
Our discussion to this point has led us to essentially the following picture of how cell differentiation occurs in plants and animals. As the fertilized egg cell undertakes mitosis—dividing first into 2 cells, then into 4, then 8, and so on—slight differences in the chemical conditions in the several cells cause corresponding slight affect the chemical composition of the fluid emanating from the cells and therefore supplement the already existing sources of diversity to cause still later cells to be even more varied in their properties. As the organism grows by further cell division, the compounding of effects ultimately results in the appearance of cells of widely differing structure and metabolism. Some of the mechanisms that respond to environmental differences to yield different types of cells were discussed in the preceding report. Let us now consider more carefully how the local environment is able to interact with the cellular regulative mechanism to produce the remarkable variety displayed by the cells of a higher plant or animal. Perhaps a good way to start our consideration would be to clear up what might appear to be an inconsistency between our present thesis and experimental evidence we have considered earlier. Specifically, as need to reconcile Driesch’s discovery that any of the earlier cells of a sea urchin embryo can develop into an entire animal with our present notion that differences must appear in the structure and metabolism of the first few cells of a newborn organism. A Swedish embryologist, Sven Hoerstadius, resolved the apparent discrepancy. In a series of beautifully planned and executed transplantation and isolation experiments he was able to show that the cytoplasm of the sea urchin egg is not uniform throughout in its composition, but contains varying proportions of two different chemical agents that have important influences on cellular metabolism. One of these agents was found to be concentrated at one “pole” of the fertilized egg, the other at the opposite pole. #RandolphHarris 1 of 24

Hoerstadius established that it was only because the early cell division involved cleavages parallel to the polar axis that the first few cells all possessed the same proportions of two agents and were therefore able to develop into entire animals. If, however, by artificial means the initial cleavage was forced to occur along such a plane that most of one stimulating agent went into one cell and most of the other into the second cell, an entirely different result was obtained: when these two cells were separated, each developed into only part of an animal, and the particular organs which developed in one “half-embryo” were different from those which developed in the other. Evidently one of the two chemical agents discovered by Hoerstadius acted as a switch to turn on the genes responsible for the construction of part of the animal, the other as a switch to turn on those responsible for the construction of the rest. And these two stimulating ingredients were already localized in different regions of the cytoplasm in the original fertilized egg. A similar polarity of the original egg cell has been demonstrated for many other species. In some cases, at least, gravity appears to be the principle factor that causes the separation of the different ingredients of the cytoplasm in the egg cell as it develops in the mother’s body. Tis is true of frogs’ eggs, for example. Their polar axes are easily visible because of the colour differences. The bulky and nutritive yolk settles to the bottom of the egg; most of the cytoplasm rise to the top. The cells that grow from the top half of the egg ultimately develop into the head parts of the frog; those that grow from the bottom half develop into the tail parts. Thus the top-to-bottom polar axis of the egg controls a most important structural feature: it determines the body axis of the developing embryo. While the environmental factor determining the important body axis orientation is gravity, quite a different factor determines the plane of symmetry. This plane is ordinarily determined, for frogs, by the point of entry of the male sperm cell into the egg during the act of fertilization. The “circle of longitude” of the sperm entry point becomes the head-to-tail belly line of the animal, while the meridian on the opposite side from the point of the entry becomes the lone of the backbone. #RandolphHarris 2 of 24

As the embryo develops, other gross physical effects play important roles in determining the configuration of the body parts. The pressure of water that collects in the developing tissue is believed to be instrumental in producing and shaping some of the cavities required for the proper conformation of the organs. The rolling up of certain groups of cells to form tubes—the neural tube which gives rise to the nervous system, for example—probably occurs because the electrical attractive forces among the molecules of substances produced by the growing cells cause them to try to make as close surface contact as possible with one another. Many physical factors must operate in conjunction with the specific chemical properties of the cells to cause different parts of the growing embryo to form different kinds of structures. And with each such characteristic structural development the chemical nature of the cells involved also changes, to become even more different than before from that of other groups of cells in the same organism, thereby facilitating even greater future differences in development. There is considerable evidence to support the hypothesis that chemical individuality of the cells usually develops gradually rather than abruptly. If, in a very young embryo, cells are surgically transplanted to the head region from a part of the organism that would ordinarily develop into a tail, the transplanted cells take on the characteristics of the material that surrounds them and grow into component head parts. However, if such transplantation is deferred for a time, a sort of fixation of properties occurs so that, after the operation, the transplanted cells grow into taillike parts, despite the fact that they must then protrude from the head of the full-grown embryo. The steady continuity in the development of the chemical fixation of the cells is shown by other observations: at intermediate stages of growth a small group of cells transplanted from any part of the tail region of the embryo will develop into an entire tail; later cells transplanted from a particular part of this region will develop into only a specific part of the tail. With the passage of time the cells seem to become more and more specialized and therefore more limited in the range of structure they are able to develop into. #RandolphHarris 3 of 24

