The committee was asked to assess the evidence base in space-related clinical research and astronaut health care (see the letter from the NASA administrator at the end of this appendix). It began by examining traditional sources of data and information, including research reports in peer-reviewed journals, conference proceedings, prior National Research Council reports, and National Aeronautics and Space Administration (NASA) publications. The committee also consulted with numerous experts in areas that included medical informatics, bone metabolism, dental disease, and the effects on health and behavior of living and working for long periods of time under extreme and remote conditions.

The single greatest source of data and information was NASA. Agency officials briefed committee members during the committee’s first meeting in Washington, D.C., in October 1999. They were Arnauld E.Nicogossian, associate director for Life and Microgravity Sciences; David Williams, director, Life Sciences Directorate; and Richard Williams, deputy chief medical officer. Then, in February 2000, committee members visited NASA’s Johnson Space Center (JSC) in Houston, Texas, for an additional 2 days of briefings by NASA staff.

Other highlights of the committee’s information-gathering efforts are presented in the pages that follow. Altogether, the committee held six public meetings during which it collected information and interacted with invited

experts and interested members of the public. Two of these meetings included workshops during which invited experts made presentations on topics of special interest. The committee gratefully acknowledges the interest and generous assistance of all who aided in its information-gathering efforts.

From February 22 to 24, 2000, committee members visited JSC in Houston, Texas, for intensive briefings by NASA administrators, scientists, and clinicians. The JSC faculty made 15 presentations to the full Institute of Medicine (IOM) committee, as well as 20 additional presentations to the committee’s three working groups on medical-surgical priorities, health care, and behavioral, social, and cultural issues.

The subject matter covered during the 2-day visit included selection and retention of astronauts, biological effects of space radiation, telemedicine, family supports, postflight rehabilitation, evaluation and validation of countermeasures, risk management, efforts to develop artificial gravity, and many others. The committee’s visit also included a luncheon discussion and sampling of food provided to astronauts during space travel and visits to space shuttle training facilities, the Flight Medicine Clinic, the Sonny Carter Neutral Buoyancy Facility, and mock-ups of portions of the International Space Station (ISS).

Agenda

NASA Johnson Space Center, Houston, Texas,

February 22–24, 2000

Welcome to Johnson Space Center

David Williams

Opening Remarks and Introduction of IOM Committee

John R.Ball

Overview of Space and Life Sciences

David Williams

Space Shuttle Clinical Experience

Roger Billica

Phase 1 Mir, Clinical Experience

Analog Environment, Clinical Experience

Longitudinal Study of Astronaut Health

An Evidence-Based Approach for Space Medicine

Ethical Issues in Space Flight

Behavioral Health and Performance

Flight Medicine Clinic

International Space Station (ISS) Mock-ups

Pathophysiology of Disease in Microgravity

Pharmacotherapeutics in Microgravity and Clinical Concerns

Biological Effects of Space Radiation

Resuscitation and Stabilization in Microgravity

Astronaut Selection and Retention—Medical Approach

Smith Johnston and Roger Billica

Problem-Oriented Approach to Space Medicine

Postflight Rehabilitation

Beth Shepherd

Countermeasure Evaluation and Validation

William Paloski

Wednesday, February 23, 2000

Risk Management

Roger Billica

Countermeasure Evaluation: Extended-Duration Orbiter Medical Program

Charles Sawin

Critical Path for Countermeasure Development

John Charles

Clinical Care Capability Program

Craig Fischer

National Space Biomedical Research Institute and Countermeasure Development

Bobby Alford and Larry Young

Bioastronautics

David Williams

Food Lab, Food, and Nutrition

Helen Lane

Mission Architecture for Exploration-Class Missions

John Charles

Artificial Gravity

Sam Pool

Special Topics in Behavioral Health and Performance

National and International Strategies for Space Medicine

International Space Station (ISS) Activities

Space Medicine and Space Exploration

David Dawson and Roger Billica

Integration of Ground-Based Medical Care

Star City (Russia) and Medical Care

Roger Billica

Emergency Medical Service Support for Shuttle Launch and Landing

Craig Fischer and David Dawson

Benefits to Terrestrial Health Care

David Williams

Members of the committee met with Capt. James Weatherbee and Dr. Steven Hawley of the Flight Control Operations Directorate and with Dr. Albert Holland of the Life Sciences Directorate on May 11, 2000, to obtain information regarding the process for selection of astronauts for space missions and with Drs. David Williams and Bobby Alford on June 22, 2000, to discuss NASA’s organizational structure and the role of the National Space Biomedical Research Institute in reference to space medicine.

