Human Mission to Mars:

Implications for Biotechnology

Jeffrey P. Sutton, M.D., Ph.D.

CEO, National Space Biomedical Research Institute May 16, 2016

• First mission – Oct 1960 – Soviet Union – flyby – launch failure

• 4 subsequent missions - 1960-1962 – Soviet Union – 3 flyby and 1

lander – 3 launch failures (failed to orbit, disintegration in LEO,

never left LEO), 1 spacecraft failure (comm loss)

• Nov 1964 - U.S. Mariner 3 – flyby - launch failure

Mariner 4 – flyby – success

- Soviet Union flyby – spacecraft failure

Robotic Missions to Mars

Landing on Mars

Viking 1 Lander

• 1969-1973 U.S. Mariners 7, 8 – flyby – successes

Mariner 8 – orbiter – launch failure

Mariner 9 – orbiter – success

Soviet Union 2 orbiters – mostly successful

(dust storms)

4 orbiters – launch failures

May 1971 – Mars 3 lander - partialsuccess

contact lost at 14.5 sec

4 other landers - spacecraft failures

1 rover – spacecraft failure

• 1975 U.S. Viking 1 – orbiter – success – 1385 orbits

Viking 1 – lander – success – 2245 sols

Viking 2 – orbiter – success – 700 orbits

Viking 2 – lander – success – 1281 sols

• 1988-1992 Soviet Union Fobos 1, 2 – spacecraft failures

U.S. Mars Observer – spacecraft failure

• 1996-1999 U.S. Mars Global Surveyor – orbiter – success

Mars Pathfinder – lander – success

Sojourner – rover – success

3 spacecraft failures

Russia, Japan – launch

and spacecraft failures

• 2003-2007 U.S., Europe – successful flybys and orbiters

U.S. – successful landers, rovers (Spirit, Opportunity)

Europe – Lander failure (Beagle 2)

Exploring Mars

• 2011- U.S. successful orbiter and rover (Curiosity)

India successful orbiter

Russia

– orbiter, Phobos sample – spacecraft failure, loss of

Chinese orbiter as part of mission

• En route Europe, Russia ExoMars Trace Gas Orbiter

lander

Future Missions to Mars

• Successful and failed attempts

• Prior exploration attempts inform subsequent missions

• Failures continue to occur

• Human missions add enormous challenges

• We are destined to explore

Space Exploration is Difficult

Example Human Missions to Mars

Long-Stay Mission

Example Human Missions to Mars

Short-Stay Mission

• Total spaceflight time: 132 crew-years

• Number of people who have flown in orbit: 544

• Cumulative spaceflight record:

Gennadi Padalka 878.5 days

• Single mission spaceflight record:

Valeri Polyakov 437.7 days

Human Space Experience as of May 2016

• Space environment

Reduced gravity

Radiation

Vacuum

Debris

• Space craft environment

Vehicle integrity

Life support

Isolation and confinement

Noise

• Space mission environment

Circadian rhythm, crew schedule, workload

Mission, payload and science hazards

Hazards of Human Spaceflight

Space Radiation

• #1 risk to astronaut health beyond low Earth orbit

Chancellor, Scott,

Sutton. Life 2014

ISS post-flight complex

chromosomal aberrations

Cucinotta et al. Radiation

Research 2008

Health Effects Due to Space Radiation Exposure

Physiological Adaptation

to Space Travel and

Biomedical Risks

Bone Mineral Density

Regional heterogeneity and differential susceptibility among astronauts

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TrochanterLoss0=7.8%Recovery Half-life=255 d

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PelvisLoss0=7.7% Recovery Half-life=97 d

Femoral NeckLoss0=6.8%Recovery Half-life=211 d

Bone Mineral Density Recovery

Risk for Renal Stones

• Astronauts are at an increased risk for developing calcium

oxalate, calcium phosphate and uric acid stones

associated with space missions

• Active U.S. astronauts have developed renal stones

• Crew’s urine typically becomes supersaturated with stone-

forming salts as a result of decreased urine output and pH,

and increased calcium excretion

• Stones can lead to urine obstruction, and if not treated,

acute renal failure, infection and sepsis

• Potassium citrate supplementation can lower risk for

certain stones (Ca oxal and uric acid stones, but not Ca

phosph stones)

