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Reengineering Translational Science

I am reposting a blog post from Sean Ekins regarding a recent communication we submitted….

“Recently, Francis Collins published a commentary in Science Translational Medicine entitled “reengineering translational science: the time is right”. and I would encourage people to read it and tell me what you think, for no other reason than this is one of the most accomplished scientists of our time. Antony Williams and I wanted to respond to some of Dr. Collins’ comments. The journal has the ability to post an E-letter so we took this route and so far it has not been published. For that matter it seems no one has responded. Does this mean that everyone agrees with his comments? If there is truly to be a dialog on the topic surely this journal should publish E-letters it receives.

Here are our comments which were submitted as an E-letter but not as yet published- we are restricted to 400 words:

Reengineering Translational Science: Is the NIH the right place for this?

Sean Ekins(1) and Antony J. Williams(2)

1 Collaborations in Chemistry, 5616 Hilltop Needmore Road, Fuquay-Varina, NC27526, U.S.A.

2 Royal Society of Chemistry, 904 Tamaras Circle, Wake Forest, NC27587, U.S.A.

We read with interest Dr. Collins’ Commentary on Reengineering Translational Science: The time is Right. We agree that there is an urgent need to revamp the way that drugs are developed, bring them to market faster and provide incentives to generate treatments for neglected and rare diseases. We question however whether the NIH as it stands can adequately pursue these goals when an entire industry is struggling with the same challenges. We wish to raise several issues that this article promotes. Many of the techniques described will not dramatically impact the process alone and be any more successful than combinatorial chemistry and high throughput screening were touted to be. Why would we want the tax payer to follow the same route as big pharma? Surely the NIH is funded to a large extent to take more exploratory directions (1, 2), and to come up with next generation discoveries and approaches, not simply apply existing technologies and hope to be more successful? It would also be more convincing if there were co-authors on the paper from outside the NIH lauding the value of repeating approaches already in use. Collaboration is important and this commentary did not demonstrate how collaborations (with academic labs or with the pharmaceutical industry) would be facilitated and data shared.

Finally, we are also concerned that an initiative described in this paper, namely the recently released NPC browser (“a comprehensive resource of clinically approved drugs to enable repurposing and chemical genomics”) from the NIH Chemical Genomics Center (NCGC) (3) may not have set the case too soundly (3). Within 24 hrs of release our analysis of the molecules in the database showed that fundamental errors were present, with valency issues, charge imbalances and stereochemistry, (4-6) to name just a few. It took over a month for NCGC to acknowledge these errors and they will still be fixing them for the foreseeable future (7). This software application and content was released in a very raw state with extremely poor quality data (7-9). While software development may appear easy and fast to do, what is required to produce the best solution is the right ideas, the right people and the right tools. The parallel with NCATS is clear. While the NIH is staffed with many clever people there are many more willing to collaborate with fresh ideas outside (10) . We define ourselves as two such willing participants.

References

1.         S. Ekins, A.J. Williams, M.D. Krasowski, J.S. Freundlich. In silico repositioning of approved drugs for rare and neglected diseases. Drug Disc Today. 16, 298-310 (2011).

2.         S. Ekins, A.J. Williams. Finding promiscuous old drugs for new uses. Pharm Res. 28, 1786-1791 (2011).

3.         R. Huang, N. Southall, Y. Wang, A. Yasgar, P. Shinn, A. Jadhav, D.T. Nguyen, C.P. Austin. The NCGC Pharmaceutical Collection: A Comprehensive Resource of Clinically Approved Drugs Enabling Repurposing and Chemical Genomics. Science translational medicine. 3, 80ps16 (2011).

4.         A.J. Williams. Reviewing Data Quality in the NCGC Pharmaceutical Collection Browser. http://www.chemconnector.com/2011/04/28/reviewing-data-quality-in-the-ncgc-pharmaceutical-collection-browser/.

5.         A.J. Williams. What is a Drug? Data Quality in the NCGC Pharmaceutical Collection Browser Part 2. http://www.chemconnector.com/2011/05/02/what-is-a-drug-data-quality-in-the-ncgc-pharmaceutical-collection-browser-part-2/.

6.         A.J. Williams. Support for Common Compounds in the NPC Browser. Data Quality Part 3. http://www.chemconnector.com/2011/05/02/support-for-common-compounds-in-the-npc-browser-data-quality-part-3/.

7.         A.J. Williams. Unreported results. Manuscript in preparation (2011).

8.         A.J. Williams, S. Ekins. A quality alert for chemistry databases. Drug Disc Today. In Press,  (2011).

9.         A.J. Williams. Rabbits, Potatoes and other Vegetables in the NCGC Database. http://www.chemconnector.com/2011/07/19/rabbits-potatoes-and-other-vegetables-in-the-ncgc-database/.

10.       S. Ekins, A.J. Williams. Reaching out to collaborators: crowdsourcing for pharmaceutical research. Pharm Res. 27, 393-395 (2010).

Conflicts of Interest

AJW is employed by the Royal Society of Chemistry which owns ChemSpider and associated technologies.

SE Consults for Collaborative Drug Discovery

 
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Posted by on July 25, 2011 in General Communications

 

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