Saturday, August 1, 2009

Misconceptions about TIGM

The CPI has posted an email (pdf) from Rick Finnell giving his take on the TIGM story. The email was in response to comments made during Brett Giroir's open forum by Prof. Mary Meagher. Excerpts:
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
Vision 1920 points out, however, that low demand is a good thing, since Giroir said TIGM loses money on producing mice from ES cells.
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.


  1. It's the biology (and expertise), stupid!

    The last person on earth one would want to rely on for an accurate history of a failed venture is the head or CEO of a front organization, particularly one that has survived an audit concluding clear mismanagement. Would one ask the CEO of Lexicon about Lexicon's role, the CEO of Xoma, the CEO of Granada for their history and role? One would want to ask the insiders, the knowledgeables who were shilled, and then cast aside and ignored.

    Granted the peer review system is rife with human shortcomings and bias, despite the whining and excuse making, the fatal flaw in TIGM as it remains today was and is weak biology and expertise, Vision 1920 in respect to stem cells and mouse genetics. The knowledgeable scientific community were well aware of the declining credibility and reliability of Lexicon as the original solid scientific expertise drifted away and was replaced by mediocrity and hype. This was well before conception of TIGM. With the skepticism of an entire scientific community that comprises the international peer review system concerning Lexicon (proven to be true) coupled with novice and fronted expertise associated with A&M related to the stated mission, it defies credibility to hope to sway the entire scientific peer review system. It is precisely this vetting that is missing at the state level in respect to distribution of taxpayers money.

    TIGM was conceived behind closed doors with token knowledgeable faculty shills invited in hopes of using their names for respect to a few sessions before being ignored and cast aside as continues today both in TIGM, but in proposals for NCTM and current ventures. It was open knowledge that secrecy was of the essence to prevent UT, Baylor and other Texas institutions from opportunity to compete.

    And to some extent the money, stupid!

    The only reason most faculty members will ally with weak biology and questionable expertise is, yes, for the money and potential to draw off support without accountability to supplement their own often mediocre program and off the mission of the stated purpose.

    The way to make a venture successful is if participants', in this case faculty's, livelihood and careers are dependent on it, not a by-the-way part time association where some trickle down is hoped for. TIGM was a hobby by-the-way venture, a research group supplement, beginning with the CEO, not a life and career commitment of those bearing the name TIGM faculty or scientist.

    At this juncture, first it is time from CEO to faculty associate listing to scrutinize the NCTM proposal and the individuals biology and expertise in regard to stated mission. Second, it is time to move through the faculty associate listing one by one and obtain their level of contractual commitment of livelihood, career particularly salary source and tenure and promotion evaluation, to the NCTM. If there is not this commitment, then the venture is doomed to failure as a front organization staffed by part time faculty who are only supplementing their often mediocre research program. When the venture fails to the tune of millions, the participants who took their temporary money and ran will simply fold back into their secure primary appointments of salary and tenure.

    BTW, why is the CEO of TIGM at the height of its scrutiny and need for leadership and engagement with system and faculty and plotting a path for its future out of the country? Is it because it is a hobby?

    Harvey Potbanger

  2. Dear Harvey,
    “…front organization staffed by part time faculty who are only supplementing their often mediocre research program”
    Can you be a little more specific? I was a visiting Professor at TIGM for 3 months early in 2009, and wonder exactly who is the subject of your bile? “their” implies they, ie more than one senior researcher. Tut, tut. Don’t be shy, Harvey, you are already hiding behind a childish moniker. Perhaps too many Wallbangers with the Potbanger.

    “BTW, why is the CEO of TIGM at the height of its scrutiny and need for leadership and engagement with system and faculty and plotting a path for its future out of the country? Is it because it is a hobby?”
    Now we are getting down to it: a personal slur . Perhaps you haven’t noticed, but Rick Finnell is actually famous internationally in his field (not just a mere “international reputation”), and is in high demand to appear on the world stage, both as a scientist AND as TIGM’s front man. Are you saying this does not have value? Could you do the same? Does your track record compare?

