Vene C. Gambell was born in Winfield, Iowa on March 8, 1863. While serving as a school principal in Rhodes, Iowa, he met Nellie Francis Webster (born April 12, 1874). Soon after their marriage, the Gambells headed for Alaska as missionaries of the Presbyterian Church in the U.S.A. They were appointed to serve on St. Lawrence Island, an isolated outpost in the Bering Sea, and arrived on the U.S. Revenue Cutter Bear in July 1894.

For three years, Vene and Nellie served the native Yupik population of about 375 inhabitants. Outside provisions arrived once a year via the USRC Bear with occasional visits from whaling crews. Vene wrote a four-part story called The Schoolhouse Farthest West and published it serially in The Youth's Companion and then in pamphlet form through the Woman's Board of Home Missions.

On April 13, 1897, their daughter Margaret was born on St. Lawrence Island. Nellie's poor health forced the family back to the United States that fall. By the next spring, Nellie had recovered so the family boarded the schooner Jane Gray in Seattle to head back to Alaska. A severe storm off the coast of Vancouver Island sank the Jane Gray on May 22, 1898, and all three of the Gambells drowned.

To honor the Gambells, St. Lawrence Island residents chose to rename the settlement of Sivuqaq, on the northwest tip of the island, Gambell.