How Zero-Gravity Changes Life at the Molecular Level

Turns out, proteins fold differently, genes express in new ways, and bacteria might not even look the same. Scientists are running space biology experiments to uncover how microgravity changes life itself.

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In a recent episode of talk is biotech! (Scispot's podcast), host Guru Singh, a biotech innovation specialist and science communicator, and Kevin Chen, CEO of Hyasynth Bio, a pioneering biotechnology company specializing in sustainable cannabinoid production, explored a provocative question: How does microgravity essentially zero gravity affect biological systems at the molecular level?

On Earth, life has evolved under a constant 1g force of gravity, standard atmospheric pressure, and the rhythm of day-night light cycles. Remove or alter these forces, and biology can change in surprising ways. This article expands on the podcast discussion with a deep, fact-checked look at what happens to proteins, genes, and microbes in space. We'll also highlight key space biology experiments (from NASA and the ISS National Lab managed by CASIS) and discuss what this means for biotech innovation and pharmaceutical development in space.

Proteins in Space: Folding Under Zero Gravity

Proteins are nature's tiny machines, and their function depends on precise three-dimensional folding. In microgravity, the absence of weight-driven convection and sedimentation leads to subtle differences in how proteins fold and aggregate. Experiments have shown that proteins can fold differently in space. For example, one study of human serum albumin (a common blood protein) found that simulated microgravity caused a significant change in the protein's tertiary structure, essentially pushing it into a looser "molten globule" state. The protein's overall shape expanded and its surface charge changed, even though the secondary structure (like alpha-helices and beta-sheets) remained intact. These findings suggest gravity plays a role in how proteins achieve and maintain their final folded form.

Why would zero-g affect a protein's shape? One reason is that fluid physics are very different in microgravity. On Earth, gravity helps create mixing currents; in orbit, fluids become more quiescent and diffusion-dominated. This can influence how proteins collide, fold, or clump. Sometimes, these differences are beneficial for science: proteins crystallized in microgravity are often higher in quality (larger and more orderly) than those grown on Earth. This happens because without gravity, crystals grow in a slow, diffusion-limited way without the convection currents that can disrupt their formation. NASA has leveraged this phenomenon in numerous experiments to determine protein structures with greater clarity and to aid drug design.

In short, zero gravity can alter protein folding pathways. Some proteins might not fold completely or correctly, while others form more perfect crystals. By studying these effects, scientists hope to understand fundamental biochemistry better. It even opens up the possibility of designing drugs in space for instance, by obtaining protein crystal structures that are hard to grow on Earth.

Gene Expression Without Gravity: Altered Signals in Space

Life in space not only changes how proteins behave it also changes the very instructions that cells follow. Microgravity has profound effects on gene expression, the process by which genes are turned on or off to produce RNA and proteins. Years of research have made one thing clear: the spaceflight environment alters gene expression in virtually every organism and cell type studied. In other words, many genes behave differently in microgravity, as cells adjust to the strange environment.

One vivid example comes from human spaceflight. Scientists have shown that when astronauts reach the International Space Station (ISS), the expression of many genes in their white blood cells shifts rapidly. In fact, immune-related genes tend to dial down in microgravity, which correlates with the observed weakening of astronauts' immune systems. Astronauts on long missions often experience latent viruses reactivating (like Epstein-Barr or shingles) and are more susceptible to rashes and respiratory infections. Upon return to Earth, most of those gene expression changes revert to normal within weeks, suggesting our bodies need Earth's gravity for optimal immune function.

Still, some changes can persist: NASA's famous Twins Study (comparing astronaut Scott Kelly's year in space to his twin Mark on Earth) found that while 91.3% of Scott's gene expression returned to baseline within 6 months after landing, a subset remained dysregulated for longer. Notably, the overall magnitude of gene expression and epigenetic changes in space was not beyond the range seen due to stresses on Earth, underscoring human resilience but also highlighting specific pathways to monitor.

