PART ONE: Historical Developments
Chapter 1: The Origins of Electrobiology
The study of the interaction between electromagnetic energy and living things involves aspects of both physical and biological science that are less than perfectly understood. Electromagnetic energy, one of the four basic forces of the universe, is neither quite particulate nor quite wave-like in nature but displays properties of both simultaneously. It is capable of propagating through space at 186,000 miles per second and effectuating an action at vast distances. Today we generate, transmit, receive, convert and use this energy in thousands of ways, yet we still lack full understanding of its basic properties. In the life sciences we have classified, determined the structure, and catalogued the functions of practically all living organisms, yet we have not the slightest idea of how these classifications, structures, and functions come together to produce that unique entity we call a living organism.
Every science is more than a collection of facts; it is also a philosophy within which the facts are organized into a unified conceptual framework which attempts to relate them all into a coherent concept of reality. Since biology is the study of living things, it is simultaneously the study of ourselves, making it the most intensely personal of the sciences and the one whose philosophy is the most subject to emotionalism and dogma. Biophilosophy has been the battle-ground for the two most antagonistic and long-lived scientific philosophies-mechanism and vitalism. Mechanism holds that life is basically no different from non-life, both being subject to the same physical and chemical laws, with the living material being simply more complex than the non-living. The mechanists firmly believe that ultimately life will be totally explicable in physical and chemical terms. The vitalists on the other hand just as fervently believe that life is something more than a complex assemblage of complex parts, that there are some life processes that are not subject to the normal physical and chemical laws, and that consequently life will never be completely explained on a physiochemical basis alone. Central to the vitalists doctrine is the concept of a "life force," a non-corporeal entity, not subject to the usual laws of nature, which animates the complex assembly and makes it "alive." This concept is not only ancient, with its roots in prehistory, but it is also practically universal, having appeared in some form or other in all societies and furnishing the basis for the religious beliefs of most of them.
Practically from the time of its discovery, electromagnetic energy was identified by the vitalists as being the "life force," and consequently it has occupied a central position in the conflict between these two opposing doctrines for the past three centuries. While the modern view of the role of electromagnetic energy in life processes is not that of the mysterious force of the vitalists, it has nevertheless inherited the emotional and dogmatic aspects of the earlier conflict. To best understand modern electrobiology it is necessary to understand its antecedents in both physics and biology and ' the constant interplay between these two branches of science over the past 300 years.
It is to the early Greek philosopher-physicians such as Hippocrates that we owe the first organized concepts of the nature of life. These concepts developed within the framework of the medicine of that time and were based upon some clinical observation and much conjecture. All functions of living things were the result of "humors" liquids of mystical properties flowing within the body. Hippocrates identified four: blood, black bile, yellow bile and phlegm-all fluids that could be observed under various clinical conditions. At the same time the body also contained the "anima" -the soul, or spirit of life, which made it alive. The early Greeks' knowledge of anatomy was scanty, and while a number of Hippocrates' philosophical concepts of medicine have survived until today, none of his functional concepts were based upon reality.
Several centuries later, as Greek influence waned, many physicians moved to the new seat of power, Rome. Among them was Galen, trained in the Hippocratic school and although an adherent of the humoral concept, he nevertheless felt it necessary to relate function and form in a more realistic fashion, and so virtually single-handedly he founded the sciences of anatomy and physiology. Dissection of the human body was prohibited at that time, so Galen was forced to base his anatomical concepts of the human body upon dissection of animals and chance observations upon wounded gladiators in the Colosseum. He was able, however, to produce a complete, complex biophilosophical system based upon these anatomical observations and an expanded concept of Hippocrates' humors. Galen's ideas were vigorously propounded and they represented such a major advance in knowledge that they became accepted and rapidly assumed the status of dogma, remaining unchallenged for more than a thousand years.
In the middle of the sixteenth century, Andreas Vesalius, professor of anatomy at Padua, while trained in the tradition of Galen, began to question the validity of Galen's anatomical concepts and performed his own dissections upon the human body, discovering that many of Galen's ideas were wrong. Vesalius published his findings in a book, De humanis corporus fabricus in 1543, the first anatomical text based upon actual dissection and honest observation. His greatest contribution was not anatomical, or course, but philosophical; for the first time in more than 1500 years blind faith in dogma had been effectively challenged by valid observation.
Twenty years after Vesalius published his revolutionary text, a young English physician, William Gilbert, started his medical practice in London. For the next twenty-five years Gilbert, profiting from the spirit of inquiry set free by Vesalius, combined the practice of medicine with a series of carefully planned and executed experiments that laid the ground-work for modern physics. In 1600 Gilbert published his monumental work De magnete, in which he established for the first time the difference between electricity and magnetism. He was the first to use the word electricity and to introduce the concept of the magnetic field. He correctly described the earth as similar to a bar magnet and invented the first instrument for the measurement of electric fields-the electroscope.
