4. The Mechanistic View of Life
While the new physics was developing in the twentieth century, the mechanistic Cartesian world view and the principles of Newtonian physics maintained their strong influence on Western scientific thinking, and even today many scientists still hold to the mechanistic paradigm, although physicists themselves have gone beyond it.
However, the new conception of the universe that has emerged from modem physics does not mean that Newtonian physics is wrong, or that quantum theory, or relativity theory, is right. Modern science has come to realize that all scientific theories are approximations to the true nature of reality; and that each theory is valid for a certain range of phenomena. Beyond this range it no longer gives a satisfactory description of nature, and new theories have to be found to replace the old one, or, rather, to extend it by improving the approximation. Thus scientists construct a sequence of limited and approximate theories, or 'models,' each more accurate than the previous one but none of them representing a complete and final account of natural phenomena. Louis Pasteur said it beautifully: 'Science advances through tentative answers to a series of more and more subtle questions which reach deeper and deeper into the essence of natural phenomena.'1
The question, then, will be: How good an approximation a the Newtonian model as a basis for various sciences, and where are the limits of the Cartesian world view in those fields? In physics the mechanistic paradigm had to be abandoned at the level of the very small (in atomic and subatomic physics) and the level of the very large (in astro-physics and cosmology). In other fields the limitations may be of differ -ent kinds; they need not be connected with the dimensions of the phenomena to be described. What we are concerned with is not so much the application of Newtonian physics to other phenomena, but rather the application of the mechanistic world view on which Newtonian physics is based. Each science will need to find out the limitations of this world view in each context.
In biology the Cartesian view of living organisms as machines, constructed from separate parts, still provides the dominant conceptual framework. Although Descartes' simple mechanistic biology could not be carried very far and had to be modified considerably during the subsequent three hundred years, the belief that all aspects of living organisms can be understood by reducing them to their smallest constituents, and by studying the mechanisms through which these interact, lies at the very basis of most contemporary biological thinking. This passage from a current textbook on modern biology is a clear expression of the reductionist credo: 'One of the acid tests of understanding an object is the ability to put it together from its component parts. Ultimately, molecular biologists will attempt to subject their understanding of cell structure and function to this sort of test by trying to synthesize a cell.'2
Although the reductionist approach has been extremely successful in biology, culminating in the understanding of the chemical nature of genes, the basic units of heredity, and in the unraveling of the genetic code, it nevertheless has its severe limitations. As the eminent biologist Paul Weiss has observed,
We can assert definitely… on the basis of strictly empirical investigations, that the sheer reversal of our prior analytic dissection of the universe by putting the pieces together again, whether in reality or just in our minds, can yield no complete explanation of the behavior of even the most elementary living system.3
This is what most contemporary biologists find hard to admit. Carried away by the successes of the reductionist method, most notable recently in the field of genetic engineering, they tend to believe that it is the only valid approach, and they have organized biological research accordingly. Students are not encouraged to develop inteerative concepts, and research institutions direct their funds almost exclusively toward the solution of problems formulated within the Cartesian framework. Biological phenomena that cannot be explained in reductionist terms are deemed unworthy of scientific investigation. Consequently biologists have developed very curious ways of dealing with living organisms. As the distinguished biologist and human ecologist Rene Dubos has pointed out, they usually feel most at ease when the thing they are studying is no longer living.4
It is not easy to determine the precise limitations of the Cartesian approach to the study of living organisms. Most biologists, being fervent reductionists, are not even interested in discussing this question, and it has taken me a long time and considerable effort to find out where the Cartesian model breaks down. ^ The problems that biologists cannot solve today, apparently because of their narrow, fragmented approach, all seem to be related to the function of living systems as wholes and to their interactions with their environment. For example, the integrative action of the nervous system remains a profound mystery. Although neuroscientists have been able to clarify many aspects of brain functioning, they still do not understand how neurons* (*Neurons are nerve cells that have the ability to receive and transmit nervous impulses.) work together - how they integrate themselves into the functioning of the whole system. In fact such a question is hardly ever asked. Biologists are busy dissecting the human body down to its minute components, and in doing so are gathering an impressive amount of knowledge about its cellular and molecular mechanisms, but they still do not know how we breathe, regulate our body temperature, digest, or focus our attention. They know some of the nervous circuits, but most of the integrative actions remain to be understood. The same is true of the healing of wounds, and the nature and pathways of pain also remain largely mysterious.
An extreme case of integrative activity that has fascinated scientists throughout the ages but has, so far, eluded all explanation is the phenomenon of embryogenesis - the formation and development of the embryo - which involves an orderly series of processes through which cells specialize to form the different tissues and organs of the adult body. The interaction of each cell with its environment is crucial to these processes, and the whole phenomenon is a result of the integral coordinating activity of the entire organism - a process far too complex to lend itself to reductionist analysis. Thus embryogenesis is considered a highly interesting but quite unrewarding topic for biological research.
