
The film starts with the funeral of the Pope in the Vatican. It then switches off to CERN, a scientific research facility in Geneva, where a research team is experimenting with the creation of antimatter. In this scene, a woman named Vittoria Vetra, a scientist in the research team is introduced. Just moments after the antimatter has been successfully created by the team, the research facility is compromised by an intruder dressed as a scientist who steals the antimatter after murdering one of the individuals guarding it. Robert Langdon, a professor at Harvard University is visited by the Vatican police official who tells him that someone has been making threats against the Vatican and has already kidnapped four cardinals (called preferiti — Italian for preferred) who were being considered to be the next Pope. The officer also tells Langdon that the kidnapper will begin executing the cardinals every hour starting at 8PM that night. After Langdon arrives at the Vatican, the Vatican police show Langdon a video of the antimatter placed in an undetermined location through a video camera specifically shooting the object that is fed into a surveillance system. After the Camerlengo, the assistant to the previous Pope, suggests the idea, the Swiss Guard decide to find the location of the antimatter by systematically shutting off sections of the city's electrical grid and monitoring the surveillance camera to see if it shuts off corresponding to the city sections being shut off. If a section of the city's power has been turned off and the camera also loses power, the theory holds that the camera is located in that section of the city.
Langdon at this point mentions the history between the Illuminati and the Vatican and the conflict that began between them in 1668. According to Langdon, during the 17th century, the Vatican purged Catholics who favored science over conflicting Church teaching. The conflict eventually led to the Illuminati becoming a secret society determined to take vengeance on the Vatican for this incident and because of the Vatican's uncompromising position opposed to the science that the Illuminati stands for. Therefore, Langdon concludes that the threat and kidnapping of the four cardinals has been done by Illuminati to take that revenge by using the antimatter to blow up Vatican City. The antimatter is contained in a battery-powered canister, and as Vittoria explains, when the battery power runs out, the magnetic force keeping the antimatter suspended will shut down and cause the antimatter to react with matter (the canister), thus creating an intense explosion. It would recreate how science believes the universe was created. Langdon then educates the police force about the symbolic meaning of kidnapping four cardinals that the Illuminati's connection to the four pillars of science: earth, water, air and fire. He then deduces that the kidnapper intends to kill each of the kidnapped cardinals using the four pillars. He then receives special permission from Camerlengo to locate clues from old texts in the Vatican archives to find where the church of Illuminati is and in the meantime trying to save the four cardinals from being executed in four different locations. He finally discovers a poem hidden in Galileo's Diagramma della Veritas; the poem is a riddle that helps Robert figure out the path of illumination, the four churches in which the cardinals will be murdered. The Camerlengo at this point urges the cardinals to evacuate the Vatican because of the bomb threat but the head of the cardinals refuses, saying that they needed to have faith in God, and also not break the tradition of the conclave. The cardinals are in a conclave in the Sistine Chapel in order to elect the new Pope. Later, the Camerlengo makes a speech to the cardinals about religion and science, saying that they should be more open, and less like the secretive Illuminati.
Meanwhile, Langdon proposes that the first altar of science is at the Pantheon, which is where the artist Raphael is buried (From Santi's earthly tomb with demon's hole). However, Vittoria notices that Raphael was put there after the path was created, meaning the Pantheon was not the first alter of science. After realizing that the poem referred to a chapel Raphael built, they learn where the first alter of science really is. Langdon encounters the first cardinal, already dead by the element of Earth with his hand cuffed behind his back, soil filled in his mouth and the word "earth" branded onto his chest. Langdon discovers he was located at Santa Maria del Popolo, a chapel Raphael once had built, through the poem that the Illuminati left along with their initial threat of killing the four cardinals. Langdon then realizes that the first marker, or sculpture that leads the way along the path, is Habakkuk and the Angel, and that, although it points two ways, the angel shows the true way (Let angels guide you on your lofty quest).
Langdon is led to the next clue when he realizes that, while they were in a chapel built by Raphael, the sculptures it contained were all Bernini. This leads him to St. Peter's Square which contains many of Bernini's colonades. There he finds the second cardinal, who also dies from the cause of Air, as the killer had punctured his lungs. Near where the cardinal died, the next sculpture in the path is found; West Ponente, an elliptical carving with 5 lines representing breath. Langdon follows the direction of the 5 breath marks on the tile.
