# Foreword # Foreword Foreword Professor Sir John Bell, Regius Professor of Medicine, University of Oxford In 1983, David Weatherall, John Ledingham, and David Warrell launched the first edition of the Oxford Textbook of Medicine. That era of medicine looked entirely different from today but the need for a scholarly repository of medical knowledge remains as important as ever. Medicine is now firmly in a digital age; sources of information abound and are readily available and the field is moving so quickly that it is harder than ever to provide up to date relevant informa- tion for the profession. Despite this, the sixth edition of the Oxford Textbook of Medicine still provides the foundation of knowledge upon which good clinical practice is based. Never before has there been such a rapid advance of medical know- ledge and practice. Since the first edition of the Oxford Textbook of Medicine, medical practice has reduced cardiovascular mortality by up to 70% in Western countries, there are now multiple new ther- apies for diseases such as rheumatoid arthritis and multiple scler- osis, disorders where the descriptions of therapeutic options in the first edition were necessarily brief. Cancer is now increasingly man- aged with immune and targeted therapies. Whole new diseases have appeared (Hepatitis C and HIV) and have been either controlled or conquered with drug therapy. The sequencing of the human genome seemed an impossible dream in 1983 while today we have sequenced more than a million genomes and have had insights into rare disease and cancer that were unimaginable then. Life expectancy has risen by nine years for men and ten for women in the United Kingdom, creating a demographic shift that will fundamentally change society and medicine forever. The pace of change has been dramatic. The Oxford Textbook of Medicine gained a reputation by moving medical practice forward from the Oslerian view of medicine ori- ginally expounded in his text book the Principles and Practice of Medicine into an era of more molecular and scientifically based understanding of disease. Constrained by the lack of tools for ex- ploring the molecular basis of pathogenesis, Osler was limited in how he could describe the world of disease, largely based on bed- side observations or those from the post-​mortem room. The Oxford Textbook of Medicine shifted this focus and aligned it with the emerging field of molecular medicine which has begun to create a new taxonomy of disease but also an approach to therapy which is based on pathogenesis. There has been a wave of new information, with new insights appearing weekly into the underlying molecular events associated with disease. Diseases characterized by phenotype are now broken down into multiple subtypes and disease is being individualized. This is rapidly leading to a very significant change in our perception of pathogenesis as well as the classification and nomenclature of disease, all crucial roles for a textbook of medicine. We now are aware that many of the classic definitions of diseases such as diabetes or cancer were descriptions of phenotypic charac- teristics. Interrogation of these disorders at a molecular level has demonstrated that these terms mask disease subtypes defined by molecular pathology where natural history and response to therapy may differ. Combine this with the explosion of new diseases coming from studies of rare disease and there is a challenge to conventional disease nomenclature. This molecular precision creates real oppor- tunities for targeted highly effective therapies, but it also creates challenges for the model of drug discovery when novel treatments can only be used in increasingly small patient populations. These are major issues for medicine, health systems, but also textbooks such as this one where, historically, the stewardship of disease nomenclature has been maintained. The therapeutic options available to practising clinicians have also advanced beyond all recognition since the first edition of the Oxford Textbook of Medicine. We have seen an era of biologic therapy which has provided important new therapeutic alternatives for many hard-​ to-​treat diseases including cancer. We are now entering a new era where modalities such as gene therapy and interfering RNA thera- peutics have demonstrated their utility in the clinic. Similarly, an era of cell therapy has also begun which will provide important new alternatives to some diseases. These new therapeutic alterna- tives and other opportunities for improving healthcare using med- ical technology or novel diagnostics such as sequencing also bring with them the challenge of how healthcare systems can continue to be affordable, either for individuals in private healthcare settings, or in state-​funded, single-​payer systems. In this context, it is remark- able that the authors and editors of the Oxford Textbook of Medicine have managed to sustain both its relevance and the accuracy of its content. The pace at which our understanding of disease, our therapeutic options, and our healthcare systems are likely to change makes it nearly impossible for a textbook of medicine to be truly comprehen- sive given the speed of change, the impact of new innovations and the multiple additional sources of information available to practi- tioners. The Oxford Textbook of Medicine has provided remarkable levels of detail in this rapidly changing world but, more importantly, the textbook continues to provide a source for readers to access information on the fundamental features of disease. This founda- tional knowledge remains crucial to our ability to understand, diag- nose, and treat patients whether they are in the developing world or Foreword vi Western healthcare systems. Having a source of such information across all major diseases accessible in a single source remains the bedrock of both teaching and practising medicine. The foundations provided by the Oxford Textbook of Medicine form a core of know- ledge which practising clinicians will continue to need. The editors of this edition have been faithful to the vision of the original three editors. Science, in all its forms, is at the heart of our understanding of disease and has enabled progress in clinical medi- cine to occur at a remarkable pace. By providing a textbook that describes the foundations of our understanding of disease and its management, the editors have successfully given us an authoritative text which practising clinicians will find invaluable to support their day-​to-​day decisions. David Weatherall, one of the three original editors and who died in 2018, would be gratified by this new edition.