X-Message-Number: 0019.1 Subject: The Technical Feasibility of Cryonics; Part #1 <<< For a more up-to-date version of this paper, see URL: >>> <<< http://merkle.com/merkleDir/techFeas.html >>> Newsgroups: sci.cryonics From: (Ralph Merkle) Subject: The Technical Feasibility of Cryonics; Part #1 Date: 22 Nov 92 21:12:17 GMT The Technical Feasibility of Cryonics PART 1 of 5. by Ralph C. Merkle Xerox PARC 3333 Coyote Hill Road Palo Alto, CA 94304 A shorter version of this article appeared in: Medical Hypotheses (1992) 39, pages 6-16. ABSTRACT Cryonic suspension is a method of stabilizing the condition of someone who is terminally ill so that they can be transported to the medical care facilities that will be available in the late 21st or 22nd century. There is little dispute that the condition of a person stored at the temperature of liquid nitrogen is stable, but the process of freezing inflicts a level of damage which cannot be reversed by current medical technology. Whether or not the damage inflicted by current methods can ever be reversed depends both on the level of damage and the ultimate limits of future medical technology. The failure to reverse freezing injury with current methods does not imply that it can never be reversed in the future, just as the inability to build a personal computer in 1890 did not imply that such machines would never be economically built. This paper considers the limits of what medical technology should eventually be able to achieve (based on the currently understood laws of chemistry and physics) and the kinds of damage caused by current methods of freezing. It then considers whether methods of repairing the kinds of damage caused by current suspension techniques are likely to be achieved in the future. INTRODUCTION Tissue preserved in liquid nitrogen can survive centuries without deterioration[ft.1]. This simple fact provides an imperfect time machine that can transport us almost unchanged from the present to the future: we need merely freeze ourselves in liquid nitrogen. If freezing damage can someday be cured, then a form of time travel to the era when the cure is available would be possible. While unappealing to the healthy this possibility is more attractive to the terminally ill, whose options are somewhat limited. Far from being idle speculation, this option is in fact available to anyone who so chooses. First seriously proposed in the 1960's by Ettinger[80] there are now three organizations in the U.S. that provide cryonic suspension services. Perhaps the most important question in evaluating this option is its technical feasibility: will it work? Given the remarkable progress of science during the past few centuries, it is difficult to dismiss cryonics out of hand. The structure of DNA was unknown prior to 1953; the chemical (rather than "vitalistic") nature of living beings was not appreciated until early in the 20th century; it was not until 1864 that spontaneous generation was put to rest by Louis Pasteur, who demonstrated that no organisms emerged from heat-sterilized growth medium kept in sealed flasks; and Sir Isaac Newton's Principia established the laws of motion in 1687, just over 300 years ago. If progress of the same magnitude occurs in the next few centuries, then it becomes difficult to argue that the repair of frozen tissue is inherently and forever infeasible. Hesitation to dismiss cryonics is not a ringing endorsement and still leaves the basic question in considerable doubt. Perhaps a closer consideration of how future technologies might be applied to the repair of frozen tissue will let us draw stronger conclusions - in one direction or the other. Ultimately, cryonics will either (a) work or (b) fail to work. It would seem useful to know in advance which of these two outcomes to expect. If it can be ruled out as infeasible, then we need not waste further time on it. If it seems likely that it will be technically feasible, then a number of nontechnical issues should be addressed in order to obtain a good probability of overall success. The reader interested in a general introduction to cryonics is referred to other sources[23, 24, 80]. Here, we focus on technical feasibility. While many isolated tissues (and a few particularly hardy organs) have been successfully cooled to the temperature of liquid nitrogen and rewarmed[59], further successes have proven elusive. While there is no particular reason to believe that a cure for freezing damage would violate any laws of physics (or is otherwise obviously infeasible), it is likely that the damage done by freezing is beyond the self-repair and recovery capabilities of the tissue itself. This does not imply that the damage cannot be repaired, only that significant elements of the repair process would have to be provided from an external source. In deciding whether such externally provided repair will (or will not) eventually prove feasible, we must keep in mind that such repair techniques can quite literally take advantage of scientific advances made during the next few centuries. Forecasting the capabilities of future technologies is therefore an integral component of determining the feasibility of cryonics. Such a forecast should, in principle, be feasible. The laws of physics and chemistry as they apply to biological structures are well understood and well defined. Whether the repair of frozen tissue will (or will not) eventually prove feasible within the framework defined by those laws is a question which we should be able to answer based on what is known today. Current research (outlined below) supports the idea that we will eventually be able to examine and manipulate structures molecule by molecule and even atom by atom. Such a technical capability has very clear implications for the kinds of damage that can (and cannot) be repaired. The most powerful repair capabilities that should eventually be possible can be defined with remarkable clarity. The question we wish to answer is conceptually straightforwards: will the most powerful repair capability that is likely to be developed in the long run (perhaps over several centuries) be adequate to repair tissue that is frozen using the best available current methods?