Introduction

Before we consider living things, let’s stop for a moment and reflect on what we have already learned about the natural world. We witnessed the discovery of how forces interact to cause matter to move, how gravitational attractions between all masses causes the earth and other planets to revolve around the sun, what forms of energy there are and what transformations of energy occur, what the elemental constituents of matter are, and how the atoms of which all matter is composed are structured. The combination of all of these remarkable discoveries has enabled people to view the physical world around them as a mechanism—without intelligence and functioning in a straightforward and predictable manner according to physical laws.

There are good sides and bad sides to this view of the physical universe. On the one hand, if we understand the mechanism of the universe, we can predict what will happen . This permits us to construct machines of our own to do things that we want done. All of the technology that helps us grow food, build houses, get from one place to another, communicate with each other, and entertain ourselves, has been made possible by our understanding of the mechanism of the universe. On the other hand, a mechanistic understanding of the universe takes away a sense of personal interaction between mankind and nature. Ancient peoples tried to get things to go their way by appealing to the gods and spirits on a personal level. Whether or not this actually worked, it provided spiritual rewards that a mechanistic view does not.

But during most of the time-period we have been considering, one phenomenon could not be explained mechanistically, and that was life. Living things have many remarkable properties that non-living matter does not have. As we shall see, thinkers such as Descartes as early as the 17^th century proposed that these living things could be explained in terms of clockwork mechanisms just like the solar system, but their explanations did not even come close to accounting for the remarkable properties of living things. Because living things are so incredibly complex, a real understanding of how they work was much longer in coming than the discoveries that are now the foundations of sciences like physics and chemistry. In fact, the word ‘biology’ did not even exist in the English language until 1819.

In this chapter, we will look at the ways people have struggled to explain life. Ultimately, we will find that none of these earlier explanations of life was really adequate. But only if we appreciate how people originally viewed life, and why their ideas made some sense given what they knew, can we fully grasp the significance of Darwin’s theory of evolution by natural selection, Mendel’s theory of how genetic characteristics are inherited, and all of the astounding advances in molecular biology and biochemistry in this century.

In other words, this chapter will deal mostly with ideas that we now do not accept as true. The experiments we will be discussing helped scientists move a little closer to a full understanding, but actually raised more questions than they answered. The answers that we want will have to wait for the discoveries that we will be talking about in the next few weeks. This examination of early studies of living things is a lesson in how scientific advances do not come right away, even if good people are working on a question to the best of their abilities. At any time, some scientific problems are just not ready to be solved. Until this century, the problem of life was one of them.

What does life do that is interesting?

Living things have a number of unique and remarkable characteristics, many of which would have been familiar to people who lived hundreds of years ago. In fact, people back then probably knew the habits of living things better than they did many other aspects of the world around them. Remember that they depended on plants and animals as sources of food, clothing, shelter, tools, pets, and ornamentation. Farmers had to know how to keep domesticated plants and animals alive and healthy. They had to know how to breed their stocks, what diseases they could be attacked by, what nourishment they needed, what natural rhythms they had, etc. People back then had a powerful incentive to study living things carefully and get to know them well. So what would they have discovered?

Two really astounding characteristics of living things is their ability to grow and reproduce. Corn stalks higher than your head grow up from tiny shoots just poking out of the ground. Large, powerful horses start out life as delicate little foals, unable to fend for themselves. When living things grow, they maintain a certain kind of organization while adding a considerable amount of mass. Corn shoots don’t look exactly like miniature stalks, but they can be recognized as corn very early, and distinguished from other plants. Similarly, newborn animals have an obviously youthful appearance but it is still easy to distinguish between foals, calves, fawns, and puppies. Very few non-living objects grow like living things do. Rust on metal is a good example of something non-living that might seem to grow like a mold, but the structure of a growing rust is much simpler than the structure of a growing horse or a growing plant. So one of the questions people wondered about early on was how living things could assimilate non-living matter (as in food) to produce more mass with the same basic structural organization.

Not only do living things grow, they also are able to produce nearly exact copies of themselves. This also is quite astonishing, and almost unheard of in the non-living world. The great bulk of living material on this earth exists only because living things do not merely grow and grow, but also divide and replicate. The northern lands of Canada and Siberia would not be covered with a carpet of spruce and hemlock trees if there were only one tree that kept getting bigger. Instead, these trees have been reproducing themselves for eons, so that now there are more trees on this earth than anyone could count.

Early farmers would have been well aware of the tremendous reproductive potential of living things. They relied on it to be able to plant next year’s crop of grains with the seeds from last year’s plants. They took care to breed their animals so they would always have enough to replace any that died, and even slaughter one from time to time to put meat on the table.

These two properties—growth and reproduction—are characteristic of all living things. In addition, people long ago recognized other characteristics that were more obvious in some living things than others. Many living things are sensitive to environmental stimuli and are able to respond in what appears to be an appropriate manner. Predators can track down and attack their prey, prey animals are wary of predators and will try to hide from or run away from them, herbivores know which plants are good to eat and will avoid poisonous ones.

We may be inclined to attribute this property more to animals than to plants. In animals we describe appropriate behavioral responses as ‘intelligent’. But plants are also capable of sensing their environment and responding accordingly. For example, many plants can sense which direction the sun is and will grow or turn towards it. Plants growing under other plants will grow upwards until they are out of the shade, and only then will they produce leaves.

