Gordon-Taylor, KB Walker, eds, Hathi 
Trust)

solution to prevent clotting, permit storage, and eliminate direct transfer. Transfusion centers, precursors of blood banks, were set up in underground bunkers where blood was drawn, cross-matched (though type O was used preferably), and sent to surgical stations. Direct transfusions became obsolete. 

         After the war, as doctors increasingly used transfusions, donors generally received money for their blood and hospitals tried to find healthy ones. Private collection agencies sometimes were less choosy. But there was always a cost, and if one could not afford a transfusion in a hospital, it often was not given. The depression of the 1930s worsened the financial issue. 

         Patients at Cook County Hospital in Chicago usually lacked financial resources. Those without family or friends as donors might die without needed blood. To remedy this, Dr. Bernard Fantus,

Bernard Fantus (Wikipedia)

director of therapeutics, instituted a novel approach. Blood transfusions fell under “therapeutics,” allowing Fantus to create a system that he termed a “blood bank,” a name deliberately chosen. Blood donors established an account, just as in a bank. If the donor needed blood for himself or his family, he could withdraw the amount deposited to his “account” at any time. Meanwhile, his deposited blood could be given to another person, who was then liable for repayment by him/herself or a proxy. Blood was drawn from healthy donors, patients in congestive heart failure (before taking digitalis!), healthy prepartum women, and elective surgery patients. The hospital kept ledgers with separate columns for debits, credits, and balances, the accounts maintained for each hospital department. The blood, typed and tested for syphilis, was stored in labeled citrated bottles and refrigerated. Febrile reactions, not uncommon and usually due to sterilization and cleaning defects, almost vanished with careful attention to detail. Other centers, the Mayo Clinic, for example, also stored blood for future use, but the “bank” concept began in Chicago.

         Fantus, often called the “father” of blood banks, published his experience in the JAMA in 1937, a widely read report that encouraged hospitals elsewhere to form similar banks, including the L.A. County and Detroit Receiving Hospitals. Eventually communities opted in. 

         As WWII began, England needed blood desperately as it coped with the blitz. An organization was formed in New York City to deliver blood and later plasma, called “Blood for Britain.” On the west coast, two San Francisco physicians, John Upton (born in England) and DeWitt Burnham, founded the Irwin Memorial Blood Bank in 1941 to collect blood for British and American use. It operated in the William Irwin mansion on Washington St. (Now replaced by Washington Tower Apartments.) Blood was collected in the mansion’s ballroom, most of it made into plasma that was stored in the wine cellar. Plasma was considered an adequate substitute for blood at the time and was much easier to ship.

Six months after Irwin Blood Bank’s founding, on December 7, the Japanese bombed Honolulu. Bernice Hemphill, a certified bioanalyst and the wife of a naval officer, volunteered the next day at the Honolulu blood bank, learning how it functioned. In 1943 she moved to San Francisco and volunteered at the Irwin Bank.

Bernice Hemphill (from her oral history,
see Sources, U.C. Library, Berkeley)

         The staff at Irwin, recognizing Hemphill’s talents, appointed her as managing director of the bank. When the war ended, the Red Cross, that had been the nation’s major blood-collecting agency, continued in this role, a function that overlapped with Irwin's. A turf battle erupted, Hemphill maintaining that the bank system, operating at a community level, was preferable to a broad, “quasi-governmental” (her term) organization. Working with Dr. Upton, the two stimulated the foundation of new community blood banks (one in Sacramento began in 1947), and worked to organize the national American Association of Blood Banks to resist the Red Cross and to coordinate business and scientific information on a national basis. Hemphill also conceived the idea of a “clearing house,” similar to that of money banks, where incoming and outgoing blood could be coordinated. It was headquartered at Irwin. Many have considered Hemphill as the “mother” of blood banking. 

         Blood banking is here to stay. Modern surgery could not exist without it. Although many factors contributed to its growth, blood banks could be said to have two “parents.” Bernard Fantus conceived the “bank” system and Bernice Hemphill expanded it to the broader community by creating the “clearing house.”

 

A link to an index of all the essays is available at:  

SOURCES:

 

Swanson, K W, Banking on the Body: The Market in Blood, Milk, and Sperm in Modern America. 2014, Harvard Univ Press.

 

Starr, D, Blood: An Epic History of Medicine and Commerce. 1999, Alfred A. Knopf.

 

“California Blood Bank Society: The Early Years.” At: https://www.cbbsweb.org/page/CCBSTheEarlyYears

 

The Mother of Blood Banking: Irwin Memorial Blood Bank and the American Association of Blood Banks. Oral History of Bernice M. Hemphill. 1998, Regents of the University of California. Accessible at: https://archive.org/details/motherbloodbank00hemprich/page/n5/mode/2up?view=theater

 

Fantus, Bernard, “The Therapy of the Cook County Hospital.” JAMA 109 (2): 128-131.

 

 Schneider, W H, “Blood Transfusion between the Wars.” J Hist of Medicine 2003; 58: 187-224.

         

         

 

                                                                       THERIAC

 

         If you are looking for a super-remedy that cures everything, reach for theriac, if you can find it. Theriac is one of the historical all-time greats of pharmaceutical success, used by emperors, kings, and anyone else who could afford it. Though it’s use has given way to the advances in pharmaceutical sciences, its history holds lessons for today.

