Lloyd Conover

The American chemist Lloyd Conover (1923–2017) was the inventor of the antibiotic tetracycline, one of the most widely used medicines of the modern era. His discovery revolutionized the way new antibiotics were and are created and produced.

Built Miniature Cannon as Child

Born June 13, 1923, in Orange, New Jersey, Lloyd Hillyard Conover was the son of attorney John Conover and artist Marguerite Anna Cameron Conover. Experimentally minded even as a child, he built a miniature cannon and cannonball by melting down some lead a building contractor had left at the house. When he watched his father mixing cement, his fascination with chemistry began. Conover entered Amherst College in Massachusetts as a chemistry major in 1941, but World War II interrupted his studies. He served in the U.S. Navy for three years, seeing action on an amphibious ship in the Pacific. Back in the United States, he graduated from Amherst in 1947 and completed his doctorate in chemistry at the University of Rochester in 1950.

Although Conover intended to pursue an academic career, family responsibilities caused him to change course. He married Virginia Kirk, his high-school sweetheart, after proposing via telegram while completing his military service, and corporate jobs paid better than academic ones. Soon after accepting a post as a research chemist with Pfizer, Inc., at its Brooklyn, New York, office, Conover was assigned to a team, headed by Nobel Prize-winning organic chemist Robert Woodward, that was talked with analyzing the chemical structure of two antibiotics generated from the tetracyclines oxytetracycline and chlorotetracycline.

During the early 20th century, scientists believed that antibiotics were naturally occurring substances that had great benefits and that finding more of them meant searching the natural world. Synthesizing these drugs would reap major benefits in human health, and Woodward had already synthesized quinine—an extract of the bark of a cinchona tree that was used to treat malaria—as well as chlorophyll, strychnine, and cortisone, among others. When the tetracycline project concluded in 1952, Woodward went to work producing publishable papers on the tetracycline project, and Pfizer marketed the synthesized oxytetracycline under the name Terramycin. Conover, however, still had questions.

Although scientists worked to reproduce naturally occurring chemical compounds in the laboratory, manipulating these compounds chemically was not thought to be useful or promising. As Conover, reflecting on the work he and his team had just finished, he wondered whether replacing a chlorine atom in chlorotetracycline and an oxygen atom in oxytetracycline with a hydrogen atom in each case might make these drugs more effective. “I would have to say one day, which was unique in my whole career, I really had a ‘Eureka’ moment,” Conover later recalled to Andrew Meacham in the Tampa Bay Times.

Successfully Modified Existing Drug

Working with just one assistant (“I didn't want an audience if we failed,” he quipped in a Cleveland Plain Dealer interview quoted by Denise Gellene in the New York Times), he stripped the chlorine atom from chlorotetracycline, an antibiotic used by veterinaries and known by its brand name, Aureomycin. The experiment worked immediately, producing a chemically stable compound that could easily be tested against a wide variety of ailments. Conover reported his findings in the Journal of the American Chemical Society in 1953, and by 1955 he had been granted a patent (No. 2,699,054) for the new drug, tetracycline. It was the first antibiotic made by chemically modifying a naturally occurring drug, but it was far from the last: in the mid-1950s drug companies began modifying drugs they already had, and this became the method by which most new antibiotics have been developed.

Tetracycline was widely hailed as a wonder drug, and in 1955, the year it was patented, it became the most widely prescribed drug in the United States. The new drug had few side effects and it was effective against many illnesses, including chlamydia, pneumonia, acne, and Lyme disease. It also helped to cure cholera, a deadly killer for much of the 19th and 20th centuries. It also provided a solution to the problem of bacteria that were beginning to develop resistance against penicillin, although its widespread use in raising healthier, bigger livestock soon began to create tetracycline-resistant organisms as well. The drug was even used as a spray for fruit trees, to make them resistant to disease.

These successes made the tetracycline patent one of the most hotly contested in the pharmaceutical business. Although Conover had filed his patent application first, three rival companies claimed that their scientists had been the first to discover tetracycline. Pfizer attempted to settle the dispute at one point by licensing the drug to its competitors, but that complicated ongoing court proceedings by adding federal antitrust charges to the mix. “I had essentially a second career, preparing for and giving depositions and testifying,” Conover recalled in a Research Management article quoted by Gellene, and the dispute—which dragged on for 27 years—took a toll on the scientist's professional relationships. In the end, the primacy of his patent was completely affirmed.

In 1958 Conover was promoted from research scientist to research supervisor at Pfizer, and in 1961 to research manager. He became the company's director of chemical and chemotherapy research in 1968, and in 1971 moved to the United Kingdom to become research director at Pfizer's branch in Sandwich, England. In 1975 he returned to the United States and took a post as senior vice president for agricultural product research and development. He was a member of the American Chemical Society and a fellow of England's Royal Chemical Society. Conover retired from Pfizer in 1984.

Granted 300 Patents

Over his career, Conover was granted about 300 patents. He worked on the team that developed the drugs Pyrantel and Morantel, used to treat cases of worm and parasite infestation. Under his direction, Pfizer scientists developed the antiprotozoal drug tinidazole, the antibiotic indanylcarbenicillin, and the anti-infection animal drug promotant carbadox. Conover was inducted into the National Inventors Hall of Fame in North Canton, Ohio, in 1992.

Conover and his wife raised four children, living for many years in Waterford, Connecticut. While they were young, he tied ropes to his children's bedposts and taught them to rappel down the side of the house if there was a fire. He also helped them plant young evergreen trees on the family property and sell them as Christmas trees, explaining that this endeavor would help them fund their college educations. Conover enjoyed theater and opera but not clothes shopping, which he left in the hands of his wife; throughout their life together, he wore whatever she chose for him. After Virginia Conover's death in 1988, he married Marie Solomons, who died in 2003.

In 2005 Conover, at age 82, married Katharine Meacham, who had twice written him letters suggesting that they date. Their marriage ceremony was a dual one, combining their wedding with that of their grandchildren, who were also marrying each other. Conover died of congestive heart failure in St. Petersburg, Florida, on March 11, 2017. Tetracycline remains commonly used to treat acne and various diseases carried by ticks, including Lyme disease. Its use in agriculture has been banned in many places due to fears about antibiotic resistance.

Books

Periodicals

Daily Telegraph (London, England), March 14, 2017, “Lloyd Conover: Inventor of Tetracycline, Used to Treat a Wide Range of Infections,” p. 31.

New York Times, January 8, 2006, Constance E. Richards, “Wendy Legerton and Dave Love; Katharine Meacham and Lloyd Conover,” p. 31; March 13, 2017, Denise Gellene, “Lloyd Conover, 93, Dies; Invented Revolutionary Drug,” p. B7.

Tampa Bay Times, March 15, 2017, Andrew Meacham, “An Epic ‘Eureka!’ Moment,” p. 1.

Washington Post, March 13, 2017, Emily Langer, “Lloyd Conover, Chemist Who Revolutionized Antibiotics, Dies at 93.”

Online

National Inventors Hall of Fame, http://www.invent.org/honor/inductees/inductee-detail/?IID=32 (August 5, 2017), “Lloyd H. Conover.”□

(MLA 8th Edition)