could a 1961 mercury comet automatic handle driving on the interstate?

As long as you remember you are driving 50 year old machinery, there will be no problem. Keep the speeds reasonable, and allow PLENTY of room for stopping. 4 wheel drum brakes do need space. It also depends on the tires. If you are running Bias ply or Bias belted, the handling will be way below what you expect. With a good set of radial tires, grip will be fine. If this is something you plan on doing regularly, though, I would plan on upgrading the brakes. The front disc, dual system from a late-60s Mustang is basically a bolt in proposition. If, though, the donor car is a V-8, you will have 5 stud wheels and 14 inch tires, instead of the 4 stud, 13 inch wheels. You can get the 4 stud discs for the Falcon. The other concern is acceleration. You will find the Falcon is SLOW to get up to speed. About 22 seconds 0-60, so you have to allow for that in your driving. I would have the old girl gone over stem to stern and checked out first, though. Remember, parts are a dead cinch, since it is the same car under the skin as a first generation Mustang, so the Mustang parts fit and are as common as dirt.

Sorry, for Falcon, read Comet. The are the same car mechanically.

Absolutely, use lead substitute unless the heads have been rebuilt using hardened valve seats. Without it, you will eventually be forced to rebuild the heads, as the seats will wear.