Gilbert's major contribution, however, was his introduction into physics of the concept of free inquiry and experiment, most probably derived from Vesalius' work. Gilbert proposed "trustworthy experiments" in place of adherence to dogma as the only way to determine the truth.
The century ushered in by Gilbert's De magnete was to be one of the most exciting in the history of science. In the early years Galileo invented the compound telescope and destroyed the earth-centered cosmology. The instrument was shortly reversed, producing the compound microscope which began to reveal a new cosmology-the intricacies within living things. In 1602 Francis Bacon proposed what was to be later considered the foundation of all science-the scientific method of experimentation, observation and verification. Despite this reputation, Bacon, in truth, not only failed to acknowledge his debt to Gilbert but actually may have presented some of Gilbert's observations as his own while at the same time caustically condemning Gilbert's work!
However, the genie was out of the bottle and science was off on the quest for truth through experimentation. In 1628 William Harvey published the first real series of (physiological) experiments, describing for the first time the circulation of blood as a closed circuit, with the heart as the pumping agent. Vitalism, however, was still the only acceptable concept and Harvey naturally located the "vital spirit" in the blood. At mid-century, Rene Descartes, the great French mathematician, attempted to unify biological concepts of structure, function and mind within a framework of mathematical physics. In Descartes' view all life was mechanical with all functions being directed by the brain and the nerves. To him we owe the beginning of the mechanistic concept of living machines-complex, but fully understandable in terms of physics and chemistry. Even Descartes did not break completely with tradition in that he believed that an "animating force" was still necessary to give the machine life. However, he modernized Galen's original humors in the light of the rapidly accumulating new knowledge postulating only one animating spirit, no longer liquid, but more "like a wind or a subtle flame" which he naturally located within the nervous system.
At about the same time Malphighi, an Italian physician and naturalist, began using the new compound microscope to study living organisms. While he did not quite discover the cellular basis of life (that remained for Robert Hooke twenty years later), his studies revealed an unsuspected wealth of detail and incredible complexity in living things. By 1660 von Guericke had pursued Gilbert's studies much further and invented the first electrical generating machine, a spinning globe of solid sulfur, which generated large static electrical charges. The century closed with the great Isaac Newton who, after proposing an "all pervading aether" filling the universe and all material bodies therein, suggested that it may be Descartes' vital principle, flowing through the nerves and producing the complex functions called life.
Accompanying the intellectual ferment and excitement of the seventeenth century was a remarkable growth in scientific communication without which progress would have been much slower. The first academy of science-the Italian Academy of the Lynx-was founded in Rome in 1603 and included among its members Galileo and the great entomologist, Faber. Similar societies were started in other countries, until in 1662. the Royal Society of London was incorporated. Besides providing a forum for discussion, the societies began the publication of scientific journals, the first issue of the Journal des Savants appearing in I665 followed in three months by the first issue of the Philosophical Transactions of the Royal Society. Several avenues were thus provided for the dissemination of new ideas and the reports of the results of "trustworthy experiments."
As the next century dawned, knowledge of electricity had advanced beyond Gilbert but was still limited to von Guericke's static charges. Biology, however, was by then firmly grounded in anatomy, both gross and microscopic, based upon actual dissection and observation. Although there had been some movement away from Galen's "humors," the postulated "vital forces" were still the necessary distinction between living and non-living things. The scientific impetus of the preceding century continued unabated however, and the results of new experiments and new ideas were quick to appear.
In the early decades of the eighteenth century a young Englishman, Stephen Gray, began a series of experiments in which he demonstrated that the static charges of electricity could be conducted by various materials for distances as great as 765 feet, discovering in the process that some materials were "conductors" while others were not. Gray is best remembered for his experiment in which he "electrified" a human subject with a static charge. Gray published his observations in the 1731 Philosophical Transactions in a paper entitled "Experiments concerning electricity." This was only five years before his death at age forty-one.
Working during the same period, also in England, was another Stephen -Stephen Hales, a young rural clergyman who had already made important contributions to the knowledge of blood circulation. Hales made the startling suggestion that perhaps nerves functioned by conducting "electrical powers" as did the conductors of his countryman Gray. Since the time of Descartes the vital role of the nervous system as the principal regulator of all biological activity had been recognized. As a result, the postulated "vital spirit" had come to be located in the nerves, and the importance of Hale's suggestion lay in the fact that he was proposing that this mysterious, all-important entity was electricity! Support for this concept was forthcoming, but from a different aspect of the problem entirely. It had occurred to both Swammerdam in Holland and Glisson at Cambridge that the humoral concept of nerve-muscle activity required that the muscle increase in volume as the active "humor" flowed into it from the stimulated nerve. In separate experiments they both showed that the muscles did not increase in volume when they contracted. Therefore the "humor" must be "etherial" in nature and Hales' electricity seemed to be a good candidate.
