Читать книгу The Energy of Life: - Guy Brown - Страница 11

The collapse of the four elements theory opened up a cornucopia of matter. If ‘air’ was a mixture of different gases, ‘water’ was a combination of hydrogen and oxygen and ‘fire’ was not an element at all, then what on earth was ‘earth’? The science of chemistry, newly constituted and emboldened at the start of the nineteenth century, was salivating at the prospect of dividing ‘earth’ into thousands of different ‘species’. The concept of species and family had been successfully used by Linnaeus in the eighteenth century to bring order to biological taxonomy, but what were the building blocks of matter and how were they to be classified?

The theory of the elements was recast by Lavoisier, so that there were at least thirty different elements (now known to be about a hundred), existing as elementary, indivisible ‘atoms’ (proposed by Dalton in 1808) and combined in fixed ratios to form more or less stable ‘molecules’. Chemists divided their task between the analysis of inorganic and organic (or ‘organized’) matter, the latter being the constituents or products of living organisms. The alchemists had treated organic matter as if it were a single substance or a small number of elements, for example they had treated distillates of egg or urine as single substances. The chemists set about analysing the many components of egg and urine, using new methods of organic analysis. Lavoisier had pioneered such analysis by burning organic compounds in jars of oxygen and collecting the carbon as carbon dioxide and hydrogen as water. By quantifying the amount of carbon (C), hydrogen (H), and oxygen (O), a formula of the compound could now be written down; starch was, for example, thought to be C₁₂H₁₀O₁₀. This formula was mistaken, and arose from the misconception that water was HO rather than H₂O. But these methods were rapidly improved and applied with great enthusiasm by several German chemists, in particular Liebig and Wöhler. In 1835, Wöhler wrote: ‘Organic chemistry appears to me like a primeval forest of the tropics, full of the most remarkable things’. These first optimistic biological chemists did not, however, comprehend the full complexity and extent of their new field. It is now thought that there may be roughly five million different organic compounds in the human body and these compounds may be organized in an almost infinite number of different ways.

Nineteenth-century Germany, although not yet united, had become the major centre for scientific and technological innovation. Perhaps partly in reaction to the rise of science and industrialism, the Romantic movement developed in late-eighteenth-century Germany producing a scientific philosophy known as Naturphilosophie. This bizarre hybrid of Romantic philosophy and science contributed to a resurgence of interest in the vital force and the relationships between all forces.

Justus von Liebig (1803–1873) dominated German chemistry and biochemistry in the nineteenth century, sometimes to the detriment of biology. The son of a dealer in drugs, dyes, oils, and chemicals, von Liebig gained an interest in chemistry assisting his father. But he did badly at school and was derided when he suggested a career as a chemist. He learned to make explosives from a travelling entertainer, terminating an apprenticeship in pharmacy when he accidentally blew up the shop. His father packed him off to university to study chemistry but he was soon arrested and sent home after becoming too involved in student politics. Somehow he eventually earned his doctorate and went to work in Paris with one of the best French chemists of the time, Joseph Gay-Lussac. In the 1820s he took a position at a small German university at Giessen, and over the next twenty-five years produced a veritable mountain of chemical data.

However, von Liebig did not produce this data himself, rather he invented the research group as a quasi-industrial means of producing scientific results. Taking over an unused barracks as a chemical laboratory, he staffed it with junior scientists as lieutenants, students as foot soldiers and with himself as the distant but all-powerful general. This model of the research group was so successful in producing the large volumes of research required in the industrial world that it was widely adopted and remains the main means of producing scientific research today. This is in strong contrast to the pre-industrial system of the individual scientist thinking up experiments and carrying them out himself, with or without assistance. Von Liebig was both arrogant and argumentative and had a number of angry disputes with other scientists. His success gave him considerable power, through his control over scientific journals, appointments, and societies. The parallels with science today are unavoidable. It is dominated by a relatively small number of politicians of science who control the boards of scientific societies, journals, conferences, grant-giving bodies, and appointment boards. Success in a scientific career still depends to a certain degree on gaining the patronage of these politician-scientists.

Von Liebig started the prodigious task of analysing the millions of different combinations of elements – molecules – that make up a human being. Some kind of order was brought to this chaos by distinguishing three main types of molecule: carbohydrates, fats, and proteins. At first it was thought that these ‘organic’ molecules could only be produced by living organisms, using some kind of vital force. But in 1828 Friedrich Wöhler, a friend and colleague of von Liebig, found that he could chemically synthesize urea (an important component of urine) without any living processes being involved. Ultimately, this would lead to the melting of the boundary between the living and the non-living, but not yet.

