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ACS News

December 18, 2006
Volume 84, Number 51
pp. 61-62

Paying Tribute To Bruce Merrifield

'Gentle giant' is remembered as an outstanding scientist and an exceptional human being

Linda Wang

More than 200 family members, friends, and former students and colleagues gathered at Rockefeller University on Nov. 13 to celebrate the scientific life and achievements of Nobel Laureate Robert Bruce Merrifield, who died in May at age 84 after a long illness (C&EN, May 29, page 8).

During a symposium that was held as part of the event, Paul Nurse, president of Rockefeller University, and David Rockefeller, honorary chairman and life trustee of Rockefeller University, accepted an award, sponsored by the ACS Division of the History of Chemistry (HIST), for Merrifield's classic 1963 paper, titled "Solid Phase Peptide Synthesis. I. The Synthesis of a Tetrapeptide" (J. Am. Chem. Soc. 1963, 85, 2149).

Rockefeller University
A Good Life Merrifield in his Rockefeller lab in 1984.

Merrifield is best known for the invention and development of solid-phase peptide synthesis, which revolutionized synthetic organic chemistry. His "simple and ingenious" idea reduced the time required for peptide synthesis from years to days and made many once-unthinkable syntheses possible.

"This research, done essentially with his own hands, singularly led to the Nobel Prize in Chemistry," said Jeffrey I. Seeman, chair of HIST and founder of the new Citation for Chemical Breakthroughs award program (C&EN, July 3, page 49). "This work advanced organic synthesis in a unique way and led to hundreds of applications and publications of importance in research and drug development." He added that he only wished Merrifield had been alive to accept the award himself.

Seeman noted that the award, one of 10 given this year, is intended to recognize not only individuals but also departments and institutions where seminal breakthroughs in science occurred. Merrifield spent virtually his entire career, which spanned six decades, at Rockefeller University, and the plaque will be hung near his laboratory on the fourth floor of Flexner Hall.

Betsy Grindstaff, one of Merrifield's six children, said her father would have been pleased to know that the award is recognizing the university he loved so much. She pointed out that in 2000, when the American Chemical Society designated research in nucleic acids and proteins at Rockefeller University as a National Historic Chemical Landmark (C&EN, Dec. 11, 2000, page 56), Merrifield asked for the entire building of Flexner Hall to be designated.

Linda Wang
Recognition Rockefeller (from left), Libby Merrifield, Nurse, and Seeman hold the ACS plaque.

"His greatest love of all was probably Rockefeller [University], in terms of science," said Maurice Manning, who worked with Merrifield from 1964 to 1965 and is now a professor of biochemistry and cancer biology at the University of Toledo College of Medicine. "It was really Rockefeller that allowed him to do what he did."

Following the presentation of the ACS award, Jane V. Aldrich, president of the American Peptide Society, presented a separate award in honor of Merrifield to Rockefeller University and gave a copy of the plaque to Merrifield's wife, Libby.

Born on July 15, 1921, in Fort Worth, Texas, Merrifield grew up in California. He graduated in 1943 from the University of California, Los Angeles, with a B.A. in chemistry, worked for a year as a technician for the Philip R. Park Research Foundation, and went on to receive a Ph.D. in biochemistry from UCLA in 1949.

He married a "red-headed girl" named Elizabeth (Libby) Furlong the day after graduation. They drove across the country together, camping the entire way, to New York City, where Merrifield had a position as a research assistant waiting for him at what was then Rockefeller Institute for Medical Research.

Under the guidance of D. W. Woolley, Merrifield studied strepogenin, a bacterial growth factor Woolley had discovered. After struggling nearly a year with a needed peptide synthesis and producing a yield of only 7%, Merrifield began thinking about a way to improve the process. "As an amateur in the field, I thought there ought to be some way to do this better, some better way to make peptides than the classical methods everybody is using," Merrifield said in a video produced for his 80th birthday, which was shown during the symposium.

