The Man Who Screened 350 Molecules
He screened 350 molecules in a New Jersey lab and found one worth keeping. Indomethacin didn't just treat gout — it named a category, saved premature infants, and became a neurological diagnostic instrument. The story of Tsung-Ying Shen.
Written by Seth Collins, Pharm.D.
Updated on May 22, 2026
Drug History
0 viewsIf you have gout, there is a reasonable chance you have been handed a prescription for indomethacin. Your doctor may have 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, or what the drug went on to do that nobody planned for. I am a pharmacist. I dispense indomethacin regularly. Until recently, I had no idea who made it either.
To understand Tsung-Ying Shen, you have to start with his father.
In 1910, Tsu Way Shen arrived at the University of Michigan on a government scholarship, one of the first waves of Chinese students sent abroad to learn what the west had built and bring it home. He graduated in civil engineering in 1914, returned to China, and spent the next two decades building things: roads, bridges, surveying lines across provinces that had never been mapped properly. He rose to vice president of the Conservancy Engineering College in Nanjing. In 1932, he died in a rural area after an exhausting inspection trip, checking bridges, doing the work himself, the way engineers of that generation did. Tsung-Ying was eight years old.
His mother, Sienhua New, was the daughter of a prominent associate of Sun Yat-Sen, the founder of the Republic of China. She was thirty-six when her husband died, with five children and a country already beginning to fracture. The Japanese invasion came in 1937. The war lasted eight years. One of her sons, a military airman, did not survive it. She raised the other four through all of it. All four eventually earned doctoral degrees in the United States.
That is the family Tsung-Ying Shen came from. His daughter's obituary description, "incredibly determined, hardworking, and devoted to his family," reads differently once you know where he came from.
In 1946, Shen graduated from National Central University in Chongqing, the same institution his father had helped build. China in 1946 was barely holding together. The Japanese occupation had just ended and civil war was coming. Shen was twenty-two, took a national exam, and won a scholarship to study organic chemistry in England. He went to Imperial College London, then the University of Manchester, earned his PhD in 1950. He came to the United States for postdoctoral work, first Ohio State, then MIT. At MIT he met Amy Lin.
Amy Lin was a physical chemist doing her own serious research, measuring the binding characteristics of anions to serum albumin. Her data contributed to the theoretical derivation of the Scatchard Equation, which became a fundamental tool in biomedical research, the standard method for analyzing how drugs bind to receptors and enzymes, used in pharmacology laboratories worldwide for decades. She was later named ACS High School Chemistry Teacher of the Year. Two chemists, one household, both doing work that mattered. In 1956, they moved to Rahway, New Jersey, where Shen joined Merck Research Laboratories.
American pharmaceutical research in the late 1950s occupied a space that no longer exists. These were not the sprawling compliance-driven enterprises of later decades. They were closer to universities with money, postwar money, a federal government that had just watched penicillin win a world war and was backing whatever came next. Chemists synthesized compounds and handed them to pharmacologists down the hall. Nobody filled out thirty forms first. The ambition was open.
The specific problem consuming everyone in 1956 was cortisone.
Cortisone had arrived in 1949 like a miracle and left like a cautionary tale. Philip Hench at the Mayo Clinic injected a woman crippled by rheumatoid arthritis with compound E and she got up and walked. The New York Times called it a modern miracle. Physicians began prescribing it confidently. Then the long-term data arrived: osteoporosis, adrenal suppression, weight gain, psychiatric effects. By 1962, one medical editor wrote publicly that the Cortisone Era was over.
That collapse created a vacuum. Every major pharmaceutical company received essentially the same directive: find something that fights inflammation without destroying the body. Find a non-steroidal anti-inflammatory drug. Nobody called them NSAIDs yet. That word did not exist. They were looking for something they did not have a name for.
