LEPROSY IN THE AMERICAN 

MIDWEST

         Leprosy in the Midwest? How was that possible?

         It entered from Scandinavia, predominantly from Norway. Present in Norway since at least the time of the Vikings, leprosy resurged in the early 1800s along with scabies, tuberculosis, and other diseases associated with poverty and poor hygiene. Severe economic hardships in Norway had followed the Napoleonic wars of the early 19^th century, providing a setting for poverty-related diseases. Before long, Norway, with a new constitution and elevated social awareness, began to tackle the problems with studies of health and poverty. One such survey, done in 1836, identified 659 leprous patients and acknowledged it as an incomplete count.

Carl Wilhelm Boeck, a dermatologist (whose nephew is

Carl Wilhelm Boeck
(Wikipedia)

associated with Boeck’s sarcoid), and Daniel C. Danielssen published a thorough study of leprosy, Om Spedalskhed (On Leprosy), in 1847, in which the investigators described the two basic clinical types of “nodular” and “anesthetic” leprosy (diffuse skin infiltration of disease and peripheral nerve involvement), a classification still in use today. The study was a factor spurring the government to open, in 1849, a hospital in Bergen devoted solely to research on leprosy, Lungegaard Hospital. It supplemented the old St.

D. C. Daniellsen
(Wikipedia)

Jørgen’s Hospital for leprosy, dating from the 15^th century, that provided what care was available. Daniellsen was appointed the first chief physician at Lungegaard Hospital.

A few years later, in 1856, the country established a national Leprosy Registry, the first of its kind, to track all patients and help guide public health measures.

Lungegaard Hospital, taken between 1900-1920 (courtesy K. Knudsen & Co: https://marcus.uib.no/instance/photograph/ubb-kk-1824-4307.html)

         Poverty in Norway, particularly in the western parts, also drove migration to the United States. The bulk of Norwegians settled in Illinois, Iowa, Minnesota, and the Dakotas, engaging mainly in farming. Some brought leprosy with them. News of leprosy in America prompted Norwegian Drs. Jean Holmboe and Wilhelm Beck to visit the area. Both noticed that the overall health of the immigrants had improved and in occasional cases their leprosy seemed to have resolved. Boeck credited the improved living conditions in America, saying “They have settled on fertile lands, where they certainly have to work hard to make a living, but they, generally, never undergo hardships, as we, in Norway, understand the term.” They also found cases developing after arrival, but all had come from endemic areas in Norway and most from families with leprosy, suggesting they were incubating the disease on arrival. Most authorities at the time considered the disease to be hereditary though some favored contagion or miasmas.

         Minnesota was an early state to develop a public health department, opened in 1873. (California’s, the second in the U.S., opened in 1870). In Minnesota, Dr. Christian Grönvold, a Norwegian immigrant with university degrees from Norway and a medical

Christian Grönvold (courtesy Goodhue County
Historical Society, Minnesota)

degree from Humboldt University in the U.S., settled in Minnesota, joined the Health Department, and took an interest in leprosy. His careful detective work confirmed that the cases appearing after arrival in Minnesota all came from endemic regions in Norway, usually with affected family members. Leprosy in settlers without such background was non-existent. To Grönvold, theories of heredity and contagion were both plausible.

Back in Bergen, the Lungegaard Hospital had taken on a young physician, Armauer Hansen, as a pathologist and researcher. He had just returned from a stint above the arctic circle caring for fishermen and native peoples. Interested in the new findings of bacteriology, Hansen searched leprous tissues microscopically and found faint clusters of thin rods, difficult to see because of the inadequate staining techniques at the time. In 1874, Hansen published his findings, promoting the idea of a bacterial cause of leprosy, though nothing grew in cultured material.

Bust of Amauer Hansen (Wikipedia)

Danielssen, under whom Hansen worked, persisted in his belief that leprosy was a hereditary disease. He injected lepromatous material into his own tissue and no disease resulted, affirming his belief. The difference of opinion, though, did not prevent Hansen from marrying his daughter. And the new son-in-law gave leprosy another name: Hansen’s disease.

