Available via license: CC BY 4.0
Content may be subject to copyright.
PERSPECTIVE
Space bioprocess engineering on the horizon
Aaron J. Berliner 1,2 ✉, Isaac Lipsky1,2, Davian Ho1,2, Jacob M. Hilzinger1,2,
Gretchen Vengerova 1,2, Georgios Makrygiorgos1,3, Matthew J. McNulty1,4,
Kevin Yates1,4, Nils J. H. Averesch 1,5, Charles S. Cockell1,6, Tyler Wallentine1,7,
Lance C. Seefeldt1,7, Craig S. Criddle1,5, Somen Nandi 1,4,8,
Karen A. McDonald1,4, Amor A. Menezes 1,9, Ali Mesbah1,3 &
Adam P. Arkin 1,2 ✉
Space bioprocess engineering (SBE) is an emerging multi-disciplinary field to design, realize,
and manage biologically-driven technologies specifically with the goal of supporting life on
long term space missions. SBE considers synthetic biology and bioprocess engineering under
the extreme constraints of the conditions of space. A coherent strategy for the long term
development of this field is lacking. In this Perspective, we describe the need for an expanded
mandate to explore biotechnological needs of the future missions. We then identify several
key parameters—metrics, deployment, and training—which together form a pathway towards
the successful development and implementation of SBE technologies of the future.
Biotechnologies may have mass, power, and volume advantages compared to abiotic
approaches for critical mission elements for long-term crewed space exploration1,2. While
there has been progress in the demonstration and evaluation of these benefits for specific
examples in this field such as for food production, and waste recycling, there is only just
emerging possible consensus on the scope of the application of biosynthetic and bio-
transformative technologies to space exploration. Additionally, there is almost no formal defi-
nition of the scope, performance needs and metrics, and technology development cycle for these
systems. It is time to formally establish the field of space bioprocess engineering (SBE) to build this
nascent community, train the workforce and develop the critical technologies for planned deep-
space missions. SBE (Fig. 1a) borrows elements from a number of related fields such as the
synthetic biology design process from Bioengineering, astronaut sustainability3,4and mission
design from Astronautics5,6, environmental-context, and constraints from the Space Sciences, and
living systems habitability and distribution concepts from Astrobiology7. SBE represents an
extension of the standard astronautics paradigm in meeting NASA’s Space Technology Grand
Challenges (STGCs) for expanding the human presence in space, managing resources in space, and
enabling transformative space exploration and scientific discovery8,9(Fig. 1b). Aspirational reali-
zations of SBE would feature prominently in establishment of in-orbit test-facilities, interplanetary
waystations, lunar habitats, and a biomanufactory on the surface of Mars10. Differentiated from
traditional efforts in space systems engineering, these SBE systems would encapsulate elements
from in situ resource utilization (ISRU) for the production of biological feedstocks such as fixed
carbon and nitrogen for use as inputs for plant, fungal, and microbial production systems11,12,
fertilizers for downstream use by plants13; in situ (bio)manufacturing (ISM) to produce materials
https://doi.org/10.1038/s44172-022-00012-9 OPEN
1Center for the Utilization of Biological Engineering in Space (CUBES), Berkeley, CA, USA. 2Department of Bioengineering, University of California Berkeley,
Berkeley, CA, USA. 3Department of Chemical and Biomolecular Engineering, University of California Berkeley, Berkeley, CA, USA. 4Department of Chemical
Engineering, University of California, Davis, Davis, CA, USA. 5Department of Civil and Environmental Engineering, Stanford University, Stanford, CA, USA.
6UK Centre for Astrobiology, School of Physics and Astronomy, University of Edinburgh, Edinburgh, UK. 7Department of Chemistry and Biochemistry, Utah
State University, Logan, UT, USA. 8Global HealthShare Initiative, Davis, CA, USA. 9Department of Mechanical and Aerospace Engineering, University of
Florida, Gainesville, FL, USA. ✉email: aaron.berliner@berkeley.edu;aparkin@lbl.gov
COMMUNICATIONS ENGINEERING | (2022) 1:13 | https://doi.org/10.1038/s44172-022-00012-9 | www.nature.com/commseng 1
1234567890():,;
requisite to forge useful tools and replacement parts14,foodand
pharmaceutical synthesis (FPS) via plant, fungal and microbial
engineering for increased productivity and resilience in space
conditions, production of nutrients and protective/therapeutic
agents for sustaining healthy astronauts15,16; and life-support loop
closure (LC) for minimizing waste and regenerating life-support
functions and biomanufacturing. Maximizing the productivity of
the biomanufacturing elements increases the delivery-independent
operating time of a biofoundry in space while minimizing cost and
risk17.(Fig.1c). Ultimately, efforts must be mounted to: (1) update
the mandate to include SBE as a tool for enabling human
exploration; (2) specialize the metrics and methods that guide SBE
technology life-cycle and development; (3) further develop the
means by which SBE technologies are designed for ground-based
testing and matured on offworld platforms (Fig. 1d); and (4) train
the minds entering the spacefaring workforce to better understand
the leverage the SBE advantages and capabilities.
