In collaboration with the Australian Medical Students Association (ASMA), Medshop Australia recently held a competition asking for participants to submit a short piece of writing based on a choice of four topics relating to medicine and healthcare. One of these topics was the future of medicine and pharmaceutical drugs. This was the topic that Cindy Guo chose to write about. Cindy received and honourable mention for his work and we enjoyed it so much that we wanted to share it with you. So without further ado, we will hand over to Cindy.
Can open source drug discovery tackle the antibiotic resistance epidemic?
Antibiotic resistance is recognised as one of the greatest challenges facing modern medicine. The discovery of penicillin in the 1940s ushered in a 'golden era' of antibiotics, characterised by a huge decline in deaths due to infectious diseases. In the decades that followed, antibiotics were widely used in humans and animals worldwide. But they more they are used, the less effective they became. Responding to such severe selective pressure, micro-organisms evolved defences against these medicines, rendering many ineffective.
A 2014 World Health Organisation (WHO) report has forecasted the approaching 'post-antibiotic' era, where common infections and minor injuries can kill1. Up to 60% of hospital infections are now drug-resistant, up from 15% in the 90's. Data collected from the CDC showed that over 2 million Americans acquired drug-resistant infections in 2011, resulting in death in 23,0002. Projections suggests multi-resistant bugs will kill 10 million people annually by 2050, surpassing cancer (AMR review).
Even 'antibiotics of last resort' such as carbapenems are now ineffective against particular strains of gram negative bacteria. Therefore, we desperately need new weapons to arm ourselves in the war against drug-resistant infections .But none are forthcoming. There has been no new class of antibiotics discovered since 1987. Funding allocated to research and development of novel anti-infectives has been reducing by 10% per annum over the past few years. The pharmaceutical industry is cutting back its antibiotic discovery programs, with Pfizer shutting down its antibiotic research facility in 2011. (3,4)
Why is the antibiotic development pipeline drying up?
The foremost reason is low potential for revenue. As with all businesses, pharmaceutical companies make investments based on potential for future profit. For example, chronic diseases which have high prevalence in Western countries, such as Alzheimer's Disease, are preferred targets to receive R&D funding. In comparison, a treatment for multi-resistant Staph Aureus will be equally as expensive to develop, while yielding much lower returns on investment: the treatment course is shorter, and they must be used judiciously to prevent further resistance from developing.
Stringent demands at the regulatory level for efficacy and safety data is another factor. For example, telavancin, an antibiotic for pneumonia, could not be approved by the FDA due to lack of statistical power in their data.(5) The relative rarity of patients who qualify for treatment with novel antibiotics presents difficulties to researchers conducting clinical trials. However, this climate is changing: to incentivise companies into antibiotic research, the Generating Antibiotic Incentives Now (GAIN) Act was passed in 2012, which extends patent exclusivity for a further 5 years and fast-tracks the FDA approval process.(6)
While novel agents are in the pipeline, antimicrobial stewardship programs have been implemented to safeguard what antibiotics we have. These are effective in cutting down inappropriate prescribing, improving patient compliance and raising awareness. Even so, more solutions are needed to keep up with the ever-evolving microbes. Open source drug discovery projects can provide the solutions that we need.
The role of open source drug discovery
Open source is a term used in software development, implying a project is open to anyone, and the final product emerges from a distributed team of participants. All data is public domain, and no patents are allowed. This model has resulted in many successes in past years, such as Wikipedia and Linux. In the context of drug discovery, compounds with biological activity are identified and improved through repeated cycles of chemical synthesis and evaluation. Online forums and communities allows for experts from all over the world to collaborate on huge non-for-profit 'open-source' projects and data can be published and analysed online.
Several projects are already either underway or complete. In 2006, Matthew Todd from the University of Sydney initiated a project to synthesize an enantiopure form of praziquantel, which could treat schistosomiasis infections with fewer side effects. The organisers experienced unexpected enthusiasm shown by industry, free input from companies and researchers worldwide, resulting in a preliminary solution after less than a year. In 2010, GlaxoSmithKline released 13,500 chemical compounds into the public domain with biological activity against malaria. This paved the way for the Open Source Malaria Project, which seeks to enhance bioactivity and selectivity with the end goal of producing a feasible antimalarial drug. This model of collaborative, transparent research is on track to discover cost-effective drugs for neglected diseases and has potential for the same in the area of antibiotic resistance.(7)
What are the advantages to this type of approach?
Firstly, all results are made available to the public, hence are accessible for all and subject to the most rigorous peer review possible. Any funding details and political/corporate affiliations are also transparent, raising accountability. Since all findings are public domain, the absence of patents will save money for patients and governments. The open source model prevents any unethical practices such as ‘evergreening’ and hiding safety data, which had been employed by the pharmaceutical industry in the past.(7) Lastly, research can be accelerated by being open- experts who wish to participate in the project can communicate and contribute directly, rather than being contacted through professional circles.
For the pharmaceutical industry, participating in open source projects and volunteering considerable resources for a charitable cause is an opportunity to improve their tarnished reputation. Open collaboration between experts from both industry and academia has the potential to reinvigorate antibiotics research, and is certainly an avenue worth
5. Davies J. Where have all the antibiotics gone? Can J Infect Dis Med Microbiol. 2006;17(5):287–90.
6. Ledford H. FDA under pressure to relax drug rules. Nature. 2012 Dec 4;492(7427):19–19.
7. Woelfle M, Olliaro P, Todd MH. Open science is a research accelerator. Nat Chem. 2011 Oct;3(10):745–8.