Dr. Steven Benner at the Foundation for Applied Molecular Evolution thought the genetic code of life could be expanded beyond its naturally occurring four building blocks. If successful, powerful new systems for developing diagnostics, therapeutics, synthesizing biopolymers, and other still unimagined uses may be possible. In 2019, he and his colleagues came a step closer to this vision. They reported in Science a genetic system with eight building blocks, increasing the amount of information a given stretch of DNA can carry. Moreover, the modified DNA can be transcribed into a modified RNA using a specially engineered RNA polymerase.
Projects like this are perfect for the NIH Director’s Transformative Research Award program, which funded Dr. Benner’s idea in 2017 (see the website for a complete list of other supported research). Now, NIH is seeking applications for the 2021 awards through a new funding opportunity (RFA-RM-20-013) recently released on Friday, May 21, 2020.
The Transformative Research Award has supported groundbreaking, unconventional, and creative ideas for over a decade as part of the NIH Common Fund’s High-Risk, High-Reward Research program (HRHR). While this kind of research has the potential to overturn fundamental paradigms, it can also be risky. That is why innovation and breadth of impact potential are emphasized more during review than a project’s feasibility and preliminary data.
Historically, however, the HRHR applicant and awardee pools have not fully represented the demographic and geographic diversity across the U.S. biomedical workforce (see here on the Common Fund’s commitment to diversity). A working group of the Advisory Committee to the NIH Director examined this issue and recommended that the Common Fund prioritize increasing institutional diversity in the program (see their Report here).
Concerns also exist about bias, be it unconscious or otherwise, generally throughout peer review at NIH. As a way to address this issue while also enhancing diversity, the HRHR program is going to anonymize the review of Transformative Research Award applications.
The Common Fund and the Center for Scientific Review devised an approach to anonymize the identity of applicant institutions and investigators until the last phase of the Transformative Research Award’s three-phase review process. By anonymizing applications, it is hoped reviewers will focus on the merit of the research and limit potential unconscious bias while encouraging applications from investigators who otherwise might not apply due to perceptions of such bias.
Previously, during the first phase of review, an “Editorial Board” (composed of senior scientists with collective expertise spanning a broad swath of the NIH portfolio) had access to the entire application package and selected a subset of applications with the greatest transformative potential for further technical review. For the new anonymized process, the Editorial Board will only be able to see the application’s Specific Aims page while considering the project’s significance, innovation, and logic. The Specific Aims page is used in an unconventional way in the Transformative Research Award application. It serves as a one-page distillation of the idea, why it is exceptionally innovative, and the potential impact. Applicants will be instructed in the funding opportunity announcement to not include any information that would reveal the investigator(s) or institution(s) in this section, essentially making the review blind.
In the second phase, only the Specific Aims page and Research Strategy section, which must also be anonymized by applicants, will be sent to “mail reviewers” with expertise relevant to the application. These reviewers will assess the innovativeness, transformative impact, and technical merit of the application while blind to the investigator(s) and institution(s).
After the technical critiques are completed, the process shifts back to the Editorial Board for the final phase of review. Informed by the technical reviews, the Editorial Board will prioritize applications for discussion. At this point, the board will have access to the complete applications and formally designate which applications are “Not Discussed.” To comply with regulations, the scoring of applications will utilize the five standard review criteria, including the investigator and environment, as well as other appropriate reviewable matters such as the use of vertebrate animals, human participants, and the Leadership Plan for multi-Principal Investigator applications. The Editorial Board will provide individual, numerical scores for each discussed application from which the overall impact score will be calculated. The applications then go to the NIH Council of Councils for second-level review.
We are excited to see if this new anonymization approach, with the identity of institutions and researchers hidden during the first phases, will lead to more diversity in investigators on applications and ideas proposed as well as its effect on scoring.
To help us support the best possible science across the nation, we would like to see the application pool reflect the full diversity of potential investigators, applicant institutions, and research areas relevant to the broad mission of NIH. Talented researchers from diverse backgrounds (see NOT-OD-20-031) are strongly encouraged to work with their institutions to apply.