The issue of the hereditability of leprosy persisted despite the bacteriologic findings. In 1887, Hansen wrote to the then Secretary of the Board of Health of Minnesota, Dr. Charles N. Hewett, saying that the heredity question would be difficult to resolve in Norway because of leprosy’s high prevalence. However, in America, by tracing the offspring of lepers in an environment with fewer cases, several would be ill if the disease was inherited. The following year, Hansen, on a trip to America, was able to report that among the numerous offspring of Scandinavian lepers (some were Swedish), including grandchildren and great-grandchildren, none showed signs of the disease. As a result, the State avoided strict isolation policies and required only that leprous patients staying home must occupy their own bedroom and bed and not share utensils. Up to 1948, Minnesota reported 108 lepers, the vast majority from Scandinavia. 

 Leprosy in neighboring states, such as Illinois, Wisconsin, Iowa, and the Dakotas, was not tracked as well, but the pattern was similar. In Wisconsin, bedroom and utensil isolation were recommended. Some states refused entry of immigrants with leprosy, but physicians realized that many cases were asymptomatic on arrival, developing features of the disease over time. Data from the other states are sparse. Gradually, the disease died out in the upper Mississippi Valley area. Overall, the number of lepers in this region may have numbered around two hundred, perhaps more. 

Studies of the leprous patients in the upper Mississippi Valley, particularly the work of Christian Grönvold in Minnesota, helped end theories of a hereditary basis for leprosy, allowed for the relatively liberal isolation policies adopted, and provided a model for international cooperation.

 

SOURCES:

 

Gussow, Z, Leprosy, Racism, and Public Health: Social Policy inChronic Disease Control. 1989, Westview Press.

 

Washburn, W L, “Leprosy among Scandinavian Settlers in the Upper Mississippi Valley, 1864-1932.” Bull Hist Med 1950; 24 (1): 123-148.

 

Grönvold, C, “Leprosy in Minnesota.” Chicago Medical J and Examiner, 1884; 48: 133-39.

 

Hewitt, C, “Leprosy and its Management in Minnesota.”  Public Health Papers and Reports 1890; 16: 172-5.

 

Feldman, W H, “Gerhard Henrik Armauer Hansen: What Did He See and When?” 1965; Int J Leprosy33 (3): 412-16.

 

Irgens, L M, “Leprosy in Norway: An Inte3rplay of Research and Public Health Work.” 1973; Int J Leprosy 41 (2): 189-198.

 

Esson, A, “Faces of the Past: Dr. Just Christian Grönvold.” Accessible at: https://www.republicaneagle.com/news/community/faces-of-the-past-dr-just-christian-gronvold/article_ce4c2711-90ed-501e-a22f-3e6ff1ed457a.html

 

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

 

 

.

 

 TALES OF THE FIRST CHOLERA

VACCINE

         

         “The bacteriologist called upon me to take off my coat and bare my arms to above the elbow. With a lancet he cut an incision just above the elbow [in both arms], and into this he injected several drops of the germ-containing bouillon.” Thus wrote the adventurous New York Herald reporter Aubrey Stanholpe after receiving the world’s first anti-cholera vaccine at the hands of Spanish investigator Jaime Ferrán y Clua. 

Ferrán, a practicing physician in Tortosa, Spain (in Cataluña), inspired by the discoveries of Pasteur, had created a bacteriology laboratory in his home. In 1884, the year that Robert Koch found the causative vibrio in Egypt, cholera invaded Marseilles. Ferrán

Jaime Ferrán y Clua (Wikipedia)

obtained a sample of vibrios in Marseilles and, using guinea pigs, produced a two-dose live vaccine that, injected subcutaneously, prevented orally induced cholera in the animals. The following year, he tried the vaccine on humans during a cholera outbreak in Valencia province. Government commissions sent to investigate the results were critical of the results, however. After about 30,000 vaccinations Ferrán returned to Tortosa to develop other vaccines, the cholera vaccine’s effectiveness unproven.

         A few years later, in 1890, a young Russian scientist at the Pasteur Institute, Waldemar Mordecai Wolfe Haffkine, began work

Waldemar Haffkine (Wikipedia)

on a cholera vaccine. Waldemar, born in Odessa, had earned a degree in zoology studying under Eli Metchnikoff and obtained a position at the Museum of Zoology in Odessa. He had also been active in student protests, a member of the Narodnaya Volya, or “Will of the People” party, members of which had assassinated Tsar Alexander II, and was Jewish. After undergoing multiple arrests, one prison term, and a severe pogrom, he left Russia in 1888 and, with Metchnikoff’s help, secured a minor position at the Pasteur Institute, from where he moved into a post as assistant to Emil Roux, Director of Services.