Although von Liebig showed that living organisms were constructed from a large number of organic chemicals, he believed that a ‘vital force’ was required to prevent these complex chemicals from spontaneously breaking down. He came to this conclusion because, in the absence of life, they did tend to break down, either by oxidation (combination with oxygen as in burning), putrefaction (as in flesh after death), or fermentation (conversion of sugar to alcohol). Von Liebig’s concept of vital force was similar to that of a physical force such as gravity or the electric force, but was only present in living organisms. Within the living body, this vital force opposed the action of the chemical forces (causing oxidation, putrefaction and fermentation), thus preventing the decay of the body so evident after death. Von Liebig also claimed that the vital force caused muscle contraction because he thought there could be no other way to account for the control of muscle by mind. When a muscle contracted, some of the vital force was used up to power the contraction. Consequently, immediately after the contraction, there was less vital force to oppose the decay (oxidation) of chemicals in the muscle, which therefore speeded up with an associated increase in respiration. The vital force acted as a brake on the chemical forces and when it was consumed by muscle contraction, the chemical forces speeded up. This is akin to the famous story of Peter, the little Dutch boy, sticking his finger in the leaking dam, trying to prevent the sea washing away the fields and town (just as the vital force prevented the chemical forces from eroding the body). This erroneous interpretation was used to explain Lavoisier and Séguin’s important discovery that respiration (the process of consuming oxygen to produce carbon dioxide and heat) greatly increased when a human or animal was working or exercising. Although von Liebig’s conception of the vital force was a form of vitalism, in the tradition of Aristotle, Paracelsus, and Stahl, the concept was more mechanistic in its appeal to Newtonian forces and foreshadows the concept of energy, formulated in the mid-nineteenth century.

Von Liebig’s belief that everything could be explained by chemistry and the vital force was opposed by Theodor Schwann (1810–1882). This clash proved catastrophic for the sensitive and as yet unestablished Schwann. Schwann’s productive work lasted just four years (1834– 1838), while he was still only in his twenties, but it was enough to spark a reorganization of biology almost as fundamental as that of Lavoisier’s of chemistry. Schwann’s first venture was to isolate a muscle from a frog and measure the force produced by the contracting muscle when it was held at different lengths or pulled against different weights. He found the muscle contracted with the greatest force when it was at the length that it was naturally found in the body. These experiments were seen as sensational in Germany, because for the very first time a vital process supposedly mediated by a vital force was treated and quantified in the same way as an ordinary physical force. It was now possible to give a physical account of vital processes, or reduce them to physical forces. This approach, however, did not please von Liebig and other champions of the vital force. Indeed Mayer later used Schwann’s experiment specifically to disprove von Liebig’s account of muscle contraction.

Schwann’s next achievement was the isolation of an enzyme which he called pepsin from the digestive juices. An enzyme is a biological substance present in small quantities which promotes a chemical reaction without being itself converted by the reaction. But ‘enzyme’ is a twentieth-century notion, in the nineteenth century they were known as ‘ferments’. For the alchemists, a ferment was a small quantity of active substance which when added to a passive substance could transform it into an active one similar to the ferment. For example, fire was the ferment converting flammable substances into flame and the philosopher’s stone was the ferment transmuting base metals into gold. Fermentation is the process responsible for the leavening of dough producing bread and for converting grapes into alcohol, making wine. This apparently magical transformation had been recognized since antiquity, but how exactly this happened was unclear, although it was known to require a ferment – yeast. Having discovered a ferment in digestive juice, Schwann concluded that digestion was a kind of fermentation. Von Liebig and the other chemists considered digestion, on the other hand, as a purely chemical process due to the action of acids on food. So when Schwann published his findings in von Liebig’s journal, von Liebig added a rather sceptical note to his paper.

Schwann then turned his attention to the nature of fermentation itself: one of the central scientific and technological problems of the nineteenth century. Von Liebig and the chemists believed fermentation was purely chemical and did not involve any biological organisms or processes. Schwann and two other researchers independently discovered that fermentation was a biological process caused by a fungus – yeast – the cells of which could be viewed through a microscope and could be destroyed by boiling. Schwann also showed that the putrefaction of meat was biologically mediated too, it could be slowed by heating and sealing the meat. These biological breakthroughs incensed the chemists who soon got their revenge. In the meantime, Schwann embarked on a microscopic study of the role of cells in animal development and in biology generally. The resulting ‘cell theory’ published in 1839 revolutionized how the body was viewed.

Since the theory of the four humours, the important components of the body had been thought to be the fluids and airs: the blood, phlegm, bile, urine, semen, cerebral-spinal fluid and pneuma. The important locations inside the body were the cavities (of heart, lungs, brain, guts, and blood vessels) where life was manifested in the turbulent motions of fluids and airs. The solid parts of the body (the ‘flesh’) were regarded as largely structural, perhaps because their very solidity and lack of motion argued against any involvement in change; therefore it was hard to conceive how they might be involved in the vital processes. Schwann changed all that, showing that the tissues were composed of cells and it was within the cells that most vital processes were generated. The cells were not static structures: they had a life of their own. They grew, reproduced, changed into different forms and died. Most importantly the power to cause change was located within the cells themselves, not their surroundings. Schwann called this power ‘metabolism’, from the Greek word for change. This ‘intracellular metabolism’ was responsible for fermentation by yeast and for respiration and heat production by all cells. If the secrets of life and energy were to be found, science would now have to follow the trail into the cell rather than pursuing phantom airs and vital forces. And this would require entirely new concepts and methods.

