Crowdsourcing Drug Discovery
Fact: The current system of finding new drugs is not working. Here’s what to do about it.
Are we in denial about the state of drug discovery? This is a question I recently asked a room full of leading thinkers from the pharmaceutical, academic, and nonprofit worlds assembled for a Wellcome Trust meeting on precompetitive boundaries in drug discovery. At the time, I certainly thought so. The current system for drug discovery is unsustainable, but I expected that the experts assembled here would rather ignore the facts than admit that the entire system is in need of major disruptive innovation. I wondered if the crisis were enough to shock people into agreeing to revolutionize the system of drug discovery with changes that will disrupt some of its very foundations.
One such change involves crowd-sourcing aspects of understanding diseases. We desperately need better predictive models of disease that are actionable at the molecular level. Better models will result in better targets. These models will require integration of clinical and molecular data at a massive scale, beyond the numbers of patients and depth of genomic data so far contemplated. This in turn will require patient-driven trials and sharing of data between labs before the publication of articles, as well as shifting to the use of data not as conclusions but as ingredients for the next better experiment. Such crowd-sourced efforts would fundamentally change the current links between drug-discovery companies and physician trialists.
Another radical concept: Declare an institutional patent (IP)–free zone that extends all the way through Phase II clinical trials. Economics and efficiency argue for collaboration on precompetitive research, but so do human factors. Chas Bountra of the Structural Genomics Consortium (SGC) provided an excellent perspective when he raised the sobering fact that 90 percent of Phase II compounds fail. When you thoughtfully consider the fact that duplicative research is being done on these compounds, you realize that this is not just a tragic waste of time, money, and careers—this is unnecessarily exposing patients to compounds that are likely to fail. As Bountra said with a powerful conviction: “It is not only a criminal waste of money, it is ethically and morally wrong.” The total lack of IP, he reasoned, is what gives SGC’s collaborative projects the agility to go from molecule to data to publication in less time than it would take to complete the IP paperwork required for a traditional collaboration. In my opinion, the SGC also serves as an excellent illustration of the transformative power of a concerted collective of leaders.
Along with the philosophical and technical considerations of precompetitive research collaboration, defined as work that increases overall knowledge and wouldn’t provide a competitive advantage to any participant, there are also legal considerations. For example, as Tania Bubela of the University of Alberta explained, there are IP issues and barriers for the sharing of data and large-scale bioresources. There are institutional impediments, she added, particularly institutional patenting of research tools, broad-based methods patents, and onerous material transfer agreements. Patenting is inversely correlated with academic collaboration, she noted.
During the final session, there was a consensus that benefits could be gained from:
• White papers, a Frontiers meeting, and a communication strategy that joins thinking between the United States, United Kingdom, Asia, and the rest of Europe
• Shining examples built using new integrative genomic models of disease
• Commons repositories such as for noncompetitive targets, and failed Phase II compounds
• A 2020 challenge around a disease-to-therapy project that might exist within an IP-free zone
• Adoption of standard legal tools to lower the barriers to sharing of materials and data
It feels as if we are getting close to walking away from relying on a handful of entities being the sole developers of drugs. Organizations such as The Wellcome Trust have a key role to play in broadening the routes by which we—as patients and scientists—help impact all diseases. This will require fundamental institutional changes in who works how, with whom, and when.
Stephen Friend, now president of Sage Bionetworks (a nonprofit), spent the last 8 years running Molecular Profiling and Cancer Research at Merck & Co. Inc.