THE PAP SMEAR 

 

         The number of lives saved by the routine use of the “Pap smear” over the last sixty to seventy years probably runs into the millions. The simple and relatively low-tech procedure has had an enormous impact on public health. Behind it is an interesting story.

         George Nikolas Papanicolaou was born in 1883 in the charming Greek town of Kymi on the island of Euboea. His father was a physician and mayor of the town. After a liberal arts education, George attended medical school, served in the military, earned a PhD in biology in Germany, and decided on a life of

Papanicolaou as young man (Wikipedia)

research rather than the practice of medicine. On return to Greece from Germany, George met and married Andromache Mavroyeni. After a short stint on an oceanographic research vessel, George served medically in the Balkan War of 1912 against the Ottomans, during which he met Greek-American volunteers who encouraged him to go to America to seek a scientific career. He decided to take their advice.

         He and “Mache” arrived in New York the next year with no job, no contacts, no knowledge of English, and $250. George worked at Gimbel’s department store selling rugs and, being a good violinist, earned extra cash playing at restaurants. He eventually contacted Thomas Hunt Morgan, the famous geneticist at Columbia University, who helped him obtain a position as a technician in the anatomy department at Cornell Medical College, with Andromache as his assistant. George investigated the role of the X and Y chromosomes in determining sex, a problem still under exploration at the time. Studying guinea pigs, George needed to obtain ovarian eggs at the precise time of ovulation. He examined samples of guinea pig vaginal discharge daily and discovered that the smears could accurately determine the day of ovulation. To see if similar changes occurred in humans, he turned to his wife, who became the first person to have a “Pap smear”, and he enrolled volunteer workers at the New York Women’s Hospital. The results demonstrated a similar human sexual cycle. 

         By chance, a smear from one of the volunteers revealed malignant cells. This generated a study of women with known cancers of the cervix and uterus, showing that the technique might prove valuable in detecting early stages. The findings were first presented at, of all places, the Third Race Betterment Conference in Battle Creek, Michigan, in 1928, a meeting of the eugenics

Cancer cells shown at Race Betterment Conference
(from report of 1928)

organization founded by John Harvey Kellogg, the inventor of breakfast cereals who worried about “race degeneracy.” The findings generated little interest, however. Papanicolaou, prodded by Cornell’s chief of anatomy and in conjunction with Cornell’s chief of gynecology, embarked on a study in 1939 to do a smear on all women admitted to the gynecological service of Cornell’s New York Hospital. The results made it clear that early cancers, with no symptoms, could be detected accurately, and established a milestone in cancer prevention. The following years were devoted to teaching the methods and refining the techniques for use on a mass scale. The “Pap smear” and an entirely new specialty, cytotechnology, were born.

         Papanicolaou was suddenly a famous man. He visited medical centers in Europe, was hosted by the royal family in Greece, received numerous awards and honorary degrees, and gazed at his portrait on postage stamps and Greek currency bills. National Cytotechnology Day, to recognize the value of the technicians who examine the smears, falls every year on his birthday, May 13. 

He was nominated five times for the Nobel Prize, though never received it. It is not clear why, but one possibility relates to near simultaneous reports of cancer cells in cervical scrapings by a Romanian, Dr. Aurel Babeș, published in the Proceedings of the Romanian Society of Gynecology of January and April of 1927 and again in April 1928 in Presse Medicale. Babeș was a highly

Cancer cells from cervical scraping by Aurel
Babeș, Presse Medicale 1928 (Hathi Trust)

regarded scientist in Romania, had his name on over 200 papers, and had published a major work on pellagra. The two sampling methods differed somewhat. Babeș used a platinum loop to scrape the cervix while Papanicolaou used a narrow pipette to obtain free cells and employed a more refined stain. Babeș did not pursue the study of vaginal smears but the presence of the Babeș reports may have caused hesitation by the Nobel committee. Additionally, Papanicolaou’s main supporter at the fifth nomination died just before the final voting. Babeș never contested Papanicolaou’s world recognition. 

 Incidentally, the uncle of Aurel Babeș, Victor Babeș, had discovered the parasite causing a disease named after him: babesiosis, and was a well-known bacteriologist. 

         George’s wife, Andromache, was instrumental in his success. She was the “special patient,” who underwent hundreds of vaginal

Andromache and George Papanicolaou
(from Exper Therap Med 18, 2019, Creative Commons License)

smears and was certainly the “most over-tested woman of all time” (Vilos). In addition, she was the breadwinner during the lean years after arrival in New York. She became an expert cytotechnologist and taught the skill to many others, while still finding time to prepare and serve Greek specialties to distinguished guests in their home.

