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Published Online: 10 October 2024 在线发布: 2024 年 10 月 10 日

Space Synthetic Biology: A Paradigm for Sustainability on Earth and Beyond
空间合成生物学:地球及其他地区的可持续发展范例

Publication: New Space
出版物New Space

Abstract 抽象

National space agencies and private entities aim to establish outposts on the Moon and Mars before the second half of the century. This goal requires new technology paradigms that must be readied now for implementation in mission architecture. Here we present the case that synthetic biology is one such enabling technology that will work in synergy with a growing bioeconomy to solve a broad array of challenges facing humans on- and off-Earth, as they establish a foothold on the Moon in the post-Artemis years and continue to the exploration and eventual habitation of Mars. We propose a phased integration of synthetic biology into Space missions over time and identify critical dual-use breakthroughs that will expand the impact of synthetic biology on both Space missions and the Terrestrial bioeconomy. Finally, we highlight actions by national space agencies and the private sector that will be critical in the coming years to harness the potential of synthetic biology for establishing a sustainable human presence off-Earth.
国家航天机构和私营实体的目标是在本世纪下半叶之前在月球和火星上建立前哨站。这个目标需要新的技术范式,现在必须准备好在任务架构中实施。在这里,我们提出了这样一个案例,即合成生物学就是这样一种使能技术,它将与不断增长的生物经济协同作用,以解决人类在地球上和地球外面临的广泛挑战,因为他们在后阿尔忒弥斯时代在月球上站稳脚跟,并继续探索和最终定居火星。我们建议随着时间的推移分阶段将合成生物学整合到太空任务中,并确定关键的军民两用突破,以扩大合成生物学对太空任务和陆地生物经济的影响。最后,我们重点介绍了国家航天机构和私营部门的行动,这些行动在未来几年对于利用合成生物学的潜力在地球外建立可持续的人类存在至关重要。

INTRODUCTION TO SPACE SYNTHETIC BIOLOGY: WHY NOW?
太空合成生物学简介:为什么是现在?

