Science of Discworld III

thalidomide could cause a type of birth defect known as phocomelia, in which arms and legs are replaced by partially developed versions that resemble a seal’s flippers.
    It took a while for anyone to notice, partly because few general practitioners had experience of phocomelia before 1957. In fart, very few of them had ever seen a case at all, but after 1957 they began to see two or three in a year. A second reason was that it was very difficult to tie this defect to a particular potion or treatment: pregnant women famously take a great variety of dietary additives, and often they don’t remember precisely what they’ve taken. Nevertheless, by 196l some medical detective work had tied the spate of phocomelia down to thalidomide.
    American doctors congratulated themselves on having missed out on the pathology, because Frances Kelsey, a medical worker for the Food and Drug Administration, had expressed misgivings about the original animal testing of the drug. Her misgivings eventually turned out to have been unfounded, but they did save much suffering in the USA. She noticed that the drug had not been tested on pregnant animals, because at that time such tests were not required. Everyone knew that the embryo has its own blueprint for development, quite separate from that of the mother. However, embryologists trained in biology departments, as distinct from medical embryologists, knew about the work of Cecil Stockard, Edward Conklin, and other embryologists of the 1920s. They had shown that many common chemicals could caused monstrous developmental defects. For instance, lithium salts easily induced cyclopia, a single central eye, in fish embryos. These alternative developmental paths, induced by chemical changes, have taught us a lot about the biological development of organisms, and how it is controlled.
    They have also taught us that an organism’s development is not rigidly determined by the DNA of its cells. Environmental insults can push the course of development along pathological paths. In addition, the genetics of organisms, particularly wild organisms, are usually organised so that ‘normal’ development happens despite a variety of environmental insults, and even despite changes in some of the genes. This so-called ‘canalised’ development is very important for evolutionary processes, because there are always temperature variations, chemical imbalances and assaults, parasitic bacteria and viruses; the growing organism must be ‘buffered’ against these variations. It must have versatile developmental paths to ensure that the ‘same’ well-adapted creature is produced, whatever the environment is doing. Within reasonable limits, at any rate.
    There are many developmental tactics and strategies that help to accomplish this. They range from simple tricks like the HSP90 protein to the very clever mammalian trade-off.
    HSP stands for ‘heat shock protein’. There are about 30 of these proteins, and they are produced in most cells in response to a sudden, not very severe, change of temperature. A different array of proteins is produced in response to other shocks; this one is called HSP90 because of where it sits in a much longer list of cell proteins. HSP90, like most HSPs, is a chaperonin: its job is to hug other proteins during their construction, so that when the long line of amino acids folds up it achieves the ‘right’ shape. HSP90 is very good at making the ‘right’ shape – even if the gene that specifies the chaperoned protein has accumulated a lot of mutations. So the resulting organism doesn’t ‘notice’ the mutations; the protein is ‘normal’ and the organism looks and behaves just like its ancestral form.
    However, if there’s a heat shock or other emergency during development, HSP90 is diverted from its role as chaperonin, and other less powerful chaperonins permit the mutational differences to be expressed in most of the progeny. The effect this has on evolution is to keep the organisms much the same until there’s an environmental stress, when suddenly, in one generation, lots of previously hidden, but hereditable, variation appears.
    Most books that describe evolution seem to assume that every time there’s a mutation, the environment promptly gets to judge it good or bad … but one little trick, HSP90, which is present in most animals and many bacteria, makes nonsense of that assertion. And from Lewontin’s discovery that a third of genes have common variants in