I am in a somewhat joint lab that has two PIs. One PI (call him PI A) runs the day to day type things, and is present at the lab meetings, etc. The other PI (PI B) runs the biggest lab at my university (which is a top 10 research university), with over 100 people, and according to almost all of my current professors, will win a Nobel prize within the next 10 years. I work directly under a postdoc who will draft the main portion of the letter, since he knows me the best, and what I've done. Now, I can either have PI A or PI B be the signer of the letter. If PI B does it, there'll be a huge huge name signing the letter, which seems to be the obvious choice. Except that PI A will probably have more time to craft it well, and he is a very suave-type guy that will probably be able to "sell" me very well (he is known for these kind of things). Also, will med. schools see the letter signed by PI B and know that he was not really the main writer since he is so famous that there's no way he knew me well enough to write all that stuff?