Yes, Weedhopper, you can have the “same” R01 for decades

A discussion ensued yesterday among several of my learned colleagues following this post by The Genomic Repairman. Therein, TGR noted that a senior person in their field had two grants in their 27th year and 26th year, respectively. In NIH grant parlance, one is called a R01 (and that’s R-zero-one, chief), an investigator-initiated grant that is the bread-and-butter type of support by which the mettle of most biomedical researchers is evaluated. The other is called a P01, or program project, a group of R01-sized projects with one or more core programs that support each other in what is intended to be synergy.

Some of my colleagues question the merits of the P01 program since some just appear to be a group of individual grants that really don’t function interdependently – I tend to think that good P01s do a great job (disclosure: our lab is part of a collaborative P01 subproject led by a great senior person in my field who is deeply committed to the development of junior scientists).

But back to TGR. In his self-admitted angry rant, he asked:

Seriously to have two grants that old, um has there never been a fucking priority shift? Ever? At some point wouldn’t the NIH cutoff funding for the grant as this dude has probably drug this shit down the road for way to long.

TGR gets clever-points from me simply for the dead, driftwood photo in Figure 1 with the caption: “The overfunded PI with grants almost as old as I am!”

Believe it or not, grants funded under the same project name for more than 30 years are quite common.  In fact, a search of the NIH RePORTER database (the successor to CRISP), reveals this 62-year-old project as the longest I could find. The grant number is 5R01GM000091-62.

NIH grant nomenclature

As an aside, you can dissect this seeming gibberish by noting that the first number denotes the stage of the grant: Most common are Types 1, 2, and 5. Type 1 grants are brand-new, type 2 grants are competing renewal applications that are submitted after the original grant period expires, type 5 grants (like this one) are in the years of a funded grant period where the grant is renewed annually without additional peer-review. Other commonly-used definitions are the type 3 which is the award when an administrative supplement is requested, for example, to fund minority scientists for new studies related to the main thrust of the grant, or the type 7 which denotes a grant that has moved with the principal investigator to a new institution. Less common types I don’t know much about are the type 4 which seems to be a flavor of type 3 grants where additional funds are awarded and the type 9 which is used to describe grants whose primary funding institute has changed.

The two letter code, GM in this case, denotes the primary funding institute, National Institute of General Medical Sciences (NIGMS). Many folks in my field have CA designations for the National Cancer Institute.  My alcohol research colleagues will often have grants from NIAAA denoted AA and substance abuse research colleagues will have DA to denote projects funded by the National Institute for Drug Abuse.

The following six numbers are simply the sequential numbers of the grant that are assigned to each application regardless of whether it is ultimately funded. Yes, this was the 91st grant submitted to the NIGMS.

And, back to this discussion, the 62 denotes the year of the grant. You’ll see some grants where the last two numbers are followed by an A1 or the now-defunct A2, denoting a revised or “amended” application, or a S1 for a type 3 grant supplement. There are other designations that I’m sure other folks will drop in the comments.  Anyway, you can tell a lot about a NIH grant from its number.

Led until 2007 by Duke biochemistry professor emeritus, K.V. Rajagopalan, the most recent version of the grant investigated an unusual molybdenum co-factor, molybdopterin, as the central prosthetic group for almost all molybdenum-containing enzymes. Molybdenum deficiency is an autosomal-recessive trait that cause seizures in infants and invariably leads to childhood death. There is no known treatment. The activity of sulfite oxidase, a Mo-containing enzyme, has been a diagnostic test for the disease used since 1983 and many of the sequelae of the disease seem to be a result of sulfite accumulation and toxicity in neurons. This round-up from the International Molybdenum Association details some of the work on the role of molybdenum in human biology.

Dr. Rajagopalan has been a prolific biochemist with 199 papers on PubMed. Two of his first four papers in 1958 and 1959 were in Nature, and his last two in 2008 and 2010 were in Biochemistry and Journal of the American Chemical Society. One of my learned colleagues mused as to whether Dr. Rajagopalan was the original principal investigator on the grant (since NIH RePORTER doesn’t have records that far back – only to 1987 or 1989 in most cases). However, the first grant would have been awarded in 1945, assuming that grant periods were still one-year in length in those days. Of course, NIGMS wasn’t established until 1962 and the NIH, which traces its history to 1887, wasn’t established in name until the Ransdell Act of 1930 when it was called the National Institute of Health (singular).

So, it is likely that this longstanding grant was originally awarded to another P.I. – perhaps Dr. Rajagopalan’s mentor – in another institute, or perhaps just plain old NIH itself. It’s rather common, even today, for a well-qualified trainee to be named as P.I. of a grant when one’s mentor passes on to The Great Study Section in the Sky. Getting that grant renewed, however, is as tough as getting a brand new grant.

