An unpromising boy in Louisville
Simon Flexner was born in Louisville, Kentucky, on March 25, 1863. His father, Moritz (Morris) Flexner, was a Jewish immigrant from a small town in Bohemia who had been sent as a boy to be raised by an uncle in Strasbourg. Around 1850 Moritz crossed to America in steerage with no money and no connections and headed for New Orleans, where yellow fever killed all five of his companions; he survived thanks to the nursing of Catholic nuns and moved up the river to Louisville, where he worked as a peddler. His wife, Esther, came from Germany. They had nine children, and Simon was the fourth of seven sons.
Simon was no scholar. He was inattentive at school, played pranks, got into trouble and was fired from several jobs. As a boy he nearly died of typhoid fever; his mother nursed him, slept beside him and talked with him, and when he recovered he felt, he said, born again. He worked in a family graphic studio and then as an indentured assistant to a local pharmacist, often on call around the clock.
From pharmacy to pathology
The pharmacy job required a short course each year, and it awakened his interest in science and, above all, in the microscope. He read anatomy, histology and bacteriology on his own and became skilled at examining tissue specimens; he won local fame when he spotted on a slide that a judge’s tumour had not been completely removed. He earned a degree from the Louisville College of Pharmacy, worked for years with his eldest brother Jacob, a pharmacist and physician, and in 1889 received his medical degree from a Louisville medical school, having, as he later admitted, never examined a patient or listened to a heart.
He wanted to be a pathologist. Johns Hopkins University turned down his application for a fellowship, and it was his younger brother Abraham, then a successful schoolteacher, who paid his way for a year. At Hopkins he impressed William Welch, the great pathologist, with his diligence and intelligence, and rose rapidly from student to assistant to professor. He investigated diphtheria and an outbreak of meningitis among miners, and he was the first to describe a characteristic pattern of cells in retinoblastoma, an eye cancer of children, still known as Flexner-Wintersteiner rosettes.
Even before medical school he had published a paper in the journal Science on the chemical nature of a granular material he found in a beehive. At Hopkins, Welch sent him in 1893 on a study tour of England, Holland, Germany and Austria, where he met Rudolf Virchow and other leaders of European pathology and admired the discipline and efficiency of German academic institutions. Cornell University tried to lure him away with a salary of $8,500 a year, a large sum at the time, but he stayed in Baltimore until Pennsylvania called. The Jewish Encyclopedia, writing while he was still at Pennsylvania, noted that he had also studied at the universities of Strasbourg and Prague, and listed his memberships of learned societies from Philadelphia to Bologna.
Disease detective
In 1899 Flexner became professor of pathology at the University of Pennsylvania, despite opposition from antisemitic factions of the faculty and trustees. Before taking up the post he went with a Johns Hopkins medical commission to the Philippines, where American troops were dying of tropical diseases, and identified a cause of a particularly severe form of dysentery. The bacterium, Shigella flexneri, still bears his name.
In 1901 he was sent to San Francisco as a member of the federal plague commission and confirmed that an outbreak there was bubonic plague. He was becoming the best-known expert on infectious disease in the United States.
At Pennsylvania he built an outstanding department. Its papers ranged across tuberculosis, cancers of the pancreas, plague, anthrax, typhoid, snake venom and kidney disease, and Flexner himself worked on experimental dysentery, pancreatitis and the way the blood’s defences recognise bacteria. He was in constant demand as a consultant whenever a mysterious outbreak appeared.
Building the Rockefeller Institute
In 1901 John D. Rockefeller, at the urging of his son and his adviser Frederick Gates, decided to found an institute for medical research modelled on the Pasteur Institute in Paris. Welch led its scientific board, and Flexner, his former student, became the first director of its laboratories, leading the new Rockefeller Institute for Medical Research in New York until 1935. Nothing like it existed in America: a place where scientists were paid simply to do research, free of teaching and private practice.
Flexner shaped it into a model for modern biomedical research. He recruited outstanding scientists and gave them freedom, among them the surgeon Alexis Carrel, who received the Nobel Prize in 1912, and later Karl Landsteiner, the discoverer of blood groups, whom Flexner brought from Europe in 1923. In 1910 the institute opened the Rockefeller Hospital, America’s first hospital devoted to clinical research, where patients were treated by doctors who also studied their diseases in the laboratory. It became Rockefeller University in 1965, and 26 Nobel laureates have been affiliated with it.