         Using techniques developed by Pasteur, Haffkine reduced the virulence of one strain of the vibrio by culturing it in the presence of moving air and enhanced the virulence of another by serial culture in animal tissue. He injected himself with the less virulent strain in the left flank and six days later injected the virulent strain in the right flank, with only modest side effects. Interestingly, the American, Theobald Smith, had reported on the successful use of killed bacteria to immunize pigeons in 1887 and later Emil Roux encouraged

Emil Roux (Wikipedia)

Haffkine to try using killed bacteria, but Haffkine continued developing live vaccine. After injecting several friends and coworkers without mishap, he offered to use the preparation more broadly. The French government declined, and, because of Haffkine’s police record and membership in Narodnaya Volya, the Russian government, though suffering a severe epidemic, also declined. 

         British authorities, however, invited Haffkine to India. He set up a laboratory to produce vaccine and inoculated thousands throughout the country. By 1896, due to shortages, he was using only the more virulent strain as a one-dose subcutaneous regimen. He strove to prove the efficacy of the vaccine, a matter that Ferrán had neglected. Various factors hampered statistical evaluation: the disease was so prevalent that many people had partial immunity, vaccination was voluntary (by British order), and the dosage of vaccine often varied due to problems of supply and transportation. 

Haffkine (in tie) vaccinating a child in the flank (from Haffkine's Protective Inoculation
against Cholera, 1913, courtesy Wellcome Library)

         Haffkine realized that to measure the preventive effect of the vaccine he needed a control group of similar individuals.  He used controls in trials in two jails, vaccinating every other prisoner. At the second jail, though, he broke the protocol because of the high mortality rate among unvaccinated prisoners, highlighting the ethical problems that arise in controlled trials. The most exacting trials were in a large tea plantation, where control groups were possible with a compliant labor force. Some analyses have supported a modest preventive effect of the vaccine lasting about six months, though skepticism persisted.

Publications by Haffkine provoked a sharp response from Ferrán, who claimed priority. Ferrán criticized Haffkine’s culture techniques and stressed that he was the first to create and use a cholera vaccine. A bitter exchange of letters and reports ensued. The issues were never fully resolved. The two antagonists were possibly placated to some degree as each received the esteemed Bréant Prize for work on cholera.

         The Bréant Prize (Le Prix Bréant) originated from an 1849 bequest of 100,000 francs by a French industrial chemist, Jean-Robert Bréant. He intended the award to go to whomever discovered a cure for cholera or discovered its cause. Meanwhile, the interest on the sum was to be awarded by the French Academy of Sciences to a person who advanced knowledge of cholera or other epidemic disease. Many have received the interest-generated awards, though Filippo Pacini, who first saw the vibrios microscopically in 1854, and John Snow, famous for halting cholera’s transmission by removing the handle of a London water pump in the same year, never received the prize (both were nominated). Robert Koch received it for

Robert Koch (Wikipedia)

discovery of the TBC bacillus, not the cholera bacillus. Ferrán received the prize in 1907 and Haffkine in 1909, both for their laboratory and field work. In neither case was their vaccine’s efficacy commented on. A recent review of the Bréant Prize files supports the conclusion of the inability to assess vaccine efficacy for each contender.

         A new disease, plague, struck India in 1896. The Indian Medical Service took over cholera control and appointed Haffkine to create a vaccine against plague. His laboratory produced millions of doses, used worldwide, and eventually grew into the Haffkine Institute in India.

         Today, Haffkine is recognized as a pioneer vaccine producer, a tireless worker in a difficult environment, and, most importantly, the first to appreciate the need for controls in evaluating vaccine efficacy and to attempt such trials. Modern cholera vaccines are given orally, their efficacy established by controlled trial.

 

SOURCES:

 

Löwy, I, “From Guinea Pigs to Man: The Development of Haffkine’s Anticholera Vaccine.” J Hist Med Allied Sci 1992; 47(3): 270-309.

 

Bornside, G H, “Waldemar Haffkine’s Cholera Vaccines and the Ferran-Haffkine Priority Dispute.” J Hist Med Allied Sci 1982; 37 (4): 399-402.

 

Bulloch, W, “Waldemar Mordecai Wolff Haffkine.” J Path Bact 1932; 34 (2): 125-29.

 

Hawgood, B, “Waldemar Mordecai Haffkine, CIE (1860-1930): Prophylactic Vaccination against Cholera and Bubonic Plague in British India.” J Med Biog 2007; 15: 9-19.

