The book starts with the Doctor giving up his dream of lengthening human life with discoveries he made on the Moon, and showing signs of despair.

The tone of the passages for the first time acknowledges 'nature red in tooth and claw': another of the Doctor's experiments, a house where scavengers and parasites can live without harming other creatures, is also doomed to failure.

The Doctor then receives an urgent call to rescue what is literally his oldest friend: Mudface the Giant Turtle, who was a passenger on Noah's Ark.

Mudface's tale of the Great Flood is told, which was missing from Lofting's 1923 novel Doctor Dolittle's Post Office.

There are many references to genocide and slavery, including a passage where animals gather outside a hut to devour the humans inside (a young man and his beloved, who are the most sympathetic characters next to Mudface and his mate).