Magic Bullets

Prevention is better than Cure

Unless you have got the Disease!

•Prevention

•Cause

•Cure

Behring’s Biological Bullets

• Part of Koch’s research team• He recognised that animals try to produce

anti-bodies to fight any invading bacteria• He successfully identified the anti-bodies

that fought Diphtheria– Removed the clotting agents– Injected it into infected people– The anti-bodies killed the germs but nothing

else• Magic Bullet

Salvarsan 606• Paul Ehrlich

– Part of Koch’s staining team– Had worked with Behring

• He wanted to create a chemical version of the Behring’s anti-bodies

– Chemicals which killed the germs but nothing else

• Using Dyes to kill the Syphilis Bacteria– These were not harmful enough to the germs– He switched to Arsenic compounds– After 605 attempts at varying the dosage they

still had no luck– Compound 606 worked

• They nearly missed it! Only when Hata retested it

Prontosil

• Gerhardt Domagk– Experimented with Dyes to fight Blood Poisoning

• Some reasonable success using mice

• His daughter accidentally chased her Guinea Pig into his research room and infected herself with some contaminated blood

• Domagk was forced to try out his discovery– Luckily it worked

• The second chemical bullet had been discovered

Industrialising Production of the Magic Bullets

• How did Prontosil work– What was the active ingredient of Prontosil– Electron Microscope invented 1931– Sulphanomide– Extracted from Coal Tar

• Sulphanomides adapted by Drug Companies– Scarlet fever, meningitis, Gonorrhoea,

Pneumonia• See graph page 155 for effectiveness of

sulphanomides

Penicillin – The Guided Missile

• Most infections caused by the powerful germs:– Staphylococci– Streptococci

• No drugs effectively killed these germs

• Infections would spread across the whole body– Death likely

Alexander Fleming’s Accidental Discovery

• In 1928, Fleming was researching the Staphylococci germ

• He had lots of Culture plates lying around (in the sink)

• He went on holiday and left the window ajar• On his return and before he cleaned up, he noticed

that the Staphylococci on one of the plates had been killed off

• He immediately rushed to see what was responsible • A small fungus called Penicillium had blown through

the window• He wrote a paper explaining what had happened but

he could not figure out a way of growing the fungus

Mass Producing Penicillin

• Howard Florey and Ernst Chain– Read Fleming’s paper with interest

• World War II broke out in 1939– Government grants to discover a way of

growing Penicillium

• The Milk Bottle Process– They needed as much surface area as

possible to grow the mould– Slowly gathered a few grams of penicillin

Does it work?

• Testing process of Penicillin– On mice

• 8 mice were injected with Staphylococci• 4 were given Penicillin, 4 were not• Which 4 died?

– On a policeman in 1941• With a spreading infection• Immediately he improved but there was not enough

Penicillin to give him– Recycled through his urine

• Unfortunately, he died as the dosage required was more than they had.

• Obviously, it was a very powerful drug, but it was so hard to produce

The USA Helps Out• Research was difficult in war torn Britain• Florey was sent to the USA to continue his research

– Spores were spread on his jacket• December 1941

– US Government invests $80 Million• 4 Multi-National Drug companies were told that the

development of Penicillin was their top priority• Huge factories were set up to mass produce the fungus• 1943

– Field Trials in North Africa• 1944

– Enough to supply all the casualties on D-Day• The Germans relied on the inferior Sulphanomides for the

duration of the war