An exception to the gradual nature of cell differentiation sometimes occurs when two previously separated parts of a growing embryo come together. The classical example of this phenomenon is the formation of the crystalline lens in the eye of a vertebrate. By following the gradual development of the embryo (of a chicken, for example), it was learned that the main body of hollowing-out process. This results in an “eye cup,” whose open end gradually grows toward the layer of skin that surrounds the brain parts. When growth finally brings the rim of the eye cup in contact with the surrounding skin, some sort of reactions occurs that cases the circular sector of skin contacted by the cup to embark upon a new process of cellular development. Before long, this piece of skin thickens, detaches from the surrounding tissue, shapes itself into a lenticular structure, and becomes incorporated into the eye cup to form the crystalline lens upon which clear vision ultimately depends. Research has confirmed the validity of the obvious inference: the tissue forming the eye cup in the brain structures contains a chemical which, upon contact with the surrounding skin, triggers metabolic processes that result in the formation of lens structures in other kinds of skin than that of the head region. The eye cup, for example, can be transplanted to the flank; upon contact with this kind of skin, a lens is formed. Or skin from another part of the body can be substituted for the head skin in the vicinity of the eye cup—upon contact of the two kinds of tissue, a lens develops. Evidently the stimulating ingredient in the eye cup is able to trigger the genes in the cells of any of the organism’s skinlike tissue to reorganize their metabolic processes in the way necessary to develop a crystalline lens. The stimulating ingredient is even more versatile: for example, the eye cup of a frog can induce a lens in head or flank epidermis of a salamander embryo. (In embryos the immunological reactions that cause transplanted foreign tissue to be rejected do not occur. Hence transplantations are possible not only between different species but between different genera, families, orders, and classes. For instance, mouse tissue can grow in the chick embryo.) However, the lens induced has the specific characteristics of a salamander eye, rather than a frog eye. #RandolphHarris 4 of 24

Evidently the inducing substance from the eye cup is a chemical that is able to switch on the genes in the cell nuclei of various species to initiate the chemical process resulting in a lens. However, the architectural details of construction are coded in the genes, and they are different for different species. Again, when flank skin of a frog embryo is transplanted to the head of a young salamander embryo, the new chemical environment induces the transplanted skin to form head structures. However, in doing so it follows its own genetic repertory and manufactures the horny jaws and teeth characteristic of the frog instead of the dentine teeth characteristic of the salamander. The explanation is, once more, entirely consistent with the picture we have developed of the genetic mechanisms. All cells in the frog contain genes capable of directing the formation of any of the many body structures, and the cytoplasmic chemicals of the flank skin cells still permit considerable flexibility in their ultimate development. When stimulated by the kind of chemical that switches on the genes appropriate for the generation of headlike structures, these flank skin cells proceed to form such structures. However, whether in the original frog body or transplanted to another species, the particular structures formed must be controlled in their detailed architecture by the genes of the frog. Hence the transplanted tissue must give rise only to froglike, not to salamanderlike, structures. An embryological problem of unusual importance and difficulty is posed by the nervous system. How can we account for the enormous mass of specialized nerve cells (neuronsa)—10 billion of them in a single human animal—that seem able to extend their tiny fibers many inches of even a few feet to make highly specific connection with other nerve cells of sense organs? To be sure, the general notions we have developed as to how cells in the embryo become more and more specialized can cause us to feel that the natural physical and chemical effects we have been dealing with might be adequate to produce even as strange a structure as that of the nerve cell. However, how are we to explain the fantastically complex “wiring diagram” that appears to govern the interconnections of so many separate neuronal units? #RandolphHarris 5 of 24

Even before we have discovered the physical mechanism underlying the construction of the nervous system, we can form some appreciation for the sheer bulk of information that would have to be handled in just specifying a definite pattern of neuronal interconnections. For most of the 10 billion neurons of the human nervous system connect, not just to one other nerve cell, but to many: the average is approximately 1,000 connections per neuron! And by no means all of these connections go to nearby cells; hookups to cells in entirely different parts of the nervous system are common. Thus, to describe in straightforward chart form the wiring diagram of the human nervous system, we would have to number the particular neurons from 1 to 10 billion and then write down for each a list of the approximately 1,000 other neurons to which it connects. We would end with a table of 10,000 billion numbers, with each number, on the average, containing 9 or 10 decimal digits. However, we have learned that the genes constitute the blueprint for the details of construction of the organism. Could they carry, in their four-letter nucleotide code, the equivalent of such a table that could in some way direct each neuron to make the right connections with its neighbours? The answer is no; they could not. We do not need to have a model of any particular physical process for enforcing neuronal wiring to be sure of that conclusion, for it rests solely and surely on the information-handling capacity of the genes. To be sure, the human genes do carry a great detail of information. There are several thousand genes in each of the 46 chromosomes, and each gene is a molecule of DNA containing a string of some thousand nucleotides. The result is a “message-carrying capacity” equivalent to that of at least several dozen large printed volumes. While this is no small library for the nucleus of each of our billions of cells to be carrying around, it still falls far short of what would be required to “write down” the wiring diagram of the neurons in the way we have specified. And even if we could somehow squeeze this information into the genes, we would then have no room left over for all the other, nonneural, specifications that cause us to turn out to be humans rather than mosquitoes! #RandolphHarris 6 of 24

