Niels Jerne

Niels Kaj Jerne was born on December 23, 1911 in London, England. His family had lived on the Danish island Fano since the seventeenth century. His father, Hans Jerne and mother, Else Lindberg, moved to London, England in 1910, the year before his birth. During the World War I the family lived in Rotterdam, Netherlands, where he spent his youth and earned his bachelors degree in 1928. After spending two years studying physics in Lieden, he moved to Copenhagen where he studied medicine, earning a medical degree in 1947 and a doctorate in 1951.

From 1943 to 1956 Jerne worked at the Danish National Serum Institute. During this time he proposed the theory of antibody selection, that the immune system produced a multitude of antibodies and through interactions with antigen (a molecule recognized by antibodies) antibodies were selected and the immune system produced more of them. This theory was later refined by David Talmadge and Frank Macfarlane Burnet, who separately proposed the genetic mechanism by which antibody producing cells each pick the DNA that will code for the cell's antibodies. Antibody producing cells are part of the body's humoral immune response. Antibodies are protein molecules that recognize and bind a particular antigen. Because they have multiple binding sites antibodies, when bound to antigen, can form large clumps. In a addition to their binding sites, antibodies have a site recognized by phagocytic cells. When large clumps of antibody/antigen complex form these recognition sites serve to signal phagocytic cells to devour it.

Starting in 1956 Jerne worked for the World Health Organization in Geneva. In 1962 he moved to the University of Pittsburg in Pittsburgh, Pennsylvania. From 1966 to 1969 he was director of the Paul-Erlich Institute and from 1969 to his retirement in 1980 he ran his own institute as director of the Basel Institute of Immunology. While there Jerne was the first to speculate about the role of the major histocompatability complex. This is a protein complex produced by cells that presents antigens on the cells surface. This is recognized by T-lymphocytes. When the antigen is recognized it means that it is foreign to the body and stimulates an immune response from the T-cell. T-cells then activate and secrete chemicals to stimulate the immune response.

Jerne's other major contribution to immunology was the idea that the immune system functions as a network, each part influencing the others. This is how the immune system is viewed today, where immune cells secrete an array of cytokines, hormones that influence the functions of the other cells of the body and the immune system. This paradigm has allowed immunologists to better understand immune cell dysfunction and the effects of the viral infection of immune cells in HIV infection. For his contributions to our understanding of immunology Jerne was awarded the 1984 Nobel Prize in Medicine, with Georges Kohler and Cesar Milstein.

Jerned died on October 7, 1994.


References:

Hoffmann, Geoffrey, W.; "Niels Jerne, Immunologist: 1911-1994"; Vaccine Research (1994)3

Nobel autobiography

Neils Gerne Wikipedia entry

Theobald Smith

Theobald Smith was born on July 31, 1859 in Albany, New York. His father, a German immigrant, ran a small tailoring shop. His mother taught him to play the piano at an early age and he was a good student in math. Smith attended public schools in Albany and won a full tuition scholarship to Cornell University. While at Cornell he earned extra money playing a church organ. He graduated from Cornell in 1881.

After graduation Smith initially intended to go into teaching, but he was unable to find a teaching job. His second choice was medicine and so he attended Albany Medical College graduating in 1883. After two years of medical school he did not feel himself ready for clinical practice so he returned to Cornell for graduate school and began working for Daniel E. Salmon at the newly established Bureau of the Animal Industry, which had been set up by the U.S. Congress in 1884 to fight animal diseases. Without any training in microbiology Smith taught himself by reading the papers of Pasteur, Koch, and Virchow. While at the BAI Smith isolated for the first time what came to be called Salmonella (named after Daniel Salmon) and was able to prove that Texas fever, a debilitating cattle disease, was carried by ticks. This was the first discovery of an arthropod borne disease.

In 1895 Smith took over running the Massachusetts State State Antitoxin Laboratory and in 1896 became professor of comparative pathology at Harvard University. While in Boston he continued his research on animal diseases and established that if animals are repeatedly exposed to a bacteria they become hypersensitive to it. This phenomena is known as anaphylaxis. His work on vaccines established that killed bacteria could act to generate immunity to living bacteria and he established that diphtheria could be vaccinated against by combining diphtheria toxin with its anti-toxin in a vaccine. In 1915 Smith left Harvard for the Rockefeller Institute for Medical Research as the head of the Department of Animal Pathology. He remained at the Rockefeller institute until his retirement in 1929.

