From Cryonics July 1988
CELL REPAIR TECHNOLOGY
by Brian Wowk
CELL REPAIR UNIT
So you're talking about being able to put on the order of 1,000 Motorola 68000 CPU's in the volume of a bacterial cell. Eric Drexler, Research Affiliate, MIT Artificial Intelligence Laboratory
This article will focus on the medical implications of a mature nanotechnology. In particular, it will be argued in broad technical terms why nanotechnology implies a medicine capable of reversing not only any organic disease (including aging), but also a host of supposedly irreversible injuries, including severe freezing injury, ischemic injury, and even destruction of all non-brain tissues. In short, a foreseeable future technology will be presented which would seem to give present cryonics practice a reasonable (perhaps even good) chance of success.
2006 note from the author: My primary regret about this article is that it inadequately credits Eric Drexler for first outlining the feasibility of molecular nanotechnology and its biological repair implications. Still, I believe there are some ideas, and ways of expressing ideas, in this paper that are original. Like much of what is now called nanomedicine, the capabilities discussed here are generally beyond what will be necessary to reverse cryopreservation by modern vitrification under good conditions.
What kind of medical advances will molecular engineering bring? Simple extrapolation of present trends in biotechnology would lead one to expect a greatly expanded range of drugs and other bioregulatory compounds. Indeed, mature nanotechnology will allow inexpensive manufacture of any molecule that does (or could) exist in nature.
Yet a larger medicine chest is only the most obvious -- and least significant -- medical implication of nanotechnology. More profoundly, nanotechnology will render obsolete drugs as we know them today.
The use of drugs (simple chemicals) in medicine epitomizes the difference between today's medicine and tomorrow's. Drugs do not heal patients; drugs merely assist patients in healing themselves. Drugs are useless when injuries greatly exceed natural healing capacities (particularly when tissues are rendered non-functional by injury). In fact, caring for patients with drugs is not unlike trying to repair and maintain an automobile using just simple fuel additives!
If today's drugs are the medical equivalent of fuel additives, then tomorrow's nanotechnology will be the equivalent of a complete repair shop for the human body. Advanced means for engineering at the molecular level will lead not only to complex new molecules (drugs), but to complex aggregates of molecules -- molecular machines -- with unprecedented medical functions. Among these functions will be abilities to vastly augment, and even bypass natural healing processes (by repairing cells and tissues directly), thus freeing medicine from its historic reliance on innate healing capacities.
Cell Repair Systems
How can medicine repair individual cells? By learning to manipulate the most basic components of cells -- atoms and molecules.
What kind of technology will allow medicine to do this? One that is not substantially different in kind compared to "technology" already existing in nature. Natural cells and organisms already perform extremely complex feats of molecular synthesis, manipulation, repair, and replacement as part of their normal function. As biologists gain more complete understanding of cell growth and development in the decades ahead, a variety of powerful techniques for augmenting natural healing processes will become available. Foreseeable developments include the use of synthetic growth factors and morphogens for inducing complex tissue regeneration, and even the introduction of novel genetic programs for reversing cellular and tissue injuries for which natural healing mechanisms do not exist. No doubt these techniques will have broad application in the control and reversal of ischemic and freezing injuries which are irreversible at present.
Even more powerful technologies are foreseeable over the long term. With a view toward advanced molecular engineering capabilities, this article will frame a "brute force" argument for the reversibility of almost any biological injury. It will be argued that practical devices are theoretically possible that, if necessary, could perform complete atom-by-atom characterization and repair of tissue.
What tools could possibly be small enough to repair cells in such detail, and how could we ever build them? The answers are: Tools like those that cells already use to repair and maintain themselves, which we will build much as cells do.
Cells maintain themselves using a variety of molecular machines (machines constructed to molecular specifications), including enzymes for fine operations and cytoskeletal structures for grosser manipulations. Nanotechnology will allow us to build any of these molecular machines (and more), and to assemble them in ways not seen in nature -- ways that achieve complex medical objectives. Among these objectives will be sophisticated cell repair.
