Bruce Merrifield dies

Bruce Merrifield, one of the fathers of modern peptide synthesis and recipient of the 1984 Nobel Prize in Chemistry, died of a long illness last week (May 14) at his home in Cresskill, N.J., according to Rockefeller University.Merrifield was best known as the creator of solid phase peptide synthesis, a process that enabled the systematic study of the structure of proteins. In 1963, he published an influential paper describing the binding of a peptide to an insoluble support so that reagents can be washed away at the end of each synthesis step. More than 20 years later, the idea earned him a Nobel Prize."Merrifield's method made peptides accessible to the non-specialist, and had vast ramifications in many areas of modern biochemistry," said George Barany, a former graduate student of Merrifield's, now at the University of Minnesota.But in the 1960s, there was not unanimous support for Merrifield's idea. At that time, scientists generally believed that every intermediate in a chemical synthesis needed to be isolated and fully characterized, said Richard DiMarchi of Indiana University, former postdoctoral fellow in Merrifield's laboratory. "But Merrifield's methodology, in its elegance and simplicity, allowed you to skip each intermediate and just focus on the final product," DiMarchi told The Scientist. "His work was iconoclastic relative to the type of synthetic work that had been done at that time."As a result, Merrifield faced intense criticism in the 1960s and 1970s about whether it was appropriate to skip such synthesis intermediates, and skepticism about whether his end products were what they were reported to be. "He answered his critics with data and dignity," DiMarchi recalled.Born in Texas in 1921, Robert Bruce Merrifield began his scientific career at the University of California, Los Angeles, where he received a BA in chemistry and a PhD in biochemistry. He arrived at the Rockefeller Institute for Medical Research, now Rockefeller University, in the summer of 1949, joining the laboratory of D.W. Woolley.At the time, Woolley had just discovered a bacterial growth factor thought to be a peptide, and Merrifield's job was to determine its structure. Merrifield was successful in isolating a pentapeptide -- one of only a few biologically active peptides known at the time -- but needed to chemically synthesize it to prove its structure. By the end of 1963, Merrifield had thought up solid phase peptide synthesis, which he would soon automate. The technique was used to synthesize proteins such as ribonuclease A, bradykinin, angiotensin, desamino-oxytocin, and insulin. Merrifield and a colleague, John Stewart, "worked in the garage to build the automated peptide synthesis machine," recalled James Tam, a colleague of Merrifield's for 30 years and a professor at the Scripps Research Institute. Merrifield never patented the machine and instead preferred to share the concept widely, Tam told The Scientist -- the sign of a "true gentleman."Indeed, Merrifield was a humble and unassuming person, said Garland Marshall, Merrifield's first graduate student and a professor at Washington University in St. Louis. "One of his standard jokes was that he was going to quit this business and go open a gas station on Highway 66," said Marshall.Merrifield became a full professor at Rockefeller University in 1966, was elected to the U.S. National Academy of Sciences in 1972, and was named John D. Rockefeller Jr. Professor in 1983. He retired in 1992, publishing his autobiography "Life during a Golden Age of Peptide Chemistry" a year later.For Lenore Martin, a postdoctoral fellow with Merrifield in the 1990s and currently at the University of Rhode Island, the book is something every scientist should read. "He was patient but relentless about science," said Martin, "but always put his family first."Robert Bruce Merrifield is survived by his wife, Elizabeth - a biologist who helped run the laboratory - as well as his three daughters and one son, along with 16 grandchildren.David Secko dsecko@the-scientist.comLinks within this articleNobel Prize in Chemistry, 1984 http://nobelprize.org/chemistry/laureates/1984/index.htmlG.R. Marshall, "Solid-phase synthesis: a paradigm shift," Journal of Peptide Science, September 2003. PM_ID: 14552416R.B. Merrifield, "Solid phase peptide synthesis. I. The synthesis of a tetrapeptide," Journal of the American Chemical Society, July 20, 1963 http://pubs.acs.org/cgi-bin/abstract.cgi/jacsat/1963/85/i14/f-pdf/f_ja00897a025.pdfGeorge Barany http://www.chem.umn.edu/groups/baranygp/georgebio.htmRichard DiMarchi http://www.indiana.edu/~rdmweb/R.B. Merrifield, "The chemical synthesis of proteins," Protein Science, September, 1996. PM_ID: 8880923 James Tam http://www.scripps.edu/research/faculty.php?rec_id=12066Garland Marshall http://www.cmd.wustl.edu/Marshall_Page.htmLenore Martin http://www.uri.edu/personal/lma8738u/INDEX.HTML

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