1. The Swarm - I don't know why I love this reason the most when ever I think about it. I mean what some believe is that The Swarm consumed all of humanity, killing the species. I think one of the Beast Wars writers wanted the Vok's origin story as they used to being The Swarm but Prime used the Matrix to purify them, which made them feel guilty over the species they had to destroy. It really gives them a very great reason for expertimenting on Earth. They were trying to strength the planet and humanity so they could overcome.
2. Human destroyed by Angolmois energy - I think one of the Japanses BW cartoons said this or implied it.
3. Humanity has cut off all ties to Cybertron
4. And this one that I found was very interesting to say the least - The Maximals and Predacons are exactly the product of Humanity and Cybertronians merging together.

What do you believe?
