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During Europe's Renaissance, the artist and scientist Leonardo da Vinci, among others, established that fossils were the natural remains of organic creatures, and in the middle of the 17th century, Nicolaus Steno of Denmark wrote a treatise proposing that sedimentary rocks were laid down in layers, with the oldest at the bottom. The physical description of fossils was permissible as long as it did not lead to dissonant conclusions regarding the age of the earth. As an example, the early 17th century saw the naming and characterization of the trilobites, an extinct but very large group of marine arthropods once abundant everywhere in the seas and, as a group, of far greater longevity than the dinosaurs. When fossil evidence was used to advance a history of the earth that contradicted a literal reading of the Bible, however, the penalties were severe.

The Age of Enlightenment in Europe sped up religion's waning grip on the interpretation of science, and paleontology as a scientific discipline may be considered to have started in the early 1800s. In the young republic of the United States, Thomas Jefferson, then vice president, in 1797 published one of the first papers on American fossil vertebrates; he also named a gigantic ground sloth that once roamed over much of the United States Megalonyx jeffersonii. At this time there was considerable congress between natural historians in Europe, Great Britain, and the United States, each eager to learn of the other's latest findings and theories. The 19th century was also the age of the quintessential "gentleman explorer," whose travels overlapped in time with government-sponsored exploring expeditions to all parts of the globe. The number of specimens returned from these expeditions led to the founding of many of the great natural history museums. In the middle of this activity, Charles Darwin boarded the Beagle for a multiyear voyage of exploration and natural observation, resulting in his writing On the Origin of Species by Means of Natural Selection in 1859, a major contribution to the blossoming of paleontology.

Contemporary paleontology is modeled on an understanding of life-forms as related in extended family trees, some of very ancient origin. In detailing ancestral and modern lineage, paleontologists want to know the precise physical, chemical, and nutritional environment that supported life and what changes in this environment forced some creatures into extinction while allowing others to thrive.