Nano medication robot:Overview What if doctors could search out and destroy the very first cancer cells

that would otherwise have caused a tumor to develop in the body? What if a broken part of a cell could be removed and replaced with a miniature biological machine? What if pumps the size of molecules could be implanted to deliver life-saving medicines precisely when and where they are needed? These scenarios may sound unbelievable, but they are the longterm goals of the NIH Roadmap's Nanomedicine initiative that we anticipate will yield medical benefits as early as 10 years from now. Nanomedicine, an offshoot of nanotechnology, refers to highly specific medical intervention at the molecular scale for curing disease or repairing damaged tissues, such as bone, muscle, or nerve. A nanometer is one-billionth of a meter, too small to be seen with a conventional lab microscope. It is at this size scale about 100 nanometers or less that biological molecules and structures inside living cells operate. Nanotechnology involves the creation and use of materials and devices at the level of molecules and atoms. Research in nanotechnology began with applications outside of

medicine and is based on discoveries in physics and chemistry. This is because it is essential to understand the physical and chemical properties of molecules or complexes of molecules in order to control them. The same holds true for the molecules and structures inside living tissues. Researchers have developed powerful tools to extensively categorize the parts of cells in vivid detail, and we know a great deal about how these intracellular structures operate. Yet, scientists have still not been able to answer questions such as, "How many?" "How big?" and "How fast?" These questions must be addressed in order to build "nano" structures or "nano" machines that are compatible with living tissues and can safely operate inside the body. Once these questions are answered, we will design better diagnostic tools and engineer structures for more specific treatments of disease and repair of tissues. The most elementary nanomedical devices will be used to diagnose illness. Chemical tests exist for this purpose; nanomachines could be employed to monitor the internal chemistry of the body. Mobile nanorobots, equipped with wireless transmitters, might circulate in the blood and lymph systems, and send out warnings when chemical imbalances occur or worsen. Similar fixed nanomachines could be planted in the nervous system to monitor pulse, brain-wave activity, and other functions. A more advanced use of nanotechnology might involve implanted devices to dispense drugs or hormones as needed in people with chronic imbalance or deficiency states. Heart defibrillators and pacemakers have been around for some time; nanomedicine carries this to the next level down in terms of physical dimension, with the potential to affect the behavior of individual cells. Ultimately, artificial antibodies, artificial white and red blood cells, and antiviral nanorobots might be devised. Molecular nanotechnology ("MNT") is an anticipated manufacturing technology that would allow precise control and positional assembly of molecule-sized building blocks through the use of nano-scale manipulator arms. Molecular nanotechnology is usually considered distinct from the more inclusive term "nanotechnology", which is now used to refer to a wide range of scientific or technological projects that focus on phenomena or properties of the nanometer scale (around 0.1-100nm). Nanotechnology is already a blossoming field, but molecular nanotechnology - the goal of productive, molecular-scale machine systems - is still in the preliminary research stage. Nanotechnology was first introduced in 1959, in a talk by the Nobel Prize-winning physicist Richard Feynman, entitled "There's Plenty of Room at the Bottom". Feynman proposed using a set of conventional-sized robot arms to construct a replica of themselves, but one-tenth the original size, then using that new set of arms to manufacture an even smaller set, and so on, until the molecular scale is reached. If we had many millions or billions of such molecular-scale arms, we could program them to work together to create macro-scale products built from individual molecules - a "bottom-up manufacturing" technique, as opposed to the usual technique of cutting away material until you have a completed component or product - "top-down manufacturing". To initiate an MNT revolution would require an "assembler" - a reprogrammable nano-

