Born in Cleveland, Ohio in 1912, he attended Dartmouth College, majored in chemistry and zoology, and received his AB degree in 1933.
He then attended Harvard Medical School and received his MD degree in 1936.
He was a professor of medicine at Harvard Medical School and a senior scientist at Massachusetts General Hospital.
Zamecnik pioneered the in vitro synthesis of proteins and helped elucidate the way cells generate proteins.
With Mahlon Hoagland he co-discovered transfer RNA (tRNA).
Through his later work, he is credited as the inventor of antisense therapeutics.
He was awarded a Finney-Howell Fellowship and a Moseley Traveling Fellowship to go to the Carlsberg Laboratory in Copenhagen where he worked with Dr. Kai Linderstrom-Lang.
His planned time in Copenhagen was cut short because of World War II—the Germans occupied Denmark from April 1940—and he and his wife, Mary Connor, returned to Boston where he became an Assistant Physician at the Huntington Memorial Hospital, studying the toxic factors involved in traumatic shock for a wartime Office of Scientific Research and Development project led by Huntington director Joseph Charles Aub.
After a year in New York at the Rockefeller Institute for Medical Research studying protein synthesis with Max Bergmann, he returned to Harvard in 1942 to join the Faculty of Medicine at Harvard Medical School where he became Instructor and then Professor of Medicine, where he served until retiring as the Collis P. Huntington Professor of Oncologic Medicine, Emeritus in 1979.
In 1952, Zamecnik was partially successful in that he made a cell-free extract from rat liver with which he was able to synthesize proteins from amino acids. In 1953, using this system, Zamecnik and Mahlon Hoagland showed that amino acids had to be energized, “activated,” by ATP before they were incorporated into a peptide chain.
Then in 1956, Hoagland followed up on an observation Zamecnik made earlier. Zamecnik noticed that low molecular weight RNA in the cell-free extract could be associated with radiolabel amino acids.
This led to the identification of tRNA? The adaptors Francis Crick predicted in his Central Dogma.
In 1956, Zamecnik was appointed head of the Huntington Laboratory.
In 1960, his lab developed a cell-free extract from the bacteria E. coli. He shared the preparation method with other scientists. Marshall Nirenberg and Johann Matthaei used the cell-free extract from E. coli to crack the genetic code.
In 1978, while working on the structure of Rous sarcoma virus (RSV) he showed that it was possible to create a short chain of nucleotides – a synthetic antisense chain – that would bind to the complementary nucleotide sequence of a messenger RNA strand.
He was successful in using antisense oligos to block the replication, transcription and translation of RSV in chicken fibroblasts.
Thus, a new chemotherapeutic concept was born, and later Zamecnik and co-workers used antisense inhibition in vitro systems to interfere with the growth of influenza virus, HIV, f. malaria and M. tuberculosis in proof of principle experiments.
Paul’s wife Mary died in 2005. Their married life together spanned 69 years. They are survived by three children, seven grand children and two great granddaughters.