Extracellular Aggregates. AGEs (advanced glycation end-products) result from undesirable cross-linking of useful molecules as a side effect of excess sugar. These cross-links interfere with the normal functioning of proteins and are key contributors to the aging process. An experimental drug called ALT-711 (phenacyldimenthylthiazolium chloride) can dissolve these cross-links without damaging the original tissue. AGEs (advanced glycation end-products) result from undesirable cross-linking of useful molecules as a side effect of excess sugar. These cross-links interfere with the normal functioning of proteins and are key contributors to the aging process. An experimental drug called ALT-711 (phenacyldimenthylthiazolium chloride) can dissolve these cross-links without damaging the original tissue.52 Other molecules with this capability have also been identified. Other molecules with this capability have also been identified.

Cell Loss and Atrophy. Our body's tissues have the means to replace worn-out cells, but this ability is limited in certain organs. For example, as we get older, the heart is unable to replace its cells at a sufficient rate, so it compensates by making surviving cells bigger using fibrous material. Over time this causes the heart to become less supple and responsive. A primary strategy here is to deploy therapeutic cloning of our own cells, as described below. Our body's tissues have the means to replace worn-out cells, but this ability is limited in certain organs. For example, as we get older, the heart is unable to replace its cells at a sufficient rate, so it compensates by making surviving cells bigger using fibrous material. Over time this causes the heart to become less supple and responsive. A primary strategy here is to deploy therapeutic cloning of our own cells, as described below.

Progress in combating all of these sources of aging is moving rapidly in animal models, and translation into human therapies will follow. Evidence from the genome project indicates that no more than a few hundred genes are involved in the aging process. By manipulating these genes, radical life extension has already been achieved in simpler animals. For example, by modifying genes in the C. elegans C. elegans worm that control its insulin and s.e.x-hormone levels, the lifespan of the test animals was expanded sixfold, to the equivalent of a five-hundred-year lifespan for a human. worm that control its insulin and s.e.x-hormone levels, the lifespan of the test animals was expanded sixfold, to the equivalent of a five-hundred-year lifespan for a human. 53 53 A hybrid scenario involving both bio- and nanotechnology contemplates turning biological cells into computers. These "enhanced intelligence" cells can then detect and destroy cancer cells and pathogens or even regrow human body parts. Princeton biochemist Ron Weiss has modified cells to incorporate a variety of logic functions that are used for basic computation.54 Boston University's Timothy Gardner has developed a cellular logic switch, another basic building block for turning cells into computers. Boston University's Timothy Gardner has developed a cellular logic switch, another basic building block for turning cells into computers.55 Scientists at the MIT Media Lab have developed ways to use wireless communication to send messages, including intricate sequences of instructions, to the computers inside modified cells. Scientists at the MIT Media Lab have developed ways to use wireless communication to send messages, including intricate sequences of instructions, to the computers inside modified cells.56 Weiss points out that "once you have the ability to program cells, you don't have to be constrained by what the cells know how to do already. You can program them to do new things, in new patterns." Weiss points out that "once you have the ability to program cells, you don't have to be constrained by what the cells know how to do already. You can program them to do new things, in new patterns."

Human Cloning: The Least Interesting Application of Cloning Technology

One of the most powerful methods of applying life's machinery involves harnessing biology's own reproductive mechanisms in the form of cloning. Cloning will be a key technology-not for cloning actual humans but for life-extension purposes, in the form of "therapeutic cloning." This process creates new tissues with "young" telomere-extended and DNA-corrected cells to replace without surgery defective tissues or organs.

All responsible ethicists, including myself, consider human cloning at the present time to be unethical. The reasons, however, for me have little to do with the slippery-slope issues of manipulating human life. Rather, the technology today simply does not yet work reliably. The current technique of fusing a cell nucleus from a donor to an egg cell using an electric spark simply causes a high level of genetic errors.57 This is the primary reason that most of the fetuses created by this method do not make it to term. Even those that do make it have genetic defects. Dolly the Sheep developed an obesity problem in adulthood, and the majority of cloned animals produced thus far have had unpredictable health problems. This is the primary reason that most of the fetuses created by this method do not make it to term. Even those that do make it have genetic defects. Dolly the Sheep developed an obesity problem in adulthood, and the majority of cloned animals produced thus far have had unpredictable health problems.58 Scientists have a number of ideas for perfecting cloning, including alternative ways of fusing the nucleus and egg cell without use of a destructive electrical spark, but until the technology is demonstrably safe, it would be unethical to create a human life with such a high likelihood of severe health problems. There is no doubt that human cloning will occur, and occur soon, driven by all the usual reasons, ranging from its publicity value to its utility as a very weak form of immortality. The methods that are demonstrable in advanced animals will work quite well in humans. Once the technology is perfected in terms of safety, the ethical barriers will be feeble if they exist at an.

Cloning is a significant technology, but the cloning of humans is not its most noteworthy usage. Let's first address its most valuable applications and then return to its most controversial one.

Why Is Cloning Important? The most immediate use for cloning is improved breeding by offering the ability to directly reproduce an animal with a desirable set of genetic traits. A powerful example is reproducing animals from transgenic embryos (embryos with foreign genes) for pharmaceutical production. A case in point: a promising anticancer treatment is an antiangiogenesis drug called aaATIII, which is produced in the milk of transgenic goats. The most immediate use for cloning is improved breeding by offering the ability to directly reproduce an animal with a desirable set of genetic traits. A powerful example is reproducing animals from transgenic embryos (embryos with foreign genes) for pharmaceutical production. A case in point: a promising anticancer treatment is an antiangiogenesis drug called aaATIII, which is produced in the milk of transgenic goats.59

