Simon Flexner

Simon Flexner was the fourth child of Esther and Morris Flexner. He came from an educated Jewish family in Czechoslovakia who immigrated to Kentucky. She was born in Alsace, France. Starting as a peddler, Morris Flexner became a successful wholesale merchant.

The student years
Simon Flexner attended public school in Louisville and was apprenticed to a druggist who sent him to the Louisville College of Pharmacy, from which he was graduated in 1882. He then worked in his eldest brother’s drugstore and studied medicine at the University of Louisville, receiving the M.D. degree in 1889. Although the medical school then provided little opportunity for laboratory study, Flexner, acquired a microscope, with which he studied pathological tissues and made microscopic examinations for doctors who patronized the Flexner pharmacy.

In 1890, at the suggestion of his brother, the educator Abraham Flexner (1866-1959), Simon went to Baltimore to study pathology and bacteriology at the Johns Hopkins Hospital with William Henry Welch (1850-1934), who gave him a fellowship. He became associate professor of pathology in 1891 and in 1892, when the Johns Hopkins Medical School opened, Welch made him his first assistant in the department of pathology. At this time Flexner first became involved in the study of cerebrospinal meningitis. In 1893 he visited Europe, working with Friedrich von Recklinghausen (1833-1910) in Strassburg, and also visited Prague.

Professor of pathology
On his return Flexner became resident pathologist at the Johns Hopkins Hospital, teaching pathological anatomy 1895-1898. By 1898 he was appointed full professor of pathological anatomy at Johns Hopkins University. In 1899, following the acquisition of the Philippine Islands by the United States, Flexner and two medical students, one of them Llewellys Frederick Barker, spent several months in Manila studying health conditions. In 1899, during this stay, he isolated an organism that causes a prevalent from of dysentery. This Bacillus dysenteriae (now Shigella dysenteriae) is still commonly known as Flexner's bacillus. On his way to Manila, Flexner visited Japan and visited the Kitasato institute

Also in 1899, he was appointed professor of pathology at the University of Pennsylvania, where he organized an excellent staff, planned a new laboratory building, and carried out important researches on experimental dysentery, on experimental pancreatitis, and on immunological problems, especially with regard to haemolysis and agglutination. One of his associates was the brilliant young Japanese physician Hideyo Noguchi (1876-1928) who came from Japan inexperienced and penniless and found in Flexner a lifelong friend and guide.

When bubonic plague broke put in California in 1901, the federal government sent Flexner to San Francisco to study the epidemic. Within a month he and a few associates confirmed the presence of the plague bacillus and made a report to health authorities that aided them in eradicating the disease.

Rockefeller Institute
In 1901 John D(avison) Rockefeller (1839-1937) and his son John D. Rockefeller, Jr. (1874-1960), were planning the creation of the Rockefeller Institute for Medical research in New York City. Flexner, now thirty eight years old and beginning to be nationally known, was appointed to the institute’s board of scientific directors, which was composed of seven eminent medical men and headed by his friend and mentor William H. Welch. In 1902 Flexner was chosen to lead a department of pathology and bacteriology in the institute, and soon he established himself as head of the whole enterprise. Flexner was head of the institute from 1920 to 1935. Under Flexner’s leadership the Rockefeller Institute became the world’s leading centre for virus research.

Flexner brought together a strong group of investigators, including Hideyo Noguchi, Samuel James Meltzer (1851-1920), Phoebus Aaron Levene (1869-1940), Jacques Loeb (1859-1924), Eugene Lindsay Opie (1873-1971), Rufus I. Cole (1872-1966), and Francis Peuton Rous (1879-1970). Alexis Carrel (1873-1944) joined the staff in 1906. Flexner’s colleagues found him a man of exceedingly keen intelligence, with a reserved manner that concealed a sympathetic heart. He directed his staff with great skill, giving free rein to those who showed independent competence while guiding with a wise hand those who needed advice. His financial acumen impressed the astute patron of the institute, who showed his confidence by successive additions of funds.

