Ralph Franz Hirschmann, Ph.D.

Ralph Franz Hirschmann
Birth: May 6, 1922, Fürth, Germany
Death: Jun. 20, 2009
Worcester, Pennsylvania, USA
(note: original first name "Rudolf" changed to "Ralph")

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 at his home in Lansdale, Pa.

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 Fürth, Germany, on May 6, 1922, the youngest of three sons of Carl and Alice Büchenbacher 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."

Burial: George Washington Memorial Park Cemetery Plymouth Meeting Montgomery County Pennsylvania, USA Plot: FF-473-B1