Ralph F. Hirschmann
Encyclopedia
Ralph Franz Hirschmann was a German American
biochemist
who led a team that was responsible for the first organic synthesis
of an enzyme
, a ribonuclease
.
, he emigrated from Nazi Germany
in 1936 and settled with his family in Kansas City, Missouri
. He became a naturalized citizen of the United States in 1944. After graduating from Oberlin College
in 1943, he served in the United States Army
for three years in the Pacific Theater of Operations
. Following the completion of his military service, Hirschmann attended the University of Wisconsin–Madison
, receiving his Doctor of Philosophy
in organic chemistry
in 1950.
, where he was hired as a researcher in 1950, he led a team that developed a method to synthesize the enzyme ribonuclease. His team was successful, with their results announced in January 1969 parallel with those from a separate team led by Bernd Gutte and Robert Bruce Merrifield
at Rockefeller University
who also achieved synthesis of the same enzyme using a different method. The comparatively simple 124-amino acid
structure of ribonuclease made it a logical target for the first enzyme to synthesize. Hirschmann's team built the enzyme in amino acid groups from six to 17 in length which were assembled into two large sections that were linked together, while Merrifield's approach was to assemble the entire enzyme by linking one amino acid at a time at the end of a chain. The achievement was front page news in The New York Times
, heralding the fact that "An Enzyme Is Synthesized for First Time" and providing coverage of a joint announcement by the two teams. While no immediate applications were foreseen, the Merck team noted that the ability to synthesize enzymes opened a new class of drugs for potential therapeutic use.
In Hirschmann's obituary in The New York Times, chemist Daniel Rich described the feat of synthesizing an enzyme as "a huge discovery" that "bridged the interface between chemistry
and biology
", and that by the time of Hirschmann's death the accomplishment was "just routine". Chemist Gary Molander of the University of Pennsylvania
described how "[d]ozens of biotechnology and drug companies were started" based on Hirschmann's developments and that "[t]he whole biotechnology
field" and new classes of medicines, such as protease inhibitors
for the treatment of AIDS
, were established through his approach.
As head of Merck's Department of New Lead Discovery starting in 1971 and as Senior Vice President for Basic Research in Chemistry starting in 1978, serving until the retirement age of 65, when he left the firm in 1987, Hirschmann played a pivotal role in the development of many of the firms products. Among the medications he was involved with was the development of the antiparasitic Ivermectin used for the treatment of river blindness, the statin
Mevacor for reducing cholesterol
in patients at risk of cardiovascular disease
, the beta-lactam
-family broad-spectrum antibiotic
Primaxin, the synthetic androgen
Proscar used for the treatment of enlarged prostate
and prostate cancer
and of the ACE inhibitor
Vasotec for treating hypertension
.
Following his departure from Merck, Hirschammn taught at the University of Pennsylvania and the University of South Carolina
until his retirement in 2006.
in 2000 by President of the United States
Bill Clinton
. He was presented the award at a December 1, 2000, dinner by Dr. Neal Francis Lane
, Assistant to the President for Science & Technology:
Hirschmann received the Arthur C. Cope Award
for achievement in the field of organic chemistry research from the American Chemical Society
in 1999. Merrifield was awarded the Nobel Prize in Chemistry
in 1984 for the invention of solid phase peptide synthesis, with some, such as Daniel Rich of the American Chemical Society
expressing that he was "surprised that Hirschmann didn't share the Nobel Prize".
The Ralph F. Hirschmann Award in Peptide Chemistry is given out "to recognize and encourage outstanding achievements in the chemistry, biochemistry, and biophysics of peptides." The award was established in 1988 by Merck Research Laboratories.
at his home in Lansdale, Pennsylvania
. He was survived by his wife, the former Lucy Aliminosa, a chemist he had met at his laboratory. He was also survived by a daughter, a son and six grandchildren.