Ecstasy of St. Theresa
As he follows the third trail, he finds one of the cardinals dying from fire by burning on top of a flame made up of wooden chairs inside Santa Maria della Vittoria also with a word — "Fire" — branded onto his chest. Bernini's Ecstasy of St. Theresa is in the chapel in proximity to the burning man. Langdon and the Swiss Guard try to save him, but the kidnapper foils their attempts by killing all of the police personnel inside the churchl. Langdon manages to escape the scene by hiding underground.
Langdon draws out the previous three locations on a map and cites the line in the poem from the Diagramma della Veritas, "'cross Rome the mystic elements unfold," and realizes that, in drawing a cross to connect the places and a church related to water, he has found the next location. He and the police team pursues the next trail to the Fountain of the Four Rivers. As soon as they arrive, they see a van pulled up next to the fountain. As the two officers accompanying Langdon notice something suspicious about the van and approach it, the assassin surprises and kills both, unloads the fourth cardinal tied with weights into the fountain, and drives off. Langdon, with the help of strangers, saves the cardinal who tells him that he was held captive in the Castel Sant'Angelo, the location of the Illuminati church. As Langdon and the police approach the location, they see the same van empty and proceed down to the church of Illuminati. At this point the assassin is checking bank account wire transfer information on his laptop. He reads an email that the final wire transfer was successful and that there is a Volkswagen with a key in the ignition waiting for him outside. As he prepares to leave, Langdon and Vetra walk in on him. As they look for the clue the assassin appears out of hiding behind a wall and leaves without shooting them, saying that it is because they are not armed, but advises them not to follow him. Langdon realizes that there is the fifth branding iron that depicts two keys crossed. Initially, he believes it is a symbol of the papacy. He then thinks that there is going to be a fifth death and is likely to be the Camerlengo. As Langdon and Vittoria run to save the Camerlengo from impending death, they witness the explosion of a car— the one the assassin had been promised in exchange for killing the four Cardinals.
They get to the Vatican and find the head of the Swiss Guard, Commander Richter, pointing a gun at the Camerlengo. The accompanying police subsequently shoot Richter to death. They also shoot a bishop who enters the room in response to Camerlengo accusing the bishop of being Illuminati. Camerlengo has the fifth symbol freshly and painfully branded onto his chest. Baseed on the fact the symbol is upside-down, they finally locate the antimatter in St. Peter's tomb in the necropolis under the Vatican. When Vittoria's attempt to diffuse it proves futile, the Camerlengo snatches the antimatter and loads it to a helicopter outside and flies with it as high as possible before it explodes when the timer reaches 12:00, supposedly sacrificing himself. Just before the huge detonation in the sky, he parachutes out and lands in St. Peter's Square with a delight of onlookers. The explosion sends shockwaves throughout the city causing minor destruction and minor injuries.
The cardinals debate whether the Camerlengo should be Pope after hearing about his heroic effort that saved the Vatican. After some deliberation about the age of Camerlengo (who is much younger than the minimum required age), they reach consensus to vote him as a candidate to be the next Pope. While this happens, Langdon and Vetra go through Commander Richter's desk to recover journals that the commander took from Vetra earlier in the movie. The journals were written by Silvano—a colleague of Vetra and a Catholic priest— killed by the terrorist. They discover a hidden surveillance system on the Commander's computer and rewind the recording to see Commander Richter confronting the Camerlengo (who is revealed much more radically religious than the previous Pope and had become increasingly uncomfortable with the Vatican's increasing openness to science) had plotted everything and had branded the fifth symbol onto his chest himself. He had poisoned and killed the previous Pope and tried to appear as the savior of Vatican from the threat from the Illuminati, which he claimed was trying to destroy the Vatican in the religion and science debate. He made an opposite act to appear as being more open to science in order to unite the Catholic church. While in the hospital recovering from injuries he received during the shockwave of the antimatter explosion, he is informed that the conclave of Cardinals wants to see him in the chapel. Upon entering the conclave and receiving a stock-still room full of accusatory eyes, he realizes that the Cardinals now know everything. He walks out of the chapel quietly, but is trapped by the Vatican police. Seeing no way of escape, he then immolates himself with candle oil while putting his hands together and asking for forgiveness.
Cardinal Baggia—the fourth cardinal and would-be victim of the assassin—is then elected pope and Langdon is given the "Diagramma della Veritas" on indefinite loan to be returned in Langdon's last will and testament. The head of the cardinals reveals to Langdon that they are all imperfect and therefore religion is also imperfect. Knowing Langdon's dissatisfaction or disagreements with the church, he also advises Langdon that in his impending publication, any mention of the Catholic church should be made "gently", just as he had instructed the seizure of Carmelengo should be carried out.
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