         In 1961 Dr. Papanicolaou accepted the directorship of a new Cancer Research Institute of Miami and early the next year the couple moved to Florida. Tragically, three months before the dedication ceremony of May 1962, George Papanicolaou was stricken with chest pain and succumbed rapidly to a failing heart. He was buried in Clinton, New Jersey, next to his niece. 

Though he missed the Nobel Prize, the gratitude of millions of women must have been a sufficient reward for the creator of the “Pap smear”.

 

SOURCES:

Vilos, G A, “The History of the Papanicolaou Smear and the Odyssey of George and Andromache Papanicolaou,” Obstet and Gynecol, 1998; 91(3): 479-83.

 

Elgert, P A and Gill, G W, “George N Papanicolaou, MD, PhD: Cytopathology.” Lab Medicine2009; 40(4): 245-6.

 

Papanicolaou, G, “New Cancer Diagnosis.” Proc Third Race Betterment Conference, Battle Creek, Mich., Jan. 2-6, 1928, pp 528-34.

 

Papanicolaou, G, traut, HF, “The Diagnostic Value of Vaginal Smears in Carcinoma of the Uterus.” Amer J Obstet Gynecol 1941; 42: 193-206.

Albert, P, “George Papanicolaou: Biography,” accessible at: https://library.weill.cornell.edu/george-papanicolaou-biography

Mammas, I N, et al, “Mache Papanicolaou (1890‐1982), the dedicated companion of the great benefactor: An interview with Dr Julie Kokkori, one of the only living relatives of Dr George N. Papanicolaou.” Exp Therap Med 2019; 18: 3248-51.

Tasca, L, et al, “History of Gynecological Pathology XII. Aurel Babeș.” Int J Gynecolog Pathol2002; 21: 198-202.

Naylor, B, et al, “In Romania It’s the Méthode Babeș-Papanicolaou.” Acta Cytologica 2002; 46(1): 1-12.

Diamantis, A, et al, “What’s in a Name? Evidence that Papanicolaou, not Babeș, Deserves Credit for the Pap Test.” Diagnostic Cytopathol 2009; 38(7): 473-6.

 

 

         

         

 

THE STRANGE CASE OF EVA PERON

 

         Here is a tale for students of medical ethics as applied to the rich and famous.

         Eva Perón, wife of Juan Perón when he was president of Argentina in the 1950s, arose from humble circumstances. She was born in 1919 to the mistress of a land manager in a small village in the Argentine “pampa” (flat, extensive plains). Her father departed to rejoin his wife about a year later, leaving the family of mother and five children in poverty. Eva left home at age 15 and headed for Buenos Aires where she worked as an actress and singer. Gradually attaining some reputation, she formed her own company. In 1944, she met Col. Juan Perón, Secretary of Labor at the time. They married in a small, semi-secret ceremony in 1945 when Peron became president. Eva, often called Evita, champion of the “descaminados” (the shirtless ones) and popular with the poor, organized the Eva Perón Foundation, a huge institution dispensing charity, and she was important in helping women obtain the right to vote. 

Eva and Juan Perón (Wikipedia)

         In 1950, the fourth year of the Perón presidency, Eva had a fainting spell, after which she had an appendectomy. One of her physicians later wrote that he had diagnosed uterine cancer and had advised a hysterectomy, but this story was not confirmed. Apparently recovered, she threw herself into her work, doling out charitable gifts in all directions. In time, she grew thinner, pale, and tired. Unknown to the public, she suffered vaginal bleeding and abdominal pain. Her doctors now made a diagnosis of cervical cancer and gave her radium implants preparatory to resectional surgery, but never told her she had cancer. Her brother and other relatives asked that Eva not be informed. Dr. Ricardo Finochietto, director of the Presidente Perón Hospital (built by Eva’s Foundation), was to do the abdominal surgery. 

Juan Perón, however, asked a local oncologist, Abel Canónico, about an outside expert, and was advised of George Pack, a renowned cancer surgeon at New York’s Memorial Hospital Sloan-Kettering Center. Pack was contacted secretly by the Argentine embassy in Washington and agreed to operate on Eva. Because of possible political ramifications, he worked in cooperation with the State Department and the ambassador to Argentina, Ellsworth Bunker, who also approved the contemplated surgery. Pack flew with Dr. Canónico to Buenos Aires, examined Eva under anesthesia without her knowledge, confirmed the diagnosis, and flew back to New York, all in complete secrecy. He returned to Argentina and performed a radical hysterectomy and lymph node dissection on November 6, 1951, again seeing Eva only under anesthesia. He left the operating room before Eva awakened and stayed in a hotel room until she had stabilized. Eva, and the public, never saw him or knew of his involvement in either encounter, believing that Finochietto had done the surgery. Dr. Pack suspected the tumor would recur, which it did. He declined to do further surgery and never sent a bill.