 

E Lutzker, C Jochnowitz, “The Curious History of Waldemar Haffkine.” Commentary 1980; 69 (6): 61-64.

         

Stanhope, A, On the Track of the Great: Recollections of a Special Correspondent.

Eveleigh Nash, London, 1914.

 

Alpuente Ferrer, et al, “Jaime Ferrán i Clúa (1851-1929), un Vacunólogo Práctico y Controvertido.” Vacunas 2009; 10 (3): 103-9.

 

Shama, S, Foreign Bodies: Pandemics, Vaccines, and the Health of Nations. Harper Collins 2023.

 

Uzcanga, C and Teira, D, “What Evidence for a Cholera Vaccine? Jaime Ferrán’s Submissions to the Prix Bréant.” J Hist Med All Sci 2025; 80 (1): 23-41.

A full index of past essays is available at: 

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

 

 

         

 THE ROYAL MINERAL WATER

HOSPITAL AT BATH

 

Romans loved bathing, and shortly after 50 AD they founded a bathing city, “Aquae Solis” (waters of the sun), on the river Avon in west England. Sumptuous baths, fed by hot springs emitting warm mineral waters, cleansed their bodies. When the Roman empire crumbled, 

Roman bath, restored    (by author)

the structures decayed, but the Anglo-Saxons who followed the Romans saw something else in the water: curative properties. Over time, a large number of the poor with various medical problems and disabilities sought relief from the sulfurous waters. Begging became widespread in the city and the well-heeled avoided it.

 Its reputation rose rapidly after a visit by Charles II in 1662 to allow his wife, Queen Catherine, to try the waters as a cure for her sterility. From then on, especially in the 18^th century, Bath developed into a major attraction, bringing the fashionable as well as the lame seeking the curative properties of the water. The splendid buildings of the architect John Woods and his son and the social activities organized by the dandy Richard (“Beau”) Nash transformed Bath into an elegant and wealthy city, offering sophisticated entertainment as well as relief of ailments. Alongside the socially prominent clientele, though, the lame and indigent remained fixtures in the city.

Pump Room, adjacent to Hospital, where the lame drink spring water, 1798. Now a restaurant and tea room. (Wikipedia)

The new combination of illness and wealth in Bath naturally attracted physicians. One of the earliest to arrive was Dr. William Oliver, educated in medicine at Cambridge and Leyden. He, Richard Nash, and Ralph Allen, another early organizer, seeing the number of  ill and lame arriving with meager resources, sought public subscription to found the General Hospital, later called the Royal Mineral Water Hospital. The hospital, designed by John Woods in Georgean style, opened in 1742 with Oliver as chief physician. The banker, Henry Hoare II, handled finances. Hospital treatments included bathing in the warm waters, drinking the waters, and a number of other remedies. Patients paid a modest entrance fee to cover clean clothing and travel home at discharge, but otherwise they received free care.

Painting of Dr. William Oliver (rt), Mr. Pierce, surgeon (cntr) examining a boy with leprosy, man 
with wrist drop (palsy), and woman with arthritis, Royal Mineral Water Hospital. By William
Hoare. (Courtesy ArtUK and NHS Foundation Trust)

Before long, disputes broke out between members of the medical staff over policies, fees, treatments, etc. Pamphlets were written, accusations made. Eventually, a triumvirate of Drs. Oliver, Abel Moysey, and Rice Charleton held power over the appointment of physicians to the hospital staff and other medical matters. Physicians who were denied appointments often retaliated with bitter articles or pamphlets against the triumvirate, but to little effect. The physician turned writer, Tobias Smollett, in Peregrine Pickle, satirized the situation, saying that the Bath physicians are “a class of animals who live in this place, like so many ravens hovering about a carcase” (sic). 

Dr. Moysey, the second of the triumvirate, had received his BM (bachelor of medicine) and MD (doctor of medicine) at Oxford, practiced briefly in Sherbourne, then moved to Bath, was appointed to the General Hospital in 1747, and enjoyed a successful practice. 

Dr. Rice Charleton, the third leader of the medical staff, also received his medical degrees at Oxford and was an enthusiastic

Dr. Rice Charleton by Gainsborough
(Photo by author)

believer in the healing power of the waters. He analyzed the water chemically, utilizing techniques published by the famous Anglo-Irish experimenter, Robert Boyle, and the prominent continental physician and professor of medicine and chemistry at the University of Leiden, Herman Boerhaave. Boerhaave was one of the first to emphasize chemistry in medical education.  

