Kitabı oku: «How to Grow a Human», sayfa 6

FIRST INTERLUDE
THE HUMAN SUPERORGANISM
HOW CELLS BECAME COMMUNITIES

To insist xthat the embryo is “us” from its first instants is to some degree a displaced religious impulse. It announces a moment of creation, as profound and abrupt as the fiat lux of the Old Testament. Because, let’s face it, the world did begin when you did, and it will end when you do: that’s a universal, experiential human truth. Symmetry alone then seems to demand a beginning that is as abrupt and all-encompassing as the end – a moment, in those monotheistic traditions, when the soul enters the body to match the one when it leaves.

But this concept of the embryo denies the true wonder of our origin, and is another expression of the flight from flesh that has been going on for centuries. The assertion of the soul as an immaterial thing, pre-existing and eternal, is a pre-scientific attempt to deal with the incommensurability between the life we lead and the life in our cells.

For the latter is truly something to be astonished at. It is contiguous with the moment life first appeared on Earth. Life is passed like a baton between living things and is not created afresh with their own beginning. In arguments about abortion and embryo research, we talk about “when life begins”, but that’s not what we mean. Life only began once, around four billion years ago, and no one knows how. It continued in an unbroken thread from primal slime and algae to the oddly shaped metazoans of the Cambrian, through to the shrew-like ancestors of all mammals, and on to our apelike forebears walking upright and wielding stone tools, and finally – for this brief, glorious moment – here you are. Life is just passing through you, so enjoy it while you can.

The ambiguity, anxiety and angst that arise when we contemplate the life of the one-cell zygote and try to reconcile it with the human form in order to formulate laws and moral codes are consequences of our being assemblies of cells living in community. So it’s worth considering how that came about.

* * *

If there was to be a competition for the least appealing organism in the world, slime moulds would be a strong contender. Bacteria get a bad press as mere “germs” to be expunged, but they also have a certain cachet too now that we know their presence in our gut is so beneficial and that they have such superpowers: metabolizing radioactive waste and oil spills, surviving in hot springs and so forth. Slime moulds, meanwhile, appear to be nothing more than their name suggests: a slightly disgusting smear of living matter whose purpose seems incidental to anything useful or inspiring in nature.

These organisms are members of a group called Mycetozoa. They are a type of amoebae, single-celled entities so “primitive” that for years microbiologists argued about whether they were closer to animals, fungi or plants. Modern genetic studies suggest that in evolutionary terms they are most closely related to the former two kingdoms, but they sit right at the boundaries – which is to say, the Mycetozoa became a distinct group around the same time in evolutionary history that animals, fungi and plants went their separate ways.

This is what makes slime moulds in fact deeply interesting. They offer a glimpse of what might have gone on when life began to get truly complex: when single-celled organisms evolved into multi-celled ones. In other words, when cell communities started to become superorganisms like us.

Amoebae played a significant role in the history of how we came to understand living matter. The word was coined originally to denote any microscopic organism that doesn’t have a fixed shape. Bacteria do: typically they are cigar-shaped, like round-ended tubes. But amoebae are shape-shifting blobs that move by extending a part of their bodies into pseudopods (“false feet”). The term “amoeboid” has entered everyday speech to denote that kind of amorphous, oozy mass.

The amoeba Proteus: a cell of no fixed shape.

But amoebae aren’t really a well-defined class of organism at all. There are types of amoebae that are truly animals, or fungi, or plants, as well as protozoans, which are single-celled organisms more “complicated” than bacteria. (I’ll say shortly what I mean by that.) Some amoebae are parasites; some are slime moulds. Even some of our own cells display amoeboid behaviour, such as white blood cells that “eat” bacteria and other pathogens by engulfing and absorbing them.

Amoebae were first reported in the eighteenth century in studies of seawater under the microscope. In 1841, the French biologist Félix Dujardin christened the jelly-like contents of amoebae “sarcode”. Renamed as “protoplasm”, this stuff became regarded as the fundamental living material. Amoebae came to be seen as the exemplar of the living cell, and to some scientists of the late nineteenth century it seemed that complex organisms like us were little more than sophisticated versions of their colonies: English physiologist Michael Foster wrote in 1880 that “The higher animals, we learn from morphological studies, may be regarded as groups of amoebae peculiarly associated together.” The German biologist Ernst Haeckel, a Darwinian committed to finding similarities and analogies among living things, attested that the amoeba was a sort of egg cell that needed nothing but itself to multiply: a “permanent ovum”, as he put it.

