Nanobots, nanomedicine, Kurzweil, Freitas and Merkle

As Tim Harper observes, with the continuing publicity surrounding Ray Kurzweil, it seems to be nanobot week. In one further contribution to the genre, I’d like to address some technical points made by Rob Freitas and Ralph Merkle in response to my article from last year, Rupturing the Nanotech Rapture, in which I was critical of their vision of nanobots (my thanks to Rob Freitas for bringing their piece to my attention in a comment on my earlier entry). Before jumping straight into the technical issues, it’s worth trying to make one point clear. While I think the vision of nanobots that underlies Kurzweil’s extravagant hopes is flawed, the enterprise of nanomedicine itself has huge promise. So what’s the difference?

We can all agree on why nanotechnology is potentially important for medicine. The fundamental operations of cell biology all take place on the nanoscale, so if we wish to intervene in those operations, there is a logic to carrying out these interventions at the right scale, the nanoscale. But the physical environment of the warm, wet nano-world is a very unfamiliar one, dominated by violent Brownian motion, the viscosity dominated regime of low Reynolds number fluid dynamics, and strong surface forces. This means that the operating principles of cell biology rely on phenomena that are completely unfamiliar in the macroscale world – phenomena like self-assembly, molecular recognition, molecular shape change, diffusive transport and molecule-based information processing. It seems to me that the most effective interventions will use the same “soft nanotechnology” paradigm, rather than being based on a mechanical paradigm that underlies the Freitas/Merkle vision of nanobots, which is inappropriate for the warm wet nanoscale world that our biology works in. We can expect to see increasingly sophisticated drug delivery devices, targeted to the cellular sites of disease, able to respond to their environment, and even able to perform simple molecule-based logical operations to decide appropriate responses to their situation. This isn’t to say that nanomedicine of any kind is going to be easy. We’re still some way away from being able to completely disentangle the sheer complexity of the cell biology that underlies diseases such as cancer or rheumatoid arthritis, while for other hugely important conditions like Alzheimer’s there isn’t even consensus on the ultimate cause of the disease. It’s certainly reasonable to expect improved treatments and better prospects for sufferers of serious diseases, including age-related ones, in twenty years or so, but this is a long way from the prospects of seamless nanobot-mediated neuron-computer interfaces and indefinite life-extension that Kurzweil hopes for.

I now move on to the specific issues raised in the response from Freitas and Merkle.

Several items that Richard Jones mentions are well-known research challenges, not showstoppers.

Until the show has actually started, this of course is a matter of opinion!

All have been previously identified as such along with many other technical challenges not mentioned by Jones that we’ve been aware of for years.

Indeed, and I’m grateful that the cited page acknowledges my earlier post Six Challenges for Molecular Nanotechnology. However, being aware of these and other challenges doesn’t make them go away.

Unfortunately, the article also evidences numerous confusions: (1) The adhesivity of proteins to nanoparticle surfaces can (and has) been engineered;

Indeed, polyethylene oxide/glycol end-grafted polymers (brushes) are commonly used to suppress protein adsorption at liquid/solid interfaces (and less commonly, brushes of other water soluble polymers, as in the link, can be used). While these methods work pretty well in vitro, they don’t work very well in vivo, as evidenced by the relatively short clearing times of “stealth” liposomes, which use a PEG layer to avoid detection by the body. The reasons for this are still aren’t clear, as the fundamental mechanisms by which brushes suppress protein adsorption aren’t yet fully understood.

(2) nanorobot gears will reside within sealed housings, safe from exposure to potentially jamming environmental bioparticles;

This assumes that “feed-throughs” permitting traffic in and out of the controlled environment while perfectly excluding contaminants are available (see point 5 of my earlier post Six Challenges for Molecular Nanotechnology). To date I don’t see a convincing design for these.

(3) microscale diamond particles are well-documented as biocompatible and chemically inert;

They’re certainly chemically inert, but the use of “biocompatible” here betrays a misunderstanding; the fact that proteins adsorb to diamond surfaces is experimentally verified and to be expected. Diamond-like carbon is used as a coating in surgical implants and stents and is biocompatible in the sense that it doesn’t cause cytotoxicity or inflammatory reactions. It’s biocompatibility with blood is also good, in the sense that it doesn’t lead to thrombus formation. But this isn’t because proteins don’t adsorb to the surface; it is because there’s a preferential adsorption of albumin rather than fibrinogen, which is correlated with a lower tendency of platelets to attach to the surface (see e.g. R. Hauert, Diamond and Related Materials 12 (2003) 583). For direct experimental measurements of protein adsorption to an amorphous diamond-like film see, for example, here. Almost all this work has been done, not on single crystal diamond, but on polycrystalline or amorphous diamond-like films, but there’s no reason to suppose the situation will be any different for single crystals; these are simply hydrophobic surfaces of the kind that proteins all too readily adsorb to.

