|
Ralph C. Merkle, Ph.D. Xerox PARC | ||||||
IntroductionOne of life's pleasures is writing an afterword for a classic- Like cresting the top of a hill and beholding, for the first time and in one sweep, the whole of a new land, our minds are both captivated by the prospects and at another level churning with plans and ideas and tasks. For at the same time we see what is possible, we are also aware of the work that remains to be done to convert this vision into reality. Nanomedicine is more than just a description of what might be, it is a call to action. While it will take decades to convert the possible to the actual, that is what we are called upon to donot only for the good of all, not only to advance our knowledge, not only to help future generations, but to help ourselves as well. The Long ViewWhile planning beyond a decade is rare in this society, our lives can span over a century. We should not be shortsighted or timid about this. When I was a child, my sister was wise and very old: all of twenty years in age! My parents, in their 40's, were old beyond concepts of antiquity. Like the sky above and the ground beneath, they had existed since the beginnings of timeat least, of my time. Yet somehow I am now 47, and when I protest my age I am laughed at by my grandmother-in-law who views me, from her 90's, as a mere youth. The field of nanomedicine will take decades to develop, but those decades will pass and that future will arrive. Most of us will find we are still here: a bit older, a bit slower, perhaps a bit wiser, yet still filled with the excitement of life and the joy of living. Think of yourself on that future day, looking back on what was and looking forward to what will be. Will the future still be bright, still be open, and still be filled with uncharted possibilities? That depends on what we do today. If we ignore the future, if we dismiss the decades ahead and focus narrowly on the next few weeks or months, then the future will catch us by surprise, unprepared. But if we start now, if we raise up our eyes from the distractions of the moment and prepare for the future that we know will come, then when that future arrives we will look back and be pleased with what we did, and will look forward and be pleased with the even greater possibilities of what we can do. |
The Tasks AheadPerhaps the first task is to decide whether the capabilities John Aubrey, a contemporary of William Harvey, wrote this
"...I heard Harvey say that after his book came out, he fell mightily in his practice. 'Twas believed by the vulgar that he was crack-brained, and all the physicians were against him. I knew several doctors in London that would not have given threepence for one of his medicines." 1 In 1873 Sir John Erichsen offered this grim assessment of the future of surgery:
"There cannot always be fresh fields of conquest by the knife; there must be portions of the human frame that will ever remain sacred from its intrusions, at least in the surgeon's hands. That we have already, if not quite, reached these final limits, there can be little question. The abdomen, the chest, and the brain will be forever shut from the intrusion of the wise and humane surgeon." 1 Nanomedicine, as Nanosystems2 before it, is based on the laws of physics which describe our world with phenomenal accuracy. Both books advance arguments grounded on those laws, and both can therefore be evaluated with respect to the accuracy of their conclusions with respect to those laws. Nanosystems was published in 1992, and no significant flaws have been found. Given the volume of public debate and the number of people who have read the book, the simplest explanation for this absence of reported errors is that its logic is basically correct and its conclusions are basically sound. Today, these conclusions are working their way into our collective decision making processes and guiding our next steps. Research is being focused on how best to develop this new technology, companies are being formed to achieve the goals that we now accept as possible, and people are beginning to grapple with the potential consequences. | |||||
|
Nanomedicine, working from the foundations laid by Nanosystems, develops the consequences of nanotechnology for medicine. These consequences are extraordinary, and must be both explained and publicly examined. We must firstly encourage the early review and more rapid acceptance of Nanomedicine, for the next steps will only be taken after concluding that its reasoning is largely sound and its conclusions mostly correctthe same pattern we saw with Nanosystems. An Immediate ConcernActually, there is one thing we must do even earlier: ensure the completion of this exceptional series of books. What you are reading is only Volume I. Volumes II and III, and the popular book to follow, do not yet (as of 1999 when this is being written) exist, except in Freitas' head. We need to support him, in order to move this first and most critical series to completion. This is always the hardest time for a new ideabefore it has been codified and laid out, before it has been clothed in words, when it exists only as thoughts. The work of making it solid and substantial is great, and yet this work is given the least support. What funding committee will agree to fund a book
describing an entire new field that has never before been dreamt of?
