Ethics of Research involving animals
Use of animals in current pharmaceutical research and development
8.5 The discovery and development of new medicines6 entails a very complex range of different methodologies (Figures 8.1 and 8.2). The process, undertaken primarily by the pharmaceutical industry, takes an average of 10–15 years.7 In this section, we describe it in terms of eight stages, beginning with target identification and ending with the launch of the new product (see Table 8.1).8 Data from animal research are crucially important to researchers in the pharmaceutical industry when deciding whether a potential medicine will be effective and safe for use in humans.9
Figure 8.2
Table 8.1: Overview of the process of discovery...
Stages 1 and 2: discovery and selection of compounds that could be effective medicines
8.6 Early stages of the discovery process can be divided into two stages. Stage 1 involves target identification (seeking, for example, to identify receptors for active molecules), and stage 2 relates to the identification of possible medicines. Both stages make use of advances in genetic and basic biological research, and of new, automated technologies including:10
- high-throughput chemistry: systematic exploration of the diversity of chemical structures to increase the number of possible candidates; the aim is to produce a shortlist of novel molecules that have the potential to be safe and effective medicines;
- ultra11-high-throughput screening: automated analysis of a very large number of novel molecules in cell-based in vitro assays, which are analysed by automated systems using advanced robotics;
- high-throughput biology: technologies such as automated administration of medicines and automated blood collection via catheters into blood vessels, which then allow a more rapid and detailed analysis of the full range of effects in whole animals.
The very large amounts of data generated from these new methods are then integrated and analysed further by means of statistical and computational methods.
Stage 1: target identification
8.7 The search for new medicines begins by focusing on areas that are of potential interest to pharmaceutical companies. These include medicines that can be used to address unmet medical needs (for example, Alzheimer’s disease), interventions against diseases that affect a great number of people, such as malaria or HIV/AIDS, medicines that are sometimes referred to as ‘lifestyle drugs’, such as Viagra or Propecia,12 and improvements to existing medicines.13 Pharmaceutical companies also sometimes seek to develop new medicines even if the medical need is already met because there appears to be access to a profitable share of the market.
8.8 Effective medicines maximise their effect on a specific biological pathway and minimise effects on all other pathways. The identification of useful targets, such as disease-associated genes or proteins that function as receptors for active molecules of new medicines, is therefore crucial. Information from the sequencing of the human and animal genomes is also important for the identification of disease mechanisms and for understanding how a person’s genes can affect both disease processes and their responses to medicines.14
Stage 2: identification of possible medicines
8.9 In the next stage, compounds that might interact with the selected targets are submitted for high-throughput screening (or HTS), which is the automated testing of tens or even hundreds of thousands of compounds in a systematic way using cell based in vitro assays. Compounds or ‘hits’ that are judged to be the most interesting are then examined further. At the start of the process there is an average of one million compounds; at the end, numbers have decreased to about 1,000.
Footnotes8 See AstraZeneca (2003) Take a Walk Along the Path to a New Medicine, available at:
http://www.astrazeneca.com/sites/7/imagebank/typeArticleparam502178/seeking_new_medicines_v15.html. Accessed on: 26 Apr 2005.
9 Samuels G (2003) Medicines: Tried And Tested - In Animals?, available at:
http://www.abpi.org.uk/publications/publication_details/mttur/mttur_ani.asp. Accessed on: 26 Apr 2005.
10 AstraZeneca (2003) Enabling technologies, available at: http://www.astrazeneca.com/article/11177. GlaxoSmithKline (2003)
New Automated Approach will Transform Discovery Research at GSK, available at:
http://science.gsk.com/news/features/030613-tres.htm; GlaxoSmithKline (2003) GSK Progresses Its Plan to Automate Discovery
Research Processes, available at: http://science.gsk.com/news/features/031021-hlw.htm. Accessed on: 26 Apr 2005.
11 The prefix ‘ultra’ refers to the very high throughput enabled by miniaturisation and automation.
12 Viagra was developed to treat impotence. Propecia is intended to help patients who suffer from baldness.
13 See paragraphs 3.13, 14.40, 14.58 and 15.83 for a brief discussion on similar medicines, sometimes known as ‘me-too’ drugs.
14 See Nuffield Council on Bioethics (2003) Pharmacogenetics: ethical issues (London: NCOB).