Acta Astronautica 56 (2005) 883 – 889 www.elsevier.com/locate/actaastro

Accomplishments in bioastronautics research aboard International Space Station John J. Uria,∗ , Cynthia P. Havenb a ISS Payloads Office, NASA Johnson Space Center, Houston, TX 77058, USA b Bioastronautics Office, NASA Johnson Space Center, Houston, TX 77058, USA

Available online 23 March 2005

Abstract The tenth long-duration expedition crew is currently in residence aboard International Space Station (ISS), continuing a permanent human presence in space that began in October 2000. During that time, expedition crews have been operators and subjects for 18 Human Life Sciences investigations, to gain a better understanding of the effects of long-duration space flight on the crewmembers and of the environment in which they live. Investigations have been conducted to study: the radiation environment in the station as well as during extravehicular activity (EVA); bone demineralization and muscle deconditioning; changes in neuromuscular reflexes; muscle forces and postflight mobility; causes and possible treatment of postflight orthostatic intolerance; risk of developing kidney stones; changes in pulmonary function caused by long-duration flight as well as EVA; crew and crew–ground interactions; changes in immune function, and evaluation of imaging techniques. The experiment mix has included some conducted in flight aboard ISS as well as several which collected data only preand postflight. The conduct of these investigations has been facilitated by the Human Research Facility (HRF). HRF Rack 1 became the first research rack on ISS when it was installed in the US laboratory module Destiny in March 2001. The rack provides a core set of experiment hardware to support investigations, as well as power, data and commanding capability, and stowage. The second HRF rack, to complement the first with additional hardware and stowage capability, will be launched once Shuttle flights resume. Future years will see additional capability to conduct human research on ISS as International Partner modules and facility racks are added to ISS. Crew availability, both as a subject count and time, will remain a major challenge to maximizing the science return from the bioastronautics research program. © 2005 Published by Elsevier Ltd.

1. Introduction The International Space Station (ISS) is a unique platform for conducting research in a variety of disciplines; to better understand the role gravity or its ∗ Corresponding author.

E-mail address: [email protected] (J.J. Uri). 0094-5765/$ - see front matter © 2005 Published by Elsevier Ltd. doi:10.1016/j.actaastro.2005.01.014

absence, plays in biological and physical processes. As a long-duration laboratory, it enables research that was not possible on earlier platforms. In particular, ISS is ideally suited for studying the effects of long-duration space flight on humans, important for perfecting counter-measures to the deleterious effects to ensure crew safety and to enable exploration missions.

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2. ISS Assembly and Operations Construction of ISS began in late 1998, with the launch of the Russian module Zarya. Since that time, 47 flights of Russian and American vehicles have added 11 major elements to the station, enlarging the platform from its original 20,000 kg single module configuration to the current 180,000 kg facility depicted in Fig. 1(a). Russian Soyuz spacecraft and American Space Shuttles have brought eight long duration crews to live aboard the station for 4–6 months each, resulting in a continuous human presence in space since October 2000, and along with unmanned Russian Progress vehicles have brought the required logistics to maintain the station and its crews in a safe and productive environment. Among the

resupply items have been seven large research racks and logistics totalling more than 6500 kg. A significant milestone for ISS-based research was the addition of the US Laboratory Module Destiny, launched on the STS 98/5A mission in February 2001. Weighing 14,000 kg at launch, Destiny is a cylindrical module, 8.5 m long with an external diameter of 4.3 m. Internally, it is configured with 24 racks lining the four surfaces. The racks contain various systems equipments such as life support, controls for the station’s robotic arms, medical hardware, a crew sleep station, and up to 10 research facilities, of which seven are already on orbit. The first research rack, to be described in more detail below, was the Human Research Facility (HRF) Rack 1, installed a month after Destiny’s arrival. Assembly of ISS will continue in the near future with completion of the trusses, addition of solar arrays for power generation and radiator panels for cooling, and the International Partner research modules, leading to a configuration represented in Fig. 1(b). The European Space Agency’s Columbus module will increase the station’s research capability with an additional 10 research rack locations, with the Japanese Kibo module adding 11 more. The full suite of research modules will also allow optimal location of life sciences research racks for maximal synergy. Concurrent with the launch of the first research rack in March 2001, the Payload Operations and Integration Center (POIC) at the Marshall Space Flight Center (MSFC) in Huntsville, AL, became operational. Additional payload-specific support beginning with Expedition 2 was provided by Telescience Support Centers at other NASA Centers, including Johnson Space Center for human life sciences investigations. Remote sites at investigators’ institutes, domestic and international, are also routinely tied in during times when those experiments are operating. The Telescience Resource Kit (TReK) developed by the MSFC has proved to be a very reliable tool providing remote payload developers the ability to monitor and control their payloads from their home locations.