German American
German Americans are citizens of the United States of German ancestry and comprise about 51 million people, or 17% of the U.S. population, the country's largest self-reported ancestral group...
biochemist
Biochemist
Biochemists are scientists who are trained in biochemistry. Typical biochemists study chemical processes and chemical transformations in living organisms. The prefix of "bio" in "biochemist" can be understood as a fusion of "biological chemist."-Role:...
who led a team that was responsible for the first organic synthesis
Organic synthesis
Organic synthesis is a special branch of chemical synthesis and is concerned with the construction of organic compounds via organic reactions. Organic molecules can often contain a higher level of complexity compared to purely inorganic compounds, so the synthesis of organic compounds has...
of an enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
, a ribonuclease
Ribonuclease
Ribonuclease is a type of nuclease that catalyzes the degradation of RNA into smaller components. Ribonucleases can be divided into endoribonucleases and exoribonucleases, and comprise several sub-classes within the EC 2.7 and 3.1 classes of enzymes.-Function:All organisms studied contain...
.
Early life and education
Born on May 6, 1922, in FürthFürth
The city of Fürth is located in northern Bavaria, Germany in the administrative region of Middle Franconia. It is now contiguous with the larger city of Nuremberg, the centres of the two cities being only 7 km apart....
, he emigrated from Nazi Germany
Nazi Germany
Nazi Germany , also known as the Third Reich , but officially called German Reich from 1933 to 1943 and Greater German Reich from 26 June 1943 onward, is the name commonly used to refer to the state of Germany from 1933 to 1945, when it was a totalitarian dictatorship ruled by...
in 1936 and settled with his family in Kansas City, Missouri
Kansas City, Missouri
Kansas City, Missouri is the largest city in the U.S. state of Missouri and is the anchor city of the Kansas City Metropolitan Area, the second largest metropolitan area in Missouri. It encompasses in parts of Jackson, Clay, Cass, and Platte counties...
. He became a naturalized citizen of the United States in 1944. After graduating from Oberlin College
Oberlin College
Oberlin College is a private liberal arts college in Oberlin, Ohio, noteworthy for having been the first American institution of higher learning to regularly admit female and black students. Connected to the college is the Oberlin Conservatory of Music, the oldest continuously operating...
in 1943, he served in the United States Army
United States Army
The United States Army is the main branch of the United States Armed Forces responsible for land-based military operations. It is the largest and oldest established branch of the U.S. military, and is one of seven U.S. uniformed services...
for three years in the Pacific Theater of Operations
Pacific Theater of Operations
The Pacific Theater of Operations was the World War II area of military activity in the Pacific Ocean and the countries bordering it, a geographic scope that reflected the operational and administrative command structures of the American forces during that period...
. Following the completion of his military service, Hirschmann attended the University of Wisconsin–Madison
University of Wisconsin–Madison
The University of Wisconsin–Madison is a public research university located in Madison, Wisconsin, United States. Founded in 1848, UW–Madison is the flagship campus of the University of Wisconsin System. It became a land-grant institution in 1866...
, receiving his Doctor of Philosophy
Doctor of Philosophy
Doctor of Philosophy, abbreviated as Ph.D., PhD, D.Phil., or DPhil , in English-speaking countries, is a postgraduate academic degree awarded by universities...
in organic chemistry
Organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, composition, reactions, and preparation of carbon-based compounds, hydrocarbons, and their derivatives...
in 1950.
Biochemistry career
While at Merck & Co.Merck & Co.
Merck & Co., Inc. , also known as Merck Sharp & Dohme or MSD outside the United States and Canada, is one of the largest pharmaceutical companies in the world. The Merck headquarters is located in Whitehouse Station, New Jersey, an unincorporated area in Readington Township...
, where he was hired as a researcher in 1950, he led a team that developed a method to synthesize the enzyme ribonuclease. His team was successful, with their results announced in January 1969 parallel with those from a separate team led by Bernd Gutte and Robert Bruce Merrifield
Robert Bruce Merrifield
Robert Bruce Merrifield was an American biochemist who won the Nobel Prize in Chemistry in 1984 for the invention of solid phase peptide synthesis.-Early life:...
at Rockefeller University
Rockefeller University
The Rockefeller University is a private university offering postgraduate and postdoctoral education. It has a strong concentration in the biological sciences. It is also known for producing numerous Nobel laureates...
who also achieved synthesis of the same enzyme using a different method. The comparatively simple 124-amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
structure of ribonuclease made it a logical target for the first enzyme to synthesize. Hirschmann's team built the enzyme in amino acid groups from six to 17 in length which were assembled into two large sections that were linked together, while Merrifield's approach was to assemble the entire enzyme by linking one amino acid at a time at the end of a chain. The achievement was front page news in The New York Times
The New York Times
The New York Times is an American daily newspaper founded and continuously published in New York City since 1851. The New York Times has won 106 Pulitzer Prizes, the most of any news organization...
