Merrifield Peptide Synthesizer, circa 1964
In 1901, the German chemist Emil Fischer synthesized the first pure dipeptide molecule; more than half a century later, most chemists were still using the same technique of adding and removing chemical accessories called “protecting groups” to the reactive parts of individual amino acids to direct organic synthesis in a controlled, linear, and stepwise fashion. The method, however, was arduous and not conducive to making large batches of more complex proteins.
In 1959, Bruce Merrifield, a Rockefeller chemist, devised a way to make peptide synthesis more efficient. Instead of working entirely in solution, Merrifield turned to a solid substrate. He attached growing chains of peptides to a resin support that could easily be removed by a simple wash procedure. This greatly increased protein yields, cut down the amount of time involved, and simplified...
The process was still time-consuming and somewhat cumbersome. Merrifield, however, realized that the technique could be easily automated. In 1964, he teamed up with his colleague John Stewart, who developed the electrical system, and working in Stewart’s basement they created the first prototype of what became known as the Merrifield peptide synthesizer. The instrument shown here (one of the first three machines ever built) used an electromechanical timing device to control the sequence of peptide syntheses, and a Teflon flow pump with a rotary selector valve to prevent residue from the plastic pellets from clogging the device. Merrifield’s invention “made it possible for just one person” to synthesize a peptide within a year, says Bernd Gutte, a University of Zurich biochemist who single-handedly produced ribonuclease A on the device as a postdoc in Merrifield’s lab in the 1960s.
Solid phase synthesis eventually transcended peptides, and was used to synthesize nucleic acids and other organic molecules. Twenty years after first building his instrument, Merrifield was awarded the Nobel Prize in chemistry, in 1984.