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Ghiselin received his B.A. 1960 from the University of Utah and a Ph.D. from Stanford University in 1965. He became a Postdoctoral Fellow at Harvard University (1964–65) and moved on to become Postdoctoral Fellow at the Marine Biological Laboratory in 1965. There he stayed until 1967 as he was appointed Assistant Professor of Zoology at the University of California, Berkeley and later was picked as a Guggenheim Fellow (1978–79). Ghiselin served as Research Professor of Biology at the University of Utah (1980–83) and was MacArthur Prize Fellow from 1981 to 1986. Since 1983 the scientist is Senior Research Fellow at the California Academy of Sciences.
Ghiselin is famous for his work on sea slugs, and has had both a species (Hypselodoris ghiselini) and the defensive chemical that it contains (ghiselinin) named after him. In 2009 he co-authored a major study on chemical defense with Guido Cimino: Chemical Defense and the Evolution of Opisthobranch Gastropods.
In 1969 he proposed the size-advantage model to explain sequential hermaphroditism. In some fish species, he reasoned, males can maximize their reproductive success by breeding with a harem of females rather than breeding only once as a female. In other species, where the fish live in pairs, it is to an individual's advantage to be male when small and to turn into a female when it is larger.
He also works on the history and philosophy of evolutionary biology. His historical publications have dealt mainly with Darwin and the history of comparative zoology. They include such topics as the influence of alchemy on nineteenth century zoology and the history of the Zoological Station at Naples, Italy. He has criticised the falsification of the history of Lamarck's theory of evolution, where schoolbooks and "textbook-writers have imbued the fictitious Lamarck with an importance that the real Lamarck never had, and they have credited him with ideas that the real Lamarck did not hold. They also have invented a myth in which those ideas are compared falsely with Darwin's ideas, to produce a bogus dichotomy."
His main contributions to philosophy have to do with the principles of classification (systematics or taxonomy). He is given much of the credit for first theorizing that biological species are not kinds of organisms, but are rather individuals in a philosophical sense (in the manner that an individual population is an individual entity, rather than an abstract type.) A human being is not a Homo sapiens for the same reason that Ontario is not a Canada.
He has many interdisciplinary interests, among which is forging links between biology and economics. He is Vice President of the International Society for Bioeconomics, and has served as the Co-Editor of the Journal of Bioeconomics since it was established in 1998. The first academic chair of bioeconomics was established at the University of Siena. As a visiting professor he was its first occupant.
As Chair of the Center for the History and Philosophy of Science his main responsibility has been to organize scholarly meetings and to serve as Editor of the volumes based on them.
- Michael T. Ghiselin and Alan E. Leviton: Darwin and the Galapagos", in the Proceedings of the California Academy of Sciences for 2010 Volume 61, Supplement 2.
- The Triumph of the Darwinian Method. University of California Press, Berkeley, 1969.
- Barbour, M.G., R.B. Craig, F.R. Drysdale, and M.T. Ghiselin: Coastal Ecology: Bodega Head. University of California Press, Berkeley, 1973.
- The Economy of Nature and the Evolution of Sex. University of California Press, Berkeley, 1974.
- Intellectual Compromise: The Bottom Line. Paragon House, New York, 1989.
- Metaphysics and the Origin of Species. State University of New York Press, Albany, 1997.
- Darwin: A Reader's Guide. Occasional Papers of the California Academy of Sciences 155: 1-185, 2009.
- Darwin and Evolution. Carmichael & Carmichael, Inc. and Knowledge Products Blackstone Audio, inc, 1993 (audiobook).
- "Academy Fellows". Calacademy.org. Retrieved 20 March 2017.
- Cimino, Guido; Ghiselin, Michael T. (2009). "Chemical Defense and the Evolution of Opisthobranch Gastropods". Proceedings of the California Academy of Sciences. Volume 60 (Issue 10). Retrieved 20 March 2017.
- Ghiselin, Michael T. (1994). "The Imaginary Lamarck: A Look at Bogus "History" in Schoolbooks". The Textbook Letter. The Textbook League (September-October 1994). Retrieved 28 May 2017.