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In 1899, Edward H. Harriman, the head of the Union Pacific Railroad, organized a sea expedition along the coast of Alaska to study the flora, fauna, and natural wonders of the area. Harriman also intended to bring back specimens of the animals and plants he encountered. The group chosen for the voyage included scientists, artists, and writers. In 2001, Tom Litwin, of the Clark Science Center at Smith College, lead a similar expedition, retracing as closely as possible the route followed by the Harriman party. Along the way, we see many of the same peoples and places as those on the first expedition. We also see the changes that Alaska has endured in the previous 100 years.

Two months after the destruction of both the Primatech and Pinehurst, and the death of Arthur Petrelli, the now-villainous Nathan returns with a vengeance by persuading the U.S. President and the government to round up all people with abilities for containment and disposal, leading to Claire, Ando, Peter, as well as Tracy to become fugitives from the people who were their former allies. In Japan, a powerless Hiro tries to live through the super-charger Ando as his latest partner. In New York, Peter struggles to find a life for himself as a paramedic, but finds that his cannot hide from his past. Claire learns about Nathan's and Angela's plans for interment of people with abilities and sets out to warn Matt Parkman who learns more about his abilities from the spirit of the African spiritualist Usutu. Elsewhere, Syler travels to Baltimore to locate his long-lost father and ends up being the only one who escapes from a government dragnet led by a mysterious agent known only as 'the Hunter'. Mohinder also learns that he has been targeted, and that Noah Bennett is apparently working with Nathan as well.