Preserving Endangered Species and Restoring Extinct Ones. Another exciting application is re-creating animals from endangered species. By cryopreserving cells from these species, they never need become extinct. It will eventually be possible to re-create animals from recently extinct species. In 2001 scientists were able to synthesize DNA for the Tasmanian tiger, which had then been extinct for sixty-five years, with the hope of bringing this species back to life. Another exciting application is re-creating animals from endangered species. By cryopreserving cells from these species, they never need become extinct. It will eventually be possible to re-create animals from recently extinct species. In 2001 scientists were able to synthesize DNA for the Tasmanian tiger, which had then been extinct for sixty-five years, with the hope of bringing this species back to life.60 As for long-extinct species (for example, dinosaurs), it is highly doubtful that we will find the fully intact DNA required in a single preserved cell (as they did in the movie As for long-extinct species (for example, dinosaurs), it is highly doubtful that we will find the fully intact DNA required in a single preserved cell (as they did in the movie Jura.s.sic Park Jura.s.sic Park). It is likely, however, that we will eventually be able to synthesize the necessary DNA by patching together the information derived from multiple inactive fragments.

Therapeutic Cloning. Perhaps the most valuable emerging application is therapeutic cloning of one's own organs. By starting with germ-line cells (inherited from the eggs or sperm and pa.s.sed on to offspring), genetic engineers can trigger differentiation into diverse types of cells. Because differentiation takes place during the prefetal stage (that is, prior to implantation of a fetus), most ethicists believe this process does not raise concerns, although the issue has remained highly contentious. Perhaps the most valuable emerging application is therapeutic cloning of one's own organs. By starting with germ-line cells (inherited from the eggs or sperm and pa.s.sed on to offspring), genetic engineers can trigger differentiation into diverse types of cells. Because differentiation takes place during the prefetal stage (that is, prior to implantation of a fetus), most ethicists believe this process does not raise concerns, although the issue has remained highly contentious.61

Human Somatic-Cell Engineering. This even more promising approach, which bypa.s.ses the controversy of using fetal stem cells entirely, is called transdifferentiation; it creates new tissues with a patient's own DNA by converting one type of cell (such as a skin cell) into another (such as a pancreatic islet cell or a heart cell). This even more promising approach, which bypa.s.ses the controversy of using fetal stem cells entirely, is called transdifferentiation; it creates new tissues with a patient's own DNA by converting one type of cell (such as a skin cell) into another (such as a pancreatic islet cell or a heart cell).62 Scientists from the United States and Norway have recently been successful in reprogramming liver cells into becoming pancreas cells. In another series of experiments, human skin cells were transformed to take on many of the characteristics of immune-system cells and nerve cells. Scientists from the United States and Norway have recently been successful in reprogramming liver cells into becoming pancreas cells. In another series of experiments, human skin cells were transformed to take on many of the characteristics of immune-system cells and nerve cells.63 Consider the question, What is the difference between a skin cell and any other type of cell in the body? After all, they all have the same DNA. As noted above, the differences are found in protein signaling factors, which include short RNA fragments and peptides, which we are now beginning to understand.64 By manipulating these proteins, we can influence gene expression and trick one type of cell into becoming another. By manipulating these proteins, we can influence gene expression and trick one type of cell into becoming another.

Perfecting this technology would not only defuse a sensitive ethical and political issue but also offer an ideal solution from a scientific perspective. If you need pancreatic islet cells or kidney tissues-or even a whole new heart-to avoid autoimmune reactions, you would strongly prefer to obtain these with your own DNA rather than the DNA from someone else's germ-line cells. In addition, this approach uses plentiful skin cells (of the patient) rather than rare and precious stem cells.

Transdifferentiation will directly grow an organ with your genetic makeup. Perhaps most important, the new organ can have its telomeres fully extended to their original youthful length, so that the new organ is effectively young again.65 We can also correct acc.u.mulated DNA errors by selecting the appropriate skin cells (that is, ones without DNA errors) prior to transdifferentiation into other types of cells. Using this method an eighty-year-old man could have his heart replaced with the same heart he had when he was, say, twenty-five. We can also correct acc.u.mulated DNA errors by selecting the appropriate skin cells (that is, ones without DNA errors) prior to transdifferentiation into other types of cells. Using this method an eighty-year-old man could have his heart replaced with the same heart he had when he was, say, twenty-five.

Current treatments for type 1 diabetes require strong antirejection drugs that can have dangerous side effects.66 With somatic-cell engineering, type 1 diabetics will be able to make pancreatic islet cells from their own cells, either from skin cells (transdifferentiation) or from adult stem cells. They would be using their own DNA, and drawing upon a relatively inexhaustible supply of cells, so no antirejection drugs would be required. (But to fully cure type 1 diabetes, we would also have to overcome the patient's autoimmune disorder, which causes his body to destroy islet cells.) With somatic-cell engineering, type 1 diabetics will be able to make pancreatic islet cells from their own cells, either from skin cells (transdifferentiation) or from adult stem cells. They would be using their own DNA, and drawing upon a relatively inexhaustible supply of cells, so no antirejection drugs would be required. (But to fully cure type 1 diabetes, we would also have to overcome the patient's autoimmune disorder, which causes his body to destroy islet cells.) Even more exciting is the prospect of replacing one's organs and tissues with their "young" replacements without surgery. Introducing cloned, telomere-extended, DNA-corrected cells into an organ will allow them to integrate themselves with the older cells. By repeated treatments of this kind over a period of time, the organ will end up being dominated by the younger cells. We normally replace our own cells on a regular basis anyway, so why not do so with youthful rejuvenated cells rather than telomere-shortened error-filled ones? There's no reason why we couldn't repeat this process for every organ and tissue in our body, enabling us to grow progressively younger.