    Let me declare my hand, and my identity (hint). I also have experience with inventing a drug, commercialising it, getting it into people, then watching its development stall. The company was Promics, my name is Steve Taylor, and Professor of Pharmacology at the University of Queensland. If you haven’t actually fought hand-to-hand in the bloody trenches of commercialisation for years on end, where so much swirls beyond sanity and control, then don’t raise your anonymous hand to criticise those who do. It is a simple fact that it is the bizarro world. As in academic research, where most money is wasted (because we generally are groping like blind men in a coal mine trying to do something that may have real meaning and genuine outcomes, but which are almost always zero- apart from enhancing one’s career etc): so it is in commercialisation. It is just that in commercialization, the scale of waste and fuckups is so much bigger. But, as in government funded research, if we don’t make an effort, take the risk, splash some money around, and hope for the best, then we may as well stay at home and play tiddlywinks.

    Human affairs are always messy, and even with the best of intent, shit happens. In commercialising science, the shit never stops flying (even without the critics). All academic institutes that I know of are propped up by the university and/or the state. 99% of all commercial scientific enterprises will fail or need to be heavily subsidised.

    Get used to it Harvey. This is how the world works.

  3. Dear Downunder Headbanger: In researching your resume I was hoping that you were Aussie Steven Taylor rugby union player of aboriginal heritage at the top of hits. But we see you are the nepotic associate of our individual topic of paranoid reaction, a case in point for Harvey's original comment regarding use of targeted funds for ventures under criticism in this forum. They are squandered by such nepotic and unthoughtful short term support of less than top of the line unbiased support of those whose lives are at stake in the venture and will build many generations of productive scientific development with the resources. In reading your random paranoid rant and raving, I assume your flat forehead is from wallbanging resentment of those more systematic and fundamental in their science, surely not the flat forehead caused by the rational academic scientist and teacher whose flathead results from the constant conservtive slapping and exclamation "Oh, why did I not think of that." By revealing your venture, your specific drug target and your philosophy of application of resources with out regard to thoughtful concept and ethical consequences driven by base animalistic egomania rather than deliberate thoughtful progression confirms every point of my original observation.

    It is unclear what you attribute the stalling of your personal venture to, but evaluating your base technology from the internet information available it is clearly obvious it is doomed to failure based on biological rationale alone. The statement "inventing a drug, commercialising it, getting it into people..." reveals the essence represents the vision 1920 level of your thinking and what we are discussing here. It is as you say, an example of the animalistic "human affairs are always messy" justification for squandering of valuable resources toward irrational emotion-based, profit-driven based ventures that not only are futile as your speciific example but can actually be dangerous to people. This if not based on adequate knowledge and rationale the development of which is the role of the academic research and teaching system of Texas A&M. It is the irrational egomanic-driven, random kneejerk goal of accolade and resources represented by your rant and raving that argues for dedication of valuable resources to rational based concept driven academic research and teaching activity that results in development of individuals to carry on that process.

    Harvey and the academic basic research and teaching faculty of Texas A&M will never "get used to" the animalistic, kneejerk, irrational, self-serving potentially dangerous for evolution of human society your rant and raving and your proteges you defend represent. It is not within our mission which is exactly the opposite. This in essence at the heart of the difference between Vision 2020 and Vision 1920 which your retrogressive rant and raves and basic approach represents.

  4. Harvey,

    Your Google-fu may be stronger than ours, but all we found about Promics was that they were involved in developing PMX53, a cyclic peptide antagonist for the complement C5a receptor. From our limited skimming, it seems that this showed promise in model systems, but, like many drug candidates, was less effective in human trials. This does not strike us as a threat to human evolution.

    We approved your comment for publication, based on our policy of approving just about anything that isn't spam. However, if you want to use our comments section to make specific attacks regarding Dr. Taylor's scientific pedigree or previous work, your case would be stronger if supported by a clearer explanation of wtf you are talking about, preferably with links.

  5. Hmmmm, uncharacteristic of Vision 1920 to support free speech. Thanks.

    There is no personal attack here anymore than that of anonymous peer review and transparent dialogue. Granted kneejerk paranoia and reactionary defensiveness is often an indicator that "the truth hurts" and one might in hindsight suggest that Dr. Taylor had not revealed himself (Googled link: Finnell + Taylor + Queensland:, but maintained the dialogue anonymously.