, heralding the fact that "An Enzyme Is Synthesized for First Time" and providing coverage of a joint announcement by the two teams. While no immediate applications were foreseen, the Merck team noted that the ability to synthesize enzymes opened a new class of drugs for potential therapeutic use.
In Hirschmann's obituary in The New York Times, chemist Daniel Rich described the feat of synthesizing an enzyme as "a huge discovery" that "bridged the interface between chemistry
Chemistry
Chemistry is the science of matter, especially its chemical reactions, but also its composition, structure and properties. Chemistry is concerned with atoms and their interactions with other atoms, and particularly with the properties of chemical bonds....
and biology
Biology
Biology is a natural science concerned with the study of life and living organisms, including their structure, function, growth, origin, evolution, distribution, and taxonomy. Biology is a vast subject containing many subdivisions, topics, and disciplines...
", and that by the time of Hirschmann's death the accomplishment was "just routine". Chemist Gary Molander of the University of Pennsylvania
University of Pennsylvania
The University of Pennsylvania is a private, Ivy League university located in Philadelphia, Pennsylvania, United States. Penn is the fourth-oldest institution of higher education in the United States,Penn is the fourth-oldest using the founding dates claimed by each institution...
described how "[d]ozens of biotechnology and drug companies were started" based on Hirschmann's developments and that "[t]he whole biotechnology
Biotechnology
Biotechnology is a field of applied biology that involves the use of living organisms and bioprocesses in engineering, technology, medicine and other fields requiring bioproducts. Biotechnology also utilizes these products for manufacturing purpose...
field" and new classes of medicines, such as protease inhibitors
Protease inhibitor (pharmacology)
Protease inhibitors are a class of drugs used to treat or prevent infection by viruses, including HIV and Hepatitis C. PIs prevent viral replication by inhibiting the activity of proteases, e.g.HIV-1 protease, enzymes used by the viruses to cleave nascent proteins for final assembly of new...
for the treatment of AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
, were established through his approach.
As head of Merck's Department of New Lead Discovery starting in 1971 and as Senior Vice President for Basic Research in Chemistry starting in 1978, serving until the retirement age of 65, when he left the firm in 1987, Hirschmann played a pivotal role in the development of many of the firms products. Among the medications he was involved with was the development of the antiparasitic Ivermectin used for the treatment of river blindness, the statin
Statin
Statins are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver. Increased cholesterol levels have been associated with cardiovascular diseases, and statins are therefore used in the...
Mevacor for reducing cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
in patients at risk of cardiovascular disease
Cardiovascular disease
Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...
, the beta-lactam
Beta-lactam
A β-lactam ring, is a four-membered lactam. It is named as such, because the nitrogen atom is attached to the β-carbon relative to the carbonyl...
-family broad-spectrum antibiotic
Broad-spectrum antibiotic
The term broad-spectrum antibiotic refers to an antibiotic that acts against a wide range of disease-causing bacteria. A broad-spectrum antibiotic acts against both Gram-positive and Gram-negative bacteria, in contrast to a narrow-spectrum antibiotic, which is effective against specific families of...
Primaxin, the synthetic androgen
Androgen
Androgen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors...
Proscar used for the treatment of enlarged prostate
Benign prostatic hyperplasia
Benign prostatic hyperplasia also known as benign prostatic hypertrophy , benign enlargement of the prostate , and adenofibromyomatous hyperplasia, refers to the increase in size of the prostate....
and prostate cancer
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
and of the ACE inhibitor
ACE inhibitor
ACE inhibitors or angiotensin-converting enzyme inhibitors are a group of drugs used primarily for the treatment of hypertension and congestive heart failure...
