Originally published on Nanotech.biz November 5, 2005. Reprinted on KurzweilAI.net February 2, 2006.

Continued from Interview with Robert Freitas: Part 1.

Robert A. Freitas Jr., J.D., published the first detailed technical design study of a mechanical nanorobot ever published in a peer-reviewed mainstream biomedical journal and is the author of nanomedicine, the first book-length technical discussion of the medical applications of nanotechnology and medical nanorobotics.

Question 1: How far can simple genetic engineering go towards curing diseases? Does pre-nanotechnology based technology have the potential to cure cancer and regrow organs?

Yes, of course. Genetic engineering is a very powerful technology. Pre-nanotechnology treatments for some forms of cancer already exist. The emerging discipline of tissue engineering is already heading in the direction of building tissues and organs using special scaffolds that are impregnated with appropriate cells which grow into the matrix to form cohesive new tissues. Single-organ cloning is also on the horizon. But all of these treatments and organ substitutions could be accomplished with greater reliability, executed with greater speed, and completed in a side-effect free manner, using the tools of nanorobotic medicine. There are also many kinds of treatments, particularly those related to physical trauma, that can only be dealt with efficiently using advanced nanorobotic medicine.

The way I like to think about all this is to recognize that “nanomedicine” is most simply and generally defined as the preservation and improvement of human health, using molecular tools and molecular knowledge of the human body. Nanomedicine involves the use of three conceptual classes of molecularly precise structures: nonbiological nanomaterials and nanoparticles, biotechnology-based materials and devices, and nonbiological devices including nanorobotics.

In the near term, say, the next 5 years, the molecular tools of nanomedicine will include biologically active materials with well-defined nanoscale structures, including those produced by the methods of genetic engineering. For example, one of the first uses of “nanotechnology” in treating cancer employs engineered nanoparticles of various kinds to attempt a general cure while staying within the usual drug-treatment paradigm. Kopelman’s group at the University of Michigan has developed dye-tagged nanoparticles that can be inserted into living cells as biosensors. This quickly led to nanomaterials incorporating a variety of plug-in modules, creating molecular nanodevices for the early detection and therapy of brain cancer. One type of particle is attached to a cancer cell antibody that adheres to cancer cells, and is also affixed with a contrast agent to make the particle highly visible during MRI, while also enhancing the selective cancer-killing effect during subsequent laser irradiation of the treated brain tissue.

Another example from the University of Michigan is thedendrimers, tree-shaped synthetic molecules with a regular branching structureemanating outward from a core. Theoutermost layer can be functionalized with other useful molecules such asgenetic therapy agents, decoys for viruses, or anti-HIV agents. The next stepis to create dendrimercluster agents,multi-component nanodevicescalledtecto-dendrimersbuilt up from a numberof single-dendrimermodules.These modules performspecialized functionssuch asdiseased cell recognition,diagnosisof disease state,therapeutic drug delivery,location reporting, and therapy outcome reporting.Theframework can be customizedto fight a particular cancersimplyby substitutingany one of many possibledistinct cancer recognitionor “targeting” dendrimers. Thelarger trend in medical nanomaterials is to migrate from single-functionmolecules to multi-module entities that can do many things, but only at certaintimes or under certain conditions – exemplifying a continuing, and, in my view,inevitable, technological evolution toward a device-oriented nanomedicine.

In the mid-term, the next 5 or 10 years or so, knowledge gained from genomics and proteomics will make possible new treatments tailored to specific individuals, new drugs targeting pathogens whose genomes have now been decoded, and stem cell treatments to repair damaged tissue, replace missing function, or slow aging. We will see genetic therapies and tissue engineering, and many other offshoots of biotechnology, becoming more common in medical practice. We should also see artificial organic devices that incorporate biological motors or self-assembled DNA-based structures for a variety of useful medical purposes. And we’ll also see biological robots, derived from bacteria or other motile cells, that have had their genomes re-engineered and re-programmed.

So yes, there is a lot that pre-nanotechnology, or, more properly, pre-nanorobotic medicine can do to improve human health. But the advent of medical nanorobotics will represent a huge leap forward.

Question 2: Are there any diseases that can’t be cured by nanotechnology? Are there any aspects of aging that can’t be stopped by nanotechnology?

If we combine the benefits of a human physiology maintained at the level of effectiveness possessed by our bodies when we were children (e.g., dechronification), along with the ability to deal with almost any form of severe trauma (via nanosurgery), then there are very few diseases or conditions that cannot be cured using nanomedicine. The only major class of incurable illness which nanorobots can’t handle is the case of brain damage in which portions of your brain have been physically destroyed. This condition might not be reversible if unique information has been irrevocably lost (say, because you neglected to make a backup copy of this information). There are several other minor “incurable” conditions, but all of these similarly relate to the loss of unique information.

