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Today, the use of penicillin and other antibiotics are common place.

The various antibiotics are used to treat a


number of what are now common diseases and to prevent the onset of infections when our skin, our first barrier to
fight off disease, is somehow broken through a simple cut or a more serious wound. It is something that we all take
for granted, today. However, many diseases and simple wounds that are so easily treated today because of the
availability of antibiotics has not always been available. Antibiotics are a relatively recent discovery and the first
practical one, penicillin, was not available until the early 1940s. Even the concept of using fungal products, such as
penicillin, to produce medicine is a relatively new one. However, many folk remedies that have included fungi have
long been utilized, but the incorporation of fungi into the remedy was inadvertent and not known. For example, over
three thousand years ago, the Chinese had put moldy soybean curd on boils and other types of skin infections. Other
cultures have placed warm earth, which contains molds and other fungi, as first aid in injuries. There was
undoubtedly antibiotics in the soybean curd and earth that were placed on injuries. So, although the concept of
antibodies is relatively recent, its use has been around for some time.
The discovery of penicillin has often been described as a miracle drug, and that is exactly what it was. Prior to the
discovery of penicillin, death could occur in what would seem, today, to be very trivial injuries and diseases. It could
occur from minor wounds that became infected or from diseases such as Strep Throat, and venereal diseases such as
syphilis and gonorrhea were a much more serious issue.
~~~
Penicillin heralded the dawn of the antibiotic age. Before its introduction there was no effective treatment for
infections such as pneumonia, gonorrhea or rheumatic fever. Hospitals were full of people with blood poisoning
contracted from a cut or a scratch, and doctors could do little for them but wait and hope.
Antibiotics are compounds produced by bacteria and fungi which are capable of killing, or inhibiting, competing
microbial species. This phenomenon has long been known; it may explain why the ancient Egyptians had the
practice of applying a poultice of moldy bread to infected wounds. But it was not until 1928 that penicillin, the first
true antibiotic, was discovered by Alexander Fleming, Professor of Bacteriology at St. Mary's Hospital in London.
Returning from holiday on September 3, 1928, Fleming began to sort through petri dishes containing colonies of
Staphylococcus, bacteria that cause boils, sore throats and abscesses. He noticed something unusual on one dish. It
was dotted with colonies, save for one area where a blob of mold was growing. The zone immediately around the
moldlater identified as a rare strain of Penicillium notatumwas clear, as if the mold had secreted something that
inhibited bacterial growth.
Fleming found that his "mold juice" was capable of killing a wide range of harmful bacteria, such as streptococcus,
meningococcus and the diphtheria bacillus. He then set his assistants, Stuart Craddock and Frederick Ridley, the
difficult task of isolating pure penicillin from the mold juice. It proved to be very unstable, and they were only able
to prepare solutions of crude material to work with. Fleming published his findings in the British Journal of
Experimental Pathology in June 1929, with only a passing reference to penicillin's potential therapeutic benefits. At
this stage it looked as if its main application would be in isolating penicillin-insensitive bacteria from penicillinsensitive bacteria in a mixed culture. This at least was of practical benefit to bacteriologists, and kept interest in
penicillin going. Others, including Harold Raistrick, Professor of Biochemistry at the London School of Hygiene
and Tropical Medicine, tried to purify penicillin but failed.

Penicillin Research at Oxford University


It was Howard Florey, Ernst Chain and their colleagues at the Sir William Dunn School of Pathology at Oxford
University who turned penicillin from a laboratory curiosity into a life-saving drug. Their work on the purification
and chemistry of penicillin began in earnest in 1939, just when wartime conditions were beginning to make research
especially difficult. To carry out a program of animal experiments and clinical trials the team needed to process up to
500 liters a week of mold filtrate. They began growing it in a strange array of culture vessels such as baths, bedpans,
milk churns and food tins. Later, a customized fermentation vessel was designed for ease of removing and, to save

space, renewing the broth beneath the surface of the mold. A team of "penicillin girls" was employed, at 2 a week,
to inoculate and generally look after the fermentation. In effect, the Oxford laboratory was being turned into a
penicillin factory.
