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Howard Florey

Howard Walter Florey, Baron Florey, (24 September 1898 – 21 February 1968) was an Australian pharmacologist and pathologist who shared the Nobel Prize in Physiology or Medicine in 1945 with Ernst Chain and Sir Alexander Fleming for his role in the development of penicillin.

Although Fleming received most of the credit for the discovery of penicillin, it was Florey and his team at the University of Oxford who made it into a useful and effective drug, ten years after Fleming had abandoned its development. They developed techniques for growing, purifying and manufacturing the drug, tested it for toxicity and efficacy on animals, and carried out the first clinical trials. In 1941, they used it to treat a police constable from Oxford. He started to recover, but subsequently died because Florey was unable, at that time, to make enough penicillin. Later trials in Britain, the United States and North Africa were highly successful.

A graduate of the University of Adelaide, Florey studied at the University of Oxford as a Rhodes Scholar and in the United States on a fellowship from the Rockefeller Foundation. In 1935, he became the director of the Sir William Dunn School of Pathology at Oxford. He assembled a multidisciplinary staff that could tackle major research projects. In addition to his work on penicillin, he researched many other subjects, most notably lysozyme, contraception and cephalosporins. He was involved in the founding of the Australian National University in Canberra and the establishment of its John Curtin School of Medical Research, and he served as chancellor of the Australian National University from 1965 until his death in 1968. He was elected a fellow of the Royal Society in 1941, and as its president from 1960 to 1965, he oversaw its move to new accommodations at Carlton House Terrace and the establishment of links with European organisations. In 1962, he became provost of The Queen's College, Oxford.

Florey's discoveries are estimated to have saved over 80 million lives, and he is regarded by the Australian scientific and medical community as one of its greatest figures. Australian prime minister Sir Robert Menzies said, "In terms of world well-being, Florey was the most important man ever born in Australia."

Early life and education
Howard Walter Florey was born in Malvern, a southern suburb of Adelaide, South Australia, on 24 September 1898. His surname rhymes with "sorry". He was the only son of Joseph Florey, a bootmaker from Oxfordshire in England, who as a boy moved to London where Florey's grandfather established a bootmaking business. Joseph Florey's first wife was Charlotte Ames, with whom he had two daughters, Charlotte, who was born in 1880, and Anne, who was born in 1882. After his wife contracted pulmonary tuberculosis, the family emigrated to South Australia, where it was hoped that the climate would be more congenial. Her health gradually declined and she died in April 1886. Joseph Florey established his own bootmaking business in Adelaide, and married Bertha Mary Waldham, the daughter of his housekeeper. Their first child together, Hilda, was born on 6 September 1890. She became a bacteriologist and a pioneer of laboratory medicine. A second daughter, Valetta, was born in 1891. Thus, Florey had two older sisters and two older half-sisters.

In 1906, the family moved to "Coreega", a mansion in the Adelaide suburb of Mitcham. Florey attended Unley Park School, a local private school, taking the 2 mi trip to school each day in a horse-drawn tram with Mollie Clampett, a friend who lived in the rectory adjacent to Coreega. At school he acquired the lifelong nickname "Floss", this being, like "Florrie", a common diminutive form of "Florence". He transferred to Kyre College, a private boys' school, in 1908. In 1911, he entered St Peter's College, Adelaide, where he excelled in chemistry, physics, mathematics and history. He played various sports for the school: cricket, Australian football, tennis, and track and field athletics as a sprinter and high jumper. The cost of his education was covered by four scholarships. He served in the Senior Cadets, in which he was commissioned as a second lieutenant in August 1916. After the First World War broke out in 1914, he wished to enlist, but parental permission was required and was not forthcoming. He was head boy in his final year at school, and was ranked twelfth in the state in his final examinations.

Rather than become a businessman like his father, Florey elected to follow in the footsteps of his sister Hilda, who studied medicine. He entered the University of Adelaide in March 1917, his fees paid entirely by a state scholarship. This allowed him to continue his studies after his father died from a heart attack on 15 September 1918, and the shoe company was found to be insolvent and went into liquidation. Coreega and other properties had to be sold, and in 1920, the family moved into a bungalow in Glen Osmond. Florey participated in university athletics and tennis. He was an editor of the Medical Students' Society's Review and the Adelaide University Magazine. It was through the latter that he met Mary Ethel Hayter Reed, a fellow medical student, when he asked her to contribute an article on Women in Medicine.

Rhodes Scholar
Florey decided to pursue medical research, a speciality that required study overseas. In August 1920, he applied for a Rhodes Scholarship to pursue his studies at the University of Oxford in England. His selection as the successful candidate for South Australia was announced on 8 December. This was a high honour, and came with a stipend of £300. The Rhodes Committee wanted him to commence in October, the start of the academic year at Oxford. This meant either postponing his scholarship for a year or deferring his final qualifying examinations for his medical degrees until he returned. Florey insisted that he would do neither; he would take his examinations and start at Oxford at the commencement of the Hilary term in January 1922. With the aid of the Governor of South Australia, Sir Archibald Weigall, Florey won the argument. He passed his examinations with second-class honours, and he was awarded his Bachelor of Medicine, Bachelor of Surgery degree in absentia in December 1921. During the summer break he went to Broken Hill Hospital, where he worked as a clinical assistant.

On 11 December 1921, Florey embarked for England from Port Adelaide on the SS Otira, an ocean liner of the Shaw, Savill & Albion Line, travelling for free as the ship's surgeon. The ship reached Hull on 24 January 1922, and Florey took a train to London, where his sister Anne met him at King's Cross Station. Two days later he left for Oxford, where he met with the Secretary of the Rhodes Trust, Francis James Wylie. He had to choose a college, and he chose to study at Magdalen College, Oxford, where his high school headmaster, Henry Girdlestone, had gone. He enrolled in the honour school of physiology, where he studied under the tutelage of Sir Charles Scott Sherrington. During the summer breaks he visited France, Belgium, Germany, Italy, Czechoslovakia and Austria. He became a demonstrator in the physiology department, and he applied for a fellowship in physiology at Merton College, but was passed over in favour of Gavin de Beer. He was awarded the degree of Bachelor of Arts in 1924. At Sherrington's instigation, he studied the cerebral cortex of cats. A paper was published in Brain in March 1925. His thesis on "The capillary circulation together with associated observations made in connexion with this investigation" was later examined by John Scott Haldane and John Gillies Priestley on 2 May 1925, and he was awarded a Bachelor of Science degree.

Florey was elected to a John Lucas Walker Studentship at the University of Cambridge for the 1924–1925 academic year. This came with a stipend of £300 plus £200 for equipment. Before taking up this new position, he participated in the 1924 Oxford University Arctic Expedition as the medical officer. In July 1925, he won a fellowship from the Rockefeller Foundation to study in the United States. He sailed for New York on the RMS Caronia (1904) on 19 September 1925, intending to study under Robert Chambers at Cornell University Medical College, but the micromanipulator he required for his research on the blood vessels of the brain was not available, so he arranged to work at the laboratory of Alfred Newton Richards at the University of Pennsylvania. He finally joined Chambers in March 1926. He hoped to be able to return to the UK via Australia and marry Ethel Reed in Adelaide, but in November 1925 he accepted an offer of a research position at London Hospital. The position came with five years' tenure and a salary of £850 per annum, but they wanted him to start immediately. Florey managed to negotiate a delay, but only until May 1926. He returned to the UK on 13 May. Ethel joined him there in September, and they were married at Holy Trinity, Paddington, on 19 October.

London Hospital
Florey was unhappy working at London Hospital; he disliked the long daily commute from Chobham that put his experimental work at the mercy of the railway timetable. In the summer Howard and Ethel lived in a flat in Belsize Park so he could devote more time to his work. He wrote up the results of the research he had done in New York on lacteals and lymphatic capillaries, which was published in the Journal of Physiology in 1927.

Florey then embarked on writing a thesis for a fellowship at Gonville and Caius College, Cambridge, where he became an unofficial fellow in 1926. His thesis on "Physiology and pathology of the circulation of the blood and lymph" was accepted, and his fellowship awarded in 1927. He also continued his work on the secretion of mucus. London Hospital's facilities for the laboratory animals he needed for his research were unsatisfactory, so these experiments were carried out at Oxford and Cambridge. However, he was able to study the lacteals in patients undergoing abdominal surgery.

University of Cambridge
The sudden death of British pathologist Thomas Strangeways on 23 December 1926 created a vacancy in the Huddersfield Lectureship in Special Pathology at Cambridge, and it was offered to Florey. At Cambridge, Florey had a secure appointment and fine laboratory facilities, although the salary of £900  was only slightly higher. He had to teach, which he disliked, preferring research, but there was satisfaction that the new tripos course was largely designed by himself and Alan Nigel Drury. He recruited fourteen-year-old Jim Kent as his assistant. It was the practice at Cambridge that laboratory technicians would rotate through the various laboratory departments, which provided them with thorough training, but was frustrating to the researcher, who had to break in a new assistant every few months. Finding a good one was difficult for Florey; his reputation for hard work, long hours and exacting standards preceded him. He arranged for Kent to be permanently assigned as his assistant, and Kent would remain in the role for the next forty years.