What causes these genomic shifts? Microgravity itself is a physical stress, and the body's cells sense the lack of gravity in various ways from altered cell architecture (as the cytoskeleton unloads) to changed fluid shear stress on cell membranes. Additionally, spaceflight entails other stressors like increased radiation and disrupted day-night cycles, which can trigger genetic and epigenetic responses. Researchers have observed changes in DNA methylation (an epigenetic mark that can turn genes on or off) in organisms ranging from worms to plants to humans in space.

For instance, plants grown from seed on the ISS showed widespread shifts in gene expression and DNA methylation patterns, effectively "reprogramming" to adapt to microgravity. Many of these changes seem to help the organism adjust (e.g. tuning growth-related genes), but they can also have negative effects like bone loss or muscle atrophy which are partly mediated by changes in gene activity.

In summary, zero gravity fundamentally alters cellular gene regulation. Thousands of genes may change their expression levels as organisms attempt to make do without gravity. This area of space biology, sometimes called "space genomics" or "epigenetics in space," is crucial for figuring out how to keep astronauts healthy on long missions and it's yielding insights that might even tell us new things about genetics here on Earth.

Bacteria Off-Earth: Behavior and Appearance in Microgravity

Perhaps some of the most startling changes in microgravity have been observed in microbes. Bacteria behave very differently in the microgravity of space than in a normal 1g lab environment. Early on, astronauts and scientists noticed unusual trends: some bacteria grow faster, form biofilms more readily, and even become more virulent (more able to cause disease) after time in space.

For example, pathogenic strains like Salmonella enterica were found to become more lethal after being cultured in the weightless conditions of orbit. In a NASA experiment, S. Typhimurium bacteria grown on the Space Shuttle were returned to Earth and injected into mice the space-grown bacteria caused more severe illness and higher mortality than control bacteria grown on Earth. The spaceflight Salmonella had altered gene expression (scientists identified a set of genes activated in microgravity, termed the "low-shear modeled microgravity regulon") and this led to heightened virulence. Findings like this were groundbreaking, showing that microgravity can indirectly boost the infectious potential of germs.

Electron microscope images comparing bacteria grown on Earth vs. in space show remarkable differences. E. coli samples cultured in microgravity aboard the ISS exhibit irregular cell shapes and numerous small outer membrane vesicles budding from their surfaces. Such morphological changes suggest that microgravity triggers stress responses in bacterial cell envelopes.

Beyond increased virulence, bacteria literally look different in space. When researchers examined bacteria under microscopes after spaceflight, they saw changes in size and shape. For instance, E. coli cells grown on the ISS were smaller and more irregular in shape than their Earth-grown counterparts, and they shed more outer membrane vesicles (tiny bubbles from the cell membrane).

Some bacteria tend to form clumps or biofilms more readily in microgravity, possibly because the lack of gravity-driven mixing leads to localized nutrient gradients that encourage cells to stick together. In one ISS experiment, even a normally benign strain of E. coli formed thicker biofilms in microgravity, which were harder to eradicate. Researchers also noted that higher doses of antibiotics are sometimes required to kill bacteria in space. This could be due to those biofilms or other stress-induced defenses the bacteria turn on.

Why do microbes respond this way? The prevailing theory is that microgravity doesn't directly alter the bacteria by "pulling" on them, but rather indirectly changes their environment. In weightlessness, fluid around cells is not well-mixed creating a low-shear, low-turbulence environment similar to certain niches in our bodies (like deep in the lungs or intestines). This altered extracellular environment triggers the bacteria to modulate gene expression as if they were in a host, often ramping up stress responses and virulence factors. It's a bit like tricking the bacteria into "thinking" they are infecting a host, because the cues they rely on (fluid forces, nutrient availability) are shifted. Gravity, it turns out, is one of those environmental forces that microbes have evolved to sense. Take gravity away, and the microbial genome "notices."

