World of Microbiology and Immunology | Florey, Howard Walter (1898-1968)

English pathologist

The work of Howard Walter Florey gave the world one of its most valuable disease-fighting drugs, penicillin. Alexander Fleming discovered, in 1929, the mold that produced an antibacterial substance, but was unable to isolate it. Nearly a decade later, Florey and his colleague, biochemist Ernst Chain, set out to isolate the active ingredient in Fleming's mold and then conduct the clinical tests that demonstrated penicillin's remarkable therapeutic value. Florey and Chain reported the initial success of their clinical trials in 1940, and the drug's value was quickly recognized. In 1945, Florey shared the Nobel Prize in medicine or physiology with Fleming and Chain.

Howard Walter Florey was born in Adelaide, Australia. He was one of three children and the only son born to Joseph Florey, a boot manufacturer, and Bertha Mary Wadham Florey, Joseph's second wife. Florey expressed an interest in science early in life. Rather than follow his father's career path, he decided to pursue a degree in medicine. Scholarships afforded him an education at St. Peter's Collegiate School and Adelaide University, the latter of which awarded him a Bachelor of Science degree in 1921. An impressive academic career earned Florey a Rhodes scholarship to Oxford University in England. There he enrolled in Magdalen College in January 1922. His academic prowess continued at Oxford, where he became an excellent student of physiology under the tutelage of renowned neurophysiologist Sir Charles Scott Sherrington. Placing first in his class in the physiology examination, he was appointed to a teaching position by Sherrington in 1923.

Florey's education continued at Cambridge University as a John Lucas Walker Student. Already fortunate enough to have learned under a master such as Sherrington, he now came under the influence of Sir Frederick Gowland Hopkins, who taught Florey the importance of studying biochemical reactions in cells. A Rockefeller Traveling Scholarship sent Florey to the United States in 1925, to work with physiologist Alfred Newton Richards at the University of Pennsylvania, a collaboration that would later prove beneficial to Florey's own research. On his return to England and Cambridge in 1926, Florey received a research fellowship in pathology at London Hospital. That same year, he married Mary Ethel Hayter Reed, an Australian whom he'd met during medical school at Adelaide University. The couple eventually had two children.

Florey received his Ph.D. from Cambridge in 1927, and remained there as Huddersfield Lecturer in Special Pathology. Equipped with a firm background in physiology, he was now in a position to pursue experimental research using an approach new to the field of pathology. Instead of describing diseased tissues and organs, Florey applied physiologic concepts to the study of healthy biological systems as a means of better recognizing the nature of disease. It was during this period in which Florey first became familiar with the work of Alexander Fleming. His own work on mucus secretion led him to investigate the intestine's resistance to bacterial infection. As he became more engrossed in antibacterial substances, Florey came across Fleming's report of 1921 describing the enzyme lysozyme, which possessed antibacterial properties. The enzyme, found in the tears, nasal secretions, and saliva of humans, piqued Florey's interest, and convinced him that collaboration with a chemist would benefit his research. His work with lysozyme showed that extracts from natural substances, such as plants, fungi and certain types of bacteria, had the ability to destroy harmful bacteria.

Florey left Cambridge in 1931 to become professor of pathology at the University of Sheffield, returning to Oxford in 1935 as director of the new Sir William Dunn School of Pathology. There, at the recommendation of Hopkins, his productive collaboration began with the German biochemist Ernst Chain. Florey remained interested in antibacterial substances even as he expanded his research projects into new areas, such as cancer studies. During the mid 1930s, sulfonamides, or sulfa drugs, had been introduced as clinically effective against streptococcal infections, an announcement which boosted Florey's interest in the field. At Florey's suggestion, Chain undertook biochemical studies of lysozyme. He read much of the scientific literature on antibacterial substances, including Fleming's 1929 report on the antibacterial properties of a substance extracted from a Penicillium mold, which he called penicillin. Chain discovered that lysozyme acted against certain bacteria by catalyzing the breakdown of polysaccharides in them, and thought that penicillin might also be an enzyme with the ability to disrupt some bacterial component. Chain and Florey began to study this hypothesis, with Chain concentrating on isolating and characterizing the enzyme, and Florey studying its biological properties.

