Guest post: Opening up drug discovery for neglected diseases

Chemsitry and chemical biology associate professor Michael Pollastri uses a drug repurposing approach to identify new treatments for neglected tropical diseases. Photo by Brooks Canaday.

Chem­sitry and chem­ical biology asso­ciate pro­fessor Michael Pol­lastri uses a drug repur­posing approach to iden­tify new treat­ments for neglected trop­ical dis­eases. Photo by Brooks Canaday.

This post was written by asso­ciate pro­fessor Michael Pol­lastri.

Neglected trop­ical dis­eases are a col­lec­tion of infec­tious dis­eases that pri­marily affect the poor in devel­oping nations, and many have extremely subpar treat­ments. Since the patients can’t pay for expen­sive new drugs, the for-​​profit phar­ma­ceu­tical industry cannot devote their research and devel­op­ment resources. I worked in the industry for a number of years, and decided to develop an inde­pen­dent aca­d­emic oper­a­tion that could focus on these dis­eases. Indeed, an increasing number of research groups in the aca­d­emic and non-​​profit envi­ron­ment are putting their focus on NTD drug discovery.

I know from my expe­ri­ence working in the industry that the typ­ical prac­tice is to keep research inter­nal­ized and secret. This is so that drug com­pa­nies can keep a com­pet­i­tive advan­tage, file patents, recoup research costs and even­tu­ally gen­erate profits. This prac­tice, because of its long-​​ingrained nature in industry, becomes a habit, and as a result is often also applied even to NTD drug dis­covery in the non-​​profit envi­ron­ment. But I recently started asking whether this really makes sense. Does keeping trade secrets really ben­efit anyone when there are min­imal profits to be made? We have expe­ri­enced first-​​hand that these secre­tive prac­tices inevitably can lead to dupli­ca­tion of effort. For example, after spending sev­eral months devel­oping a project to dis­cover new malaria drugs, we dis­cov­ered (via casual con­ver­sa­tion) that another research team had done exactly the same thing, and decided that the results that they were get­ting were not worth pur­suing fur­ther. Had we known that this other team was working in the same space, we would have engaged with them to divide and con­quer the work, and shared and com­pared our plans and results with them.

Unfor­tu­nately, this sit­u­a­tion is common, and is truly uncon­scionable in a resource-​​poor research envi­ron­ment like NTD drug dis­covery. There is simply no money to waste.

How­ever, it requires a totally dif­ferent mindset to per­form research out in the open, where new mol­e­cules are syn­the­sized and tested for their utility as drugs, and all the data is shared in the public domain. Taking a page from the open source model of soft­ware devel­op­ment (think Linux, or Firefox…), more groups are starting to look at open models of col­lab­o­ra­tion. One such group is the Open Source Drug Discovery-​​Malaria (OSDD-​​Malaria), where a multi­na­tional team of col­lab­o­ra­tors agree to share the work­load of syn­thesis, testing, and mod­eling, with the agree­ment that all data will be posted to the public as the data is gen­er­ated, in real time. Anyone who wishes to par­tic­i­pate can dial into reg­ular project meeting tele­con­fer­ences, and can con­tribute research efforts and exper­tise. It is an exciting model that is quickly gaining trac­tion, and is sure to change the ways in which we think about how to do research in NTDs.

How­ever, not everyone is totally com­fort­able with the fully open model of sharing, espe­cially those of us who had for­ma­tive expe­ri­ences in pharma. I won­dered whether there was another way to reduce redun­dancy and improve infor­ma­tion sharing, and have started estab­lishing an alter­na­tive. In con­trast to the fully open model (where all data is shared with everyone, every­where), we are forming a con­sor­tium of par­tic­i­pants who agree to openly share data amongst each other. The con­sor­tium will be open to anyone who wishes to par­tic­i­pate, pro­vided that they agree to fully trans­parent data sharing within the con­sor­tium, and agree to keep each other’s data pri­vate. In this way, research teams can share infor­ma­tion and results with people they know and trust, and keep some mod­icum of con­trol over their own data. This will help reduce dupli­ca­tion of efforts, and will pro­vide a mech­a­nism for par­tic­i­pants to easily release their data to the gen­eral public when they are ready to do so, expanding the value of their research results far beyond our consortium!

What next? We are cur­rently recruiting research groups working on NTD drug dis­covery that would like to try out our “Hybrid Open” dis­covery model for research. Our Lab­o­ra­tory for NTD Drug Dis­covery will pre-​​populate the data­base with our own results in African sleeping sick­ness, malaria, leish­ma­ni­asis, and Chagas dis­ease, and we invite other research teams like ours to participate.

In this way we hope to both make an impact on dis­cov­ering drugs for these NTDs, and also (per­haps more impor­tantly) influ­ence the ways in which such research is done.

The Lab­o­ra­tory for NTD Drug Dis­covery is a com­po­nent of the North­eastern Uni­ver­sity Inte­grated Ini­tia­tive in Global Health. For more infor­ma­tion about this ini­tia­tive and how you can get involved, see www​.north​eastern​.edu/​g​l​o​b​a​l​h​e​a​lth.