>> BTW, all I really want to do is modify the From: field based on the
>> recipients (for every email, with no default From). I'll welcome
>> suggestions for existing ways to do that. I Googled a little, but didn't
>> find a clear good solution. Furthermore, I expect over time the rules by
>> which I pick the From: field will get more complex than my knowledge of
>> Elisp.

I don't know how practical the following is but an alternative which
would keep you entirely outside lisp would be to configure
sendmail-program to be your python script and let it modify the message
and then send it on to whatever sendmail program you use.

Getting everything right with command line arguments and the message on
stdin (I guess) and keeping any sane form of error handling may be difficult 

Also, note that sendmail-program is not notmuch specific so if you
configure it might affect other emacs mail stuff like gnus.

Best wishes

Mark