get a dose of history. antibiotic – 3. an antibiotic substance: one of a class of substances...

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antibiotic – 3. an antibiotic substance: one of a class of substances produced by living organisms and capable of destroying or inhibiting the growth of micro-organisms;

Oxford English Dictionary

In other words:a living thing (e.g. mould) acting to kill another living thing (bacteria)

First of all, what is 'antibiotic'?


Does the discovery of penicillin belong

to the twentieth century?


The Middle AgesIt is recognised that

injured horses wearing mouldy saddles heal

quicker than those with mould-free saddles.

1871Joseph Lister

observes the action of penicillium glaucum on

bacteria.Not taken further.

1876John Tyndall, a British physicist, notes that penicillin notatum

(mould) slows down bacterial growth.Not taken further.

1897Ernest Duchesne, a French physician,

discovers the healing properties of

penicillium glaucum. Aged only 23 he isn't taken seriously. Army

service prevents further investigation.

1640John Parkinson, herbalist to King Charles I, records the healing properties of

mould for infections.

1928Alexander Fleming observes the effect penicillium notatum

has on bacterial growth. He grows a

pure culture and isolates the

'antibiotic' which he calls penicillin

Timeline

1939

Background to penicillin


Research team at the Sir William Dunn School of Pathology at Oxford University.Do you know the names of individuals?

They were interested in furthering studies of antibacterial substances produced by bacteria or mould. Penicillin was just one of 3 or 4 substances they were investigating.

Background to Penicillin

Research grant from the Rockefeller Foundation, the Medical Research Council and the Nuffield Trust.

Penicillin was successfully extracted using mould cultures grown by Fleming. The new antibiotic could be tested for the first time as a possible life-saving medicine.


What was really special about penicillin was that it wasn't toxic. Other medicines had been developed which had some antibiotic properties but could make the patient even more sick.

The team also found that penicillin worked both in vitro, meaning within the glass (in a petri dish or test tube) and in vivo, meaning within the living (in a living subject). These two discoveries meant that Florey's team knew they were on to something potentially very exciting.

The first human to be given penicillin was a policeman aged 43

Patient admitted to hospital October 12, 1940 with pus discharging from his face, scalp and eye sockets. This developed into multiple abscesses over his head and body and his bones were shown to have been infected by the bacteria by January 1941. By February he was very ill indeed and his lungs were also infected with the bacteria.

On February 12 the patient was given his first dose of penicillin and after 24 hours there was a striking improvement. After 5 days of measured doses, the patient was much improved, with no fever, his abscesses significantly improved and his appetite much better. The supply ran out at this point and although his condition remained stable for 10 days, he began to dramatically deteriorate particularly in his lungs.

The patient died on March 15.

Information taken from an article by Florey and team in The Lancet August 16 1941

This man's illness began with a small sore in the corner of his mouth!

Background to Penicillin


You are going to be looking at a range of different primary sources connected to the development of

penicillin.

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Some might suggest new ideas that you haven't considered

before.

You will need to assess the evidence and decide

how valuable theyare as sources.

Some might be effected by bias or opinion.

Will this makethem totally useless?

Once you've assessed all the evidence, you

will need to select those that back up your own opinion about the discovery of penicillin.

With these thoughts in mind, consider the following sources.

photograph publicinformation

contemporary account


The team at Sir William Dunn School of Pathology circa 1940. Those named in the photograph were on the penicillin research project.

Once it was discovered how remarkable penicillin was, all resources were spent on only furthering this research; the other projects were

postponed.(MA Jennings, CM Fletcher and AG Sanders were also involved in the

penicillin project but are not in this photograph)

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HW. Florey AD. Gardner

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Norman Heatley was a 25 year old biochemist when he arrived at the Sir William Dunn School of Pathology in 1936. He was invited by Florey to join the penicillin research team in October 1939 after his Rockefeller fellowship fell through

due to the outbreak of World War II.

Oral history extractNorman Heatley's thoughts on Professor Howard Florey 1:10.5

Norman Heatley's thoughts on Dr Ernst Chain 48.6

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Norman Heatley was interviewed on 30th March 1994 at the Royal Pharmaceutical Society Headquarters in Lambeth.

You will hear some more of Heatley's interview with the next few slides.

Things to think about:

● What are the benefits of having● oral history as evidence?

● What are the limitations of oral ● history?

● Do you find Norman Heatley's ● account useful in understanding● the development of penicillin?

Norman Heatley (1911 – 2004)

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DiscussionWhat do you think this mystery object is and how is it connected with the story of penicillin?

This is a PENICILLIN CULTURE VESSEL made by potters Macyntyre & Co in 1940. Norman Heatley designed the vessel as a means of growing enough of the culture to carry out tests on human cases at the beginning of 1941.

Oral history extract

1:51:15

Norman Heatley's account of the search for a suitable culture vessel

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This is a photograph of Alexander Fleming in his laboratory at St Mary's Hospital, Paddington.

DiscussionWhen do you think this photograph was taken and why?

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This photograph was taken in 1943, 15 years after Fleming's discovery!

It was one of a set of images for a pamphlet called “Penicillin: Past, Present & Future” produced by the Ministry of Information.

You will see some more of these photographs over the next few slides.

