Waiting for the transgenic chicken

Animals with Novel Genes - The Frankenstein Syndrome
November 3, 1995

Animals with Novel Genes is clearly directed at the scientist with a basic knowledge and understanding of the principles and methods of molecular genetics. It successfully summarises recent advances in research and development of transgenic animals - ie animals that carry "a foreign piece of DNA stably integrated into the genome of every cell in that animal" - from a scientist's perspective. The book is divided into reviews of research on different animal groups with separate chapters on insects, fish, birds, rodents and large mammals. In a final chapter, the editor Norman Maclean comments briefly on the limited amount of work on other organisms.

Each chapter adopts the same structure, with emphasis on the methodology of introduction of the transgene, facilitation of identification of transgene integration, and the determination of transgene expression. The authors, mostly from British academia, provide considerable technical information on methods of introduction of the transgene. The "traditional" method involves some form of injection into gametes or early embryos, but new methodologies of introduction are being developed to improve rates of incorporation. These include sperm mediated transfer, retroviral infection, electroporation and ballistic delivery (the cell is bombarded with DNA-coated particles). Several authors cite the development of culture techniques and the relatively simple methods of in vitro transfection of embryonic stem cells as a major recent technological advance. These embryonic stem cells produce chimeras when injected into the host embryo. Some germ cells will be derived from the cultured embryonic stem cells, thus providing a route to the production of true transgenic animals in the next generation.

To determine integration and expression it is necessary to differentiate transient expression of extra chromosomal DNA from that of incorporated DNA. One elegant tool in determining incorporation is the inclusion of reporter genes linked to the transgene.

It is surprising to discover the relatively small number of species in which true transgenics have been produced. This book emphasises the striking differences in the rate of progress of transgenic research between the different animal groups. This is largely the result of technical difficulties associated with the induction process rather than being linked with the importance of potential applications. The relative ease of pronucleus injection in rodents has resulted in a large and expanding number of lines of transgenic mice. Birds have proved trickiest in this respect: clearly it will be some time before we have the option of buying transgenic chicken from our supermarket shelves.

Transgenic mice and to a lesser extent larger mammals are increasingly being developed for the study of human diseases and genetic disorders, including Alzheimer's disease and cystic fibrosis. Research into transgenic fish and larger animals is focused on increasing yields from agriculture through enhancement of growth, reproduction and disease resistance. Other interesting avenues of research are the development of transgenic animals for human organ donation and as "gene farms", for example mammary gland specific transgene expression for the production of therapeutic or diagnostic proteins.

Animals With Novel Genes is an excellent series of reviews of the developments in this fascinating and potentially hugely important area of genetics research. The illustrations are much less satisfactory. And this area seems to suffer particularly from "technospeak". But the book should become a staple on the library shelves of institutes involved in transgenic research. Having said that, it will be out of date almost immediately. I look forward to the next edition.

Maclean largely dismisses the environmental and ethical issues raised by transgenic animals in a few paragraphs. While it is true that discussion of this topic lies outside the scope of his book, Maclean is conforming to type for "scientists" or "experts", according to Bernard Rollin, author of The Frankenstein Syndrome. Much of this thought-provoking and well-researched book, which is an excellent complement to Maclean's, argues that experts should not be the people to assess the risks of and establish the ethical guidelines for genetic engineering. This argument is well articulated and persuasive, although I would like to think that the examples of the arrogance of experts Rollins cites are the exception rather than the rule.

His first chapter deals, perhaps at unnecessary length, with the difficult concept of whether some areas of science, and specifically genetic engineering, are inherently wrong. The second section, the most interesting to a scientist such as myself, concerns the assessment of the biological, environmental and social risks of genetic engineering. The third section attempts the more awkward task of examining the potential effects of genetic engineering on animal welfare. (One has only to look at some bizarre breeds of dog, at bubble-eyed goldfish and at turkeys too fat to mate, to realise that concerns over animal welfare have not constrained the "progress" of genetic change by traditional selective breeding - how much more will this be so for genetic engineering.)

The author wanders from the point rather in the first section, which becomes a more general examination of the philosophy and philosophers of science. Rollin quotes from environmental philosophers and theologians but fails to unravel satisfactorily the issue. One is left with the conclusion that judgements of right and wrong should turn upon issues of real and perceived risk to both humans and animals.

The experts are admonished for not keeping the public fully informed, which is undoubtedly true. However, as any scientist who has tried to talk to the press will attest, there exists no appropriate medium for this dialogue, a point that Rollin seems to have missed. There is little doubt that the risks of genetic engineering are fundamentally different to those of more established techniques of genetic modification (and they are not negligible), principally because the technique introduces novel DNA into the animal, the short and long-term effects of which cannot be precisely predicted. A further significant factor is that the changes are so rapid, leaving little time for their comprehensive evaluation. Rollin is rightly convinced that the present control and legislation (at least in the US) is inadequate and he proposes a model for the regulation of genetic engineering.

Rollin's writings are clearly well informed and I found myself agreeing with many and most of the arguments presented, including those against my profession. Overall the book is balanced, being neither an attack on nor a vindication of the present trend in the development and regulation of genetic engineering. Unlike Animals with Novel Genes, The Frankenstein Syndrome will appeal to the nonacademic interested in these issues.

Graham C. Mair is a research fellow in the school of biological sciences, University of Wales, Swansea.

Animals with Novel Genes

Editor - Norman Maclean
ISBN - 0 521 43256 1
Publisher - Cambridge University Press
Price - £30.00
Pages - 266

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