Baron Florey

Australian pathologist

• Born: September 24, 1898
• Birthplace: Adelaide, South Australia, Australia
• Died: February 21, 1968
• Place of death: Oxford, Oxfordshire, England

A wide-ranging intellect, extensive training in the sciences on which medicine has become progressively more dependent, and the capacity for organizing resources and directing efforts effectively made it possible for Florey to unlock the fundamental scientific secrets of Alexander Fleming’s discoveries of lysozyme and penicillin and to make antibiotic therapy a cornerstone of the practice of modern medicine. His isolation of the active antimicrobial ingredient in Penicillium notatum made it readily available to physicians and stands as one of the more significant scientific achievements of the twentieth century.

Early Life

Howard Walter Florey (later known as Baron Florey) was born in Adelaide, Australia, one of the larger cities of that subcontinent. His mother was Bertha Wadham, the second wife of his father, Joseph Florey, a prosperous businessman who had built up a successful boot-making company. Howard was the third of their three children. The family wealth made it possible for young Florey to have the best possible training, and he was educated first at a private school, Unley Park; then at Kyre College, where he was both the best student and a superior athlete; and finally at St. Peter’s Collegiate School, which was modeled on an English public school and was one of the best schools in Australia.

It was at St. Peter’s that Florey acquired his enthusiasm for chemistry, even though he also excelled in physics, mathematics, and history, under the tutelage of J. S. Thompson, who also imbued the boy with a love for research. As a result, Florey decided against entering his father’s business and determined to pursue a career of scientific research. Another factor in arriving at his career choice may have come from the achievements of his sister Hilda, who studied medicine and became a successful pathologist. On completing his studies at St. Peter’s, Florey elected to study medicine at the University of Adelaide, despite the fact that his interests were in scientific research rather than the clinical treatment of patients.

In 1916, Florey entered the university to pursue a course of medical study. It was the height of World War I, and despite his strong desire to enlist and serve the country, his parents both forbade his enlistment and persuaded him that he could serve better as a physician than as a simple soldier. At Adelaide, Florey continued his success in academics and sports, and since he knew that he had little interest in clinical practice and wanted to be a researcher, he sought to win a Rhodes Scholarship so that he could study physiology at Oxford University. Receiving the Rhodes Scholarship for South Australia, Florey left for England in December, 1920.

Entering Oxford to study physiology under the great Sir Charles Scott Sherrington, then sixty-five years of age and president of the Royal Society, proved to be the crucial decision of Florey’s career. It not only brought him into daily contact with and enabled him to learn from one of the greatest living scientists but also introduced him to the complex international scientific community. Under Sherrington’s guidance, Florey won first-class honors in physiology; decided to secure a D. Phil., Oxford’s highest research degree; and was launched on a career in experimental medicine with an appointment to a studentship at Cambridge University. By the end of the 1920’s, when he turned his attention to lysozyme, he was well established as a promising young scientist.

Life’s Work

Florey’s papers do not reveal how he learned about the discovery of lysozyme by Alexander Fleming, but in all probability his own research led him to Fleming’s work. Florey had begun studying the mucous secretions of the stomach, and since lysozyme was produced by human mucosa, it seems likely that Florey read of Fleming’s discovery in the Proceedings of the Royal Society or the British Journal of Experimental Pathology. While Florey’s first great achievement, of isolating lysozyme and its substrate, brought him renown and brought Fleming’s discovery to a brilliant conclusion, he also learned valuable lessons along the way. Aware of his own limitations as well as his strengths, he noted, for example, that complex research problems require a team effort to achieve solution, for if he had not been able to find talented collaborators, his work on lysozyme would never have been completed. Florey also learned that chemistry was the key to unraveling the strands of difficult problems in physiology. Florey is rightly credited with bringing the discovery of lysozyme to a conclusion, but the significance of the fact that it was done by a team he led that included a cytologist, a biochemist, and several specialized physiologists was not lost on him. Such knowledge was to serve him well later in his work on penicillin.

