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Space synthetic biology emerging as key technology for Space Exploration and deep space manned missions

We are currently entering a new era of Space exploration, with humans preparing to travel further from the Earth than ever before. The US National Aeronautics and Space Administration’s (NASA) Artemis program, in collaboration with the European, Canadian, and Japanese space agencies, proposes to build an orbiting lunar Space station (Gateway) to support landing humans on the lunar surface by 2024. This will be followed by the establishment of a permanent inhabited lunar base in the following decade, which will in turn be used to support crewed missions to Mars after 2039. China has also announced a similar program, with crewed lunar missions planned in the 2030s, followed by crewed missions to Mars.

 

One of the biggest challenges to manned space missions is the expense. The NASA rule-of-thumb is that every unit mass of payload launched requires the support of an additional 99 units of mass, with “support” encompassing everything from fuel to oxygen to food and medicine for the astronauts, etc. Given the technical challenges and costs associated with leaving Earth and landing on planetary bodies , sending all consumables needed to sustain crews is unrealistic in the long term.

 

Thus, the time we can stay in remote settlements will depend on our ability to be independent of Earth. This can be achieved by relying on resources found on site, through an approach referred to as in situ resource utilization (ISRU). As explorers go farther and stay longer, supply missions from Earth will become increasingly unsustainable, and outposts will need to become self-sufficient. Explorers will need to supply themselves with the very same list of basic human needs such as food, materials, plus renewable, shelter, and medicine.

 

 Synthetic Biology for Deep Space Missions

Synthetic biology is the application of science, technology and engineering to facilitate and accelerate the design, manufacture and/or modification of genetic materials in living organisms, as defined by the European Commission. It envisions the redesign of natural biological systems for greater efficiency, as well as create new organisms as well as molecules with desired bio-attributes.

 

Among the potential applications of this new field is the creation of bioengineered microorganisms (and possibly other life forms) that can produce pharmaceuticals, detect toxic chemicals, break down pollutants, repair defective genes, destroy cancer cells, and generate hydrogen for the post-petroleum economy. Synthetic biology is already established on Earth. Now Experts believe that synthetic biology also holds the key to manned space exploration of the Moon and Mars.

 

“Not only does synthetic biology promise to make the travel to extraterrestrial locations more practical and bearable, it could also be transformative once explorers arrive at their destination,” says Adam Arkin, director of Berkeley Lab’s Physical Biosciences Division (PBD) and a leading authority on synthetic and systems biology.

 

Researchers are looking at four target areas: fuel generation, food production, biopolymer synthesis, and pharmaceutical manufacture. They showed that for a 916 day manned mission to Mars, the use of microbial biomanufacturing capabilities could reduce the mass of fuel manufacturing by 56-percent, the mass of food-shipments by 38-percent, and the shipped mass to 3D-print a habitat for six by a whopping 85-percent. In addition, microbes could also completely replenish expired or irradiated stocks of pharmaceuticals, which would provide independence from unmanned re-supply spacecraft that take up to 210 days to arrive.

 

As a manufacturing platform, biology’s method of choice is fermentation. The same age-old process by which microbes convert sugar into everything from yogurt to wine can be applied to make antibiotics, chemical polymers, and more. Fermentation is well-suited to space because it relies on the same equipment whether you’re making food, medicine, or polymers. The DNA in fermentation microbes can be thought of as programmable matter. Scientists on Earth could send instructions to DNA synthesizers in space, which could in turn create the microbes to produce chemicals and materials whose need might never have been anticipated

 

The first demonstrations of synthetic biology nutrients will employ yeast engineered to produce Zeaxanthin when activated. Zeaxanthin is a carotenoid, which is an important antioxidant for ocular health, a known risk for astronauts who spend extended periods of time in space.

 

Berkeley Lab researchers have used synthetic biology to produce an inexpensive and reliable microbial-based alternative to the world’s most effective anti-malaria drug, and to develop clean, green and sustainable alternatives to gasoline, diesel and jet fuels. In the future, synthetic biology could also be used to make manned space missions more practical.

 

“We’re breathing oxygen that was biologically produced,” says Lynn Rothschild, the head of the synthetic biology program at NASA’s Ames Research Center. “I’m wearing cotton that was biologically produced.” “Not only does synthetic biology promise to make the travel to extraterrestrial locations more practical and bearable, it could also be transformative once explorers arrive at their destination,” says Adam Arkin, director of Berkeley Lab’s Physical Biosciences Division (PBD) and a leading authority on synthetic and systems biology. BioNutrients for Astronaut Health.