Synthetic biology (SynBio) is the application of engineering principles to biology for the design and construction of units or systems with new functions. Propelled by the ever accelerating advances in integrating life and computer science, from bioinformatics to deep learning to artificial intelligence, SynBio is poised to deliver breakthrough technologies that play a pivotal role in the emergence of a new bio-based economy. This bioeconomy is expected to redefine aspects of the energy, materials, food, and pharma sectors, related to but not limited to areas such as safety, security, and sustainability.
合成生物学 (SynBio) 是将工程原理应用于生物学,用于设计和构建具有新功能的单元或系统。从生物信息学到深度学习再到人工智能,生命科学和计算机科学的整合不断加速进步,SynBio 已准备好提供突破性技术,这些技术在新的生物经济的出现中发挥着关键作用。预计这种生物经济将重新定义能源、材料、食品和制药行业的各个方面,包括但不限于安全、安保和可持续性等领域。
Given a projected global annual impact of USD 2–4 trillion by 2040,1,2 the U.S. government has taken several actions to secure the position of the USA as a major stakeholder in bioindustrial manufacturing. Consortia of national laboratories such as Agile BioFoundry, funded by the U.S. Department of Energy, serve to “operate as a distributed biofoundry in collaboration with industry and academia.”3 Federally sponsored manufacturing innovation institutes such as the bioindustrial manufacturing and design ecosystem (BioMADE), which is sponsored by the U.S. Department of Defense, have been formed to spawn a “sustainable, domestic end-to-end bioindustrial manufacturing ecosystem.”4 White House Executive Order 140815 announced a “whole-of-government approach to advance biotechnology and biomanufacturing towards innovative solutions in health, climate change, energy, food security, agriculture, supply chain resilience, and national and economic security.” Given the wide range of industry verticals that could be affected by an expanding bioeconomy, “Bold Goals” have been defined for U.S.-based biotechnology and biomanufacturing,3 substantiating EO 14081.
预计到 2040 年,全球每年的影响将达到 2-4 万亿美元,1,2 美国政府已采取多项行动,以确保美国作为生物工业制造主要利益相关者的地位。由美国能源部资助的 Agile BioFoundry 等国家实验室联盟致力于“与工业界和学术界合作,作为分布式生物铸造厂运作”。3 由美国国防部赞助的生物工业制造和设计生态系统 (BioMADE) 等联邦资助的制造创新机构已经成立,旨在催生一个“可持续的国内端到端生物工业制造生态系统”。4 白宫第 14081 号行政命令5 宣布了“一种全政府方法,以推进生物技术和生物制造,在健康、气候变化、能源、粮食安全、农业、供应链弹性以及国家和经济安全方面提供创新解决方案。鉴于生物经济扩张可能影响的广泛垂直行业,美国生物技术和生物制造定义了“大胆目标”,3 证实了 EO 14081。
A sustainable biochemical industry is seen as a foundation of an eventual circular economy, transforming the life cycle of commodities with regular demand and high turnover, both on Earth and in space.6 Hence, in addition to driving the bioeconomy, SynBio-based solutions are relevant to the current United Nations Sustainable Development Goals,7,8 with potentially major economic and social benefits worldwide.9–12
可持续的生化工业被视为最终循环经济的基础,它改变了地球和太空中具有固定需求和高周转率的商品的生命周期。6 因此,除了推动生物经济外,基于合成生物的解决方案还与当前的联合国可持续发展目标相关,7,8 在全球范围内具有潜在的重大经济和社会效益。9-12
The bioeconomy will also extend into the new Space Age13 as SynBio has several unique advantages with regard to Space versus Terrestrial applications (examples are discussed below). First, SynBio has the potential to solve upmass constraints on missions, thus increasing mission capabilities.14 Second, there are no indigenous manufacturing industries or jobs off-Earth that would be disrupted by designing systems and processes that are inherently sustainable. Third, the potential for establishing new jobs and new economies through SynBio in Space is attractive for investing in the Space-specific education, functionalities, and markets that tie back to the Terrestrial bioeconomy.15
生物经济也将延伸到新的太空时代13,因为 SynBio 在太空与地面应用方面具有几个独特的优势(示例将在下面讨论)。首先,SynBio 有可能解决任务中的质量限制,从而提高任务能力。14 其次,地球以外的本土制造业或工作岗位不会因设计本质上可持续的系统和流程而受到干扰。第三,通过太空合成生物创造新就业机会和新经济的潜力对于投资于与陆地生物经济相关的太空特定教育、功能和市场具有吸引力。15
Perhaps most importantly, SynBio will also be key to addressing the recommendations of the National Academies’ 2023 Decadal Survey on Biological and Physical Sciences (BPS) Research in Space that will empower humans to live and travel in Space,16 as we argue below.
也许最重要的是,SynBio 也将是解决美国国家科学院 2023 年太空生物和物理科学 (BPS) 研究十年调查建议的关键,这些建议将使人类能够在太空中生活和旅行,16 正如我们在下面所说的那样。
What are the major challenges to human long-duration Space travel and settlement across the solar system? The 2020 NASA Space Technology Taxonomy identifies distinct challenges,17 such as radiation and physiological adaptation to lower gravity. Although SynBio conceivably could be applicable in nearly all of these areas, we must consider whether it should. Although there are strong arguments for using existing systems that are proven to support humans off-planet, extended missions will need to address additional payload constraints, particularly limits to the mass launched into Space (upmass) and the shelf-life of the cargo.18 Critically, reliability and resilience as well as redundancy and flexibility will be key to mission success and crew safety, given the increasing fragility of supply chains when advancing into deep Space. These considerations motivate our focus here on three NASA technology taxonomy areas in particular: TX06 (human health, lifesupport, and habitation systems), TX07 (exploration destination systems), and TX12 (materials, structures, mechanical systems, and manufacturing). SynBio is also relevant to recurring tenets of NASA’s Moon to Mars objectives, including: RT-1, International Collaboration; RT-2, Industry Collaboration; RT-3, Crew Return; RT-5, Maintainability, and Reuse.19
人类在太阳系中的长期太空旅行和定居面临的主要挑战是什么?2020 年 NASA 空间技术分类法确定了不同的挑战,17 例如辐射和对较低重力的生理适应。尽管可以想象 SynBio 几乎可以应用于所有这些领域,但我们必须考虑它是否应该适用。尽管有强有力的论据支持使用已被证明可以支持人类在地球外飞行的现有系统,但扩展任务需要解决额外的有效载荷限制,特别是对发射到太空的质量 (upmass) 和货物保质期的限制。18 至关重要的是,鉴于供应链在进入深空时日益脆弱,可靠性和弹性以及冗余和灵活性将是任务成功和机组人员安全的关键。这些考虑因素促使我们特别关注 NASA 的三个技术分类领域:TX06(人类健康、生命支持和居住系统)、TX07(探索目的地系统)和 TX12(材料、结构、机械系统和制造)。SynBio 还与 NASA 月球到火星目标的反复出现的原则相关,包括:RT-1,国际合作;RT-2,行业合作;RT-3,机组人员返航;RT-5、可维护性和重用。19

