Nanomedicine, Volume I: Basic Capabilities

© 1999 Robert A. Freitas Jr. All Rights Reserved.

Robert A. Freitas Jr., Nanomedicine, Volume I: Basic Capabilities, Landes Bioscience, Georgetown, TX, 1999


 

Afterword

 

Ralph C. Merkle, Ph.D., Xerox PARC

Institute for Molecular Manufacturing

 

Introduction

One of life's pleasures is writing an afterword for a classic-in-the-making. Not only will some of the glory inevitably rub off, there's also the illicit pleasure of having peeked at the future, like peeking at the Christmas presents before Christmas. A few of the possibilities of this new field of nanomedicine have been hinted at, a few more have been sketched in some research papers, but only with the publication of Nanomedicine have we started to see the full richness of it.

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 View

While 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 time -- at 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 Ahead

Perhaps the first task is to decide whether the capabilities described so well in Nanomedicine are indeed possible. If they are, then developing this new technology is a matter, quite literally, of life and death for many of us, our children, and future generations. Making this decision is harder than it might seem. As a society, we deal with new ideas poorly if we deal with them at all. Most people do not have the intellectual resources to directly evaluate new proposals, and so must rely on the statements of others. But those who in principle might be able to evaluate a new idea and so help our collective understanding often get it wrong. Looking back at a few historical examples, we can begin to see the magnitude of the difficulty.

John Aubrey, a contemporary of William Harvey, wrote this account of the response to the publication in 1628 of Harvey's book De Motu Cordis in which Harvey described his discovery of the blood's circulation:

"...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 correct -- the same pattern we saw with Nanosystems.

 

An Immediate Concern

Actually, 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 idea -- before 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 individuals -- individuals 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 action, who will nurture the truly new and the truly groundbreaking without having to first seek the approval of others. For there are no others! On the far frontiers there are very few, and sometimes there is only one.

 

The Research That Must Be Done

What 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 accomplishes two purposes: it moves us closer to the goal, and it makes it easier for people to understand that the goal is feasible.

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 Chaining

Theoretical 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 observation that a red blood cell stores very little oxygen when compared with a tank of similar size which holds oxygen compressed to ~1,000 atmospheres. The design calls for strong materials (to hold oxygen at high pressure) and very finely detailed structural components (to control the release and storage of the oxygen). On a theoretical and computational front, sub-components that are composed of not-too-many atoms can be modeled in great detail. The position of each atom and the forces between the atoms can be modeled using techniques that provide remarkable accuracy and simultaneously impose a discipline and rigor on the designer. Compelling the designer to account for the location of every atom, and to propose a design that fully satisfies the physical laws incorporated into the computational model -- a model that has been checked and verified against countless other molecular structures -- prevents the designer from sidestepping awkward issues that might cause the design to fail.

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) applications is typically diamond and variants on diamond (structures with a stiff hydrocarbon backbone and surface terminations that are chemically stable; hydrogenated diamond surfaces are common, as are the use of oxygen on (100) surfaces, nitrogen on (111) surfaces, and the like). If stiff hydrocarbons are important, then we must have good PEFs (Potential Energy Functions) for such structures in order to perform molecular mechanics and molecular dynamics calculations that are accurate. The use of Brenner's potential for modeling hydrocarbons is common today, and extensions to this potential to incorporate elements other than hydrogen and carbon, as well as to improve its accuracy, are clearly of great importance to the computational research aimed at developing nanotechnology.

The requirement for highly detailed structures made of stiff hydrocarbons in turn implies we must analyze chemical reactions able to synthesize such materials. The chemical reactions involved 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 devices -- both 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 Knowledge

Every 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 recursive spiral of knowledge, research emboldens our interest and increasing interest produces yet more research. The rate-limiting process is the speed with which people take the first step, for having taken the first step the second step comes a little faster, and the third step faster still.

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 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 Medicine

We 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 indeed this severe. Molecular nanotechnology is feasible. As we master the ability to design molecular machines that can continue to function when the living system around them has failed, those molecular machines can restore the function of the living system. They can support and sustain the processes of the living system until that living system can once again function on its own. Whether this is done by a temporary assist from respirocytes3 or by any of the myriad other techniques discussed in Nanomedicine, the underlying message is clear: life and health can be restored and sustained in the face of greater injury, greater damage, greater trauma, and greater dysfunction than has ever before been realized. This will usher in a new era of medicine -- an era in which health and long life will be the usual state of affairs while sickness, debility and death will be the mercifully rare exceptions.

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 expected time. Heart attacks and cancer can strike us down even in the prime of our lives. They do not always wait their turn and politely arrive only when expected. How can today's dying patient take advantage of a future medical technology that is as yet only described in a handful of theoretical publications? How can we preserve the physical structure of our bodies well enough to permit that future medical technology to restore our health?

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 decades or even centuries until the necessary medical technology to restore health is developed. Called cryonics, this service is now available from several companies. Because final proof that this will work must wait until after we have developed a medical technology based on the foundation of a mature nanotechnology, the procedure is experimental. We cannot prove today that medical technology will (or will not) be able to reverse freezing injury 100 years from now. But the patient dying today must choose whether to join the experimental group or the control group. The luxury of waiting for a definitive answer before choosing is simply not available. So the decision must be made today, on the basis of incomplete information. We already know what happens to the control group. The outcome for the experimental group has not yet been confirmed. But given the wonderful advances that we see coming, it seems likely that we should be able to reverse freezing injury -- especially when that injury is minimized by the rapid introduction through the vascular system of cryoprotectants and other chemicals to cushion the tissues against further injury.

 

Conclusion

The 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 idea -- certainly better than the alternative.

 

References

1. 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

 


Last updated on 16 February 2003