[ft. 2] The general purpose ability to manipulate structures with atomic precision and low cost is often called nanotechnology (other terms, such as molecular engineering, molecular manufacturing, molecular nanotechnology, etc. are also often applied). There is widespread belief that such a capability will eventually be developed [1, 2, 3, 4, 7, 8, 10, 19, 41, 47, 49, 83, 84, 85, 106] though exactly how long it will take is unclear. The long storage times possible with cryonic suspension make the precise development time of such technologies noncritical. Development any time during the next few centuries would be sufficient to save the lives of those suspended with current technology. In this paper, we give a brief introduction to nanotechnology and then clarify the technical issues involved in applying it in the conceptually simplest and most powerful fashion to the repair of frozen tissue. NANOTECHNOLOGY Broadly speaking, the central thesis of nanotechnology is that almost any chemically stable structure that can be specified can in fact be built. This possibility was first advanced by Richard Feynman in 1959 [4] when he said: "The principles of physics, as far as I can see, do not speak against the possibility of maneuvering things atom by atom." (Feynman won the 1965 Nobel prize in physics). This concept is receiving increasing attention in the research community. There have been two international conferences directly on molecular nanotechnology[83,84] as well as a broad range of conferences on related subjects. Science [47, page 26] said "The ability to design and manufacture devices that are only tens or hundreds of atoms across promises rich rewards in electronics, catalysis, and materials. The scientific rewards should be just as great, as researchers approach an ultimate level of control - assembling matter one atom at a time." "Within the decade, [John] Foster [at IBM Almaden] or some other scientist is likely to learn how to piece together atoms and molecules one at a time using the STM [Scanning Tunnelling Microscope]." Eigler and Schweizer[49] at IBM reported on "...the use of the STM at low temperatures (4 K) to position individual xenon atoms on a single- crystal nickel surface with atomic precision. This capacity has allowed us to fabricate rudimentary structures of our own design, atom by atom. The processes we describe are in principle applicable to molecules also. In view of the device-like characteristics reported for single atoms on surfaces [omitted references], the possibilities for perhaps the ultimate in device miniaturization are evident." J. A. Armstrong, IBM Chief Scientist and Vice President for Science and Technology[106] said I believe that nanoscience and nanotechnology will be central to the next epoch of the information age, and will be as revolutionary as science and technology at the micron scale have been since the early '70's.... Indeed, we will have the ability to make electronic and mechanical devices atom-by-atom when that is appropriate to the job at hand. The New York Times said[107]: Scientists are beginning to gain the ability to manipulate matter by its most basic components - molecule by molecule and even atom by atom. That ability, while now very crude, might one day allow people to build almost unimaginably small electronic circuits and machines, producing, for example, a supercomputer invisible to the naked eye. Some futurists even imagine building tiny robots that could travel through the body performing surgery on damaged cells. Drexler[1,10,19,41,85] has proposed the assembler, a small device resembling an industrial robot which would be capable of holding and positioning reactive compounds in order to control the precise location at which chemical reactions take place. This general approach should allow the construction of large atomically precise objects by a sequence of precisely controlled chemical reactions. The foundational technical discussion of nanotechnology has recently been provided by Drexler[85]. Ribosomes The plausibility of this approach can be illustrated by the ribosome. Ribosomes manufacture all the proteins used in all living things on this planet. A typical ribosome is relatively small (a few thousand cubic nanometers) and is capable of building almost any protein by stringing together amino acids (the building blocks of proteins) in a precise linear sequence. To do this, the ribosome has a means of grasping a specific amino acid (more precisely, it has a means of selectively grasping a specific transfer RNA, which in turn is chemically bonded by a specific enzyme to a specific amino acid), of grasping the growing polypeptide, and of causing the specific amino acid to react with and be added to the