Foresight Update 52

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A publication of the Foresight Institute

Foresight Update 52 - Table of Contents | Page1 | Page2 | Page3 | Page4 | Page5


Drexler Writes Smalley Open Letter on Assemblers

Lack of Response from Smalley Leads to Second Open Letter

Foresight Chairman K. Eric Drexler has sent Nobel laureate Richard Smalley an open letter to rebut Smalley's statements that molecular assemblers are not possible. The letter was also sent directly to several dozen leading researchers, decision makers, and journalists in the field. Reportedly Prof. Smalley had promised Drexler a response. On April 16, 2003, Drexler wrote to Smalley the following open letter.

Prof. Smalley:

I have written this open letter to correct your public misrepresentation of my work.

As you know, I introduced the term "nanotechnology" in the mid-1980s to describe advanced capabilities based on molecular assemblers: proposed devices able to guide chemical reactions by positioning reactive molecules with atomic precision. Since "nanotechnology" is now used label diverse current activities, I have attempted to minimize confusion by relabelling the longer term goal "molecular manufacturing". The consequences of molecular manufacturing are widely understood to be enormous, posing opportunities and dangers of first-rank importance to the long-term security of the United States and the world. Theoretical studies of its implementation and capabilities are therefore of more than academic interest, and are akin to pre-Sputnik studies of spaceflight, or to pre-Manhattan-Project calculations regarding nuclear chain reactions.

You have attempted to dismiss my work in this field by misrepresenting it. From what I hear of a press conference at the recent NNI conference, you continue to do so. In particular, you have described molecular assemblers as having multiple "fingers" that manipulate individual atoms and suffer from so-called "fat finger" and "sticky finger" problems, and you have dismissed their feasibility on this basis [1]. I find this puzzling because, like enzymes and ribosomes, proposed assemblers neither have nor need these "Smalley fingers" [2]. The task of positioning reactive molecules simply doesn't require them.

I have a twenty year history of technical publications in this area [3 - 12] and consistently describe systems quite unlike the straw man you attack. My proposal is, and always has been, to guide the chemical synthesis of complex structures by mechanically positioning reactive molecules, not by manipulating individual atoms. This proposal has been defended successfully again and again, in journal articles, in my MIT doctoral thesis, and before scientific audiences around the world. It rests on well-established physical principles.

The impossibility of "Smalley fingers" has raised no concern in the research community because these fingers solve no problems and thus appear in no proposals. Your reliance on this straw-man attack might lead a thoughtful observer to suspect that no one has identified a valid criticism of my work. For this I should, perhaps, thank you.

You apparently fear that my warnings of long-term dangers [13] will hinder funding of current research, stating that "We should not let this fuzzy-minded nightmare dream scare us away from nanotechnology....NNI should go forward" [14]. However, I have from the beginning argued that the potential for abuse of advanced nanotechnologies makes vigorous research by the U.S and its allies imperative [13]. Many have found these arguments persuasive. In an open discussion, I believe they will prevail. In contrast, your attempt to calm the public through false claims of impossibility will inevitably fail, placing your colleagues at risk of a destructive backlash.

Your misdirected arguments have needlessly confused public discussion of genuine long-term security concerns. If you value the accuracy of information used in decisions of importance to national and global security, I urge you to seek some way to help set the record straight. Endorsing calls for an independent scientific review of molecular manufacturing concepts [15] would be constructive.

A scientist whose research I respect has observed that "when a scientist says something is possible, they're probably underestimating how long it will take. But if they say it's impossible, they're probably wrong." The scientist quoted is, of course, yourself [16].

