First, the RFA that TIGM responded to from the NIH specifically requested conventional over conditional clones. If you read the RFA, and I trust that you have since you specifically commented on this point, then you would see that the request was for a straight (conventional) knockout with a reporter in C57BL/6 ES cells. That is it. While the scientific community, of which I am a part, would have preferred that NIH invest in a conditional asset, that is NOT what the RFA requested. So TIGM was absolutely responding to the RFA.Vision 1920 blogged about the RFA here. Our tame faculty member says Finnell is correct that the RFA expressed concerns about high-throughput generation of conditional knockouts. However,
- Finnell does not address the requirement in the RFA for a plan to go after at least 25% of the genes missed by prior gene trapping approaches. TIGM is still based on gene traps, while the RFA emphasized the need for a targeted approach.
- Meagher's comment about conditional knockouts may not be relevant to what happened during the KOMP grant process, but it is relevant to the likely demand for TIGM knockout mice going forward
The fact that TIGM barely existed (I was the only TIGM member, devoting 25% of my effort at the time of the submission), we had no track record which, as you know from submitting grant proposals to NIH, weighs heavily upon the reviewers. Yes, we could pretty much guarantee a successful outcome to Francis Collins, as we were in the position to put up the 273,000 ES cell clones from the 129 OmniBank 1 gene‐trap library, up to 3000 already made Lexicon knockout mice, and the 350,000 C57 ES cell clone gene‐trap library that was under construction. But we lacked credibility as we had no reputation for shipping products to end users...Who could have predicted that a lack of a track record was an issue when the prospect of the KOMP grant was used as the basis for its original TIGM business plan?
Finnell also suggests shenanigans:
One could speculate endlessly about the other reasons why TIGM did not get the KOMP RFA (see the attached Science article), but that is really only self‐serving and no good can come of it at this point in time. Suffice to say that the review and its outcome were highly irregular, prompting Francis Collins and his senior KOMP staff to fly to Houston to try to explain to us in person why we were not funded. I don’t know about you, but when my NIH applications are not funded, my program officer doesn’t spontaneously call me and jump on a plane to talk to me in person about it. Quite the contrary, they are usually hard to find. This was unusual. That is all I can really say.If Collins went forward with KOMP funding to TIGM rivals despite a "highly irregular" review, perhaps he should be asked about it when he comes up for confirmation as NIH director.