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Quesenberry PJ, Stein GS, eds. (£65.00.) Wiley, 1998. ISBN 0 47114 656 0.
The importance of stem cell and gene therapy has been evident both to scientists and clinicians for some time, but increasingly it has become a very live issue for the general public. It is the focus of enormous investment by pharmaceutical and biotechnology companies the world over, reflecting the novelty and the power of techniques that allow us to reach within the tissue or the genome itself to correct defects in a way never previously imagined possible.
Ethical debate is rightly vigorous and the advance of the new technology is raising new issues seemingly daily. The US congress is holding hearings to discuss legislation that would allow federally funded scientists to derive human embryonic stem cell lines, one of the basic requirements for stem cell therapy. With views ranging between Christopher Reeves's: “is it more ethical for a woman to donate unused embryos or let them be tossed away as garbage” to accusations of Nazi experimentation, the debate is heated, ethically complex and, importantly, commercially highly sensitive. The case of Adam Nash, the baby whose stem cells have been used in an attempt to save the life of his sister with Fanconi's anaemia, is featured in my copy of the Sunday paper today, and raises even more questions about the use of prenatal selection for stem cell therapeutic purposes.
The prospects for novel therapeutic approaches to a range of diseases ranging from congenital gene deficiencies to neoplasia have never been brighter, and despite the rather disappointing results of gene and stem cell therapy to date, improvements in our understanding of the biology of stem cells and control of stem cell gene expression offer the brighter, in this author's personal opinion, even the brightest prospects of all. It is always gratifying to see one's own prejudices shared by others and certainly in this book the emphasis on the understanding of stem cell biology and the control of gene expression underlines the power of the stem cell approach to gene therapy, which in other collections of this sort are often neglected in favour of the technical problems and approaches to gene delivery and tissue targeting. This is not to say, however, that these important areas have been left out of this volume and they are admirably covered by experts in the fields; the approaches discussed include adenovirus, adeno associated virus, herpes simplex virus, retroviruses, and direct DNA delivery. The book contains excellent chapters on the use of ribozymes in IRV therapy by Wong-Staal and co-workers, and DNA vaccines, an increasingly important technology. Both these chapters and those on the delivery systems are excellent and for the most part critical and realistic about the problems with our existing delivery methods; given the hype in the field (often generated by commercial interests), this is refreshing. But for me the star chapters are those considering the control of stem cell proliferation and differentiation—a tour de force by Stein and co-authors—and the detailed chapters on the control of haematopoietic stem cell proliferation and its extrinsic and intrinsic control mechanisms.
The book is rounded off by a set of chapters on particular clinical applications of gene therapy, considering haematopoietic defects, cancer, cardiovascular disease, and neurological diseases. These offer a sound and well balanced view of successes to date and indications for future therapeutic routes. I was however somewhat disappointed at the dominance of the haematopoietic system in the book. To a great extent this inevitably reflects the historical development of the field and seems at the outset to be the most tractable system for stem cell and gene therapy, but I would have thought that the inclusion of muscle stem cell therapy—for example, would have been useful, and its omission leaves the book rather incomplete.
A more serious omission still is the lack of a chapter on embryonic stem cell manipulation and differentiation, which even when the book was written—given the inevitable delay between writing and publication—would still have merited one or two chapters. It is clear that embryonic stem cell manipulation, and the avenues it opens up, are going to be vital routes to gene delivery and stem cell repopulation in many disorders.
One is often stung by referees' comments, which carp about experiments not attempted, rather than the data actually presented, and I would not like to criticise this excellent volume by emphasising too much the omissions. The editors comment in the preface that their aim was not to be inclusive, and indeed this would have increased the size of the task enormously. As a summary of the field and (almost, given the publication date) a state of the art review, I can recommend this book highly and hope that a second volume might be produced in the same enlightened way, including some of the newer approaches to stem cell therapy via the manipulation of both embryonic and adult stem cell populations of other tissues in addition to those of the blood.
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