THE NÉLATON PROBE: GARIBALDI’S 

ANKLE AND OTHER TALES

 

           In 1862, Guiseppi Garibaldi, the Italian patriot intent on uniting Italy, crossed from Sicily to Italy’s boot, beginning a march toward Rome. In the town of Aspromonte, Garibaldi met soldiers sent to

Giuseppe Garibaldi (Wikipedia)

oppose him. Recognizing them as fellow Italians and reluctant to fire, he ventured forward to arrange a truce. Three bullets caught him, two of no consequence and one that ricocheted off a rock into his right ankle. After his capture, at least six doctors examined him and all but one felt that the bullet was no longer in his ankle. Before the
availability of X-rays, locating a bullet in a wound was a challenge for military surgeons. The stakes were high as a retained missile could lead to infection and death.

         In faraway England, Garibaldi’s campaign was highly popular and his backers raised money to send a surgeon, Richard Partridge, to assist. Partridge agreed that the bullet was no longer present. Inflammation increased substantially, however, and the Italian doctors invited a French surgeon, Auguste Nélaton, to see Garibaldi. After probing the

Auguste Nélaton (Wikipedia)

 wound, Nélaton opined that the bullet was    still in place. But, he wondered, was it bone, and not bullet, that halted his probe? On return to France, he developed a porcelain probe that was unglazed at the tip, which, if rubbed against a bullet, would show traces of lead. He sent the probe to one of Garibaldi’s surgeons, Zanetti, who confirmed that the bullet was still in place. 

         Partridge heard of this and returned to Italy, this time accompanied by Nicolai Pirogov, the famous Russian surgeon (see essay of Dec. 2016). Partridge reversed his opinion, agreeing with Pirogov that the bullet was present. Zanetti enlarged the wound and extracted the bullet fragment (fragmented because of the ricochet), allowing the wound to slowly heal. 

Nélaton probe with unglazed porcelain tip
(National Museum of American History)

      On return to England, Partridge’s reputation fell. The medical

Richard Partridge (Wikipedia)

profession accused him of “stealing a patient,” since he saw Garibaldi without an invitation, and the public disparaged him for his error in diagnosis. His practice dwindled and he died poor.

         Auguste Nélaton, conversely, enjoyed increased renown. Aged 56 at the time, he had spent six years as an intern and extern under the famous surgeon Guillaume Dupuytren at the Saint Louis Hospital in Paris, rising later to a surgical professorship. In 1867, Emperor Napoleon III appointed him as his personal surgeon, and he attained membership in the French Academy of Sciences. He made contributions to pelvic surgery, lithotomy, and especially to surgery on the maxilla and mandible. He invented the flexible urinary catheter still in use today, a much-appreciated advance over the stiff ones in use at the time. He wrote a large text on surgical pathology and several other works. He accumulated a large fortune but lived modestly.

         The prominent Harvard professor of surgery, J. Collins Warren, during study in Europe in 1866 had met both men and wrote that Partridge “was never regarded by his colleagues as an exceptionally brilliant exponent of surgical art.” Nélaton, by contrast, he found refined and highly regarded in surgical circles. Nélaton probes became standard equipment in the military surgeon’s tool kit. Parenthetically, Warren, on his trip  had also watched Joseph Lister apply his new antibacterial techniques for preventing wound infections, work as yet unpublished.

         The Nélaton probe later found a use on two American presidents. Three years after Garibaldi’s episode, John Wilkes Booth shot Abraham Lincoln in the back of the head in Ford’s Theater, Washington. Dr. Charles Leale, in a nearby box, heard the fatal shot and rushed to help. Leale, a recent graduate of the Bellevue Hospital Medical College in New York, was a young surgeon in the U.S. Army

Dr. Charles Leale (Wikipedia)

Hospital in Washington. He found Lincoln slumped forward, unconscious. A clot over part of the occiput showed the wound, which Dr. Leale probed with his finger. Volunteers carried Lincoln across the road to a private home where Dr. R.K. Stone, Lincoln’s personal physician, the Surgeon General, Dr. Joseph K. Barnes, and other volunteer physicians arrived to help. Barnes sent for a Nélaton probe while keeping the wound open with a silver probe (to reduce intracranial pressure). At about 2 AM, as the President was dying, Barnes inserted the Nélaton probe into the wound, twice, and on the second try he claimed to have encountered the bullet, though it was of no help. Five hours later, after a period of loud and “stertorous” breathing, the President expired at 7:20 AM.