Solving World Hunger. Cloning technologies even offer a possible solution for world hunger: creating meat and other protein sources in a factory without animals by cloning animal muscle tissue. Benefits would include extremely low cost, avoidance of pesticides and hormones that occur in natural meat, greatly reduced environmental impact (compared to factory farming), improved nutritional profile, and no animal suffering. As with therapeutic cloning, we would not be creating the entire animal but rather directly producing the desired animal parts or flesh. Essentially, all of the meat-billions of pounds of it-would be derived from a single animal. Cloning technologies even offer a possible solution for world hunger: creating meat and other protein sources in a factory without animals by cloning animal muscle tissue. Benefits would include extremely low cost, avoidance of pesticides and hormones that occur in natural meat, greatly reduced environmental impact (compared to factory farming), improved nutritional profile, and no animal suffering. As with therapeutic cloning, we would not be creating the entire animal but rather directly producing the desired animal parts or flesh. Essentially, all of the meat-billions of pounds of it-would be derived from a single animal.

There are other benefits to this process besides ending hunger. By creating meat in this way, it becomes subject to the law of accelerating returns-the exponential improvements in price-performance of information-based technologies over time-and will thus become extremely inexpensive. Even though hunger in the world today is certainly exacerbated by political issues and conflicts, meat could become so inexpensive that it would have a profound effect on the affordability of food.

The advent of animal-less meat will also eliminate animal suffering. The economics of factory farming place a very low priority on the comfort of animals, which are treated as cogs in a machine. The meat produced in this manner, although normal in all other respects, would not be part of an animal with a nervous system, which is generally regarded as a necessary element for suffering to occur, at least in a biological animal. We could use the same approach to produce such animal by-products as leather and fur. Other major advantages would be to eliminate the enormous ecological and environmental damage created by factory farming as well as the risk of prion-based diseases, such as mad-cow disease and its human counterpart, vCJD.67 Human Cloning Revisited. This brings us again to human cloning. I predict that once the technology is perfected, neither the acute dilemmas seen by ethicists nor the profound promise heralded by enthusiasts will predominate. So what if we have genetic twins separated by one or more generations? Cloning is likely to prove to be like other reproductive technologies that were briefly controversial but rapidly accepted. Physical cloning is far different from mental cloning, in which a person's entire personality, memory, skills, and history will ultimately be downloaded into a different, and most likely more powerful, thinking medium. There's no issue of philosophical ident.i.ty with genetic cloning, since such clones would be different people, even more so than conventional twins are today. This brings us again to human cloning. I predict that once the technology is perfected, neither the acute dilemmas seen by ethicists nor the profound promise heralded by enthusiasts will predominate. So what if we have genetic twins separated by one or more generations? Cloning is likely to prove to be like other reproductive technologies that were briefly controversial but rapidly accepted. Physical cloning is far different from mental cloning, in which a person's entire personality, memory, skills, and history will ultimately be downloaded into a different, and most likely more powerful, thinking medium. There's no issue of philosophical ident.i.ty with genetic cloning, since such clones would be different people, even more so than conventional twins are today.

If we consider the full concept of cloning, from cell to organisms, its benefits have enormous synergy with the other revolutions occurring in biology as well as in computer technology. As we learn to understand the genome and proteome (the expression of the genome into proteins) of both humans and animals, and as we develop powerful new means of harnessing genetic information, cloning provides the means to replicate animals, organs, and cells. And that has profound implications for the health and well-being of both ourselves and our evolutionary cousins in the animal kingdom.

NED LUDD: If everyone can change their genes, then everyone will choose to be "perfect" in every way, so there'll be no diversity and excelling will become meaningless. If everyone can change their genes, then everyone will choose to be "perfect" in every way, so there'll be no diversity and excelling will become meaningless.

RAY: Not exactly. Genes are obviously important, but our nature-skills, knowledge, memory, personality-reflects the design information in our genes, as our bodies and brains self-organize through our experience. This is also readily evident in our health. I personally have a genetic disposition to type 2 diabetes, having actually been diagnosed with that disease more than twenty years ago. But I don't have any indication of diabetes today because I've overcome this genetic disposition as a result of reprogramming my biochemistry through lifestyle choices such as nutrition, exercise, and aggressive supplementation. With regard to our brains, we all have various apt.i.tudes, but our actual talents are a function of what we've learned, developed, and experienced. Our genes reflect dispositions only. We can see how this works in the development of the brain. The genes describe certain rules and constraints for patterns of interneuronal connections, but the actual connections we have as adults are the result of a self-organizing process based on our learning. The final result-who we are-is deeply influenced by both nature (genes) and nurture (experience). Not exactly. Genes are obviously important, but our nature-skills, knowledge, memory, personality-reflects the design information in our genes, as our bodies and brains self-organize through our experience. This is also readily evident in our health. I personally have a genetic disposition to type 2 diabetes, having actually been diagnosed with that disease more than twenty years ago. But I don't have any indication of diabetes today because I've overcome this genetic disposition as a result of reprogramming my biochemistry through lifestyle choices such as nutrition, exercise, and aggressive supplementation. With regard to our brains, we all have various apt.i.tudes, but our actual talents are a function of what we've learned, developed, and experienced. Our genes reflect dispositions only. We can see how this works in the development of the brain. The genes describe certain rules and constraints for patterns of interneuronal connections, but the actual connections we have as adults are the result of a self-organizing process based on our learning. The final result-who we are-is deeply influenced by both nature (genes) and nurture (experience).

So when we gain the opportunity to change our genes as adults, we won't wipe out the influence of our earlier genes. Experiences prior to the gene therapy will have been translated through the pretherapy genes, so one's character and personality would still be shaped primarily by the original genes. For example, if someone added genes for musical apt.i.tude to his brain through gene therapy, he would not suddenly become a music genius.

NED:Okay, I understand that designer baby boomers can't get away completely from their predesigner genes, but with designer babies they'll have the genes and the time to express them.

