Michael Heidelberger - AbsoluteAstronomy.com

Michael Heidelberger was an American

United States

The United States of America is a federal constitutional republic comprising fifty states and a federal district...

immunologist who is regarded as the father of modern immunology. He and Oswald Avery

Oswald Avery

Oswald Theodore Avery ForMemRS was a Canadian-born American physician and medical researcher. The major part of his career was spent at the Rockefeller University Hospital in New York City...

showed that the polysaccharide

Polysaccharide

Polysaccharides are long carbohydrate molecules, of repeated monomer units joined together by glycosidic bonds. They range in structure from linear to highly branched. Polysaccharides are often quite heterogeneous, containing slight modifications of the repeating unit. Depending on the structure,...

s of pneumococcus are antigen

Antigen

An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...

s, enabling him to show that antibodies

Antibody

An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...

are protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

s. He spent almost his entire career at Columbia University

Columbia University

Columbia University in the City of New York is a private, Ivy League university in Manhattan, New York City. Columbia is the oldest institution of higher learning in the state of New York, the fifth oldest in the United States, and one of the country's nine Colonial Colleges founded before the...

, though in his later years he was also on the faculty of New York University

New York University

New York University is a private, nonsectarian research university based in New York City. NYU's main campus is situated in the Greenwich Village section of Manhattan...

. In 1934 and 1936 he received the Guggenheim Fellowship

Guggenheim Fellowship

Guggenheim Fellowships are American grants that have been awarded annually since 1925 by the John Simon Guggenheim Memorial Foundation to those "who have demonstrated exceptional capacity for productive scholarship or exceptional creative ability in the arts." Each year, the foundation makes...

. In 1967 he received the National Medal of Science

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 sciences, biology, chemistry, engineering, mathematics and...

, and then he earned the Lasker Award

Lasker Award

The Lasker Awards have been awarded annually since 1946 to living persons who have made major contributions to medical science or who have performed public service on behalf of medicine. They are administered by the Lasker Foundation, founded by advertising pioneer Albert Lasker and his wife Mary...

for basic medical research in 1953 and again in 1978.

Early life

Heidelberger was born in 1888 in New York City

New York City

New York is the most populous city in the United States and the center of the New York Metropolitan Area, one of the most populous metropolitan areas in the world. New York exerts a significant impact upon global commerce, finance, media, art, fashion, research, technology, education, and...

to David and Fannie Campe Heidelberger, a traveling salesman and a homemaker respectively. An older brother had died shortly after birth; a younger brother, David, was born 21 months after Michael. His paternal grandfather, also named Michael, was a German Jew who had emigrated to the United States in the wake of the German Revolution

German Revolution

The German Revolution was the politically-driven civil conflict in Germany at the end of World War I, which resulted in the replacement of Germany's imperial government with a republic...

of 1848.

Heidelberger's father had only an elementary school education, and was on the road for six months out of the year selling window curtains. It fell to Heidelberger's mother to take charge of the household and of Michael's education. She had attended a private girl's school in Norfolk, Virginia, and after graduation had stayed with relatives in Germany for a year. Until Michael was twelve, she taught him and his younger brother at home. They attended classical concerts, had to speak German at the table, and were taught French by a nanny during outings to nearby Central Park

Central Park

Central Park is a public park in the center of Manhattan in New York City, United States. The park initially opened in 1857, on of city-owned land. In 1858, Frederick Law Olmsted and Calvert Vaux won a design competition to improve and expand the park with a plan they entitled the Greensward Plan...

. Later in life he came to appreciate his early training in languages that were central to scientific discourse during the first half of the twentieth century.

Heidelberger decided at age eight that he wanted to be a chemist, for reasons he could never quite articulate or recall, but which he later judged no more than a "pigheaded idea." He experimented at home by mixing medicines and the very basic ingredients included in children's chemistry sets of the time, until he began his formal training in botany, zoology, physics, and chemistry at the Ethical Culture School, a private high school on New York's Upper West Side founded by the Ethical Culture Society, a Humanist

Humanism

Humanism is an approach in study, philosophy, world view or practice that focuses on human values and concerns. In philosophy and social science, humanism is a perspective which affirms some notion of human nature, and is contrasted with anti-humanism....

religious movement of which his parents were members. He maintained a connection with the school throughout his life, inviting student groups to visit his laboratory every year.

Heidelberger loved music and started playing the clarinet

Clarinet

The clarinet is a musical instrument of woodwind type. The name derives from adding the suffix -et to the Italian word clarino , as the first clarinets had a strident tone similar to that of a trumpet. The instrument has an approximately cylindrical bore, and uses a single reed...

in the high school orchestra. Heidelberger was talented enough that concert musicians encouraged him to consider a professional career in music. Instead, it became his "chief relaxation." He played the same two handmade wood instruments, a B flat and an A clarinet, all of his life, taking them with him wherever he went to join in chamber music performances at conferences or at the homes of friends.