A few results of Charleton’s work indicate the level of analysis. The waters are alkaline, reacting with acids. Fine particles are attracted to loadstone, suggesting iron, and other particles give a blue flame on a red-hot poker (as sulfur does). Adding powdered oak gall to the water yields a deep purple color, suggesting iron (tannic acid in gall reacts with iron to produce the coloring). This mixture was an old way of making ink. The temperature of the main bath varied between 100-103 degrees utilizing “Fahrenheit’s mercurial thermometer.” Charleton attributes the heat in the waters to the presence of fire, a substance he considered an element, dissolved in water.

Charleton also recorded the restorative powers of the baths. For people with “apoplexy” (strokes) there was little improvement and patients with injuries and other disabilities showed variable results. The patients that showed most improvement were heavy cider drinkers, painters, and plumbers with upper limb peripheral nerve palsies and abdominal pain. Charleton correctly diagnosed them as victims of lead poisoning, generally related to their occupations. They improved when away from lead. Apple juice leached lead from the cider presses, sickening the cider drinkers.

Thomas Gainsborough, self-portrait
(Wikipedia)

One of Dr. Charleton’s patients was the painter, Thomas Gainsborough. What Gainsborough suffered from is unclear, but one illness seems to have been a prolonged fever and another an extended anxiety attack provoked by a visit to London, during which he, according to a letter, committed “a foolish act.” Gainsborough and his family also sought the services of Abel Moseley, known for his high fees and probably the person mentioned in a satirical book, Bath Characters, as “Dr. Fleecem.” Gainsborough painted full-length portraits of both doctors.

Dr. Abel Moysey by Gainsborough
(Wikimedia)

At the Hospital, finances were a constant problem. Because of budget restraints in early years, the number of patients under its roof varied roughly between 40 and 112, and donations were constantly sought. With more subscriptions, a second story was built, in place by the time Jane Austin arrived in Bath in 1797. Gradually the hospital became a center for treatment of rheumatic diseases and rehabilitation. In 2019, the aging building was vacated and services moved to a new building on the outskirts of Bath, the Royal National Hospital for Rheumatic Diseases. There are plans to install a hotel at the original site, but, as yet, the old building remains unchanged.

 

Royal Mineral Water Hospital, Bath, today (by author)

SOURCES:

Foster, F, “Bath: Physicians and Literature.” Bull Med Libr Assoc 1944; 32: 2-22.

Jenkins, J, “Thomas Gainsborough’s Doctors.” J Med Biog 2005; 13: 58-63.

Van Opstal, M T, et al, “Physicians as the Firat Analytical Chemists: Gall Nut Extract Determination of Iron Ion (Fe²⁺) Concentration.”  J Chem Educat 2018; 95: 456-62.

Heywood, A, “A Trial of the Waters: The Treatment of Lead Poisoning.” Med History, 1990; Suppl No. 10, 82-101.

Hamilton, James, Gainsborough: A Portrait. 2017; Orion Books, U. K.

Powers, John C, Inventing Chemistry: Herman Boerhaave and the Reform of the Chemical Arts. 2012, Univ of Chicago Press.

Charleton, R, Three Tracts on Bath Water. 1774; R. Cruttwell, Printer.

Christopher, “The Royal National Hospital for Rheumatic Diseasses: History and Bath Medical Museum.” Available at: https://thephysiologist.org/2016/10/31/the-royal-national-hospital-for-rheumatic-diseases-history-and-bath-medical-museum/

 

Falconer, R W and Brabazon, A B, History of the Royal Mineral Water Hospital Bath, 3^rd ed., 1888, Charles Hallett.

A full index of past essays is available at: 

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

 

 

 

 THE FAME OF PADUA 

         In the fifteenth to seventeenth centuries, students from all over Europe seeking the best education, especially in medicine, headed for the University of Padua. For those studying medicine, a degree from Padua was a mark of distinction. The revered names of Vesalius, Fabricius da Aquapendente, Giovanni Battista da Monte, Fracastoro, Galileo, and many others are associated with Padua. Why was the school such a magnet? What created the “lure of Padua,” as the scholar C. D. O’Malley put it?

         In 1222 a group of disaffected law students and faculty left the University of Bologna and formed a new university in Padua. This was not too uncommon at that time. Since student fees provided virtually all the income, students and faculty could move whenever circumstances proved burdensome. The new Paduan university added medical teaching in 1250. Almost from inception, the university had a reputation for tolerance of different beliefs and philosophies, largely ignoring clerical charges of heresy. The state of Venice assumed control of the University when it absorbed the town of Padua in 1440 and reinforced the secular attitude.