The surgery and the concomitant maneuverings took place against the background of a violent campaign for a presidential election. Juan Perón felt that the survival of Eva was important to his reelection and her popularity was cetainly evident when a crowd of 20,000 gathered outside the hospital on the day of her surgery. Five days later, Eva cast her presidential vote from a hospital bed, helping her husband win the election. Then, fortified by large doses of pain medicine and a plaster frame, she stood next to him in an open automobile during the victory parade. She finally passed away on July 26, 1952, weighing less than 80 pounds.

A number of features of this case would not pass muster today. Regarding the diagnosis, Pap smears were uncommon in Argentina at the time and relatively new in the U.S. Though available in the late 1940s, the first time an Argentinian cancer organization advised Pap smears was in 1950. It received little public response and remained under-utilized. The dangers of vaginal bleeding were also not publicized. Furthermore, doctors were still wary of telling patients they had cancer, both in the U.S. and even more so in Argentina. In a survey of the staff of the Michael Reese Hospital in Chicago, published in 1961, fewer that 5% never told a patient of cancer but many couched the diagnosis in ambiguous terms, often leaving the patients confused. Even if Eva knew the diagnosis, she might have resisted further diagnostic measures, given her tendency to brush off illness. According to the priest who gave her last rites, she was never told the diagnosis.

More bizarre, the surgery was carried out secretly by a surgeon not known to the patient and without the patient’s knowledge or permission. In addition, the State Department and the U.S. ambassador to Argentina encouraged the plan, almost certainly to accommodate political considerations. The Assistant Secretary of State, Edward Miller, Jr., praised Pack for his skills “in such an important and critical situation.” Pack himself felt that he could render a service by performing an operation not well known in Argentina and he was flattered to be asked. He wanted to tell the story publicly one day but respected the privacy of the matter and died before the facts came out.

Medical care of the rich and famous, especially of political figures, can lead to compromises and unusual medical practices that would not meet today’s ethical standards. In addition to Eva’s surgery, the secret operation on President Cleveland and the care of the Shah of Iran raise similar questions.

 

SOURCES:

Lerner, Barron H, “The Illness and Death of Eva Perón: Cancer, Politics, and Secrecy,” Lancet 2000; 355: 1988-91. (Dr. Lerner is a bioethicist and Professor of Medicine at New York University)

 

Fraser, N and Navarro, M, Eva Perón. W.W. Norton, 1980.

 

Oken, Donald, “What to Tell Cancer Patients: A Study of Mental Attitudes.” JAMA 1961; 175(13): 1120-28.

 

Grant, Ronald M, “Never Say Die: A Personal tribute to George T. Pack, MD (1898-1969).” CA: A Cancer Journal for Clinicians, 2008; 19(3): 198-200.

 

De Gonzales, V, et al, “Argentina: Telling the Truth to Cancer Patients.” Bull NY Acad Science 1997; 809: 152-62.

 

Altman, Lawrence, “From the Life of Evita, a New Chapter on Medical Secrecy.” NY Times, June 6, 2000.

 

      

  

 

THE LIFE AND DEATH

OF CHLOROFORM

 

      Ether burst onto the medical stage in October of 1846 when a dentist, William Thomas Green Morton, administered the volatile compound to twenty-year-old Edward Abbott while the noted Boston surgeon, Dr. John Warren removed a neck tumor. Painless surgery had arrived.

         News of the dramatic effect of ether flew across the Atlantic. That December, Dr. James Simpson, Professor of Midwifery in

James Simpson (Wikipedia)

Edinburgh, traveled to London to witness its use in an operation by his old teacher, Robert Liston. Liston took 28 seconds (surgeons before anesthesia had to be quick) to amputate a leg without any complaint from the etherized patient. He announced after the procedure, “This Yankee dodge, gentlemen, beats mesmerism hollow.” Simpson eagerly took up ether anesthesia to ease the pains of labor as well as in surgeries. He ignored objections from clergy and other quarters that pain was natural in childbirth and should not be suppressed.

But difficulties administering and transporting ether led Simpson to assess many other agents. After trying somewhat indiscriminately, primarily on himself, various volatile compounds, a chemist friend suggested chloroform. On the evening of November 4, 1847, Simpson and two assistants sat at his dining room table and inhaled a small amount of the sweet-smelling substance. Simpson soon found himself on the floor along with his two semiconscious companions. The trio were so delighted with the result that they inhaled the substance several times more, finally heading home at 3 AM, determined to use it.