Meanwhile, biochemist Norman Heatley extracted penicillin from huge volumes of filtrate coming off the
production line by extracting it into amyl acetate and then back into water, using a countercurrent system. Edward
Abraham, another biochemist who was employed to help step up production, then used the newly discovered
technique of alumina column chromatography to remove impurities from the penicillin prior to clinical trials.
In 1940, Florey carried out vital experiments, showing that penicillin could protect mice against infection from
deadly Streptococci. Then, on February 12, 1941, a 43-year old policeman, Albert Alexander, became the first
recipient of the Oxford penicillin. He had scratched the side of his mouth while pruning roses, and had developed a
life-threatening infection with huge abscesses affecting his eyes, face, and lungs. Penicillin was injected and within
days he made a remarkable recovery. But supplies of the drug ran out and he died a few days later. Better results
followed with other patients though and soon there were plans to make penicillin available for British troops on the
battlefield.
War-time conditions made industrial production of penicillin difficult. A number of British companies, including
Glaxo (now GlaxoSmithKline) and Kemball Bishop, a London firm later bought by Pfizer, took up the challenge.

Penicillin Production in the United States during WWII


Substantial amounts of penicillin would be needed for the extensive clinical trials required to confirm the promise of
the early results and to provide adequate supplies of the drug for therapeutic use if it did live up to its potential.
Florey recognized that large-scale production of penicillin was probably out of the question in Britain, where the
chemical industry was fully absorbed in the war effort. With the support of the Rockefeller Foundation, Florey and
his colleague Norman Heatley traveled to the United States in the summer of 1941 to see if they could interest the
American pharmaceutical industry in the effort to produce penicillin on a large scale.
Yale physiologist John Fulton helped to put his British colleagues in touch with individuals who might be able to
assist them in their goal. They were referred to Robert Thom of the Department of Agriculture, a foremost
mycologist and authority on the Penicillium mold, and eventually to the Department's Northern Regional Research
Laboratory (NRRL) in Peoria, Illinois, because of the expertise of its Fermentation Division. This contact proved to
be crucial to the success of the project, as the NRRL was a key contributor of innovations that made large-scale
production of penicillin possible.

~~~
This landmark work began in 1938 when Florey, who had long been interested in the ways that bacteria and mold
naturally kill each other, came across Flemings paper on the penicillium mold while leafing through some back
issues of The British Journal of Experimental Pathology. Soon after, Florey and his colleagues assembled in his
well-stocked laboratory. They decided to unravel the science beneath what Fleming called penicilliums
antibacterial action.
One of Floreys brightest employees was a biochemist, Dr. Ernst Chain, a Jewish German migr. Chain was an
abrupt, abrasive and acutely sensitive man who fought constantly with Florey over who deserved credit for
developing penicillin. Despite their battles, they produced a series of crude penicillium-mold culture fluid extracts.
During the summer of 1940, their experiments centered on a group of 50 mice that they had infected with deadly
streptococcus. Half the mice died miserable deaths from overwhelming sepsis. The others, which received penicillin
injections, survived.
It was at that point that Florey realized that he had enough promising information to test the drug on people. But the
problem remained: how to produce enough pure penicillin to treat people. In spite of efforts to increase the yield

from the mold cultures, it took 2,000 liters of mold culture fluid to obtain enough pure penicillin to treat a single
case of sepsis in a person.
In September 1940, an Oxford police constable, Albert Alexander, 48, provided the first test case. Alexander nicked
his face working in his rose garden. The scratch, infected with streptococci and staphylococci, spread to his eyes and
scalp. Although Alexander was admitted to the Radcliffe Infirmary and treated with doses of sulfa drugs, the
infection worsened and resulted in smoldering abscesses in the eye, lungs and shoulder. Florey and Chain heard
about the horrible case at high table one evening and, immediately, asked the Radcliffe physicians if they could try
their purified penicillin.
