Jacques Fresco, 'a major figure in the birth of modern molecular biology,' dies at 93

Jacques Robert Fresco, the Damon B. Pfeiffer Professor in the Life Sciences, Emeritus, died on Dec. 5 of complications from heart disease, surrounded by his family. He was 93.

Jacques Robert Fresco, professor of biology emeritus

Jacques Robert Fresco, Princeton's Damon B. Pfeiffer Professor in the Life Sciences, Emeritus

“Jacques was a pioneer in the biochemistry of nucleic acids,” said Lynn Enquist, the Henry L. Hillman Professor of Molecular Biology, Emeritus. “He has a remarkable history of training students and mentoring spectacular faculty.”

“He was a great mentor, a brilliant scientist and an amazing storyteller who has lived through and created so many of the important milestones of the scientific revolution in molecular biology,” said Oguzhan Atay, a 2011 graduate who wrote his thesis with Fresco. “Listening to him was listening to the history of science. He had so many amazing stories about Crick, Pauling, Oppenheimer, Delbruck and so on. If it were not for Jacques, we would not have had so many monumental contributions to science, either through his own work, such as the understanding of the mechanism of mutations and their connection to DNA structure, or through the students he mentored, a remarkable list that includes Nobel laureates and National Academy of Science members.”

Tomas Lindahl, winner of the 2015 Nobel Prize in Chemistry, was a postdoctoral researcher in Fresco’s lab from 1964-67. “He made impressive contributions to biology throughout his career,” said Lindahl, an emeritus scientist at the Francis Crick Institute. “Together with a brilliant student, Bruce Alberts, Fresco proposed the now generally accepted conformation of RNA.”

“He was a giant in the field of RNA structure — indeed he created the field,” said Edward Ziff, a 1969 Ph.D. graduate who is now a professor of biochemistry and molecular pharmacology at NYU Grossman School of Medicine. “He was forthright, knew his own mind and left a great legacy by fostering the growth of the original Program in Biochemical Sciences of the 1960’s into the rich and varied community of biologists that flourishes at Princeton today.”

Fresco joined Princeton in 1960 and retired in 2013 — a 53-year tenure that makes him one of the longest-serving members of the University’s storied faculty. "When I was chair of the department, Jacques was a regular visitor to my office," Enquist said. "What I liked most was his regular deliveries of reprints of his early papers and the discussion of the ‘good old days’ that followed."

He initially joined the Department of Chemistry, and he soon helped found the Program in Biochemical Sciences, which then grew into a department that he chaired from 1974 to 1980. The Department of Molecular Biology was created in 1984, and Fresco soon moved to that department. He continued to conduct full-time research long after his transfer to emeritus status, ultimately publishing more than 170 papers, abstracts and patents, many written with former students or fellows.

“A remarkable thing about Jacques was his drive to keep doing science well into his 90s,” said Stephen Buratowski, a professor of biological chemistry and molecular pharmacology at Harvard Medical School who did his undergraduate thesis with Fresco in 1984. “Every time I would speak or email with him, he absolutely had to tell me about some new idea or paper he was working on. He put off retirement for quite a long time, and even when he went emeritus, he just couldn’t stop being an active scientist. His love for science will always inspire me.”

Jacques Fresco constructing a model of DNA

Jacques Fresco, seen here with a 3-D model of the standard Watson-Crick DNA double helix, made seminal contributions to the understanding of RNA and DNA. He died surrounded by his family on Dec. 5, 2021, at the age of 93. Keenly aware of the importance of visualizing genetic structures as well as performing experiments, Fresco designated a room within his lab for physical models like this one. The plastic “atoms” snapped together to build molecules in which each element -- oxygen, carbon, nitrogen and others -- had its own color.

I coauthored papers with Jacques in 1961 and in 2002!” recalled Arthur Lesk, who followed Fresco from Harvard to Princeton. “I wonder whether that is some kind of record.”

Many of his students mentioned what an enormous role Fresco played in shaping their careers, in large and small ways. “Jacques treated everybody with the same respect, irreverence and love of life,” said Steven Broitman, a professor of biology at West Chester University in Pennsylvania who completed his Ph.D. with Fresco in 1988. “In addition to all he taught me about science, he also modeled the simple enjoyment in doing science that I have always tried to keep with me and pass on to my own students. He was larger than life, a major figure in the birth of modern molecular biology. He was deeply loved, and he will be missed.”

“Jacques Fresco was a great man,” said Juan Alvarez-Dominguez of the Class of 2009, one of Fresco’s last thesis students; he is now a professor at the University of Pennsylvania Perelman School of Medicine. “His contributions to science and mentoring ushered in an enlightened era of passionate endeavor. His infectious enthusiasm and unwavering support birthed a cadre of trainees that have gone on to win a Nobel Prize, preside over the National Academy of Sciences, and further his legacy among the world’s most prestigious academic institutions.”

The Guatamalan-born scientist added: “Jacques not only spoke my mother tongue, Spanish, he spoke a 15th-century Judeo-Spanish called Ladino. His ancestors fled Spain then, and their language remained frozen in time through the generations. I will never forget how Jacques explained, in elegant Ladino, how his grandmother passed it on to him.”

