Plenge Lab
Date posted: August 16, 2014 | Author: | No Comments »

Categories: Drug Discovery Human Genetics

Question: What can we learn from Sputnik (see here), DARPA (see here) and disruptive innovation (see here) to invent new drugs?

Answer: The best way to prevent surprise is to create it. And if you don’t create the surprise, someone else will. (This is a cryptic answer, I know, but I hope the answer will become clearer by the end of the blog.)

My previous blogs highlighted (1) the pressing need to match an innovative R&D culture with an innovative R&D strategy rooted in basic science (see here), and (2) the importance of phenotype in target ID and validation (TIDVAL) efforts anchored in human genetics (see here).  Now, I want to flesh out more of the scientific strategy around human genetics – with a focus on single genes and single drug targets.

To start, I want to frame the problem using an unexpected source of innovation: the US government.

There is an interesting article in Harvard Business Review on DARPA and “Pasteur’s Quadrant” – use-inspired, basic-science research (see here and here).  This theme is critically important for drug discovery, as the biopharma industry has a profound responsibility to identify new targets with increased probability-of-success and unambiguous promotable advantage (see here).   …

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Date posted: May 17, 2013 | Author: | No Comments »

Categories: Drug Discovery Human Genetics

After all, baseball is a metaphor for life.

Bill James developed the “Keltner list” to serve as a series of gut-check questions to test a baseball player’s suitability for the Hall of Fame (see here).  The list comprises 15 questions designed to aid in the thought process, where each question is designed to be relatively easy to answer.  As a subjective method, the Keltner list is not designed to yield an undeniable answer about a player’s worthiness.  Says James: “You can’t total up the score and say that everybody who is at eight or above should be in, or anything like that.”

The Keltner list concept has been adapted to address to serve as a common sense assessment of non-baseball events, including political scandals (see here) and rock bands like Devo (see here).

Here, I try out this concept for genetics and drug discovery.  That is, I ask a series of question designed to answer the question: “Would a drug against the product of this gene be a useful drug?”  I use PCSK9 as one of the best examples (see brief PCSK9 slide deck here).  I also used in on our recent study of CD40 in rheumatoid arthritis, published in PLoS Genetics (see here).…

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