3. Facilities for human research Fig. 1. (a) Current configuration of ISS; (b) configuration of ISS including International Partner modules.

The two HRF Racks (Fig. 2) provide a core set of experiment hardware to support science investiga-

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Fig. 2. Human Research Facility Racks 1 and 2. Subcomponents described in text.

tions, as well as power, command and data handling and stowage, described below. The first rack has been on orbit since March 2001, while the second will be launched on the first mission after shuttles resume flying. These racks will initially reside in Destiny, but will be relocated to Columbus once that module arrives, where they will be joined by the European Physiology Module (EPM) and the Muscle Atrophy Research and Exercise System (MARES) racks. The EPM rack will provide the infrastructure for up to eight Science Modules in a variety of life science research disciplines, while the MARES facility is capable of assessing strength of muscle groups around a single joint or complete limb. These combined facilities, along with cold stowage capability provided by the ESA-provided Minus Eighty-degree Laboratory Freezer for ISS (MELFI), which can store materials at −80 ◦ C, −22 ◦ C and +4 ◦ C, will establish a powerful suite of instruments for conducting in-depth studies of human physiology in microgravity. Integral to the functioning of the HRF Racks are the computer Workstations and laptops. Each rack has its own Workstation, with the Rack 2 Workstation containing enhanced technologies allowed by its later launch. The workstations provide for data collection and storage, software interfaces to various experiments, data downlinking, video processing and graphics support. The laptop provides a platform for installing and executing software to perform various rack functions as well as experiment procedures. The Pulmonary Function System (PFS) is a collaborative effort between the United States and

ESA to develop a system for pulmonary physiology monitoring. The system will be complete once both HRF racks are on orbit. The components of the system are: Pulmonary Function Module (PFM), provided by ESA; Photoacoustic Analyzer Module (PAM), provided by ESA; Gas Analyzer System for Metabolic Analysis Physiology (GASMAP), provided by NASA; and Gas Delivery System (GDS), provided by NASA. The PFM plus GDS can operate together with either GASMAP or PAM; in the latter case the system is portable instead of rack-based as in the former case. The system can provide a wide range of respiratory and cardiovascular measurements, including breath-by-breath measurements, pulmonary volumes and capacities, spirometry, cardiac output and other specialized tests of pulmonary function. The ultrasound device located in HRF Rack 1 provides for multiple imaging modes including Doppler for a variety of applications, both for science investigations as well as operational medical diagnostics. The upgradable system can both record images locally and downlink imagery. In addition to 2D imaging, it can also provide post-image processing to yield 3D reconstructions. Of importance to many biomedical investigations as well as to medical operations is the ability to accurately measure crewmember body mass. The Space Linear Acceleration Mass Measurement Device (SLAMMD) follows Newton’s Second Law of Motion by having two springs generate a known force against a crewmember mounted on an extension arm, the resulting acceleration being used to calculate the subject’s mass. The device is accurate to 0.25 kg over a range from 40 to 115 kg.

