What is the hardest puzzle you have ever come across?

Question: What is the hardest puzzle you have ever come across?
- Keywords:
  hardest,
  puzzle
Asked by 242medb42 to Samantha on 6 Mar 2015.
- Samantha Terry answered on 6 Mar 2015:
  
  The hardest science puzzle I have had to answer so far is determining the mechanism of how chromosomes get damaged after radiation. I spent 3 years working on this!

Question: What is the hardest puzzle you have ever come across?