Although plants may sense and respond, there are some things that only animals do. Only animals have muscles that they use to move around from place to place. Only animals care for their young. For the most part, only animals eat other living things. Exceptions to all of these statements could be found nowadays—for example, we now know that many bacteria and fungi live off of other organisms. But people back then were not aware of these things and drew more of an absolute distinction between plants, which flourish in the sun, and animals, which move from place to place in search of food.

One final characteristic of some living things, maybe only of humans, is conscious experience. This is a remarkable phenomenon in any person’s life, though one which many people take for granted. Opinions have differed about whether other animals besides humans are conscious. In folk tales, animals are often made to talk and think just like people, but until recently, most intellectuals felt fairly sure that only humans were conscious. Our consciousness was often explained in terms of an immortal, rational soul which was supposed to be independent of our physical bodies yet somehow interacting with them. Since animals do not have rational souls, it was thought, they must not be conscious.

Early explanations of life

How did people explain all of these remarkable characteristics of living things? The earliest attempts at rational explanations for these phenomena were made by the ancient Greeks, around the 6^th century BC Their explanations fell into three general classes:

1) life is a kind of matter

2) life is a non-physical principle imposed on matter

3) life is a kind of organization of matter

These three types of explanations did not come one after another. Instead, they have all coexisted for long periods of time as rival solutions to the problem of life.

Some of the early Greek philosophers proposed that life is in some way the same thing as air. In fact, the Greek word for ‘spirit’ is pneuma, which was also their word for ‘breath’. Just as we might nowadays refer to ‘the breath of life’, the connection between breathing and being alive seemed especially fundamental to them. Other early Greek philosophers equated life with fire. Perhaps they did this because of the four elements, fire is the most active and lifelike. It has no apparent substance, yet it is powerful and fearsome. It ‘lives’ on the bodies of the things that it consumes, moving from body to body without going out, and it ‘reproduces’ itself by spreading from flammable object to flammable object. Also, the idea that people are alive only as long as their ‘inner fire’ burns has been around for a long time, showing up here and there in various guises. Like other mammals, humans generate heat. And when a person dies, they become cold. These and other observations probably stimulated the idea that life is somehow like fire.

The Greek philosophers also pioneered the idea of life as something non-physical imposed on matter. Plato is probably the person most closely associated with this idea. His works were admired by early Christian thinkers, because his idea of a non-physical soul which gave life to the physical body fitted most readily with Christian theology. According to this idea, even a human body is just a mixture of lifeless matter unless it is ‘inspired’ by a soul. Exactly what sort of existence this soul was thought to have is not entirely clear, but it was not imagined as being corporeal like physical bodies. Nevertheless, the soul was said to interact with the body in some ways. In reproduction, for example, the life-giving principle was thought to pass through ducts to permit the generation of babies who have souls of their own.

In Plato’s system, the human soul is just one of a number of kinds of souls in the universe. Plato also spoke of a cosmic soul that moves the planets in their orbits. And since the activities other living things besides humans also require explanation, he imagined a kind of soul that is characteristic of animals and another one characteristic of plants.

The other great philosopher of the Athenian golden age, Aristotle, also described life in terms of souls, but his idea of soul was very different from Plato’s. Aristotle viewed the essential principle of life not as something non-physical, imposed on matter, but as a special kind of organization of matter. For Aristotle, souls were not mysterious cosmic beings but were physical organizing principles.

The four souls in Aristotle’s system were:

1) a nutritive soul, found in plants and animals, controlling growth and nutrition

2) a sensitive soul, found only in animals, enabling them to respond to environmental stimuli

3) a locomotor soul, found only in animals, enabling them to move around

4) a rational soul, found only in humans, producing thought and consciousness

Once again, Aristotle’s thoughts on the subject represent a kind of culmination of the thinking of his time. And many of his ideas on these subjects, like his ideas on other subjects we have looked at this semester, survived through the Middle Ages and into the period of the Scientific Renaissance. Aristotle made many observations of living things and even conducted some simple experiments. Although he had a fuller awareness of the phenomena of living things than any other person alive in his time, he did not have enough information to describe how processes like nutrition, sensitivity, locomotion, and reason were controlled.

We nowadays might say he was generally right in thinking that all of these processes can be understood in terms of a particular kind of organization of matter. But his explanations of these processes, in terms of organizing principles, is actually a sort of non-explanation. If you accept that all of these processes result from particular kinds of physical organization, then what you really want to know is what kind of organization makes them possible and how? Just saying that plants have a nutritive soul, an organizing principle that enables them to grow, explains nothing. The big question is: how exactly is this organization maintained? What are the specific physical characteristics of this ‘organizing principle’ that makes growth possible? People started addressing this question when they started looking for mechanisms at work in living things.

The replacement of soul with mechanism

As we just saw, the idea of a soul was used by ancient Greek philosophers in two very different ways: either as a non-physical entity imposed on the physical body and giving life to it, or as a physical organizing principle, the exact mechanism of which is unknown. The former idea is most closely associated with Plato and the latter with Aristotle. During the period of the Middle Ages, when Christian theology was the dominant unifying idea in European culture, Plato’s idea of a soul as something added to the physical body was the accepted explanation for the characteristics of living things.

This idea of life as being caused by a soul or spirit that is (1) not physical, and (2) not found in any non-living things, seems to be a natural, intuitive way to explain life. It could be described as a natural response to the sense of wonder that living things inspire in us. There does indeed seem to be a kind of ‘vital spark’ in living things that inspires awe. Who after all can be unmoved by the reawakening of plant and animal life in the spring, by the miracle of birth, or by the remarkable ability of living things to sense what is going on around them and respond in a seemingly intelligent way? Even a common housefly exhibits such a remarkable array of properties and behaviors that it is difficult to accept that it could be a mere machine. And consider how much more inconceivable it must be to mechanistically explain an animal as beautiful and mysterious as a lion, able to hunt down pray by stealth and calculation, interact socially with other lions, and raise its young with loving care.

