replication and proliferation drives evolution. Life is not what makes this propagation of cells possible; rather, that is what life is.
Biologists towards the end of the nineteenth century recognized that reproduction of cells happens not by the spontaneous formation of new cells, as Schwann believed, but by cell division as Virchow asserted: one cell dividing in two. Single-celled organisms such as bacteria simply replicate their chromosomes and then bud in two, a process called binary fission. But in eukaryotic cells the process is considerably more complex. Cell “fission” was first seen in the 1830s and was called mitosis in 1882 by the German anatomist Walther Flemming, who studied the process in detail in amphibian cells.
Flemming was a champion of the filamentary model of cells – the idea that their contents are organized mainly as long fibrous structures. In the 1870s, he showed that as animal cells divide, the dense blob of the nucleus dissolves into a tangle of thread-like structures (mitosis stems from the Greek word for thread). The threads then condense into X-shaped structures that are arranged on a set of star-like protein filaments dubbed an aster. (The word means “star”, but actually the appearance is more reminiscent of an aster flower.) Flemming saw that the aster gets elongated and then rearranged into two asters, on which the chromosomes break in half. As the cell body itself splits in two, these chromosomal fragments are separated into the two “daughter” cells and enclosed once again within nuclei.6
Various stages of cell division or mitosis as recorded by Walther Flemming in his 1882 book Zellsubstanz, Kern und Zelltheilung (Cell Substance, Nucleus and Cell Division).
So cell division is preceded by a reorganization of its contents: apparently, they are apportioned rather carefully into two. The thread-like material seen by Flemming unravelling from the nucleus readily takes up a staining dye (so that it is more easily seen under the microscope), leading it to be called, after the Greek word for colour, chromatin. The individual threads themselves were christened chromosomes – “coloured bodies” – in 1888.
In that same year, the German biologist Theodor Boveri discovered that the movement of chromosomes during cell division is controlled by a structure he called the centrosome, from which the strands of asters radiate. The two asters that appear just before a cell splits in two, each with a centrosome at their core, could in fact be seen to be connected by a bulging bridge of fine filaments, called the mitotic spindle. Flemming became convinced that these spindle fibres act as a kind of scaffold to direct the segregation of the chromosome threads into two groups. He was right, but he lacked a sufficiently sharply resolved microscopic technique to prove it.
So the division of animal cells isn’t just like the splitting of a water droplet into two. It has to be accompanied by a great deal of internal reorganization. Flemming and others identified a series of distinct stages along the way. While cells are going about their business with no sign of dividing, they are said to be in the interphase state. The unpacking of the nucleus into filamentary chromosomes is called prophase, and the formation and elongation of the aster is called metaphase. As the aster-like cluster splits in two, the cell enters the anaphase, from where it is downhill all the way to fission and the re-compaction of the nucleus.
This procedure is called the cell cycle, which is an interesting phrase when you think about it. Its implication is that, rather than thinking of biology as being composed of cells that do their thing until they eventually divide, we might regard it as a process of continual replication and proliferation that involves cells. With all due warning about the artificiality of narratives in biology, we might thus reframe the Great Chain of Being as instead a Great Chain of Becoming.
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It was a fundamental – perhaps the fundamental – turning point for modern biology when, around the turn of the century, scientists came to appreciate that much of the complicated reorganization that goes on when cells divide is in order to pass on the genes, the basic units of inheritance, that are written into the strands called chromosomes. What they were seeing here in their microscopes is the underlying principle that enables inheritance and evolution.
The notion of the gene as a physical entity that confers inheritance of traits appeared in parallel with the development of cell theory in the mid-nineteenth century. The story of how “particulate factors” governing inheritance were posited by the Moravian monk Gregor Mendel from his studies on the cultivation of pea plants has been so often told that we needn’t dwell on it. In the 1850s and ’60s Mendel observed that inheritance seemed to be an all-or-nothing affair: peas made by interbreeding plants that make smooth or wrinkly versions are either one type or the other, not a blend (“a bit wrinkly”) of the two. Of course, real inheritance in humans is more complicated: some traits (like hair or eye colour) may be inherited discretely, like Mendel’s peas, others (like height or skin pigmentation) may be intermediate between those of the biological parents. The puzzle Mendel’s observations raised was why inheritance is not always such mix, given that it comes from a merging of the parental gametes.
Charles Darwin didn’t know of Mendel’s work, but he invoked a similar idea of particulate inheritance in his theory of evolution by natural selection. Darwin believed that the body’s cells produced particles that he called gemmules, which influence an organism’s development and are passed on to offspring. In this view, all the cells and tissues of the body play a role in inheritance, whence the term “pangenesis” that Darwin coined for his speculative mechanism of evolution. These gemmules may be modified at random by influences from the environment, and the variations are acquired by progeny. In the 1890s, the Dutch botanist Hugo de Vries and German biologist August Weismann independently modified Darwin’s theory by proposing that transmission of gemmules could not occur between body (somatic) cells and the so-called “germ cells” that produce gametes. Only the latter could contribute to inheritance. De Vries used the term “pangene” instead of gemmule to distinguish his theory from Darwin’s.
At the start of the twentieth century, the Danish botanist Wilhelm Johannsen shortened the word for these particulate units of inheritance to “gene”. He also drew the central distinction between an organism’s genotype – the genes it inherits from the biological parents – and its phenotype, the expression of those genes in appearance and behaviour.
In 1902 Theodor Boveri, working on sea urchins in Germany, and independently the American zoologist Walter Sutton, who was studying grasshoppers, noticed that the faithful passing on of chromosomes across generations of cells mirrored the way that genes were inherited. Perhaps, they concluded, chromosomes are in fact the carriers of the genes. Around 1915, the American biologist Thomas Hunt Morgan established, from painstaking studies of the inheritance of characteristics in fruit flies, that this is so. Moreover, Morgan showed how one could deduce the approximate positions of two different genes relative to one another on the chromosomes by observing how often the two genes – or rather, the manifestation of the corresponding phenotypes – appear together in fruit flies made by mating of individuals with the respective genes. As the chromosomes were divvied up to form egg and sperm cells, genes that sat close together were more likely to remain together in the offspring. Morgan’s work established the idea of a genetic map: literally a picture of where genes sit on the various chromosomes.
The sum total of an organism’s genetic material is called its genome, a word introduced in 1920. For many years after Morgan’s work, it was suspected that genes are composed of the molecules called proteins, in which the much smaller molecules called amino acids are linked together in chains. Proteins, after all, seemed to be responsible for most of what goes on in cells – they are the stuff of enzymes. And chromosomes were indeed found to consist partly of protein. But those threads of heredity were also known to contain a molecule called DNA, belonging to the class known as nucleic acids (that’s what the “NA” stands for).
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