THE POWER OF BIOTECHNOLOGY TO OVERCOME UPMASS CONSTRAINTS
生物技术克服 UPMASS 限制的力量

Imagine a manufacturing technology that is self-replicating and self-repairing, modular, reprogrammable, and exceedingly flexible in terms of the input. It can create fine chemicals and polymers with monomeric precision, is remarkably resilient, and can be stabilized simply by dewatering, with a shelf-life at room temperature on the order of years to centuries.20 That technology is life.
想象一下一种制造技术,它是自我复制和自我修复的、模块化的、可重新编程的,并且在输入方面非常灵活。它可以制造具有单体精度的精细化学品和聚合物,具有极强的弹性,并且只需脱水即可稳定,在室温下的保质期约为数年到数百年。20 技术就是生活。
Biotechnology has the power to solve many of the upmass constraints of Space travel by enabling the reuse of resources and basic feedstocks that are available en route (through so-called “loop closure”) and/or at destination (through “in situ resource utilization” (ISRU)). In the former case, the feedstock can be derived through the recycling of waste streams derived from supplies that have been transported from Earth such as food and packaging. In contrast, ISRU takes advantage of feedstocks that are available in significant, accessible quantities on-site, such as H2O, atmospheric CO2 and N2, and minerals, in the case of Mars.18,21–23 On Earth, advanced manufacturing approaches that leverage these resources usually require bulky (heavy) and sophisticated hardware and infrastructure such as chemical reactors, rectification columns, and cleanrooms, as well as costly and potentially environmentally damaging inputs such as fossil fuels, rare earths, and noble metals. But there is no more precise nanotechnologist and molecular factory than a living cell.24 For example, several biochemical mechanisms exist for fixing CO2 and N2; metals are bound to various biomolecules with precision, potentially paving the way for extraction and separation of ore as well as spent electronics.25,26
生物技术能够通过实现途中(通过所谓的“闭环”)和/或目的地(通过“原位资源利用”(ISRU))可用的资源和基本原料的再利用,解决太空旅行的许多质量限制。在前一种情况下,原料可以通过回收从地球运输的用品(如食品和包装)产生的废物流来获得。相比之下,ISRU 利用了现场可获得的大量原料,例如 H2O、大气中的 CO2 和 N2,以及火星的矿物。18,21–23在地球上,利用这些资源的先进制造方法通常需要笨重且复杂的硬件和基础设施,例如化学反应器、精馏塔和洁净室,以及昂贵且可能对环境造成破坏的投入,例如化石燃料、稀土和贵金属。但是,没有比活细胞更精确的纳米技术人员和分子工厂了。24 例如,存在几种固定 CO2 和 N2 的生化机制;金属与各种生物分子精确结合,可能为矿石以及废电子产品的提取和分离铺平道路。25,26
Further, many supplies of regular use,18,27,28 such as food and pharmaceuticals but also materials, lack the long-term stability required for a nominal ∼2.5-year roundtrip Mars mission (conjunction class).29 Thus, a “take” strategy must be supplemented with “make” strategies to enable sustainable exploration.18,27,28 Examples of such supplies include food30 as well as pharmaceuticals—especially peptide-based biologics that support crew health, such as human growth hormone (hGH)—and have shelf-lives of much less than a year, even with refrigeration.31 An on-site, on-demand “astropharmacy” based on the transgenic SynBio production of such pharmaceuticals may be part of the solution,32–34 supplementing abiotic approaches.35 Importantly, such technologies have dual applications on Earth, particularly for austere locations with unreliable supply chains or when needs are restricted to a small number of people, such as orphan drugs.36 Further, Space Biotechnology could include self-renewing recycling and manufacturing systems (biorefineries) for materials, as well as power plants, sensors, and diagnostics.14
此外,许多经常使用的供应,18,27,28,如食品和药品,以及材料,缺乏名义上 ∼2.5 年往返火星任务(合相类)所需的长期稳定性。29 因此,“获取”策略必须与“制造”策略相辅相成,以实现可持续勘探。18,27,28 元此类供应的例子包括食品30 以及药品,尤其是支持船员健康的基于肽的生物制剂,例如人类生长激素 (hGH),即使冷藏,其保质期也远不到一年。31 基于此类药物的转基因 SynBio 生产的现场按需“天体药房”可能是解决方案的一部分,32-34 补充非生物方法。35 重要的是,此类技术在地球上具有双重应用,特别是对于供应链不可靠的严峻地区,或者当需求仅限于少数人时,例如孤儿药。36 此外,空间生物技术可以包括用于材料的自我更新回收和制造系统(生物精炼厂),以及发电厂、传感器和诊断。14
The major challenge to harnessing the power of biology in support of Space activities pertains to the fact that Terrestrial life evolved on Earth. Natural biological organisms and their underlying biochemistries have evolved for survival and competitive advantage on Earth, rather than being optimized for one specific task. Thus, most organisms taken out of their natural ecological niche and possibly even off-planet should and perhaps must be adapted (evolved or engineered) to the altered conditions (such as higher radiation and lower gravity). SynBio provides the means to tailor organisms or ecosystems for specific off-planet needs.37,38 This strategy may reduce the engineering required for designing and operating bioprocesses in Space, thus decreasing mass and power requirements while delivering robust and potentially flexible mission capabilities. For example, a microbial cell factory that has already been modified on Earth for a particular biomanufacturing task may only require additional genetic engineering to withstand the higher radiation levels of Space.39 Alternatively, a species must be cultivated in a controlled environment closer to its Terrestrial environment, which has the benefit of relying on well-studied systems that do not need significant further modifications. In either case, planetary protection concerns need to be considered to avoid contamination of potential research targets for astrobiology.14,36,40,41
利用生物学的力量来支持太空活动的主要挑战与地球生命在地球上进化的事实有关。自然生物有机体及其潜在的生物化学已经进化为地球上的生存和竞争优势,而不是针对一项特定任务进行优化。因此,大多数脱离自然生态位甚至可能在地球外的生物都应该而且也许必须适应(进化或工程化)以适应改变的条件(例如更高的辐射和更低的重力)。SynBio 提供了为特定的地球需求定制生物体或生态系统的方法。37,38 元这种策略可以减少在太空中设计和操作生物过程所需的工程设计,从而降低质量和功率要求,同时提供强大且可能灵活的任务能力。例如,已经在地球上针对特定生物制造任务进行了改造的微生物细胞工厂可能只需要额外的基因工程来承受太空的更高辐射水平。39 或者,一个物种必须在更接近其陆地环境的受控环境中进行培养,其好处是依赖于经过充分研究的系统,不需要重大的进一步改造。无论哪种情况,都需要考虑行星保护问题,以避免污染天体生物学的潜在研究目标。14364041