Ladino was Fresco’s first language. The son of Sephardic Jewish immigrants Robert Fresco of Istanbul and Lucie Asséo Fresco of Edirne, Turkey, Jacques was born in New York in 1928, the first of three children. After skipping three grades, he graduated from Bronx High School of Science at age 16 in June 1944, months before losing his father. He headed to New York University (living at home and attending classes on the Bronx campus) and completed his B.A. in biology and chemistry at age 18 in January 1947, followed by an M.S. in biology and then a Ph.D. in biochemistry in 1952, all from NYU. He did postdoctoral work at Sloan-Kettering Institute for Cancer Research, then worked as a research fellow at Harvard University. 

“Jacques spent his entire career working on the chemistry of nucleic acids (DNA and RNA), starting with his Ph.D. dissertation in 1952,” said Buratowski. “So when the famous Watson and Crick paper proposing a structure for DNA came out in 1953, he was perfectly positioned to ride the resulting wave of DNA mania. As a postdoc with Paul Doty in Watson’s new department at Harvard, and then as a faculty member at Princeton, he was a leader in showing that DNA and RNA conformations go well beyond the canonical ‘Watson-Crick’ base pairing of A-T and G-C within the double helix. Jacques’ studies of triple helices and alternative base-pairings were foundational for understanding how DNA mutations occur and how RNA-based enzymes (for example, ribosomes, RNAi, and CRISPR) can function.”

His work in Doty’s lab, performing the first experiments in thermal melting of DNA, RNA, and RNA:DNA hybrids using UV absorbance, would much later earn him a nomination (along with Julius Marmur and Paul Doty) for the Nobel Prize. 

While at Harvard, Jacques mentored then-undergraduate Bruce Alberts, who taught at Princeton from 1966 to 1976, served as president of the National Academy of Sciences and wrote the seminal textbook, “The Molecular Biology of the Cell.”

In addition to reassuring Alberts’ parents that they shouldn’t worry about their son’s choice to pursue science instead of medical school — a story Fresco enjoyed telling — he also played a key role in bringing the young scientist to Princeton. “Before I had even completed my Ph.D., he convinced Princeton to offer me an assistant professorship that I did not deserve,” Alberts recalled. “And at Princeton for 10 years, we of course spent an enormous amount of time together. So Jacques was very central to my life as a scientist and a close friend.”

From Harvard, Fresco was invited by Francis Crick to Cambridge to tackle a problem that he solved in weeks instead of months, so he went on to Paris to research with Marianne Grunberg-Manago at the Institut de Biologie Physico-Chimique. 

While walking the streets of Paris to cool down after an experiment got knocked over, he met his future wife Rosalie Burns, lost on the Place Saint-Michel with her parents. His offer to guide them through the streets of Paris led to a loving marriage of nearly 64 years that gave them three daughters and much happiness. 

Fresco’s research included many fields within molecular biology and biochemistry, including gene repair for sickle cell anemia, fluorescent cytogenetic probes for genes that are amplified in cancers, and the evolution of the genetic code. He was one of the early leaders in the field of triple-stranded nucleic acid helices — DNA oddities that can form under special conditions.

“Shapeshifting polynucleotides were unraveled as much by his scientific rigor as by the sheer force of his creativity,” Alvarez-Domingo said. “Paving the way for fleshing out transfer RNA helped unlock how the code of life itself is translated. Widening DNA base pairing possibilities provided a chemical basis for the origin of substitution mutations. And discovering that DNA can self-mutate offered a mechanism for the evolution and potentiation of genetic diversity.”

Fresco received the American Scientist Writing award in 1962; a Guggenheim fellowship to the Medical Research Council Laboratory of Molecular Biology in Cambridge, England, in 1969-70; a visiting professorship at the Hebrew University of Jerusalem in 1973; an endowed chair from Princeton, the Damon B. Pfeiffer Professor in the Life Sciences, in 1977; an honorary doctorate (M.D. honoris causa) from University of Gothenburg, Sweden, in 1979; and many other awards. 

When he transferred to emeritus status in 2013, a colleague noted, “One cannot pass by Jacques in the hall without him catching your eye, smiling and remarking with excitement about the new ideas that are coming from his laboratory.”

His family describes him as a liberal thinker with a creative mind and a strong sense of tradition and obligation, outspoken and detail-oriented; a devoted family man and friend who promoted the careers of mentees in his lab and courses and maintained life-long close contacts with extended family, in-laws and friends; and a nurturing and dedicated tutor who strove to inspire his children and grandchildren. He was a humanitarian who spoke out against antisemitism and other forms of prejudice, a staunch defender of teaching evolution, a champion for animals and the less fortunate — and joined in all of these by his beloved wife. 

He is survived by his wife Rosalie Fresco, his daughter Lucille (Lulu) Fresco-Cohen and her husband Moshe Cohen, his daughter Suzette (Suzi) Fresco Johnson and her husband David Johnson, his daughter Linda Fresco and her husband Craig Comiter, as well as eight grandchildren — Erik Johnson (and his wife Jaclyn), Nicole Johnson of Princeton’s Class of 2012, Mikaela Johnson, Jacqueline Comiter, Golan Cohen, Galil Cohen, Laurel Comiter and Hayley Cohen — and two great-grandchildren, Ben Johnson and Tommy Johnson, as well as cousins, nieces, and a nephew. Funeral services and burial were private at the Sephardic Jewish Brotherhood section of Cedar Park Cemetery.

You are invited to view and contribute comments on a memorial blog honoring Fresco’s life and legacy. In lieu of flowers, contributions in his memory may be made to the Southern Poverty Law Center, the World Jewish Congress, or Disabled American Veterans.