Plenge Lab
Date posted: July 28, 2016 | Author: | No Comments »

Categories: Drug Discovery

I know it may seem strange that I am commenting on my own commentary. While writing the Science Translational Medicine (STM) article (here, here), I wanted to focus on a clear vision for improving R&D productivity via integrating human biology, therapeutic modulation, pharmacodynamics biomarkers, and proof-of-concept clinical trials (see Figure 1 of the manuscript, also above). Too often, these four key concepts get lost amongst the many steps in drug development.  I won’t revisit these concepts here, as I encourage you to read the article itself.

However, there is much more to R&D productivity than just these four concepts, and the purpose of this blog is to broaden the perspective piece a bit.

[Disclaimer: I am a Merck/MSD employee. The opinions I am expressing are my own and do not necessarily represent the position of my employer.]

1. Drug discovery should always start with the patient. Every drug discovery journey must begin with a clear definition of the unmet medical need. As a former practicing rheumatologist, I always try to keep in mind the questions that a patient would ask me: “Why did I develop this disease?” “Will I respond to this medication?” “What is my prognosis?” “Will I ever be cured?“

These questions are also important in the context of the translational medicine model proposed in the STM article.…

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Date posted: December 8, 2015 | Author: | No Comments »

Categories: Uncategorized

My daughter, on a team of fifth grade all-girls from Wellesley MA, recently competed in a First Lego League (FLL) robotics competition. My wife and I served as coaches, which was a demanding but thoroughly rewarding experience. This year’s team got me thinking about design principles for complex systems, as the goal of the annual Challenge is to build from simple (individual Lego pieces) to complex (navigating a robot built from those Lego pieces around a field with missions created from the same Lego pieces) with efficiency and precision.

For those not familiar with FLL, a video link to our team’s performance can be found here. A graphic from Google trends (link here) and the number of views on YouTube (link here) gives you a sense of the magnitude of participation across the world. Overall, FLL is a wonderful example of STEM (Science, Technology, Engineering, Math) in action. The FLL event also fits very well with evolving views on our educational system, as described in a new documentary “Most Likely To Succeed”.

[Disclaimer: I am a Merck/MSD employee. The opinions I am expressing are my own and do not necessarily represent the position of my employer.

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Date posted: October 9, 2015 | Author: | No Comments »

Categories: Drug Discovery

It is not uncommon that I am asked the following question during public talks: “Does innovation happen in large pharmaceutical companies?” Sometimes, the question is just a critical comment, disguised as a question: “Large pharma does not innovate, they just conduct clinical trials and drive up the cost of drugs. Right?” Other times the questions are more thoughtful: “As an academic, I don’t see what happens in industry. Can you describe examples of innovation driven out of large pharma?

[Disclaimer: I am a Merck/MSD employee. The opinions I am expressing are my own and do not necessarily represent the position of my employer.]

At the risk of sounding defensive, here are some answers to the “pharma innovation” question. I know there are many more, and I invite readers to share their examples. Admittedly, the examples are biased towards examples at Merck, but that is just because I know these examples better.

First, the past couple of weeks have been particularly good for industry scientists. These recent examples provide objective evidence to answer the pharma innovation question.

(a) 2015 Nobel Prize in Physiology or Medicine. Former Merck scientist Dr. William Campbell was awarded the Nobel Prize for the discovery of an antiparasitic agent used to treat river blindness in places like Latin America, Africa and Yemen.…

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Date posted: August 8, 2014 | Author: | No Comments »

Categories: Drug Discovery Human Genetics Uncategorized

phe·no·type  n.

1.The observable physical or biochemical characteristics of an organism, as determined by both genetic makeup and environmental influences.

2. An individual or group of organisms exhibiting a particular phenotype.


There are many different phenotypes: strength in the face of adversity (see here); self-reflection in a time of uncertainty (see here); and creativity amidst a sea of sameness (see here).

Phenotypes also refer to disease states such as risk of disease, response to therapy, a quantitative biomarker of medical relevance, or a physical trait such as height (as in the figure above).

For drug discovery, I have put forth the premise that human genetics is a useful tool to uncover novel drug targets that are likely to have unambiguous promotable advantage (see here).  The starting point in a genetic study is to pick the right phenotype, one that is an appropriate surrogate for drug efficacy.

And phenotype matters!

Two illustrative examples are the autoimmune diseases type 1 diabetes and rheumatoid arthritis. In type 1 diabetes the immune system destroys the pancreas, thereby preventing insulin secretion and the control of blood glucose levels.

Human genetics has identified many alleles associated with the risk of type 1 diabetes, nearly all of which act on the immune system (see here). …

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