One day, he presented the idea to Woolley, with whom he was riding in the elevator up to the fourth floor. As reported in Merrifield's autobiography in the ACS series "Profiles, Pathways & Dreams," Woolley exited without saying a word. But the next day, he came into the lab and said to Merrifield, "That's a pretty good idea; maybe you ought to work on it."

Linda Wang
Keepsake Merrifield's lab notebook from 1959, opened to the page describing his Nobel Prize-winning idea, sits in a glass case at Rockefeller University, along with other mementos.

A May 26, 1959, entry in one of Merrifield's lab notebooks describes his new idea: "There is a need for a rapid, quantitative, automatic method for synthesis of long-chain peptides," the entry reads. "A possible approach may be the use of chromatographic columns where the peptide is attached to the polymeric packing and added to by an activated amino acid, followed by removal of the protecting group and with repetition of the process until the desired peptide is built up. Finally, the peptide must be removed from the supporting medium."

This new approach, which Merrifield called solid-phase peptide synthesis, reduced the time required for peptide synthesis dramatically. It stimulated progress in biochemistry, molecular biology, pharmacology, and medicine. And in recent years, the method has been adapted for oligonucleotides, carbohydrates, and other organic molecules. The work earned Merrifield the Nobel Prize in Chemistry in 1984.

During the morning session of the symposium, former colleagues offered their recollections of Merrifield. Arthur M. Felix, who worked with Merrifield from 1968 to 1969 and is now an associate professor of chemistry and biochemistry at Ramapo College of New Jersey and an adjunct professor at the University of Medicine & Dentistry of New Jersey, recalled that when a reporter asked Merrifield what he would do with his Nobel Prize money, he said, "I could use a new car." Felix noted that was the most appropriate response, as Merrifield was in the habit of keeping his cars "long beyond their expiration dates."

John M. Stewart, who worked with Merrifield from 1952 to 1968 and is now a professor of biochemistry at the University of Colorado Health Sciences Center, recalled their work on the design of the first automated solid-phase peptide synthesizer, which now belongs to the Smithsonian Institution.

And Cecille G. Unson, who began working with Merrifield in 1978 and is a research associate professor at Rockefeller University, recalled how Merrifield was determined to remain active in his lab even during the late stages of his life. "I can say with certainty that I never saw him happier than when he was getting his hands dirty, his lab coat dirty, and really getting into his work." She drove home the point with a photograph of Merrifield standing on a stool, bent over in the fume hood doing experiments. She added that one of his last notebooks, number 339, describes his ideas to minimize incomplete reactions that lead to deletion peptides, or peptides missing an amino acid. Merrifield followed that up with several experiments.

Many of the speakers echoed the sentiment that Merrifield was not only an outstanding scientist but also a genuinely "nice guy." He was modest and unpretentious, humble and soft-spoken, and "wonderfully grounded in dedication to family and friends," Nurse said. Some former colleagues shared photographs from lab Christmas parties and annual picnics at the Merrifield home. "Bruce considered his students and postdocs and associates to be his other family," Felix said.

The afternoon session included technical talks by Garland Marshall of Washington University School of Medicine, who worked across the bench from Merrifield between 1963 and 1966; Bernd Gutte of the University of Zurich, who was a postdoc in Merrifield's lab from 1967 to 1971; and George Barany of the University of Minnesota, who was a graduate student in Merrifield's lab in the early '70s.

Libby Merrifield said it was particularly meaningful to see her husband's colleagues again and to celebrate Merrifield's legacy together. Rockefeller University is establishing the Bruce Merrifield Endowed Lectureship to honor Merrifield's memory.

Solid-phase peptide synthesis has come a long way, Felix noted. A recent Google search he conducted on the phrase yielded more than 1.7 million hits, "a remarkable testament to this humble, self-effacing, modest gentle giant of peptide chemistry."

"His influence continues to spread today," Felix said. "The long-term consequences of his work provide the basis for the next generation of breakthroughs in medicinal chemistry and drug discovery."

Chemical & Engineering News
ISSN 0009-2347
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