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Species 8472 are discovered by the Borg in 2373 when the Borg invade fluidic space (as revealed in the episode Scorpion, Part II) by opening a rift in space using a deflector dish. The Borg discover Species 8472 in the Delta Quadrant and try to assimilate its biotechnology, which is more advanced than anything the Borg have seen. The Borg quickly realize that 8472 is immune to assimilation, and that contemporary Borg technology is no match for it. In fact, 8472 is one of the few species so advanced that its ships are able to destroy Borg cubes in seconds. Species 8472 then invades the Delta Quadrant in retaliation to Borg aggression and begins a systematic extermination of the Borg and innocent species as well. Over the course of five months, tens of billions of drones are lost, as well as several hundred planets. When the crew of Voyager realizes that it has no choice but to go through Borg space to continue home in any kind of timely manner, Captain Kathryn Janeway hatches a plan to construct a weapon to kill Species 8472 and use it as a bargaining chip with the Borg in exchange for safe passage through Borg space. The Borg accept. In conjunction with Janeway, the Borg develop a high-yield warhead armed with modified nanoprobes, developed by the Doctor, the ship's Emergency Medical Hologram (EMH), from the Borg's own technology, that is extremely effective at killing 8472 and forces it to retreat to fluidic space. In return for Janeway's help, the Borg allow Voyager safe passage through their space for the duration of their cooperative efforts. However, upon Species 8472's retreat from normal space, the Borg terminate the alliance in favor of (unsuccessfully) assimilating Voyager.
A member of Species 8472 is left in the Delta Quadrant during the retreat and is relentlessly hunted by a group of Hirogen for several months.
Concerned about the threat posed by humanity, Species 8472 builds 13 "terraspheres" in the Delta Quadrant and recreates Starfleet Academy within as a staging ground for an intelligence gathering mission on Earth. The plan is uncovered by Voyager and peace talks commence. Janeway convinces 8472, led by an individual posing as Boothby, that the United Federation of Planets has no quarrel with them – in fact, the Federation is not even aware of the existence of Species 8472, except for the Voyager crew, and the crew is well aware that the Borg themselves started the war between the two species by invading fluidic space to assimilate the superior technology of Species 8472.
