NEWS & VIEWS NATURE|Vol 441|15 June 2006

ciple, that a technique that prevented the full OBITUARY characterization of synthetic intermediates could not give rise to authentic peptide prod- ucts. The objections of traditional chemists Bruce Merrifield (1921–2006) were ultimately refuted by the systematic Inventor of solid-phase peptide synthesis. development of improved solid-phase syn- thetic chemistry in Merrifield’s and other lab- oratories during the 1970s and 1980s, and by the emergence of powerful analytical tech- The death of Bruce Merrifield on 14 May 2006 niques for determining the structure and brings to a close the life of one of the most purity of synthetic peptides. The solid-phase original scientists of the second half of the method is now used routinely for the chemical twentieth century. Between 1959 and 1963, synthesis of peptides and proteins up to 50 or

BETTMANN/CORBIS Merrifield revolutionized organic chemistry so amino acids in length. by his invention of solid-phase peptide syn- Today, the discovery of vast numbers of thesis. This “simple and ingenious” technique, potent peptide natural products is leading to a as it was described in the citation for Merri- resurgence in pharmaceutical research on field’s 1984 Nobel Prize in Chemistry, created peptides. Solid-phase synthesis is the unri- a paradigm shift in synthetic chemistry and valled technique for the preparation of such profoundly affected biomedical research. compounds in order to determine the chemi- Robert Bruce Merrifield was born in Fort cal basis of their biological function. Merri- Worth, Texas, on 15 July 1921, the only son of field’s ingenious concept led directly to the George and Lorene (Lucas) Merrifield. He development of efficient methods for prepar- obtained his PhD in 1949 from the University ing synthetic nucleic acids — essential for of California, Los Angeles. Immedi- modern molecular biology and biotechnology. ately after graduating, Merrifield The solid-phase principle is also at the heart of joined the Rockefeller Institute for combinatorial chemistry, which enables the Medical Research in New York, simultaneous preparation of thousands of where he spent his entire career. He compounds, and which has changed the became professor in 1966, and was fabric of medicinal chemistry and drug elected to the US National Acad- discovery since the early 1990s. emy of Sciences in 1972. Bruce Merrifield is survived by At the Rockefeller Institute, Libby, his wife of 56 years, their six Merrifield worked with D. Wayne children and sixteen grandchildren. Woolley on nucleotide biochem- He was a devoted family man who istry, and then on the identification loved hiking and camping with his and chemical synthesis of putative family. In the last 45 years of his life, peptide growth factors. This was Merrifield was afflicted with a pro- the period shortly after the Second gressive skin cancer — apparently the World War, when chemists world- result of radiation treatment for acne wide were devising methods for the in his youth. A man of extraordinary preparation of biologically active peptides. would greatly facilitate the preparation of resilience, Merrifield bore this devastating ill- These molecules were important targets for peptides by enabling the recovery of support- ness with grace and fortitude. In his later years, organic synthesis, because they constituted a bound intermediate products by simple filtra- he nursed his wife back to health after she suf- new class of natural product. Synthetic tech- tion and washing; in turn, this would enable fered a serious stroke. niques had improved rapidly, but were still the use of excess reactants at each step, giving In the 1960s and 1970s, the Merrifield labo- rather cumbersome. Using the available rapid reactions and high yields of the final ratory was a hotbed of new peptide science. chemistries, Merrifield prepared a series of peptide product. Those who were fortunate enough to work synthetic peptides containing up to seven From the start, Merrifield had also envis- with Bruce came to know a man who was amino acids, a process that took five years of aged the automation of chemical synthesis. By devoted to the Rockefeller University, to his laborious research. On 26 May 1959, Merri- 1965 he had implemented this idea in collabo- research group, and to intellectually rigorous field wrote in his laboratory notebook: “There ration with John Stewart, a faculty colleague. science. His unique approach to his discipline is a need for a rapid, quantitative, automatic With Nils Jernberg of the machine shop at was recounted in an excellent autobiographi- method for the synthesis of long chain the Rockefeller University (as it was known by cal memoir, Life During a Golden Age of Pep- peptides.” He then outlined the principles of a then), they built an automated synthesizer that tide Chemistry (American Chemical Society, radically new approach to chemical peptide could prepare peptides 20 times faster than 1993). By creating a completely new approach synthesis. Four years later, Merrifield pub- solution methods, and that allowed the prepa- to organic synthesis, Merrifield pioneered the lished a seminal paper, entitled “Solid Phase ration of longer peptide chains. effective application of synthetic chemistry to Peptide Synthesis. I. The Synthesis of a Solid-phase peptide synthesis was quickly the study of biological molecules. His scientific Tetrapeptide” in the Journal of the American adopted throughout the world, and was used creativity has been equalled by few and rarely Chemical Society. to make numerous analogues of biologically surpassed. ■ The solid-phase method consisted of chem- active peptides. Merrifield and his young Stephen Kent ically attaching the last amino acid of the tar- colleagues concentrated on developing the Stephen Kent is in the Department of get peptide to a solid support, then carrying technique and extending it to new targets. Biochemistry & Molecular Biology, and out all the chemical steps necessary to build But as solid-phase synthesis was applied to the Department of Chemistry, University the peptide’s amino-acid sequence, and finally ever-larger molecules, established peptide of Chicago, 929 East 57 Street, Chicago, releasing the product from the support. As researchers harshly criticized both Merrifield Illinois 60637, USA. Merrifield envisaged it, solid-phase synthesis and his method. It was felt, as a matter of prin- e-mail: [email protected]

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