CHRISTMAS DISEASE

 

 

         In the final issue of the British Medical Journal for 1952, an article appeared with the intriguing title: “Christmas Disease: A Condition Previously Mistaken for Hemophilia.” The authors described a new bleeding disorder found in seven patients. Case number one was a five-year-old boy named Christmas (not stated if this was a first or last name), who had suffered several bleeding episodes after play-induced injuries. All seven cases were indistinguishable from standard clinical hemophilia except that, strangely, bleeding could be stopped by transfusion of plasma taken from hemophilic patients. The authors explain the name given to the disorder, noting that the practice of naming diseases after patients was introduced by Sir Jonathan Hutchinson and had the advantage that “no hypothetical implication is attached to such a name.”

Jonathan Hutchinson was born into a Quaker family in northern England. He was apprenticed briefly to a local doctor, attended

 Jonathan Hutchinson (Wikipedia)

medical school in York, and, in 1850, finished medical training at St. Bartholomew’s Hospital in London. There he befriended other Quakers, such as Thomas Hodgkin, Joseph Lister, and Wilson Fox (later physician in ordinary to the queen), the latter two still in medical school. He became a member of the Royal College of Surgeons and opened a practice. He joined the staff of the Royal London Ophthalmic Hospital, where one of his assistants was Warren Tay, first describer of Tay-Sachs disease, and he attended at the Blackfriar’s Hospital for Skin Diseases. In this way he accumulated broad clinical experience, earning a reputation as a “generalized specialist.” He became an authority on syphilis, wroting a large book on the subject, and created the Archives of Surgery, a journal lasting a decade that was truly his own since he wrote virtually all the articles. 

 Skin cancers arising in arsenic-related keratitis (from Hutchinson's Archives of Surgery,
1890, v 2. (Hathi Trust)

           With a friend, he resurrected the expired Sydenham Society as  the “New Sydenham Society.” It brought translated European medical works (and writings of British authors) to British doctors. He persuaded the British Medical Association to open a medical museum, edited the British Medical Journal for a time, and even opened his own private museum (focusing on natural history), a sign of his passion for collecting. He started a postgraduate school where practitioners, from home and abroad, could be brought up to date on the latest findings. This endeavor floundered, however, from lack of interest.

         He is known for two failings. Although a keen observer and ardent collector, he did not investigate, as did the great surgeon and collector, John Hunter, with whom he was often compared. Secondly, he inexplicably insisted that leprosy was caused by the consumption of spoiled or rotting fish, even after the discovery of the causative organism was widely accepted. The breadth of his clinical acumen is what impressed colleagues, though. He was, as William Osler put it, “the last of the polymaths, the man at home in all spheres of medical practice.”

         What about naming diseases after patients? Hutchinson, an astute observer, is said to have published over 1000 case reports and, indeed, many contained names coined after patients. Examples are Mortimer’s malady (later considered sarcoidosis), Penman disease, Hilliard’s lupus, and Branford legs. Readers of his reports often reversed the process and invented eponyms in the Hutchinson name. “Hutchinson’s triad” is known to medical students as designating three features of congenital syphilis, one of which is “Hutchinson’s teeth,” (notched and small central incisor teeth). Hutchinson’s facies, Hutchinson’s angina, Hutchinson’s patch, and others placed his name for posterity in various publications. 

         

          But back to Christmas disease, which is of great historical interest. As knowledge of genetics and hematology progressed, “Christmas disease” took the name factor IX deficiency or hemophilia B, a sex-linked recessive bleeding disorder carried by females but affecting males almost exclusively. It constitutes about 15-20% of hemophilia cases. This disorder was a burden on royal families, the afflicted males all descending from Queen Victoria. Queen Victoria’s granddaughter, Princess Alexandra, married to Tsar Nicholas II of the Romanov family, had a son, Alexei, heir to the throne, who bled easily. The family's bodies were unearthed from a grave near the Ural town of Yekaterinburg in 1979. Forensic DNA

Female carriers and males are shown. Maurice is the only male not to die of bleeding. (Wikipedia)  

studies showed them to be members of the Romanov family. Samples from the exhumed body of Alexander III, Nicholas’s father, and from living descendants were examined to confirm the relationships. Remains of two of the royal children were missing, however: Alexei, the potential heir, and Anastasia. Only in 2007, were bone fragments found buried nearby that proved on DNA analysis to belong to the two missing children. Further study revealed that Alexei had the genetic mutation characteristic of factor IX deficiency, or Christmas disease.