To his surprise, Chain discovered that penicillin was not a protein, therefore it could not be an enzyme. His challenge now was to determine the chemical nature of penicillin, made all the more difficult because it was so unstable in the laboratory. It was, in part, for this very reason that Fleming eventually abandoned a focused pursuit of the active ingredient in Penicillium mold. Eventually, work by Chain and others led to a protocol for keeping penicillin stable in solution. By the end of 1938, Florey began to seek funds to support more vigorous research into penicillin. He was becoming convinced that this antibacterial substance could have great practical clinical value. Florey was successful in obtaining two major grants, one from the Medical Research Council in England, the other from the Rockefeller Foundation in the United States.

By March of 1940, Chain had finally isolated about one hundred milligrams of penicillin from broth cultures. Employing a freeze-drying technique, he extracted the yellowish-brown powder in a form that was yet only ten percent pure. It was non-toxic when injected into mice and retained antibacterial properties against many different pathogens. In May of 1940, Florey conducted an important experiment to test this promising new drug. He infected eight mice with lethal doses of streptococci bacteria, then treated four of them with penicillin. The following day, the four untreated mice were dead, while three of the four mice treated with penicillin had survived. Though one of the mice that had been given a smaller dose died two days later, Florey showed that penicillin had excellent prospects, and began additional tests. In 1941, enough penicillin had been produced to run the first clinical trial on humans. Patients suffering from severe staphylococcal and streptococcal infections recovered at a remarkable rate, bearing out the earlier success of the drugs in animals. At the outset of World War II, however, the facilities needed to produce large quantities of penicillin were not available. Florey went to the United States where, with the help of his former colleague, Alfred Richards, he was able to arrange for a U.S. government lab to begin large-scale penicillin production. By 1943, penicillin was being used to treat infections suffered by wounded soldiers on the battlefront.

Recognition for Florey's work came quickly. In 1942, he was elected a fellow in the prestigious British scientific organization, the Royal Society, even before the importance of penicillin was fully realized. Two years later, Florey was knighted. In 1945, Florey, Chain and Fleming shared the Nobel Prize in medicine or physiology for the discovery of penicillin.

Penicillin prevents bacteria from synthesizing intact cell walls. Without the rigid, protective cell wall, a bacterium usually bursts and dies. Penicillin does not kill resting bacteria, only prevents their proliferation. Penicillin is active against many of the gram positive and a few gram negative bacteria. (The gram negative/positive designation refers to a staining technique used in identification of microbes.) Penicillin has been used in the treatment of pneumonia, meningitis, many throat and ear infections, Scarlet Fever, endocarditis (heart infection), gonorrhea, and syphilis.

Following his work with penicillin, Florey retained an interest in antibacterial substances, including the cephalosporins, a group of drugs that produced effects similar to penicillin. He also returned to his study of capillaries, which he had begun under Sherrington, but would now be aided by the recently developed electron microscope. Florey remained interested in Australia, as well. In 1944, the prime minister of Australia asked Florey to conduct a review of the country's medical research. During his trip, Florey found laboratories and research facilities to be far below the quality he expected. The trip inspired efforts to establish graduate-level research programs at the Australian National University. For a while, it looked as if Florey might even return to Australia to head a new medical institute at the University. That never occurred, although Florey did do much to help plan the institute and recruit scientists to it. During the late 1940s and 1950s, Florey made trips almost every year to Australia to provide consultation to the new Australian National University, to which he was appointed Chancellor in 1965.

Florey's stature as a scientist earned him many honors in addition to the Nobel Prize. In 1960, he became president of the Royal Society, a position he held until 1965. Tapping his experience as an administrator, Florey invigorated this prestigious scientific organization by boosting its membership and increasing its role in society. In 1962, he was elected Provost of Queen's College, Oxford University, the first scientist to hold that position. He accepted the presidency of the British Family Planning Association in 1965, and used the post to promote more research on contraception and the legalization of abortion. That same year, he was granted a peerage, becoming Baron Florey of Adelaide and Marston.