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I had a pub from my first lab but didn't ask the PI for a letter and it worked out fine for me. Granted, I didn't list that as MME but I don't think it would be a big deal.

Understand that adcoms are composed of people too and they understand that there could be a million reasons why you didn't have a letter from that PI that they could never be sure of. It would be silly to think they would automatically assume there is any bad blood. And that's assuming they even give it that level of thought to begin with, which I highly doubt.
 
Why not ask your med student to write one (if they accept of course) and have the PI sign it? I also didn't know my PI very well, and at first just wanted my postdoc to write a LOR for me. He told me that the letter would mean a lot more coming from my PI and offered to write it and have the PI sign it off or make any edits if he wished.
 
Is there another researcher you worked with? I had the same situation where I had a publication but the PI didn't write an LOR for me (he actually passed away) and I was able to get another collaborator who didn't know me as well, but knew enough about my work to write a letter in his place.
 
@LizzyM @Goro @gyngyn

Would appreciate some Adcom insight. At your schools, would you not invite an applicant to an interview because of a lack of a research lor? Let's assume they have 3 strong professor LORs.
DO schools don't care about research.

The PI LOR seems to be most need for MD/PhD, and for the research wh......um, sex workers.
 
It could be flagged by a pre-interview reader and the interviewer could be asked to ask about it. With a borderline-for-interview candidate it could be one of half dozen reasons not to offer an interview. In a borderline-admit/waitlist applicant, it could be a negative that would be brought up even if one had the minimum number of letters... why no PI letter? Did the person have a problem with the PI? Does that tell us something about the candidate's ability to get along with others? If there was no paper and no letter but a long tenure in the lab, then it might tell us that the candidate was there but didn't work hard enough to have something to show for the time spent in the lab.... It shouldn't be a big deal but as Goro says, the research wh0re schools will make a big deal out of something that the other schools will ignore.
 
I only had one pub officially published at the time of application (first lab in undergrad). I didn't ask that PI for a rec letter (even though he was more than happy to write one) because it had been years since I worked with him, and I had a LOR from my most recent PI.

In a vacuum, I don't think it's a huge issue imo. If that's the biggest "red flag" on your app, then your app is fine. I was never asked why I didn't have a LOR from my first PI that I published under. If I had been asked, I would have just said that I wanted to get rec letters that were from people who knew me more recently. As long as your PI doesn't trash you if a school calls them to verify information (which it doesn't sound like he would), you're good to go.