Previous studies showed increased antibiotic production during short duration space flights. The CGBA-APS investigation examined actinomycin D production, an antibiotic, during long term exposure to microgravity to determine the mechanism that caused the increased antibiotic production. Once the mechanism is determined, it can be applied to Earth based pharmaceutical manufacturing techniques.Principal Investigator(s)
University of Colorado at Boulder, BioServe Space Technologies, Boulder, CO, United States
National Aeronautics and Space Administration (NASA)Sponsoring Organization
Human Exploration and Operations Mission Directorate (HEOMD)Research Benefits
Information PendingISS Expedition Duration:
March 2001 - June 2002Expeditions Assigned
2,4Previous ISS Missions
CGBA investigations have been performed on STS-77, STS-80 and STS-95. The first CGBA investigation was performed during Increment 0.
The objective of this experiment was to determine if secondary metabolite production in microbes was impacted by long-duration space flight. Previous research, conducted during short-duration Space Shuttle flights, identified significant potential for antibiotic production by microorganisms in orbit. The CGBA-Antibiotic Production in Space (APS) experiment was the first ISS investigation to test whether long-duration exposure to microgravity stimulated antibiotic production in microorganisms. CGBA-APS spent at total of 72 days in orbit on ISS. The experiment used Streptomyces plicatus to produce the antibiotic compound actinomycin D. Actinomycin D is an anti-tumor antibiotic used to treat tumors of the bone, urogential
tract, skeletal muscle, kidney, and testis.
The Commercial Generic Bioprocessing Apparatus (CGBA) provided automated processing for biological experiments. For CGBA-APS, the CGBA hardware included the isothermal containment module (ICM v.3) The ICM v.3 contained the Multiple Orbital Bioreactor with Instrumentation and Automated Sampling (MOBIAS), a fermentation, cell culture, and tissue engineering apparatus.
The ICM v.3 provided highly-accurate temperature control between 4 degrees C and 37 degrees C and was equipped with data, video, and telemetry electronics to allow telescience remote operation. The ICM held six stackable MOBIAS trays, each of which provided the appropriate controlled, sterile sample processing environment, with passive gas exchange and automated sampling and waste removal. The samples that were fermented were kept in 5 ml teflon bags and processed in separate culture bags. Waste and media, to feed the experiments, were contained in 350 ml bags. Each tray contained its own array of sample, culture, media, waste bags, and connectors. The CGBA provided independent, adjustable temperature control for both the sample and culture bags.
Bacteria produce antibiotics at an accelerated rate in microgravity when compared to those that are produced on Earth. The ability to grow large quantities of antibiotics in microgravity will further pharmaceutical research.Earth Applications
Scientists will apply the insight gained from observations made in the microgravity environment of space towards improving antibiotic production and efficiency in facilities on Earth. The economic gain would be substantial in a small increase in fermentation efficiency, realized as a result of the knowledge gained from the space flight data. The microgravity environment is essential in determining the critical factors observed in increasing an antibiotic production.
CGBA-APS required continuous power which was provided through an EXPRESS Rack. A total of 42 culture samples were used in this investigation. The ICM required minimal crew time and the MOBIAS was fully automated. The Remote Payload Operations Center (R-POCC) at the University of Colorado monitored the downlinked data and sent commands directly to the EXPRESS Rack.Operational Protocols
The culture samples were loaded in the CGBA assembly preflight and launched on the Space Shuttle. Once the equipment was transferred to ISS, the crewmembers installed the CGBA hardware into an EXPRESS Rack. From this point, the investigation is automated and the crew performed only the required daily hardware health checks and weekly cleaning.
The cultures were kept at a temperature of 10 degrees C for the first 21 days of the mission. To initiate growth, the temperature was increased to 22 degrees C by the ground-based science team and monitored from the BioServe Remote Payload Operations Control Center in Boulder, CO, via video and data downlink. The samples that produced actinomycin D were stored in a thermally isolated portion of the locker at 4 degrees C for analysis by the ground teams following return to Earth.
CGBA-APS originally flew on Expedition 2 but was not able to function due to technical issues. Its re-flight took place during Expedition 4 where the hardware performed as planned. Samples of antibiotic were taken at four-day intervals. A total of 48 samples of Streptomyces plicatus were used to produce the antibiotic compound actinomycin D for a span of 72 days on orbit. The initial production of actinomycin D from on-orbit samples was higher than those produced during the ground tests. This was true for samples that were taken on day 8 (15.6 % increase) and day 12 (28.5% increase) of the investigation. Beginning at day 16, the ground experiment produced more antibiotic than the on-orbit experiment. This trend continued for the remainder of the experiment. The causes for the higher yield during the first 12 days of the experiment are still unknown. One theory is that there is a shorter lag phase, which allowed ISS samples to reach the growth and production phases sooner than the ground samples (Benoit et al. 2005).
Identifying the mechanism that caused increased production of antibiotics while in microgravity and applying them to production on Earth could be advantageous to the pharmaceutical industry. A method for transferring the microgravity research results to Earth-based production has not yet been identified. (Evans et al. 2009)
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