FROM EARTH TO SPACE: PHASED INTEGRATION Of Synthetic Biology
从地球到太空:合成生物学的分阶段整合

Harnessing the power of SynBio in support of human exploration and settlement of the Moon and Mars requires the coordination of two rapidly moving fields: (1) the planning and implementation of space-exploration programs, and (2) the advancement of SynBio and its applications.40 Replacing existing abiotic technologies with potentially superior but less flight-tested biological solutions introduces risk until proven by design-build-test-learn (DBTL) cycles designed to increase the technology readiness level (TRL) of the biotic solutions. Ideally, such technologies will drop into the existing mission architecture, minimizing the extent of changes required and disruption to other systems, thus enabling rapid deployment.
利用 SynBio 的力量来支持人类对月球和火星的探索和定居,需要协调两个快速发展的领域:(1) 太空探索计划的规划和实施,以及 (2) SynBio 及其应用的进步。40 用可能更优越但经过较少飞行测试的生物解决方案取代现有的非生物技术会带来风险,直到通过旨在提高生物解决方案的技术就绪水平 (TRL) 的设计-构建-测试-学习 (DBTL) 循环得到验证。理想情况下,此类技术将融入现有的任务架构中,最大限度地减少所需的更改和对其他系统的干扰程度,从而实现快速部署。
Therefore, we envision a phased approach toward integration of SynBio in which missions during the 10-year horizon focus on “carry-along” and “drop-in” SynBio-based technologies that have a track record of success on Earth or in some cases in low Earth orbit (LEO). Within 5 years of the first Artemis astronauts setting foot on the Moon, “make it there” SynBio approaches with the greatest potential to be transformative for space missions (e.g., by dramatically decreasing upmass) should be prioritized to deliver reliable applications within the 10–30 year horizon. Such prioritized SynBio approaches would include ones that tackle problems for which there are no abiotic approaches currently available, such as the shelf-life issue of pharmaceuticals described above. Ideally, these approaches will be highly automated and resilient, minimizing burdens on crew training and active time during a mission. The specific benefits of implementing such advanced support functions will depend on many factors that determine the concept of operations for a given mission scenario, which will be informed by explicit techno-economic analyses and backed by calculations of equivalent systems mass to validate biotechnological approaches for in situ manufacturing.41 Potentially pivotal “stretch goals” for SynBio in Space should be defined and researched as soon as possible to enable proof-of-principle work and, if promising, the required DBTL cycles to raise their TRL to where they are robust and reliable solutions. Consistent with this latter approach, the 2023 Decadal Survey on BPS Research in Space recommended that NASA pursue a research campaign in Bioregenerative Life-Support Systems (BLiSS).16
因此,我们设想了一种分阶段的 SynBio 整合方法,其中 10 年范围内的任务侧重于“随身携带”和“即用型”基于 SynBio 的技术,这些技术在地球上或在某些情况下在近地轨道 (LEO) 上都有成功的记录。在第一批 Artemis 宇航员踏上月球后的 5 年内,应优先考虑最有可能对太空任务产生变革性影响(例如,通过大幅降低质量)的 SynBio 方法,以便在 10-30 年内提供可靠的应用。这种优先的合成生物方法将包括解决目前没有非生物方法的问题的方法,例如上述药物的保质期问题。理想情况下,这些方法将是高度自动化和弹性的,最大限度地减少任务期间对机组人员培训和活动时间的负担。实施此类高级支持功能的具体好处将取决于决定给定任务场景操作概念的许多因素,这些因素将由明确的技术经济分析提供信息,并以等效系统质量的计算为后盾,以验证原位制造的生物技术方法。41 应尽快定义和研究 SynBio 在太空中可能的关键“延伸目标”,以实现原理验证工作,如果有希望,则进行所需的 DBTL 循环,以将其 TRL 提高到稳健可靠的解决方案。与后一种方法一致,2023 年 BPS 太空研究十年调查建议 NASA 开展生物再生生命支持系统 (BLiSS) 的研究活动。16
We believe that SynBio will be key for both of these recommended research campaigns, which constitute science and engineering fundamental to life off-planet. When biological engineering at destinations like Mars becomes possible, an ecosystem of biomanufacturing facilities co-localized to spacecraft, -stations, or bases could underpin sustainable communities of people, delivering the food, air, water, and waste processing that will enable long-duration or even permanent human habitation off-Earth while protecting environments such as the surfaces of the Moon and Mars.
我们相信 SynBio 将成为这两项推荐研究活动的关键,这些活动构成了地球外生命的基础科学和工程。当火星等目的地的生物工程成为可能时,与航天器、空间站或基地共址的生物制造设施生态系统可以支撑可持续的人类社区,提供食物、空气、水和废物处理,使人类能够在地球外长期甚至永久居住,同时保护月球和火星表面等环境。