The Floreys bought a house in Cambridge, and Florey cycled to work every day, including Sundays, arriving at 10:00, except on class days when he had to be there earlier. Ethel collaborated on two papers, co-written with Drury and Albert Szent-Györgyi respectively, but stopped coming to the laboratory after she became pregnant. Nonetheless, during the summer break in 1929, she accompanied Florey to Spain, where Sherrington had arranged for him to study methods of nerve staining under Santiago Ramón y Cajal. They decided to commemorate this trip by naming their daughter, who was born on 26 September 1929, Paquita Mary Joanna. Two years later they spent the summer with the French histologist and endocrinologist Pol Bouin at the University of Strasbourg, where Florey studied mucinogen, the chemical precursor to mucin.

In January 1929, Florey began a study of lysozyme, an enzyme that forms part of the immune system in animals. For Florey this was a natural extension of his work with mucus. Lysozyme occurs in secretions containing mucus, and Florey wondered if it was a property of mucus. He mastered lysozyme assay, and chemically identified it. He tested various animals for its presence; dogs, rabbits and guinea pigs all had it in their secretions, but cats had very little, and goats had none, except in their tears. In a paper published in 1930, Florey concluded that lysozyme played little part in natural immunity.

University of Sheffield
There was little prospect for promotion at Cambridge; Florey hoped that a chair of experimental medicine would be created, but this did not occur until 1945. He collaborated with biochemist Marjory Stephenson on his lysozyme project, but she did not have enough time to spare for a researcher in another department, and their results were not published. He yearned to have an interdisciplinary team and funds for work other than his own. The death of James Sholto Cameron Douglas on 30 October 1931 created a vacancy in the Joseph Hunter chair of pathology at the University of Sheffield, and Florey decided to apply.

That Florey was not a pathologist was not overlooked; the Scottish pathologist Robert Muir declared: "There is no pathologist named Florey." The faculty board decided to take a chance on Florey, and he was appointed on 9 December. He took up the appointment in March 1932. The Floreys moved for the fourth time in five years, this time to a Victorian manor on 1 acre of ground about 1 mi from the university, which later became student accommodation with the name "Florey Lodge". The chair came with a salary of £1,000  per annum, but there was no provision for an assistant. He took Kent with him anyway, eventually securing 50 shillings a week for him from the Medical Research Council (MRC). Guy's Hospital in London offered Florey a chair in pathology in February 1933. This caused alarm at the university, for it had recently lost two of its senior professors through the retirement of John Beresford Leathes and the departure of Edward Mellanby to become the secretary of the MRC. The university officials did not wish to lose Florey as well, and they raised his salary to £1,200 per annum to induce him to stay.

The Sheffield Medical School was small, with only about fourteen students each year. The lack of a first-rate pathologist was remedied when Beatrice Pullinger joined the staff in January 1934, and she became Florey's ally in successfully lifting the standard of research and teaching in the department. While Florey's main interest was lysozyme, he pursued other lines of research as well. The death of his brother-in-law, John Gardner, from tetanus led to an interest in treating the disease, which he pursued in collaboration with Paul Fildes and H. E. Harding. He also researched the structure and function of the lymphatic system with Pullinger, and continued his studies of contraception with Harry Carleton that had begun at London Hospital.

Florey's son Charles du Vé was born in Sheffield on 11 September 1934, but for a time Florey's relationship with Ethel had deteriorated to the point where they were communicating in writing and contemplating a legal separation. This was regarded as a serious matter; no Oxford fellow divorced without resigning his fellowship until the 1950s.

University of Oxford
Despite his success in revitalising the pathology department at Sheffield, Florey had grander ambitions than following the example of Douglas and dying in office. An opportunity arose with the death of Georges Dreyer on 17 August 1934, the holder of the chair of pathology in the Sir William Dunn School of Pathology at Oxford. Dreyer had overseen the construction of a palatial new laboratory, but by 1934 it had attracted few students and researchers. While Florey had reservations about leaving Sheffield for Guy's, he had none about Oxford. The electoral board met on 22 January 1935, and Florey was appointed Professor of Pathology and Fellow of Lincoln College, Oxford, which controlled the chair, effective 1 May 1935. The chair came with an annual salary of £1,700. The school's budget was £3,432 a year  for all equipment and salaries except Florey's. He enforced strict economy measures such as forbidding the use of the lift, which saved £25 a year.

While the building could accommodate a staff of thirty researchers, twenty-five technicians and forty to fifty students, there was only a fraction of that number, and morale was low. Florey retained Jean Orr-Ewing and Margaret Campbell-Renton, who had been working with Dreyer, and brought Kent with him. Pullinger joined them soon after as demonstrator of pathology. Florey and Pullinger restructured the pathology course. He hired Margaret Jennings as a gastroenterologist in October 1936, and she worked with him on his studies of mucus secretion. She became Florey's mistress in 1940; their affair was a poorly-kept secret. He appointed P. J. Smart as the office administrator, and she remained in the role until she retired in 1976. He attracted Rhodes Scholars such as Australian Brian Maegraith and Americans Robert H. Ebert and Leslie Epstein to the Sir William Dunn School of Pathology; other doctoral students included Peter Medawar, Gordon Sanders and Jean Taylor.

Arthur Duncan Gardner headed the MRC's Standards Laboratory, which was located on the premises, and Gardner expected that his unit would have to move out, but Florey moved to keep him, as he needed a good bacteriologist. He arranged for Gardner to become head of his bacteriological section, with the title of reader of bacteriology in 1936. The Standards Laboratory eventually moved to the MRC's laboratories at Colindale, but not until 1946.

Florey also wanted a biochemist on his staff, but this proved difficult. He acquired the services of E. A. H. Roberts with a £300 MRC grant in July 1935, and for the next two years Roberts worked with Florey and Maegraith on Florey's lysozyme project. Still, Florey wanted a biochemist on his own staff. He tried to get Hugh Macdonald Sinclair, but Sinclair declined the offer. Norman Pirie asked Florey if he could assume the role, but when Florey approached Sir Frederick Gowland Hopkins, Pirie's boss, Hopkins refused to release Pirie. He tempered this refusal by recommending Ernst Boris Chain, one of many Jewish refugees from Nazi Germany who had found sanctuary in the UK. Chain had recently completed his PhD thesis under Hopkins's supervision. He gratefully accepted Florey's offer of an appointment although it was initially for one year only, and with an annual salary of £200. In turn, Chain felt that he needed a collaborator, and he had one in mind: Norman Heatley, who was finishing his PhD in Hopkins's department. Heatley was happy to come, and Florey was able to arrange for the MRC to fund the position.

In 1936, Florey received a letter from Hilda stating that their mother Bertha had terminal cancer, so he arranged to travel to Australia with Ethel, Paquita and Charles during the summer break. They travelled on the SS Orsova (1908) to Melbourne, where they were met by Bertha, Charlotte, Hilda, Valetta and Hilda's daughter Joan Gardner. In addition to spending time with his family, he visited Peter MacCallum at his laboratory. MacCallum introduced Florey to Roy Douglas (Pansy) Wright, an experimental physiologist, and they arranged for Wright to come to Oxford the following year to assist Florey and Jennings with their work on mucus secretion. Florey then joined Ethel and the children in Adelaide. The family returned to Oxford in October. Bertha died on 27 November.

Henceforth, Florey would lead an interdisciplinary team in an attack on a particular problem. Each member of the team tackled a particular aspect in their own way, with simultaneous research along different lines building up a complete picture. This was a manner of collaboration that was practically unknown in the UK at the time. However, the team members, including Florey, all worked on multiple projects at the same time. Florey was strict with his own collaborators, but gave considerable latitude to those working on other aspects of a project. He did not hold team meetings, although he encouraged team members to discuss issues with himself and each other, and he dropped by each laboratory nearly every day to view progress and provide suggestions.

The first such project was an investigation of lymphocytes. Florey developed a detailed project plan and deployed eight graduate researchers on it, including Sanders, Medawar and Taylor. Florey performed delicate surgery on rabbits to examine the effects of lymphocyte deprivation. The project, not completed for many years, resulted in several papers and advances in the understanding of the immune system.

Florey continued with his lysozyme project. Although the MRC had agreed to pay Roberts's salary, it baulked at providing money for a piece of apparatus that he required. Florey then turned to the Rockefeller Foundation for assistance, and was provided with US$1,250 (about £320). Florey and Maegraith harvested lysozyme from animals, and Roberts was able to purify it. Edward Abraham then managed to crystallize it in 1937. Chain and Epstein then studied it and determined that it was a polysaccharidase and, with Gardner's help, were able to determine its structure, and how it acted on polysaccharides. The lysozyme research was successful, but while it was lethal to micrococci, these bacteria are not usually pathogenic, and were of little concern to medicine.

