[1] In fall 1980, while at a campus pub, Seeman was inspired by the M. C. Escher woodcut Depth to realize that a three-dimensional lattice could be constructed from DNA.

He realized that this could be used to orient target molecules, simplifying their crystallographic study by eliminating the difficult process of obtaining pure crystals.

[5][6] In pursuit of this goal, Seeman's laboratory published the synthesis of the first three-dimensional nanoscale object, a cube made of DNA, in 1991.

The goal of demonstrating designed three-dimensional DNA crystals was achieved by Seeman in 2009, nearly thirty years after his original elucidation of the idea.

[10] He shared the Kavli Prize in Nanoscience 2010 with Donald Eigler “for their development of unprecedented methods to control matter on the nanoscale.”[10][11] He was a fellow of the Norwegian Academy of Science and Letters.