K. Eric Drexler, Chairman, Foresight Institute


  1. Smalley, R. E. (2001) Of chemistry, love and nanobots - How soon will we see the nanometer-scale robots envisaged by K. Eric Drexler and other molecular nanotechologists? The simple answer is never. Scientific American, September, 68-69.
  2. Drexler, K. E., D. Forrest, R. A. Freitas Jr., J. S. Hall, N. Jacobstein, T. McKendree, R. Merkle, C. Peterson (2001) A Debate About Assemblers.
  3. Drexler, K. E. (1981) Molecular engineering: An approach to the development of general capabilities for molecular manipulation. Proc. Natnl. Acad. Sci. U.S.A.. 78:5275-5278.
  4. Drexler, K. E. (1987) Nanomachinery: Atomically precise gears and bearings. IEEE Micro Robots and Teleoperators Workshop. Hyannis, Massachusetts: IEEE.
  5. Drexler, K. E., and J. S. Foster. (1990) Synthetic tips. Nature. 343:600.
  6. Drexler, K. E. (1991) Molecular tip arrays for molecular imaging and nanofabrication. Journal of Vacuum Science and Technology-B. 9:1394-1397.
  7. Drexler K. E., (1991) Molecular Machinery and Manufacturing with Applications to Computation. MIT doctoral thesis.
  8. Drexler, K. E. (1992) Nanosystems: Molecular Machinery, Manufacturing, and Computation. New York: John Wiley & Sons.
  9. Drexler, K. E. (1992) Molecular Directions in Nanotechnology. Nanotechnology (2:113).
  10. Drexler, K. E. (1994) Molecular machines: physical principles and implementation strategies. Annual Review of Biophysics and Biomolecular Structure (23:337-405).
  11. Drexler, K. E. (1995) Molecular manufacturing: perspectives on the ultimate limits of fabrication. Phil. Trans. R. Soc. London A (353:323-331).
  12. Drexler, K. E. (1999) Building molecular machine systems. Trends in Biotechnology, 17: 5-7.
  13. Drexler, K. E. (1986) Engines of Creation: The Coming Era of Nanotechnology. New York: Anchor Press/Doubleday.
  14. Smalley, R. E. (2000) quoted in: W. Schulz, Crafting A National Nanotechnology Effort. Chemical & Engineering News, October 16.
  15. Peterson, C. L. Testimony before the Committee on Science, U.S. House of Representatives, 9 April 2003. (see previous article)
  16. Smalley, R. E. (2000) quoted in N. Thompson, Downsizing: Nanotechnology—Why you should sweat the small stuff . The Washington Monthly Online, October.

Second Open Letter Seeks Closure

The open letter was published on ( and elsewhere (; A version was printed in Small Times (May/June, p.10). Drexler reports that there have been ongoing inquiries from the press regarding a response from Smalley. The absence of the promised response after more than two months prompted a second open letter.

In the follow-up letter, Eric Drexler points out that Prof. Smalley has apparently retracted his position regarding the impossibility of building with atom-by-atom control. In an open letter dated 2 July 2003, Drexler wrote to Smalley:

Prof. Smalley:

Thanks for your prompt note promising to respond to my 16 April open letter [1] within a few weeks; more than two months have now passed, and it would be good to hear from you. The issues under discussion are fundamental to understanding both the feasible objectives and the natural consequences of nanotechnology research. It would be a service to the community to reach closure.

As you know, I follow Feynman [2] in arguing the feasibility of building with atom-by-atom control. You endorsed this goal in 1999, stating that we will "learn to build things at the ultimate level of control, one atom at a time" [3], then rejected it in 2001, stating that "To put every atom in its place — the vision articulated by some nanotechnologists — would require magic fingers" [4], but apparently retract this rejection in 2003, stating that "The ultimate nanotechnology builds at the ultimate level of finesse one atom at a time, and does it with molecular perfection" [5].

Your 2001 essay [4] created the impression that you had shown building with atom-by-atom control to be impossible, but my open letter [1] pointed out that your argument misrepresents the basic idea (shared by myself and Feynman) that the goal is to control where each atom ends up in the product structure — as happens in chemical and biological synthesis — not to grab and manipulate impossibly many neighboring atoms separately and simultaneously. Your recent silence and 2003 statement (above) now suggest that you have abandoned your 2001 position and rejoined Feynman in endorsing the feasibility of atom-by-atom control. Can the nanotechnology research community take this as your best judgment on the question?

I would not ordinarily raise an issue so persistently, but the question of what nanotechnology can ultimately achieve is perhaps the most fundamental issue in the field today — it shapes basic objectives and expectations — and your words have been remarkably effective in changing how this issue is perceived.

Yours in search of closure,

K. Eric Drexler, Chairman, Foresight Institute


  1. Drexler, K. E., 2003. "Open Letter to Richard Smalley." Reprinted in Small Times, May/June, p.10.
  2. Feynman, R., 1959. "There's Plenty of Room at the Bottom: An invitation to Enter a New Field of Physics," Talk at the Annual Meeting of the American Physical Society.
  3. Smalley, R. E, 1999. Written statement, U.S. Senate Committee on Commerce, Science, and Transportation, May 12.
  4. Smalley, R. E,, 2001. "Of chemistry, love and nanobots - How soon will we see the nanometer-scale robots envisaged by K. Eric Drexler and other molecular nanotechologists? The simple answer is never." Scientific American, September, 68-69.
  5. Smalley, 2003. Presentation to the President's Council of Advisors on Science and Technology, March 3.