On July 2, 1881, the mentally deranged Charles J. Guiteau shot President Garfield in the back while in a railroad station. Dr. Doctor Willard Bliss (Doctor was his first name), one of the first physicians to examine Garfield, in addition to inserting his unwashed finger into the bullet wound,

Doctor Willard Bliss (Wikipedia)

inserted a Nélaton probe. The probe encountered only a fractured rib and the bulb on the end, entrapped in the bone fragments, could only be released by pressing on the President’s chest, a painful maneuver. A rib had deflected the bullet so that a straight, rigid probe, such as the Nélaton probe, would not reach the bullet in any case. 

Another attempt to find the bullet was made by Alexander Graham Bell. He created a device based on magnetic induction that would produce sound when metal entered the circuit. It failed in Garfield's case, Bell surmising that the metal bedsprings interfered with the detection.

Alexander Graham Bell applying his metal detector to President Garfield. Man on the right is 
listening for sounds if metal found. (From Frank Leslie's Illustrated Newspaper, courtesy Library 
of Congress)

Garfield lingered on for three months, undergoing repeated probes with unclean fingers, until he expired from secondary infection. By this time, the role of germs in wound infections was well known to many in the medical profession, though most of those caring for President Garfield were not believers. 

The advent of X-rays, discovered in 1895, soon made the Nélaton probe obsolete. Until then, it was a standard instrument in a military surgeon’s kit.

 

SOURCES:

Rutkow, Ira, James A. Garfield. 2006; Times Books, Henry Holt & Co.

Dobson, J, “A Surgical Problem of the Last Century.” Ann Roy Coll Surg Engl, 1953; 13: 266-69.

Moscucci, O, “Garibaldi and the Surgeons.” J Roy Soc Med 2002; 94: 248-52.

Sabbatani, S, “Garibaldi’s Wounds.” Le Infezioni nella storia della Medicina. 2010; 18(4): 274-87. (Translated by Google)

 

Curca, F P and Patrascu, T, “Historical Landmarks of the Use of Nélaton’s Probe in the Surgical Diagnosis of Gunshot Wounds and Two Famous Applications: Garibaldi’s and Lincoln’s Cases.” Roman J Legal Med, 2019; 27: 388-94.

 

Warren, J Collins, “The Nélaton Probe.” Boston Med Surg J  1919; 181 (8): 235-6.

Dunea, G, "The Bullet in Garibaldi's Ankle." Hektoen International 2021; 13 (3).

 

Mylonis, A I, “Glances in the History of Medicine: Auguste Nélaton.” Hellenic Arch Oral Maxillofacial Surg 2021; 3: 207-12.

 

Papaioannou, H I and Stowell, D W, “Dr. Charles A. Leale’s Report on the Assassination of Abraham Lincoln.” Accessed at: https://quod.lib.umich.edu/j/jala/2629860.0034.105/--dr-charles-a-leales-report-on-the-assassination-of-abraham?rgn=main;view=fulltext

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

 

 

 

 

 

 

 

         

         

      

 WILLIAM BEAN: WINNER OF 2025

IG NOBEL PRIZE

 

         You may have heard of an interesting publication entitled the Journal of Improbable Research. Each year the publishers award a group of “Ig Nobel” Prizes to investigators whose research produces exceptional work that makes people “laugh, then think.” This year the Ig Nobel Prize for literature, not medicine, went to Dr. William Bennett Bean. The writings in medical journals that earned him the prize, given posthumously, are entitled:

 

“A Note on Fingernail Growth”

“A Discourse on Nail Growth and Unusual Fingernails”

“Nail Growth: Twenty-Five Years’ Observation”

“Nail Growth: 30 Years of Observation”

“Nail Growth. Thirty-Five Years of Observation”

“Some Notes of an Aging Nail Watcher”

 

         In the final paper on the list he wrote, “The impetus to study nail growth is analogous to the curiosity that leads observers to look at tree rings, the baleen plate of the whale, or the growth of the tooth of the bear.”