The committee held an invitational workshop, Space Dentistry: Maintaining Astronauts’ Oral Health on Long Missions, in Washington, D.C., on April 17, 2000. In planning the workshop, the committee solicited program ideas and the names of potential speakers from the dental practice and dental research communities. At the committee’s request, the American Dental Association (ADA) helped secure a moderator for the workshop. The committee invited 20 dental researchers, dental practitioners, and materials scientists to attend the workshop and contribute to the information-gathering session. The workshop program and list of participants appear below.

The purpose of the workshop was to examine a variety of oral health issues in the context of space travel beyond Earth orbit. The committee was interested in learning of recent developments and whether dental disease or dental trauma, or both, are likely to emerge as problems on long missions. If they are, the committee wanted to know the available treatment options. The committee also wanted to hear updates on caries prevention; the linkage between diet and dental disease; oral hygiene in space; and progress on developing instruments, materials, and equipment suitable for use in a cramped and weightless environment.

Space Dentistry:

Maintaining Astronauts’ Oral Health on Long Missions

Monday, April 17, 2000, Institute of Medicine

Agenda

Welcome and Opening Remarks

Introduction

Effects of Hypogravity on Calcified Tissue

Dental Caries: Initiation, Progression, and Prevention

Managing Dental Trauma in Microgravity

Atraumatic Restorative Treatment (ART): A Potentially Useful Approach to Managing Dental Lesions in Space

Open Discussion

Acknowledgments

Workshop Guests

Dr. A.David Brandling-Bennett

Pan American Health Organization

Col. Gerry Caron

Office of the Surgeon General, U.S. Air Force

Dr. Robert J. “Skip” Collins

International and American Associations for Dental Research

Dr. Ray Dionne

National Institute of Dental and Craniofacial Research

Dr. Fred Eichmiller

American Dental Association Health Foundation, Paffenbarger Research Center

Dr. Isabel Garcia

National Institute of Dental and Craniofacial Research

Ms. Elise Handelman

Occupational Safety and Health Administration

Dr. Joseph G.Handelman

Private Practice, Annapolis, Maryland

Dr. Herschel Horowitz

National Institute of Dental and Craniofacial Research

Mr. Jonathan McLeod

American Dental Association

Dr. David Metzler

American Academy of Periodontology

Mr. Trevor Milner

Pan American Health Organization

Dr. Russell B.Rayman

Aerospace Medical Association

Dr. Gordon Rovelstad

American College of Dentistry

Dr. Gary Schumacher

ADA Health Foundation, Paffenbarger Research Center

Panel Discussion

Erik Johnson Conference Center, The National Academies,

Woods Hole, Massahcusetts,

July 27, 2000

In 30 years in space, only a handful of health care professionals have found themselves in a position to observe directly the symptoms of ill health in microgravity and to treat patients (including themselves) in a spacecraft. They are veteran astronauts who also happen to be physicians. One of them, Bernard A.Harris, M.D., is a member of the IOM committee that prepared this report. A retired astronaut and veteran of two shuttle missions, Dr. Harris helped organize a panel of one current and four former physician-astronauts. The purpose was to give committee members an opportunity to discuss firsthand issues of astronaut health and care during a space mission from the perspectives of astronauts who are also physicians.

Each of the physician-astronauts discussed with the committee their views on health care priorities for extended missions as well as a “top 10” list of astronaut health issues.

Bernard A.Harris, Jr., M.D., Moderator

SPACEHAB, Inc.

Houston, Texas

F.Andrew (Drew) Gaffney, M.D.

Vanderbilt University Medical Center

Chiaki Mukai, M.D.

Japanese Space Agency

Rhea Seddon, M.D.

Vanderbilt University Medical Center

Norman Thagard, M.D.

Florida State University

J.Erik Jonsson Woods Hole Center, The National Academies, Woods Hole, Massachusetts, July 28, 2000

The workshop covered planning for missions; evaluation of treatment priorities; selection of personnel; crew training; and selection of supplies and equipment for long-duration submerged submarine, Antarctic, and North Sea and North Slope environments

Invited discussants were as follows:

Professor David H.Elliott, OBE, D. Phil.