CRITICAL BREAKTHROUGHS WILL DELIVER DUAL-USE TECHNOLOGIES
关键突破将带来军民两用技术

All technologies, including SynBio, must become efficient, reliable, and flexible before they can become critical pieces of infrastructure that drive circular economies on Earth or in Space. We have identified critical breakthroughs that will enable the development of dual-use technologies, having the potential to benefit both Earth and Space (Fig. 1). Specifically, the successful application of SynBio in Space will require purposefully created reagents, chassis organisms, methods, and hardware with maximum fidelity for cross-platform application.
包括 SynBio 在内的所有技术都必须变得高效、可靠和灵活,然后才能成为推动地球或太空循环经济的关键基础设施。我们已经确定了关键突破,这些突破将使军民两用技术的发展成为可能,有可能使地球和太空受益(图 1)。具体来说,SynBio 在太空中的成功应用将需要有目的地创建的试剂、底盘生物、方法和硬件,以实现跨平台应用的最大保真度。
Fig. 1. Critical dual-use breakthroughs of SynBio for Space. Pursuing critical technologies to advance SynBio in Space will benefit basic science, technology development, business, and ultimately daily life on and off Earth. These critical breakthroughs largely align with overarching research and development needs to fulfill the Bold Goals for U.S. Biotechnology and Biomanufacturing, (2) as well as the recommendations of the Decadal Survey on BPS Research in Space (9). LC, loop-closure; ISRU, in situ resource utilization; SynBio, Synthetic Biology.
图 1.SynBio 在太空中的关键军民两用突破。追求关键技术以推进太空合成生物将有利于基础科学、技术开发、商业,并最终有利于地球上和地球外的日常生活。这些关键突破在很大程度上与实现美国生物技术和生物制造的大胆目标 (2) 以及 BPS 太空研究十年调查 (9) 的建议基本一致。LC,闭环;ISRU,原位资源利用;SynBio,合成生物学。
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Molecular biology requires reagents that are manufactured and formulated to exceedingly high standards, while key components require cold storage to deliver even limited shelf-life. This limitation constrains the deployment of molecular biology on Space missions, where power for temperature control is at a premium and fresh reagents cannot be readily obtained (even “just” for resupply to LEO); holding times of payloads in anticipation of launch can be excessive. There is already movement toward adapting more robust and functional molecular biology for rugged conditions, for example by creating shelf-stable diagnostic tests that can be freeze-dried and rehydrated for use.33 Further investing in the development of simple, robust reagents for molecular biology such as highly stable dried cell-free transcription/translation systems will accelerate the field by opening up new application areas in Space and on Earth, for example in remote and resource-constrained locations.
分子生物学需要按照极高标准制造和配制的试剂,而关键成分需要冷藏才能提供有限的保质期。这种限制限制了分子生物学在太空任务中的部署,在太空任务中,温度控制的能力非常宝贵,而且无法轻易获得新鲜试剂(甚至“仅”用于重新供应给 LEO);在预期发射时保持有效载荷的时间可能过长。已经有趋势使更强大和功能性的分子生物学适应恶劣的条件,例如通过创建可以冷冻干燥和再水化以供使用的耐储存诊断测试。33 进一步投资于开发简单、强大的分子生物学试剂,例如高度稳定的干燥无细胞转录/翻译系统,将通过在太空和地球上开辟新的应用领域来加速该领域,例如在偏远和资源受限的地方。
A second critical breakthrough is the development of Space-worthy chassis organisms. Today, we know of extremophiles that tolerate or thrive in many of the exotic conditions that are more like places elsewhere in the solar system than the rest of Earth’s biosphere. Nevertheless, organisms that match the combined demands of a specific extraterrestrial environment are lacking. Harnessing the natural diversity of life on Earth to find or engineer microbes that are designed for use in specific unusual environments is a breakthrough critical for effective biomanufacturing—and not only in Space.37 This task will involve applying the entire modern toolkit of SynBio bioprospecting,23 adaptive evolution,38,39 and genetic manipulation toward new Space-focused applications. On Earth, advancing the engineering of extremophilic organisms will enable industrial bioprocesses to operate under