 

Microorganisms could be extremely useful to cover our daily needs in space and on foreign planetary bodies as we do on Earth. For example, Humans have been consuming and otherwise using microorganism-produced resources on Earth throughout their history: oxygen produced by cyanobacteria and eukaryotic microalgae, food and drinks as edible microorganisms and fermented products (e.g., wine and yoghurt), drugs, various chemicals, biomaterials, biofuels, mined metals and so on. We also rely on them for many critical processes such as, for instance, waste recycling.

 

Synthetic Biology has the potential to significantly improve the safety and stability of missions in deep space. NASA is investigating two potential applications of synthetic biology—one to advance nutrition and one to increase in-space manufacturing capabilities.

 

BioNutrients for Astronaut Health

Astronauts aboard the International Space Station receive regular resupply shipments from Earth, providing them with nutritious food during their expeditions. Future astronauts on the journey to Mars will be much farther away, outside the reach of current cargo resupply capabilities. Even with the most advanced preservation and packaging technologies, food can lose its nutritional value during long-duration missions. Much like the discovery that citrus fruits cured the scurvy ailments of seafarers and other explorers in the 18th century, science is hard at work again to address the nutrient concerns of deep space explorers.

 

Synthetic biology developments under way will provide on-demand nutrients through hydratable, single-use packets that contain microbes engineered to produce target nutrients for human consumption. The packets will be hydrated to allow the microbes to grow for a short period before they are deactivated, at which point the nutrient content can be consumed.

 

The first demonstrations of synthetic biology nutrients will employ yeast engineered to produce Zeaxanthin when activated. Zeaxanthin is a carotenoid, which is an important antioxidant for ocular health, a known risk for astronauts who spend extended periods of time in space.

 

BioManufacturing for In-space Construction

On Earth, we use the products of refineries every day. One example is crude oil that is used to produce hundreds of every-day commodities such as gasoline, plastics, fabrics, cosmetics, and construction materials. Crude oil is harvested from Earth after organic compounds have been transformed for millions of years far below our planet’s surface.

 

Using rapid physical and chemical methods, we can expedite nature’s refinery process to convert carbon dioxide to organic materials. These organic materials are then used by genetically engineered microbes to produce plastics, fibers, and other types of feedstock for in-space manufacturing. Starting with a few raw materials found in the atmosphere and on the surface of Mars, and using advanced manufacturing techniques such as 3-D printing, microbial workers could enable the construction of habitats, tools, and spare parts on-demand.

 

“The possibilities of space synthetic biology are truly endless, yet each of them has immense importance back on Earth,” says Menezes.

 

Synthetic biological solutions to space problems in medicine, food, and carbon dioxide can address similar issues on Earth: personalized medicine, agriculture for growing populations, and fixing our carbon-dioxide-laden atmosphere. And while paraterraformed spaces give astronauts a safe place to sleep, the technologies can also help us learn to live sustainably on Earth. A Martian colony would be the ultimate zero-waste green space, whose ethos every earthling should get behind.

 

“I find the notion of doing ‘far-out space stuff’ that is simultaneously a priority on Earth really captivating and compelling,” says Menezes.

 

However, the harsh environmental conditions faced directly on Mars’s surface do not allow any known microorganism to grow efficiently: there are low temperatures, low pressure (5–11 mbar) and a high UV flux including UV-C radiation. The atmosphere is mostly composed of carbon dioxide (95.3 %), little nitrogen (2.7 %) and even less oxygen (0.13 %), and low moisture. Elaborated culture hardware providing Earth-like conditions could be suggested, but they would be highly energy consuming, very massive and consequently extremely costly to send to Mars (Lehto et al. 2006) even for small-scale cultures and would have many possible causes of failure due to relying on complex technologies.

 

Synthetic biology  can even allow genetic alteration of organisms to make them more space-worthy — resistant to radiation or heat, for instance — and to make them useful to space missions — like turning Martian dirt into concrete. Synthetic biology could be used to increase the resistance of microorganisms to Martian conditions, probably not enough to make them thrive at the surface but enough to reduce both hardware needs and risks of culture loss.

 

We’re not going to take sheep on space missions, she clarifies, but we could take the capabilities of oxygen- and cotton-making plants and put them into the DNA of more portable life, like yeast. “Start looking at biology as technology,” she says, a “genetic hardware story” that could infuse all aspects of space missions.

 

Rothschild advises the Stanford-Brown team in the International Genetically Engineered Machine competition, where her groups have, among other things, made wires using DNA as a template; created a biodegradable drone; and taken genes from extreme bacteria and inserted them into E. coli to create hybrid organisms that resist extreme pH, temperature, and dryness. They called it the Hell Cell.