An inclusive mandate to leverage SBE
While previous strategic surveys such as NASA’s Journey to Mars
program18 and the 2018 Biological and Physical Sciences (BPS)
Decadal Survey19 have acknowledged that plants and microbes
may be integral parts of life support and recycling systems, but
can present challenges to the environmental operation of engi-
neering systems in space due to contamination and other
inherent drawbacks. However, no such survey has coherently
called for the development of science and technology to engineer
these organisms and their biotransformative processes in support
of space exploration. The SBE community requires a mandate
that identifies mission designs and elements for which engi-
neering biosystems would be most appropriate, and defines the
productivity, risk, and efficiency targets for these systems in an
integrated context with other mission elements and in fair com-
parison to abiotic approaches. This will require integration of SBE
resources and knowledge across government, industry, and aca-
demia. Previous biological strategies should now specifically call
for (1) definition of the physical engineering constraints on the
production systems and development of optimized reactor/pro-
cessing systems for these elements; (2) quantitative assessment of
the bioengineering required to meet performance goals in space
given the special physiology required in an offworld environment;
and (3) development of efficient tooling for offworld genetic
engineering along with the proper containment and clean-up
protocols.
Such a mandate would result in: (1) a deeper, more mechanistic
understanding of the growth and phenotypic characteristics of
organisms operating in space-based bioprocesses taking into
account issues of differences in gravity, radiation, light, water
quality; (2) new applications of these organisms off-planet; (3)
new reactors, bioprocess control designs and product processing/
delivery technologies accounting for these conditions and the
specific constraints of scaling and operational simplicity in space.
The development of open, publicly accessible data and tools
would enable rigorous comparison among biotechnologies and
abiotic (physical and chemical) approaches, and across mission-
scenarios of higher-fidelity. Ideally, this should create interative
sub-communities that may collaborate and compete on different
approaches to meet bioengineering goals and metricize results
against the mission specifications.
SBE is an emerging engineering discipline and there are long
but feasible routes from discovery, through invention to appli-
cation. Furthermore, SBE is multidisciplinary and its utility
within the larger space community demands specialized cross-
training of diverse teams. In such situations, agencies like the
Department of Energy have found it effective to ensure there is
specific funding to support longer-term team science to accom-
plish ambitious scientific and technical goals. The Industrial
Assessment Centers (IACs) program is one of the longest-
running Department of Energy programs (started in 1976) and
Fig. 1 Overview of space bioprocess engineering challenges, components, and platforms. a Venn Diagram-based definition of Space Bioprocess
Engineering (SBE) as an interdisciplinary field. bNASA's space technology grand challenges8key by shape and colored by group. cPossible SBE
components separated by colors for in situ resource utilization (ISRU), food and pharmaceutical synthesis (FPS), in situ manufacturing (ISM), and loop
closure (LC), with the biological processes inherent to each represented below in circles. dPlatform evolution for biological experiments starting with
Earth-orbit CubeSats and proceeding through the ISS, Mars-and-Luna-based rovers, to Lunar and cis-Lunar based human and autonomous systems via the
Artemis program.
PERSPECTIVE COMMUNICATIONS ENGINEERING | https://doi.org/10.1038/s44172-022-00012-9
2COMMUNICATIONS ENGINEERING | (2022) 1:13 | https://doi.org/10.1038/s44172-022-00012-9 | www.nature.com/commseng
has provided nearly 20,000 no-cost assessments for small- and
medium-sized manufacturers and more than 147,000 recom-
mendations in an effort to reduce greenhouse gas emissions
without compromising U.S. manufacturing’s competitive edge
globally20. Conversely, successful examples for demonstrating the
effect of fostering multidisciplinary centers for space-based bio-
technology can be found in NASA’s Center for the Utilization of
Biological Engineering in Space (CUBES), or ESA’s Micro-
Ecological Life Support System Alternative (MELiSSA) program
—with the capabilities to design, prototype, and ultimately
translate biological technologies to space while training the
necessary workforce. Such centers are tasked with the develop-
ment of initial concept trade studies; defining requirements;
managing life-support interfaces; evaluating ground integration,
operations, and maintenance; coordinating mission operations;
and supporting and sustaining engineering and logistics21,22.
However, these programs are generally restricted to shorter
operation timelines—and would benefit from a longer horizon.
This is especially true for SBE as biological developments gen-
erally require a longer timeframe for integration in industrial
endeavors.
Specialization of SBE metrics and methods
Response to the proposed expanded mandate above requires
careful consideration of the space-specific performance metrics
that SBE must fulfill. Payload volume, mass, and power
requirements are made as small as possible and are limited in
envelope by their carrier system. One of the most compelling
aspects of biotechnology is the ability of such systems to adapt to
these constraints relative to certain industrial alternatives. To
efficiently evaluate and deploy novel biotechnologies, SBE
experiments should begin with standardized unit operations that
clearly define the desired biological function. This allows for a
standardized experimental framework to test modular bio-
technologies not only within the system to be engineered, but also
within and between research groups. To define the minimal basis
set of unit operations for a given mission, test and optimize the
biotechnologies for each unit operation, and integrate each unit
operation into a stable system, we propose to adopt the methods
from standard bioengineering in the form of a Design-Build-Test-
Learn (DBTL) cycle23 (Fig. 2).
