Human Space Travel: Medical Challenges Present and Future

1. Human Space Travel: Medical Challenges Present and Future Diane Byerly, Ph.D. NASA Johnson Space Center Houston, TX

2. Contributors • Neal Pellis, Ph.D. • Marguerite Sognier, Ph.D. • Diana Risin, MD., Ph.D. • Lalita Sundaresan, Ph.D. • Thomas Goodwin, Ph.D. • Steve Gonda, Ph.D. • Dennis Morrison, Ph.D. • Diane Byerly, Ph.D. • Mark Clarke, Ph.D. • John Charles, Ph.D. • Tacey Baker, M.S. • J. Milburn Jessup, MD. • Gordana Vunjak-Novakovoc, Ph.D. • Lisa Freed, M.D., Ph.D. • Robert Akins, Ph.D. • Timothy Hammond, M.D. • Lelund Chung, Ph.D. • Anil Kulkarni, Ph.D. • Arthur Sytkowski, M.D.

3. Space exploration imposes new challenges on human systems and terrestrial life in general.

4. Present Orbital Missions Known medical risks Communications Access to Earth Minimum autonomy Future Moon (Short duration) Mostly known medical risks Communications 2-3 day to access Earth facilities Greater autonomy necessary Future (con’t) Moon (Long duration) Many known medical risks, others unknown but anticipated Communication 2-3 day to access Earth facilities Greater autonomy necessary Mars Many medical risks (known, unknown, unanticipated) Communications difficult Probably no access to Earth facilities Autonomous medical care absolutely required Challenges

5. Flight Profile Transit out: 161 days Mars surface stay: 573 days Return: 154 days Human Mars Mission Trajectory Mars Departure Jan. 24, 2022 3 Earth Departure Jan. 20, 2020 1 Mars Arrival June 30, 2020 2 4 Earth Arrival June 26, 2022 Earth Orbit Mars Orbit Piloted Trajectories Stay on Mars Surface

6. Physical factors that influence nature • Life evolved on earth while the force of gravity has been constant for 4.8 billion years. • Therefore, there is little or no genetic memory of life responding to gravitational force changes. • As we transition terrestrial life to low gravity environments and study the adaptive processes in cells, our understanding of the role of gravity in shaping evolution on Earth will increase. • The response of higher organisms to this ‘new’ environment may be less ordered than the response to say, thermal change.

7. Risks to Humans in Microgravity • Exposure to ionizing radiation • Bone density decrease • Muscle Atrophy • Cardiovascular Deconditioning • Psychosocial impacts • Fluid Shifting • Vestibular Dysfunction • Hematological changes • Immune Dysfunction • Delayed wound healing • Gastrointestinal Distress • Orthostatic Intolerance • Renal stones

8. What happens to humans in space? • Long Duration (6 months to 3 years) • Radiation exposure • Muscle atrophy • Cardiovascular deconditioning • GI disturbances • Hematological changes • Declining immunity • Renal stone risk • Early response (<3 weeks) • Cephalad fluid shift • Neurovestibular disturbances • Sleep disturbances • Bone demineralization • Intermediate (3 weeks to 6 months) • Radiation exposure • Bone resorption • Muscle atrophy • Cardiovascular deconditioning • GI disturbances • Hematological changes • Long Duration (6 months to 3 years) • Radiation exposure • Muscle atrophy • Cardiovascular deconditioning • GI disturbances • Hematological changes • Declining immunity

9. Impacts of Extended Weightlessness Physical tolerance of stresses during aerobraking, landing, and launch phases, and strenuous surface activities • Bone loss • no documented end-point or adapted state • countermeasures in work on ground but not yet flight tested • Cardiovascular alterations • pharmacological treatments for autonomic insufficiency • Neurovestibular adaptations • vehicle modifications, including centrifuge • may require auto-land capability • Muscle atrophy • resistive exercise under evaluation

10. Radiation • Different from ionizing radiations on Earth • Two types • Galactic cosmic radiation (GCR) dominated by neutrons • Solar particle events (SPE)- sun storms dominated by protons • Earth is protected by the magnetosphere (van Allen Belt)

11. Radiation Issue: Radiation Environment • Attenuation of GCR and SPE by atmosphere and bulk of planet • Possible risk from neutron backscatter from surface • TBD shielding for vehicle and habitat • Shielding high energy particles is difficult Radiation effects (possible synergy with hypogravity and other environmental factors) • Early or Acute Effects from Radiation Exposure (esp. damage to Central Nervous System) • Carcinogenesis Caused by Radiation • Immune system compromises

