Sir Alexander Fleming & Selman Waksman

Sir Alexander Fleming,

(born August 6, 1881, Ayrshire, Scotland—died March 11, 1955, London, England)

 ·         Scottish bacteriologist

·         Best known for his discovery of penicillin.

·         work on wound infection and lysozyme, an antibacterial enzyme found in tears and saliva

·         Discovery of penicillin in 1928 started the antibiotic revolution.

·         Received the Nobel Prize for Physiology or Medicine in 1945, along with Australian pathologist Howard Walter Florey and German-born British biochemist Ernst Boris Chain, both of whom isolated and purified penicillin

 

History

• ·         Fleming was the seventh of eight children of a Scottish hill farmer
• ·         He began his elementary schooling at Scotland
• ·         In 1895 he moved to London to live with his elder brother Thomas
• ·     After working as a London shipping clerk, Fleming began his medical studies at St. Mary’s Hospital Medical School in 1901.
• ·         There he won the 1908 gold medal as top medical student at the University of London.
• ·     Alexander was persuaded by Sir Almroth Wright, an authority in immunology, to become a researcher in his bacteriology group at St Mary’s Hospital Medical School. While carrying out this research Fleming graduated, in 1908, with a degree in bacteriology and the Gold Medal for top student. St Mary’s Hospital Medical School then promoted him to the role of bacteriology lecturer.
• ·         Almroth Wright was interested in our bodies’ natural ability to fight infection. Fleming became particularly fascinated by the fact that although people suffer bacterial infections from time to time, our natural defenses usually prevent infections from taking hold.
• ·         Fleming was one of the first doctors in Britain to administer arsphenamine (Salvarsan), a drug effective against syphilis that was discovered by German scientist Paul Ehrlich in 1910.
• ·         During World War I, Fleming had a commission in the Royal Army Medical Corps and worked as a bacteriologist studying wound infections in a laboratory that Wright had set up in a military hospital housed in a casino in Boulogne, France.
• ·         There he demonstrated that the use of strong antiseptics on wounds did more harm than good and recommended that the wounds simply be kept clean with a mild saline solution.
• ·         In 1914 World War 1 broke out and Fleming, age 33, joined the army, becoming a captain in the Royal Army Medical Corps working in field hospitals in France. There, in a series of brilliant experiments, he established that antiseptic agents used to treat wounds and prevent infection were actually killing more soldiers than the infections were.
• ·         The antiseptics, such as carbolic acid, boric acid and hydrogen peroxide, were failing to kill bacteria deep in wounds; worse, they were in fact lowering the soldier’s natural resistance to infection because they were killing white blood cells.
• ·         Fleming demonstrated that antiseptic agents were only useful in treating superficial wounds, but were harmful when applied to deep wounds.
• ·         Almroth Wright believed that a saline solution – salt water – should be used to clean deep wounds, because this did not interfere with the body’s own defenses and in fact attracted white cells. Fleming proved this result in the field.
• ·         Wright and Fleming published their results, but most army doctors refused to change their ways, resulting in many preventable deaths.
• ·         Fleming returned to St. Mary’s after the war and was promoted to assistant director of the Inoculation Department.
• ·         Years later, in 1946, he succeeded Wright as principal of the department, which was renamed the Wright-Fleming Institute.
• ·         In November 1921 Fleming discovered lysozyme, an enzyme present in body fluids such as saliva and tears that has a mild antiseptic effect. That was the first of his major discoveries.
• ·          It came about when he had a cold and a drop of his nasal mucus fell onto a culture plate of bacteria. Realizing that his mucus might have an effect on bacterial growth, he mixed the mucus into the culture and a few weeks later saw signs of the bacteria’s having been dissolved.
• ·          Fleming’s study of lysozyme, which he considered his best work as a scientist, was a significant contribution to the understanding of how the body fights infection. Unfortunately, lysozyme had no effect on the most-pathogenic bacteria.

Discovery of Penicillin

• ·         On September 3, 1928, shortly after his appointment as professor of bacteriology, Fleming noticed that a culture plate of Staphylococcus aureus he had been working on had become contaminated by a fungus.
• ·         A mold, later identified as Penicillium notatum, had inhibited the growth of the bacteria. He at first called the substance “mould juice” and then “penicillin,” after the mold that produced it.
• ·         Fleming decided to investigate further, because he thought that he had found an enzyme more potent than lysozyme. In fact, it was not an enzyme but an antibiotic —one of the first to be discovered.
• ·         By the time Fleming had established that, he was interested in penicillin for itself.
• ·         But the therapeutic development of penicillin required multidisciplinary teamwork.
• ·         Fleming, working with two young researchers, failed to stabilize and purify penicillin. However, he did point out that penicillin had clinical potential, both as a topical antiseptic and as an injectable antibiotic, if it could be isolated and purified.
• ·         Penicillin eventually came into use during World War II as the result of the work of a team of scientists led by Howard Florey at the University of Oxford.
• ·         In 1945 Fleming, Florey and Chain shared the Nobel Prize in Medicine.
• ·         Fleming wrote numerous papers on bacteriology, immunology and chemotherapy.
• ·         He was elected professor of the medical school in 1928 and emeritus professor of bacteriology at the University of London in 1948.
• ·         He was elected fellow of the Royal Society in 1943 and knighted in 1944.
• ·         For the last decade of his life, Fleming was renowned universally for his discovery of penicillin and acted as a world ambassador for medicine and science.
• ·         Initially a shy uncommunicative man and a poor lecturer, he became one of the world’s best-known scientists.
• ·         Fleming died on 11 March 1955. 