Education and early research career

When Heidelberger entered Columbia University

Columbia University

in 1905, his family moved to the Upper West Side so that he could live nearer to the school. He resided there for the rest of his long life. He received all of his academic degrees from Columbia, culminating with a Ph.D. 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 1911. His dissertation dealt with quinazoline

Quinazoline

Quinazoline is a compound made up of two fused six-membered simple aromatic rings, a benzene ring and a pyrimidine ring. Its chemical formula is C8H6N2. Quinazoline is yellow and crystalline...

analogs, alkaloids that his adviser, Marston Taylor Bogert, hoped—wrongly, as Heidelberger proved—would produce useful dyes when combined with phthalic acid

Phthalic acid

Phthalic acid is an aromatic dicarboxylic acid, with formula C6H42. It is an isomer of isophthalic acid and terephthalic acid. Although phthalic acid is of modest commercial importance, the closely related derivative phthalic anhydride is a commodity chemical produced on a large...

. As a student he supported himself by selling Virginia hams to hotels and wholesale grocers around the city on Friday afternoons, earning up to $50 per week, and by teaching analytical chemistry under Irving Langmuir at Stevens Institute in Hoboken, New Jersey.

Urged on by his parents, Heidelberger after graduation with his Ph.D. arranged for a visit with his former family physician, Samuel J. Meltzer, who had seen him through typhoid fever as a young child and who had since become the first chair of the Department of Physiology at the newly-founded Rockefeller Institute of Medical Research. Meltzer curtly advised Heidelberger that he ought not to go into science, because "science is no profession for a poor man's son." Heidelberger quickly realized that Meltzer was testing his commitment to science, and he insisted that he wanted to become a chemist. Meltzer relented, and sent him on to meet with the Institute's chemists, Phoebus A. T. Levene

Phoebus Levene

Phoebus Aaron Theodore Levene, M.D. was a Russian-American biochemist who studied the structure and function of nucleic acids...

, Donald D. Van Slyke

Donald Van Slyke

Donald Dexter Van Slyke was a renowned Dutch American biochemist. His achievements included the publication of 317 journal articles and 5 books, as well as numerous awards, among them the National Medal of Science and the first AMA Scientific Achievement Award.-Early days and education:Van Slyke...

, and Walter A. Jacobs, whom Heidelberger found assembled over tea. They advised him to go to Europe for postdoctoral

Postdoctoral researcher

Postdoctoral research is scholarly research conducted by a person who has recently completed doctoral studies, normally within the previous five years. It is intended to further deepen expertise in a specialist subject, including acquiring novel skills and methods...

training, then a requirement for any scientist who wanted to find a position at a leading research university in the United States.

Heidelberger took their advice and in 1911 went to Zurich to work for a year in the laboratory of the organic chemist and future Nobel Laureate Richard Willstätter

Richard Willstätter

Richard Martin Willstätter was a German organic chemist whose study of the structure of plant pigments, chlorophyll included, won him the 1915 Nobel Prize for Chemistry. Willstätter invented paper chromatography independently of Mikhail Tsvet.-Biography:Willstätter was born in to a Jewish family...

at the Eidgenössische Technische Hochschule. There he perfected the synthesis of cyclooctatetraene

Cyclooctatetraene

1,3,5,7-Cyclooctatetraene is an unsaturated derivative of cyclooctane, with the formula C8H8. It is also known as [8]annulene. This polyunsaturated hydrocarbon is a colorless to light yellow flammable liquid at room temperature...

, an important intermediate in organic research. Willstätter helped his somewhat impecunious American student by sharing the cost of laboratory supplies with him, arranging that when expensive materials, such as silver nitrate, were to be bought, it was his turn to pay, while Heidelberger took turns buying cheaper materials like sulfuric acid. "Better training than that you couldn't have," Heidelberger summed up his experience with Willstätter. They remained friends for three decades, through Willstätter's flight from Germany in 1938 and until his death in Switzerland in 1942.

While visiting relatives in Germany on his return from Zurich, Heidelberger received a telegram from his father relating an offer of a position of Fellow of the Rockefeller Institute, conditional upon a personal interview and approval by the Institute's director, Simon Flexner.

Rockefeller Institute

Heidelberger passed muster, and in September 1912 began working in Walter Abraham Jacobs‎' laboratory on a derivative of hexamethylene tetramine, a complex that seemed to prolong the life of monkeys suffering from polio, and that Flexner hoped could be adapted for use in humans. Results appeared promising at first, but Heidelberger and Jacobs later attributed them to loss of virulence of the virus.

