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Nanomedicine FAQ

by
Robert A. Freitas Jr.

© Copyright 1998, Robert A. Freitas Jr.
All rights reserved.

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  1. What chemical elements would medical nanorobots be made of?
  2. Could human body fluids get inside the nanorobot?
  3. What would be the physical appearance of a human who has been injected with medical nanorobots?
  4. What would a typical nanorobot look like?
  5. Can you give a concrete example of a simple medical nanorobot?
  6. Will "old nanorobots" left in the body cause problems when they eventually fail?
  7. How would the nanorobots be retrieved from the body?
  8. Won't medical nanorobots be attacked by the immune system, as soon as they are placed inside the human body?
  9. How fast can medical nanorobots replicate inside the human body?
  10. Will medical nanorobots possess a humanlike artificial intelligence?
  11. How would a medical nanorobot be powered?
  12. How would you communicate with the machines as they do their work?
  13. If medical nanorobots are infused into the human body, intravenously, how would one track their location?
  14. What form of detection system would medical nanorobots use to distinguish between differing cell types?
  15. How would chemical agents (e.g. an anti-cancer drug) be transported and delivered to a target cell?
  16. 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?
  17. To monitor the progress of the nanorobots during a treatment, could you biopsy the tissue and the image the machines using transmission electron microscopy?
  18. What could go wrong during a nanomedical procedure?
  19. What would be the biggest benefit to be gained for human society from nanomedicine?

Readers who wish to learn more technical details about nanomedicine are invited to visit the Nanomedicine Book Site at http://www.nanomedicine.com, where the complete text of the book Nanomedicine by Robert Freitas is freely available online.

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 nanocompositesemdashlargely 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.

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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.

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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.

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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 and testing has been completed.

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5. Can you give a concrete example of a simple medical nanorobot?

One very simple nanorobot that I designed a few years ago is the artificial mechanical red cell, which I call a "respirocyte." The respirocyte measures about 1 micron in diameter and just floats along in the bloodstream. It is a spherical nanorobot made of 18 billion atoms. These atoms are mostly carbon atoms arranged as diamond in a porous lattice structure inside the spherical shell. The respirocyte is essentially a tiny pressure tank that can be pumped full of up to 9 billion oxygen (O2) and carbon dioxide (CO2) molecules. Later on, these gases can be released from the tiny tank in a controlled manner. The gases are stored onboard at pressures up to about 1000 atmospheres. (Respirocytes can be rendered completely nonflammable by constructing the device internally of sapphire, a flameproof material with chemical and mechanical properties otherwise similar to diamond.)

The surface of each respirocyte is 37% covered with 29,160 molecular sorting rotors (Nanosystems, page 374) that can load and unload gases into the tanks. There are also gas concentration sensors on the outside of each device. When the nanorobot passes through the lung capillaries, O2 partial pressure is high and CO2 partial pressure is low, so the onboard computer tells the sorting rotors to load the tanks with oxygen and to dump the CO2. When the device later finds itself in the oxygen-starved peripheral tissues, the sensor readings are reversed. That is, CO2 partial pressure is relatively high and O2 partial pressure relatively low, so the onboard computer commands the sorting rotors to release O2 and to absorb CO2.

Respirocytes mimic the action of the natural hemoglobin-filled red blood cells. But a respirocyte can deliver 236 times more oxygen per unit volume than a natural red cell. This nanorobot is far more efficient than biology, mainly because its diamondoid construction permits a much higher operating pressure. (The operating pressure of the natural red blood cell is the equivalent of only about 0.51 atm, of which only about 0.13 atm is deliverable to tissues.) So the injection of a 5 cm3 dose of 50% respirocyte aqueous suspension into the bloodstream can exactly replace the entire O2 and CO2 carrying capacity of the patient's entire 5,400 cm3 of blood!

Respirocytes will have pressure sensors to receive acoustic signals from the doctor, who will use an ultrasound-like transmitter device to give the respirocytes commands to modify their behavior while they are still inside the patient's body. For example, the doctor might order all the respirocytes to just stop pumping, and become dormant. Later, the doctor might order them all to turn on again.

What if you added 1 liter of respirocytes into your bloodstream, the maximum that could possibly be safe? You could then hold your breath for nearly 4 hours if sitting quietly at the bottom of a swimming pool. Or if you were sprinting at top speed, you could run for at least 15 minutes before you had to take a breath!

It is clear that very "simple" medical nanodevices can have extremely useful abilities, even when applied in relatively small doses. Other more complex devices will have a broader range of capabilities. Some devices may have mobilityemdashthe ability to swim 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.

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6. 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 fail-operational and fail-safe performance, further reducing the medical risk.

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7. How would the nanorobots be retrieved from the body?

Some nanodevices will be able to exfuse themselves from the body via the usual human 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."

(Quoted from Robert A. Freitas Jr., "Exploratory Design in Medical Nanotechnology: A Mechanical Artificial Red Cell," Artificial Cells, Volume 26, 1998, pp. 411-430. This paper is apparently the first detailed design study of a specific medical nanodevice (of the general type proposed by Drexler in Nanosystems) that has been published. See earlier description in: Robert A. Freitas Jr., "Respirocytes: High Performance Artificial Nanotechnology Red Blood Cells," Nanotechnology Magazine, Volume 2, October 1996, pp. 1, 8-13.)

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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 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 some ways it may even be an easier problem, 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 ideal. Several experimental studies hint that the smoother and more flawless the diamond surface, the less leukocyte activity and the less fibrinogen adsorption you will get. So it seems reasonable to hope that when diamond coatings can be laid down with almost flawless atomic precision, making nanorobot exterior surfaces with near-nanometer smoothness, that these surfaces may have very low bioactivity. Due to the extremely high surface energy of the passivated diamond surface and the strong hydrophobicity of the diamond surface, the diamond exterior is almost completely chemically inert and so opsonization should be minimized.

However, even if flawless diamond surfaces alone do not prove fully bioinactive as hoped, active surface management of the nanorobot exterior can be used to ensure complete nanodevice biocompatibility. Allergic and shock reactions are similarly easily avoided.

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9. 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 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.

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10. 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 deviceemdashfar 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.

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11. How would a medical nanorobot be powered?

One of the earliest proposals by Drexler in Engines of Creation 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 of Nanomedicine.

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12. 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 broadcast-type 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 wellemdashthis one is just the easiest to describe.

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13. 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.

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14. 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 individualemdasha 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 early in the 21st century.

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15. 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" applicationemdashone 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.

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16. 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 workemdashsay, 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 designemdashupon 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.

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17. 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.

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18. 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 missionemdashespecially 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 interactionemdashthe 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.

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19. 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 capabilitiesemdashmost 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.

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© Copyright 1998, Robert A. Freitas Jr. All rights reserved.

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