|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
First published online November 21, 2006
doi: 10.1242/10.1242/dev.02645
Book Review |
Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK
e-mail: j.m.w.slack{at}bath.ac.uk
Christiane (Janni) Nüsslein-Volhard is our representative in the wider
world. Along with Eric Wieschaus and Ed Lewis, she was the recipient of the
1995 Nobel Prize for Physiology, which was awarded for her genetic screens on
Drosophila that led to the discovery of most of the genes that
control development, not just in Drosophila, but in all
animals.
|
The first two chapters of this book contain an account of the basic concepts without which nothing in biology can be explained: evolution, cells, chromosomes and genes are all introduced at the level of an educated layman. The next three chapters deal with Drosophila development and cover the morphology of development, the different classes of developmental gene and how these genes work together to assemble an animal. Very modestly, Janni does not say that much of the material in these chapters was her own work. Then, there is a chapter about more general aspects of development, including cell division and growth, followed by one on the development of vertebrates, which is a sort of whistle-stop tour of the model organisms (Xenopus, zebrafish, chick and mouse). I think she might have said a little more about the inducing factors in vertebrates, as I believe that their discovery, along with that of the developmental genes of Drosophila, created a synergistic research programme that became the core of modern developmental biology.
Finally there are three chapters that extend the story in directions that Janni obviously feels will be of interest to her readers: human development, evolution from a molecular standpoint, and the ethical-legal debates about human embryo research and embryonic stem cells.
In effect, it is a summary of the great endeavour that the readers of Development are engaged in, and with which some of us have been occupied for a very long time
So, how much of a success is the book? It is clearly written and covers most of the main themes that I myself would include in an introductory account. I think it will be regarded as too technical for the general reader, but I would certainly recommend it to a high-school student or a new undergraduate who was interested in this area. It is also a success in that it brings to the front of my mind some topics for discussion, although here I suspect that the author will not agree with all of my reactions.
First, is developmental biology finished? If it is possible to write a book like this and have another professional developmental biologist to agree that the content and conclusions are appropriate for an introductory account, then it would seem that we have arrived at a `classicism' - a mature subject that will, in future, not develop through basic concepts but just by increments of detail at the margins. Of course no subject is ever really finished, as there are always more details to elucidate. As long as science budgets are constantly expanding, every field can go on growing forever. But as budgets reach their natural limits, the relentless competition for funds may force a reduction in funding of fields that are perceived from outside as being `mature'. I know that none of my colleagues agrees with this line of thought, but I mention it nonetheless, if only to encourage people to think of more arguments as to why developmental biology should continue to be funded.
Second, I am struck by the fact that the last three chapters do not really flow from the previous four, in which the principles of modern developmental biology are set out. All of us who engage in teaching know that students like to hear about human embryos, diseases and medical applications, and are less interested in lower organisms, techniques or theory. I don't really know what Janni's personal motivation was as she embarked on her historic genetic screens, but I doubt whether she did it in order to cure serious human diseases. What has actually happened is that collectively the community has solved the scientific problems of development, to a degree of detail that I would not have believed possible in the 1970s, but at the same time this knowledge has had remarkably little impact on practical affairs. I fear that this is why there is a significant disjunction in this book between chapters 2 and 6 (about developmental biology), and chapters 7 and 9 (about topics of interest to the public).
Third, what about the much-vaunted model organisms? Janni states that `knowledge gained from one organism can readily be transferred to another' (p. 91). Later, she suggests that cancer research will benefit from the study in model organisms of genes that, when mutated, contribute to the cause of cancer in humans. It is true that many human cancer genes do encode components of signal transduction pathways that are used in development. But I am worried. The long-range evolutionary homology of developmental mechanisms was one of the big discoveries of the past 20 years. These results are important, and are perhaps underemphasised in Chapter 9, which deals with evolutionary mechanisms. But the more work we do, the more we find that the details are different. The august journal Development today contains plenty of keynote papers announcing, for example, that the Wnt pathway in zebrafish and Drosophila are slightly different. Given the nature of evolution by natural selection, it is hardly surprising that the broad brush picture is similar and the details are different. But it does inexorably follow that if your funding is coming from medical research bodies that want cures for human diseases, then the value of model organisms will decline once the early discoveries have been made. For example, just because APC (adenomatous polyposis coli) is involved in Wnt signal transduction in both human and Drosophila, does that really mean that study of the minutiae of functions of APC in Drosophila will really tell us useful things about human cancer? I doubt it. The more detailed the questions, the more important it will be to work on human cells and tissues. Fourth, we authors are uncomfortably aware that books always contain errors or ambiguities. However hard you try, there are always a few that get through. We are actually grateful to reviewers for pointing them out, so that they can be removed from the next edition. So here goes. On p. 48, it should read nerve cord not chord. In Fig. 23, the explanation of maternal effect mutation is somewhat obscure to me, so might fool the general reader. On p. 85, somatic stem cells need not undergo asymmetrical cell division. On, p. 88, the text seems to suggest that jawless fish are not vertebrates. On p. 98, the text says that imprinting is unique to mammals but it does actually also occur in flowering plants. Imprinted genes also affect much more than just development of the trophectoderm. And finally, on p. 137, Gurdon did not carry out the first cloning experiments in amphibians. These were reported by Briggs and King in 1952. Gurdon did pursue the subject very thoroughly, to the limit of using nuclei from indubitably differentiated cells (adult keratinocytes), although he showed that these nuclei worked very much less well than embryonic nuclei.
Finally, a word on stem cells. Many people, including myself, are thinking that stem cell research should represent the applied science that grows out of academic developmental biology. Stem cells feature in this book in Chapter 6 and again in Chapter 10. There is now a general consensus that the protocols for turning human embryonic stem cells into useful differentiated cells will need to recapitulate the normal sequence of inductive signals for each step of commitment from the inner cell mass to the final product. These steps have been worked out by developmental biologists and are currently being used in many laboratories to design a variety of relevant protocols.
In my view, Janni is unduly dismissive of adult stem cells (p. 143), suggesting that nothing is likely to come from them. In fact adult stem cells are already in clinical use and have saved many lives! These include haematopoietic stem cell grafts for haematological diseases or cancer therapy; in vitro expansion of keratinocyte holoclones to regenerate skin for severe burns; grafts of the limbus, which contains the stem cells for the cornea; and one might perhaps even include the grafting of pancreatic islets for treatment of diabetes, as this sometimes involves in vitro culture. However, we have to admit that none of these existing applications owe much to developmental biology. In future, I hope this will change and that the elegant science represented by this book does eventually deliver some practical benefits to wider society.
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||
