The Man Who Screened 350 Molecules
If you have gout, there is a reasonable chance you have been handed a prescription for indomethacin. Your doctor called it a strong NSAID, told you to take it with food, warned you about your stomach. What they almost certainly did not tell you is who made it, or what that person’s life looked like. I am a pharmacist. I dispense it regularly. Until recently I had no idea who made it either.
Tsung-Ying Shen was born in China in 1924 to a family that understood what it meant to build things under difficult conditions. His father, Tsu Way Shen, had gone to the University of Michigan in 1910 on a government scholarship, one of the first waves of Chinese students sent abroad to learn western engineering and bring it home. He returned to China, built infrastructure across provinces, rose to vice president of the Conservancy Engineering College in Nanjing, and died in 1932 doing a bridge inspection in a rural area. Tsung-Ying was eight years old.
His mother, a widow at thirty-six with five children, raised the family through the Japanese invasion, through World War II, through the years that killed one of her sons, a military airman. The other four all earned doctoral degrees in the United States. That is the family Tsung-Ying came from.
In 1946 he graduated from National Central University, won a national scholarship, and left a country sliding toward civil war to study organic chemistry in England. PhD from Manchester in 1950, postdoctoral work at Ohio State and then MIT, where he met Amy Lin, a physical chemist whose own research data would contribute to the Scatchard Equation, a foundational tool in receptor pharmacology still used in drug development today. In 1956, they moved to Rahway, New Jersey. Shen joined Merck.
The pharmaceutical industry in the late 1950s was chasing a specific problem. Cortisone had arrived in 1949 as a miracle treatment for rheumatoid arthritis and spent the next decade revealing its costs: osteoporosis, adrenal suppression, psychiatric effects. By 1962 the Cortisone Era was declared over, and every major drug company was looking for something that fought inflammation without destroying the body. The term NSAID did not yet exist. They were looking for something they did not have a name for.
Shen screened approximately 350 indole derivatives for anti-inflammatory activity. Three hundred and forty-nine did nothing. One did. He called it indomethacin. FDA-approved in 1965, it was the first drug announced under the new term “non-steroidal anti-inflammatory agent.” It did not just fill the vacuum cortisone had left. It named the category.
For gout specifically, indomethacin was a significant development. Acute gout flares involve uric acid crystals triggering an immune response so aggressive that the joint becomes untouchable within hours. Indomethacin’s potency made it particularly suited to that kind of inflammatory cascade, working faster and harder than the alternatives. It remains a first-line option today. The warnings on your prescription bottle trace directly back to what clinicians learned in the years after 1965: take it short-term, protect your stomach, know your kidney function.
In 1976, something unexpected happened. Two independent research groups published back-to-back papers in the New England Journal of Medicine reporting that indomethacin could pharmacologically close patent ductus arteriosus, a heart defect in premature infants that had previously required surgery on babies sometimes weighing under a kilogram. Prostaglandins were keeping the vessel open. Indomethacin blocked prostaglandin synthesis. The vessel closed. Nobody at Merck in 1956 had designed a drug for premature infant hearts. It became standard neonatal care for nearly three decades anyway.
That same year Shen used a Merck research award to establish a visiting lectureship at MIT. The inaugural speaker was Bengt Samuelsson, who would later win the Nobel Prize for his work on prostaglandins, the exact mechanism explaining why Shen’s molecule was saving premature infants. Shen did not win the Nobel. Samuelsson did, for explaining what Shen’s molecule had been doing for twenty years.
Shen retired from Merck in 1986, became a professor at the University of Virginia, and continued research until 2001. In 2012 he established a fellowship at MIT in his wife’s name, supporting female graduate students in physical chemistry. He died September 1, 2024, in Greenbrae, California. He was ninety-nine.
If you have gout, the molecule he built from 350 failed attempts is probably in your medicine cabinet. It was prescribed over 500,000 times in the United States last year. Some molecules outlast the people who made them. This one already has.