Ralph F. Hirschmann, Leading Scientist On Early Enzyme Research, 87, NY Times
DGH
http://www.nytimes.com/2009/07/19/science/19hirschmann.html?ref=obituaries
Ralph F. Hirschmann, Leading Scientist on Early Enzyme Research, Dies at 87
By DENNIS HEVESI [New York Time]
Published: July 18, 2009
Ralph F. Hirschmann, a leader of a team of biochemists that for the first
time synthesized an enzyme, one of the master chemicals of life, died June
20 [2009] at his home in Lansdale, Pa. He was 87.
The cause was kidney failure, his daughter Carla Hummel said.
Along with Robert G. Denkewalter, Dr. Hirschmann headed the research team at
Merck Laboratories in Rahway, N.J., that in the late 1960s designed one of
two groundbreaking methods to synthesize the enzyme, ribonuclease. At the
same time, a team of scientists at Rockefeller University in New York, led
by R. Bruce Merrifield and Bernd Gutte, was completing work on another
method.
The success of the parallel projects, which proved to be seminal
breakthroughs in the way medicines are invented, was front-page news in The
New York Times on Jan. 17, 1969.
"The two reports together instantaneously corroborated each other's work,"
Daniel Rich, a former chairman of the American Chemical Society's division
of chemical medicine, said in an interview Thursday. "What made Hirschmann
and Merrifield's work so important was that they bridged the interface
between chemistry and biology, two fields that until then weren't talking to
each other very much."
"It was a huge discovery," Dr. Rich continued. "Nowadays it's just routine."
Gary Molander, the chairman of the chemistry department at the University of
Pennsylvania, concurred. "The whole biotechnology field came out of the
recognition that one could actually synthesize these biomolecules," Dr.
Molander said. "Dozens of biotechnology and drug companies were started on
the basis of this concept, and scores of drugs were subsequently developed."
One consequential result was the first pure samples of a key enzyme called
H.I.V. protease. "This work led to the development at many pharmaceutical
companies of protease inhibitors, a major drug for treating AIDS in humans,"
Dr. Rich said.
Dr. Hirschmann was a research director at Merck Laboratories from 1971 until
1978. After his pioneering work on ribonuclease, he led a team that produced
a string of important new pharmaceuticals. Among them are Mevacor, which
lowers cholesterol; Vasotec, for treating high blood pressure; Proscar,
which is used to treat an enlarged prostate and has now been found to reduce
the incidence of prostate cancer; Primaxin, an intravenous antibiotic that
is used frequently to treat complicated infections; and Ivermectin, which
has significantly reduced the scourge of river blindness in sub-Saharan
Africa.
President Bill Clinton awarded Dr. Hirschmann the National Medal of Science
in 2000.
In the studies of ribonuclease in the 1960s, the two research teams focused
on that enzyme because of its comparatively simple structure. Enzymes enable
animals to eat and breathe. With them, the body converts sugar and other
basic foods into many of the substances needed for bodily functions. They
are essential to tissue-building, blood cell replacement and the release of
chemical energy for muscle movement.
Ribonuclease consists of 124 molecular units, known as amino acids, linked
chemically by a long chain. As with other enzymes, ribonuclease belongs to
the larger family of chemicals known as proteins. While there are millions
of different proteins, some with thousands of amino acids, all are formed
from the same 20 kinds of amino acids.
Ribonuclease is formed from 19 types of amino acid; producing it is like
assembling a train made up of 19 kinds of freight cars - box cars, flat
cars, cement cars. What made synthesis so difficult was assembling the
microscopic parts in the right order.
The Merck synthesis was achieved over an 18-month period in a multistage
process in which a number of short amino acid chains were linked to form two
large units. They were then combined into a full-length molecule of
ribonuclease. The resulting material performed like its natural counterpart.
A similar result was achieved at Rockefeller University by hooking the 124
amino acids one by one.
Beyond the pharmaceutical breakthrough that the combined research proved to
be, it also made more comprehensible the way enzymes had been formed when
the chemistry of life was evolving on a lifeless planet.
Ralph Franz Hirschmann was born in F�rth, Germany, on May 6, 1922, the
youngest of three sons of Carl and Alice B�chenbacher Hirschmann. His father
was a banker. In 1936, three years after the Nazis rose to power, the family
emigrated to the United States and settled in Kansas City, Mo.
Dr. Hirschmann graduated from Oberlin College in 1943, then served in the
Army for three years in the Pacific. After receiving his doctorate in
organic chemistry from the University of Wisconsin, Madison, in 1950, he was
hired as a researcher at Merck Laboratories.
Another chemist at the laboratory, Lucy Aliminosa, caught his eye; they
married a year later. Besides his wife and his daughter, Dr. Hirschmann is
survived by his son, Ralph, and six grandchildren.
After retiring from Merck in 1987, Dr. Hirschmann taught at the University
of Pennsylvania and, traveling from campus to campus, at the University of
South Carolina. He retired from teaching in 2006.
In 1984, Dr. Merrifield, who had led the Rockefeller University team,
received the Nobel Prize in chemistry.
Dr. Rich, the former chairman of chemical medicine at the American Chemical
Society, said Thursday, "A lot of people were surprised that Hirschmann
didn't share the Nobel Prize."