The upshot: microgravity can make microbes tougher, meaner, and weirdly shaped. This has serious implications for long-term space travel managing infections in space could be more challenging and it also presents opportunities to learn how to better control bacteria on Earth. Space microbiology experiments have prompted new ideas about biofilm formation and antibiotic resistance that are being investigated in normal labs as well.

Gravity, Pressure, Light: Environmental Forces Shaping Life

Gravity is just one of several fundamental forces in the environment that shape biological processes. On Earth, organisms are also influenced by atmospheric pressure and by light (from sunlight cycles to specific wavelengths). Studying life in space where gravity is near zero, pressure and atmosphere are tightly controlled, and light/dark cycles are artificial highlights just how much organisms respond to these cues.

Gravity as a developmental constant: Virtually all life on Earth evolved with the constant pull of gravity. Remove that, and weird things happen. Plants, for example, no longer know which way to send their roots (since in normal conditions gravity tells roots to grow downward). Human vestibular systems (inner ear balance organs) get confused, leading to space motion sickness. At a molecular level, gravity has guided the evolution of structures like bone (which maintains density under load) and the cytoskeleton of cells (which often acts as a scaffold resisting gravitational force). It's no surprise that gravity changes can significantly influence an organism's health and function.

Even partial gravity environments, like the Moon's 0.16g or Mars's 0.38g, are enough to alter biological processes which is a key concern as space agencies plan for long-duration lunar and Martian habitats.

Pressure and fluid forces: Earth's creatures are used to 1 atm of pressure at sea level. In spacecraft, cabin pressure is usually kept close to Earth-normal, but the distribution of fluids in organisms still shifts without gravity. Astronauts experience the infamous "puffy face, bird legs" syndrome where fluids move upward in the body.

At the cellular scale, microgravity results in lower fluid shear stress around cells. On Earth, slight pressure differences help drive blood flow and lymphatic drainage; in microgravity those systems have to rely purely on heart pumping and other mechanisms. Extremes of pressure on Earth (deep oceans with high pressure, or high altitude with low pressure) also drive biological adaptations for example, deep-sea microbes have special protein structures to withstand huge pressure. By comparing how biology reacts to zero pressure difference (microgravity) versus high-pressure scenarios, scientists can learn how cell membranes, protein complexes, and other structures sense mechanical force.

Light and radiation: Space introduces unique light conditions. Although spacecraft provide electric lighting to maintain astronauts' circadian rhythms, the absence of a 24-hour day-night cycle and the presence of cosmic radiation and high-energy solar particles form a very different environment. Certain genes in plants and microbes respond to light; in space, those signals might be absent or altered.

Astronauts on the ISS experience 16 sunsets and sunrises a day as they orbit Earth, which necessitates careful planning of lighting schedules to avoid disrupting human circadian gene expression. The high radiation in space (outside Earth's protective magnetosphere) can damage DNA and has been shown to induce specific stress responses at the molecular level.

Gravity, pressure, and light all influence gene regulation they are cues that life uses to tune its physiology. Space removes or changes these cues, forcing life to adapt on the fly. The key takeaway is that biology is context-dependent. Our cells and molecules are products of Earth's environment. Studying how they behave under microgravity (or other extreme conditions) not only prepares us for exploration, it also teaches us new biology. It underscores, for example, which cellular processes are truly governed by internal genetic programming versus which rely on external physical cues like weight or force.

Pioneering Space Biology Experiments (NASA, ISS, CASIS)

Space agencies and researchers have been conducting biological experiments beyond Earth for decades, from simple microorganisms to complex human studies. Here are some landmark space biology experiments and ongoing projects that illuminate how microgravity changes life:

Early Orbital Microbes (1960s): Even before humans orbited Earth, microbes were sent to space. The USSR launched bacteria on Sputnik-era satellites, and NASA's Biosatellite missions in the 1960s carried bacteria like E. coli and Salmonella. These pioneering studies showed that microbes could survive and reproduce in microgravity, and hinted at changes like increased population density in flight. Over the past 50+ years, more than 100 spaceflight experiments have involved microorganisms, building the foundation of space microbiology.