Smith was considered on of the most notable figures in American medicine at the time. Honors won by Smith include the Copley Medal, awarded by the Royal Society in 1933 and eleven honorary degrees from prestigious universities.

Smith died on December 10, 1934.

References:

Schultz, Myron; "Theobald Smith"; Emerging Infectious Diseases 14:1940-1942 (2008)

Zinsser, Hans; "Biographical Memior of Theobald Smith: 1859-1934" in Biographical Memiors Vol. 17; National Academy Press 1936

Theobald Smith Wikipedia Entry

Marian Elliot Koshland

Marian Elliot Koshland was born in New Haven, Connecticut on October 15, 1921 to Margarethe Smith Elliot, a teacher and Walter Elliot a hardware salesman. When she was four, her younger brother contracted typhoid fever. While her parents sat vigil at her brother's hospital bedside, two girls next door taught her to read and do math. After her brother returned home, she and her brother were kept in quarantine by her parents for the next year. Her father took the part of schoolmaster, teaching his daughter. When she went to schools she was more advanced than her peers, giving her a confidence in her ability to learn. In high school she took the hardest classes and after graduation was admitted to Vassar College, where she supported herself with scholarships and lived in a co-op dormitory. She graduated in 1942 with a B.A. in bacteriology.

After graduation she spent one year at medical school, but opted to go to the University of Chicago where she earned a M.S. in bacteriology (1943) and a Ph.D. in immunology (1949). While at the University of Chicago she worked on two projects, one was a vaccine for cholera, intended to help service men serving in the Far East and the other was working on ways to prevent the spread of disease among military recruits. In 1945 she married Daniel Koshland and went to Oak Ridge, Tennessee to be with her husband and work on the Manhattan Project. In Oak Ridge she studied the biological effects of radiation. After she and her husband graduated, in 1949, they moved to Boston, Massachusetts, where both had postdoctoral positions at Harvard. After two years they moved to Long Island, where they both worked at Brookhaven National Laboratory and in 1965 they moved to Berkeley. At Brookhaven she was initially refused a position, but in exchange for editing the publications that followed Brookhaven symposia she was able to get a laboratory and an assistant. The Koshlands had five children, the first comming while they were graduate students at the University of Chicago, the second in 1949, two years later they had twins and the youngest child was born in 1953.

Koshland's research dealt with antibodies. Antibodies are molecules that are secreted by immune cells that attach to molecules that are foreign to the body and signal the immune system's other cells to destroy them. In the 1950's at Brookhaven, Koshland determined that there were more than one type of antibodies. She discovered that immune cells that protect mucosal cells (cells that compose outer layers of tissue, exposed to an environment, in the stomach or lungs for example) secrete a different type of antibody than the immune cells that circulate in the blood. Later, during the 1960s, she determined the amino acid structure of antibodies that bind to different pathogens is different. At the time it was believed that antibodies could bind to different things by means of different protein folds. She proved that it was different amino acids in the structure of antibodies that give them the ability to bind to different things. In the 1970s she identified a antibody protein called the j-chain (or joining chain) that allows antibodies to assemble into multiple units. The antibody secreted by circulating immune cells (called IgG) is composed of four protein molecules and has only two spaces where it binds to another protein. Some antibody complexes are larger and as many as five or six of these IgG-like units (composed of four protein molecules with two binding spots) which give them as many as ten or twelve spots to bind foreign molecules and some use this j-chain to put more than one IgG-like unit together (for an article about the structure of the different types of antibodies go here).

In 1991 Koshland was elected to the National Academy of Science. She served as the chair of the U.C. Berkeley Department of Immunology and Bacteriology from 1981 to 1989 and she has been awarded numerous honorary degrees.

She died of lung cancer on October 28, 1996.


References:

Guyer, Ruth Levey; "Marian Elliot Koshland"; Biographical Memoirs Vol. 90; National Academy Press; 2009

Saunders, Robert; Press Release on the death of Marian Koshland; November 6, 1997

Wasserman, Elga; The Door in the Dream: Conversations with Eminent Women in Science; Joseph Henry Press; 2002

Jules Bordet

Jules Jean Baptiste Vincent Bordet was born on June 13, 1870 in Soignies, Belgium, a small town 23 miles south west of Brussels. In 1874 his father, Charles Bordet, a schoolteacher, was appointed to the Ecole Moyenne, a primary school. Both, Jules and his older brother Charles Jr. attended the Ecole Moyenne and then received their secondary education at the Athenne Royal of Brussels.

