After he finished college, Karlen wrote for many magazines and spent a couple of years traveling around Europe writing about food and culture.
Eventually, he became editor of several magazines, including Holiday and Newsweek, and published a short stories book called White Apples at the age of 24.
In the 1970s, Karlen became an Associate Professor in the English Department Writing Program at Penn State University.
Karlen won the 1996 Rhone-Poulenc Prize for science books with Plague's Progress, but did not attend the award ceremony due to illness.
They had two sons; Karlen's book tracks the friends, foes and ancestors of Borrelia burgdorferi (Bb), a "silvery, wriggling corkscrew-like" bacterium which causes Lyme disease.