Translating Basic Research to Astronaut Health in Space: NASA Ames Rodent Specimen Biobanking for the Human Research Program

The present effort builds upon more than 50 years of highly successful Ames collaborative investigations that have a proven track record for maximizing utilization and scientific return from unique animal specimens derived from NASA spaceflight research (Ronca et al., 2015). In the 1960s there were 21 biospecimen sharing experiments conducted on US Biosatellite I/II and III to determine whether basic biological processes (cell division, growth, and reproduction) occur in the absence of gravity.

Biosatellite II was a repeat of Biosatellite I, which was never recovered

The Biospecimen Sharing Program (BSP) concept was originally pioneered during the early US/USSR collaborations conducted aboard unmanned Russian Cosmos flights. During these flights, small teams of dissectors worked in field laboratories at the landing site to expedite recovery of samples for return to multiple investigators in Moscow for subsequent analyses. Later, during the NASA Space Shuttle Era, there were eight missions with BSP activities on animals. The formal BSP began with the Spacelab 3 mission launched in 1985 from Kennedy Space Center (KSC) on the Space Transportation System (STS-51B). The program continued with three dedicated missions (1991–1998): Spacelab Life Sciences-1, Spacelab Life Sciences-2, and Neurolab, and involved a total of 48 collaborative experiments and principal investigators (PIs) from the US, Russia, Germany, France, and Japan. In 2005 and 2007, US and Russia collaborated again on the Foton M2 and Foton M3 flights. The US experiments on both were joint experiments, and although not a formal BSP, the overall objectives were essentially a BSP (i.e., multiple investigators sharing flight specimens). In the late Shuttle era (2010–2011), STS-131, STS-133, and STS-135 carried parent immunology and bone experiments with 10, 10, and 32 (respectively) secondary BSP investigations. The 30-day Bion-M1 flew in April 2013. Biospecimen Sharing involved 15 recovered mice and nine US investigations. New data on the impact of spaceflight on cerebral arteries, spinal cord, inner ear, and genetic processes are presently being analyzed. The 37/38-day Rodent Research-1 Validation Mission flown in September 2014 resulted in a highly successful, large scale post-flight BSP, in which flight mouse carcasses were euthanized and then fast-frozen on ISS (Choi and Ronca, 2015).

During the Shuttle era, as an extension of the BSP, flight and ground specimens not utilized by investigators were collected and subsequently stored and archived at the ARC Biospecimen Storage Facility. In a continued effort to maximize utilization of rare and valuable specimens, these spaceflight samples are available to the international science community. Since 1995, NASA has shipped samples to numerous investigators enabling new fundamental and translational insights on the regulatory effects of multiple mature and developing systems, including: skeletal, muscular, bone, cardiovascular circulatory, nervous, endocrine, reproductive, gastrointestinal and immune development, muscle, and regulatory physiology.

Large-scale, biospecimen sharing activities require a veritable orchestra of well-timed events. A single mistake can flow down to adversely affect multiple BSP experiments. However, all tissues and science achieved from BSP would be lost if sharing was not a part of these rare, complex, and costly experiments. For these reasons, BSP success requires intricate planning, careful coordination, and extensive, repeated practice. Once biospecimens for the primary, or parent, experiment are harvested, the secondary BSP dissection flow is initiated. A Central Dissector rapidly dissects the remaining biospecimens that are handed off, in turn, to ‘runners’ charged with the immediate transfer of biospecimens to specific dissection stations. Primary dissectors at each dissection station (ten or more) perform further sub-dissection and/or cleaning of specific organs, weighing samples, centrifuging samples, or otherwise preparing them to preserve optimal scientific quality (fresh, frozen, or chemical treatment). Depending upon the investigations selected for BSP, there may even be multiple investigators at various stations involved in processing a single organ or structure (e.g., distinct components of the inner ear). Postmortem decay is essential to avoid, particularly for tissues identified for molecular analyses that require RNA protection from degradation. Advance planning enables specimen quality verification before the protocol is used on spaceflown animals. Thus, repeated practice by the entire dissection team is required to insure that the flow operates smoothly, with sufficient speed and precision, and that operations at one dissection station don’t interfere with those at another, or compromise tissue harvested and preserved later in the overall flow. The process of resolving these conflicts involves: Practice, Assess, Practice Refine, Practice, over and over until all of the scientific aims can be achieved as planned. Success is established when consensus on the activity is achieved among investigators utilizing diverse and potentially incongruent dissection requirements. There are many areas of possible adverse overlap, and most investigators have little to no experience sharing tissues from individual animals with multiple stakeholders. Thus, the overall process frequently involves a good deal of creativity and team problem solving.

One added benefit of BSP and this iterative process is the emergence of novel ‘team science’ efforts. One (of many) examples comes from the NIH Rodent (R)1 and (R)2 payloads flown on STS-66 and STS-72, respectively, that carried pregnant rats. Two investigative teams examining fetal development in space were interested post-flight in either behavioral responses or brain morphological changes. Because of the ongoing, cooperative efforts required for sharing the experimental subjects, the team members (previously unknown to each other) were able to identify complementary aims in their research, resulting in two joint publications (Ronca et al., 2000; Ronca et al., 2008).

NASA sharing of the animal cells and tissues and archival collections of rare products of animal flight studies was spearheaded by NASA ARC over 50 years ago. Since that time, advances in biopreservation techniques and ‘omics’ analyses, coupled with an increased clinical focus on personalized medicine, have led to the evolution of tissue archiving into the contemporary scientific discipline of biobanking. The term ‘biobank’ first appeared in the scientific literature in 1996, and for the next five years was used mainly to describe human population-based biobanks (Hewitt and Watson, 2013). The term is now applied to the growing numbers of biological collections of human, animal, plant, or microbial samples, specifically applied to sample archives with associated sample data (structural, descriptive, and administrative metadata), and to collections that are managed according to professional standards (International Society for Biological and Environmental Repositories (ISBER), 2013).

Most animal repositories are DNA banks for rare and endangered animal species (Ryder et al., 2000), although a few focus on animal health, e.g., the Morris Animal Foundation, and others provide insights into various human diseases derived from animal research, e.g., the NIA Aged Rodent Tissue Bank. The goal of the ARC BSP activities is to enhance the capacity and quality of research samples for space and gravitational biology. The program has recently been expanded to HRP supported research, the infrastructure augmented by adopting contemporary biobanking techniques for sample accrual, preservation, and archiving. In this way, we can establish common standards for spaceflight and ground-based studies across NASA programs, including Space Biology, GeneLab, and the HRP.