 

A strategy could be to express genes from other organisms known to confer an advantage in coping with targeted stresses to increase microorganism’s fitness under conditions found beyond Earth (Cumbers and Rothschild 2010).  Once specific genes have been shown to confer an advantage to the targeted stress when expressed in the microorganism, they can be improved using various computational and molecular biology tools and methods. This approach is becoming more and more efficient, with notably a sharp decrease in DNA synthesis cost, the improvement of automated gene assembly methods, knowledge gained from systems biology, and the development of biological computer aided design (BioCAD) and other computational tools. Directed evolution provides an alternative approach that can allow complex modifications at an organismal level without an a priori knowledge of mechanisms.

 

“Because synthetic biology allows us to engineer biological processes to our advantage, we found in our analysis that technologies, when using common space metrics such as mass, power and volume, have the potential to provide substantial cost savings, especially in mass,” Menezes says.

 

Space Synthetic Biology (SynBio)

In the future, NASA’s long-duration lunar and Mars missions will require that we minimize the amounts of supplies launched, increase reuse and recycling, and use local resources to make crucial products for the crew. When possible, we want to make it there, not take it there.

 

The Space Synthetic Biology (SynBio) project, located at NASA’s Ames Research Center in California’s Silicon Valley, is developing technologies to biomanufacture valuable products on-demand such as vitamins and medicines. In addition, biomanufacturing processes will allow crews to produce valuable materials, such as a healthy fats, proteins and even a form of cement, from local resources.

 

The BioNutrients experiment is part of NASA’s SynBio project and will test an in-space nutrient production method that uses genetically-engineered baker’s yeast and an extended shelf-life growth substrate to produce specific antioxidants, such as beta carotene and zeaxanthin, typically found in carrots, bell peppers and other vegetables. In April 2019, the SynBio team launched their first batch of “BioNutrient” packs to the International Space Station for a five-year experiment. The BioNutrient packs are filled with dehydrated yeast and their food source. To initiate the tests, astronauts aboard the space station add sterile water to the pack, mix well and keep the packet warm for 48 hours. Then, they freeze it to be analyzed later, back on Earth. NASA scientists will check how the system performed, including how much yeast grew in the packets and how much nutrient the experiment produced.

 

The SynBio project team is also developing a technology that chemically converts carbon dioxide (CO2) and water to organic compounds that can “feed” microbial biomanufacturing systems to make a wide range of products such as food, medicines and plastics. This same method could be widely applied to sustainably create these products on Earth. To further advance these efforts, NASA’s Space Technology Mission Directorate asked scientists and engineers across the country to convert CO2 to molecules to enable biomanufacturing in space. These synthetic biology technologies will be an important part of astronaut health and the sustainability of future NASA missions to the Moon and beyond

 

Food

Food production in situ is key to making Space exploration viable. Currently, the cost of sending food to the International Space Station (ISS) is estimated as USD$ 20 000–40 000/kg, with each crew member receiving ∼1.8 kg of food (plus packaging) per day. Re-stocking from Earth, a lunar orbiting Space station or Mars habitation with food will be significantly more costly. The first trips to Mars are expected to be a three-year round trip, and it has been estimated that a four-person crew would need 10–11 000 kgs of food.

 

From the simple inputs of CO2, H2O and mineral nutrients, photosynthetic organisms create a vast array of molecules. In Space, where sustainability and resource limitation is paramount, plants have enormous potential for the production of nutritious food, pharmaceuticals, and biomaterials. Plants could also assist with air regeneration, water recycling, and astronaut mental health. To make this a reality, substantial advances in plant design are needed. These will need to occur in tandem with the development of automated and highly sustainable growth facilities.

 

Space Challenges

While there are many physical and biological constraints to growing plants during Space travel or on planetary surfaces, they can be summarized into two major challenges: (i) robust, efficient and automated CEA facilities; and (ii) crops optimised for the controlled environment, where plant metabolism can be tuned to meet a broad and changing array of needs.

 

CEA is a method of creating fully controlled environments for growing plants. This is sometimes referred to as ‘vertical farming’ or ‘indoor farming’. As the name suggests, these facilities are sealed off from the outside environment. Everything plants need at their various growing stages is provided artificially, including water, temperature, humidity levels, ventilation, light and CO2.

 

In Space, physical constraints dominate both during space-flight and on planetary surfaces. Many issues are familiar to those developing CEA on Earth, including space, power, water, light, temperature, atmospheric control, growth substrate and minimization of waste and costs.