Shen synthesized indole derivatives and screened them for anti-inflammatory activity. He screened approximately 350 of them. Three hundred and forty-nine did nothing. One did. He called it indomethacin. It was patented in 1961, announced in 1963, FDA-approved in 1965. The announcement introduced a new term to medicine: non-steroidal anti-inflammatory agent. Indomethacin did not just fill the post-cortisone vacuum. It named the category.
Gout patients were among the first to benefit. Indomethacin's potency made it particularly suited to acute inflammatory flares, the kind where uric acid crystals trigger an immune response so aggressive that the joint becomes untouchable. It worked faster and harder than anything available. It still does. When physicians today reach for an NSAID to abort a gout flare, they are reaching for the category Shen built, and often for the original molecule itself.
It had a temper. The same aggressive COX inhibition that made it effective made it brutal on the GI tract, the kidneys, the cardiovascular system. Physicians learned quickly this was not a drug for the careless. Take it with food. Use it short-term. Know your kidney function. The warnings on your prescription bottle trace directly back to what clinicians learned in the late 1960s.
1976
The 1970s arrived with a different energy. The space race was winding down. Vietnam was ending badly. American institutions were being examined with new suspicion. Inside hospital neonatology units, however, something quietly extraordinary was happening.
Neonatology itself was new. The specialized care of premature infants as a distinct discipline had only emerged in the 1960s. One of the most common and lethal complications was patent ductus arteriosus, a fetal blood vessel that normally closes within days of birth but in premature infants often stayed open, flooding immature lungs with blood and causing heart failure and respiratory collapse. Before the mid-1970s, the only solution was surgery on a baby that might weigh under a kilogram.
In 1976, two independent research groups published back-to-back papers in the same issue of the New England Journal of Medicine. Friedman at UC San Diego and Heymann at UC San Francisco had each arrived at the same finding: indomethacin could close a patent ductus arteriosus without surgery. Prostaglandins were keeping the vessel dilated. Indomethacin blocked prostaglandin synthesis. The vessel closed. It was elegant, and completely accidental from the perspective of anyone who had been in that Merck lab in the late 1950s designing a drug for arthritic joints.
It became standard neonatal care almost immediately and stayed there for nearly three decades.
That same year, Merck gave Shen a Director's Scientific Award. He used the money to establish a visiting lectureship at MIT, in the department where he had met Amy, where her data had fed the Scatchard Equation. The inaugural speaker was Bengt Samuelsson, a Swedish biochemist who would go on to win the Nobel Prize in 1982 partly for his foundational work on prostaglandins, the very mechanism that explained why Shen's molecule was saving premature infants across the country.
Shen did not win the Nobel. Samuelsson did, for explaining the thing Shen's molecule had been doing for twenty years.
The Headache Nobody Could Explain
Neurologists found it gradually, through accumulated case reports, through the slow recognition that something did not fit existing frameworks.
There was a class of headache disorders, rare and poorly understood, that responded to indomethacin. Not to ibuprofen. Not to naproxen. Not to aspirin or any of the dozens of anti-inflammatory compounds that had proliferated since 1965. Specifically and exclusively to this one molecule. The conditions, paroxysmal hemicrania and hemicrania continua, were one-sided, relentless, and completely disabling. They were also catastrophically misdiagnosed for years, treated as migraines or cluster headaches that were not responding to treatment.
The indomethacin response changed that. It was so absolute and so consistent that it was eventually written into the formal diagnostic criteria of the International Headache Society. You could not confirm the diagnosis without demonstrating that indomethacin, and nothing else, abolished the pain. A drug designed for inflamed joints had become a neurological diagnostic instrument.
Why this molecule, of all the NSAIDs, produces this specific effect has never been fully explained. There are theories involving cerebral blood flow, blood-brain barrier penetration, intracranial pressure. None are definitive. It just works, exclusively, in a way nobody completely understands.
Rahway to Greenbrae
Shen retired from Merck in 1986 as vice president of research, thirty years after arriving in New Jersey. He became the Alfred Burger Professor of Medicinal Chemistry at the University of Virginia, a chair jointly endowed by the Merck Foundation and the State of Virginia. He continued his research until 2001.
