Sean Penn had some harsh words for former President George W. Bush and former Vice President Dick Cheney during his Wednesday night appearance on Conan.

“These are the guys, [Cheney] and President Bush and some others, who invented Daesh, or ISIS,” Penn told host Conan O’Brien, to rapturous audience applause. “They really are that which created it, so I wanted to give them a shout-out, thanks for that.”

Penn didn’t hold back in going after Cheney, whom he called an “embittered bacteria of humanity.”

“It’s always a surprise to me to remember that, through bionic technology and so on, the guy’s still here,” Penn said.

“But then we have people like Harvey Milk, who were beautiful, brilliant, impactful guys, and you know, it’s just, no good deed will go unpunished, and then you got the Cheneys,” Penn, who won a Best Actor Oscar in 2009 for his portrayal of Milk, continued. “This is just me musing.”

Conan then switched the topic to Cuba, asking Penn if he believed “real change” would be coming to the country. Penn has in the past met with both Fidel and Raul Castro.

“There’s certainly going to be real change in Cuba,” Penn replied. “Separate and apart from the Castros, I think, as you saw, the Cuban people have incredible spirit and incredible intelligence and are very bright. Among the positive things the revolution brought were literacy. And so with access, that will increase. I think it’s going to be a very exciting change in what they can bring to us culturally, it will be very exciting.”

Penn appeared on Conan to promote his film The Gunman, in theaters Friday. Check out the rest of his interview below: