How genetics unlocked the mysteries of development.
Coming to Life: How Genes Drive Development
- Christiane Nüsslein-Volhard
It is easy to forget how little was known about the development of living organisms just 30 years ago. Today we have whole genome sequences of many species that can be compared, endless patterns of gene expression that are just beginning to be pieced together, and technologies such as RNA interference that allow us to do genetics at amazing speeds and depths. Together these provide an opportunity to understand the mechanics of life and the details of how plants and animals are formed. And yet, at the beginning of the 1970s, the development of an organism from a fertilized egg was still a marvel with a hidden secret.
Yes, there were hints that the secret would soon be unlocked. The uncovering of genetic regulatory circuits in bacteria had famously led Jacques Monod to state that what was true for Escherichia coli would also be true for the elephant. However, despite these high hopes, the secret remained out of reach. In the 1980s there was a watershed. It came not from the application of biochemistry to the problem, which had been tried before without much success, but from applying a judicious mixture of genetics and molecular biology to two invertebrates: the nematode Caenorhabditis elegans and the fruitfly Drosophila melanogaster.
Christiane Nüsslein-Volhard has played a central role in the process of discovery that has enlightened our understanding of how one cell becomes an organism. Her contributions have the virtue of having explored the issue both in invertebrates, with her pioneering studies of the early development of Drosophila, and more recently in vertebrates, through her work on the developmental genetics of the zebrafish Danio rerio. It is a range allowing her a rare insight into the development of organisms, and this permeates Coming to Life, an account of where we stand in our understanding of the process of embryonic development.
The content of the book ranges from history to evolutionary biology, and includes a crash course in molecular biology and insights into the molecular embryology of different organisms. Surprisingly, all this ground is covered in 140-odd pages of main text with a style that is direct, simple and easy to read. The book is carefully produced and the illustrations are hand drawn and full of personal insight.
The thread of the book is the importance of genetic analysis as an essential tool to understanding the development of organisms, and the principles that have been derived from this. A second important message is the sense of unity of mechanism that underlies the diversity of animal form. Naturally, Drosophila is central to the book, and we have clear accounts of the role that genetics has played, and continues to play, in uncovering developmental principles.
Nüsslein-Volhard highlights some of the barriers that have been broken in the process of establishing the existence of these principles. Nowhere is this better illustrated than in the uncovering of informational gradients and their role in pattern formation. Classical embryological experiments hinted at their existence, but brute-force biochemistry had failed to identify such factors. It was a genetic approach that led to the breakthrough with the bicoid gene and its role in early Drosophila development. Genetics also provided the logic behind patterning along the axes and revealed that different organisms represent different outputs of a conserved molecular kit made up of transcription factors, such as the Hox proteins, and signalling molecules that allow cells to communicate with each other. Nüsslein-Volhard's book establishes the link between Drosophila and vertebrates, and discusses the basic facts of human embryology as another, albeit special, case of vertebrate embryology.
For the most part, the book is an account of a mature field of study with some personal touches. The mostly objective mould is broken in the final chapter, in which Nüsslein-Volhard tackles several sensitive issues concerning the nature of life and its implications for human welfare and reproduction, and the potential of stem cells and genetic therapies. She is not afraid of giving her opinion: “Although the criteria used for the definitions rely on biological events, they are not a scientific but a moral issue. Dignity, right of life and protection are not biological but moral categories ... these issues should be decided not by scientists but by our society as a whole through our political representatives.” The function of the scientist, as most of us will agree, is to find out how things work and to provide information that can be used to help others take decisions. Our role is not to cast shadows or to mediate those decisions. This chapter also makes clear what is possible and what, at the moment, is a utopia.
Coming to Life is said to be aimed at “those who are curious and who would like to understand the process of life a little better without having to deal with highly specialized knowledge”. The final chapter in particular makes one wonder whether reading this book would not also benefit politicians, social activists and journalists who ponder issues such as cloning and stem-cell or genetic therapies in the public realm. They might find the science rather challenging in places, but it would certainly give them a perspective for their judgements.