Isaac was born in the Northeastern American seaboard sector, and is the son of renowned ship designer, Paul Clarke, who left for space when Isaac was still a child. In her husband's absence, his mother Octavia turned to the Church of Unitology. Isaac took after his father and obtained education in electrical and mechanical engineering and was selected to attend a prominent engineering academy. However, he was unable to afford the tuition because his mother had purchased a vested-level title in the Unitologist Church. This began Isaac's dislike for the religion.
Nonetheless, Isaac graduated with high honors from a lesser college and became a systems engineer just like his father. After several years when it became apparent to his superiors that Isaac possessed the ability for original engineering solutions, he was promoted to a position closer to the major shipping lines after signing up for the Merchant Marines division. Isaac has been attempting to reunite with his father for some time, who had mysteriously gone missing; his personnel files classified by high levels of the Earth Government. Isaac previously lived with his girlfriend Nicole Brennan, but his career had begun to stagnate about the same time as her assignment - and promotion - to the USG Ishimura two years prior to its communication blackout.
Engineer Isaac Clarke was one of the five crew members stationed aboard the USG Kellion when it was dispatched to repair the communications array of the USG Ishimura. While Isaac volunteered for the mission due to his resourceful engineering specialties, his ulterior motives for taking part in the hasty operation were to track down his past girlfriend and possibly fiancée, Nicole, who was serving on the Ishimura since her promotion to senior medical officer two years prior. Soon after emerging from hyperspace near the Ishimura's last known position above colony world Aegis VII, the Kellion was severely damaged during a malfunction in the docking procedures and was forced to crash land in the Ishimura's hangar bay. Shortly after disembarking from the damaged Kellion and noticing that the ship seemed deserted, the party was set upon by unknown assailants, horribly mutated members of the Ishimura's crew, exhibiting murderous rage, in the Flight Lounge. The wake of the attack left only Computer Specialist Kendra Daniels and the team's commander Captain Zach Hammond alive. Isaac, in the chaos, is separated from the rest of the group, and avoids his pursuers by escaping down a nearby elevator. Isaac is left with no way out in sight, as the Kellion is destroyed when Isaac attempts to repair it after returning to the docking bay.
Still in touch with Kendra and Hammond via comlink and hololink, Isaac aided in the Ishimura's repair through orders involving numerous tasks across the ship. Despite being opposed at every turn by a severe Necromorphic infestation, and later the deranged Unitologist zealot Dr. Challus Mercer, a C.Q.D beacon was eventually placed on an asteroid chunk undergoing ore extraction and purged from the mining hold. The signal attracted the attention of a military vessel, the USM Valor. However, the crew of the Valor was slaughtered by a Necromorph shortly thereafter when they retrieved an Ishimura escape pod which contained a Slasher, trapped and jettisoned from the ship's bridge by Hammond.
With its crew dead, the Valor was left to drift out of control and subsequently sideswiped the Ishimura amidships. A successful attempt to retrieve the Valor's singularity core nonetheless resulted in Hammond's death at the hands of an Enhanced necromorph, the Brute. Returning to the Ishimura, Isaac is contacted by Dr. Terrence Kyne, a scientist who plans to return the Red Marker to colony below, via the remaining shuttle. After Isaac repairs the shuttle with the Valor's singularity core and restores its navigation discs, Kyne is shot and killed by the duplicitous Kendra Daniels. She departs with the marker, revealing herself to be a covert government agent, and that the entire conflict on Aegis 7 was due to C.E.C. interference with the Marker.
Left for dead on the Ishimura, Isaac is saved by Nicole. She appears and compels him to take the Marker back to Aegis 7, recalling the shuttle in the process and forcing Kendra to evacuate. Once on the colony world, Isaac finds the colony to be in a shape of abandoned disarray: covered in gore and the same unitologist writings found on the Red Marker.
Pulling the Marker through the Necromorph-infested colony, Isaac finally succeeds in returning it to its pedestal. This results in a massive, blinding pulse of unknown energy that disables the gravity tethers holding the cracked chunk of Aegis 7. However, Kendra Daniels appears and removes the Marker from the pedestal, intending to load it into the shuttle and return to Earth. Before leaving Isaac to his fate Kendra insists that he has gone insane, and forces him to watch Nicole's last hololog to the end. After professing her love for Isaac, it is revealed Nicole commits suicide in the wake of the spreading Necromorph massacre. It seems that the Marker itself caused Isaac to hallucinate Nicole's voice and appearance during his horrifying journey through the bowels of the ill-fated Ishimura. Despondent yet determined, Isaac returns to the shuttle pad in time to see a tentacle brutally kill Kendra. Seconds after the tentacle discards her body, the ground shakes and the smoky air fills with an ear-splitting roar as the "Hive Mind" rears up from the planet crack crater. Finally revealed after having previously been kept at bay by the Marker, the Hive Mind viciously attacks Isaac. He nonetheless manages to defeat the beast by destroying its "organs" just in time to escape the colony as the tectonic load crashes down.
After his narrow escape, Isaac is left alone on the shuttle to lament his experience. While removing his helmet, Nicole's final message begins playing on the main holoconsole. In his heartbroken state, Isaac stops the video before it finishes. Deactivating all holographic displays, he stares disconsolately into space. A sudden, soft movement to his right catches his eye, and he spins around to face a stow-away Necromorph that unnervingly resembles Nicole - and lunges at him while the screen goes red and unitologist writings is shown while a high pitched scream is heard as the game cuts to the ending credits. However, as he will return in the sequel, it is likely this was either another illusion, either created by his mind or the Marker, or that he survives, killing his attacker.
After drifting for an unknown amount of time, Isaac's Shuttle's distress signal was picked up by a Pleasure Cruise, and then picked up by Recovery Patrol X22376. The Commander, Maxamillian Reinhardt, was suspicious, while 2nd Xander Sklar wanted to find an exposure. They plotted their course to pick up the shuttle, and unwittingly Isaac.
A much more grizzled Isaac Clarke will return in the upcoming sequel, Dead Space 2. He has been confined to a mental hospital, and is suffering from dementia, PTSD and amnesia, having most likely forgotten all that transpired after killing the Hive Mind in the original Dead Space. After awakening from a coma, Isaac, equipped with a new RIG, tools and chased by the Government, necromorphs and images of his girlfriend, he has to help as many people on the Sprawl as he can, while he attempts to make his way to a mysterious doctor that can apparently treat his dementia. It's been stated that Isaac's dementia is a unique strand and it is evidently lethal if left unchecked. This may just mean he will lose his sanity to the point of being unable to fend against the Necromorphs.
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