Performance metrics. The design phase of the DBTL cycle begins
with the establishment of core constraints and engineering targets
that can be explored by standardizing the high-priority perfor-
mance metrics ({Modularity, Recyclability, Supportability,
Autonomy, Sustainability})—which we argue gain special weight
in space—from which downstream technoeconomic and life-cycle
analysis decisions can be explored (Fig. 2a). The space-specific
constraints on performance include: (1) an exceptionally strong
weighting on a low mass/volume/power footprint for the inte-
grated bioprocess; (2) limited logistic supply of materials and a
narrow band of specifically chosen feedstocks; (3) added
emphasis on simplicity of set-up, operation and autonomous
function to free up astronaut time; (4) mission-context de-risking
against cascading failure; (5) strong requirements for efficiency
and closed-loop function to maximize efficient resource use and
minimize waste products; (5) a critical need for modularity and
’maintainability’so that parts can be swapped easily, new func-
tions added easily, and repairs can be done without logistical
support beyond the crew; (6) an increased dependence on other
mission elements such as provision of water, gases, astronaut
wastes, power, and other raw materials such a regolith which may
vary in abundance, quality, and composition in unpredictable
ways; (7) the need to design sustainable and supportable opera-
tion across long time horizons without logistical support beyond
the bounds of the local mission; (8) increased ability to operate in
more extreme environments including low gravity, high radia-
tion, low nutrient input, and other stressors; (9) process com-
patibility among common media and operational modes to allow
for easy process integration and risk-reduction through redun-
dancy of systems; and (10) further consideration and develop-
ment of biocontainment of engineered organisms to prevent (or
at least mitigate) unexpected dispersal of unwanted living systems
in pristine or tightly controlled environments24–26.
Ideally, this combination of performance metrics provides
informative constraints on biology and technology choices.
Feedstock, loop-closure, environmental parameters and product
needs will constrain the minimal set of organisms to develop and
test for growth rate, optimal cultivation, robustness and resilience
to space conditions and shelf-life, safety and genetic tractability,
product yield, titer and rate, feedstock utilization, ease of
biocontainment, streamlining of purification, and waste
streams27. Once suitable chassis organisms have been evaluated
Fig. 2 Overview of space systems bioengineering (SBE) performance metrics and the SBE-specific Design, Build, Test, Learn (DBTL) cycle. The SBE
performance metrics in aare shaded to correspond to the top level core constraints and engineering targets within the bDBTL cycle.
COMMUNICATIONS ENGINEERING | https://doi.org/10.1038/s44172-022-00012-9 PERSPECTIVE
COMMUNICATIONS ENGINEERING | (2022) 1:13 | https://doi.org/10.1038/s44172-022-00012-9 | www.nature.com/commseng 3
and selected, the DBTL cycle can integrate staged co-design of the
optimal process hardware (e.g., molecular biological set-ups,
genetic engineering tools, bioreactors, and product post-
processing systems) configuration, operating parameters, and
process controllers. Aerobic organisms may be much more
efficient but only viable in systems in which oxygen is available
and easily obtainable. This in particular provides insight into the
specific questions that require further study in terms of organism
engineering. The question of anaerobic versus aerobic metabolism
really depends on the product and the style of process—at small
scale aerobics may have an advantage in terms of yield and rate,
due to more energy being derived from the transfer of reducing
equivalents to cellular metabolism—while at large scale, mass-
transfer limitations are dominating these parameters (yield and
rate), which gives anaerobics an advantage28. Additionally,
bioproduct isolation and purification processes need to be
considered beyond the Earth-centric means of fermentation.
For example, cell-free bioproduction systems may prove critical
in biotransformation and point-of-care biosensing as shown in
recent space pharming techoeconomic analyses29. Operation of
the cycle over increasing scale and ever more realistic deployment
environments permits controlled traversal of the technology
readiness levels for each technology and mission.
Design-build-test-learn. In the design phase, we argue that efforts
must be made to (1) create a database of engineering targets
(products, production rates, production yields, production titers,
risk factors, waste/recyclability factors, material costs, operational
costs, weight, power demand/generation) that set the core con-
straints for workflow and mission optimization; (2) leverage
emerging pathway design software and knowledge bases30 to
identify the key types of biological production workflows (i.e.,
metabolic engineering strategies31) that need to be modified for
different space-based scenarios; (3) identify the supporting bio-
manufactory design elements within which these production
workflows could be implemented32–34; and (4) identify the chassis
organisms and other biological components35–37 that will be
required to compose the complete set for downstream engineering
specifications. Systems designed from a minimal set of reliable
parts, standard interconnects, and common controller languages
also offer the best possible chance of characterized reliability under
changing environmental conditions. Therefore, control of hard-
ware and wetware should be augmented through the design and
operation of software support. We see a fundamental effort in SBE
as the amalgamation of space-driven hardware, software, and
wetware that follows a synthetic biology DBTL cycle38.
The foundation of new SBE performance metrics that guide the
design phase of the DBTL cycle must be augmented with
additional downstream efforts in the build and test phases to (1)
develop a process design framework that takes in specific
production needs in amounts/time over acceptable ranges under
the constraints expected across different offworld scenarios; (2)
create the biological, process, and mission design software
platforms to allow sophisticated DBTL, risk assessment, and
mission choice support; (3) create the sensor/controller sets that
will allow real-time optimization of biological production work-
flows; and (4) develop the online process controller framework
that coordinates reactor conditions and inter-reactor flows to
optimize reliable production across all units within acceptable
ranges with minimal power and risk. The realization of this SBE
DBTL cycle depends on the integration of such benchmark
models and modeling standards. These benchmarks describe the
dynamics of all SBE processes and relate to the SBE metrics in the
design phase from which optimization can be carried out in the
learn phase.
DBTL cycles within the scope of SBE must prepare for both
ground- and flight-based system operations. Ground-based
developments must prioritize designs that meet the requirements
for flight-based testing, during which system behaviors may be
better characterized in unique environments such as those offered
in micro- and zero-gravity. For instance, a biological nitrogen-
fixing system on Earth must at least be designed to meet the mass
and volumetric constraints required for validated ground-based
simulators of microgravity, galactic cosmic radiation, and other
physical stressors. Meeting certain requirements for time, power,
and substrate usage is essential for any degree of long-term
operation. This allows for the in-flight testing of bioreactors
previously evaluated on Earth that can more directly measure the
effects micro-gravity, radiation, and other stressors on the
bioprocessing system. A combination of ground- and flight-
based tests are required for the development of functional and
robust space biosystems.