The development of nanotechnological cell repair systems can, in part, be viewed as the creation of artificial microorganisms for medical purposes. (Indeed, experimental usage of modified retroviruses for gene therapy today is a kind of cell repair technology.) It therefore follows that appropriately designed medical microbes, or cell repair devices, could at a minimum do anything that natural cells and their components are known to do today.
White blood cells show that molecular machines can leave a patient's blood stream and move through tissues in a very general manner. Cell repair devices with non-antigenic (or immune compatible) exteriors will therefore similarly be able to similarly reach most any cell in the body.
Viruses demonstrate that systems of molecular machinery can penetrate cell membranes and enter their interiors. More dramatically, successful transplantation of cell nuclei by today's biologists demonstrates that cells can often naturally recover from even extreme membrane and cytoplasmic trauma. Repair devices the size of ordinary organelles will therefore be able enter the interior of cells and move about freely without causing significant harm. (Note that this does not even consider the potential of repair devices to themselves repair structures they disturb.)
Digestive enzymes show that molecular machines can disassemble large molecular aggregates. Repair devices incorporating tools analogous to these enzymes will therefore be able to perform controlled disassembly of cell structures as part of analysis and repair processes.
The ability of antibodies to distinguish among proteins, the ability of enzymes to distinguish among potential substrates, and many other biological processes demonstrate that molecular machines can recognize specific kinds molecules on the basis of shape and charge distribution. Cell repair devices will therefore be able to employ sets of tools for identifying and analyzing biomolecules by touch. Since larger cell structures generally contain biomolecules unique to them, repair devices will be able to similarly identify these structures by "feeling" them.
The molecular synthesis machinery of natural cells shows that damaged cell structures can be rebuilt and/or reassembled by molecular machines. Indeed, cell replication is direct proof that every structure in a cell can be assembled from even simple nutrient molecules by molecular machinery.
The above discussion shows that every basic capability required for a sophisticated cell repair technology is already demonstrated in nature. Molecular tools already exist (and undoubtedly others are possible) that could be implemented in future medical devices to allow controlled disassembly, analysis, and repair of cell structures at the molecular level. It remains for advancing molecular technology (which at a highly advanced point will become true nanotechnology) to integrate these tools into microscopic devices capable of advanced medical functions.
The inherent feasibility of constructing such cell repair devices can be viewed in terms of their chemical stability. My article on nanotechnology argued that progress in protein engineering (and other fields) is leading to a technology base that will eventually be broad enough to assemble molecular structures of arbitrary complexity. Therefore, as long as the cell repair hardware proposed in this article is chemically stable, it should eventually be manufacturable.
Thus we appear to already have all the basic components needed for cell repair devices, and are only awaiting the means to assemble them. In the meantime, we can use current physical, biological, and engineering knowledge to outline the possible nature of these devices -- and their ultimate capabilities.
Although not strictly necessary for many repair tasks, the most broadly powerful way to control the activities of a cell repair device would be to equip it with an onboard nanocomputer. Theoretical design concepts suggest that data storage densities on the order of a gigabyte per cubic micron (one thousandth the volume of a typical cell) may be achievable in computers built to atomic specifications. This is sufficient storage to characterize an entire cell in complete molecular detail (see notes). While packing a mainframe computer inside a cell may seem like overkill, knowing that this may be possible provides the security of knowing that nanotechnological cell repair systems could fix virtually anything.
Consider aging for example. We do not at present know all the changes that occur in cells with aging, although they are probably quite extensive. Regardless of how extensive, however, none would escape detection by a nanocomputer-equipped repair system capable of entering a cell and probing its entire molecular inventory. On the basis of such complete characterization (and general comparison with data obtained from similar young cells) onboard software could determine what repairs were necessary to return an aged cell to a youthful state. Once repairs were completed, the repaired cell would be in every way indistinguishable from a young cell. Indeed, it would once again be a young cell.
