From the editor

Apocalypse – when?

Most physicians (listening, no doubt, to BBC Radio 4 one early March morning) will have been struck by Dame Sally Davies’ use of the ‘A-word’ as she described the prospect of a post-antibiotic era in which the development of resistance by currently susceptible micro-organisms turns back the clock to the early 20th century.¹ The second part of her annual report on the health of the nation, published on 11 March, describes the challenges from both established and emerging diseases.² It highlights the relative lack of investment in antibiotic development and charts the rate of emergence of new diseases. One of the most striking illustrations in the report is a timeline for the recognition of new diseases since 1980 – coincidentally the same year the last new class of antibiotics was discovered and developed. The report comprises both the chief medical officer’s advice to the government and a series of authoritative reports on which she has based that advice – in particular, highlighting the risks and challenges to people in different age groups. Bacterial infections and the emerging dominance of resistant Gram-negative organisms constitute a growing menace in adults.

The barriers to the development of new antibiotics have been well rehearsed – the cost of development scarcely stacks up against the payback, since a highly successful new antibiotic would only be prescribed in courses lasting from a few days to weeks. The contrast with a successful lipid-lowering drug, a drug for arthritic pain or an antihypertensive is striking. The contrast with many anti-viral drugs is also marked; when suppression rather than cure is the outcome, as in HIV and HBV for example, extended courses offer the prospect of greater return on investment. Such considerations open up the question of what alternatives to the pharmaceutical company model of innovation and drug discovery might be encouraged.

Dame Sally advocates further actions by the Innovative Medicines Initiative (IMI), a private–public partnership aimed at improving drug development, currently backed by €2 billion (half from the European Commission and half from members of the European Federation of Pharmaceutical Industries and Associations).² Its rather tweely named ND4BB (New Developments for Bad Bugs) programme may dispose up to €400 million. Its €200 million COMBACTE project brings together three major pharmaceutical companies – GlaxoSmithKline Research and Development, AstraZeneca AB and Janssen Infectious Disease Diagnostics BVBA – with 16 European universities and research organisations, to design and implement improvements to clinical trials for antibiotics. No doubt the UK is well-represented among these international academic and research partners, one would have thought. All credit to the North Bristol NHS Trust – the only UK institution in the list.³

While the concentration on improving and speeding up clinical trials (topic 1 of the IMI) is, of course, welcome, physicians and academic researchers might wish for an additional scientific initiative to discover new drugs. Discovery and development of new drugs combating Gram-negative infections remains a future topic on the ND4BB suggested architecture.⁴ However, there is already one – albeit smaller – IMI programme directly addressing bacterial susceptibility. TRANSLOCATION is aimed at increasing understanding of how to get antibiotics into multi-resistant Gram-negative bacteria. Here at least two of the fourteen universities, research organisations etc, are British (step forward Newcastle and St Andrews).⁵

What other approaches, outside the involvement of large (and necessarily bureaucratic?) European Organisations, should be encouraged to prevent this apocalypse and, in particular, how should the UK respond? The MRC’s Infection and Immunology Board lists microbiology and microbial resistance as a key area being stimulated through the development of research partnerships and consortia. Its website highlights £4 million in 2011 for two such grants.⁶ It is more difficult to discern how much funding in total is directed at front-line in vitro research into microbial metabolism – both through centres such as the MRC Centre for Molecular Bacteriology and Infection, and through project-specific funding through the MRC and the Wellcome trust. However, if Dame Sally’s warnings are to be taken at face value, the funding bodies – and UK academic and clinical institutions – should be concentrating resources and enhancing priorities in this area. The history of the development of anti-HIV drugs in the 1990s in response to urgent investment shows clearly that research endeavour can be channelled to specific aims by directing research funds to the area of need. If the risks are as stated, the current response seems limited. In stimulating research on new antibiotics, the strategy of leaving the windows open in Praed Street has probably fulfilled its potential.