scale manipulator capable of creating a wide range of molecular structures, including a complete copy of itself. The first assemblers will only function effectively in labcontrolled environments, such as a vacuum. The advent of self-replicating molecular nanomachines could quickly lead to "desktop nanofactories", tabletop appliances that consume modest amounts of power and contain the software required to manufacture an interesting range of useful products. The arrival of MNT would revolutionize wide sectors of human activity, including manufacturing, medicine, scientific research, communication, computing, and warfare. When full-blown molecular nanotechnology will arrive is currently unknown, but many experts foresee its arrival between 2010 and 2020. Nanomedicine may be defined as the monitoring, repair, construction and control of human biological systems at the molecular level, using engineered nanodevices and nanostructures. Basic nanostructured materials, engineered enzymes, and the many products of biotechnology will be enormously useful in near-term medical applications. However, the full promise of nanomedicine is unlikely to arrive until after the development of precisely controlled or programmable medical nanomachines and nanorobots. Once nanomachines are available, the ultimate dream of every healer, medicine man, and physician throughout recorded history will, at last, become a reality. Programmable and controllable microscale robots comprised of nanoscale parts fabricated to nanometer precision will allow medical doctors to execute curative and reconstructive procedures in the human body at the cellular and molecular levels. Nanomedical physicians of the early 21st century will still make good use of the body's natural healing powers and homeostatic mechanisms, because, all else equal, those interventions are best that intervene least. But the ability to direct events in a controlled fashion at the cellular level is the key that will unlock the indefinite extension of human health and the expansion of human abilities.

1. What chemical elements would medical nanorobots be made of? The typical medical nanodevice will probably be a micron-scale robot assembled from nanoscale parts. These parts could range in size from 1-100 nm (1 nm = 10-9 meter), and might be fitted together to make a working machine measuring perhaps 0.5-3 microns (1 micron = 10-6 meter) in diameter. Three microns is about the maximum size for bloodborne medical nanorobots, due to the capillary passage requirement. Carbon will likely be the principal element comprising the bulk of a medical nanorobot, probably in the form of diamond or diamondoid/fullerene nanocomposites largely because of the tremendous strength and chemical inertness of diamond. Many other light elements such as hydrogen, sulfur, oxygen, nitrogen, fluorine, silicon, etc. will be used for special purposes in nanoscale gears and other components.

2. Could human body fluids get inside the nanorobot? From a medical standpoint, it makes sense to regard the nanorobot as having two spaces which should be considered separately its interior and its exterior. It is true that the nanorobot exterior will be exposed to the diverse chemical brew that makes up our human biochemistry. But the interior of the nanorobot may be a highly controlled environment, possibly a vacuum, into which external liquids cannot normally intrude. Of course it may often be necessary for a nanorobot to import external fluids in a controlled manner for chemical analysis or other purposes. But the important thing is that the device will be watertight and airtight. Body fluids cannot get into the interior of the device, unless these fluids are purposely pumped in for some specific reason. 3. What would be the physical appearance of a human who has been injected with medical nanorobots? In most cases a human patient who is is undergoing a nanomedical treatment is going to look just like anyone else who is sick. The typical nanomedical treatment (e.g. to combat a bacterial or viral infection) will consist of an injection of perhaps a few cubic centimeters of micron-sized nanorobots suspended in fluid (probably a water/saline suspension). The typical therapeutic dose may include up to 1-10 trillion (1 trillion = 1012) individual nanorobots, although in some cases treatment may only require a few million or a few billion individual devices to be injected. Each nanorobot will be on the order of perhaps 0.5 micron up to perhaps 3 microns in diameter. (The exact size depends on the design, and on exactly what the nanorobots are intended to do.) The adult human body has a volume of perhaps 100,000 cm3 and a blood volume of ~5400 cm3, so adding a mere ~3 cm3 dose of nanorobots is not particularly invasive. The nanorobots are going to be doing exactly what the doctor tells them to do, and nothing more (barring malfunctions). So the only physical change you will see in the patient is that he or she will very rapidly become well again. Most symptoms such as fever and itching have specific biochemical causes which can also be managed, reduced, and eliminated using the appropriate injected nanorobots. Major rashes or lesions such as those that occur when you have the measles will take a bit longer to reverse, because in this case the broken skin must also be repaired. 4. What would a typical nanorobot look like? It is impossible to say exactly what a generic nanorobot would look like. Nanorobots intended to travel through the bloodstream to their target will probably be 500-3000 nanometers (1 nanometer = 10-9 meter) in characteristic dimension. Nonbloodborne tissue-traversing nanorobots might be as large as 50-100 microns, and alimentary or bronchial-traveling nanorobots may be even larger still. Each species of medical nanorobot will be designed to accomplish a specific task, and many shapes and sizes are possible. Finally, and perhaps most importantly, no actual working nanorobot has yet been built. Many theoretical designs have been proposed that look good on paper, but these preliminary designs could change significantly after the necessary research, development

through the blood, or crawl through body tissue or along the walls of arteries. Others will have different shapes, colors, and surface textures, depending on the functions they must perform. They will have different types of robotic manipulators, different sensor arrays, and so forth. Each medical nanorobot will be designed to do a particular job extremely well, and will have a unique shape and behavior.

