The main difference being that we have plenty of examples of lock-based code scaling well. Even large, non-trivial systems, such as the Linux kernel. It used to rely solely on the BKL - big kernel lock - for synchronization, but they have moved to finer grained, data structure level locking.

That makes me think that an implementation of Python that uses fine-grained (or at least finer grained) locks that scales is possible. It's just a question of how feasible is it to transform CPython into such an implementation. Beazley's experiment indicates that the changes may have to be fundamental, such as moving away from reference counting.