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 Plain Dealer of Cleveland 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 discovered tetracycline before Dr. Conover, although 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 article in the journal Research Management.
At scientific meetings, he wrote, he felt a coolness from peers who thought 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. To control bacterial resistance, many European countries and the United States now restrict the nontherapeutic use of tetracycline in agriculture.
Lloyd Hillyard Conover was born on June 13, 1923, in Orange, N.J. His father, John, was a lawyer; his mother, the former Marguerite Anna Cameron, was an artist. His interest in chemistry began in childhood when he watched his father mix cement to repair a retaining wall.
“There was something about the physical change in matter that really fascinated me,” he said in an interview for this obituary.
To feed his curiosity, he devised science projects with items he found around his house. In one instance, he took his mother’s pots and pans and melted down lead left behind by a plumber to make a miniature cannon that fired lead pellets, powered by steam.
He entered Amherst College in 1941 to study chemistry, but his education was interrupted by World War II. He spent three years in the Navy, serving on an amphibious ship in the Pacific and rising to lieutenant junior grade.
After the war, he returned to Amherst, and he received his bachelor’s degree in 1947. He received his doctorate in chemistry from the University of Rochester in 1950 and went to work for Pfizer, where salaries were higher than in academia, to support his family.
His first wife, the former Virginia Kirk, died in 1988; his second wife, the former Marie Solomons, died in 2003.
Besides his son Craig, survivors include his wife, the former Katharine Meacham; two other sons, Kirk and Roger; a daughter, Heather Conover; four stepdaughters, Sue Love, Virginia Karpovich, Katharine Meacham and Laura Keane; two stepsons, Walter Solomons and Andrew Meacham; 16 grandchildren; and seven great-grandchildren.
At Pfizer, Dr. Conover was assigned to a team working to determine the chemical structures of the antibiotics oxytetracycline and chlortetracycline — a project that laid the groundwork for Dr. Conover’s discovery. After the team completed its task, 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 for 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.”
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