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Shelley des Etages says less alchemy than inspiration, developing new medications requires systematic problem solving.

Topic: Finding new treatments.

Shelley des Etages: The first step is, we can start two ways, we can start with a disease.  Let's say we want to think about transplant rejection.  You try to think about what's happening in the body, in your cells at the molecular level, that's causing your body to say, "Yes, I need this organ, but I did not make it.  It's not mine, and I want this foreign material out of here."  And you think about what are the proteins that are at work?  Why are they doing that?  And are there any proteins whose functions I can modify or change such that they don't work to reject this organ.  So you start brainstorming.  You're coming up with ideas, what might be happening.  You're looking at what's known and trying to think about what are the points at which I can go to try to alter this to try to figure it out?  That's where the basic process actually begins.

Question: How do you identify those points?

Shelley des Etages: I'll stay with the transplant rejection example.  This was an idea that one of our researchers in immunology came up with.  Now, he saw a paper published about SCID.  SCID is an acronym for Severe Combined Immunodeficiency Syndrome.  Most people know it as "Bubble Boy Disease"; two bubble boy movies, John Travolta in the seventies and the more recent one.  And basically what's happening is that the immune system is not functioning.  And there was a paper published about mice that had the SCID disease, and he had the idea if your immune system is what's at work when you're rejecting an organ, and you have a disease where the immune system is not working.  And we found out, because in this paper they identified a particular protein that wasn't functioning properly in those animals.  So based on just what we call the phenotype, the symptoms of that disease, they were able to make a link between that protein and that function.  So he thought, "Can we alter that protein's function in patients who might be receiving transplants to see if we can help them keep their transplanted organs healthier and for a longer period of time.  So that's one way, an example where that came about.  It's the combination of finding out what's known and thinking about what's known in new ways.  There's an element of creativity.  You go, "What if?"  And what comes after is the light bulb.  Like, what if we can do that?

Recorded on: 06/25/2008