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Resident Evil: Extinction entered pre-production in July 2005 under the working title of Resident Evil: Afterlife, with a pitch of it being set in a Mad Max-style near-future after a T-virus apocalypse. While the general outline remained the same throughout production, significant changes were made after the August draft regarding cast and the fates of certain characters.
Alice wakes up naked and injured in the Looking Glass House having no memory of how she got there or indeed ever being in the house before. A red dress is left lying for her, and she explores the house, finding it has her wedding photographs. The house however is not real, having concrete walls rather than windows. When she heads out the front door, Alice instead finds herself in the Hive's glass corridor, which she also does not remember. As if by instinct, Alice escapes a high-power laser beam and climbs into a vent, coming out at Raccoon City Hospital where she destroys a gurney by setting off a wire-trap. Stepping back in reaction, she sets off a mine which destroys her chest. Dr. Alexander Isaacs enters the room with two Umbrella researchers in haz-mat suits, nonchalantly ordering a blood sample be taken before being disposed of. They are in fact within a top-secret underground laboratory called The Complex, and this was a cloned Alice. The haz-mat team takes her body up an elevator to the surface of a weather station in Death Valley and dumps it in a mass-grave with over a hundred other Alice clones. The weather station is itself surrounded by thousands of Undead, trying to break through the 15ft high fence.
The real Alice - Janice Prospero - drives down Interstate 10 in Nevada, her Honda Fireblade driving around a series of wrecked cars. She soon pulls up outside KNAC, a local TV station, to answer an emergency radio transmission. Exploring the station, she finds the corpse of a local employee - Bob Smythee - who killed himself with a shotgun some time ago. With him is a red notebook he used as a journal, but is soon distracted when her pet dog Paco begins barking, being confronted by three Undead Dogs which she kills with Smythee's shotgun. Leaving the building, Alice's watch begins beeping, revealing a countdown timer. She rushes back inside, revealing an Umbrella satellite has been periodically looking for her. After a few moments, Alice and Paco leave and drive off.
In a flashback narrated by Alice, it is explained that the incident in Raccoon City was not contained by Umbrella as once thought, with sewer rats successfully spreading the infection to other locations. Within weeks, the United States had fallen into total anarchy, with Canada, Mexico and Cuba executing refugees to prevent the same happening elsewhere. This still failed, and soon France, Germany and Japan fell. Attempts by the UN to put Umbrella's leadership on trial failed when the Hague was attacked by Undead, allowing Dr. Alexander Isaacs to escape. In the past few years, surviving humans have abandoned the cities and begun a nomadic existence.
An armoured convoy drives along a desert road in Arizona (given as Lat. 45.2, Long. 74.3). The vehicles have all been modified for their own purposes for the convoy. Jill Valentine drives a Hummer with K-Mart, intent as the lead and scout vehicle. Carlos Olivera drives a fire truck. L.J. Wayne rides in an Arco oil tanker where reserve petrol is stored. A Denver KT7 news van is used for long-range radio communications. An ambulance houses medical supplies. A flatbed provides services for broken vehicles. Finally, a school bus carries other refugees. While driving along the freeway, Valentine drops behind to refuel; with Undead roaming the roads from a scattering of car dealerships the group has learnt how to refuel in transit.
Back in Death Valley, Dr. Isaacs returns from surface with a captured Undead test-subject. He is greeted by Slater, who drives him to the briefing room. The committee meets by hologram across the world's remaining Umbrella facilities, and is chaired by Commander Okamoto. Asked for his research findings, Isaacs tells them the Undead have no real need for sustenance so could survive for decades unless exposed to extreme temperatures or environment. Isaacs has for a time been working on a 'domestication' project which would allow the Undead to regain a fraction of their humanity, but needs a blood sample from the original Alice to obtain her antibodies, with her clones so far failing to develop immunity.