In 2012, he established the Amy Lin Shen Summer Fellowship at MIT, graduate financial assistance for female students in physical chemistry, in the department where Amy's experimental work had contributed to a foundational equation in receptor pharmacology. The kind of thing you do when you have spent sixty years watching what gets credited and what does not.
He died on September 1, 2024, in Greenbrae, California. He was ninety-nine.
His father had gone to Michigan in 1910 to learn how to build things China needed, and died inspecting the results. His mother kept four children alive through invasion and loss. His wife's data became a cornerstone of the field her husband was reshaping from the other direction. He left Chongqing in 1947 with a scholarship and a country collapsing behind him, screened 350 molecules in a New Jersey lab, and found one worth keeping.
If you have gout, that molecule is probably in your medicine cabinet right now. It was prescribed over 500,000 times in the United States last year alone. Some molecules outlast the people who made them. This one already has.
Sources
Sienhua New and Tsu Way Shen Memorial Award Fund. University of Michigan Scholarships and Fellowships. https://scholarships.engin.umich.edu/featured/sienhua-new-and-tsu-way-shen-memorial-award-fund/
Evelyn Shen. Obituary: Tsung-Ying Shen. Chemical and Engineering News. January 28, 2025. https://cen.acs.org/people/obituaries/Obituary-Tsung-Ying-Shen/103/web/2025/01
Postdoc T.Y. Shen Honors his Wife. MIT Department of Chemistry. https://chemistry.mit.edu/support-chemistry/meet-our-major-supporters/postdoc-t-y-shen-honors-his-wife/
Shen TY, Windholz TB, Rosegay A, et al. Non-Steroidal Anti-Inflammatory Agents. Journal of the American Chemical Society. 1963;85(4):488-489.
Friedman WF, Hirschklau MJ, Printz MP, Pitlick PT, Kirkpatrick SE. Pharmacologic Closure of Patent Ductus Arteriosus in the Premature Infant. New England Journal of Medicine. 1976;295(10):526-529.
The Pillars is a series on the foundational molecules of modern medicine. Written by Seth Collins, Pharm.D.
To understand Tsung-Ying Shen, you have to start with his father.
In 1910, Tsu Way Shen arrived at the University of Michigan on a government scholarship, one of the first waves of Chinese students sent abroad to learn what the west had built and bring it home. He graduated in civil engineering in 1914, returned to China, and spent the next two decades building things: roads, bridges, surveying lines across provinces that had never been mapped properly. He rose to vice president of the Conservancy Engineering College in Nanjing. In 1932, he died in a rural area after an exhausting inspection trip, checking bridges, doing the work himself, the way engineers of that generation did. Tsung-Ying was eight years old.
His mother, Sienhua New, was the daughter of a prominent associate of Sun Yat-Sen, the founder of the Republic of China. She was thirty-six when her husband died, with five children and a country already beginning to fracture. The Japanese invasion came in 1937. The war lasted eight years. One of her sons, a military airman, did not survive it. She raised the other four through all of it. All four eventually earned doctoral degrees in the United States.
That is the family Tsung-Ying Shen came from. His daughter's obituary description, "incredibly determined, hardworking, and devoted to his family," reads differently once you know where he came from.
In 1946, Shen graduated from National Central University in Chongqing, the same institution his father had helped build. China in 1946 was barely holding together. The Japanese occupation had just ended and civil war was coming. Shen was twenty-two, took a national exam, and won a scholarship to study organic chemistry in England. He went to Imperial College London, then the University of Manchester, earned his PhD in 1950. He came to the United States for postdoctoral work, first Ohio State, then MIT. At MIT he met Amy Lin.