He had an eye for talent. Among the young scientists who worked in his laboratory were Hideyo Noguchi, the Japanese bacteriologist who later isolated the spirochaete that causes syphilis, and Cornelius Rhoads, who went on to direct the Sloan-Kettering Institute for cancer research. Flexner’s style was to hire gifted people, protect their time and judge them by results.
A serum against meningitis
Epidemic cerebrospinal meningitis, an infection of the membranes around the brain and spinal cord by the meningococcus bacterium, terrified cities in the early 1900s. It struck suddenly, and most of its victims died. Flexner and his colleagues at the institute developed an antiserum, an antibody-rich serum from animals immunised against the bacteria, and gave it by injection directly into the space around the spinal cord, where the infection was.
The serum was first used on patients in 1906, and the Rockefeller Institute supplied it to doctors across a wide territory. In 1913 Flexner published the results of 1,300 treated cases gathered from a wide territory over several years. Treatment cut the death rate from about 75 per cent to about 25 per cent, and the earlier the serum was given, the better patients did. It was one of the first effective treatments for a deadly bacterial infection, decades before antibiotics, and it saved many lives until sulfa drugs and penicillin replaced it.
Polio and beyond
Flexner also took on poliomyelitis, the paralysing disease of children. In 1909, working with Paul Lewis, he transmitted polio from monkey to monkey and showed that it was caused by an agent small enough to pass through filters that stopped bacteria, a virus. This work, done at the same time as that of Karl Landsteiner and Erwin Popper in Vienna, laid the foundations of knowledge about the cause and immunology of polio on which the vaccines of the 1950s would eventually build. His institute also worked on hookworm and tropical sprue in Puerto Rico.
As early as 1907 he predicted in a lecture at the University of Chicago that surgeons would one day replace diseased organs, including arteries, stomachs, kidneys and the heart, with healthy ones, a vision realised in the second half of the century.
A remarkable Jewish family
Flexner grew up in the Jewish community of Louisville, and his family became one of the most distinguished Jewish families in America. His brother Abraham, who had paid for his studies, wrote the Flexner Report on medical education, which reshaped how doctors are trained in North America, and later founded the Institute for Advanced Study in Princeton. Another brother, Bernard, a lawyer, became a leader of the Zionist movement in the United States. The Jewish Encyclopedia, published in the early 1900s, already included an entry on Simon.
His Jewish background was not irrelevant to his career: his appointment at the University of Pennsylvania went through over the objections of antisemitic members of the faculty and trustees. In 1903 he married Helen Thomas, from a prominent Quaker family in Baltimore, who became a professor of English; their son James Thomas Flexner became a celebrated historian, best known for his biography of George Washington.
Last years and legacy
Flexner retired as director of the Rockefeller Institute in 1935. In 1937 he went to Oxford as Eastman Visiting Professor. He had been elected to the National Academy of Sciences in 1908 and served as a trustee of the Rockefeller Foundation and as a close adviser to John D. Rockefeller Jr. He died of a heart attack in New York City on May 2, 1946, at the age of 83. His papers are held at the American Philosophical Society.
Flexner’s greatest legacy is an idea of how medical progress is made: by full-time scientists, well supported and free to follow their questions, working alongside doctors who treat patients. The Rockefeller Institute proved the idea in America, and research institutes and hospitals that followed adopted the same pattern. The boy from Louisville who was fired from his first jobs helped create the system that produced much of modern medicine, and his meningitis serum gave thousands of children a chance to grow up.
Sources & further reading
Simon Flexner: infectious diseases pioneer, Hektoen International · The results of the serum treatment in thirteen hundred cases of epidemic meningitis (Flexner, 1913), Journal of Experimental Medicine (PMC) · Flexner, Simon, Jewish Encyclopedia · Rockefeller University, Wikipedia · Simon Flexner, Wikipedia · Researched from the sources above and checked against them. Spotted an error? Tell us.
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