Ralph F. Hirschmann
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Ralph Franz Hirschmann (May 6, 1922 – June 20, 2009) was a German American
chemist A chemist (from Greek ''chēm(ía)'' alchemy; replacing ''chymist'' from Medieval Latin ''alchemist'') is a scientist trained in the study of chemistry. Chemists study the composition of matter and its properties. Chemists carefully describe t ...
who led a team that was responsible for the first organic synthesis of an
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
, a
ribonuclease Ribonuclease (commonly abbreviated RNase) 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 ...
.


Early life and education

Born on May 6, 1922, in
Fürth Fürth (; East Franconian: ; yi, פיורדא, Fiurda) is a city in northern Bavaria, Germany, in the administrative division ('' Regierungsbezirk'') of Middle Franconia. It is now contiguous with the larger city of Nuremberg, the centres of the ...
, he emigrated from
Nazi Germany Nazi Germany (lit. "National Socialist State"), ' (lit. "Nazi State") for short; also ' (lit. "National Socialist Germany") (officially known as the German Reich from 1933 until 1943, and the Greater German Reich from 1943 to 1945) was ...
in 1936 and settled with his family in Kansas City, Missouri. He became a
naturalized citizen Naturalization (or naturalisation) is the legal act or process by which a non-citizen of a country may acquire citizenship or nationality of that country. It may be done automatically by a statute, i.e., without any effort on the part of the in ...
of the United States in 1944. After graduating from Oberlin College in 1943, he served in the
United States Army The United States Army (USA) is the land warfare, land military branch, service branch of the United States Armed Forces. It is one of the eight Uniformed services of the United States, U.S. uniformed services, and is designated as the Army o ...
for three years in the Pacific Theater of Operations. Following the completion of his military service, Hirschmann attended the
University of Wisconsin–Madison A university () is an institution of higher (or tertiary) education and research which awards academic degrees in several academic disciplines. Universities typically offer both undergraduate and postgraduate programs. In the United Stat ...
, receiving his
Doctor of Philosophy A Doctor of Philosophy (PhD, Ph.D., or DPhil; Latin: or ') is the most common degree at the highest academic level awarded following a course of study. PhDs are awarded for programs across the whole breadth of academic fields. Because it is ...
in
organic chemistry Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms.Clayden, ...
in 1950.


Medicinal Chemistry career

While at Merck & Co., 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 (July 15, 1921 – May 14, 2006) was an American biochemist who won the Nobel Prize in Chemistry in 1984 for the invention of solid phase peptide synthesis. Early life He was born in Fort Worth, Texas, on 15 July 1921, ...
at Rockefeller University who also achieved synthesis of the same enzyme using a different method. The comparatively simple 124-
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...
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 Times'', ''NYT'', or the Gray Lady) is a daily newspaper based in New York City with a worldwide readership reported in 2020 to comprise a declining 840,000 paid print subscribers, and a growing 6 million paid d ...
'', 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 Biology is the scientific study of life. It is a natural science with a broad scope but has several unifying themes that tie it together as a single, coherent field. For instance, all organisms are made up of cells that process hereditary i ...
", and that by the time of Hirschmann's death the accomplishment was "just routine". Chemist Gary Molander of the
University of Pennsylvania The University of Pennsylvania (also known as Penn or UPenn) is a private research university in Philadelphia. It is the fourth-oldest institution of higher education in the United States and is ranked among the highest-regarded universitie ...
described how " zens of biotechnology and drug companies were started" based on Hirschmann's developments and that " e whole
biotechnology Biotechnology is the integration of natural sciences and engineering sciences in order to achieve the application of organisms, cells, parts thereof and molecular analogues for products and services. The term ''biotechnology'' was first used ...
field" and new classes of medicines, such as
protease inhibitors Protease inhibitors (PIs) are medications that act by interfering with enzymes that cleave proteins. Some of the most well known are antiviral drugs widely used to treat HIV/AIDS and hepatitis C. These protease inhibitors prevent viral replicat ...
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 firm's products.Staff
"Alumni Ralph Hirschmann Passes Away at 87"
,
University of Wisconsin A university () is an institution of higher (or tertiary) education and research which awards academic degrees in several academic disciplines. Universities typically offer both undergraduate and postgraduate programs. In the United States, ...
press release. Accessed July 19, 2009.
Among the medications he was involved with was the development of the
antiparasitic Antiparasitics are a class of medications which are indicated for the treatment of parasitic diseases, such as those caused by helminths, amoeba, ectoparasites, parasitic fungi, and protozoa, among others. Antiparasitics target the parasitic age ...
Ivermectin Ivermectin (, '' EYE-vər-MEK-tin'') is an antiparasitic drug. After its discovery in 1975, its first uses were in veterinary medicine to prevent and treat heartworm and acariasis. Approved for human use in 1987, today it is used to treat i ...
used for the treatment of
river blindness Onchocerciasis, also known as river blindness, is a disease caused by infection with the parasitic worm ''Onchocerca volvulus''. Symptoms include severe itching, bumps under the skin, and blindness. It is the second-most common cause of blindne ...
, the
statin Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease. They are the most common cholesterol-lowering drugs. Low ...
Mevacor Lovastatin, sold under the brand name Mevacor among others, is a statin medication, to treat high blood cholesterol and reduce the risk of cardiovascular disease. Its use is recommended together with lifestyle changes. It is taken by mouth. ...
for reducing
cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...
in patients at risk of cardiovascular disease, the
beta-lactam A beta-lactam (β-lactam) ring is a four-membered lactam. A ''lactam'' is a cyclic amide, and ''beta''-lactams are named so because the nitrogen atom is attached to the β-carbon atom relative to the carbonyl. The simplest β-lactam possible i ...
-family
broad-spectrum antibiotic A broad-spectrum antibiotic is an antibiotic that acts on the two major bacterial groups, Gram-positive and Gram-negative, or any antibiotic that acts against a wide range of disease-causing bacteria. These medications are used when a bacterial ...
Primaxin, the synthetic
androgen An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This in ...
Proscar used for the treatment of
enlarged prostate Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. Symptoms may include frequent urination, trouble starting to urinate, weak stream, inability to urinate, or loss o ...
and prostate cancer and of the ACE inhibitor Vasotec for treating hypertension. Following his departure from Merck, Hirschmann taught at the University of Pennsylvania and the
Medical University of South Carolina The Medical University of South Carolina (MUSC) is a public medical school in South Carolina. It opened in 1824 in Charleston as a small private college aimed at training physicians and has since established hospitals and medical facilities ac ...
until his retirement in 2006.