The reason why most biologists are not concerned with the limitations of the reductionist approach is understandable. The Cartesian method has brought spectacular progress in certain areas and continues to produce exciting results. The fact that it is inappropriate for solving other problems has left these problems neglected, if not outright shunned, even though the proportions of the field as a whole are thereby severely distorted.
How, then, is this situation going to change? I believe that the change will come through medicine. The functions of a living organism that do not lend themselves to a reductionist description - those representing the organism's integrative activities and its interactions with the environment - are precisely the functions that are crucial for the organism's health. Because Western medicine has adopted the reductionist approach of modern biology, adhering to the Cartesian division and neglecting to treat the patient as a whole person, physicians now find themselves unable to understand, or to cure, many of today's major illnesses. There is a growing awareness among them that many of the nroblems our medical system faces stem from the reductionist model of the human organism on which it is based. This is recognized not only by physicians but also, and even more so, by nurses and other health professionals, and by the public at large. There is already considerable pressure on physicians to go beyond the narrow, mechanistic framework of contemporary medicine and develop a broader, holistic approach to health.
Transcending the Cartesian model will amount to a major revolution in medical science, and since current medical research is closely linked to research in biology - both conceptually and in its organization - such a revolution is bound to have a strong impact on the further development of biology. To see where this development may lead, it is useful to review the evolution of the Cartesian model in the history of biology. Such a historical perspective also shows that the association of biology with medicine is not something new but goes back to ancient times and has been an important factor throughout its history.6
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The two outstanding Greek physicians, Hippocrates and Galen, both contributed decisively to the biological knowledge of antiquity and remained authoritative figures for medicine and biology throughout the Middle Ages. During the medieval era, when the Arabs became the custodians of Western science and dominated all its disciplines, biology was again advanced by physicians, the most famous being Rhazes, Avicenna, and Averroes, all of whom were also outstanding philosophers. During that rime Arab alchemists, whose science was traditionally associated with medicine, were the first to attempt chemical analyses of living matter and, in doing so, became the precursors of modern biochemists.
The close association between biology and medicine continued through the Renaissance and into the modem era, where decisive advances in the life sciences were achieved again and again by scientists with medical backgrounds. Thus Linnaeus, the great classifier of the eighteenth century, was not only a botanist and zoologist but also a physician, and in fact botany itself developed from the study of plants with healing powers. Pasteur, though not a physician himself, laid the foundations of microbiology that were to revolutionize medical science. Claude Bernard, the founder of modem physiology, was a physician; Matthias Schleiden and Theodor Schwann, the originators of cell theory, had medical degrees, and so did Rudolf Virchow, who formulated cell theory in its modern form. Lamarck had medical training, and Darwin also studied medicine, albeit with very little success. These are just a few examples of the constant interplay between biology and medicine which is continuing in our time, where a significant proportion of funds for biological research is provided by medical institutions, [t is quite likely, therefore, that medicine and biology will once more be revolutionized together when biomedical researchers recognize the need to go beyond the Cartesian paradigm to make further progress in the understanding of health and illness.
The Cartesian model of biology has had many failures and many successes since the seventeenth century. Descartes created an uncompromising image of living organisms as mechanical systems and thus established a rigid conceptual framework for subsequent research in physiology, but he did not spend much time on physiological observation or experiments and left it to his followers to work out the details of the mechanistic view of life. The first to be successful in this attempt was Giovanni Borelli, a student ofGalileo, who managed to explain some basic aspects of muscle action in mechanistic terms. But the great triumph of seventeenth-century physiology came when William Harvey applied the mechanistic model to the phenomenon of blood circulation and solved what had been the most fundamental and difficult problem in physiology since ancient times. His treatise, On the Movement of the Heart, gives a lucid description of all that could be known of the blood system in terms of anatomy and hydraulics without the aid of a microscope. It represents the crowning achievement of mechanistic physiology and was praised as such with great enthusiasm by Descartes himself.
Inspired by Harvey's success, the physiologists of his time tried to apply the mechanistic method to describe other bodily functions, such as digestion and metabolism, but all their attempts were dismal failures. The phenomena physiologists tried to explain - often with the help of grotesque mechanical analogies - involved chemical and electrical processes that were unknown at the time and could not be described in mechanical terms. Although chemistry did not advance very far in the seventeenth century, there was a school of thought, rooted in alchemical tradition, that tried to explain the functioning of living organisms in terms of chemical processes. The originator of this school was Paracelsus von Hohenheim, a sixteenth-century medical pioneer and extremely successful healer, half sorcerer and half scientist, and altogether a most extraordinary figure in the history of medicine and biology. Paracelsus, who practiced his medicine as an art and an occult science based on alchemical concepts, believed that life was a chemical process and that disease was the result of an imbalance in the body chemistry. Such a view of illness was far too revolutionary for the science of his time and had to wait several hundred years to gain broad acceptance.
