The story is set in the year 2021. The Republic of Costigar, in Africa, is a country that has been plagued by warfare for over a decade, and is finally on the road to peace. However, they still struggle with attacks by guerrilla militants, land mines, and many refugees. Despite this, the country is slowly on its way to becoming a peaceful nation. Countries around the world have been sending aid to the country, as well as building hospitals to help the citizens of Costigar. However, they are very short on staff and need more to be able to take care of all of the patients.
Doctor Derek Stiles, along with his faithful nurse Angie Thompson, get called to the war-ravaged country. After saving a patient, Doctor Adel Tulba comes into the scene. He, however, makes a misdiagnosis and forces Dr. Stiles to operate. Later, a friend of Angie's named Sylvia Warenburg leaves to pick up supplies for the camp. A soldier returns to the doctors informing them that the car Sylvia was traveling in hit a landmine. An operation on Sylvia's chest soon follows.
Following the operation, Caduceus USA informs Derek that he and Angie must return the United States immediately. Derek then announces the news to Angie and Adel. Derek gives Adel the option to come with them and be mentored in being a doctor. Adel couldn't decide right away, so Stiles gave him 3 days to decide. Finally, just as Angie and Derek were just about to leave, Adel decides to go with them.
The three of them then fly to America, and Adel is in awe as he gets a glimpse of the first city he has ever been in. They then report to Caduceus for an explanation as to why they had to leave so soon. Robert Hoffman and Sidney Kasal give them the briefing. A disease everyone thought was eradicated in the past is now infecting people all over the world. The three then learn about Post-GUILT Syndrome, or PGS. PGS is a disease that affects previous hosts to the bio-terrorist disease, GUILT. Throughout the game, seven types of PGS exist, but only four are identifiable (via patient backgrounds). Currently identifiable cases of PGS are from Kyriaki, Triti, Pempti, and Savato.
The first one seen in the game is PGS-Kyriaki. It was affecting Linda Reid, the first GUILT patient Derek sees. After this operation, a boy named Emilio Juarez, a "sinner," or a child captured by Delphi three years ago and was used as a GUILT test subject, treated for Pempti 3 years earlier, had PGS-Pempti. Prior to that operation, however, Emilio required a liver transplant due to the extremely severe damage to his liver. Just as that operation is ending, Derek witnesses the first strain of Neo-GUILT, or more refined GUILT specimens. It is called Nous and its purpose is so far unknown.
After that operation, a woman who looks young due to the use of Aletheia, belying the fact that she isn't very young in age, named Ms. Mayuzumi, president of the Acropolis Pharmaceutical, meets with Derek and bribes him money in an attempt to make him work for her. Unknowingly to him, Ms. Mayuzumi wants to unlock the secret of his Healing Touch, which she does by having Dr. Stiles filmed while performing an operation on a man with aneurysms.
Soon after, a GUILT outbreak occurs at Elysium, a hospital for people who are recovering from GUILT. The Caduceus GUILT team mobilizes and then heads for Elysium. Four people are infected and must be operated on in rapid succession. The four who are infected, excluding the first one, are infected with a mutated form of Kyriaki. Instead of fighting the Stage 2 Kyriaki after all Stage 1 Kyriaki are killed, you would face a Stage 3 Queen Kyriaki. The queen releases Stage 1 Kyriaki eggs every time she dives into the organ, which, after a little bit, hatch and release more Kyriaki. However, after the third patient, Heather Ross, whom you meet earlier in the game, the fourth patient is Emilio Juarez. He is never operated on in actual gameplay. For a couple of seconds, Emilio seems stable, but then he flatlines, or has no heartbeat. Derek tries desperately to revive him using a defibrillator at 100 volts, then 200, 300, finally 360 volts, but his efforts are to no avail. Derek then tries to use the Healing Touch, but that fails as well. The episode ends with Angie trying to comfort Derek over Emilio's death, to no avail. At the very conclusion of the operation portion of the chapter, the screen reads "operation failed."
Derek has changed, and this change is made quite obvious as the story progresses. Derek, though still traumatized by Emilio Juarez's death, attempts to operate on Adel Tulba because he came down with the Cost disease, where blood pools under the skin. Derek reaches the point of the operation where it would be most beneficial to use the Healing Touch, but it seems to "short out." Derek desperately tries to tap into his extreme concentration multiple times, to no avail. Dr. Hoffman takes over the procedure, and once again, Derek fails to successfully complete an operation. Derek then sinks into a deep depression, and it is decided that he will transfer to Hope Hospital for the time being.
At Hope he is mentored by Greg Kasal and Cybil Kasal, formerly Cybil Myers, and by Mary Fulton. They take Derek under their wing for a period of time, until Derek is asked by Angie to return to Caduceus. He accepts the offer, and still without his ability, returns to Caduceus. When Tyler Chase and Leslie Sears get the news of this, they make note of the love interest between Derek and Angie. When Derek hears this, because the four are talking directly to each other, he blushes and remains silent. Angie, however, who despises the fact that many people think that she and Derek love each other, responds rather fiercely to the comment and says that nothing like that would never happen.
Soon, Angie learns that her father, Kenneth Blackwell, currently imprisoned, has PGS-Savato and must be operated on. Derek, though still without his Healing Touch, and Angie proceed to the State Prison and start to talk with him. About half way through the conversation, Kenneth complains about chest pain, difficulty breathing, and finally collapses. Derek immediately opens Blackwell's chest up and finds color changing, mutated tumors on his heart which he must excise with speed and precision. After excising the "normal" ones, a last, final tumor that very rapidly changes colors, must be treated. Derek realizes that he can't remove the last tumor without the Healing Touch. He closes Kennneth up and the procedure is finished. Later on, he then tries a second time to try to cure Blackwell, and in order to keep his promise to Angie, he declares that he refuses to let Kenneth die. Derek successfully uses his Healing Touch, and completes the procedure.