Nowadays, biologists pretty uniformly reject the idea of a non-physical soul or spirit, in favor of a more Aristotelian approach, explaining life as a particular type of organization of purely physical material: as a mechanism. Yet many non-scientists still find the idea of a special kind of non-physical entity—a soul or spirit—to be an agreeable explanation for life. Biologists might explain this tendency by supposing that people who don’t know much about how life actually works simply cannot imagine a mechanism as complex as what goes on in the cells of living things. Instead they go with their gut intuition and view life as the product of matter and spirit, even though they have no concrete evidence for this belief.

Regardless of the continuing belief in spirit among laypersons, people who have made a special study of life over the past several hundred years have become increasingly convinced that everything about life can be explained mechanistically. While a biologist today may agree with this trend, and may feel that recent discoveries in biology have thoroughly supported this conviction, one must also admit that the conviction appeared long before there were adequate explanations to support it. Aristotle taught that the nutritive, sensitive, locomotor, and rational functions of living things were produced by physical organizing principles even though he had no idea what those organizing principles actually did. As we will see, Descartes further developed this idea in the seventeenth century, arguing vigorously that everything but human consciousness could be explained mechanistically, but his particular explanations for biological processes appear absurdly simplistic from our perspective today.

The willingness of people life Aristotle and Descartes, and their followers, to accept the idea that life can be explained mechanistically was a product of their basic conviction that everything in the world ought to be explained physically, using the scientific method. This conviction is called naturalism and it is the basis of all scientific work. Whether or not it is true is not our concern here.

In any event, the first attempts to explain biological processes mechanistically were not promising. Descartes was especially aggressive in offering speculative hypotheses about life functions. For example, he accepted the idea of Galen, an ancient Roman medical writer, that the nerves are hollow tubes filled with an especially pure bodily fluid. Descartes’ model for how animals could sense pain and respond by moving their muscles was based on the hydraulic mechanisms that in his time were used in church organs and in our time are used in automobile braking systems. According to his model, when a person’s foot came to close to a fire, the heat excited the fluid in their nerves, causing a pressure wave to travel up to their brain. The reflex response in the muscles was in his view achieved by means of similar hydraulic mechanisms.

Descartes also proposed many other mechanistic explanations for other biological processes. The explanations he offered were highly imaginative and almost uniformly wrong. The reason Descartes is not universally admired and respected by scientists today is that his approach is now viewed as being too speculative. By contrast, his English contemporary Robert Boyle performed many more experiments and was much more cautious in drawing speculative conclusions based on his observations. He wasn’t able to offer as many intriguing new ideas, but more of the ideas he did offer turned out to be right.

In fairness to Descartes, however, he did make a point of stressing that his explanations were only intended as examples of how biological processes could be explained. In Descartes’ view, there are no limits to what God can do so no one can claim to say how God must have created the universe. We can therefore only offer plausible explanations for how God could have arranged things. Descartes’ goal was to convince his contemporaries that even the remarkable characteristics of living things can in principle be explained mechanistically. He therefore wanted to be able to offer explanations that were at least plausible given what people knew at that time, even if he could not be confident that they were in fact true.
The inadequacy of mechanistic explanations

Descartes was one of the first noteworthy advocates of a mechanistic explanation for living things. In his opinion, everything but the rational soul of human beings should be explainable in terms of purely physical mechanisms. He therefore considered all animals except human beings to be nothing more than complex, subtle machines, more ingenious perhaps but in principle no different than a machine. The machine was an attractive analogy for living things because, in Descartes’ day, people were constructing some remarkable ‘automata’. One such device was a bird that could eat solid food and then break it up in a process resembling digestion and even excrete solid waste! Machines like this were exhibited at shows and bought by the wealthy as amusements for their friends. The idea of comparing living things to these machines was reminiscent of the tendency people have nowadays to compare the human brain with a computer—people naturally try to explain mysteries in terms of the common technologies of their day.

In Descartes’ system, humans were constructed of physical mechanisms similar to those of other animals, but in addition to the physical body they also were thought to have a non-physical soul. Descartes identified one small brain structure called the pineal gland as the point where the physical body and the soul interacted with each other. He chose this structure because it sits atop the fluid-filled ventricles in the brain (the space that Descartes, according to his hydraulic model, thought were the sites of sensory and motor signals), and it is one of the few structures in the brain that does not occur in a symmetrical pair, one on each side of the brain.

In the eighteenth century, another French philosopher named La Mettrie went one step further than Descartes, proposing that even human beings are purely physical mechanisms. He wrote a book entitled, “Man, A Machine” in which he proposed one of the first completely materialistic models of human existence. This book was highly controversial in the European culture its day, since it directly contradicted the Christian conception of a non-physical, immortal soul.

It is hard to imagine nowadays how violently many people reacted to La Mettrie’s ideas, since materialism is a much more common viewpoint now than it was in La Mettrie’s day. In La Mettrie’s day, many people who were committed to mechanistic explanations for physical phenomena nevertheless rejected the idea that life could be explained mechanistically. There were at the time many good reasons for rejecting that idea, and regardless of whether or not you personally side with La Mettrie, it is worth noting that the materialistic position that he was championing was a highly speculative hypothesis.

Viewed from our perspective today, the mechanistic explanations offered by Descartes appear absurdly simplistic.