High latitude view of a single respirocyte in iridescent colors, showing the circumpolar concentric-circle bar coding and a conventional 12-fold pumping station layout.

5. Will "old nanorobots" left in the body cause problems when they eventually fail? Following most simple treatments, nanodoctors of the 21st century will want to remove their therapeutic nanorobots from the patient's body as soon as the nanodevices have finished the job. So there will be little danger of "old nanorobots" breaking down or malfunctioning, or causing something unpleasant to happen to the patient after the original disease or traumatic condition has been treated. Additionally, nanorobots will be designed with a high level of redundancy to ensure failoperational and fail-safe performance, further reducing the medical risk. 6. How would the nanorobots be retrieved from the body? Some nanodevices will be able to exfuse themselves from the body via the usual human

7. How fast can medical nanorobots replicate inside the human body?
This is a very common error. Medical nanorobots need not EVER replicate. In fact, it is unlikely that the FDA (or its future equivalent) would ever approve for general use a medical nanodevice that was capable of in vivo excretory channels; others will be designed to allow ready exfusion by medical personnel using apheresis-like processes (commonly called nanapheresis) or active scavenger systems. It is very design dependent. In the case of the respirocytes, the removal procedure is fairly simple: "Once a therapeutic purpose is completed, it may be desirable to extract artificial devices from circulation. Onboard water ballast control is extremely useful during respirocyte exfusion from the blood. Blood to be cleared may be passed from the patient to a specialized centrifugation apparatus where acoustic transmitters command respirocytes to establish neutral buoyancy. No other solid blood component can maintain exact neutral buoyancy, hence those other components precipitate outward during gentle centrifugation and are drawn off and added back to filtered plasma on the other side of the apparatus. Meanwhile, after a period of centrifugation, the plasma, containing mostly suspended respirocytes but few other solids, is drawn off through a 1-micron filter, removing the respirocytes. Filtered plasma is recombined with centrifuged solid components and returned undamaged to the patient's body. The rate of separation is further enhanced either by commanding respirocytes to empty all tanks, lowering net density to 66% of blood plasma density, or by commanding respirocytes to blow a 5-micron O2 gas bubble to which the device may adhere via surface tension, allowing it to rise at 45 mm/hour under normal gravitational acceleration." 8. Won't medical nanorobots be attacked by the immune system, as soon as they are placed inside the human body? Immune system response is primarily a reaction to a "foreign" surface. Nanorobot size is also an important variable, along with because many medical nanorobots will have only temporary residence in the body. Even today, application of immunosuppressive agents during the treatment period would allow poorly-engineered non-bioinactive nanorobots to perform their repair work without trouble. Passive diamond exteriors may turn out to be i device mobility, surface roughness, surface mobility, and other factors. Yet the problem of nanodevice biocompatibility is in principle no more difficult than the biocompatibility of medical implants generally. In replication. Except in the most unusual of circumstances, you would never want anything that could replicate itself to be turned loose inside your body. Replicating bacteria are trouble enough! Replication is a crucial basic capability for molecular manufacturing. But aside from the most aggressive applications, there is simply no good reason to risk manufacturing "fertile" nanorobots inside the human body, when "mule" nanorobots can be manufactured so cheaply, conveniently, and in such vast numbers outside of the human body. Replicators will almost certainly be very tightly regulated by governments everywhere.

8. Will medical nanorobots possess a humanlike artificial intelligence?

This is another common error. Many medical nanorobots will have very simple computers on board each device. Respirocytes, for example, have only a ~1,000 operations/sec computer on board each device far less computing power than an old Apple II. Most cellular repair nanorobots will not need more than 106-109 operations/sec of onboard computing capacity to do their work. This is a full 4-7 orders of magnitude below (even the potential for) true human-equivalent computing at 10 teraflops (~1013 operations/sec). Faster computing capacity is simply not required for most medical nanorobots.