RAY: The "designer baby" revolution is going to be a very slow one; it won't be a significant factor in this century. Other revolutions will overtake it. We won't have the technology for designer babies for another ten to twenty years. To the extent that it is used, it would be adopted gradually, and then it will take those generations another twenty years to reach maturity. By that time, we're approaching the Singularity, with the real revolution being the predominance of nonbiological intelligence. That will go far beyond the capabilities of any designer genes. The idea of designer babies and baby boomers is just the reprogramming of the information processes in biology. But it's still biology, with all its profound limitations. The "designer baby" revolution is going to be a very slow one; it won't be a significant factor in this century. Other revolutions will overtake it. We won't have the technology for designer babies for another ten to twenty years. To the extent that it is used, it would be adopted gradually, and then it will take those generations another twenty years to reach maturity. By that time, we're approaching the Singularity, with the real revolution being the predominance of nonbiological intelligence. That will go far beyond the capabilities of any designer genes. The idea of designer babies and baby boomers is just the reprogramming of the information processes in biology. But it's still biology, with all its profound limitations.

NED:You're missing something. Biological is what we are. I think most people would agree that being biological is the quintessential attribute of being human. .

RAY: That's certainly true today. That's certainly true today.

NED:And I plan to keep it that way.

RAY: Well, if you're speaking for yourself, that's fine with 'me. But if you stay biological and don't reprogram your genes, you won't be around for very long to influence the debate. Well, if you're speaking for yourself, that's fine with 'me. But if you stay biological and don't reprogram your genes, you won't be around for very long to influence the debate.

Nanotechnology: The Intersection of Information and the Physical World

The role of the infinitely small is infinitely large.-LOUIS PASTEUR But I am not afraid to consider the final question as to whether, ultimately, in the great future, we can arrange the atoms the way we want; the very atoms, all the way down!-RICHARD FEYNMAN Nanotechnology has the potential to enhance human performance, to bring sustainable development for materials, water, energy, and food, to protect against unknown bacteria and viruses, and even to diminish the reasons for breaking the peace [by creating universal abundance].-NATIONAL SCIENCE FOUNDATION NANOTECHNOLOGY REPORT

Nanotechnology promises the tools to rebuild the physical world-our bodies and brains included-molecular fragment by molecular fragment, potentially atom by atom. We are shrinking the key feature size of technology, in accordance with the law of accelerating returns, at the exponential rate of approximately a factor of four per linear dimension per decade.68 At this rate the key feature sizes for most electronic and many mechanical technologies will be in the nanotechnology range-generally considered to be under one hundred nanometers-by the 2020s. (Electronics has already dipped below this threshold, although not yet in three-dimensional structures and not yet self-a.s.sembling.) Meanwhile rapid progress has been made, particularly in the last several years, in preparing the conceptual framework and design ideas for the coming age of nanotechnology. At this rate the key feature sizes for most electronic and many mechanical technologies will be in the nanotechnology range-generally considered to be under one hundred nanometers-by the 2020s. (Electronics has already dipped below this threshold, although not yet in three-dimensional structures and not yet self-a.s.sembling.) Meanwhile rapid progress has been made, particularly in the last several years, in preparing the conceptual framework and design ideas for the coming age of nanotechnology.

As important as the biotechnology revolution discussed above will be, once its methods are fully mature, limits will be encountered in biology itself. Although biological systems are remarkable in their cleverness, we have also discovered that they are dramatically suboptimal. I've mentioned the extremely slow speed of communication in the brain, and as I discuss below (see p. 253), robotic replacements for our red blood cells could be thousands of times more efficient than their biological counterparts.69 Biology will never be able to match what we will be capable of engineering once we fully understand biology's principles of operation. Biology will never be able to match what we will be capable of engineering once we fully understand biology's principles of operation.

The revolution in nanotechnology, however, will ultimately enable us to redesign and rebuild, molecule by molecule, our bodies and brains and the world with which we interact.70 These two revolutions are overlapping, but the full realization of nanotechnology lags behind the biotechnology revolution by about one decade. These two revolutions are overlapping, but the full realization of nanotechnology lags behind the biotechnology revolution by about one decade.

Most nanotechnology historians date the conceptual birth of nanotechnology to physicist Richard Feynman's seminal speech in 1959, "There's Plenty of Room at the Bottom," in which he described the inevitability and profound implications of engineering machines at the level of atoms:

The principles of physics, as far as I can see, do not speak against the possibility of maneuvering things atom by atom. It would be, in principle, possible ... for a physicist to synthesize any chemical substance that the chemist writes down. . . . How? Put the atoms down where the chemist says, and so you make the substance. The problems of chemistry and biology can be greatly helped if our ability to see what we are doing, and to do things on an atomic level, is ultimately developed-a development which I think cannot be avoided.71

An even earlier conceptual foundation for nanotechnology was formulated by the information theorist John von Neumann in the early 1950s with his model of a self-replicating system based on a universal constructor, combined with a universal computer.72 In this proposal the computer runs a program that directs the constructor, which in turn constructs a copy of both the computer (including its self-replication program) and the constructor. At this level of description von Neumann's proposal is quite abstract-the computer and constructor could be made in a great variety of ways, as well as from diverse materials, and could even be a theoretical mathematical construction. But he took the concept one step further and proposed a "kinematic constructor": a robot with at least one manipulator (arm) that would build a replica of itself from a "sea of parts" in its midst. In this proposal the computer runs a program that directs the constructor, which in turn constructs a copy of both the computer (including its self-replication program) and the constructor. At this level of description von Neumann's proposal is quite abstract-the computer and constructor could be made in a great variety of ways, as well as from diverse materials, and could even be a theoretical mathematical construction. But he took the concept one step further and proposed a "kinematic constructor": a robot with at least one manipulator (arm) that would build a replica of itself from a "sea of parts" in its midst.73 It was left to Eric Drexler to found the modern field of nanotechnology, with a draft of his landmark Ph.D. thesis in the mid-1980s, in which he essentially combined these two intriguing suggestions. Drexler described a von Neumann kinematic constructor, which for its sea of parts used atoms and molecular fragments, as suggested in Feynman's speech. Drexler's vision cut across many disciplinary boundaries and was so far-reaching that no one was daring enough to be his thesis adviser except for my own mentor, Marvin Minsky. Drexler's dissertation (which became his book Engines of Creation Engines of Creation in 1986 and was articulated technically in his 1992 book, in 1986 and was articulated technically in his 1992 book, Nanosystems Nanosystems) laid out the foundation of nanotechnology and provided the road map still being followed today.74 Drexler's "molecular a.s.sembler" will be able to make almost anything in the world. It has been referred to as a "universal a.s.sembler," but Drexler and other nanotechnology theorists do not use the word "universal" because the products of such a system necessarily have to be subject to the laws of physics and chemistry, so only atomically stable structures would be viable. Furthermore, any specific a.s.sembler would be restricted to building products from its sea of parts, although the feasibility of using individual atoms has been shown. Nevertheless, such an a.s.sembler could make just about any physical device we would want, including highly efficient computers and subsystems for other a.s.semblers.