end of the polypeptide[14]. The instructions that the ribosome follows in building a protein are provided by mRNA (messenger RNA). This is a polymer formed from the four bases adenine, cytosine, guanine, and uracil. A sequence of several hundred to a few thousand such bases codes for a specific protein. The ribosome "reads" this "control tape" sequentially, and acts on the directions it provides. Assemblers In an analogous fashion, an assembler will build an arbitrary molecular structure following a sequence of instructions. The assembler, however, will provide three-dimensional positional and full orientational control over the molecular component (analogous to the individual amino acid) being added to a growing complex molecular structure (analogous to the growing polypeptide). In addition, the assembler will be able to form any one of several different kinds of chemical bonds, not just the single kind (the peptide bond) that the ribosome makes. Calculations indicate that an assembler need not inherently be very large. Enzymes "typically" weigh about 10^5 amu (atomic mass units[ft. 3]), while the ribosome itself is about 3 x 10^6 amu[14]. The smallest assembler might be a factor of ten or so larger than a ribosome. Current design ideas for an assembler are somewhat larger than this: cylindrical "arms" about 100 nanometers in length and 30 nanometers in diameter, rotary joints to allow arbitrary positioning of the tip of the arm, and a worst-case positional accuracy at the tip of perhaps 0.1 to 0.2 nanometers, even in the presence of thermal noise[18]. Even a solid block of diamond as large as such an arm weighs only sixteen million amu, so we can safely conclude that a hollow arm of such dimensions would weigh less. Six such arms would weigh less than 10^8 amu. Molecular Computers The assembler requires a detailed sequence of control signals, just as the ribosome requires mRNA to control its actions. Such detailed control signals can be provided by a computer. A feasible design for a molecular computer has been presented by Drexler[2,19]. This design is mechanical in nature, and is based on sliding rods that interact by blocking or unblocking each other at "locks."[ft. 4] This design has a size of about 5 cubic nanometers per "lock" (roughly equivalent to a single logic gate). Quadrupling this size to 20 cubic nanometers (to allow for power, interfaces, and the like) and assuming that we require a minimum of 10^4 "locks" to provide minimal control results in a volume of 2 x 10^5 cubic nanometers (.0002 cubic microns) for the computational element. This many gates is sufficient to build a simple 4-bit or 8-bit general purpose computer. For example, the 6502 8-bit microprocessor can be implemented in about 10,000 gates, while an individual 1-bit processor in the Connection Machine has about 3,000 gates. Assuming that each cubic nanometer is occupied by roughly 100 atoms of carbon, this 2 x 10^5 cubic nanometer computer will have a mass of about 2 x 10^8 amu. An assembler might have a kilobyte of high speed (rod-logic based) RAM, (similar to the amount of RAM used in a modern one-chip computer) and 100 kilobytes of slower but more dense "tape" storage - this tape storage would have a mass of 10^8 amu or less (roughly 10 atoms per bit - see below). Some additional mass will be used for communications (sending and receiving signals from other computers) and power. In addition, there will probably be a "toolkit" of interchangable tips that can be placed at the ends of the assembler's arms. When everything is added up a small assembler, with arms, computer, "toolkit," etc. should weigh less than 10^9 amu. Escherichia coli (a common bacterium) weigh about 10^12 amu[14, page 123]. Thus, an assembler should be much larger than a ribosome, but much smaller than a bacterium. Self Replicating Systems It is also interesting to compare Drexler's architecture for an assembler with the Von Neumann architecture for a self replicating device. Von Neumann's "universal constructing automaton"[45] had both a universal Turing machine to control its functions and a "constructing arm" to build the "secondary automaton." The constructing arm can be positioned in a two-dimensional plane, and the "head" at the end of the constructing arm is used to build the desired structure. While Von Neumann's construction was theoretical (existing in a two dimensional cellular automata world), it still embodied many of the critical elements that now appear in the assembler. Further work on self-replicating systems was done by NASA in 1980 in a report that considered the feasibility of implementing a self- replicating lunar manufacturing facility with conventional technology[48]. One of their conclusions was that "The theoretical concept of machine duplication is well developed. There are several alternative strategies by which machine self-replication can be carried out in a practical engineering setting." They estimated it would require 20 years to develop such a system. While they were considering the design of a macroscopic self-replicating system (the proposed "seed" was 100 tons) many of the concepts and problems involved in such systems are similar regardless of size. Positional Chemistry Chemists have been remarkably successful at synthesizing a wide range of compounds with atomic precision. Their successes, however, are usually small in size (with the notable exception of various polymers). Thus, we know that a wide range of