         The mutation exerted tragic effects on descendants of Queen Victoria. One son, two grandsons, and five great-grandsons died of excessive bleeding. The remaining great-grandson, Alexei, was murdered before the disease took its course. One can only speculate on what other avenues history might have taken if the family had not been plagued by the bleeding disorder. Victoria’s own son, Leopold, grew old enough to marry and have a child, but at age 30 he had a fall, dying while his wife was pregnant with their second child. Prince Maurice, son of Victoria’s daughter Beatrice (a known carrier), died on the front in WWI, and probably did not have the disease, or at most a very mild form. No antecedents to Queen Victoria with the altered gene have been discovered and it is presumed that a spontaneous mutation occurred in her genes or those of the immediate prior generation.

 

         But enough of this melancholy narrative on Christmas disease. More joyfully: Merry Christmas and Happy Holidays to all!

 

SOURCES:

Biggs, R. et al, “Christmas Disease: A Condition Previously Mistaken for Hemophilia.” Brit Med J, 1952; Dec 27: 1378-82.

Van Ruth, J and Toonstra, J, “Eponyms of Sir Jonathan Hutchinson.” 2008; Int J Dermatology 47: 754-58.

The Moscow Times, July 16, 2018 (online at: https://www.themoscowtimes.com/2018/07/16/investigators-confirm-authenticity-tsar-nicholas-ii-body-burial-site-a62263

Anon., “Case Closed: Famous Royals Suffered from Hemophilia.” Science Oct. 8, 2009.

Ellis, H, “Jonathan Hutchinson (1828-1913).” J Medical Biography 1993; 1 (1): 11-16.

 Godlee, R., “Sir Jonathan Hutchinson, F.R.S., 1828-1913.” Brit J Ophthalmology 1925; 9 (6): 257-81. 

Ewing, M., “Jonathan Hutchinson FRCS.” Ann Roy Coll Surg 1975; 57: 296-308.

Rogaev, E.I., et al, “Genomic Identification in the Historical Case of the Nicholas II Royal Family.” Proc Nat Acad Science (early edition), 2009; 106 (13): 5258-63. Online at: https://www.pnas.org/content/106/13/5258

                                MEDICINE AT HIGH ALTITUDES

 

         In the late nineteenth century, high-altitude ballooning became popular and adventurous mountain trekkers found ever-higher peaks to conquer. At the extreme elevations participants in both activities encountered difficulties that eventually led to a new specialty: high-altitude medicine. 

         The title, “father” of high-altitude physiology (and of aviation medicine),” is usually awarded to Paul Bert, a French physician and investigator. Another French physician, though, deserves to be included as a “co-father” – Denis Jourdanet. The work of the two might be considered a collaboration between a laboratory investigator, Bert, and a clinically oriented physician, Jourdanet, with Jourdanet supplying the funds.

         Paul Bert (1833-1886) was born in the Burgundy area. He trained as a lawyer but he was intrigued by the mysteries of nature and

Paul Bert (Wikipedia)

eventually took enough courses to sit for a degree. Claude Bernard, one of his examiners, was so impressed with his thesis on respiratory physiology that he took him on as an assistant after he first obtained his medical degree. Bert did experiments on tissue grafting, said to have been helpful to surgeons in the Franco-Prussian War and for which he received a prize from the Academy of Sciences. Bernard got him a professorship at the University of Bordeaux followed by one at the Sorbonne. Bert was politically active, very left-wing, and constantly at odds with the Jesuits. His university appointment was opposed by a group of bishops but, with the influence of Louis Pasteur, he obtained it.

         Denis Jourdanet (1815-1892) was born in the Pyrénée

Denis Jourdanet (Wellcome Library)

mountains and remained there until university age, then studied medicine in Paris. Restless, he shipped off to Mexico before finishing his degree and set up a practice in the Yucatan peninsula. Through the French consul he became well-connected and married the daughter of a wealthy Mexican diplomat. After a return to Paris to obtain his medical degree he moved to Mexico with his wife, who had tuberculosis, and settled, eventually, in Mexico City, where he joined the faculty of the medical school. His wife improved temporarily at their 2240-meter altitude leading Jourdanet to become interested in the effects of altitude and measure barometric pressures on various mountaintops. His wife succumbed to TB in 1859 and he returned to Paris, where he published on the beneficial effects of higher altitudes and drew attention to the similarity of the symptoms of anemia and those seen after rapid ascent to high altitude.

         He designed low pressure air chambers for treatment of tuberculosis and other illnesses and published a book on his work in 1861. That same year France invaded Mexico and shortly after

Low-pressure chamber used by Jourdanet
for treatments (from La Pression Barométrique, 
Hathi Trust)

installed Maximilian as Emperor. Maximilian asked Jourdanet to be his personal physician but Jourdanet declined (wisely). In 1865 he remarried into another wealthy Mexican family and eventually settled in Paris to conduct research. It was then that he met Paul Bert.