Many repair tasks (especially ones as extensive as cryoinjury repair) will require communications between widely distributed devices both within and outside of cells. Rather than lugging a cubic micron nanocomputer all over a cell to perform repairs, for example, it would seem simpler to have the computer supervise the operation of many smaller devices from a central location in the cell.
One possible communications system would use serial data channels two to three nanometers in diameter consisting of sheathed carbyne rods. Carbyne is a polymer consisting of carbon atoms joined by alternating single and triple bonds (a molecular structure exploited extensively in theoretical nanocomputer designs). Since the speed of sound in carbyne is over ten kilometers per second, a mechanical signal transmission rate of a gigabaud (billion bits per second) seems a conservative performance estimate for such channels. Many other communication schemes suitable for cell repair systems are also conceivable, such as electrically conductive channels or diffusible chemicals analogous to morphogens and hormones in nature.
As well as providing a means for coordinating repairs within the body, it should also be noted that these communications channels could be used to transfer data processing tasks to computers outside the body. This might be useful in instances of extremely severe brain injury (such as a day of ischemia), when inferring the correct pre-injury state becomes a problem too complicated for in-situ computers. A communications system consisting of just one gigabaud channel per cell could, for example, transmit a complete atom-by-atom description of a biostatic brain (assuming one byte per atom) to external computers in less than a month. Thus, data processing requirements will never be a fundamental obstacle to solving biological repair problems.
Like natural cells, cell repair devices will require power to perform their activities. For most diagnostic and repair tasks, tapping into the same chemical energy sources as natural cells (such as glucose/oxygen and ATP) should be sufficient. As long as repair processes proceeded at a pace comparable to normal cell functions, utilization of these chemicals need not overtax natural supplies.
Repair of non-functional tissue presents a problem. Tissues with blocked circulation or failed metabolism could not naturally supply energy to fuel repair processes. One possible solution would be an active transport system, similar to axoplasmic transport in nerve cells. Fibrils originating at distant sites could penetrate inactive tissues and cytoplasm to power repair devices by moving nutrients in a conveyor system through hollow interiors. Raw materials for repairs and fibril growth could be similarly supplied.
In fact, a network of trophic fibrils raises the possibility of powering cell repair devices by an entirely non-biological means: electricity. Part of the fibril structure could incorporate an insulated organic conductor, such as doped polyacetylene (which could serve communications needs as well). Electrochemical processes within the repair device could then continuously recycle a chemical energy currency, such as ATP, which would directly energize enzymatic repair functions. Alternatively, nano-scale electrostatic actuators or enzymes with electric field-sensitive conformational states might be able to make direct use of electric power for performing repair tasks.
One particular application of future cell repair technology -- recovery of today's cryonic suspension patients -- will optimally require repairs at cryogenic temperatures (temperatures below -100°C). Operations best performed at these temperatures would include inhibiting metabolic enzymes (until repairs were completed), locking loose structures in place, and analyzing ice crystal positions to aid in proper restoration of mechanically disturbed cell structures. In fact, warming present-day suspension patients before disruptive ice crystals could be properly analyzed might even be fatal (i.e., lead to irreversible loss of critical identity information).
Fortunately, a variety of design possibilities exist for cryogenic repair devices. One possibility would be molecular machines similar to natural cells, but with water replaced by a cryogenic solvent. Some natural enzymes are known to retain their function in liquid ammonia, others in supercritical carbon dioxide, thus demonstrating that water does not have a monopoly on support of biological processes. Artificial enzyme systems based on natural peptides, or other polymers with protein-like conformational properties, could in principle operate in cryogenic solvents such as tetrafluoromethane, or perhaps even liquid nitrogen. Although conventional biochemistry is nonexistent at these temperatures, faster alternate chemistries could be exploited.
In fact, chemistry (in the sense of forming and breaking chemical bonds) is not even necessary for the operation of some molecular machines. The rod logic systems which underlie current (theoretical) nanocomputer designs, for example, are a clockwork of precisely-configured molecular components interacting mechanically, not chemically. Not only is random jostling (heat) unnecessary for the operation of such a system, it is a handicap. Repair devices of this sort -- molecular machines resembling conventional machines on a nanoscale -- would find ultra-low temperatures an ideal operating environment.
