IARPA-RFI-21-02

Request for Information (RFI): Targeted Evaluation of Ionizing Radiation Exposure  (TEI-REX)

IARPA is seeking information on research efforts, established datasets, and novel methodologies in the area of non-invasive biodosimetry focusing on protein, lipid, or other small-molecule associated biomarker signatures.  This RFI is issued solely for planning purposes and does not constitute a formal solicitation for proposals. The following sections of this announcement contain details on the specific technology areas of interest, along with instructions for the submission of responses.

Background and Scope:

The current ‘gold standard’ for biodosimetry is the dicentric chromosome assay (DCA). In use for decades with validated protocols, DCA assays can reproducibly evaluate low- and high- dose exposures (~0.1 - ~15 Gy), can be integrated into automated screening, and can perform qualitative evaluation of partial body exposures.[1-5] More recently developed biodosimetry approaches include analyses of lymphocyte cell depletion, protein-based DNA repair responses, gene expression profiling, and micro-RNA profiling.[6-10] While these methods have demonstrated utility for specific use cases, they are heavily dependent upon transient signatures and often require baseline evaluation to accurately quantify exposure.[11-13] In addition, these methods rely on secondary or tertiary biomarkers from the actual ionizing energy or free radical effects, provide limited information on the exposure environment, and mostly require invasive or serial sampling (i.e. multiple blood draws).[12,13]

Advancements across multiple technical fields over the past decade provides the opportunity to research and develop new biodosimetry methods to overcome the shortcomings of current approaches. Such advancements include novel or improved analytical methodologies or platforms; expanded knowledge space associated with the impact of ionizing radiation to target tissues; and computational techniques to enabling detection of signatures from the background noise.[14-17] Further research into this field, leveraging these advances, will enable development of new approaches for discovery, detection, and analysis of biomarker signatures associated with ionizing radiation exposure and enable improved protection of individuals who are accidentally or professionally exposed, especially at sub-clinical doses.[18,19]

The objective of this RFI is to identify basic and fundamental research capabilities that would inform advancement towards discovery, detection, and analysis of radiation-induced biomarker signatures. Capabilities may include but are not limited to: viable analytical platforms capable of discovery and detection of signatures from minimally to non-invasive samples; examples of potential or demonstrated signatures associated with ionizing radiation exposure; and/or examples or demonstrations of models for quantifying signatures associated with radiation exposure/absorption and the exposure environment. Sample types analyzed should reference skin, hair, nails, sweat, natural surface oils, saliva, dermal interstitial fluid, and/or mucosal cells from the mouth.

Expanded information from the exposure environment may include the exposure dose, exposure length, length of time since exposure, emitter involved in the exposure, radiation type, potential shielding environment, and likelihood of chronic vs acute exposure. Exposure dose can range from near natural baseline to 10 to 15 Gy. All results referenced and submitted through the RFI, either formally published or internally developed, should include appropriate statistical analysis of the data to ensure a full evaluation of the capability and results is possible.

Radiation Units and Exposure Range:

The key challenge associated with this RFI is the identification of signatures from low-dose exposures. The higher ranges identified in this RFI are aimed to be threshold measurements and signatures acting as demonstration of feasibility to capture these signatures at non-cosmic dose ranges. Evidence of amino acid and peptide sensitivities to extremely high levels of ionizing radiation, >10kGy, has been published and is currently investigated within the astrobiology community – these ranges are not of interest to this RFI.

While most human exposures would be quantified as equivalent or effective dose exposures measured in Sieverts, this calculation may not be appropriate for these signatures. The current tissue specific radiation ratio used to calculate Sievert dose is dependent upon best known theory of the health physics community and these values have changed over the years as the community has devised better methods for detecting biological impact.[20-22] This moving target has not been demonstrated when looking specifically for peptide or amino acid scale changes and sensitivities. As such, it may be more appropriate to capture the range of radiation energy absorbed. Responders to this RFI may respond as they feel appropriate, taking this into account, referencing the exposure or energy dose exposure units and supporting examples as deemed most appropriate.

Responses to this RFI should answer any or all of the following questions:

1. Has your organization performed any research associated with detecting exposure to ionizing radiation via biomarkers? Please provide a brief summary of the research and the potential application towards low-dose biodosimetry to answer the question and submit, in an appendix, the referenced publications, drawings, and/or figures. If the research was U.S. Government funded please provide the name of the program manager, agency funding the work, and contract number.
2. What type of biomarker signatures has your group identified or believe would fit the scope of this RFI based upon the scope of research described in the background section?
3. What biomarker signatures may be shared or similar from an intra-species (human to human) perspective, across age, gender, race, etc., as well as an inter-species (human to nonhuman) perspective?
4. How has your group leveraged or demonstrated these similarities previously and how would it align with the scope of this RFI?
5. What affect does age, chemicals, or other confounders have on your identified biomarker signatures?
6. What range of exposure doses has your group worked with when evaluating ionizing radiation-induced biomarkers? Gray or rad values acceptable.
7. Have you identified a range of exposure in which any biomarker is detectable?
8. What type of emitters has your group worked with when evaluating ionizing radiation-induced biomarkers?
9. What type of laboratory models has your group worked with when evaluating ionizing radiation-induced biomarkers?
10. What newer models could be leveraged to effectively measure, retrospectively over days/weeks/months, ionizing radiation exposure? This could include cell line matrices, iPSCs, organ-on-a-chip, organoids, small animal models, large animal models, or human volunteers.
    • How would these model systems be effectively leveraged against the potential sample types identified earlier in this RFI?
11. What sources of sample data – digital or physical – do you have available or know are publicly available to support discovery and environment modeling of biomarkers including emitter type, exposure duration, exposure timeline, and/or partial or whole-body exposures?
12. What are appropriate test and evaluation ground truth data, training data, and metrics to measure the performance of novel Biodosimetry approaches? Are there datasets or archival samples currently available which could support these efforts?

Elements Specifically Out-of-Scope for this RFI:

• Samples types including direct blood collection (intravenous or arterial), urine or feces, and/or tissue biopsies.
• Approaches focused on evaluation of signatures which are not reliable, persistent, quantifiable, consistent, and collectable via minimally invasive (<10 seconds and minimal discomfort).
• Approaches or signatures which are feasible only at high dose radiation exposures (>2Gy).
• Improvements in throughput or scalability of established biodosimetry methodologies.  

Preparation Instructions to Respondents:

IARPA requests that respondents submit answers to the above questions directly or in the form of ideas or potential approaches related to this topic. IARPA requests that submittals briefly and clearly describe the potential approach or concept, outline critical technical issues/obstacles, describe how the approach may address those issues/obstacles and comment on the expected performance and robustness of the proposed approach. If appropriate, respondents may also choose to provide a non-proprietary rough order of magnitude (ROM) estimate regarding what such approaches might require in terms of funding and other resources for one or more years. This announcement contains all of the information required to submit a response. No additional forms, kits, or other materials are needed.

IARPA welcomes responses from all capable and qualified sources from within and outside of the U.S.

Because IARPA is interested in an integrated approach, responses from teams with complementary areas of expertise are encouraged.

Submissions from Federally funded research and development centers (FFRDCs) and University Affiliated Research Centers (UARCs) are permitted but with an understanding that neither groups are able to propose against any IARPA program. Instead, any submissions from these groups should consider the technical elements described above but include reflection upon how they would support program efforts as a potential test and evaluation partner enabling IARPA to validate different potential approaches to meet the research challenge.

 Responses have the following formatting requirements:

1. A one page cover sheet that identifies the title, organization(s), respondent's technical and administrative points of contact - including names, addresses, phone and fax numbers, and email addresses of all co-authors, and clearly indicating its association with RFI-21-02;
2. A substantive, focused, one-half page executive summary;
3. Answers to the above questions including potential research approaches capable of achieving a potential program on this topic limited to 5 pages in minimum 12-point Times New Roman font, appropriate for single-sided, single-spaced 8.5 by 11-inch paper, with 1-inch margins);
4. A list of citations (any significant claims or reports of success must be accompanied by citations);
5. Optionally, a single overview briefing chart graphically depicting the key ideas;
6. An appendix of critical reference papers or white papers (no more than 3) associated with answers or potential approaches.

Submission Instructions to Respondents:

Responses to this RFI are due no later than 5 p.m., Eastern Time, on 19 February, 2021. All submissions must be electronically submitted to [email protected] as a PDF document. Inquiries to this RFI must be submitted to [email protected]. Do not send questions with proprietary content. No telephone inquiries will be accepted.

Disclaimers and Important Notes:

This is an RFI issued solely for information and planning purposes and does not constitute a solicitation. Respondents are advised that IARPA is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted under this RFI.

Responses to this notice are not offers and cannot be accepted by the Government to form a binding contract. Respondents are solely responsible for all expenses associated with responding to this RFI. IARPA will not provide reimbursement for costs incurred in responding to this RFI. It is the respondent's responsibility to ensure that the submitted material has been approved for public release by the information owner.

The Government does not intend to award a contract on the basis of this RFI or to otherwise pay for the information solicited, nor is the Government obligated to issue a solicitation based on responses received. Neither proprietary nor classified concepts or information should be included in the submittal. However, should a respondent wish to submit classified concepts or information, prior coordination must be made with the IARPA Chief of Security. Email the Primary Point of Contact with a request for coordination with the IARPA Chief of Security.

Input on technical aspects of the responses may be solicited by IARPA from non-Government consultants/experts who are bound by appropriate non-disclosure requirements. Submissions may be reviewed and followed up on by an assigned technical contractor supporting the designated IARPA POC.

Contracting Office Address:

Office of the Director of National Intelligence

Intelligence Advanced Research Projects Activity

Washington, District of Columbia 20511

United States

Primary Point of Contact:

Robert Rahmer

Director - Office of Analysis Research

Intelligence Advanced Research Projects Activity

[email protected]