    The points of the original thread remain:

    1. Unlike an academic department head, to be competitive, the leadership of Institutes and Centers must have an international track record in the stated mission and theme of the venture. They should be recruited independently and without bias through systematic and open process.

    2. Institutes and Centers will only be successful if resources are utilized for the stated mission to recruit the most excellent independent scientists whose careers (salary, evaluations and advancement, space) are dependent on the institute or Center. Institutes and Centers comprised of part-time faculty, Visiting Scientists, and faculty whose primary appointments are in other units are doomed to failure and have high probability of merely subsidizing existent programs, or cronies of the Program Director. The key question is "If an Institute or Center were to dissolve, would the career of the member be affected?" Otherwise the participation is a "hobby."

    2. Otherwise the scarce resources should be utilized to buttress revitalization, new recruitment and promotion of theme within proven existent organizational frameworks within the system.

    Now on the new issue of drug discovery Professor Taylor's wallbanging statement speaks loud and clear why Texas A&M has no business in direct participation in the insanity and waste: ".....the bloody trenches of commercialisation for years on end, where so much swirls beyond sanity and control....It is a simple fact that it is the bizarro world....It is just that in commercialization, the scale of waste and fuckups is so much bigger."

    Yet Professor Taylor's astounding denigration of academic conceptual science and the long term generation of basic knowledge generated via the tedious scientific method that takes place only in the university setting again argues for more resources for that endeavor. It argues against throwing resources down the endless sink of unscientific trial and error "bizarro" world of "irrational" drug design with endless "splashing" of money at the expense of basic knowledge. Basic knowledge essential for his C5a receptor antagonist to ever have (had?) a faith-based "hope" of working.

    Perhaps it is time for those prototypes represented by Professor Taylor's statements (nothing personal here, just a prototypic generalization based on stated philosophy) to stay at home and play tiddlywinks (or the stock market or implementation of Ponzi schemes).

    Harvey Potbanger

  6. Hullo again Harvey.

    Well, I see I caught your eye, along with your bile. And there is much more bile than meets the eye.

    Even the editors of the blog were obliged to point out (rather politely, too, I thought), that your attacks on me needed some evidence. But where’s the fun in that?

    On a gentler note, I am always happy to match my scientific record up with anyone in a vaguely similar area, and would relish the chance to do so with you. Unhappily, we both know that this will not happen.

    I wish I could say that I enjoyed reading your missile directed at me, but Harvey, it was so badly written, that I lost interest very quickly in. If you have points to make, please make them with some degree of literacy –if you are leading the new TAMU revolution, then it is important that followers have some clue as to what you are on about.

    Frankly, I haven’t. Calm down, take a breath, then get someone to read this back to you: “ It is the irrational egomanic-driven, random kneejerk goal of accolade and resources represented by your rant and raving that argues for dedication of valuable resources to rational based concept driven academic research and teaching activity that results in development of individuals to carry on that process”. (P.S. Also please learn to use commas effectively- it’s like taking a breath).

    Huh? You should work for the government- sludge like this is urgently needed elsewhere, to flower in a thousand bureaucratic cubicles, not hidden in a little TAMU blog. If this is your idea of clarity of thought, then perhaps academia is actually not for you. You do seem to hate it so. Do you speak to your students in this fashion? Are you even an academic, or is your hate catholic? No offence Harvey, but who’s the egomaniac here? At least I can write clearly- can we at least agree on this?

    Rant and raving? I simply pointed out what I thought were some mildly obvious points, and now I find I am a tool of something or other (the Dark Side has taken over this dimwit, eh?), but I can’t actually grasp what from the tirade. The internal politics of TIGM and TAMU interest me not one whit-all institutions have them to amuse the inmates.

