NEW YORK — Lloyd H. Conover, a chemist whose breakthrough invention of one of the most effective and widely prescribed antibiotics, tetracycline, led to a whole new approach to developing such drugs, died on Saturday in St. Petersburg, Fla. He was 93.
His death was confirmed by his son Craig.
Dr.Conover started his research at Pfizer in Brooklyn in 1950, when pharmaceutical companies, spurred by the success of penicillin against battlefield infections during World War II, were racing to find new antibiotics. Most early antibiotics were naturally occurring chemicals produced by microorganisms that lived in soil or on decaying fruit; the strain of penicillin used to protect wounded soldiers came from a moldy melon.
Few scientists at the time thought it was possible to improve on antibiotics, which they viewed as a result of an evolutionary process that equipped microorganisms with the ultimate chemical weapons to survive.
Dr.Conover, however, became intrigued with two naturally occurring antibiotics that, except for two atoms, were chemically identical. To Dr.Conover, the atoms seemed out of place. Each antibiotic had a chlorine or oxygen atom where he expected to find a hydrogen atom. Would swapping in hydrogen improve the potency of the drugs?
Using a routine chemical procedure, he stripped chlorine from one antibiotic and inserted hydrogen, creating a more stable molecule. He worked with a single assistant. “I didn’t want an audience if we failed,” he told The Cleveland Plain Dealer in 1992.
The result was tetracycline, a powerful antibiotic with fewer side effects than the drug from which it was derived — proof, Dr.Conover wrote, that “a superior drug could be made by chemical modification.”
Virtually all antibiotics today are semisynthetic, meaning they are chemically altered to increase the number of infections that can be treated or to reduce side effects.
Hailed as a wonder drug, tetracycline proved effective against numerous potentially deadly infections, including salmonella, which causes food poisoning, and bacteria responsible for bloodstream, skin, and urinary infections; gonorrhea; pneumonia; and strep throat.
Hog and chicken farmers embraced the drug, which was used to encourage growth and ward off infections among animals raised in close quarters. Fruit growers sprayed tetracycline in orchards to prevent fire blight and other diseases.
With tetracycline’s commercial success, however, came a slew of patent challenges. Three pharmaceutical companies claimed that their scientists had invented tetracycline before Dr.Conover, though their patent applications were filed later. After Pfizer licensed tetracycline to its competitors to end the dispute, the federal government challenged the licensing deals as anticompetitive, along with the validity of the patent.
“I had essentially a second career: preparing for and giving depositions and testifying,” Dr.Conover wrote in a 1984 journal article.
At scientific meetings, he wrote, he felt a coolness from peers who believed that his patent claim was false. A federal appeals court in Philadelphia finally affirmed the patent — and, by extension, the licensing agreements — in 1982, three decades after Dr.Conover invented tetracycline.
By the time the litigation ended, widespread use of tetracycline had caused many kinds of bacteria to become resistant to the antibiotic, reducing its potency against many infections.
Tetracycline is still commonly used against acne and certain tick-borne diseases, such as Lyme disease, Rocky Mountain spotted fever, and Q fever.
At Pfizer, Dr.Conover was assigned to a team working to determine the chemical structures of two antibiotics that turned out to be very similar. When the task was completed, the senior scientists went off to write papers about their findings, leaving Dr.Conover with time on his hands.
“Everyone thought that was the end of the project,” Dr.Conover said in the interview. “But I wanted to keep working with these wonderfully interesting molecules.”
Dr.Conover completed his tetracycline experiment in a matter of months. “It worked the first time, unlike most of the experiments I ever ran,” he said. Within a year, Pfizer was testing tetracycline on people.
Dr.Conover spent his entire career at Pfizer. He went on to help invent Pyrantel and Morantel, which are used to treat parasitic worm infections, and rose through the company’s executive ranks to become senior vice president of agricultural products research and development. He retired in 1984.
Although Pfizer vigorously defended Dr.Conover’s patent, the company was less aggressive than competitors in marketing his invention.
“Pfizer sold tetracycline, but never pushed it,” Dr.Conover said. “That was a disappointment.”