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Collection and in situ processing, such as densitybased separation of fluid samples is integral to many biomedical experiments and to flight medicine. The 6-chamber rotor in the refrigerated centrifuge can accommodate sample sizes from 0.5 to 50 ml, with speeds ranging from 1000 to 5000 rpm. The rotor chamber is maintained at +4 ◦ C. Integral to most human life sciences investigations is the collection of pre- and postflight data. Facilities for ground-based data collection are established at Johnson Space Center in Texas where astronauts train, at Kennedy Space Center in Florida, the launch site and primary landing site for space shuttles, and Dryden Flight Research center in California, the alternate Shuttle landing site. In the aftermath of the Columbia accident, Russian Soyuz vehicles temporarily replaced the shuttle as the crew transport vehicle. Therefore, data collection capabilities were established on short notice at Gagarin Cosmonaut Training center outside of Moscow to enable US investigations.

4. Investigations Through the current tenth long-duration ISS expedition, 18 unique investigations in human life sciences have been completed or are still in progress (Table 1). The following research areas have been studied: radiation monitoring; bone demineralization; muscle deconditioning; neurosciences; cardiovascular physiology, in particular orthostatic intolerance; pulmonary physiology; regulatory physiology, specifically the risk of development of kidney stones; immunology; crew psychology, and evaluation of diagnostic imaging techniques. Most of the studies include data collection during space flight; the remainders rely on comparison of pre- and postflight data. The number of investigations will continue to grow and diversify into other areas as additional capability is added to ISS. The first group of investigations was begun during Expedition 2 and involved a suite of radiation monitoring hardware provided by three international partners, the United States, ESA/DLR and Japan. The United States provided the PHANTOM TORSO experiment, consisting primarily of a tissue–muscle plastic equivalent of a human head and torso. Passive and active dosimeters contained within the torso model provide

calculated organ dose levels of radiation exposure levels. The ESA/DLR-provided DOSMAP experiment was composed of four different types of dosimeters: passive Nuclear Track Detector Packages to measure the absorbed dose, neutron dose and heavy ion influences along with spectral composition with respect to charge, energy and linear energy transfer; Mobile Dosimetry Units consisting of four miniature dosimeter–radiometers; Dosimetric Telescopes to measure the flux of charged particles; and Thermoluminescence Detectors to measure dose rates for ionizing radiation and neutrons. The Japanese Bonner Ball Neutron Detector (BBND) contained six detector spheres containing 3He to measure the neutron flux inside the station, at two specific locations in Destiny. Two additional investigations have been the studying aspects of the space radiation environment. The aim of the Canadian EVARM experiment is to determine levels of radiation doses received by the skin, eyes and blood forming organs of crewmembers during Extra-Vehicular Activity (EVA). Crewmembers wear three small active dosimeters, located on the leg, torso and near the eye, during EVA, and these data are compared to background measurements inside the station. The German biodosimetric experiment CHROMOSOME is studying chromosomal aberrations in crewmembers’ lymphocytes as an indicator of the mutagenic impact of ionizing radiation. One of the well-documented (from Skylab and Mir studies) effects of long-duration space flight is bone demineralization. The SUBREGIONAL BONE experiment is designed to measure the loss of bone mass and its recovery postflight. Bone mineral density in the hip and spine are measured before and after flight using Quantitative Computed Tomography (QCT), a technique that allows examination of trabecular and cortical bone separately to localize the loss. The QCT results are compared with Dual X-Ray Absorptiometry (DXA) measurements of the spine, hip and heel, and Quantitative Ultrasound (QUS) measurements of the heel taken concurrently. Postflight recovery of bone mineral density is monitored until one year after landing. Along with bone demineralization; changes in muscle size, tone and function have also been documented during and after space flight. The goals of the BIOPSY experiment are to determine the time course and extent of functional and structural changes in limb

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Table 1 Investigations in human life sciences completed or in progress through ISS Expedition 8 Investigation

Investigator

Sponsor

Exped.

