Biological nano-scale engineering has an additional constraint: it must be evolvable. The amount of bandwidth transmitted into the genome from the world via selection is surprisingly small.
In terms of software architecture, brownian motion gives a sort of message-broadcasting architecture - very decoupled. The messages (proteins) know how to execute themselves (very object oriented). The entity building it from data (ribosome) doesn't know what it's building. The entity powering it (ATP synthase) doesn't know what it's powering.
In this design, in order to one location to communicate a message to another location, some mass has to brownian-motion its way across. Suppose in a redesign, locations that needed to communicate messages were wired together with flexible polymers. Moving electrons, waves of configuration changes, or even molecular messages along a guide would be significantly faster, particularly over long distances; latency is proportional to square of distance for brownian motion. (Indeed, in latency-critical applications, biology does use wire-ish communication; neurons.)
Even admitting that Drexler's nanomachines probably look more ridiculous to a future experienced nanoscale engineer than Da Vinci's machines do to a mechanical engineer, there's obvious room for improvements. We cannot assume that biology is anywhere close to the limits on efficiency imposed by the laws of physics.
Biological nano-scale engineering has an additional constraint: it must be evolvable.
Could you explain this claim?
What are the plausible scientific limits of molecular nanotechnology?
Richard Jones, author of Soft Machines has written an interesting critique of the room-temperature molecular nanomachinery propounded by Drexler:
Rupturing The Nanotech Rapture
The entire article is definitely worth a read. Jones advocates more attention to "soft" nanotech, which is nanomachinery with similar design principles to biology -- the biomimetic approach -- as the most plausible means of making progress in nanotech.
As far as near-term room-temperature innovations, he seems to make a compelling case. However the claim that "If ... such devices can function only at low temperatures and in a vacuum, their impact and economic importance would be virtually nil" strikes me as questionable. It seems to me that atomic-precision nanotech could be used to create hard vacuums and more perfectly reflective surfaces, and hence bring the costs of cryogenics down considerably. Desktop factories using these conditions could still be feasible.
Furthermore, it bears mentioning that cryonics patients could still benefit from molecular machinery subject to such limitations, even if the machinery is not functional at anything remotely close to human body temperature. The necessity of a complete cellular-level rebuild is not a good excuse not to cryopreserve. As long as this kind of rebuild technology is physically plausible, there arguably remains an ethical imperative to cryopreserve patients facing the imminent prospect of decay.
In fact, this proposed limitation could hint at an alternative use for cryosuspension that is entirely separate from its present role as an ambulance to the future. It could perhaps turn out that there are forms of cellular surgery and repair which are only feasible at those temperatures, which are nonetheless necessary to combat aging and its complications. The people of the future might actually need to undergo routine periods of cryogenic nanosurgery in order to achieve robust rejuvenation. This would be a more pleasant prospect than cryonics in that it would be a proven technology at that point; and most likely the vitrification process could be improved sufficiently via soft nanotech to reduce the damage from cooling itself significantly.