Penicillin

The invention: The first successful and widely used antibiotic

drug, penicillin has been called the twentieth century’s greatest

“wonder drug.”

The people behind the invention:

Sir Alexander Fleming (1881-1955), a Scottish bacteriologist,

cowinner of the 1945 Nobel Prize in Physiology or Medicine

Baron Florey (1898-1968), an Australian pathologist, cowinner

of the 1945 Nobel Prize in Physiology or Medicine

Ernst Boris Chain (1906-1979), an émigré German biochemist,

cowinner of the 1945 Nobel Prize in Physiology or Medicine

The Search for the Perfect Antibiotic

During the early twentieth century, scientists were aware of antibacterial

substances but did not know how to make full use of them

in the treatment of diseases. Sir Alexander Fleming discovered penicillin

in 1928, but he was unable to duplicate his laboratory results

of its antibiotic properties in clinical tests; as a result, he did not recognize

the medical potential of penicillin. Between 1935 and 1940,

penicillin was purified, concentrated, and clinically tested by pathologist

Baron Florey, biochemist Ernst Boris Chain, and members

of their Oxford research group. Their achievement has since been regarded

as one of the greatest medical discoveries of the twentieth

century.

Florey was a professor at Oxford University in charge of the Sir

William Dunn School of Pathology. Chain had worked for two years

at Cambridge University in the laboratory of Frederick Gowland

Hopkins, an eminent chemist and discoverer of vitamins. Hopkins

recommended Chain to Florey, who was searching for a candidate

to lead a new biochemical unit in the Dunn School of Pathology.

In 1938, Florey and Chain formed a research group to investigate

the phenomenon of antibiosis, or the antagonistic association between

different forms of life. The union of Florey’s medical knowledge

and Chain’s biochemical expertise proved to be an ideal combination for exploring the antibiosis potential of penicillin. Florey

and Chain began their investigation with a literature search in

which Chain came across Fleming’s work and added penicillin to

their list of potential antibiotics.

Their first task was to isolate pure penicillin from a crude liquid

extract. A culture of Fleming’s original Penicillium notatum was

maintained at Oxford and was used by the Oxford group for penicillin

production. Extracting large quantities of penicillin from the

medium was a painstaking task, as the solution contained only one

part of the antibiotic in ten million. When enough of the raw juice

was collected, the Oxford group focused on eliminating impurities

and concentrating the penicillin. The concentrated liquid was then

freeze-dried, leaving a soluble brown powder.

Spectacular Results

In May, 1940, Florey’s clinical tests of the crude penicillin proved

its value as an antibiotic. Following extensive controlled experiments

with mice, the Oxford group concluded that they had discovered

an antibiotic that was nontoxic and far more effective against

pathogenic bacteria than any of the known sulfa drugs. Furthermore,

penicillin was not inactivated after injection into the bloodstream

but was excreted unchanged in the urine. Continued tests

showed that penicillin did not interfere with white blood cells and

had no adverse effect on living cells. Bacteria susceptible to the antibiotic

included those responsible for gas gangrene, pneumonia,

meningitis, diphtheria, and gonorrhea. American researchers later

proved that penicillin was also effective against syphilis.

In January, 1941, Florey injected a volunteer with penicillin

and found that there were no side effects to treatment with the

antibiotic. In February, the group began treatment of Albert Alexander,

a forty-three-year-old policeman with a serious staphylococci

and streptococci infection that was resisting massive doses of

sulfa drugs. Alexander had been hospitalized for two months after

an infection in the corner of his mouth had spread to his face,

shoulder, and lungs. After receiving an injection of 200 milligrams

of penicillin, Alexander showed remarkable progress, and for the

next ten days his condition improved. Unfortunately, the Oxford production facility was unable to generate enough penicillin to

overcome Alexander’s advanced infection completely, and he died

on March 15. A later case involving a fourteen-year-old boy with

staphylococcal septicemia and osteomyelitis had a more spectacular

result: The patient made a complete recovery in two months. In

all the early clinical treatments, patients showed vast improvement,

and most recovered completely from infections that resisted

all other treatment.

Impact

Penicillin is among the greatest medical discoveries of the twentieth

century. Florey and Chain’s chemical and clinical research

brought about a revolution in the treatment of infectious disease.

Almost every organ in the body is vulnerable to bacteria. Before

penicillin, the only antimicrobial drugs available were quinine, arsenic,

and sulfa drugs. Of these, only the sulfa drugs were useful for

treatment of bacterial infection, but their high toxicity often limited

their use. With this small arsenal, doctors were helpless to treat

thousands of patients with bacterial infections.

The work of Florey and Chain achieved particular attention because

ofWorldWar II and the need for treatments of such scourges

as gas gangrene, which had infected the wounds of numerous

World War I soldiers. With the help of Florey and Chain’s Oxford

group, scientists at the U.S. Department of Agriculture’s Northern

Regional Research Laboratory developed a highly efficient method

for producing penicillin using fermentation. After an extended search,

scientists were also able to isolate a more productive penicillin

strain, Penicillium chrysogenum. By 1945, a strain was developed that

produced five hundred times more penicillin than Fleming’s original

mold had.

Penicillin, the first of the “wonder drugs,” remains one of the

most powerful antibiotic in existence. Diseases such as pneumonia,

meningitis, and syphilis are still treated with penicillin. Penicillin

and other antibiotics also had a broad impact on other fields of medicine,

as major operations such as heart surgery, organ transplants,

and management of severe burns became possible once the threat of

bacterial infection was minimized.Florey and Chain received numerous awards for their achievement,

the greatest of which was the 1945 Nobel Prize in Physiology

or Medicine, which they shared with Fleming for his original discovery.

Florey was among the most effective medical scientists of

his generation, and Chain earned similar accolades in the science of

biochemistry. This combination of outstanding medical and chemical

expertise made possible one of the greatest discoveries in human

history.