Eager to have control of his own research projects and concerned about his lack of independence at Cambridge, Florey accepted a position as professor of pathology at Sheffield in 1931. There, as early as 1932, Florey learned of penicillin through C. G. Paine, who had been with Fleming at St. Mary’s and had brought a Penicillium culture to Sheffield so that he could use the “mold juice” in treating various superficial infections. Florey was not, however, particularly impressed by the results of Paine’s treatments, so the “mold juice” was relegated to obscurity while other physiological research areas were explored and he revitalized the physiology department at Sheffield. He published several papers on lysozyme, lymphatics, and related topics, but in 1934 an opportunity arose for Florey to return to Oxford.

In 1934, Professor George Dreyer, then the head of the pathology department at Oxford, died unexpectedly at the age of sixty-one. A stepchild of physiology, the Department of Pathology had been generously endowed in 1922 by the trustees of Sir William Dunn’s estate, and the post was ideally suited for someone of Florey’s training and temperament. Consequently, in May, 1935, he returned to Oxford as head of the Dunn School of Pathology, in charge of dozens of researchers, technicians, and students. As head of the Dunn School, Florey soon turned it into one of the world’s outstanding biological research centers. Productive himself as a researcher, he published several important papers on secretions in conjunction with different collaborators, and his belief in building strong research teams soon brought about a critical change in his own career.

While trying to recruit a biochemist from Cambridge, Florey was advised by the head of that school’s department to consider hiring a German refugee from the Hitler regime, Ernst B. Chain. Although Chain was not the individual Florey originally wanted for the Dunn School, he nevertheless decided to bring him to Oxford. It proved to be a fateful decision. A brilliant biochemist who was only twenty-seven when he joined Florey, Chain had already worked out the biochemistry of snake venom, was an accomplished pianist, and bore a remarkable resemblance to another famous émigré from National Socialist Germany, Albert Einstein. The partnership of Florey and Chain, which began because of Florey’s continuing pursuit of the structure and properties of lysozyme, was soon to produce dramatic results far beyond anything lysozyme could offer, for the two brilliant research scientists were perfectly suited to form an extraordinary team. Chain provided intuition and originality, and Florey, equally as intuitive, supplied flawless methodology to their experiments.

It was through lysozyme that Florey and Chain began their work on penicillin. A general interest in antibacterial substances led Chain in 1938 to discover Fleming’s paper on penicillin, and soon he and Florey determined that the substance might provide a fundable research project. Neither scientist thought initially about the practical medical uses of penicillin, but rather both were intrigued by the research challenges it offered and the fact that its properties resembled those of lysozyme. Once the two learned more about the actions of penicillin, however, they were so excited by it that Florey soon came to devote all of his considerable energy to developing an antibacterial biological materials program at the Dunn School. Florey began raising money to support the project, organizing the resources necessary to see it through, and working with Chain in the laboratory to discover the secret the active antimicrobial ingredient that had eluded Fleming for so many years. The task was by no means an easy one.

The main problem with penicillin as an antimicrobial substance was never the question of whether it could kill a wide range of bacteria, which Fleming had already proved, but rather how could it be concentrated to reach therapeutic levels and whether it would be harmful to the patient. It was the great achievement of Florey and Chain to unravel the molecular structure of penicillin and refine it in such a way that it could be used with devastating effect against disease-causing microbes. By employing the new technique of “freeze-drying” to produce a refined, concentrated powder that consisted of the essential antibacterial agent in Penicillium notatum, Florey was prepared by May, 1940, to perform an experiment that proved to be a turning point in medical history. On that date he proved conclusively that penicillin could be used with dramatic effect in cases of diseases caused by bacterial infection, by infecting mice with a pathogen of the Streptococci group and then treating them with subcutaneous injections of penicillin. The experiment left no doubt of the power of penicillin, and it ensured Florey’s place in the history of modern medicine.