In the summer of 1915, after attending officer training camp in Plattsburgh, New York, for a proposed volunteer army (an outgrowth of the movement to prepare the United States for entry into World War I

World War I

World War I , which was predominantly called the World War or the Great War from its occurrence until 1939, and the First World War or World War I thereafter, was a major war centred in Europe that began on 28 July 1914 and lasted until 11 November 1918...

) and earning a commendation as a marksman, Heidelberger traveled to Lake Kezar in Maine for a vacation. After performing Pergolese's Nina there, his piano accompanist exclaimed, "meet Nina," and in walked a young lady, Nina Tachau. They were married in 1916 to the strains of a wedding march composed by Heidelberger. She was a writer and activist for the New York chapter of the League of Women Voters

League of Women Voters

The League of Women Voters is an American political organization founded in 1920 by Carrie Chapman Catt during the last meeting of the National American Woman Suffrage Association approximately six months before the Nineteenth Amendment to the United States Constitution gave women the right to vote...

and, during the 1940s, for the American Association for the United Nations. After her death from cancer in 1946, Heidelberger continued her work on behalf of the United Nations

United Nations

The United Nations is an international organization whose stated aims are facilitating cooperation in international law, international security, economic development, social progress, human rights, and achievement of world peace...

, and was a member of the U.S. delegation to meetings of the World Federation of United Nations Organizations in Prague, Bangkok, and other cities. He met his second wife Charlotte Rosen at a concert. She was the violist in a Mozart trio in which Heidelberger performed. They married in 1956. For ten years prior to her death in 1988, he took care of her at home while she suffered from Alzheimer's disease.

After the United States declared war on Germany in April 1917, Heidelberger was commissioned in the Sanitary Corps and assigned to the Rockefeller Institute. He continued to work with Jacobs, a collaboration that lasted more than nine years and produced 44 papers. They synthesized many chemotherapeutical drugs, namely aromatic arsenicals, for the treatment for infectious diseases, in particular syphilis

Syphilis

Syphilis is a sexually transmitted infection caused by the spirochete bacterium Treponema pallidum subspecies pallidum. The primary route of transmission is through sexual contact; however, it may also be transmitted from mother to fetus during pregnancy or at birth, resulting in congenital syphilis...

and African sleeping sickness. In 1919 they developed a variant of Paul Ehrlich's "magic bullet" for syphilis, Salvarsan, which proved effective against trypanosome

Trypanosoma brucei

Trypanosoma brucei is a parasitic protist species that causes African trypanosomiasis in humans and nagana in animals in Africa. There are 3 sub-species of T. brucei: T. b. brucei, T. b. gambiense and T. b. rhodesiense.These obligate parasites have two hosts - an insect vector and mammalian host...

s, the parasites that cause African sleeping sickness. Variants of tryparsamide, as Flexner named it, continue to be administered today. In 1953 the king of Belgium, colonial ruler of parts of Africa in which African sleeping sickness had been endemic, honored Heidelberger and Jacobs for their discovery.

In 1921 Heidelberger transferred to the laboratory of Donald D. Van Slyke at the Rockefeller hospital, where he spent the next two years developing a method for preparing large quantities of purified oxyhemoglobin, with its oxygen-carrying capacity intact, for Van Slyke's studies of the uptake and release of oxygen in the blood. When Karl Landsteiner

Karl Landsteiner

Karl Landsteiner , was an Austrian-born American biologist and physician of Jewish origin. He is noted for having first distinguished the main blood groups in 1900, having developed the modern system of classification of blood groups from his identification of the presence of agglutinins in the...

, the famous Austrian immunologist and discoverer of human blood groups, arrived at the Institute in 1922, Heidelberger embarked with him on studies of the antigen

Antigen

ic properties of different types of hemoglobin

Hemoglobin

Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...

. Throughout his life Heidelberger was proud to state that he first learned immunology from Landsteiner.

During this time Heidelberger was approached by the bacteriologist Oswald Avery

Oswald Avery

Oswald Theodore Avery ForMemRS was a Canadian-born American physician and medical researcher. The major part of his career was spent at the Rockefeller University Hospital in New York City...

to help him elucidate the chemistry of the "specific soluble substance" Avery and Alphonse R. Dochez had found in the spherical capsule that envelops pneumococcus and many other species of bacteria. In 1923, Heidelberger and Avery reported that this capsular substance, which determined the specific type of pneumococcus and, with it, its virulence, consisted of polysaccharide

Polysaccharide

s, carbohydrate molecules made up of more than three monosaccharide units. Their discovery for the first time established a relationship between chemical constitution and immunological specificity of antigens, thereby putting the field of immunology on a firm biochemical footing. It also disproved prevailing assumptions among scientists that only proteins could act as antigens.