Palazzo Bo, seat of University since 1493. Anatomy theater is located here (Wikipedia)

         Padua lay about twenty miles from Venice, connected by river. Venice at the time was immensely wealthy, prospering from industry and from maritime trade with both the east and west.After the Ottoman conquest of Constantinople in 1453, Greek-speaking people fled to Venice, bringing valuable works with them, including works of Galen and Hippocrates in the original Greek. Printing flourished in Venice and in 1469 the first book on pediatrics (and possibly the first printed book on any medical subject), by the Paduan professor Paolo Bagellardi, appeared in 1472. By 1515 there were over 493 printers, publishers, and booksellers in Venice. Vesalius’ atlas and subsequent anatomy texts relied on this nearby source.

         The university was closed in the early 1500s due to war conditions, but after 1517 Venice was in peace. It was a semi-

Main entrance to University of Padua 
(from Castiglione, Ann Med Hist)

republic. About 5% of the population (male noblemen over twenty-five) elected the senators who controlled legislation and most of the agencies. At the top was the elected “Doge,” the state representative. Religious tolerance was assured and the Inquisition kept at bay.

         After 1517, the university was managed by four senators, the Rifformatori, who set rules, salaries (some of the highest in Europe), and student fees (kept low due to Venetian subsidies). Local citizens could not hold the senior faculty positions (called “ordinary” chairs), a rule that attracted talented foreign professors. Vesalius, a twenty-three-year-old Belgian, was offered the chair of anatomy and surgery the day after he passed his examinations in 1537.

Andreas Vesalius, by Jan de Calcar
(Wikipedia)

Faculty from the Venetian area took the “extraordinary” chairs and faculty that failed to attract many students found themselves out of work. Lifetime tenure was unusual. Students could nominate professors for various chairs and elected a student “rector” that was involved in administrative decisions and sat in on examinations. 

         For medical students, degrees were granted in medicine (three years of study), medicine and philosophy (eight years), and surgery (five to eight years). By the latter sixteenth century, with the influx of many Protestants, the pope required swearing an oath to the Roman Catholic Church to obtain a degree. The University circumvented the restriction by examining Protestants in the home of a Count Palatine. Count Palatine was a title handed out liberally by the Holy Roman Emperor for favors and conferred the authority to grant university degrees. William Harvey obtained his degree in this manner. In 1616, the University founded a separate college only for Protestants, able to grant degrees. 

William Harvey (Wikipedia)

         Jewish students were also welcome and received degrees through this and other routes. They could wear the usual black caps of the other students rather than the yellow ones required in other institutions. Vesalius gave Hebrew names to a number of structures (along with Latin and Greek names). 

As foreign students increased, the University created “Nations,” separate residential groups containing students from their respective countries of origin. The school year began on October 18 (St. Luke’s day) and ended on August 15. The student was also required to spend a year with an approved practitioner. In 1543 Giambattista Da Monte began clinical rounds at the nearby St. Francis Hospital, considered a first in teaching methods. At examination time, the student had to pass a formal examination and defend a thesis. A student representative was present who could silence an examiner who showed personal animosity. 

In 1533 the University established the first European chair in botany (materia medica) to teach the medicinal uses of plants. Species were hard to identify from ancient sources such as

Diagram of first botanical garden (from book by
Materia Medica Professor Giacomo Cartusi)

Dioscorides, so in 1543 the University established the first botanical garden in Europe. Plants were imported, some from the recently discovered Americas, planted, and standardized. The garden continues today and is a UNESCO World Heritage Site.

 The anatomy department had perhaps the highest reputation, heightened with the professorship of Vesalius, and maintained by professors Realdus Columbus, Gabriel Falloppius, and Fabricius ab Aquapendente, the last being the teacher of William Harvey. In spite of such excellence in anatomy, a permanent anatomy theater was not constructed until 1594, named the Fabricius Theater. Students found the lectures of Fabricius erudite but tedious and attendance fell.

Padua's anatomical theater (Wikipedia)

The University of Padua blossomed as the western hemisphere was discovered, Greek learning entered Venice from the east, and printing flourished. Venice provided a secular environment, generous financial support, an openness to foreign students and faculty, and a focus on investigations to advance knowledge. No wonder the University was a tantalizing lure to young medical, and other, scholars throughout Europe. By the seventeenth century a new focus on physiology brought Bologna into the spotlight, but that’s another story.

