Frank O'Brien was involved in the murder of Luther Garland.
Background[]
Sam and Dean arrived at the morgue in Rock Ridge, CO to view Frank O'Brien's body, as he was one of three perfectly healthy men to drop dead of heart attacks in the area within the prior three days. Frank, who was only 44 years old, was also a marathon runner. The coroner, unimpressed by those facts, had failed to perform an autopsy. "FBI Agents Tyler and Perry" insisted that he do so immediately. He did so almost casually, enlisting Dean to hold the man's heart, and accidentally squirting Sam in the face with "spleen juice." He declared that Frank was "pretty damn healthy." The boys note some strange abrasions on Frank's arm and a tan line around his wedding finger.
Sam and Dean then went to see the town's sheriff, Al Britton. He had known Frank since high school and was on a softball team with him. The sheriff, who seemed to have some OCD issues involving hand sanitizer and shoe removal, reported that Frank seemed very jumpy just before he died.
The Winchesters next visited Frank's next door neighbor, Mark Hutchins, who told them that he'd known Frank to be a bully in high school, but that he'd gotten better over the years. He confirmed that Frank had been married, but that his wife had died about 20 years earlier. As for his demeanor before he died, Mark rattled off a list of mostly benign things that Frank seemed to be terrified of.
By this point in their investigation, Dean had begun to develop the type of anxious behavior that they had been hearing about and seeing. A consult with Bobby resulted in the diagnosis of ghost sickness, a condition that was passed on like a virus that was initiated by a buruburu. Since Frank O'Brien was the first man to have died from it, they designated him their "patient zero."
After Dean coughed up a wood chip as his sickness progressed, it dawned on Sam that more clues about who the buruburu was would probably be found at the lumber mill. As they searched the mill they found a ring inscribed "To Frank. Love, Jessie": Frank O'Brien's missing ring. They then found Luther Garland's employee badge next to a portrait they recognized as Jessie O'Brien. When Dean accidentally ripped the portrait, the mill machinery mysteriously started whirring, and Luther Garland's ghost appeared.
A trip to see Luther's brother, John Garland, revealed that Frank O'Brien killed Luther by road-hauling him, mistakenly believing him to have been responsible for his wife Jessie's disappearance.