         Bert was aware of Jourdanet’s idea that a deficiency of oxygen was the common factor responsible for the comparable symptoms seen with anemia and high-altitude exertion and wanted to study this using low-pressure chambers. Lacking funds, he advertised openly for money and Jourdanet, now wealthy, answered the call. Meanwhile Jourdanet continued treatment of various diseases with the low-pressure chamber, which he called “aerotherapy.” (He was not the first to use this treatment.) In 1875, he published a large tome, Influence de la Pression de l’Air sur la Vie de l’Homme, a two-volume work with numerous illustrations. Following an extensive historical background, he describes his treatment methods and lays out his ideas on hypoxia as the common problem in anemia and high altitude.

         Paul Bert, grateful for the support of Jourdanet, used both high and low-pressure chambers to establish the critical role of oxygen. He subjected animals and humans, including himself, to low pressure states, then reversed the symptoms with added oxygen.

Concentrations in blood of O2 (bottom) and CO2 (top)
plotted against partial pressures (horizontal)
from Pression Barométrique (Hathi Trust)

Conversely, he deprived the air of oxygen at normal pressures, all the while measuring partial pressures of oxygen and CO₂ in the blood. He was the first to map the hemoglobin disassociation curve, though his version was incomplete, and establish that the partial pressure of oxygen is the determinant factor.

         Bert eventually, in 1878, produced his magnum opus, La Pression Barométrique: Recherches de Physiologie Expérimentale. In it he describes his experimental work and presents a thorough history of high-altitude studies and lore up to 1878. In the introduction he gives full recognition to the help he received from Jourdanet, both financial and scientific. The work did not achieve the praise it deserved at first, allegedly because Bert was involved in several political activities that diverted attention, but in time it was recognized as a master work that has endured.

Bert's lab at the Sorbonne. Presure chambers on right wall, air pump in center
(from Regnard, P, La Cure d'Altitude, Hathi Trust)

         Bert was indeed involved in political activities. He was especially forceful in promoting free, secular, and obligatory education with no church involvement. He wrote a science textbook for use in schools. He became a member of the Chamber of Deputies and eventually Minister of Public Instruction. Finally, he was sent to Hanoi to become Governor General of French Indochina, where he liberalized the French rule and reduced the role of the military in governance. Sadly, after only five months in office, his life and career ended with a bout of severe dysentery.

         Many investigators subsequently refined the relation of oxygen to hemoglobin, determined that oxygen diffused into blood and was not secreted (the latter a position held by J. S. Haldane), and worked out the physiology of high-altitude pulmonary edema and acute and chronic mountain sickness. The benefits continue to flow to mountaineers, pilots, and intensive care units. 

 

SOURCES:

West, John B., High Life: A History of High-Altitude Physiology and Medicine. 1998, Oxford Univ. Press.

Olmstead, J. M. D., “Father of Aviation Medicine." 1952; Scientific American, 186 (1): 66-73.

West, John B. and Richalet, Jean-Paul, “Denis Jourdanet (1815-1892) and the Early Recognition of the Role of Hypoxia at High Altitude.” 2013; Am J Physiol Cell Mol Physiol 305: L333-L340.

 

         

         

     

   

         

         

 

TWO DOCTORS WITH ACROMEGALY

 

                Dr. Leonard Portal Mark, born in 1855, son of the British Consul in Marseille, enjoyed an uneventful childhood, studied medicine, and entered practice in London. He was also draughtsman in the St. Bartholomew Hospital Pathology Department (medical illustrator). At age 24 he noted a stuffed feeling in the left ear, followed by pain in the left face, sensitivity to light in his eyes, frequent runny nose, fatigue, and frequent headaches. Eventually he noted enlargement of glove, shoe, and hat sizes, protuberance of his jaw and lower lip, and problems with chewing his food. Amazingly, he failed to see that anything serious was wrong until one day, 25-6 years after his symptoms started, he suddenly realized that he must have acromegaly. For years, he admitted, looking in the mirror every day, “there was a typical acromegalic literally staring me in the face.”

Leonard Mark, ages 24 and 57 (from Acromegaly:A Personal Experience)

Yet, he failed to see the diagnosis. Consulting his St. Bartholomew Hospital colleague, Archibald Garrod (a pioneer in inherited diseases of metabolism and discoverer of alkaptonuria), Mark discovered that Garrod and other physician friends, even his brother and his dentist, knew the diagnosis and assumed that he was aware of it. They had simply avoided discussing an unpleasant topic with him.

          Seven years later, at the age of 57 (1912), Dr. Mark published a memoir recounting his symptoms. He wrote that “I felt some resentment having been kept in the dark for so many years.” But this feeling passed away and soon, “I realized that my friends had acted for the best.” He felt that in some ways he had benefitted psychologically from not knowing that he had a serious malady.