atomically precise structures with perhaps a few hundreds of atoms in them are quite feasible. Larger atomically precise structures with complex three-dimensional shapes can be viewed as a connected sequence of small atomically precise structures. While chemists have the ability to precisely sculpt small collections of atoms there is currently no ability to extend this capability in a general way to structures of larger size. An obvious structure of considerable scientific and economic interest is the computer. The ability to manufacture a computer from atomically precise logic elements of molecular size, and to position those logic elements into a three- dimensional volume with a highly precise and intricate interconnection pattern would have revolutionary consequences for the computer industry. A large atomically precise structure, however, can be viewed as simply a collection of small atomically precise objects which are then linked together. To build a truly broad range of large atomically precise objects requires the ability to create highly specific positionally controlled bonds. A variety of highly flexible synthetic techniques have been considered in [85]. We shall describe two such methods here to give the reader a feeling for the kind of methods that will eventually be feasible. We assume that positional control is available and that all reactions take place in a hard vacuum. The use of a hard vacuum allows highly reactive intermediate structures to be used, e.g., a variety of radicals with one or more dangling bonds. Because the intermediates are in a vacuum, and because their position is controlled (as opposed to solutions, where the position and orientation of a molecule are largely random), such radicals will not react with the wrong thing for the very simple reason that they will not come into contact with the wrong thing. Note that the requirement for hard vacuum can be met even when dealing with biological structures by keeping the temperature sufficiently low. Normal solution-based chemistry offers a smaller range of controlled synthetic possibilities. For example, highly reactive compounds in solution will promptly react with the solution. In addition, because positional control is not provided, compounds randomly collide with other compounds. Any reactive compound will collide randomly and react randomly with anything available. Solution-based chemistry requires extremely careful selection of compounds that are reactive enough to participate in the desired reaction, but sufficiently non-reactive that they do not accidentally participate in an undesired side reaction. Synthesis under these conditions is somewhat like placing the parts of a radio into a box, shaking, and pulling out an assembled radio. The ability of chemists to synthesize what they want under these conditions is amazing. Much of current solution-based chemical synthesis is devoted to preventing unwanted reactions. With assembler-based synthesis, such prevention is a virtually free by-product of positional control. To illustrate positional synthesis in vacuum somewhat more concretely, let us suppose we wish to bond two compounds, A and B. As a first step, we could utilize positional control to selectively abstract a specific hydrogen atom from compound A. To do this, we would employ a radical that had two spatially distinct regions: one region would have a high affinity for hydrogen while the other region could be built into a larger "tip" structure that would be subject to positional control. A simple example would be the 1-propynyl radical, which consists of three co-linear carbon atoms and three hydrogen atoms bonded to the sp3 carbon at the "base" end. The radical carbon at the radical end is triply bonded to the middle carbon, which in turn is singly bonded to the base carbon. In a real abstraction tool, the base carbon would be bonded to other carbon atoms in a larger diamondoid structure which provides positional control, and the tip might be further stabilized by a surrounding "collar" of unreactive atoms attached near the base that would prevent lateral motions of the reactive tip. The affinity of this structure for hydrogen is quite high. Propyne (the same structure but with a hydrogen atom bonded to the "radical" carbon) has a hydrogen-carbon bond dissociation energy in the vicinity of 132 kilocalories per mole. As a consequence, a hydrogen atom will prefer being bonded to the 1-propynyl hydrogen abstraction tool in preference to being bonded to almost any other structure. By positioning the hydrogen abstraction tool over a specific hydrogen atom on compound A, we can perform a site specific hydrogen abstraction reaction. This requires positional accuracy of roughly a bond length (to prevent abstraction of an adjacent hydrogen). Quantum chemical analysis of this reaction by Musgrave et. al.