(Serendipity to Surreal)
Prof. B. M. Hegde,
Penicillin,
as an antibiotic, was the first great breakthrough in medical research to win a
battle between man and germ. Like in many other fields of research there are
several actors in this drama of discovery. Lots of people think that scientists
invent new things. Far from it: they only unravel the mysteries of Nature in
all scientific discoveries and, it is Nature that should rightfully get the
Nobel Prize for having invented so many wonders. “This world is a wonderful
wonder,” wrote Albert Einstein in the evening of his life. “We always stand on
the shoulders of tall men,” was another of Einstein’s quotes, referring to
Isaac Newton’s work that propelled his Relativity
Theory in the beginning. The drama of penicillin is still more interesting
from its human angle.
Louis
Pasteur was the first to show that germs and man are, at times, at loggerheads
with one another. Man can not live without germs in this universe, but, when
the environment changes they could become enemies. However, no germ, in its
proper senses, would want to attack man. If the germ wins and man gets any
disease, there are two possibilities; both of which are bad for the germ! If
man dies of the disease the germ gets burnt or buried deep. If, on the other
hand, man wins the battle, man’s immune system kills the germ, anyway. In
either case the germ ruins itself by attacking man. They normally co-habit
without a proper marriage, though.
Although
Paul Ehrlich was the first to think of the horrors of man’s immune system
destroying man himself, progress in immunology took a long time. Thanks to the
thinking American physician, Theobald Smith, who in 1915 propounded the Grimm’s
Law: “while any disease is directly proportionate to the virulence of its
cause, it is inversely related the resistance
of the host.” This idea, coupled with the “horror auto-toxicus” theory
of Paul Ehrlich, laid the foundation for the great science of immunology that
has eventually paved the way for organ transplants and what have you.
Robert
Koch’s postulates helped research very much but, at the same time, they halted
the progress of medical research for nearly one hundred years. People never
ever thought of the human immune system because of the cardinal principles of
the Koch’s postulates. People have been using germ killers for centuries on the
skin surface, but internal use of chemicals to kill germs was thought to be
taboo because of the fear of damage inside. Lots of work eventually resulted in
arsenic being used in syphilis.
Professor
Alexander Fleming was the head of microbiology at the then famous St. Mary’s
Medical School in Paddington, London, in the early part of the last century. He
was obsessed with the idea that body produces its own germ killers. This
thought first occurred to him one day when he inadvertently sneezed on to the
culture plate in his laboratory. A very keen observer that he was, he saw that
the germs got killed in the area where his nasal mucus had fallen. He was able
to later show that it is the lysozyme
in the mucus that had killed the germs.
Serendipity
enters the story here after. Fleming had gone on a long summer holiday in 1928
August or so. London was exceptionally hot that year, a record that was
probably beaten only in the last two summers in London when the temperatures
were sky high. In the basement of
Fleming’s lab. was the mycology laboratory. The hot air from the basement was
coming to the first floor balcony where inside was Fleming’s microbiology unit
situated.
Since
the professor was on leave, the laboratory assistants forgot to clean the used
Petri dishes. When Fleming, the curious observer came back, he was upset that
the dirty dishes were still there. He, however, noticed a strange phenomenon.
In one of the dishes where there was luxuriant grow of the common germ,
staphylococcus, he noticed a large island of clearing. On close observation he
saw a fungus growing there. He was able to identify the fungus as penicillium
notatum. He found out that this fungus kills staphylococcus. He never realized
that it could help mankind. He left his observations there but wanted to get
lots of publicity. He was very good at it. He was Knighted by the King in 1929
and had lots of media publicity too.
Away
in Oxford was this great brain, a great researcher, an able administrator who
got people to work for him and, an innovator par excellence in Professor Howard
Florey, an Australian, who was the Chief of the famous William Dunn School of
Pathology, at the Oxford University. Florey was working feverishly on lysozyme
and other body fluids that had anti-microbial properties for decades. Egged on
by Dogmack’s success with sulpha drugs, Florey was looking for some other
chemical to use safely in humans against germs. He always appointed the right
people for the right job. In his bio-chemistry laboratory he had a brilliant
brain in Dr. Ernst Chain, who had fled Hitler’s Germany to England, who was
working on all kinds of fungi and was able to extract the active principle in
the fungus penicillium notatum. Florey was looking through the voluminous
literature to see if anyone had worked on the fungus. After days of search he
came up with the work of Alexander Fleming in 1928.