Cells were first seen by Robert Hooke in the early days of microscopes. But Hooke had only seen the large woody cells of plants. It was much harder to see animal cells, because they were smaller and their walls (membranes) were almost invisible. So the structure of animal tissue was unclear, and it had mostly been described in terms of fibres and ‘globules’ of unknown function. Schwann benefited from a great improvement in microscope optics, using this to show that not only were cells everywhere in the body, but that they were the body’s organizing principle. All cells in the body were derived from embryonic cells which divided and differentiated to form the hundreds of different types of cell making up the organism. If there was a vital principle in the body, Schwann believed that it had to be located in the cells, because all the essential processes, such as reproduction, growth, and respiration, were located in individual cells. Doubting the possibility of a vital force, Schwann thought all the properties of cells could be explained in terms of physical and chemical forces. He also believed that living processes within cells could be explained in terms of the physical structures and movements of the molecules. This was an important and influential insight which foreshadowed the spectacular explosion of cellular and molecular biology in the twentieth century. Though intensely religious, Schwann argued persuasively that the concept of a vital force was completely unnecessary, denying God’s achievement in originally producing the Universe and its physical forces: these were all that was necessary to create life.

Schwann did not have the whole answer to how cells created life, but he had found important clues in his notion of ‘metabolism’ and his discovery that digestion was partly due to pepsin. Pepsin was thought to be a ‘ferment’, but at the end of the nineteenth century it was found that ferments consisted of single biological molecules, now called ‘enzymes’. Enzymes are the magic molecules inside cells that actually cause the ‘change’ of metabolism. Enzymes are made from protein. They act on the chemicals and structures inside and outside the cell changing them from one form to another. For example, pepsin cuts other proteins into pieces without itself being cut up. Each type of enzyme can cause only one type of change but there are roughly 10,000 different types of enzyme in a cell. These enzymes are the alchemists of the cell. But each enzyme molecule can be regarded as a minute, exquisitely designed, molecular machine. Machines, because they are designed structures, performing specific tasks and transforming things by physically interacting with them; and molecular, because they consist of single molecules. Enzymes and the other molecular machines of the cell are the engines of life.

Enzymes were first discovered within yeast, as the word itself reflects – ‘enzyme’ means ‘in yeast’. Although Schwann and others had shown that fermentation was caused by yeast cells, this discovery was ridiculed by von Liebig and the chemists and replaced by von Liebig’s own nebulous chemical theory. So, the biological theory of fermentation (that it is caused by living cells rather than dead chemicals) had to be re-established later in the century by Louis Pasteur. Pasteur was unable, however, to isolate from yeast cells a ‘ferment’ which could cause the fermentation of grape juice into alcohol, in the absence of live cells. Thus it was unclear whether fermentation was a truly vital process, only occurring within living cells. This was crucial because if the sub-processes of life such as the transformation of chemicals, could not occur in isolation from a living cell, then this implied that there was indeed some vital force involved. In more practical terms, it also meant that science would never penetrate far into the cell, because the individual processes could not be studied in isolation. It was left to Buchner at the very end of the century to at last successfully grind up yeast cells, and isolate something (a bunch of enzymes) that could cause fermentation in the absence of living yeast cells. It is this event that marks the true beginning of Biochemistry, in part because it destroyed the concept of the vital force, but mainly because science had finally broken into the cell and was able to study the processes of life at the molecular level.

Schwann had opposed von Liebig and the other chemists’ views on virtually everything: the role of biology rather than chemistry in digestion, fermentation, putrefaction, metabolism, tissue structure, muscle function and the vital force. The chemists, clearly rattled by this upstart, went onto the attack, writing a satirical article on the views of the ‘biologists’ on fermentation. This article, drafted by Wöhler and made more vitriolic by von Liebig, ridiculed the cell theory of Schwann and others, scathingly describing it in terms of anthropomorphized cells shaped like distilling flasks with big mouths and stomachs, gulping down grape juice and belching out gases and alcohol. Schwann’s credibility was destroyed, he lost his job and was prevented from obtaining another academic post in Germany. He escaped into exile in Belgium, with a post in the Catholic University of Louvain, where his time was filled teaching anatomy. He never did any significant biological research again, keeping his head well below the parapet, and the chemists held the field once again in Germany. However, the experiments and book Schwann had produced in his four years of active research proved immensely influential, eventually leading to the demise of von Liebig’s ascendancy and the transformation of biology. Von Liebig publicly battled on against Pasteur, but after thirty years of denial eventually had to admit that he had been mistaken about the biological basis of fermentation. The stresses of the struggle and eventual defeat may well have contributed to his death soon afterwards. The idea of the vital force died with him, later to be reborn in the transmuted form of ‘Energy’.

We have now learnt our ‘chemistry’. We know life is not created by spirits sucked in from the air to push and pull the body’s levers; but rather an element of air, oxygen, is combined with molecules of food within the cells of the body, producing something then able to animate our bodies and minds. The stage is now set for the discovery of energy itself.