How to Build a Human: Adventures in How We Are Made and Who We Are. Philip Ball

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How to Build a Human: Adventures in How We Are Made and Who We Are - Philip  Ball

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of the Great Depression when soils were under threat from drought and wind erosion on the American prairies. That man was Harvard microbiologist Kenneth Raper.

      What fascinated Raper was that Dicty has a peculiar life cycle. When food or moisture becomes scarce, the cells give up their individuality and turn into a multi-cellular superorganism. They send out chemical signals that attract one another, and the amoeboid cells gather into a “slug” a few millimetres long that contains hundreds of thousands of them. The slug undergoes some shape changes before narrowing at one end and ballooning at the other, becoming a tiny plant-like structure standing upright on a stalk. The bulbous head is the “fruiting body”, filled with cells that have become robust spores in suspended animation, ready to be released when conditions are conducive to start the cycle again. In the fruiting body, cells that were once identical have become distinct: they have differentiated, acquiring specialized skills.

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      Left: The life cycle of Dictyostelium discoideum. Some of these forms are shown in sequence under the microscope on the right.

      There is sacrifice involved. The spores will survive, but the supporting tissue of the fruiting body will die. That seemed curious to Raper: these autonomous cells make a choice, some voluntarily renouncing immortality for the sake of the others. It’s not unlike the way, during the development of the human embryo, a ball of identical cells apportions into tissues with separate fates. Some become body (somatic) cells, which will die with the person. Others become germ cells, which can in principle keep propagating forever.

      What’s more, just as this cooperative behaviour of our cells depends on their exchanging chemical signals that allow them to self-organize into pattern and shape, so we see that too in Dicty. There the patterns are remarkable, even beautiful, and certainly adequate to make the case that slime moulds deserve a bit more respect. Some of the cells in the community become pacemakers, exuding pulses of a chemical that diffuses out into the surroundings and induces neighbouring cells to start moving, pseudopod by pseudopod, towards the signalling cell. Because the attractive chemical comes in pulses, the cells advance in waves, resembling the concentric patterns of ripples on water. Eventually these motions coalesce into streams that converge on the place where the fruiting body will grow.

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       The patterns formed by Dicty cells as they aggregate into multi-celled fruiting bodies.

      This behaviour supplies a model system for understanding the appearance of pattern in cell biology more generally. It’s not really what human cells do, but there are resemblances. The way Dicty’s signalling molecules travel in waves through the cell community is also mathematically analogous to how waves of electrical excitation pass through the cells of the human heart, inducing a steady heartbeat.

      Still, Dicty seems deeply alien. Blurring our categories even more, the cells sometimes reproduce by simple division, like bacteria, but sometimes by sex between two of the three different “mating types” – three different genders, if you will.

      But as I watched my skin cells turn into a mini-brain in a dish, I had to wonder if we are really so unlike Dicty after all. We are single, autonomous beings, but we are also aggregates of microscopic entities that might each one give rise to another entire organism. Here were my swarming cells, making their individual ways in the world. They may divide and proliferate, they may cluster into clumps from which organs will grow. They’re a part of me, but they can live apart too.

      We are not, though, superorganisms in quite the way that Dicty is. For one thing, any pieces of us that become detached will normally perish fast, whereas if you cut off a piece of Dicty’s fruiting body it will grow into another fruiting body. Our own cells need to stay and work together for our entire life cycle, whereas when the Dicty spores are revived, they can grow into communities in which single cells can do their own thing again. For Dicty, multi-celled existence is just a passing phase.

      Yet the origin of multi-cellularity must have looked a little like this: single cells finding out the benefits of forming temporary unions, of taking specialized tasks, of reproducing sexually. That history used to seem so distant from us – perhaps a billion years ago – that it barely seemed part of our human heritage at all. Now we can see under the microscope that this past has never quite gone away.

      As much as a recent shared ancestry with simian cousins, the origin of humans as colonies of cooperating cells was what seemed so unsettling about Charles Darwin’s evolutionary theory, which implied a chain of being extending all the way back to amoebic “protoplasmic slime”. That we possessed ape-like ancestors might have been deemed undignified. But to collapse the human body to the cell and turn identity into unstructured living matter – that seemed an absurd affront. To some people, it still does.

      * * *

      Slime moulds are one of the simplest members of the domain of living organisms called eukaryotes, which also includes plants, fungi and animals. What else does that leave in nature? Just single-celled organisms: bacteria and archaea, the so-called prokaryotes.

      It has taken much of the century and a half since Darwin to shake off the notion that these distinctions imply a hierarchy of status, with evolution being a progressive elaboration and improvement of living matter at the pinnacle of which is … guess who? The simplest way to dispel that illusion is to recognize that all the other types of organism are still with us, many of them thriving (if we let them). Cell for cell, bacteria outnumber us humans by a factor of several tens of millions. So who is truly the most successful?

      The question is then why bacteria and other prokaryotes have stayed resolutely single-celled, while many eukaryotes are multi-cellular organisms.

      Being a eukaryote is a necessary but not sufficient criterion for getting multi-cellular. The word comes from the Greek for “true/good kernel”. It reflects the fact that eukaryotic cells have a kind of kernel, while prokaryotes don’t – namely the dense cell nucleus where the gene-laden chromosomes reside. Prokaryotes have genes too, but they are not sequestered in a separate cell compartment, and neither are the genes apportioned between several chromosomes as they are in eukaryotes. The genes of bacteria are mostly housed on one double-helical loop of DNA, wound into coils and floating freely in the cytoplasm, sometimes along with several smaller, circular segments of DNA called plasmids.

      The organization of chromosomes is just one respect in which the structure of eukaryotic cells is more complex than that of prokaryotes. Along with the nucleus, eukaryotes generally also contain a host of other compartments or “organelles”, bounded by membranes, that carry out particular functions: the mitochondrion, the chloroplast, the endoplasmic reticulum and so on. We know what roles these organelles fulfil, but there’s a puzzle about that “good kernel”, the nucleus itself.

      The usual story is that it protects the DNA. But as biochemist Nick Lane asks, protects it from what? What is there to fear in the rest of the cell?

      Well, it could be from viruses. But another hypothesis has been suggested by evolutionary biologists Eugene Koonin and Bill Martin: the nucleus is there to slow down the process of protein production from the genome. Recall that the genome of eukaryotic cells (but not that of prokaryotes) is full of rogue bits of DNA called introns that interrupt the gene sequences encoding proteins. It’s thought that these introns might be the remnants of an infestation of so-called “jumping genes” – pieces of DNA that are adept at splicing themselves at random places in the genome. Many eukaryotic introns are ancient: they appear in the same places in equivalent genes in a variety of eukaryotic organisms ranging from humans to yeast. This suggests that there was an episode far in the evolutionary past when the

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