9. How would a medical nanorobot be powered?

One of the earliest proposals by Drexler in Engines of Creation <../EOC/index.html> was that an in vivo medical nanodevice could metabolize local glucose and oxygen for energy. Another possibility is externally supplied acoustic power, which is probably most appropriate in a clinical setting. There are literally dozens of useful power sources that are potentially available in the human body, as described in Chapter 6 <NanoMedTOC.html> of Nanomedicine <http://www.nanomedicine.com>.

10. How would you communicate with the machines as they do their work?
There are many different ways to do this. One of the simplest ways to send broadcasttype messages into the body, to be received by in vivo nanorobots, is acoustic messaging. A device similar to an ultrasound probe would encode messages on acoustic carrier waves at frequencies between 1-10 MHz. Thus the supervising physician can easily send new commands or parameters to nanorobots already at work inside the body. Each nanorobot has its own power supply, computer, and sensorium, thus can receive the physician's messages via acoustic sensors, then compute and implement the appropriate response. The other half of the process is getting messages back out of the body, from the working nanodevices out to the physician. This can also be done acoustically. However, onboard power requirements for micron-scale acoustic wave generators in water dictate a maximum practical transmission range of at most a few hundred microns for each individual nanorobot. Therefore it is convenient to establish an internal communications network that can collect local messages and pass them along to a central location, which the physician can then monitor using sensitive ultrasound detectors to receive the messages. Such a network can probably be deployed inside a patient in less than an hour, may involve up to 100 billion mobile nanorobotic network nodes, and may release at most 60 watts of waste heat (less than the 100-watt human body basal rate) assuming a (worst case) full 100% network duty cycle. There are many other techniques that may be used as well this one is just the easiest to

describe.

11. If medical nanorobots are infused into the human body, intravenously, how would one track their location?
A navigational network may be installed in the body, with stationkeeping navigational elements providing high positional accuracy to all passing nanorobots that interrogate them, wanting to know their location. Physical positions can be reported continuously using an in vivo communications network. Since the typical therapeutic dose may involve billions or trillions of nanorobots (e.g. up to a few cm3 of injection), it will usually be impractical to address nanorobots individually, though this is in principle possible for treatments involving only a few million devices, or fewer.

12. What form of detection system would medical nanorobots use to distinguish between differing cell types?
Each cell type has its own unique set of surface antigens. Other cell surface antigens indicate the health status of the cell, the parent organ type, the species of the animal, and even the identity of the individual a kind of biochemical Social Security Number. So the short answer to this question is: Use chemotactic sensors (crudely analogous to chemical force microscopy), keyed to the specific known antigens on the target cells you are looking for. Knowledge of these antigens will become extensive, soon after the completion of the Human Genome Project <http://www.ornl.gov/hgmis/> early in the 21st century.

13. How would chemical agents (e.g. an anti-cancer drug) be transported and delivered to a target cell?
Once you've identified a group of cells that needs some chemical substance delivered to it, you can simply release the agent from onboard tanks after the nanorobot arrives on the scene. A 1 cm3 injection of 1-micron nanodevices could probably hold at least 0.5 cm3 of chemical agent. Virtually all of these billions of nanites (in the 1 cm3) will be smart enough to show up at the correct group of cells that are targeted for destruction, so delivery efficiency is virtually 100%. Onboard sensors can test for ambient levels of the chemical agent, to prevent overdose. However, this question is a good example of an "anachronistic" application one that could be done using medical nanorobots, but in fact would probably never be done that way, because in an era of advanced nanotechnology much more efficient and much less destructive ways would exist to get the same job done. In the above example, bulk delivery of cytotoxins to tissue cells is completely unnecessary if the means exists to reverse the carcinomatous process at the cellular and genetic level.

