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CHAPTER ONE FRONTIERS OF BIO L O GY Life, the most important and most fascinating phenomenon within the ken of man, is the subject of this chapter. It is our purpose to offer a brief overview of present understanding of life in its variegated manifestations. No attempt has been made to be comprehensive; examples and illustrations have been chosen because of the drama of certain findings or for the insight they provide. Necessarily, much has gone unsaid. The theme of this presentation is that life can be understood in terms of the laws that govern and flee phenomena that characterize the inanimate, physical universe and' indeed, that living processes can be described only in the language of chemistry and physics. Until the laws of physics and chemistry had been elucidated, it was not possible even to formulate most of the important, penetrating questions concerning the nature of life. For centuries, students of biology, in con- sidering the diversity of life, its seeming distinction from inanimate phenomena, and its general inexplicability, found it necessary, in their imaginations, to invest all living objects with a mysterious life force, "vitalism." But in the late eighteenth century, Lavoisier and Laplace were able to show, within the considerable limits of error of the methods available to them, that the recently formulated laws of conservation of energy and 32
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FRONTIERS OF BIOLOGY 33 mass were valid also in a living guinea pig. The endeavors of thousands of life scientists over the succeeding two centuries have gone far to document the thesis thus begun. Living phenomena are indeed intelligible in physical terms. And although much remains to be learned and understood and the details of many processes remain elusive, those engaged in such studies hold no doubt that answers will be forthcoming in the reasonably near future. Indeed, only two truly major questions remain enshrouded in not quite fathomable mystery: (1) the origin of life, the events that first gave rise to the remarkable cooperative functioning of nucleic acids and proteins that constitutes the genetic apparatus, and (2) the mind-body problem, the physical basis for self-awareness and personality. Great strides have been made in the approaches to both of these problems, but ultimate explana- tions are perceived very dimly indeed. What follows, therefore, is a record of the present "state of the art." Treated are such questions as: Of what chemical compounds are living things composed? By what means are the materials of the environment converted into the compounds characteristic of life? What techniques have been employed to reveal the structures of the huge macromolecules of living cells? How are living cells organized to accomplish their diverse tasks? What is a gene and what does it do? What are the mechanisms that make possible cellular duplication? How does a single fertilized egg utilize its genetic information in the wondrous process by which it develops into a highly differentiated multicellular creature of many widely differing cell types? Flow do differentiated cell types, combined to form organs and tissues, cooperate to make their distinct contributions to the welfare of the organism? What is understood of the structure and function of the nervous system? What is a species? How does speciation occur? What factors give direction to evolution? Is evolution still occurring? Is man evolving still, and if so, can he control his own evolution? What relations obtain among the species in a given habitat? What governs the numbers of any one species in that habitat? Are there defined physiological bases for be- havior? What is known of the bases for perception, emotions, cognition, learning, or memory, for hunger or satiety? For few of these questions, today, are there exact answers; yet the extent to which these are approxi- mated, even now, constitutes a satisfying and exciting tale. In the space available, there is little opportunity to describe how the facts and concepts considered have been garnered in the laboratory or field. The popular press occasionally presents descriptions of scientific "break- throughs," while failing to indicate that no such event stands alone. Each research accomplishment is a bit of information in a large and growing multidimensional mosaic. Each investigator is aware of the history of the problem to which he has addressed himself and of the past and current