Meningitis
In 1892, Simon Flexner began research on cerebrospinal meningitis, a meningococcal disease with an untreated mortality rate between 70 and 90 %. At the Rockefeller Institute, experimenting on Monkeys, he developed a promising serum treatment for the disease by 1903, which he used extensively during the epidemic of cerebrospinal meningitis that hit New York in 1906.

Also in 1906, the German physician Georg Jochmann (1874-1915), independent of Flexner, published on serodiagnostics and serum therapy for epidemic meningitis. Among 1300 patients Flexner reported in 1913, mortality was reduced to 31 percent. Among 169 children with meningococcal meningitis treated with intrathecal antiserum at Bellevue Hospital, New York, between 1928 and 1936, the outcome was even more favourable, with mortality of about 20 percent.

This serum remained the best treatment until the sulpha drugs were introduced in the late 1930's. The first sulpha drug, protonsil, was discovered by the German physician and chemist Gerhard Johannes Paul Domagk (1895-1964) in 1935. His discovery earned Domagk the Nobel Prize in Physiology or Medicine for 1939.

For several years, Flexner kept his serum under his close supervision, with the result that the Rockefeller Institute became the primary source for knowledge about meningitis and its treatment.

Infecting monkeys with poliomyelitis
Flexner led the research team that identified the virus causing poliomyelitis. In 1910, when poliomyelitis was epidemic in New York, Flexner and his assistants determined the way in which the virus is transmitted and showed that it enters the body through the nose, attacking the olfactory nerve. With Paul Aldin Lewis (1879-1929) he demonstrated that monkeys can be infected by administering poliomyelitis virus in the nasopharynx.

This success enabled the investigators to keep the virus alive in the laboratory and thus ultimately led to the preparation of protective vaccines in the 1950's by Albert Bruce Sabin (1906-1993) and Jonas Edward Salk (1914-1995).

The Rockefeller Institute, quite early in its history, came under strong attack from organizations opposed to the use of animals in experiments on the causes of disease. Flexner’s accomplishments in such work and his calm generalship made him a natural leader in the successful deterrence of these opponents.

A man for all seasons
Flexner’s medical and biographical accomplishments led to public service in various health fields, as chairman of the Public Health Commission of New York State, as medical consultant of the U.S. Army during World War I, and as member of the China Medical Board of the Rockefeller Foundation. In 1902 he succeeded William H. Welch as editor of the The Journal of Experimental Medicine.

His executive competence was recognized by trusteeships of the Rockefeller Foundation, the Carnegie Foundation for the Advancement of Teaching, and the Johns Hopkins University. A little known, but very important public service was his leadership in establishing fellowships of the National Research Council, provided by the Rockefeller Foundation, for promising young medical scientists.

Flexner was elected member of the American Philosophical Society in 1901, the National Academy of Sciences in 1908, and foreign member of the Royal Society in 1919.

In 1937-1938 Oxford University in England called him to its george Eastman professorship, at a time when his counsel was needed in the organization of medical professorships endowed by Lord Nuffield at Oxford's Radcliffe Infirmary. William Richard Morris Nuffield, Viscount, Baron Nuffield of Nuffield (1877-1963), was a British industrialist and philanthropist whose automobile manufacturing firm introduced the Morris cars.

In 1903 Flexner married Helen Whitall Thomas, member of a prominent Quaker Family of Baltimore. Helen's father played an important role in establishing The Johns Hopkins University and its Medical School, and Bryn Mawr College, of which her sister, Martha Carey Thomas (1857-1935), was president. She helped to expand Flexner's intellectual interests beyond the medical sciences, giving him an appreciation of literature and the arts. Of their two sons, William became a physicist and James Thomas (1908-2003) a writer and historian of American culture.

During his long career Flexner published several hundred scientific papers, lectures, and essays. At the age of seventy-eight he published jointly with his son James a notable biography, William H. Welch and the Heroic Age of American Medicine (New York, 1941). He quietly resigned the directorship of the Rockefeller Institute in 1935.

We thank Patrick Jucker-Kupper, Switzerland, and David Cox, for information submitted.

