Jerne, Niels K. (1911-1994)

Danish immunologist

Often considered the founder of modern cellular immunology , Niels K. Jerne shared the 1984 Nobel Prize for medicine or physiology with César Milstein and Georges J. F. Köhler for his body of work that explained the function of the immune system , the body's defense mechanism against disease and infection. He is best known for three theories showing how antibodies—the substances which protect the body from foreign substances such as viruses and poisons—are produced, formed, and regulated by the immune system. His theories were initially met with skepticism, but they later became the cornerstones of immunological knowledge. By 1984, when Jerne received the prize, colleagues agreed that he should have been recognized for his important contributions to the field much earlier than he was. Jerne's theories became the starting point from which other scientists, notably 1960 Nobel Prize winner Frank MacFarlane Burnett, furthered understanding of how the body protects itself against disease.

Niels Kaj (sometimes translated Kai) Jerne was born in London, England, to Danish parents Else Marie Lindberg and Hans Jessen Jerne. The family moved to the Netherlands at the beginning of World War I. Jerne earned his baccalaureate in Rotterdam in 1928, and studied physics for two years at the University of Leiden. Twelve years later, he entered the University of Copenhagen to study medicine, receiving his doctorate in 1951 at the age of forty. From 1943 until 1956 he worked at the Danish State Serum Institute, conducting research in immunology.

In 1955, Jerne traveled to the United States with noted molecular biologist Max Delbrück to become a research fellow at the California Institute of Technology at Pasadena. The two worked closely together, and it was not until his final two weeks at the institute that Jerne completed work on his first major theory—on selective antibody formation . At this time, scientists accepted that specific antibodies do not exist until an antigen—any substance originating outside the body (e.g., a virus, snake venom, transplanted organs, etc.)—is introduced, and acts as a template from which cells in the immune system create the appropriate antibody to eliminate it. Antigens and antibodies have surface patches, called combining sites, with distinct patterns. When an antibody and antigen with complementary combining sites meet, they become attached, fitting together like a lock and key. Jerne's theory postulated instead that the immune system inherently contains all the specific antibodies it needs to fight specific antigens. The appropriate antibody, one of millions that are already present in the body, attaches to the antigen , thus neutralizing or destroying the antigen and its threat to the body.

Not until some months after developing his theory did Jerne shared it with Delbrück, who sent it to the Proceedings of the National Academy of Sciences for publication. Jerne later noted that his theory probably would have been forgotten, except that it caught the attention of Burnett, leading him to the development in 1959 of his clonal selection theory, which built on Jerne's hypothesis to show how specific antibody-producing cells multiply to produce necessary quantities of an antigen's antibody. The following year, Jerne left his research in immunology to become chief medical officer with the World Health Organization in Geneva, Switzerland, where he oversaw the departments of biological standards and immunology. From 1960 to 1962, he served on the faculty at the University of Geneva's biophysics department.

From 1962 to 1966, Jerne was professor of microbiology at the University of Pittsburgh in Pennsylvania. During this period, he developed a method, now known as the Jerne plaque assay, to count antibody-producing cells by first mixing them with other cells containing antigen material, causing the cells to produce an antibody that combines with red blood cells. Once combined, the blood cells are then destroyed, leaving a substance called plaque surrounding the original antibody-producing cells, which can then be counted. Jerne became director of the Paul Ehrlich Institute, in Frankfurt, Germany, in 1966, and, in 1969, established the Basel Institute for Immunology in Switzerland, where he remained until taking emeritus status in 1980.

In 1971, Jerne unveiled his second major theory, which deals with how the immune system identifies and differentiates between self molecules (belonging to its host) and nonself molecules (invaders). Noting that the immune system is specific to each individual, immunologists had concluded that the body's self-tolerance cannot be inherited, and is therefore learned. Jerne postulated that such immune system "learning" occurs in the thymus, an organ in the upper chest cavity where the cells that recognize and attack antigens multiply, while those that could attack the body's own cells are suppressed. Over time, mutations among cells that recognize antigens increase the number of different antibodies the body has at hand, thereby increasing the immune system's arsenal against disease.

Jerne introduced what is considered his most significant work in 1974—the network theory, wherein he proposed that the immune system is a dynamic self-regulating network that activates itself when necessary and shuts down when not needed. At that time, scientists knew that the immune system contains two types of immune system cells, or lymphocytes: B cells , which produce antibodies, and T cells , which function as "helpers" to the B cells by killing foreign cells, or by regulating the B cells either by suppressing or stimulating their antibody producing activity. Further, antibody molecules produced by the B cells also contain antigen-like components that can attract another antibody (anti-idiotype), allowing one antibody to recognize another antibody as well as an antigen. Jerne's theory expanded on this knowledge, speculating that a delicate balance of lymphocytes and antibodies and their idiotypes and anti-idiotypes exists in the immune system until an antigen is introduced. The antigen, he argued, replaces the anti-idiotype attached to the antibody. The immune system then senses the displacement and, in an attempt to find the anti-idiotype a "mate," produces more of the original antibody. This chain-reaction strengthens the body's immunity to the invading antigen. Experiments later demonstrated that immunization with an anti-idiotype would stimulate the production of the required antibody. It may well be that because of Jerne's network theory, vaccinations of the future will administer antibodies rather than antigens to bring about immunity to disease.

Jerne retired to southern France with his wife. A citizen of both Denmark and Great Britain, Jerne received honorary degrees from American and European universities, was a foreign honorary member of the American Academy of Arts and Sciences, a member of the Royal Danish Academy of Sciences, and won, among other honors, the Marcel Benorst Prize in 1979, and the Paul Ehrlich Prize in 1982.

See also B cells or B lymphocytes; Immunity, active, passive and delayed; Immunity, cell mediated; Immunity, humoral regulation; Immunochemistry; T cells or T lymphocytes