William Tilley (Class of 1967, PhD, 1971), professor of biological engineering at MIT, died on December 24 at his home in Winchester, Massachusetts. He was 79 years old.
A pioneer in the study of human gene mutations, Dr. Tilly has been on the MIT faculty since 1972. Throughout his career, Dr. Tilly has developed new methods to measure the effects of environmental mutagens on human cells, creating analytical methods now widely used in toxicology and drug development.
He also served as director of MIT’s Center for Environmental Health Sciences and founded MIT’s first Superfund research program in the 1980s, an example of his dedication to making sure MIT research had a real impact on the world, colleagues said.
“He was really a giant in the field,” said Bevin Engelward, a professor of biological engineering at MIT. “He took his scientific understanding and said, ‘Let’s use this as a tool to solve real-world problems.'” One of the things Bill urges people to do is ask themselves, ‘Does this research matter? Does this make a difference in the real world?'”
In a letter to the MIT community today, MIT President Sally Kornbluth noted that Tilley’s students and postdoctoral researchers had called him a “wise but tough leader.”
“Many of the students and postdocs mentored by Bill have become industry leaders in the fields of drug evaluation and toxicology, and he has changed the lives of even more MIT students through his generous support of scholarships for undergraduates from a wide range of educational backgrounds,” Kornbluth wrote.
Solving real problems
Tilley was born in Staten Island, New York, before his family moved to a farm in Rush Township in central Pennsylvania. He received his Bachelor of Science in Biology from MIT in 1967 and his Doctor of Science in Nutritional Biochemistry in 1971. In 1972, he joined the MIT faculty as an assistant professor of genetic toxicology.
His research group began work with the goal of discovering the origins of mutations that cause human disease. In the 1970s, his lab developed an assay that could quantitatively measure mutations in human cells. The test, called the TK6 assay, allowed researchers to identify compounds that could cause mutations and is now used by pharmaceutical companies to test whether new drug compounds are safe for use in humans.
Unlike many previous tests that could only identify one mutation at a time, Thilly’s TK6 test can detect any mutation that could disrupt the function of a gene.
Tilley served as director of the MIT Center for Environmental Health Sciences from 1980 to 2001. During that time, he assembled interdisciplinary teams, including experts from several MIT departments, to study the health effects of burning fossil fuels.
“Working collaboratively, our teams were able to establish more efficient ways to burn fuel and, more importantly, evaluate which combustion methods have the fewest impacts on human health and the environment,” said John Essigman, the William R. and Betsy P. Leach Professor of Chemistry, Toxicology and Bioengineering at MIT.
Tilley also played a key role in developing MIT’s first Superfund program: In the 1980s, he mobilized a team of MIT researchers from various disciplines to study the effects of toxic waste at the Superfund site in Woburn, Massachusetts, and help develop a remediation plan.
Tilly’s colleagues say bringing together scientists and engineers from different disciplines that were then very separate in their departments was a feat of creativity and leadership, and an example of his dedication to solving practical problems.
Tilly then used a protocol called denaturing gel electrophoresis to visualize environmentally induced mutations through its ability to alter the melting temperature of double-stranded DNA. Using this tool, he studied human tissue from people exposed to substances such as cigarette smoke, and was able to create a rough sketch of the range of mutations that those substances induce in human cells. This work led to the theory that mutations in many cancers are likely due to inaccurate DNA replication by specialized polymerases called non-replicating polymerases.
One of Tilly’s most important discoveries was the fact that cells lacking a DNA repair process called mismatch repair are resistant to certain DNA-damaging agents. Subsequent work by Nobel laureate Paul Modrich (1968) showed how cells lacking mismatch repair become resistant to anti-cancer drugs.
In 2001, Tilly joined MIT’s newly formed Department of Biological Engineering. In the 2000s, Tilly’s wife, MIT research scientist Elena Gostcheva, discovered unusual bell-shaped structures called “supernuclei” in plant cell nuclei. Tilly and Gostcheva then discovered these nuclei in mammalian stem cells. In recent years, researchers have investigated the ability of these cells to form tumors and have studied compounds that could be used to prevent the development of such tumors.
Wrestling Spirit
Tilley was a dedicated teacher and in 1974 received the Everett Moore Baker Award for excellence in undergraduate teaching. In 1991, a course series he helped establish called “Chemistry in the Environment” won the Irwin Sizer Award for most significant improvement in MIT education. Many of the students and postdocs he mentored have become industry leaders in the fields of drug evaluation and toxicology. Last semester, Tilley and Gostcheva co-taught two undergraduate courses on the biology of metacalorimetric stem cells.
Tilley was a champion wrestler in his youth and told a colleague that he had considered teaching “martial arts.” “He has a wrestling spirit. He wants a challenge,” Engelward said. “He was willing to go all out on whatever scientific problem he felt needed solving.”
In addition to wrestling, Tilley was captain of the MIT Rugby Club in the 1970s and was one of the founders of New England Rugby League.
Tilly loved to talk about science, and would often give talks in the hallway outside her office on the seventh floor of Building 16, to colleagues and students who passed by.
“Bill was the type of guy who would pull you aside and start talking to you about some aspect of his work and why it was so important, and he was very passionate about it,” Essigman recalled. “He was a great scholar of not only genetic toxicology but also the early literature in molecular biology. His education was excellent, and if you had any questions, he was the person to go to.”
Tilley also sees it as her job to question students about their research and see if they’ve thought about whether their work has real-world applications.
“He was a really tough guy, but I think he really took it as his responsibility. I think he felt that in the real world, you always have to inspire people to be better,” Engelward said. “That’s a great legacy. He gave lots of seminars for graduate students, he was always asking questions, he was always inspiring people, so he probably influenced hundreds of students.”
Tilley has been a vocal advocate for recruiting more underprivileged students to MIT, making multiple visits to historically black colleges to recruit candidates, and has donated more than $1 million to a scholarship fund for underprivileged students, according to colleagues.
During his time as an undergrad at MIT, Tilley also made his mark on the world of breakfast cereal. According to breakfast blog Extra Crispy, in the summer of 1965, he worked as an intern at Kellogg’s, where he got the opportunity to develop his own cereal. His experiments with dried apples and leftover O’s led to the invention of the cereal that would become Applejack.
Besides his wife, Mr. Tilley is survived by five children, William, Grete, Walter, Audrey Tilley and Fyodor Gostcheva, a brother, Walter’s sister, Joan Harmon and two grandchildren.