 

SOURCES:

 

Martin, J, “The Vesalian School of Anatomy in Renaissance Padua.” 1982; Books at Iowa 18 (1): 3-17 (available at: https://pubs.lib.uiowa.edu/bai/article/id/29087/)

 

Castiglione, A, “The Medical School at Padua and the Renaissance of Medicine.” 1935; Ann Med Hist 7: 214-27.

 

O’Malley, C D, “The Lure of Padua.” 1970; Medical History 14: 1-9.

 

Zampieri, F, et al, “Origin and Development of Modern Medicine at the University of Padua and the Role of the “Serenissima” Republic of Venice.” Global Cardiol Sci Practice 2013: 21 (available at: http://dx.doi.org/ 10.5339/gcsp.2013.21)

 

Tinker, M, “The Importance of Padua/Venice in Sixteenth Century Medicine.” Thesis for Master’s Degree, UCSF, 1980.

 

Massry, S G, et al, “Jewish Medicine and the University of Padua: Contribution of the Padua Graduate Toviah Cohen to Nephrology.” 1999; Amer J Nephrology 19: 213-221.

 

Whitteridge, G, William Harvey and the Circulation of the Blood 1971, American Elsevier, N.Y.

 

A full index of past essays is available at: 

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

 

 

         

 DISCOVERING THE LYMPHATICS

 

         The widespread lymphatic vessels in the body are difficult to see and escaped proper study for centuries. These delicate, thin-walled vessels bring intestinally absorbed fat and tissue fluid from all parts of the body back to the general circulation, providing immunologic and antibacterial functions as they pass through numerous lymph nodes. The first to describe lymphatic vessels in some detail was Galen, the famous second-century Greek-Roman physician. During animal dissections he saw lymph nodes, that he considered “cushions” to protect organs, and described slender vessels running between abdominal lymph nodes and the intestines. In Galen’s concept of circulation, the liver manufactured blood that flowed in veins out to the intestines and other peripheral sites, nourishing them, while “spiritous” blood also flowed peripherally through arteries. The blood was absorbed in the periphery; it did not circulate back. 

         Andreas Vesalius, the great sixteenth century Belgian anatomist, still anchored to Galenic physiology, had a similar conception. Like Galen, he saw the tiny abdominal vessels without blood (lymphatics) leading to the liver, believing they connected to a portal vein that flowed bidirectionally, in part carrying chyle to the liver to aid in making blood. 

         By the early decades of the next century, experimentation to

Gaspare Aselli (Wikipedia)

establish knowledge, as opposed to genuflecting to ancient teachings, had come into vogue. In this vein, Gaspare Aselli, professor of anatomy and surgery at the University of Pavia, on July 23, 1622, dissected a dog for two colleagues who wanted to see the “recurrent nerves.” Pressing down on the intestines to view the diaphragm, he noticed in the mesentery “numberless fine white cords.” He thought they were nerves but on cutting one he saw a milky fluid emerge. When he opened another dog and could not find the vessels he remembered that the first

Woodblock print from Aselli's 1627
De lactibus, sive lacteis venis, quarto vasorum
mesaraicorum dissertatio (Wikipedia)
The slender white lines are lymph vessels passing
through the mesentery.

dog had eaten before the dissection. He soon proved that the tiny vessels indeed carried fat-laden fluid (chyle), absorbed after meals, through the mesentery toward the liver where he assumed they terminated, supplying nutrients for blood formation according to Galen’s scheme.

         Aselli died three years later, at age 44. Two of his colleagues, Alessandro Tadini and Senatore Settala, published his findings in 1627, one year before William Harvey’s publication on the circulation of the blood, a publication that shed doubt on Galen’s teaching of the liver as the source of blood.

Did these chylous vessels exist in humans? Nicolas-Claude Fabri de Peiresc, a wealthy senator in Provence and supporter of science, “caused a man which was condemned to be hanged to be fed lustily and securely before sentence was pronounced….and an hour and a half after he was turned off, he caused the Body to be brought into the Anatomical Theater.” (Gassendi). There de Peiresc found similar chylous vessels emerging from the intestines.