[108] show that the activation energy for this reaction is low, and that for the abstraction of hydrogen from the hydrogenated diamond (111) surface (modeled by isobutane) the barrier is very likely zero. Having once abstracted a specific hydrogen atom from compound A, we can repeat the process for compound B. We can now join compound A to compound B by positioning the two compounds so that the two dangling bonds are adjacent to each other, and allowing them to bond. This illustrates a reaction using a single radical. With positional control, we could also use two radicals simultaneously to achieve a specific objective. Suppose, for example, that two atoms A1 and A2 which are part of some larger molecule are bonded to each other. If we were to position the two radicals X1 and X2 adjacent to A1 and A2, respectively, then a bonding structure of much lower free energy would be one in which the A1-A2 bond was broken, and two new bonds A1-X1 and A2-X2 were formed. Because this reaction involves breaking one bond and making two bonds (i.e., the reaction product is not a radical and is chemically stable) the exact nature of the radicals is not critical. Breaking one bond to form two bonds is a favored reaction for a wide range of cases. Thus, the positional control of two radicals can be used to break any of a wide range of bonds. A range of other reactions involving a variety of reactive intermediate compounds (carbenes are among the more interesting ones) are proposed in [85], along with the results of semi-empirical and ab initio quantum calculations and the available experimental evidence. Another general principle that can be employed with positional synthesis is the controlled use of force. Activation energy, normally provided by thermal energy in conventional chemistry, can also be provided by mechanical means. Pressures of 1.7 megabars have been achieved experimentally in macroscopic systems[30]. At the molecular level such pressure corresponds to forces that are a large fraction of the force required to break a chemical bond. A molecular vise made of hard diamond-like material with a cavity designed with the same precision as the reactive site of an enzyme can provide activation energy by the extremely precise application of force, thus causing a highly specific reaction between two compounds. To achieve the low activation energy needed in reactions involving radicals requires little force, allowing a wider range of reactions to be caused by simpler devices (e.g., devices that are able to generate only small force). Further analysis is provided in [85]. Feynman said: "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." Drexler has provided the substantive analysis required before this objective can be turned into a reality. We are nearing an era when we will be able to build virtually any structure that is specified in atomic detail and which is consistent with the laws of chemistry and physics. This has substantial implications for future medical technologies and capabilities. Repair Devices A repair device is an assembler which is specialized for repair of tissue in general, and frozen tissue in particular. We assume that a repair device has a mass of between 10^9 and 10^10 amu (e.g., we assume that a repair device might be as much as a factor of 10 more complicated than a simple assembler). This provides ample margin for increasing the capabilities of the repair device if this should prove necessary. A single repair device of the kind described will not, by itself, have sufficient memory to store the programs required to perform all the repairs. However, if it is connected to a network (in the same way that current computers can be connected into a local area network) then a single large "file server" can provide the needed information for all the repair devices on the network. The file server can be dedicated to storing information: all the software and data that the repair devices will need. Almost the entire mass of the file server can be dedicated to storage, it can service many repair devices, and can be many times the size of one device without greatly increasing system size. Combining these advantages implies the file server will have ample storage to hold whatever programs might be required during the course of repair. In a similar fashion, if further computational resources are required they can be provided by "large" compute servers located on the network. Cost One consequence of the existence of assemblers is that they are cheap. Because an assembler can be programmed to build almost any structure, it can in particular be programmed to build another assembler. Thus, self reproducing assemblers should be feasible and in consequence the manufacturing costs of assemblers would be primarily the cost of the raw materials and energy required in their construction. Eventually (after amortization of possibly quite high development costs), the price of assemblers (and of the objects they build) should be no higher than the price of other complex structures made by self-replicating systems. Potatoes - which have a staggering design complexity involving tens of thousands of different genes and different proteins directed by many megabits of genetic information - cost well under a dollar per pound. DESCRIBING THE BRAIN AT THE MOLECULAR AND ATOMIC LEVEL In principle we need only repair the frozen brain, for the brain is the most critical and important structure in the body. Faithfully repairing the liver (or any other secondary tissue) molecule by molecule (or perhaps atom by atom) appears to offer no benefit over simpler techniques - such as replacement. The calculations and discussions that follow are therefore based on the size and composition of the brain. It should be clear that if repair of the brain is feasible, then the methods employed could (if we wished) be extended in the obvious way to the rest of the body. The brain, like all the familiar matter in the world around us, is made of atoms. It is the spatial arrangement of these atoms that distinguishes an arm from a leg, the head from the