In the recent nine months we have been reading about the impact of sequestration on various aspects of life – from defense spending to basic biomedical research. Some articles highlight dramatic consequences.  I write this from the region of the USA (Boston/Cambridge area) that attracts the most amount of research funding from governmental sources per capita.

Despite having been in the academic system for most of my career, it does not bother me – not the least because I am not in academics anymore and am an ardent learner and practitioner of capitalism. That does not mean I don’t care – that is a reason why I am writing this. I am more concerned about a bigger problem that plagues the efficient use of federal resources, our review system. Peer review is hailed to be the best system we have so far to evaluate work of significance that gets funded or published. But, in fact, peer review is what is failing us consistently from achieving greater things, largely favoring incremental progress. Thus, our system needs to develop ways to improve the peer review system, as we explore other models of review and evaluation. That is notwithstanding the fact that the US research leads the world in progress through cumulative incremental progress.

Here I propose one solution: Our peer review system needs a way to penalize poor peer reviewers who are outright wrong and have no vision whatsoever, and can’t recognize a good idea when presented to them – even if we have to determine that fact post hoc. This will get us to promote innovation faster and get beyond just largely incremental progress. This will also weed out the substandard grants and publications that take away the bulk of our resources and leads to repetitive, largely non-reproducible and incremental publications. In addition, this will weed out the PIs (Principal Investigators) who are holding back important advances in our research endeavors that are largely built on these research grants.

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An exemplary case from the recent past in my career:

I have been a consistent predictor of important mechanistic breakthroughs in the life sciences and the real world significance of these discoveries based on a limited amount of disparate data (hence some statement in my LinkedIn profile summary). You can find some of my past work released here.

I highlight my above concern and the proposed solution using one of my three grant applications that I put in public domain: (i) application referenced below; (ii) reapply of the one referenced below; (iii) another application on a different topic – for view and download, that I submitted to US National Institute of Health (NIH) between 2008 and 2009. Though my case is certainly not the first in history that a good idea was not funded, I highlight the problem with the peer review system with one compelling example (of many) from my past career and propose a solution. I am sharing them with the hope that these will help researchers in academia and industry get different thought process with respect to those topics and beyond.

The biomedical significance statements of the grant I highlight (submitted in November 2008, and resubmitted in March, 2009 to the US NIH):

1. I hypothesized an immune response to viral pathogens (RNAi) to be operative but masked due to complexity in humans and other mammals.
2. I hypothesized that we can identify native viruses using simple model organisms (and by extension in higher organisms) from remnants left by the RNAi related immune system.
3. I proposed to study cross-regulation of this immune mechanism with other classes of innate immune mechanisms, so we can manipulate them effectively to overcome infection and other immune related disease.
4. I proposed to study multi-pathogen infections (especially involving bacterial and viral pathogens, that I spent the bulk of my life studying). I hypothesized relevance to HIV and other infections that cause one to become susceptible to multiple pathogens – or even normally innocuous microbes.

This was critiqued by reviewers underplaying the significance with comments implying:

1. There is no evidence pointing towards my primary hypothesis, and
2. The intermediate goal of finding viruses native to one of the model organisms is (i) not feasible, and (ii) will not be useful or usable, even if I find them.

Imagine the impact on the microbiome project if we had looked at it in the same light.

My primary hypothesis has been proven recently, October 2013, by way of two papers in the journal Science (considered one of the top two journals by people in various fields, though things that do not belong there slip in at various times), considered controversial by some.

1. RNA Interference Functions as an Antiviral Immunity Mechanism in Mammals
2. Antiviral RNA interference in mammalian cells
3. Two different perspectives written on those articles. http://bit.ly/17tkyRN; http://bit.ly/17FTxB9

My intermediate hypothesis of being able to identify new viruses in those model organisms (that is simply a proof of concept for even wider application to other organisms), was proved in Feb. 2009.

1. Virus discovery by deep sequencing and assembly of virus-derived small silencing RNAs(Feb. 2009).
2. Six RNA viruses and forty-one hosts: viral small RNAs and modulation of small RNA repertoires in vertebrate and invertebrate systems.(Feb. 2009).
3. Complete viral genome sequence and discovery of novel viruses by deep sequencing of small RNAs: a generic method for diagnosis, discovery and sequencing of viruses(May2009).

When the intermediate step of being able to find new viruses (using remnants left by this defense system) was proven correct despite being slammed by reviewers,I wrote to the division to which I applied, twice, Sep. 2009, and Oct. 2010, and then called one of the division leaders at NIH to discuss the issue. This gentleman said how sorry he feels and how our peer review system can be unduly penalizing on some people. Further he elaborated that despite extensive efforts we (as a scientific community and society) have not come up with a viable alternative to replace the peer review system.

Here is the solution again: Our grant systems needs a way to penalize poor peer reviewers who are wrong and have no vision whatsoever, so we will not be repeating the same mistakes over and over.  This will promote rapid innovation and go beyond simply incremental progress. Yes, incremental progress is safe, but we are in a position to return more to the tax payers who fund this research.

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*Picture based on a reflection captured from subway window in Zurich.