From Genome to Therapy

Abstract

The dogma of genomics is that DNA leads to RNA, which leads to proteins that provide function. Thus, to fundamentally change things, the gene might be the place to start. Gene therapy entails development of new technology along the entire product development process. This book covers the presentations delivered during the symposium ‘From genome to therapy’ that was held at the Hotel Europe, Basel, Switzerland, 22–24 June 1999. The first chapter includes an introduction by Craig Venter. Venter emphasizes that in recent years there has been a tremendous number of genes discovered and that we are in the early part of an exponential growth phase in which genomes of all types are being deciphered. The original aim of the genome project was to decode the genomes of only five organisms (Eschericia coli, Saccharomyces cerevisiae, Drosophila, mouse and human). A challenge that now faces all researchers is that roughly half of the genes in each species that have been sequenced are completely unknown genes that appear to be species specific. Another challenging issue is the central dogma that one gene leads to a transcript that leads to one protein with a single function. However, current evidence suggests that this central dogma is more complicated; one gene product can probably have cellular interactions that result in a wide variety of outcomes. Later on in the book, Venter discusses the genomic impact on pharmaceutical development and emphasizes that, in the near future, the development of important new pharmaceutical compounds will undergo considerable changes. Target discovery, lead compound identifications, pharmaco-toxicology and clinical studies will probably merge with the science of bioinformatics into a powerful new approach for the discovery of effective new medicines. He foresees a paradigm of ‘cyberpharmaceutical’ testing that will help to speed up the selection of promising new drugs, compounds that are likely to exhibit toxicity will be eliminated and the costs and risks associated with the current approaches of drug development will be decreased. A chapter by William Efcavitch presents the current state of automated DNA sequencing technology and additional technical advances that will continue to decrease and increase throughput of automated DNA sequencing. He points out that the demands for the sequencing of the human genome to be completed, coupled with the increased use of genomics in the pharmaceutical discovery process, has led to the recent development and introduction-scale DNA analysers based on capillary electrophoresis. Although electrophoretic-based DNA sequencing technology has been in place for some time, continued advances in basic separation science, detection methodologies, automation and sample preparation, promise to keep this methodology in the forefront of genetic analysis. In an account on large-scale experimental approaches, Matthias Mann suggests that mass spectrometry will resurrect protein-based approaches in functional genomics and Allen Roses welcomes the era of susceptibility gene identification and ‘right medicine for right patient’ therapeutics. The pharmaceutical industry perspective of genome therapy is outlined in a chapter by Paul Herling. He emphasizes that functional genomics will impact pharmaceutical R&D beyond discovery research. It will allow the profiling of efficacy, as well as of the side effects associated with novel and existing medicines, which will lead to ‘personalized’medical needs. Research in the pharmaceutical industry will be targeted towards disease-relevant targets and will provide a starting point for the discovery of what causes disease and therapies that modify it. Peter Goodfellow then goes on to describe the impact of genomics on drug research and emphasizes that by increasing the spectrum of available targets for drug discovery, functional genomics will improve the chances of producing novel pharmaceutical products. The ethical issues raised by the application of genetic therapy are described in a chapter by David Magnus. Although short-term problems concern mostly the ethical impact in diagnostics, with the primary therapies being prenatal diagnosis and abortion, long-term issues might be slightly different. Given that technology will probably permit the creation of artificial chromosomes ‘from scratch’within 10–20 years, the potential to design synthesised life forms will give rise to a new era of biotechnology. There will be concerns over ownership and control of living things and of genetic material. The consideration of the legal and ethical aspects of patenting genes and gene therapy led Joseph Strauss to conclude that although for many groups and regulatory bodies resistance to gene therapy is primarily based on the principle that neither patents on any life forms or on discoveries should be allowed, the pharmaceutical industry is more concerned that patents issued on expressed sequence tags (ESTs) and single polymorphisms (SNPs) could hamper the development of new therapies. Finally, although the book is a little out of date owing to the tremendous explosion of recent data and progress in this research area, it is nevertheless easy to read and includes many interesting discussions about the broad field of genomics with many active researchers and experts cited.