Adapting humans to an oxygen-free environment through gene regulation to support space travel is a very challenging and cutting-edge topic. The following analysis is carried out from the aspects of scientific feasibility, potential paths and ethical challenges： ###1. Scientific principles and potential paths 1. **Biological basis of anaerobic metabolism** -Existing cases in nature: some nematodes (such as sponge symbiotic nematodes) and deep-sea organisms (such as vulcanized worms) can survive through anaerobic metabolism. -Key metabolic substitution pathway： * Use sulfides instead of oxygen as electron acceptors * ATP is produced by the Yanhusuo acid reductase system * Activate glycolysis-an enhanced version of the fermentation pathway 2. **Gene editing targets** -Hemoglobin transformation: improve oxygen binding/storage efficiency (such as whale myoglobin mutants) -Mitochondrial reprogramming： * Introduction of [NADH-quinone oxidoreductase] instead of complex IV *Enhance the continuous activation of hypoxia inducing factor (HIF-1a) -Enhanced antioxidant system： *Superexpression of superoxide dismutase (SOD2) * Introduction of Dps protein of radiation-resistant cocci 3. **Synthetic biology program** -Design artificial anaerobic metabolism module： ```mermaid graph LR A[glucose]--> B[enhanced glycolysis] B-->C[pyruvate→lactate dehydrogenase mutant] C--> D [electron transfer to fumaric acid] D--> E [ATP generation efficiency increased by 30%] ``` ###2. Technical challenges 1. **Complexity of metabolic remodeling** -The synergistic expression of 200+ genes needs to be modified at the same time -Energy efficiency issues: The ATP output of anaerobic metabolism is only 1/18 of that of aerobic. 2. **Organization-specific problems** -Special transformation needs of neuronal cells (accounting for 20% of energy consumption) -Metabolic conversion of cardiomyocytes may cause arrhythmia 3. **Epigenetic disorders** -Conflict between hypoxia response elements and gene regulatory networks for embryonic development -Long-term hypoxia may cause epigenetic drift ###3. Analysis of aerospace application scenarios | Parameters | Earth Standards | Transformation Goals | Existing biological References | |--------------|----------|----------|--------------| | Blood oxygen saturation / 95-100% / ≤30% / Tibetan vulture | / ATP output rate | 100% / ≥35% | Deep-sea tube-dwelling worms | / Lactic acid tolerance| 4 mmol/L|50 mmol/L / Horse racing muscle tissue| ###4. Ethical and safety considerations 1. **Risk-benefit ratio assessment** -Short-term space missions (<1 year) May not be worth the risk - It may be reasonable in long-term missions such as interstellar immigration 2. **Intergenerational impact** -Germ cell editing may produce irreversible evolutionary branches -The compatibility of "new humans" and the earth's ecology needs to be considered At present, the closest thing to feasibility is the phased plan： 1. Short-term: drug-induced metabolic inhibition (such as bear hibernation mechanism simulation) 2. Mid-term: Engineering of red blood cells (culturing high oxygen storage blood cells in vitro) 3. Long-term: Systematic gene network reconstruction of embryonic stem cells In 2023, NASA's breakthrough research has discovered a transferable hypoxia protective protein in slow-moving animals (water bear insects), which provides new ideas for progressive transformation. It is recommended to give priority to the development of organ-specific hypoxia protection technology, rather than pursuing completely oxygen-free survival.