An interactive computer-based tutorial to introduce the
principles of the drug discovery process

This highly interactive program combines a tutorial and a self-assessment exercise in the form of a ‘game’.

Tutorial – this is divided into several sections, each of which may be accessed in any order:

• The Pharmaceutical Industry - setting the scene: an introduction to the industry, some historical aspects of drug discovery, different functions of medicines;
• Selecting a Disease Area: describes the sort of issues which the industry will consider in deciding what sort of drug they wish to develop;
• Selecting the target: introduces potential drug targets (enzymes, receptors and ion channels) and uses examples of common diseases to illustrate how different drugs act;
• Initial Screening: describes techniques (high throughput screening) and principles of using an assay to test large libraries of potential compounds;
• The Screening Cascade: covers the methods (enzyme assay, cell assay, mode of action test, selectivity test and optimization) used to identify a small number of potential compounds with which to proceed into development;
• Safety Testing and Clinical Trials: describes methods of toxicity testing, and phase I, II and III of clinical trials;
• Self-assessment section: contains a number of largely multiple-choice questions covering each of the sections

High quality colour graphics are used extensively throughout the program, and features such as animation, a glossary and hotword facility are used to enhance student learning. The program is highly interactive and uses several features to promote this. For example, the main sections all have associated student tasks/self-assessment questions, e.g., true/false questions with feedback, drag-and-drop exercises, data interpretation exercises, calculations, case histories, role-play decision-making group activities. These are designed to consolidate knowledge and to allow students to self-assess their understanding of the section they have completed. They are also used to present additional information and explanations through the feedback. Glossary (definitions of terms) and hotword/hypertext links (fuller explanations of terms and concepts) are used throughout. The section of multiple-choice questions allows students to self-assess their knowledge.

The learning package is intended to be used either: to support existing teaching of modules containing pharmacology, or for independent study. Brief trials with high school students have indicated that it would occupy students for one to two hours of study and that it works best when students study in pairs.

Student Exercise - takes the form of a ‘game’ and is designed to complement the interactive tutorial. Students are placed in the shoes of a project team working for a fictitious pharmaceutical company ‘Lion Pharmaceuticals’. They have a brief to identify three potential new medicines to treat prostate cancer (the selected disease area) starting with Lion’s library of compounds and an identified target (a key enzyme).

The team have to make crucial decisions at each step of the process. Poor decisions trigger the intervention of a Project Manager whose job is to keep the team within budget and on schedule. He advises the team when he intervenes but also penalizes them with the loss of a ‘life’. The team have to complete the task with the loss of fewer than five ‘lives’.

The game is divided into four sections which follow closely mirror the approach of the tutorial program.

• High Throughput Screening – students must decide the number of compounds from the library to test and, using a simulated spread-sheet to help them, decide on the optimum use of resources (human and machine) to complete the task.
• The Screening Cascade (enzyme assay, cell assay, mode of action test) - students have to decide on the best way of conducting this series of tests – either to develop and carry out the tests in series or in parallel.
• Compound Profiling - here students study the properties (water solubility, toxicity, ionic charge and chemical ‘attractiveness’) of the small number of families of compounds and singletons and select three to take into the final stage.
• Animal (in vivo) testing - at this stage there are ten possible compounds remaining. Students have to reduce this number to three by eliminating ‘candidates’ from results of five ‘in vivo’ studies in animals. They are presented with results of the compounds on: plasma concentration (after oral dosing in mice); target enzyme activity in rats; prostate gland weight in rabbits in which prostate cancer has been induced; tumour cell growth rate; and preliminary safety and toxicity testing.

The emphasis is on reinforcing their learning and highlighting important principles of the discovery process e.g. efficient use of resources, use relatively inexpensive in vitro testing for preliminary screening, in vivo (animal) studies are expensive, the discovery process is long (several years) and very costly.

System Requirements: Windows: Intel Pentium II 450MHz or faster processor (or equivalent), 128MB of RAM; Microsoft Windows 98, Windows Me, Windows 2000, Windows XP or Windows Server 2003 Macintosh: PowerPC G3 500MHz or faster processor, 128MB of RAM; Mac OS X v.10.1.x, 10.2.x, 10.3.x, or 10.4.x

Recommended browser software: Windows: Internet Explorer; Macintosh: Safari or Firefox; Both: Adobe Flash Player plug-in, version 8 or higher.