Reflections on Weinberg's "Lost Generation"

SciBlings Alex Palazzo (The Daily Transcript) and Mike the Mad Biologist have both held forth recently on Robert Weinberg's editorial in Cell. Weinberg, one of the big daddies of early oncogene research and mentor to some of the best cancer researchers of my generation, expressed his fears that the US investment in training biomedical researchers in the 1990s is going to waste as these trainees move through postdocs and toward faculty positions that simply do not exist. The problem: so-called "Big Biology" initiatives and failure to protect the basic mechanisms of investigator-initiated research, an modest grant program the US NIH terms the "R01."

A comparison for those outside of science would be, say, to fund a triple-digit billion-dollar military conflict, give tax cuts to the nation's most wealthy, yet leave public school teachers appealing to the general public for donations for the hundreds or thousands of bucks to conduct their daily work. (Again, heartiest thanks to the visionaries who contributed to the Sb DonorsChoose drive.).

In particular, Mike has posed some of his observations on behavior in response to the lowest funding paylines for NIH-supported research since the 1980s. Of greatest concern to me is that his several sources tell him that NIH study sections, one of over 110 panels of experts convened to evaluate the scientific merit of research proposals in a given discipline, might be exhibiting scoring bias toward more-established investigators relative to newly-established independent investigators going in for their first or second grants. If this is a general behavior, I am even more troubled than by the Weinberg editoral alone.

Without feeling that I'm telling tales out of school, I can offer that my study section experience has been somewhat different the past few cycles (these are generalities and I don't have solid data to support them, but this is what my gut recalls): I'd say that most reviewers went out of their way to give the benefit of the doubt to junior investigators, even knowing that first-time R01 applicants also get cut a break of 3-7 pct points. Among the groups I have deliberated is a palpable fear of losing highly-promising junior investigators. More senior investigators with multiple R01s were evaluated much more critically than in the past, even though budget is not supposed to be part of the scoring process.

Where I will agree is that highly innovative or risky projects do not fare well, in part, due to that conservatism Mike describes. However, I've been serving ad hoc for over 10 yrs and rarely found that true innvovation and risk taking has even been rewarded at the NIH R01 level because it is so difficult for three primary reviewers and a panel of forty or so to come to consensus on what kinds of risk are likely to generate truly outstanding advances.

Yet another travesty not discussed by Weinberg come from something I read in the 21 April issue of Boyd-Goldberg's The Cancer Letter (subscription only but you should have access to it at NCI Cancer Centers): some mid-level multiinvestigator programs that support some junior investigators have also been cut: E. Gail Eckhardt, MD at Colorado led a team that got the top or 2nd best scores on the NCI AP4 (academic public-private partnership program) that was intended to build bridges between academic oncology and pharma big and small to accelerate the translation of academic drug discoveries to the clinic. The program was eliminated after the study section met, before a single dollar of funds were awarded. (In a related note, the 7 April issue of The Cancer Letter gave a prelude to the Weinberg editorial in Kristen Boyd-Goldberg's reporting of his recent talk under the headline:, "MIT's Robert Weinberg says he doesn't advise young people to enter career in cancer research. Young people can't get grants, he says.")

Not only was this a slap in the face to Dr Eckhardt, Colorado (and wasted what she calculated was $100,000 of personnel time in preparing the 500-page application), and the other top-rated programs, but it has now made certain kinds of businesses very wary about collaborating with academic researchers. Multiple that $100,000 by the number of competing institutions and the money wasted by convening a special emphasis panel of such wide breadth and depth to score these applications and you could've funded at least one or two of the programs.

I'll finish by saying that the US NIH needs comprehensive leadership with a vision that looks with commitment across the entire spectrum of scientific careers, not just feeding the fat cats with more double- and triple-digit million dollar Big Biology. There must be increased focus on making investments in people sustainable. In the States, we've trained twice the number of postdocs in the 1990s vs. the 1980s, but we have no similar doubling of available faculty positions due to the strangling of the R01 budget allocations and unwillingness of states (and state legislatures) to gamble on leveraging new positions.

I pray that Weinberg is wrong about his "Lost Generation" but his analysis does not lend optimism. The current funding situation and the growth of places like Singapore's Biopolis and their recruitment of the best minds from around the world tells me that the pre-eminence of the American biomedical research enterprise is at serious risk.

However, I welcome suggestions as to how mid-career scientists (like the greying Pharmboy) can be of help in retaining our best and brightest junior compatriots.

In future posts, I'll share some of my advice on how I made it through starting a faculty position during the 2nd worst funding crisis between the 1980s and now.