Jan de Wale (Wikipedia)

The picture of the lymphatic circulation was still incomplete. The Dutch anatomist, Jan de Wale (Johannes Walaeus) established, using ligatures of portal and lymphatic vessels, that the portal veins carrying blood from the intestines were distinct from the lymphatic vessels carrying chyle. He communicated these findings to Thomas Bartholin, who published them in 1641 and in enlarged form in 1645 in his anatomy text, Institutiones Anatomicae. Bartholin was one of Europe’s most

Thomas Bartholin (Wikipedia)

distinguished anatomists, based in Copenhagen. 

The liver remained the perceived endpoint of lymphatic flow, however, until animal dissections by the French physician Jean Pecquet found that chylous lymph from the intestines actually bypasses the liver, runs to a sac that gathers lymph (the cisterna chyli) and then rises through the thorax via the thoracic duct, a vessel that carries the lymph to the bloodstream. In short, the liver is not nourished by lymph.

Illustration from Picquet's Experimenta Nova Anatomica showing the chyli receptaculum
(cisterna chyli)  labeled "I" and thoracic ducts above. (Internet Archive) Click on image to enlarge.

Thomas Bartholin extended these observations and summarized the findings in 1653 under the title Vasa Lymphatica, Nuper Hafniae in Animantibus inventa, et Hepatis Exsequiae. The last two words translate as “obsequies of the liver,” a piece of humor by which he meant to convey the death of Galen’s teaching of the liver as the source of blood. 

Bartholin's Vasa Lymphatica
(Internet Archive)

Unbeknownst to Bartholin and Pecquet, a Swedish medical student, Olof Rudbeck, while dissecting a calf, had noticed “whey-like fluid” emanating from its upper thorax. He eventually traced out much of the lymphatic system, including, for the first time, the myriad vessels from the periphery, again showing that no lymph drained into the liver. In April 1652 he demonstrated his findings before Queen Christine and in May defended a thesis on the subject, published in 1653. He learned about Bartholin’s publications later that year and in 1654 a Leiden publisher produced a book containing publications of Pecquet, Bartholin, and Rudbeck. Rudbeck claimed that for this book Bartholin had backdated his work to 1652 (It is not certain this is true). 

Olof Rudbeck (Wikipedia)

A priority dispute arose between Rudbeck and Bartholin, fought out bitterly in various pamphlets and publications. Bartholin largely abstained from the quarrel as his supporters fanned the flames. One scholar who has studied the controversy, Charles Ambrose, credits Pecquet with discovering that abdominal lymph vessels bypass the liver to the thorax and the bloodstream, and Rudbeck with the discovery of the wider system of lymphatic drainage. In Rudbeck’s day, the public presentation of a scientific finding, such as before the Queen, was viewed as a date of communication. Rudbeck was a gifted scholar who taught several subjects and at age 31 was appointed rector of the University in Upsala. He used the name vasa glandularum serosa to describe the lymphatic system, but Bartholin’s vasa lymphatica is the name that survived in English as lymphatic vessels. 

The wonders of the lymphatic system are still unfolding, in particular its immunological functions.

 

SOURCES:

 

Suy, R, et al, “The Discovery of Lymphatic System in the Seventeenth Century: Part I: the Early History.” 2016; Acta Chirurgica Belgica 116 (4): 260-66 and "Part II," 116 (5): 325-331.

Park, J and Riva, M, “Gaspare Aselli (1581-1625) and Lacteis Venis: Four Centuries from the Discovery of Lymphatic System.” 2023; Amer Surgeon 89 (6): 2325-8.

Gassendus, Petrus, The Life of the Renowned Nicolaus Claudius Fabricius Lord of Peiresk, Senator of the Parliament at Aix. 1657, London.

Natale, G, et al, “Scholars and Scientists in the History of the Lymphatic System.” 2017; J Anatomy 231: 417-29.

Leeds, S, “Three Centuries of History of the Lymphatic System.” 1977; Surg Gyn Obs 144: 927-34.

Guerrini, A, “Experiments, Causation, and the Uses of Vivisection in the First Half of the Seventeenth Century.” 2013; J Hist Biology 46: 227-54.

Tonetti, L, “The Discovery of Lymphatic System as a Turning Point in Medical Knowledge: Aselli, Pecquet and the End of Hepatocentrism.” 2017; J Theoret Applied Vascular Research 2(2): 67-76.

Ambrose, C, “Immunology’s First Priority Dispute – An Account of the 17^th Century Rudbeck-Bartholin Feud.” 2006; Cellular Immunology 242: 1-8.

A full index of past essays is available at: 

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