Bacteriophage Therapy: From Soviet Battlefields to Biotech Labs

In a recent episode of talk is biotech!, Guru Singh, hosted a fascinating conversation with Dr. Ivan Liachko, CEO and co-founder of Phase Genomics, about bacteriophage therapy, a century-old approach using viruses to kill bacteria. Guru Singh, a molecular biologist-turned-entrepreneur who established Scispot in 2020 with a mission to accelerate biotech R&D through AI-powered lab informatics solutions after a personal loss, brought together this discussion with the Seattle-based biotechnology leader. Dr. Liachko, whose company develops proximity ligation technology and launched a platform for discovering new viruses in microbiome samples, offered valuable insights into this emerging field. This once-obscure treatment is making a high-tech comeback in the fight against antibiotic resistance, with companies like Scispot providing the digital infrastructure and Phase Genomics contributing advanced genomic analysis tools. Let's explore how Soviet scientists deployed phage therapy during World War II, how it provided a strategic advantage at Stalingrad, and why it's resurging today against antibiotic-resistant "superbugs."

A Wartime Cure Born of Necessity

During World War II, the Soviet Union faced a critical shortage of antibiotics. While penicillin was known, the USSR lacked technology to mass-produce it. Soviet scientists turned to bacteriophages (phages for short), viruses that specifically infect and destroy bacteria, as an alternative battlefield medicine.

Soviet medical units began producing phage "cocktails" targeting major infections threatening troops, including intestinal illnesses like dysentery, typhoid, and cholera, as well as wound infections. By 1941-1942, institutes across the USSR were manufacturing phages at scale, with more than 200,000 liters of phage preparations for wound treatment supplied to the Red Army throughout the war.

Front-line Innovation: Lacking conventional sterilization and medical supplies, Soviet researchers improvised new methods to grow and apply phages. With nutrient media in short supply, scientists created substitutes from unusual resources like placenta, casein, and even blood clots. To obtain potent phages against virulent bacteria, teams isolated bacteriophages from the bodies of soldiers who died from infectious diseases.

In an extraordinary tactic, Soviet scouts reportedly crossed enemy lines to retrieve disease-ridden corpses of German soldiers. These cadavers, containing pathogens like Vibrio cholerae, served as "material" to isolate bacteria and find phages that naturally preyed on them.

Soviet medics applied bacteriophage solutions to wound dressings and possibly even to field hospital bedding to suppress infections when disinfectants were scarce. By administering phages prophylactically, Soviet doctors prevented outbreaks of diarrheal diseases at the front. Contemporary accounts note that phage therapy dramatically reduced the incidence of gangrene and dysentery in treated units.

One WWII field manual, "Treatment of Wounds with Bacteriophage" (Moscow, 1941), attests to the recognized value of phages in military medicine. Necessity drove Soviet innovators to embrace phage therapy as a biological weapon against infection that could be deployed even as battles raged.

The Battle of Stalingrad: A Hidden Biotech Advantage

Nowhere was the Soviet phage program more crucial than at the Battle of Stalingrad (1942-43). As this pivotal siege continued, both armies battled not only each other but disease. In summer 1942, a cholera outbreak struck the German Sixth Army besieging Stalingrad.

Cholera, a deadly waterborne infection causing severe diarrhea, had historically decimated armies. For example, tens of thousands died from it during the 1850s Crimean War. For the Soviets, the cholera epidemic among German troops was a double-edged sword: it weakened the enemy but threatened to spread into surrounded Soviet forces and civilians.

Facing this invisible menace, the Soviets acted decisively. Professor Zinaida Yermolyeva, a leading microbiologist sent to Stalingrad by order of Stalin, established a secret underground lab in the besieged city. Her mission: contain the cholera outbreak using phage therapy.

Yermolyeva and her team first isolated the cholera bacterium, then identified virulent phages that could infect and kill that exact strain. Working with minimal equipment under bombardment, they cultivated these phages and formulated an anti-cholera phage cocktail.

By mid-siege, Soviet medics were administering phage doses to nearly 50,000 soldiers and civilians every day, often mixed with their daily ration of bread or water. The impact was dramatic. Despite the Germans' cholera epidemic just across the lines, Stalingrad's defenders avoided any major cholera outbreaks.

