Mutants by Armand Marie Leroi Read Free Book Online Page B

early 1990s recombinant DNA technology was applied to the problem. By 1993 a protein was identified that, when injected into the embryos of African clawed toads, gave conjoined-twin tadpoles. At last it was possible to obtain – without crude surgery – the results that Hilda Pröscholdt had found somany years before. The protein was especially good at turning naive ectoderm into spinal cord and brain. With a whimsy that is pervasive in this area of biology, it was named ‘noggin’. By this time techniques had been developed that made it possible to see where in an embryo genes were being switched on and off. The noggin gene was turned on at the far end of the blastopore’s lip, just where the gene encoding an organising morphogen should be.
    Noggin is a signalling molecule – that is, a molecule by which one cell communicates with another. Animals have an inordinate number of them. Of the thirty thousand genes in the human genome, at least twelve hundred are thought to encode proteins involved in communication between cells. They come in great families of related molecules: the transforming growth factor-betas (TGF-?), the hedgehogs and the fibroblast growth factors (FGFs) to name but a few, and some families contain more than a dozen members. The way they work varies in detail, but the theme is the same. Secreted by one cell, they attach to receptors on the surfaces of other cells and in doing so begin a sequence of molecular events that reaches into the recipient cell. The chain of information finally reaches the nucleus, where batteries of other genes are either activated or repressed, and the cell adopts a fate, an identity.
    When noggin was first discovered, it was supposed that its uncanny powers lay in an ability to define the back of the embryo from the front – more precisely, to instruct naive ectodermal cells to become spinal column rather than skin. This was the simplest interpretation of the data. Noggin, the thinkingwent, spurred ectodermal cells on to higher things; without it, they would languish as humble skin.
    The truth is a bit more subtle. The probability that a cell becomes spinal column rather than skin is not just a function of the quantity of noggin that finds its way to its receptors, but is rather the outcome of molecular conflict over its fate. I said that our genomes encode an inordinate number of signalling molecules. This implies that the cells in our bodies must be continually bathed in many signals emanating from many sources. Some of these signals speak with one voice, but others offer conflicting advice. Noggin from the organiser may urge ectoderm to become neurons, but as it does so, from the opposite side of the embryo another molecule, bone morphogenetic protein 4 (BMP4) instructs those same cells to become skin.
    The manner in which the embryo resolves the conflict between these two signals is ingenious. Each signal has its own receptor to which it will attach, but noggin, with cunning versatility, can also attach to free BMP4 molecules as they filter through the intercellular spaces, and disable them. Cells close to the organiser are not only induced to become neurons, but are also inhibited from becoming skin; far from the organiser the opposite obtains. The fate of a given cell depends on the balance of the concentration between the two competing molecules. It is an ingenious device, only one of many like it that work throughout the development of vertebrate bodies, at scales large and small, to a variety of ends; but here the end is a toad or a child that has a front and a back. In a way, the embryo is just a microcosm of the cognitive world that we inhabit, the world of signals that insistently urge us to travel to onedestination rather than another, eschew some goals in favour of others, hold some things to be true and others false; in short, that moulds us into what we are.
    It is actually quite hard to prove that a gene, or the protein that it encodes, does what one