    I have my own little area of research expertise, I go to work every day to try to push back the frontiers of science and to try to improve clinical therapies (yes, my hubris is boundless), mindful that apart from a few other researchers in my field, my students and collaborators, that no-one gives a tinker’s damn about what I am trying to do. That’s the problem with having a flat forehead, I guess. I may be so stupid I don’t know what stupid is. But at least I try, in my own pathetic, pinhead way. And the forces arrayed against me, including obtaining funding, finding inspiration, keeping up with new technologies, running a large lab filled with clever young people (I readily admit, cleverer than I), when combined with my own dimwittedness, do indeed hold me back. Indeed, gazing in the mirror, my forehead is indeed completely flat. No wonder I struggle to make a worthwhile scientific contribution- I was handicapped before I began. Gadzooks!

    You accuse me of being “with out regard to thoughtful concept and ethical consequences driven by base animalistic egomania rather than deliberate thoughtful progression confirms every point of my original observation”. Ummm. But you don’t even know me. And I do so wish I could divine what you are actually trying to say. If it was explained lucidly, without the jabbering and incoherence, I might be tempted to have a dialogue.

    Finally, if I am writing “random paranoid rant and raving”, I do indeed need someone to tell me, but I’m not quite sure you are the one.

  7. Oh Harvey,
    You can write a sentence. Jolly well done.

    But the H potbanger is painting the kettle rather black when you accuse ME of anonymity. “Dr. Taylor had not revealed himself... but maintained the dialogue anonymously.” Anonymously? Moi? Have you no sense of irony? Can you not hear the other readers of this blog guffaw when it comes to a shootout over anonymity? I have previously given you access to everything public about me with a little dash of google. Pub Med me and you will find I worked with Rick Finnell 25 years ago (but not since then until I recently needed his particular expertise). Jesus, that’s a long time between drinks.

    You may recall that I mentioned in my original blog that I spent three months sabbatical at TIGM earlier this year. No secret there. Well it was visiting the Finnell group- for my own selfish ends. Does that make me an apologist or conspirator? Oh, and I did follow your link to Rick Finnell’s CV- and let’s face it, it’s pretty damn impressive, isn’t it?

    “Yet Professor Taylor's astounding denigration of academic conceptual science and the long term generation of basic knowledge generated via the tedious scientific method that takes place only in the university...”. Actually, you twist my words, mate. If you follow the blog trail, it is totally untrue what you claim I said. Totally. Untrue.

    I am, in fact, an old fashioned university researcher who spent 10 painful years inventing a new class of anti-inflammatory drug totally in a university environment (the complement C5a receptor antagonists- then another seven trying to progress/develop it in the direction of the clinic. It damn near killed me. I hated commercialisation then and still do today. It is total bullshit, but unavoidable bullshit.

    My forays into commercialisation were pacts with the venture capitalist devils, but the devils had the money needed for the next step- no-one else did. Should I stop then, before the job is done, because their money stinks, and they are nasty people?

    I am all for increasing the resources into the university sector. In my institution, research institutes have sprouted like mightily expensive mushrooms: they are supported by the state, by my university, and they bring in some government grants to support their lavish lifestyle, but they are very heavily subsidised for more than half their funding base. Now, I can choose to be bitter about this, leave the table-or I can work with the cards I am dealt. But, being a bit of a mongrel bastard, I will find a way to do the work that drives me- and that is basic, fundamental research using the pedestrian scientific method. Yup, we agree on this. In my latest research direction I needed to find someone who had true expertise in neural tube defects, and I did what we all do- I called on someone I knew was an expert in the field, and someone I had worked with previously (decades ago), and so knew his character. Lucky for me, he took an interest.

    Harvey, you and I are not so different (except I write better than you). But, guess what. Drug development (not discovery), takes a huge bundle of private (ie soiled) money, which is almost never available from the public purse. We are talking about several hundreds of millions of dollars, and the reality is, only Big Pharma can fund it through to the end. I am no friend of Big Pharma, nor indeed of the patent system- I don’t believe in monopolies, and I think the IP game is corrupt. Now, I reckon if you are looking for leeches, this is a good place to wade. But the reality is this. Science costs a lot of money. It just does. Developing therapeutics costs a helluva lot more. They just do. And, like it or not, human affairs ARE messy. We are a herd species, who are not happy unless bickering and complaining endlessly, and pointing the bone. Look at you and I. Perfect examples of wanking timewasters.

    Anyway. I’ve enjoyed our little repartee, but I need to get back to other things. Hooroo.