By contrast, the mechanistic explanations that are generally accepted today are based on a wealth of observations and evidence that were unavailable in Descartes’ time. The mechanisms involved in biological processes function on the level of individual molecules interacting within cells. The microscopes of La Mettrie’s day were capable of distinguishing some types of cells, but no one then had any idea what sort of molecules existed within those cells. We now understand living things to be many times more complex than any of the phenomena that were being explained mechanistically back then. So it is not surprising that adequate mechanistic explanations for living things were much longer in coming than the mechanistic explanations of physics and chemistry.

One example that illustrates the difficulty of explaining biological processes in the 17^th and 18^th century is the question of the circulation of blood. According to the ancient explanation of blood, food was heated in the stomach, producing a purer distillation of the nutritive material, which was then heated again in the heart, producing blood. This blood, whose function was to provide nutrients to the tissues, then slowly oozed out from the heart to the tissues, where it was consumed in the process of tissue growth, movement of muscles, etc. Tissues derived nutrients from consuming blood just as we derive nutrients by consuming food.

In the early 17^th century, William Harvey, one of the royal physicians to the court of England, performed a series of experiments that convinced him that the ancient view was mistaken. Instead, he proposed that blood circulates from the heart, through the arteries, into and out of the tissues, and then back through the veins. His evidence was based primarily on two observations: the rate of flow of blood was much greater than would be predicted if blood was slowly consumed in tissues, and he could demonstrate that blood in veins actually moved from the tissues towards the heart rather than the reverse.

Although Harvey’s experiments were fairly conclusive in demonstrating that blood circulates, that conclusion was nevertheless rejected by many people. The main argument against his conclusion was that he could offer no explanation for how blood could provide nutrients to the tissues if it merely circulated and was not actually consumed in the tissues. We can nowadays explain this by noting (1) that most of the volume of blood is water which for the most part is not taken up by tissues, (2) the glucose and other nutrient molecules taken up by tissues make up only a small part of the volume of blood, and (3) the main reason why blood must circulate fairly rapidly through the body is the need to deliver oxygen and remove carbon dioxide from tissues. The observations on which these ideas are based had not been made in Harvey’s time. And important issues like why tissues consume oxygen and produce carbon dioxide, how exactly tissues are able to generate energy from glucose molecules, and what need tissues have for other nutrient molecules like amino acids, could not be resolved until well into the 20^th century.

You might think it was unreasonable of Harvey’s contemporaries to demand explanations for things that would not be completely explained until hundreds of years later. But the purpose of scientific hypotheses is to explain things, and it is only natural for people to be dissatisfied with incomplete explanations. The ancient explanation of blood might have been wrong, but at least it provided an intuitively plausible idea of how blood was nutritious for tissues, by analogy to the consumption of food by the whole organism. By contrast, Harvey’s description of the movement of blood cut the ground out from under the supposed explanation that people in his time had grown accustomed to. It is therefore not surprising that many people preferred to ignore his findings rather than be confronted with a new mystery.

Another major challenge to early mechanistic models of life was the problem of reproduction. Perhaps the most remarkable characteristic of living things is their ability to produce more of their kind, the offspring resembling the parents but not exactly the same as the parents. In a non-mechanistic explanation of life, each new individual comes into being when a non-physical soul unites with a bit of the right kind of matter and then directs its further development into a new individual. If there is no soul, as in a mechanistic explanation, how is each new living thing produced? Where do the organized structures—the arms, the legs, the internal organs—come from?

The two main historical views of biological development are commonly labeled preformationism and epigenesis. According to preformationism, a tiny, fully formed structure pre-exists in each newly formed embryo. During development, the parts of this structure simply grow larger by adding more material to the preformed structure to make an adult body. In the Aristotelian model, the female was supposed to provide the matter for the body and the male the form, so the preformationists typically hypothesized that the generative structure was to be found in the sperm cells of the male. There were even claims that the outlines of this structure could be discerned by examining sperm cells with a microscope.

Epigeneticists, on the other hand, felt there were profound problems with the preformationist model. If all of the structures in an adult were to be preformed in the sperm, then wouldn’t that sperm also have to contain preformed structures to correspond to all of the sperm that would eventually be produced by the adult male? And wouldn’t the sperm precursors in the grandfather’s sperm have to contain preformed structures to correspond to all of the sperm that would eventually be produced by his grandsons, and so on? Taken to an extreme, this model would imply that all of the bodies of all of the human beings who have ever lived or will live must have been preformed in Adam’s testes. This is a daunting thought, to say the least!

Faced with such logical implications, the epigeneticists instead hypothesized that the structures of the adult body are not present in the early embryo but instead manifest themselves during the development of the fetus. In fact, a microscopic examination of embryonic development shows that the cell from which the embryo develops looks pretty much like any other cell. As this cell divides and divides, the embryo starts as a kind of hollow ball and only later takes on more of a tubular shape. One end then swells up (later becoming the head), the buds of limbs begin to appear at the appropriate points along the tube (later becoming arms and legs), and so on.

So the appearances would seem to support the epigenetic viewpoint, but that didn’t keep preformationists of the 19^th century from reporting the existence of little man-like creatures, called ‘homunculi’, in the head of sperm. Textbooks of that day even include figures depicting these non-existent structures. Also, when challenged by preformationists, the epigeneticists could not satisfactorily explain how structures could come into being where there were no visible precursors of those structures before. If one supposed the existence of a soul, this would not be such a problem, since the soul could contain within it some sort of developmental intelligence that directed how the matter of the body should be arranged. But in the absence of a soul, where were the instructions coming from that directed the development of the embryo?