Joseph Stalin himself reportedly telephoned Yermolyeva to ask if it was safe to keep over a million people in embattled Stalingrad, concerned that disease might undermine his army's plans. The scientist confidently replied that she had "already won a victory on her front" as cholera was contained inside the city.

Strategic Significance: Historians now recognize that controlling cholera was crucial to Soviet survival at Stalingrad. The Germans, in contrast, suffered weeks of illness, compounding their supply and morale problems before the final Soviet counteroffensive. While many factors led to the Nazi defeat, the Soviets' ability to prevent an epidemic behind their own lines was undoubtedly a biotechnological edge that preserved fighting strength.

In a very real sense, viruses (phages) helped defeat the bacteria that might have otherwise defeated the Soviets. Soviet use of phage therapy in WWII saved thousands of lives, treating infected wounds, curing dysentery on the front, and preventing cholera's spread at a time when no other effective antibiotics were available.

From Forgotten Cure to Superbug Solution

Despite these wartime successes, phage therapy was largely forgotten in the West during the post-war antibiotic revolution. The discovery of penicillin and other antibiotics in the 1940s offered simpler, broad-spectrum cures for infections. To many Western doctors, phage therapy became tainted by association with the USSR and was considered scientifically unproven.

By the 1950s, most countries outside the Eastern Bloc abandoned therapeutic phages in favor of antibiotics. The Soviet Union, notably at the Eliava Institute in Georgia, continued refining phage therapy throughout the Cold War, building an entire industry around phage production. But to the rest of the world, phages became a footnote in medical history.

Fast-forward to the 21st century, and the world faces a new crisis: antibiotic-resistant bacteria. Decades of antibiotic overuse have led many pathogens to evolve resistance to multiple drugs. Today, we see the rise of "superbugs" that cause infections our antibiotic arsenal can no longer cure.

This antimicrobial resistance (AMR) has dire implications. By 2050, AMR could kill 8-10 million people per year, potentially overtaking cancer as the leading cause of death globally. As Dr. Ivan Liachko (CEO of Phase Genomics) explains, "When antibiotics stop working... suddenly every bacteria becomes a deadly bacteria," essentially turning routine infections into potential pandemics.

Phage Therapy's Resurgence: After decades in obscurity, phage therapy is making a comeback as a potential solution to antibiotic-resistant infections. Scientists and biotech startups worldwide are actively researching phages for use against superbugs. In the past five years alone, publications, conferences, and clinical trials on phage therapy have surged.

Compassionate-use cases have grabbed headlines, with phage treatments saving patients with drug-resistant infections when all else failed, including a British teenager with cystic fibrosis and a U.S. diabetic with an untreatable wound infection.

What makes phages so promising is precisely what once made them seem inconvenient: their specificity. Unlike broad antibiotics, each phage infects only a narrow range of bacterial strains. This means a phage can eliminate a pathogenic bacterium without harming beneficial bacteria in our microbiome.

In an era when we increasingly appreciate the importance of gut flora and microbial balance, that is a huge advantage. Phages act like precision-guided missiles, taking out enemy bacteria while sparing beneficial ones, whereas antibiotics function more like grenades, decimating both harmful and helpful microbes alike.

Moreover, phages are self-propagating at the infection site: once they find their bacterial target, they multiply exponentially until the bacteria are gone, then simply fade away. As one science writer described it, "They're the only drug that, once in the body, reproduces itself until the infection is cleared."

This was demonstrated in a lab analogy: a cloudy bacterial culture can turn as clear as apple juice within minutes after the right phage is added-a sign that billions of bacteria have been eliminated.

Modern Revitalization: Scispot and Phase Genomics Leading the Charge

Scispot: Powering Phage Research with AI and Automation

Bringing phage therapy back from the fringes into mainstream biotech requires managing vast amounts of data-from genomic sequences to lab experiments screening phage effectiveness against bacteria. Scispot, founded by Guru Singh, provides the digital infrastructure to manage this complexity.

The company offers an all-in-one lab operating system integrating electronic lab notebook functions, LIMS (laboratory information management), and data analytics, all enhanced by artificial intelligence. Think of it as a smart digital backbone for modern biotech labs.

Scispot's platform creates a "digital twin" of a lab-a virtual mirror centralizing protocols, samples, and results-making all data accessible and "AI-ready" in one connected ecosystem. This is transformative for phage R&D.