After five days of injections, Alexander began to recover. But Chain and Florey did not have enough pure penicillin
to eradicate the infection, and Alexander ultimately died.
Another vital figure in the lab was a biochemist, Dr. Norman Heatley, who used every available container, bottle and
bedpan to grow vats of the penicillin mold, suction off the fluid and develop ways to purify the antibiotic. The
makeshift mold factory he put together was about as far removed as one could get from the enormous fermentation
tanks and sophisticated chemical engineering that characterize modern antibiotic production today.
In the summer of 1941, shortly before the United States entered World War II, Florey and Heatley flew to the United
States, where they worked with American scientists in Peoria, Ill., to develop a means of mass producing what
became known as the wonder drug.
Aware that the fungus Penicillium notatum would never yield enough penicillin to treat people reliably, Florey and
Heatley searched for a more productive species.
One hot summer day, a laboratory assistant, Mary Hunt, arrived with a cantaloupe that she had picked up at the
market and that was covered with a pretty, golden mold. Serendipitously, the mold turned out to be the fungus
Penicillium chrysogeum, and it yielded 200 times the amount of penicillin as the species that Fleming had described.
Yet even that species required enhancing with mutation-causing X-rays and filtration, ultimately producing 1,000
times as much penicillin as the first batches from Penicillium notatum.
In the war, penicillin proved its mettle. Throughout history, the major killer in wars had been infection rather than
battle injuries. In World War I, the death rate from bacterial pneumonia was 18 percent; in World War II, it fell, to
less than 1 percent.
From January to May in 1942, 400 million units of pure penicillin were manufactured. By the end of the war,
American pharmaceutical companies were producing 650 billion units a month.
Ironically, Fleming did little work on penicillin after his initial observations in 1928. Beginning in 1941, after news
reporters began to cover the early trials of the antibiotic on people, the unprepossessing and gentle Fleming was
lionized as the discoverer of penicillin. And much to the quiet consternation of Florey, the Oxford groups
contributions were virtually ignored.

~~~
Life in the 1940's centered around World War II. Men were going off to war and women were doing the men's jobs,
They did what they could have not done when the men were there, such as play a professional sports or do jobs that
men usually took . Many soldiers suffered from war wounds and often died from them. Some were lucky to survive
long enough to see their family, friends, and spouses; but they died eventually from the infections. Of course, this
could have happened to anyone in the 1940's or before. A simple cut from knife could lead to your death because
there were no antibiotics to stop bacteria from growing and entering your body. Due to this, people were not really
expected to live past the age of 60 or 68. People could have also died from surgeries. People who had surgeries had a
higher chance of getting an infection than those of us today because, again, there was nothing to stop bacteria to
grow. People began to collect scrap metals to help the war effort, especially after the tragic bombing of Pearl Harbor.
The center of everyone's life in the world was World War II, and people all over the globe were affected by the
outcomes of the war.

Penicillin was accidentally invented by Alexander Fleming. Around August or September of 1928 Sir Alexander
Fleming started growing staphylococcus bacteria in a culture plate. He left it untouched for a while and he had
accidentally let it grow mold. He noticed that the mold had been killing the bacteria. Instead of throwing out the
bacteria like any other person would, he began to study the mold and bacteria. Fleming realized that the mold is
called Penicillium notatum, hence the name penicillin. At first, Fleming thought of this discovery as useless because
it was very hard to produce, meaning it can not be easily mass produced to be distributed among people. He
eventually gave up, but his work was later used to create the first mass produced antibiotic.
In the late 1930's, Howard Florey and Ernst Chain found Flemming's research and helped to develop penicillin.