Obviously, the notion of the detailed genetic control of the interconnections of the neurons is untenable. What about the opposite assumption—that the neurons in the embryo just “grow like Topsy” in the uncontrolled fashion, making random connections as they come in contact with one another? This assumption depends for its credibility on the theory that learning processes are subsequently able to strengthen and weaken the various neuronal connections so as ultimately to provide the coordination of the physical and mental activity that constitutes the unique accomplishment of the nervous system. In higher animals, at least, any general theory of neuronal connectivity must be able to account for the phenomena associated with vision. In the human, more than half of the several million never fibers that leave the brain for other parts of the body go to the eyes. If a random-connection/subsequent-learning theory is the complete answer to our information-handling problem, we would expect that meaningful visual patterns would not occur in newborn animals, but would arise only after a period of trial-and-error learning. One of the most interesting experiments testing this hypothesis was performed by R. W. Sperry, Professor of Biology at the California Institute of Technology. In his work he took advantage of the fact that the nervous system of many lower animals possess a regenerative capacity: if nerves are cut, they grow back and ultimately function once again. Neuroregeneration in humans is new technology. The complex, delicate structures that make up the nervous system—the brain, spinal cord, and peripheral nerves—are susceptible to various types of injury ranging from trauma to neurodegenerative disease that cause progressive deterioration: Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS, also known as Lou Ghrig’s disease), multiple sclerosis and multiple system atrophy. Unfortunately, in humans, because of the complexity of the brain and spinal cord, little spontaneous regeneration, repair or healing occurs. Therefore, brain damage, paralysis from spinal cord injury and peripheral nerve damage are often permanent and incapacitating. #RandolphHarris 7 of 24

Patients with serious nervous system injuries or strokes often require lifelong assistance, which puts a tremendous burden on patients, their families and society. Innovative, paradigm-shifting strategies are required to advance treatment of neurological injury. However, neuroregeneration research is at the forefront of healing the nervous system. Regrowth of nerve fibers (axons) is essential to repair the functional recovery of the spinal cord. Tissue destruction with cysts and gliosis at the site of injury forms a barrier to regeneration. Ongoing research is using tissue engineering with biodegradable polymer scaffolds (PLGA, PCLF, OPF) loaded with different growth-promoting cells (Schwann cells, neural progenitor cells, mesenchymal stem cells) and different growth factors (GDNF, NT3, BDNF) to bridge the gap, and to promote axonal regeneration and functional restoration in the spina cords of rates and mice, eventually for future use in human patients. Further, researchers are investigating the effects of exercise training and local delivery of steroids on axon regeneration and functional recovery. Peripheral nerve regeneration and repair is another strategy to expand the time window of opportunity and improve the functional recovery following peripheral nerve injury and repair. One strategy is to apply polymer microsphere to deliver vascular endothelial growth factor (VEGF) to the nerve repair suite in a controlled sustainable release manner. VEGF promotes angiogenesis and neurogenesis, and thus leads to a better functional outcome and larger window of opportunity for the nerve to be permissive to prolonged regeneration. The other strategy is to counteract the lack of healthy Schwann cells at the nerve repair site by supplementing functioning Schwann cells derived from nerves prepared in an invitro system of Schwann cells induced from stem cells of the adipose tissue. Novel animal models are being developed to delineate the nature and time course of denervation muscle changes; identify the key indicators of muscle receptivity, including electromyographic changes, muscle fiber type changes and changes of myogenic genes; and evaluate the impact of these changes on nerve regeneration and the potential success of a nerve repair. #RandolphHarris 8 of 24

Nerve cell regrowth: Axogenesis is another possibility. Researchers are using zebrafish as an animal model system to investigate how special cues in the brain and spinal cord can entice or block nerve cell growth—experiments that help scientists understand why conditions at the site of nerve injury retard regeneration. This work is providing new understanding into how nerve cells grow during development of the nervous system and how nerve regeneration might be improved after injury. There are many other forms of neuroregeneration understudy. Hearing about Sperry’s research with animals made me a little excited. Now, back to Sperry. Sperry was able to establish, in an adult toad, the equivalent of a “newborn” visual systems. He performed an operation wherein the optic nerves were cut and reconnected inversely—that is, the right eye was connected to the nerve from the brain that previously had gone to the left eye, and vice versa. Of course, in such an operation, “reconnection” consisted only of butting the cut ends of the nerves together and waiting for natural processes to reestablish connections from the many tens of thousands of cut fibers to the brain. Even in an uncut optic nerve, these fibers cross and twist in what appears to be a highly random fashion. In view of such twisting and turnings (which are also characteristic of the human optic nerve), it has always seemed hard to believe that there was any precise built-in pattern of interconnection between retinal receptors and neurons in the brain; such anatomical observations had lent strength to the hypothesis that visual capability was acquired through learning, and not wired in. Yet, after a few weeks, the toad was able to see again, apparently as well as ever! Certainly, the presence of a moving fly within its normal range of vision caused it to react in toadlike manner by darting out its tongue for food. This and other tests led to the conclusion that, somehow, the fibers of the neurons of the visual cortex of the brain had managed to seek out and reconnect themselves, one by one, with the receptor cells of the eye in such a way as to reestablish in the brain a clear image, with normal topological properties of up/down and right/left continuity. #RandolphHarris 9 of 24