Although Drexler did not provide a detailed design for an a.s.sembler-such a design has still not been fully specified-his thesis did provide extensive feasibility arguments for each of the princ.i.p.al components of a molecular a.s.sembler, which include the following subsystems:

The The computer computer: to provide the intelligence to control the a.s.sembly process. As with all of the device's subsystems, the computer needs to be small and simple. As I described in chapter 3, Drexler provides an intriguing conceptual description of a mechanical computer with molecular "locks" instead of transistor gates. Each lock would require only sixteen cubic nanometers of s.p.a.ce and could switch ten billion times per second. This proposal remains more compet.i.tive than any known electronic technology, although electronic computers built from three-dimensional arrays of carbon nanotubes appear to provide even higher densities of computation (that is, calculations per second per gram).75 The The instruction architecture instruction architecture: Drexler and his colleague Ralph Merkle have proposed an SIMD (single instruction multiple data) architecture in which a single data store would record the instructions and transmit them to trillions of molecular-sized a.s.semblers (each with its own simple computer) simultaneously. I discussed some of the limitations of the SIMD architecture in chapter 3, but this design (which is easier to implement than the more flexible multiple-instruction multiple-data approach) is sufficient for the computer in a universal nanotechnology a.s.sembler. With this approach each a.s.sembler would not have to store the entire program for creating the desired product. A "broadcast" architecture also addresses a key safety concern: the self-replication process could be shut down, if it got out of control, by terminating the centralized source of the replication instructions.However, as Drexler points out, a nanoscale a.s.sembler does not necessarily have to be self-replicating.76 Given the inherent dangers in self-replication, the ethical standards proposed by the Foresight Inst.i.tute (a think tank founded by Eric Drexler and Christine Peterson) contain prohibitions against unrestricted self-replication, especially in a natural environment. Given the inherent dangers in self-replication, the ethical standards proposed by the Foresight Inst.i.tute (a think tank founded by Eric Drexler and Christine Peterson) contain prohibitions against unrestricted self-replication, especially in a natural environment.As I will discuss in chapter 8, this approach should be reasonably effective against inadvertent dangers, although it could be circ.u.mvented by a determined and knowledgeable adversary. Instruction transmission Instruction transmission: Transmission of the instructions from the centralized data store to each of the many a.s.semblers would be accomplished electronically if the computer is electronic or through mechanical vibrations if Drexler's concept of a mechanical computer were used. The The construction robot construction robot: The constructor would be a simple molecular robot with a single arm, similar to von Neumann's kinematic constructor but on a tiny scale. There are already examples of experimental molecular-scale systems that can act as motors and robot legs, as I discuss below. The The robot arm tip robot arm tip: Drexler's Nanosystems Nanosystems provided a number of feasible chemistries for the tip of the robot arm to make it capable of grasping (using appropriate atomic-force fields) a molecular fragment, or even a single atom, and then depositing it in a desired location. In the chemical-vapor deposition process used to construct artificial diamonds, individual carbon atoms, as well as molecular fragments, are moved to other locations through chemical reactions at the tip. Building artificial diamonds is a chaotic process involving trillions of atoms, but conceptual proposals by Robert Freitas and Ralph Merkle contemplate robot arm tips that can remove hydrogen atoms from a source material and deposit them at desired locations in the construction of a molecular machine. In this proposal, the tiny machines are built out of a diamondoid material. In addition to having great strength, the material can be doped with impurities in a precise fashion to create electronic components such as transistors. Simulations have shown that such molecular-scale gears, levers, motors, and other mechanical systems would operate properly as intended. provided a number of feasible chemistries for the tip of the robot arm to make it capable of grasping (using appropriate atomic-force fields) a molecular fragment, or even a single atom, and then depositing it in a desired location. In the chemical-vapor deposition process used to construct artificial diamonds, individual carbon atoms, as well as molecular fragments, are moved to other locations through chemical reactions at the tip. Building artificial diamonds is a chaotic process involving trillions of atoms, but conceptual proposals by Robert Freitas and Ralph Merkle contemplate robot arm tips that can remove hydrogen atoms from a source material and deposit them at desired locations in the construction of a molecular machine. In this proposal, the tiny machines are built out of a diamondoid material. In addition to having great strength, the material can be doped with impurities in a precise fashion to create electronic components such as transistors. Simulations have shown that such molecular-scale gears, levers, motors, and other mechanical systems would operate properly as intended.77 More recently attention has been focused on carbon nanotubes, comprising hexagonal arrays of carbon atoms a.s.sembled in three dimensions, which are also capable of providing both mechanical and electronic functions at the molecular level. I provide examples below of molecular-scale machines that have already been built . More recently attention has been focused on carbon nanotubes, comprising hexagonal arrays of carbon atoms a.s.sembled in three dimensions, which are also capable of providing both mechanical and electronic functions at the molecular level. I provide examples below of molecular-scale machines that have already been built . The a.s.sembler's The a.s.sembler's internal environment internal environment needs to prevent environmental impurities from interfering with the delicate a.s.sembly process. Drexler's proposal is to maintain a near vacuum and build the a.s.sembler walls out of the same diamondoid material that the a.s.sembler itself is capable of making. needs to prevent environmental impurities from interfering with the delicate a.s.sembly process. Drexler's proposal is to maintain a near vacuum and build the a.s.sembler walls out of the same diamondoid material that the a.s.sembler itself is capable of making. The The energy energy required for the a.s.sembly process can be provided either through electricity or through chemical energy. Drexler proposed a chemical process with the fuel interlaced with the raw building material. More recent proposals use nanoengineered fuel cells incorporating hydrogen and oxygen or glucose and oxygen, or acoustic power at ultrasonic frequencies. required for the a.s.sembly process can be provided either through electricity or through chemical energy. Drexler proposed a chemical process with the fuel interlaced with the raw building material. More recent proposals use nanoengineered fuel cells incorporating hydrogen and oxygen or glucose and oxygen, or acoustic power at ultrasonic frequencies.78

