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In The End of The World, Lady Cassandra - a stretched out piece of skin witnessing the destruction of Earth in the year 5 billion, was widely regarded as the last of the human race. Her death in New Earth would seem to imply that she is the end of the line for the human race.

And yet, at the very end of time - 100 billion years in the future, the Tocalfane are explicitly called out as being regressed humans in Utopia, and clearly appear to be human. Indeed, this fact is the shocking twist in Last of the Time Lords is that the Master had persuaded them to come back to 20th Century earth and create a paradox by destroying their ancestors.

The question is - how can the Toclafane be human if they died out nearly 95 billion years earlier with Cassandra? Is there an in-universe explanation?

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Or maybe Doctor Who writers play fast and loose with continuity. No, that would never happen. –  Wikis Mar 18 at 15:40
    
I think the implication is that humans mixed with other races (or "dance" as Nine put it) to the extent that Cassandra was the last full-blooded human. Still, the descendants survive. Though not 100% human, they are primarily human and can be called human. –  Tim S. Mar 18 at 18:43

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Lady Cassandra was the last "pure" human, as she defined "purity". Rose pointed this out to her in "New Earth", that the world was populated by millions of humans, but Cassandra discounted all of them as less pure than her. The implication could be that she was the last human born on Earth to humans also born on Earth ("my father was a Texan"), and that anything else has less claim to the term "human", but that is her particular racist viewpoint only.

In short, Lady Cassandra was only the last human by her definition of the word, but humanity itself merely grew and adapted, changed and evolved by their travels through the galaxy.

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Bravo, this is a great answer –  giacomo casanova Mar 23 at 2:23

Per my answer here, the "humans" you see at the end of the universe aren't modern humans (as we know them) but are the result of highly advanced transhumans periodically devolving back into a physical form resembling modern humanity (e.g. in between their various attempts to become pure energy, gas beings, thought-based entities, etc, etc)

DOCTOR: Don't you see that? The ripe old smell of humans. You survived. Oh, you might have spent a million years evolving into clouds of gas, and another million as downloads, but you always revert to the same basic shape. The fundamental humans. ... End of the universe and here you are. Indomitable! That's the word. Indomitable! Ha!

This, arguably is one of the main reasons the Doctor and the Daleks are so interested in humanity, basically because we outlive the both of them by billions of years.

As to Cassandra being the "last Human", that may be her opinion but it doesn't seem to be one that's shared by Rose who, arguably is more human than Cassandra.The population of "New Earth" apparently numbers into the millions of humans (with even more spread out among the stars) but Cassandra doesn't think they're pure enough to qualify as 'pure human' because she's basically presented as being a bigot.

CASSANDRA: But I'm so alone, hidden down here. The last Human in existence.

ROSE: [...] there's millions of Humans out there. Millions of them.

CASSANDRA: Mutant stock.

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