14. Is it possible to image in vivo medical nanomachines using an imaging technique such as MRI, or would one have to look directly at tissue?
Yes, nanodevices could probably be observed at work inside the body using MRI, especially if their diamond components were manufactured using mostly 13C atoms rather than the more common natural 12C isotope of carbon, since 13C has a nonzero nuclear magnetic moment. But in the nanomedical era, such an approach may again be somewhat anachronistic. Here's why. Applying the classical medical model to a typical nanomedical treatment, the medical nanodevices would first be injected into a human body, and would then go to work say, in a specific organ or tissue mass. The physician wants to be able to monitor their progress, and make certain that the nanodevices have gotten to the correct target treatment region. So the first instinct of the contemporary physician who is contemplating a prospective nanomedical treatment will be to insist on the ability to directly image the nanorobots. In other words, the doctor wants to be able to scan a section of the body, and actually see the nanodevices congregated neatly around their target, say, a tumor mass, so that he can be absolutely certain that the therapy is proceeding as (and where) planned. However, if the technology exists to fabricate nanorobots to molecular precision, then this same technology will allow communication and navigational mechanisms to be designed and built into each and every nanorobot, and will also allow communications and navigational networks to be deployed inside the body. Therapeutic nanodevices may be programmed to home in on a very precisely-specified set of surface antigens populating the surface of the target tumor mass. As an additional guide, internal reference frame navigation with millimeter (or better) accuracy may be used to direct the nanorobots to the close vicinity of the target treatment volume. So the correct medical treatment model in the nanomedical era is as follows: Injected and circulating nanorobots would remain absolutely inactive outside of the target volume. Even once inside the target treatment volume, nanorobots would still remain inactive until the precise antigenic signature of the target tissue was chemotactically detected by nanorobot sensors. The nanorobots could further be programmed to remain inactive until they received an acoustic command from the physician telling them that they were free to begin the active treatment, perhaps after the physician receives confirmation through the navigational grid that most of the devices have reached their proper destinations. The physician retains complete control throughout the course of the treatment process; a signal ordering all nanorobots to halt may be sent at any time. Equally important, nanorobots can communicate their positions, operational statuses, and the success or failure of the treatment as the treatment progresses. Bandwidth limitations will require considerable information pooling, but this should not present a problem. In this treatment model, the physician receives continuous reports from the active nanorobots. They tell you their physical coordinates in the body, so you know where they are. They tell you how many cancer cells they have encountered and inactivated (or whatever is the appropriate metric to establish progress for the particular treatment). They

will have multiple-redundant systems (like the five consensus computers onboard the Space Shuttle), establishing a fail-operational or a fail-safe design upon detecting a critical component failure, the device places itself in shutdown mode in preparation for exfusion. So in this kind of scenario, it may be quite unnecessary to image the nanodevices directly, because the feedback available to the supervising physician from other means will be far more sophisticated, reliable, useful, and complete.

15. To monitor the progress of the nanorobots during a treatment, could you biopsy the tissue and the image the machines using transmission electron microscopy?
Yes, it would be possible to biopsy tissue and then image the embedded nanomachines using transmission electron microscopy. However, the normal presumption will be that your medical nanorobots are working properly. Because of fail-safe design, the nanodevices should only rarely be a part of the problem. On the contrary, they will likely be a major part of the solution. In the usual biopsy situation, your primary interest is in the condition of the tissue, not the condition of the nanodevices embedded in it. But nanodevices can be used to rapidly examine a given piece of tissue, surveying its biochemistry, biomechanics, and histometric characteristics in great detail. Indeed, in an era of proficient nanomedicine, it should rarely be necessary to remove tissue samples from patients for testing at all. Most testing should be possible in situ, with the added benefits of reduced intrusiveness, increased patient comfort, and greater fidelity of results since the target tissue can be examined in its active state in the actual host environment.

16. What could go wrong during a nanomedical procedure?

The incompetence or negligence of medical personnel is always a potential concern. However, in the nanomedical era, as today, such occurrences should be infrequent and notorious. A true glitch will come from some direction that nobody anticipated. Biocompatibility problems are well anticipated, and multiple-redundant onboard computers should ensure safe operation, correct operation, and reprogrammability of operational parameters even after the devices have been launched on their mission especially to permit deactivation if anything goes wrong. Fail-stop protocols may be particularly appropriate in high-risk missions where large numbers of replacement nanorobots are readily available. Therefore, the most serious problems may devolve from the inherent complexity of a trillion machines independently trying to cooperatively work on a very complex repair problem in a short period of time. One class of malfunction might involve some unexpected emergent machine-machine interaction the kind of subtle interaction that is unlikely to have been exhaustively tested in full-up systems, in advance.