Amy Lin was a physical chemist doing her own serious research, measuring the binding characteristics of anions to serum albumin. Her data contributed to the theoretical derivation of the Scatchard Equation, which became a fundamental tool in biomedical research, the standard method for analyzing how drugs bind to receptors and enzymes, used in pharmacology laboratories worldwide for decades. She was later named ACS High School Chemistry Teacher of the Year. Two chemists, one household, both doing work that mattered. In 1956, they moved to Rahway, New Jersey, where Shen joined Merck Research Laboratories.
American pharmaceutical research in the late 1950s occupied a space that no longer exists. These were not the sprawling compliance-driven enterprises of later decades. They were closer to universities with money, postwar money, a federal government that had just watched penicillin win a world war and was backing whatever came next. Chemists synthesized compounds and handed them to pharmacologists down the hall. Nobody filled out thirty forms first. The ambition was open.
The specific problem consuming everyone in 1956 was cortisone.
Cortisone had arrived in 1949 like a miracle and left like a cautionary tale. Philip Hench at the Mayo Clinic injected a woman crippled by rheumatoid arthritis with compound E and she got up and walked. The New York Times called it a modern miracle. Physicians began prescribing it confidently. Then the long-term data arrived: osteoporosis, adrenal suppression, weight gain, psychiatric effects. By 1962, one medical editor wrote publicly that the Cortisone Era was over.
That collapse created a vacuum. Every major pharmaceutical company received essentially the same directive: find something that fights inflammation without destroying the body. Find a non-steroidal anti-inflammatory drug. Nobody called them NSAIDs yet. That word did not exist. They were looking for something they did not have a name for.
Shen synthesized indole derivatives and screened them for anti-inflammatory activity. He screened approximately 350 of them. Three hundred and forty-nine did nothing. One did. He called it indomethacin. It was patented in 1961, announced in 1963, FDA-approved in 1965. The announcement introduced a new term to medicine: non-steroidal anti-inflammatory agent. Indomethacin did not just fill the post-cortisone vacuum. It named the category.
Gout patients were among the first to benefit. Indomethacin's potency made it particularly suited to acute inflammatory flares, the kind where uric acid crystals trigger an immune response so aggressive that the joint becomes untouchable. It worked faster and harder than anything available. It still does. When physicians today reach for an NSAID to abort a gout flare, they are reaching for the category Shen built, and often for the original molecule itself.
It had a temper. The same aggressive COX inhibition that made it effective made it brutal on the GI tract, the kidneys, the cardiovascular system. Physicians learned quickly this was not a drug for the careless. Take it with food. Use it short-term. Know your kidney function. The warnings on your prescription bottle trace directly back to what clinicians learned in the late 1960s.
1976
The 1970s arrived with a different energy. The space race was winding down. Vietnam was ending badly. American institutions were being examined with new suspicion. Inside hospital neonatology units, however, something quietly extraordinary was happening.
Neonatology itself was new. The specialized care of premature infants as a distinct discipline had only emerged in the 1960s. One of the most common and lethal complications was patent ductus arteriosus, a fetal blood vessel that normally closes within days of birth but in premature infants often stayed open, flooding immature lungs with blood and causing heart failure and respiratory collapse. Before the mid-1970s, the only solution was surgery on a baby that might weigh under a kilogram.
In 1976, two independent research groups published back-to-back papers in the same issue of the New England Journal of Medicine. Friedman at UC San Diego and Heymann at UC San Francisco had each arrived at the same finding: indomethacin could close a patent ductus arteriosus without surgery. Prostaglandins were keeping the vessel dilated. Indomethacin blocked prostaglandin synthesis. The vessel closed. It was elegant, and completely accidental from the perspective of anyone who had been in that Merck lab in the late 1950s designing a drug for arthritic joints.
It became standard neonatal care almost immediately and stayed there for nearly three decades.
That same year, Merck gave Shen a Director's Scientific Award. He used the money to establish a visiting lectureship at MIT, in the department where he had met Amy, where her data had fed the Scatchard Equation. The inaugural speaker was Bengt Samuelsson, a Swedish biochemist who would go on to win the Nobel Prize in 1982 partly for his foundational work on prostaglandins, the very mechanism that explained why Shen's molecule was saving premature infants across the country.