Development
In the course of his work on lysozyme, Chain read papers on the enzyme in the British Journal of Experimental Pathology by Alexander Fleming in volumes 3 and 8, and by Florey in volume 11. While doing so he came across Fleming's paper discussing the antibacterial effects of Penicillium notatum mould in volume 10. The erroneous impression given by Fleming that penicillin was a bactericidal enzyme led Chain to consider that it would be similar to lysozyme. Money was short at the time; the office had an overdraft of £500 and Florey had to forbid the purchase of any further equipment. Chain and Florey decided to create a large research project on antibacterial substances produced by micro-organisms that could attract long-term funding. Three sources were initially chosen for investigation: Bacillus subtilis, Trueperella pyogenes and penicillin mould. Florey later said: "People sometimes think that I and the others worked on penicillin because we were interested in suffering humanity. I don't think it ever crossed our minds about suffering humanity. This was an interesting scientific exercise, and because it was of some use in medicine is very gratifying, but this was not the reason that we started working on it."

Florey approached the MRC for funding in September 1939, shortly after the outbreak of the Second World War, and Mellanby authorised the project, allocating £250 to launch the project, with £300 for salaries and £100 for expenses per annum for three years. Florey felt that more would be required. On 1 November 1939, Henry M. "Dusty" Miller, Jr, from the Natural Sciences Division of the Rockefeller Foundation dropped by to discuss funding Heatley's position. Heatley had fallen out with Chain, and had accepted a new position at the Carlsberg Laboratory in Copenhagen on a Rockefeller Fellowship, but due to the outbreak of the Second World War, he had decided to remain at Oxford. Miller arranged for Heatley to retain his fellowship. Instead of working for Chain, Heatley would report directly to Florey as his personal research assistant.

As a bacteriologist, Miller was enthusiastic about the antibacterial project; he encouraged Florey to apply for a grant from the Rockefeller Foundation, and recommended to his headquarters that the request for financial support be given serious consideration. "The work proposed", Florey wrote in his application letter, "in addition to its theoretical importance, may have practical value for therapeutic purposes." Florey's application was approved, with the Rockefeller Foundation allocating US$5,000 (£1,250) per annum for five years.

Florey's team already had a sample of penicillin mould; Dreyer had been given a sample of the mould in 1930 for his work on bacteriophages. He had lost interest in penicillin when he discovered that it was not a bacteriophage, but Campbell-Renton had continued to cultivate it. The team developed techniques for growing the mould on a surface of liquid Czapek-Dox medium. Most laboratory containers did not provide a large, flat area, so glass bottles laid on their sides were used. Later, specially-made containers were fabricated. As the laboratory gradually became a penicillin factory, Florey hired six women to perform the cultivation and extraction work. It had to be carried out under sterile conditions; Abraham and Chain discovered that some airborne bacteria produced penicillinase, an enzyme that destroys penicillin.

Heatley and Chain tackled the problem of how penicillin could be extracted from the mould. The liquid was filtered through parachute silk to remove the mycelium, spores and other solid debris. The pH was lowered by the addition of phosphoric acid and the liquid was then cooled. In this form the penicillin could be drawn off by a solvent. Initially diethyl ether was used, but it is highly inflammable. At Chain's suggestion, they tried the much less flammable amyl acetate, and found that it also worked. Penicillin-bearing solvent was easily separated, but now they encountered the problem that had stymied earlier attempts: recovering the penicillin from the solvent. Heatley reasoned that if the penicillin could pass from water to solvent when the solution was acidic, maybe it would pass back again if the solution was alkaline. Florey told him to give it a try. This method, which Heatley called "reverse extraction", was found to work. Chain hit upon the idea of freeze drying to enable the water to be removed without damaging the penicillin. The team had thus developed a complete process for growing, extracting and purifying penicillin, resulting in a dry, brown powder. By early 1942, they could prepare a highly purified compound, and had proposed the chemical formula. Heatley developed an assay method. An Oxford unit was defined as the purity required to produce a 25 mm bacteria-free ring. It was an arbitrary measurement, as the chemistry of penicillin was not yet known; the first research was conducted with solutions containing four or five Oxford units per milligram. Later, highly pure penicillin became available with 2,000 Oxford units per milligram.

The team discovered that Penicillium extract killed several types of bacteria. Gardner and Orr-Ewing tested it against gonococci (against which it was most effective), meningococci, streptococci, staphylococci, anthrax bacteria, Actinomyces and the organisms that caused tetanus and gangrene. Florey and Jennings experimented on rats, mice, rabbits and cats in which penicillin was administered in various ways, and found no evidence of toxicity. On 25 May 1940, Florey injected eight mice with a virulent strain of streptococcus, and then four of them with penicillin. A day later all four of the untreated mice were dead, but all of the treated ones were still alive, although one died two days later. Over the following weeks Jennings and Florey repeated the experiment with ever-larger batches of mice, and with different bacteria. They found that penicillin was also effective against staphylococci and the bacteria that cause gangrene. They published their findings in The Lancet on 24 August 1940. Florey reminded his staff that as promising as their results were, a man weighed 3,000 times as much as a mouse.

In February 1941, Florey and Chain treated their first patient, Albert Alexander, who had had a small sore at the corner of his mouth, which then spread, leading to a severe facial infection involving streptococci and staphylococci. His whole face, eyes and scalp were swollen to the extent that he had had an eye removed to relieve the pain. Within a day of being given penicillin, he started to recover. However, the researchers did not have enough penicillin to help him to a full recovery, and he relapsed and died. Because of this experience and the difficulty in producing sufficient penicillin, Florey switched his focus to children, who could be treated with smaller quantities of penicillin.

Florey expected that penicillin would be hailed as a breakthrough, but he was disappointed; his results aroused little interest. He spent the next two years attempting to generate interest in what he believed to be the most important medical discovery of the century. He was elected a Fellow of the Royal Society in March 1941, but his work with penicillin played little part in this.

North American supply
As the war intensified with German air raids on the UK, Florey and Ethel decided to send their children away to a safer country in July 1940. The United States was not yet at war, and John Fulton, the Sterling Professor of Physiology at Yale University, and his wife Lucia agreed to care for them at their home in New Haven, Connecticut, "for the duration". In April 1941, the Rockefeller Foundation's Warren Weaver met with Florey, and they discussed the difficulty of producing sufficient penicillin to conduct clinical trials. Weaver arranged for the foundation to fund a three-month visit to the United States for Florey and a colleague so they could explore the possibility of the production of penicillin there.

Since his aim was to persuade a firm to manufacture penicillin, and Heatley knew the most about penicillin production, Florey chose to take Heatley with him, and did not tell Chain until the morning of their departure. Chain, who saw penicillin as a joint project between himself and Florey, with Heatley as a laboratory technician, was greatly offended. Chain later wrote: "I left the room silently but shattered by the experience of this underhand trick and act of bad faith, the worst so far in my experience of Florey. It spoiled my initially good relations with this man for ever."

Florey and Heatley left for the United States by air on 27 June 1941. In New Haven Florey met Fulton and was reunited with his children. Fulton introduced him to Ross Harrison, the Chairman of the National Research Council, and Harrison introduced him to Charles Thom, the chief mycologist at the Bureau of Plant Industry of the United States Department of Agriculture (USDA), and the man who had identified the mould reported by Fleming. Thom took them to Washington, D.C., to see Percy Wells, the acting head of the USDA's four laboratories, and Wells sent them to Orville May, the director of the UDSA's Northern Regional Research Laboratory (NRRL) in Peoria, Illinois. May arranged for them to meet with Robert D. Coghill, the chief of the NRRL's fermentation division, who raised the possibility that fermentation in large vessels (deep submergence) might be the key to large-scale production.

On 17 August, Florey met with Richards, who had become the chairman of the Medical Research Committee of the Office of Scientific Research and Development, who promised his support. Florey returned to Oxford in September without undertakings to produce the kilogram quantities of penicillin required for clinical trials, but the Japanese attack on Pearl Harbor in December 1941 brought the United States into the war and infused a new urgency into penicillin production.

Chain suggested applying for a patent on the penicillin process. His motivation was not potential profits, but the danger of it being patented elsewhere. Florey took up the issue with Sir Henry Dale, the chairman of the Wellcome Trust and a member of the Scientific Advisory Panel to the British Cabinet, and John William Trevan, the director of the Wellcome Trust Research Laboratory, but they were adamantly opposed, as they considered the notion of researchers profiting from their work as unethical. The Americans had no such scruples, and took out patents on the deep submergence processes they developed. Chain regarded Florey as naive for not patenting the penicillin production process.