As a simple example, consider two nanorobot species that are jointly repairing a given block of tissue. If the nanorobot programming allows species A to interpret the repair work of species B as a new tissue flaw that lies within species A's original repair mission parameters, and vice versa, then it would be possible for the two species to become locked in an endless recursive cycle, as each species attempted repeatedly to undo the other's work. But even in such cases, control over the devices is not lost. The supervising physician, upon observing the fault, would simply shut down one or the other species to allow the work to proceed, or would shut down both species and reprogram them both (while they are still inside the body) to avoid the unwanted emergent behavior. The doctor must always be able to "pull the plug" on the nanomachines. This is one of the most important design constraints, one that will probably become a strict and universal regulatory requirement for all medical nanodevices.

17. What would be the biggest benefit to be gained for human society from nanomedicine?
Nanomedicine will eliminate virtually all common diseases of the 20th century, virtually all medical pain and suffering, and allow the extension of human capabilities most especially our mental abilities. Consider that a nanostructured data storage device measuring ~8,000 micron3, a cubic volume about the size of a single human liver cell and smaller than a typical neuron, could store an amount of information equivalent to the entire Library of Congress. If implanted somewhere in the human brain, together with the appropriate interface mechanisms, such a device could allow extremely rapid access to this information. A single nanocomputer CPU, also having the volume of just one tiny human cell, could compute at the rate of 10 teraflops (1013 floating-point operations per second), approximately equalling (by many estimates) the computational output of the entire human brain. Such a nanocomputer might produce only about 0.001 watt of waste heat, as compared to the ~25 watts of waste heat for the biological brain in which the nanocomputer might be embedded. But perhaps the most important long-term benefit to human society as a whole could be the dawning of a new era of peace. We could hope that people who are independently well-fed, well-clothed, well-housed, smart, well-educated, healthy and happy will have little motivation to make war. Human beings who have a reasonable prospect of living many "normal" lifetimes will learn patience from experience, and will be extremely unlikely to risk those "many lifetimes" for any but the most compelling of reasons.

Foresight Nanotechnology Challenges

17.1 Meeting global energy needs with clean solutions

Balancing humanitys energy demands while protecting the environment is a major challenge. Nanotechnology will help to solve the dilemma of energy needs and limited

planetary resources through more efficient generation, storage and distribution. Meeting Global Energy Needs With Clean Solutions <energy.html>

17.2. Providing Abundant Clean Water Globally

The demand for fresh water is increasing. Considering the current rate of consumption and projected population growth, some two-thirds of the world will be affected by drought by the year 2050. Nanotechnology can help solve this problem through improved water purification and filtration. Providing Abundant Clean Water Globally <water.html>

17.3. Increasing Health and Longevity of Human Life

Humans are living longer lives, yet infectious diseases and cancer continue to kill millions annually. Because of an aging population there could be a 50% increase of new cancer cases by the year 2020. Nanotechnology will enhance the quality of life for human beings through medical diagnostics, drug delivery and customized therapy.
Nanocomputers, assemblers, and even replicators are in the first phase. I believe a replicator is about as complex as a modern automated factory even though it has the advantage of working in an environment rich in pre-fabricated parts. Relatively simple cellular repair machines are also part of the first phase. Things like very ambitious cell repair, AI (which is what I think of when you speak of making people obsolete), and very ambitious re-working of the human body are part of the second phase. The things you are pointing to are part of Phase II Nanotechnology -- nanotechnology combined with very powerful design capabilities, probably in a world that has real artificial intelligence.

Abstract
Disease and ill health are caused largely by damage at the molecular and cellular level. Today's surgical tools are, at this scale, large and crude. From the viewpoint of a cell, even a fine scalpel is a blunt instrument more suited to tear and injure than heal and cure. Modern surgery works only because cells have a remarkable ability to regroup, bury their dead and heal over the injury. Nanotechnology, "the manufacturing technology of the 21st century," should let us economically build a broad range of complex molecular machines (including, not incidentally, molecular computers). It will let us build fleets of computer controlled molecular tools much smaller than a human cell and built with the accuracy and precision of drug molecules. Such tools will let medicine, for the first time, intervene in a sophisticated and controlled way at the cellular and molecular level. They could remove obstructions in the circulatory system, kill cancer cells, or take over the function of subcellular organelles. Just as today we have the artifical heart, so in the future we could have the artificial mitochondrion. Equally dramatic, nanotechnology will give us new instruments to examine tissue in unprecedented detail. Sensors smaller than a cell would give us an inside and exquisitely precise look at ongoing function. Tissue that was either chemically fixed or flash frozen could be analyzed literally down to the molecular level, giving a completely detailed "snapshot" of cellular, subcellular and molecular activities.

