March 2010

Retrospective: Paul C. Zamecnik (1912 – 2009)

 

ZamecnikPaul C. Zamecnik, senior scientist at Massachusetts General Hospital and professor emeritus of oncologic medicine at Harvard Medical School, was among the most important biochemical scientists of the 20th century. He passed away Oct. 27, 2009, at the age of 96.

Paul received his undergraduate degree from Dartmouth College in 1933, majoring in chemistry and zoology. He obtained his medical degree from Harvard Medical School in 1936 and followed it with internships at Huntington Memorial Hospital in Boston and Lakeside Hospital in Cleveland, Ohio. During his Lakeside Hospital internship, Paul was awarded a Finney-Howell Fellowship and a Moseley Traveling Fellowship to go to the Carlsberg Laboratory in Copenhagen, where he worked with Kaj Linderstrom-Lang. After he returned to the United States, Paul worked at the Rockefeller Institute for Medical Research in New York for two years, studying protein synthesis with Max Bergmann. He returned to Cambridge, Mass., in 1942 to join the faculty of medicine at Harvard Medical School and established his laboratory at Massachusetts General Hospital.

At Harvard, Paul worked with Fritz Lipmann, and the pair subsequently shared the Massachusetts General Hospital’s Warren Triennial Prize for their seminal study on the mechanism of action of clostridium α-toxin. In 1956, Paul became the Collis P. Huntington professor of oncologic medicine at Harvard Medical School, and he remained in that position until his retirement in 1979, after which he continued at the Worcester Foundation for Biomedical Research.

In the 1950s, Paul elucidated, through the development of cell-free systems, the biochemistry of protein synthesis. He and colleagues Philip Siekevitz, Robert B. Loftfield, Mahlon Hoagland and Mary Stephenson showed that ATP is necessary for amino acid activation leading to peptide bond formation, which, therefore, is not a reversal of proteolysis. They discovered transfer RNAs and showed that the linkage of amino acids to these small RNAs was the penultimate step of polypeptide synthesis. Paul’s group was also the first to identify the ribosome as the site of protein synthesis.

After that breakthrough, Paul continued to perform outstanding research. His RNA sequencing revealed that Rous sarcoma virus RNA has a 3’-OH tail of poly(A) bounded by a sequence that is identical to one at the 5’ end, suggesting that a cDNA-mediated circularization might occur during reverse transcription. A 13-mer oligodeoxynucleotide complementary to the terminus of RSV inhibited both the translation of viral mRNA in a cell-free system and virus replication. He showed that inhibition depends on both the ability of deoxynucleotides to enter intact cells and on Watson-Crick base pairing. His pioneering studies on antisense DNA and its inhibitory activity arose from that work. Antisense oligonucleotides immediately became important research tools for experimentally silencing gene expression. Those papers launched the era of antisense DNA. He applied those concepts to medicine, targeting the tuberculosis bacterium and the defective cystic fibrosis gene. Paul is regarded as the founder of the antisense therapy field.

Paul’s wife of 69 years, Mary Connor, died in 2005. He leaves daughters Karen Pierson and Elizabeth Coakley, son John, seven grandchildren and two great-grandchildren.

Paul’s major “side interest” was the company and conversation of interesting people. He learned to ski at Dartmouth and enjoyed skiing every winter. He was a good swimmer and tennis player. Later in life, he and Mary went to St. John in the Virgin Islands, where he loved to swim and snorkle. When he no longer participated in sports, he enjoyed watching football, basketball and tennis and knew all the players and their quirks.

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