Development of means for SBE flight
Deployment of SBE platforms as mission critical elements will
likely be reserved for longer duration human exploration mis-
sions such as those in the Artemis or Mars programs10. These
future programs are still in the concept and planning stage in
development, but will certainly be composed of a myriad of
technologies that range in degree of flight-readiness as standar-
dized by NASA’s Technology Readiness Level39 (TRL, used to
rate the maturity of a given technology during the acquisition
phase of a program). Recent updates in NASA’sdefinitions of and
best-practices for applying the TRL paradigm led to the stan-
dardization and merging of exit criteria between hardware and
software systems40. However, the TRL concept as it relates to SBE
must be further expanded to include definitions and exit criteria
for ‘wetware’in addition and in relationship to hardware and
software elements.
Deployment of SBE in space requires a level of rigor in tech-
nology acceptance that is of a different order than most Earth-
based systems because mission failures are exceptionally costly
and difficult to recover from. The missions into which SBE
processes will integrate are hugely complicated and as noted
above will be interdependent in complex ways. Thus while low
levels TRLs can be reached through unit testing in modest for-
mats both on Earth and in limited flight experiments, the inte-
grated nature of the bioprocess control and engineering will
require integration testing even at the TRL 4 and 5 levels40.To
meet acceptance at TRL 6 and beyond will require long term
planning realistic integration and deployment testing with actual
sophisticated space missions and their logistics.
Even at low TRLs, research on the timescales needed to validate
extended-use systems as would be leveraged on extended-stay
forward deployment such as Martian or lunar missions are not
possible given the current ISS capabilities and constraints. Con-
straints in astronaut time and limitations in hardware designed
for shorter experiments prevent testing times comparable to long
duration missions. Table 1outlines a number of constraints on
past and current experimental platforms and provides some basis
for constraints of future systems (Fig. 1d). Here we note that
extended multigenerational studies, especially in microbiology,
can be difficult with some of the operational lifetimes41. Volume
is also constrained, and available space is broken up into seg-
mented rack testbeds and independent machines, which can
prevent aspects of a system from interacting with each other
(Table 1). Much of the testing hardware on the ISS is designed for
front-end processing and basic science. Experiments in microbial
observation42,43, hybrid life support44, and antibiotic response45
require returning samples to Earth for efficient processing,
PERSPECTIVE COMMUNICATIONS ENGINEERING | https://doi.org/10.1038/s44172-022-00012-9
4COMMUNICATIONS ENGINEERING | (2022) 1:13 | https://doi.org/10.1038/s44172-022-00012-9 | www.nature.com/commseng
Table 1 Constraints on past and current experimental platforms including small satellites, space stations, rovers, planned lunar habitation, and martian habitation.
Platform Volume Power Op. lifetime Temperature Air comp.
CubeSat 0.0187 m320–45 W ~20 years Requires heating unit within constraints Self-contained
PocketQube 0.000125 m3Variable ~5 years
Bioculture System Not stated 140 W ~60 days 37–45 °C in main chamber, ambient to 5C in
cooling chamber
Self-contained medical grade gas
WetLab-2 (SmartCycler) 235.97 m3350 W Extractions <3 h, no
lifetime stated
50–95 °C None, reliant on cabin air system
Rodent Habitat Hardware System 0.019 m3Not stated ~30 day experiments Ambient temp, no heating module
Compact Science Experiment Module 0.0015 m33.2 W >1 month experiments
Vegetable Production System (Veggie) 0.48 m3growth area Not stated >12 day experiments, can
replace crops
Advanced Plant Habitat (APH) 889.44 m3growth area ~1 year 18–30 °C Self-contained gas supply
Spectrum 10 × 12.7 cm
internal area
12 day experiments 18–37 °C None, reliant on cabin air comp
BRIC-60 11.03 m3Unpowered >12 day experiments Ambient temp, no heating module 60 M variant can draw from an
external gas tank
BRIC-100 38.78 m3Self-contained gas canister of
designated composition
BRIC-100VC 16.33 m34.5 months
KSC Fixation Tubes (KFTs) 0.2387 m367 days
miniPCR 0.00066 m365 W ~2 year <120 °C Airtight, reliant on cabin air comp
Group Activation Pack-Fluid Processing
Apparatus (GAP-FPA)
Eight 6.5 cm3
test tubes
Unpowered
for manual
Not stated 4–37 °C
Multi-use Variable-g Platform (MVP) Twelve 800 cm3
modules
Not stated 14–40 °C
MinION 0.0796 m35 W ~1 year Ambient temp, no heating module
Perseverance (MOXIE) 0.017 m3300 W ~2 years 800 °C operational −60 °C ambient CO
2
input CH
4
output
Gateway (HALO) >125 m3planned
internal volume
~60 kW >2 years ~18 °C Pressurized cabin air
Mars Hab (6 Crew) 300 m3~100 kW 600 day nominal, 619 day
maximum
~18 °C Pressurized cabin air
COMMUNICATIONS ENGINEERING | https://doi.org/10.1038/s44172-022-00012-9 PERSPECTIVE
COMMUNICATIONS ENGINEERING | (2022) 1:13 | https://doi.org/10.1038/s44172-022-00012-9 | www.nature.com/commseng 5
limiting the end-product downstream analysis and use as feed-
stocks for other integrated processes, as is needed to advance TRL
beyond 6. This also cuts down on the ability to run DBTL
diagnostics and SBE performance metrics on the system in toto as
recyclability and sustainability are reliant on those end-products,
and supportability if the processing is often reliant on Earth
resources. Though much of the potential testing: polymerase
chain reaction46, imaging, and DNA sequencing47,48 is possible
with current miniaturized ISS modules, it may not all be at the
scale needed for future experiments, and there may be gaps in
capability as the field matures. Improved in situ data analysis
through the development of new, high-throughput instruments
could help close those gaps49 and allow better metricization of
whole systems under these new performance paradigms.
