Implications for Human Health Curing Cancer Fixing Genes

It is very likely that the single largest impact of our understanding of animal development will be on human health. This is not because most human diseases are developmental in nature. Developmental conditions can result in devastating birth defects, and many of these diseases are likely to involve defects in molecules we have discussed in this book; however, the number of such medical conditions is actually fairly limited. Rather, the impact of our knowledge of development on health derives from our greatly sharpened image of how cells acquire their identities and how they communicate with one another. For example, nearly all of the growth factor signaling pathways we have discussed in this book, such as the Dpp, Hh, and Notch pathways, have been implicated in human cancer. Because cell proliferation (i.e., multiplication by cell division) is intimately connected with development, many genes regulating developmental decisions also control cell proliferation. For example, activation of the Dpp and Notch pathways is required for outgrowth of appendages during adult fly development, and these pathways are also activated in developing vertebrate appendages. During adult life, mutations in these same signaling pathways can result in excess cell proliferation and, ultimately, in cancer. In some cases, loss of gene function, such as disruption of a component required for Dpp signaling, loss of a Hedgehog receptor, or mutation of the Notch receptor, leads to aggressive tumor formation because these signaling systems normally function to limit cell proliferation in adults. When this constraint on cell growth is lifted, cells proliferate inappropriately and take the first step to becoming cancerous. In other cases, mutations in growth factor receptors, which normally are involved in promoting cell growth, result in receptors that are active even in the absence of signal. This independence of receptor activity from normal activation by signals also causes cells to proliferate where and when they should not. Many forms of leukemia are caused by such misregu-lation of receptors and signaling pathways. Because of the intimate link between development and cellular growth control, advances made in understanding mechanisms guiding development will have a profound impact on treatment strategies and on rational drug design. One direct consequence of basic research on signaling pathways in model organisms like flies and worms is likely to be the identification of optimal targets for cancer drug therapy.

Another very important, although controversial, contribution of the molecular biology revolution to human disease is the looming gene replacement technology, or gene therapy. The idea of gene replacement therapy is to repair a defective disease-causing gene in an afflicted patient. For example, it is currently possible to take human blood cells from a patient suffering from p-thalassemia, a condition in which the oxygen-binding molecule hemoglobin is abnormal, fix the genetic defect in isolated blood cells in a test tube, and reintroduce these genetically repaired cells into the patient after that person has been irradiated to eliminate his or her own defective blood cells. The result of such a gene replacement treatment is that the future blood cells produced by the person will make a normal functional version of hemoglobin, and their disease will be cured for life. Treatments such as this are now at the experimental stage in clinical trials and undoubtedly will be improved over the next decade until they become as routine as in vitro fertilization is today. In a subsequent section, I consider the impact of this powerful gene-altering technology further, because there are some very significant ethical issues that arise from the ability to alter the genetic makeup of human cells, particularly if such changes are made in reproductive cells and become heritable.

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