          Pierre Marie, a student and colleague of Charcot, whose name

Pierre Marie (Wikipedia)

is most often connected with Charcot-Marie-Tooth disease, a form of muscular dystrophy, described, in 1886, 2 cases with typical features, naming the syndrome “acromegaly” (enlarged extremity). He distinguished it from myxedema and Paget’s disease. Previous similar cases were pulled from the literature and, the following year, Oskar Minkowski noted an association of acromegaly with enlargement of the sella turcica and, perceptively, suggested that giantism might be another form of the same disease process. Dr. Mark’s symptoms, then, began

One of Pierre Marie's 2 cases (Rev Med)

 

before Marie’s report, but the medical world was aware of it soon after. Mark lived to the age of 75, though it was probably not a comfortable life.

         The Latin word pituita means phlegm. Galen believed that the pituitary was a structure that funneled waste products from the brain to the nose in the form of phlegm. Though other possible functions of the gland were subsequently discussed, no real progress was made (primarily because of its inaccessibility) until the reports of Marie and Minkowski.

         Leonard Mark’s autobiography made it across the Atlantic in an ironic way. William Coley, a talented young surgeon at New York Hospital, was consulted in 1890 by a 17-year-old woman, Bessie

William Coley (Nat Library Medicine)

Daschiell, seeking help for a non-healing injury to her right hand. Coley biopsied the swelling, revealing a “round cell sarcoma” of the bone. Bessie underwent an amputation of her right arm below the elbow but succumbed to metastatic disease 2 ½ months later. The incident deeply affected Coley himself and Daschiell’s closest friend, John D. Rockefeller Jr., who considered Daschiell his “adopted sister” (she was the sister of a close school friend).

     Coley, now driven to study sarcomas, found in the hospital records a case of a German immigrant whose large bone sarcoma, incompletely resected from the neck, had disappeared after a serious bout of erysipelas (a streptococcal infection). Coley tracked the man down and found him, amazingly, to be tumor-free and healthy, 6 years after the surgery. Coley treated future sarcoma patients by infecting them with streptococci, later with injections of fluid from cultured combinations of bacteria, usually streptococci and Serratia marscescens. A significant minority improved or were cured, as were occasional non-sarcoma patients. However, because radiotherapy became popular and the side effects of the vaccine treatment could be severe, his treatment languished. His methods were opposed particularly by James Ewing, a prominent pathologist at Cornell University Medical College, where Coley worked.

     Rockefeller, also stunned by Daschiell’s rapid death, saw the need to fight cancer and provided major funding for a new Memorial Hospital near the Cornell site that eventually became the Memorial Sloan-Kettering Cancer Center of today. He remained friends with Coley.

     A number of years later, when Coley was 51 years old (1913) and vaguely aware of enlarging hands and feet, a friend gave him a copy of Leonard Mark’s autobiography. The friend had received it from an anonymous source, apparently an attempt to discredit Coley. Coley read it in detail. It is unclear whether he already suspected that he had acromegaly, but after reading the book he certainly realized it. He downsized his practice. He apparently did not undergo pituitary surgery but left instructions for his brain to go to his friend, Harvey Cushing, for study. He also suffered from bleeding ulcers and in his seventies died of bowel gangrene from previous adhesions.

Only in modern times has interest in what is now called “immunotherapy” of cancer been revived. Coley is frequently cited as the father of this approach. The plethora of cytokines, including “tumor necrosis factor,” uncovered in recent years has reopened the field on a much more scientific basis.

         Coley never met Leonard Mark, but he must have been deeply impressed reading the story of a colleague on the other side of the ocean who, possibly like himself, took time to appreciate the significance of the slow changes in his physiognomy.

 

 

SOURCES:

Mark, L P, Acromegaly: A Personal Experience. Balliere, London, 1912.

Aron, D C, “The Path to the Soul: Harvey Cushing and Surgery on the Pituitary and its Environs in 1916.” Perspect Biol Med 1994; 37 (4): 551-65.

Kaplan, S A, “The Pituitary Gland: A Brief History.” Pituitary 2007; 10: 323-25.

Marie, P, “Sur Deux Cas d’Acromégalie.” Revue de Médecine 1886; 6: 297-333.

Cohen, H, “Pierre Marie 1853-1940.” Proc Royal Soc Med 1953; 46: 1047-1054.

Hall, S S. A Commotion in the Blood: Life Death, and the Immune System. 1997; Henry Holt & Co.

 

    

 A SPECIAL NOBEL PRIZE

         

         There is a story that the 1930 winner of the Nobel Prize in medicine and physiology first learned of his award from a Swedish journalist. After hearing the journalist, he asked what the prize was for. That was not false modesty; it was because the recipient, Karl Landsteiner, had made so many discoveries that he had to speculate on the winning one. The prize was, in fact, for the determination of the blood groups, a breakthrough that made possible the whole field of transfusions. True or not, the anecdote illustrates the wide range of Landsteiner’s achievements.