Clinical trials
In addition to the increased production at the Dunn School, commercial production from a pilot plant established by Imperial Chemical Industries became available in January 1942, and Kembel, Bishop and Company delivered its first batch of 200 impgal on 11 September. Florey conducted a second series of clinical trials. Ethel was placed in charge, but while Florey was a consulting pathologist at Oxford hospitals and therefore entitled to use their wards and services, Ethel, to his annoyance, was accredited merely as his assistant. Doctors tended to refer patients to the trial who were in desperate circumstances rather than those who were the most suitable candidates for treatment, but when penicillin did succeed anyway, confidence in its efficacy rose.

Harry Lambert, a friend of Fleming's dying from a meningococcal infection, became the twelfth case on 5 August 1942. He survived, but someone at St. Mary's Hospital leaked the result to the press, resulting in an editorial in The Times on 27 August. Florey was appalled; this could only create a public demand for penicillin when all available supplies were needed for the clinical trials. On 25 September, Florey met with Sir Cecil McAlpine Weir, the Director-General of Equipment and Stores at the Ministry of Supply, who promised overriding priority for the mass production of penicillin. Ethel and Howard Florey published the results of clinical trials of 187 cases of treatment with penicillin in The Lancet on 27 March 1943.

North Africa
The Medical Research Council decided that the time had come for field trials of penicillin. The location of centres to receive the drug was kept secret so as to not provoke demand for the drug when it was still in short supply. Florey was asked to go to North Africa, where the North African campaign was ongoing. He travelled to Algiers on the hospital ship in May 1943. On 29 June he was joined by Hugh Cairns, another Rhodes Scholar from Adelaide, who now held the rank of brigadier in the British Army, and was in charge of St Hugh's Military Hospital (Head Injuries) in Oxford, who brought with him a stockpile of 40 million Oxford units of penicillin. Florey resisted well-intentioned efforts by the War Office to grant him military rank.

Over the next two months Florey and Cairns flew back and forth between Algiers, Sousse and Tripoli, with a week in Cairo. They treated over one hundred cases and compiled a report that ran to over one hundred pages. He gave lectures on penicillin, and his report contained recommendations for training of medical officers in its use. The fighting in North Africa ended in May 1943, so most of the cases Florey saw were not recently wounded soldiers, but ones with old wounds that had not healed; battle casualties began arriving again after the Allied invasion of Sicily in July. He considered that the source of infection in many cases was from the hospital rather than the battlefield, and advocated changes to the way that patients were treated to take advantage of the properties of penicillin. He argued that wounds should be cleaned and sealed up promptly. This was a radical idea; normally this would have been inviting gas gangrene, but Florey proposed leaving that to the penicillin. His recommendations were acted upon, and the War Office established a training course for pathologists and clinicians at the Royal Herbert Hospital, which made use of film that Florey shot in North Africa.

Although he intended that penicillin be used to treat the seriously wounded, there were large numbers of venereal disease cases, against which penicillin was particularly effective, and from a military point of view being able to cure gonorrhea in 48 hours was a breakthrough. The supply situation improved, and 20 million units per day were made available for the Allied invasion of Italy in September. Two out of three gas gangrene casualties now survived.

Soviet Union
One result of the Tehran Conference in November 1943 was an invitation for an Anglo-American scientific mission to visit the Soviet Union. The British team consisted of Florey and Sanders; the American of Albert Baird Hastings and Michael Boris Shimkin. After a month's travel via North Africa and Iran, they reached Moscow on 23 January 1944, where they met Soviet microbiologist Zinaida Yermolyeva. Florey gave her samples of penicillin, and she gave him a sample of the antibiotic Gramicidin S. He arrived back at Oxford on 29 March 1944.

Australia
In May 1944, the Prime Minister, John Curtin and the Commander-in-Chief of the Australian Army, General Sir Thomas Blamey, visited London for the 1944 Commonwealth Prime Ministers' Conference. At Blamey's request, Curtin asked Florey if he would visit Australia as an advisor on the use of penicillin. Florey arrived in Australia in August 1944 to a hero's welcome, and was awarded the degree of Doctor of Medicine (MD) by the University of Adelaide.

In accepting the degree, he recapitulated his own career, and spoke about the need to make it easier for research to be conducted in Australia. Florey met with Blamey; the two men got along well and chatted for several hours. It ended with Blamey convinced that Florey was the man to head a project Blamey had in mind: a medical research institute in Canberra, the national capital. Blamey put his proposal to Curtin on 24 October. It was quickly approved, but Curtin became ill, and he died in July 1945.

Florey discovered that penicillin production was already underway in Australia at the Commonwealth Serum Laboratories (CSL) in Melbourne. In 1943, the War Cabinet had agreed to produce penicillin in Australia, and Colonel E. V. (Bill) Keogh, the Army's Director of Hygiene and Pathology, detailed Captain Percival Bazeley and Lieutenant H. H. Kretchmar to establish a production facility. They visited Peoria, and obtained penicillin cultures from Coghill. The first Australian-made penicillin began reaching the troops in New Guinea in December 1943. Florey was full of praise for their achievement, but disturbed that they had turned to the Americans for advice instead of him. "Am I not Australian?" he asked Keogh, "Have I not had some leading role in this thing?"

Recognition
Florey returned to the UK in October 1944, collecting his children from Fulton while en route. He was created a Knight Bachelor on 8 June 1944, and invested by King George VI at Buckingham Palace on 4 July 1944. He shared the Nobel Prize in Physiology or Medicine in 1945 with Ernst Boris Chain and Alexander Fleming. Fleming first observed the antibiotic properties of the mould that makes penicillin, but it was Chain and Florey who developed it into a useful treatment. Florey maintained that the penicillin project was originally driven by scientific interests, and that the medicinal discovery was a bonus. The neuroscientist W. Maxwell Cowan observed that: "Fleming was the first person Florey saved. Without Florey's work he would have gone down as a somewhat eccentric microbiologist."

Florey always insisted that the development of penicillin was a team effort and that he received more credit than he deserved, but the team itself was his creation. The philanthropist Lord Nuffield offered Florey £50,000 as a personal gift; Florey asked him instead to use it to establish research fellowships at the Sir William Dunn School. The first beneficiaries included Abraham, Heatley and Sanders. When the Albert and Mary Lasker Foundation asked if it could reward him, as it had the staff at Peoria, he arranged for a commemorative rose garden with a memorial stone honouring Abraham, Chain, Fletcher, himself, Ethel Florey, Gardner, Jennings, Orr-Ewing and Sanders.

Cephalosporins
After the war ended, Florey directed his team at the Sir William Dunn School in the investigation of antibiotic substances produced by plants and microorganisms. They studied claviformin, proactinomycin, helvolic acid, mycophenolic acid, hirsutic acid, bacitracin and micrococcin. In 1949, they published Antibiotics: A Survey of Penicillin, Streptomycin, and Other Antimicrobial Substances from Fungi, Actinomycetes, Bacteria and Plants, a massive two-volume work. Florey also edited Lectures on General Pathology, which was published in 1954. Chain departed in 1948, but Guy Newton joined the team in his place as its biochemist. Financial support came from the Medical Research Council, the Albert and Mary Lasker Foundation, and American pharmaceutical companies.

In September 1953 Newton and Abraham isolated crystalline cephalosporin C from a fungus originally isolated by Giuseppe Brotzu in Sardinia, and found that it had antibiotic properties. Their initial evaluation of the antibiotic activity of cephalosporin C was that it was low, so Abraham sent Florey, who was in Australia, a letter asking if research should continue. Florey saw an intellectually challenging line of research, and told them to continue. They found that it was resistant to penicillinase produced by gram-positive bacteria. When he returned to Oxford, Florey and Jennings conducted a series of experiments that determined that it was not toxic to mice but could protect them against streptococci and penicillinase-producing staphylococci. The Oxford team analysed the chemical properties of the cephalosporin ring system, opening the door to the production of semisynthetic cephalosporins created through replacing side chains, as had been done with penicillin to create semisynthetic penicillins. "Everybody I have questioned who was involved in the development of cephalosporin C," science writer David Wilson reported, "when asked if one man was responsible for keeping the project going, replied: 'Florey'."

Controversy over British firms having to pay royalties to American ones for the use of the deep submergence techniques developed in the United States to produce penicillin when penicillin was seen as a British innovation led to the establishment of the National Research Development Corporation (NRDC) in June 1948. The Oxford team patented their work on cephalosporins and assigned the patents to the NRDC. By 1978, the annual world sales of cephalosporins were worth over £600,000 and the NRDC was reaping £100,000  a year in royalties. Florey received a 0.5 per cent share in the last two years of his life.