That is has nothing to do with learning was proved by an interesting anomaly in the toad’s new behaviour: If a fly appeared opposite the toad’s right eye, it darted its tongue out to the left to attempt to capture it; if the food appeared to the left, the toad would always go to the right. To the animal, since the optic nerve of the right eye was connected to the part of the brain designed to be used with the left eye and vice versa, the image formed in the right eye always appeared to be coming from the left and the image formed in the left eye always appeared to be coming from the right. No amount of experience ever caused the toad to learn to correct its mistake. It was obvious that the left-ness and rightness of the vision were “wired-in” and not learned concepts. Sperry’s experiment was only one of many which have established that, despite the obvious ability of parts of the brain and nervous system to adapt and presumably modify themselves through learning, there is also a great deal of permanent wiring involved. Many of the neuronal interconnections are formed during the embryological development period, and they are formed precisely, in the sense that the right neurons are tied to one another or to just the right sensory receptors or motor effectors. Thus the hope that learning processes alone would provide a solution for our interconnectivity problem has proved to be a false one. The problem is still with us. It is safe to say that no one yet knows for sure what physical or chemical factors are involved in the phenomenon of embryological neuronal wiring. However, there is a general hypothesis that seems able to account for most of the observed facts. This hypothesis is suggested by studies of the movements of cells in tissue cultures. Individual cells can be broken loose from the tissue of which they are a part and mixed with other cells in a liquid suspension. If in this way different types of cells—kidney and cartilage, say—are mixed together, a curious sorting out occurs. Under the microscope the cells, on encountering one another, are seen to slide over each other’s surface in seemingly aimless fashion but with the ultimate result that cells of the one type seek out one another and aggregate in one lump or layer, while cells of the other types form their own similar but separate association. Experiments have been performed with solutions containing several different types of cell, with the same results. Evidently, chemical substances in the cells result in an attractive or cohesive forces, specific to cell type, that tend to cause like cells to stick together, unlike cells to remain unconnected. #RandolphHarris 10 of 24

The extension of this principle to the formation of the connections between retinal receptors and cortical neurons in the visual system, for example, involves the following line of speculation. The receptor neurons in the retina of the eye are assumed to contain two separate chemical ingredients that vary in concentration in accordance with the position of the neuron on the retina. One of these chemical ingredients might appear in very small concentration in the rods and cones located at the extreme left-hand side of the retinal field, with the concentration of this ingredient increasing steadily across the retina to reach a maximum at the extreme right-hand side of the field. Similarly, the other chemical from the bottom to the top of the retina. With such an arrangement, the relative proportions of these two chemical ingredients in a given receptor neuron would provide an accurate indication of the position of the neuron on the retina, both left and right and up and down. Similar concentration gradients are presumed to exist in the interneurons and the neurons in the brain with which the retinal receptors need to be ultimately connected. The embryonic growth process is assumed to be dynamic enough to cause each outgrowing nerve cell fibers to wander close to a wide range of candidate terminating cells. By the operation of attraction or cohesive forces similar to, but much more specific than, those required to explain the sorting out of dissimilar cells in liquid suspension, the searching nerve fiber is assumed ablet to seek out and make connection with receiving neurons of similar composition of the two key chemical ingredients. In this way there results a continuous one-to-one correspondence between points on the retina and those on the visual cortex of the brain, and the picture we finally see is coherent and unscrambled. Future work may or may not confirm the controlling role of “connectivity” ingredients in determining the built-in wiring of the nervous system. If not, however, it seems inevitable that some other effect will be discovered that produces the same result-an ability of growing nerve fibers, through physical or chemical interaction with the local environment, to search out and connect to other specific neurons or terminal organs. #RandolphHarris 11 of 24

The embryological prewiring in the nervous system will almost certainly turn out to employ mechanisms that different only in degree, but not in quality, from those which control the development of structure in the rest of the organism. Whether our concern is the development of neurons or of heart, liver, or skin, it now seems clear that the genes exercise architectural control over a growing multicellular organism by a combination of direct and indirect methods. Their delineation of the structure of the enzymes, which in turn specific the chemical reactions permitted in the growing cells, is an important direct method of influencing the final outcome. However, we have seen that the physical and chemical conditions of the extranuclear environment are also vitally important—that local physical forces distort and shape the growing tissue and that chemical agents in the surrounding fluids enter the cells to modulate the enzymatic reactions in the cytoplasm and to trigger on and off individual genes in the nucleus. To be sure, these local physical and chemical environmental factors are themselves results of the previous detailed development of the various parts of the organism which, in turn, depended on the genetic mechanisms and the local environment, and so back to the initial fertilized egg. Thus it is still correct to say that the genetic mechanisms exercise primary architectural control over all the design features of the organism. However, they do not do so by means of a direct reading out of the nucleus of completely detailed specifications for each cell, followed by a single-minded manufacturing operation that follows such detailed instructions to generate the specified product, without regard for what may be happening in other nearby cells. Instead, the genetic mechanisms seem to have learned how to minimize their own detailed architectural chores by supplying to each cell a sort of do-it-yourself kit of structural and chemical features that automatically cause the cells to develop properly through the normal operation of physical principles as it interacts with the local environment that it and its neighbours continually create and modify. #RandolphHarris 12 of 24