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Foresight Update 52 - Table of Contents


Book Review: How does the body react to medical nanodevices?

Reviewed by Ralph C. Merkle

Nanomedicine, Volume IIA: Biocompatibility

By Robert A. Freitas Jr.
Landes Bioscience, September 2003
Hardcover. $99
ISBN 1-57059-700-6

For the last 4 years, Robert Freitas has been teasing us with brief extracts from his forthcoming Nanomedicine, Volume IIA, in his quarterly nanomedicine articles for Foresight Update. The second installment of this famous series is in press and should be out by September 2003. A full online version will appear in the months to come, though an outline is available now at Robert's nanomedicine site

There are now four books in the Nanomedicine trilogy — what began as a single chapter in Volume II has grown into a book: Volume IIA. This is hardly surprising when we consider how critical biocompatibility is to the safety, effectiveness, and utility of medical nanorobotic devices, and the magnitude and complexity of the subject matter.

In his usual thorough fashion, Freitas gives us an overview of essentially the entire field of biocompatibility as it relates to medical nanorobots and the materials that might be used in their construction. While the target audience is "biomedical engineers, biocompatibility engineers, medical systems engineers, research physiologists, clinical laboratory analysts, and other technical and professional people who are seriously interested in the future of medical technology" this volume comes at a timely juncture: published concerns about the biocompatibility of nanotechnology are growing in the environmental community, and a solid foundation on which to base the discussion is greatly welcomed. This new book provides a technical tour-de-force and a treasure trove of facts, ideas, and recent research results, with an extensive 1400-entry glossary and over 6100 literature citations in the reference list, representing 8000 man-hours of effort by the author. This book should be the starting point for anyone planning a serious research program in medical nanorobot design.

Perhaps the best way to give the reader an overview of what Nanomedicine Volume IIA is all about is to quote a few words from Freitas describing just part of this Magnum Opus:

"Compatibility" most broadly refers to the suitability of two distinct systems or classes of things to be mixed or taken together without unfavorable results. More specifically, the safety, effectiveness, and utility of medical nanorobotic devices will critically depend upon their biocompatibility with human organs, tissues, cells, and biochemical systems. Classical biocompatibility has often focused on the immunological and thrombogenic reactions of the body to foreign substances placed within it. In this Volume, we broaden the definition of nanomedical biocompatibility to include all of the mechanical, physiological, immunological, cytological, and biochemical responses of the human body to the introduction of medical nanodevices, whether "particulate" or "bulk" in form. That is, medical nanodevices may include large doses of independent micron-sized individual nanorobots, or alternatively may include macroscale nanoorgans (nanorobotic organs) assembled either as solid objects or built up from trillions of smaller artificial cells or docked nanorobots inside the body. We also discuss the effects on the nanorobot of being placed inside the human body.

In most cases, the biocompatibility of nanomedical devices may be regarded as a problem of equivalent difficulty to finding biocompatible surfaces for implants and prostheses that will only be present in vivo for a relatively short time. That's because fast-acting medical nanorobots will usually be removed from the body after their diagnostic or therapeutic purpose is complete. In these instances, special surface coatings along with arrays of active presentation semaphores may suffice. At the other extreme, very long-lived prostheses are already feasible with macroscale implants such as artificial knee joints, pins, and metal plates that are embedded in bone. As our control of material properties extends more completely into the molecular realm, surface characteristics can be modulated and reprogrammed, hopefully permitting long-term biocompatibility to be achieved. In some cases, nanoorgans may be coated with an adherent layer of immune-compatible natural or engineered cells in order to blend in and integrate thoroughly with their surroundings. Today (in 2002), the broad outlines of the general solutions to nanodevice biocompatibility are already apparent. However, data on the long-term effects of implants is at best incomplete and many important aspects of nanomedical biocompatibility are still unresolved — and will remain unresolved until an active experimental program is undertaken to systematically investigate them.

