BPS 1101 Lecture Notes - Agostino Bassi, Louis Pasteur, Gerhard Domagk

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TOPIC 7 REVIEW ANTIBIOTICS
Antibiotics are the second best health invention in human history!!
- life expectancy has dramatically increased due to such things as antibiotics and vaccinations (now main cause of
death is wear n’ tear it used to be infections!)
History of Infections
Plagues were common throughout history
- Bubonic Plague: mortality rate maybe 25%, and in some areas the mortality was 50%
- cause of death was unknown
- people thought it was due to God, therefore would search for reasons why God was mad (burn heretics,
etc.)
- cures and treatments failed
- if you were lucky, the treatments were harmless
- people who had knowledge of the disease fled from the area
- you were left with “plague doctors”: they would cover themselves from head to toe and wear beak mask
with spices with strong scents (thought it was due to unhealthy airs). They’d have stick to poke the patient
Maternal mortality rate
- post natal infections were common therefore maternal mortality rate was 30%
Surgery survival rate was less than 30%
- if you had any kind of surgery, you would likely die from infection
WWI and WWII - more deaths due to infection than combat
- You died from malaria, influenza, or cholera, but #1 cause of death was SEXUALLY TRANSMITTED DISEASE
Historical Road to Improvements
John Snow disproved miasma theory 1854
- miasma theory = disease caused by bad smells
- he carried out scientific investigation during cholera outbreak in London (Soho)
- Snow made a map of cholera infections, and through this identified the source
- the most infections were closest to an area of a particular water pump, which was close to a cesspit which
harvested the cholera bacteria (lived in foeces)
- they removed the handle from the pump so no one could get the water, but the City Fathers thought that foeces in
the water was a distasteful conclusion, so they ordered the handle to be put back on
- water pump is now a historical landmark, where each year they have a ceremony to remove the handle
and put it back on
Agostino Bassi showed microbes cause disease
- showed silkworks could get disease through fungus
Atharva-Veda identifies living animals causing disease
- therefore, not a new idea!
- these Hindu texts recorded almost 4000 years ago proposed this principal
Louis Pasteur develops pasteurization, 1864
- used knowledge that microbes caused disease as well as spoilage to improve milk
- if you heat milk at a low temperature, you maintain milk’s flavour and kill the baceteria
- people debated this, thought that heating milk destroyed nutrients (wrong!)
Lister develops antisepsis
- sprayed material toxic to microbes to protect patients during surgery
H.C. Gram stains bacteria in 1884
- using different dyes, you could colour different kinds of bacteria
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- blue dye has different affinity for different classes of bacteria
- blue = gram +, pink = gram
On the Way to Antibiotics The Magic Bullet
Paul Erlich and the magic bullet 1907
- if you could colour bacteria selectively, you could KILL bacteria selectively
- magic bullet = naturally find target on its own
- trypan red selectively colours trypanosomes (which cause sleeping sickness spread by flies)
- Erlich knew arsenic was similar to N (same column of periodic table), but more poisonous
- created Sarlvarsan 606
- salv = safe, arsan = arsenic
- not successful but it worked
- used to treat Syphilis, which caused 140 000 deaths/year in North America (now known as the Great Pox)
- drug is not soluble in water so it had to be dissolved in large bottles of water (had to inject large amount
over a while)
- problem if injected into the muscle, it could destroy the muscle, BUT if given properly, it’s good
- Erlich won Nobel Prize in Medicine in 1908
Gerhard Domagk at IG Farben 1932
- chemist experimenting with different dyes to find medical uses (goes back to Gram stain)
- what he found: red dye called Prontosil was able to kill certain bacteria in his cells
- daughter had serious blood infection, so gave it to his daughter health improved!
- Prontosil only worked in vivo (could not kill bacteria in a dish but could eliminate infection in a rat) because it was
metabolized from prontosil to sulphanilamide
Sulfanilamide became the first sulfa drug in 1932
- sulfa drugs saved lives in WWII (if you ever see in a movie, a soldier get shot and a doctor spray powder on the
wound, that’s sulfa drug)
- sulfa drugs inhibit bacterial growth
- bacterial enzyme produces coenzyme F
- sulfa drug mimics natural substrate, so that it gets “jammed” into the enzyme
- Gerhardt Domagk wins Nobel Prize in Medicine in 1939
- was prevented acceptance because of the Nazis
The Discovery of Penicillin
Alexander Fleming contaminates culture in 1928
- found mould that would lead to the discovery of penicillin
- mould prevented bacterial growth
- Fleming published his results in 1929, in an obscure journal and nobody read it
- Fleming used penicillin to purify bacteria
- He did NOT do the key experiment!
- gave penicillin to mice, but thought that if you artificially injected a mouse with disease, it would be
different from a natural infection
Howard Florey & Ernst Chain isolated penicillin in 1941
- during WWII, they were trying to come up with new ways to kill bacteria
- found Fleming’s paper and isolated penicillin
- penicillin was first produced in milk bottles
- 1000 kg mould gave 1 g penicillin
- grown in milk bottles because the mould requires oxygen
- used home built machines to isolate penicillin (had to divert funds from their other research because no
one believed their research)
- did the key experiment infected mice with bacteria: half given penicillin, have a placebo. The ones with a
placebo died, the ones with penicillin got better
- first experiment on a human someone cut himself shaving, and because of this, had a severe infection on his
head. Was able to slightly recover with penicillin but they didn’t have enough so he died eventually
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