heart, and sickness from health. This view of the brain is the framework for our problem, and it is within this framework that we must work. Our problem, broadly stated, is that the atoms in a frozen brain are in the wrong places. We must put them back where they belong (with perhaps some minor additions and removals, as well as just rearrangements) if we expect to restore the natural functions of this most wonderful organ. In principle, the most that we could usefully know about the frozen brain would be the coordinates of each and every atom in it (though confer footnote 5). This knowledge would put us in the best possible position to determine where each and every atom should go. This knowledge, combined with a technology that allowed us to rearrange atomic structure in virtually any fashion consistent with the laws of chemistry and physics, would clearly let us restore the frozen structure to a fully functional and healthy state. In short, we must answer three questions: 1.) Where are the atoms? 2.) Where should they go? 3.) How do we move them from where they are to where they should be? Regardless of the specific technical details involved, any method of restoring a person in suspension must answer these three questions, if only implicitly. Current efforts to freeze and then thaw tissue (e.g., experimental work aimed at freezing and then reviving sperm, kidneys, etc) answer these three questions indirectly and implicitly. Ultimately, technical advances should allow us to answer these questions in a direct and explicit fashion. Rather than directly consider these questions at once, we shall first consider a simpler problem: how would we go about describing the position of every atom if somehow this information was known to us? The answer to this question will let us better understand the harder questions. How Many Bits to Describe One Atom Each atom has a location in three-space that we can represent with three coordinates: X, Y, and Z. Atoms are usually a few tenths of a nanometer apart. If we could record the position of each atom to within 0.01 nanometers, we would know its position accurately enough to know what chemicals it was a part of, what bonds it had formed, and so on. The brain is roughly .1 meters across, so .01 nanometers is about 1 part in 10^10. That is, we would have to know the position of the atom in each coordinate to within one part in ten billion. A number of this size can be represented with about 33 bits. There are three coordinates, X, Y, and Z, each of which requires 33 bits to represent, so the position of an atom can be represented in 99 bits. An additional few bits are needed to store the type of the atom (whether hydrogen, oxygen, carbon, etc.), bringing the total to slightly over 100 bits[ft. 5]. Thus, if we could store 100 bits of information for every atom in the brain, we could fully describe its structure in as exacting and precise a manner as we could possibly need. A memory device of this capacity should be quite literally possible. To quote Feynman[4]: "Suppose, to be conservative, that a bit of information is going to require a little cube of atoms 5 x 5 x 5 - that is 125 atoms." This is indeed conservative. Single stranded DNA already stores a single bit in about 16 atoms (excluding the water that it's in). It seems likely we can reduce this to only a few atoms[1]. The work at IBM[49] suggests a rather obvious way in which the presence or absence of a single atom could be used to encode a single bit of information (although some sort of structure for the atom to rest upon and some method of sensing the presence or absence of the atom will still be required, so we would actually need more than one atom per bit in this case). If we conservatively assume that the laws of chemistry inherently require 10 atoms to store a single bit of information, we still find that the 100 bits required to describe a single atom in the brain can be represented by about 1,000 atoms. Put another way, the location of every atom in a frozen structure is (in a sense) already encoded in that structure in an analog format. If we convert from this analog encoding to a digital encoding, we will increase the space required to store the same amount of information. That is, an atom in three-space encodes its own position in the analog value of its three spatial coordinates. If we convert this spatial information from its analog format to a digital format, we inflate the number of atoms we need by perhaps as much as 1,000. If we digitally encoded the location of every atom in the brain, we would need 1,000 times as many atoms to hold this encoded data as there are atoms in the brain. This means we would require roughly 1,000 times the volume. The brain is somewhat over one cubic decimeter, so it would require somewhat over one cubic meter of material to encode the location of each and every atom in the brain in a digital format suitable for examination and modification by a computer. While this much memory is remarkable by today's standards, its construction clearly does not violate any laws of physics or chemistry. That is, it should literally be possible to store a digital description of each and every atom in the brain in a memory device that we will eventually be able to build. How Many Bits to Describe a Molecule While such a feat is remarkable, it is also much more than we need. Chemists usually think of atoms in groups - called molecules. For example, water is a molecule made of