Australian National University
In the original design of the city of Canberra, the architect, Walter Burley Griffin had provided for a university, and had set aside land for it at the base of Black Mountain, where it would ultimately be built. Sir David Rivett chaired a committee constituted to investigate the proposed medical research institute, how much it would cost, and how it would affect existing and proposed institutions. Florey mailed Rivett a 19-page proposal on 7 April 1945. Florey envisaged a funding body in Australia similar to the Medical Research Council in the UK. The institute would be headed by a director, and have about one hundred staff, which he calculated would cost about £100,000. His estimate of the cost of the building was too low; Florey estimated that £240,000 would be enough for a building for 60 researchers, but it would eventually cost almost four times as much.

The Australian National University Act received royal assent on 1 August 1946. The act created the Australian National University (ANU), and gave the medical research institute the name "John Curtin School of Medical Research". H. C. "Nugget" Coombs, an economist and head of the Department of Post-War Reconstruction, accompanied the Prime Minister, Ben Chifley, on an official visit to the UK as his principal advisor. Coombs met with Florey in Oxford in May 1946. They agreed that the success of the new university would depend on the quality of faculty they could attract, and he wanted four eminent scholars to lead the four research schools: Florey for medicine, Mark Oliphant for physics, Keith Hancock for history, and Raymond William Firth for Pacific studies. Each received an official invitation in April 1947, and they were invited to come to Canberra for consultation in December 1947 and January 1948. They would constitute an academic advisory committee, for which they would be paid £250  plus £200  expenses per annum. Since they were all located in the UK, a London office of the university was opened to provide liaison.

Florey never moved to Canberra, but he did accept the position of acting director of the John Curtin School of Medical Research for a five-year term commencing in May 1948 in order to establish it. Brian Lewis had been appointed university architect, but Florey hired Stephen Welsh, the professor of architecture at Sheffield University. Outfitting a scientific building with five laboratories full of the latest world-class specialised equipment such as biosafety cabinets, cold rooms, sterilisers and incubators was never going to be cheap or simple in a relatively remote location like Canberra, and much of the equipment had to be paid for in scarce US dollars. The Cabinet approved a 50,000 sqft building at £3 per square foot in 1947, but the design Florey and Sanders agreed upon was a 235,000 sqft building at £4 per square foot. In 1950, the Cabinet approved £810,000  for the building and £200,000   for equipment. People were also important, and Florey had a fairly free hand hiring his professors. He recruited Hugh Ennor as his professor of biochemistry, Adrien Albert as professor of medical chemistry, and Frank Fenner as professor of microbiology. A. F. Bunker was appointed the laboratory manager, and he outfitted the building.

Florey visited Canberra in March 1953, but he made it clear that he did not wish to continue as acting director of the John Curtin School of Medical Research, nor take up the position of director, although he reluctantly agreed to continue as an advisor. He was pessimistic about the project, writing home to Jennings that "it will be a miracle if this place can be given a real university atmosphere". By this time the project was in jeopardy; while the prime minister, Robert Menzies, supported it, a faction in the Cabinet led by Richard Casey and Wilfrid Kent Hughes did not; they were chagrined that it was named after a man they despised, and that it called itself a school when it would not train doctors. Changing the name required amending the act, and this did not occur. In November 1953, Florey was informed that works would proceed as planned.

On 27 March 1958, Florey ceremoniously opened the John Curtin School of Medical Research and received an honorary Doctor of Science degree along with Sir Norman Gregg. Menzies, Coombes, Ennor and Curtin's family were in attendance. This was not the end of Florey's association with the ANU. In 1964, he accepted the role of chancellor, a position he held from 1965 until his death in 1968.

President of the Royal Society
One of the most prestigious institutions in the UK was the Royal Society. Mellanby put Florey's name forward for membership in 1937, but at that time it accepted only twenty new members each year. He was elected a fellow in 1941. The Royal Society was governed by a council of twenty-one fellows, and Florey served on the council from 1942 to 1943, and again from 1951 to 1953, when he was vice president. He received the Royal Society's Royal Medal in 1951 and its Copley Medal in 1957. By custom, the president of the Royal Society served for five years, and the position alternated between the mathematical and physical sciences, and the biological sciences, so Florey was eligible in 1960. Since the president was a public figure, his private life had to be beyond reproach, which was a sore point due to his relationship with Margaret Jennings.

Florey became the President of the Royal Society on 30 November 1960. Since 1873, the Royal Society had occupied Burlington House. While it had a sumptuous Meeting Room and Council Room, the administrative staff, who numbered about seventy in 1960, worked in cramped conditions in the awkward-to-access offices in the attic and basement. Florey decided to seek better accommodation.

In December 1960, Florey was informed that plans to build new accommodation for the Foreign Office at Carlton House Terrace had fallen though and that the Crown Estate Commissioners had suggested that the premises might be suitable for the headquarters of cultural bodies. Florey inspected the property and lodged a formal application to occupy four houses on the site, numbers 6 to 9. Florey raised the money required to realise the architect Sir William Holford's vision for the interiors. While the government paid the rent and upkeep on the Royal Society's accommodation, about £45,000 in 1963, repairs and alterations were at the Royal Society's expense and ultimately came to around £850,000. The move was not completed during Florey's term of office; the new building was opened by Queen Elizabeth II on 21 November 1967.

Florey pursued a more progressive and internationalist outlook for the Royal Society. He hosted Yuri Gagarin at a luncheon at Burlington House, and led Royal Society visits to Russia in 1965 and 1967. He saw that Britain's future lay in being part of the European Economic Community, and he established ties with the European Organization for Nuclear Research (CERN), the European Molecular Biology Organization (EMBO) and the European Space Research Organization (ESRO). In 1959, the Royal Society provided for only one research fellowship, the Foulerton Professorship, but in 1961, at his suggestion, the Henry Dale Research Professorship was created for a researcher in physiology and pharmacology. Government funding was provided to create three more professorships in 1964, and another two in 1967. Reflecting his attempt to move with the times, a chair was established for the social sciences, and two new lecture series were instituted, for technology and the behavioural sciences. Aware of the acute danger of overpopulation that the life-saving drugs that he had pioneered could cause, he established a population study group, and in 1967, he became the president of the Family Planning Association.

Provost of Queen's College, Oxford
As he approached the age of sixty, Florey faced mandatory retirement. He had to vacate the university house he had occupied since 1935, which was subsequently demolished, with a new school erected on the site. He bought a parcel of land in Marston, Oxford, and built a house on it. No sooner had they moved in than Florey accepted the position of Provost of The Queen's College, Oxford, to which he was elected on 25 June 1962, and he moved into the provost's lodgings. This meant relinquishing his chair at the Sir William Dunn School. He was succeeded by Henry Harris, a fellow Australian scientist who had been invited to study at the Sir William Dunn School by Florey in 1952 on an ANU scholarship. Florey was the first provost of Queen's College with no prior association with the college as an undergraduate, graduate researcher or fellow, and the first scientist. The role was closely associated with the academic establishment, of which he had been critical, but he could stay until 1971, the lodgings came with a housekeeper, and he could make use of its facilities to entertain visiting scientists and dignitaries. Florey had a lift installed to make it easier for Ethel and himself to reach the upstairs bedrooms.

Based on his own experience as a Rhodes Scholar, Florey created a version for European students. The European Studentship scheme provided support for graduates from eleven western European and Scandinavian countries with an annual stipend of £1,100 for two years. Florey raised the money for nine studentships. Florey did not live to see the first studentship awarded in 1969, and without him additional funding was not forthcoming and the money was exhausted by 1980. By then 76 students had benefited from the scheme, and they had published 15 books and 250 articles in peer-reviewed journals.

During his term as provost, there was a major construction program to provide enough accommodation for all undergraduates to be able to spend at least two years in residence. This involved three developments, the largest of which was Florey's personal project: the construction of a new building on the River Cherwell at St Clement's, Oxford. The cost was substantial—the purchase price of the site alone was £500,000 —but Florey was accustomed to raising large sums of money. It was designed by the British architect Sir James Stirling. Florey died the day that construction work was scheduled to begin. When the building was opened in 1971, it was named the Florey Building in his honour. Buildings were also named after Florey in Adelaide, Melbourne, and Canberra, where his refurbished original John Curtin School of Medicine Building was renamed the Florey Building in 2015.

Personal life
Ethel Florey's health deteriorated. She had hypertension and respiratory and heart problems, and walked with a stick. She travelled to Australia one more time in 1965 to give lectures on penicillin, but collapsed in Canberra and was hospitalised in Sydney. She recovered sufficiently to return to Oxford. When she found out that her son Charles was getting married at Fulton's house in New Haven in 1966, she wanted to attend. Florey refused to pay for this; if she collapsed in the United States the cost of medical care would be astronomical. Robert Webb, an American friend from the Cambridge days arranged for US$5,000  of insurance cover to allow her to attend. She died in Oxford on 10 October 1966.