Shen did not win the Nobel. Samuelsson did, for explaining the thing Shen's molecule had been doing for twenty years.
The Headache Nobody Could Explain
Neurologists found it gradually, through accumulated case reports, through the slow recognition that something did not fit existing frameworks.
There was a class of headache disorders, rare and poorly understood, that responded to indomethacin. Not to ibuprofen. Not to naproxen. Not to aspirin or any of the dozens of anti-inflammatory compounds that had proliferated since 1965. Specifically and exclusively to this one molecule. The conditions, paroxysmal hemicrania and hemicrania continua, were one-sided, relentless, and completely disabling. They were also catastrophically misdiagnosed for years, treated as migraines or cluster headaches that were not responding to treatment.
The indomethacin response changed that. It was so absolute and so consistent that it was eventually written into the formal diagnostic criteria of the International Headache Society. You could not confirm the diagnosis without demonstrating that indomethacin, and nothing else, abolished the pain. A drug designed for inflamed joints had become a neurological diagnostic instrument.
Why this molecule, of all the NSAIDs, produces this specific effect has never been fully explained. There are theories involving cerebral blood flow, blood-brain barrier penetration, intracranial pressure. None are definitive. It just works, exclusively, in a way nobody completely understands.
Rahway to Greenbrae
Shen retired from Merck in 1986 as vice president of research, thirty years after arriving in New Jersey. He became the Alfred Burger Professor of Medicinal Chemistry at the University of Virginia, a chair jointly endowed by the Merck Foundation and the State of Virginia. He continued his research until 2001.
In 2012, he established the Amy Lin Shen Summer Fellowship at MIT, graduate financial assistance for female students in physical chemistry, in the department where Amy's experimental work had contributed to a foundational equation in receptor pharmacology. The kind of thing you do when you have spent sixty years watching what gets credited and what does not.
He died on September 1, 2024, in Greenbrae, California. He was ninety-nine.
His father had gone to Michigan in 1910 to learn how to build things China needed, and died inspecting the results. His mother kept four children alive through invasion and loss. His wife's data became a cornerstone of the field her husband was reshaping from the other direction. He left Chongqing in 1947 with a scholarship and a country collapsing behind him, screened 350 molecules in a New Jersey lab, and found one worth keeping.
If you have gout, that molecule is probably in your medicine cabinet right now. It was prescribed over 500,000 times in the United States last year alone. Some molecules outlast the people who made them. This one already has.
Sources
Sienhua New and Tsu Way Shen Memorial Award Fund. University of Michigan Scholarships and Fellowships. https://scholarships.engin.umich.edu/featured/sienhua-new-and-tsu-way-shen-memorial-award-fund/
Evelyn Shen. Obituary: Tsung-Ying Shen. Chemical and Engineering News. January 28, 2025. https://cen.acs.org/people/obituaries/Obituary-Tsung-Ying-Shen/103/web/2025/01
Postdoc T.Y. Shen Honors his Wife. MIT Department of Chemistry. https://chemistry.mit.edu/support-chemistry/meet-our-major-supporters/postdoc-t-y-shen-honors-his-wife/
Shen TY, Windholz TB, Rosegay A, et al. Non-Steroidal Anti-Inflammatory Agents. Journal of the American Chemical Society. 1963;85(4):488-489.
Friedman WF, Hirschklau MJ, Printz MP, Pitlick PT, Kirkpatrick SE. Pharmacologic Closure of Patent Ductus Arteriosus in the Premature Infant. New England Journal of Medicine. 1976;295(10):526-529.
The Pillars is a series on the foundational molecules of modern medicine. Written by Seth Collins, Pharm.D.
Tags
Issue 004
Drug History
Indomethacin
NSAIDs
Pharmacology