R. Bruce Merrifield | Biography

R. Bruce Merrifield was born July 15, 1921, in Fort Worth, Texas, the only son of George E. and Lorene Lucas Merrifield. In high school, Merrifield became interested in science, especially chemistry and astronomy. When he graduated from high school in 1939, Merrifield entered Pasadena Junior College, and transferred at the end of two years to the University of California at Los Angeles (UCLA), where he worked in the laboratory of Max S. Dunn.

After receiving a Bachelor of Arts degree with a major in chemistry from UCLA in 1943, Merrifield went to work at the Philip R. Park Research Foundation as a chemist. The experience convinced Merrifield that to pursue his goals he would need to return to school. He returned to UCLA for graduate school, and served as a chemistry instructor from 1944 until 1947. He then returned to Professor Dunn's laboratory as a research assistant from 1948 through 1949. In 1949, he received his Ph.D. in biochemistry, and accepted an appointment as an assistant chemist at the Rockefeller University, then known as the Rockefeller Institute for Medical Research, in New York City. He remained at the institute, becoming a John D. Rockefeller Jr. Professor--the institution's highest academic rank--in 1984.

At the Institute, Merrifield first worked as an assistant to Dr. Dilworth W. Woolley, whom he considered a profound influence on his later career. At this time, having recognized that proteins are the key components of all living organisms, he chose to focus on this aspect of their research. Their studies centered on peptide growth factors that Dr. Woolley had discovered and on the dinucleotide growth factors Merrifield had discovered during his graduate study. Merrifield's research required him to isolate biologically active peptides. For his experiments, he had to synthesize analogues of the materials. However, the research pointed out the need to improve the techniques of peptide synthesis. The methods pioneered by Emil Fischer at the turn of the century for peptide synthesis were laborious and time consuming. Preparing a single experiment's sample could take months of work. Fischer's process involved activating the link in a chain of peptides to which one would attach the next peptide. Before the bond could be activated, however, all the other bonds in the chain would have to be protected. Then, after the required bond had formed, all other protected bonds needed to be cleared of their chemical caps. The process would then be repeated however many times necessary to gradually build the desired molecule.

Realizing that the critical step involved activating the peptide bond while protecting all others in a long chain, Merrifield hit on the notion of anchoring the chain to a solid base. The first amino acid in the sequence would be tightly bonded to a polymeric support, an insoluble foundation that would not react during the peptide bond additions but, following the reactions, could easily be removed by the proper solvents. This solid-phase method acted like the frame of a loom, holding the ends of the chain taunt while link after link was sewn in. Not only did this save one of the most cumbersome steps in the Fischer process, the need to purify the intermediate product prior to the addition of another bond, it also allowed much more reagent to be flushed in due to the secure hold at the polymeric end. The reactions could be driven longer and harder, producing a purer product. Purities of 99.5% were achieved, as Merrifield announced at a 1962 meeting of the Federation of American Societies of Experimental Biology.

Despite being simplified, however, the steps were still so repetitive Merrifield felt they could be automated. Working in the basement of his house, he devised the first prototype of an automated peptide synthesizer by 1965.The machine was a technological success. In 1969, Merrifield used his box of computer switches filled with jars and tubes to carry out the complete synthesis of one of the first enzymes he had begun his work on years earlier. It took 369 separate chemical reactions in 11,391 steps to make the ribonuclease molecule, but it took far less time than before. However, the practical advantage had a price. Because the step of isolating--and thereby purifying--the intermediates had been circumvented, trace side reactions were no longer washed out of the product during a protein's synthesis. While Merrifield could boast that each stage's yield had a high degree of purity, the overall synthesis after so many steps may have had an appreciable number of undesirable side products. Advances since then have dramatically improved product purity. But the key advance was in the speed and simplification of a once unimaginably complex task, and his work was recognized with the Nobel Prize in 1984 in chemistry. The process--which has never been patented, either by Merrifield or Rockefeller University--has been used widely and is seen as one of the fundamental techniques of genetic and biochemical research.

Merrifield was invited to be a Nobel Guest Professor and traveled to Uppsala University in 1968. Beginning in 1969 he served as editor of the International Journal of Peptide and Protein Research (now the Journal of Peptide Research). He is currently on the publication's editorial board. Merrifield has received many academic and professional awards, including the Ralph F. Hirschmann Award in Peptide Chemistry from the American Chemical Society (1990); the Josef Rudinger Award (1990), and the Seaborg Medal (1993). Merrifield and his wife, Elizabeth, a biologist, live in Cresskill, New Jersey. They have six children.

Currently an adjunct professor at the Oregon Institute of Science and Medicine, Merrifield is also an emeritus professor at Rockefeller University. In 1993 he published the semibiographical Life During a Golden Age of Peptide Chemistry: The Concept and Development of Solid-Phase Peptide Synthesis (Oxford University Press-USA). The American Peptide Society now offers an annual Merrifield Award for outstanding career achievements in peptide research.