They discovered an easier way to purify penicillin. When Florey and Chain first tested penicillin, they did not use
humans. They actually used eight mice. Four of the mice were given penicillin and four were not. Six mice died
and two given the medicine survived. Then, Florey and Chain tested penicillin on a human.On February 1, 1941, a
policeman with a severe case of staphylococcus was given the antibiotic. The penicillin ran out and the man died,
but he did get much better over the time he had penicillin. Chain and Florey soon discovered that the corn steep
liquor could be used to mass produce penicillin. On top of that Ernest Chain and Howard Florey convinced a big
company to produce and sell penicillin. This event plus the discovery of using corn steep liquid really helped to
launch the reign and mass impacts of penicillin. This was the era of the "wonder drug." Penicillin was a huge
accomplishment and saved many lives.

~~~
Penicillin's ability to cure people of many once-fatal bacterial infections has saved so many lives that it is easy to
understand why it was once called a "miracle drug".
Antibiotics are chemicals, effective at very low concentrations, created as part of the life process of one organism,
which can kill or stop the growth of a disease-causing microbe--a germ. In 1929, Alexander Fleming, a doctor and
researcher at St. Mary's Hospital in London, England, published a paper on a chemical he called "penicillin", which
he had isolated from from a mold, Penicillium notatum. Penicillin, Fleming wrote, had prevented the growth of a
neighboring colony of germs in the same petri dish. Dr. Fleming was never able to purify his samples of penicillin,
but he became the first person to publish the news of its germ-killing power. Howard Florey, Ernst Chain and
Norman Heatley expanded on Fleming's work in 1938, at Oxford University. They and their staff developed methods
for growing, extracting and purifying enough penicillin to prove its value as a drug.
World War II (1939-1945) had begun by the time their research was showing results. The main research and
production was moved to the United States in 1941, to protect it from the bombs pounding England. Work began on
how to grow the mold efficiently to make penicillin in the large quantities that would be needed for thousands of
soldiers. As the destruction of the war grew, so did interest in penicillin in laboratories, universities and drug
companies on both sides of the Atlantic. The scientists knew they were in a race against death, because an infection
was as likely to kill a wounded soldier as his wound.

Creating the right environment for growth was the first step in producing enough penicillin to be used as a drug. In
Oxford, experiments showed that Penicillium notatum grew best in small shallow containers on a broth of nutrients.
Penicillium need lots of air. In the United States, it was discovered that huge "deep fermentation" tanks could be
used if sterilized air was pumped continually through the tanks. Production increased even more when corn steep
liquor, a thick, sticky by-product of corn processing, was added to the tanks. Corn steep liquor contained
concentrated nutrients that increased the yield 12-20 times. Formerly considered a waste material, corn steep liquor
became a crucial ingredient in the large-scale production of penicillin.
Scientists were also determined to find another strain of Penicillium that might grow better in the huge deep
fermentation tanks. Army pilots sent back soil samples from all over the world to be tested for molds. Residents of
Peoria, Illinois, were encouraged to bring moldy household objects to the local U.S. Department of Agriculture
laboratory, where penicillin research was being conducted. Laboratory staff members also kept an eye out for
promising molds while grocery shopping or cleaning out their refrigerators.

In 1943, laboratory worker Mary Hunt brought in an ordinary supermarket cantaloupe infected with a mold that had
"a pretty, golden look." This Penicillium species, Penicillium chrysogenum grew so well in a tank that it more than
doubled the amount of penicillin produced. The deep fermentation method, the use of corn steep liquor and the
discovery of P. chrysogenumby Mary Hunt made the commercial production of penicillin possible. Researchers
continued to find higher-yielding Penicillium molds, and also produced higher yielding strains by exposing molds to
x-rays or ultraviolet light.
Penicillin kills by preventing some bacteria from forming new cell walls. One by one, the bacteria die because they
cannot complete the process of division that produces two new "daughter" bacteria from a single "parent" bacterium.
The new cell wall that needs to be made to separate the "daughters" is never formed.
Some bacteria are able to resist the action of antibiotic drugs, including penicillin. Antibiotic resistance occurs
because not all bacteria of the same species are alike, just as people in your own family are not exactly alike.