Commander Wayne G.Horn, M.D., USN

Desmond J.Lugg, M.D.

Harry Mahar, Ph.D.

Antarctic Sciences Section, National Science Foundation

Lawrence A.Palinkas, Ph.D.

Department of Family and Preventive Medicine

University of California at San Diego

Space may be the ultimate hostile environment, and astronauts traverse it in isolation and confinement. Protection of their well-being and preservation of their efficiency are of paramount concern during space missions. Delivery of medical care is rendered difficult, however, by weightlessness, limited equipment (because of payload restrictions), and the lack of information about the short- and long-term effects of exposure of humans to zero gravity. Experiments and data collection in studies with astronauts has been hampered by the small numbers of participants, the short durations of the studies, and the lack of available pre- and postflight data. There are numerous indications that some of the variability in findings may be due to genetic differences, but so far, no genetic studies have been undertaken.

At present, there is no way of simulating zero gravity for prolonged periods on Earth, but there is the opportunity to study small and large populations of volunteers in isolated, confined, and sometimes hostile environments. The planning procedures, personnel screening and training procedures, and equipment selected and used in various situations in analog environments can be used to prepare for long-duration space missions beyond Earth orbit, as well as to study common effects on physiology and behavior. Such studies may increase understanding of the changes produced by factors independent of the effects of zero gravity, such as loss of the normal diurnal cycle, sleep disorders, immune system changes, and changes in calcium metabolism. Health care problems in analog environments that appear to be most relevant for the Committee on Creating a Vision for Space Medicine During Travel Beyond Earth Orbit are the Antarctic experience, extended underwater submarine missions, and remote oil exploration activities.

Australian National Antarctic Research Expeditions (ANARE) has been collecting and analyzing data for more than 40 years under the guidance of

Desmond Lugg, and numerous publications on those experiences are available. Since 1993, ANARE has been engaged in cooperative international research and has recently forged alliances with NASA researchers. ANARE’s organization, length of experience, ability to counter the problem of studies with small numbers of participants, and control of the isolation, confinement, and stress inherent in its experimental community make ANARE a valuable resource. ANARE has identified a number of health care issues that may be of interest to the committee.

It has long been assumed that stress causes alterations in the immune system. Studies with volunteers in confinement in Antarctica show an impaired immune response, an almost 50 percent reduction in T-cell proliferation after a challenge with phytohemagglutinin, and increased shedding of herpesviruses and Epstein-Barr virus. Researchers at Baylor University also found increased shedding of viruses in astronauts, but they noted more shedding before spaceflight, leading them to conclude that there was greater stress before flight than during or after the flight. ANARE noted a difference in immune impairment between individuals on two Antarctic stations, with the individuals at the more isolated station (with less communication and evacuation potential) showing a higher incidence of defects. Impairment of neutrophil function has also been detected in deep-sea divers. To date, none of the members of these isolated groups have suffered any recognizable immune-related infectious disease problems.

Alterations in vitamin D metabolism related to the absence of ultraviolet type B (UV-B) radiation have been noted in submariners as well as in groups who have spent the winter in Antarctica, but there is no evidence of decreased bone mass over experimental periods up to 1 year. There has been a greater than expected incidence of renal calculi among members of the ANARE group, but not among submariners, who were observed over a much shorter period. Both groups are sufficiently large to support controlled clinical studies.

Numerous observations of changes in hormone levels have been made, with documented changes in the pituitary-thyroid axis, named the polar T3 syndrome. Changes in parathyroid hormone (PTH) levels have been noted during space travel and may be related to bone mineral density loss. Furthermore, Antarctica, like space beyond Earth orbit, lacks an ozone layer to filter UV radiation; this may offer another avenue for research.

One would expect behavioral and psychiatric problems to be significant in the isolation and confinement of a 30-month mission. Hence, the ability to study the volunteers before, during, and after a winter in Antarctica would

be valuable. Some studies have been done and published by ANARE (by J. A.Wood, D.J.Lugg and colleagues) and by Lawrence Palinkas at the Naval Health Research Center, among others. Although sleep disorders, anxiety, depression, irritability, fatigue, and several other symptoms are common, they very rarely impair function with any significance and are often transient. High levels of individual motivation and careful screening may be responsible for the minimization of symptoms. There is considerable variation in individual behavioral responses, with minimal impairment of group function. The implications of these and future studies are of great importance to long-duration space missions.

