Salk Institute
Melvin Cohn
Professor Emeritus
Conceptual Immunology Group
Melvin Cohn

Professor Emeritus
Conceptual Immunology Group


Melvin Cohn, a founding and resident fellow of the Salk Institute, is a professor in the Conceptual Immunology Group.

Cohn studies the body's immune response, which protects vertebrates from the lethal effects of pathogens. Though the immune system cannot predict which of the diverse array of pathogens it will encounter, it nevertheless must respond promptly to defend the host organism from that invader.

His investigations are theoretical and deal with the evolutionary selection pressures that shape the immune system. A major thrust of his recent work has been the creation of a computer simulation of immune responses using the principles of nested cellular automata and adapting them to programs that can be run on typical desk-top computers or on a remote internet server.

Prior to joining Salk in 1963, Cohn was a National Science Foundation fellow at the Pasteur Institute in Paris, France. He also was a professor of biochemistry at the Stanford University School of Medicine, and a professor of microbiology at Washington University School of Medicine in St. Louis, Mo.

"The immune system is a complex of organs—highly specialized cells and even a circulatory system separate from blood vessels—all of which work together to protect the body from invading pathogens. Unlike most immunologists, who wield pipettes and petri dishes, I use my brain to bring order to what might well be one of biology's most complex fields."

Unable to predict which of the diverse array of pathogens it will encounter, the immune system must nevertheless respond promptly to defend the host organism from that invader. Complicating matters, pathogens evolve at a rate that is vastly more rapid than that of their hosts. Cohn's solution was to establish a set of basic immunologic rules based on the immune system's evolutionary origins.

Invertebrates invented a number of biodestructive and ridding mechanisms to deal with pathogens, but their limited flexibility was not enough to keep up with the rapidly changing landscape of disease-causing agents. This created a selective pressure to invent a mechanism expressed in vertebrates that generated a large and random repertoire of molecules able to recognize foreign invaders, which in turn required two new regulatory mechanisms: 1) a somatic decision mechanism to sort the repertoire into anti-self (the portion that needs to be inactivated to avoid autoimmune diseases) and anti-nonself (the activated portion that is now available to recognize invading pathogens and protect the host) and 2) a germline-selected decision mechanism to control the kind and magnitude of the immune response.

The rules Cohn developed cover most of immune behavior: the Combinatorial Theory of the nature of the repertoire; the Associative Recognition Theory of the self-nonself discrimination; Trauma Theory for the determination of the magnitude and effector class of the response; the B-Protecton Theory of humoral responsiveness and the T-Protecton Theory of cell-mediated responsiveness. These theories are linked together by a computer program based on cellular automata principles called the Synthetic Immune System. Available online, the Synthetic Immune System allows Cohn and others to test their assumptions about how the real immune system works, facilitating understanding and predictability.

While understanding how the immune system functions is Cohn's primary goal, being able to predict the consequence of any given antigenic input would be an invaluable guide for the development of new vaccines, the treatment of autoimmune and allergic disorders, as well as the enhancement of the body's response to infectious disease.

Selected Publications

Cohn, M. (2001) Logic of the Self-Nonself discrimination: principles and history. in: Dialogues With Selves. Historical Issues and Contemporary Debates in Immunology, eds. Alberto Cambrosio and Anne Marie Moulin, Editions Elsevier, France, pgs. 53-85.

Cohn, M., Langman, R.E. and Mata, J. (2002) A computerized model for the self-nonself discrimination at the level of the T-helper (Th genesis).  I.  The origin of “primer” effector T-helpers  Intl. Immunol. 14:1105-1112.

Langman, R.E., Mata, J. and Cohn, M. (2003) A computerized model for the self-nonself discrimination at the level of the T-helper (Th genesis) II.  The behavior of the system upon encounter with nonself antigens. Int. Immunol. 15:593-609.

Cohn, M. (2003) Tritope model of restrictive recognition by the TCR. Trends in Immunol. 24:127-131.

Cohn, M. (2004) If the “adaptive” immune system can recognize a significant portion of the pathogenic universe to which the “innate” immune system is blind, then... Scand. J. Immunol. 60:1-2.

Cohn, M. (2004) Whither T-suppressors: If they didn’t exist would we have to invent them? Cell. Immunol. 227:81-92.

Cohn, M. (2005) Degeneracy, Mimicry and Crossreactivity in Immune Recognition. Mol. Immunol. 42:651-655.

Cohn, M. (2005) A biological context for the Self-Nonself discrimination and the regulation of effector class by the immune system, Immunol. Res. 31:133-150.

Cohn, M. (2005) The common sense of the Self-Nonself discrimination. Springer Seminars in Immunopathology 27:3-17.

Cohn, M. (2005) The Tritope model for restrictive recognition of antigen by T-cells: I. What assumptions about structure are needed to explain function?  Mol. Immunol. 42:1419-1443.

Cohn, M. (2006) What are the commonalities governing the behavior of immune recognitive repertoires?  Dev. & Comp. Immunol. 30:19-42.

Awards and Honors

  • Eli Lilly Award in Microbiology and Immunology, 1956
  • Sandoz Prize in Basic Immunology, 1995
  • American Academy of Arts and Sciences


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