Eventually, the small differences among the bacteria often mean that some will be able to resist the attack of an
antibiotic. If the sick person's own defenses can not kill off these resistant bacteria, they will multiply. This
antibiotic-resistant form of a disease can re-infect the patient, or be passed on to another person.
Taking antibiotics for viral illnesses like colds can also cause antibiotic resistant bacteria to develop. Antibiotics
have no effect on viruses, but it will kill off harmless and even the beneficial bacteria living in the patient's body.
The surviving resistant bacteria, free from competition, will live and multiply and may eventually cause disease.
Patients with bacterial infections, who don't finish their antibiotic prescriptions completely, also allow resistant
bacteria to develop. This happens because a small number of semi-resistant bacteria, which needed the full course of
antibiotics to kill them, survive. Instead of being a small part of the bacteria causing an infection, the more resistant
bacteria take over when sensitive bacteria are killed by the antibiotic.
Today, in the United States, deaths by infectious bacterial diseases are only one-twentieth of what they were in 1900,
before any antibiotic chemicals had been discovered. The main causes of death today are what are referred to as "the
diseases of old age": heart disease, kidney disease and cancer. We would be shocked to hear of someone dying from
an infection that started in a scratch, but, before antibiotics like penicillin, it was common for people to die from
such infections.
Humans can slow the creation of antibiotic resistant diseases by understanding the uses and limits of antibiotics.
Take all of an antibiotic, and only take them when prescribed by a doctor. Research to develop new antibiotics to
treat resistant bacteria continues, but research takes time. Time is running out because the world's biodiversity is
decreasing--the source of half of our disease-fighting chemicals.
An example of the importance of preserving the world's biodiversity occurred in 1996, in New York state. Students
at Cornell University collected a fungus that finally made it possible to identify the two very different life stages of
the mold that produces the drug cyclosporin. Cyclosporin prevents the rejection of transplanted organs. Without it,
transplant operations would be impossible. Knowing the full life history of the cyclosporin-producing fungus may
make it easier to find related molds. Even people who see no special beauty or value in the world's biodiversity may
one day benefit from the currently unknown and powerful substances, produced by fungi and other microbes, that
are waiting for discovery in familiar places.

~~~
How It Works
Penicillin works by preventing cells from dividing. It does not allow them to synthesize cell wall, and thus when the
cells attempt to duplicate, they rupture and end up killing themselves. Because penicillin has such a strong focus on
a bacterias cell wall, it is far more effective on Gram-positive organisms. When a Gram-positive organism attempts
to duplicate itself, it must create more cell wall and split off, the penicillin causes there not to be any new cell wall,
and instead of duplicating, the cell will simply rupture, effectively killing it.

Diseases Cured with Penicillin


Penicillin antibiotics are most effective against gram-positive bacteria, e.g. the genera bacillus, clostridium,
streptococcus, and staphylococcus). There are many different bacterial infections, diseases, and conditions that have
been combated with the help of Penicillin. Here is a brief list of examples: Chlamydia Penicillin can be prescribed
to pregnant women in order to prevent the child from contracting the disease as well. Stomach Ulcers Penicillin
was found to be effective in controlling the effects of stomach ulcers. Tooth Abscesses Penicillin kills the bacteria
responsible for causing these infections. Step Throat and Scarlett Fever - caused by the Group A Streptococcus
bacterium streptococcus pyogenes, which penicillin can kill. Staph Infections - can lead to amputation of affected
limbs and appendages if left untreated, or even death in cases in which the infection enters the blood stream.
Fortunately, Penicillin was found to be effective in killing staphylococcus aureus, the bacterial cause of the
infections. Leptospirosis (Weils Syndrome) Can cause kidney and liver failure if left untreated. Lyme Disease
Penicillin can help prevent the disease from spreading throughout the body; which could lead to further
complications with the heart and nervous system in the later stages of the disease. Typhoid Fever can lead to
kidney failure and eventually death if left untreated. Before penicillin, was much more widespread in the US; 35,000
reported cases during the 1920s, about 400 cases reported annually in modern times. Gas Gangrene can prevent
further spread of this condition which is caused by a clostridium perfringens infection. Necrotizing Fasciitis (Flesheating disease) destroys soft tissues around infection site; will spread without treatment.