On 6 June 1967, Florey married Margaret Jennings at the Old Register Office in St Giles', Oxford, in a ceremony deliberately kept as quiet as possible. The only other persons present were Jim Kent and Cecilia Little, Jennings's housekeeper, who acted as witnesses. There was a small celebration in Florey's rooms at Queen's College and they honeymooned in the Caribbean before visiting Fulton in New Haven.

Honours and awards
Florey was awarded the Cameron Prize for Therapeutics of the University of Edinburgh and the Lister Medal in 1945, for his contributions to surgical science. The corresponding Lister Oration, given at the Royal College of Surgeons of England later that year, was titled "Use of Micro-organisms for Therapeutic Purposes". He was awarded many honorary degrees from British and foreign universities, including University of São Paulo in Brazil. He won the Gold Medal of the Royal Society of Medicine in 1947. He became a commander of the French Legion of Honour in 1946 and was awarded the American Medal for Merit in 1948 and the James Smithson Medal in 1965.

Florey was elected to the United States National Academy of Sciences and the American Philosophical Society in 1963, and was elected to the American Academy of Arts and Sciences the following year. He became an honorary Fellow of the Royal College of Surgeons in 1961.

On 4 February 1965, Florey was created a life peer and became Baron Florey, of Adelaide in the Commonwealth of Australia and of Marston in the City of Oxford. This was a higher honour than the knighthood awarded to Sir Alexander Fleming, and it recognised the monumental work Florey had done in making penicillin available in sufficient quantities to save millions of lives. He was formally introduced to the House of Lords in April, sponsored by Lord Cottesloe, Margaret Jennings's brother, and Lord Adrian, one of Florey's predecessors as President of the Royal Society. On 15 July 1965 he was appointed a member of the Order of Merit.

Death
Florey published his last scientific paper, co-written with Jennings, in 1967. He had written or co-written over two hundred papers. He died at his home at the provost's lodgings, of congestive heart failure on 21 February 1968. Although Florey was an agnostic, a funeral service was held in the St. Nicholas' parish church in Marston. A memorial plaque was placed on the outside wall near the entrance; the church refused to allow it to be placed inside because Florey had been so outspoken in his disbelief. A larger service at Westminster Abbey in London was attended by about 500 people. His remains were cremated.

In 1980, Lady Hamilton Fairley, the widow of Sir Neil Hamilton Fairley began a campaign to have a memorial to Florey in London. The Premier of South Australia, David Tonkin, agreed to provide South Australian marble for a memorial stone. South Australian sculptor Paul Trappe was commissioned to engrave it from a design by John Peters. The 60 by stone was flown to London by the Royal Australian Air Force, and unveiled by Lady (Margaret) Florey on 2 November 1981. The inscription on the stone reads:"In grateful memory of HOWARD WALTER BARON FLOREY O.M. His vision, leadership and research made penicillin available to mankind. Born Adelaide 1898 Died Oxford 1968"

Posthumous honours and legacy
Florey's portrait appeared on the Australian fifty-dollar note for 22 years between 1973 and 1995. The note also depicted the Sir William Dunn School of Pathology, Penicillin notatum, mice used in penicillin experiments, colonies of mould inhibiting bacterial growth on a Petri dish, and Heatley's assay method.

The street of Florey Drive and suburb of Florey in the Australian Capital Territory, the Florey Institute of Neuroscience and Mental Health at the University of Melbourne, Victoria, the Florey Unit of the Royal Berkshire Hospital in Reading, Berkshire, the Florey Institute for Host–Pathogen Interactions at the University of Sheffield, and a lecture theatre in the University of Adelaide's medical school are named after him. The Electoral district of Florey, a single-member electoral district for the South Australian House of Assembly, is also named after him.

It was estimated that the development of penicillin saved over 80 million lives.

In film
Penicillin: The Magic Bullet is a 2006 Australian film production written by Gordon Glenn and financed by the Film Finance Corporation and Arcimedia Productions in association with Film Victoria. Breaking The Mould is a 2009 historical drama that tells the story of the development of penicillin in the 1930s and 1940s, by the group of scientists at Oxford headed by Florey at the William Dunn School of Pathology. The film stars Dominic West as Florey, Denis Lawson as Fleming, and Oliver Dimsdale as Chain; and was written by Kate Brooke and directed by Peter Hoar.

title: Howard Florey


text:
Lac (resin)

Lac is the resinous secretion of a number of species of lac insects, of which the most commonly cultivated is Kerria lacca.

Cultivation begins when a farmer gets a stick that contains eggs ready to hatch and ties it to the tree to be infested. Thousands of lac insects colonize the branches of the host trees and secrete the resinous pigment. The coated branches of the host trees are cut and harvested as sticklac.

The harvested sticklac is crushed and sieved to remove impurities. The sieved material is then repeatedly washed to remove insect parts and other material. The resulting product is known as seedlac. The prefix seed refers to its pellet shape. Seedlac, which still contains 3–5% impurity, is processed into shellac by heat treatment or solvent extraction.

The leading producer of lac is Jharkhand, followed by the Chhattisgarh, West Bengal, and Maharashtra states of India. Lac production is also found in Bangladesh, Myanmar, Thailand, Laos, Vietnam, parts of China, and Mexico.

Etymology
The word Lac is derived from the Sanskrit word lākshā '(लाक्षा) representing the number 100 thousand, which was used for both the Lac insect (because of their enormous number) and the scarlet resinous secretion it produces that was used as wood finish, lacquerware, skin cosmetic, ornaments and dye for wool and silk in ancient India and neighbouring areas. Lac resin was once imported in sizeable quantity into Europe from India along with Eastern woods. These were being used very widely.

Host trees

Kerria lacca can be cultivated on either cultivated or wild host plants.
 * In India the most common host plants are:
 * Dhak (Butea monosperma)
 * Ber (Ziziphus mauritiana)
 * Kusum (Schleichera oleosa) (reported to give the best quality and yield)
 * In Thailand the most common host plants are
 * Rain tree (Albizia saman)
 * Pigeon pea (Cajanus cajan)
 * In China the common host plants include
 * Pigeon pea (Cajanus cajan)
 * Hibiscus species
 * In Mexico
 * Barbados nut (Jatropha curcas)

Estimated yields per tree in India are 6–10 kg for kusum, 1.5–6 kg for ber, and 1–4 kg for dhak. The bugs' life cycles can produce two sticklac yields per year, though it may be better to rest for six months to let the host tree recover.

Harvesting
Lac is harvested by cutting the tree branches that hold sticklac. If dye is being produced, the insects are kept in the sticklac because the dye colour comes from the insects rather than their resin. They may be killed by exposure to the sun. On the other hand, if seedlac or shellac is being produced, most insects can escape because less coloured pale lac is generally more desired.

Uses
The use of lac dye goes back to ancient times. It was used in ancient India and neighbouring areas as wood finish, lacquareware, skin cosmetic, lacquerware and dye for wool and silk. In China, it is a traditional dye for leather goods. Lac for dye has been somewhat replaced by the emergence of synthetic dyes, though it remains in use, and some juices, carbonated drinks, wine, jam, sauce, and candy are coloured using it. It is still used as sealing wax by the India Post but its use is being phased out.

Lac is used in folk medicine as a hepatoprotective and anti-obesity drug. It is used in violin and other varnish and is soluble in alcohol. This type of lac was used in the finishing of 18th-century fowling guns in the United States.

Production levels
India exported significant amounts of sticklac derivatives, especially lac dye, from the 1700s to the late 1800s. Production declined as synthetic dyes emerged, and after the late 1940s, production of seedlac and shellac also declined due to replacement.

In the mid-1950s, India annually produced about 50,000 tons of sticklac and exported about 29,000 tons of lac; by the late 1980s the figures were about 12,000 tons and 7,000 tons, respectively. By 1992–93, India's lac exports fell further to 4,500 tons. In the same period, Thailand's production increased somewhat, with annual lac exports of around 7,000 tons in the 1990s, mainly of seedlac. China exported only about 500 tons of shellac per year in the 1990s but produced more lac internally: 4,000-5,000 tons of sticklac and 2,000–3,000 tons of shellac in Yunnan province, with additional, smaller production in Fujian province. While India, Thailand, and China are the major lac producers, Bangladesh, Myanmar, Vietnam, and Sri Lanka also play small roles.

Description in ancient texts
Usage of lac/lah/laksha is described in ancient Hindu literature Atharvaveda also. Kand 5 and Sukta 5 (chapter 5, verse 5) is called as Laksha Sukti - verse related to lac. This entire verse is dedicated to lac and its usage. It has description of many ancient practices.

The Mahabharata mentions the Lakshagriha, which was built by the Kauravas to house the Pandavas. The intention of Kauravan was to burn the Pandavas by setting fire to the Lakshagriha.

