How penicillin was discovered, and how WWII let this miracle drug reach millions

Sorry Mary, you’re no hero after all: Real penicillin star is unknown housewife (1976)

By Ronald Kotulak – The Dispatch (Moline, Illinois) Oct 10, 1976

IT WASN’T Moldy Mary after all. Not that she wouldn’t like to take the credit for helping to save the world from germs.

But more than three decades after the drama unfolded in the dark days of World War II, it turns out that it was an unsung and unknown Peoria housewife who helped make penicillin a household word.

IF THERE IS such a thing as a miracle drug, penicillin is it. The first antibiotic to be discovered, penicillin conquered bacterial infections, ushering in the modern era of medicine.

It gave doctors their first true curative powers. With penicillin, a physician could cure once fatal common infections. Before that, he could merely sit by the bedside of the patient, hoping for the best, but usually powerless to prevent death.

All this might have been denied to mankind, at least for some time, if it had not been for some key people in Peoria. Certainly, the magic drug would not have been available to treat Allied troops during the critical closing years of the war without the Peoria “miracle.”

WHEN THE War Production Board placed the development of penicillin on a high-priority basis, it turned for help to the United States Department of Agriculture’s Northern Regional Research Laboratory in Peoria. The laboratory had the country’s biggest and most sophisticated fermentation process for growing molds.

Penicillin is produced by molds of the Penicillium notatum family. Hundreds of different penicillin molds from all over the world were shipped to Peoria for testing, but all proved disappointing because their penicillin output was too little.

AT THE SAME time, a young laboratory technician named Mary was given the assignment of visiting Peoria markets every Monday to pick up moldy fruit. Naturally, she earned the nickname “Moldy Mary.”

According to the snidely told story, Mary returned to the lab with a rotten cantaloupe after one of her Monday morning rounds. When scientists grew the cantaloupe mold, their hearts began to pound with excitement. Penicillin was pouring out at a rate 50 times higher than the original penicillin mold first identified by Alexander Fleming in 1928.

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With a little refinement, they selected some mutant molds that had a penicillin output 900 times higher than Fleming’s original. The cantaloupe strain was so remarkable that all of the penicillin produced in the world today is descended from that Peoria mold.

BUT IT WASN’T Moldy Mary who found it, according to Dr. Kenneth B. Raper, who was then in charge of isolating molds at the Peoria laboratory.

“A housewife in town knew we were looking for moldy food, and she brought in the moldy cantaloupe,” said Raper, now a microbiologist at the University of Wisconsin in Madison.

She handed the cantaloupe over to a guard and vanished. She was never thanked, never given any medals for helping to save tens of thousands of lives. No one knew who she was. And she never found out that it was her cantaloupe that made penicillin available worldwide.

THERE WAS YET a third development that could have happened only in Peoria. The penicillin mold is a finicky eater. Its growth rate remained relatively poor despite all the different nutrients scientists fed it.

But one nutrient combination that a Peoria scientist stumbled on turned the molds into gluttons, greatly increasing their production of penicillin. The nutrient was corn steep liquor, a waste product of corn milling.

One of the reason’s the government set up the Peoria laboratory in the late 30s was to find uses for waste products from farming processes. The late Dr. Andrew Moyer discovered that corn liquor could be used to grow molds and that the penicillin mold had a craving for it. The liquor increased penicillin production tenfold.

“THE PEORIA FACILITY was the only laboratory in the country where the corn steep liquor medium would have been discovered,” said Dr. Robert D. Coghill, former chief of the fermentation division. Retired and living in Tacoma, Wash., Coghill looks at the development of penicillin in Peoria as a series of “little-understood miracles.”

“We were lucky. So many things came together unexpectedly. It was the scientific problem of the century handed to us on a silver platter, and we solved it,” he said.

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THE HISTORY of penicillin is notable for its lucky accidents. In fact, it came close to not being discovered, and once discovered came very near to being forgotten.