While Penicillin antibiotics were at first extremely killing the bacteria that cause these diseases, the bacteria soon
built up immunity to these antibiotics as they were overprescribed. Due to this, many bacterial strains are now
resistant to Penicillin, and some of these diseases are no longer able to be treated using Penicillin antibiotics. This
development has led pharmaceutical companies to have to produce new antibiotics that work in the same way as
Penicillin antibiotics once did.

Developments from Penicillin


Although penicillin itself has a narrow spectrum of activity, virtually every antibiotic discovered or developed postpenicillin owes its existence to it. Not only do the penam sub-class of Beta- Lactam antibiotics stem directly from
this first miracle drug; but the discovery of penicillin also ignited the desire in scientists to find and/ or develop
other antibiotics as well (the first of which was streptomycin, which effectively cured Tuberculosis). The penam
subclass, which is the most widely used group of antibiotics, consists of penicillin and its derivatives- all of which
end in cillin and possess a central Beta- Lactam ring structure. The penams can be broken up into two camps:
Extended spectrum and Narrow spectrum antibiotics. The extended spectrum penams include amoxicillin,
ampicillin, and mezlocillin, among others, and as their name suggest, these antibiotics work against very wide range
of bacteria. Some extended spectrum penams (called antipseudomonal penicillins) even proved useful against Gramnegative bacterial cells, including pipericillin, carbenicillin, and ticarcillin.
The Narrow spectrum antibiotics, on the other hand, act on a smaller, more specific group of bacteria. Narrow
spectrum drugs can be broken up into those that are B- Lactamase sensitive (e.g.- benzylpenicillin, azidocillin) and
those that are B- Lactamase resistant. B- Lactamase is an enzyme that many bacteria started producing as a means to
resist the B- Lactam antibiotics. New antibiotics, the B- Lactamase resistant set, were then developed to combat the
bacterias resistance to penicillin and penicillin- like drugs. Antibiotics that are resistant to the B- Lactamase
enzyme, and thus can kill bacteria that the other penams cannot, include oxicillin, flucloxicillin, and methicillin;
however, only two years after methicillin hit the market, strains of Staphylococcus aureus began exhibiting signs of
resistance to it. Now Methicillin- resistant Staphylococcus aureus (MRSA) has become one of the infections most
feared in hospitals and on athletic fields.

~~~

Maker of the Miracle Mould

The story of penicillin - the first antibiotic used successfully to treat people with serious infectious diseases - begins
with a bit of luck. Alexander Fleming, a British scientist, noticed in 1928 that mould had prevented the growth of
bacteria in his lab. But the main plot of the story involves the rediscovery of penicillin 10 years later by an
Australian scientist born one hundred years ago this year. Howard Florey and his dedicated team's systematic,
detailed work transformed penicillin from an interesting observation into a life saver.
Emma Burkervisc used to be the tea lady at the Australian National University's John Curtin School of Medical
Research (Howard Florey played a crucial role in the establishment of the School and University later in his life).
Emma's life was saved by penicillin in a German refugee camp after World War II. Imagine how she felt many years
later, bumping into Florey in the corridors where she worked - the man who made the supply of penicillin possible.
Imagine how you'd feel if you met someone who saved your life; and think of Florey and his team's impact on the
world.
Breaking the Mould
Florey gathered a team of scientists at Oxford University in Britain in the 1930s, when working together on
scientific discoveries as a group was not at all common. Nowadays scientists work together all the time, but Florey
realised that science had reached a point where a team of specialists was needed - the job was too big for one person.
His team commenced a careful investigation of the properties of anti-bacterial substances that are produced by
mould. One member of the team, Ernst Chain, found an article about Alexander Fleming's work while flicking
through a medical journal, and this prompted them to begin looking at penicillin.