Awards and recognition

When Merrifield was awarded the
Nobel Prize in Chemistry ) , image = Nobel Prize.png , alt = A golden medallion with an embossed image of a bearded man facing left in profile. To the left of the man is the text "ALFR•" then "NOBEL", and on the right, the text (smaller) "NAT•" then "M ...
in 1984 for the invention of
solid phase peptide synthesis In organic chemistry, peptide synthesis is the production of peptides, compounds where multiple amino acids are linked via amide bonds, also known as peptide bonds. Peptides are chemically synthesized by the condensation reaction of the carboxy ...
some, such as Daniel Rich of the
American Chemical Society The American Chemical Society (ACS) 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 155,000 members at all ...
expressed the view that he was "surprised that Hirschmann didn't share the Nobel Prize". He was awarded the
National 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 scienc ...
in 2000 by
President of the United States The president of the United States (POTUS) is the head of state and head of government of the United States of America. The president directs the executive branch of the federal government and is the commander-in-chief of the United States ...
Bill Clinton William Jefferson Clinton ( né Blythe III; born August 19, 1946) is an American politician who served as the 42nd president of the United States from 1993 to 2001. He previously served as governor of Arkansas from 1979 to 1981 and agai ...
. He was presented the award at a December 1, 2000, dinner by Dr. Neal Francis Lane, 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 The Arthur C. Cope Award is a prize awarded for achievement in the field of organic chemistry research. It is sponsored by the Arthur C. Cope Fund, and has been awarded annually since 1973 by the American Chemical Society. It consists of $25,000, ...
for achievement in the field of organic chemistry research from the
American Chemical Society The American Chemical Society (ACS) 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 155,000 members at all ...
in 1999Downey, Sally A
"Medicinal chemist honored nationally"
''
The Philadelphia Inquirer ''The Philadelphia Inquirer'' is a daily newspaper headquartered in Philadelphia, Pennsylvania. The newspaper's circulation is the largest in both the U.S. state of Pennsylvania and the Delaware Valley metropolitan region of Southeastern Pennsy ...
'', June 28, 2009. Accessed July 19, 2009.
and the
American Institute of Chemists Gold Medal The American Institute of Chemists Gold Medal is the highest award of the American Institute of Chemists The American Institute of Chemists (AIC) is an organization founded in 1923 with the goal of advancing the chemistry profession in the Uni ...
in 2003. 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 failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
at his home in
Lansdale, Pennsylvania Lansdale is a borough in Montgomery County, Pennsylvania, United States. It is a densely-populated commuter town, with many residents traveling daily to Philadelphia using SEPTA Regional Rail's Lansdale/Doylestown Line. In 1900, 2,754 people live ...
.


References

{{DEFAULTSORT:Hirschmann, Ralph American biochemists United States Army personnel of World War II Deaths from kidney failure Bavarian emigrants to the United States National Medal of Science laureates Oberlin College alumni University of Wisconsin–Madison College of Letters and Science alumni People from Fürth People from Lansdale, Pennsylvania Scientists from Kansas City, Missouri United States Army soldiers University of Pennsylvania faculty Medical University of South Carolina faculty 1922 births 2009 deaths Members of the United States National Academy of Sciences Chemists from Missouri Members of the National Academy of Medicine