In the seventeenth century physiology was divided into two opposing camps. On the one side were the followers of Paracelsus, who called themselves 'iatrochemists'* (*From the Greek iatros (physician).) and believed that physiological functions could be explained in chemical terms. On the other side were those known as 'tatromechanists/ who followed the Cartesian approach and held that mechanical principles were the basis of all bodily functions. The mechanists, of course, were in the majority and continued to construct elaborate mechanical models which were often patently false but adhered to the paradigm thai dominated seventeenth-century scientific thought.
This situation changed considerably in the eighteenth century, which saw a scries of important discoveries in chemistry, including the discovery of oxygen and Antoine Lavoisier's formulation of the modern theory of combustion. The 'father of modern chemistry' also demonstrated that respiration is a special form of oxidation and thus confirmed the relevance of chemical processes to the functioning of living organisms. At the end of the eighteenth century a further dimension was added to physiology when Luigi Galvani demonstrated that the transmission of nerve impulses was associated with an electric current. This led Alessandro Volta to the study of electricity and thus became the source of two new sciences, neurophysiology and electrodynamics.
These developments raised physiology to a new level of sophistication. The simplistic mechanical models of living organisms were abandoned, but the essence of the Cartesian idea survived. Animals were still machines, although they were much more complicated than mechanical clockworks, involving chemical and electrical phenomena. Thus biology ceased to be Cartesian in the sense of Descartes' strictly mechanical image of living organisms, but it remained Cartesian in the wider sense of attempting to reduce all aspects of living organisms to the physical and chemical interactions of their smallest constituents. At the same time the strict mechanistic physiology found its most forceful and elaborate expression in the polemical treatise, Man a Machine, by La Mettrie, which remained famous well beyond the eighteenth century. La Mettrie abandoned the mind-body dualism of Descartes, denying that humans were essentially different from animals and comparing the human organisms, including its mind, to an intricate clockwork:
Does one need more … to prove that Man is but an Animal, or an assemblage of springs which all wind up one another in such a way that one cannot say at which point of the human circle Nature has begun? ... Indeed, I am not mistaken; the human body is a clock, but immense and constructed with such ingenuity and skill that if the wheel whose function it is to mark the seconds comes to a halt, that of the minutes turns and continues its course. 7
La Mettrie's extreme materialism generated many debates and controversies, some of which reached into the twentieth century. As a young biologist Joseph Needham wrote an essay in defense of La Mettrie, published in 1928 and entitled, like La Mettrie's original, Man a Machine 8 Needham made it clear that for him - at least at that time - science was to be identified with the mechanistic Cartesian approach. ^Mechanism and materialism,' he wrote, 'lie at the foundation of scientific thought,'9 and he explicitly included the study of mental phenomena in such a science: *I by no means accept the opinion that the phenomena of the mind are not amenable to physico-chemical description. All that we shall ever know of them scientifically will be mechanistic . . . '10
Toward the end of his essay Needham summed up his position on the scientific view of human nature with the forceful statement: 'In science, man is a machine; or if he is not, then he is nothing at all.'11 Nevertheless, Needham later left the Held of biology to become one of the leading historians of Chinese science and, as such, an ardent advocate of the organismic world view that is the basis of Chinese thought.
It would be foolish to categorically deny Needham's claim that scientists will be able, some day, to describe all biological phenomena in terms of the laws of physics and chemistry, or rather, as we would say today, in terms of biophysics and biochemistry. But this does not mean that these laws will be based on the view of living organisms as machines. To say so would be restricting science to Newtonian science. To understand the essence of living systems, scientists - whether in biophysics, biochemistry, or any other discipline concerned with the study of life - will have to abandon the reductionist belief that complex organisms can be described completely, like machines, in terms of the properties and behavior of their constituents. This should be easier to do today than in the 1920s, since the reductionist approach has had to be abandoned even in the study of inorganic matter.
In the history of the Cartesian model in the life sciences^ the nineteenth century brought impressive new developments because of the remarkable advances in many areas of biology. The nineteenth century is best known for the establishment of the theory of evolution, but it also saw the formulation of cell theory, the beginning of modern embryology, the rise of microbiology, and the discovery of the laws of heredity. Biology was now firmly grounded in physics and chemistry, and scientists devoted all their efforts to the search for physicochemical explanations of life.
One of the most powerful generalizations in all of biology was the recognition that all animals and plants are composed of cells. It marked a decisive turn in the biologists' understanding of body structure, inheritance, fertilization, development and differentiation, evolution, and many other characteristics of life. The term 'cell' was coined by Robert Hooke in the seventeenth century to describe various minute structures he saw through the newly invented microscope, but the development of a proper cell theory was a slow and gradual process that involved the work of many researchers and culminated in the nineteenth century, when biologists thought that they had definitely found the fundamental units of life. This belief gave the Cartesian paradigm a new meaning. From now on, all functions of a living organism had to be understood in terms of its cells. Rather than reflecting the organization of the organism as a whole, biological functions were seen as the results of the interactions between the cellular building blocks.
