Isaac Grier Strain (March 4, 1821, in Roxbury, Franklin County, Pennsylvania – May 14, 1857, in Aspinwall, (alternative name of Colón, Panama) Colombia), an American midshipman. At age 17 he joined the U.S. Navy to apprentice at sea.

Naturally inclined toward exploration, he commanded an 1843 (1845 by some sources) exploratory expedition to the interior of Brazil, Province of São Paulo. In 1848 he began an exploration of the peninsula of Lower California; he worked with the U.S. Mexican Boundary Commission. He was promoted to lieutenant in 1850. Lieutenant Strain was a Corresponding Member of the Academy of Natural Sciences of Philadelphia; the Historical and Geographical Institute of Brazil; and the American Ethnological Society of New York. In 1849 he explored parts of South America and wrote Cordillera and Pampa, Mountain and Plain: Sketches of a Journey in Chili and The Argentine Provinces in 1849, published in New York in 1853.

Leading a United States at peace, and in exercise of Manifest Destiny to expand from the Atlantic seaboard to the Pacific Ocean, U. S. President Franklin Pierce envisioned an Atlantic to Pacific canal route through the Isthmus of Darién, a region also known as the Darién Gap, located in Colombia, presently Panama. Henceforth, Secretary of the Navy James C. Dobbin in late 1853 ordered Lieutenant Strain to form and lead the United States Navy Darien Exploring Expedition in 1854. Setting forth from the Atlantic side of the Isthmus of Darién, his expedition into the Isthmus of Darién began January 20, 1854.

It was in the densely jungled Darién that France and England had sent explorers of their own. The Englishman Gisborne had put pen to perhaps fallacious or inaccurate, but certainly misleading, journals that would lend ambiguity and deaths to Strain's route for traversing the Gap.

The Strain party, in part proceeding upon Gisborne's records, wandered circuitously, split, and became plagued by deteriorating equipment, unreliable and often dangerous native guides, malnourishment, foot-soreness, flesh-embedding parasites, and infectious tropical diseases. Six of Strain's party of 27 died by starvation. The courageous but ill-fated expedition nevertheless contributed to future establishments of land routes, a railroad, and the eventual linking of the Atlantic and Pacific Oceans by a Panama Canal. The canal was completed in 1914, 60 years after Strain's expedition.