Catherine Brooksbank

Disease models: relevance is everything.

Welcome to a new addition to MMT – a section dedicated to modelling disease. Disease models are a vital tool for molecular medicine; we use them not only to gain insight into the molecular basis of disease, but also as pre-clinical screens to test the safety and efficacy of potential new therapies. For both applications, the relevance of the model is a key determinant of success and, in the past, too little importance has been placed on this. Many novel therapeutics have yielded disappointing results in clinical trials despite encouraging results at the pre-clinical testing stage; there are many reasons for such failures, but pre-clinical testing of new treatments in inappropriate models can be a significant and avoidable contributor.Knockout and transgenic technologies have made the creation of mouse models of monogenic disorders almost routine; ‘knocking in’ specific mutations and conditionally knocking out genes in a tissue-specific and/or time-dependent manner adds extra layers of sophistication that can answer increasingly specific questions about the molecular basis of disease, as well as solving important problems in fundamental biology. But more complex diseases present a more formidable challenge: it is difficult to produce a model that accurately reflects any disease for which the fundamental cause is poorly understood. Instead, we often have to rely on mimicking symptoms. For example, the hemiparkinsonian rat, a classical animal model of Parkinsons disease (PD), is the result of acute chemical destruction of the neurons in the substantia nigra; although the result mimics advanced PD well enough, the cause and time-course bear little resemblance to the disease being modelled. Although models such as the hemiparkinsonian rat have served us well in the past, as therapies evolve from symptomatic treatment to causative treatment, so must our models.The Disease models section is designed to do the assessment for you: each model is compared and contrasted with the human disease to ensure that the reader can decide how appropriate a certain model is for a particular application. We hope that Disease models will not only be of educational value but will also stimulate the use and development of models that are truly relevant to human disease, which will eventually catalyse the development of safe and efficacious therapeutics for human use.We are keen to hear your comments about the Disease models section, as well as suggestions for articles. Please e-mail comments and suggestions to: mmt.trends@elsevier.co.uk

How much molecular medicine do medical students need to learn

This issue of Molecular Medicine Today contains three letters that address the evolving needs of medical education. Many clinicians argue that molecular medicine has yet to have any real clinical impact, and that until it does they need not clutter their minds with molecular details that seem irrelevant to clinical practice, but this scene is set to change in the near future. Several recombinant proteins are on the market; the first antisense drug, Vitravene®, has received approval from the US Food and Drug Administration (FDA) for the treatment of cytomegalovirus (CMV) retinitis; several gene therapy protocols are in Phase III clinical trials; and a number of molecular diagnostic kits are on the market. The clinicians of the future will be faced with a burgeoning number of treatment choices, and making the right decision will depend on an increased understanding of what is happening at the molecular level. Medical schools now have an obligation to produce clinicians who are confident in the concepts of molecular medicine.Traditional medical school curricula are not designed to cope with this concept. The basics of biochemistry and molecular biology, which are arguably necessary for a thorough understanding of molecular medicine, are typically taught in the first year of medical school; the students often commit this material to short-term memory because it seems much less relevant to clinical practice than other pre-clinical subjects. How many clinicians can remember the citric-acid cycle by the time they are qualified doctors – and why did they have to learn it anyway?The authors of the following letters each have a different, but complementary approach to revising the curriculum: Athanasios Papavassiliou advocates rethinking the way that biochemistry is taught to pre-clinical students, whereas Harold Smith and Edward Hundert are planning to integrate molecular medicine into all parts of the curriculum at the University of Rochester (NY, USA). Other medical schools are, no doubt, considering revising their curricula to a greater or lesser extent, but Timothy Cox reinforces the subtext that runs through all of these letters: it is one thing to add molecular medicine to an already overcrowded curriculum, but quite another to stimulate enthusiasm for it.These letters mark the beginning of a debate that will run not only in the pages of Molecular Medicine Today but also online in issue 51 of HMS Beagle (http://www.biomednet.com/hmsbeagle). We welcome all our readers to join in; it is hoped that this sharing of opinions will contribute, eventually, to the successful incorporation of the new medicine into the minds of our future physicians; without them, molecular medicine will never become established practice.

Targeted transgenics from the creators of Dolly

PPL Therapeutics (Edinburgh, UK) have announced the birth of two lambs (Cupid and Diana) carrying a gene that was inserted at a specific chromosomal site. It has been possible to create transgenic livestock animals for some time, but the novelty of the new technique lies in the combination of two techniques: (1) replacing a specific gene in vitro, followed by (2) nuclear transfer (a la Dolly). PPL are intending to use this technology to produce large amounts of human proteins, uncontaminated by their ovine or bovine equivalents, in the milk of farm animals. One potential application is the production of human serum albumin, used to treat burn victims. This is currently produced from human serum.

A taste of the Zeitgeist

The Cancer Genome Anatomy Project (CGAP) http://www.ncbi.nlm.nih.gov/ncicgap/The Human Genome Sequencing Index (HGSI) http://www.ncbi.nlm.nih.gov/HUGO/The Institute of Genome Research (TIGR) database (includes microbial genome sequencing projects) http://www.tigr.org/tdb/tdb.htmlThe German Human Genome Project (DHGP, currently in German only) http://www.dhgp.de/Congress of Molecular Medicine Home Page http://www.cmm.springer.de/

Divide and conquer: understanding the natural history of cancer

Abstract XVth Meeting of the European Association for Cancer Research: five natural histories of human cancer Stockholm, Sweden, 15–19 August 1998

The new cardiology

Abstract The American College of Cardiology 47th Annual Scientific Session Atlanta, GA, USA, 29 March—1 April 1998

Molecular medicine through the kaleidoscope

Abstract The 30th Miami Winter Symposium: Molecular Biology in the Conquest of Disease Miami, FL, USA, 7–11 February 1998