Submariners have been confined below the ocean’s surface for periods of up to 3 months or more. Environmental changes include the absence of sunlight (and UV-B radiation), increased carbon dioxide levels (two to six times the normal level) with accompanying mild respiratory acidosis, and dietary restrictions. Dlugos and colleagues (Dlugos et al., 1995) found a decrease in the levels of urinary calcium excretion and increased PTH levels, along with other changes that seemed to protect against the formation of renal calculi. However, they caution that individuals who were known to form renal calculi were rejected from the missions, which may limit the comparability of submarine missions to spaceflight. Further data must be collected to assess the effect of elevated PTH levels on bone resorption, since no clinical effect was noted. There are many other areas in which controlled clinical studies will provide valuable information for space medicine.

Finally, experience in another analog environment, diving in the North Sea, is unique in that it is directed and financed by commercial organizations. Occupational health among divers is of paramount importance, and David Elliott and coworkers are experts on compression and decompression injuries and physiology, as well as immersion problems. The rigorous screening of divers is appropriate for their tasks, and the planning and delivery of medical care have been given high priorities.

The patterns of illness and injury among individuals in these diverse analog environments show considerable similarities, with some variations caused by methods of reporting, the durations of the missions, and the completeness of the medical studies. Roger Billica, chief of NASA’s Medical Operations Branch, has noted that the Antarctic experience bears the closest resemblance to spaceflight, and emphasis will be placed on using data and information from that experience to prepare for flight beyond Earth orbit.

The examples of studies in analog environments noted above provide

only a portion of the information already available, and there is the potential to acquire much more. Further cooperative studies can be done with greater safety, control, and follow-up than those available for spaceflight studies alone.

It was a great pleasure to meet with you at the Baylor College of Medicine in November. I am very pleased with the progress of the STS-88 mission, marking the beginning of construction of the International Space Station (ISS). We are underway to establish a permanent human presence in low-Earth orbit. There remains, however, a multitude of questions to be answered and problems to be solved for our explorers and international crews to safely live and work in the extreme environment of space beyond low-earth orbit, using the ISS as a research platform to prepare for the exploration of the solar system.

Space is arguably the most extreme environment that humans have ever entered. Prolonged presence in microgravity results in a number of adaptations that may not be completely reversible. Space crews are isolated, and spacecrafts provide limited room in which to live and work. Future exploration of the solar system also requires crews to land on other planets (such as Mars) and perhaps establish colonies on the Moon. Currently, radiation protection in deep space missions is an unsolved issue, and the threat of dysbarism is ever present, especially during extravehicular activities.

There are notable efforts underway to develop physiological countermeasures to maintain crew health and allow a rapid and uneventful readaptation upon return to Earth. The extramural Principal Investigators, funded under the NASA National Research Announcement grants system and the National Space Biomedical Research Institute, are two extremely talented groups that are addressing these issues. Efforts to develop a more capable medical-care delivery system in space, however, have largely been internal to NASA. We have traditionally depended on a preventive approach to maintain health, reflected in strict astronaut-selection standards and close monitoring of astronaut-health status. This has proven adequate for short-duration flight, and our crew has been essentially free of major illness during flight. This may not be the case in the future.

Your assistance is requested in evaluating our current medical-care system and recommending the type of infrastructure we will need to develop to support long-duration missions, including interplanetary travel in which timely evacuation of crew members will not be an option. Medical-care-provider training, specialty mix, nonmedical crewmember skills, use of advanced technology, surgical/intensive care capability in space, rehabilitation approaches to cope with exposures to gravitational fields following exposures to microgravity, psychological/human-factors challenges and use of robotics for health monitoring, education, and possible surgery are examples of the types of issues we would like you to address. We would also like you to consider the use of analog environments, such as remote Antarctic stations, for training and research. Ethical considerations in the face of limited medical-care capability are also important issues that need examination.

You and your colleagues will surely find this an interesting and stimulating project in which your efforts will prove critical to the overall success of long-duration human space flight. I have designated Dr. Arnauld E.Nicogossian, Associate Administrator for Life and Microgravity Sciences and Applications, as the NASA contact point in this matter. We look forward to engaging the Institute of Medicine in this important task.

Sincerely,

Daniel S. Goldin

Administrator