Joaquín Guzmán was extradited last year to face drug conspiracy charges in the United States.
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He is accused of having a hand in dozens of murders and smuggling more than 200 tons of cocaine.
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Guzman's criminal pedigree prompted authorities in New York to hold him in solitary confinement in a high-security wing of a federal jail in Manhattan that has held notorious terrorists and mobsters.
For pre-trial hearings, authorities transported Guzman to and from jail by shutting down the Brooklyn Bridge to make way for a police motorcade that included a SWAT team and an ambulance, all tracked by helicopters.
At the time, the judge noted the expense and logistical nightmare it could create, particularly for New Yorkers who rely on the bridge to commute.
The trial could last as long as four months.
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Now, there's speculation that a special cell for Guzman has been set up deep inside the Brooklyn courthouse.
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El Chapo escaped jail twice in Mexico through a tunnel.
Jurors will be kept anonymous and escorted to and from the courthouse by federal officers, and heavily armed federal agents will turn the courthouse into a fortress.
Prosecutors say Guzman was in the habit of ordering the killings of anyone who got in his way during his heyday in Mexico as boss of the Sinaloa cartel.
In his way now is a lineup of government witnesses who survived the wave of violence and are expected to give details about the ruthless way he kept power for 20 years in the cutthroat world of international drug trafficking. The defense says the witnesses are the true bad guys whose testimony shouldn't be trusted.
The names of the witnesses have been blacked out on court documents with prosecutors saying their identities need to be protected because their cooperation could put them in the crosshairs of a vengeful cartel. According to court papers, some are being held in special jail units for their protection, while others are in witness protection programs.
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The list of people who could turn up on the witness stand is long. Two standout possibilities are twin brothers Pedro and Margarito Flores, former Chicago-based narcotics wholesalers who did business with Guzman before their arrest in 2008. They agreed to cooperate and record phone conversations with Guzman about the size of shipments smuggled on boats and airplanes.
In one, a voice identified as Guzman's asks, "How much can you get rid of in a month?"
The now imprisoned brothers paid a steep price for flipping: Prosecutors say in 2009 their father was murdered in Mexico by a cartel hit team.
(The Associated Press contributed to this report)