more extreme (non-natural) conditions—such as high pressure, temperature, or excess concentrations of chemicals (e.g., solvents)—to optimize production (rate, titer, yield) and thereby reduce process costs. Longer-term, Space-worthy chassis organisms may one day be the backbone of in situ biomanufacturing on Mars. To this end, the 2023 Decadal Survey on BPS Research in Space16 recommended that NASA increase investigations into the impacts of the Space environment on biological growth, reproduction, and evolution, fundamental scientific knowledge that will be key to sustainable SynBio with live organisms.
第二个关键突破是开发具有太空价值的底盘生物。今天,我们知道极端微生物可以忍受或茁壮成长于许多奇特的条件,这些条件更像是太阳系其他地方的地方,而不是地球生物圈的其他地方。然而,缺乏符合特定外星环境综合需求的生物体。利用地球上生命的自然多样性来寻找或设计专为特定不寻常环境而设计的微生物,对于有效的生物制造至关重要,而且不仅仅是在太空中。37 这项任务将涉及将 SynBio 生物勘探、23 适应性进化、38,39 和遗传操作的整个现代工具包应用于以太空为中心的新应用。在地球上,推进极端微生物的工程设计将使工业生物过程能够在更极端(非自然)条件下运行,例如高压、高温或过浓度的化学品(例如溶剂),以优化生产(速率、滴度、产量),从而降低工艺成本。长期、适于太空的底盘生物有朝一日可能会成为火星原生物制造的支柱。为此,2023 年太空16 号 BPS 研究十年调查建议 NASA 加强对太空环境对生物生长、繁殖和进化影响的调查,这些基础科学知识将是活体生物可持续合成生物的关键。
The lack of hardware for biomanufacturing in Space, under conditions of lower gravity and higher radiation than on Earth,42 is a crucial bottleneck that presently limits the speed of progress in the field. Most notably absent is flight-tested hardware for DNA synthesis and manipulation where low gravity makes standard methods impossible. Bioprocessing in Space42 is still in its infancy, with some basic techniques such as DNA sequencing, DNA amplification,43 and gel electrophoresis44 performed in Space; facilities such as the Wet Lab RNA SmartCycler45 and a bioreactor (Multiple Orbital Bioreactor with Instrumentation and Automated Sampling (MOBIAS))46 are already operational on the ISS. The ability to synthesize DNA remotely, and thus program biological instructions on demand, unlocks the full utility of SynBio as a highly flexible and programmable technology platform for manufacturing and sensing. A critical breakthrough for the field will be translating the existing capabilities of ground-based biofabs to Space,47 allowing the rapid prototyping and building of any molecule. The existing infrastructure on the ISS has previously been sufficient to test SynBio capabilities, especially with an emphasis on miniaturization and automation, while accounting for lower gravitational forces (e.g., the use of microfluidic rather than “test-tube” platforms42). As ISS is decommissioned, small satellites, commercial platforms for LEO, Gateway, and other upcoming cis-Lunar operations must provide opportunities for extended testing and translation of biofoundry components.
在比地球更低的重力和更高的辐射条件下,太空中缺乏用于生物制造的硬件,42 是目前限制该领域进展速度的关键瓶颈。最值得注意的是,没有用于 DNA 合成和操作的经过飞行测试的硬件,其中低重力使标准方法不可能。Space42 中的生物工艺仍处于起步阶段,一些基本技术,如 DNA 测序、DNA 扩增43 和凝胶电泳44 都在 Space 中进行;Wet Lab RNA SmartCycler45 和生物反应器(带仪器和自动采样的多轨道生物反应器 (MOBIAS))46 等设施已在国际空间站运行。远程合成 DNA 的能力,从而按需编程生物指令,释放了 SynBio 作为高度灵活和可编程的制造和传感技术平台的全部功能。该领域的一个关键突破是将地面生物工厂的现有能力转化为太空,47 允许快速原型制作和构建任何分子。国际空间站上的现有基础设施以前足以测试 SynBio 的能力,特别是强调小型化和自动化,同时考虑较低的重力(例如,使用微流体而不是“试管”平台42)。随着国际空间站退役,小型卫星、LEO、Gateway 和其他即将到来的月操作的商业平台必须为生物铸造组件的扩展测试和转换提供机会。
A suite of hardware for SynBio in Space may in the short term allow for rapid iteration on biomanufacturing protein-based biomaterials in LEO, or deployment of similar devices in low-resource environments, benefiting developing countries in particular. In the long term, it will enable on-demand synthesis of chemicals that were not or could not be brought along (for example to Mars), significantly improving the resilience and feasibility of future missions.
一套用于太空合成生物的硬件可能在短期内允许在 LEO 中快速迭代基于生物制造蛋白质的生物材料,或在资源匮乏的环境中部署类似设备,特别是使发展中国家受益。从长远来看,它将能够按需合成没有或无法携带的化学物质(例如,带到火星),从而显著提高未来任务的弹性和可行性。