Understanding the structure and functioning of cells involves a problem that has become characteristic of all modern biology. The organization of a cell has often been compared to that of a factory, where different parts are manufactured at different sites, stored in intermediate facilities, and transported to assembly plants to be combined into finished products that are either used up by the cell itself or exporteu to other cells. Cell biology has made enormous progress in understanding the structures and functions of many of the cell's subunits, but it has remained largely ignorant about the coordinating activities that ntegrate those operations into the functioning of the cell as a whole. The complexity of this problem is increased considerably by the fact that, unlike those of a human-made factory, the equipment and machinery of a cell are not nermanent fixtures but are periodically disassembled and rebuilt, always according to specific patterns and in harmony with the overall dynamics of cell functioning. Biologists have come to realize that cells are organisms in their own right, and they are becoming increasingly aware that the integrative activities of these living systems - especially the balancing of their interdependent metabolic* (* Metabolism, from the Greek meiaboie ('change'), denotes the sum of i-'heniical changes, occurring in living organisms, and in particular in celh, •hai are necessary in sustain life.) pathways and cycles-cannot be understood within the reductionist framework.
The invention of the microscope in the seventeenth century had opened up a new dimension for biology, but the instrument was not fully exploited until the nineteenth century, when various technical problems with the old lens system were finally solved. The newly perfected microscope generated an entire new field of research, microbiology, which revealed an unsuspected richness and complexity of living organisms of microscopic dimensions. Research in this field was dominated by the genius of Louis Pasteur, whose penetrating insights and clear formulations made a lasting impact on chemistry, biology, and medicine.
With the use of ingenious experimental techniques, Pasteur was able to clarify a question that had agitated biologists throughout the eighteenth century, the question of the origin of life. Since ancient times it had been the common belief that life, at least in its lower forms, could arise spontaneously from nonliving matter. During the seventeenth and eighteenth centuries that idea - known as 'spontaneous generation' - was questioned, but the argument could not be settled until Pasteur demonstrated conclusively, with a series of clearly designed and rigorous experiments, that any microorganisms which developed under suitable conditions came from other microorganisms. It was Pasteur who brought to light the immense variety of the organic world at the level of the very small. In particular he was able to establish the role of bacteria in certain chemical processes, such as fermentation, and thus helped to lay the foundations of the new science of biochemistry.
After twenty years of research on bacteria, Pasteur turned to the study of diseases in higher animals and achieved another major advance - the demonstration of a definite correlation between germs* (^Germ* and 'microbe' are early synonyms for the now generally used term ' microorganism', 'bacterium' denotes a large group of microorganisms and 'bacillus' refers to a particular kind of bacterium. ) and disease. Although this discovery had a tremendous impact on the development of medicine, the exact nature of the correlation between bacteria and disease is still widely misunderstood. Pasteur's 'germ theory of disease,' in its simplistic and reductionist interpretation, meant that biomedical researchers tended to regard bacteria as the only cause of disease. Consequently, they became obsessed with the identification of microbes and with the illusory goal of designing 'magic bullets,' drugs that would destroy specific bacteria without damaging the rest of the organism.
The reductionist view of disease eclipsed an alternative theory that had been taught a few decades earlier by Claude Bernard, a celebrated physician who is generally considered the founder of modern physiology. Although Bernard, adhering to the paradigm of his time, saw the living organism as 'a machine which necessarily works by virtue of the physico-chemical properties of its constituent elements,'12 his view of physiological functions was much subtler than those of his contemporaries. He insisted on the close and intimate relation between an organism and its environment, and was the first to point out that there was also a milieu interieur, an internal environment in which the organs and tissues of the organism lived. Bernard observed that in a healthy organism this milieu inlerieur remains essentially constant, even when the external environment fluctuates considerably. This discovery led him to formulate the famous dictum: The constancy of the internal environment is the essential condition of independent life.''3
Claude Bernard's strong emphasis on internal balance as a condition for health could not hold its ground against the rapid spread of the reductionist view of disease among biologists and physicians. The importance of his theory was rediscovered only in the twentieth century, when researchers became more aware of the crucial role of the environment in biological phenomena. Bernard's concept of the constancy of the internal environment has now been further elaborated and has led to the important notion of homeosta&is, a word coined by the neurologist "Walter Cannon to denote the tendency of living organisms to maintain a state of internal balance.14
The theory of evolution was biology's major contribution to the history of ideas in the nineteenth century. It forced scientists to abandon the Newtonian picture of the world as a machine that had emerged fully constructed from the hands of its Creator, and to replace it with the concept of an evolving and ever changing system. This did not, however, lead biologists to modify the reductionist paradigm; on the contrary, they concentrated on fitting the Darwinian theory into the Cartesian framework. They were extremely successful in explaining many of the physical and chemical mechanisms of heredity, but were unable to understand the essential nature of development and evolution.15
The first theory of evolution was formulated by Jean Bap-tiste Lamarck, a self-taught scientist who invented the word 'biology' and turned to the study of animal species at the age of almost fifty. Lamarck observed that animals changed under environmental pressure, and he believed that they could pass on these changes to their offspring. This passing on of acquired characteristics was for him the main mechanism of evolution. Although it turned out that Lamarck was wrong in that respect,"' his recognition of the phenomenon of evolution - the emergence of new biological structures in the history of species - was a revolutionary insight that profoundly affected all subsequent scientific thought.
