Bioethics in Space Exploration
The Mercury and Gemini programs were conducted with the primary objective of establishing capabilities required by the Apollo program in order to land man on the Moon. The Mercury program (1961–1963) included seven “experiments,” which were basically limited physiological monitoring that required crew participation. Gemini (1964–1966) included 27 experiments with 20 human subjects conducted over ten spaceflight missions. These limited studies analyzed chromosomal changes, effects on blood volume, cardiopulmonary changes, and bone demineralization. Further studies analyzed visual acuity, assayed body fluids, and determined exercise tolerance. Participation in these studies was not voluntary; it was required as part of mission assignments. The Apollo program (1968–1972) included approximately 123 biomedical evaluations on the 33 human subjects (ten missions), involving 30 investigators. Radiation was assessed in some detail, while other studies were conducted to determine changes in endocrines, exercise response, microbial populations, nutritional status, and clinical health. Participation was mandatory without informed consent.
The Skylab program (1973–1974) was unique in that life sciences experiments were a number one priority for the first time in NASA’s history. Nine crewmen performed 74 experiments on three missions. This high priority on life sciences experiments remains unique to that program. The resulting new knowledge regarding human physiological responses to spaceflight remains unmatched in spaceflight history.
Initiation of Formal Bioethics Committee Within NASA
The term “research” refers to a class of activities designed to develop or contribute to generalizable knowledge. Generalizable knowledge consists of theories, principles, or relationships (or the accumulation of data on which they may be based) that can be corroborated by accepted scientific observation and inference (Levine 1986).
The fact that NASA was conducting and planning future human research required that it develop an IRB. Formal bioethics policies and procedures started with the establishment of the Johnson Space Center (JSC) Institutional Review Board (IRB) known as the Human Research Policy and Procedures Committee (HRPPC) in response to NASA NMI 7100.8 in 1972 (DHHS 1974). The Belmont Report (1979) required updates to NMI 7100.8.
The HRPPC initially published guidelines for investigators, known as the “Red Book” in 1984. NASA and 15 other federal departments adopted the Common Rule (C.F.R. Part 46) in 1991. In 2003, NASA Procedures and Guidelines (NPG 7100.1) replaced NMI 7100.8. The Redbook (2004) has been revised periodically to refine information associated with ethical issues, selection or deselection of astronauts as test subjects, and such things as formalizing data sharing and maintaining subject privacy and confidentiality of data (JSC 20483 Rev. C, 2004).
The JSC HRPPC has been renamed periodically (i.e., Committee for Protection of Human Subjects) but remains essentially an IRB, which is a common entity in all institutions that perform human research. Diverse membership of the JSC IRB includes several individuals with medical and research backgrounds, an attorney, a Protocol Compliance Officer, and astronauts with medical degrees. The astronaut members are essentially “community members” who provide input for their cohort with respect to perceived safety of conducting an experiment in flight and the reasonableness of the research protocol.
Scientific peer review of all research proposals is conducted by NASA Headquarters Peer Review Panels, modeled after those used by the National Institutes of Health. All flight experiments and NASA ground-based experiments that utilize radioisotopes are referred to the Radiation Safety Committee and/or Radioisotope Subcommittee as appropriate for safety screening.
Many important issues must be resolved during the IRB review, including development of a detailed data sharing plan and steps to protect the privacy of medical data. A JSC Management Instruction (JMI 1382.5 – Maintaining Privacy of Biomedical Data) was developed to ensure that research findings did not impact an individual’s flight status. Specifically, no data attributable to an individual are publically released without the consent of that subject. This policy requires sufficient pooling of data to preclude determining an individual’s identity by combining or cross-referencing data. Furthermore, data collected during biomedical research protocols will not be used to determine the aeromedical certification of a crewmember; however, data that indicate a life-threatening condition may require additional medical evaluation to ensure appropriate follow-up for the individual.
Anomalous data are reliably described or measured phenomena that are not consistent with current theories (NAS 2015). Study designs should include a plan for identifying and reporting anomalous data. Possible subject or investigator misconduct and resulting anomalous data must be carefully reviewed.
Moral excellence of human subjects’ research requires minimizing risk to research subjects in study design, conduct, and reporting; strict adherence to requirements of informed consent; responsible management of conflicts of interest of investigators, funders, and sponsoring organizations; and responsible management of conflicts of commitment of investigators, funders, and sponsoring organizations. Conflicts of commitment are conflicts between obligations to protect research subjects and obligations to others than the research subjects. These are difficult to manage responsibly.