How to get there—a call to action
如何实现 - 行动号召

The bioeconomies of the USA and other countries will contribute to making reliable, cost-effective, and sustainable biomanufacturing a staple of life on Earth and in Space, driven by the private space sector and national (space) agencies alike.12
在私营航天部门和国家(太空)机构的推动下,美国和其他国家/地区的生物经济将有助于使可靠、经济高效和可持续的生物制造成为地球和太空生活的主要内容。12
Fundamental improvements to the resource requirements, reliability, and scale of biomanufacturing are best addressed by the global bioeconomy.2 Today, biomanufacturing processes often require expensive (and often unsustainable) feedstocks, are prone to variability in product quality, and are difficult to scale. Decreasing costs and improving the reliability of biomanufacturing is therefore essential. The global bioeconomy is collectively tackling these fundamentals by experimenting with new low-cost feedstocks derived from waste streams, creating low-cost purification strategies, developing processes that are more scalable, and engineering pathways to produce new products. For example, the USA has substantial renewable carbon resources that could support large-scale biomanufacturing efforts, which will likely incentivize investments into the development of the infrastructure required to leverage these resources.48,49 The result will be a thriving bioeconomy that creates jobs and is reliable, cost-effective, and sustainable. In this article, we call for the expansion of this vision to encompass humanity’s future off-Earth, positioning SynBio to address the recommendations of the National Academies as fundamental to human success in Space.16
全球生物经济最好地解决生物制造的资源需求、可靠性和规模的根本性改进。2 如今,生物制造工艺通常需要昂贵(且通常不可持续)的原料,产品质量容易出现变化,并且难以扩展。因此,降低成本和提高生物制造的可靠性至关重要。全球生物经济正在通过试验从废物流中提取的新型低成本原料、制定低成本净化策略、开发更具可扩展性的工艺以及设计生产新产品的途径来共同解决这些基本问题。例如,美国拥有大量的可再生碳资源,可以支持大规模的生物制造工作,这可能会激励投资开发利用这些资源所需的基础设施。48,49 元结果将是一个繁荣的生物经济,创造就业机会,并且可靠、具有成本效益和可持续性。在本文中,我们呼吁将这一愿景扩展到人类在地球以外的未来,将 SynBio 定位为满足美国国家科学院的建议,将其作为人类在太空取得成功的基础。16
Meanwhile, the private sector is well positioned to address many of the new hardware needs that come with the use of SynBio off-planet. Several companies have developed and are flight-testing cell-culture devices to conduct bioengineering and biomanufacturing in a microgravity environment.12 Expanding this repertoire of devices, particularly through open-access frameworks, will benefit these for-profit companies as well as national space agencies. This public-private integration will be critical for expanding both the pool of contributors to key advances in Space and the set of stakeholders in a sustainable human future.
与此同时,私营部门完全有能力满足在地球外使用 SynBio 带来的许多新硬件需求。几家公司已经开发并正在对细胞培养设备进行飞行测试,以在微重力环境中进行生物工程和生物制造。12 扩展这些设备,特别是通过开放获取框架,将使这些营利性公司和国家航天机构受益。这种公私融合对于扩大太空关键进步的贡献者群体和可持续人类未来的利益相关者群体至关重要。
Due to the exceptional flexibility of this technology, it is challenging to isolate a single best first use case of SynBio in Space that extends further than technology demonstration; the first use case will be determined based on mission needs and associated quantitative analyses such as equivalent systems mass.41 For example, is it better to ignore drugs that have a short shelf-life or make them fresh on demand? Most importantly, the multitude of national space agencies (e.g., NASA, CSA, ESA, JAXA, CNSA, and ISRO) can uniquely and in combination contribute to advancing the field by putting biomanufacturing solutions through the rigorous flight-testing process, ensuring that these processes are ready for human missions.
由于这项技术具有非凡的灵活性,因此很难分离出 SynBio 在太空中的第一个最佳第一个用例,该用例的范围超出了技术演示的范围;第一个用例将根据任务需求和相关的定量分析(例如等效系统质量)来确定。41 例如,忽略保质期短的药物还是按需新鲜的药物更好?最重要的是,众多国家航天机构(例如 NASA、CSA、ESA、JAXA、CNSA 和 ISRO)可以通过将生物制造解决方案通过严格的飞行测试过程,确保这些过程为人类任务做好准备,从而以独特的方式为该领域的发展做出贡献。