Interest in electricity and its relationship to biology increased and experiments involving electricity and living things became commonplace. The Abbe Nollet expanded Gray's observations on the electrification of the human body using von Guericke's machines to produce larger static charges. He also attempted to remedy paralysis in patients by administering such charges, but without success. Another rural English clergyman, Abraham Bennet, invented the gold-leaf electroscope, far superior to Gilbert's for detecting and measuring electric charges. Van Musschenbroeck in Holland invented the Leyden jar for the storage of electrical charges (priority probably should have gone to von Kleist, a German), and by the mid-1700's electricity was being generated, stored and transmitted through wires for distances exceeding two miles! Watson, Cavendish and others even attempted to measure its speed of transmission through wires and decided that it was "instantaneous." Many physicians, unfortunately including a number of outright charlatans, were by now empirically using this new modality to treat a number of afflictions and reporting success. One, Johann Schaeffer, went so far in his enthusiasm as to publish a book called Electrical Medicine in Regensburg in 1752 .
While speculation concerning the role of electricity in living things was increasing, particularly regarding the nervous system, physical knowledge of its properties did little to support this idea. The most prominent physiologists of the era, Haller at Gottingen and Monro at Edinburgh, rejected it as impossible, basing their opinions on the then available knowledge of metallic conduction and the need for insulation. Despite obvious difficulties, the "humors" and "vital spirits" were still invoked as the best explanation of how living things differed from non-living. This, of course, did not daunt the majority of practicing physicians who continued to use this new modality with enthusiasm for an increasing number of clinical conditions.
It was as though the stage was set for a major event; for 200 years a spirit of free inquiry and communication had produced a revolution in the way man looked at the world and himself. Yet the central question remained unanswered-what was the essential difference between the living and the non-living? The vitalist doctrine of a mysterious, non-corporeal entity was still the best available, despite increasing evidence against it. Not only were there theoretical objections to electricity being the "vital force," but also no-one had produced any evidence of a scientific nature to indicate that it played any role in living things whatsoever.
Fig.1.1. Luigi Galvani, physician, surgeon, anatomist and teacher. As professor of anatomy, Galvani's lectures were more experimental demonstrations than didactic discussions. A quotation frequently attributed to him states, "For it is easy in experimentation to be deceived and to think one has seen and discovered what we desire to see and discover." In addition to being a scientist, Galvani was foremost a physician, treating rich and poor alike.
The major event was to be provided by a shy, retiring physician and professor of anatomy at Bologna, Luigi Galvani. Since 1775 he had been interested in the relationship between electricity and biology and had acquired the apparatus necessary to conduct his experiments. In 1786 quite by accident, while dissecting the muscles of a frog leg, one of Galvani's assistants happened to touch the nerve to the muscles with his scalpel while a static electrical machine was operating on a table nearby. Every time the machine produced a spark the muscle contracted-obviously the electrical force somehow had gone through the air to the metal in contact with the nerve. But most importantly, the electricity went down the nerve and produced the muscle contraction. Electricity did have something to do with how nerves worked! Galvani spent the next five years experimenting on the relationship between metals in contact with nerves and muscle contraction. We can now speculate that he wished to avoid the use of the electrical generating machine so that he could produce a muscle contraction by contact between the nerve and metal only, in order to prove that the nervous principle was electrical. He must have found that single metals in various circuits did not produce the desired muscular contraction, and so he then tried using more than one metal in the circuit. He found that if a continuous circuit was made between the nerve, two dissimilar metals in series, and another portion of the animals body, muscular contraction would occur. Galvani reported his findings in the Proceedings of the Bologna Academy of Science in 1791 concluding that the electricity was generated within the animal's body, the wires only providing the circuit completion. He called this electricity "animal electricity," and identified it as the long sought for "vital force". Considering his quiet, unassuming nature, it must have been with some trepidation that he published such a far-reaching conclusion concerning the most controversial subject of the time. Nevertheless, he had twelve extra copies printed at his own expense for private distribution to other scientists, one copy being sent to Alessandro Volta, professor of physics at Pavia.
