[.ca] Animal Transgenesis and Cloning (ISBN 0470848286)

A good overview:
The subject of animal transgenesis is both interesting and controversial, and its ramifications for all life on Earth are awesome. Once a highly specialized area in biology, and employing very unreliable experimental techniques, it has grown into a field that employs hundreds of individuals in science and industry, and along with using more reliable laboratory procedures, it makes use of highly sophisticated mathematical algorithms and results. The author gives a fine overview of the subject, and with some prior exposure to molecular biology, the book can be read by anyone needing a background in it or anyone merely curious about the current status and capabilities of the field. The book addresses both the science and technology of transgenic animals, and the profound ethical considerations involved with its widespread use in the natural world. The creation of transgenic animals has not been as controversial as that of plants, but the advent of xenotransplantation and the possibility of transgenic animals being released in great numbers in wild populations will no doubt raise the level of debate and truculence. One can only hope that the harsh and bitter vitriole that characterizes both sides of the debate on genetic engineering will evolve into dialog of a more calm and rational nature. If the techniques of genetic engineering are proven unsafe or not viable, then they should not be used. If they are safe, they should be employed immediately in plants and animals, including humans. The author endeavors in all places in the book to be up-to-date, quoting the latest papers and preprints on the subject. There are places in the book the read more like a literature survey, but most of the book is a detailed account of the experimental techniques used in animal transgenesis, and for someone like myself who is not an expert in wet biology, it has some interesting surprises, such as the fact that cloned goats were normal in all cases attempted, even in those where the oocytes were obtained after in vitro maturation. But as a sign of the rapid developments in molecular biology, the recent developments showing that some mammalian cloning, such as that for primates, faces severe difficulties, is not discussed in the book, despite its publication date. Also, in the discussion on gene therapy as applied to severe combined immunodeficiency, the author does not mention the recent problems with patients developing leukemia after this kind of therapy. Throughout the book the author is very honest about the current limitations of transgenic technology. She states explicitly that all the mechanisms controlling gene expression are not known and that the construction of a gene may eliminate essential signals or combine incompatible signals. This will lead to disappointing transgene expression, according to the author. This assertion is also interesting in that it casts some doubt on the viewpoint that the genome of an organism is 'flexible' or easily changed. It is quite possible that they are instead conservative over time, and highly resistant to stable modification. In fact, recent experiments with mosquitos have given evidence supporting the latter point of view. The author gives additional evidence in the human genome, the major part of which is non-functional. Therefore, the author concludes, a foreign gene added to the human genome has a small probability of being integrated into a host gene, and is therefore silent. The possibility of vectors used for animal transgenesis to be transmitted to intestinal bacteria and then disseminated into the environment is only briefly mentioned by the author, stating only that such a transfer can be avoided by removing the prokaryotic origin of replication. It would have been nice if the author had spent more time on this, given the current controversies on this kind of transfer. A very interesting discussion given by the author concerns the use of what she calls 'non-classical' vectors for the recombination of targeted genes, one being the use of bacterial recombinases. The author mentions one example of this, involving a bacterial Rec A enzyme that is associated in vitro with a mononstrand DNA sequence. Such a technique was able to induce a homologous recombination of the corresponding gene in mammalian cells and mouse embryos using microinjection, but she cautions that conformation of these experiments is yet to be performed. The author also includes a discussion of the use of the triple helix between RNA and DNA as a technique for animal transgenesis. Such a technique involves the targeted inhibition of a gene by the formation of the triple helix in pyrimidine-rich regions. The triple helix blocks transcription by RNA polymerase II and RNA synthesis can be directed by the transgene. The author reminds the reader though that such techniques have yet to be successful though in animal transgenesis. Another topic of current interest is that of RNA interference, and the author discusses it in the context of animal transgenesis. She discusses experiments in which (double-stranded) RNA interference can be implemented in cultured cells to inhibit gene expression. The author considers the possibility, yet to be explored, of the expression of transgenes coding for double-stranded RNA inhibiting gene expression in mammals. The author discusses many applications of animal transgenesis, including the study of human diseases, models for viral infections and prion diseases, Alzheimer's disease, xenografting, the production of pharmaceuticals, and improved animal production. As the techniques of animal transgenesis are improved, there will no doubt be many more beneficial applications. There will also be the delightful possibility of the creation of new types of animals with the sole purpose of making the natural world a much more diverse and interesting place to live.