• The histological changes in experimental diphteria.
  W. H. Welch and S. Flexner.
  The Johns Hopkins Hospital Bulletin, Baltimore, 1891, 2: 107-110.
  See also: The Johns Hopkins Hospital Bulletin, Baltimore, 1892, 3: 17-18.
• Tuberculosis of knee. Proceedings: Johns Hopkins Medical Society.
  The Johns Hopkins Hospital Bulletin, 1891, 2: 63.
• A peculiar glioma (neuroepithelioma?) of the retina.
  The Johns Hopkins Hospital Bulletin, 1891, 2: 115.
• The histological lesions produced by the tox-albumen of diphtheria.
  W. H. Welch and S. Flexner.
  The Johns Hopkins Hospital Bulletin, Baltimore, 1892, 3: 17-18.
• Tuberculosis of aorta. Proceedings: Johns Hopkins Medical Society.
  The Johns Hopkins Hospital Bulletin, 1891, 2: 120.
• Lympho-sarcomata.
  (Proceedings). The Johns Hopkins Hospital Bulletin, 1892, 3: 32.
• A case of primary carcinoma of the pancreas with multiple carcinosis. The organisms of cancer.
  The Johns Hopkins Hospital Bulletin, 1892, 3: 54.
• Amoebae in an abscess of the jaw.
  The Johns Hopkins Hospital Bulletin, 1892, 3: 104.
• Sarcoma of the peri-pancreatic lymph glands with miliary sarcomatosis of the peritoneum, etc. (Proceedings: The Johns Hopkins Hospital Bulletin, 1892, 3: 121.
• Tuberculosis of oesophagus. The Johns Hopkins Hospital Bulletin, 1893, 4: 4.
• Primary tuberculosis of the intestine.
  (Proceedings). The Johns Hopkins Hospital Bulletin, 1893, 4: 13.
• Tuberculosis of clavicle, infection of pleura and peritoneum, and general miliary tuberculosis. Proceedings: Johns Hopkins Medical Society .
  The Johns Hopkins Hospital Bulletin, 1893, 4: 13.
  The Johns Hopkins Hospital Bulletin, 1893, 4: 16, 31, 51, 67, 80, 98, 119, 136.
• Diphtheria with broncho-pneumonia.
  The Johns Hopkins Hospital Bulletin, 1893, 4: 32.
• Peritonitis caused by the Proteus vulgaris.
  The Johns Hopkins Hospital Bulletin, 1893, 4: 34.
• Demonstration of specimen of amoebic abscess of liver. (Proceedings).
  With William Sydney Thayer (1864-1932).
  The Johns Hopkins Hospital Bulletin, 1893, 4: 56.
• Exhibition of specimens of cystic kidney. (Proceedings).
  The Johns Hopkins Hospital Bulletin, 1893, 4: 110.
• Exhibition of specimens from a case of acute pericarditis, pleuritis, and peritonitis, associated with contracted kidney.
  (Proceedings). The Johns Hopkins Hospital Bulletin, 1894, 5: 17.
• Fatty degeneration of the heart muscle.
  The Johns Hopkins Hospital Bulletin, 1894, 5: 26.
• The bacillus of the plague. The Johns Hopkins Hospital Bulletin, 1894, 5: 96.
• Primary diphtheria of the lips and gums. With Herbert D. Pease.
  The Johns Hopkins Hospital Bulletin, 1895, 6: 22.
• Peritonitis caused by the invasion of the Micrococcus lanceolatus from the intestine. The Johns Hopkins Hospital Bulletin, 1895, 6: 64.
• Phthisis pulmonalis with the formation of the large trabeculated cavities.
  (Proceedings). The Johns Hopkins Hospital Bulletin, 1895, 6: 69.
• Primary tuberculosis of the serous membranes, involving the pleura and peritoneum. (Proceedings). The Johns Hopkins Hospital Bulletin, 1895, 6: 69.
• A case of anthrax in a human being. (Proceedings).
  The Johns Hopkins Hospital Bulletin, 1895, 6: 94.
• Obituary: Oppenheimer, Arthur R. .
  The Johns Hopkins Hospital Bulletin, 1895, 6: 95.
• Bacillus pyogenes filiformis (Nov. spec.).
  The Johns Hopkins Hospital Bulletin, 1895, 6: 147.
• A case of combined protozoan and bacterial infection.
  The Johns Hopkins Hospital Bulletin, 1896, 7: 171.
• The bubonic plague. The Johns Hopkins Hospital Bulletin, 1896, 7: 181.
• Pseudo-tuberculosis hominis streptothricha.