Cartoon of Simpson's home trial of chloroform (Wellcome Library)

Chloroform, like ether, had been around for a while before its anesthetic potential was realized. Credit for the first synthesis goes to an American, Samuel Guthrie. Trained as a physician, Guthrie became more interested in business and set up a gunpowder plant and other enterprises near the shore of Lake Ontario. Interested in chemistry, he read in writings of the Yale University chemist,

Samuel Guthrie (Wikipedia)

Benjamin Silliman, about a compound named “chloric ether,” whose sweet aroma might have uses in medicine. Dr. Guthrie devised a simpler method, in 1831, of making it by combining “best whisky” with chloride of lime and distilling the result. What he actually made was an alcoholic solution of chloroform. Sippers of this solution became pleasantly tipsy, sometimes drunk. Silliman chemically removed the alcohol, producing pure chloroform, but the mild alcoholic solution was used by American doctors for its pleasant and seemingly beneficial effects. Its anesthetic properties remained unknown.

Just over one year following Dr. Warren’s first use of ether and five days after Simpson’s chloroform experiment at home, a young woman in Edinburgh, Scotland, entered her second labor. She had previously endured an agonizing three-day labor resulting in a dead child. Simpson was her accoucheur, as he was called, and, anxious to avoid a second tortuous labor, he anesthetized her with chloroform – its first use in a patient. The young lady delivered a healthy child after a three-hour, painless labor. Within a few weeks Simpson helped over 50 women avoid labor pains and surgeons quickly adopted it for operations. His successful experience made him an enthusiast of the new agent and he publicized it relentlessly. It was cheap, easy to administer, acted rapidly, had a pleasant smell, lacked the irritating qualities of ether, and was not flammable. 

In London, when ether was first in use, the highly educated but relatively obscure practitioner, John Snow (later of cholera fame), took an interest. He had worked on respiratory physiology and

John Snow (Wikipedia)

surmised that the varying results with ether might be due to varying dosage. He measured the amount of ether in air at varying temperatures, devised a breathing apparatus that produced a predictable amount for administration, and characterized five levels of anesthesia. Later, responding to the enthusiasm for chloroform, Snow devised a similar breathing apparatus to administer an exact dose. He helped Queen Victoria through two labors with the new agent, though without the apparatus since she was lightly dosed. Most practitioners, in fact, continued to pour chloroform onto a sponge or cloth-covered cone. During the American Civil War and the Crimean War chloroform was the chief anesthetic employed. The agent also made headlines as an instrument in kidnappings, rapes, and other crimes, though much of this was exaggerated.

Before long, reports of sudden death during chloroform anesthesia appeared, often during induction, that were unrelated to dose or underlying medical problems. The Lancet criticized Snow for using it on Queen Victoria, citing reports of unexpected deaths. Not until 1911 did Goodman Levy show that ventricular fibrillation occurred in cats under chloroform, suggesting a mechanism. He later published data showing that over two decades chloroform use constituted between 72 and 90 percent of all anesthetic deaths in Britain. In these cases British doctors were obliged to testify at a coroner’s inquest, but none were charged with anesthetic

Henry J. Bigelow (Wikipedia)

malpractice throughout the nineteenth century. In the northern United states, however, doctors were sued for anesthetic deaths and, additionally, Henry J. Bigelow, Professor of Surgery at Harvard, used his influence to champion the use of ether as the safer choice. Chloroform usage died quickly in the north, though in the southern states its use continued for some time. 

Levy’s publications were persuasive and eventually the mortality statistics could not be ignored on either side of the Atlantic. Chloroform usage declined everywhere, replaced by ether and eventually newer agents.

Pierre Louis in Paris pioneered the use of statistical methods in the early 1800s to question the value of bloodletting as treatment for pneumonia. His methods, after over half a century, finally convinced chloroform users to choose another anesthetic.

 

SOURCES:

Stratmann, Linda, Chloroform: The Quest for Oblivion, Sutton Publishing, 2003

 

Johansen, Peter V, et al, Cholera, Chloroform, and the Science of Medicine: A Life of John Snow, Oxford University Press, 2003.

 

Shepherd, John A, Simpson and Syme of Edinburgh, E&S Livingston, 1969.

 

Snow, Stephanie J, Blessed Days of Anaesthesia: How Anaesthetics Changed the World, Oxford University Press, 2008.

 

Levy, A. Goodman, Chloroform Anesthesia, William Wood & Co. 1922

 

Bigelow, Henry J, “Death by Chloroform and Alleged Death by Ether,” Boston Med Surg Journal, 1872; 86: 277-9.

