Should humanity ever commit to space exploration, a compelling justification will be essential for such an endeavor. While optimists posit that our innate desire for discovery is the primary driver, historical precedence suggests that the pursuit of profit has more frequently motivated humans to venture into new territories. Consequently, it is logical to infer that genuine space colonization will require a commercial imperative. A recent paper from Srivatsan Raman’s lab at the University of Wisconsin-Madison, published in PLOS Biology, outlines one potential basis for such a commercial venture: genetically engineering bacteriophages to combat antibiotic-resistant bacteria.
Utilizing the harsh realities of space as a testing ground for genetic alterations is not a novel concept. Nevertheless, this particular study marks one of the initial practical applications of the idea. The original experiment was launched in September 2020, supported by Rhodium Scientific, a biotech firm facilitating research aboard the International Space Station (ISS). Their custom cryovials were engineered to prevent leaks and maintain a storage temperature of -80℃ throughout the launch sequence.
Even before the experiment reached orbit, the labs faced a substantial preparatory task. They curated a “library” of 1,660 distinct, pre-modified phage variations, aiming to see which would prevail in a space-based “survival of the fittest” competition. This approach was significantly more efficient than simply awaiting random mutations induced solely by the space environment, notwithstanding the elevated radiation levels.
As a baseline control, the same blend of phages and bacteria was maintained on Earth, allowing researchers to contrast their co-evolutionary dynamics in the familiar terrestrial environment versus the microgravity conditions of space. Initially, a clear divergence emerged: space-faring bacteriophages required substantially more time to eradicate their bacterial counterparts. Terrestrial bacteriophages dispatched them swiftly, generally within 2–4 hours, whereas the phages in space showed no immediate acceleration in efficacy.
This sluggish performance was likely attributable to microgravity, which eliminated convection—the fluid movement driven by external forces such as temperature or pressure gradients. The phages had to depend on diffusion, a considerably slower mechanism, to locate their targets. Furthermore, those targets were not stationary.
In the space environment, the E. coli bacteria in the experiment experienced immense strain. The same lack of convection that hindered phage movement led to a build-up of waste products directly surrounding the bacterial cells. Moreover, essential nutrients, typically distributed via convection, became harder to access. To adapt, the bacteria underwent their own set of mutations.
Specifically, they modified the mlaA gene, which governs the movement of phospholipids toward the inner leaflet of the membrane. In space, this gene mutated to favor the outward transposition of phospholipids. Since bacteriophages interact with bacteria at the cell surface, this necessitated a corresponding shift in the phages’ offensive strategy.
On Earth, the phages that proved superior in the competition displayed typical evolutionary adaptations, such as developing positively charged tips to grip the negatively charged bacteria. However, in space, the victorious phages evolved hydrophobic substitutions within the receptor-binding protein they use for attachment. According to the paper, this likely rendered the tail fiber either more pliable or more rigid, enabling the phages to successfully bind to the “peculiar” bacterial membranes that had flipped their phospholipids outward.
Even more remarkably, when the mutated phages were subsequently returned to Earth, they demonstrated a particular aptitude for destroying the bacteria responsible for urinary tract infections—one of the most common infection types globally, known for very high antibiotic resistance. Notably, the variants that remained on Earth failed to conquer these antibiotic-resistant UTI-causing “superbugs.”
While counterintuitive, researchers speculate that the stressors the bacteria endure within the human urinary tract—such as chemical exposure and nutrient scarcity—somehow mimic the environment their space-borne counterparts encountered. Consequently, they acquired the same evolutionary advantages and became vulnerable to the identical attack method devised by the space phages.
From a business perspective, this holds enormous promise: if a method can be established to utilize orbital bioreactors to manufacture “super-phages” capable of eradicating Earth’s antibiotic-resistant bacteria, it could spawn a multi-billion dollar industry. However, it is currently premature to draw definitive conclusions, and significant development work remains before such a system sees widespread implementation. Large-scale deployment will necessitate infrastructure far exceeding the ISS.
It remains an open question whether this will materialize into one of the “breakthrough applications” that truly propels commercial space efforts forward. Nevertheless, it offers an intriguing illustration of how the evolutionary interplay between two long-standing adversaries transforms under different physical conditions. Hopefully, this acquired knowledge can eventually be leveraged for the benefit of a significant portion of humanity.
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