Fig. 1.2. The discovery of "animal electricity." When a spark was drawn from the electrical machine (left) the frog's leg would twitch if a metal scalpel was touching the nerve to that leg. We now know that the expanding and collapsing electric field induced a charge in the scalpel, which then stimulated the nerve. Galvani however, apparently believed that the metal scalpel permitted the electricity in the nerve to function. He embarked on a long series of experiments that today seem to have been going in the wrong direction (see figure 1.3), but we must take into consideration the state of knowledge of electricity at that time.
Fig. 1.3. Galvani's demonstration of bimetallic generation of electricity. The vertebral column of the frog, with nerves attached to the muscles of the legs, rests on a plate of silver (F) with the legs on a plate of copper (G). When the experimenter connects the two plates with an iron rod, the circuit is completed, and current flows through the preparation, stimulating the nerves and producing muscle contraction in the legs. Galvani, of course, believed the source of the current to be in the animal tissues.
Volta repeated and confirmed Galvani's observations, at first agreeing with his conclusions of "animal electricity," but later he became convinced that the electricity was generated not by the nerve, but by the two dissimilar metals in the circuit. Volta must have immediately realized that this was a new kind of electricity being continually produced-a steady current, as opposed to the instantaneous discharges from the friction machines of von Guericke. Volta immediately improved the apparatus, constructing several types of bimetallic "piles" for the generation of continuous current. His observations were published in the Philosophical Transactions of 1793 setting in motion both a major advance in the knowledge of electricity, as well as a particularly strident controversy that was to occupy the life sciences for the next century and a half. While Volta acknowledged his debt to Galvani, he left no doubt that in his mind there simply was no electricity in living things-Galvani had simply misinterpreted his findings.
Fig. 1 4. Alessandro Volta, physicist and experimenter. At age 34 Volta became professor of physics at the university in Pavia, remaining in that post until his retirement 40 years later. Volta had been elected to the Royal Society in 1791 in recognition of his work on electricity. After Galvani published his classic paper in that same year, Volta became interested in these observations of his countryman, duplicated them, made the proper deduction and discovered bimetallic continuous electricity. He reported these observations in the Transactions of 1793 and in 1800 reported the invention of the Voltaic Pile, a sample of which stands on the table before him.
Fig. 1.5. The first demonstration of true animal electricity. When the leg of the frog, held in the left hand, is brought into contact with the exposed spinal cord, the other leg will twitch. This was first reported in the anonymous paper published in Bologna in 1794. We now know that the muscular contraction is the result of electrical currents of injury coming from the skinned leg of the frog.
Galvani was not well suited to scientific controversy. His only reply to Volta's attack was to publish, unfortunately anonymously, a tract reporting several additional experiments in which muscular contraction was produced without any metal in the circuit. The experiments actually demonstrated the generation of electricity by injured tissue, although Galvani did not make this connection, thinking still in terms of his animal electricity. Volta responded immediately, depreciating these experiments with obviously specious, non-experimental, theoretical arguments. While Galvani himself never responded to these arguments of Volta's, his nephew, Giovanni Aldini, a physicist, was convinced that Galvani was right and was not at all loath to engage in scientific controversy. Volta was of similar temperament and in a short time Galvani was all but forgotten in the heat of a particularly acrimonious debate between Volta and Aldini. In June 1796, just five years after the publication of Galvani's first paper, Bologna came under French control, Galvani was dismissed from his university position, losing his home and his fortune at the same time. He was forced to seek refuge in the home of his brother, where, cut off from science and with no facilities to communicate with other scientists, he died in I798. Two years later Volta presented his discoveries to Napoleon himself, receiving a special award and unusual honors. Not too surprisingly, Volta never made another substantive contribution to science.
In the welter of acrimony and debate over "animal electricity" one voice of reason and moderation was heard. Humboldt was then a young man in his 30's and had just completed his studies as a mining engineer. While employed as an inspector of mines for the Prussian government, Humboldt carried with him the equipment to conduct experiments on the controversy. His publication in I797, just before Galvani's death, clearly established that both Volta and Galvani were simultaneously right and wrong. Bimetallic electricity existed but so did animal electricity. Humboldt went on to become a spectacular scientist, traveling widely around the world and making many of the original observations that established geology as a science.
Aldini continued to vigorously promote the cause of animal electricity in the early years of the next century. Being a physicist with no medical background, his experiments, such as the animation of corpses with electrical currents (generated incidentally by the bimetallic piles discovered by his arch enemy Volta), often verged on the grotesque. However, in one instance Aldini treated a patient who would today be diagnosed as a schizophrenic. Administering the currents through the head, Aldini reported a steady improvement in the patient's personality and ultimately, his complete rehabilitation. Nevertheless, all the advantages lay with Volta. His world of bimetallic electricity was both a quantum jump in technology and a simple, easily verifiable phenomenon. Galvani's world of living things on the other hand was incredibly complex and imperfectly understood as it remains even today.