Landsteiner was born into a Jewish family in Vienna in 1868. His father, a prominent journalist, died when Karl was six. His

Karl Landsteiner (Wikipedia)

mother saw him through a gymnasium (university prep school) education, after which he entered the University of Vienna Medical School at age 17, graduating in 1891. Interested in biochemistry, he spent 5 years with prominent chemists, including Emil Fischer, and soon after learned bacteriology as assistant to Anton Weichselbaum, who had discovered the meningococcus as a cause of meningitis. He continued to work in Vienna until 1919, rising to Professor of Pathologic Anatomy at the University of Vienna and director of laboratories at the Wilhelmina Hospital. During this time his scientific output was prodigious.

In the infectious diseases, he and Ernest Finger (chief of Dermatology and Venereal Diseases) transmitted syphilis to monkeys (though preceded by Metchnikoff and Roux). On his own, Landsteiner discovered the value of dark field illumination in identifying the spirochete and found that extracts of beef heart improved the Wasserman reaction. Both were discoveries widely used. 

In 1908, during a polio epidemic, he and an assistant were the first to transmit the disease to monkeys. Landsteiner, with

 Constantin Levaditi (Wikipedia)

Constantin Levaditi, a Romanian-born scientist, established that the poliovirus was ultrafiltrable and that it was recoverable from the pharynx, salivary glands, tonsils, and in lymph nodes draining the intestines, proving that polio was a systemic infection. Landsteiner found that convalescent serum inactivated the virus and even created a vaccine. The vaccine failed to prevent disease in monkeys, though, and he abandoned the project. Landsteiner also described the pancreatic findings in what later became known as cystic fibrosis.

  

 Busts mounted in Polio Hall  of Fame, Warm Springs, GA. Landsteiner is fourth from left, 
Franklin Roosevelt is second from right. (Wikipedia)

     Regarding his Nobel Prize work, Landsteiner was long interested in blood transfusion reactions. Familiar with the phenomena of agglutination and lysis of red blood cells, he mixed serum from different donors with washed red cells. The resultant agglutinations distinguished 3 different blood groups, the fourth one discovered by his assistants soon after. This opened the door to transfusion services, especially after the introduction of the anticoagulant, citric acid. Landsteiner later uncovered other blood antigens and, finally, in 1940, he and Philip Levine discovered the Rh factor, which led to the unraveling of the perplexing problem of jaundice of the newborn. 

Diagram of Blood Groups (Wikipedia)

Landsteiner’s life was not always smooth. His mother died in 1908, a traumatic event for a man so close to her (he kept her death mask on his bedroom wall until his own death). Both he and his mother had converted to Catholicism years earlier, not an unusual practice at the time and possibly seen as an aid to his career. Though a tireless and determined worker, socially he was withdrawn and made few friends. Eight years after the death of his mother, and during WWI, he married the daughter of the verger of a Greek Orthodox Church, Helene Wlasto, who agreed to give up her Orthodox connection. A year later, 1917, a son, Ernest Karl, was born.

World War One was hard on Austria. Vienna’s glittering fin-de siècle life had disappeared and its inhabitants were barely surviving. Facilities (and salaries) deteriorated at the University and food was scarce. Landsteiner bought a goat to provide milk for his son as he watched destitute locals, desperate for firewood, cut down trees around his property. To feed his family, he moved to a job as pathologist at a Catholic hospital at The Hague. Despite the heavy workload and poor facilities, he managed to publish 12 papers. His difficulties drifted up to

 Simon Flexner (Wikipedia)

 Simon Flexner at the Rockefeller Institute in New York and, aware of his work, Flexner promptly offered him a position. 

The three Landsteiners started New York life in an apartment above a butcher shop, awakened often by the noise of passing trolleys, though he soon found a small house on Nantucket for quiet weekends. At the Institute, Landsteiner continued his impressive scientific output, concentrating on problems in immunology and serology. His work culminated in the publication of The Specificity of Serological Reactions, a landmark work in a field he had largely pioneered. He considered the work so important that, in another version of the Nobel Prize story, he thought the prize might be for his immunology research. He later collaborated with the chemist, Linus Pauling, on a new edition of his book that was published posthumously by his son, Ernest Karl, a surgeon in Boston. 

Landsteiner’s shyness and aversion to publicity caused him anxiety at the Nobel ceremonies. So much so, that when he was asked to speak at a dinner, Landsteiner deferred to that year's winner of the Prize in literature, Sinclair Lewis, who praised him as “in a thousand cases the master of death.”