We now understand how the DNA sequence of a cell causes certain proteins to be produced, which determine how cells grow, divide, change shape, perform metabolic functions, etc. An organism’s DNA contains the instructions that control not only development but also all of the life functions of the mature organism. This DNA and the proteins made from it are so much smaller than cells that the microscopes available during the great preformationist/epigeneticist debate in the 19^th century could not even come close to making them visible. And while the epigeneticists may have been right in rejecting the overly simplistic explanation offered by the preformationists, their model left so many questions unanswered that it is not surprising if not everyone chose to agree with them.

Faced with inadequacies such as these in mechanistic explanations for life, a significant number of scientists instead embraced the idea that there was something irreducibly special about life—something that was not found in any other physical objects. This idea in its various forms has been referred to as vitalism. One form of vitalism is the idea that living things differ from non-living matter in that they have a non-physical soul. Some vitalists, on the other hand, accepting the materialist position that there isn’t anything that is non-physical, instead supposed that life is (or includes) a special kind of matter which has properties that are unlike any of the materials that make up non-living objects. A third, more cautious form of vitalism posits that there is some physical process that is unique to living things, and that it is therefore impossible to explain life simply in terms of the forces and energies by which we have already explained physical and chemical phenomena. In other words, there are forms of ‘vitalism’ that do not differ much from the modern mechanistic explanation of living things. Nevertheless, the root fundamental between mechanism and vitalism was fairly states by Theodore Schwann in the following passage from an 1847 paper (bracketed material is added):

The various opinions entertained with respect to the fundamental powers of an organized body [a living organism] may be reduced to two, which are essentially different from one another. The first [vitalism] is, that every organisms originates with an inherent power, which models it into conformity with a predominant idea, arranging the molecules in the relation necessary for accomplishing certain purposes held forth by this idea. Here, therefore, that which arranges and combines the molecules is a power acting with a definite purpose. A power of this kind would be essentially different from all the powers of inorganic nature, because action goes on in the latter quire blindly…The other view [mechanism] is, that the fundamental powers of organized bodies agree essentially with those of inorganic nature, that they work altogether blindly according to laws of necessity and irrespective of any purpose, that they are powers which are as much established with the existence of matter as the physical powers are.

Given how much more complete our mechanistic explanations of life are now, vitalism is now in disrepute. Biologists feel that they have achieved a reasonably complete description of life that is based entirely on the forces and energies that have also been observed in non-living matter. Granted, there are molecules (like proteins and DNA) that would never exist if it weren’t for living things, but those molecules are synthesized by means of chemical reactions that follow the same laws of chemical reactions that operate on non-living matter. And once formed, those molecules are subject to the same thermodynamic equations that explain the energy transformations in non-living matter.

From the perspective of a modern-day biologist, vitalism seems like a cop-out. Given how incredibly complex living things are, it is only natural that people would have been tempted to explain them by positing some hitherto unknown type of matter or physical process. Like Aristotle’s souls, however, that would be an explanation that doesn’t really explain anything until you are able to describe how that unique type of matter or physical process makes living things function as they do. One or two hundred years ago, no one could have definitely predicted whether the mechanists or vitalists would turn out to be correct. But as it has turned out, it does appear that mechanical explanations have finally succeeded. Before we heap too much glory on the early mechanists like Descartes and La Mettrie, however, we should acknowledge that the mechanical explanations that have finally succeeded are utterly unlike anything they ever imagined.

The major advances that made our modern understanding of life possible were (1) Darwin’s conceptualization of the history of life as an evolution driven by the natural selection of useful variations, (2) the description of the laws of genetic inheritance by Gregor Mendel, T. H. Morgan and others, (3) the discovery of how DNA acts as the genetic material to regulate the functions of living cells, and (4) the discovery of how living things capture energy from the sun and use the energy stored in organic molecules to fuel cellular functions. These advances will be described in the next three weeks. In the remainder of this reading, I will describe five developments in the 19^th century that prepared the ground for the major advances that were to come. The order in which I’m presenting them does not necessarily reflect the order in which advances occurred. Actually, these issues were being debated concurrently, throughout much of the 19^th century.

The cell theory

We now understand that every function of a living thing takes place inside of a cell, and that large living things like human beings and oak trees are made up of many tiny cells. But this idea was not immediately obvious until microscope technology enabled people to see small things with more precision. The first microscopic investigations were conducted in the 17^th century by Robert Hooke, Antony van Leewenhoek, and others. In the 1660’s, Robert Hooke published a drawing of a sample of cork, showing the many little compartments, or cells, of which it was constructed. Just after that, van Leeuwenhoek published his drawings of tiny little creatures, or animalcules, that he observed in microscopic investigations of samples of pond water.

But the idea that all living things were entirely made up of cells was not by any means obvious at that time. Because they don’t have cell walls, the individual cells in animal tissues are not nearly as evident as the plant cells in a piece of cork. Before they could be seen, better microscopes as well as innovative new techniques for staining the tissue had to be invented.

The two scientists who get most of the credit for the idea that all living things are made up of cells are Matthias Schleiden and Theodore Schwann. They were not, however, the first to propose such an idea. They just happened to be championing the idea when enough evidence had accumulated for it that the scientific community finally became convinced. In such cases, earlier investigators like Lamarck, Dutrochet, and Meyen seldom get the credit they deserve for proposing ideas that they could not adequately back up.