Lunar and Martian gravity is likely to have distinct biological
effects compared to Earth gravity, resource composition, and
radiation profile—and the ISS has only a limited volume in which
to simulate them50. Additionally, both ambient environmental
and target temperature windows span an extensive range across
extraterrestrial environments, as do gas compositions, making
representative testing more difficult in growth and testing
chambers (plant, animal, and microbial) without full environ-
mental control (Table 1). Environmental Control and Life Sup-
port System (ECLSS) systems for large-scale plant science
requisite for advancing TRL for downstream lunar and Martian
missions also require larger volume bounding boxes than is
currently provided on the ISS51. Here we note the trade-offs with
the tight volume and power stores on board. Smaller satellite
modules can get technologies off the ground to advance TRL52–54,
but feature even greater size handicaps, and may prevent testing
at the integrated, factory level in the DBTL cycle55,56. Scientific
instruments and modules on rovers have been geared primarily
for exploration and observation, not technology validation.
Dedicated rovers or simply landing SBE payloads onto extra-
terrestrial sites, SBE-ready orbiters, and Artemis operations as a
stepping-stone to Mars can all demonstrate technology within a
representative context and stand as some of the premier testbeds
to flight qualify SBE prototypes39. In situ testing is key to the
proposed SBE performance metrics: it forces technology and
bioprocesses into accurate, integrated environments, and provides
better confidence under radiation, microgravity, and isolation.
Training of SBE minds
Maturation of space bioprocess engineering requires specializa-
tion of the training needed to produce the next generation of
spacefaring scientists, engineers, astronauts, policy makers, and
support staff57. Lessons learned from the Space Transportation
System era led to calls for an increase in Science-Technology-
Engineering-Mathematics (STEM) educational programs58
beginning in secondary schools59 and propagating to novel
astronautics-based undergraduate60 and graduate programs, and
to the establishment of specialty space research centers focused
on technology transfer61. The calls for workforce development
were repeated just prior to the collapse of the Space Transpor-
tation System program, noting the dangers likely to arise from the
lack of educational and training resources for those entering the
space industry.62. Such a risk as described is especially poignant
in the case of space-based biotechnologies given that mature
technologies are far fewer, the new applications more futuristic,
and the disciplines are not well represented in the traditional
physics and engineering curricula. The Universities Space
Research Association (USRA) lists 114 institutions with Space
Technologies/Science academic programs while recent account-
ing of bioastronautics programs numbers 3663. However, the
intersection between these lists yields only 22 schools. Given that
US News names 250 world schools that have tagged themselves
with Space Science programs, only ~8% of these are currently
offering bioastronautics specialization—demonstrating that
efforts that integrate human performance, life support, and
bioengineering are under-served. Furthermore, the bioas-
tronautics programs such as those offered by schools like
SBE Track Specialization
Introduction to the Space Ecosystem
Molecular
Bioengineering
Computational
Biology
Genetics/
Genetic Engineering
Systems Biology
Cell Biology/
Cellular Engineering
Synthetic Biology
Engineering
Mechanics
Orbital
Mechanics
Space
Structures
Signals and Systems
Control Theory
Rocket
Propulsion
General
Astronomy
Atmospheric Physics
Geomorphology
Planetary
Astrophysics
Geodynamics
Stellar Physics
Core STEM
Single Variable
Di erential and
Integral Calculus
General and Organic
Chemistry
Multivariable
Calculus
Linear Algebra and
Di erential
Equations
General and Modern
Physics
General Computer
Science
Thermodynamics Fluid Mechanics
Probability and
Statistics
Dynamical Systems
Signals and Systems
Control Theory
Simulation Modeling
and Analysis
Optimization
Methods
Human Factors
Bioengineering Astronautics Planetary Science/
Astronomy
Systems
Engineering
Space and Society Space Economics Space Policy
Fig. 3 Conceptual undergraduate SBE program. The SBE program is broken in three sections: core STEM (Science-Technology-Engineering-Mathematics)
courses, introduction to space ecosystem courses, and track specialization courses for tracks in bioengineering, astronautics, planetary science&
astronomy, and systems engineering.
PERSPECTIVE COMMUNICATIONS ENGINEERING | https://doi.org/10.1038/s44172-022-00012-9
6COMMUNICATIONS ENGINEERING | (2022) 1:13 | https://doi.org/10.1038/s44172-022-00012-9 | www.nature.com/commseng
Harvard-MIT, University of Colorado Boulder, and Baylor Uni-
versity are not focused on biomanufacturing aspects that underlie
SBE64.