Salmonella Virulence on the Space Shuttle: In 2006-2007, a series of Shuttle experiments (STS-115 and STS-123) grew Salmonella in orbit to test its disease-causing potential. The startling result, published by NASA researchers in 2007, was that mice infected with the space-grown bacteria had increased mortality compared to those infected by Earth-grown Salmonella. This was the first direct evidence that microgravity can enhance pathogen virulence, and it led to the discovery of a genetic regulon (set of genes) that Salmonella switches on in low-shear, microgravity-like conditions. This insight has driven ongoing research into developing countermeasures for astronaut health.

NASA Twins Study (2015–2016): NASA's Twins Study was a unique full-body systems biology experiment. Astronaut Scott Kelly spent one year on the ISS while his twin brother Mark stayed on Earth, allowing scientists to compare everything from gene expression to microbiome changes to cognitive shifts. The study found changes in thousands of genes during spaceflight (especially related to immune function and DNA repair) and noted increases in inflammation and shifts in the gut microbiome. Most changes reverted after return to Earth, but a small percentage of gene expression changes and chromosomal adjustments persisted longer. The Twins Study provided an integrated view of human adaptation to microgravity and informed how we monitor astronaut health on long missions.

ISS National Lab - CASIS Projects: The International Space Station U.S. National Laboratory, managed by the Center for the Advancement of Science in Space (CASIS), has enabled dozens of biotech and pharmaceutical experiments in microgravity. Commercial and academic partnerships are using the ISS to push the frontiers of drug discovery and tissue engineering.

For example, pharmaceutical company Merck & Co. collaborated with CASIS to study the crystallization of pembrolizumab (the active ingredient in the cancer immunotherapy Keytruda®) in microgravity. The space-grown antibody crystals were more uniform and stable, leading to insights for an improved injectable formulation on Earth. This is a striking case where an ISS experiment directly informed a drug development process, potentially reducing manufacturing costs and improving patient outcomes.

Other ISS National Lab projects have grown protein crystals for osteoporosis drugs, cultivated 3D human cell cultures (organoids) to model diseases, and tested stem cell therapies in microgravity. NASA, CASIS, and partners like NIH have also run "tissue-on-a-chip" experiments on the ISS, probing how heart tissue, bones, or the blood-brain barrier behave in space.

Plant Biology and Ecology in Space: Not to forget our fellow life forms, plants and even small animals have been part of space biology. The Veggie and Advanced Plant Habitat experiments on the ISS have successfully grown lettuce, flowers, and other plants in microgravity, examining how lack of gravity affects root orientation, nutrient uptake, and gene expression in crops. Experiments with model organisms like fruit flies, worms (C. elegans), and fish have revealed effects of microgravity on development and reproduction.

For instance, JAXA's (Japan Aerospace Exploration Agency) C. elegans experiments showed epigenetic changes that passed down through generations in space, and NASA's aquarium on the ISS (Biolab) observed how fish balance organs and swimming behaviors change without gravity. These studies are key as we consider bioregenerative life support (growing food in space) and the broader impacts of space on whole ecosystems.

Each of these experiments contributes a piece to the puzzle of space biology a field that is rapidly expanding as access to space increases. As private spaceflight grows and initiatives like NASA's Artemis program plan for Moon bases and Mars journeys, understanding biology in fractional gravity (Moon, Mars) and prolonged zero-g is more important than ever. The ISS has essentially been humanity's orbital laboratory for biology for over 20 years, and its legacy will guide the design of future experiments on commercial space stations or planetary habitats.

