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.

Brain interfacing with Kurzweil

The ongoing discussion of Ray Kurzweil’s much publicized plans for a Singularity University prompted me to take another look at his book “The Singularity is Near”. It also prompted me to look up the full context of the somewhat derogatory quote from Douglas Hofstadter that the Guardian used and I reproduced in my earlier post. This can be found in this interview“it’s a very bizarre mixture of ideas that are solid and good with ideas that are crazy. It’s as if you took a lot of very good food and some dog excrement and blended it all up so that you can’t possibly figure out what’s good or bad. It’s an intimate mixture of rubbish and good ideas, and it’s very hard to disentangle the two, because these are smart people; they’re not stupid.” Looking again at the book, it’s clear this is right on the mark. One difficulty is that Kurzweil makes many references to current developments in science and technology, and most readers are going to take it on trust that Kurzweil’s account of these developments is accurate. All too often, though, what one finds is that there’s a huge gulf between the conclusions Kurzweil draws from these papers and what they actually say – it’s the process I described in my article The Economy of Promises taken to extremes – “a transformation of vague possible future impacts into near-certain outcomes”. Here’s a fairly randomly chosen, but important, example.

In this prediction, we’re in the year 2030 (p313 in my edition). “Nanobot technology will provide fully immersive, totally convincing virtual reality”. What is the basis for this prediction? “We already have the technology for electronic devices to communicate with neurons in both directions, yet requiring no direct physical contact with the neurons. For example, scientists at the Max Planck Institute have developed “neuron transistors” that can detect the firing of a nearby neuron, or alternatively can cause a nearby neuron to fire or suppress it from firing. This amounts to two-way communication between neurons and the electronic-based neuron transistors. As mentioned above, quantum dots have also shown the ability to provide non-invasive communication between neurons and electronics.” The statements are supported by footnotes, with impressive looking references to the scientific literature. The only problem is, that if one goes to the trouble of looking up the references, one finds that they don’t say what he says they do.

The reference to “scientists at the MPI” refers to Peter Fromherz, who has been extremely active in developing ways of interfacing nerve cells with electronic devices – field effect transistors to be precise. I discussed this research in an earlier post – Brain chips – the paper cited by Kurzweil is Weis and Fromherz, PRE, 55 877 (1977) (abstract). Fromherz’s work does indeed demonstrate two-way communication between neurons and transistors. However, it emphatically does not do this in a way that needs no physical contact with neurons – the neurons need to be in direct contact with the gate of the FET, and this is achieved by culturing neurons in-situ. This restricts the method to specially grown, 2-dimensional arrays of neurons, not real brains. The method hasn’t been demonstrated to work in-vivo, and it’s actually rather difficult to see how this could be done. As Fromherz himself says, “Of course, visionary dreams of bioelectronic neurocomputers and microelectronic neuroprostheses are unavoidable and exciting. However, they should not obscure the numerous practical problems.”

What of the quantum dots, that “have also shown the ability to provide non-invasive communication between neurons and electronics”? The paper referred to here is Winter et al, Recognition Molecule Directed Interfacing Between Semiconductor Quantum Dots and Nerve Cells, Advanced Materials 13 1673 (2001) ( Richard JonesPosted on Categories General

The Economy of Promises

This essay was first published in Nature Nanotechnology 3 p65 (2008), doi:10.1038/nnano.2008.14.

Can nanotechnology cure cancer by 2015? That’s the impression that many people will have taken from the USA’s National Cancer Institute’s Cancer Nanotechnology Plan [1], which begins with the ringing statement “to help meet the Challenge Goal of eliminating suffering and death from cancer by 2015, the National Cancer Institute (NCI) is engaged in a concerted effort to harness the power of nanotechnology to radically change the way we diagnose, treat, and prevent cancer.” No-one doubts that nanotechnology potentially has a great deal to contribute to the struggle against cancer; new sensors promise earlier diagnosis, and new drug delivery systems for chemotherapy offer useful increases in survival rates. But this is a long way from eliminating suffering and death within 7 years. Now, a close textual analysis of the NCI’s document shows that actually there’s no explicit claim that nanotechnology will cure cancer by 2015; the talk is of “challenge goals” and “lowering barriers”. But is it wise to make it so easy to draw this conclusion from a careless reading?

It’s hardly a new insight to observe that the development of nanotechnology has been accompanied by exaggeration and oversold promises (there is, indeed, a comprehensive book documenting this aspect of the subject’s history – Nanohype, by David Berube [2]). It’s tempting for scientists to plead their innocence and try to maintain some distance from this. After all, the origin of the science fiction visions of nanobots and universal assemblers is in fringe movements such as the transhumanists and singularitarians, rather than mainstream nanoscience. And the hucksterism that has gone with some aspects of the business of nanotechnology seems to many scientists a long way from academia. But are scientists completely blameless in the development of an “economy of promises” surrounding nanotechnology?

Of course, the way most people hear about new scientific developments is through the mass media rather than through the scientific literature. The process by which a result from an academic nano-laboratory is turned into an item in the mainstream media naturally emphasises dramatic and newsworthy potential impacts of the research; the road from the an academic paper to a press release from a University press office is characterised by a systematic stripping away of the cautious language, and a transformation of vague possible future impacts into near-certain outcomes. The key word here is “could” – how often do we read in the press release accompanying a solid, but not revolutionary, paper in Nature or Physical Review Letters that the research “could” lead to revolutionary and radical developments in technology or medicine?

Practical journalism can’t deal with the constant hedging that comes so naturally to scientists, we’re told, so many scientists acquiesce in this process. The chosen “expert” commentators on these stories are often not those with the deepest technical knowledge of issues, but those who combine communication skills with a willingness to press an agenda of superlative technology outcomes.