Species

 * Kerria lacca – the true lac scale
 * Paratachardina decorella – the rosette lac scale
 * Paratachardina pseudolobata – the lobate lac scale
 * Kerria javana

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: Lac (resin)


text:
Greater London Authority

The Greater London Authority (GLA), colloquially known by the metonym City Hall, is the devolved regional governance body of Greater London, England. It consists of two political branches: an executive Mayor (currently Sadiq Khan) and the 25-member London Assembly, which serves as a means of checks and balances on the Mayor. Since May 2016, both branches have been under the control of the London Labour Party. The authority was established in 2000, following a local referendum, and derives most of its powers from the Greater London Authority Act 1999 and the Greater London Authority Act 2007.

It is a strategic regional authority, with powers over transport, policing, economic development, and fire and emergency planning. Three functional bodies—Transport for London, the Mayor's Office for Policing and Crime, and the London Fire Commissioner—are responsible for delivery of services in these areas. The planning policies of the Mayor of London are detailed in a statutory London Plan which is regularly updated and published.

The Greater London Authority is mostly funded by direct government grant and it is also a precepting authority, with some money collected with local Council Tax. The GLA is unique in the British devolved and local government system, in terms of structure (it uses a presidential system-esque model), elections and selection of powers. The authority was established to replace a range of joint boards and quangos and provided an elected upper tier of local government in Greater London for the first time since the abolition of the Greater London Council in 1986.

Purpose
The GLA is responsible for the strategic administration of the 1579 km2 of Greater London. It shares local government powers with the councils of 32 London boroughs and the City of London Corporation. It was created to improve the co-ordination between the local authorities in Greater London, while the Mayor of London's role is to provide a single representative for the capital. The Mayor proposes policy and the GLA's budget, and makes appointments to the capital's strategic executive such as Transport for London. The primary purpose of the London Assembly is to hold the Mayor of London to account by scrutiny of his or her actions and decisions. The assembly must also accept or amend the mayor's budget on an annual basis. The GLA is based at City Hall in the London Borough of Newham, situated next to the redeveloped Royal Victoria Dock in Canning Town. The GLA moved to this building from the previous City Hall, in Southwark, in January 2022.

The GLA is different from the corporation of the City of London with its largely ceremonial lord mayors, which controls only the square mile of the city, London's chief financial centre.

Background
In 1986, the Greater London Council was abolished by the Conservative government of Margaret Thatcher. Many people have surmised that the decision to abolish the GLC was made because of the existence of a high-spending left-wing Labour administration under Ken Livingstone, although pressure for the abolition of the GLC had arisen before Livingstone took over, and was largely driven by the belief among the outer London borough councils that they could perform the functions of the GLC just as well.

On abolition, the strategic functions of the GLC were transferred to bodies controlled by central government or joint boards nominated by the London borough councils. Some of the service delivery functions were transferred down to the councils themselves. For the next 14 years there was no single elected body for the whole of London. The Labour Party never supported the abolition of the GLC and made it a policy to re-establish some form of citywide elected authority.

Creation
The Labour Party advocated a government structure comprising a single, directly elected mayor (a policy first suggested by Tony Banks in 1990), together with an elected deliberative assembly to scrutinise him. This model was based on the mayor–council government of many American and Canadian cities rather than the parliamentary-style GLC. Indeed, it was partly aimed at making sure the new body resembled the erstwhile GLC as little as possible. After Labour won the 1997 general election, the policy was outlined in a white paper entitled A Mayor and Assembly for London (March 1998).

Simultaneously with the elections to the London Borough councils, a referendum was held on the establishment of the GLA in May 1998, which was approved with 72% of the vote. The Greater London Authority Act 1999 passed through Parliament, receiving royal assent in October 1999. Most polling showed that Livingstone, the last leader of the GLC, would easily win the mayoral election. However, in a controversial election campaign, the then prime minister, Tony Blair, attempted to block the nomination of Livingstone, a factional rival, and imposed his own candidate. In reaction, Livingstone stood as an independent candidate, resulting in his expulsion from the Labour Party. In March 2000, he was elected as Mayor of London, pushing Labour's candidate into third place. Following an interim period in which the mayor and assembly had been elected but had no powers, the GLA was formally established on 3 July 2000.

Headquarters
For the first two years of its existence, the Greater London Authority was based at Romney House, 47 Marsham Street in Westminster. Meetings of the London Assembly took place at Emmanuel Centre, also on Marsham Street.

Between July 2002 and December 2021, the Greater London Authority was based at a building known as City Hall in Southwark, on the banks of the River Thames, close to Tower Bridge. City Hall was designed by Norman Foster and constructed at a cost of £43 million on a site formerly occupied by wharves serving the Pool of London. This building did not belong to the GLA but was leased under a 25-year rental agreement from the Kuwait Investment Authority.

In November 2020, Mayor of London Sadiq Khan announced plans to vacate City Hall at the end of 2021 and relocate to The Crystal in the Canning Town area of East London. The Crystal building is owned by the Greater London Authority and is currently under-occupied. City Hall was not owned by the authority itself and the proposed move would save the Greater London Authority £12.6 million a year in rental costs. The decision was confirmed on 3 November 2020. Newham Borough Council gave permission for a change of use for the building in December 2020. The authority vacated City Hall on 2 December 2021 and the move is due to completed in the first week of January 2022. The Crystal was renamed "City Hall" in December 2021.

In addition to City Hall, staff of the Greater London Authority are also based at Palestra House on Blackfriars Road and at the London Fire Brigade headquarters on Union Street, both in Southwark.

The predecessors of the Greater London Authority, the Greater London Council and the London County Council, had their headquarters at County Hall, upstream on the South Bank. Although County Hall's old council chamber is still intact, the building is unavailable for use by the GLA because of its conversion into, among other things, a luxury hotel, amusement arcade and aquarium.

Functional bodies
Areas which the GLA has responsibility for include transport, policing, fire and rescue, development and strategic planning. The GLA does not directly provide any services itself. Instead, its work is carried out by functional bodies which, together with the GLA itself, form the GLA Group and work under the policy direction of the mayor and assembly. These functional bodies (defined in section 424 (1) of the Greater London Authority Act 1999) are:
 * Transport for London (TfL) – Responsible for managing most aspects of London's transport system, including public transport, main roads, and traffic management, and administering the London congestion charge.
 * Mayor's Office for Policing and Crime – Responsible for overseeing the Metropolitan Police Service, which provides policing throughout Greater London. Replaced the Metropolitan Police Authority in January 2012 under the provisions of the Police Reform and Social Responsibility Act 2011.
 * The London Fire Commissioner – Administers the London Fire Brigade and co-ordinates emergency planning. Until April 2017 this was the responsibility of the London Fire and Emergency Planning Authority (LFEPA).
 * The London Legacy Development Corporation and Old Oak and Park Royal Development Corporation, which are Mayoral development corporations. Before April 2012 the London Development Agency (LDA) was responsible for development across London but was wound up following the Localism Act 2011. The London Legacy Development Corporation and Old Oak and Park Royal Development Corporation were set up using powers in the Localism Act to create Mayoral development corporations.

In November 2005, the government published a consultation document reviewing the powers of the GLA, making proposals for additional powers, including waste management, planning, housing, and learning and skills. The result of the consultation and final proposals were published by the Department for Communities and Local Government on 13 July 2006.

A range of back office services for the GLA and its functional bodies are provided collectively by the GLA Group using the common provision powers of section 401A of the 1999 Act. The most senior member of staff within the GLA Group is the GLA Head of Paid Service.

Planning
The GLA is responsible for co-ordinating land use planning in Greater London. The mayor produces a strategic plan, the "London Plan". The individual London Borough councils are legally bound to comply with the plan. The mayor has the power to over-ride planning decisions made by the London Boroughs if they are believed to be against the interests of London as a whole.

Energy policy
As of 2006, London generates 42 million tonnes of carbon emissions per year, 7% of the UK's total. 44% of this comes from housing, 28% from commercial premises, 21% from transport, and 7% from industry.

The Mayor's energy strategy planned to cut carbon emission levels by 20% by 2010 and 60% by 2050 (although achieving the first of these targets is unlikely). Measures taken to achieve this have included the creation of the London Climate Change Agency, the London Energy Partnership and the founding of the international Large Cities Climate Leadership Group.

The London Sustainable Development Commission has calculated that for housing to meet the 60% target, all new developments would have to be constructed to be carbon-neutral with immediate effect (using zero energy building techniques), in addition to cutting energy used in existing housing by 40%.

Political control
After the 2024 elections, Labour has the largest representation on the GLA with the mayor as well as eleven assembly members, followed by eight from the Conservatives, three Greens, two from the Liberal Democrats, and one from Reform UK.

