Chemistry-based Innovation: There’s life in the old science (literally)
Special Report - 07/07/17
Professor Colin Suckling discusses chemistry-based innovation and research benefits that can be seen during our lifetimes.
Many people have written off traditional sciences as having little value to the modern world. The real excitement in science is said to be in the big things like the Higgs boson and gravitational waves. I’m a fan of basic science but even so, it is hard to see how these expensive studies will have a substantial benefit on daily life. Or perhaps I should write life and death. Equally headline catching in the past several years has been the problem of failing antibiotics because of the increasing prevalence of resistance in disease-causing agents including bacteria, fungi, viruses, and parasites. It’s widely known that infectious disease is causing substantially increased mortality and morbidity world wide. Here are two instances relating to antibacterial infection:
- “In South Africa, we have people living in the community with TB that we can’t cure, because there are no drugs left. So, it is back to the Victorian age, really,” [R. McNerney, Guardian, Monday 23 May 2016].
- “ Clostridium difficile is very unpleasant for patients. It is exceedingly unpleasant and distressing for relatives to see an old, loved patient in a bed in a pool of faeces. It is very difficult for nursing staff to have to clean a patient nine, ten times a day who is demented, immobile, (and) can’t help the nurse with moving.” [Vale of Leven Hospital Inquiry, Scotland, 2014].
So when you read of a chemistry-based innovation that tackles antimicrobial resistance successfully it’s good to be able to emphasise the life-giving benefits. I’ve written already about our own efforts at the University of Strathclyde using heterocyclic chemistry to tackle antimicrobial resistance in a very wide range of diseases in these Special Reports and in profiles for Adjacent Government publications. In this report, however, I want to highlight a beautiful piece of science from Dale Boger’s laboratory at the Scripps Institute, California [doi: 10.1073/pnas.1704125114].
The antibiotic, vancomycin, has been regarded as a drug of last resort by many clinicians and accordingly has had its use restricted to the most severe cases of bacterial infection. Nevertheless, resistant strains of bacteria have evolved; the way bacteria have achieved this is to modify the detailed chemical structure of their cell wall, which is associated with the activity of vancomycin, so that vancomycin no longer works. Boger and his colleagues have devised and synthesised a close structural analogue of vancomycin that gets round this problem and also introduces two new structural features that cause the new drug to attack the bacteria by two additional but different mechanisms. So if one mechanism of action is voided by bacterial evolution there are two others remaining. This means that the chances that resistance to the ‘new vancomycin’ will be negligibly small over a clinically significant timescale. I hope that in due course it makes a difference in the clinic.
The study is a beautiful example of chemistry and biology working together: the biology informed the chemist what the possibilities were to create the ‘new vancomycin’ and the chemists’ skill designed and synthesised the molecule returning it to the biologist for evaluation. It’s hard to think of a better application of both sciences in terms of public health. Of course the bacteria that the ‘new vancomycin’ can treat are not the only pathogenic microorganisms that challenge public health in different parts of the world. We need further examples of new compounds with new activities and mechanisms to avoid the rapid development of resistance. Our own efforts with our partner company, MGB Biopharma, are working towards similar goals in human and animal health and seeking treatments for bacterial, fungal, and parasitic infections but using simpler, more accessible compounds than ‘new vancomycin’.