Schwann did however appreciate the importance of the cell theory for the theory of life, and he was articulate enough to convey this appreciation to his colleagues. Schwann realized that each cell, even in a multicellular organism, is a living system. Although the cells in our bodies could not live on their own ‘in the wild’, they are able to perform all of the basic metabolic functions that are associated with life, and they can in fact be kept alive in petri dishes if provided with the water, nutrients, and oxygen that they need. Schwann pointed out, in 1847, that if each cell is alive, then the question “what is life” is a cellular question. This represented a much-needed simplification of the mystery of life.

As long as people focused on multicellular organisms like human beings, plants, and even insects, life did indeed seem something truly miraculous. But Schwann stressed in his papers that the activities of complex, multicellular organisms were nothing more than the combined activities of the cells that made them up. This means that whatever the mysterious life process is, it is something that is no more complex than a single cell. From our perspective today, we now understand even single cells to be rather complex, but nevertheless reducing the problem of life to the level of single cells made a mechanistic explanation seem much more plausible.

The synthesis of organic molecules

Following Lavoisier’s reform of chemistry and the discovery of some of the elements that make up all matter, there was a burst of chemical investigations in the early 19^th century. For the first time, people were able to determine what elements complex molecules were made of. During this period, chemists realized that extracts of living matter were predominantly composed of four elements—carbon, hydrogen, oxygen, and nitrogen—with smaller amounts of sulphur, phosphorus, and other elements. They also characterized a number of molecules, such as glucose and various amino acids, that are only found in association with living things. This was the beginning of the field of organic chemistry: the study of the molecules found in ‘organized bodies’, which was the early 19^th century term for what we would now call ‘organisms’.

The fact that many molecules were only found in association with living things initially seemed to support some types of vitalistic explanations of life. It seems strange from our perspective today, but at the time people seriously supposed that these molecules could only be synthesized in living systems. But in 1828 Friedrich Wohler, one of the leading organic chemists of his day, accidentally synthesized urea from lead cyanate and ammonia. Urea is a molecule produced in the kidneys of mammals and some other animals and excreted in the urine. This is often described as the first time an organic molecule had been synthesized from inorganic molecules, and Wohler in his report of his experiments did in fact remark on his ability to synthesize urea “without needing a kidney.” However, lead cyanate was at that time prepared from animal sources, so the materials from which Wohler synthesized urea were not completely inorganic.

But is wasn’t long after that, in 1845, that Kolbe synthesized acetic acid, another organic molecule, from completely inorganic materials. In the years to come, chemists would become accustomed to the completely inorganic synthesis of many different types of organic molecules, demonstrating that the chemistry of living things is not fundamentally different from chemistry in general. This was one more step away from vitalism, towards mechanism.

The fermentation controversy

Although there is no fundamental difference between the chemistry of organic vs. inorganic molecules, there are nevertheless a number of chemical reactions that are ordinarily only found in association with organic matter. Among these are the souring of milk, the fermentation of fruits and grains to produce alcohol, and the putrefaction and decay of plant and animal carcasses. Throughout the 19^th century, there was an active debate over whether these processes were simply chemical reactions among organic molecules or whether they required the activity of cellular microorganisms, like bacteria and yeast cells.

During this debate, special attention was focused on the fermentation reactions in the production of alcohol and the souring of milk because these were easy to produce in a laboratory setting and they had potential economic applications in preserving milk and improving the beer and wine-making process. For centuries, people had appreciated that the ‘yeast’, a material that formed like a scum on the surface of the fermentation vats, needed to be added to the mash to produce the most rapid and successful fermentations. This suggested that the product of previous fermentations somehow assisted the development of fermentation in new organic material. In the early 19^th century, chemists had also observed how metals and other simple molecules could be added to other materials and dramatically speed up certain chemical reactions. A similar effect had also been observed using organic extracts like gastric juice and material from plant roots. In 1835, Jons Jacob Berzelius proposed the term catalysis to describe the capability of one molecule to speed up a chemical reaction involving other molecules. The molecule that facilitated the chemical reaction without itself being changed in the reaction was called a catalyst. In fermentation reactions, the yeast produced in a previous fermentation appeared to have catalytic properties.

Friedrich Wohler and Justus Liebig argued vigorously that these processes simply represented the natural chemical reactions that occurred among organic molecules. Liebig hypothesized that because carbon, hydrogen, nitrogen, and other elements in organic molecules had differing attractions for the oxygen in the atmosphere, the elements in organic molecules would spontaneously rearrange themselves once the organizing mechanism operating in living things ceases to function after death. In their view, molecules in the process of becoming ‘disorganized’ trigger a similar process of disorganization in other molecules. The yeast remaining from a previous fermentation, having been produced in a disorganizing process, could also stimulate the disorganization of the new organic matter that it was brought into contact with.

My impression is that the enthusiasm of chemists like Wohler and Liebig for a purely chemical explanation of fermentation was driven in part by their desire to advance mechanistic explanations for living processes. Just as the laboratory synthesis of organic molecules struck a small blow against vitalism, the demonstration that many of the chemical reactions associated with living things could take place using just the physical materials of those living things would further argue that life was just a special kind of physical process.

However, by the time Wohler and Liebig were advocating their views, a number of investigators had already made observations suggesting that cellular microorganisms were involved in the process of fermentation. In 1803, Louis Jacques Thenard reported that the yeasty material produced in fermentation had roughly the same chemical makeup (including a certain amount of nitrogen) that is found in animal matter. This led him to conclude that, “the germ of fermentation was of animal nature.” In 1810, Nicolas Appert and then Joseph Louis Gay-Lussac reported that food would not decay if first heated and then bottled so as not to be in contact with air. On the basis of these experiments, Gay-Lussac hypothesized that the fermentation involved in food spoilage requires oxygen. We now take this as evidence that living things are involved, but note how Liebig and Wohler (above) were able to incorporate the involvement of oxygen into a purely chemical model of fermentation reactions.