 

Much progress has been made in recent years, particularly in the development of low energy LED lights suitable for plant growth. As a result, the global CEA market was estimated at USD$75M in 2020, and predicted to grow to USD$172M by 2025.

 

Space growth conditions can also have some unexpected effects. CO2 concentrations on the ISS can be much higher than the Earth’s atmosphere. Brassica rapa (Chinese cabbage) grown on the ISS in the Veggie growth system showed reduced biomass and necrosis, and the phenotype was eventually shown to be due to the elevated CO2 (which averaged 2800 ppm during the experiment)

 

Optimisation of plant architecture will also be critical to maximise space efficiency and reduce waste. Root systems can likely be minimised, and dwarf varieties of crops developed to allow vertical stacking of plants. Considerable research on the response of plants to hypoxia exists and biotechnological solutions for improving growth of plants in hypoxic conditions have been recently proposed

 

Additional stresses which arise from spaceflight, including DNA damage and mitochondrial dysfunction, have been well characterised in humans, and similar issues have been reported in plants

 

NASA’s Space Biology Program

The measurement of the effects of space-relevant stresses on organisms, and fundamental research into the underlying mechanisms of those effects, are core components of NASA’s Space Biology Program. These stresses include galactic cosmic radiation (GCR), solar particle events (SPEs), and reduced gravity. Notably, to date, biological experiments in space have mainly been conducted within Low Earth Orbit (LEO) (e.g., via the Space Shuttle Program, on the International Space Station (ISS), or small satellite missions). Only a few biological experiments have been conducted beyond LEO; therefore, the biological effects of conditions beyond LEO are still poorly understood.

 

The selected research projects seek to widen our understanding of biological responses beyond LEO by preparing experiments in which yeast, a eukaryotic microorganism, will be grown and monitored on the lunar surface utilizing the BioSensor hardware. This hardware consists of a microfluidic system that allows for the culturing of yeast and the measurement of cell growth and metabolic activity. The lunar surface is particularly distinctive in that organisms will experience a radiation environment that is unique from that found in LEO on the ISS, that includes GCR and neutrons, the latter of which are secondary particles generated from the interactions of primary particles with the lunar surface.

 

The announced awards will not involve the flight opportunity itself, but rather the integration of the proposed experimental payloads into the Biosensor hardware and biocompatibility testing on the ground to establish a functional experimental payload that is flight-ready for future missions. Awards will also support additional ground-based studies to examine the effects of simulated lunar conditions on the proposed model system.

 

When the projects are ready for integration, the selected investigators will work with a team of NASA engineers for hardware integration and testing. These tests will include verifying the systems’ performance with the biology and the required reagents to confirm functionality. Flight readiness testing will demonstrate that the payload can execute operations as designed during a flight-like configuration and yield data readouts to ensure that science objectives will be met during a future flight mission.

 

These space biology investigations will be conducted by three investigators from two institutions in two states. When fully implemented, about $900,000 will be awarded in fiscal years 2022-2025.

 

Space Bioprinter

In an opinion piece published online in Trends in Biotechnology, researchers from the Universities Space Research Association (USRA), MIT Lincoln Laboratory, and NASA outline ways that synthetic biology and 3-D printing can support life during deep-space human missions. Astronauts can pack  Earth’s unique renewable resource: cells. Cells of fungi and bacteria, for example, can be reprogrammed with synthetic DNA to produce specific materials, like bioplastics. These materials can then be fed into 3-D printers to manufacture things the astronauts may need during spaceflight — everything from hardware and medical devices to medicine and food.

 

The authors envision using synthetic biology to produce custom biological “ink” to 3-D print whatever may be needed over the course of a mission. Such a process would give scientists “the autonomy to design for the unknown,” says Jessica Snyder, a USRA researcher who leads the synthetic biology task for the NASA Academic Mission Services.

 

Bioprinter company Allevi and Made in Space have teamed up to put the first bioprinter in space. Made in Space already has two 3D printers on the ISS, but with the addition of Allevi’s ZeroG extruder, they’re hoping to open up opportunities for research. The extruder would slot into the existing printer and print with biomaterials such as hydrogels or hyperelastic bone. The ZeroG extruder is designed with zero gravity in mind. Extrusion is carefully executed so each layer will stick to the last even without gravity to help. Special systems are also in place to regulate temperatures, since heat flows differently in space.

 

References and resources also include:

https://www.sciencedirect.com/science/article/pii/S0958166921001646

 

 

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