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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.
The story opens with Alice waking up in a recreation of the Looking Glass House, contained within a reinforced concrete bunker. She soon finds herself in the Hive's class corridor, where by instinct she knows to escape a high-power laser and escape through a ceiling vent, coming out in a booby-trapped Raccoon City Hospital. Shocked by setting off a wire-trap, she triggers a second trap and is killed as a mine impacts into her abdomen. Her body is dragged out by an Umbrella haz-mat team led by Dr. J. Isaacs, revealing the Umbrella facility to be beneath a weather station in Death Valley. The body is dumped in a ditch with dozens of other Alice clones, as thousands of Undead stare hungrily on the other side of a 15 ft high fence, revealing the world has fallen to a T-virus pandemic.
Elsewhere Janice Prospero - the real Alice - drives down Nevada's I-10 in a Honda Fireblade carrying her pet dog, Paco. Alice stops at the KNAC TV station to answer an emergency transmission, but finds the caller, Bob Smythee, killed himself with a shotgun some time ago. When Paco is confronted by Undead Dogs outside, Alice takes them out with the shotgun and returns indoors to hide from an Umbrella spy satellite which periodically looks for her.
Alice narrates a flashback explaining how the world ended over a period of months after the Raccoon City incident, as infected sewer rates escaped the destruction and spread the virus across the United States. North American governments were ill-equipped to halt the vast migration of American refugees and fell soon after. The UN was able to put Umbrella's leadership on trial - Dr. Isaacs included - but an Undead attack on The Hague allowed them to flee. Since then, survivors have regressed to a nomadic hunter-gatherer tribal culture, recovering what they can find from the towns but always avoiding the cities.
Out in Arizona, an armoured convoy consisting of a variety of vehicles drives by, led by Jill Valentine. This consists of a hummer, a Denver KT7 news van, a fire truck, an Arco oil tanker, a flat bed, an ambulance and a school bus. For some time they have been circling around the Mojave desert, taking supplies from motels and other isolated buildings on the highways. On this particular stretch of road is a scattering of car dealerships where hundreds of Undead have clustered towards. Due to these challenges, the survivors have learnt how to refuel in transit to avoid being caught out.
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.