12. Bone Loss in Weightlessness 2 years post-menopause, n=13 Space flight 5 (for comparison only) n=22 0 -5 -10 Change from pre-flight (%) -15 -20 ? -25 (months) 6 18 12 24 30 36

13. Causes of bone loss • No load because of low gravity • Poor muscle performance • Metabolic and hormonal changes • Fluid dynamic changes in the bone marrow sinusoids • Decreased hydrodynamic shear • Loss of hydrostatic pressure gradient mG 1 G

14. Countermeasures for bone loss • Resistive Exercise • Loading • Nutrition • Bisphosphonates

15. Muscle • Disuse Atrophy • Most locomotion achieved with the upper body • No load • No position based use and deployment of muscle activity akin to 1G environment • Unusual uses of selected muscle groups • Countermeasures • Exercise, exercise, exercise • Before, during, and after the mission

16. Physical Challenges Gravity Acceleration Earth Launch up to 3 g boost phase (8min); TMI (min) 0 1 g to 0 g Mars Landing 3-5 g aerobraking (min); parachute braking (30s); powered descent(30s) Mars Surface 1/3 g 18 months Mars Launch TBD g boost phase (min); TEI (min) 22-24 months 1/3 g to 0 g Earth Landing 3-5 g aerobraking (min); parachute braking (min) 26-30 months 0 g to 1g Transit 0 g 4-6 months Transit 0 g 4-6 months G-Load Notes Cumulative hypo-g G transition 4-6 months 0 g to 1/3 g TMI: trans-Mars injection TEI: trans-Earth injection

17. Transitions in G levels Physical tolerance of stresses during aerobraking, landing, and launch phases, and strenuous surface activities • Musculo-skeletal atrophy • Inability to perform tasks due to loss of skeletal muscle mass, strength, and/or endurance • Injury of muscle, bone, and connective tissue • Fracture and impaired fracture healing • Renal stone formation • Cardiovascular alterations • Manifestation of serious cardiac dysrhythmias and latent disease • Impaired cardiovascular response to orthostatic stress and to exercise stress • Neurovestibular alterations • Disorientation • Impaired coordination • Impaired cognition

18. Human Behavior and Performance • Issues: • Small group size • Multi-cultural composition • Extended duration • Remote location • High autonomy • High risk (to health and mission) • High visibility (e.g., high pressure to succeed) • Behavior and Performance • Sleep and circadian rhythm problems • Poor psychosocial adaptation • Neurobehavioral dysfunction • Human-robotic interface • Episodic cognition problems

19. Human Behavior and Performance • Human intrinsic rhythm = 24.1 + 0.15 hr • synchronization not assured – may require (chronic) intervention? • Synchronization successful (best case): Unknown efficacy in maintaining circadian health • Daylight EVA ops: safety, efficiency • Complicated Earth-based support • Failure to synchronize (worst case): • Crew awake during Mars night every 41 days (40 sols) • Well-rested “night-time” ops vs. fatigued daylight ops • Limited visibility: increased risk of accident, trauma • Radiation minimized: reduced SPE influence at night (?)

20. Clinical Problems • Expected illnesses and problems • Orthopedic and musculoskeletal problems (esp. in hypogravity) • Infectious, hematological, and immune-related diseases • Dermatological, ophthalmologic, and ENT problems • Acute medical emergencies • Wounds, lacerations, and burns • Toxic exposure and acute anaphylaxis • Acute radiation illness • Development and treatment of decompression sickness • Dental, ophthalmologic, and psychiatric • Chronic diseases • Radiation-induced problems • Responses to dust exposure • Presentation or acute manifestation of nascent illness • Medical care systems for prevention, diagnosis or treatment • Difficulty of rehabilitation following landing • Trauma and acute medical problems • Illness and ambulatory health problems • Altered pharmacodynamics and adverse drug reaction

21. Incidence Common (>50%) skin rash, irritation foreign body eye irritation, corneal abrasion headache, backache, congestion gastrointestinal disturbance cut, scrape, bruise musculoskeletal strain, sprain fatigue, sleep disturbance space motion sickness post-landing orthostatic intolerance post-landing neurovestibular symptoms Conceptualization of crew healthcare & exercise facilities Illness and injury during space flight Incidence Uncertain • infectious disease • cardiac dysrhythmia, trauma, burn • toxic exposure • psychological stress, illness • kidney stones • pneumonitis • urinary tract infection • spinal disc disease • unplanned radiation exposure Data from R. Billica, Jan. 8, 1998

