I posted a link to a NYTimes article earlier this week that discussed a NASA report that predicted a failure due to collision with orbital debris. This report can be read in full courtesy of the National Academy of Sciences.
But here's the zinger: I just happen to share 23 chromosomes with one of the authors of the report. One of his contributions to the paper was a section that called for a way to perform in-flight repairs to components of the orbiter outside the crew compartments. The report notes that NASA had considered solutions for this, but had refused to fly the Shuttle with the necessary equipment to perform these repairs mostly because of "confidence that the [insulation tiles] would perform effectively".
This report also discusses the weakness of the wing leading edges and considers significant damage to critical on reentry, noting that a hole larger than 0.63cm (about 1/4") in the insulation meets this criteria. In summary, the report estimates a one in 84 chance of failure due to orbital debris and meteorites.
The Columbia disaster was the 107th launch of the Shuttle.