Although many configurations have been proposed, the typical a.s.sembler has been described as a tabletop unit that can manufacture almost any physically possible product for which we have a software description, ranging from computers, clothes, and works of art to cooked meals.79 Larger products, such as furniture, cars, or even houses, can be built in a modular fashion or using larger a.s.semblers. Of particular importance is the fact that an a.s.sembler can create copies of itself, unless its design specifically prohibits this (to avoid potentially dangerous self-replication), The incremental cost of creating any physical product, including the a.s.semblers themselves, would be pennies per pound-basically the cost of the raw materials. Drexler estimates total manufacturing cost for a molecular-manufacturing process in the range of ten cents to fifty cents per kilogram, regardless of whether the manufactured product were clothing, ma.s.sively parallel supercomputers, or additional manufacturing systems. Larger products, such as furniture, cars, or even houses, can be built in a modular fashion or using larger a.s.semblers. Of particular importance is the fact that an a.s.sembler can create copies of itself, unless its design specifically prohibits this (to avoid potentially dangerous self-replication), The incremental cost of creating any physical product, including the a.s.semblers themselves, would be pennies per pound-basically the cost of the raw materials. Drexler estimates total manufacturing cost for a molecular-manufacturing process in the range of ten cents to fifty cents per kilogram, regardless of whether the manufactured product were clothing, ma.s.sively parallel supercomputers, or additional manufacturing systems.80 The real cost, of course, would be the value of the information describing each type of product-that is, the software that controls the a.s.sembly process. In other words, the value of everything in the world, including physical objects, would be based essentially on information. We are not that far from this situation today, since the information content of products is rapidly increasing, gradually approaching an asymptote of 100 percent of their value.

The design of the software controlling molecular-manufacturing systems would itself itself be extensively automated, much as chip design is today. Chip designers don't specify the location of each of the billions of wires and components but rather the specific functions and features, which computer-aided design (CAD) systems translate into actual chip layouts. Similarly, CAD systems would produce the molecular-manufacturing control software from high-level specifications. This would include the ability to reverse engineer a Product by scanning it in three dimensions and then generating the software needed to replicate its overall capabilities. be extensively automated, much as chip design is today. Chip designers don't specify the location of each of the billions of wires and components but rather the specific functions and features, which computer-aided design (CAD) systems translate into actual chip layouts. Similarly, CAD systems would produce the molecular-manufacturing control software from high-level specifications. This would include the ability to reverse engineer a Product by scanning it in three dimensions and then generating the software needed to replicate its overall capabilities.

In operation, the centralized data store would send out commands simultaneously to many trillions (some estimates as high as 1018) of robots in an a.s.sembler, each receiving the same instruction at the same time. The a.s.sembler would create these molecular robots by starting with a small number and then using these robots to create additional ones in an iterative fashion, until the requisite number had been created. Each robot would have a local data storage that specifies the type of mechanism it's building. This storage would be used to mask the global instructions being sent from the centralized data store so that certain instructions are blocked and local parameters are filled in. In this way, even though all of the a.s.semblers are receiving the same sequence of instructions, there is a level of customization to the part being built by each molecular robot. This process is a.n.a.logous to gene expression in biological systems. Although every cell has every gene, only those genes relevant to a particular cell type are expressed. Each robot extracts the raw materials and fuel it needs, which include individual carbon atoms and molecular fragments, from the source material.

The Biological a.s.sembler

Nature shows that molecules can serve as machines because living things work by means of such machinery. Enzymes are molecular machines that make, break, and rearrange the bonds holding other molecules together. Muscles are driven by molecular machines that haul fibers past one another. DNA serves as a data-storage system, transmitting digital instructions to molecular machines, the ribosomes, that manufacture protein molecules. And these protein molecules, in turn, make up most of the molecular machinery.-ERIC DREXLER

The ultimate existence proof of the feasibility of a molecular a.s.sembler is life itself. Indeed, as we deepen our understanding of the information basis of life processes, we are discovering specific ideas that are applicable to the design requirements of a generalized molecular a.s.sembler. For example, proposals have been made to use a molecular energy source of glucose and ATP, similar to that used by biological cells.

Consider how biology solves each of the design challenges of a Drexler a.s.sembler. The ribosome represents both the computer and the construction robot. Life does not use centralized data storage but provides the entire code to every cell. The ability to restrict the local data storage of a nanoengineered robot to only a small part of the a.s.sembly code (using the "broadcast" architecture), particularly when doing self-replication, is one critical way nanotechnology can be engineered to be safer than biology.

Life's local data storage is, of course, the DNA strands, broken into specific genes on the chromosomes. The task of instruction masking (blocking genes that do not contribute to a particular cell type) is controlled by the short RNA molecules and peptides that govern gene expression. The internal environment in which the ribosome is able to function is the particular chemical environment maintained inside the cell, which includes a particular acid-alkaline equilibrium (pH around 7 in human cells) and other chemical balances. The cell membrane is responsible for protecting this internal environment from disturbance.

