Part 6 of a series prompted by the recent 50th anniversary of Feynman’s historic talk, “There’s Plenty of Room at the Bottom”. This is arguably the most important post of the series, or of this blog to date.
— The most credible study of molecular manufacturing to date
— The study’s recommendations for Federal research support
— The current state of progress toward implementation
— The critical problem: not science, but institutions and focus
A formal, Federal-level study has examined the physical principles of high-throughput atomically precise manufacturing (aka molecular manufacturing), assessing its feasibility and closing with a call for experimental research.
Surprisingly, this recommendation smacks of heresy in some circles, and the very idea of examining the subject met strong opposition.
The process in outline: Congress voted to direct the U.S. National Research Council, the working arm of the U.S. National Academies, to conduct, as part of the lengthy Triennial Review of the National Nanotechnology Initiative, what in the House version had been described as a “Study on molecular manufacturing…to determine the technical feasibility of the manufacture of materials and devices at the molecular scale”, and in response, the NRC convened a study committee that organized a workshop, examined the literature, deliberated, and reported their conclusions, recommending appropriate research directions for moving the field forward, including experimental research directed toward development of molecular manufacturing.
NRC studies are not haphazard processes, and the National Academies website describes its procedures in substantial detail. Because the NRC often advises the Federal government on politically charged questions, “Checks and balances are applied at every step in the study process to protect the integrity of the reports and to maintain public confidence in them.” These include independent scientific review of reports that are themselves the product of independent experts assembled with attention to potential conflicts of interest.
It’s worth taking a moment to compare the NRC to the three previous leading sources of information on molecular manufacturing: committed advocates, committed critics, and self-propagating mythologies. None of these is remotely comparable. Unless one has studied the topic closely and in technical detail, it seems reasonable to adopt the committee’s conclusions as a rough-draft version of reality, and to proceed from there.
Here are some excerpts that I think deserve special emphasis, followed by the concluding paragraph of the report:
Technical Feasibility of Site-Specific Chemistry
for Large-Scale Manufacturing
The proposed manufacturing systems can be viewed as highly miniaturized, highly articulated versions of today’s scanning probe systems, or perhaps as engineered ribosome-like systems…
…The technical arguments make use of accepted scientific knowledge but constitute a “theoretical analysis demonstrating the possibility of a class of as-yet unrealizable devices.”22
Construction of extended structures with three-dimensional covalent bonding may be easy to conceive and might be readily accomplished, but only by using tools that do not yet exist.25 In other words, the tool structures and other components cannot yet be built, but they can be computationally modeled.
[ ... concluding paragraph:]
Although theoretical calculations can be made today, the eventually attainable range of chemical reaction cycles, error rates, speed of operation, and thermodynamic efficiencies of such bottom-up manufacturing systems cannot be reliably predicted at this time. Thus, the eventually attainable perfection and complexity of manufactured products, while they can be calculated in theory, cannot be predicted with confidence. Finally, the optimum research paths [to advanced systems] cannot be reliably predicted at this time. Research funding that is based on the ability of investigators to produce experimental demonstrations that link to abstract models and guide long-term vision is most appropriate to achieve this goal.
22. K.E. Drexler. 1992. Nanosystems, Molecular Machinery, Manufacturing and Computation. New York: Wiley & Sons.
[see page on my website]
25. M. Rieth and W. Schommers, eds. 2005. Handbook of Computational and Theoretical Nanotechnology. American Scientific Publishers.
[see chapter pdf]
Source pages, NRC report [pdf ]
My summary in a nutshell:
I should note that the tone of the report is skeptical, emphasizing what the committee [correctly] sees as the unusual approach and the [resulting, methodologically inherent] incompleteness of the results. A quick skim could easily suggest a negative assessment. A closer reading, however, shows that points raised are in the end presented, not as errors, nor even as specific, concrete weaknesses in the analysis, but instead as work not yet done, motivating the development of a research program directed toward validating and achieving the proposed technological objectives.
