Ralph Franz Hirschmann (May 6, 1922 – June 20, 2009) was a

German American German Americans (, ) are Americans who have full or partial German ancestry. According to the United States Census Bureau's figures from 2022, German Americans make up roughly 41 million people in the US, which is approximately 12% of the pop ...

chemist A chemist (from Greek ''chēm(ía)'' alchemy; replacing ''chymist'' from Medieval Latin ''alchemist'') is a graduated scientist trained in the study of chemistry, or an officially enrolled student in the field. Chemists study the composition of ...

who led a team that was responsible for the first

organic synthesis Organic synthesis is a branch of chemical synthesis concerned with the construction of organic compounds. Organic compounds are molecules consisting of combinations of covalently-linked hydrogen, carbon, oxygen, and nitrogen atoms. Within the gen ...

of an

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

, 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 th ...

Early life and education

Born on May 6, 1922, in

Fürth Fürth (; East Franconian German, East Franconian: ; ) is a List of cities and towns in Germany, city in northern Bavaria, Germany, in the administrative division (''Regierungsbezirk'') of Middle Franconia. It is the Franconia#Towns and cities, s ...

, he emigrated from

Nazi Germany Nazi Germany, officially known as the German Reich and later the Greater German Reich, was the German Reich, German state between 1933 and 1945, when Adolf Hitler and the Nazi Party controlled the country, transforming it into a Totalit ...

in 1936 and settled with his family in

Kansas City, Missouri Kansas City, Missouri, abbreviated KC or KCMO, is the largest city in the U.S. state of Missouri by List of cities in Missouri, population and area. The city lies within Jackson County, Missouri, Jackson, Clay County, Missouri, Clay, and Pl ...

. He became a

naturalized citizen Naturalization (or naturalisation) is the legal act or process by which a non-national of a country acquires the nationality of that country after birth. The definition of naturalization by the International Organization for Migration of the ...

of the United States in 1944. After graduating from

Oberlin College Oberlin College is a Private university, private Liberal arts colleges in the United States, liberal arts college and conservatory of music in Oberlin, Ohio, United States. Founded in 1833, it is the oldest Mixed-sex education, coeducational lib ...

in 1943, he served in the

United States Army The United States Army (USA) is the primary Land warfare, land service branch of the United States Department of Defense. It is designated as the Army of the United States in the United States Constitution.Article II, section 2, clause 1 of th ...

for three years in the Pacific Theater of Operations. Following the completion of his military service, Hirschmann attended the

University of Wisconsin–Madison The University of Wisconsin–Madison (University of Wisconsin, Wisconsin, UW, UW–Madison, or simply Madison) is a public land-grant research university in Madison, Wisconsin, United States. It was founded in 1848 when Wisconsin achieved st ...

, receiving his

Doctor of Philosophy A Doctor of Philosophy (PhD, DPhil; or ) is a terminal degree that usually denotes the highest level of academic achievement in a given discipline and is awarded following a course of Postgraduate education, graduate study and original resear ...

organic chemistry Organic chemistry is a subdiscipline within chemistry involving the science, scientific study of the structure, properties, and reactions of organic compounds and organic matter, organic materials, i.e., matter in its various forms that contain ...

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 at

Rockefeller University The Rockefeller University is a Private university, private Medical research, biomedical Research university, research and graduate-only university in New York City, New York. It focuses primarily on the biological and medical sciences and pro ...

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 over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 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'' (''NYT'') is an American daily newspaper based in New York City. ''The New York Times'' covers domestic, national, and international news, and publishes opinion pieces, investigative reports, and reviews. As one of ...

'', 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 is the scientific study of the properties and behavior of matter. It is a physical science within the natural sciences that studies the chemical elements that make up matter and chemical compound, compounds made of atoms, molecules a ...

and

biology Biology is the scientific study of life and living organisms. It is a broad natural science that encompasses a wide range of fields and unifying principles that explain the structure, function, growth, History of life, origin, evolution, and ...

", 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 (Penn or UPenn) is a Private university, private Ivy League research university in Philadelphia, Pennsylvania, United States. One of nine colonial colleges, it was chartered in 1755 through the efforts of f ...

described how " zens of biotechnology and drug companies were started" based on Hirschmann's developments and that " e whole

biotechnology Biotechnology is a multidisciplinary field that involves the integration of natural sciences and Engineering Science, engineering sciences in order to achieve the application of organisms and parts thereof for products and services. Specialists ...

field" and new classes of medicines, such as

protease inhibitors Protease inhibitors (PIs) are medications that act by interfering with protease, enzymes that cleave proteins. Some of the most well known are antiviral drugs widely used to treat HIV/AIDS, hepatitis C and COVID-19. These protease inhibitors pre ...

for the treatment of

AIDS The HIV, human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system. Without treatment, it can lead to a spectrum of conditions including acquired immunodeficiency syndrome (AIDS). It is a Preventive healthcare, pr ...

, 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 tertiary education and research which awards academic degrees in several academic disciplines. ''University'' is derived from the Latin phrase , which roughly means "community of teachers and scholars". Uni ...

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 ...

Ivermectin Ivermectin 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, it is used to treat infestations including head lice ...

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 (or HMG-CoA reductase inhibitors) are a class of medications that lower cholesterol. They are prescribed typically to people who are at high risk of cardiovascular disease. Low-density lipoprotein (LDL) carriers of cholesterol play ...

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 the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all anima ...

in patients at risk of

cardiovascular disease Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina, heart attack), heart failure, hypertensive heart disease, rheumati ...

, the beta-lactam-family

broad-spectrum antibiotic A broad-antimicrobial spectrum, 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 ...

Primaxin, the synthetic

androgen An androgen (from Greek ''andr-'', the stem of the word meaning ) is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This includes ...

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 lo ...

and

prostate cancer Prostate cancer is the neoplasm, uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Abnormal growth of the prostate tissue is usually detected through Screening (medicine), screening tests, ...

and of the

ACE inhibitor Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of high blood pressure and heart failure. This class of medicine works by causing relaxation of blood vessels as well as a decr ...

Vasotec for treating

hypertension Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...

. 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 Charleston, South Carolina. It opened in 1824 as a small private college aimed at training physicians and has since established hospitals and medical facilities acros ...

until his retirement in 2006.

Awards and recognition

When Merrifield was awarded the

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 outst ...

in 1984 for the invention of solid phase peptide synthesis 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 science, behavior ...

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. The president directs the Federal government of the United States#Executive branch, executive branch of the Federal government of t ...

Bill Clinton William Jefferson Clinton (né Blythe III; born August 19, 1946) is an American politician and lawyer who was the 42nd president of the United States from 1993 to 2001. A member of the Democratic Party (United States), Democratic Party, ...

. 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 for achievement in the field of organic chemistry research from the

in 1999Downey, Sally A
"Medicinal chemist honored nationally"
''

The Philadelphia Inquirer ''The Philadelphia Inquirer'', often referred to simply as ''The Inquirer'', is a daily newspaper headquartered in Philadelphia, Pennsylvania. Founded on June 1, 1829, ''The Philadelphia Inquirer'' is the third-longest continuously operating da ...

'', 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 and has been awarded since 1926. It is presented annually to a person who has most encouraged the science of chemistry or the profession of ...

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 renal failure or end-stage renal disease (ESRD), 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 fa ...

at his home in

Lansdale, Pennsylvania Lansdale is a Borough (Pennsylvania), 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. I ...

References

{{DEFAULTSORT:Hirschmann, Ralph American biochemists United States Army personnel of World War II Deaths from kidney failure in the United States Emigrants from Nazi Germany 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