 

Holmes, Oliver Wendell, “Henry Jacob Bigelow,” Proc Amer Acad Arts Sci 1891; 

26; 339-51.

 

Thomas, K B, “The Early Use of Chloroform,” Anesthesia” 26(3): 348-62, 1971.

 

 

 

 

 

 THEODOR ESCHERICH AND HIS BACTERIUM

 

         Last month the CDC reported on an outbreak of diarrhea due to a strain of Escherichia coli, thought to be associated with the consumption of romaine lettuce. Certain strains of this bacterium frequently cause diarrheal illness while others are innocuous inhabitants of the lower intestinal tract. This tongue-twister of a name derives from its discoverer, Theodor Escherich, a pioneering pediatrician who originally called the organism Bacterium coli. 

  

Theodor Escherich (Wikipedia)

       Escherich was born in 1857 in Ansbach, Germany. His father was a district health officer, concerned with health of the poor and high infant mortality rates, passing these concerns on to his son. Theodor completed his medical education in different German cities, as was the custom at the time, served briefly in the military, and became an assistant to Prof. Karl Gerhardt in Würzburg. Although Gerhardt was an internist, he was interested in pediatrics and eventually wrote a large, sixteen-volume work on the subject.
Inspired by Gerhardt and by the newly developing science of bacteriology, Escherich studied further at the St. Anna Children’s Hospital in Vienna, where he attended lectures by Hermann von Widerhofer, who held the city’s first Chair of Pediatrics at the University of Vienna. After a brief time in Paris, he moved to Munich where he learned bacteriology skills from a former student of Robert Koch. He learned well, and focused his efforts on

Hermann von Widerhofer

examining the intestinal bacteria of the newborn. He characterized two distinct new bacteria that he called Bacterium coli commune (now known as Escherichia coli) and Bacterium lactis aërogenes (now called Klebsiella pneumoniae). He determined that at birth the intestinal canal was sterile but acquired these and other bacteria almost immediately. His thesis paper on the subject was published and a translated version eventually saw print in the U.S in 1988.

         In 1890, at age 33, he moved to the St. Anna Children’s Hospital in Graz, as a professor of pediatrics, soon being elevated to a full professor and director of the hospital. In this capacity he supervised an expansion of the hospital, including laboratories and incubator rooms. He and a colleague demonstrated antitoxin in children recovering from diphtheria, he promoted Emil von Behring’s diphtheria antitoxin treatment, and he wrote a book on diphtheria. He also established Bacterium coli as a cause of diarrheal disease and urinary tract infections in children. After Roentgen’s discovery of X-rays, he installed an X-ray camera. He attracted numerous students, including Clemens von Pirquet and Bella Schick. These two studied and described in detail serum sickness, a complication of serum therapy. Pirquet also developed the tuberculin skin test, and Schick developed the Schick test for diphtheria, then widely used but now obsolete. 

         Escherich’s talents as a teacher, researcher, and humanitarian did not go unnoticed. After the death of his old teacher, von Widerhofer, in 1901, he accepted an offer from the University of Vienna to fill his shoes as Chair of Pediatrics and Director of the St. 
Anna Children’s Hospital (separate from the one in Graz), where he had studied 18 years previously. Escherich did not slow down in his new role. He expanded the hospital laboratories and X-ray facilities and instituted training of pediatric nurses. Infant mortality in Vienna was still high and Escherich combatted it by establishing organizations enhancing the hygiene and welfare of children, such as an infant welfare society, a Society for Children’s Research, and the Association of Pediatricians in Vienna. He continued his interest and research in infectious diseases and was considered the best pediatric bacteriologist in Europe. The Emperor Franz Joseph named him Court Counselor in 1906 and invited him to dine at court several times. 

St Anna Hospital, Vienna, 1850s (Wikimedia Commons) 

         His accomplishments in pediatrics and his connections were essential in the construction of a new Imperial Institute for Maternal and Infant Care in Vienna and the first human milk bank. Escherich’s bacteriologic studies of neonatal stool of breast-fed and non-breast-fed infants taught him the importance of breast feeding. Boston opened a similar bank the next year and as of 2017 about 500 milk banks were operating worldwide. In short, his influence was global. 

Sadly, in 1911, as he was making ward rounds, he began to uncontrollably speak in several languages. It was the first sign of a cerebrovascular accident that ended his life the next day. Numerous obituaries lamented his loss and praised his contributions to medical science and his humanity toward children. He had published several works: on infant intestinal flora, on tetanus, and on diphtheria, authored numerous articles, and trained a generation of pediatricians. 