Kenneth does survive and gets follow up treatment from the Caduceus staff that just arrived. Soon after, two new threats appear to the Caduceus staff. The first is the Hands of Asclepius, which continues to drain the staff of its members, including Adel Tulba. The other is the fact that Delphi is now behind the GUILT outbreaks. Though Eric von Raitenau, or Adam is dead, the terrorist group is under new leadership. His name is [Heinrich von Raitenau], Adam's grandson. Derek meets him towards the end of the 6th chapter of episodes when Derek and Angie are kidnapped by Heinrich's henchmen, who, oddly, all look exactly the same. Heinrich then reveals to Derek and Angie that he plans to release new, mutated forms of GUILT all over the world. He also reveals that he will use Angie as a breeding chamber for the new GUILT. Derek becomes furious with Heinrich and Angie remains silent, horrified of the idea. Derek swears that if Heinrich infects Angie with GUILT, he will surgically remove it. However, Heinrich has Derek and Angie thrown into a holding chamber for the time being. The two then work together to destroy various locks to open the door to the chamber, and escape. After escaping, the two locate a phone and call the police, who then contact the HOA and Caduceus. The three groups mobilize, and assemble a search and destroy/rescue team and they later surround the Delphi estate and commence the attack. The three main objectives are to eliminate Heinrich von Raitenau, to rescue Derek and Angie, and to eliminate the threat of GUILT once and for all. The police then give the order to commence with the operation. all goes smoothly with a gunfight here and there. The teams find Derek and Angie and escort them out into safety. Then the police report that they've found Heinrich and are attempting to move in and capture him. Derek and Angie insist that they go in as well to prevent the possible spread of any GUILT. So they go into the basement and find Heinrich and two other kids floating in a preservation tank. They are the Prince and Princess that were mentioned earlier. The two are sinners and they are Heinrich's son and daughter, Christine and Karl. They, as you will find out are one, non-English speaking Austrians, and their well being, in the sense that if the GUILT inside attacks them or not, is linked to their father's GUILT. So when the team finds Heinrich, he sprays a hallucinagenic gas into the air. But just before the effects of the gas set in, Adel Tulba injects a GUILT neutralizing serum that is supposed to kill the GUILT inside Heinrich, Christine, and Karl. However the serum backfires and starts to cause the GUILT inside Heinrich to go beserk and attack Heinrich's body. So in agony, he screams out in severe pain. Karl then yells, "Vater?, Vater!", which means father?,father!, in German. Christine then says something like, "my stomach hurts", in German. Then, because the condition of the GUILT inside the three is linked, Karl and Christine start to fall ill. An operation must be done on the three in rapid succession. The first patient, Heirich, is infected with the mutated strain of Tetarti. The second patient, Karl, is infected with the mutated strain of Kyriaki. The last patient, Christine, is infected with the somewhat-mutated strain of Pempti. After the operation von Raitenau is eventually taken to prison and an international criminal by the world court.
Several weeks after that, Derek and Angie operate on a major tennis player in secret, discovering she is harboring a new strain of GUILT. With some prompting, she admits that she took special steroids provided by the HOA and Acropolis, and that they greatly enhanced her concentration and physical prowess. Meanwhile, Heather visits a hospital where her mother is in a coma. She has an icy conversation with her father, Patrick Mercer. The police and Caduceus raid the HOA and Acropolis headquarters acting on info provided from Blackwell, who had been reporting to Dr. Hoffman. No sign of Mercer and Mayuzumi, but the doctors augmented by the HOA are suffering from debilitating aneurysms caused by GUILT. After operating on several patients, Derek, Angie, and Blackwell confront Adel, who is holed up in Mercer's office. Adel goes insane and tries to kill Derek using the Healing Touch, but is subdued and operated on, removing another new strain of GUILT. He returns to normal shortly thereafter. A few days later, Caduceus and the police raid Acropolis' main manufacturing plant, and Derek, Angie, and Heather confront Mercer, who reveals his true intent - he created new strains of GUILT in an attempt to reach a revitalizing stage that would revive his wife and Heather's mother, Tracy, who he removed from the hospital shortly after Heather's visit. He infects Tracy with a strain of GUILT, and she goes into a critical stage. Derek, Angie, and Heather operate on her, but Mercer escapes in the confusion. The three follow him into the basement of Acropolis, where they find Mercer, as well as Mayuzumi, who is hooked up to a series of tanks. Mayuzumi explains she has been keeping her youth and looks by voluntarily being the host of Aletheia, the final strain of GUILT. She taunts Derek, explaining that if she is forcibly removed from the machines or killed, they will release a gas of GUILT fatal to anyone who breathes it. Mercer injects her with a new compound in a final attempt to find a GUILT to save Tracy, and she is drained and reduced to an old woman. Tyler arrives with a new serum to treat it developed by Victor, and goes to disable the GUILT containers with Heather while Derek and Angie operate. The operation is successful, and the GUILT is neutralized. The police arrive and shoot Mercer, killing him instantly. Over the following few months, Caduceus regains its standing in the medical community, Adel returns to Africa, and Derek and Angie begin traveling the world to improve their skills. The game ends with them on a flight to meet up with Professor Irvine, a cranial nerve surgeon, reading a letter of thanks from Heather and discussing Derek's training with him (possibly awakening Tracy Mercer as a result). Angie then chooses that moment to implicitly confess her feelings for Derek, with the closing text strongly suggesting a romantic relationship.
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