three atoms: an oxygen and two hydrogens. If we describe each atom separately, we will require 100 bits per atom, or 300 bits total. If, however, we give the position of the oxygen atom and give the orientation of the molecule, we need: 99 bits for the location of the oxygen atom + 20 bits to describe the type of molecule ("water", in this case) and perhaps another 30 bits to give the orientation of the water molecule (10 bits for each of the three rotational axes). This means we can store the description of a water molecule in only 150 bits, instead of the 300 bits required to describe the three atoms separately. (The 20 bits used to describe the type of the molecule can describe up to 1,000,000 different molecules - many more than are present in the brain). As the molecule we are describing gets larger and larger, the savings in storage gets bigger and bigger. A whole protein molecule will still require only 150 bits to describe, even though it is made of thousands of atoms. The canonical position of every atom in the molecule is specified once the type of the molecule (which occupies a mere 20 bits) is given. A large molecule might adopt many configurations, so it might at first seem that we'd require many more bits to describe it. However, biological macromolecules typically assume one favored configuration rather than a random configuration, and it is this favored configuration that we will describe[ft. 6]. We can do even better: the molecules in the brain are packed in next to each other. Having once described the position of one, we can describe the position of the next molecule as being such-and-such a distance from the first. If we assume that two adjacent molecules are within 10 nanometers of each other (a reasonable assumption) then we need only store 10 bits of "delta X," 10 bits of "delta Y," and 10 bits of "delta Z" rather than 33 bits of X, 33 bits of Y, and 33 bits of Z. This means our molecule can be described in only 10+10+10+20+30 or 80 bits. We can compress this further by using various other clever strategems (50 bits or less is quite achievable), but the essential point should be clear. We are interested in molecules, and describing a molecule takes fewer bits than describing an atom. Do We Really Need to Describe Each Molecule? A further point will be obvious to any biologist. Describing the exact position and orientation of a hemoglobin molecule within a red blood cell is completely unnecessary. Each hemoglobin molecule bounces around within the red blood cell in a random fashion, and it really doesn't matter exactly where it is, nor exactly which way it's pointing. All we need do is say, "It's in that red blood cell!" So, too, for any other molecule that is floating at random in a "cellular compartment:" we need only say which compartment it's in. Many other molecules, even though they do not diffuse freely within a cellular compartment, are still able to diffuse fairly freely over a signficant range. The description of their position can be appropriately compressed. While this reduces our storage requirements quite a bit, we could go much further. Instead of describing molecules, we could describe entire sub-cellular organelles. It seems excessive to describe a mitochondrion by describing each and every molecule in it. It would be sufficient simply to note the location and perhaps the size of the mitochondrion, for all mitochondria perform the same function: they produce energy for the cell. While there are indeed minor differences from mitochondrion to mitochondrion, these differences don't matter much and could reasonably be neglected. We could go still further, and describe an entire cell with only a general description of the function it performs: this nerve cell has synapses of a certain type with that other cell, it has a certain shape, and so on. We might even describe groups of cells in terms of their function: this group of cells in the retina performs a "center surround" computation, while that group of cells performs edge enhancement. Cherniak[115] said: "On the usual assumption that the synapse is the necessary substrate of memory, supposing very roughly that (given anatomical and physiological 'noise') each synapse encodes about one binary bit of information, and a thousand synapses per neuron are available for this task: 10^10 cortical neurons x 10^3 synapses = 10^13 bits of arbitrary information (1.25 terabytes) that could be stored in the cerebral cortex." How Many Bits Do We Really Need? This kind of logic can be continued, but where does it stop? What is the most compact description which captures all the essential information? While many minor details of neural structure are irrelevant, our memories clearly matter. Any method of describing the human brain which resulted in loss of long term memory has rather clearly gone too far. When we examine this quantitatively, we find that preserving the information in our long term memory might require as little as 10^9 bits (somewhat over 100 megabytes)[37]. We can say rather confidently that it will take at least this much information to adequately describe an individual brain. The gap between this lower bound and the molecule-by-molecule upper bound is rather large, and it is not immediately obvious where in this range the true answer falls. We shall not attempt to answer this question, but will instead (conservatively) simply adopt the upper bound. Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=0019.1