If your wife loses 2.9 seconds per 10 feet of uphill, but gains 3.1 seconds per 10 feet of downhill, she should just find an absolutely crazy hilly course and set massive PRs.
She should run a full 26 minutes faster on the Pike's Peak marathon than she would on a flat course, with its 7800 feet each of uphill and downhill.
If we can find a faster marathon, she could do even better! Your wife is probably the only person who gets faster as the course gets tougher! If we find a hilly enough course, she could set the world record!
To drop an hour off of her flat course marathon using your calculations, she would need a course with 18,000 feet of uphill and downhill. That is an average slop of 25%. That sounds really high, but there are some backroads with slopes that high, it isnt just limited to paths. So just find a nice mile long stretch of road with an average of 25% grade and create a course that goes up and down it 13 times. If your wife's PR is under 3 hours, she could be the first woman to run under 2 hours! Suck it Kipchoge!