Vasotec for treating hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
.
Following his departure from Merck, Hirschammn taught at the University of Pennsylvania and the University of South Carolina
University of South Carolina
The University of South Carolina is a public, co-educational research university located in Columbia, South Carolina, United States, with 7 surrounding satellite campuses. Its historic campus covers over in downtown Columbia not far from the South Carolina State House...
until his retirement in 2006.
Awards and recognition
He was awarded the National Medal of ScienceNational Medal of Science
The National Medal of Science is an honor bestowed by the President of the United States to individuals in science and engineering who have made important contributions to the advancement of knowledge in the fields of behavioral and social sciences, biology, chemistry, engineering, mathematics and...
in 2000 by President of the United States
President of the United States
The President of the United States of America is the head of state and head of government of the United States. The president leads the executive branch of the federal government and is the commander-in-chief of the United States Armed Forces....
Bill Clinton
Bill Clinton
William Jefferson "Bill" Clinton is an American politician who served as the 42nd President of the United States from 1993 to 2001. Inaugurated at age 46, he was the third-youngest president. He took office at the end of the Cold War, and was the first president of the baby boomer generation...
. He was presented the award at a December 1, 2000, dinner by Dr. Neal Francis Lane
Neal Francis Lane
Neal Francis Lane , is a U.S. physicist. He served as provost of Rice University and served as Science Advisor to the President of the United States. He has written extensively on theoretical physics and technology policy for the James A...
, Assistant to the President for Science & Technology:
"For his seminal contributions to organic and to medicinal chemistry including the synthesis in solution of an enzyme (ribonuclease), his stimulation of peptide research in the Pharmaceutical Industry and for his leadership role in fostering interdisciplinary research in academia and in industry, which led to the discovery of several widely prescribed medications for human and animal health."
Hirschmann received the Arthur C. Cope Award
Arthur C. Cope Award
The Arthur C. Cope Award is a prize awarded for achievement in the field of organic chemistry research. It is generally considered one of the highest honors in the field. It is sponsored by the Arthur C. Cope Fund, and has been awarded since 1973 by the American Chemical Society.Recipients...
for achievement in the field of organic chemistry research from the American Chemical Society
American Chemical Society
The American Chemical Society is a scientific society based in the United States that supports scientific inquiry in the field of chemistry. Founded in 1876 at New York University, the ACS currently has more than 161,000 members at all degree-levels and in all fields of chemistry, chemical...
in 1999. Merrifield was awarded the Nobel Prize in Chemistry
Nobel Prize in Chemistry
The Nobel Prize in Chemistry is awarded annually by the Royal Swedish Academy of Sciences to scientists in the various fields of chemistry. It is one of the five Nobel Prizes established by the will of Alfred Nobel in 1895, awarded for outstanding contributions in chemistry, physics, literature,...
in 1984 for the invention of solid phase peptide synthesis, with some, such as Daniel Rich of the American Chemical Society
American Chemical Society
The American Chemical Society is a scientific society based in the United States that supports scientific inquiry in the field of chemistry. Founded in 1876 at New York University, the ACS currently has more than 161,000 members at all degree-levels and in all fields of chemistry, chemical...
expressing that he was "surprised that Hirschmann didn't share the Nobel Prize".
The Ralph F. Hirschmann Award in Peptide Chemistry is given out "to recognize and encourage outstanding achievements in the chemistry, biochemistry, and biophysics of peptides." The award was established in 1988 by Merck Research Laboratories.
Personal
Hirschmann died at age 87 on June 29, 2009, due to renal failureRenal failure
Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
at his home in Lansdale, Pennsylvania
Lansdale, Pennsylvania
Lansdale is a borough in Montgomery County, Pennsylvania, 28 miles northwest of Philadelphia. Early in the 20th century, its industries included agricultural implement works, a canning factory, foundries, brickyards, a silk mill, and manufacturers of cigars, stoves, shirts, rope, iron drain pipe,...
. He was survived by his wife, the former Lucy Aliminosa, a chemist he had met at his laboratory. He was also survived by a daughter, a son and six grandchildren.