Paul Zamecnik (1912-2009) was the Collis P. Huntington Professor of Oncologic Medicine at Harvard Medical School, Boston, Massachusetts, and headed laboratories at the Cancer Center, Massachusetts General Hospital, Boston (1947-1979, 1997-2009) and the Worcester Foundation for Biomedical Foundation, Worcester, Massachusetts (1979-1997). He is known for his work across multiple fields of biochemistry and molecular biology, including the identification and characterization of the principal components of protein synthesis. He was among those who discovered soluble molecular RNA, later known as transfer RNA (tRNA,) and discovered antisense RNAs and their therapeutic potential; Zamecnik produced the first evidence for the presence and potential role of microRNAs. The Center for the History of Medicine is pleased to report that the Paul Zamecnik papers, a product of his research and career as an author and professor at Harvard Medical School, are currently being processed.
Paul Charles Zamecnik was born 22 November 1912 in Cleveland, Ohio, and at sixteen, enrolled at Dartmouth College, Hanover, New Hampshire. Zamecnik completed bachelor’s degrees at Dartmouth in both chemistry and zoology (1933), and received his medical degree from Harvard Medical School, Boston, Massachusetts (1936). He interned at Harvard’s Colllis P. Huntington Laboratories for Cancer Research and in 1938, was an intern at University Hospitals, Cleveland, Ohio. Zamecnik was a fellow at the Carlsberg Laboratories, Copenhagen, Denmark, but returned to the work at the Rockefeller Institute for Medical Research, New York, New York, after the 1940 Nazi invasion of Denmark. He held a teaching position at Harvard Medical School during the war, and was then given his own laboratory at Massachusetts General Hospital focusing on the mechanisms of protein synthesis. In 1956, Zamecnik became the Collis P. Huntington Professor of Oncologic Medicine at Harvard Medical School, and continued his research at Massachusetts General Hospital until his retirement to Professor Emeritus in 1979. At that time, he moved his research laboratory to the Worcester Foundation for Biomedical Research, where he remained until 1997 when that foundation was absorbed by the University of Massachusetts. Zamecnik returned to Massachusetts General Hospital’s Cancer Center as a Senior Scientist, where he continued to work until weeks prior to his death in 2009. He was also a cofounder of Hybridon, Incorporated, Cambridge, Massachusetts, in 1990 to work on the development of antisense drugs; this company merged with Idera Pharmaceuticals in 2004.
Zamecnik is known for his work on protein synthesis, and the discovery of transfer RNA, as well as antisense RNAs and their therapeutic potential. During his early career, he was able to show the incorporation of C14 amino acid into the protein in rat liver slices, which led him to develop a cell-free system with Nancy L. Bucher (1913-) in order to dissect the intermediary events. In 1956, with this system in place, Zamecnik worked with Mahlon B. Hoagland (1921-2009) and Mary Louise Stephenson (1921-2009) to show that ATP was required for protein synthesis via the formation of amino acid adenylates. During this work, Zamecnik noted that ribosomes were the site of protein assembly, which led to the discovery of a small soluble molecular RNA, first called soluble RNA (sRNA) and later transfer RNA (tRNA). Zamecnik then created the cell-free system in E. coli, which led to the deciphering of the genetic code. In 1978, while working on the structure of the Rous sarcoma virus, he showed that it was possible to create a short chain of nucleotides, or a synthetic antisense chain, that would bind to the complementary nucleotide sequence of the messenger RNA (mRNA) strand. He was successful in using antisense oligos to block the replication, transcription, and translation of Rous sarcoma virus in chicken fibroblasts, from which a new chemotherapeutic concept was born. Later in his career, Zamecnik and his coworkers used antisense inhibition in in vitro systems to interfere with the growth of the influenza virus, HIV, f. malaria and M. tuberculosis. He was the first to publish evidence for the existence of microRNA, and showed that the insertion of oligonucleotides by transhybridization could correct the cystic fibrosis gene mutation and that antisense oligos could inhibit cell wall synthesis.
Throughout his career, Paul Zamecnik was an active professor and administrator at Harvard Medical School and Massachusetts General Hospital. He received several awards for his research efforts, including honorary doctorates from Columbia University, New York, New York (1971) and Dartmouth College, Hanover, New Hampshire (1987), as well as the National Medal of Science (1991), and the Albert Lasker Award for Special Achievement in the Medical Sciences (1996).
The papers, created throughout Zamecnik’s research, professional, and publishing activities, include research data and notes, grant and patent materials, correspondence, and writings and drafts. They are expected to be opened to research by July 2017. For more information on the processing of these papers, contact Elizabeth Coup, Processing Assistant.