18.2. The von Neumann architecture for a general manufacturing system

Von Neumann's proposal consisted of two central elements: a universal computer and a universal constructor (see figure 1). The universal computer contains a program that directs the behavior of the universal constructor. The universal constructor, in turn, is used to manufacture both another universal computer and another universal constructor. Once construction is finished the program contained in the original universal computer is copied to the new universal computer and program execution is started.

18.3. Drexler's architecture for an assembler

Drexler's assembler follows the von Neumann kinematic architecture, but is specialized for dealing with systems made of atoms. The essential components in Drexler's assembler are shown in figure 2. The emphasis here (in contrast to von Neumann's proposal) is on small size. The computer and constructor both shrink to the molecular scale, while the constructor takes on additional detail consistent with the desire to manipulate molecular structures with atomic precision. The molecular constructor has two major subsystems: (1) a positional capability and (2) the tip chemistry.

18.4. Size of devices

Drexler's proposal for molecular mechanical logic [REF06] is the most compact and, from the system point of view, the best worked out. The logic elements ("locks," roughly the equivalent of a single transistor) need occupy a volume of only a few cubic nanometers. Even including system overhead (power, connections, etc). the volume per element should still be less than 100 cubic nanometers. A 10,000 element logic system (enough to hold a small processor) would occupy a cube no more than 100 nanometers on a side. That is, a volume only slightly larger than 0.001 cubic microns would be sufficient to hold a small computer. This compares favorably with the volume of a typical cell (thousands of cubic microns) and is even substantially smaller than subcellular organelles A variety of molecular sensors and actuators would also fit in such a volume. A molecular "robotic arm" less than 100 nanometers long should be quite feasible, as well as molecular binding sites 10 nanometers in size or less. By contrast, a single red blood cell is about 8 microns in diameter (over 80 times larger in linear dimensions than our 100 nanometer processor). Devices of the size range suggested above (~0.1 microns) would easily fit in the circulatory system and would even be able to enter individual cells.

18.5. An application: killing cancer cells

Given such molecular tools, we could design a small device able to identify and kill cancer cells. The device would have a small computer, several binding sites to determine the concentration of specific molecules, and a supply of some poison which could be selectively released and was able to kill a cell identified as cancerous.

18.6. An application: providing oxygen

A second application would be to provide metabolic support in the event of impaired circulation. Poor blood flow, caused by a variety of conditions, can result in serious tissue damage. A major

cause of tissue damage is inadequate oxygen. A simple method of improving the levels of available oxygen despite reduced blood flow would be to provide an "artificial red blood cell."

11. How Long?

The abilities discussed here might well take years or decades to develop. It is quite natural to ask: "When might we see these systems actually used?" The scientifically correct answer is, of course, "We don't know." That said, it is worth noting that if progress in computer hardware continues as the trend lines of the last 50 years suggest, we should have some form of molecular manufacturing in the 2010 to 2020 time frame. After this, the medical applications will require some additional time to develop. The remarkably steady trend lines in computer hardware, however, give a false sense that there is a "schedule" and that developments will spontaneously happen at their appointed time. This is

incorrect. How long it will take to develop these systems depends very much on what we do. If focused efforts to develop molecular manufacturing and its medical applications are pursued, we will have such systems well within our lifetimes. If we make no special efforts the schedule will slip, possibly by a great deal. As might be appreciated, developing these systems within our lifetimes would be advantageous for a variety of reasons.

In this fanciful image, mobile nanorobotic janitors (green) patrol the lungs, collecting inhaled debris and transporting it to recycling stations (blue-gray).

