Not all R01s are created equal. When should you let a project go?

The second R01 is done and it was very different from the first one.

The first one was very hard to write, in the sense that the choice of what was going to be in it, what the flow of the experiments was going to be, and how to properly balance the aims was difficult. I took into account opinions from many readers, mostly on the Specific Aims, and worked it and reworked it for almost four months. Some thoughts here. It was discussed, scored poorly. Comments from everyone were very positive about the structure of the grant, but not the writing and the feasibility. My lab is working on all feasibility issues and the proposal will go in again as soon as we are ready.

The second one was not too hard to write, the flow is simple and logical, because the flow of that project has always been simple. However, putting it all together was a nightmare that took months and months of coaxing collaborators to provide preliminary data and information, getting permissions and accesses to patients, and just coordinating multiple moving pieces. It was the first time I had to delegate a part of the writing to other people. The structure was laid out as early as February of last year, but by October we were still not there. Since most of the writing was done over the holiday break and at the beginning of the semester nobody apart from my lab and my collaborators read it, so I had no external feedback. I based my tone and amount of detail in the approach based on the comments I had for R01 #1, but this will go to a different institute and a different study section. To a study section I don't know and with whom nobody I know has anything to do. It's like aiming a dart in the dark. An enormous amount of work had been done to polish and aim the first grant to a specific study section, but then the Center for Scientific Review decided to change things up completely and put it elsewhere. I thought, why bother? Make it as clear as possible for a variety of scientists, put as much detail as possible, as much big picture as possible, and hope this little Frankenstein finds someone to love him....if it doesn't, I'm not sure I can do this again. Which brings me to the question in the title. When should you let a project go?

I started the project for R01 #1 almost 10 years ago. It took us 2 years to just figure out where the darn protein was. My postdoctoral advisor told me to drop it at 6 month intervals, I replied I had a hunch. Halfway through, I decided to drop it because I hated the darn protein with all my heart, my K99 was awarded and I was bound to it for 5 more years. The first paper was published after 8 years! The second paper after 9.5. We have 3 papers in the pipeline for year 10 and my current data is the most beautiful data I have ever seen in my entire life. It was like this nasty poisonous caterpillar finally turned into a stunning ethereal butterfly. AFTER 10 YEARS!

Project for R01 #2 started around the same time and yielded a paper/year very consistently and several grants, but recently it has come to a screeching halt. I cannot find the right people to staff it, I cannot control it, and I am keeping it going out of sheer willpower, as I generate 90% of the data myself and coordinate all the parts. Putting together this grant was utterly exhausting and as my career advances I cannot just will it into existence like a golem! So, part of me wonders whether I should let it go....forget the years of networking, the emotional and financial expense.

Maybe, it's just the let down following R01 submission, but it is a tricky question to answer and I believe that it's a question many new investigators (probably, investigators period) face all the time. Will this pay off or am I banging my head against a rock wall? How do I know I am not driving my lab into a ditch? Ah, fun times! Maybe one day I'll write a book like this one...