The result is the scene of activity constantly viewed by the embryologist—a delicately balanced and fantastically complex interplay between the genetic mechanisms of the cells and their varied and changing surroundings. This is the secret of the diversity of structure and metabolism that makes multicellular plants and animals possible. Only by such methods is nature able to mold its raw material into such an impressive end product as a living higher organism—a sea urchin, or a human. A final comment about the evolutionary origin of the mechanisms on which multicellular life is based may be in order. For despite the compelling nature of the evidence, normal human experience does not seem compatible with the conclusion that such remarkably complex and intricately interrelated mechanisms could have arisen solely through the blindly probabilistic workings of evolution. The antidote to such a feeling of skepticism is a reconsideration of the frequency of past occurrence of the typical sequence of small accidental change of structure or metabolism, competition for survival, and ultimate proliferation of the best-adapted species. The fantastically large number of such small refinements that must have taken place among trillions of individual organisms during billions of years is also far beyond normal human experience. The essence of the theory of evolution is the balancing of the near inconceivability of its accomplishments against the correspondingly near inconceivability of its painstaking attention to detail. Since we are talking about biology, it is a good idea to consider some brain functions and treatments. When clozapine (brand name Clozaril) was approved in 1990 for use as the first atypical antipsychotic drug in the United States of America, it opened the door to more effective and safer treatments for schizophrenia. However, the early use of this drug in the United States of America brought only frustration and heartache to hundreds of thousands of prospective users. The problem with clozapine began with the discovery that a small percentage of people who take this drug develop agranulocytosis, a life-threatening drop in white blood cell count. #RandolphHarris 13 of 24

The U.S. Food and Drug Administration (FDA) thus approved clozapine with the requirement that patients who take it must have their blood tested every week for signs of agranulocytosis. Unfortunately, the drug’s manufacturer decided to require all clozapine users in the United States of America to purchase an entire treatment package consisting of the medication and weekly testing by the drug company’s own subsidiaries. Most patients in the United State could not afford the company’s fee for this combination—a whopping $9,000 a year. What is more, their insurance companies refused to pay for it. Clearly patients were caught in the middle between big business and the health industry. A flurry of lawsuits followed. So did federal investigations and hearings. After several years the drug’s manufacture finally agreed to sell clozapine separately, allowing patients to get blood tests elsewhere at a lower cost, Moreover, the FDA reduced its requirement for such every two weeks, rather than every week, after patients have received clozapine treatment for six months. Sadly, however, many patents had already lost valuable time. Unable to fully appreciate or bring such injustices to the public’s attention, persons with schizophrenia had been victimized by society once again—a tradition whose roots date back to past “treatments” such as asylums, the lobotomy, and deinstitutionalization. Many wonder, if it is possible to rehabilitate 66 percent of patients, why are we not? A variety of insight therapies, from cognitive to psychodynamic may be used in cases of schizophrenia. Such approaches may be offered in individual or group formats. Studies suggest that the particular orientations of insight therapists are often less important than their levels of experience with schizophrenia. In addition, the therapists who are most successful tend to be those who take an active role, setting limits, expressing opinions, challenging patients’ statements, providing guidance, displaying empathy, and gaining trust. #RandolphHarris 14 of 24

Certainly the most thrilling and romantic happening of these years is the adventures in space, surpassing in promise the voyages of the fifteenth and sixteenth centuries. This adventure makes life worth the trouble again. When the Russians beat us out, we are miffed but we can be proud that these exploits have been performed by men and man is great; Copernicus was a Pole, Galileo an Italian, Kepler a German, Newton an Englishman—and the rockets were Chinese; and we hope that we shall win the next round, for it belongs to America to achieve first in this kind of enterprise. The experiments are expensive, but it seems mean-spirited to question the appropriations and few have done so. So far, grand. However, now we have opened the exploration of space and allowed even corporations to build spaceships. Boeing is building a spacecraft called CST-100 Starliner with an LEO range. Sierra Nevada Corporation is building the Dream Chaser Space System with an LEO range. SpaceX is building Dragon 2 with an LEO range, and Starship with a range to reach Mars. LEO spacecrafts can be used for a Mission to the Moon. Have you every heard of Project Argus? Well in 1958, the United States of America’s military withheld the wave length of a satellite for strategic reasons. Next, they carried out a secret nuclear experiment in the ionosphere, and this was kept secret not from the Russians from military reasons, but from the American people, because of possible objections to the fall-out. The Times kept the secret till the Russians were about to publish it, explaining (March 19, 1959), that “it has learned of the plans for Project Argus last summer, some weeks before it took place. Nevertheless, scientists associated with the government said they feared that prior announcements of the experiment might lead to protests that would force its cancellation.” A. J Muste and editor of Liberation magazine, sked the for an apology for this unexampled betrayal of journalistic responsibility, and got the astounding replay: It seems to me that you are suggesting that the Times enter the propaganda field and, in effect, set its judgment above that of the military men and scientists as to what can be published…After all, the Times is a responsible newspaper. [!!] [Robert Garst, Assistant Managing Editor. In Liberation, May, 1959.] #RandolphHarris 15 of 24

