The Advent Of Wonder Drugs -- Broad Spectrum Of Antibiotics Saved The World From Once-Fatal Infections

BETHESDA, Md. - In the last 50 years, millions of Americans have survived infectious diseases that would have killed them off in the 50 years before.

No one knows for certain just how many lives have been saved, but broad-spectrum antibiotics rescued the world from the insidious and fatal bacterial infections that haunted mankind through the millennia.

Imagine the world before antibiotics when chance colds could turn to deadly pneumonia, when tuberculosis struck down the rich and poor, when an accidental cut would invite an infection that spread through the body as fast as the bacteria could reproduce, when a wounded soldier would die not of the bullet but of the infected wound.

Nearly every family lost someone because scientific luck came a little late.

And, when it came, how natural it was to name the rainbow of antibiotics that it spawned The Wonder Drugs.

This is the century of The Wonder Drugs.

The first heroes on the scene became a metaphor for the 20th century. They were the antibiotics that later set the stage for daring advances in surgery by barring the door to ubiquitous and lethal bacteria.

Before the turn of the century, the specter of "The White Plague," tuberculosis, hung over the cities of Western Europe and the new cities of the United States.

Tuberculosis became a thief robbing Western culture. It took the lives of Anton Checkov in 1904, Franz Kafka in 1924, D.H. Lawrence in 1930, George Orwell in 1950. And before that Chopin, Robert Louis Stevenson, Heinrich Heine, John Keats.

So common are the Wonder Drugs now that much of today's world takes them for granted. Indeed, tuberculosis is coming back for two reasons: The poor and homeless go untreated and, among the more affluent with respiratory ills, doctors frequently overlook the possibility because they haven't seen TB cases in years.

Medicine by habit tends to look forward. Although it would be possible to crunch the numbers from mortality figures, apparently no one has done it.

One researcher in 1958 estimated that 1.5 million Americans had been spared death in the 10 to 15 years after penicillin's arrival in 1945. Life expectancy for Americans at birth was 63 when sulfa drugs became available in the 1930s and 65 when penicillin came on the scene in mid-century. By 1978 it was 72. Today it is 74 1/2.

Says Dr. Gladys Hobby in her book "Penicillin": "Not only did it decrease the incidence and severity of many infectious diseases . . . it made possible cardiac surgery, organ transplantation and the management of severe burns."

The discovery of the antibiotics is a wonderment in itself. It began with the concepts of antibiosis and immunology that were born in the 19th century from the minds of Louis Pasteur and Paul Ehrlich.

Then, in the World War II era, the story began to unfold, punctuated by the death of a London police officer who cut himself shaving and a moldy cantaloupe in a fruit stand in Peoria, Ill.

"Man's discovery of antimicrobial agents," as one scientific historian said, "must surely rank as one of his greatest triumphs."

In the history of science probably no stroke of luck is better known than that of Alexander Fleming's chance discovery in 1928 that one of his bacterial culture plates was contaminated by Penicillium mold, similar to the blue-green mold that grows on old bread. He was going to throw the tainted culture away when he discovered that the bacteria on the glass plate was not growing around the mold.

The next year he published a paper. He had proved that the substance he called penicillin was safe for laboratory animals but it was devastating to certain bacteria, even in the meager, impure doses he eked out of his mold sample. Maybe, he thought with cautious optimism, it might be useful as an antiseptic applied externally.

He passed out samples of the mold to other researchers. But the few attempts to isolate the active element from the mold juice or to use it clinically came to naught.

Enter Howard Florey, an Australian-born pathologist, and Ernst Chain, a young Jewish biochemist who fled the Nazis.

Florey and Chain, working at Oxford University in England, came across Fleming's old paper on penicillin and obtained samples of the mold which they proceeded to grow. Then in 1939, as Europe was exploding in war, another scientist, Rene Dubos, spurred the search for antibiotics by discovering substances in soil bacteria which could attack other organisms. Further research showed them to be too toxic for humans, but it stimulated new research by Dubos' former teacher, Selman Waksman.

"Actually," says Dr. John Parascandola, chief of the History of Medicine for the National Library of Medicine in Bethesda, Md., "penicillin was so much more effective as an anti-bacterial agent than any other drug known at the time, including the then-recently introduced sulfonamides, that the Oxford team at first greatly underestimated its potency."

They began to increase their production of penicillin that the mold yielded in scant quantities. Joined by Norman Heatley and E.P. Abraham, they began to try their short supplies on human volunteers. The first was a terminal-cancer patient, not to treat the cancer, but to test the toxicity of the drug. It was safe. Then they tried it on a terminally ill policeman who was near death from both staph and strep infections that developed after he had cut himself while shaving. The policeman made a striking recovery until the supply of penicillin ran out. He relapsed and died.

Florey decided that future tests would have to be made on children who required smaller doses. He also knew he would need much more penicillin.

But Britain was fighting off the Germans. Experimental drugs had low priority.

The summer of 1941, Florey and Heatley took their search for support to the United States. They were directed to the Northern Regional Research Laboratory of the Department of Agriculture in Peoria. Scientists there were experienced in fermentation as part of their effort to find new products and markets for American farmers. They were delighted to find that corn-steep liquor, a practically useless agricultural byproduct, was an ideal nutrient for the mold.

They devised ways of growing the Penicillium mold in huge fermentation vats where they could feed in oxygen and churn the hundreds of gallons of nutrient and mold, thereby greatly increasing the growing area and the penicillin production.

They also began to sift through thousands of Penicillium molds gathered from all over the world to find one that might produce more penicillin than Fleming's.

"The one that turned out to be the most productive," Parascandola said, "was one they found growing on a moldy cantaloupe in a Peoria fruit market. . . .

"Over the years they improved that strain by producing mutations with ultraviolet radiation or chemicals. But I think even today the penicillin that is produced is derived from that moldy cantaloupe."

The U.S. War Production Board set up a cooperative penicillin project involving about 20 laboratories. Word got around and the demand for the wonder drug spread.