Paul C. Zamecnik, Biologist Who Helped Discover an RNA Molecule, Dies at 96

November 7, 2009
Paul C. Zamecnik, Biologist Who Helped Discover an RNA Molecule, Dies at
96
By VICKI GLASER

Paul C. Zamecnik, a molecular biologist whose determination to unlock
the secrets of how a protein is made led to his co-discovery of transfer
RNA, a molecule that is essential to the process, died on Oct. 27 at his
home in Boston. He was 96.

The cause was cancer, his daughter Karen Zamecnik Pierson said.

Dr. Zamecnik also discovered a method for blocking individual genes that
pointed the way to a new class of drugs.

In the 1950s, Dr. Zamecnik (pronounced zam-ESS-nik) devised a system for
modeling protein synthesis in a test tube, so he could more easily track
the steps involved in translating the genetic information encoded in DNA
into a chain of amino acids, the building blocks of a protein.

In 1956, Dr. Zamecnik and his colleagues Dr. Mahlon Hoagland (who died
on Sept. 18) and Dr. Mary Stephenson discovered a critical element of
the protein synthesis pathway: the molecule that shuttles amino acids to
the cell's protein factory, called the ribosome. There they are linked
to create a chain that folds to form a protein. This newfound molecule
they called transfer RNA, or tRNA. The discovery was a milestone in
molecular biology.

Dr. Zamecnik's work "advanced the study of protein synthesis," taking it
from a purely metabolic process "into proper biochemistry for the first
time," said Thoru Pederson, the Vitold Arnett professor of cell biology
at the University of Massachusetts Medical School, who was a colleague
and a friend. Dr. Pederson described him as "a transformative figure"
during the very early years of molecular biology research.

In 1978, Dr. Zamecnik published the first work showing that a short,
synthetic series of nucleotides, the chemical components of DNA and RNA,
could be used to inactivate a specific gene. The concept, which he
called antisense technology, is based on the double-stranded structure
of a DNA molecule. One strand, called the sense strand, carries the
genetic instructions; it is intertwined with the complementary antisense
strand to form the double helix. A cell reads the genetic information
encoded on the sense strand and creates a corresponding messenger RNA
(mRNA) molecule, which delivers the genetic message to the ribosome.

In antisense technology, a short series of nucleotides recognizes a
specific sequence on an mRNA strand, preventing it from being translated
into a protein and blocking expression of a gene.

Although Dr. Zamecnik's antisense concept was first met with skepticism,
it has given rise to a new class of therapeutic compounds called
antisense drugs, which are under active development in the biotechnology
industry. One antisense drug is already on the market, and about a dozen
more are in clinical trials.

Dr. Zamecnik's antisense work "will change how medicines are developed,"
said Sudhir Agrawal, president and chief executive of Idera
Pharmaceuticals, who worked with Dr. Zamecnik over the years on
developing the technology.

Paul Charles Zamecnik was born in Cleveland in 1912. He enrolled at
Dartmouth at the age of 16. Five years later, in 1934, he had completed
both his undergraduate degree and the two-year program at Dartmouth
Medical School. He completed his medical degree at Harvard Medical
School, graduating in 1936.

After he was put on a waiting list for a surgical internship, he did an
internship in oncology at Huntington Memorial Hospital, work that first
led to his interest in scientific research. He did a subsequent
internship in medicine at University Hospitals in Cleveland. When an
obese patient abruptly died there and the autopsy showed an abundance of
fat tissue and too little muscle and protein, he began to seek answers
to the question of how proteins are made.

To expand his knowledge of biochemistry, and protein chemistry in
particular, he took additional classes and pursued a fellowship at the
Carlsberg Laboratories in Copenhagen. After he returned to the United
States, he worked for two years at the Rockefeller Institute for Medical
Research in New York City. He then became an instructor at Harvard
Medical School and established his laboratory at Massachusetts General
Hospital. In 1956, he became the Collis P. Huntington Professor of
Oncologic Medicine at Harvard Medical School.

Reaching the mandatory retirement age in 1979, he left Harvard and
continued his research at the Worcester Foundation for Biomedical
Research, in Massachusetts, where his former colleague, Dr. Hoagland,
was the director. When the foundation merged with the University of
Massachusetts Medical School in 1997, Dr. Zamecnik moved his laboratory
once again, to Massachusetts General, becoming a senior scientist. He
continued to work in his laboratory until several weeks before his
death.

Dr. Zamecnik's wife of 69 years, the former Mary Connor, who worked in
his laboratory, died in 2005. In addition to his daughter Karen, of
Cambridge, who also worked alongside him, survivors include his son,
John, of Argentina and Washington; another daughter, Elizabeth Coakley,
of Sedgwick, Me.; seven grandchildren; and two great-grandchildren.

In 1996, Dr. Zamecnik received the Albert Lasker Award for Special
Achievement in Medical Science "for brilliant and original science that
revolutionized biochemistry and spawned new avenues of scientific
inquiry." In 1991 he was awarded the National Medal of Science.

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