Of course, regardless of how they operate internally, repair devices will have to make chemical changes to tissues they are repairing. Yet even this does not require high temperatures in the ordinary sense. Molecular tools driven by electrical (or low-temperature chemical) actuators could provide localized kinetic energy for forming or breaking chemical bonds. Indeed, by suitably "banging" or "grabbing" target molecules it is possible to create effectively any "temperature" at a single reaction site. Thus a fairly wide range of biological repair processes could in principle be carried out at cryogenic temperatures, thereby giving future cell repair technology a greater degree of versatility -- and present cryonics practice a greater chance of success.
Assuming future molecular engineering capabilities (nanotechnology), this article has sketched the outlines of a medical technology which would operate at the most fundamental level of living things -- the molecular level. What would be the practical implications of a technology which could take apart, analyze, and repair cells like so many machine parts?
Disease, whether its causes be internal or external, is a malfunction of the human body -- a breakdown that detracts from well-being. Curing, not just alleviating, disease has always been a difficult task for medicine: both the tools and the knowledge required to effectively repair the body have been lacking. Thus medicine has historically been (and largely still is) an uncertain art, with very limited understanding of disease processes, and even less understanding of how to intervene in them. Indeed, physicians today are in a predicament similar to that which would be faced by 18th-century engineers trying to maintain a 20th-century automobile: repairs would be crude at best, and breakdown inevitable.
Like primitive engineers faced with advanced technology, medicine must "catch up" with the technology level of the human body before it can become really effective. What is this "technology level"? Since the human body is basically an extremely complex system of interacting molecules (i.e., a molecular machine), the technology required to truly understand and repair the body is molecular machine technology -- nanotechnology.
Mature nanotechnology will mean an ability to routinely design and build "machines" as intricate as our cells from scratch. A natural consequence of this level of technology will be the ability to analyze and repair the human body as completely and effectively as we can repair any conventional machine today. Nanotechnology will mean no more guesswork, uncertain cures, or untreatable organic conditions; medicine will finally be equal to the task of understanding and controlling the body in terms of its most fundamental machine components -- atoms and molecules.
Future medicine will attain this degree of understanding and control through cell repair systems based on technologies and devices like those outlined in this article -- microscopic devices able to roam throughout cells and tissues diagnosing and repairing problems at the cellular and molecular levels. Since disease is a malfunction of the body, and since the body functions by means of molecular machinery, it follows that molecular-level medicine will be able to cure any disease.
This observation particularly applies to the most prevalent and deadly disease on earth today -- aging. Whatever biological changes underlie aging, they must involve changes in molecules, and must therefore be amenable to control by molecular-level medicine. It seems clear that cell repair technology would allow one's biological age to be not only arrested, but reversed, and even adjusted at whim. These are the implications of a technology able to repair and maintain the body at a molecular level. With sufficiently advanced repair technology our bodies need never deteriorate or break down as they do today.
Cell repair technology will allow a variety of powerful approaches for reversing injuries that cannot be healed naturally.
On a basic level, cell repair technology will naturally mean an ability to repair individual cells. This will be particularly important for cells which contain crucial, irreplaceable information, such as brain cells. On this level, the potential of cell repair technology appears quite broad. Even when cells are rendered completely non-functional by poison, infection, ischemia, freezing injury, and indeed any other injury, repair devices will always be able to enter cells, assess the situation, and restore the cells to a healthy condition matching an inferred pre-injury state.
On another level, cell repair technology will also mean a very general ability to replace cells. Cell repair devices will be able to exercise complete control over cell growth and development: they will be able to control and modify cell DNA in sophisticated ways to achieve virtually any desired growth objectives. Among these objectives will be many kinds of healing not seen in nature, such as healing of major injuries, severed spinal cords, and even replacement of lost brain tissue. More ambitiously, regrowth of lost limbs, organs, and even entire bodies is implicitly possible with complete control over cell growth and development. (After all, nature already demonstrates an ability to grow these items from scratch.)
