Dr. Arthur Kornberg and his family ---- from the book "For the love of enzymes: The odyssey of a Biochemist. Harvard University Press.
1991.
Arthur Kornberg: For the love of enzymes: The Odyssey of a
of Physiology or Medicine in1959 and first done the chemical
synthesis of a infectious phage, a virus of bacteria in 1967) wrote
about penicillin.
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Penicillin and other antibiotics are the most dramatic therapeutic advance in medicine in my lifetime. When I was a
student and intern before the advent of antibiotics, the
treatment of lobar pneumonia was discouraging ineffective.
One out of four patients died. Subacute bacterial endocarditis
was invariably fatal. Rheumatic fever and acute nephritis
were prevent.
Many people know that antibiotic therapy was not discovered
at bedsides nor even in a clinical pharmacology laboratory.
Bullrings in Spain have a statures of Alexander Fleming,
penicillin mold contaminated his Petri plate.
The apotheosis of Fleming gored bullfighters is exaggerated
because the practical use of the penicillin mold was not
discovered by Fleming. It took Ernst Chain, a biochemist,
and Howard Florey, a pathologist, to apply this knowledge
ten years later to isolate penicillin and demonstrated its
clinical utility.
There is much more to the penicillin story than that.
Basic inquiries and findings essential to Fleming's discovery
started at least fifty years earlier. Fleming would never have
made his observation without the agar Petri plate. But, more
important, he would never have understood what he saw on
the plate were it not for the firm foundations of bacteriology
and immunology.
One might assume that Chain and Florey undertook the
isolation of penicillin because of its possible clinical potential.
his research on penicillin only because he was curious about
the dissolution of bacterial walls by enzymes such as lysozyme.
He thought penicillin was an enzyme too and wanted to
understand the mechanism of its action. He surprised to find
that penicillin was a molecule small enough to pass readily
through the pores of a dialysis membrane which stopped
passage of molecules as large as enzymes.
Penicillin was not enzyme at all. This discovery immediately
presented the possibility that penicillin, as a low-molecular-
weight compound, could be administered as a drug to animals.
With the technique of freeze-drying, which had just become
available, Chain was able to concentrate and preserve
penicillin and then to prove its therapeutic efficacy.
Why were Chain and Florey so quickly to test their very
crude penicillin preparations for clinical efficacy? Their
prompt decision was likely conditioned by the discovery in
the mid-1930s that sulfonamides inhibit microbes and yet are
not toxic to animals.
Thus, an agent could selectively interrupt growth of microbes
without affecting the animal host, and this observation gave
Chain and Florey the confidence to test their penicillin prepa-
rations in infected mice.
It may also explain why Fleming, ten years earlier, believing
that only the host immune system could combat infections,
regarded chemotherapy as implausible and so failed to test
his crude penicillin preparations for therapeutic value.
I choose penicillin as an example of the importance of basic
research because its history is so recent and dramatic.
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Arthur Kornberg: For the love of enzymes: The Odyssey of a
Biochemist. Harvard University Press. 1991.
Any questions: write to Keiji Hagiwara, MD
keijihagiwara@gmail.com
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