The most potent evidence for an involvement of cellular microorganisms in fermentation came from technical improvements in the design of microscopes. The microscopes produced in the 1830’s magnified 300 to 400 times more than previous microscopes. In 1837, Charles Cagniard-Latour reported that he had observed, “a mass of little globular bodies able to reproduce themselves,” in the yeast of beer. These bodies appeared to promote fermentation only as long as they were living.

Theodore Schwann further supported this conclusion in another study published in the same year. Schwann reported that when a flask of fermentable material was first placed in boiling water to kill any microorganisms, cooled, and then exposed to atmospheric air that had been heated while passing through a thin glass tube, fermentation would not occur even after 4 to 6 weeks. Material treated in the same manner but exposed to unheated air did ferment. This experiment suggested that something living must enter the flask through the air, but that heating the air is sufficient to kill airborne microorganisms.

Schwann also reported observing, “oval granules of a yellowish-white color,” when beer yeast was put under the microscope. He found that a poison known to kill both bacteria and molds would destroy these granules and stop fermentation, while another poison that killed bacteria but not molds did not harm these microorganisms. Based on this finding, Schwann concluded that the granules in beer yeast were fungi—a conclusion that has proved true.

The findings of Cagniard-Latour, Schwann, and other advocates of a biological explanation for fermentations were not accepted by Wohler and Liebig. In 1839, an anonymous letter to the scientific journal Annalen der Pharmacie ridiculed the reports of cellular microorganisms in yeasts. The writer of that letter, now thought to be Friedrich Wohler, facetiously reported the characteristics of animals he claimed to have observed in yeasts:

These animals have the form of a Beindorf still (without the cooling apparatus)… From the moment that they escape from the egg, one sees that these animals swallow sugar from the surrounding solution; one can see it arrive in the stomach quite clearly. It is instantly digested, and this digestion is instantly and most definitely recognized by the subsequent expulsion of excrement. In a word, these infusoria eat sugar, empty wine alcohol from the intestinal canal, and carbonic acid from the bladder. In the full condition, the bladder possesses the form of a champagne bottle….

In 1857, Louis Pasteur performed a series of experiments that further supported the biological interpretation of fermentation. His experiments were no more conclusive than those previously performed, but he controlled his experimental conditions more thoroughly than other investigators had, making the case for biological fermentation stronger but still not decisive. In perhaps the most persuasive of his experiments, Pasteur concocted a solution of organic material that could support either alcoholic fermentation or the lactic acid fermentation that occurs in spoiling milk. He showed that when this solution was exposed to beer yeast, alcohol was produced. When it was exposed to lactic acid yeast, lactic acid was produced. When a solution was not seeded with cells of one type, a community of various different types of microorganisms grew up, producing a variety of fermentation reactions. He also showed that the rate of fermentation increased as more cellular microorganisms were present, as determined by microscopic observations. Pasteur’s experiments incidentally led to the process of pasteurization of milk—preserving the milk by heating it to kill off all microorganisms.

Pasteur’s experiments did not really resolve the question of fermentation. The interesting thing about this controversy is that among the ‘fermentations’ being studied in the 19^th century, some reactions did involve the proliferation of cellular microorganisms while some could be activated by cell-free extracts of living things. Pasteur and other proponents of the biological explanation concentrated their efforts on those fermentations that did involve cells, while Liebig and Wohler studied fermentations that were possible with cell-free extracts. Examples of these fermentations included the splitting of amygdalin by an extract of bitter almonds and the digestive reactions that could be produced by extracts of gastric juices.

The true nature of fermentations was somewhat resolved in 1897, when Eduard Buchner demonstrated that alcoholic fermentation could be produced by cell-free extracts of yeasts. This finding suggested that the ultimate mechanisms of fermentations were in fact molecules, but that these molecules were produced in the cells of living things. Yeast was essential to start alcoholic fermentation not, as Liebig and Wohler had thought, because decomposing matter induces decomposition in other matter, but because the proliferation of yeast cells is accompanied by the synthesis of large quantities of the molecules that catalyze fermentation reactions. In 1878, Kuhne had already coined the term enzyme to describe a biological substance that catalyzes a chemical reaction. We now understand these enzymes to be protein molecules produced in the cells of living things.

Cryptobiology

Many of the early hypotheses about the nature of life focused on life as a process. The metabolic activity of living things consumes food and oxygen to enable animals to grow, move around, reproduce, etc. This metabolic activity also produces heat. Before any of this was understood on the cellular and molecular level, it must indeed have seemed that life was a kind of inner fire, activating what would otherwise be inanimate matter. Since the ‘fire’ of metabolism, and along with it the need to breathe, is continuous throughout life and stops at the very moment of death, when the organism becomes still and cold, people not surprisingly felt that the maintenance of metabolic activity was an essential part of being alive.

This view was challenged in the 18^th century when people reported the resurrection of small creatures that had appeared to be dead. The first such report that captured people’s attention was John Needham’s account of small eel worms that can dry up to the point where all metabolism stops and can then be revitalized by the addition of water. After Needham described this phenomenon, people quite naturally doubted that the life process had indeed stopped completely in the dried-up worms. To test this, Lazzaro Spallanzani (who had doubted Needham’s findings) subjected the dried nematodes to high temperatures, exposure to a vacuum, and electric shocks, all of which would have killed a normally living worm but none of which prevented the subsequent resurrection of the dried-up ones.