Academia must be prepared to capitalize on the opportunities
of future SBE applications starting with either the creation of new
and interdisciplinary programs or by assembling those from
related disciplines (Fig. 1a). Because scientific and mathematical
core courses are relatively standard across SBE-related disciplines,
an effective foundation of technical skills could be easily con-
structed from the shared curriculum (Fig. 3). From there, specific
SBE-driven training can be offered in (1) effects of space on plant
and microbes; (2) process design for low gravity/high radiation;
(3) management and storage of biological materials in space-
based operations; (4) low energy/low mass bioreactor/biopro-
cessor design; (5) integrated biological systems engineering; (6)
biological mission planning and logistics; (7) risk and uncertainty
management; (8) containment and environmental impact of
biological escape, films, corrosion, and cleanup; (9) policy
awareness/development; and (10) ethics of cultivation and
deployment. While the logistics for organizing such pathways for
formal SBE training are non-trivial within the academic machine,
we note that nearly all schools listed by USRA offer the compo-
nent programs in bioengineering, planetary science or astronomy,
and electrical or systems engineering. Since the courses for such
engineering programs are standardized65, it stands to reason that
establishing focused SBE programs can begin by collecting and
highlighting course combinations. As programs grow, additional
faculty with SBE-driven research can be sourced. Such openings
offer a much-needed opportunity to address systemic issues of
diversity, equity, and inclusion both within SBE-based academia
and the industrial space community at large66.
Moving forward
Making progress on the program above requires scientists, engi-
neers, and policy experts to work together to verify, open, and
update campaign specifications. The science requires scientists
from multiple disciplines spanning biological and space systems
engineering that require a degree of modularity, small footprints,
and robustness not found elsewhere. Additionally, bioprocess and
biological engineering must be applied to the building of cross-
compatible and scalable processing systems and optimized
organisms within the confines of space reactor and product.
Finally, coordination mission specialists are critical to deploy tests
into space during the run-up and through crewed missions. We
argue that such groundwork requires multidisciplinary centers
that can build long term partnerships and understanding; train
the workforce in this unique application space; and perform the
large-scale, long-term science necessary to succeed.
Received: 12 January 2022; Accepted: 17 May 2022;
References
1. Menezes, A. A., Cumbers, J., Hogan, J. A. & Arkin, A. P. Towards synthetic
biological approaches to resource utilization on space missions. J. R. Soc.
Interface 12, 20140715 (2015).
2. Nangle, S. N. et al. The case for biotech on Mars. Nat. Biotechnol. 38, 401–407
(2020).
3. Young, L. R. & Sutton, J. P. Handbook of Bioastronautics 1 edn (Springer,
2020).
4. Whitmore, M., Boyer, J. & Holubec, K. NASA-STD-3001, space flight human-
system standard and the human integration design handbook. In Industrial
and Systems Engineering Research Conference (International Council on
Systems Engineering (INCOSE), 2012).
5. Hoffman, S. J. & Kaplan, D. I. Human Exploration of Mars: The Reference
Mission of the NASA Mars Exploration Study Team Vol. 6107 (National
Aeronautics and Space Administration, Lyndon B. Johnson Space Center,
1997).
6. Drake, B. G., Hoffman, S. J. & Beaty, D. W. Human exploration of Mars,
design reference architecture 5.0. In Aerospace Conference, 2010 IEEE 1–24
(IEEE, 2010).
7. Fridlund, M. & Lammer, H. The astrobiology habitability primer. Astrobiology
10,1–4 (2010).
8. Talbert, T. & Green, M. Space Technology Grand Challenges (National
Aeronautics and Space Administration, 2010).
9. Menezes, A. A., Montague, M. G., Cumbers, J., Hogan, J. A. & Arkin, A. P.
Grand challenges in space synthetic biology. J. R. Soc. Interface 12, 20150803
(2015).
10. Berliner, A. J. et al. Towards a biomanufactory on mars. Front. Astron. Space
Sci. 8, 120 (2021).
11. Cestellos-Blanco, S. et al. Production of PHB from CO
2
-derived acetate with
minimal processing assessed for space biomanufacturing. Front. Microbiol. 12,
2126 (2021).
12. Langenfeld, N. J. et al. Optimizing nitrogen fixation and recycling for food
production in regenerative life support systems. Front. Astron. Space Sci. 8,
105 (2021).
13. Rapp, D. Use of Extraterrestrial Resources for Human Space Missions to Moon
or Mars 31–90 (Springer, 2013).
14. Werkheiser, N. In-Space Manufacturing: Pioneering a Sustainable Path to
Mars Tech. Rep., N, Washington DC. https://ntrs.nasa.gov/citations/
20150022327 (2015).
15. Cannon, K. M. & Britt, D. T. Feeding one million people on Mars. New Space
7, 245–254 (2019).
16. McNulty, M. J. et al. Molecular pharming to support human life on the Moon,
Mars, and beyond. Crit. Rev. Biotechnol. 0,1–16 (2020).
17. Poughon, L., Farges, B., Dussap, C. G., Godia, F. & Lasseur, C. Simulation of
the MELiSSA closed loop system as a tool to define its integration strategy.
Adv. Space Res. 44, 1392–1403 (2009).
18. NASA’s Journey to Mars: Pioneering Next Steps in Space Exploration. Tech.
Rep., National Aeronautics and Space Administration, Washington DC.
https://www.lpi.usra.edu/lunar/strategies/NP-2015-08-2018-HQ (2015).
19. A Midterm Assessment of Implementation of the Decadal Survey on Life and
Physical Sciences Research at NASA. Tech. Rep., National Academy of
Sciences, Washington, DC. https://nap.nationalacademies.org/catalog/24966/
a-midterm-assessment-of-implementation-of-the-decadal-survey-on-life-and-
physical-sciences-research-at-nasa (2018).
20. DOE Announces New $ 60 Million Investment to Increase Energy Efficiency in
Manufacturing.https://www.energy.gov/articles/doe-announces-new-60-
million-investment-increase-energy-efficiency-manufacturing (2021).