Concluding remarks and visionary outlook
结语和远见卓识

The vast majority of humans are and likely will stay, on planet Earth for the foreseeable future. So what is to gain from advancing SynBio for Space applications? Simply put, SynBio has the potential to revolutionize manufacturing, healthcare, environmental remediation, energy dependence, and other problem spaces. Critically, on Earth, solutions to these issues are pursued through legacy approaches that may not meet the needs of future generations. Game-changing solutions often do not gain traction as there is no immediate economic advantage to replacing legacy solutions. Planning for Space empowers us to reimagine solutions to Terrestrial problems by focusing on a use case that either does not currently have a solution, or replacing the planned solution has little socioeconomic or geopolitical ramification. Further, these solutions must ultimately be closed-loop—where all inputs and outputs as well as their dynamic fluctuations are known and accounted for—thus providing a template for a circular economy at a global scale.
在可预见的未来,绝大多数人类现在和将来都留在地球上。那么,推进 SynBio for Space 应用有什么好处呢?简而言之,SynBio 有可能彻底改变制造业、医疗保健、环境修复、能源依赖和其他问题领域。至关重要的是,在地球上,这些问题的解决方案是通过可能无法满足子孙后代需求的传统方法寻求的。改变游戏规则的解决方案通常不会受到关注,因为取代传统解决方案没有直接的经济优势。“太空规划”使我们能够重新构想地球问题的解决方案,方法是专注于当前没有解决方案的用例,或者替换计划的解决方案几乎没有社会经济或地缘政治影响。此外,这些解决方案最终必须是闭环的,其中所有输入和输出及其动态波动都是已知的并考虑到的,从而为全球范围内的循环经济提供模板。
Vulnerabilities in bioeconomy supply chains were exposed during the COVID-19 pandemic. Off-planet, supply chains are limited and fragile. A Mars supply chain would be the ultimate onshoring effort. Given the wide spacing of launch windows for Mars (currently a 2-year cadence),50 supply chains should be short, flexible, and resilient to unexpected events and geopolitics.
在 COVID-19 大流行期间,生物经济供应链的脆弱性暴露无遗。在地球之外,供应链有限且脆弱。Mars 供应链将是最终的在岸工作。鉴于火星的发射窗口间隔很宽(目前为 2 年),50 供应链应该简短、灵活,并且能够抵御意外事件和地缘政治。
The Terrestrial SynBio ecosystem has other requirements, such as scalability, near-term profitability, and environmental and geopolitical concerns such as national laws and competing economic interests. A Space-based SynBio ecosystem allows the industry to bypass many of these impediments. The Space Industry provides an unusual opportunity in that there are specific needs that currently lack a fully established ecosystem; default plans such as the Mars Design Reference Architecture 5.0 are currently in place but are in flux and can be improved.51 Further, given the global effort to wean ourselves from petrochemistry, new planetary bodies devoid of fossil fuels will force novel solutions without perturbing the legacy systems that exist on Earth. Thus, we firmly believe that aggressively pursuing SynBio for Space applications will not only solve urgent problems of human health, habitats, life support, and materials production for off-Earth applications but will ultimately deliver the game-changing solutions that will empower humans to thrive in the Anthropocene, wherever we call home.
陆地合成生物生态系统还有其他要求,例如可扩展性、近期盈利能力以及环境和地缘政治问题,例如国家法律和相互竞争的经济利益。天基 SynBio 生态系统使该行业能够绕过其中的许多障碍。航天工业提供了一个不寻常的机会,因为目前存在缺乏完全建立的生态系统的特定需求;默认计划(如 Mars Design Reference Architecture 5.0)目前已实施,但正在变化中,可以进行改进。51 此外,鉴于全球都在努力摆脱石油化学,没有化石燃料的新行星体将迫使人们提出新的解决方案,而不会干扰地球上存在的遗留系统。因此,我们坚信,积极寻求 SynBio for Space 应用不仅将解决人类健康、栖息地、生命支持和离地球应用材料生产等紧迫问题,而且最终将提供改变游戏规则的解决方案,使人类能够在人类世中茁壮成长,无论我们在哪里称之为家。

ACKNOWLEDGMENTS 确认

The authors wish to thank Chris Carberry and Explore Mars, Inc. for initiating the formation of the group that encouraged the writing of this article. The authors are grateful to the following individuals for fruitful discussions during the inception of the article: David Bray, Daniela Billi, Jennifer Brophy, Christopher Hernandez, and Andrew Hessel.
作者要感谢 Chris Carberry 和 Explore Mars, Inc. 发起了鼓励撰写本文的小组的成立。作者感谢以下人员在文章撰写期间进行的富有成效的讨论:David Bray、Daniela Billi、Jennifer Brophy、Christopher Hernandez 和 Andrew Hessel。

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