"When you talk to these people -- like Charlie Manson and [the Co-Ed Butcher] Ed Kemper -- you go in there and talk to these guys in a non-judgmental way, putting them at ease, laughing at their jokes," he told ABCNews.com.
"A lot of people couldn't do that," Lanning said. "He had to develop a rapport with them and enter their world and rationalize and justify their behavior. John was very good at that."
The case work -- hundreds in a year -- took a toll on Douglas's health. "Not a human being in the world can work a 10- or 13-hour day, and he got caught up in the rate race," said Lanning. "To a certain extent it was self-induced."
In 1983, while working on the Green River case in Washington -- 48 prostitutes were murdered in a 16-year killing spree that ended in 2003 -- Douglas didn't show up for breakfast and two agents he was training found him collapsed in his hotel room.
Douglas was in a coma for a week with viral encephalitis. When he awoke, his entire left side was paralyzed and he couldn't speak.
"The doctors who treated me said I was 'burned out and burning both ends of a candle,'" said Douglas.
After five months of physical and psychological rehabilitation, he returned to the FBI.
In 1995, Douglas retired from the FBI, writing the books "Mind Hunter" and "BTK Strangler" and consulting on films. At his retirement party his colleague Lanning was wheeled in on a gurney as Hannibal Lecter, complete with a lacrosse mask resembling the mask Anthony Hopkins' character wore in the movie.
Though some fellow agents resented the fact that Douglas "went Hollywood," he left a legacy of almost "psychic" insight into the mind of a serial killer, according to Lanning.
After retirement, he was hired by the parents of Jon-Benet Ramsey in a murder case that is still unsolved.
One real-life case that Douglas analyzed resembled the fictional "Lovely Bones" murder.
Robert Hansen killed between 17 and 21 prostitutes in Alaska between 1980 and 1983. After paying for the women's services, Hansen would kidnap and rape them, then fly them out in his private plane to his wilderness cabin, release them and stalk them like animals with either a hunting knife or a rifle.
At the request of local police, Douglas looked into Hansen's background, finding he was of slight build and heavily pockmarked, with a severe speech impediment.
He surmised that Hansen had suffered from teasing as a child and would seek isolation due to his low self-esteem. He was also a skilled hunter.
Douglas also suggested that Hansen, like Harvey, might collect souvenirs of his killings. Police later found victims' jewelry, newspaper clippings and an array of firearms which led to the killer's capture in 1993.
Hansen, like the fictional George Harvey who was an ordinary doll maker in the community, was a baker who even waited on local police, but slipped under their radar.
Douglas maintains that today, an estimated 500 murders -- most thought to be serial killings -- are still unsolved.
As a parent of three grown children, Douglas says knows what it's like to be paranoid.
"When my daughter was young, she'd go to the mall and dance ballet," he said. "I'd be looking at the crowds when people were looking at their kids."
So does Tucci, who admits that "a little fear is OK."