Whitson PA, et al. Journal of Urology. 2009;182:2490-2496

• 2 Concerns and 31 Risks based on current evidence

• Path to Risk Reduction

Human Research Roadmap

Path to Risk Reduction

Human Research Roadmap

Planetary Design Reference Mission

Concerns (2) Unpredict med effects Intervertebral disc damage

Risks (31) CNS radiation Acute radiation syndrome

Psychiatric probs Dust exposure Host-microorg interactions

Altered immunity Med conditions Incompatible vehicle design

Bone changes Cardiac arrythmias Degen effects of radiation

Decompression probs Early osteoporosis Impaired flight control

Reduced muscle Human/robotic interact Human/computer interaction

Inadeq mission design Inadequate nutrition Ineffective meds

Injury from EVA Injury from loads Orthostatic intolerance

Inadequate teaming Inadequate food sys Sleep loss, circadian desyn

Training deficiencies Rad carcinogenesis Reduced physical perform

Renal stone formation Intracranial HT/vis

Human Research Roadmap

Planetary Design Reference Mission

Concerns (2) Unpredict med effects Intervertebral disc damage

Risks (31) CNS radiation Acute radiation syndrome

Psychiatric probs Dust exposure Host-microorg interactions

Altered immunity Med conditions Incompatible vehicle design

Bone changes Cardiac arrythmias Degen effects of radiation

Decompression probs Early osteoporosis Impaired flight control

Reduced muscle Human/robotic interact Human/computer interaction

Inadeq mission design Inadequate nutrition Ineffective meds

Injury from EVA Injury from loads Orthostatic intolerance

Inadequate teaming Inadequate food sys Sleep loss, circadian desyn

Training deficiencies Rad carcinogenesis Reduced physical perform

Renal stone formation Intracranial HT/vis

Concern of Clinically Relevant Unpredicted

Effects of Medication

Gaps

• We do not know the extent to which spaceflight alters

pharmacokinetics

Animal studies show spaceflight-associated changes (e.g., decreased

cytochrome P450) could alter pharmacokinetics but paucity and variability of

data preclude definitive conclusion

• We do not know the extent to which spaceflight alters

pharmacodynamics

• We do not know the extent to which current antimicrobial therapies

are effective against microbes that have been altered by spaceflight

Medication Use by U.S.

Crewmembers on the

International Space Station

Wotring VE. FASEB J. 2015

Nov;29(11):4417-23

Risk of Ineffective or Toxic Medications

Due to Long Term Storage

Gaps

• We do not know how

medications are used during

spaceflight

• We do not know how long

medications may be safe and

effective beyond their

expiration dates

Risk of Adverse Health Outcomes and Decrements in

Performance due to Inflight Medical Conditions

22 Gaps

Parabolic Flight for Analog Studies

• Unique, national translational research and development program

– Product-driven focus on countermeasures

– Hybrid NIH/DOD model

– Multidisciplinary distributed teams

– Aligned with NASA goals

– Virtual institute Enhanced by

core facility

– Cost effective

National Space Biomedical Research Institute

• Established in 1997

• Unparalleled intellectual and institutional resources, leveraging the

nation’s investment in biomedical research and development, are

brought to bear on solving problems for NASA

– High caliber and productivity of investigators from ~70 institutions

INTEGRATED RESEARCH TEAMS

Cardiovascular Alterations

Human Factors and Performance

Musculoskeletal Alterations

Neurobehavioral and Psychosocial Factors

Radiation Effects

Sensorimotor Adaptation

Smart Medical Systems and Technology

USER PANEL

INDUSTRY FORUM

EDUCATION PROGRAMS

NSBRI Components

• Advanced Diagnostic Ultrasound in Microgravity

Development of effective training procedures and new medical applications

Ultrasound atlas of human anatomy and physiology in space

First scientific paper ever from space [Radiology 2005;234(2):319-322]

• Earth-based applications

Human performance with real-time imaging

Global health care

NSBRI Achievements

Ensuring Health in Space, Benefiting Life on Earth

Introducing Astro-Omics as a First Step to

Deploying Precision Medicine in Space

Scott Kelly – ISS for one year

Mark Kelly – Earth control

Telomere Length

Bailey

DNA Mutations

Feinberg

DNA Hydroxy-methylation

Mason

Chromatin

Feinberg

large/small RNA

& RNA Methylation

Mason

Proteomics

Lee/Rana

Antibodies

Mignot/Snyder

Cytokines

Mignot

DNA Methylation

Feinberg & Mason

B-cells / T-cells

Mignot

Targeted and Global Metabolomics

Lee/Rana, Mignot/Snyder & Smith

Microbiome

TurekCognition

Basner

Vasculature

Lee

• MARS 500 Project – first high-fidelity

simulation of a 520-day crewed

mission to Mars

• NASA restricted in its participation

• Demonstration of differential vulnerability

in crew members, with the majority

experiencing sleep-wake disturbances

International Collaborations

• Newly recognized syndrome with 4 Gaps

• #1 risk to astronaut health in low Earth orbit

• 70% of International Space Station astronauts affected

• Many hypotheses

Prevailing hypothesis - elevated intracranial pressure during spaceflight

contributes to the visual alterations and ophthalmological findings

Normal Globe Flat Globe

Globe Flattening

Increased Optic Nerve Sheath Diameter

Optic Disc Edema

Hyperopic Shifts

Up to +1.75

diopters

Choroidal Folds

+ICP?

“Cotton wool” Spots

Scotoma

Risk of Spaceflight-induced Intracranial

Hypertension/Visual Alterations

Non-invasive Measurement of

Intracranial Pressure – Vittamed Device

Integrated Ultrasound Imaging and

Therapeutics for Non-invasive Surgery

Ultrasonic propulsion of renal stones

using acoustic radiation force

generated by a series of 50 ms, 2 MHz

ultrasound pulses

High intensity focused

ultrasound for non-invasive

hemostasis

• Established in 2008

• First time space medicine codified at the level of an academic

center or department in a university or medical school

• Academic home to all physician astronauts worldwide

• First four-year Space Medicine Track

inspiring and training the next generation

• Cutting-edge research and laboratories

BCM Center in Space Medicine

XMed3D printing for

exploration medicine

Autonomous care

capabilities

• Fuel for roundtrip – methane and oxygen can be produced using

Martian H20 (ice) and atmospheric CO2

• Other propulsion (e.g., ion, nuclear)

• Continuous source of food (e.g., plant farm)

• Water recovery

• Oxygen generation

• Habitat construction and sustainability

• Mars spacesuit

• Rover

• Energy – solar, radioisotope thermoelectric generator

• Cost

• Geopolitical factors

Beyond the Path for Risk Reduction

for a Human Mission to Mars

The Future is Happening Here and Now