Karl Landsteiner worked into his seventies, succumbing to a heart attack in 1943. Cancer took his wife six months later. Peyton Rous, a friend since his arrival in New York, wrote in an obituary appreciation that Landsteiner was “as pure a medical scientist as his material would allow… He believed that facts would make their own way and he left them to do so…” A fitting tribute. 

 

SOURCES:

Bendiner, E. “Karl Landsteiner: Dissector of the Blood.” Hospital Practice March 30, 1991, pp 93-104.

Gottlieb, A M, “Karl Landsteiner, the Melancholy Genius: His Time and His Colleagues.” 1998; Transfusion Medicine Reviews 12 (1): 18-27.

Goldman, A S and Schmalstieg, F C, “Karl Otto Landsteiner (1868-1943). Physician-biochemist-immunologist.” 2019; J Med Biography 27 (2) 67-75.

Bayne-Jones, S, “Dr. Karl Landsteiner: Nobel Prize Laureate in Medicine, 1930.” 1931; Science 73 (1901): 599-604.

Rous, P. “Karl Landsteiner.” In “Obituary Notices: Fellows of the Royal Society.” 1947; Proceedings of the Royal Society 5: 295-324.

Paul, J R, A History of Poliomyelitis. Chapter 11. 1971, Yale University Press.

          

 

 

         

 

 

  BURN DOWN THE QUARANTINE STATION!

 

         In the 1850s ships disgorged over two million immigrants into New York City, packing crowded tenement buildings to the limit. Cargo arrived too, much of it from the Caribbean where yellow fever was endemic. Frequently vessels carried epidemic diseases, of which four triggered a quarantine: smallpox, yellow fever, cholera, and typhus. Before the discoveries of bacteriology and the role of insects in disease transmission, informed opinion cited miasmas, polluted air, and fermenting ship holds as sources of these maladies. To protect the public New York had erected, in 1799, a quarantine station on Staten Island, about five miles from lower Manhattan and quite close to New Jersey. 

Map of Staten Island in 1858. X marks quarantine station. Brooklyn is to the right and Manhattan is 5 miles north. (Wikipedia and N.Y. Public Library digital collection)

Over the years, the station enlarged and played frequent host to the four diseases mentioned. Surrounding the station was a six-foot-high brick wall, sealing it from the surrounding village of Tompkinsville, while inside there were as many as 1500 people in quarantine during years of peak immigration (1840s and 1850s). Numerous personnel lived and worked within, including the medical director, a few physicians, nurses, orderlies, and various hospital employees. Resident boatmen rowed in the immigrants and stevedores brought in cargo from infected ships. 

View of station, 1858. White building with cupola behind the pier is St. Nicolas Hospital, for cabin
class passengers and VIPs only. Vegetable garden is on slope. (Wikipedia and N.Y. Public Library)

                              

Duty was considered hazardous. Four physicians died of typhus in 1851 and another in 1856. Thirty-three workers came down with yellow fever in 1856. Needless to say, the residents of the surrounding towns feared this fountain of pestilence next door. Though much of Staten Island was thinly-populated farmland, several villages and towns along the eastern shore, near the station, suffered yellow fever outbreaks over the years. Whether they originated from the quarantine station or not, the locals saw the quarantine station as the source. They were particularly angry at the staff, who, in defiance of rules, often visited the local communities for shopping or pleasure. 

Staten Islanders had actually resisted the quarantine station from the start, but New York State, heedless, exerted “the right of eminent domain” over 30 acres of land and built the station. Small outbreaks of cholera and yellow fever harassed the communities intermittently and large outbreaks of yellow fever attacked in 1848 and 1856. After the 1848 flare-up, the New York legislature agreed to move the station to Sandy Hook, New Jersey, but New Jersey objected, shippers did not want a change, and the matter drifted. After the 1856 episode, the N. Y. Legislature authorized a station on the other side of Staten Island but the residents there burned it down twice during construction. Meanwhile, at the original station, the locals put up their own fence and insisted on a Harbor Police force to keep station personnel from wandering out. Threats and counterthreats mounted. Finally, on September 1, 1858, the Tompkinsville Board of Health met and recommended that citizens protect themselves by “abating this abominable nuisance without delay.”

That very night men crept through a hole in the station’s wall, stuffed straw mattresses in strategic sites in both hospital and residential buildings and set them on fire. The Fire Department arrived, but did nothing, claiming that their hoses had been cut. The Harbor Police were overwhelmed. The mob’s ringleader agreed to spare a building to house the patients in exchange for releasing prisoners taken. The mob grew to several hundred, opened another hole in the wall with a battering ram, and incinerated more buildings. Some patients were placed in the spared Female Hospital, others remained outdoors. 