The call for research
The report closes with a call for research on pathways toward molecular manufacturing, quoted above, and an earlier section outlines some appropriate objectives:
To bring this field forward, meaningful connections are needed between the relevant scientific communities. Examples include:
- Delineating desirable research directions not already being pursued by the biochemistry community;
- Defining and focusing on some basic experimental steps that are critical to advancing long-term goals; and
- Outlining some “proof-of-principle” studies that, if successful, would provide knowledge or engineering demonstrations of key principles or components with immediate value.
The response and progress
The technology roadmap
Research directions toward molecular manufacturing have been charted in the subsequent Technology Roadmap for Productive Nanosystems, the result of a project led by the Battelle Memorial Institute, the manager of research at U.S. National Laboratories that include Pacific Northwest, Oak Ridge, and Brookhaven. These labs hosted several Roadmap workshops and provided many of the participating scientists and engineers; I served as the lead technical consultant for the project.
The Roadmap is responsive to the NRC request above, and recommends research that includes work along the lines I describe below.
Molecular engineering methodologies
The crucial research objective is the development of systematic experimental and design methodologies that enable the fabrication of large, multicomponent, atomically precise nanostructures by means of self-assembly. This research direction fits the NRC committee’s criteria: it is, by nature, strongly experimental, and in mimicking macromolecular structures and processes in biology, it holds promise for near-term biomedical applications.
Structural DNA nanotechnology
In the year the NRC report reached print, a Nature paper reported a breakthrough-level development, “DNA origami”. This technology opened the door to systematic, atomically precise engineering on a scale of hundreds of nanometers and millions of atoms.
Polypeptide foldamer nanotechnology
There’s also been rapid progress in design methodologies for complex, atomically precise nanoscale structures made from polypeptide foldamers (aka proteins). In recent years, protein engineering has achieved a functional milestone: systematically engineering devices that perform controlled molecular transformations (see “Computational tools for designing and engineering biocatalysts”).
Framework-directed assembly of composite systems
Looking forward, promising next steps involve integrating structural DNA frameworks with polypeptide foldamers, other foldamers, and other organic and inorganic materials. These classes of components have complementary properties (as discussed in my comments on “Modular Molecular Composite Nanosystems”).
Here, too, progress has been extensive. For DNA-centered perspectives, see “DNA origami as a nanoscale template for protein assembly”, “Assembling Materials with DNA as the Guide”, and “DNA-templated nanofabrication”. For a review of polypeptide-centered perspectives, see “Molecular biomimetics: nanotechnology and bionanotechnology using genetically engineered peptides”.
Why these developments are important
As is now well recognized, “existing biological systems for protein fabrication could be harnessed to produce nanoscale molecular machines with designed functions” (“Computational protein design promises to revolutionize protein engineering”). Further, as biological systems demonstrate, programmable molecular machine systems can be harnessed to build programmable molecular machine systems.
As I’ve discussed, this capability could be exploited to pursue a spiral of improvement in materials, components, and molecular machine systems.
The path ahead
This spiral of development, in which molecular tools are used to construct more capable next-generation molecular tools, could be exploited to develop products with expanding applications, falling cost, and increasing value.
As I discussed in “Making vs. Modeling: A paradox of progress in nanotechnology”, each generation of tools can be expected to enable fabrication processes and products that are more robust, more susceptible to computational simulation, and better suited to established systems engineering design methodologies. This indicates the potential for an accelerating pace of development toward a technology platform that can support the implementation of high-throughput atomically precise fabrication.
This path is being followed today, yet the level of support and organization, of mission and urgency, does not come close to matching its potential for solving long-term yet urgent problems.
