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.