#ernst chain

[girlactionfigure]

[gregorygalloway]

Ernst Chain (19 June 1906 – 12 August 1979)

While Alexander Fleming had discovered penicillin by accident in 1928 (a fungal spore blew into an uncovered petri dish Fleming had left on his lab table while he was away for the weekend), it was not until Ernst Chain and Howard Florey ran across Fleming’s discovery (published in an obscure journal) in 1938 and began to scientifically develop penicillin as a viable drug.

Working in London with Europe on the verge of war, Ernst and Chain knew the impending necessity of the drug (about 1/3 of all deaths in World War I were from infection). By 1941, Chain and Ernst had developed a viable vaccine, and by 1944 it was internationally available.

[gillarbuthnott]

Our Microbe Friends #6 Miracle Mould

In 1939 the search was on for chemicals that could treat bacterial infections – a really serious issue with war looming. In Oxford Howard Florey and Ernst Chain came across Fleming’s work and started to look at penicillin. They infected mice with pneumonia and injected half of them with penicillin. The next day all the injected mice were fine, and all the others were dead. Chain rightly described…

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[mona-the-monkey]

When I envision of the only woman I’ve truly loved I cannot begin to think of arguing against Nobel Prize-winning biochemist Ernst Boris Chain’s observation.  There is something so deeply spiritual about her, so angelic in nature, that only divinity could have created the likes of her.

(”...”)

Yes, the pain of the loss of knowing her is intense, Me, but if I come to know nothing else in this world, I have learned something of most import about God.  I shall be forever grateful to her for that.

(”...?”)

In all my years I have met no flesh and bone match to her.  Without even realizing it she has demonstrated God’s nature to me.  In that there can be no regret.

[phil-iannaccone]

Penicillin Pots, Bacterial Infection and Ebola

October 14th, 2014:

We started the story of Penicillin last time to illustrate why it takes so long to move concepts from the laboratory to clinical use.  We will continue the story and draw a parallel to current events.

  Penicillin is released by the mold Penicillium, so getting any useful quantity meant figuring out how to grow large amounts of the mold. Penicillium is a surface mold which means that it grows on the surface of fluid rather than in it. Thus having a lot of the mold to make lots of penicillin meant having a very big pond with sufficient surface area. Clearly, having a vast pool of media in a laboratory would be impractical at best, so how could they efficiently grow the mold?

The ingenious Oxford-based Norman Heatley solved this and many other overwhelming problems on the bumpy road to success. He designed pots from ceramic that were flat and easily stacked. They were shallow like a brownie tin so that the maximum surface area with the minimum volume could be attained. They had an opening at the end of an angled neck that allowed the mold and nutrient liquid to be added and growth fluids containing the penicillin to be easily removed.

Despite the war with Germany (this was late in the year 1940), Norman found a ceramics dealer in the northern Britain town of Stoke-on-Trent to make hundreds of these pots to his specifications. The pottery plant made them and he traveled there during the blitz despite bombing damage in Birmingham.  There was no way for them to be delivered to the lab in Oxford with all the war effort so Heatley drove an old rickety pickup truck to the plant in Stoke-on-Trent and brought them back to the labs himself.  

Birmingham after a blitzkrieg bombing.

Years later as a young graduate student sitting in Norman’s garden I discovered the fate of those pots; they had been made into Professor Heatley’s garden wall! I am the proud recipient of one them as he graciously responded to my fascination with them, the innovation they represented, the history embedded in them and the perseverance they represented.

A ceramic penicillin pot given to me by Norman Heatley.

Heatley working with Ernst Chain developed an ingenious method to isolate and concentrate penicillin from the mold broth (that this was done in Oxford is the reason penicillin was measured in "Oxford Units").  Chain was an extremely talented chemist that joined the group early on and eventually shared the Nobel prize with Fleming and Florey.  Florey's wife Ethel identified a patient, a constable, Albert Alexander, who was dying from septicemia (blood infection) caused by a scratch from a rose thorn.  In February of 1941 they gave him all the penicillin they had, even recovering what he excreted into his urine. He made a striking recovery and then the penicillin ran out.  He died a little more than a week later. 

A room stacked with ceramic penicillin pots.

This is eerily reminiscent of current news headlines where the deadly RNA thread virus, Ebola, was defeated in emergency, compassionate use of ZMapp, which is a human monoclonal antibody cocktail under experimental investigation.  Genes that code for the monoclonal antibodies that recognize two different parts of the Ebola virus are engineered into tobacco plants!  The antibodies are removed from the tobacco leaf and given to the patient. 

This treatment has not yet undergone ethical testing in human populations but because the infected health care workers would almost certainly have died without treatment this therapy was used.  And then it was all used up.  Production is now proceeding apace and more will soon be ready for more definitive testing.

Developing large scale production methods for Penicillin was also a complicated effort.  It did not involve tobacco plants.  That part of the story took place in the United States and we will discuss it in the next post. 

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