Mutants by Armand Marie Leroi Read Free Book Online Page A

far edge of one embryo’s blastopore – the newt equivalent of the human primitive streak – and transplanting it onto another embryo. Observing that the embryo’s tissue layers and geometry arose from cells that had passed through the blastopore, Spemann reasoned that the tissues at the blastopore’s lip had some special power to instruct the cells that were travelling past it. If so, then embryos that had extra bits of blastopore lip grafted onto them might have – what? Surplus quantities of mesoderm and endoderm? A fatally scrambled geometry? Completely normal development? Earlier experiments that Spemann himself had carried out had yielded intriguing but ambiguous results. Now Hilda Pröscholdt was going to do the thing properly.
    Between 1921 and 1923 she carried out 259 transplantation experiments. Most of her embryos did not survive the surgery. Butsix embryos that did make it are among the most famous in developmental biology, for each contained the makings of not one newt but two. Each had the beginnings of two heads, two tails, two neural tubes, two sets of muscles, two notochords, and two guts. She had made conjoined-twin newts, oriented belly to belly.
    This was remarkable, but the real beauty of the experiment lay in Pröscholdt’s use of two different species of newts as donor and host. The common newt, the donor species, has darkly pigmented cells where the great-crested newt, the host species, does not. The extra organs, it was clear, belonged to the host embryo rather than the donor. This implied that the transplanted piece of blastopore lip had not
become
an extra newt, but rather had
induced
one out of undifferentiated host cells. This tiny piece of tissue seemed to have the power to instruct a whole new creature, complete in nearly all its parts. Spemann, with no sense of hyperbole, called the far lip of the newt’s blastopore ‘the organiser’, the name by which it is still known.
    For seventy years, developmental biologists searched in vain for the source of the organiser’s power. They knew roughly what they were looking for: a molecule secreted by one cell that would tell another cell what to do, what to become, and where to go.
    Very quickly it became apparent that the potency of the organiser lay in a small part of mesoderm just underneath the lip of the blastopore. The idea was simple: the cells that had migrated through the blastopore into the interior of the embryo were naive, uninformed, but their potential was unlimited. Spemann aphorised this idea when he said ‘We are standing andwalking with parts of our body that could have been used for thinking had they developed in another part of the embryo.’ The mesodermal cells of the blastopore edge were the source of a signal that filtered into the embryo, or to use the term that was soon invented, a
morphogen
. This signal was strong near its source but gradually became fainter and fainter as it dissipated away. There was, in short, a three-dimensional gradient in the concentration of morphogen. Cells perceived this gradient and knew accordingly where and what they were. If the signal was strong, then ectodermal cells formed into the spinal cord that runs the length of our back; if it was faint, then they became the skin that covers our body. The same logic applied to the other germ layers. If the organiser signal was strong, mesoderm would become muscle; fainter, kidneys; fainter yet, connective tissue and blood cells. What the organiser did was pattern the cells beneath it.
    It would be tedious to recount the many false starts, the years wasted on the search for the organiser morphogen, the hecatombs of frog and newt embryos ground up in the search for the elusive substance, and then, in the 1960s, the growing belief that the problem was intractable and should simply be abandoned. ‘Science,’ Peter Medawar once said, ‘is the Art of the Soluble.’ But the soluble was precisely what the art of the day could not find.
    In the