1. National Aeronautics and Space Administration Human Research Program NASA’s Approach to Critical Risks for Extended Human Space Flight FISO Telecon 2 April 2014 Mark Shelhamer, Sc.D. Chief Scientist NASA Human Research Program mark.j.shelhamer@nasa.gov

2. Human Research Program 2 HRP Mandate within NASA NASA Administrator Aeronautics Research Mission Directorate Science Mission Directorate Human Exploration & Operations Mission Directorate Space Technology Mission Directorate Human Research Program

3. 3 Human Research Program Goal The goal of HRP is to provide human health and performance countermeasures, knowledge, technologies, and tools to enable safe, reliable, and productive human space exploration. Seat layout for contingency EVA Example of a study on the effects of center of gravity on performance Clay Anderson centrifuges Nutrition blood samples during Increment 15

4. Human Research Program 4 Future Missions: The Flexible Path Schedules for the next destinations are unknown, but the goals are all beyond Low Earth Orbit (LEO) Schedules for the next destinations are unknown, but the goals are all beyond Low Earth Orbit (LEO) 4

5. Human Research Program 5 Primary Hazards to Humans during Space Flight  Decreased gravity (including gravity transitions & launch/landing loads) bone, muscle, cardiovascular, sensorimotor, nutrition, immunology behavior/performance,, human factors, clinical medicine  Isolation/confinement/altered light-dark cycles behavior/performance  Hostile/closed environment (including habitability: atmosphere, microbes, dust, volume/configuration, displays/controls) behavior/performance, nutrition, immunology, toxicology, microbiology  Increased radiation immunology, carcinogenesis, behavior/performance, tissue degeneration, pharmaceutical stability  Distance from Earth behavior/performance, autonomy, food systems, clinical medicine

6. Notional qualitative view of changes assuming currently known and effective countermeasures used Increased dash size = increased uncertainty in trend Individual variability not shown In-Flight Physiological Changes ? ? ? ? ? ? ? Acceptable Decrement (based on current standards) trend dynamics unknown

7. Human Research Program 7 7 Components of HRP HRP is composed of six Elements –Human Health Countermeasures Physiology –Behavioral Health and Performance Individual and interpersonal –Space Human Factors and Habitability Interfaces between humans and vehicles/habitats –Space Radiation Radiation exposure and biological effects –Exploration Medical Capability Medical care for missions –ISS Medical Project Infrastructure for flight experiments HRP funds the National Space Biomedical Research Institute (NSBRI) through a cooperative agreement to pursue research that complements the HRP portfolio Sunita Williams inserting blood samples into the Minus Eighty Degree Laboratory Freezer Nutrition SMO

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9. Human Research Program 9 Human Research Program Architecture What? When? Why? How? Who? Where? Knowledge Gaps Disposition Gaps TasksDeliverablesEvidenceRisksGaps Insufficient Data Unacceptable Acceptable Controlled Correlate knowledge Develop Standards Countermeasure/Technology Clinical Guidelines Understand Risk Correlate knowledge Validate Standards Countermeasure/Technology Clinical Guidelines Optimize (DRM specific) Standards Countermeasure/Technology Clinical Guidelines Gap Metrics

10. Human Research Program 10 HRP Path To Risk Reduction

11. Human Research Program 11 Examples Bone & Muscle –Possibly controlled Need to validate and refine countermeasure Behavior and Performance –Psychological and performance issues Need to develop measures and countermeasures VIIP –New critical risk Need to formulate and test hypotheses CO 2 –Unknown significance of chronic exposure Need to acquire information Radiation –Major risk beyond LEO Ground-based models

12. Musculoskeletal  Unloading  - Bone loss  increased risk of renal stone - Muscle loss (strength/power/endurance ) - Spinal elongation Seated height can increase up to 6%  Bone loss countermeasures - Resistive exercise plus bisphosphonates - very effective to date  Muscle atrophy countermeasures - Aerobic and resistive training - Highly variable response - 60-80% contributed by genetics - Non-response in some astronauts Osteoporosis International (2012): 1-10. 12 April 201312

13. ARED Effective but too big to take to Mars

14.  Behavioral areas susceptible to increased risk over a one year mission: (1) sleep loss, circadian desynchrony, workload and fatigue (2) stress, morale and mood changes* (3) cognitive functioning (4) interpersonal conflicts* (5) motivational challenges* (6) family separation and personal communications  Desire realistic environment and population to validate countermeasures.  Preliminary analysis for ISS (ongoing study): Available measures of subjective stress, sleep quality, and vigilance not all monotonic with mission time do not plateau by six months Sleep quality and vigilance have similar trends which suggest increasing performance deficits for longer missions. There are correlations between stress, sleep, tiredness, and physical exhaustion that suggest an underlying physiological factor. Even if stress is compensated and does not affect performance, it may produce adverse physiological changes (immune function). Behavioral Health

15.  ISS Journal entries on conflict by mission quarter One-Year ISS Missions Behavioral Concerns Interpersonal Conflicts  ISS Group Interaction Positivity Ratings by mission quarter (244 entries) Interpersonal conflict can impact crew performance and mission success (De Dreu & Weingart, 2003)

16. Human Exploration Research Analog HERA HRP 2013 16  Analog for simulation of isolation, confinement and remote conditions of mission exploration scenarios. To support studies such as: Behavioral health and performance assessments Communication and autonomy Human factors evaluations Exploration medical capabilities assessments and operations