In particular, Lamarck had a strong influence on Charles Darwin, who started his scientific career as a geologist but became interested in biology during an expedition to the Galapagos Islands, where he observed the great richness and variety of island fauna. These observations stimulated Darwin to speculate about the effect of geographical isolation on the formation of species and led him, eventually, to the formulation of his theory of evolution. Other major influences on Darwin's thought were the evolutionary ideas of geologist Charles Lyell, and the economist Thomas Malthus' idea of a competitive struggle for survival. Out of these observations and studies emerged the twin concepts on which Darwin based his theory - the concept of chance variation, later to be called random mutation, and the idea of natural selection through the 'survival of the fittest.'
Darwin published his theory of evolution in 1859 in his monumental On the Origin of Species and completed it twelve years later with The Descent of Man, in which the concept of evolutionary transformation of one species into another is extended to include human beings. Here Darwin showed that his ideas about human traits were strongly colored by the patriarchal bias of his time, in spite of the revolutionary nature of his theory. He saw the typical male as strong, brave and intelligent; the typical female was passive, weak in body, and deficient in brains. 'Man,' he wrote, 'is more courageous, pugnacious, and energetic than woman, and has more inventive genius'17
Although Darwin's concepts of chance variation and natural selection were to remain the cornerstones of modern evolutionary theory, it soon became clear that chance variations, as envisaged by Darwin, could never explain the emergence of new characteristics in the evolution of species. Nineteenth-century views of heredity were based on the assumption that the biological characteristics of an individual represented a 'blend' of those of its parents, with bothparents contributing more or less equal parts to the mixture. This meant that an offspring of a parent with a useful chance variation would inherit only 50 percent of the new characteristic and would be able to pass on only 25 percent of it to the next' generation. Thus the new characteristic would be diluted rapidly, with very little chance of establishing itself through natural selection. Darwin himself recognized that this was a serious flaw in. his theory for which he had no
It is ironic that the solution to Darwin's problem was discovered by Gregor Mendel only a few years after the publication of the Darwinian theory, but was ignored until the rediscovery of Mendel's work at the turn of the century. From his careful experiments with garden peas, Mendel deduced that there were 'units of heredity' - later to be called genes - that did not blend in the process of reproduction and thus become diluted, but were transmitted from generation to generation without changing their identity. With this discovery it could be assumed that random mutations would not disappear within a few generations but would be preserved, to be either reinforced or eliminated by natural selection.
Mendel's discovery not only played a decisive role in establishing the Darwinian theory of evolution but also opened up a whole new field of research - the study of heredity through the investigation of the chemical and physical nature of genes. William Bateson, a fervent advocate and popularizer of Mendel's work, named this new field "genetics' at the biginning of the century and introduced many of the terms now used by geneticists. He also named his youngest son Gregory, in MendeFs honor.
In the twentieth century genetics became the most active area in biological research and provided a strong reinforcement of the Cartesian approach to living organisms. It became clear quite early that the material of heredity lay in the chromosomes, those threadlike bodies that are present in the nucleus of every cell. Soon thereafter it was recognized that the genes occupied specific positions within the chromosomes; to be precise, they are arranged along the chromosomes in linear order. With these discoveries geneticists believed that they had now pinned down the 'atoms of heredity' and proceeded to explain the biological characteristics of living organisms in terms of their elementary units, the genes, with each gene corresponding to a definite hereditary trait. Soon, however, further research showed that a single gene may affect a wide range of traits and that, conversely, many separate genes often combine to produce a single trait. Obviously the study of the cooperation and integrative activity of genes is of first importance, but here too the Cartesian framework has made it difficult to deal with these questions. When scientists reduce an integral whole to fundamental building blocks - whether they are cells, genes, or elementary particles — and try to explain all phenomena in terms of these elements, they lose the ability to understand the coordinating activities of the whole system.
Another fallacy of the reductionist approach in genetics is the belief that the character traits of an organism are uniquely determined by its genetic makeup. This 'genetic determinism' is a direct consequence of regarding living organisms as machines controlled by linear chains of cause and effect. It ignores the fact that the organisms are multileveled systems, the genes being embedded in the chromosomes, the chromosomes functioning within the nuclei of their cells, the cells incorporated in the tissues, and so on. All these levels are involved in mutual interactions that influence the organism's development and result in wide variations of the 'genetic blueprint.'
