Drexler thinks we underestimate the difficulty of building run-away replicators. Nature's had 4 billion years and hasn't managed it. Yes, I'm aware of the wheel argument.
Second, you say it is difficult with many failure modes. So was going to the moon. How can you possibly think it's so difficult that it will never get done? In a thousand years?
Third, you cite Drexler to claim that we underestimate the difficulty. (Who underestimates it? Me? The irrational people who Drexler is afraid will take away his funding, or the handful of academics who seriously consider the issue?) The argument for extreme caution does not rely on it being easy to build run-away replicators, only that it is reasonably possible and that the results are catastrophic. Can you really argue with 99% certainty against the feasibility of future technologies without any sort of restriction based on physical law?
Fourth, you say you are aware of the wheel argument...so...what is your reponse? Should we also consider the laser argument? The computer argument? The space-ship argument? Or the argument from any of the nearly countless things that humanity has created in the past 40 years that never existed in the previous 4,000,000,000 that life was around?
I do think it's interesting the amount of anger I encounter whenever I even remotely question one of the Singularitarians' babies. There seems to be more ... emotional attachment ... than is healthy for skeptical inquiry.
I'd very much like to hear what you have to say, because even when I've discussed this with academics who work in nanotech (though I've never spoken to anyone working directly on replicators), I've never heard a better argument than "it's really, really hard".