Appropriate and inappropriate responses
to the NRC report on molecular manufacturing
The evaluation of the feasibility of molecular manufacturing and recommendations for research form the concluding section of the body of the NRC’s Triennial Review of the National Nanotechnology Initiative. In the three years since the publication of the NRC report, I have seen no document from a Federal-level source that acknowledges these conclusions, and, of course, none that offers a substantive response.
This is of concern, because the NRC report calls for a sharp break with past thinking. To put it bluntly, much of the opinion in general circulation about molecular manufacturing (both pro and con) is rubbish because it is based on mythology, and not on the scientific literature. The NRC report can be criticized on several points, but it isn’t rubbish.
Fulfilling the initial promise of nanotechnology
Atomically precise fabrication technologies exist today, and as I have noted, advanced atomically precise fabrication is the promise that initially defined the field of nanotechnology. I believe the record shows that advanced atomically precise fabrication is also the promise that got it funded.
Building on recent advances, strategically targeted research in atomically precise fabrication could draw on and contribute to fields across the spectrum of modern nanotechnologies, from materials to devices, and could bring them together to elevate the technology platform for further advances. Ultimately, as the NRC report suggests, those advances could potentially deliver what was promised at the inception of the field.
Make no mistake: the path to high-throughput atomically precise manufacturing will not be short, and it will not be direct. It will be a multi-stage development process, and as I have discussed, the early steps differ greatly from the ultimate results in both their form and their potential applications.
Today, the potential promise of high-throughput atomically precise manufacturing must be regarded as credible. As a consequence of its inherent productive capacity, it offers a credible potential solution to problems of energy production and climate change. The National Research Council of the U.S. National Academies of Science, Engineering, and Medicine has called for the support of research explicitly directed toward the development of this technology. This has become urgent.
The strength and limitations of current research support
It is both laudable and problematic that the research I’ve reported above is chiefly funded by programs in biology and medicine. This support has enabled great progress, and I know from long discussion that researchers in these areas have ambitious visions for the future. There are, however, limits to what can be achieved while developing molecular engineering within the framework of biotechnology, much as there would have been if aeronautical engineering research had been developed as a field of ornithology.
The critical need today is not for new scientific results, but for an integrative approach to molecular systems engineering, directed toward strategic technology objectives. The science is ready. The institutions are not.
A word to readers:
The implications of the NRC report call for reconsidering views that have shaped policy in the research disciplines critical to progress toward molecular manufacturing, yet like many other NRC reports, it is virtually unknown. Directing other readers to what I have written here could help to remedy this problem.
(And a further note to readers who are bursting with frustration: Please don’t. It is counterproductive, and generates far more heat than light.)
Note: I say in the first paragraph that Congress voted for “…what in the House version had been described as a ‘Study on molecular manufacturing…to determine the technical feasibility of the manufacture of materials and devices at the molecular scale’” to reflect an oddity of the legislative history behind the study: After the House transmitted the bill to the Senate, a nanotechnology business association successfully lobbied to replace “molecular manufacturing”, thereby calling for a (puzzling) “Study on molecular self-assembly”. An uproar followed. In the end, the NRC did a study of molecular self-assembly, as directed in the final bill, but also responded to the request by the House for a study of molecular manufacturing. In the end, molecular manufacturing dominated the agenda of the workshop. [I corrected the main text and this description after reviewing the GPO documents, several hours after the initial posting.]
In a later section, I note that “I have seen no document from a Federal-level source that acknowledges these conclusions”. There is, in fact, a document that quotes from the conclusions, but the quoted material is edited in a way that wrongly indicates that the recommendations regarding molecular manufacturing are, instead, recommendations regarding molecular self-assembly (see “The National Nanotechnology Initiative: Second Assessment and Recommendations of the National Nanotechnology Advisory Panel”, p.43).
[Dec 8: Updated to add the paragraph beginning “I should note that the tone of the report is skeptical...” I would expect this tone to strongly influence the impression left on casual readers, blunting the impact of what, in substance, amounts to a sharp rebuke to the conventional wisdom.]
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