Isaac was the first of three United States Marshals based in Mercy, Nevada in 1870. He protected Kahler-Jex because the alien had helped to rebuild their town with electricity and stopped a cholera outbreak. He referred to Jex as "Doc", and both men saw each other as a friend. He was also the last human marshal for Mercy for some time, giving the title to the Doctor, who then gave it to the Gunslinger.
He first met the Eleventh Doctor when he saved the Time Lord from being caught by Kahler-Tek — a cyborg more commonly known as "the Gunslinger". Since Isaac had already reasoned that the cyborg was in fact looking for Kahler-Jex, he knew the town was wrong to try to offer the Doctor to the gunslinger (who demanded "the doctor"). He and Rory Williams distracted the Gunslinger in the desert while the Doctor went out to find The TARDIS.
Upon realising that the Gunslinger was going to kill Jex as a war criminal, he pushed Jex out of the way and was killed himself. As he lay dying, he made the Doctor the new marshal and told the Doctor to protect Jex from harm.
Isaac was a good-hearted marshal and a loyal friend who gave his life to protect Kahler-Jex. He quickly grew to respect and trust the Doctor and made him into the next marshal as he lay dying. (TV: A Town Called Mercy)