A large part of Galápagos takes place in Ecuador in 1986, one year after it was published. It was the author's intention for readers to view this story as one possible outcome of the events that took place in the eighties. Two of the main drivers of the story share many similarities with real-life events.

A first is the outbreak of a financial crisis. When the protagonists arrive in Ecuador for "Nature Cruise of the Century", the country is in a dire state because of a crash in the value of the Ecuadorian sucre. Basic goods such as food, shelter and clothing have become very expensive and rare because of this. The eventual food shortage that arises forces the protagonists to flee the country and eventually end up on Santa Rosalia. The beginning of the eighties was the stage for a similar event in the form of the Latin American debt crisis. The international capital markets lost faith in the ability of certain developing nations to pay back the foreign debt they had accumulated. A flight of capital followed and caused exchange rates to depreciate. The whole region was plunged into an economic recession that severely diminished the purchasing power of its inhabitants. Vonnegut blames the human brain for the existence of financial crises and its devastating consequences throughout the book. A second important element in the book is the birth of a bacterium that makes women infertile. It quickly spreads across the globe and eventually leads to the extinction of humanity except for the people stranded on Santa Rosalia. It is likely that the AIDS virus served as an inspiration for this fictional pandemic. AIDS quickly became a pandemic during the eighties and grabbed headlines everywhere as more and more people became infected.

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