Little Boxes of Life

A Little History Of Science: Little Boxes of Life

There are things we simply cannot see or hear. Many stars are beyond our gaze, and we can’t see atoms, or even the tiny creatures that teem in puddles of rainwater. We can’t hear sounds that many birds or mice can. But we can still learn about them, asking questions and using instruments that let us see or hear far better than with our eyes and ears alone. Just as telescopes let us see further into space, microscopes help us see further into the tiny building- blocks of living creatures.

In the seventeenth century, the pioneer of microbiology, Antonie van Leeuwenhoek, had used his small microscopes to look at blood cells and the hairs on a fly’s legs. A century later, more advanced microscopes were allowing naturalists to examine these finer details of anatomy, and the wonderful array of tiny life. A ‘compound’ microscope could make things appear even bigger than a simple microscope. It is a tube with two lenses, the second of which magnifies the first image, so you get their combined magnification. Many thoughtful people did not completely trust microscopes. Early compound microscopes produced distortions or illusions of various kinds – for example, strange colours or lines where none existed. At the same time, there were only crude methods of cutting things into thin slices to examine them, and of trying to fix these slices on to a slide (a thin glass sheet).
Consequently, many scientists thought using microscopes was not worth the effort.

Yet doctors and biologists wanted to understand how bodies work in the finest possible detail. In France, Xavier Bichat (1771– 1802) began to investigate the different substances – what we call the ‘tissues’, whether hard like bone, soft like fat, or liquid like blood – that make up the human body. Bichat realised that the same kinds of tissues behaved in similar ways, no matter where they were in the human body. Thus, all muscles were composed of the same sort of tissue whether they were busy contracting in legs, arms, hands or feet. All tendons (the bits connecting muscle to bone), or the thin coating called serous tissue (like that surrounding the heart), were similar in all parts of the body. The study of cells and tissues is called ‘histology’ and Bichat was ‘the father of histology’. Yet Bichat was one of those who were suspicious of microscopes, and he used only a simple magnifying glass. Bichat’s work inspired others to try to understand plants and animals in terms of their smaller, and more basic, building-blocks.

In the early decades of the 1800s, there were several competing ideas about just what these fundamental building-blocks of plants and animals were. The technical problems of compound micro- scopes began to be solved in France and Britain from the late 1820s. From then on people looking down their instruments could be more confident that what they were seeing was an accurate picture of what was really there.

In the 1830s, the new microscopes helped two German scientists argue that the crucial building-blocks of life were cells, and that all plants and animals are composed of cells. One of these scientists was a botanist named Schleiden. The other was a doctor, Theodor Schwann (1810–82). Schwann explored how cells worked and how they were created. In the cells of plants and animals, activities take place that allow such things as movement, digestion, breathing and sensing. The cells act together, and they are the key to under- standing how plants and animals function and live.

When you injure yourself – say, you cut your finger – more skin tissue will grow to heal the wound. But if tissues are made of cells, how are the new cells made? Schwann was very interested in chemistry, and he proposed that new cells crystallise out of a special kind of fluid, just as crystals can be grown in a laboratory from certain solutions. He wanted to explain how embryos develop in an egg, or the womb. He also wondered where the cells come from, those which appear if you get a scratch or a bruise. As a doctor, he could see that the area around an injury gets red and it may get full of pus cells. These pus cells, he thought, crystallise out of the watery fluid that we see as the swelling. It was an attractive theory, combining chemistry and biology, but it was quickly shown to be too simple.

As microscopes improved, more and more scientists began to watch what happens in cells. One of the most important cell- watchers was Rudolf Virchow (1821–1902). A man of wide inter- ests, Virchow, mostly a pathologist, was also active in public health, politics, anthropology and archaeology. (He helped excavate the city of Troy, written about by Homer around 800 bc.) In the 1850s, Virchow began to think what the cell theory meant for medicine, and for the study of disease, known as pathology. Like Schwann, he saw cells as the basic units of living bodies. Understanding their functions in health and disease would be key to a new kind of medicine, based on science. He presented his ideas in a very important book called Cellular Pathology (1858). He showed that the diseases doctors see in their sick patients, and can later examine in the autopsy room (when studying their dead bodies), were always the result of events in the cells. These included the growth of cancer (which he was especially interested in), inflammation, with its pus and swelling, and heart disease. ‘Learn to see micro- scopically,’ he always taught his students in their pathology classes: peer down to the level of the cells.

Virchow combined his brilliant microscopic observations with a profound statement of a biological truth: ‘All cells come from cells.’ This is where he overtook Schwann. What he meant was that the pus cells in an angry swelling – after a splinter or a scrape, for example – actually came from other cells. They were not crystallised from body fluids. It also meant that cancer growths resulted from other cells, in this case cells that were behaving incorrectly and dividing when they should not. Every cell we can observe under the microscope has been produced by an existing cell (known as the ‘mother’ cell) dividing into two (the ‘daughter’ cells).

Indeed, as biologists watched more and more, they sometimes saw this cell division taking place. And they noticed that the interior of the cells seemed to change when the cell divided into two. Something special was happening.