Then on the story moved very fast as there was
the governmental pressure on scientists as the war casualties due to gas
gangrene and other infections far outnumbered those deaths due to bullets and
bombs. Florey had an obsessive personality that helps research. He was also
guilty that he had avoided being drafted during the First World War. He knew
how to get the funding from the government of the day. He also had nearly
twenty people working for him in the lab. with Ernst Chain, Heatley and other
technicians. To cut the long story short it was Florey’s group that ultimately
discovered penicillin as a drug and got a couple of US scientists from the
Agricultural department there, Andrew Moyer and Kenneth Raper, of Peoria in
Illinois, to mass produce penicillin for war use. It should be noted here that
Howard Florey was a very shy man and was media shy too. He was worried that if
he publicized his work, the demand for penicillin would be such that he would
not be able to meet the demand. He kept quiet and, in the meantime, the flamboyant Alexander
Fleming claimed all credit for discovering penicillin and even bagged the coveted
Nobel Prize alone!
When
all this was going on, Winston Churchill, the Great War hero, came down with
pneumococcal pneumonia, and was in his death bed, partly because of his smoke
filled emphysematous lungs and the declining age. The life giver, Alexander
Fleming, was quickly summoned and the administration of penicillin saved the
great hero’s life! There is a celestial side to this story here. Fleming was
the son of a poor farmer in England. One morning his father, the senior
Fleming, working in his farm, heard a desperate cry for help from the nearby
marshy bushes. When he rushed to look, senior Fleming found a Nobleman’s son
drowning there struggling for breath in neck deep marshes. He pulled the boy
out and saved his life. The following morning the nobleman was in Fleming’s
farm to thank the farmer and offer him financial assistance. The humble farmer
did not accept any cash. The nobleman, however, insisted that the farmer send
his son to Oxford for which the former would foot the bill. That was how
Alexander Fleming became a doctor and an Oxford graduate. The farmer’s son
providentially saved the nobleman’s son, Sir Winston Churchill, decades later,
a real quirk of fate.
Alexander
Fleming was more like the Indian Bolly wood actors or politicians going after
publicity, most of the time not deserving though. When he was appointed the
Vice Chancellor of the famous Edinburgh University, he agreed to be taken in a
large procession through the streets of Edinburgh, carried on the shoulders of
tall Scots! If one were to see those pictures they remind one of some victory
rally in India or the post Filmfare awards jamboree. He went round the world
extolling the virtues of his great discovery while keeping the people in the
dark about the whole story. In fact, the whole story is still murky, filled
with the drama of missed opportunities and bad luck. Serendipity did smile on
many people before Alexander Fleming in this area but no one was there to help
like Howard Florey. Florey was very naïve in matters of making money and name
from his research. It is unbelievable that he did not even patent penicillin
and the two agricultural scientists from the US, who helped him to mass
manufacture penicillin patented it and later Florey had to buy penicillin from
them! That is bad luck indeed. Read on.
It
was Joseph Lister, the great English Surgeon, who found out, way back in 1871,
that urine samples from patients did not grow any microbials when contaminated
by molds. In the year 1874 another scientist, William Roberts, observed that no
germ contaminated his mold cultures. In 1877, Louis Pasteur and Jules Francois
Joubert together noticed that the anthrax bacillus culture was inhibited by
growth of molds inside the culture plates. None of them went any further. The
sad story of young Ernest Duchesne in 1897 who did his PhD thesis on the
competition between micro-organisms is there for all of us to see. He studied
E.coli being destroyed by Penicillium glucuum and was on the way to extract the
active principle. He was then drafted to the First World War and died there.
This is misfortune at its best. Bad luck. Luck is the blessing of God without
His signature attached to it! Still worse is the story of two poor researchers,
Andre Gratia and Sara Dath (?Indian), who in 1920, showed in a paper they read in one of the conferences
in England about the suppression of Staphylococcus Aureus by a fungus called
penicillium glucuum. But the senior scientists laughed them off and the two
left research for ever. They were looking to extract the active principle. That
was not to be.
The
anticlimax to the whole story is that the dream of the scientific world that
anti-biotics will one day rid man of all infections has been belied one hundred
percent. Whereas ninety-five percent of staphylococci were sensitive to
penicillin to begin with now ninety-five percent of them are resistant.
Antibiotic resistance has become a nightmare for doctors and hospitals. The
curse of these super-bugs that live on most antibiotics is the dreaded
reality. Many hospitals had to close
their operation theatres because of these bugs. In the US, in one year, nearly
80,000 people die from nosocomial infections with these bugs! Man had to go
back to Nature to fight germs with other living organisms. Maggots have staged
a come back in a big way to help man fight the bad germs. This is the irony of
fate- the real surreal.
This
is the long and short of the penicillin story. It has all the characters of a
human drama- daring, keen observation, opportunity, mishaps, jealousy,
cheating, pride, super ego, man’s struggle against disease, sacrifice, naivety,
God’s will (chance for an atheist),
and, of course, the great lessen of humility that Nature is superior to man in
any sphere. Howard Florey though, is a national hero in his motherland,
Australia for ever. This is not the solitary tale of medical research or, for
that matter, any scientific research. In a manner of speaking, what is not in
this story, about human qualities of head and heart, is no where.