Indeed, the biological repair potential of cell repair technology appears so vast that it might just be simplest to ask whether there is anything this technology couldn't fix.
The answer to this question becomes apparent as one contemplates the effect of increasingly extensive repairs to the body. It is possible to imagine instances of repair so extensive that the healed patient would no longer be the "original" patient. Specifically, this will occur when injuries begin to impinge on a patient's brain. Although cell repair technology appears capable of reversing any injury, it will not be able to restore brain information lost during injury. Brain information loss will pose a fundamental limitation for future medicine -- and the ultimate dividing line between life and death.
The only causes of death for 22nd century medicine will be severe injuries directly to the brain.
Offhand, this might not seem plausible: wouldn't, say, drowning or gunshot wounds to the heart be fatal? No, these injuries can cause cardiac arrest and ensuing coma, but they are not in themselves fatal. Oxygen starvation, cessation of circulation, even complete collapse of normal tissue metabolism does not mean a person is really dead.
Consider a patient whose ischemic (non-functional) body is recovered several hours after drowning. Although such a patient would be relegated to a morgue today, this would be unthinkable in an era of cell repair technology (or even today, with cryonic suspension available). With the basic structure of the person's brain still intact, cell repair devices could be deployed throughout the body to repair cellular injuries caused by the hours of absent blood flow. After several days of repairs conducted at deep hypothermic temperatures (to prevent further deterioration), staged restart of metabolism would be performed by selective unblocking of metabolic enzymes as the patient was warmed. The patient would then emerge from his coma in perfect health, with perhaps mild amnesia as the only remnant of what had happened. Indeed, not until decomposition led to major loss of brain structure would drowning victims, or other victims of protracted ischemia (absent blood flow), be beyond recovery by cell repair technology. (The apparent persistence of brain structures critical to memory and identity after hours of ischemia will be discussed in another article.)
A significant point about future fatalities (one particularly relevant to appreciating cryonics) is how it will be known when patients are beyond recovery: in most cases, it won't be known. As long as some brain structure remains, it will always be possible to reconstruct a patient's brain and body on the basis of persisting information. The success of such reconstruction -- the extent to which to the patient's life would be saved -- would depend on how much memory and personality could be salvaged by the repair process. Only if complete loss of memory and personality were evident after repair (and perhaps not even then) would the original patient likely be regarded as dead.
Thus death (as rare as it will be) will have a radically different character in the future. There will never be "dead" bodies, only lost bodies, ischemic bodies, or amnesiac bodies following extensive injury repair. A future variation on a contemporary cliche might be, "Where there's brain structure, there's hope."
With disease, aging, and primitive medicine all unpleasant memories, just how long people could live in a nanotechnic era is very much an open question.
Many books about "life extension" quote 600 years as a probable life expectancy if aging were ever eliminated (a figure arrived at on the basis of "fatal" accident statistics). Yet this figure cannot be accepted as valid: it assumes fatal accidents to consist of injuries causing cardiac arrest -- no consideration is given to advanced means of reversing ischemic injuries following cardiac arrest (as discussed above). Indeed, if people were routinely fitted with emergency transmitters to facilitate prompt rescue in the event of severe injury (say, within several hours of cardiac arrest), the only causes of death in an era of advanced cell repair would be immediately -- and dramatically -- destructive accidents. Just how destructive such accidents might have to be is suggested at the end of the next and final section.
All discussion thus far has focused on the potential of nanotechnology for restoring and maintaining health. Yet technologies as powerful as those described here cannot help but invite an additional line of inquiry: What might we do to our bodies beyond just healing them?
Consider the potential of nanocomputers for not just repairing the nervous system, but for augmenting it. A nanocomputer one cubic millimeter in volume could hold one billion gigabytes of data -- more information than in all the world's libraries at present. Implanting such a computer within the brain, and routing its output to visual centers, would be the ultimate in library service -- all of human knowledge available for instant mental lookup.