Earlier observations had already shown that the cell is not just a sack, full of the same kind of stuff. In the 1830s, an English botanist, Robert Brown (1773–1858), had argued that every cell has something at its centre: a nucleus, which is darker than the surrounding substance. Brown had looked at a lot of cells under his microscope and they all seemed to have this nucleus. The nucleus soon became accepted as a part of all cells. All the other material enclosed within the cell walls became known as protoplasm. This word means literally ‘first mould’, because at the time the proto- plasm was viewed as the living stuff within the cells, whose functions gave life to plants and animals. In time other structures besides the nucleus were seen and named in cells.

Scientists quickly accepted the discovery of the nucleus and other parts of cells. But it was quite a different story for the very old debate about ‘spontaneous generation’, the observation that rotting meat and stagnant water seemed to spawn all kinds of tiny, but living, creatures. People knew that if they left a piece of uncovered meat on a table, in a couple of days they could expect to see maggots. They didn’t know that flies lay eggs that hatch into maggots, so how could they explain where the maggots came from? Examine a drop of pond water under a microscope, and you will see that it is swarming with tiny creatures. How did they get there?

To nineteenth-century scientists, the easiest explanation was that these creatures had been made by, or generated from, their nourishing environments by a kind of chemical process. This was the common view, and it seemed to make sense. Since the maggots were not there when the meat was put down, how better to explain their presence than to assume that as the flesh decomposed it actually produced these rather disgusting creatures? Few people thought that complex things – elephants or oak trees – were spontaneously generated, but simple forms of life seemed to pop up without obvious explanation, except that they were somehow generated from their surroundings. Even Schwann’s notion of living cells crystallising from the special bodily fluid was a kind of spontaneous generation, living cells coming from non-living material.

Naturalists in the 1600s and 1700s thought that they had shown that spontaneous generation does not occur, but the problem did not go away. It was hotly debated from the late 1850s by two French scientists. The winner finally convinced the scientific community that there was no spontaneous generation. But the story is not a simple one: the winner (who was correct) did not exactly play fair.

The first of these two French scientists was a chemist, Louis Pasteur (1822–95). In the 1850s he had begun to suspect that living cells could do quite extraordinary things. He was used to investigating the chemical properties of various compounds. He was also familiar with fermentation, the process in which grapes are mixed with yeast to make wine, and flour is mixed with yeast to make bread rise before baking it. Before Pasteur, fermentation was thought to be a particular kind of chemical reaction in which the yeast just acted as a catalyst – something to speed things up but remaining unchanged by the reaction. Pasteur would show instead that fermentation was a biological process caused by the yeast as it lived, feeding on the sugars in grapes and flour. The cells in the yeast were dividing to produce more cells, and in the process their living activities caused the desired alcohol in the wine or made the bread light and soft. Of course, these processes had to be stopped at the right time, by heating. If the yeast was allowed to go on and on living, the wine would turn to vinegar and the bread dough would eventually sink again. If this was happening in fermentation, Pasteur wondered about how other living micro-organisms might be involved in processes attributed to chemical reactions – such as spontaneous generation. So he turned it into a public competition with his fellow countryman, Félix Pouchet (1800–72), a supporter of spontaneous generation.

In a series of experiments, Pasteur boiled mixtures of straw and water to make them sterile. He then left them exposed to the air and the dust particles floating in it. Usually, if you examined the liquid after a few days, it would be teeming with micro-organisms.

Pasteur showed that if you excluded the dust particles from the air, the solution would stay sterile. To show that these micro- organisms came with the dust particles, and not the air itself, he designed a special flask with a curved neck, like a swan’s, that allowed in the air but not the dust. When Pouchet did similar experiments, his flasks contained micro-organisms after a few days. He interpreted his results as proving that spontaneous generation can occur. Pasteur assumed that when his experiments didn’t turn out as he anticipated, it was because he hadn’t cleaned his flasks well enough – and he presumed that Pouchet was always sloppy. Pasteur won the day, even if he quietly ignored the results of some of his experiments when they didn’t give him what he wanted and appeared to support Pouchet! He triumphed partly because he was a dogged, determined scientist, who believed he was right, but also because Virchow’s important statement that ‘all cells come from cells’ was gaining support. People wanted to believe Pasteur because his theories were a big step forward from old-fashioned ideas, and that’s very important in science too.

Microscopy allowed great advances in medical and biological research. Microscopes were improved, and so were the tools to prepare specimens to examine under the lenses. Stains – special chemicals that acted like dyes – were especially important, because they could colour and highlight features of a cell’s structure that would otherwise be overlooked. The stained nucleus, in particular, was observed to have a series of dark-staining strands that were given the name ‘chromosomes’. (Chromo comes from the Greek for ‘colour’.) When a cell was dividing, the chromosomes could actually be seen to swell. The significance of this discovery, and of the other parts of the cell that scientists identified, had to wait until the twentieth century. But nineteenth-century doctors and biologists started the ball rolling. Above all, they showed that if you want to understand how whole plants and animals function, in both health and disease, you needed to start with the cells that they are made of. One kind of cell – single-celled organisms called bacteria – became especially important in understanding diseases. We are not done with Louis Pasteur, for he played a central role in the link between germs and disease, and in understanding how micro- organisms play their part in many aspects of our daily lives.