Heidelberger devoted the rest of his career largely to pursuing the consequences of his and Avery's seminal discovery. He identified and analyzed the structure of different pneumococcal polysaccharides—over one hundred have since been found—as well as of other microorganisms, and studied their role in immune reactions. In 1927 he left the Rockefeller Institute to become head of the chemical laboratory at Mount Sinai Hospital

Mount Sinai Hospital, New York

Mount Sinai Hospital, founded in 1852, is one of the oldest and largest teaching hospitals in the United States. In 2011-2012, Mount Sinai Hospital was ranked as one of America's best hospitals by U.S...

. A year later he moved to the Columbia University College of Physicians and Surgeons

Columbia University College of Physicians and Surgeons

Columbia University College of Physicians and Surgeons, often known as P&S, is a graduate school of Columbia University that is located on the health sciences campus in the Washington Heights neighborhood of Manhattan...

Columbia University

His role as consulting chemist in its Department of Medicine suited his generous temperament. The door to his office, which he likened to "42nd Street and Broadway" because of its traffic, was open for anyone, especially junior researchers, to stop by, discuss matters of science or politics, and seek his advice. During his 27 years there he used his unique knowledge of polysaccharide antigen chemistry to develop methods, in particular the precipitin

Precipitin

A precipitin is an antibody which can precipitate out of a solution upon antigen binding.-Precipitin reaction:The precipitin reaction provided the first quantitative assay for antibody, which has since been rendered obsolete by current diagnostic techniques such as ELISA and RIA...

reaction, for isolating pure antibodies, which he proved were protein and which he measured in absolute units of weight for the first time.

He and his collaborators Forrest E. Kendall and Elvin A. Kabat

Elvin A. Kabat

Elvin Abraham Kabat was an Americanbiomedical scientist who is considered one of the founding fathers of modern quantitative immunochemistry together with his mentor Michael Heidelberger...

formulated a quantitative theory of precipitin and other immune reactions, which showed that such reactions unfolded in three distinct stages and which posited that antigens and antibodies were bi-or multivalent, meaning that they could combine in varying proportions. These findings enabled Heidelberger to develop a much more potent antiserum to meningitis

Meningitis

Meningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs...

in infants, as well as a simple but effective vaccine against several forms of pneumonia, which was successfully tested among Army Air Force recruits in 1944.

Later life

Upon his retirement from Columbia in 1954, Heidelberger moved to the Institute of Microbiology at Rutgers University

Rutgers University

Rutgers, The State University of New Jersey , is the largest institution for higher education in New Jersey, United States. It was originally chartered as Queen's College in 1766. It is the eighth-oldest college in the United States and one of the nine Colonial colleges founded before the American...

, and in 1964 to the New York University School of Medicine

New York University School of Medicine

The New York University School of Medicine is one of the graduate schools of New York University. Founded in 1841 as the University Medical College, the NYU School of Medicine is one of the foremost medical schools in the United States....

. There he continued his research on pneumococcal polysaccharides and their cross-reactions with various types of antisera, always in pursuit of his lifelong objective to relate chemical structure to immunological specificity, until his death in 1991.

Heidelberger received fifteen honorary degrees and 46 medals, citations, and awards for his work, including two Albert Lasker Awards in 1953 and 1978, the Louisa Gross Horwitz Prize

Louisa Gross Horwitz Prize

Louisa Gross Horwitz Prize for Biology or Biochemistry is an annual prize awarded by Columbia University to a researcher or group of researchers that have made an outstanding contribution in basic research in the fields of biology or biochemistry....

in 1977,the National Medal of Science

National Medal of Science

from President Lyndon B. Johnson in 1967, and the Bronze Medal of the City of Paris in 1964. He was a member of the National Academy of Sciences and the New York Academy of Medicine, as well as an officer of the Légion d'honneur of France. He served twice as president of the American Association of Immunologists, in 1947 and 1949. Both times his presidential addresses urged scientists to resist nuclear armament and restrictions on free exchanges among scientists across national boundaries imposed in the name of national loyalty and security.

External Links

Eisen, H. N. Michael Heidelberger, Biographical Memoirs of the National Academy of Sciences
The Official Site of Louisa Gross Horwitz Prize
Michael Heidelberger Papers (1901-1990) - National Library of Medicine finding aid
The Michael Heidelberger Papers - Profiles in Science, National Library of Medicine

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