Then there is also the physical side of nanotechnology. The physical capacities of our body are the result of blind choices of evolutionary development, not optimum design. These capacities are often far from the limits of what is theoretically possible.
Consider muscle function. Microstructured materials analogous to muscle tissue have been designed as part of contemporary efforts to better understand nanotechnology. One particular design consists of electrostatic motors 50 nanometers in diameter driving a matrix of fine diamond fiber. The resultant material has the tensile strength of steel, and could efficiently deliver megawatts of mechanical power per cubic centimeter (see notes). By replacing ordinary muscle with material of this sort we could (conservatively) increase our physical strength hundreds of times.
Finally, not only could we make ourselves stronger and smarter with nanotechnology, we could also make ourselves tougher. How much tougher? By replacing connective and skeletal proteins with covalent carbon microstructures (a necessary prerequisite for greatly increased strength) tough enough to routinely survive some of the most destructive accidents known today -- even aircraft accidents.
Perhaps most remarkable of all, none of these changes would require any dramatic change in our external appearance.
1. "So you're talking about . . ." (at the top of this article) is a quote from Molecular Technology And Cell Repair Machines, a talk delivered by K. Eric Drexler at the 1985 Lake Tahoe Life Extension Festival on May 25, 1985.
My article on nanotechnology (Cryonics, May 1988) argued that the technology base required to assemble molecular structures as complex as cell repair devices is essentially unavoidable if technological progress continues through the next century. Relevant arguments and references will not be repeated here.
A typical cell contains several billion macromolecules of perhaps 100,000 different types -- arranged in a decidedly non-random pattern. By employing specialized coordinate systems and data structures suited to natural cellular organization, a gigabyte (one cubic micron of nanocomputer storage) should be more than adequate to hold a complete molecular description of a cell. (See the article on nanotechnology [Cryonics, May 1988] for a more detailed discussion of projected nanocomputing technologies.)
2. "none would escape detection . . ."; It is a virtual tautology that any molecular changes significant enough to adversely affect normal cell operation would not escape detection by molecular-level repair systems.
The two proposed design strategies for cryogenic repair devices (enzymes in a cryogenic solvent vs. precisely-configured molecular machinery) are respective examples of type O and type M molecular technology. Type O (organic) technology refers to molecular machines patterned after natural cells (bags of reacting chemicals), whereas type M (mechanical) technology refers to molecular machines patterned after conventional macromachines on a nanoscale (arrays of inert mechanically interacting components). Low temperature behavior is only one respect in which these two technologies differ. Further fundamental differences are explored in "Biological and Nanomechanical Systems: Contrasts in Evolutionary Capacity", by K. Eric Drexler, in Artificial Life, edited by Christopher Langton, Addison-Wesley, 1988.
One extremely important point made in the above essay is that type M technology is completely incapable of harmful mutation. While natural microorganisms (type O molecular machines) have a high evolutionary capacity (indeed, they have evolved to evolve), type M molecular machines will be no more capable of evolution than household appliances. (Alterations in structure would generally result in outright breakdown rather than a change in basic function.) Thus, while cell repair devices are often described as artificial "microbes" to aid in visualizing them, it should be realized that they will be more like miniature conventional machines than true life forms. As such, they will pose no danger whatsoever to the environment or other human beings (unless they are deliberately designed to do so).
Synthetic muscle with power densities of megawatts per cubic centimeter would in practice always be limited by power and heat dissipation constraints. Yet even within these constraints fantastic feats of strength would be possible. In an anaerobic burst of effort, a nanotechnological "super human" could for example lift a 4,000 pound automobile over his/her head with a body temperature rise of only 2°F, and energy consumption of 100 calories -- less energy than in a typical candy bar (assuming only 10% efficient conversion). This is not comic book fantasy, but firm physical calculation. For more detailed discussion of a "muscle" design which would make this possible, see pp. 258-259, Engines Of Creation, by K. Eric Drexler, Anchor Press/Doubleday, Garden City, NY, 1986.