21. Marshall Space Flight Center Space Systems. Tech. Rep., National Aeronautics
and Space Administration, Marshall Space Flight Center, Huntsville, AL.
https://www.nasa.gov/sites/default/files/atoms/files/space_systems.pdf (2011).
22. Chapline, G. & Sullivan, S. Systems Engineering for Lifecycle of Complex
Systems (Engineering Innovations (NASA), 2010).
23. Cohen, J. The crucial role of CS in systems and synthetic biology. Commun.
ACM 51,15–18 (2008).
24. Mandell, D. J. et al. Biocontainment of genetically modified organisms by
synthetic protein design. Nature 518,55–60 (2015).
25. Tian, R. et al. Titrating bacterial growth and chemical biosynthesis for efficient
N-acetylglucosamine and N-acetylneuraminic acid bioproduction. Nat.
Commun.11, 5078 (2020).
26. Lee, H. J., Choi, J.-I. & Woo, H. M. Biocontainment of engineered
Synechococcus elongatus PCC 7942 for photosynthetic production of α-
Farnesene from CO(2). J. Agric. Food Chem. 69, 698–703 (2021).
27. Averesch, N. J. H. Choice of microbial system for in-situ resource utilization
on Mars. Front. Astron. Space Sci. 8, 116 (2021).
28. Weusthuis, R. A., Lamot, I., van der Oost, J. & Sanders, J. P. M. Microbial
production of bulk chemicals: Development of anaerobic processes. Trends
Biotechnol. 29, 153–158 (2011).
29. McNulty, M. J. et al. Evaluating the cost of pharmaceutical purification for a
long-duration space exploration medical foundry. Front. Microbiol. 12,
700863 (2021).
30. Arkin, A. P. et al. KBase: The United States department of energy systems
biology knowledgebase. Nat. Biotechnol. 36, 566–569 (2018).
31. Lucks, J. B., Qi, L., Whitaker, W. R. & Arkin, A. P. Toward scalable parts
families for predictable design of biological circuits. Curr. Opin. Microbiol. 11,
567–573 (2008).
32. Carbonell, P. Metabolic Pathway Design 3–10 (Springer, 2019).
33. Appleton, E., Madsen, C., Roehner, N. & Densmore, D. Design automation in
synthetic biology. Cold Spring Harbor Perspect. Biol. 9, a023978 (2017).
34. Goñi-Moreno, A. et al. An implementation-focused bio/algorithmic workflow
for synthetic biology. ACS Synthetic Biol. 5, 1127–1135 (2016).
COMMUNICATIONS ENGINEERING | https://doi.org/10.1038/s44172-022-00012-9 PERSPECTIVE
COMMUNICATIONS ENGINEERING | (2022) 1:13 | https://doi.org/10.1038/s44172-022-00012-9 | www.nature.com/commseng 7
35. Shetty, R. P., Endy, D. & Knight, T. F. Engineering BioBrick vectors from
BioBrick parts. J. Biol. Eng. 2,1–12 (2008).
36. Canton, B., Labno, A. & Endy, D. Refinement and standardization of synthetic
biological parts and devices. Nat. Biotechnol. 26, 787–793 (2008).
37. Cox, R. S. et al. Synthetic biology open language (SBOL) version 2.2. 0. J.
Integrative Bioinform. 15, 20180001 (2018).
38. Cheng, A. A. & Lu, T. K. Synthetic biology: An emerging engineering
discipline. Annu. Rev. Biomed. Eng. 14, 155–178 (2012).
39. Mankins, J. C. Technology readiness assessments: A retrospective. Acta
Astronautica 65, 1216–1223 (2009).
40. Hirshorn, S. & Jefferies, S. Final report of the NASA Technology Readiness
Assessment (TRA) study team Tech. Rep., National Aeronautics and Space
Administration. https://ntrs.nasa.gov/citations/20170005794 (2016).
41. Castro, S. L, Smith, D. J & Ott, M. Researcher’s Guide to: International Space
Station Microbial Research (Government Printing Office, 2014).
42. Khodadad, C. L. M. et al. Microbiological and nutritional analysis of lettuce
crops grown on the International Space Station. Front. Plant Sci. 11, 199
(2020).
43. Burton, A. S. et al. Off earth identification of bacterial populations using 16S
rDNA nanopore sequencing. Genes 11, 76 (2020).
44. Keppler, J. et al. The final configuration of the algae-based ISS experiment
PBR@ LSR. In 48th International Conference on Environmental Systems
(Institute of Space Systems, University of Stuttgart, Germany, Albuquerque,
NM, 2018).
45. Aunins, T. R. et al. Spaceflight modifies Escherichia coli gene expression in
response to antibiotic exposure and reveals role of oxidative stress response.
Fronti. Microbiol. 9, 310 (2018).
46. Boguraev, A.-S. et al. Successful amplification of DNA aboard the
International Space Station. npj Microgravity 3, 26 (2017).
47. McIntyre, A. B. R. et al. Nanopore sequencing in microgravity. npj
Microgravity 2,1–9 (2016).
48. Joannès, J. Feasibility study of a DNA-sequencing cubesat satellite. J. British
Interplanet. Soc. 70, 287–299 (2017).
49. Karouia, F., Peyvan, K. & Pohorille, A. Toward biotechnology in space: High-
throughput instruments for in situ biological research beyond earth.
Biotechnology Adv. 35, 905–932 (2017).
50. Zavaleta, J., Iyer, J., Mhatre, S., Dolling-Boreham, R. & Bhattacharya, S. An
automated behavioral analysis of Drosophila melanogaster. In Annual Meeting
of the American Society for Gravitational and Space Research.https://ntrs.nasa.
gov/citations/20190033964 (2019).