Fleming, the easy-going British bacteriologist known for his sloppy laboratory, one day noticed a strange mold contaminating a bacterial culture in a Petri dish. The culture was ruined, and the natural inclination would be to toss the dish out.

But Fleming looked more closely, always the inquisitive scientist. He saw that the mold growths were surrounded by clear areas. The molds were killing the bacteria, and they were no ordinary bacteria. The dish contained streptococci bacteria, the germ that causes strep throat, rheumatic fever, and scarlet fever.

Excitedly, he transferred the penicillin mold to other cultures containing bacteria that cause diphtheria, and pneumonia. These germs also were killed.

FLEMING’S MOMENTOUS discovery was greeted by a huge yawn from tile scientific community, said Coghill, because its killing action was weak and the chemical was very unstable. Fleming himself could do no more with it.

Eleven years later, the situation changed drastically. World War II was in progress, and the Germans had cut off exports of the sulfa drugs. The sulfas had some effect on infections, but they were like a peashooter when later compared to the shotgun impact of penicillin.

Forced to look for other drugs, two English scientists, Howard Florey and Ernest B. Chain, took a fresh look at penicillin. Fleming, Florey, and Chain later received a Nobel Prize for their work. Morey and Chain conducted the key experiments that showed the drug might be useful to medicine.

Mice were injected with big doses of germs that would surely kill them. Then some of the mice were given a crude extract of penicillin. These mice survived, but control mice not given penicillin died. The English researchers were hot on the trail, but they were unable to continue their work because of intense German bombing in 1940.

COMING TO THE United States, they learned through another accidental set of circumstances of the big fermentation lab in Peoria. With their help, the lab, which had been completed only a few months earlier, immediately began trying to grow penicillin molds. Soon, however, it found critical supplies cut short because of the war.

The War Production Board stepped in and put the lab on a high-priority basis in 1941. Their goal was to have ample stocks of penicillin on hand for Gen. Dwight Eisenhower’s invasion of Europe in the spring of 1944.

The first patient to get American-made penicillin successfully recovered from progressive streptococcal septicemia on March 14, 1942. Two and a half months later, enough penicillin was available to treat 10 patients.

Penicillin was highly effective. Even in dilute solutions of one part of penicillin per 100 million parts of solution, it was capable of arresting infections. The cantaloupe mold was doing its job. At best, Fleming was able to get only three units of penicillin per milliliter [ml.] of solution. The cantaloupe strain boosted the output to 250 units per ml. Some of the mutant molds were coaxed into giving up 1,500 units per ml.

The first wounded soldiers were treated with penicillin in 1943. The word leaked out, and the country began clamoring for the drug. Headlines screamed: “Penicillin, ‘New Miracle’ Drug Combats Bacterial Infections.”

THE PEORIA laboratory turned over its successful penicillin mold-grooving process to drug companies in 1943. Supplies have increased and the costs went down.

In the early days, penicillin cost $20 per 100,000 units or about $200,000 a pound. Today the cost is about 1.3 cents per 100,000 units.

Scientists generally concede that if it were not for the war, penicillin would not have been developed so rapidly. Today, 34 years after its first successful use, penicillin is still the most widely used antibiotic in the world.

History: The dramatic race to get enough penicillin during WWII (Article from 1944)

Chemists strive against time to provide gigantic doses needed by helpless victims of deadly endocarditis

by Robert D Potter, Science Editor – San Antonio Light (San Antonio, Texas) February 6, 1944

With the lives of thousands of human beings at stake, American chemists are engaged today in a strange and dramatic race.

The goal is to start mass production of penicillin, new potent germ-killing drug made from mold, in time to save the lives of many persons who cannot now obtain it. The best brains of American chemistry, plus $20,000,000, and the resources of 19 great chemical companies are in this race of mercy.

Helpless on the sidelines, mutely praying, are sufferers of some of man’s most deadly, baffling maladies. No unfortunate group of sick persons stands more to gain by mass production of penicillin than those victims of bacterial endocarditis; a dreaded almost-always-fatal disease that attacks the heart of so many human sufferers.