In 1919, Drs. Castellani and Chalmers, in a text on tropical diseases, proposed that the name Escherichia coli replace Bacterium coli, but the change was not official until 1958. E coli has been a popular laboratory organism for years. Studies of the bacterium have yielded three Nobel Prizes. One was for the mechanism of transfer of genetic material, one for mechanisms of enzyme control, and one, using phages, for the replication and genetic structure of viruses. Interestingly, a sample of the original strain studied by Escherich turned up in the National Culture Type Collection in London (formerly the Lister Institute), a collection that holds strains from the beginnings of bacteriology. Theodor Escherich’s brother-in-law had sent it to a laboratory in Cambridge in 1900 and it eventually landed in the Lister Institute. Its presence was “rediscovered” in 2015.

Theodor Escherich’s work in bacteriology and pediatrics resulted in major contributions to medicine and child health. Authors of a paper in 2007 felt that he could justifiably be considered “the first pediatric infectious disease physician,” a fitting and well-deserved designation.

 

SOURCES:

Schulman, S T, et al, “Theodor Escherich: The First Pediatric Infectious Disease Physician?” 2007; Clin Infect Dis 45: 1025-9.

 

Méric, G, et al, “From Escherich to the Escherichia coli Genome.” 2016; Lancet Inf Dis 16 (6): 634-36.

 

 Friedmann, H C, “Escherich and Escherichia.” 2006; Advances Appl Microbiol 60: 133-196.

 

Escherich, Theodor, “The Foundations and Aims of Modern Pediatrics.” 1905; American Medicine 9 (2): 55-62.

 

 

 

 

A FAMOUS NAVAL HOSPITAL:

HASLAR

 

         By the mid-eighteenth century, Britain had established colonies around the world. To protect the new possessions and maintain the trade routes that rendered the colonies profitable required an expanded navy. Larger ships, into which hundreds of crewmen were crowded in close quarters, sailed ever-longer routes far from land. Though the seamen’s diet, measured in calories and meat content, was richer that that found in most homes at the time, it did not included perishable fruits or vegetables.

         The diet rendered the crews susceptible to scurvy, brought on by the lack of vitamin C, and the killer of more men than combat wounds and other diseases combined. Crowding also permitted infectious diseases to flourish. Among the latter, typhus was the most common, though smallpox and yellow fever appeared intermittently.

         In the early years of naval expansion, the sick arriving in a port were placed in homes, lodging houses, or small private hospitals contracted to care for them. Such a system, however, failed. Fraud was rampant; the host facilities padded the bills and provided minimum care. Alcohol was traded for clothing and the few contract doctors available were often busy with private patients. Faced with over 15,000 men yearly invalided ashore, the Navy decided to build substantial hospitals to provide better care. The largest, Haslar Hospital, went up across the bay from Plymouth, home of the Navy’s principal docks.

         Originally designed as a large four-sided building around a large square central court, only three sides were constructed to allow more ventilation. The central portion was primarily for

Plan of Haslar Hospital (from Tait, History of Haslar Hospital)

administrative functions (the administration was civilian) and the side wings featured double pavilions three stories high and separated by a small, aerated area. The building opened in 1754, allowing accommodation for 1200 patients, and was the largest brick building in England and perhaps in Europe. Lighting was by gas, replaced by electricity in 1905. Water closets were installed at the end of each ward, and sewage emptied into Portsmouth Harbor via a nearby creek. Wells supplied fresh water. The first chief physician was James Lind, a civilian at the time.

James Lind (Wikipedia)

         Lind was a Scot who learned surgery as an apprentice and went to sea as a surgeon’s mate at age 23. While serving in the Channel Fleet he conducted his famous trial of remedies for scurvy, noting that the most effective curative was juice from lemons and oranges. He then left the Navy to earn an MD degree at Edinburgh, entered private practice, and found time to write A Treatise on Scurvy, published in 1753, in which he detailed his success with citrus juice to prevent scurvy. Strangely, though, Lind did not emphasize citrus juice for the treatment of scurvy, believing it to have other causes. Lind held the post at Haslar until 1783, succeeded by his son.

         By the time of the American revolt against England, Haslar held 2100 patients, making it four times the size of Guy’s Hospital in London. Not all seamen wanted to be there. Many had been impressed into service out of prisons or poorhouses and frequently escaped during the night or had alcohol smuggled in. To discourage desertion, bars were put on the windows, a wall twelve feet high surrounded the hospital, and guards patrolled outside. Yet in1794, 226 still managed to escape. Nursing care was unreliable, with alcohol often bartered for clothing, and sometimes nurses or attendants coaxed sick patients into willing their property over. Mortality overall was substantial. In 1780, 909 deaths were recorded.

