Can open science and crowd-sourcing make the drug discovery process advance?

The interplay between the public world of Universities, or research institutes, and the private side of pharmaceutical industries and corporations is an important but also delicate aspect of medical research.

The drug discovery process will be presented as example, where bridging private and public sectors could bring new vigor to this research field.

The development of a new drug is a rather long and expensive process regulated by government’s agencies. These assure that all the requirements in terms of safety and efficacy are met by the novel medicament. Europe and United States together make half of the global market of pharmaceuticals, but they also have more complex and strict regulations to follow. [1]

The procedure that leads to the launch of a new drug on the market can be nicely pictured as a big sieve (Figure 1): from a huge number of candidate compounds the best one is selected through many different phases where tests are performed to rule out the molecules that fail either safety or efficacy conditions.

In the last decade, the amount of money invested in drug development has grown exponentially, reaching the average of 2.6 billion $ per drug [2]; this increased funding of the Research & Development in pharmaceuticals is not reflected in the number of approved new drugs that can enter the market. [3]

This has been interpreted as a sign of crisis in the system of drug discovery and development in the pharmaceutical business. The discovery part of such process has been deeply influenced by the advances introduced in basic research, where new targets for the treatment of a diseases are identified. Novel compounds are then screened to understand their interaction with these targets, being it a reduction of the symptoms or a complete withdrawal of the condition.

This part of the process is also carried in public entities, such as Universities and Research Institutes, where the diffusion of the “omics” (i.e. genomics, metabolomics, etc.) disciplines produce large amounts of new information. These results cannot be processed fast enough in the development phase that follows. The overall process can take up to 15 years or more. [2] This is problematic since it might happen that while a drug is being developed for a specific target, a more suitable one is discovered in the meantime.

This issue has been tackled with a new strategy called “quick win, fast fail” that would substitute the traditional process. This innovative scheme is based on the probability of the new compound to pass the clinical trials, which are the most expensive, long and risky steps of the whole process. [4]

The probability of success is considered inside the so called 5R framework:

– Right target

– Right tissue

– Right safety

– Right patients

– Right commercial potential. [5]

The problems in the R&D department of pharmaceutical companies are also due to the uttermost competition, which prevents the flow of information and innovative approaches; this leaves the industrial part of the process under-developed with respect to the pre-clinical part, carried as basic research in universities or research institutes.

The crisis in the production of new drugs has pushed industries to open towards external inputs from academia and to adopt part of its philosophy.

It is difficult to conceive the combination of commercial competition with open science, but there are already a few nice examples reported of this new trend.

The concept of open science in medical research will be presented in three main categories: goal driven collaborations, open data and crowd-sourcing. [6]

Collaboration between private and public entities, with an established common goal is becoming more common nowadays: our ITN framework is a good example having many non-academic partners included in the research projects. Such agreements aim to discover new medicaments; the drug discovery stage is usually carried by public entities, which then pass the new findings to the non-academic partner. The private entity though can also lead the direction of the basic research towards more profitable results.

Such collaborations also promote research towards neglected disorders: in such cases the project is driven by the fundamental research spirit since the economic return would be very small. This applies to diseases that affect only the developing part of the world or extremely rare conditions.

This is the case of the Medicine for Malaria Venture project, which is almost open source and falls inside the category of Public-Private Partnership for Health initiatives. The structure of such “open source” projects might be extended in the future to the development of common drugs as response to the crisis that is affecting the R&D in pharmaceutic companies. [7]

The idea of open databases is already largely employed in the scientific community: the most known is the Protein Data Bank (http://www.rcsb.org/pdb/home/home.do), where crystallographic structures of proteins are deposited.

This practice, standard in basic science, is slowly moving to more advanced phases of drug development, like the clinical trials phase. An open database that collects the results of these trials, not only would help improving the methods adopted or avoid unnecessary repetitions, but it would also be more ethical towards the volunteers. They usually are informed about the risks they are exposed to, participating in these trials, but they are not informed about the overall results of such tests. [8]

Crowd sourcing is not a new concept and nowadays is becoming an extremely popular tool to seek for new ideas (design especially); it is in fact easy to reach a huge number of people around the world with a minimum effort posting the query online.

The advantage that crowd sourcing offers is the large amount of people that might actively help completing the submitted task, without restriction in age, gender, nationality or instruction. There are different tasks that are suitable for crowd-sourcing: problem solving, data processing, monitoring and surveying. [9]

Considering the pharmaceutical field, one of the most important pharmaceutical companies, Eli Lilly, has indeed founded the web platform InnoCentive (https://www.innocentive.com), where scientific challenges are published. These challenges are open and anybody can prove himself trying to solve them, sometimes with remarkable rewards offered in exchange.

In InnoCentive the scientific issue is usually complex but there are other crowd sourcing experiences where the real problem is hidden inside a puzzle game for example.

Here the player, solving the challenge, is actually trying to solve the tertiary structure of a protein (Fold.it) [9] or the sequence of the human genome (Phylo). [10]

The players have sometimes outperformed algorithms specifically developed to solve such problems (like the Rosetta algorithm that employs Monte Carlo search in the conformational space of proteins). So, if you are a good puzzle solver, challenge yourself helping medical research!

Martina De Vetta

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References

[1] Kashyap, U Nitin, Vishal Gupta, and H V Raghunandan. “Comparison of Drug Approval Process in United States & Europe.”

[2] Pharma -2016 Profile (http://phrma-docs.phrma.org/sites/default/files/pdf/biopharmaceutical-industry-profile.pdf)

[3] Kaitin, KI. 2010. “Deconstructing the Drug Development Process: The New Face of Innovation.” Clin Pharmacol Ther. 87(3): 356–61.

[4] Paul, Steven M. et al. 2010. “How to Improve R&D Productivity: The Pharmaceutical Industry’s Grand Challenge.” Nature Reviews Drug Discovery.

[5] Cook, David et al. 2014. “Lessons Learned from the Fate of AstraZeneca’s Drug Pipeline: A Five-Dimensional Framework.” Nature Reviews Drug Discovery.

[6] Shaw, Daniel L. 2017. “Is Open Science the Future of Drug Development?” YALE JOURNAL OF BIOLOGY AND MEDICINE 90: 147–51.

[7] Munos, Bernard. 2006. “Can open-source R&D reinvigorate drug research?” Nature Reviews Drug Discovery.

[8] Tse, Tony, Rebecca J. Williams, and Deborah A. Zarin. 2009. “Reporting ‘basic Results’ in ClinicalTrials.gov.” Chest 136(1): 295–303.

[9] Ranard, Benjamin L. et al. 2014. “Crowdsourcing–Harnessing the Masses to Advance Health and Medicine, a Systematic Review.” Journal of general internal medicine.

[10] Fold.it website (https://fold.it/portal/)

[11] Phylo website (http://phylo.cs.mcgill.ca/)

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