However, what is the effect on our people when we are told that our chief newspaper does not print the news? Constitutionally, for instance, how in a democracy do they then deserve their mailing privileges, to circulate their official press releases and advertisements for department stores? [The purpose of second-class mail I to circulate information.] When Muste wrote a letter for publication about the Times’ handling of the story, the Times found no space for that letter. However, to my mind, even more important is the effect of cutting people off from the adventure of science, no matter what the risks. What an illiberal and dishonourable policy to purse! Our government cannot see that noble things must not be made base, romance must not be turned into disillusion, or what will become of the young people? Take another example. This glorious enterprise of space! And now we have chosen seven astronauts for special training. However, the nemesis of the organized system haunts us. All prove to be European American Protestant, in their early or middle thirties, married, with small children, and coming from small towns—in brief, models of salesmen or junior executives for International Business Machines. And these seven have now made a solemn pact, reported in the press, that whichever one goes aloft will split evenly with the others his take from syndicated stories and TV appearances. Concerning them, Dr. George Ruff, the Air Force psychiatrist who tested them, has explained, “Knowing the qualities that made them this way, and working hard at applying those qualities in your daily life, can help you [too] to come closer to achieving what they have become: comfortable, mature, and well-integrated individuals. It is a worthwhile goal.” Of course, by this writing (June 1960), it is commonly accepted that our new NROL-82 satellite has the function of espionage. However, it has remained for a proper scientist to hit the bottom: the professor who has advised us not to reply to any signals we might receive from outer space because the astral beings are likely to be technically more advanced than we and they will come down and eat us up. This projection of the Cold War into the starry vault was favourably reported by the science editor of the Herald Tribune. #RandolphHarris 16 of 24

Is there a possible solution beyond the alternative of an absolutism that breaks down in every radical change of history and a relativism that makes change itself the ultimate principle? I believe that there is, and I think it is implied in the basis of Christian ethics, namely, in the principle of love in the sense of the Greek word agape. This is not said in terms of an apology for Christianity, but under the impetus of the actual problem in our present World-situation. Love, agape, offers a principle of ethics that maintains an eternal, unchangeable element, but makes its realization dependent on continuous acts of a creative intuition. Love is above the law, and also above the natural law in Stoicism and the supranatural law in Catholicism. We can express it as a law; we can say as Jesus and the apostles did, “Thou shalt love.” However, in doing so, we know that this is a paradoxical way of speaking, indicating that the ultimate principle of ethics, which, on the one hand, the power breaking through all commands. And just this ambiguous character of love enables it to be the solution of the question of ethics in a changing World. If we look at the principles of natural law as embodied in the Bill of Rights, we will discover that, taken as the concrete embodiments of the principle of love in a special situation, they are great and true and powerful; they represent love by establishing freedom and equal rights against willfulness and suppression and the destruction of the dignity of human beings. However, taken as eternal laws and applied legalistically to different situations—for example, the early Middle Ages, or the decay and transformation of economic capitalism—these principles become bad ideologies used for the maintenance of decaying institutions and powers. This is why Paul and Luther struggled so profoundly against the “Law,” and why they insisted on the deadening consequences of the law and the vivifying power of love. Love alone can transform itself according to the concrete demands of every individual and social situation without losing its eternity and dignity and unconditional validity. Love can adapt itself to every phase of a changing World. #RandolphHarris 17 of 24

I should like to introduce at this point another Greek word, Kairos, “the right time.” This word, used in everyday Greek, received an emphatic meaning in the language of the New Testament, designating the fulfillment of time in the appearance of the Christ. It has been reinterpreted by German religious socialism in the sense of a special gift and a special task, breaking from eternity into history at a special time. Kairos in this sense is the historical moment when some new, eternally important, manifests itself in temporal forms, in the potentialities and tasks of a special period. It is the power of the prophetic spirit in all period of history to pronounce the coming of such a Kairos, to discover its meaning, and to express the criticism of what is given and the hope for what is to come. All great changes in history are accompanied by a strong consciousness of a Kairos at hand. Therefore, ethics in a changing World must be understood as ethics of the Kairos. The answer to the demand for ethics in a changing World is ethics determined by the Kairos. However, only love is able to appear in every Kairos. Law is not able, because law is the attempt to impose what belonged to a special time on all times. An ideal that appeared at the right time and was valid for this time is now considered to be the ideal for history as a whole, as the form of life in which history shall find its end. The outcome of this attitude is inevitably disillusionment and the rise of ethical libertarianism and relativism. This point at which the dynamic-naturalistic solution, despite its destructive consequences, was in the right, and still battles rightly against Catholic and bourgeois ethics. Or, expressed in terms of church history, this is the point at which Luther was right in his opposition to Aquinas and Calvin. Love, realizing itself from Kairos to Kairos, creates an ethics that is beyond the alternatives of absolute and relative ethics. Though premarital female virginity is one of humankind’s great common denominators, most societies impose standards of conduct on young males as well. These range from strict celibacy to licentious experimentation, often with women of the evening or less affluent women. #RandolphHarris 18 of 24