         The few doctors assigned to the hospital were allowed to engage private practice and when needed might be miles away with a patient. Only after 1797, was private practice forbidden. At first, surgeons operated without anesthesia on the wards, but after patients objected a separate operating room was installed. Surgeries were infrequent, however, until the arrival of anesthesia in the 1850s.

         In the early days, scurvy and typhus were the most common medical problems in the hospital. Typhus most commonly broke out on a ship after men from jails or from other ships carrying typhus were put aboard as crewmembers. Most medical men considered it “contagious,” not recognizing the role of the louse in its

Thomas Trotter (Wikipedia)

transmission. Thomas Trotter, appointed Physician to the Hospital in 1793, improved hygiene enormously. New patients were bathed (as before), shaved, their hair cut short, and given clean clothes. Thereafter they were washed daily and given twice-weekly changes of hospital gowns, which undoubtedly helped prevent new typhus cases. Trotter halted the treatment of bleeding for fevers and supplied a rich diet, speeding recovery. By this time, the value of fruits and vegetables for scurvy was evident. Trotter also revised the administrative structure, pleaded for more personnel to attend the sick, and recommended that the Navy take over the previous civilian administration.

         The Navy did assume responsibility for the hospital and introduced a teaching program aimed at medical problems peculiar to shipboard life. Courses in new subjects, such as bacteriology, were introduced. Anesthesia allowed a more active surgical service. The hospital, over time, cared for casualties from the Napoleonic wars, the Crimean War, and both World Wars. The country’s first blood bank opened there in 1940. The National Health Service took over the site in 2007 and closed it in 2009. The hospital now contains flats for retirees. Over 10,000 bodies are believed to be buried on the grounds. Forensic scientists have recently examined a few skeletal remains and documented osseous signs of scurvy, once a persistent threat to a seaman’s life.

 

Modern view of the hospital, showing a guard tower (Wikipedia)

SOURCES:

 

William Tait, A History of Haslar Hospital, 1906; Griffin & Co.

Kenneth J. Carpenter, The History of Scurvy and Vitamin C, 1986; Cambridge Univ Press.

Bryan Vale and Griffith Edwards, Physician to the Fleet: The Life and Times of Thomas Trotter. 2011; Boydell Press, Woodbridge.

James Lind, A Treatise on the Scurvy, 3^rd ed. 1772; London.

Eric Birbeck, “Royal Naval Hospital Haslar: Paragon of Nautical Medicine.” The Grog Ration 5 (2): 2-5, 2010.

Eric Birbeck, “The Royal Hospital Haslar: from Lind to the 21^st century.” The James Lind Library, accessible at: https://www.jameslindlibrary.org/articles/the-royal-hospital-haslar-from-lind-to-the-21st-century/

 

 

                     THE VIBRANT LIFE AND TRAGIC DEATH OF

RENÉ FAVALORO

 

            René Favaloro, an Argentinian cardiac surgeon, is best known to the world as the “father” of coronary artery bypass surgery. His life in medicine, however, ranges well beyond cardiac surgery.

         René was born in La Plata, Argentina, in 1923, the son of an artisan carpenter of Sicilian origin. After medical school and internship in La Plata, he decided on a career in surgery. But he declined a residency when he was required to sign a declaration of allegiance to the Peronist party. Coincidentally, a letter came from an uncle in a remote village in the Pampa asking him to fill in while the local doctor was absent for medical treatment. René accepted and traveled to Jacinto Aráuz, a village in flat, desolate land whose inhabitants, mainly of German descent, labored at raising livestock and farming in barren land with unpredictable weather conditions. The previous doctor soon died, and René brought in his brother,

René Favaloro (Wikipedia)

recently graduated from medical school, to set up a more modern clinic. They expanded their area of activity, acquired used X-ray equipment, medical books and journals, a reliable automobile, and materials for local and spinal anesthesia. They taught midwives to be nurses and others to educate villagers about hygiene, clean water, and ways to stay healthy. Cesarian sections, gallbladder surgery, hernia repair, and many other procedures became possible. He tabulated the blood types of all the residents, thus establishing a “mobile blood bank” in case of emergencies. René married and built a house, but after twelve years of hard work and little vacation, decided to broaden his horizons. He wanted to study thoracic surgery.

         His old professor of surgery, José María Mainetti, encouraged him to go to the Cleveland Clinic. René took some quick English lessons and flew north. George Crile, one of the Clinic's founders, greeted him and referred him to the cardiac surgery service under Dr. Donald Effler. Effler found that Favaloro had not passed any U.S. exams and spoke halting English and told him he could work only as an unpaid aid. Using modest savings, René carried out aid duties and earned enough confidence to be allowed to scrub in on operations. He learned English, crammed every night to pass the National and State Board exams, and was accepted as a cardiac surgery resident. 

