Chemist James Trudell, whose research led to greater understanding of anesthetics, dies

For five decades, James Trudell studied how anesthetics work on the human body to cause unconsciousness.

James Trudell

James Trudell, PhD, a Stanford Medicine chemist who spent 50 years hunting down molecular clues to help make anesthetic drugs safer for patients, died July 29 at his home in Woodside, California, with his wife by his side. He was 77.

The cause was complications from acute myeloid leukemia.

Trudell was a professor of anesthesiology, perioperative and pain medicine at the School of Medicine, where he could be seen for most of his career bicycling to his lab in the Grant Building. His many decades of research advanced the understanding of how anesthetics work to limit pain and contributed to the ongoing pursuit to make newer, better anesthetics with fewer dangerous side effects.

“He was very obviously fascinated with understanding, as a chemist, how molecules work,” said Ron Pearl, MD, professor and chair of anesthesiology, perioperative and pain medicine and the Dr. Richard K. and Erika N. Richards Professor,who worked with Trudell since 1985. “How exactly do they interact? How can we make them do things we want them to do and not do things we don’t want them to? It was important to him that his basic research would make people’s lives better.”

Trudell’s fascination with chemistry began early in life when his parents gave him a chemistry kit at the age of 9. His passion for the work never waned, continuing until the day he died, with a laptop computer and molecular modeling research papers still open on his desk, said his wife, WeiQi Lin, MD, PhD.

“For 50 years, Dr. Trudell’s innovative research played a major role in advancing the field of anesthetics and improving patient safety,” said Lloyd Minor, MD, dean of the School of Medicine. “More than just an exceptional scientist, he also strengthened the Stanford Medicine community by serving as a caring mentor and thoughtful collaborator to so many.”

Native of Michigan

Trudell was born in Iron Mountain, Michigan, in 1941. He graduated magna cum laude from the University of Michigan before going on to earn a PhD in organic chemistry at Stanford in 1969. While a student at Stanford, he studied under Carl Djerassi, PhD, a chemistry professor at the time, who later became known as the father of the birth control pill. They remained lifelong friends. Before starting graduate school, Trudell served two years on the aircraft carrier USS Randolph as a photo and electronics officer during the Vietnam War.

He joined the Anesthesiology Department at Stanford in 1969, just four years after it was created. He initially studied the molecular mechanisms that made halothane, one of the first modern-day general anesthetics, toxic to the liver. At the time, there were only 12 faculty members in the department; today there are 200, Pearl said. Trudell met Lin, his future wife, when she came to work as a postdoctoral scholar in in his lab.

Lin describes her husband as the consummate scientist, for whom chemistry was more than just a job. 

“He was a true scientist at heart,” Lin said. “He followed his research wherever it took him. He was never discouraged by any failure. He would just take a break and go to one of his many hobbies, and come right back to his work. “

Trudell was also an accomplished athlete who enjoyed a variety of activities, from rock climbing, paragliding and running marathons in his earlier years to bicycling and sailing throughout his life. 

“We expected him to live to 100,” said longtime friend and Stanford colleague Edward Bertaccini, MD, professor of anesthesiology, perioperative and pain medicine. “This guy was in the best shape all of his life. He was windsurfing up until 15 years ago and always riding his bike.”   

Study of drug metabolism

Trudell’s early work involved studying how drugs metabolize within the human body. After figuring out how the drug halothane causes liver failure, he examined the same problem in other anesthetics. Along the way, he discovered that anesthetics work through specific protein interactions rather than interactions with lipids, the fatty molecules in tissues, as was believed at the time.

His early work eventually led him to what was a new approach 30 years ago: the use of molecular modeling to study receptor sites, the binding structures on the surface of cells involved in how drugs cause unconsciousness. He began collaborating with Bertaccini in the early 1990s, using this research to help create new anesthetics with fewer side effects, including liver toxicity and lowering blood pressure.

“Our research, the molecular mechanism of how anesthesia works, is a small niche in the world, but he played a key role,” Bertaccini said.

At times, during their long collaboration, the two scientists would delve into the metaphysical questions surrounding their search to understand how people become unconscious to begin with — what scientists refer to as “the human off switch,” Bertaccini said. “It’s a metaphysical question, this idea that all human beings have the same ‘off switch.’ What happens to the human soul when you are anesthetized? These drugs are used thousands of times a day throughout the world. People wake up and they are still there. We know it works; we just don’t know how it works.”

He continued: “Jim probably knows the answer now and is laughing at us.”

Trudell’s dogged pursuit toward solving these mysteries continued throughout his illness. He worked from his laptop while at the hospital undergoing chemotherapy and a bone marrow transplant, Bertaccini said.

“His contributions continued to flow as we just had spoken and set up calculations during the week before he died,” Bertaccini said. 

Trudell co-authored more than 170 papers. He was a member of Stanford Bio-X and the Wu Tsai Neurosciences Institute at Stanford. 

In addition to Lin, Trudell is survived by his brother Ronald Trudell and his sister Cher Trudell, both of Michigan.

Per his wishes, Trudell’s ashes were scattered outside of the Golden Gate Bridge, on the San Francisco Bay, on an outgoing tide. Donations in his memory may be made to the Department of Anesthesiology, Perioperative and Pain Medicine at Stanford.



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