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.

5 Responses to “Nanobots, nanomedicine, Kurzweil, Freitas and Merkle”

  1. Dave Howorth says:

    I find it very interesting to read your comments at the same time as recent posts in Eric Drexler’s blog. The last paragraph in his latest is particularly relevant:

    “Are soft and hard machines at odds with each other? Surely not. Soft biomolecules and hard inorganic solids have worked together since a bacterium first succeeded in gluing itself to a mineral grain, and perhaps long before, at the origin of life itself. There is no gap between soft and hard nanomachines: The technologies form a continuum, and working together, they can form a bridge.”

  2. Hi, Richard. Thanks for your excellent comments on our response. Your engagement on the technical issues is always informative and very much appreciated. Please rest assured that we share your spirit of rational skepticism. We currently spend most of our time doing technical research on mechanosynthesis and diamondoid machine systems, seeking possible pitfalls and solutions, and publishing our results in refereed journals, e.g.:

    2003
    http://www.molecularassembler.com/Papers/JNNDimerTool.pdf

    2004
    http://www.molecularassembler.com/Papers/JCTNPengMar04.pdf

    2005-6
    http://www.molecularassembler.com/Papers/JCTNPengFeb06.pdf

    2006
    http://pubs.acs.org/doi/abs/10.1021/jp061821e

    2007
    http://pubs.acs.org/doi/abs/10.1021/jp071797k
    http://www.molecularassembler.com/Papers/DPTMotifs.pdf

    2008
    http://www.molecularassembler.com/Papers/MinToolset.pdf

    F&M: “(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”

    RJ: “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.”

    The research on diamondoid nanomachinery and mechanosynthesis done by us during our four respective years at Zyvex (Freitas 2000-2004, Merkle 1999-2003) additionally included mainly one PhD part-time during 2001-3 and another PhD part-time during 2002-5. I’d estimate about $900K was directly spent on this effort during 1999-2005. Total funding provided by IMM for our work has not exceeded $100K. A couple of other people have written a paper or two. It’s difficult to regard efforts by a small handful of people collectively supported by $150K/yr (on avg) or less over the last 15 years as “intense research”, compared, say, to the $1B/yr invested by the U.S. NNI employing tens of thousands of researchers since 2001. The correct perspective is that there have been 15 years of “modest research” by a few, but zero years of “intense research”, on diamondoid nanomachinery and mechanosynthesis.

    RJ: “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.”

    Indeed. The existence of these analogous and supportive technologies (e.g., SPM, PALE, NEMS, MEMS) underlies our growing confidence that mechanosynthesis and, ultimately, diamondoid nanomachinery and the rest of the mechanical paradigm for nanomedicine, are feasible technical objectives.

    RJ: “(3)…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.”

    We understand that nanorobots will need biocompatible coatings. There’s a sizeable literature on protein adsorption to diamond, and related topics, most of it summarized or cited in Nanomedicine Vol. IIA: Biocompatibility (Landes Bioscience, 2003).
    http://www.nanomedicine.com/NMIIA.htm

    RJ: “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.”

    RJ: “(1) …The reasons for this are still aren’t clear, as the fundamental mechanisms by which brushes suppress protein adsorption aren’t yet fully understood.”

    RJ: “(2) nanorobot gears…within sealed housings…To date I don’t see a convincing design for these.”

    RJ: “(5) …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.”

    RJ: “(6) …diamondoid nanomachines are going to be rather floppy…we need to see some simulations of dynamic friction in “properly designed rigid nanomachinery”.”

    We entirely agree and are seeking resources to help us address these and other challenges
    http://www.molecularassembler.com/Nanofactory/Challenges.htm
    and to perform urgently needed designs, simulations, and calculations (with experiments following theory to conserve money). Perhaps you could suggest collaborators or funding sources to accelerate our item-by-item progress through both our lists? Without significant resources, it’s difficult to produce more than 1-2 high-quality technical papers per year.

    Robert A. Freitas Jr.
    Ralph C. Merkle

  3. Richard Jones says:

    Dave, it’s clear that Drexler is developing a very interesting line of argument on his blog. There are many important examples of soft structures being used to template hard materials in nature, and the work of Jeff Brinker (at Sandia) and Steve Mann (at Bristol), to give just two examples, shows what can be done by way of using this principle in synthetic materials to make hybrid hard/soft nanostructures. What I’m not sure about, and I stand to be corrected here, is whether there are biological examples where hard materials are used, not just as structural elements, but as mechanical components of functional nanomachines.

    Rob, with respect to how to find money – the short answer is simply to identify relevant agencies and write some proposals. A longer answer would consider the dynamics by which research fields take off and become self-sustaining. The case of DNA nanotechnology is an interesting one; this is clearly now an active and well-funded field, despite the fact that at no point has anyone called for a national initiative in the area, nor is the field particularly close to any marketable products that would pull in any industrial interest. For a long time it was sustained by the single-minded enthusiasm of Ned Seeman, then beginning in the late 90′s we saw more and more talented people being drawn into the field, both established scientists and bright newcomers. This sets up a dynamic combining mutual competition and mutual support, which brings about a self-reinforcing cycle of high profile papers being published and successful funding proposals being written.

  4. The case of DNA nanotechnology is an interesting one; this is clearly now an active and well-funded field, despite the fact that at no point has anyone called for a national initiative in the area, nor is the field particularly close to any marketable products that would pull in any industrial interest.

    How remarkable! A massively influential and extremely important area of (nano)science arising “organically” with no external driving strategy from the funding bodies/research councils nor any consideration of future economic impact. Who’d have thunk it?

    Apologies for the sledgehammer sarcasm, Richard – couldn’t resist. As you know, the issue of having to lay out (in some detail) potential (economic) impact in grant proposals has been exercising me and many others of late .

    Best wishes,

    Philip

  5. Phillip Huggan says:

    I’m still waiting for some mechanosynthesis Boron/Nitrogen on diamond lattice simulations, or of course, a procedure for a real AFM passivate/unpassivate diamond surface site specific reaction.

    Without the Ni/Bo doping, this is like trying to design a wind turbine without copper, without magnetism. A PZT economy seems expensive. There’s been a food crisis, a developed world recession, and probably England will win the World Cup before progress in this field occurs (hahaha obviously just kidding about soccer Argentina is getting revenge)