In-flight (Y/N)

Field of Study

DOSMAP TORSO BBND BONE INTERACTIONS HREFLEX RENAL STONE XENON1 PUFF EVARM BIOPSY MOBILITY MIDODRINE EPSTEIN-BARR CHROMOSOME FOOT JOURNALS ADVANCED ULTRASOUND

G. Reitz G. Badhwar T. Goka T. Lang N. Kanas D. Watt P. Whitson A. Gabrielsen J. West I. Thompson R. Fitts J. Bloomberg J. Meck R. Stowe G. Obe P. Cavanagh J. Stuster S. Dulchavsky

Germany US Japan US US Canada US Denmark US Canada US US US US Denmark US US US

2 2 2–3 2–8 2–5,7–9 2–4 3–6,8a 3–5 3–6 4–6 5,7,9–10a 5–10a 5a 5–6a 6–10a 6,8a 8–10a 8–10a

Y Y Y N Y Y Y N Y Y N N N N N Y Y Y

Radiation Radiation Radiation Bone Crew psychology Neurosciences Regulatory physiol. Cardiovascular Pulmonary Radiation Muscle atrophy Neurosciences Cardiovascular Immunology Radiation Neuromuscular Crew psychology Diagnostic imaging

a Study continuing beyond Expedition 8.

skeletal muscle and to establish the cellular mechanisms of the observed changes. To measure functional changes, crewmembers test the performance of their calf muscle using a Torque Velocity Dynamometer (TVD) several times before flight and after flight, beginning as soon after landing as possible. Magnetic Resonance Imaging (MRI) is performed on the crewmembers’ calves to measure any macroscopic structural changes. A needle biopsy is obtained from the soleus and gastrocnemeus muscles before and after flight, and the muscle samples undergo immunohistochemical analysis to assess any shift from fast to slow isozyme of myosin as well as electron microscopy to assess any structural changes in myofilaments. One of the causes of both bone demineralization and muscle changes is the decreased loading of lower extremities during everyday life during long-duration space flight. The FOOT experiment is designed to quantify this decreased mechanical loading. Crewmembers are instrumented for 12 h during a normal workday to measure ankle, knee and hip joint movements, loads on the lower extremities, and muscle activity, and compared against similar data on the ground. In addition, DXA scans of the proximal femur, MRI of leg muscles and maximum ankle, knee

and hip torques will be completed before and after flight to document any changes in bone mineral density, muscle volume and muscle strength as a result of the space flight. One other aspect of muscle changes during longduration space flight is a decrease in muscle recruitment. The Canadian HREFLEX experiment used Hoffmann reflex testing to measure reductions in spinal cord excitability, meaning a greater descending activity required to activate the same number of motor neurons. This would be manifest as an increase in apparent effort for the same level of exercise, or conversely a decrease in the level of exercise for the same apparent effort. This could in turn make inflight exercise potentially less effective at maintaining muscle mass and strength. During the experiment, an electrical stimulus was applied to the subjects’ posterior tibial nerve, and electromyography of the soleus muscle recorded the muscle response. The experiment was performed before flight, several times during the mission, and as soon after landing as possible. Following space flight, crewmembers experience postural and locomotor instability, posing a potential risk in an emergency. The goal of the MOBILITY experiment is to first document the postflight

