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Lessons in molecular gymnastics

Viewing the future of nanotechnology through rose-tinted spectacles.

Travels to the Nanoworld: Miniature Machinery in Nature and Technology

  • Michael Gross
Perseus: 1999. 254 pp. $25.95
Nano-landscape: the energetics of protein folding.

For his survey of nanoscale science and engineering, Michael Gross is so upbeat, so genial a guide that one feels churlish to dwell on the dark side. “Assuming that the peaceful use of nanotechnology flourishes and the military misuse will be suppressed efficiently,” he breezes, appearing to imply that scientists have routinely managed this in the past. Meanwhile, China brandishes at troublesome Taiwan a wasp-sized spy helicopter measuring just 3×5×18 millimetres. Not quite nano, but give them time.

All technology is politicized, one point that has not eluded Eric Drexler in his campaign to advertise his vision of the nanotechnological future. Gross's book does not set out to address this dimension, and there is no absolute requirement that it should. Yet this is one illustration of the extent to which I missed critical analysis in an otherwise enjoyable tour of the nanoworld.

I was keen to read the book, because I imagined it would provide a choice selection of vignettes from the frontiers of chemical biology, and I was not disappointed. Here we have the molecular gymnastics of kinesin and myosin, the intricacies of chaperonin-assisted protein folding, the machinations of nitrogenase's inorganic heart.

From these biological nanomachines, we proceed to the factories: to cells that do clever things, such as orientate themselves to the geomagnetic field, register single-photon light sensitivity or engage in antibiotic chemical warfare.

Yet I was constantly left with the question: what does this tell the nanoengineers? Or perhaps more specifically, what does it tell them as opposed to the drug developers, the food scientists, the oncologists? The issue becomes still more pertinent in the chapter on biotechnology. I was fascinated to learn about the pressure-processed jams available in Japan, and glad to be updated on methods of cryopreservation; but where does the nano fit in? We are dealing here with weak interactions of the sort that are the bread and butter of supramolecular chemistry; but then, so was van der Waals, so (on occasion) was Faraday.

The biological world provides ‘existence proofs’ and endless inspiration to would-be nanotechnologists, but this is not enough. At least, I do not imagine it will be enough for the general readers for whom this book is presumably intended, who will struggle to fill in the intervening steps, to relate force-microscopic atom pushing to the mechanics of the cell. I missed an exposition of what lessons we should be drawing from nature.

To take one example, consider G-protein signalling. “Maybe future engineers can borrow a switch or two from here,” suggests Gross; but, with an engineer's hat on, G-protein transduction looks absurdly cumbersome, “an intriguingly complex mesh of structural interdependencies and interactions”, as the author admits. Would it be more fruitful to look, not at structural details, but at algorithmic questions such as receptor redundancy — should the artificial nose have one-analyte, one-receptor correspondence, or (as it appears) a specificity defined at the system-wide level?

Gross is more persuasive where he is most at home, with protein structure and design. What are the prospects for cracking the ‘folding code’, the relationship between sequence and structure? As Gross points out, for all the rapidity of structural solutions, we have data on only a pitiful fraction of this sophisticated language, and those are biased towards relatively small and easily crystallized proteins. The big, difficult cases might contain secondary motifs still unguessed.

With this in mind, the successes so far in protein design are impressive — although it seems significant that these have come largely from mutation of extant proteins rather than from de novo design, which does not (I am assured) yet achieve the same tightly packed, robust motifs as nature's constructions. Peptides are best regarded at present as potentially useful construction materials for the synthetic chemist, rather than the stuff of enzymes built from scratch. The same is true of nucleic acids, from which nanoscale polyhedra and chain-mail can now be built, except that in this case the standard agents of the biotechnologist — ligases, restriction enzymes, polymerases — give us a unique set of versatile tools.

Some of these developments are highlighted in a whistle-stop tour of supramolecular chemistry, which introduces all the usual suspects: crown ethers, rotaxanes, lock- and-key catalysts, Langmuir–Blodgett films, self-assembled monolayers. Fullerenes and carbon nanotubes get their due; however, here, minor errors leave me vaguely anxious about the material with which I am less familiar. Sumio Iijima, whose name is misspelt, might not appreciate being described as “infected” with “fullerene fever” (did anyone really call it that?), given his prior history of work on carbon microstructures; and Don Huffman's lab is a long way from Heidelberg.

There are other lapses in the chemical discussion. What, I wonder, is meant by calling the transition state “a futile arrangement of molecules”? I was puzzled about why gold chemistry was made to sound quite so odd (“it might almost be mistaken for a normal chemical element”), or why its practitioners should ever have been “suspected of secretly practising alchemy”. And I thought the time long past when alchemy must be characterized as chemistry's “dubious heritage”.

The style of writing is hard to place — I suspect the target audience is the legendary educated lay person, but the level is often close to a News and Views article in Nature. I sympathize with Gross about how easy it is to forget that words like ‘moiety‘ are not common usage, or that there comes a point at which the accumulation of technical terms becomes gibberish to the non-scientist, no matter how carefully each term has been defined. Molecular science has a particularly difficult barrier to overcome, although Gross's humour and enthusiasm are considerable compensation.

But in the end, I'm left feeling that a topic as broad, indeed ill-defined, as nanotechnology needs a strong element of interpretation, evaluation and organization, before an outsider can see the what, the how and, most of all, the why. This book provides captivating snapshots, but sometimes lacks the narrative of a good movie, or book for that matter.

On the same scale

Carbon Nanotubes and Related Structures: New Materials for the Twenty-first Century by Peter J. F. Harris Cambridge University Press , £50, $80

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  1. Philip Ball is a consultant editor at Nature.

    • Philip Ball
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Ball, P. Lessons in molecular gymnastics. Nature 402, 119–120 (1999). https://doi.org/10.1038/45914

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