By 1942, Florey’s accomplishments with penicillin and lysozyme were sufficiently well known among British scientists to result in his election as a Fellow of the Royal Society, which, short of the award of a Nobel Prize, was the highest honor to which any scientist could aspire. Ironically, 1942 was also the year when Fleming, who had originally discovered the antimicrobial properties of Penicillium notatum, contacted Florey and used the refined penicillin provided by the Australian to cure a patient dying of bacterial meningitis. Many other honors were showered on Florey during the remainder of his career. He was knighted in 1944, became president of the Royal Society in 1960, and was created a life peer in 1965. Perhaps the greatest recognition of all came in 1945, when Florey, along with his colleagues Chain and Fleming, received the Nobel Prize in Physiology or Medicine for their collective work in the discovery and development of penicillin. If ever there was proof of Florey’s belief that teamwork was essential to scientific research, it came with the award of the 1945 Nobel Prize, for without Fleming’s discovery, Chain’s analytical brilliance, and Florey’s leadership qualities and meticulous experimental methodology, penicillin would never have brought about the medical revolution that occurred early in the 1940’s.

Significance

Florey may not have had the good fortune and extraordinarily well-developed powers of observation that made it possible for Fleming to notice the effect of Penicillium notatum “mold juice” on bacterial growth. Florey was a different kind of scientist, whose broad-based training, particularly in chemistry, was better suited to the precise attack of scientific problems than it was to the free-ranging curiosity that so characterized Fleming’s career. Above all else, Florey combined three attributes in roughly equal proportions that made him a research scientist of unique capability: He had leadership qualities that were quite exceptional among his peers, he was an organizer whose management of resources and skill at securing financial support for research were unrivaled, and he was an accomplished bench scientist who had the respect of brilliant colleagues. Just as Fleming’s observation of a contaminated petri dish led to the discovery of penicillin, so Florey’s isolation of the active antimicrobial substance made it possible for the entire range of diseases caused by susceptible bacteria to be brought under control through antibiotic therapy. If Florey had not, as a young scientist, been intrigued by the antibiosis of lysozyme and pursued that interest on to study penicillin, then the most powerful weapon available to modern physicians in their struggle against infectious disease, antibiotics, simply would not be available. Without the work of Florey and those he led at the Dunn School, most of the diseases that today are routinely treated as commonplace subjects for antibiotic therapy would continue to baffle physicians and significantly increase the level of human suffering and death.

Bibliography

Bud, Robert. Penicillin: Triumph and Tragedy. New York: Oxford University Press, 2007. Describes the discovery and development of penicillin, initially considered a miracle drug until it proved nonresistant to “superbugs.”

Lax, Eric. The Mold in Dr. Florey’s Coat: The Story of the Penicillin Miracle. New York: Henry Holt, 2004. Lax seeks to correct the misconception that Fleming developed penicillin. While discussing Fleming’s discovery of penicillin, Lax describes how Fleming then abandoned his research and how Florey and other scientists at Oxford University later resumed research and developed the substance.

Macfarlane, Gwyn. Alexander Fleming: The Man and the Myth. Cambridge, Mass.: Harvard University Press, 1984. While this work concentrates on Fleming’s career, it is still very useful for the insights it provides into Florey’s work on the development of penicillin in the context of the interplay between Fleming, Florey, Chain, and others who worked on the project. It also has the merit of incorporating updated scholarship on the development of penicillin.

‗‗‗‗‗‗‗. Howard Florey: The Making of a Great Scientist. New York: Oxford University Press, 1979. The only full-scale biography of Florey, this is a sympathetic but nevertheless scholarly and well-written assessment of his career and achievements. Florey’s letters and papers were utilized extensively and effectively, and the very difficult scientific problems faced by Florey and Chain are explained with admirable clarity.

Sheehan, John. The Enchanted Ring: The Untold Story of Penicillin. Cambridge, Mass.: MIT Press, 1982. A well-written account of the complex series of events that began with Fleming’s initial discovery and concluded with the practical use of penicillin as an antibiotic. This study includes some particularly impressive scholarly detective work and is especially useful for providing a backdrop for Florey’s accomplishment.