Committees base their conclusions on a shared understanding of a common
body of knowledge. Their members are drawn from an existing society
of experts to evaluate the next incremental improvement. What
do you do when there are no experts? Who lays claim to expertise
in nanomedicine? Who has spent their life in this field which is
just being conceived? No one. The committee process breaks down
when we move into truly new terrain. It fails us just when failure is
most expensive: at the beginnings of new things. Here we must fall
back on individualsindividuals who are bold enough to believe
in themselves when there are no experts to turn to for help and
support. Individuals who are willing to back up their own beliefs with The Research That Must Be DoneWhat happens later, when some significant part of society agrees that nanomedicine will happen? Research.
· Research to clarify the goals and objectives. Just because people agree it will happen doesn't mean they agree about how it will happen, or when, or which sub-objectives should be given higher priority, or.... · Research to persuade more people that nanomedicine is feasible. Don't forget that this society runs on majority rule. If 20% of a committee thinks an idea is worthwhile and should be pursued, it still gets voted down. · Research to identify early applications. The sooner we can identify profitable opportunities that move us closer to the long-term objectives, the sooner we can establish support that doesn't require persuading committees. · Research to advance our
experimental capabilities. This Broadly speaking, the research that must be done can be divided into theoretical and experimental. The theoretical work includes |
both traditional paper-and-pencil methods, and also the newer methods of computational modeling and "digital experiments" made possible by the computer. Theoretical and computational methods can be applied to the proposals advanced in Nanomedicine both to check feasibility and to provide more detailed understanding of the performance and capabilities. Computational models in particular, especially when they are based on detailed descriptions of physical interactions, force a very thorough treatment of the design and bring into the light any hidden assumptions. Backward ChainingTheoretical and computational methods can also be applied to near-term and intermediate-term proposals. Achieving a long-term objective often requires taking many steps, and all of those steps except the first one are (pretty much by definition) not experimentally accessible. While experimental work is focused on taking the next step, the theoretical and computational work should be focused on clarifying the whole pathway from today's technology to the future applications. This feeds back into the experimental work in two ways. First, it provides information about which approaches are more likely or less likely to succeed. Second, it provides a reason for supporting the experimental work. The value and feasibility of the long-term objectives makes experimental progress more valuable, and as this understanding spreads it becomes easier for experimentalists to get funding for work that moves us closer to those long-range objectives. Consider one example: Freitas'
respirocyte3 is based on the Such a design then feeds back important constraints on
earlier steps in the development process. For example, we must be able
to make very precise, very detailed, and very strong structures.
The material often proposed for this (and other nanotechnological) The requirement for highly detailed structures made of stiff | |||
|
recursive spiral would be to discover a fundamental objection that makes molecular machine systems impossible. As we are surrounded by biological molecular machines, this possibility seems remote. If thermal noise was a fundamental obstacle to molecular machine design, then biological systems could not copy DNA and molecular rotary motors could not rotate. If quantum uncertainty was a fundamental obstacle, then ribosomes could not synthesize proteins and sodium channels could not distinguish between sodium and potassium. A New Medical Technology And A New Era Of MedicineWe are left, then, with a fairly clear set of conclusions.
