Adapting humans to an oxygen-free environment to support space travel through gene regulation is a very challenging and cutting-edge scientific idea. The following are step-by-step analysis and potential research directions： --- ### **1. Understanding the biological basis of anaerobic survival** -**Human metabolic restrictions**: Human cells rely on mitochondrial aerobic respiration to produce ATP (energy), and can only survive for a short time (about 2-5 minutes) through inefficient glycolysis during hypoxia, accompanied by the accumulation of lactic acid, which leads to acidosis. -**Reference model of nature**： -**Anaerobic organisms**: Some archaea (such as methanogenic bacteria) use anaerobic respiration or fermentation pathways. -**Extreme creatures**: The hermaphrodite state of water bear insects (slow-moving animals) can suspend metabolism, but it is not long-term oxygen-free survival. -**Vertebrate cases**: Carp and turtles survive for several hours by reducing metabolic rate, enhancing glycolysis, and tolerating lactic acid during hypoxia. --- ### **2. Potential strategies for gene regulation** ####**2.1 Enhance anaerobic metabolism** -**Import of exogenous metabolic genes**： -Introduce **Pyruvate-ferritin oxidoreductase** of anaerobic bacteria (instead of mitochondrial oxidative phosphorylation), which directly uses the electron transfer chain to generate ATP. -Introduce the **hydrogenase**gene to enable cells to use hydrogen as an electron donor (a hydrogen supply system is required). -**Optimize glycolysis efficiency**： -Overexpression of key enzymes of glycolysis (such as **HK, PFK, PK**) and inhibition of their negative regulatory factors (such as ATP inhibitory effects). -Introduce ** Lactate dehydrogenase isozyme** (such as LDH-B in some fish) to convert lactic acid into pyruvate to extend the anaerobic metabolism cycle. ####**2.2Solve lactic acid accumulation and acidosis** -**Transformation of lactic acid metabolism pathway**： - The introduction of ** Lactic acid uses genes** (such as lactic acid oxidase of some bacteria) to convert lactic acid into acetyl coenzyme A and enter the metabolic cycle. -Enhance the expression of **Bicarbonate buffer system** and improve the cell's pH regulation ability. -**Alternative end product**： -Through gene editing, cells convert pyruvate into ethanol or acetic acid (similar to yeast), reducing acidic by-products. ####**2.3Regulating the mechanism of hypoxia response** -**Activate the HIF-1a pathway**： -Stabilize HIF-1a protein to promote angiogenesis (VEGF), erythropoiesis (EPO) and glycolytic enzyme expression. -Inhibit HIF-1a degradation factors (such as PHD enzymes) to simulate chronic hypoxia adaptation. -**Mitochondrial function reprogramming**： -Downregulate genes related to mitochondrial oxidation and metabolism to reduce oxygen-dependent pathways; or introduce alternating oxidase (AOX) to maintain part of the electron transfer chain function. ####**2.4Symbiotic Engineering and Synthetic Biology** -**Artificial symbiosis system**： -Transform skin or intestinal microorganisms to provide short-chain fatty acids or other energy molecules to the host under anaerobic conditions. -Design implantable synthetic organelles to perform anaerobic ATP synthesis. --- ### **3. Technical challenges and ethical risks** -**Multi-gene collaborative regulation**: Dozens of genes need to be edited at the same time and the expression timing is accurately regulated, which far exceeds the current CRISPR technology capabilities. -**Energy supply bottleneck**: The ATP production of anaerobic metabolism is only 1/18 of that of aerobic, and it may need to be combined with ** To reduce the metabolic rate** (such as inducing a state similar to hibernation). -**Accumulation of toxic substances**: Metabolites such as lactic acid and ethanol may damage cell membranes or interfere with signal transmission. -**Risk of cancer**: Enhancing glycolysis and inhibiting apoptosis may promote tumor growth. - **Ethical disputes**: The long-term safety of human gene editing, social fairness, and the ethical boundaries of “enhancing mankind”. --- ### **4. Phased research route** 1. **In vitro cell experiments**: The feasibility of testing a single anaerobic metabolism gene in human cell lines. 2. **Animal model verification**: Construct transgenic mice to evaluate anaerobic survival time, organ damage and side effects. 3. **Metabolism-gene circuit design**: Develop hypoxia-responsive gene switches to realize conditional activation of oxygen-free pathways. 4. **Synthetic biology integration**: Combining engineering tissues (such as artificial skin and blood vessels) and gene regulation to build a local anaerobic adaptation system. 5. **Preclinical safety assessment**: Verify the safety of multi-gene editing through organoids or human trial models. --- ### **5. conclusion** Although current technology is still decades away from achieving a completely oxygen-free survival of mankind, through progressive research (such as enhancing hypoxia tolerance and short-term metabolic transformation), it may provide partial solutions for extreme environments in space. In the future, it is necessary to combine interdisciplinary breakthroughs in gene editing, synthetic biology and aerospace medicine, while carefully weighing scientific exploration and ethical responsibilities.