(4) unlike biological molecular motors, thermal noise is not essential to the operation of diamondoid molecular motors;

Indeed, in contrast to the operation of biological motors, which depend on thermal noise, noise is likely to be highly detrimental to the operation of diamondoid motors. Which, to state the obvious, is a difficulty in the environment of the body where such thermal noise is inescapable.

(5) most nanodiamond crystals don’t graphitize if properly passivated;

Depends what you mean by most, I suppose. Raty et al. (Phys Rev Letts 90 art037401, 2003) did quantum simulation calculations showing that 1.2 nm and 1.4 nm ideally terminated diamond particles would undergo spontaneous surface reconstruction at low temperature. The equilibrium surface structure will depend on shape and size, of course, but you won’t know until you do the calculations or have some experiments.

(6) theory has long supported the idea that contacting incommensurate surfaces should easily slide and superlubricity has been demonstrated experimentally, potentially allowing dramatic reductions in friction inside properly designed rigid nanomachinery;

Superlubricity is an interesting phenomenon in which friction falls to very low (though probably non-zero) values when rigid surfaces are put together out of crystalline register and slide past one another. The key sentence above is “properly designed rigid nanomachinery”. Diamond has very low friction macroscopically because it is very stiff, but nanomachines aren’t going to be built out of semi-infinite blocks of the stuff. Measured by, for example, the average relative thermal displacements observed at 300K diamondoid nanomachines are going to be rather floppy. It remains to be seen how important this is going to be in permitting leakage of energy out of the driving modes of the machine into thermal energy, and we need to see some simulations of dynamic friction in “properly designed rigid nanomachinery”.

(7) it is hardly surprising that nanorobots, like most manufactured objects, must be fabricated in a controlled environment that differs from the application environment;

This is a fair point as far as it goes. But consider why it is that an integrated circuit, made in a controlled ultra-clean environment, works when it is brought out into the scruffiness of my office. It’s because it can be completely sealed off, with traffic in and out of the IC carried out entirely by electrical signals. Our nanobot, on the other hand, will need to communicate with its environment by the actual traffic of molecules, hence the difficulty of the feed-through problem referred to above.

(8) there are no obvious physical similarities between a microscale nanorobot navigating inside a human body (a viscous environment where adhesive forces control) and a macroscale rubber clock bouncing inside a clothes dryer (a ballistic environment where inertia and gravitational forces control);

The somewhat strained nature of this simile illustrates the difficulty of conceiving the very foreign and counter-intuitive nature of the warm, wet, nanoscale world. This is exactly why the mechanical engineering intuitions that underlie the diamondoid nanobot vision are so misleading.

and (9) there have been zero years, not 15 years, of “intense research” on diamondoid nanomachinery (as opposed to “nanotechnology”). Such intense research, while clearly valuable, awaits adequate funding

I have two replies to this. Firstly, even accepting the very narrow restriction to diamondoid nanomachinery, I don’t see how the claim of “zero years” squares with what Freitas and Merkle have been doing themselves, as I know that both were employed as research scientists at Zyvex, and subsequently at the Institute of Molecular Manufacturing. Secondly, there has been a huge amount of work in nanomedicine and nanoscience directly related to these issues. For example, the field of manipulation and reaction of individual atoms on surfaces directly underlies the visions of mechanosynthesis that are so important to the Freitas/Merkle route to nanotechnology dates back to Don Eigler’s famous 1990 Nature paper; this paper has since been cited by more than 1300 other papers, which gives an indication of how much work there’s been in this area worldwide.

— as is now just beginning.

And I’m delighted by Philip Moriarty’s fellowship too!

I’ve responded to these points at length, since we frequently read complaints from proponents of MNT that no-one is prepared to debate the issues at a technical level. But I do this with some misgivings. It’s very difficult to prove a negative, and none of my objections amounts to a proof of physical impossibility. But what is not forbidden by the laws of physics is not necessarily likely, let alone inevitable. When one is talking about such powerful human drives as the desire not to die, and the urge to reanimate deceased loved ones, it’s difficult to avoid the conclusion that rational scepticism may be displaced by deeper, older human drives.