Since a common building material for medical nanorobots is likely to be diamond or diamondoid substances, the first and most obvious question is whether diamondoid devices or their components are likely to be hazardous to the human body. Chapter 15.1 briefly explores the potential for crude mechanical damage to human tissues caused by the ingestion or inhalation of diamond or related particles. There are varying degrees of potential mechanical injury and these are probably ultimately dose-dependent. It will be part of any medical nanorobot research project to determine the actual amount of diamondoid particulate matter necessary to cause clinically significant injury.

A great deal of preliminary information is already available on the biocompatibility of various materials that are likely to find extensive use in medical nanorobots. Chapter 15.3 includes a review of the experimental literature describing the known overall biocompatibility of diamond, carbon fullerenes and nanotubes, nondiamondoid carbon, fluorinated carbon (e.g., Teflon), sapphire and alumina, and a few other possible nanomedical materials such as DNA and dendrimers — in both bulk and particulate forms.

One of the more interesting issues is that medical nanorobots might be consumed by the body's defenders, the white cells. Thus, nanorobots will have to dodge, pacify, or escape from their embrace. As Freitas observes: "... all nanorobots that are of a size capable of ingestion by phagocytic cells must incorporate physical mechanisms and operational protocols for avoiding and escaping from phagocytes. The basic strategy is first to avoid phagocytic contact, recognition, or binding and activation, and secondly, if this fails, then to inhibit phagocytic engulfment or enclosure and scission of the phagosome. If trapped, the medical nanorobot can induce exocytosis of the phagosomal vacuole in which it is lodged or inhibit both phagolysosomal fusion and phagosome metabolism. In rare circumstances, it may be necessary to kill the phagocyte or to blockade the entire phagocytic system. Of course, the most direct approach for a fully-functional medical nanorobot is to employ its motility mechanisms to locomote out of, or away from, the phagocytic cell that is attempting to engulf it. This may involve reverse cytopenetration, which must be done cautiously (e.g., the rapid exit of nonenveloped viruses from cells can be cytotoxic). It is possible that frustrated phagocytosis may induce a localized compensatory granulomatous reaction. Medical nanorobots therefore may also need to employ simple but active defensive strategies to forestall granuloma formation."

    But if we don't act today, then we might one day wake up in a future where we are old and infirm and the promise of nanomedicine is still just that: a promise.    

And, as always, Freitas is famous not just for his thorough coverage of the field, but also for the historical side lights that enliven his text. Pounded diamond dust, for example, was used by assassins through the ages—an observation that inspired Freitas to investigate the issue more directly by examining pounded diamonds with a scanning electron microscope (SEM) and confirming that—"even a single hammer blow produced numerous particles of a wide variety of sizes (0.1-100 micron), many possessing sharp ragged 'fishhook' edges, deep angular concavities, serrations, irregular holes, and other interesting features." No doubt of greater concern to his wife was his earlier report ( of self-experimentation with (albeit uncrushed) diamond powder, finding that "even irregularly-shaped diamondoid particles ~3 microns and smaller apparently roll smoothly out of the way when ground between the teeth, whereas particles larger than ~3 microns cannot roll sufficiently and retain a sensible grittiness."

This excellent volume provides us with yet another authoritative analysis of issues that are critical to the development of nanomedicine — and again makes clear that, while there is much to do there are no insurmountable obstacles nor fundamental barriers that stand in our way.

To end with a question: do you expect to be alive in thirty years? If so — and most people do — then the development of nanomedicine within that time frame will benefit you directly. The medical nanorobots we are talking about could save your life, the lives of your loved ones and the lives of your friends. This is possible and even likely, but not inevitable. How long it takes to develop this life saving technology depends on what we do — it is not happening according to some cosmic plan, with a date engraved in stone that neither you nor I can change — but rather it will take as long as we let it take. Yes, thirty years is a long time. Yes, most people have a hard time thinking about the next year, let alone the next decade, let alone a few decades hence. But if we don't act today, then we might one day wake up in a future where we are old and infirm and the promise of nanomedicine is still just that: a promise. To paraphrase a famous slogan: think long term, act short term.

[Editor's note: An editorial titled "Nanomedicine: grounds for optimism, and a call for papers" in the prestigious medical journal The Lancet (Volume 362, Number 9385, 30 August 2003) cites "the extraordinary possibilities that nanoscience opens up for medicine" and calls for papers on nanomedicine to be published in a theme issue of the journal planned for spring of 2004. See also the article "Leading Medical Journal Hails Arrival of Nanomedicine" on the BetterHumans web site at]

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From Foresight Update 52, originally published 31 August 2003.