Couple things... is it eating away at your memory (RAM) or storage (disk space)?
If you mean RAM, the answer is no. The computer memory used to run simplewallet and the daemon are not dependent on where things are being stored, at least in any measurable sense.
If you mean disk space, yes, kind of. What I mean by this is that you should still "run" bitmonerod and simplewallet from your primary disk, but specify a data directory on your external hard drive for bitmonerod. On macOS, this involves running the daemon like dEBRUYNE said, as such:
./bitmonerod --data-dir /Volumes/<my external HDD>
Note that you should run this command in the Terminal from the directory where you've save the bitmonerod executable.
To figure out what goes in
<my external HDD>, open a Terminal and type
This should display a list of all connected volumes. Find your HDD (say,
MyHDD), then do
./bitmonerod --data-dir /Volumes/MyHDD
Note that if you have already synced a blockchain in a previous location, you may need to move it or resync.