Coercion must be avoided during subject selection, when considering flight assignment, and during withdrawal of flight crew subjects. Maintaining privacy and confidentiality remains a challenge because most experiments have relatively small numbers of subjects.
Especially risky protocols often require a Data and Safety Monitoring Board (DSMB).
A DSMB provides independent oversight for scientific, clinical, and ethical integrity.
Enrollment, data completeness, and data validity
Well-defined stopping rules for success in testing primary hypotheses
Well-defined stopping rules and deliberative clinical judgment regarding unacceptable outcomes/subject risk
Adverse events attributable to study participation
An issue worthy of reflection is how to prospectively manage the ethical challenges in NASA’s culture of informal incentives and disincentives to become a research subject. In the present era of constrained budgets, might these ethical challenges become more intense?
All reviews must consider trade-offs between risks and benefits to the subject. In clinical research, as opposed to space research, there may be individual benefits to be accrued. In space research, the individual may not receive a direct benefit while accepting certain risks. Subjects typically participate in multiple protocols during a mission, which complicates risk assessment. Medical capabilities are limited on orbit; there is no nearby “emergency room.” A more subtle issue is that voluntary participation in a flight experiment could reveal previously unknown anomalies that might result in disqualification from future flights.
Three outcomes are possible following the completion of IRB reviews: An experiment is approved, approved with recommendations, or disapproved.
Substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data.
Drafting the article or revising it critically for important intellectual content.
Final approval of the version to be published.
Authors should meet all three conditions.
Multicultural research missions introduce additional considerations. Numerous multinational life sciences payloads have flown on NASA spacecraft. Simpler studies were performed on the space shuttle middeck, where experiments were packaged into lockers. Complex studies were conducted within the Spacelab module, which was essentially a large laboratory for spaceflight. Spacelab-1 flew in 1983 and began an era that included nine missions, culminating with the Neurolab mission in 1998. Crew selection for these missions was handled in a unique manner. The astronaut office proposed a group of potential subjects who expressed interest in the science to be performed on a particular Spacelab mission. This “self-selection” process ensured excellent voluntary participation as test subjects.
Spacelab experiments were jointly selected by NASA and international space agencies that participated in a given mission (i.e., European Space Agency (ESA), Japanese National Space Agency (JAXA), or the Canadian Space Agency (CSA)). Several Spacelab crews included international payload specialists. Experiment success was ultimately due to the combined efforts of flight surgeons, principal investigators, and support personnel who worked as a team to implement them.
Extended Duration Orbiter Medical Project (1989–1995)
Biomedical research conducted during the EDOMP provided information that was essential to safely increase space shuttle missions from approximately 4–6 days to 20 days in duration. The operational nature of this project encouraged broad astronaut participation. Over 30 experiments designated as Detailed Supplementary Objectives (DSOs) were performed on 42 missions. Subjects typically participated in multiple DSOs (i.e., four to seven studies) on a mission. All DSOs were reviewed and approved by the JSC IRB. A physician astronaut actively participated as one of the EDOMP managers. The head of the Flight Medicine Clinic was intimately involved in prioritizing experiment manifests to ensure operational relevance of the studies.
Participation in the Russian Mir Program
The Russian Space Agency (RSA) invited NASA to participate in their program during the period 1994–1998. Seven astronauts flew long-duration Mir station missions. The NASA IRB reviewed and approved all human research studies. Additional studies were performed by astronauts on the seven short-duration shuttle flights that ferried crew to and from the Mir.
International Space Station (ISS) Research
International Space Station began by establishing an intergovernmental partnership between NASA, RSA, ESA, JAXA, and CSA. Onset of ISS development made it necessary to formulate a multinational IRB with equal participation by the partner agencies, hence the new Human Research Multilateral Review Board (HRMRB).
The HRMRB was established following 3 years of international meetings that were necessary to standardize policies and procedures for human research. Participants included bioethicists and flight surgeons from each international partner. The HRMRB was chartered just prior to the initial ISS mission in 2000.
Quarterly HRMRB meetings are held via video teleconferencing.
All HRMRB decisions are reached by consensus. Chairmanship is occasionally rotated among the partner organizations, but NASA typically chairs the meetings.
