The Development of Human Gene Therapy: Monograph 36
Edited by:- Theodore Friedmann
The transfer of specific genetic material to treat disease has been one of the most exciting potential applications of modern genetics. Given the complexity of the task, it is perhaps not surprising that progress has been slow in terms of clinical gain. The main stumbling block right from the start has been in getting DNA to the right place in a form that permits its expression at the right time in enough cells. The problem of effective in vivo gene targeting still bedevils the field a decade after the first trials began.
The collection of reviews in The Development of Human Gene Therapy begins with a historical overview going back to Archibald Garrod, the senior physician at St Bartholomew's Hospital, London, who, around the turn of the century, discovered what he termed the “inborn errors in metabolism”. It covers the abortive and potentially unethical beginnings of human globin-gene transfer for thalassaemia in the early 1970s, when globin genes were introduced into the bone marrow cells of two patients. Gene expression was unlikely, and no ethical approval had been obtained. The first successes came with cystic fibrosis, adenosine-deaminase deficiency and cancer. Success, of course, is only relative. Real success equates with clinical benefit in terms of improved quality of life or increased survival, and this has so far proved elusive.
The chapters on the major vehicles for gene delivery cover retroviruses, adenoviruses, herpes viruses, lentiviruses, a range of more unusual vectors and, of course, physical delivery systems. Much of the information is dreadfully old and can be found in greater detail elsewhere. Although the major targets for clinical exploitation are discussed, it seems strange to omit the remarkable clinical developments in cystic fibrosis, ischaemic heart disease and the rare single-gene disorders. Some clinical possibilities that are now the focus of much current activity, such as arthritis, retinopathies, collagen disorders, asthma, diabetes and obesity, are not even mentioned.
Highlights of this large volume include an excellent chapter on naked DNA injection into various tissues. The fact that this leads to gene expression at all is remarkably encouraging for the future. Another chapter considers targeted gene repair in mammalian cells using chimaeric oligonucleotides. Although a long way from the clinic, this represents the beginnings of genetic surgery. The short review on stem-cell transplantation is concise, yet informative, while the ethics of the subject are well reviewed in a historical context.
There are several excellent short books reviewing gene therapy. Unfortunately, this is not one of them; its content is outdated and the artwork incredibly poor, and, a major criticism, despite the encyclopaedic coverage of the field, the material comes almost exclusively from US-based authors. Human-gene therapy is now an international endeavour, with clinical protocols in place in more than 25 countries. True, the Americans got there first, but please, the rest of the world does exist.
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Edited by:- H. William Detrich III
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Sikora, K. The laying on of genes. Nature 398, 387 (1999). https://doi.org/10.1038/18812
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DOI: https://doi.org/10.1038/18812