Volta's observations were extended and his apparatus refined by many other workers. Voltaic batteries of several tons in weight were constructed, enabling Humphry Davy to do his experiments laying the foundation for electrochemistry, and leading to a better understanding of the material world at the atomic level. In 1809 von Soemmering, a German physician, demonstrated the first battery-operated telegraph, and the following year Davy displayed the first electric arc light using the 2000 plate voltaic battery of the Royal Society. Electricity was beginning to move from the status of a laboratory curiosity to that of a tool for probing the material world, simultaneously showing promise of future technical applications in commerce and industry.
Again, another surprising discovery was made quite by accident. Hans Christian Oersted, then professor of natural philosophy at Copenhagen, was giving a lecture-demonstration of voltaic electricity to his students early in 1820. A compass happened to be on the same demonstration table and Oersted noticed that every time the electrical circuit was made the compass needle moved. In a few months he completed his experiments on this chance observation and in July 1820 he published the observation that an electrical current flowing in a conductor generated a circular magnetic field around the conductor. Oersted had discovered electromagnetism. More than 200 years after Gilbert had shown the difference between the two forces, he had proven the interrelationship between them. His discovery provided the basis for much of our present day technology.1
1 There is an interesting aside to Oersted's career. In 1801 after finishing his training as a physicist, he traveled throughout Europe visiting other scientists. For several weeks he stayed with Carl Ritter, a prominent physicist in Jena. Ritter had discovered the existence of ultraviolet light, invisible to the eye, and was very much interested in the Galvani-Volta controversy. he was the eccentric genius type, given to both sound experiment and wild speculation. After Oersted left, the two continued to correspond, and in May 1803 Ritter wrote to Oersted that in the years in the which earth's plane of the ecliptic was maximally inclined, major discoveries were made in the science of electricity. He predicted that another major discovery would be made in 1819-1820---it was, by Oersted himself.
The controversy over "animal electricity" continued unabated even though most of the original protagonists had retired from the scene. A major technological discovery did much to both clarify and to cloud the issue. Working from Oersted's discovery, Nobeli, professor of physics at Florence invented the static galvanometer, which was capable of sensing extremely small currents. In the 1830's Carlo Matteucci, professor of physics at Pisa, began a series of experiments that were to continue until his death in 1865. His primary interest was in the "animal electricity" demonstrated by Galvani in his second series of experiments not involving contact with metals. Using Nobeli's galvanometer Matteucci was able to prove beyond a doubt that an electrical current was generated by injured tissues and that in fact, serial stacking of such tissue could multiply the current in the same fashion as adding more bimetallic elements to a Voltaic pile. The current was continuously flowing--a direct current-- and the existence of at least this type of "animal electricity" was finally and unequivocally proven. However, it was not located within the central nervous system per se and seemed to have little relationship to the long sought "vital force."
Matteucci published many of his observations in a book in 1847 which came to the attention of Johannes Müller, then the foremost physiologist in the world and professor at the medical school in Berlin. Müller had been of the opinion that while electricity could stimulate a nerve, it was not involved in its normal function in any manner, and he continued to embrace the vitalistic doctrine of a mysterious "vital force." When he obtained a copy of Matteucci's book he gave it to one of his best students, Du Bois-Reymond, with the suggestion that he attempt to duplicate Matteucci's experiments. Du Bois-Reymond was a skilled technical experimenter and within a year he had not only duplicated Matteucci's experiments. but had extended them in a most important fashion. he discovered that when a nerve was stimulated an electrically-measurable impulse was produced at the site of stimulation and then traveled at high speed down the nerve producing the muscular contraction. Du Bois-Reymond had discovered the nerve impulse, the basic mechanism of information transfer in the nervous system. he was not unaware of the importance of his discovery, writing, " I have succeeded in realizing in full actuality (albeit under a slightly different aspect) the hundred years dream of physicists an physiologists."
This great contribution was tarnished somewhat by Du Bois-Reymond's intemperate and uncalled for attacks upon Matteucci. In fact he seemed to be of a particularly argumentative nature for he shortly became embroiled in a bitter dispute with one of his own students--Hermann--over the resting potential. The resting potential was a steady voltage that could be observed on unstimulated nerve or muscle. Hermann believed that all resting potentials were due to the injury currents of Matteucci and that without injury there would be no measurable potential. Du Bois-Reymond was equally adamant that injury potentials were a minor matter and that they would add only a small part to the resting potentials. As usual both parties were partially right and partially wrong. In fact Du Bois-Reymond was not even fully correct in his interpretation of his primary observation of the nerve impulse. He visualized it as being due to localized masses of "electromotive particles" on the surface of the nerve, a concept seemingly related to the then known mechanism of metallic conduction along a wire. The old objections still applied--the resistance of the nerve was too high and it lacked appropriate insulation. Nonetheless, the impulse was there, a fact easily verified with the equipment then available.
