Directed Genome Sequencing: the Key to Deciphering the Fabric of Life in 1993

Seeing the #AAASmtg hashtag flowing on my twitter stream over the last few days reminded my that my former post-doc advisor Sue Celniker must be enjoying her well-deserved election to the American Association for the Advancement of Science (AAAS). Sue has made a number of major contributions to Drosophila genomics, and I personally owe her for the chance to spend my journeyman years with her and so many other talented people in the Berkeley Drosophila Genome Project. I even would go so far as to say that it was Sue’s 1995 paper with Ed Lewis on the “Complete sequence of the bithorax complex of Drosophila” that first got me interested in “genomics.” I remember being completely in awe of the Genbank accession from this paper which was over 300,000 bp long! Man, this had to be the future. (In fact the accession number for the BX-C region, U31961, is etched in my brain like some telephone numbers from my childhood.) By the time I arrived at BDGP in 2001, the sequencing of the BX-C was already ancient history, as was the directed sequencing strategy used for this project.  These rapid changes made discovery of a set of discarded propaganda posters collecting dust in Reed George’s office that were made at the time (circa 1993) extolling the virtues of “Directed Genome Sequencing” as the key to “Deciphering the Fabric of Life” all the more poignant. I dug a photo I took of one of these posters today to commemerate the recognition of this pioneering effort (below). Here’s to a bygone era, and hats off to pioneers like Sue who paved the road for the rest of us in (Drosophila) genomics!

Directed-genome-sequencing

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A Case for Junior/Senior Partnership Grants

Much has been made in recently years over funding crises in the US and Europe, which are the inevitable result of the Great Recession superimposed on top of the end of exponential growth in Science. Governments hamstrung by austerity measures or lack of political will have been forced to abandon increases in scientific funding, going so far even as to freeze funds for awarded grants in Spain (see translation here). The consequences of this stagnant period of inputs to scientific progress will be felt for many years to come, materially in terms of basic and applied discoveries, but also socially in terms of the impacts on an entire generation of scientists who are just beginning their independent careers.

Why are early stage researchers hit hardest by stagnation or decreases in funding? Simply because access to funding is not a level playing field for all scientists, and is in fact highly dependent on career stage and experience. Therefore, increased competition for resources is expected to hit younger scientists disproportionately harder relative to established researchers because of many factors, including:

  • less experience in the art of writing grants,
  • less experience in reviewing grants,
  • less experience serving on grant panels,
  • shorter scientific and management track record,
  • and a less highly developed social network.

The specific negative effect that a general increase in resource competition has on young researchers is (in my view) the best explanation for the extremely worrying downward trends in the proportion of young PIs receiving NIH grants, and the increasing upward trend in the age to receipt of first RO1 in the USA, shown in the following diagrams from the NIH Rock Talk Blog:

Thankfully, this issue which is being discussed seriously by NIH’s Deputy Director for Extramural Research, Dr. Sally Rockey, as publication of these data attests to.  [I would very much welcome if other funding agencies published similar demographic breakdowns of their funding to address whether this is a global effect.] However, not all see these trends as worrying and interpret them on socially-neutral demographic grounds.

To help combat the inherent age-based iniquities in access research funding, funding agencies typically ring-fence funding for early-stage researchers under a “New Investigator” type umbrella. In fact, Sally Rockey provides a link to an impressive history of initiatives the NIH has undertaken to tackle the New Investigator issue. But what is striking to me is that despite putting a series of different New Investigator mechanisms in place, the negative impacts on early-stage researchers have only worsened over the last three decades. Thus New Investigator programmes are clearly not enough to redress this issue, and new solutions must be sought out. Furthermore ring-fencing funding for junior researchers necessarily creates an us-vs-them mentality, which can have counterproductive repercussions among different scientific cohorts. And while New Investigator programmes are widely supported in principle, trade-offs in resource allocation can lead to unstable to changes in policy, as witnessed in the case of the now-defunct NERC New Investigator programme.

So, what of it? Is this post just another bemoaning the sorry state of affairs in funding for early-stage researchers? No, or at least, not only. Actually, my motivation is to constructively propose a relatively simple (naive?) mechanism to fund research projects that can address the inequities in funding across career stages, but which also has the additional benefit of engendering mentorship and transfer of skills across the generations: the Junior/Senior Partnership Grant. [As with all (good) ideas, such a model has been proposed before by the Women’s Cancer Network, but does not appear to be adopted by major federal funding agencies.]

The idea behind a Junior/Senior Partnership funding “scheme” is simple. Based on some criteria (years since PhD or first tenure-track position, number of successful PI awards, number of wrinkles, etc.) researchers would be classified as Junior or Senior. Based on your classification, to be eligible for an award under such a programme, at least one Junior and one Senior PI would need to be co-applicants on grant and have distinct contributions to the grant and project management. This simple mechanism would ensure that young PIs get a piece of the funding pie and allow them to establish a track record, just as a New Investigator schemes do.  But it would also obviate the need for reform to rely on the altruistic stepping aside by Senior scientists to make way for their Junior colleagues, as there would be positive (financial) incentives for them to lend a hand down the generations. And by reconfiguring resource allocation from “us-vs-them” to “we’re-all-in-this-together,” Junior/Senior Partnership Grants would further provide a natural mechanism for Senior PIs to transfer expertise in grant writing and project management to their Junior colleagues in a meaningful way, rather than in the lip-service manner that is normally paid in most institutions. Finally, and most importantly, the knowledge transfer through such a scheme would strengthen the future expertise base in Science, which all indicators would suggest is currently at risk.

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