While attending the Athenne Royal Bordet became interested in chemistry and constructed a laboratory at home. He entered the medical program at the free University of Brussels at the age of sixteen, graduating, with his doctorate in 1892. He began doing research while still in medical school, publishing a paper in the Annels de l'Institute Pasteur in 1892.

In 1794 Bordet went to Paris to work at the Pasteur Institute sponsored by a scholarship from the Belgian government. In Paris he worked in the laboratory of the Ukrainian born scientist Ilya Metchnikoff. Bordet's experiments showed that there were two distinct elements present in immune sera needed to cause the lysis of bacterial cell walls. The first was a specific antibody, recognizing the particular kind of bacteria present, generated by the immune system in response to the bacteria. Antibodies are protein molecules that specifically bind to bacteria. The second is a nonspecific response, that is heat sensitive, that works in concert with the antibody response to lyse invading bacteria. Bordet called this second element "alexine", today it is called compliment. The insight that allowed Bordet to distinguish the two elements was that the compliment is sensitive to heat and can be destroyed by heating above 57 degrees Celsius, the antibody response is not destroyed by heating above 57 degrees.

Compliment is a biochemical cascade that works in concert with the antibody response to kill invading bacteria. The bacteria is first tagged when antibody molecules generated by lymphocytes bind to its surface. The compliment, a series of circulating proteins generated by the liver, recognize the antibody bound to the surface of the bacteria and through a series of reactions produce a pore in the cell wall of the bacteria. Fluid rushes in through the hole, driven by osmotic pressure, flooding the inside of the bacterial cell wall, eventually causing the bacterial cell to lyse.

In 1904 Bordet returned to Brussels to found the Pasteur Institute Brussels. In 1906, working with Octave Gengou, Bordet succeeded in isolating a pure culture of Bordatella pertussis, the organism that causes whooping cough, and was able to develop a vaccine against the disease. In 1919 Bordet was awarded the Nobel Prize in physiology and medicine for "for his discoveries relating to immunity".

Bordet died on April 6, 1960.

References:

Laurell, A.B.; "Jules Bordet - A Giant in Immunology"; Scandinavian Journal of Immunology (1990)429-432

"Jules Bordet Biography" at faqs.org

Jules Bordet Nobel Biography

Jules Bordet Wikipedia Entry

August Paul von Wassermann

August Paul von Wassermann was born on February 21, 1866, in Bamberg Germany. He was the son of a Bavarian court banker Angelo Wassermann (who was elevated to hereditary nobility in 1910) and Dora Bauer. He attended the Gymnasium at Bamberg and studied medicine at the Universities of Erlangen, Vienna, and Munich. He graduated with his medical degree from the University of Strasbourg in 1888.

He joined Robert Koch's newly established Institute for Infectious Diseases in 1891 as an unpaid assistant under Bernhard Proskauer. In 1893 he became a temporary assistant working on the problems related to cholera. In 1895 he became the inspecting physician at the Institute's control station for diphtheria. In 1902 he became the director of the clinical division of the Institute. In 1913 he left the Institute to become the director of the department of experimental therapy at the Kaiser Wilhelm Institute, a position he held until his death.

Wassermann was quick to understand the importance of the young science of bacteriology and he made the acquaintance of Paul Ehrlich of whom he became a pupil and colleague. After 1900 he became interested in complement, which was still being investigated. Complement is series of serum proteins that functions as a part of the immune system which, in concert with antibodies, attach to invading bacteria to cause lysis and phagocytosis (see here for the Wikipedia article on the complement system). Starting in 1901 Wassermann unsuccessfully worked to develop a complement based test to diagnose tuberculosis. Later, in 1906, working with Albert Neisser, he developed a complement based test to detect antibodies to the causative agent for syphilis. This test, known as the Wassermann test, was widely used to diagnose syphilis, was developed only one year after the discovery of the causative agent by Fritz Richard Schaudinn and Paul Erich Hoffmann.

During World War I, Wassermann's research was curtailed and eventually suspended completely. During the war he served as a hygienist and bacteriologist, supervising epidemic control on the eastern front. In 1924 he began to suffer from Bright's disease, which took his life on March 16, 1925.

References:

Firkin, Barry G. and Whitworth Judith A.; "Wasserman Test" in Dictionary of Medical Eponyms, Second Edition, Paperback; Informa Healthcare, 2001

"World of Microbiology and Immunology: Von Wassermann, August Paul (1866-1925)"; found at enotes.com

"August Paul von Wassermann" at whonamedit.com

"A First Cure for Syphlis" at the Magnus Hirschfield Archive for Sexology, hosted at www2.hu-berlin.de