He developed the technique of nucleic acid hybridization, which helped to lay the groundwork for advances in recombinant DNA technology.

He attended the City College of New York and was initially interested in biology, but found the courses uninspiring and instead chose to focus on math and physics.

Spiegelman joined Steinbach in his move to Washington University School of Medicine two years later, and received his PhD from that institution in 1944.

[1] His graduate work focused on what was then known as enzymatic "induction" or "adaptation", now known to reflect changes in gene expression in response to environmental factors.

[1][3] In 1949, Spiegelman joined the faculty at the University of Illinois, where he would spend the next 20 years of his academic career.