Implications for Biotech Innovation and Pharmaceutical Development

What do these scientific insights mean for the future? In true McKinsey fashion, let's translate knowledge into strategy. The fact that zero gravity profoundly changes life at the molecular level carries both challenges and opportunities:

Healthcare for Astronauts: On the challenge side, we must mitigate the negative effects (immune suppression, bone loss, altered drug responses). Pharmaceutical companies may need to tailor medications for space use higher antibiotic doses, drugs for bone density loss, or treatments that account for altered metabolism in microgravity. The flipside is that studying these problems spurs innovation. For example, understanding microgravity-induced bone loss has led to research on new osteoporosis treatments that could help people on Earth as well.

Space-Enabled Drug Discovery: On the opportunity side, microgravity offers a unique platform for biotech R&D. As seen with the protein crystal growth experiments, zero-g can produce biomolecules (like crystals of proteins or viruses) of a quality not attainable on Earth, aiding structure-guided drug design. This has already led to improvements in drug formulations and identification of new therapeutic targets.

We are witnessing the rise of "space-enabled" biotech innovation companies using the ISS (and soon, private stations like Axiom) as extensions of their laboratory. In cancer research, microgravity is being used to grow 3D tumor organoids that mimic how cancer behaves in the body, potentially revealing vulnerabilities that 2D petri-dish cultures miss. There is even exploration of manufacturing certain biomaterials and pharmaceuticals in orbit if it proves more efficient or yields superior products.

Biotech for Space Colonies: As humans plan to venture deeper into space, biotechnology will play a pivotal role in sustaining life. The knowledge that genes and proteins behave differently will inform the development of robust life support systems (like engineered microbes for life support that work well in microgravity) and biofabrication techniques (such as 3D-printing tissues or growing food). Space biology findings might enable bio-innovation such as radiation-resistant probiotics to protect astronaut gut health, or plants genetically tuned to grow in low-gravity greenhouses on Mars.

New Insights for Earthly Medicine: The space environment can be seen as an extreme "laboratory" that forces biological systems to reveal their flexibility and limits. By studying stress responses in space, scientists are uncovering mechanisms of disease that might be hidden under normal gravity. For instance, research on cardiovascular changes in astronauts (like heart muscle deconditioning) parallels studies of sedentary lifestyle effects on Earth, providing a accelerated model to test countermeasures.

Space-triggered changes in gene expression could highlight which genes are essential for basic cellular stability knowledge that might lead to novel drugs that simulate or block certain pathways (think of a drug that could trigger the same beneficial effects as microgravity on tissue regeneration, or conversely prevent the deleterious effects).

In essence, space is the new frontier for biotech innovation and pharmaceutical development. We are still in the early days, but the trajectory is clear. Just as the microchip industry drove an information revolution, access to microgravity and space environments could drive a revolution in life sciences. Companies like Merck, Eli Lilly, Novartis, and startup biotech firms have already sent experiments to the ISS to gain an edge in drug R&D. The convergence of AI (for data analysis and experiment design) with real space biology testing something Scispot's platform could empower means faster iteration and translation of findings.

Conclusion

Gravity has been a constant in biology for billions of years, but humanity's push into space has revealed just how dynamic life can be when that constant is removed. Proteins fold into new shapes, genes switch their activity, and microbes take on new personalities in the petri dish of space. These changes are not just academic curiosities; they hold the keys to keeping astronauts healthy and unlocking new biotechnologies.

As NASA, CASIS, and innovators worldwide continue to run ISS experiments and plan missions to the Moon and Mars, every result deepens our understanding of biology's fundamentals. The implications span from safeguarding crews in space to designing better medicines on Earth. Microgravity, once an unknown, is now becoming a tool a tool to probe the mechanics of life at the molecular level and to spark creative solutions that benefit all of us, planet-bound or not.

In the coming decades, expect the term "space biology" to shift from sci-fi novelty to a mainstream pillar of biotech R&D. After all, when it comes to innovation, the sky (or perhaps the microgravity lab in the sky) is no longer the limit.