         In fact, Dr. Bean’s contributions to literature and to medicine extended well beyond the above list and deserve mention. He was

William Bennett Bean (Wikipedia)

born in Manila in 1909, when his father served as head of the anatomy department of the University of the Philippines. The family moved to Virginia, where William went to university and medical school, after which he completed house officer training in Boston. He joined the faculty at the University of Cincinnati Medical School where he embarked, in the pre-WWII years, on studies of pellagra.                   

             Pellagra, a nutritional deficiency disease due to lack of niacin in the diet, was prevalent in early twentieth-century America, especially in southern states. Joseph Goldberger, a careful investigator and one of our first epidemiologists, disproved a prevalent theory that it was an

Patient with pellagra, showing skin changes exacerbated by
sun exposure (Wikipedia)

infectious disease and demonstrated the culprit to be a diet common among the poor, largely composed of corn, that was deficient in niacin. Bean conducted some of the earliest studies treating pellagra with these agents, establishing himself as an expert on nutrition. 

         As 1942 dawned, America was at war. Bean, with a team of investigators at the Kettering Laboratory at the University of Cincinnati, joined the Armored Medical Research Laboratory, concerned with preparations for desert tank warfare in North Africa. Bean and his team investigated problems of heat tolerance and, as a recognized nutritionist, how to improve soldiers’ hard-to-stomach C-Rations. Heat studies were conducted in the California desert, where a temperature-controlled room was constructed in which human subjects spent 9 hours at 120 degrees, performing work, and the remainder at 90 degrees (rest-time). They found that, after acclimatization, salt virtually disappeared from urine and sweat, that thirst was a poor guide to dehydration, and that with adequate water intake and balanced diet salt tablets were unnecessary. Humid heat at 95 degrees made physiological demands similar to dry heat at 120 degrees. Many design problems in tanks were improved to better accommodate human crew.

         Dietary and nutritional requirements were studied intensively and daily requirements of vitamins, calories, etc. worked out. C-Rations were infamous for their lack of acceptance. New “K-Rations” fared equally poorly: “even desert rodents avoided them,” according to Bean. Studies made clear that even the tastiest diet proved unpleasant if repeated too often, a problem resolved by increased variety and flavor in the K-Rations. Troops in combat surviving on Bean's improved K-Rations for weeks at a time were grateful for the change. In 1944, the Army produced 105 million K-Rations. 

Samples of K-Rations (Wikipedia)

         Bean and his colleagues, working at Fort Knox, also studied the metabolism and dosage of the antimalarial atabrine, used as a substitute for quinine whose supplies the Japanese had taken over in Asia. These studies established a regimen used successfully in the Pacific theater, where Bean also visited.

Malaria patient, New Guinea, WWII (National Archives)

         After the war, Bean returned to academic medicine in Cincinnati and continued with physiologic studies. He also served as chief of medicine at the University of Iowa and as Director of the Institute for Medical Humanities at the University of Texas Medical Branch at Galveston. His final move was back to the University of Iowa in 1980. He died in 1989, much revered. He wrote several papers on skin manifestations of disease and was highly valued as a teacher.

            A literature prize is appropriate for Dr. Bean for several reasons, aside from his musings on fingernails. In addition to his skills as a clinician, teacher, and investigator, he was known for his wide reading in the humanities, his wit, and his writing. He was book editor at the Archives of Internal Medicine from 1955 to 1963 and chief editor for four additional years. He served on the editorial board of the Journal of the History of Medicine and the Allied Sciences for several years. He wrote numerous book reviews and articles on a variety of topics on the periphery of medicine, such as the role of religion in medicine, climatology, ethics, medical history and tips on good writing. He deplored the benumbed style of much medical writing, which often “condemns the reader to a Chinese water torture of the mind.” 

         Other Bean writings include an excellent biography of Walter Reed and a witty poem entitled “Omphalosophy: An Inquiry into the Inner (and Outer) Significance of the Belly Button.” 

         He was an admirer of William Osler, who was chief of the medical service at John Hopkins Hospital for many years and was, at the time, perhaps the physician best known to the public. Bean co-founded the American Osler Society, dedicated to the principles that Osler espoused, including the importance to physicians of the humanities and the history of medicine, and he published a book of Osler’s aphorisms.

