In the summer of 1918, Cleland assisted Bradley Moore Davis in research on Oenothera by investigating the behavior of the chromosomes which resulted in a startling discovery. Some of the chromosomes in the Oenothera behaved in the normal manner while others regularly arranged themselves end to end in a circle, adjacent chromosomes going into different reproductive cells. Although such chromosomal behavior had been sporadically noted no one had recognized that it occurred regularly for some chromosomes of some organisms. Cleland felt that his discovery might be the clue to understanding the already known erratic pattern of heredity in Oenothera and thereby converting one of the apparent discrepancies with the chromosome theory into one of its strongest supports. Furthermore, his discovery might explain the sudden large hereditary variations which occurred in Oenothera and had been the main basis of the theory of mutation proposed in 1901 by the Dutch botanist Hugo de Vries as an alternative to Darwin's theory of evolution. Cleland demonstrated the causes and the effects of the circles of chromosomes on patterns of heredity and on the origin of large hereditary variations. He used what he had discovered to reconstruct the evolutionary history of Oenothera. A comprehensive study of Oenotheras of North America and to a lesser degree of Central and South America culminated in his history of Oenothera. Shortly before his death the manuscript entitled "Oenothera, Cytogenetics and Evolution" was sent to the publisher.