17. Behavioral Health and Performance Countermeasure plan Measure/ Countermeasure NameAnalogs Tested InAnticipated Ready Date for ISS Reaction Self-Testn/aCurrently In Flight Cogntion (Basner)HERAPlanned Flight Study FY15 AD ASTRAHERA, FARU, HiSEASFY 16 Team Performance TaskHERA, AntarcticFY 16 BHP DashboardHERAFY 16 SmartOPMCCFY 16 Actigraphy/EEG (SBIR Phase III)TBDFY 16 Communication Delay ProceduresHERAFY 16 (if comm. delay) Sociometric BadgeHERA, HiSEASFY 17 Baseline Standardized BMed MeasuresHERA, AntarcticFY 18 Neurobehavioral Conditions ListHERA, AntarcticFY 18 Integrated Testing of MeasuresHERAFY 19 Team Mental Model Monitoring Tool (SBIR Phase III) TBDFY 19 Sensory Stimulation Augmentation ToolsHERA, Antarctic, Long-Duration Chamber FY 19 Integrated Testing of CountermeasuresHERAFY 20 VR Technologies for Behavioral HealthHERAFY 21  Maximize use of ground-based analogs for development  Ultimate validation on ISS

18. Current U.S. ISS VIIP Incidence 41 U.S. ISS astronauts flown to date as of Expedition 32: –Unclassified astronauts N=16 (No MRI, OCT or ocular US) –Non-cases N=6 –Confirmed cases: 19 –Class One N=2 –Class Two N=11 –Class Three N=2 –Class Four N=4 68.4 % Class 1&2 31.6 % Class 3&4 Current VIIP Incidence as a % of U.S. ISS astronauts tested= 76.0% Increasing severity Clinical Classification:

19. NASA ISS Astronaut LPs to Date  LPs are done in crewmembers if clinically indicated  5 LPs conducted postflight in crewmembers with optic disc edema, no preflight LP as baseline  Postflight LP measurements have demonstrated mild – moderate elevation in ICP, an inadequate surrogate to in-flight measurement of ICP (cephalad fluid shift & CO2 challenge removed) Case Opening pressure (cm H 2 O) Normal range 10-20 cm H 2 O Opening pressure (mmHg) Normal range 5-15 cm H 2 O Time after flight (days) A2216.266 B2115.419 C2820.612 D28.521.057 E1813.28

20. X Normal Globe Flat Globe Globe Flattening Increased Optic Nerve Sheath Diameter Optic Disc Edema (swelling) 1. Headward fluid shift due to microgravity 2. Fluid shift causes increased intracranial pressure (ICP) Hyperopic Shifts Up to +1.75 diopters Choroidal Folds Parallel grooves posterior pole 3. Elevated ICP transmitted to the eye and optic nerve +ICP Altered Blood Flow “Cotton wool” spots Scotoma Abnormal Visual Field VIIP Pathophysiology

21. Ocular Health  Occupational exposure study: Define changes in crew due to ISS environment, occurring in: Ocular CNS Cardiovascular  Mechanistic only by observation & measurement  Limited physiologic manipulation in comparison to FS TCD measurement during tilt testing pre/post

22. Fluid Shifts  Mechanistic study Direct manipulation of volume and fluid shift using tilt and LBNP with simultaneous measurement of changes in following systems: Ocular CNS Cardiovascular Assessment of Compartmental Fluid Shift

23. Ground-based Evidence Decision-making performance (n=22) reaches dysfunctional levels for several measures during 2 ½ hour exposures to CO 2 at 1.9 mmHg Visual effects reported (n=3) after ~30 min at 19 mmHg CO 2 : decreased depth perception (Sun, et al., 1996), motion detection (Yang, et al., 1997) Risk of headache increases with increasing 24-hr average levels of CO 2 in the range of 2-5 mmHg aboard ISS Occurrence of numerous “space viscosity” events aboard ISS Increased cerebral blood flow at high CO 2 ISS level: 3 mmHg mean, >5 mmHg peak (normal atmosphere: 0.30 mmHg) State of Knowledge (New Evidence) CO 2 Current Status

24. Radiation-induced damage  Terrestrial radiation exposure - Primarily photons  Spaceflight radiation exposure - Primarily high energy protons and heavy nuclei - Secondary protons, neutrons and heavy nuclei  Risks - Acute Radiation Syndromes (in-flight) - Central Nervous System (in-flight, post-flight) - Cancer (post-flight) - Degenerative (post-flight) Cardiovascular Circulatory Digestive Cataracts  Responses being characterized - Phenomenological and mechanistic - Countermeasure development awaits mechanistic understanding ControlIron Nuclei Vasculature Damage by GCR 12 April 201324

25. Summary  The Human Research Program uses a formal process of risk management to: Identify the major risks to human health and performance in space Determine gaps in knowledge and procedures to address the risks Establish appropriate research tasks to close the gaps and mitigate and control the risks  Flexibility to replan or address new issues as needed.  Limited time to get the “best” answer.  Unique constraints. Small “n” HRP considers ISS 1 year mission and ‘n’= 1 worthwhile Constrained environments and often poorly controlled research conditions  HRP & NASA must make important decisions based on current information. 25