[5][6][7][8][9] Wiley received his doctoral degree in biophysics in 1971 from Harvard University, where he worked under the direction of the subsequent 1976 chemistry Nobel Prize winner William N. Lipscomb, Jr.[10] There, Wiley did early work on the structure of aspartate carbamoyltransferase, the largest molecular structure determined at that time.

[11] Noteworthy in this effort was that Wiley managed to grow crystals of aspartate carbamoyltransferase suitable for obtaining its X-ray structure, a particularly difficult task in the case of this molecular complex.

Wiley was world-renowned for finding new ways to help the human immune system battle such viral scourges as smallpox, influenza, HIV/AIDS and herpes simplex.

In 1999, Wiley and another Harvard professor, Jack L. Strominger, won the Japan Prize for their discoveries of how the immune system protects humans from infections.

The official coroner's report stated that Wiley died after falling off a bridge near Memphis, Tennessee; his body was found in the Mississippi River 300 miles (480 km) downstream in Vidalia, Louisiana a month later and his death was ruled to be an accident.