Question 3: The Foresight community has deemphasized molecular assemblers in favor of a desktop manufacturing paradigm. How will medical nanorobots be constructed?

As noted in the previous interview, my view is that this change of emphasis is unlikely to affect the conduct of research in the field, or the activities of those few of us who are actually doing the research involved, because the distinction between “molecular assemblers” and “nanofactories” is largely cosmetic and because both approaches require almost exactly the same set of enabling technologies. At present we’re concentrating our efforts mostly on developing these component enabling technologies, not on integration of these technologies into larger systems. Systems analysis will come next.

Medical nanorobots small enough to go into the human bloodstream will be very complex machines.  We don’t know exactly how to build them yet, but the overall pathway from here to there is slowly starting to come into focus.  Building and deploying nanorobotic systems will require first the ability to build diamondoid structures to molecular precision, using atomic force microscopy or similar means along with the techniques of diamond mechanosynthesis. My early work on diamond mechanosynthesis is described in a lecture I gave at the 2004 Foresight Conference in Washington DC, the text of which (plus many images) is available online. I’m currently involved in 6 collaborations with university groups in the U.S, U.K. and Russia (including both theoretical and experimental efforts) to push forward the technology in this area, and I have several new papers nearing completion for journal submission very soon on this work.

This must be followed by developing the ability to design and manufacture rigid machine parts and then to assemble them into larger machine systems, up to and including nanorobots. My forthcoming book with Josh Hall (Fundamentals of Nanomechanical Engineering) and the development of the NanoEngineer software by Nanorex should advance our ability to design nanomechanical components, and further simulations and experiments will be required to learn how to build these systems and then assemble them into larger structures.

Once diamond mechanosynthesis and the fabrication of nanoparts becomes feasible, we will also need a massively parallel manufacturing capability to assemble nanorobots cheaply, precisely, and in vast quantities. My recently published technical book, co-authored with Merkle and titled Kinematic Self-Replicating Machines (Landes Bioscience, 2004), surveys all known current work in the field of self-replication and replicative manufacturing, including concepts of molecular assemblers and nanofactories. (This book is freely available online at the Molecular Assembler website.)

Finally, the reliable mass-production of medical nanorobots must be followed by a period of testing and approval for biocompatibility and safety by the FDA or its equivalent in other countries. I would not be surprised if the first deployment of such systems occurred during the 2020s.  But until we can build these devices experimentally, we are limited to theoretical analyses and computational chemistry simulations (some of which are now so good that their accuracy rivals the results of actual experiments).

So we can take two approaches, both of which I’m pursuing.  First, we can use our knowledge of the laws of physics and the principles of good engineering to create exemplar designs of nanorobots, and to analyze potential capabilities and uses of these devices, and determine which applications are likely to be possible and which seem not to be feasible.  This helps to establish a clear long-term goal.  Second, we can examine the implementation pathways that could lead from where we are today to the future time when we may be able to build nanorobotic devices.  As noted above, this may require diamond mechanosynthesis and massively parallel nanofabrication capabilities.  Earlier this year I submitted the first-ever U.S. patent on diamond mechanosynthesis that describes one possible specific experimental process for achieving molecularly precise diamond structures in a practical way.

Question 4: How will nanorobots avoid being destroyed by our immune systems? Won’t our immune systems identify them as foreign organisms and immediately attack them?

Nanorobots constructed of diamondoid materials cannot be destroyed by our immune system. They can be made to be essentially impervious to chemical attack. However, the body may react to their presence in a way that may interfere with their function. This raises the issue of nanorobot biocompatibility.

The biocompatibility of medical nanorobots is a complex and important issue. That’s why I expanded my original discussion in the Nanomedicine book series from a single chapter (Chapter 15, Nanomedicine Vol. II) to an entire book-length treatment (Nanomedicine, Vol. IIA) (NMIIA). My exploration of the particular problem you raise, nanorobot immunoreactivity, spans 16 pages in NMIIA. There is not enough space here to go into details, so interested readers should refer to that extended discussion. The short answer to your question is that the immune system invokes several different responses to foreign objects placed within the body, including complement activation and antibody response. Phagocytosis and foreign-body granulomatous reaction are additional major immune system issues for medical nanorobots intended to remain in the body for extended durations. The NMIIA book discusses all of these issues and suggests numerous methods by which antigenic reactions to nanorobots can be prevented or avoided, including (but not limited to) camouflage, chemical inhibition, decoys, active neutralization, tolerization, and clonal deletion. NMIIA also has an extensive discussion of nanorobotic phagocytosis, including details of all steps in the phagocytic process and possible techniques for phagocyte avoidance and escape by medical nanorobots. To summarize: the problems appear arduous but surmountable with good design.