That was the heyday of the amoeba, which by and by came to be seen as too primitive a creature to take us very far in understanding life in all its variety. But if you suspected that amoebae don’t seem likely to hold much of interest in their gelatinous lives, Dictyostelium discoideum will set you right. It lives in soils and consumes bacteria, helping to maintain a balance in the microbial ecosystem that is as important for the health of the soil as harmony among our gut microbiota is for our own well-being. It’s appropriate, then, that Dictyostelium discoideum – which I shall call Dicty – was discovered by the son of a farmer, working during the years 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.

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.

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 genomes of eukaryotes became particularly vulnerable to infestation by jumping genes.¹

Whatever the reason, introns now need to be cut out before proteins are made. This happens after the transcription of DNA into RNA, the intermediary molecules that serve as the templates for protein synthesis on the structure called the ribosome. An RNA transcript of a gene is made from DNA, and then it is edited by special enzymes before being used by the ribosome to guide protein synthesis.

In bacteria, this sequence of transcription to ribosomal RNA followed by translation to proteins happens all at once; the RNA is translated even while it is being transcribed. If that happened in eukaryotes, there would be no time for proper intron editing. But the nucleus separates the process of transcription, which happens inside its membrane, from translation, which happens outside. Maybe, say Koonin and Martin, this spatial separation of transcription from translation ensures that the job is done properly.

* * *

Since eukaryotes are more complex than prokaryotes, it seems natural to suppose that the latter cells appeared first and eukaryotes evolved from them. This is indeed what is suggested by both the fossil record (even single-celled organisms leave fossils of a kind) and studies of DNA, from which we can deduce how the “tree” of evolution branched.² However, the differences between prokaryotes and eukaryotes are rather profound, and it’s not obvious how to get from one to the other along the gradual steps that evolution tends to take.

It’s now believed that this isn’t how it happened. Rather, eukaryotes are thought to have appeared by the abrupt merging of simpler cells.

The Earth is about 4.6 billion years old, and life seems to have begun at least by 3.8 billion years ago. It consisted of nothing but single-celled prokaryotes for perhaps as much as three billion years after that; the first multi-celled eukaryotes don’t appear in the fossil record until around 600 million years ago. No one knows what those first organisms were like, but it’s possible that they resembled the slug-like aggregates of Dicty, now permanently united into a single body. Alternatively, they might have been similar to some of today’s sponges.³ At any rate, they were preceded by single-celled eukaryotes, comparable to the organisms called protists today, which include algae and some amoebae (like Dicty). Multi-cellularity evolved independently many times among different types of eukaryote, which is tantamount to saying that it is a pretty good adaptive strategy in many circumstances.

The bigger question is how eukaryotes arose in the first place. They form one of the three fundamental domains of living organism. Bacteria comprise another domain, and the third is made up from that other type of prokaryote, the archaea. Until about 40 years ago, archaea were thought to be just a subgroup of bacteria, until the microbiologist Carl Woese showed by deducing evolutionary relationships from microbial RNA that they are distinct. These studies implied that the first division into domains separated bacteria from archaea, and that eukaryotes later split from the archaea.

The domains of life. As you see here, multi-celled animals and plants are, from the evolutionary point of view, relatively minor branches of the evolutionary tree (top right), and most life is single-celled. Notice too how “close” to us slime moulds like Dicty are in this representation.

I said that what distinguishes eukaryotes from prokaryotes is that they possess a cell nucleus. That’s true, but it doesn’t mean that what turned prokaryotes into eukaryotes was the acquisition of such a nucleus. When the “primal eukaryote” – the last common ancestor of all eukaryotes – lived is surprisingly unclear: estimates put it at between 1 and 1.9 billion years ago. But it’s generally thought that this organism had many of the key features of eukaryotes today, such as the major cell compartments and organelles. Perhaps the most important of these was not the nucleus, but the energy-producing compartments called the mitochondria – which in that primeval organism were not mere organelles but equal partners in a cellular union.

In the 1960s, microbiologist Lynn Margulis proposed that mitochrondria are the remnants of what were once separate prokaryotic organisms in their own right, which had become “swallowed” by other cells to form a symbiotic relationship. That eukaryotic organelles in general might have originated in such symbiotic mergers was an old idea, proposed in the early twentieth century, but Margulis championed that view in the face of much opposition and ridicule, and it is now accepted.