In a technical triumph for that time, von Helmholtz, a colleague of Du Bois-Reymond in Berlin, succeeded in measuring the velocity of the nerve impulse, obtaining a value of 30 meters per second, in full agreement with "instantaneous" measurements on currents in a wire--this was a different phenomenon entirely. The problem was given to another of Du Bois-Reymond's students, Julius Bernstein. He repeated and confirmed von Helmoltz's velocity measurement, at the same time making precision measurements on the nerve impulse itself. His studied led to the proposal in 1868 of his theory of nerve action and bioelectricity in general, which has come to be the cornerstone of all modern concepts. The "Bernstein hypothesis" postulated that the membrane of the nerve cell was able to selectively pass certain kinds of ions (atoms with electric charges resulting from dissolving salts in water). Situated within the membrane was a mechanism that separated negative from positive ions, permitting the positive ones to enter the cell and leaving the negative ions in the fluid outside the cell. Obviously when equilibrium had been reached an electrical potential would then exist across the membrane-the "transmembrane potential." The nerve impulse was simply a localized region of "depolarization," or loss of this transmembrane potential, that traveled down the nerve fiber with the membrane potential being immediately restored behind it. This was a most powerful concept, in that it not only avoided the problems associated with electrical currents per se, but it relied upon established concepts of chemistry and satisfactorily explained how the impulse could be observed electrically and yet not be electrical in nature. Bernstein, realizing the power of the concept, postulated that all cells possessed such a transmembrane potential, similarly derived from separation of ions, and he explained Matteucci's current of injury as being due to damaged cell membranes "leaking" their transmembrane potentialsintellectually, a most satisfying explanation at that time.
Fig. 1.6. Electricity and nerves. Top: the sample anatomy of a single nerve cell or neurone. The cell body is either in the brain or the spinal cord, and the nerve fiber is in the peripheral nerves such as in the arms and legs. Middle: the concept of Du Bois-Reymond-electrical "particles" moving along the nerve fiber. Bottom: a simplified version of the Bernstein hypothesis. The only moving charges are ions moving into or out of the nerve fiber at a site of membrane "depolarization." This site of membrane change moves along the nerve fiber.
In fact, just as Galvani's animal electricity came at just the right time, Bernstein's hypothesis came at the time when the scientific establishment was most anxious to rid biology of electricity, the last vestige of vitalism.
Darwin had published the Origin of Species only nine years before and the cellular basis of all life had recently been verified by Virchow's linking of all disease to basic cellular pathology. Pasteur had already shown that infectious diseases were the result of infestation with bacteria, not "miasmas" of unspecified type, and Claude Bernard had established the biochemical basis of digestion and energy utilization in the body. Science had clearly profited from the spirit of inquiry that had characterized seventeenth and eighteenth centuries and stood on the threshold of being the sole interpreter of nature, both living and non-living. There was no place for "vital forces" or for electricity in living things, and Bernstein's hypothesis was eagerly accepted. Now all of life from its creation, through its evolution, to its present state was explicable in terms of chemistry and physics. As von Helmholtz put it-"no other forces than the common physical-chemical ones are active within the organism." Life began as a chance aggregation of molecules in some long ago, warm sea and evolved into complex physical-chemical machines, nothing more.
A profound turning point had been reached in science. Since living things were machines, they could be broken down into their component parts just like machines, and these component parts could be studied in isolation with the confidence that their functions would reflect those when in the intact organism. This has proven to be a powerful tool indeed, and much has been learned by this approach, but something has not been learned-we still do not know how these functions and systems integrate together to produce the organism. Nevertheless, at that time it appeared that this approach was to be the one destined to reveal all of life's secrets and the power and prestige of the Berlin school increased until it became, along with Heidelberg, the world center for the new scientific medicine (Wissenschaftliches Medicine). Its disciples spread the word widely. Freud for example, in his formative years was profoundly influenced by his work in the laboratory of Ernst Brucke, a friend and staunch supporter of von Helmholtz.