22. Projected Rates of Illness or Injury • Based on U.S. and Russian space flight data, U.S. astronaut longitudinal data, and submarine, Antarctic winter-over, and military aviation experience: • Incidence of significant illness or injury is0.06 per person- year • as defined by U.S. standards • requiring emergency room (ER) visit or hospital admission • Subset requiring intensive care (ICU) support is 0.02 person per year Past Experience 0.06 person/year For DRM of 6 crewmembers on a 2½ year mission, expect: • 0.9 persons per mission, or ~one person per mission, to require ER capability • 0.3 persons per mission, or ~once per three missions, to require ICU capability • ~80% require intensive care only 4-5 days • ~20% do not. Mars DRM 0.90 person/mission • Note: Decreased productivity, increased risk while crew reduced by 1-2 (including care-giver) Data from R. Billica, January 1998, and D. Hamilton, June 1998

23. Autonomous Clinical Care • Crew Health Care Facility • non-invasive diagnostic capabilities for medical/surgical care • “smart” systems • non-invasive imaging systems • definitive surgical therapy including robotic surgical assist devices and surgical simulators • blood replacement therapy • laboratory support Telemedicine • preventive health care • diagnostic/therapeutic capabilities from ground-based consultants

24. Mars Surface Stay Requirements Autonomous facilities Crew health care • Radiation Protection • Medical Surgical care • Nutrition - Food Supply • Psychological support • meaningful work • surface science • planetary • biomedical • simulations of Mars launch, trans-Earth injection, and contingencies • progressive debriefs, sample processing, etc. • housekeeping • communications capability Habitat • Maintenance/housekeeping • workshop with HRET capabilities • Exercise supplemental to Mars surface activities • Recreation • Privacy HRET: human-robotic exploration team

25. H uman H ealth & P erformance Risk Elements & Categories Space Medicine • in-flight debilitation, long-term failure to recover, clinical capabilities, and skill retention Medical Care Advanced Life Support • atmosphere, water, thermal control, logistics, waste disposal Environmental Health • atmosphere, water, contaminants Planetary Extra-Vehicular Activity • dust, suit design, serviceability Radiation Effects • carcinogenesis, CNS damage, fertility, sterility, heredity Environment & Technology Human Behavior & Performance Human Performance • psychosocial, workload, sleep

26. H uman H ealth & P erformance Risk Elements & Categories Bone Loss • fractures, renal stones, osteoporosis, drug reactions Cardiovascular Alterations • dysrhythmias, orthostatic intolerance, exercise capacity Food and Nutrition • malnutrition, food spoilage Immunology & Hematology • infection, carcinogenesis, wound healing, allergens, hemodynamics Muscle Alteration • mass, strength, endurance, and atrophy Neurovestibular Adaptations • monitoring and perception errors, postural instability, gaze deficits, fatigue, loss of motivation and concentration Human Health/ Physiology

27. Mars Transit Requirements artwork from Constance Adams and Kris Kennedy for the JSC TransHab Team Facilities must be mostly autonomous (one-way Earth-Mars communications time is 3-22 min.) Health care functions • Nutrition • Exercise • Psychological support • planned activities • entry/landing simulations • housekeeping • refresher training • cruise science (rover operations/site preparation, microgravity, astronomy, and biomedicine) • communications • reliable contact with mission control, family, & friends • Health Care • autonomous care • telemedicine Habitat facilities Exercise & conditioning for Mars surface activities Recreation & privacy Maintenance & housekeeping (including workshop)

28. Conclusions • Mars Design Reference Missionrequires novel technologies that allow human adaptation to: • interplanetary space travel • planetary habitation • The medical and physiological challenges associated with interplanetary space travel will depend upon • mission duration • propulsion system • The integration of human and robotic activities will be a critical determinant of the success of planetary exploration

29. Bed Rest Studies • 6o head tilt down • Remain in bed continually for various time intervals; i.e., 60 days • Mimics many alterations that occur in microgravity due to fluid shift to head and lack of weight bearing lower limbs; i.e., bone loss & muscle atrophy • Often involved in countermeasure testing ESA, WISE

30. NASA Microgravity Analog Cell Culture System Manufactured by Synthecon, Inc.