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When John Marston is shot in the ribs by one of Bill Williamson's men, Bonnie MacFarlane, along with Amos, take him to Doctor Johnston in Armadillo. Johnston removes the bullet from John and bandages the wound. According to Bonnie MacFarlane, he said John would be fine as soon as he saw he wasn't dead.
Sometime after John Marston had recovered, John and Bonnie returned to Armadillo. There, Johnston gave John some Medicine, previously paid for by Bonnie. Here after, Dr. Johnston is always available in Armadillo, where Marston can purchase medical supplies.
- He has exactly the same character model as Clyde Garrison, but with two exceptions: Johnston's hat is black instead of white, and he sports a string tie instead of a neck tie. He also shares a character head with Hal Pollard, Harvey Skaggs, Ralph Bagley, and Tripp Lockley.
- He may comment while John walks into his store about getting a bullet removed from his leg, despite the fact that John walks perfectly and suffers from no wounds as far as anyone can tell.
- According to Bonnie MacFarlane, Nathanial is the doctor who saved John Marston's life.
- According to an ad in The Blackwater Ledger, Johnston claims that Chewing Tobacco has "wonderful health benefits." This is only confirmed with John Marston, although this was most likely a sales scam.
- Nigel West Dickens gets treated for his wounds by Johnston. It is implied Johnston is highly skeptical, if not outright dismissive, of West Dickens's "miracle cures". This makes Dickens angry, and he never wants anything to do with him again.
- He is the only doctor in Red Dead Redemption that is relevant to the storyline.
- He sometimes remarks "I've got one of them electric belts if you wanna lose weight." This is a reference to electric abdominal muscle stimulaters, which were a popular trend in the early 20th century.