T4 bacterial virus, an assembly of protein components, is a simple biological "nanomachine". The head is a protein membrane, shaped like a kind of prolate icosahedron with 30 facets and filled with deoxyribonucleic acid (DNA). It is attached by a neck to a tail consisting of a hollow core surrounded by a contractile sheath and based on a spiked end plate to which six fibers are attached. The spikes and fibers affix the virus to a bacterial cell wall. The sheath contracts, driving the core through the wall, and viral DNA enters the cell. Bacteriophages are being studied in anti-bacterial applications as phage therapy.

nanomachine swimming through a capillary attacks a fat deposit (such as normally may accompany an arteriosclerotic lesion). The classic original image!

hairjacks Evoking a humorous sense of lumberjacks felling trees, this image shows buzzsaw-wielding nanorobots mowing down a thick stand of follicles. Apparently the owner treated his hair with green mousse before deciding to go with a buzzcut instead. You can almost feel your scalp humming!

A remote-controlled nanorobots examine and clean the subocclusal surfaces of a patient's teeth, near the gumline. As an aid to visualization, the artist has depicted the dental nanorobots about 1000 times larger than actual size.

A fanciful illustration of mechanical-looking medical nanorobots navigating the bloodstream in pursuit of invading viruses

Imagine an army of tiny robots, each no bigger than a bacterium, swimming through your bloodstream. One platoon takes continuous readings of blood pressure in different parts of your body; another monitors cholesterol; still others measure blood sugar, hormone levels, incipient arterial blockages and immune-system activity. Such are the dreams of the nanotechnologists, engineers at places like M.I.T., Princeton University and Carnegie Mellon, who are already redefining the meaning of the word miniature. The prefix nano- refers to a billionth part of a unit -- the size range these visionaries are talking about. Already, nanotechnologists have built gears and rotors

devices, and many consumer products, may someday be made with nanotechnology.

nanodevices could augment the immune system by finding and disabling unwanted bacteria and viruses. The immune device in the foreground of this image has found a virus; the other has touched a red blood cell.
Medical

It is useful to think in terms of medical nanomachines that resemble small submarines. Each of these is large enough to carry a nanocomputer as powerful as a mid-1980s mainframe, along with a huge database (a billion bytes), a complete set of instruments for identifying biological surfaces, and tools for clobbering viruses, bacteria, and other invaders. Immune machines, with their onboard sensors and computers, will be able to react to the same molecular signals that the immune system does, but with greater discrimination. Before being sent into the body on their search-and-destroy mission, they could be programmed with a set of characteristics that lets them clearly distinguish their targets from everything else. The body's immune system can respond only to invading organisms that had been encountered by that individual's body. Immune machines, however, could be programmed to respond to anything that had been encountered by world medicine. Immune machines can be designed for use in the bloodstream or the digestive tract. They could float and circulate, as antibiotics do, while searching for intruders to neutralize. To escape being engulfed by white blood cells making their own patrols, immune machines could display standard molecules on their surfacemolecules the body knows and trusts already like a fellow police officer wearing a familiar uniform.

drillers In a classical laboratory experiment which all first-year nanomedical students are required to perform, the simple mechanical drilling of a small tumor mass (seen in foreground) induces nonspecific adhesions of red cells and later of other cells in vitro, thus demonstrating once again the age-old wisdom of avoiding mechanical necrotic cell lysis in vivo, in favor of apoptotic or digestive mechanisms

The blue, octopus-like nanobot is one of billions of brain cell enhancers. The central sphere houses a computer, with a storehouse of information equal to many large libraries. Billions of spheres are in contact with one another, as well as with the brain cells, creating a secondary gestalt mind that interfaces with the brain's original gestalt mind. For this image, the circuit board background was chosen to impart a surreal tone. bloodstream of an anesthetized animal to validate safety protocols prior to human use.

dock bots Nanorobots (shown in light green and blue) adhered to blood vessel walls incorporate a hollow tip projecting out into the vascular lumen, allowing other passing nanorobots (shown as spheres in dark green) to dock with them and exchange information or materials.

a laboratory diagnostic test, a "stinger" nanorobot (designed by Erik Viktor) grabs a sick T lymphocyte and injects a glucocorticoid designed to induce cellular apoptosis.
During

A metallic-looking medical nanorobot in the foreground extends a pincer-like mechanism and begins removing a yellow fatty deposit from an arterial surface; another similar device is seen working in the background. Hovering nearby is a supervisory nanorobot.