While the biological and medical scientists were busily establishing science as the basis for biology and medicine and expelling vitalism, including electricity, from any function in living things, the situation was quite different in the real world of the practicing physicians. Electrotherapeutics, which had its start with the experiments of the Abbe Nollet in the mid-eighteenth century, had become popular for the treatment of numerous and varied clinical conditions; from the obviously functional psychogenic disturbances, to such concrete pathology as fractures that had failed to heal. By 1884 Bigelow estimated that "10,000 physicians within the borders of the United states use electricity as a therapeutic agent daily in their practice." All of this persisted without the blessing of the scientific establishment until after the turn of the century when the most obvious of the charlatans entered the scene. They, in concert with the almost total lack of standards in medical education and practice at that time, produced a really deplorable situation.
This situation was recognized by the Carnegie Foundation, which established a commission to investigate it. The commission was headed by Abraham Flexner and the now famous "Flexner Report" published in 1910 produced an almost instantaneous revision of medical education with the closing of most of the marginal schools and the establishment of science as the sole basis for medicine and medical education. This was firmly reinforced a few years later when Flexner compared the American and British schools unfavorably with the German. By 1930 American medicine was practically totally patterned after the Germanic "Wissenschaftliches Medicine." Electrotherapy became a scientifically unsupportable technique and disappeared from medical practice, with most of its proponents embracing the technology of Roentgen's X-rays, and the biomedical scientists set about solving the remaining few riddles of life with chemistry as their prime tool.
During the 20's and 30's these reformers received considerable support from two quite divergent sources. Knowledge of the physics of electricity and magnetism had progressed from Oersted's demonstration of the relationship between the two, to Faraday's generation of electrical current by magnetic induction, and to Maxwell's profound insight on the nature of electromagnetic radiation, the latter predicting the existence of a whole spectrum of electromagnetic radiation. After Hertz had proven Maxwell's predictions in 1888 the age of electrical technology began. By 1897 Marconi was using this radiation to send signals over distances of twelve miles and within four years a message was instantaneously sent across the Atlantic ocean. Edison perfected his first electric light in 1879, and by 1882 the first central electrical generating station, the Pearl Street Station in New York City, began operating.
By 1900 the electric age was well on its way and within a few short years was to result in the total electrification of the entire world. Man began to live in an electromagnetic environment that deviated significantly from the natural, but since the social and economic advantages were obvious, the technology was enthusiastically embraced. When questions were raised as to the possible effects of all this progress upon human health, scientists reassured the populace that since electricity played absolutely no role in living things there was nothing to fear. (It would seem obvious also that the investors who stood to gain considerably from further expansion of the technology would be similarly pleased.) A few experiments were performed in a rather perfunctory but spectacular fashion, particularly in Edison's own laboratory. In one instance a dog was placed in a strong magnetic field for five hours without obvious discomfort" (no other determinations were apparently made); in another, five human volunteers reported no subjective sensations whatever when they placed their head within a strong magnetic field, whether the field was on steadily or switched on and off repeatedly. This reported lack of sensation is particularly intriguing since d'Arsonval reported at the same time that such changing fields (from the field on-off) when applied to the human head produced the subjective sensation of light! A few years later Beer substantiated this observation and named it the "magnetic phosphene." It has been studied extensively since then and its existence is unquestioned. It is difficult to understand why it was not reported from the experiments in Edison's laboratory, since they were performed under circumstances known to produce it. At any rate the rapidly expanding electric utility and communications industry joined with the scientists in totally denying the existence of any effects of electromagnetic fields on living things.
During the period another area of industry was also rapidly expanding, the manufacture of chemical drugs. It would seem likely that the biochemical view of life then being promoted by scientific medicine would be most attractive to these companies and indeed, they actively contributed to the campaign to discredit the electrotherapeutic techniques. Only within the past few years has it become possible to raise questions about the Flexner Report. While Flexner himself unquestionably was motivated by the best of intentions, the initial funding for most of his reports was derived from somewhat suspect sources.
By 1930 the convergence of powerful forces had brought to a final conclusion the debate that had begun with Galvani in 1791. Anyone who aspired to a career in the medical or biological sciences was well advised to hesitate before publicly proposing that electromagnetic forces had any effect on living things, other than to produce shock or heating of the tissues, or that such forces played any sort of functional role in living things. Yet precisely such reports did appear in the scientific literature.