Longtime grantees – Deadwood? Driftwood? Or Clue Stick?

TGR may also care to note that the convention in the old days was to have a very broad grant title with the grant competitively reviewed for renewal on newly designed experiments. Much effort is expended on the merits on long-time renewed grants with young(er) folks like TGR criticizing longtime grantees as “deadwood” while more seasoned investigators note that a renewal means not only proposing new ideas but also being more carefully reviewed for progress on the previous aims of the grant.

For example, one of the fathers of my field – and one of the most encouraging people I have ever met in cancer research – Joe Bertino, had a grant entitled, “Mechanism of Action of Folate Antagonists,” that expired in year 45 only six weeks ago. Bertino was, and is, still doing cutting edge work on a class of drugs represented by methotrexate, whose clinical use he launched with Bruce Chabner and others quite early in his career. Even with a couple of high level administrative positions at the Cancer Institute of New Jersey and the University of Medicine and Dentistry of New Jersey, Bertino led a project on microRNA regulation of dihydrofolate reductase (DHFR) that appeared recently in PLoS ONE. Bertino’s group showed that miR-24, a tumor-suppressor microRNA normally modulates DHFR activity (required for nucleotide biosynthesis and cell proliferation) but a polymorphism in the DHFR 3-UTR prevents miR-24 action leading to high level production of DHFR that contributes to neoplastic transformation. Melding novel concepts of carcinogenesis with a career of work on DHFR is an example of the kind of thing that longtime grant renewals support.

Grant renewals were the norm when I was coming up in the 1980s and my tenure decision in the 1990s was highly dependent on the renewal of my first R01 that came through a few months before the review committee met. I don’t have statistics handy but my anecdotal experience on NIH study sections over the last decade of so have led me to think that grants renewed more than twice are becoming less common.

So rather than view double-digit-year grants as evidence of driftwood or deadwood, I would argue to TGR that such grants are evidence of a long career of investigator productivity together with the sustained ability to compete at the top 10-15 percentile of scientists in the field. Does a grant with a -26 influence a reviewer’s perception, especially a first-time grant reviewer? Perhaps. But in both ways. Some reviewers, especially first-time reviewers, might feel that they might be missing something if the grant appears to be shite while others might simply dismiss the -26 before they even start reviewing as though the grant carries a “Kick Me” sign.

My personal opinion is that most grants with more than 20 years of support have clearly earned it. I can’t argue individual cases whose history I don’t know – especially those outside my field as the example of TGR seems to be. However, my dear weedhopper may care to consider some of these points in his angry rant.

Real deadwood would be faculty who occupy positions without any grant funding who also shirk teaching responsibilities, resist any change or innovation by junior faculty, hold forth with painful, droning, and meaningless diatribes at faculty meetings, and bitch to you about the tough old days (when grants were funded at the 35th or 40th percentile) when they had to synthesize phosphate buffer from the elements..uphill, both ways, in blinding snow and ice.

But, then again, young investigators are supposed to be full of piss and vinegar.

ADDENDUM: Colleagues who have also weighed in:

DrDrA – Blue Lab Coats

JUNIORPROF

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6 thoughts on “Yes, Weedhopper, you can have the “same” R01 for decades

  1. Pingback: Long standing R-series grants are not the problem « JUNIORPROF

  2. Real deadwood would be faculty who occupy positions without any grant funding who also shirk teaching responsibilities, resist any change or innovation by junior faculty, hold forth with painful, droning, and meaningless diatribes at faculty meetings, and bitch to you about the tough old days (when grants were funded at the 35th or 40th percentile) when they had to synthesize phosphate buffer from the elements..uphill, both ways, in blinding snow and ice.

    Hmmm … I think I know a few of these …

    • I think we must know a lot of the same people. I do not object to long-term grants, it is tenure that is the enemy. I know a lot of people who rely on it to keep their jobs, I only know one person who uses it to allow him to pursue work his department does not appreciate (and he will never be promoted to full-professor).

      It is a shame when universities have to pay lots of money to get rid of someone either by buying-back tenure, or in legal fees. (Personally, I would rather the lawyers got the money instead of the duds.) My undergrad alma mater spent 5 or 6 years in court getting rid of someone who never should have had tenure in the first place. Just after they fired him I met a fellow graduate who, knowing only that we attended the same school, knew I would be happy to hear the news. As he said “They knew he was a jerk when they gave him tenure, what were they thinking?”

  3. Pingback: The youngsters are ranting…. (updated w/links) « Blue Lab Coats

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