51. Suffredini, M. T. Reference Guide to the International Space Station. Tech.
Rep., National Aeronautics and Space Administration, Johnson Space Center,
Houston, TX (2014).
52. Marzioli, P. et al. CultCube: Experiments in autonomous in-orbit cultivation
on-board a 12-Units CubeSat platform. Life Scie. Space Res. 25,42–52 (2020).
53. Luna, A., Meisel, J., Hsu, K., Russi, S. & Fernandez, D. Protein structural
changes on a CubeSat under rocket acceleration profile. npj Microgravity 6,12
(2020).
54. Santoni, F. et al. GreenCube: Microgreens cultivation and growth monitoring
on-board a 3U CubeSat. In 2020 IEEE 7th International Workshop on
Metrology for AeroSpace (MetroAeroSpace) 130–135 (Institute of Electrical and
Electronics Engineers (IEEE), 2020).
55. Cubesat 101: Basic Concepts and Processes for First-Time CubeSat Developers.
Tech. Rep., National Aeronautics and Space Administration, Washington DC.
https://www.nasa.gov/sites/default/files/atoms/files/nasa_csli_cubesat_101_
508.pdf (2017).
56. Johnstone, A. CubeSat design specification (1U-12U) rev 14 CP-CDS-R14.
Tech. Rep., (California Polytechnic State University, San Luis Obispo, CA,
2020).
57. Hurlbert, K. et al. Human Health, Life Support and Habitation Systems
Technology Area 06. Tech. Rep., National Research Council, Washington DC.
https://nap.nationalacademies.org/catalog/13354/nasa-space-technology-
roadmaps-and-priorities-restoring-nasas-technological-edge (2012).
58. Farmer, T. A STEM Brainstorm at NASA. Techniques: Connecting Education
Careers 84,42–43 (2009).
59. Engle, H. A. & Christensen, D. L. Identification and evaluation of educational
uses and users for the STS. Educational planning for utilization of space
shuttle ED-PLUSS. Tech. Rep., Washington DC. https://ntrs.nasa.gov/
citations/19740027152 (1974).
60. Brodsky, R. F. The time has come for the BS in astronautical engineering. Eng.
Education 76, 149–152 (1985).
61. Fletcher, L. S. & Page, R. H. Technology transfer: The key to successful space
engineering education. Acta Astronautica 29, 141–146 (1993).
62. Gruntman, M. The time for academic departments in astronautical
engineering. In AIAA SPACE 2007 Conference & Exposition https://doi.org/10.
2514/6.2007-6042 (2007).
63. Young, L. R. & Natapoff, A. The Harvard-MIT PHD program in
bioastronautics. Life Space for Life on Earth 553, 90 (2008).
64. Klaus, D. M. Incorporating bioastronautics into an engineering curriculum. In
44th International Conference on Environmental Systems (Tucson, AZ, 2014).
65. Criteria for Accrediting Engineering Programs, 2020–2021 ∣ABET https://
www.abet.org/accreditation/accreditation-criteria/criteria-for-accrediting-
engineering-programs-2020-2021/ (2021).
66. National Aeronautics And Space Administration (NASA) Model Equal
Employment Opportunity Program Status Report: FY 2019. Tech. Rep.,
National Aeronautics and Space Administration, Washington DC. https://
www.nasa.gov/sites/default/files/atoms/files/fy2020_md_715_report_signed_
tagged.pdf (2020).
Acknowledgements
This work is supported by the grant from the National Aeronautics and Space
Administration (NASA, award number NNX17AJ31G).
Author contributions
A.J.B., A.M., J.M.H., and A.P.A. conceived the concept based on the Center for the
Utilization of Biological Engineering in Space (CUBES). D.H. led the graphics effort with
assistance from A.J.B. G.M., I.L., N.J.H.A., A.A.M., A.M., and A.P.A. contributed to
research and analyses. All authors (A.J.B., I.L., D.H., J.M.H., G.V., G.M., M.J.M., K.Y.,
N.J.H.A., C.S.C., T.W., L.C.S., C.S.C., S.M., K.A.M., A.A.M., A.M., and A.P.A.) wrote and
edited the manuscript.
Competing interests
The authors declare no competing interests.
Additional information
Supplementary information The online version contains supplementary material
available at https://doi.org/10.1038/s44172-022-00012-9.
Correspondence and requests for materials should be addressed to Aaron J. Berliner or
Adam P. Arkin.
Peer review information Communications Engineering thanks Yanfeng Liu, Matthew
Gilliham, and the other, anonymous, reviewer for their contribution to the peer review of
this work.
Reprints and permission information is available at http://www.nature.com/reprints
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.
Open Access This article is licensed under a Creative Commons
Attribution 4.0 International License, which permits use, sharing,
adaptation, distribution and reproduction in any medium or format, as long as you give
appropriate credit to the original author(s) and the source, provide a link to the Creative
Commons license, and indicate if changes were made. The images or other third party
material in this article are included in the article’s Creative Commons license, unless
indicated otherwise in a credit line to the material. If material is not included in the
article’s Creative Commons license and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to obtain permission directly from
the copyright holder. To view a copy of this license, visit http://creativecommons.org/
licenses/by/4.0/.
© The Author(s) 2022
PERSPECTIVE COMMUNICATIONS ENGINEERING | https://doi.org/10.1038/s44172-022-00012-9
8COMMUNICATIONS ENGINEERING | (2022) 1:13 | https://doi.org/10.1038/s44172-022-00012-9 | www.nature.com/commseng