Curiously, most cultures either frown on “self-love” or flat out condemn it, as a dangerous squandering of the precious vital force or at the very least, a serious breach of decent behaviour. Tellingly, most societies that urge virginity on their young males do little or nothing to punish those who disobey. At various times in the nineteenth and early twentieth centuries, for instance, British and North American morals included caveats against male premarital pleasures of the flesh. However, these changed more precepts never permeated mainstream cultures, and in any case, a penalty for randy male pleasures of the flesh was nonexistent. The only attempts made to enforce male chastity—of which the Male Purity Movement was the most widespread, cohesive, and forceful—were based on moral suasion and/or fear, usually of diseases, sterility, permanent damage to the tender organ, or the loss of vital powers through the lost of vital force. The Aztec revered celibacy for both men and women, though like some Greeks, they also believed it had harmful side effects. The virgin daughter of leading Aztec once came upon an unclothed man and was consumed by desire for him; afterward, she sickened and swelled up. This was a cautionary tale, but it was one to which the Aztecs had no easy solutions. Aztec society reflected this dichotomy. Celibacy was requisite for youth from high-ranking families; indeed, it distinguished them from plebeians, whose intimate indulges were regarded as a mark of inferiority. Among the privileged, celibacy was rigidly enforced for both males and females. Harsh physical punishment awaited transgressors, but the belief that the bodies of the unchaste would remain immature and their brains degenerate was just as compelling a reason to remain chaste. There was also the fear of exposure during penitential exercises. To honour the gods, young men pierced their organ, and anyone who fainted was automatically considered wanton. Celibacy was also mandatory for students at the calmecac or temple. All these privileged youth from high-ranking families has to swear an oath of chastity, and violators—boy or girl—were executed: either strangled, roasted, alive, or pierced by arrows. #RandolphHarris 19 of 24

Every great truth has to fight its way anew. Enemies are obstinate and entrenched, while the memory of a human is weak. The mind’s power is being unscrupulously misused when it seeks to influence others against their own interest and for its selfish purpose. Where there is fierce hatred or monstrous cruelty, be sure that evil forces are present too. One may dispense to others only what one has oneself. If one’s mind is steeped in nihilism, it will be despair which one offers them at worst, or selfish cynicism at best. When we take into consideration of rapid de-massification of interest and lifeways in a largely Third Wave America, we have been using the analogy of nine cars on the highway and a police officer on a motor cycle. Now, picking up where we lift off yesterday. At twenty-five miles per hour: Sputtering along in the slow lane, government bureaucracies and regulatory agencies. Skilled at deflecting criticism and delaying change for decades at a time, pyramidal bureaucracies run the day-to-day affairs of governments all over the World. Politicians know that it is far easier to start a new bureaucracy than to close down an old one, no matter how obsolete or purposeless. Not only do they themselves change slowly; they slow the pace at which business can respond to fast-moving market conditions. A case in point is the excruciatingly long time it takes the U.S. Food and Drug Administration to test and approve new drugs while desperate victims of disease wait—and sometimes die. Government decision-making is so sluggish that it typically takes a decade or more to gain approval for building a new airport runway and often seven or more years to okay a highway project. Ten miles per hour: However, even bureaucrats, as they look out their rearview mirror, can glimpse a car far behind them. This one shoulders along with a flat tire and steam coming our of its radiator, slowing down all the traffic behind it. It is possible it costs $400 billion to maintain this broken heap? The answer is yes, every year. It is the American school system. Designed for mass production, operated like factories, managed bureaucratically, protected by powerful trade unions and politicians dependent on teachers’ votes, America’s schools are perfect reflection of the early twentieth-century economy. The best that can be said of them is that they are no worse than schools in most other advanced countries. #RandolphHarris 20 of 24

While businesses are drive to change by high-speed competition, public school systems are protected monopolies. Parents, innovative teachers and the media clamour for change. Yet, despite a growing number of educational experiments, the core of the U.S. public education remains the factory-style school designed for the industrial age. Can a ten-mile-per-hour education system prepare students for jobs in companies moving at a hundred miles per hour? Five miles per hour: Not all dysfunctional institutions that affect the World economy are national. The economy of every country in the World is substantially influenced, whether directly or not, by global governance—a collection of international Monetary Fund, the World Trade Organization scored of less visible entities that set rules for cross-boundary activities. Some, like the Universal Postal Union, are over a century old. Others sprang up roughly seventy-five years ago during the League of Nations era. Most of the remainder—the WWTO and the World Intellectual Property Organization are exceptions—were created after World War II, half a century ago. Today national sovereignty is being challenged by new forces. New players and new problems are arriving on the international stage. However, the bureaucratic structures and practices of the IGOs remain largely in place. When the 184 nations that form the IMF chose a new head recently, the United States and Germany disagreed sharply over the choice. In the end the German candidate was selected because President Clinton and his secretary Treasury, Larry Summers, concluded that “they could not violate the 50-year-old rule that allows Europe to fill the IMF post.” Three miles per hour: Even slower changing, however, are political structures in the rich countries. U.S. political institutions, from Congress and the White House to the political parties themselves, are being bombarded by demands from more and more different groups, all of which expect faster reaction times from systems built for leisurely debate and bureaucratic indolence. #RandolphHarris 21 of 24