Newspaper sketch of burning the quarantine station. (Wikipedia and N.Y. Public Library)

                      

The next day the N.Y. Mayor and the Police Chief promised police backup, but none arrived. Meanwhile Richmond County, where the station was, had a stormy meeting during which angered residents resolved to finish the job. Station staff moved their furniture to the street and watched that night as the mob burned down all the remaining buildings, including the Female Hospital and the pier. Patients from the hospital, moved outside, were stuck between two burning buildings and had to be cooled down with buckets of water. Other patients and staff sat in the rain that fell during the night.

The New York Times castigated the Staten Islanders as lawless and selfish, while the New York Herald, Horace Greely’s paper, was more sympathetic, criticizing the New York authorities for not heeding the Staten Islanders’ repeated pleas for relief. To maintain peace, this time over 100 policemen and the State militia arrived  and tents were supplied to house the sick. Several of the mob were jailed for breaking quarantine regulations but Cornelius Vanderbilt, born on Staten Island, bailed them out. Two ringleaders were prosecuted by the State. Their defense, buttressed by witnesses, was that the station personnel had repeatedly broken rules by wandering into the neighboring communities, spreading disease, and that the mob had acted in self-defense and were seeking “freedom from State tyranny.” The judge ruled in their favor, brushing aside the charges of violence and property destruction. The judge, probably not impartial, owned property on the island and his brother-in-law had died of yellow fever.

The quarantine station moved temporarily to a large vessel, the Florence Nightingale, anchored further out in the harbor. Meanwhile, two islands, Hoffman and Swinburne Islands, were created artificially (opened in 1866) to house quarantined passengers, one island for the sick, and one for those who were well but exposed to disease. 

Quarantine hospital on Swinburne Island, 1879 (Wikipedia and 
New York Public Library)

The moral of the story? Quarantine is fine, but "not in my back yard." Using islands, as New York finally did, frequently solved the problem. Another example was the choice of Angel Island for the quarantine station at San Francisco.

 

SOURCES:

Garrison, F, “The Destruction of the Quarantine Station on Staten Island in 1858.” 1926; Bull N Y Acad Med 2 (1): 1-5.

N Y Times, Sept. 2 through 5, 1858.

N Y Herald, Sept 2 through 5, 1858.

Stephenson, K, “The Quarantine War: The Burning of the New York Marine Hospital in 1858.” 2004; Pub Health Reports 119 (Jan-Feb): 79-92.

 

 

 

 

 THE GUILLAIN-BARRÉ SYNDROME:

ORIGINS

 

     

     The FDA recently altered the labeling on the J&J Covid vaccine, warning of a small risk of Guillain-Barré syndrome in recipients. GBS, as it is sometimes called, has an interesting history. 

     Guillain, Barré, and Strohl (yes, three authors) first described the syndrome in two French soldiers during the First World War. The soldiers suffered from an ascending paralysis extending up to their arms, and dysesthesias, from which they recovered almost completely. Lumbar punctures were done on both, the fluid showing a high protein content and no polymorphonuclear (inflammatory) cells, a finding the authors said was distinctive. Lumbar puncture was relatively new at the time. Heinrich Quincke and Walter Wynter

Heinrich Quincke (Wikipedia)

had almost simultaneously published the technique in 1891. Both physicians aimed to relieve elevated pressure and not to study the fluid.

     The first of the 3 GBS authors, Georges Guillain, trained in neurology under Pierre Marie at the famous Salpêtrière Hospital in Paris. He was working his way up the academic ladder when the war broke out and promptly volunteered for service. He served in various field units, eventually becoming chief physician of the neurology section of the Sixth

Georges Guillain (Wikipedia)

Army. Jean-Alexandre Barré trained under Joseph Babinski and Pierre Marie. In the war he also worked in various field stations, eventually heading a military neurology center in the Eastern Region. 

     Neurologic and brain injuries were especially common in the early years of WWI because of poorly designed French helmets that provided inadequate protection. Both La Salpêtrière and La Pitié hospitals militarized their neurology departments to handle the flood of patients. At the former, Pierre Marie noted that “War injuries have shown us a different set of facts: lesions of the cortex, with more or less exclusion of white

Jean-Alexandre Barré (Wikipedia)

matter. Consequently, this new pathology is infinitely closer to the data of experimental physiology than was the old cerebral pathology.” At La Pitié Hospital, Joseph Babinski ran the military neurology unit. Guillain and Barré enjoyed a fruitful collaboration, publishing important papers on injuries to the brain and the spinal cord and delineating indications for surgery.