Individual members of the group concentrated their attention on areas in which they had the most knowledge, but
they often met to exchange ideas. Chain worked on purifying penicillin with Edward Abraham. Norman Heatley
improvised methods for extracting penicillin using ether and bedpans (see 'penicillin production' below). A. D.
Gardner and Jena Orr-Ewing studied how penicillin reacted with other organisms. Howard Florey looked with
Margaret Jennings at the impact of penicillin on animals. Ethel Florey later worked with her husband on clinical
trials of penicillin.

In May, 1940 they performed one of the most important medical experiments in history. The work was so urgent that
they came in to begin the experiment on the weekend, and on Saturday 25 May, Florey's team tested penicillin on
eight mice injected with a lethal dose of streptococci bacteria. Four of the mice were treated with penicillin, while
four were used as controls. By the next day, the treated mice had recovered and the untreated mice were dead. In the
early days of World War II, the lives of eight mice may seem insignificant. But their rescue by penicillin led to the
treatment of Allied soldiers as early as D-Day, in June 1944, and probably influenced the outcome of the war.
The First Patient
The results were so exciting Florey knew that it was time to test the drug on humans. The first patient in 1941 had
been scratched by a rose thorn. Albert Alexander's whole face, eyes and scalp had swollen. He had already had an
eye removed and abscesses drained; even his remaining eye had to be lanced to relieve the pain of the swelling. He
was given penicillin, and within a day he began to recover. But Florey's team didn't have enough of the drug to see
the patient through to a full recovery. Their efforts to recycle the penicillin by extracting it from his urine failed, and
he unfortunately had a re-lapse and died. Because of the awful experience, the team then concentrated their efforts
on sick children, who did not require such large quantities.
In 1943 Florey travelled to North Africa to test the effects of penicillin on wounded soldiers. His trials were seen as
a miracle. Instead of amputating wounded limbs or simply leave them to heal, he suggested soldiers' wounds be
cleaned and sewn up, and that the patients then be given penicillin. Thanks to Florey and his team, the drug was
available to treat Allied troops by the end of World War II. It has since revolutionised medical science, saving
millions of lives.
Before Penicillin

How many times have you accidentally pricked your finger on a rose thorn, or perhaps a sewing needle? Nowadays,
if the wound became infected you'd be cured almost immediately. But before the second half of this century, you
could have been in big trouble. Infections were feared then as cancer is feared today. Your glands would swell up
and require lancing to release the pus. A surgeon might even have to amputate your arm in an attempt to save your
life. This was the nightmare of many infectious diseases before Howard Florey developed penicillin.
Setting the Stage for Penicillin
Three thousand years before penicillin, moulds and fermented materials had been used to cure various skin
infections, although without an understanding of how they actually worked. But it wasn't until the late 1800s that
scientific studies of antibiotics began. French chemist Louis Pasteur, after discovering that infectious diseases are
spread by bacteria, observed that mould inhibited the growth of anthrax (an infectious disease spread from animals
to humans). British surgeon Joseph Lister noted that samples of urine contaminated with mould didn't allow bacteria
to grow, but he was unable to identify the substance in the mould. French medical student Ernest Duchesne
successfully tested a substance from mould that inhibited bacterial growth in animals, but died at an early age in
1912, never seeing the world's acceptance and use of his important discovery.
After World War I, Alexander Fleming was conducting an experiment with bacteria when a tear fell from his eye
into a culture plate. He later noticed that a substance in his tear (which he named lysozyme) killed the bacteria, but
was harmless to the body's white blood cells. Years later, Fleming was doing research on the flu when a similar
coincidence occurred. While he was on holidays, a bit of mould had fallen into a discarded culture plate containing
bacteria, forming a clear patch. When he returned he recognised this pattern from his previous experience with
lysozyme. He concluded that the mould was producing an antibiotic substance and named the antibiotic penicillin,
after the Penicillium mould that produced it.