The timing was propitious. A brilliant cardiologist at the Cleveland Clinic, Mason Sones, was the first to use a rapid frame motion picture camera to photograph dye in the coronary arteries and clearly demonstrate obstructive lesions. Favaloro worked with Sones

Mason Sones with Favaloro (Wikimedia Commons)

intensively and before long tried bypassing the lesions using a saphenous vein graft. The coronary artery bypass graft (CABG), as the procedure was called, replaced the less effective Vineberg operation (implanting a mammary artery in the myocardium) and became a favored operation worldwide. Favaloro justifiably earned many honors, especially for his rigorous collection of data to establish the value of the procedure. 

During his time at the Cleveland Clinic, he was still mindful of the lagging state of surgery in his native city and wanted no less than to bring the Cleveland Clinic to La Plata. At the height of his fame, he resigned his position at the Clinic, moved to La Plata in June of 1971, and began to assemble a cardiac institute. As Chief of Cardiac Surgery at the Clinica Güemes Hospital, he and his brother put together, in 1975, the Favaloro Foundation, a nonprofit organization devoted to cardiology and cardiac surgery. Tragically, René’s brother died in an accident one year later and René helped raise his four children, two of whom became physicians. In 1978 an eight-story building was donated to the Foundation as a research institute. Two years later, René performed the first cardiac transplant in Argentina and established a teaching unit in the hospital. 

René's worldwide reputation helped him raise funds for a new institute that combined cardiology, teaching, and research into one unit: The Institute of Cardiology and Cardiovascular Surgery. It resembled the National Heart, Lung, and Blood Institute in the U.S. and opened in 1992 as part of the Favaloro Foundation. It was a nonprofit entity, providing care to all, regardless of ability to pay. About 25% of surgical patients had no insurance. By the seventh year, the Institute had trained at least 400 cardiologists and cardiac surgeons for work throughout South America and beyond.

Planet Heart (Corazón Planetario), by Gyula Kosice, at the Favaloro Foundation 
(Wikimedia Commons)

Outside his medical work, René was an active member of the National Commission on the Disappearance of Persons, a group investigating the tragedies of thousands of “disappeared” citizens during the military Junta regime. He took an interest in Argentina’s history and wrote two books on the life of its founding father, San Martín. He wrote a book on his life as a country doctor and another on his life at the Cleveland Clinic. His favorite fictional character was said to be Don Quixote, and many friends felt his entire life resembled a quixotic quest.

Maintaining a nonprofit foundation requires money, and when times were prosperous the Institute received adequate funds. However, in the late 1900s Argentina’s finances fell into serious trouble. The usual subsidies from government and private agencies dried up. René struggled with the Institute’s increasing debt, but to no avail. Letters to the government went unheeded. In desperation, on July 29, 2000, at the age of 77, René shook the conscience of Argentina to the core when he pointed a revolver to his chest and ended his life. He left a long letter detailing his accomplishments in his home country and the corruption he was surrounded with. He said a goodbye to his family and ordered that his body be cremated and his ashes scattered in the hills near Jacinto Aráuz, where he had labored for twelve years as a rural physician.

Public outrage helped the Favaloro Foundation survive the crisis and René would be happy to know that the Foundation now is a major cardiac center in Argentina, as he dreamed it would be.

 

SOURCES:

 

Captur, Gabriella, “Memento for René Favaloro.” Texas Heart Institute Journal 2004; 31(1): 47-60.

Favaloro, René, “Landmarks in the Development of Coronary Bypass Surgery.” Circulation 1998; 98(5): 466-78.

Favoloro suicide letter, available at:    https://web.archive.org/web/20160305021334/http://www.avizora.com/publicaciones/biografias/textos/textos_f/0013_favaloro_rene_anexo_01.htm

Fye, Bruce, Caring for the Heart: Mayo Clinic and the Rise of Specialization, 2015; Oxford Univ Press, pp 315-342.

Rubenstein, Robyn, et al, “René Gerónimo Favaloro (1923-2000): A Man Who Struggled with Matters of the Heart.” American Surgeon, January 2018, 7-11.

Favaloro, R, Recuerdos de un Médico Rural, 2^nd edition, Editorial Sudamericana, 2018.

Favaloro, R, De la Pampa a Los Estados Unidos, digital edition, Random House, 2012.

"Argentina Searches it Soul over a Suicide," New York Times, August 7, 2000.