Living systems exist. Living systems can usually heal and cure their
own injuries, unless those injuries are severe enough to prevent the
living system from functioning. Too often, we suffer injuries that are The future capabilities of nanomedicine give hope and
inspiration to those of us who still have decades of life to look forward to,
but some are not so fortunate. Many others who rightfully should
live several decades more might find that chance cuts short their The extraordinary medical prospects ahead of us have
renewed interest in a proposal made long ago: that the dying patient
could be frozen, then stored at the temperature of liquid nitrogen for | ||||
|
in the growth of diamond are reasonably well understood, and many reaction pathways have been proposed by which such growth can occur. We can adopt reaction pathways similar to those seen in the chemical vapor deposition (CVD) growth of diamond, but provide finer control over where they occur by positioning the reacting compounds using positional devices. Better computational methods for analyzing individual reactions are possible using ab initio methods, which can also provide accurate descriptions of the interactions of small numbers of atoms which then feed into the design of better PEFs. Better understanding of reactions relevant to the growth of diamond can also be pursued experimentally, and particular reactions of interest can be looked at in the laboratory as well as on a computer. The need to position molecular components in its turn implies we must consider positional devicesboth improvements to today's SPMs (Scanning Probe Microscopes) and future molecular scale versions that are faster, more accurate, and have a greater range of tip configurations. This implies a strong interest in experimental and theoretical work on positioning devices, as well as work aimed at improving SPM tips. Experimental work that shows greater flexibility in arranging individual atoms and molecules should be supported, as the potential consequences of this work are very great. This process of working backwards from our desired goal to near-term research objectives was called backward chaining by Drexler.2 As can be seen, it is a method of analyzing a long-term objective (e.g. using respirocytes to treat medical conditions) and breaking down the steps needed to achieve that objective into nearer-term objectives (e.g. improving PEFs, experimental work in SPMs). While the outline of the process given here is necessarily very short, it should give the reader a feeling for the basic idea. The procedure of targeting near-term research goals based on their utility in achieving long-term objectives not only provides a focus for research, it also produces a wealth of results which further bolster the underlying arguments supporting the feasibility of the objectives and the desirability of such research. This creates a recursive spiral of knowledge. A little research shows there are no fundamental barriers that prevent us from achieving the objectives of molecular nanotechnology. Further research gives a better understanding of which molecular machine systems should be feasible and provides initial targets for additional research. Ongoing work is providing a clearer picture of the routes that can move us from our present technology base to the proposed molecular machines of the future, and produces yet more targets for near-term efforts. The Recursive Spiral of KnowledgeEvery time we pursue further research in nanotechnology
we find that our original assessment of its basic feasibility is
strengthened, our understanding of the specific near-term research targets that
we must pursue is broadened, our conviction that further research
can speed the development of this fundamentally new and
revolutionary technology grows stronger, and our awareness of the
astonishingly pervasive benefits this technology can bring is widened. In this This should come as no real surprise, for either the ability to arrange and rearrange molecular structures in most of the ways permitted by physical law is feasible, or, alternatively, it is not. But since Feynman's famous 1959 talk There's Plenty of Room at the Bottom,4 every informed observer who has studied the issue has drawn the same conclusion: it's feasible. The only way to break the | ||||
References1. For more examples of this kind and references for the above quotations, see http://www.foresight.org/News/negativeComments.html#loc026). 2. K. Eric Drexler, Nanosystems: Molecular Machinery, Manufacturing, and Computation, John Wiley & Sons, NY, 1992. 3. Robert A. Freitas Jr., "Exploratory Design in Medical Nanotechnology: A Mechanical Artificial Red Cell," Artificial Cells, Blood Substitutes, and Immobil. Biotech. 26(1998):411-430. See also: http://www.foresight.org/Nanomedicine/Respirocytes.html. 4. Richard P. Feynman, "There's Plenty of Room at the Bottom," Engineering and Science (California Institute of Technology), February 1960, pp. 22-36. Reprinted in B.C. Crandall, James Lewis, eds, Nanotechnology: Research and Perspectives, MIT Press, 1992. pp. 34763, and in D.H. Gilbert, ed, Miniaturization, Reinhold, New York, 1961, pp. 282-296. See also: http://nano.xerox.com/nanotech/feynman.html. | ||||
ConclusionThe development of nanomedicine depends on us: what we do and how rapidly we do it. Research is not done by a faceless "them," nor is it something that happens spontaneously and without any human intervention. It is done by and supported by people. Unless we decide to support and pursue this research, it won't happen. How long it takes to develop depends on us. We are not idle bystanders watching the world go by. We are a part of it. If we sit and wait for someone else to develop this technology, it will happen much more slowly. If we jump in and work to make it happen, it will happen sooner. And developing a life saving medical technology within our lifetimes seems like a very good ideacertainly better than the alternative. | ||||