His discovery was an amazing piece of luck. If Fleming hadn't left a petri dish of bacteria on his bench when he
went on holidays; if he had properly disinfected the dish; if the weather had been different from the ideal conditions
for bacteria and mould growth in the laboratory; and especially if Fleming hadn't the experience to recognise the
importance of the observation, penicillin may not have been discovered as an antibiotic.
But Fleming couldn't extract the bacteria-killing substance, so he couldn't try it as a treatment for general infections.
He moved on to other research - leaving Howard Florey and his team to pave the way for penicillin's use as a
lifesaver more than a decade later.
Fabulous Fungus
Penicillin was the first naturally occurring antibiotic discovered (Prontosil, the first chemical used to cure certain
infectious diseases, had been discovered in 1933 but had serious side effects). There are now more than 60
antibiotics, which are substances that fight bacteria, fungi and other microbes harmful to humans - the word means
against (anti) life (bio).
An antibiotic is a drug produced by microbes. Penicillin is obtained in a number of forms from Penicillium moulds.
Penicillin G is the most widely used form, and is the one that killed bacteria during Duchesne's work in 1896,
Fleming's work in 1928 and Florey's work in 1939.
Bacteria reproduce by dividing to produce two new cells. They enlarge to about twice their size before the DNA
chromosome is copied. The two new chromosomes move apart and a cell wall forms between them. But if penicillin
is around the new cell wall won't be able to form. It doesn't harm old bacterial cell walls, it just stops new ones
forming. This means the bacteria can't reproduce, so the disease can't spread.
Natural penicillin is administered by injection, because if it's swallowed stomach acids destroy the drug before it
reaches the bloodstream. One shot of penicillin these days is more than the entire amount used by Florey's team in
all its clinical trials! About one in 10 people is allergic to penicillin, showing symptoms ranging from minor rashes
to serious breathing difficulties. If you're allergic to penicillin, there are now other antibiotics that can be taken as a
substitute.

Penicillin Production
Florey's team worked under difficult circumstances with a lack of funding and equipment, but ensured penicillin
production grew from the manufacture of a scarce and very impure brown powder to the commercial production of a
purified and powerful antibiotic.
At first penicillin was made using old dairy equipment. Hospital bedpans were used to grow mould. Liquid
containing penicillin was drained from beneath the growing mould and filtered through parachute silk on
bookshelves. But the team needed drug companies to help it produce the large amounts required for test patients.
Companies in Britain were unable to help out on a large scale because of the war, so Howard Florey and Norman
Heatley took a dangerous flight to the United States in a blacked-out plane across the Atlantic. The trip was against
the wishes of Ernst Chain, who wanted to first patent their ideas in Britain. This would have made the team very rich
indeed, but it was thought in Britain at the time that patenting medical discoveries was unethical.
Florey explained his penicillin-making methods to people in the US, and there happened to be a Department of
Agriculture laboratory looking for a new use for a thick liquid that was a by product from the corn-milling process.
When this liquid was used, 10 times the amount of penicillin was able to be produced than before. Mary Hunt,
known as Mouldy Mary for her enthusiasm in finding new sources of mould, then found mould growing in
cantaloupe (rockmelon) was twice as successful again at producing penicillin.
By late 1943, mass production of the drug had commenced - only four years after the first mouse experiments and in
spite of the war, a sign of Florey's persistence and determination. By the end of the war, many laboratories were
manufacturing the drug, including the Merck, Squibb and Pfizer companies in the US and the Commonwealth
Serum Laboratories in Australia. In fact, Australia was the first country that made the drug available for civilian use.
However, several strains of bacteria became resistant to penicillin after a few years, through mutation of the cells. To
overcome this problem, scientists in the 1950s made artificial penicillin by chemically changing natural penicillin.
Resistant bacteria multiply when non-resistant bacteria die. Hospitals in Australia and around the world are now
seeing the arrival of antibiotic-resistant bacteria due to the overuse of antibiotics, exposing the very young, very old
and very sick people to infections and diseases.

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