     The third author of the original paper, André Strohl, had trained in physics and medicine. Strohl performed electromyograms on the calf muscles of the two

André Strohl (Wikipedia)

patients, showing a weakening or absence of the reflex response and a delay in response. It was an early use of the technique. After the war, Strohl worked as professor of physiologic medicine in Algiers and later professor of physical medicine at the University of Paris. He was elected to the Académie de Médecine at the age of 35, an unusual honor. He wrote several books on nerve and muscle physiology, on nuclear isotopes, and a text on physical medicine. 

     Of course, other physicians had published cases of ascending paralysis before the war. Jean Baptiste Octave Landry, the best-known, had reported on acute ascending paralysis (10 cases) in 1859, before the age of lumbar puncture. Other reports followed, and a few earlier ones came to light. The term “Guillain-Barré syndrome” was first used by Barré at a neurology conference in 1927.  Guillain and Barré maintained that their syndrome (they actually called it “notre syndrome”) was distinct, emphasizing the favorable recovery and the findings in the spinal fluid. Why the name Strohl was dropped from “our syndrome” by Guillain and Barré, was never quite clear. Various reasons have been suggested: his German name and his origin from Alsace and the fact that he was not a neurologist. Only one month after the original Guillain-Barré-Strohl report, Pierre Marie and Charles Chatelin published 3 more cases in soldiers, acknowledging the earlier report by G, B, and S. With slightly different timing, might this have been dubbed the “Marie-Chatelin” syndrome? 

Salpêtrière Hospital, about 1660, after conversion from gunpowder factory (saltpeter was used to make
gunpowder). Image by Jean-Pol GRANDMONT of engraving by Adam Pérelle (Wikipedia).

     Over the years, many more cases of ascending paralysis came to light, presenting with varying degrees of paralysis and recovery and not always with “typical” spinal fluid findings. Many were fatal. Guillain and Barré resisted the trend to broaden the spectrum of “their syndrome” but eventually they had to yield. The GBS syndrome now includes a wide range of presentations.

     The range is wide enough, in fact, that a group of 5 authors recently wondered if Franklin D. Roosevelt might have suffered from GBS instead of polio. In early August 1921, Roosevelt, a 39-year-old practicing lawyer, was vacationing on Campobello Island, New Brunswick. After a day of vigorous activity, he developed aches and sensitivity to touch in his legs. His legs weakened and over a few days were completely paralyzed. Eventually the family consulted Robert W. Lovett, professor of orthopedics at Harvard, who had organized the first polio clinic at Boston Children’s Hospital. He diagnosed poliomyelitis and recommended a spinal tap, though it appears not to have been done. Roosevelt entered Presbyterian Hospital in New York under the care of Dr. George Draper, a classmate of FDR’s at Groton and Harvard, who had written a book on polio in 1917. As we all know, Roosevelt’s legs never recovered.

          Was FDR’s disease really polio? Or could it have been Guillain-Barré syndrome? To make a case for GBS, the 5 authors pointed out differences between typical polio and GBS syndromes, using a statistical analysis to conclude that GBS was the more likely diagnosis. A subsequent paper challenged that conclusion. Lovett and Draper may not have seen the G, B, and S paper of 1916, written in French. Whatever the truth, it is likely that if Roosevelt’s diagnosis had not been polio the March of Dimes, the principal driver of the first polio vaccine, would not have come into being.

 

SOURCES:

Waclawik, A J, “The Legacy of the Seminal Publication by Guillain, Barré, and Strohl: The History Behind the Eponym.” 2018; Wisconsin Med J 117: 160-3.

 

Pietrzak, K, et al, “Georges Guillain.” 2016;  J Neurol 263: 2148-9.

 

Green, D, “Infectious Polyneuritis and Professor André Strohl – A Historical Note.” 1962; New Engl J Med 267: 821-2.

 

Goldman, A S, et al, “Franklin Delano Roosevelt’s (FDR’s) (1882-1945) 1921 Neurologic Disease Revisited; the Most Likely Diagnosis Remains Guillain-Barré Syndrome.” 2015; J Med Biog 24 (4): 452-9.

 

Goldman, A S, et al, “What Was the Cause of Franklin Delano Roosevelt’s Paralytic Illness?” 2003; J Med Biog 11: 232-40.

 

Dittuno, J F, et al, “Franklin Delano Roosevelt: The Diagnosis of Poliomyelitis Revisited.” 2016; J Phys Med Rehab 8: 883-93.

 

Guillain, G, Barré, J-A, et Strohl, A, “Sur un Syndrome de Radiculo-Névrite avec Hyperalbuminose du Liquide Céphalo-Radicien sans Reaction Cellulaire.” 1916; Bull Memoires Société Hosp Parisser 3, v40,prt 2: 1462-70.

 

Walusinski, O, et al, “French Neurologists During World War One.” 2016; Frontiers Neurol Neuroscience 38: 107-118.