Similar arguments apply to the evolution of a species. The Darwinian concepts of chance variation and natural selection are only two aspects of a complex phenomenon that can be understood much better within a holistic, or systemic, framework.18 Such a framework is much more subtle and useful than the dogm-'tic position of so-called neo-Darwinian theory, forcefully expressed by the geneticist and Nobel laureate Jacques Monod:
Chance alone is at the source of every innovation, of all creation in the biosphere. Pure chance, absolutely free but blind, at the very root of the stupendous edificeof evolution: this central concept of modern biology is no longer one among other conceivable hypotheses. It is today the sole conceivable hypothesis, the only one that squares with observed and tested fact. And nothing warrants the supposition - or the hope - that on this score our position is likely ever to be revised.'19
More recently the fallacy of genetic determinism has given rise to a widely discussed theory known as sociobiology, in which all social behavior is seen as predetermined by genetic structure.20 Numerous critics have pointed out that this view is not only scientifically unsound but also quite dangerous. It encourages pseudoscientific justifications for racism and sexism by interpreting differences in human behavior as genetically preprogrammed and unchangeable.21
Although genetics was very successful in clarifying many aspects of heredity during the first half of the twentieth century, the exact chemical and physical nature of its central concept, the gene, remained a mystery. The complicated chemistry of the chromosomes was not understood until the 1950s and 1960s, a full century after Darwin and Mendel.
Meanwhile, the new science of biochemistry progressed steadily and established the firm belief among biologists that all properties and functions of living organisms would eventually be explained in chemical and physical terms. This belief was most clearly expressed by Jacques Loeb in The Mechanistic Conception of Life, which had a tremendous influence on the biological thinking of its time. 'Living organisms are chemical machines,' wrote Loeb,22 'possessing the peculiarity of preserving and reproducing themselves.' To explain the functioning of these machines completely in terms of their basic building blocks was for Loeb, as for all redLctionists, the essence of the scientific approach: 'The ultimate aim of the physical sciences is the visualization of all phenomena in terms of groupings and displacements of ultimate particles, and since there is no discontinuity between the matter constituting the living and the non-living world, the goal of biology can be expressed in the same way.'23
An extremely unfortunate consequence of the view of living things as machines has been excessive use of vivisection* (^Vivisection, in a broad sense, includes all types of experiments on living animals, whether or not cutting is done, and especially those considered to cause distress, to the subject. ) in biomedical and behavioral research.24 Descartes himself defended vivisection, believing that animals do not suffer and asserting that their cries meant nothing more than the creaking of a wheel; today the inhuman practice of systematically torturing animals still exists in the life sciences.
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In the twentieth century a significant shift occurred in biological research that may well turn out to be the last step in the reductionist approach to the phenomena of life, leading to its greatest triumph and, at the same time, to its end. Whereas cells were regarded as the basic building blocks of living organisms during the nineteenth century, the attention shifted from cells to molecules toward the middle of our century, when geneticists began to explore the molecular structure of the gene. Their research culminated in the elucidation of the physical structure of DNA - the molecular basis of chromosomes - which stands as one of the greatest achievements of twentieth-century science. This triumph of molecular biology has led biologists to believe that all biological functions can be explained in terms of molecular structures and mechanisms, which has considerably distorted research in the life sciences.
In a general sense the term 'molecular biology* refers to the study of any biological phenomenon in terms of the molecular structures and interactions involved in it. More specifically, it has come to mean the study of the very large biological molecules known as macromolecules. During the first half of the century it became clear that the essential constituents of all living cells - the proteins and nucleic acids** (Nucleic acids - the acids found in cell nuclei - are of two basically different kinds, known as DNA and RNA.) - were highly complex, chamlike structures containing thousands of atoms. The investigation of the chemical properties and exact three-dimensional form of these large chain molecules became the principal task of molecular biology.25
The first important step toward a molecular genetics came with the discovery that cells contain agents, called enzymes, that can promote specific chemical reactions. During the first half of the century biochemists managed to specify most of the chemical reactions that occur in cells, and found out that the most important of these reactions are essentially the same in all living organisms. Each of them depends crucially on the presence of a particular enzyme, and thus the study of enzymes became of primary importance.
During the 1940s geneticists achieved another decisive insight when they discovered that the primary function of genes was to control the synthesis of enzymes. With this discovery the broad outlines of the hereditary process emerged: genes determine hereditary traits by directing the synthesis of enzymes, which in turn promote the chemical reactions corresponding to those traits. Although these discoveries represented major advances in understanding heredity, the nature of the gene remained unknown during this period. Geneticists ignored its chemical structure and were unable to explain how it managed to carry out its essential functions: the synthesis of enzymes, its own faithful replication in the process of cell division, and the sudden permanent changes known as mutations. As far as the enzymes were concerned, it was known that they were proteins, but their precise chemical structure was unknown and so, as a consequence, was the process by which enzymes promote chemical reactions.