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THE LIFE SCIENCES contributions of others. Most successful demonstrations have occurred only when the time has been right and the stage set. Frequently, the idea had been discussed in one or another sense before a definitive demonstration was available. And each bit of information that illuminates a problem reveals a yet deeper layer of questioning to be explored. Most particularly is it necessary to recognize the dependence of the investigator on his experimental tools. Indeed, the history of science, including the life sciences, is the history of the manner in which major problems have been attacked as more powerful and definitive tools have become available. Thus, living cells are invisible to the naked eye, appear as minute boxes or spheres with a denser nucleus by light microscopy, and exhibit an elaborate wealth of subcellular structural detail by electron microscopy. Techniques for isolation of pure proteins were developed in the 1930's and 1940's, but understanding of their structure seemed im- possibly remote. Analytical tools such as electrophoresis (separation of molecules by virtue of differences in their electrical charge), ultracentrif- u~ation (separation by virtue of differences in mass ~ chromatography (separation bv virtue of their varying affinities for adsorption onto diverse ~ ~ , , _ solid surfaces combined with their varying SolUclllly in diverse solvents), and appreciation of the specificity of action of certain hydrolytic enzymes permitted resolution of the linear sequences of amino acids along the strand that constitutes the protein chain. Without each of these tools, primary protein structure would remain a mystery. As they became available, the tools were rapidly applied to the problem by a waiting battalion of scientists, and a seemingly herculean task became almost routine. But there remained the problem of deciphering the three-dimensional structure of these large molecules. It was already known that x-ray crystallography could establish the structure of much smaller molecules; a series of refinements was re- quired before this technique could be applied to proteins. But when these refinements were made, there remained a prodigious body of calculations required to convert the data into a model of a protein molecule. Fortu- nately, it was just at this time that the high-speed digital computer made its appearance. And the three-dimensional structures of proteins emerged as the triumphal accomplishment of this pyramid of scientific endeavor. Until all the bricks had been laid, the apex would have remained invisible and unattainable. Biology has become a mature science as it has become precise and quantifiable. The biologist is no less dependent upon his apparatus than the physicist. Yet the biologist does not use distinctively biological tools; he is an opportunist who employs a nuclear magnetic resonance spec- trometer, a telemetry assembly, or an airplane equipped for infrared pho
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FRONTIERS OF BIOLOGY tography, depending upon the biological problem he is attacking. In any case, he is always grateful to the physicists, chemists, and engineers who have provided the tools he has adapted to his trade. Much as the biologist will employ whatever tool appears necessary to his inquiry, so too is he catholic in his use of biological forms for investi- gations. While mindful of the potential practical implications of his studies, the biologist does not restrict himself to the utilization of those species that appear closest to human concern. Rather does he select biological material particularly suitable for the problem at hand. Thus, the "alarm reaction" of the clam, among the least frantic of animals, reveals in slow motion the essentials of reactions that, in most other species, are too rapid to be readily analyzed. Escherichia coli, the innocuous colon bacillus, is utilized in a great variety of metabolic and genetic studies, largely because it can be safely handled in large quantities and is now a well-characterized organism. Other aspects of genetics are best observed in the huge chromosomes of fruit flies. The giant axon of the squid lends itself to studies of neurophysi- ology, particularly the mechanism of neuronal conduction, while the kidney tubules of the kangaroo rat have proved invaluable in elucidating the mechanism by which the kidney secretes an extraordinarily concentrated urine. Plant galls are simplified analogues of animal tumors that permit dissection of the elements of neoplasia. Domestic rodents-mice, rats, guinea pigs have been employed on a large scale because they are cheap, breed relatively easily in captivity, are available in genetically homogeneous stocks, offer useful models of human disease states, and are now more thoroughly understood than are most other animal species. The cellular events of viral infection have been elucidated through detailed examination of infection of bacteria with bacteria-specific viruses, the bacteriophages. The simpler nervous systems of invertebrates such as insects and crabs offer models of neuronal integration, and their understanding paves the way for the immensely more complex nervous activity of the mammalian brain. In each instance, the vast diversity of life permits selection of a par- ticularly suitable study object. With the understanding so gained, subse- quent examination of man or of the plants or animals important to his well-being is enormously simplified. In this sense, the approach to bio- logical problems resembles the approach to many physical problems: the investigator seeks the most appropriate conditions for his experiments, conditions involving a minimum number of variables, all of which he may bring under control. It is regrettable that even well-intentioned critics have occasionally mistaken the biologists' search for the simplest possible model for dabbling with the inconsequential, failing to comprehend that, through
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