His formative years as an independent medical researcher were at Tulane University School of Medicine.
He was invited to write regular essays in the New England Journal of Medicine, and won a National Book Award for the 1974 collection of those essays, The Lives of a Cell: Notes of a Biology Watcher.
He also won a Christopher Award for this book. Two other collections of essays (from NEJM and other sources) are The Medusa and the Snail and Late Night Thoughts on Listening to Mahler's Ninth Symphony.
His autobiography, The Youngest Science: Notes of a Medicine Watcher is a record of a century of medicine and the changes which occurred in it. He also published a book on etymology entitled Et Cetera, Et Cetera, poems, and numerous scientific papers.
Many of his essays discuss relationships among ideas or concepts using etymology as a starting point. Others concern the cultural implications of scientific discoveries and the growing awareness of ecology.
In his essay on Mahler's Ninth Symphony, Thomas addresses the anxieties produced by the development of nuclear weapons. Thomas is often quoted, given his notably eclectic interests and superlative prose style.
The Lewis Thomas Prize is awarded annually by The Rockefeller University to a scientist for artistic achievement.