Upgrading the Cell Nucleus with a Nanocomputer and Nan.o.bot. Here's a conceptually simple proposal to overcome all biological pathogens except for prions (self-replicating pathological proteins). With the advent of full-scale nanotechnology in the 2020s we will have the potential to replace biology's genetic-information repository in the cell nucleus with a nanoengineered system that would maintain the genetic code and simulate the actions of RNA, the ribosome, and other elements of the computer in biology's a.s.sembler. A nanocomputer would maintain the genetic code and implement the gene-expression algorithms. A nan.o.bot would then construct the amino-acid sequences for the expressed genes. Here's a conceptually simple proposal to overcome all biological pathogens except for prions (self-replicating pathological proteins). With the advent of full-scale nanotechnology in the 2020s we will have the potential to replace biology's genetic-information repository in the cell nucleus with a nanoengineered system that would maintain the genetic code and simulate the actions of RNA, the ribosome, and other elements of the computer in biology's a.s.sembler. A nanocomputer would maintain the genetic code and implement the gene-expression algorithms. A nan.o.bot would then construct the amino-acid sequences for the expressed genes.

There would be significant benefits in adopting such a mechanism. We could eliminate the acc.u.mulation of DNA transcription errors, one major source of the aging process. We could introduce DNA changes to essentially reprogram our genes (something we'll be able to do long before this scenario, using gene-therapy techniques). We would also be able to defeat biological pathogens (bacteria, viruses, and cancer cells) by blocking any unwanted replication of genetic information.

With such a nanoengineered system the recommended broadcast architecture would enable us to turn off unwanted replication, thereby defeating cancer, autoimmune reactions, and other disease processes. Although most of these disease processes will already have been vanquished by the biotechnology methods described in the previous section, reengineering the computer of life using nanotechnology could eliminate any remaining obstacles and create a level of durability and flexibility that goes beyond the inherent capabilities of biology.

The robot arm tip would use the ribosome's ability to implement enzymatic reactions to break off an individual amino acid, each of which is bound to a specific tRNA, and to connect it to its adjoining amino acid using a peptide bond. Thus, such a system could utilize portions of the ribosome itself, since this biological machine is capable of constructing the requisite string of amino acids.

However, the goal of molecular manufacturing is not merely to replicate the molecular-a.s.sembly capabilities of biology. Biological systems are limited to building systems from protein, which has profound limitations in strength and speed. Although biological proteins are three-dimensional, biology is restricted to that cla.s.s of chemicals that can be folded from a one-dimensional string of amino acids. Nan.o.bots built from diamondoid gears and rotors can also be thousands of times faster and stronger than biological cells.

The comparison is even more dramatic with regard to computation: the switching speed of nanotube-based computation would be millions of times faster than the extremely slow transaction speed of the electrochemical switching used in mammalian interneuronal connections.

The concept of a diamondoid a.s.sembler described above uses a consistent input material (for construction and fuel), which represents one of several protections against molecular-scale replication of robots in an uncontrolled fashion in the outside world. Biology's replication robot, the ribosome, also requires carefully controlled source and fuel materials, which are provided by our digestive system. AB nan.o.based replicators become more sophisticated, more capable of extracting carbon atoms and carbon-based molecular fragments from less well-controlled source materials, and able to operate outside of controlled replicator enclosures such as in the biological world, they will have the potential to present a grave threat to that world. This is particularly true in view of the vastly greater strength and speed of nan.o.based replicators over any biological system. That ability is, of course, the source of great controversy, which I discuss in chapter 8.

In the decade since publication of Drexler's Nanosystems Nanosystems, each aspect of Drexler's conceptual designs has been validated through additional design proposals.81 supercomputer simulations, and, most important, actual construction of related molecular machines. Boston College chemistry professor T. Ross Kelly reported that he constructed a chemically powered nanomotor out of seventy-eight atoms. supercomputer simulations, and, most important, actual construction of related molecular machines. Boston College chemistry professor T. Ross Kelly reported that he constructed a chemically powered nanomotor out of seventy-eight atoms.82 A biomolecular research group headed by Carlo Montemagno created an ATP-fueled nanomotor. A biomolecular research group headed by Carlo Montemagno created an ATP-fueled nanomotor.83 Another molecule-sized motor fueled by solar energy was created out of fifty-eight atoms by Ben Feringa at the University of Groningen in the Netherlands. Another molecule-sized motor fueled by solar energy was created out of fifty-eight atoms by Ben Feringa at the University of Groningen in the Netherlands.84 Similar progress has been made on other molecular-scale mechanical components such as gears, rotors, and levers. Systems demonstrating the use of chemical energy and acoustic energy (as originally described by Drexler) have been designed, simulated, and actually constructed. Substantial progress has also been made in developing various types of electronic components from molecular-scale devices, particularly in the area of carbon nanotubes, an area that Richard Smalley has pioneered. Similar progress has been made on other molecular-scale mechanical components such as gears, rotors, and levers. Systems demonstrating the use of chemical energy and acoustic energy (as originally described by Drexler) have been designed, simulated, and actually constructed. Substantial progress has also been made in developing various types of electronic components from molecular-scale devices, particularly in the area of carbon nanotubes, an area that Richard Smalley has pioneered.