In bacterial endocarditis, germs known as streptococcus viridans attack the valves of the heart. Before penicillin, doctors did what they could for this condition. Complete rest and a few remedies… there was little they could do for acute cases. But recent discoveries have established that penicillin can strike dramatically against this fatal ill.

Dr Leo Loewe and his associates at Brooklyn Jewish Hospital have treated 10 “hopeless” cases of bacterial endocarditis with penicillin. Eight of the patients are now germ-free of the streptococcus viridans.

Not a “cure” — but still a success

The Brooklyn doctors, in their cautious medical way, claim this is no “cure.” But for the eight patients, penicillin has been a miracle drug. The trouble with the treatment — and here is where the race with death comes in — is that huge quantities of penicillin must be used. And there just isn’t enough penicillin.

For a single case of subacute bacterial endocarditis, from 1,000,000 to 8,000,000 units of penicillin must be employed, says Dr Loewe. In contrast, doctors can conquer a case of pneumonia with only 100,000 units. Or they can whip a serious case of staphylococcus infections with only 30,000 to 50,000 penicillin units.

Doctors are thus faced with the dilemma of risking ten pneumonia patients for every case in which they use penicillin for bacterial endocarditis. Or they risk from 20 to 30 cases of osteomyelitis by the same decision.

Instead of putting the civilian coordinator of penicillin, Dr Chester Reefer of Boston, on the spot in making such decisions, the simplest way would be to increase production. Since two months is about the limit for patients suffering from acute bacterial endocarditis, can production be increased quickly enough to save victims who now have the disease?

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Everything hinges on the next few months. Rush production is already underway. And according to an announcement in the authoritative American Medical Journal, enough penicillin for civilian, as well as military, needs should be available by June.

Medical history: How penicillin is made

Three major methods are used for making penicillin. The first, already being used, is to grow the mold of penicillin in small one-liter bottles where the mold grows on the surface of the liquid. The bottle method alone has produced penicillin up to the present time.

Scientists at Stanford University have discovered, however, that penicillin can be produced in tall towers in a manner already used in producing “quick” vinegar. In the quick process of making vinegar, a tall cylinder is filled with wood shavings.

A culture of the bacteria that makes acetic acid is “planted” on the shavings. Cider or wine are then trickled down the tower. Vinegar comes off in quantity at the bottom of the column.

Professor C E Clifton of Stanford has adapted this technique for the production of penicillin. The shavings are moistened with a solution of 4% glucose (sugar) and 0.1% yeast extract. This food is planted with the spores of the penicillin mold. Nutrient solution for the mold is then trickled down the tower.

The mold digests the liquid. Out of the bottom of the cylinder comes a solution rich in penicillin.

But the biggest method, and the one expected to yield vast production in penicillin, is the vat method. Here the mold is grown in great tanks, up to 10,000 gallons in capacity. Government WPB contracts have been let to obtain large-scale production by the vat method. While this $20,000,000 production program is going on, independent research seeks still more production.

Great efforts are being made to find a strain of the penicillin mold which will give an even greater yield of the drug, or perhaps produce still some other chemical which will be as good or better. 

Intensive research is underway, but at the end of 1943, the original mold used by Prof Alexander Fleming in England in 1929 still was the best penicillin producer. This mold is called Penicillium notatum.

When mass production of penicillin is underway, the cost will drop greatly. Formerly, the price for treatment was about $20 for a million units. Already, the cost is down to $8 for a million units.

Synthetics a goal

The real drop will come when chemists synthesize the drug, and create it from chemicals in the laboratory as they now produce the sulfa drug. This is the ultimate goal. Using a mold to produce penicillin is merely stopgap, for it utilizes a most delicate form of plant life as an intermediate chemical factory.

There are rumors but no authentic announcement that the synthesis of penicillin is on the way. Stories are making the rounds that the structure of penicillin has already been determined. If true, this is a sure step on the path of man-made penicillin.

When the synthesis of penicillin is achieved it will probably make obsolete the $20,000,000 plant installations now being rushed.