         Though the Ig Nobel prize is partly in jest, the award to Bean highlights the career of an influential physician, devoted to medicine, literature, and the humanities.

           A happy holiday season to all!

           I'll see you in January.

 

SOURCES:

Series of articles on William Bean’s life and writings in AMA Arch Int Med, 1974; 134 (5): 809-877.

 

Bean, W B, “Omphalosophy: An Inquiry into the Inner (and Outer) Significance of the Belly Button.” 1974; AMA Arch Int Med 134 (5): 866-70.

 

Bean, W B, “Nail Growth: Thirty-five Years of Observation.” 1980; AMA Arch Int Med 140 (1) 73-6.

 

Massey, R U, “William Bennett Bean, 1909-1989: Clinical Scholar and Historian of Medicine.” 1989; J Hist Med Allied Sci 44: 285-87.

 

Koehler, F A, “Army Operational Rations: Historical Background.” 1958; Quartermaster Corps Historical Studies Series II, number 6. Accessed at: https://qmmuseum.army.mil/research/history-heritage/subsistence/Army-Operational-Rations-Historical-background.html

 

Bean, W B, “Field Testing of Army Rations.” 1948; J Appl Physiol 1 (6): 448-57.

 

Bean, W B, “The Ecology of the Soldier in World War II.” 1968; Persp Biol Med 11 (4): 675-86.

 

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

 

 

 

 

 

 

 

 

          

 

 MEASLES VACCINATION:

OLD AND NEW

 

         In 1824, King Kamehameha II of Hawaii and his queen embarked on a near-six-month journey to England. The British host arrangements included a visit to the Royal Military Asylum, a home for orphans of fallen soldiers known for outbreaks of contagious

Kamehamaha II (Wikipedia)

diseases. Several days later, measles struck he entire Hawaiian royal party and, despite efforts of London’s leading physicians, the king and queen succumbed to the disease. Twenty-four years later, a measles epidemic swept away an estimated 10% to 30% of the population in their home country. 

A similar outbreak devastated the Fiji Islands in 1874, after the return of a royal visit to Australia. And measles, along with smallpox, were the principal diseases that devastated the native populations of the New World after the arrival of the Spanish in the 16^th century.

         Europe was not spared. The measles death rate in Edinburgh of the mid-18^th century was about 10% and in Glasgow it ranged from about 4% to 20%. Young children faced the highest mortality rates. Americans suffered equally. The Fairfield, New Jersey, farmer, Ephraim Harris, wrote, “That fatal and never-to-be-forgotten year, 1759, when the Lord sent the destroying angel to pass through this place, and removed many of our friends into eternity in a short space of time; not a house exempt, not a family spared from the calamity. So dreadful was it, that it made every ear tingle, every heart bleed; in which time I and my family was exercised with that dreadful disorder, the measles.”

Child with measles (CDC Public Health Image Library)

During WWI, the military assembled thousands of recruits from all over America in training camps, where measles circulated freely among the many unexposed recruits. The lungs are a target in measles, and combined with spreading streptococcal infections (the cause of “strep throat”), widespread pneumonia claimed the lives of over 3200 young soldiers. 

         Scientific study of measles began in the nineteenth century. During an epidemic in the 1840s in the Faroe Islands, 26-year-old Dr. Peter Panum, sent by the Danish government, investigated the scattered, chronically undernourished population. He determined the incubation period, documented the rapid transmission of infection, and noted that all ages up to age 65 were susceptible. Older residents were still immune after surviving a 1781 epidemic.         

         The long-lasting immunity after measles stimulated attempts at deliberate immunization. Adopting a procedure known as variolation, introduced into England in the early 1700s to prevent smallpox, in

francis Home (Wikipedia)

1758 a Scottish physician, Dr. Frances Home, took a small amount of blood from a measles patient during the early stage of rash and placed it in a small cut in the arm of another child, producing a mild case of measles. Using similar techniques in subsequent years, several trials, large and small, induced generally mild disease in young children after injecting blood, serum, or oral secretions. The largest trial, in Hungary, in 1841, involved 1122 children and claimed a 79% success rate preventing measles. Administering immune serum to exposed children was also tried. 