Nanotubes are also proving to be very versatile as a structural component. A conveyor belt constructed out of nanotubes was demonstrated recently by scientists at Lawrence Berkeley National Laboratory.85 The nanoscale conveyor belt was used to transport tiny indium particles from one location to another, although the technique could be adapted to move a variety of molecule-sized objects. By controlling an electrical current applied to the device, the direction and velocity of movement can be modulated. "It's the equivalent of turning a k.n.o.b ... and taking macroscale control of nanoscale ma.s.s transport," said Chris Regan, one of the designers. "And it's reversible: we can change the current's polarity and drive the indium back to its original position." The ability to rapidly shuttle molecule-sized building blocks to precise locations is a key step toward building molecular a.s.sembly lines. The nanoscale conveyor belt was used to transport tiny indium particles from one location to another, although the technique could be adapted to move a variety of molecule-sized objects. By controlling an electrical current applied to the device, the direction and velocity of movement can be modulated. "It's the equivalent of turning a k.n.o.b ... and taking macroscale control of nanoscale ma.s.s transport," said Chris Regan, one of the designers. "And it's reversible: we can change the current's polarity and drive the indium back to its original position." The ability to rapidly shuttle molecule-sized building blocks to precise locations is a key step toward building molecular a.s.sembly lines.

A study conducted for NASA by General Dynamics has demonstrated the feasibility of self-replicating nanoscale machines.86 Using computer simulations, the researchers showed that molecularly precise robots called kinematic cellular automata, built from reconfigurable molecular modules, were capable of reproducing themselves. The designs also used the broadcast architecture, which established the feasibility of this safer form of self-replication. Using computer simulations, the researchers showed that molecularly precise robots called kinematic cellular automata, built from reconfigurable molecular modules, were capable of reproducing themselves. The designs also used the broadcast architecture, which established the feasibility of this safer form of self-replication.

DNA is proving to be as versatile as nanotubes for building molecular structures. DNA's proclivity to link up with itself makes it a useful structural component. Future designs may combine this attribute as well as its capacity for storing information. Both nanotubes and DNA have outstanding properties for information storage and logical control, as well as for building strong three-dimensional structures.

A research team at Ludwig Maximilians University in Munich has built a "DNA hand" that can select one of several proteins, bind to it, and then release it upon command.87 Important steps in creating a DNA a.s.sembler mechanism akin to the ribosome were demonstrated recently by nanotechnology researchers Shiping Liao and Nadrian Seeman. Important steps in creating a DNA a.s.sembler mechanism akin to the ribosome were demonstrated recently by nanotechnology researchers Shiping Liao and Nadrian Seeman.88 Grasping and letting go of molecular objects in a controlled manner is another important enabling capability for molecular nanotechnology a.s.sembly. Grasping and letting go of molecular objects in a controlled manner is another important enabling capability for molecular nanotechnology a.s.sembly.

Scientists at the Scripps Research Inst.i.tute demonstrated the ability to create DNA building blocks by generating many copies of a 1,669-nucleotide strand of DNA that had carefully placed self-complementary regions.89 The strands self-a.s.sembled spontaneously into rigid octahedrons, which could be used as blocks for elaborate three-dimensional structures. Another application of this process could be to employ the octahedrons as compartments to deliver proteins, which Gerald F. Joyce, one of the Scripps researchers, called a "virus in reverse." Viruses, which are also self-a.s.sembling, usually have outer sh.e.l.ls of protein with DNA (or RNA) on the inside. "With this," Joyce points out, "you could in principle have DNA on the outside and proteins on the inside." The strands self-a.s.sembled spontaneously into rigid octahedrons, which could be used as blocks for elaborate three-dimensional structures. Another application of this process could be to employ the octahedrons as compartments to deliver proteins, which Gerald F. Joyce, one of the Scripps researchers, called a "virus in reverse." Viruses, which are also self-a.s.sembling, usually have outer sh.e.l.ls of protein with DNA (or RNA) on the inside. "With this," Joyce points out, "you could in principle have DNA on the outside and proteins on the inside."

A particularly impressive demonstration of a nanoscale device constructed from DNA is a tiny biped robot that can walk on legs that are ten nanometers long.90 Both the legs and the walking track are built from DNA, again chosen for the molecule's ability to attach and detach itself in a controlled manner. The nanorobot, a project of chemistry professors Nadrian Seeman and William Sherman of New York University, walks by detaching its legs from the track, moving down it, and then reattaching its legs to the track. The project is another impressive demonstration of the ability of nanoscale machines to execute precise maneuvers. Both the legs and the walking track are built from DNA, again chosen for the molecule's ability to attach and detach itself in a controlled manner. The nanorobot, a project of chemistry professors Nadrian Seeman and William Sherman of New York University, walks by detaching its legs from the track, moving down it, and then reattaching its legs to the track. The project is another impressive demonstration of the ability of nanoscale machines to execute precise maneuvers.

An alternate method of designing nan.o.bots is to learn from nature. Nanotechnologist Michael Simpson of Oak Ridge National Laboratory describes the possibility of exploiting bacteria "as ready-made machine[s]." Bacteria, which are natural nan.o.bot-size objects, are able to move, swim, and pump liquids.91 Linda Turner, a scientist at the Rowland Inst.i.tute at Harvard, has focused on their thread-size arms, called fimbriae, which are able to perform a wide variety of tasks, including carrying other nanoscale objects and mixing fluids. Another approach is to use only parts of bacteria. A research group headed by Viola Vogel at the University of Washington built a system using just the limbs of Linda Turner, a scientist at the Rowland Inst.i.tute at Harvard, has focused on their thread-size arms, called fimbriae, which are able to perform a wide variety of tasks, including carrying other nanoscale objects and mixing fluids. Another approach is to use only parts of bacteria. A research group headed by Viola Vogel at the University of Washington built a system using just the limbs of E. coli E. coli bacteria that was able to sort out nanoscale beads of different sizes. Since bacteria are natural nanoscale systems that can perform a wide variety of functions, the ultimate goal of this research will be to reverse engineer the bacteria so that the same design principles can be applied to our own nan.o.bot designs. bacteria that was able to sort out nanoscale beads of different sizes. Since bacteria are natural nanoscale systems that can perform a wide variety of functions, the ultimate goal of this research will be to reverse engineer the bacteria so that the same design principles can be applied to our own nan.o.bot designs.

Fat and Sticky Fingers