Question 5: Ray Kurzweil has proposed having billions of nanorobots positioned in our brains, in order to create full-immersion virtual reality. Do you think that such a scenario will ever be feasible?

Yes of course. I first described the foundational concepts necessary for this in Nanomedicine, Vol. I (1999), including noninvasive neuroelectric monitoring (i.e., nanorobots monitoring neuroelectric signal traffic without being resident inside the neuron cell body, using >5 different methods), neural macrosensing (i.e., nanorobots eavesdropping on the body’s sensory traffic, including auditory and optic nerve taps), modification of natural cellular message traffic by nanorobots stationed nearby (including signal amplification, suppression, replacement, and linkage of previously disparate neural signal sources), inmessaging from neurons (nanorobots receiving signals from the neural traffic), outmessaging to neurons (nanorobots inserting signals into the neural traffic), direct stimulation of somesthetic, kinesthetic, auditory, gustatory, auditory, and ocular sensory nerves (including ganglionic stimulation and direct photoreceptor stimulation) by nanorobots, and the many neuron biocompatibility issues related to nanorobots in the brain, with special attention to the blood-brain barrier.

The key issue for enabling full-immersion reality is obtaining the necessary bandwidth inside the body, which should be available using the in vivo fiber network I first proposed in Nanomedicine, Vol. I (1999). Such a network can handle 10¹⁸ bits/sec of data traffic, capacious enough for real-time brain-state monitoring. The fiber network has a 30 cm³ volume and generates 4-6 watts waste heat, both small enough for safe installation in a 1400 cm³ 25-watt human brain. Signals travel at most a few meters at nearly the speed of light, so transit time from signal origination at neuron sites inside the brain to the external computer system mediating the upload are ~0.00001 millisec which is considerably less than the minimum ~5 millisec neuron discharge cycle time. Neuron-monitoring chemical sensors located on average ~2 microns apart can capture relevant chemical events occurring within a ~5 millisec time window, since this is the approximate diffusion time for, say, a small neuropeptide across a 2-micron distance. Thus human brain state monitoring can probably be “instantaneous,” at least on the timescale of human neural response, in the sense of “nothing of significance was missed.”

I believe Ray was relying upon these earlier analyses, among others, when making his proposals.

Question 6: What is your best guess regarding the development of advanced medical nanotechnology? Will it appear within a decade of the first desktop assembler?

The availability of practical molecular manufacturing is an obvious and necessary precursor to the widespread use of medical nanorobotics. I would not be surprised if the 2020’s are eventually dubbed the “Decade of Medical Nanorobots.”

Question 7: Will nanorobots be able to eradicate all infectious disease? After all, bacteria and viruses are extremely adaptable, and have developed a plethora of effective techniques to thwart the immune system.

It will probably not be possible to eradicate all infectious disease. The current bacterial population of Earth may be ~10³¹ organisms and so the chances are good that most of them are going to survive in some host reservoir, somewhere on the planet, for as long as life exists here, despite our best efforts to eradicate them. However, it should be possible to eliminate all harmful effects, and all harmful natural disease organisms, from the human body, allowing us to lead lives that are free of pathogen-mediated illness (at least most of the time). A simple antimicrobial nanorobot like the microbivore should be able to eliminate even the most severe bloodborne infections in treatment times on the order of an hour; more sophisticated devices could be used to tackle more difficult infection scenarios.

Regarding microbial adaptability, it makes no difference if a bacterium has acquired multiple drug resistance to antibiotics or to any other traditional treatment – the microbivore will eat it anyway, achieving complete clearance of even the most severe septicemic infections in minutes to hours, as compared to weeks or even months for antibiotic-assisted natural phagocytic defenses, without increasing the risk of sepsis or septic shock. Hence microbivores, each 2-3 microns in size, appear to be up to ~1000 times faster-acting than either unaided natural or antibiotic-assisted biological phagocytic defenses, and can extend the doctor’s reach to the entire range of potential bacterial threats, including locally dense infections.

Question 8: Have you made any detailed, molecularly precise simulations of medical nanorobots?

The greatest power of nanomedicine will emerge in a decade or two as we learn to design and construct complete artificial nanorobots using diamondoid nanometer-scale parts and subsystems including sensors, motors, manipulators, power plants, and molecular computers. The development pathway will be lengthy and difficult. First, theoretical scaling studies must be used to assess basic concept feasibility. These initial studies would then be followed by more detailed computational simulations of specific nanorobot components and assemblies, and ultimately full systems simulations, all thoroughly integrated with additional simulations of massively parallel manufacturing processes from start to finish consistent with a design-for-assembly engineering philosophy. Once molecular manufacturing capabilities become available, experimental efforts may progress from component fabrication and testing, to component assembly, and finally to prototypes and mass manufacture, ultimately leading to clinical trials.