This situation changed dramatically over the next two decades, which brought the major breakthrough in modem genetics, often referred to as the breaking of the genetic code:
the discovery of the precise chemical structure of genes and enzymes, of the molecular mechanisms of protein synthesis, and of the mechanisms of gene replication and mutation.26 This revolutionary achievement involved tremendous struggle and fierce competition, as well as stimulating collaboration, among a group of outstanding and highly original men and women, the main protagonists being Francis Crick, James Watson, Maurice Wilkins, Rosalind Franklin, Linus Pauling, Salvador Luria, and Max Delbriick.
A crucial element in the breaking of the genetic code was the fact that physicists moved into biology. Max Delbriick, Francis Crick, Maurice Wilkins, and several others had backgrounds in physics before they joined the biochemists and geneticists in their study of heredity. These scientists brought with them a new rigor, a new perspective, and new methods that thoroughly transformed genetic research. The interest of physicists in biology had begun in the 1930s, when Niels Bohr speculated about the relevance of the uncertainty principle and the concept of complementarity to biological research.27 Bohr's speculations were further elaborated by Delbnick, whose ideas about the physical nature of genes led Erwin Schrodinger to write a small book entitled What Is Life? This book became a major influence on biological thought in the 1940s and was the main reason for several scientists to leave physics and turn to genetics.
The fascination of What Is Life? came from the clear and compelling way in which Schrodinger treated the gene not as an abstract unit but as a concrete physical substance, advancing definite hypotheses about its molecular structure that stimulated scientists to think about genetics in a new way. He was the first to suggest that the gene could be viewed as an information carrier whose physical structure corresponds to a succession of elements in a hereditary code script. Schro-dinger's enthusiasm convinced physicists, biochemists, and geneticists that a new frontier of science had opened where great discoveries were imminent. From now on these scientists began to refer to themselves as ^molecular biologists.'
The basic structure of the biological molecules was discovered in the early 1950s through the confluence of three powerful methods of observation - chemical analysis, electron microscopy, and X-ray crystallography.* (*X-ray crystallography, invented in 1912 by Lawrence Bragg, is the ineltiod of determining the orderly array of atoms in molecular structures - criginally crystals - by analyzing the ways in which X-rays are scattered by those structures. ) The first breakthrough came when Linus Pauling determined the structure of the protein molecule. Proteins were known to be long chain molecules, consisting of a sequence of different compounds, known asamino acids, linked end-to-end. Pauling showed that the backbone of the protein structure is coiled in a left-handed or right-handed helix, and that the rest of the structure is determined by the exact linear sequence of amino acids along this helical path. Subsequent further studies of the protein molecule showed how the specific structure of enzymes allows them to bind the molecules whose chemical reactions they promote.
Pauling's great success inspired James Watson and Francis Crick to concentrate all their efforts on elucidating the structure of DNA, which by then had been recognized as the genetic material in the chromosomes. After two years of strenuous work, of many false starts and great disappointments, Watson and Crick were finally rewarded with success. Using the X-ray data of Rosalind Franklin and Maurice Wilkins, they were able to determine the precise architecture of DNA, which is called the Watson-Crick structure. It is a double helix made up of two intertwined, structurally complementary chains. The compounds arranged on these chains in linear order are complex structures, known as nucleotides and existing in four different kinds.
It took another decade to understand the basic mechanism through which the DNA carries out its two fundamental functions: self-replication and protein synthesis. This research, again led by Watson and Crick, revealed explicitly how genetic information is encoded in the chromosomes. To put it in greatly simplified terms, chromosomes are made of DNA molecules exhibiting me Watson-Crick structure. A gene is that length of a DNA double helix which specifies the structure of a particular enzyme. The synthesis of this enzyme occurs through a complicated two-step process involving RNA, the second nucleic acid. The elements of the hereditary code script are the four nucleotides which embody the genetic information in their aperiodic sequence along the chain. This linear sequence of nucleotides in the gene determines the linear sequence ofamino acids in the corresponding enzyme. In the process of chromosome division, the two chains of the double helix separate, and each of them serves as a template for the construction of a new complementary chain. Gene mutation is caused by a chance error in this duplication process by which one nucleotide is substituted for another, resulting in a permanent change in the information carried by the gene.
These, then., are the basic elements of what has been hailed as the greatest discovery in biology since Darwin's theory of evolution. Advancing to ever smaller levels in their exploration of the phenomena of life, biologists found that the characteristics of all living organisms - from bacteria to humans - were encoded in their chromosomes in the same chemical substance, using the same code script. After two decades of intensive research, the precise details of this code had been unraveled. Biologists had discovered the alphabet of a truly universal language of life.
