Virtually all the approaches against spam have been either against the spammers directly (blacklists or legislation), or on filtering (SpamAssassin), but I wonder if it might be better to approach this from the demand side.

Spammers only spam because it works - sell products, get downline for MLM, etc - but what if ISPs put "You may not respond to spam" as part of their terms and conditions, and those found doing so get their internet accounts suspended/terminated. If you find out that your friends bought something via spam, shun them. It's already socially unacceptable to send spam: why not expand the circle?

I really have no idea how this could be implemented (without intrusive monitoring, at least), but it seems to me that if the demand dried up, so would the supply.

My guess this is a hopeless approach, but it's much easier for me to understand the mentality of a spammer (self interest) than of the moron who responds to it.