As a then-leading member of the U.S. State Senate, Connie Mack, one complained to us: We never have more than two and a half uninterrupted minutes for anything on Capitol Hill. There’s no time to stop and think or to have anything approaching an intellectual conversation…We have to spend two thirds of our time doing public relations, campaigning or raising campaign funds. I’m on this committee, that task force, the other working group, and who know what else. Do you think I can possibly know enough to make intelligent decisions about all the different things I’m supposed to know about? It’s impossible. There’s no time. So my staff makes more and more decisions. We thanked him for his honesty. And then asked: “and who exactly elected your staff?” The current political system was never designed to deal with the high complexity and frenetic pace of a knowledge-based economy. Parties and elections may come and go. New methods for fund-raising and campaigning are emerging, but the United States of America, where the knowledge economy is most advanced and the Internet allows new political constituencies to form almost instantly, significant change in political structure comes so slowly as to be almost imperceptible. One hardly needs to defend the economic and social importance of political stability. However, immobility is another matter. The U.S. political system, two centuries old, changed fundamentally after the Civil War of 1861-1865 and again in the 1930s after the Great Depression, when it adapted itself more fully to the industrial era. Since then the government has certainly grown. However, as far as basic institutional reform is involved, the U.S. political structure will continue crawling along at three miles per hour, with frequent rest stops at the side of the road, until a constitutional crisis strikes. That could happen sooner than the World thinks. The election of 2000—when the president of the United States was essentially elected by one vote in the Supreme Court—came dangerously close. One mile per hour: Which brings us, finally, to the slowest of all our slow-changing institutions: the law. The law has two parts. One is organizational—courts, bar associations, law schools and law firms. The other is the actual body of law these organizations interpret and defend. #RandolphHarris 22 of 24

While American law firms are changing rapidly—merging, advertising, developing new specialties such as intellectual-property law, teleconferencing, globalizing and struggling to adapt to new competitive realities—American courts and law schools remain basically unaltered. And the pace at which the system operates has remained glacial, with important cases dragging listlessly through the court for years. During the landmark antitrust case against Microsoft, widespread speculation arose that the U.S. government might attempt to break up the company. That, however, would take years to accomplish, by which time technological advances would have rendered the entire case irrelevant. It was, wrote Silicon Valley chronicler Robert X. Cringley, a collision between “hyper-accelerated Internet time” and “judicial time.” The body of law is said to be “living”—but only barely so. It changes every day as Congress writes new laws and courts add new interpretations to existing law. However, the additions represent a minute, if not infinitesimal, percentage of the total. They inflate the volume and sheer mass of law without significantly recodifying or in any way restructuring the system as a whole. Of course, law should change slowly. It provides a needed degree of predictability to society and the economy, applying brakes in times of overly rapid economic and social change However, how slow is slow? Until 2000, a law reduced the benefits paid to U.S. Social Security recipients aged sixty-five to sixty-nine by one dollar for every three the earned over a set amount. Written at a time of massive unemployment, its original purpose was to discourage seniors from working so that more jobs would be available for young people. The law stayed on the books for almost seventy years, prompting Forbes, tongue in cheek, to hail the change under the headlines, “Flash! The Great Depression Is Over.” The U.S. Congress, after decades of debate, also rewrote two of the fundamental laws governing the knowledge economy. Until 1996, one of the fastest-changing industries in the World—telecommunications—was regulated by a sixty-two-year-old laws passed in 1934. #RandolphHarris 23 of 24

In finance, the Glass Steagall Act, which supervised banking in the United States of America, also went unchanged for sixty years. Basic rules for the issuance of stocks and other securities in the United States of America today were written into law in 1933. Today there are more than 8,300 mutual funds representing nearly 250 million accounts and assets of nearly $7 trillion. Yet these massive investments are still basically subject to a law written in 1940, when there were fewer than 300,000 accounts, managed in only 68 funds, with assets amounting to 1/146,000 of today’s total. In yet another field, when a blackout swept across America’s Northeast in 2003, technicians struggling to restore electricity were crippled because they were forced to use “rules developed decades earlier when most power was generated reasonably close to consumers.” Critical laws directly affecting the advanced economy in field such as copyright, patents and privacy remain hopelessly out of date. The knowledge economy has emerged not because of these laws but in spite of them. This is neither stability nor immobility. It is legal rigor mortis. Lawyers may be changing how they work. However, itself is barely in motion. God thought He kept the Universe alone; for all the voice in answer he could wake was but the mocking echo of his own for some tree-hidden cliff across the lake. Some morning from the boulder-broken beach, He would cry out on life, that what it wants is not its own love back in copy speech, but counter-love, original response. And nothing ever came of what He cried unless it was the embodiment that crashed in the cliff’s talus on the other side, and then in the far distant water splashed, but after a time allowed for it to swim, instead of proving human when it neared and someone else additional to Him, as a great buck it powerfully appeared, pushing the crumpled water up ahead, and landed pouring like a waterfall, and stumbled through the rocks with wild tread, and forced the underbrush—and that was all. Our God and God of our fathers, do Thou bless us as we gather here with grateful hearts to consecrate ourselves to Thee. Because Thou wast with us in all our endeavours, our efforts were fruitful, our work not in vain. Be with us, we pray Thee, in years still before us, to show us the way and to guide us, O Lord. May this, Thy House, be our fortress of strength, to give us courage for the challenges in life. #RandolphHarris 24 of 24

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