The spectacular success of molecular biology in the field of genetics led scientists to apply its methods to all areas of biology in an attempt to solve all problems by reducing them to their molecular level. Thus most biologists became fervent reductionists, concerned with molecular details. Molecular biology, originally a small branch of the life sciences, has now become a general, and exclusive, way of thinking that has led to a severe distortion of biological research. Funds are directed toward quick solutions and fashionable topics, while important theoretical problems that do not lend themselves to the reductionist approach are ignored. As Sidney Brenner, one of the leading researchers in the field, has noted, 'Nobody publishes theory in biology - with few exceptions. Instead, they get out the structure of still another protein.'28
The problems that resisted the reductionist approach of molecular biology became apparent around 1970, when the structure of DNA and the molecular mechanisms of heredity were well understood for simple single-cell organisms, such as bacteria, but had still to be worked out for multicellular organisms. This brought biologists face to face with the problems of cell development and differentiation that had been eclipsed during the unraveling of the genetic code. In the very early stages of the development of higher organisms, the number of their cells goes from one to two, to four, to eight, to sixteen, and so on. As the genetic information is thought to be identical in each cell, how can it happen that cells specialize in different ways, becoming muscle cells, blood cells, bone cells, nerve cells, and so on? This basic problem of development, which appears in many variations throughout biology, clearly shows the limitations of the reductionist approach. Today's biologists know the precise structure of a few genes, but they know very little of the ways in which genes communicate and cooperate in the development of an organism - how they interact, how they are grouped together, when they are switched on and off and in what order. Biologists know the alphabet of the genetic code but have almost no idea of its syntax. It is now apparent that only a small percentage of the DNA - less than 5 percent - is used to specify proteins; all the rest may well be used for integrative activities about which biologists are likely to remain ignorant as long as they adhere to their reductionist models.
The other area in which the limitations of the reductionist approach are quite apparent is the field ofneurobiology. The higher nervous system is a holistic system par excellence whose integrative activities cannot be understood by reducing them to molecular mechanisms. At the same time, nerve cells are the largest cells and thus easiest to study. Neuroscientists may therefore be the first to propose holistic models of brain functioning to explain phenomena like perception, memory, and pain, which cannot be understood within the current reductionist framework. We shall see that some attempts in thk direction have already been made, and promise exciting new perspectives. To go beyond the current reductionist approach, biologists will need to acknowledge that, as Paul Weiss has put it, 'there is no phenomenon in a living system that is not molecular, but there is none that is only molecular either.129 This will require a much broader conceptual framework than the one biology uses today. The biologists' spectacular advances have not broadened their basic philosophy; the Cartesian paradigm still dominates the life sciences.
A comparison between biology and physics is appropriate here. In the study of heredity, the period before 1940 is often called classical genetics,' as distinguished from the 'modern genetics' of the subsequent decades. These terms probably derive from an analogy with the transition from classical to modern physics at the turn of the century.30 As the atom was an indivisible unit of unknown structure in classical physics, so was the gene in classical genetics. But this analogy breaks down in a significant respect. The exploration of the atom has forced physicists to revise their basic concepts about the nature of physical reality in a radical way. The result of this revision is a coherent dynamic theory, quantum mechanics, which transcends the principal concepts of Cartesian-Newtonian science. In biology, on the other hand, the exploration of the gene has not led to a comparable revision of basic concepts, nor has it resulted in a universal dynamic theory. There is no unifying framework that would enable biologists to overcome the fragmentation of their science by evaluating the relative importance of research problems and recognizing how they interrelate. The only framework used for such an evaluation is still the Cartesian, in which living organisms are seen as physical and biochemical machines, to be explained completely in terms of their molecular mechanisms.
However, a few leading biologists of our time have expressed the feeling that molecular biology may be reaching the end of its usefulness. Francis Crick, who has dominated the field from the very beginning, acknowledges the severe limitations of the molecular approach in trying to understand basic biological phenomena:
In one way, you could say all the genetic and molecular biological work of the last sixty years could be considered as a long interlude . . . Now that that program has been completed, we have come full circle - back to the problems , . . left behind unsolved. How does a wounded organism regenerate to exactly the same structure it had before? How does the egg form the organism?31
What is needed, to solve these problems, is a new paradigm; a new dimension of concepts transcending the Cartesian view. It is likely that the systems view of life will form the conceptual background of this new biology, as Sidney Brenner seems to indicate, without saying so explicitly, in some recent speculations about the future of his science:
I think in the next twenty-five years we are going to have to teach biologists another language . . . t don't know what it's called yet; nobody knows. But what one is aiming at, I think, is the fundamental problem of the theory of elaborate systems . . - And here there is a grave problem of levels: it may he wrong to believe that all the logic is at the molecular level. We may need to get beyond the clock mechanisms.32
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