  The Johns Hopkins Hospital Bulletin, 1897, 8: 128.
• The pathology of toxalbumin intoxication.
  The Johns Hopkins Hospital Reports, 1897, 6: 259.
• Typhoid infection without intestinal lesions.
  With Norman Mac Leod Harris (1870-1953).
  The Johns Hopkins Hospital Bulletin, 1897, 8: 259
• Pseudo-tuberculosis hominis streptotricha.
  The Johns Hopkins Hospital Bulletin, Baltimore, 75, 1897.
• Perforation of the inferior vena cava in amoebic abscesses of the liver.
  The American Journal of the Medical Sciences, No. 5, 1897.
• The histological changes produced by ricin and abrin intoxications.
  The Journal of Experimental Medicine, New York, 1897, 2:197.
• On the occurrence of the fat-splitting ferment in the peritoneal fat necroses and the histology of these lesions.
  The Journal of Experimental Medicine, New York, 1897, 2: 413, 1897.
• Report upon an expedition sent by Johns Hopkins University to investigate the prevalent diseases in the Philippines.
  With Llewellys Franklin Barker (1867-1943).
  The Johns Hopkins Hospital Bulletin, 1898, 9: 37
• On the etiology of tropical dysentery.
  The Johns Hopkins Hospital Bulletin, 1900, 11: 231-242.
  The organism isolated by Flexner was at first thought to be identical with Shiga's bacillus. In 1902 Martini and Otto Lentz (1873-1952) showed it to be different. It was named bacterium flexneri, and later Shigella flexneri.
• The Prevalent Diseases in the Philippines.
  With L. F. Barker. Science, 1900, 11: 521-28.
• On the Etiology of Tropical Dysentery.
  Philadelphia Medical Journal, 1900, 6: 414-24.
• Snake venom in relation to haemolysis, bacteriolusys, and toxicity.
  With Hideyo Noguchi.
  The Journal of Experimental Medicine, New York, 1902, 6: 277-301.
• Bacillary Dysentery. Therapeutic Gazette, 1902, 26: 218-20.
• Concerning a serum therpay for experimental infection with Diplococcus intracellularis. The Journal of Experimental Medicine, 1907, 9: 168-185.
• Serum treatment of epidemic cerebrospinal meningitis.
  With James Wesley Jobling (born 1876).
  The Journal of Experimental Medicine, New York, 1908, 10: 131-203.
• Experimental poliomyelitis in monkeys: active immunization and passive serum protection. With Paul A. Lewis (1879-1929).
  The Journal of the American Medical Association, 1910, 54: 1780-1782.
  Demonstration of antibodies in convalescent serum in monkeys.
• The results of the serum treatment in thirteen hundred cases of epidemic meningitis. The Journal of Experimental Medicine, 1913, 17: 553-576.
• Physiological stimulation of the choroid plexus and experimental poliomyelitis.
  With Harold Lindsay Amoss (1886-1956) and Frederick Eberson.
  The Journal of Experimental Medicine, 1918, 27: 679-687.
• The passage of neutralizing substance from the blood into the cerebrospinal fluid in actively immunized monkeys. With Harold L. Amoss.
  The Journal of Experimental Medicine, 1918, 28: 11-17.
• Control of meningitis.
  Journal of the American Medical Association, 1918, 71: 638-639.
• Persistence of the virus of poliomyelitis in the nasopharynx.
  With Harold L. Amoss.
  The Journal of Experimental Medicine, 1919, 29: 379-395.
• Epidemiology and recent epidemics, Science, 1919, 50: 313-319.
• Epidemiology and recent epidemics.
  Journal of the American Medical Association, 1919, 73: 949-952.
• Experiments on the nasal route of infection in poliomyelitis.
  With Harold L. Amoss. The Journal of Experimental Medicine, 1920, 31: 123-134.
• Twenty-five years of bacteriology: a fragment of medical research.
  Science, 1920, 52: 615-632.