         The origins of the theriac recipe are obscure. The story allegedly begins with Mithridates VI, king of Pontus, a large kingdom surrounding most of the eastern Black Sea. He believed that his father, Mithridates V, was poisoned (120 B.C.) and, in an attempt to head off a similar fate, he regularly took small doses of poisonous substances to build resistance. After Mithridates VI’s death, the ingredients he was taking were incorporated into a poison-preventive remedy known as Mithridatium that soon became a preventive for a number of illnesses unrelated to poisoning. Later, Andromachus, physician to Emperor Nero, modified the formula, most notably by substituting viper’s flesh for that of the lizard, in order to prevent poisoning by venomous bites. He also added opium and several other ingredients, including Lemnian earth (a red soil from the island of Lemnos), roasted copper, bitumen, additional herbal plants, and squills (a medicinal plant). The new formula eventually acquired the name “theriac,” derived from the Greek theriake, an adjective signifying “of a wild or venomous animal.” 

         Galen used both theriac and Mithridatium and wrote that he had tried theriac on roosters “with creeping poisonous beasts among

Galen (Wellcome Library)

them” and found it successful. In addition to anti-poison and antivenom effects, Galen modified theriac doses to take advantage of ingredients known to heat, dry, moisten, or cool the humors, according to the Galenic scheme. He used it for malaria with mixed results.

         The use of theriac survived the fall of the Roman Empire. After the Islamic takeover of territory east of Europe, recommendations for theriac surfaced in writings of Rhazes, Avicenna, and others and in some form was in use in medieval Europe. As the Renaissance dawned, the western world relearned theriac’s formula (or formulas, as by then pharmacists puzzled over the identity of certain ingredients or could not obtain them). Different formulas contained 40 to 60 ingredients, though numerous simplified versions of “theriac” flooded the market, prompting many cities to establish days when an official version was manufactured. Physicians, pharmacists, and government dignitaries supervised the process publicly, and certified it as genuine. 

Pharmacist making theriac under physician supervision (woodcut, Hieronymus Brunschwig,
approximately 1512. Wellcome Library)

    Modern study of old recipes shows variation in ingredients, some of whose names are no longer decipherable. The medicine developed a reputation as a cure or preventative for a variety of illnesses in addition to its actions on venoms and poisons. It was used extensively in plague epidemics both to prevent and to treat the pestilence and was considered effective for either. The ingredients, especially opium, could reduce diarrhea and cough and induce analgesia, sweating and sedation, adding patient satisfaction. Doctors gave it orally, usually in wine, or rectally, as a plaster, or by inhalation. 

Partial list of ingredients, 16th cent.
book (Wellcome Library)

         During Renaissance times the Republic of Venice enjoyed a booming pharmacy business. The state’s extensive trading with the East supplied many of theriac’s ingredients. The first chair of materia medica was established in Padua in 1533 and a botanical garden followed soon after. By 1565 there were 71 pharmacies in the Republic, organized into a Collegio, whose pharmacists underwent years of training and an examination to obtain licensure. The Collegio fixed pharmacy prices so that a pharmacist’s success rested on the quality of his products (especially theriac) and his relationship with physicians. Physicians could not own pharmacies but worked closely with favored ones. The Campana d’Oro in Verona, the most famous pharmacy, also maintained a natural history museum that was a known tourist attraction. Another one, the Farmacia Dell’Orso, still operates in Venice.

Photo of model of 16th century Italian pharmacy (Wellcome Library)

         Crowds gathered in the city every spring to witness the manufacture of theriac. Outside the licensed pharmacies benches supported numerous majolica jars containing herbs, spices, roots, gums, and other ingredients while larger jars on the top row held the snakes whose flesh was the vital component. Priors of the College of Medicine arrived to inspect the ingredients and spectators crowded in to witness the butchery of the vipers and watch the costumed workers grind and mix the herbs. Travelers sometimes came from afar to witness the spectacle. Up to 800 snakes (only females could be used) per month in some years disappeared into the concoction, eventually depleting the usual supply area near Padua.

Even at this time, arguments about the possible harms of “polypharmacy,” such as seen in theriac, appeared in print and they gained credence as botanical and pharmaceutic knowledge increased. A particular influence in the decline of theriac’s popularity in

William Heberden (Wellcome Library)

England was a publication by William Heberden, Antitheriaka: An Essay on Mithridatium and Theriaca (1745). The essay details theriac’s poorly documented recipes and debunks the agent’s supposed curative properties. Regarding its opium content, Heberden urged that if the doctor needs opium, he should prescribe it separately. Heberden was generally skeptical of reliance on ancient authorities.

In Paris, residents last witnessed a Venice-like, public theriac manufacture in 1798 and the French Pharmacopeia listed theriac until 1884. Theriac is now a historical curiosity. Why did it have such a long life? The significant opium content certainly contributed to public and medical acceptance. And no doubt heavy promotion by purveyors, from doctors and elite pharmacies to itinerant peddlers, influenced an expectant public. Not unlike purveyors of vitamins and immunity boosters today.

A full index of past essays is available at: https://museumofmedicalhistory.org/j-gordon-frierson%2C-md

 

SOURCES:

 

Eamon, William, The Professor of Secrets: Mystery, Medicine, and Alchemy in Renaissance Italy. 2010; National Geographic.

 

Heberden, W, Antitheriaka. An essay on mithridatium and theriaca. 1745. Available at: https://wellcomecollection.org/works/ty3m7h5g

 

Berman, A, “The Persistence of Theriac in France.” 1970; Pharmacy in History 12(1): 5-12.

 

Fabbri, C N, “Treating Medieval Plague: The Wonderful Virtues of Theriac.” 2007; Early Science and Medicine 12: 247-83.

 

Rankin, A, “On Anecdote and Antidotes: Poison Trials in Sixteenth-Century Europe.” 2017; Bull Hist Med 91 (2): 274-302.

 

Palmer, R, “Pharmacy in the Republic of Venice in the Sixteenth Century.” Chapter in The Medical Renaissance of the Sixteenth Century, A. Wear, R K French, I M Lonie eds. 1985, Cambridge Univ Press.