Leduc, in 1902, claimed to produce a state of narcosis in animals by passing an alternating current (110 hz at 35 v) through the animal's head. This report was confirmed and expanded by a number of workers in many countries, and variations of the technique have been used clinically, particularly in France and the Soviet Union. In 1938 Cerletti began experimenting with electroshock therapy for schizophrenia (shades of Aldini!) and this technique subsequently found wide application in psychiatry. In 1929, Hans Berger discovered the electroencephalogram (brain waves) which has, with refinements, become one of the standard testing and diagnostic procedures in neurology. In the following decade Burr began a long series of experiments on the steady-state or DC potentials measurable on the surface of a wide variety of organisms. He related changes in these potentials to a number of physiological functions including growth, development and sleep. He formulated the concept of a "bioelectric field" generated by the sum total of electrical activity of all the cells of the organism, and postulated that the field itself directed and controlled these activities. Lund in Texas and Barth at Columbia University in New York also postulated a physiological role for these DC potentials, particularly in regard to growth and development. In the same decade Leao demonstrated that depression of activity in the brain (as judged by changes in the rate of nerve impulse production) was always accompanied by the appearance of specific type DC potentials, regardless of the primary causative factor. Gerard and Libet expanded this concept in a series of experiments in which they concluded that the basic functions of the brain-excitation, depression and integration-were directed and controlled by these DC potentials.
The generating source for the DC potentials observed by all of these workers was obscure. It could not be the transmembrane potentials of Bernstein, nor could it be the single, short duration impulses produced by the transient breakdowns in the transmembrane potential in nerve or muscle. As a result, established science either ignored or rejected outright these observations as artifactual or as by-products of underlying chemical activities and therefore of no importance. While the action potential was well established as the mechanism of information transmission along the nerve fiber, and was satisfactorily explained by the Bernstein hypothesis, a problem still existed. At the junction between the nerve and its end organ (i.e. muscle) the microscope had revealed a gap, the synapse. Could not the action potential become changed into an electrical current to cross this gap?
In a series of experiments in the 1920's, Otto Loewi at New York University proved conclusively that the transmission across the synaptic gap was chemical-acetylcholine was released into the gap where it then stimulated the receptor site on the end organ. Finally, the broad outlines of the Bernstein hypothesis were proven by Hodgkin, Huxley and Eccles in the 1940's. Using microelectrodes that could penetrate the nerve cell membrane, they demonstrated that the normal transmembrane potential is produced by sodium ions being excluded from the nerve cell interior, and when stimulated to produce an action potential the membrane permits these ions to enter.
The tidy world of the mechanists was complete. There was no vital principle, and electricity, which had been identified with it, had no place in the biological world. Three hundred years of intellectual ferment and experiment had come to a close with the establishment of a new biophilosophy-the universal machine now included all living things. As vitalism gradually lost the battle, bioelectricity, which had been its central theme for more than a century, was also gradually excluded from biology until all that remained was the gross effects of large forces, shock and heat.
The concepts of the new philosophy fitted the observed facts so well that in its enthusiasm, science ignored all evidence of electrical phenomena in living things as well as the fact that there were biological functions that were poorly explained, if at all, by the chemical concept. However, there was a much larger flaw. All of the concepts that excluded electromagnetic effects and processes in biology were based upon the knowledge of this force extant at the time. In the early years of the present century the only mechanisms of electrical conduction were metallic and ionic. Even then a strange class of minor substances was known to exist, located between the conductors and the insulators, called semiconductors. These were of no practical significance at the time and since they existed only as solid, crystalline materials, they were ipso facto excluded from the biological world, which as everyone knew was water-based to permit the all-important chemical reactions. As knowledge at the atomic level increased, better understanding of the semiconductor substances was acquired. It became known that instead of large numbers of electrons moving in clouds along the surface of metals, small numbers of electrons existed within the organized crystalline lattice of the semiconductor where they were not associated with any single atom but were free to move throughout the entire crystal with ease.
In 1941, Szent-Gyorgyi, a physician and biochemist who had already been awarded the Nobel Prize for his work on biological oxidation mechanisms and vitamin C, made the startling suggestion that such phenomena as semiconduction could exist within living systems. He postulated that the atomic structure of such biological molecules as proteins was sufficiently organized to function as a crystalline lattice. In the case of the fibrous proteins he proposed that they could join together in "extended systems" with common energy levels permitting semiconduction current flow over long distances. Szent-Gyorgyi, while certainly not subscribing to the mystical vitalistic philosophy, nevertheless felt compelled to state that he believed biological knowledge was considerably less complete than advertised by the mechanistic establishment. In the Koranyi Lecture delivered in Budapest that year he stated, "It looks as if some basic fact about life is still missing, without which any real understanding is impossible."
The modern concept of electrobiology can be considered to have originated with these thoughts of Szent-Gyorgyi. As the remainder of this volume will show, it is not a return to the vitalism of imponderable forces and actions, but rather the introduction into biology of advances in knowledge that have occurred in the field of solid-state electronics. The resulting weight of the evidence seems to indicate that steady-state or DC currents exist within living organisms where they serve to transmit information at a basic level. This concept has proven to be of considerable value in understanding many of the life functions that are poorly explained when viewed solely within the framework of biochemistry.
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