• William Henry Welch. A biographical sketch. Science, 1920, 52: 417-433.
• Encephalitis and poliomyelitis.
  Proceedings of the National Academy of Sciences, 1920, 6: 103-104.
• Lethargic encephalitis. Poliomyelitis and Australian x-disease.
  The Johns Hopkins Hospital Bulletin, 1920, 31:249-252.
• Serum treatment of bacillary dysentery.
  Journal of the American Medical Association, 1921, 76: 108-109.
• General consideration regarding serum and vaccine therapy.
  Journal of the American Medical Association. 1921, 76: 33-34.
• A physical basis for epidemiology. With Harold L. Amoss.
  Proceedings of the National Academy of Sciences, 1921, 7: 319-322.
• Experimental epidemiology. Introductory.
  The Journal of Experimental Medicine,.1922, 36: 9-14.
• Tributes to Dr. Biggs from some of his colleagues.
  Health News, 1923, 38: 166-167.
  Herman Michael Biggs (1859-1923) established the first bacteriological laboratory under the New York public health system.
• Vagaries of a typhoid carrier. Health News, 1923, 38: 4-6.
• Epidemic (lethargic) encephalitis and allied conditions.
  Journal of the American Medical Association. 1923, 81: 1785-1789.
• Epidemic (lethargic) encephalitis and allied conditions.
  Journal of the American Medical Association. 1923, 81: 1688-1693.
• The Edward K. Dunham Lectureship for the Promotion of Medical Science.
  Science. 1923, 57: 683-685.
• Revived activity of the virus of poliomyelitis. With Harold L. Amoss.
  The Journal of Experimental Medicine,. 1924, 39: 191-197.
• An immunizing strain of the virus of poliomyeltis. With Harold L. Amoss.
  The Journal of Experimental Medicine, 1924, 39: 625-630.
• T. Mitchell Prudden, 1849-1924. Science, 1924, 60: 415-419.
  Theophil Mitchell Prudden, American anthropologist, one of the foremost students of Southwestern archaeology during the late nineteenth and early twentieth centuries.
• Memorial to Jacques Loeb. Jacques Loeb and The Rockefeller Institute for Medical Research.
  Proceedings of the Society for Experimental Biology & Medicine. 1924, 21: xiii-xiv
• Contributions to the pathology of experimental virus encephalitis. 1. An exotic strain of encephalitogenic virus. With Harold L. Amoss.
  The Journal of Experimental Medicine, 1925, 41: 215-231.
• Contributions to the pathology of experimental virus encephalitis. 2. Heroetic strains of encephalitogenic virus. With Harold L. Amoss.
  The Journal of Experimental Medicine, 1925;41:233-244
• Contributions to the pathology of experimental virus encephalitis. 3. Varieties and properties of the herpes virus. With Harold L. Amoss.
  The Journal of Experimental Medicine, 1925, 41: 357-377.
• Virus encephalitis in the rabbit.
  Proceedings of the National Academy of Sciences. 1925, 11: 84-87.
• The advancement of epidemiology through experiment.
  American journal of the medical sciences. 1926;171:469-479.
• The advancement of epidemiology through experiment.
  American journal of the medical sciences. 1926;171:625-635.
• Dr. Welch and the Johns Hopkins University. Science. 1926;63:272-273.
• The Evolution and Organization of the University Clinic. Oxford, UK, 1939.
• G. Jochmann:
  Versuche zur Serodiagnostik und Serotherapie der epidemischen Genickstarre.
  Deutsche medizinische Wochenschrift, 1906, 1: 788-793.
  Jochmann, independent of Flexner, published on serodiagnostics and serum therapy for epidemic meningitis.
• George W. Corner (1889-1981):
  Flexner, Simon. In: Charles Coulston Gillispie, editor in chief: Dictionary of Scientific Biographies. Charles Scribner’s Sons. New York, 1970.