         But measles persisted, and the investigators were operating in the dark. The trials lacked control groups to assess rates of naturally acquired infection, lacked ability to measure the immune status of mothers or children, and had no method to titrate the inoculum. No one had isolated the virus, and parents were reluctant to infect their children with a potentially dangerous agent.

         Scientific progress eventually filled the voids. Techniques for culturing virus in eggs, chick embryos, and eventually in tissue culture had advanced quickly. In the laboratory of John Enders,

John Enders (Wikipedia)

recipient of the 1954 Nobel Prize (with Thomas Weller and Frederick Robbins) for growing polio virus in tissue culture, Thomas Peebles grew measles virus in human kidney cells. The blood of an eleven-year-old boarding school student with measles, David Edmonston, provided the “Edmonston strain” of virus from which the first modern measles vaccine emerged. After multiple passages in human and animal cells to weaken the virus and extensive testing, it was released for use in 1963, along with a killed vaccine made from the same strain. However, the killed vaccine was later withdrawn because of a short-lived immune response, and the live vaccine frequently evoked a fever over 103 degrees. There was room for improvement. 

         Maurice Hillerman, a scientist at Merk Laboratories, stepped in. Obtaining samples from Enders’ lab, he passed the virus forty more times through chick embryo cells, using virus-free chickens he raised on Merk property (chicken leukemia virus had unknowingly contaminated the eggs in Enders’ lab, though it proved to be

Maurice Hilleman (Wikipedia)

harmless). The resulting vaccine, released in 1968, had few side effects and is the one in use today. Hillerman, raised on a Montana farm, worked at Merk for years and, in addition to measles, created the current mumps vaccine, two Hepatitis B vaccines, vaccines for hepatitis A, rubella, chickenpox, meningococcus, pneumococcus, Japanese encephalitis, the 1957 flu vaccine, and the MMR combination. He discovered the SV40 monkey virus that induced cancer when injected into rodents, a finding that drove future vaccines to be derived from virus-free fetal cells rather than animal tissue. His work has saved millions of lives. Though the recipient of many awards, he never received a Nobel Prize.

         According to the CDC, in the decade before the first measles vaccine there were an estimated 3 to 4 million cases of measles in the U.S. annually. Of the reported cases each year, approximately 400-500 people died, 48,000 were hospitalized, and 1800 suffered from encephalitis (brain infection). After introduction of the measles vaccines and the addition of a booster dose, the incidence fell drastically, both in the U.S. and abroad. Eventually, measles elimination became a realistic goal, since there is no animal reservoir.

In recent times that goal is proving elusive, though still achievable. Meanwhile, much of the world is, thankfully, measles-free.

 

SOURCES:

Berche, P, “History of Measles.” Presse Med 2022; 51 (3), September, special issue. Available at: https://www.sciencedirect.com/science/article/pii/S0755498222000422?via=ihubP

Duffy, J, Epidemics in Colonial America. 1972 (2^nd ed.) Kennikat Press, pp 164-79.

Plotkin, S A, “Vaccination against Measles in the 18^th Century.” Clin Pediatrics 1967; 6 (5): 312-15.

Enders, J F, “Francis Home and his Experimental Approach to Medicine.” Bull Hist Med 1964; 38 (2):101-112.

Morens, D M, Taubenberger, J K, “A Forgotten Epidemic that Changed Medicine: Measles in the U S Army, 191-18.” Lancet Infect Dis 2015; 15 (7): 852-861.

Shulman, S, et al, “The Tragic 1824 Journey of the Hawaiian King and Queen to London.” Pediatric Infect Dis J 2009; 28 (8): 728-33.

Offitt, P A, Vaccinated: One Man’s Quest to Defeat the World’s Deadliest Diseases. 2007; Smithsonian Books, Harper Collins.

CDC website: “History of Measles.” Available at: https://www.cdc.gov/measles/about/history.html

Baker, J P, “The First Measles Vaccine.” Pediatrics 2011; 128 (3): 435-7.

Tulchinsky, T H, “Maurice Hilleman: Creator of Vaccines that Changed the World.” Case Studies in Public Health, 2018; Academic Press, pp 443-470. Available at: https://www.sciencedirect.com/science/article/pii/B9780128045718000032?via=ihub

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

 

 

 

         

         

 

         

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.

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