 

• ·         Penicillin made a difference during the first half of the 20th century. The first patient was successfully treated for streptococcal septicaemia in the United States in 1942. However, supply was limited and demand was high in the early days of penicillin.
• ·         Penicillin helped reduce the number of deaths and amputations of troops during World War II. According to records, there were only 400 million units of penicillin available during the first five months of 1943; by the time World War II ended, U.S. companies were making 650 billion units a month.

 

Selman Waksman

• Selman Abraham Waksman, renamed the term 'antibiosis' to 'antibiotics'. He discovered a number of antibiotics, and is often called the 'Father of Antibiotics'. 
• One of his antibiotic, streptomycin, was the first antibiotic to treat tuberculosis and was also listed as one of the top ten patents that changed the world.
•  Nobel Prize in physiology or medicine in 1952 “for his discovery of streptomycin.

History

• Selman Abraham Waksman (1888-1973) was born in the rural Ukrainian town. The town and its nearby villages were surrounded by a rich black soil that supported abundant agricultural life. The chemistry of the fertile soil incited a curiosity in him.
• In 1910, after completing his matriculation diploma, Waksman migrated to the United States. He worked for a few years on a family farm in New Jersey and then enrolled in Rutgers College. 
• There he studied bacteria in culture samples from successive soil layers, which resulted in his introduction to the actinomycetes. Waksman studied these bacteria for both his Master's and Doctorate degrees and  eventually become a major expert.
• After receiving his doctorate from the University of California, Berkeley, in 1918, Waksman secured a position at the Rutgers Bacteriology Department where he continued his research on soil micro flora.

 

•  In  1921 Waksman isolated  sulphur oxidizing Thiobacillus thiooxidans
•  1922-  Enzymes, he  co-authored a book with W.C. Davison, New York.
•  1927- Authored, Principles of Soil Microbiology

 

• Several years later, a young French biologist named Rene Dubois joined his laboratory. By 1927, Dubois was studying the one-on one effects of soil organisms in decomposing cellulose and was beginning an approach that would lead to modern antibiotics.
• In collaboration with Oswald Avery at the Rockefeller Institute Hospital, Dubois isolated a soil bacterium that could attack the capsular polysaccharide of Streptococcus pneumoniae. This discovery inspired Waksman to look for more pre-existing antibacterial organisms in soil samples.

 

• In 1930s – he started exploring soil microorganisms for activity against Tubercle Bacillus
•  1939- Waksman & colleagues – search for antibiotics from soil actinomycetes and fungi -Ten antibiotics within a decade 
  
• By 1940, Waksman and H. Boyd Woodru had devised a technique for identifying natural substances with antibacterial properties. The screening was done by looking for growth inhibition zones around single colonies of systematically isolated soil microbes, grown under a variety of culture conditions, and then testing the inhibition on specically targeted pathogenic bacteria.
• Waksman identied from Actinomyces antibioticus, a substance, actinomycin, that had both bacteriostatic and bactericidal properties. The compound is highly active against various gram-positive bacteria but less active against gram-negative organisms. 
• Unfortunately, actinomycin was extremely toxic to experimental animals and thus of little therapeutic value.

• Waksman followed this initial failure with an extensive screening of actinomycetes for their ability to produce antibacterials. He identified more than 20 new natural inhibitory substances, including streptomycin and neomycin, and proposed the now standard term “antibiotics” for this class of natural growth inhibitors.

 

•  Streptomycin was discovered in 1944, by Waksman and his student, Albert Schatz.It was the first antibiotic effective against tuberculosis. Waksman collaborated with Merck and Company to develop the fermentation process for producing bulk quantities of streptomycin. Waksman patented and licensed his promising antibiotics, he gave 80% of his patent earnings to Rutgers University. 
•  1949- Neomycin (against streptomycin-resistant bacteria)

 

• In 1951 he established an Institute of Microbiology in association with Rutgers. Waksman established the Foundation for Microbiology in 1951.

• During his lifetime, Waksman received ~ 66 awards and 22 honorary degrees for his scientific work. He was elected to the National Academy of Sciences in 1942. However, Waksman's greatest honor came when he won the Nobel Prize in physiology or medicine in 1952 “for his discovery of streptomycin.