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Puopolo grew up in the Jamaica Plain section of Boston and graduated from the prestigious Boston Latin School before enrolling at Harvard. A senior and the starting cornerback for the Crimson during the 1976 season, he was scheduled to graduate the following spring with a degree in biology. He was planning to attend medical school.
On Tuesday November 15, 1976, Puopolo and a group of his Harvard Crimson teammates spent the evening out. During the early morning hours of November 16, Puopolo's teammate Charlie Kaye was approached by a prostitute while he was sitting in a van. Reaching into the van, the prostitute distracted Kaye by fondling him and then stole his wallet. As the prostitute ran away, Puopolo pursued her. Three men came to the aid of the woman, and in the ensuing altercation one of the men stabbed Puopolo.
Deprived of oxygen as a result of his injuries, Puopolo suffered extensive brain damage. He remained in a coma for 31 days before suffering a fatal heart attack on December 17, 1976. He died while still attached to the respirator that had been keeping him alive.
The men convicted of Puopolo's murder were all black and appealed their first degree murder convictions in part on a claim that the prosecution used peremptory challenges led to exclude blacks from the jury. The Massachusetts Supreme Judicial Court remanded the case for new trial after finding that eleven of twelve deliberating jurors were white.