Plos Blogs. October 22, 2015. By Mat Todd
Contributors in this series on drug prices and access to medicines have mentioned important issues related to policy, finance and intellectual property. I’d like to make a few comments from the point of view of a researcher dealing with the discovery and development of new medicines at the earlier stages – the generation of the pipeline of new potential medicines at the bench.
The view from the lab bench
One might think that issues to do with how we carry out basic science are unrelated to pricing and access – that the way scientists conduct themselves is not linked to the way medicines are marketed and distributed. They’re strongly linked, and the complexities that happen at the later stages can be toxic to the way we do the science.
The issue is secrecy. It is essential, as things stand, for the discovery process to be secretive, whether in academia or industry. This situation arises from a simple argument: drugs are expensive to develop and one has to be able to recoup the costs of the research and development through the granting of a monopoly. Whether this argument is true or not is today as good as irrelevant since it is so stridently argued that it influences any number of decisions on investments in the discovery of new medicines. For example, on grant applications I must provide a “route to commercialization” and I do not have the space to argue for a revolution.
Clearly there is also more at stake than just making money back – there is a great deal of natural human excitement around financial profit, and the granting of a monopoly gives shareholders confidence in a revenue stream. As other posts in this series have pointed out, this can result in odd behavior.
The effect of secrecy on the basic R&D process is unfortunate. Efficient research thrives through the rapid sharing of data. Science is effective when it is a meritocracy of ideas, and we can build models that are useful to people (What is Alzheimer’s disease? How do Superbugs become Super?) on the basis of all the available data, rather than just some.
If you and I work on the same research problem, we might be duplicating each other’s work. Duplication as verification is crucial in science, but not when the separate labs don’t talk. If we are encouraged to be positive about our findings (if we are being measured on successes, academia or industry) we may be hesitant to share data that do not support what we hoped we would discover, condemning those that come after us to repeat the same dead-end line of experiments. The public would be shocked to discover the percentage of experiments funded through tax dollars that never see the light of day.
An openly sourced drug for a “silent pandemic”
A few years ago I borrowed well-established principles from the open source software movement and applied them to a research problem concerning the drug used by millions of people in the treatment of the terrible tropical disease schistosomiasis. My lab, working with the World Health Organisation, took the step of replacing our paper lab notebooks on our desks with an electronic version on the internet so that everyone could see what we were doing all the time and suggest alternatives for missteps. Through spontaneous contributions mainly from the private sector, given free of charge, an expert team of committed people self-assembled to solve the research problem quicker than if we had remained closed to the outside world. We were faster because we were open.
It was important to demonstrate this – to run the pilot. But deep down we all acknowledge the truism: if you share what you’re doing, people will help out and the end result will be better – maybe faster, cheaper, more robust. We see this with open source software all the time, and even though science involves some differences (physical materials) the same ideas apply. None of us is as smart as all of us.
If we could work openly, and bring medicines from discovery to clinical trials without secrecy we could essentially feed a ravenous generics industry, which could take approved medicines to market with little or no protection of intellectual property in a financial environment that keeps costs low.
What about big pharma?
Open source relies on the world to be a collaborative medium, and my lab has received the very highest quality inputs to open projects from scientists in major pharma companies who want to solve pressing biomedical research problems and help people just as much as everyone else.
The power of open source is instead that we create a competing model, one that can run in parallel with a model based on secrecy and compete in areas of mutual interest, as well as tackle areas where pharma is simply unable to operate (market failure arising from either low return on investment or high risk). A competition of models in how we discover and develop medicines will be both healthy and an important global experiment. We are in a sense doing Pharma an injustice in expecting it to cure all our ills.
We are seeing some initiatives that adopt openness in drug discovery. With the Medicines for Malaria Venture (MMV) I have been running a project called Open Source Malaria that adopts strict open source rules day to day. MMV themselves have pioneered the sharing of physical samples for the community through their Malaria Box. The Structural Genomics Consortium place important early stage research (part-sponsored by pharma) on a variety of diseases into the public domain, Pubchem and ChEMBL help researchers the world over to share data, and the Indian OSDD project has effectively crowdsourced discovery from large populations of students. With funding from Tata Trusts in Mumbai some colleagues and I will start an Open Source Pharma Foundation that seeks to support in-kind any open source drug project worldwide through finding resources and .
Borrowing from Open Access publishing
The rules (the licence) covering any such work ought to be something simple like a Creative Commons licence that says people may take whatever they wish from the research and use it for any purpose, including to make money, provided the original is cited. This sort of arrangement covers Wikipedia. What is to stop people taking Wikipedia content and using it to make money? Nothing – if a market can be found, it can be used, subject to certain conditions. There is a mantra in open source software – one does not make money with open source, one makes money using open source. How much does a start-up save by not having to purchase web browsers or other basic software? How much faster do we work if we use robust, interoperable solutions?
How to move ahead with a new model of Open Source drug development
Open source research in drug discovery and development has the potential to change the pricing, IP and legal situation radically through a de-linkage of R&D costs and prices of medicines. How open source will achieve this is unclear because we’ve never had a molecule that was “born open” – one that has navigated all the way from discovery to market in the public domain. There are examples of drugs reaching the market with no IP protection, but no end-to-end story of an open source drug. I find this tremendously exciting.
So we have some first steps, but now we need to scale up to be effective. We need parallel shots on goal here if we are not to wait around during a century of serial projects that don’t make it because of the usual attrition rates in the development of medicines.
Who pays? Philanthropists have changed the game in neglected disease research (the Gates Foundation spent nearly half what the US government spent in this sector in 2013), and we will see more of this as a source of money. The public sector funds about a third of biomedical R&D, but this remains a very small percentage of GDP, a small increase in which would have a big impact. There is a great deal of money that could be invested in drug discovery and development provided we do not use such money lazily and just try to mimic Big Pharma, but instead embrace the privilege we have in using public funds and make the research openly available. There are many other interesting financing models that have been proposed, such as the Health Impact Fund, or the MSF 3P proposal, or the idea of a Megafund, but none of these have ever been combined with the idea of an open source research model up front.
It would be fascinating to flesh out this new, competing model: to see if we can plot a sustainable, economically valid path to new medicines that acknowledges the enormous profits that arise from a healthier population.
Mat Todd was born in Manchester, England. He obtained his PhD in organic chemistry from Cambridge University in 1999, was a Wellcome Trust postdoc at The University of California, Berkeley, a college fellow back at Cambridge University, a lecturer at Queen Mary, University of London and since 2005 has been at the School of Chemistry, The University of Sydney where he is Associate Professor.
His research interests center on the development of new ways to make molecules. His lab motto is “To make the right molecule in the right place at the right time”, and his students try to work out what this means.
He has a significant interest in open science, and how it may be used to accelerate research, with particular emphasis on open source discovery of new medicines. He founded and currently leads the Open Source Malaria (OSM) and Open Source TB (OSTB) consortia, and is a founder of a broader Open Source Pharma movement. In 2011 he was awarded a NSW Scientist of the Year award in the Emerging Research category for his work in open science and in 2013 the OSM consortium was awarded one of three Wellcome Trust/Google/PLoS Accelerating Science Awards. He is on the Editorial Boards of PLoS One, Chemistry Central Journal, ChemistryOpen and Nature Scientific Reports. On twitter @