Given the counter-intuitive nature of this phenomenon, which is called cryptobiosis (hidden life), many scientists refused to believe that metabolism had indeed stopped in the dried-up eel worms, even after Spallanzani reported his experiments. Nevertheless, the resurrection of eel worms became a kind of popular fad. People would purchase these dried-up worms and then revive them with water and, with their friends, watch them return to life under a microscope.

By the middle of the 19^th century, a number of other organisms that can be dried up and then revived had been discovered, including a group of organisms known as tardigrades, or ‘water bears’. Tardigrades live near the surface of many soils, where they feed on decaying organic matter as long as water is available and then enter a state of cryptobiosis when the soil dries up. Further experiments in the 19^th century subjected cryptobiotic organisms to as much as 82 days under vacuum, heating to 100 degrees centigrade (the boiling point of water), enormous doses of ionizing radiation, and still they could be revived by the addition of water.

The importance of the phenomenon of cryptobiosis is that it encouraged the idea of life not as a process (metabolism) but as a particular kind of organized structure. To people who believed that cryptobiotic organisms were indeed not metabolizing at all, the essence of life must be in the particular form of organization of living things. Some organisms appear to be able to maintain this organization even when they dry up and cease metabolizing. And when they take up water again, this preserved organization supports the resumption of normal metabolism. In truth, it is difficult from our perspective today to adequately assess how influential this phenomenon in changing people’s view of life, but it at least foreshadowed the newer understanding of life that was eventually to emerge in the 20^th century.

Spontaneous generation

The question of how life emerges was also actively debated in the 19^th century. Some people believed that under the right conditions, living things will come into existence from non-living matter. For example, maggots were widely thought to emerge spontaneously when organic matter was left to decay. This belief was based on the observation that, without introducing maggots, they would nevertheless appear when material was allowed to rot. Of course, we now understand that the maggots just hatch from microscopic eggs that had already been laid in the organic material and had been lying dormant. And in fact this particular form of supposed spontaneous generation was disproved when it was shown that organic material which was first heated to kill off eggs and then protected from further contamination would not give rise to maggots.

But people still continued to believe that microorganisms could spontaneously come into existence in the right nutrient media. The role of Pasteur in (supposedly) resolving this question, and the debates between Pasteur and Pouchet on this issue, are described in the reading for this Friday.

Why was life not understood until recently?

By the beginning of the 20^th century, many of the key discoveries in physics and chemistry had already been made. These sciences are of course still evolving, and we have already seen how many of the key discoveries of the atomic structure were not made until earlier in this century. Even now, high-energy physicists using supercolliders are further exploring the nature of the smallest atomic particles. But it would still be accurate to describe the physics and chemistry at the turn of this century as relatively mature and complete sciences. By contrast, the biology of 100 years ago was still in its infancy, and most of the fundamental questions about the nature of life were still far from being answered.

Why has biology been so long in maturing? Why have the key advances in biology come so long after key advances in physics and chemistry? In part, this is because the study of living things is a special application of the sciences of physics and chemistry. Living things function in the context of the fundamental physical laws that make up the sciences of physics and chemistry. For example, biological chemistry could not possibly be understood until Lavoisier and others had correctly identified the elements that make up all molecules. And the description of biological metabolism, as we shall see in topic 11, followed key advances in the understanding of chemical thermodynamics.

But another reason advances in biology have lagged behind advances in physics and chemistry is because biological organisms are astoundingly complex structures. The protein and nucleic acid molecules that are key to biological functions are among the most complex molecules known, and are hundreds to thousands of times larger than most inorganic molecules. Given the central importance of DNA and proteins in determining the functional characteristics of living things, we could not hope to understand life until we had developed technology to enable us to study the molecular structure of these molecules.

A single cell consists of an organized and regulated combination of billions of these complex biological molecules, each one of which performs a specific task that is necessary for the survival of the cell. In comparison even to one cell, the structures that had been studied by physicists and chemists were childishly simple and many times easier to understand. But macroscopic organisms such as most animals and plants are made up of billions of individual cells. These cells have many different shapes and functional properties, and they are organized into tissues that have complex structural and functional properties of their own. Moreover, for a multicellular organism to survive, the individual cells must communicate with each other to regulate the state of the organism as a whole. An understanding of these interactions between cells—the physiology of an organism—has also required the efforts of many scientists working for years and using the most modern technological devices.

The knowledge that we now have of living things is on the one hand quite astounding and yet still in many respects incomplete. One area of intense research at the end of the 20^th century is the control of the embryonic development of multicellular organisms. This process involves the cooperative interaction of literally thousands of different genes to produce just the right tissues in just the right combinations. Imagine, for example, if your heart were perfect in every way but half the size it is now. This doesn’t happen because the molecular genetic mechanisms that control human development are so exquisitely well regulated.

The study of the brain is another hot area in biological research. The brain is far and away the most complex organ in the body, and we still have very little detailed understanding of how the electrical activity in networks of neurons makes possible the complex cognitive processing involved in detecting objects in a visual image or understanding words written on a page.

Ecology is another field in which our understanding is still evolving. This science investigates the interactions between many different types of organisms in a community, as well as the effects that each organism has on the physical environment and vice versa. Like the study of the brain, ecology represents the highest level of complexity in biological systems. In an ecosystem, many different organisms, each of which is itself a marvel of physical complexity, are influencing each other in ways that we still only partly understand.