Elections

 * 2000 London Assembly election
 * 2000 London mayoral election
 * 2004 London Assembly election
 * 2004 London mayoral election
 * 2008 London Assembly election
 * 2008 London mayoral election
 * 2012 London Assembly election
 * 2012 London mayoral election
 * 2016 London Assembly election
 * 2016 London mayoral election
 * 2021 London Assembly election
 * 2021 London mayoral election
 * 2024 London Assembly election
 * 2024 London mayoral election

title: Greater London Authority


text:
1256

Year 1256 (MCCLVI) was a leap year starting on Saturday (link will display the full calendar) of the Julian calendar.

Mongol Empire

 * Spring – Mongol forces (some 80,000 men), under Hulagu Khan, cross the Oxus River, and begin their campaign to destroy the remaining Muslim states in southwestern Asia – with the first objectives being the Nizari Ismaili strongholds and Baghdad, the capital of the Abbasid Caliphate. The roads across Turkestan and Persia are repaired, and bridges built. Carts are requisitioned to bring siege machines from China.
 * October – Mongol forces led by Baiju Noyan (operating under Hulagu Khan's command) win a victory over Kaykaus II, Seljuk ruler of the Sultanate of Rum, and capture Anatolia. Kaykaus flees to the Byzantine court where he seeks refuge at Constantinople. The Empire of Trebizond fearing a potential punitive Mongol expedition, becomes a vassal state and is forced to pay a tribute tax every year in gold and silk.
 * November 8–23 – Siege of Maymun-Diz: Mongol forces under Hulagu Khan successfully besiege the mountain castle of Maymun-Diz. Hulagu encircles the fortress and begins a bombardment for three days by mangonels from a nearby hilltop. On November 19, Nizari Isma'ili imam Rukn al-Din Khurshah surrenders, but a small part of the garrison refuses and fights a last stand, until they are killed after three days.
 * December 15 – Mongol forces under Hulagu Khan capture and dismantle Alamut Castle (near the Masoudabad region) after the surrender of the Nizari Ismaili leaders. Hulagu founds the Ilkhanate dynasty of Persia, which becomes one of the four main divisions of the Mongol Empire. The Nizari Ismaili government is disestablished, some of them migrate to Afghanistan, Badakhshan and Sindh (modern Pakistan).

Europe

 * War of the Euboeote Succession: Achaean forces under William II of Villehardouin attempt to gain control of the island of Euboea, which is resisted by the local Lombard barons (or "triarchs") with the aid of the Republic of Venice. William launches devastating raids in Euboea. Guy I de la Roche, the "Great Lord" of Athens and Thebes, enters the war against William, along with other barons of Central Greece.
 * 30 July – The Venetian Marsilio Zorzi recaptures Curzola in Dalmatia, and re-establishes himself as Count of Curzola and Mèleda.

British Isles

 * Prince Llywelyn ap Gruffudd invades the northern coastal areas that have agreed to English rule (see 1254). Edward (the Lord Edward), who has been given the areas to govern himself by his father, King Henry III, asks him for support but Henry refuses.
 * The ancient Irish Kingdom of Breifne splits into East Breifne and West Breifne, after a war between the O'Reillys and the O'Rourkes.

Levant

 * Venetian–Genoese War: A dispute between Venice and Genoa arises about concerning land in Acre owned by Mar Saba but claimed by both Venice and Genoa – which leads to a Genoese attack of the monastery in the Venetian quarter. The Venetians are supported by Pisa and the Knights Templar, while the Genoese are joined by the Knights Hospitaller.

Asia

 * October – The Japanese Kenchō era ends and the Kōgen era begins during the reign of the 13-year-old Emperor Go-Fukakusa.

Natural Disaster

 * June 30 – A large volcanic eruption in Harrat Rahat (near Medina) is associated with an Islamic prophecy.

Religion

 * May 4 – Pope Alexander IV issues the papal bull Licet ecclesiae catholicae, constituting the Order of Saint Augustine at Lecceto Monastery.
 * August 25 – In Bologna, slavery and serfdom are abolished; this event is recorded in the document called Liber Paradisus (or Heaven Book).

Births

 * January 6 – Gertrude the Great, German mystic (d. 1302)
 * January 24 – Alonso Pérez de Guzmán, Spanish nobleman (d. 1309)
 * February 9 – William de Warenne, English nobleman (d. 1286)
 * March 21 – Henry I (Lackland), German nobleman (d. 1318)
 * October 23 – Möngke Temür, Mongol ruler of Shiraz (d. 1282)
 * Abu Hayyan al-Gharnati, Andalusian grammarian (d. 1344)
 * Adolph VI, count of Holstein-Pinneberg-Schauenburg (d. 1315)
 * Ahmad al-Suhrawardi, Persian calligrapher and musician (d. 1340)
 * Al-Dimashqi, Syrian geographer, explorer and writer (d. 1327)
 * Andrea Dotti, Italian nobleman, preacher and saint (d. 1315)
 * Ibn al-Banna, Almohad scholar and mathematician (d. 1321)
 * Jamal al-Din al-Mizzi, Syrian scholar and philologist (d. 1341)
 * John Segrave, English nobleman and seneschal (d. 1325)
 * Padishah Khatun, Mongol female ruler and writer (d. 1295)
 * Robert of Clermont, French prince and nobleman (d. 1317)
 * Roger Mortimer, English nobleman and constable (d. 1326)

Deaths

 * January 4 – Bernhard von Spanheim, German nobleman
 * January 18 – Maria of Brabant, duchess of Bavaria (b. 1226)
 * January 28 – William II of Holland, king of Germany (b. 1227)
 * February 9 – Alice de Lusigan, English noblewoman (b. 1224)
 * February 16 – Nicola Paglia, Italian Dominican priest (b. 1197)
 * April 12 – Margaret of Bourbon, queen of Navarre (b. 1217)
 * April 23 – Sabrisho V, patriarch of the Church of the East
 * May 1 – Mafalda of Portugal, Spanish abbess and queen
 * May 6 – Peter Nolasco, French religious leader (b. 1189)
 * May 12 – Matilda of Amboise, French noblewoman (b. 1200)
 * May 28 – Guglielmo Fieschi, Italian deacon and cardinal
 * June 13 – Tankei, Japanese Buddhist sculptor (b. 1173)
 * September 1 – Kujō Yoritsune, Japanese shogun (b. 1218)
 * September 21 – William of Kilkenny, English bishop of Ely
 * October 14 – Kujō Yoritsugu, Japanese shogun (b. 1239)
 * November 5 – Christina de Valognes, Scottish noblewoman
 * Bertram de Criol (or Criel), English constable and diplomat
 * Jacob Anatoli, French Jewish translator and writer (b. 1194)
 * Johannes de Sacrobosco, English scholar and astronomer
 * Klement of Ruszcza, Polish nobleman and knight (b. 1190)
 * Najm al-Din Razi, Persian philosopher and writer (b. 1177)
 * Pandulf of Anagni, Italian bishop and military commander
 * Peter de Ramsay, Scottish nobleman, cleric and bishop
 * Þórður kakali Sighvatsson, Icelandic chieftain (b. 1210)
 * Rodrigo González Girón, Spanish nobleman and knight
 * Sibt ibn al-Jawzi, Arab preacher and historian (b. 1185)

title: 1256


text:
Apostolicam Actuositatem

Apostolicam Actuositatem (Apostolic Activity), also known as the "Decree on the Apostolate of the Laity", is one of the 16 magisterial documents of the Second Vatican Council.

The final text was approved on 10 November, 1965 by a vote of 2,201 to 2. On 18 November, 1965, it was promulgated by Pope Paul VI, after another vote, this time of 2,340 to 2.

The purpose of the document was to encourage and guide lay Catholics in their Christian service. In this decree the Council sought to describe the nature, character, and diversity of the lay apostolate, to state its basic principles, and to give pastoral directives for its more effective exercise. The specific objectives of lay ministry are: evangelization and sanctification, renewal of the temporal order whereby Christ is first in all things, and charitable works and social aid. The decree quotes Colossians 3:17: "Whatever you do in word or work, do all in the name of the Lord Jesus Christ, giving thanks to God the Father through Him".

Background
Apostolicam Actuositatem follows upon Lumen gentium, the "Dogmatic Constitution on the Church", of 21 November 1964, which in Chapter IV, discusses the laity, by which they mean all the faithful except those in Holy Orders or religious institutes. "They live in the ordinary circumstances of family and social life, from which the very web of their existence is woven. ...led by the spirit of the Gospel they may work for the sanctification of the world from within as a leaven. In this way they may make Christ known to others, especially by the testimony of a life resplendent in faith, hope and charity.

After
The Pontifical Council for the Laity had its foundation in Vatican II's Apostolicam Actuositatem, §26. The Pontifical council was created in January 1967 by Pope Paul VI's motu proprio Catholicam Christi Ecclesiam. In December 1976, the council was included as a permanent fixture of the Roman Curia. In September 2016, its functions were shifted to the new Dicastery for the Laity, Family and Life.

title: Apostolicam Actuositatem