Significant differences exist between policies and practices exercised by the RSA and the broader biomedical research community. The RSA prefers not to perform invasive studies in space unless an MD is onboard as a crewman. Russian science and flight medical operations are highly intertwined, with the result that medical studies and data collected during their compulsory medical monitoring are similar to what NASA considers to be elective research, which would require HRMRB approval and voluntary participation. The ethics of cosmonaut compensation had to be resolved, since a significant portion of their total compensation comes from their participation as test subjects for biomedical experiments. American policies consider this type of payment to be coercive.
Exploration Missions and Unique Ethical Issues
Total available spacecraft volume will be very restricted. Resupply will not be possible once the spacecraft has departed Earth orbit.
Long-duration missions beyond Earth orbit, space colony habitation, or interplanetary travel will create special circumstances for which ethical standards developed for terrestrial medical care and research may be inadequate for astronauts. These ethical standards may require reevaluation (Institute of Medicine 2001).
Astronauts will live and work in space environments for longer and longer periods of time. The longer the environment is inhabited, the more it will come to resemble a workplace rather than a temporary spacecraft. Issues of occupational health and safety will arise with increasing frequency. In the occupational health context, the confidentiality of the individual’s medical information can be judged to be less important when balanced against the safety of the workplace for all “workers” (i.e., astronauts) (Institute of Medicine 2001).
Limited doctor–patient confidentiality also exists in dual-agency settings in which the clinician has a duty both to the organization and to the individual. Examples of dual-agency settings include the military, prisons, schools, and other government agencies (Institute of Medicine 2001).
A long-duration space mission is, among other things, a traveling space laboratory where experiments, including self-experimentation, are performed. Astronauts in such a traveling laboratory play many roles: a single individual may be both a scientist and a subject, an explorer and a worker, and a doctor and a patient. These complicated and multiple roles require rethinking the usual boundaries of medical confidentiality (Institute of Medicine 2001).
Preflight informed consent briefings for mission participants should provide a detailed understanding of mission risks.
- Appropriate medical policies must be formalized to deal with known issues including:
Onboard medical resources will be strictly limited (i.e., stowage will permit only limited quantities of medications, bandages, disinfectants, etc.).
A requirement for a crew medical officer(s) seems mandatory. The present concept for the Crew Exploration Vehicle (CEV) accommodates six crewmen.
There will be no possibility of immediate return/evacuation. Failure of critical subsystems (i.e., environmental control) could mean loss of crew.
Communication time delays will complicate emergency responses and telemedicine assistance from the Earth.
- Additional anticipated issues:
Inflight changes in crew health status
Radiation effects (spacecraft can provide only limited shielding from radiation encountered in deep space)
Nutritional deficiencies (unknown causes)
Evolving psychological stress (a highly significant problem as shown in numerous Earth analog studies)
Strict limitations on crew physical exercise equipment due to space, power, stowage, etc. (exploration craft as currently conceived cannot accommodate large resistive exercise devices or treadmills)
- Medical screening criteria
- Genomic screening to eliminate high-risk issues has many ethical issues associated with it:
Genome sequences cannot be treated as de-identified.
Genomic sequences of human research subjects should only be accessible to researchers with legitimate research interests behind appropriate firewalls with strict provisions to protect privacy.
- Consideration must be given to categories of genomic results to be returned to research subjects:
- Risk assessment
Early vs. later onset
Variants of unknown clinical significance
Should mandatory appendectomies be required to eliminate risk for acute appendicitis during the mission?
Should mandatory blood group compatibility be required to provide a blood source for limited transfusion during the mission?
Is it reasonable (ethically acceptable) to mandate a single gender crew to minimize complications of crew cohesion and performance?
Fortunately, the approaches initiated by NASA during the 1970s to establish an IRB have proven successful. No life-threatening incident has occurred during the performance of IRB-approved research on the Space Shuttle Program, NASA-Mir, or the ISS. This result is a testimony to the combined efforts of IRB members, flight surgeons, and biomedical investigators.
- Department of Health and Human Services (1974) Code of federal regulations—title 45 (part 46) protection of human subjectsGoogle Scholar
- Institute of Medicine (2001) Safe passage, astronaut care for exploration missions. National Academy Press, Washington, DCGoogle Scholar
- JSC Committee for the Protection of Human Subjects Guidelines for Investigators Proposing Human Research for Space Flight and Related Investigations (2004) JSC 20483, Revision CGoogle Scholar
- Levine RJ (1986) Ethics and regulation of clinical research. Yale University Press, New Haven/LondonGoogle Scholar
- National Academy of Sciences, National Academy of Engineering, and Institute of Medicine (2015) On being a scientist. A guide to responsible conduct in research. National Academy Press, Washington, DCGoogle Scholar