What is the origin of the phrase 'What's up'?

Contrary to the popular belief that the phrase is derived from the the famous catchphrase 'Whats'up, Doc?' of the cartoon character Bugs Bunny, it is not.

The phrase appears in Jack London's The Sea Wolf (1904), chapter 25 (-- "What's up?" I asked Wolf Larson.--)

Another referance to 'whatsup' can be found in a short story The Adventures of Shamrock Jolnes from the collection Sixes and Sevens (1911) by acclaimed American short story writer O' Henry (1862-1910). The character Shamrock Jolnes says, "Good morning, Whatsup."

Bugs Bunny made his first appearance in 'A Wild Hare' on 27 July 1940, many years after both of these references. However it can be said the phrase was made popular by Bugs Bunny.