An odd and unexpected feature of the way the nanotechnology debate has unfolded is that the concern to anticipate societal impacts and consider ethical dimensions of nanotechnology has itself contributed to the climate of heightened expectations. As the philosopher Alfred Nordmann notes in his paper If and then: a critique of speculative nanoethics (PDF) [3], speculations on the ethical and societal implications of the more extreme extrapolations of nanotechnology serve implicitly to give credibility to such visions. If a particular outcome of technology is conceivable and cannot be demonstrated to be contrary to the laws of nature, then we are told it is irresponsible not to consider its possible impacts on society. In this way questions of plausibility or practicality are put aside. In the case of nanotechnology, we have organisations like the Foresight Nanotech Institute and the Centre for Responsible Nanotechnology, whose ostensible purpose is to consider the societal implications of advanced nanotechnology, but which in reality are advocacy organisations for the particular visions of radical nanotechnology originally associated with Eric Drexler. As the field of “nanoethics” grows, and brings in philosophers and social scientists, it’s inevitable that there will be a tendency to give these views more credibility than academic nanoscientists would like.

Scientists, then, can feel a certain powerlessness about the way the more radical visions of nanotechnology have taken root in the public sphere and retain their vigour. It may seem that there’s not a lot scientists can do about the media treats science stories; certainly no-one made much of a media career by underplaying the potential significance of scientific developments. This isn’t to say that within the constraints of the requirements of the media, scientists shouldn’t exercise responsibility and integrity. But perhaps the “economy of promises” is embedded more deeply in the scientific enterprise than this.

One class of document that is absolutely predicated on promises is the research proposal. As we see more and more pressure from funding agencies to do research with a potential economic impact, it’s inevitable that scientists will get into the habit of making more firmly what might be quite tenuous claims that their research will lead to spectacular outcomes. It’s perhaps also understandable that the conflict between this and more traditional academic values might lead to a certain cynicism; scientists have their own ways of justifying their work to themselves, which might mitigate any guilt they might feel about making inflated or unfeasible claims about the ultimate applications of their work. One way of justifying what might seem somewhat reckless claims about is the observation that science and technology have indeed produced huge impacts on society and the economy, even if these impacts were unforeseen at the time of the original research work. Thus one might argue to oneself that even though the claims made by researchers individually might be implausible, collectively one might have a great deal more confidence that the research enterprise as a whole will deliver important results.

Thus scientists may not be at all confident that their own work will have a big impact, but are confident that science in general will deliver big benefits. On the other hand, the public have long memories for promises that science and technology have made but failed to deliver (the idea that nuclear power would produce electricity “too cheap to meter” being one of the most notorious). This, if nothing else, suggests that the nanoscience community would do well to be responsible in what they promise.

2. Berube, D. Nanohype, (Prometheus Books, Amherst NY, 2006)
3. Nordmann, A. NanoEthics 1, 31-46 (2007).

The Singularity gets a University

There’s been a huge amount of worldwide press coverage of the news that Ray Kurzweil has launched a “Singularity University”, to promote his vision (not to mention his books and forthcoming film) of an exponential growth in technology leading to computers more intelligent than humans and an end to aging and death. The coverage is largely uncritical – even the normally sober Financial Times says only that some critics think that the Singularity may be dangerous. To the majority of critics, though, the idea isn’t so much dangerous as completely misguided.

The Guardian, at least, quotes the iconic cognitive science and computer researcher Douglas Hofstadter as saying that Kurzweil’s ideas included “the craziest sort of dog excrement”, which is graphic, if not entirely illuminating. For a number of more substantial critiques, take a look at the special singularity issue of the magazine IEEE Spectrum, published last summer. Unsurprisingly, the IEEE blog takes a dim view.

Many of the press reports refer to the role of nanotechnology in Kurzweil’s vision of the singularity – according to the Guardian, for example, “Kurzweil predicts the creation of “nanobots” that will patrol our bloodstreams, repairing wear and tear as they go, and keeping our bodies perpetually young.” It was this vision that I criticised in my own contribution to the IEEE Singularity special, Rupturing the Nanotech Rapture; I notice that the main promoters of these ideas, Robert Freitas and Ralph Merkle, are among the founding advisors. At the time, I found it interesting in the responses to my article, that a number of self-identified transhumanists and singularitarians attempted to distance themselves from Kurzweil’s views, characterising them as atypical of their movement. It will be interesting to see how strenuously they now attempt to counter what seems to be a PR coup by Kurzweil.

It’s worth stressing that what’s been established isn’t really a university; it’s not going to do research and it won’t give degrees. Instead, it will offer 3-day, 10-day and 9 week courses, where, to quote from the website, one could imagine, for example, that issues such as global poverty, hunger, climate crisis could be studied from an interdisciplinary standpoint where the power of artificial intelligence, nanotechnology, genomics, etc are brought to bare in a cooperate fashion to seek solutions” (sic). Singularitarianism is an ideology, and this is a vehicle to promote it.

Among the partners in the venture, Google has succeeded in getting a huge amount of publicity for its $250,000 contribution, though whether it’s a wise cause for it to be associated with remains to be seen. As for the role of NASA and space entrepreneur Peter Diamandis, I leave the last word to that ever-reliable source of technology news, The Register: “There will be the traditional strong friendship between IT/net/AI enthusiasm and space-o-philia. In keeping with the NASA setting, SU will have strong involvement from the International Space University. ISU, founded in 1987 by Diamandis and others, is seen as having been key to the vast strides humanity has made in space technology and exploration in the last two decades”