Everything else is but a detail...

It's been said that once the cell evolved, everything else in life is but a detail. It sounds like glib reference to the fact that all life (well, all cellular life--viruses excluded) is cellular. But as we've noted in an earlier post on cognition in bacteria, and in our books and writing, even single-celled organisms have complex abilities to evaluate and respond to their environments. Those abilities include, in many or even perhaps most such organisms, the ability to form multicellular organisms under some conditions (slime mold, bacterial biofilms, and others).

In fact, this is not a trivial kind of exception, but a profound one. The same kinds of mechanisms that make you a single, multicellular entity lead otherwise single-celled organisms to do remarkable things. These 'simple' cells have sophisticated ways to monitor their environment, respond collectively (even sometimes as collections of different species) in response. That is, they are adaptable, one of the basic principles of life.

An example that has been noted by others, but that we learned about this week on the BBC World Service radio program, The Forum, with biologist Brian J Ford, is the amoeba called Difflugia coronata. This single celled organism, living in ponds or other watery worlds, builds a house of sand which it lives in and carries around as it moves. The house is 150 thousandths of a millimeter in diameter, but apparently carefully constructed in a replicable form. As the amoeba grows, it ingests sand of varying sizes and when it divides to reproduce, one of the daughter cells inherits the house and the other gets the ingested sand so that it can build a house of its own. You can read more about it in the book, Built by Animals: The Natural History of Animal Architecture by Mike Hansell [Oxford University Press. 2008] (which can be found online in abbreviated Google form here). This gorgeous picture of one Difflugia's house is from that book.

It's not only the amoeba, of course. Cells of red algae even circle around a wounded peer, protecting it from the outside environment and providing its physiological needs until it recovers. And so on.

If we think about life in this way, and not in terms of exceptionalism for 'higher' organisms, life becomes more of a unitary phenomenon. Also, many things, including perhaps especially behaviors, that we might wish to credit adaptive evolution for having produced in our own precious ancestry as a species, have been around billions of years before the first hominids had that lusty gleam in their eyes. And, with little doubt, these 'primitive' amoebae and algae will still have their orderly social life eons after we advanced creatures have departed this Earth.

How does a cell know what to become?

This week on The Forum, a BBC World Service radio program, Lewis Wolpert, a distinguished Emeritus Professor of Cell and Developmental Biology at University College London, and two non-scientists were interviewed. Prof. Wolpert was asked to explain development, and how cells 'know' what kind of cell they will be. The interviewer, Bridget Kendall, is quite well-versed in scientific issues, but when she asked Wolpert to tell her how a cell knows what it will become, while he got some of it right, and certainly knows enough to answer the question, in the end his answer was quite unsatisfying and confused the interviewer as well as her other guests.

Cells talk to each other, Wolpert said. It's to do with signaling. And nobody is in charge.

So far, so good. Cells have to be prepared to receive a signal, and in normal development they have been primed, usually by earlier signals, to respond appropriately.

But then Kendall asked how cells arrange themselves in a certain pattern. How does a cell know it should be in the right or the left hand? A basic and fascinating question, the likes of which has hooked many a developmental biologist.

There is no fundamental difference between the right and left hand, he said.

This didn't help at all. Kendall pressed him.

Cells get instructions from other cells about what to do, he said.

Now one of the other guests was confused. Understandably. He wanted to know how chaos ends in order if no one is in charge. "There has to be a blueprint somewhere so that a human doesn't end up a frog."

"That's the cleverness of cells," Wolpert said. "There is no blueprint whatsoever." He was adamant about this. It's due to genes that a human cell becomes a human and not a frog, he went on to explain. Bringing us frustratingly back to Kendall's first question of how cells develop.

And, indeed, the listener could be forgiven for not being able to quite tell the difference between genes, which tell a cell whether it's to be a human or a frog, which Wolpert allows are important, though boring, and a blueprint, which is an outside document that tells a builder whether to construct a skyscraper or a factory and which Wolpert categorically denied as a useful metaphor for development.

But, are genes a blueprint for an organism? Certainly not literally -- unlike a blueprint, an organism has no designer, for starters. And, much more is inherited along with genes (by which is usually meant classical protein-coding segments of DNA, which make up only 5% of the genome, after all, and by no means all of the kinds of functional elements in genomes), so genes alone don't tell a cell what to become.

Is the whole genome the blueprint, then? Still no, since the fertilized egg contains more than DNA, and environmental factors have a significant influence over how a cell develops -- ambient temperature determines the sex of a developing turtle egg, for example. But the genes in a human cell can't instruct the cell to become a frog, so in some metaphorical sense, they are a blueprint but, unlike a blueprint, the DNA does not come into an awaiting cell and tell it what to do: an organism is already a complete cell, with its DNA and its other materials that interpret the DNA.

How does a cell know what to become?

Wolpert was right that it depends on signaling, but it would have helped if he had gone on to say that signaling happens in order, and what a cell does next is contingent on what it has just done. Step by step, cells all over thee embryo are single-mindedly, so to speak, responding independently to different signals, each one oblivious to what's happening even several cells away. Signal upon signal, response after response, cell division upon cell division, all these steps combined lead to differentiated, semi-autonomous cells all working together to make an organism. Preparing to respond to signals, and then responding, is what cells do.

It's fairly simple -- unless you're concerned with how one cell becomes part of the thyroid gland and another becomes part of the retina of an eye, and you want to know the specific genetic and timing details. Otherwise, it's enough to know that genes code for proteins that become signals, cell-surface receptors to read those signals, and then to respond. Cells know nothing about the bigger picture, and there is no master painter, but step-by-step, because of contingency and cooperation among cells, the bigger picture emerges. These generalizations are, in fact, rather universal and reflect basic properties of the nature of life -- what we might call parts of a broader theory of life.

Smart bacteria

Last week Ken was at a meeting at the Santa Fe Institute, which was discussing the problem of the traditional concept of the 'gene' in the face of all the new discoveries of DNA-based functions that are very different from simple protein codes. That could be the subject of a future posting, but at the meeting was a well-known microbiologist, Jim Shapiro from the University of Chicago. In the course of conversation, we learned of a recent paper of Jim's that points out how sophisticated even a single bacterial cell is (you can get this from his website: scroll to the bottom and click on the second to last paper, Bacteria are small but not stupid). Indeed, Jim refers to 'cognition' in single cells.

This paper points out how very complex a single cell is, in terms of its internal structure, its diverse ability to sense and evaluate the environment, and its repertoire of responses. He stresses that a cell is not a stupid automaton in that sense. This is wholly consistent with points we tried to make in our book, and is sobering for attempts to boil even more complex traits, like multicellular organisms, into simple genetic causation. Of course genomes contribute to behavior of cells and organisms, but not in ways that are always simple. An important question is how enumerable such genomic effects are, and how 'hard-wired' even single cells are. Like so many other terms one might use, 'cognition' is a word with social or human-specific meanings, but using it for bacteria it is probably an important challenge to our hubris about ourselves. Bacteria may be 'just' bags of chemicals....but so are our brains. Where automated responses end and evaluative, facultative ones begin is not an easy question to answer.