Dr. Spence held academic positions in the University of California system from 1970 until 2004. She is currently Professor Emerita in the Department of Pediatrics, UC Irvine. Among her various positions, she served as Associate Dean in the Graduate Division at UCLA and Vice Chancellor of Academic Programs at the University of California, Irvine from 1992-94. She was the first to hold this position. According to the Los Angeles Times, the position was created in 1992 to help shape student affairs during lean budget years. Dr Spence was active in teaching at the undergraduate and graduate levels as well as medical school. Her research in human genetics focused on birth defects including both neurological, e.g., autism, and physical, e.g., cleft lip and palate. She employed mathematical models and statistical approaches via complex computer algorithms for the analysis of family data and applications for improved recurrence risks for genetic counseling.

Dr. Spence earned a bachelor of arts degree in biology from Grinnell in 1966. After earning her Ph.D. Human Genetics from the University of Hawaii in 1969, she received the NIH fellowship for post-doctoral studies at the University of North Carolina. In 1979, Dr. Spence received the Woman of Science Award at UCLA.

She was a member of the American Society of Human Genetics, the Genetics Society of America, and the Behavioral Genetics Association. Grinnell College awarded her an honorary degree in 1999 and an alumni award in 1990.

Dr. Spence served on various editorial boards including the American Journal of Human Genetics, Journal of Genetic Epidemiology, and the Alzheimer's Disease and Associated Disorders Journal. She served on the board of directors for the American Board of Medical Genetics and was President of that Board when it was recognized as a medical subspecialty by ACGME. She has won numerous awards, including the National Standard Oil Foundation Merit Scholarship and the Guttmann Foundation Scholarship. She was named to the 1976 and subsequent editions of American Men and Women of Science. In2001, she was awarded the annual Leadership Award by The International Genetic Epidemiology Society.