Things to think about:• How valuable are the • photographs as evidence?• • Why do you think they were• produced?• • Do they contradict any other• evidence that you have learnt• about?

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The queer stuff inside that resembles a well browned, well peaked meringue pie, is full grown penicillium mould...The full grown mould excretes a substance...from which penicillin is obtained.

Caption from Penicillin: Past, Present & Future, 1943

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In 1929, Professor Alexander Fleming... noticed that a mould which had accidentally contaminated a culture...had stopped the growth of the bacteria... he at once saw the importance of the discovery and investigated it further...

Caption from Penicillin: Past, Present & Future, 1943

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...there are 4,000 flasks in this lot, ready for the mould to grow. It takes only a few days before the first white fluff will appear on the brown medium [corn steep]...The room is kept at a temperature of 75°F.

Caption from Penicillin: Past, Present & Future, 1943©

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The next 8 slides show more primary sources. Investigate each of them, thinking about:

• How useful they are as a source?

• Are there any problems with the source?

• Are they fact or opinion?

• What do they tell you about the story of the development of penicillin?


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War in itself is essentially evil yet it has often acted as a stimulus toward developments of great value to humanity. An outstanding example of this is the mass production of penicillin; ordinarily this would have required a decade or more for its accomplishment, but in the present emergency only a fraction of that time intervened from the time research was begun until enough plants were in actual operation.

Although the original discoveries were British, large-scale manufacture is a monument to American scientific genius.

From an article in the Journal for the American Pharmaceutical Association, 1944

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Florey had… been trying to get…somebody to set up a pilot plant…and he learned fairly soon that it wouldn’t be possible at that time...He was in touch with the Rockafeller people and they suggested that he went over to the States to try and get people there interested, which he did …there was no idea of trying to collaborate or anything, he just wanted someone to make him a kilo of the crude stuff we’d been using at Oxford to do further clinical trials...

Transcript from an oral history interview with Dr Norman Heatley,interviewed 30 March 1994

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On September 28, Mr WD Kendall (Independent Party, Grantham) asked the Minister of Health whether in view of the fact that penicillin is available to German prisoners for wounds or diseases of all types in which it was effective, he would take immediate steps to make it available to British civilians in those cases where death would otherwise result.

Mr WILLINK replied that the Government was required by the Geneva Convention to care for wounded prisoners of war, without distinction of nationality equally with our own personnel. The bulk of penicillin available is at present required for Service cases, and the amount which could be released for the treatment of civilians was not sufficient to enable penicillin to be given in every case which might conceivably benefit from it. It was necessary therefore to reserve this small amount for the treatment of cases in which it might be the only means of saving life or of effecting recovery from grave illness and in which the prospects of recovery were high.

Mr KENDALL: Is it not a fact that we are getting large supplies now from the United States of America? I want to ask whether or not it is more desirable to give British citizens a chance of living than the Germans?

Mr WILLINK: I have made it quite clear that His Majesty's Government are bound in this matter by the Geneva Convention.

From the Parliamentary News section of The Pharmaceutical Journal, October 7 1944

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During the last year methods have devised here for obtaining a considerable yield of penicillin, and of rapid assay [analysis] of its inhibitory power. From the culture medium a brown powder has been obtained which is freely soluble in water. It and its solution are stable for a considerable time and though it is not a pure substance, its anti-bacterial activity is very great.

From an article in The Lancet, August 24, 1940 written by Florey and his team, describing their early antibacterial experiments.

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Taken from The Chemist & Druggist, September 25 1943, Volume 140

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Penicillin takes it place among the valuable drugs available to the physician from the pharmacist. Penicillin born during the war emergency, matured rapidly to relieve the infections and suffering of battle, will serve mankind in years to come. Penicillin is the first of an entirely new group of therapeutic agents - the antibiotics.

From an article in the Journal for the American Pharmaceutical Association, 1944

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Norman Heatley's thoughts on the discovery of penicillin. 1:38:75

From an oral history interview with Dr Norman Heatley, interviewed 30 March 1994

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So what happened

next?

Did everyone live happily ever after?

Not quite!


At first penicillin was reserved for the military and experimental use only.Finally on June 1st 1946 penicillin was released to pharmacies and hospitals.

This photograph of a pharmacy shop front was taken in 1955. Penicillin is displayed in the window under the sign Modern Medicinal Products.

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The development of penicillin prompted searches for more antibiotic substances.

Streptomycin was developed in 1944 and could fight tuberculosis, one of the world's biggest killers. This was a massive breakthrough for medical science.

However it was also discovered early on that bacteria could become resistant to antibiotic substances if used incorrectly.

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From Alexander Fleming's Nobel Prize lecture, December 11 1945

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Get a dose of historyGet a dose of history

By 1995, one in seven cases of

tuberculosis was resistant to all

known antibiotics!


New superbug could make antibiotics 'redundant' 11th August 2010

Britain has the highest rates of dangerous superbug in Europe 16th

November 2010

Unstoppable bug to spread worldwide 11th August 2010

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Public awareness campaign to discourage misuse of antibiotics,

2008

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Is penicillin the greatestmedical discovery of the

twentieth century?

So...

What do you think?

get a dose of history. antibiotic – 3. an antibiotic substance: one of a class of substances...

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