How to Build a Human: Adventures in How We Are Made and Who We Are. Philip Ball
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The human cell.
By the early twentieth century, it was clear that what sets living matter apart from the inanimate is not merely a question of composition: of what life is made of. Neither is it just a question of structure. Organisms and cells clearly did have a hierarchy of significant, specific yet hard-to-interpret structures reaching down to the microscopic and beyond. And that mattered. But the real reason living matter is not equivalent to some other state of matter such as liquids and gases is that it is dynamic: always changing, always in the process of doing something, never reaching a steady equilibrium. Staying alive is not a matter of luxuriating in the state of aliveness but is a relentless task of keeping balls in the air.
Researchers today might rightly point out that this dynamic, out-of-equilibrium character is not unique to life. Our planet’s climate system is like that too: a constant channelling of the energies of the sun and of the hot planetary interior into orchestrated cycling movements of the oceans, atmosphere and sluggish rocky mantle, accompanied by flows of chemical elements and heat between the different components of the planetary system. The system is responsive and adaptive. But this is precisely the point: there are parallels between a living organism and the planet itself, which is why the independent scientist James Lovelock pushed the point from analogy to the verge of genuine equivalence in his Gaia hypothesis. Arguments about whether the planet can be truly considered “alive” are moot, because the living systems – rainforests, ocean microfauna, every creature that takes in chemicals and turns them into something else plus heat – are in any case a crucial, active part of the planet’s “physiology”.
This activity of the planetary biosphere commenced close to four billion years ago and has not ceased since. Virchow’s omnia cellula e cellula has a significance barely any lesser than that of Darwinian evolution, which ultimately depends on it (ironically, given Virchow’s views on Darwin). It establishes a basis for what Aristotle imagined as a Great Chain of Being, in which the fundamental unit is no longer the reproducing organism but the dividing cell. All cells are, in evolutionary terms, related to one another, and the question of origin reduces to that of how the first cell came into being. Since that obscure primeval event, to the best of our knowledge no new cell has appeared de novo.
At the same time, Virchow’s slogan is a description, not an explanation. Why is a cell not content to remain as it is, happily metabolizing until its time runs out? One answer just begs the question: if that is all cells did, they would not exist, because their de novo formation from a chemical chaos is far too improbable. Then we risk falling back again on anthropomorphism – cells intrinsically want to reproduce by division – or on tautology, saying that the basic biological function of a cell is to make more cells (“the dream of every cell is to become two cells”, said the Nobel laureate biologist François Jacob). Biological discourse seldom does much better than this. Cell and molecular biologists and geneticists have a phenomenal understanding of how cells propagate themselves. But explaining why they do so is a very subtle affair, and it’s fair to say that most biologists don’t even think about it. Yet that “impulse” is the engine of Darwinian evolution and consequently at the root of all that matters in biology.
There is not a goal to this process of life, towards which all the machinery of the cell somehow strives. We can’t help thinking of it that way, of course, because we are natural storytellers (and because we do have goals, and can meaningfully ascribe them to other animals too). So we persuade ourselves that life aims to make babies, to build organisms, to evolve towards perfection (or at least self-improvement), to perpetuate genes. These are all stories, and they can be lovely as well as cognitively useful. But they do not sum up what life is about. It is a thing that, once begun, is astonishingly hard to stop; actually we do not know how that could be accomplished short of destroying the planet itself.
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Life’s unit is the cell. Nothing less than the complete cell has a claim to be called genuinely alive.5 It’s common to see our body’s cells referred to as “building blocks” of tissues, much like assemblies of bricks that constitute a house. To look at the cells in a slice of plant tissue, such as Wilson’s drawing of the onion earlier, you can understand why. But that image fails to convey the dynamic aspect of cells. They move, they respond to their environment, and they have life cycles: a birth and a death. They receive and process information. As Virchow suggested, cells are to some degree autonomous agents: little living entities, making their way in the world.
Anything less than a cell, then, has at best a questionable claim to be alive; from cells, you can make every organism on Earth. We have known about the fundamental status of the cell for about two centuries but have not always acknowledged it. For much of the late twentieth century, the cell was relegated before the supremacy of the gene: the biological “unit of information” inherited between generations. Now the tide has turned again. “The cell is making a particular kind of reappearance as a central actor in today’s biomedical, biological, and biotechnological settings,” writes sociologist of biology Hannah Landecker. “At the beginning of the 21st century, the cell has emerged as a central unit of biological thought and practice … the cell has deposed the gene as the candidate for the role of life itself.”
Cells do more than persist. Crucially, they can replicate: produce copies of themselves. Ultimately, cell 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