As of 2005, progress in medical nanorobotics remains largely at the concept feasibility stage – since 1998, the author has published four theoretical nanorobot scaling studies, including the respirocytes (artificial red cells), microbivores (artificial white cells), clottocytes (artificial platelets), and the vasculoid (an artificial vascular system). These studies have not been intended to yield an actual engineering design for a future nanomedical product. Rather, the purpose was merely to examine a set of appropriate design constraints, scaling issues, and reference designs to assess whether or not the core idea might be feasible, and to determine key limitations of such designs.

The basic diamondoid structure of the respirocyte, the simplest nanorobot designed to date, includes 18 billion atoms. Molecular mechanics simulations of systems including 10-40 billion atoms have recently been reported using cluster supercomputers. So it is now possible, at least in principle, to attempt a basic simulation of an entire working medical nanorobot. The problems with actually doing this are many, and include the lack of a detailed atomic-level description of the respirocyte, a lack of reliable nanopart designs for components comprising the respirocyte, the difficulties of preparing input files and running massive simulations, and access to the personnel and computer time necessary to run the simulation. Such a simulation might well be attempted sometime in the next 5-10 years. Meanwhile we must content ourselves with molecular mechanics simulations of molecularly precise nanocomponents, starting with structures of up to 100,000 atoms using, for instance, the new NanoEngineer software produced by Nanorex.

Question 9: How has the mainstream medical community reacted to your research?

I think the biggest impact so far has been in solidifying the long-term vision of where the technology can go. Typically articles describing future medicine, especially nanotechnology-based medicine, will lead off with a mention of “nanorobots in the bloodstream” as an idea that lies out there somewhere in the distant future, before moving on to a more substantive discussion of the latest news in medical nanoparticle research. This is entirely understandable and logical. Doctors are faced with the immediacy of sick or dying patients, and can only employ the instruments at their command today. Realistically, there will only be some small fraction of the traditional medical community that “gets it” right off the bat. The intended audience of my Nanomedicine book series is technical and professional people who are seriously interested in the future of medical technology. Many practicing physicians do not – and quite correctly should not – fit this description. But I know I’m having an impact. I’ve received dozens of emails from students and young researchers thanking me for inspiring them to consider new career directions. (I’ve also been told, only partly tongue-in-cheek, that my Nanomedicine books are often used by postdocs to help prepare their grant proposals because of all the relevant literature references collected in each volume.)

As medical nanorobotics proceeds along the development pathway I’ve outlined above – moving from drawing board, to computer simulation, to laboratory demonstration of mechanosynthesis, to component design and fabrication, to parts assembly and integration, and finally to device performance and safety testing – members of the mainstream medical community will naturally pay increasing attention to it, because it will become more directly relevant to them. By mid-century, medical nanorobotics will completely dominate medical practice. By writing the Nanomedicine book series, KSRM, and the rest, I hope to accelerate the process of technological development and adoption of nanorobotics in modern medicine. To this end, the Nanomedicine book series and my other books are being made freely available online, with the generous consent of my publisher, Landes Bioscience. Such generosity is still almost unheard of among conventional book publishers. The main reason we’re doing this is to promote a broader discussion of the technical issues and a rapid assessment of the possibilities by the worldwide biomedical and engineering community.

Question 10: How far along are you in writing your Nanomedicine book series? What else have you been up to lately, in the nanomedicine area?

I’ve been writing the Nanomedicine book series since 1994. It was originally conceived as a single book, then became a trilogy until I realized I needed an entire volume devoted solely to biocompatibility, whereupon it became a tetralogy. Volume I was published by Landes Bioscience in 1999 and Volume IIA came out in 2003, also published by Landes Bioscience.  I’m still writing the last 2 volumes (NMIIB, NMIII) of this book series, an ongoing effort that will continue during 2005-2010. Earlier this year I published two reviews on the current status of nanomedicine, available online at http://www.nanomedicine.com/Papers/WhatIsNMMar05.pdf and http://www.nanomedicine.com/Papers/NMRevMar05.pdf. The first of these papers was the leadoff article for the premier issue of the new journal Nanomedicine (the first journal exclusively devoted to this field, published by Elsevier), on whose Editorial Board I also serve.

In a recent major collaborative effort, artist Gina Miller has finished work on a 3-minute long animation that nicely illustrates the workings of my proposed programmable dermal display (essentially, a video-touchscreen nano-tattoo that reports real-time medical information to the user, as reported back by numerous nanorobots stationed in various locations inside the body). I think this is a very cool animation. And of course you can always visit my Nanomedicine Art Gallery (hosted for me by Foresight Institute) with all the nice nanorobot images, where I continue on as curator.

©2006 Sander Olson. Reprinted with permission.