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changes in locomotor responses, and then later to employ a variable in-flight treadmill protocol to facilitate a more rapid postflight recovery. Locomotor responses are tested before and after flight using a treadmill locomotion test, with the subject walking on a motorized treadmill while performing goal-directed gaze stabilizing tasks, and a functional mobility test, which has the subject walking through a simple obstacle course. One of the observed effects of space flight is postflight orthostatic hypotension, the inability to maintain arterial blood pressure upon standing. The Danish XENON1 experiment examined whether changes in a local veno-arteriolar reflex in the lower leg contribute to orthostatic hypotension. Before and after space flight, subcutaneous blood flow in the lower leg is measured by the 133Xenon washout method before and after lowering the leg with the subject in a supine position, while also measuring finger arterial blood pressure. The MIDODRINE experiment evaluates the efficacy of the drug midodrine in protecting returning crewmembers from orthostatic hypotension, as measured by operational tilt tests after landing. The two major goals of the PUFF experiment were to determine the effects of long-duration space flight on pulmonary function, and to determine any effects on pulmonary function from EVA, areas that have not been well studied during long missions. Standard respiratory function measurements were utilized to monitor changes caused by long-term microgravity, such as possible anatomical alterations, or by effects caused by long-term confinement, such as possible pulmonary impacts of accumulated particulates or contaminants. Monthly assessments of pulmonary function provided a time course of changes over the mission. Any EVArelated changes, such as possible formation of venous gas microemboli, were measured by pulmonary tests before and as soon after EVA’s as possible. Previous studies on shuttle and during long-duration Mir missions have demonstrated an increased risk of renal stone development during and immediately after space flight. The RENAL STONE experiment, a continuation of the previous space flight studies, will assess the renal stone-forming potential during longduration ISS missions, and also test the efficacy of potassium citrate, a proven therapy on the ground to minimize the risk of certain renal stones. Crewmembers collect 24 h urine samples before, during and after

flight, while recording food and fluid intake, exercise and any medications taken before and during the collection period. Aliquots of the collected in-flight urine are returned to Earth for analysis of stone-forming markers and inhibitors. Previous studies have shown possible alterations in human immune function as a result of long-duration space flight. While the studies did not conclusively indicate depressed immune function during flight, and no clinical experience would indicate increases in infectious illnesses, immunosuppression during space flight could be a potential hazard. One method to measure immunosuppression is to measure the reactivation of a latent virus, such as the Epstein–Barr virus (EBV), with which approximately 90% of the adult population is infected. The German EPSTEIN–BARR experiment, using blood and urine collections before and after flight, seeks to assess the immune system of crewmembers engaged in long-duration space flights. The samples are analyzed quantitatively for EBV replication, determining virus-specific T-cell immune function, and levels of stress hormones. Space analog studies and anecdotal reports from space flight indicate possible changes over time in the interpersonal relationships within a crew and between the crew and ground controllers, which may influence the crew’s ability to function safely and effectively. Cultural differences in multinational crews may compound these changes. During the INTERACTIONS investigation, crewmembers complete standard mood and interpersonal group climate questionnaires on a weekly basis. Mission controllers who have direct interaction with the crew and their tasking also complete the same questionnaires. Cumulated data over multiple expeditions will be analyzed for a number of important interpersonal factors, such as tension, cohesion, leadership role, and the relationship between the crew and the ground controllers. Another crew psychology investigation called JOURNALS, based on experience from ground-based analog environments, analyzes crewmember journal entries to obtain behavioral and human factors data relevant to equipment and procedures design to support sustained human performance during longduration space flight. The results will provide information on the relevance of various behavioral issues to prepare for long-duration missions, including exploration voyages. While in flight, crewmembers make

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journal entries at least three times per week, either on paper or electronically, which are then analyzed after the mission. As noted above, the HRF Rack 1 contains an ultrasound device, available for both research and clinical diagnosis. The ADVANCED ULTRASOUND investigation utilizes the Ultrasound hardware to demonstrate its utility in novel clinical conditions and to assess its feasibility to monitor realtime bone alterations. In addition, optimal training strategies will be developed to ensure that crewmembers, with guidance from the ground, can perform imaging of sufficient quality for remote medical diagnosis. These objectives have relevance both to space flight, during which unforeseen medical emergencies may require untrained crewmembers to image their comrades, as well as to similar terrestrial situations, such as remote location telemedicine. Typically, two crewmembers alternate

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as subject and operator and perform a variety of scanning exams of different organs and tissues, as well as monthly bone scans which are ultimately downlinked for analysis. 5. Summary The International Space Station is still under construction, with many challenges yet to come. Despite somewhat constrained resources available for research to date, much has already been accomplished. Eighteen unique investigations in human life sciences have been completed or are still in progress, utilizing available facilities on board, such as the Human Research Facility. Additional facilities and capability will be added in the coming years, and new types of investigations will be enabled.