Arthur P. Arnold

Arthur Palmer Arnold (born March 16, 1946, Philadelphia PA USA) is an American biologist who specializes in sex differences in physiology and disease, genetics, neuroendocrinology, and behavior. He is Distinguished Professor of Integrative Biology & Physiology at the University of California, Los Angeles (UCLA). His research has included discovery of large structural sex differences in the central nervous system, and studies of how hormones and genes cause sex differences in numerous tissues. His program of research suggested major revisions to concepts of mammalian sexual differentiation and forms a foundation for understanding sex difference in disease.
==Career==
* A.B. degree in Psychology from Grinnell College, 1967
* Ph.D. in Neurobiology and Behavior from The Rockefeller University in 1974, Advisor Fernando Nottebohm, mentors Peter Marler, Donald Pfaff, and Bruce McEwen
* Postdoctoral research at The Rockefeller University with Hiroshi Asanuma during 1974-1976. 
* Faculty member, UCLA Psychology, 1976-1994. UCLA Department of Integrative Biology & Physiology since 1994. 
* Associate Director, UCLA Brain Research Institute (1989-2001)
* Chair, Department of Integrative Biology & Physiology (2011-2009)
* Director, UCLA Laboratory of Neuroendocrinology of the Brain Research Institute (2001-2017)
* Inaugural President of the Society for Behavior Neuroendocrinoloogy (1997-1999)
* Co-founded the Organization for the Study of Sex Differences (OSSD, 2006, https://www.ossdweb.org/founders) and served as a director of the OSSD (2012-2018)
* Founding Editor-in-Chief of the OSSD’s official journal, Biology of Sex Differences (2010-2018). 
==Research==
In 1976, Fernando Nottebohm and Arnold reported the first example of large morphological sex differences in the brain of any vertebrate, in the neural circuit controlling singing in passerine birds. The report had broad impact, triggering a reevaluation of the magnitude and significance of biological sex differences in the structure and function of the brain, including in humans. The report inspired the discovery of numerous other structural sex differences in the brains of other vertebrate species such as humans and other mammals.. In the rat spinal cord, Arnold and Marc Breedlove established an advantageous model for studying how androgens act to cause sex differences in neural development. Before these discoveries, sex differences in the brain were inferred to be small. The identification of groups of cells that differed, in specific brain regions of males and females, moved the study of sexual differentiation to the cellular and molecular level, ultimately enabling discovery of the molecular mechanisms of sexual differentiation in the brain. Arnold and co-workers uncovered hormonal control of cellular mechanisms (cell death, dendritic growth, cell growth, synapse elimination) to cause differential nervous system development in males and females. These studies contributed to the general conclusion of 20th century biologists that all sex differences outside of the gonad were caused by differential effects of ovarian and testicular hormones. 
Beginning in 1996, Arnold’s research contributed to a major shift away from this hormones-only theory. Particularly striking was the investigation of a gynandromorphic zebra finch, whose brain was genetically male on one side and genetically female on the other side . The two sides differed in the degree of masculinity of the neural song circuit, implying that sex chromosomes operated within brain cells to contribute to sex differences, beyond any gonadal hormonal mechanism; . Arnold and collaborators tested this new idea extensively since 2002, using “Four Core Genotypes” and other mouse models with altered sex chromosomes. These models showed that mice with different sex chromosomes (for example, XX vs. XY), but with the same type of gonadal hormones, have large sex differences caused by sex chromosomes, not by gonadal hormones. The models were used to demonstrate sex chromosome effects causing sex differences in a wide variety of disease models: autoimmune, metabolic, cardiovascular, cancer, neural and behavioral. Arnold’s research shifted the conceptual framework for understanding the differences between the sexes, and contributed to the rationale for the US National Institutes of Health to increase focus on sex differences in preclinical research. It also led to the discovery of specific X and Y genes that cause sex differences in mouse models of disease, therefore increasing understanding of sex-biasing functions of genes on the mammalian X and Y chromosome. Arnold and colleagues also published the first genome-wide study of sex chromosome dosage compensation in birds, demonstrating that unlike many other species, birds do not have a sex-chromosome-wide dosage compensation mechanism at the mRNA level.
Arnold has mentored 13 Ph.D. students, 24 postdoctoral fellows, and 6 M.S. students.
==Awards and Honors==
* Phi Beta Kappa, 1966
* Fellow, John Simon Guggenheim Foundation, 1998
* Fellow, American Association for the Advancement of Science, 1998
* Inaugural President, Society for Behavioral Neuroendocrinology, 1997-1999, https://sbn.org/about/presidents.aspx
* Daniel S. Lehrman Lifetime Achievement Award from Society for Behavioral Neuroendocrinology, 2010, https://sbn.org/awards/daniel-s-lehrman-award.aspx
* Frank Beach Lecture, University of California, Berkeley, 1988
* Magoun Lecture, UCLA Brain Research Institute, 2003
* Robert Goy Lecture, University of Wisconsin Primate Center, 2016
* Charles Sawyer Distinguished Lecture, UCLA, 2019
* Arthur Arnold Lecture established in 2018 by Organization for the Study of Sex Differences
* Arthur Arnold Innovator Lecture established in 2019 by the Laboratory of Neuroendocrinology of the UCLA Brain Research Institute.
==Notable Publications==
* Agate RJ, Grisham W, Wade J, Mann S, Wingfield J, Schanen C, Palotie A, Arnold AP. "Neural not gonadal origin of brain sex differences in a gynandromorphic finch." Proceedings of the National Academy of Sciences USA. 2003;100:4873-8. https://pubmed.ncbi.nlm.nih.gov/12672961/
* Arnold AP. "The end of gonad-centric sex determination in mammals." Trends in Genetics. 2012;28(2):55-61. https://pubmed.ncbi.nlm.nih.gov/22078126/
* Arnold AP. "A general theory of sexual differentiation." Journal of Neuroscience Research. 2017;95(1-2):291-300. https://pubmed.ncbi.nlm.nih.gov/27870435/
* Arnold AP. "Four Core Genotypes and XY* mouse models: Update on impact on SABV research." Neuroscience and Biobehavioral Reviews, 2020; 119:1-8. https://pubmed.ncbi.nlm.nih.gov/32980399/
* Arnold AP. "X chromosome agents of sexual differentiation". Nature Reviews Endocrinology. 2022; 18(9):574-583. https://pubmed.ncbi.nlm.nih.gov/35705742/
Category:1946 births
Category:People from Philadelphia
Category:American people
Category:Biologists
Category:Researchers