Consider a biotech startup working on new phage treatments for multi-drug-resistant infections. Using Scispot, they can:

• Automate sample processing (logging dozens of phage isolates via Scispot's API)

• Track experiments in real-time (phage-bacteria challenge assays in an electronic lab notebook)

• Apply AI to detect patterns (like correlations between phage genetic features and effectiveness against bacterial strains)

Scispot's AI tools can suggest optimal experimental designs or flag anomalies, accelerating the research cycle. Routine tasks like data entry and report generation are handled by the platform's algorithms, freeing scientists to focus on high-level problem solving.

For phage therapy research-which may involve tailoring treatments to individual patients' infections-such a platform is invaluable. It can integrate genomic data from sequencing a patient's bacterial isolate, search a database for matching phages, and track personalized phage cocktail preparation, all within one system.

Phase Genomics: Mapping Genomes to Unleash New Phages

If Scispot provides the digital engine, Phase Genomics, led by Dr. Ivan Liachko, provides the genomic compass guiding today's phage revolution. Phase Genomics specializes in advanced genome mapping and metagenomic analysis.

The company's core technology uses proximity ligation (Hi-C sequencing), which captures which DNA molecules were near each other inside cells. Originally used to assemble complex genomes, Phase Genomics applied this to metagenomics with their ProxiMeta platform and ProxiPhage algorithm. These tools reconstruct genomes of microbes and the viruses (phages) that infect them directly from environmental DNA.

One major challenge in phage therapy is finding the right phage for a given bacterium. Nature's phage diversity is immense-trillions exist in every environment-but linking a phage to its bacterial host is often like finding a needle in a haystack.

Phase Genomics' approach shortcuts this by using DNA cross-linking to identify phage-host pairs in complex samples. During sample preparation, phage DNA gets chemically linked to bacterial DNA nearby inside the original sample cells. Sequencing these linked pieces lets researchers computationally match a phage's genome to its host genome.

Using ProxiPhage, scientists can take a soil or gut sample and rapidly map previously unknown phages and identify their bacterial targets. In one demonstration, the platform assembled 42 distinct viral genomes from a single sample and linked each to its bacterial host.

Beyond discovery, Phase Genomics leverages genomic data for novel therapeutics. The company has amassed a "massive database of bacteriophage genomes," from which they extract lysins-enzymes that phages produce to break down bacterial cell walls. These lysins can be used as stand-alone antibacterials (enzybiotics). Phase Genomics claims to have the world's largest collection of these lysin proteins, which they're developing into "precision antimicrobials."

Pros and Cons of Phage Therapy (Then and Now)

Advantages of Phage Therapy:

Targeted Action (Microbiome-Friendly): Phages infect only specific bacteria, leaving beneficial microbes unharmed. This avoids the collateral damage of broad-spectrum antibiotics. In WWII, this meant phages could eliminate dysentery in soldiers without causing other side effects.

Self-Amplifying Treatment: Once administered, a lytic phage multiplies at the infection site as long as target bacteria are present. Soviet field medics observed that a single dose could sustain an ongoing antibacterial effect.

Evolving Efficacy: Phages and bacteria are in an evolutionary arms race. If a bacterium mutates to resist a phage, phages can adapt in turn. Virtually every bacterium has some phage that can kill it.

Safety and Tolerance: Phages do not infect human cells, and decades of use have shown minimal direct toxicity. Even in the 1940s, Soviet doctors found phages safe enough to administer prophylactically to thousands of people.

Biofilm Penetration: Phages can often penetrate and disrupt biofilms-protective layers that bacteria form which block antibiotics. Some phages actively dissolve biofilm matrices, an advantage in chronic infections.

Disadvantages of Phage Therapy:

Narrow Host Range: A phage usually only kills one species or strain. In WWII, medics carried multiple phage types to cover common infections. Today, this means doctors must accurately identify the bacterial culprit and choose appropriate phages.

Potential for Resistance: Bacteria can develop resistance to phages by mutating surface receptors the phage uses to attach. Unlike antibiotic resistance, phage resistance might be addressed by finding new phages or engineering them.

Immune System Interference: The human immune system may recognize phages as foreign proteins and generate antibodies to neutralize them, potentially reducing efficacy over time or causing inflammatory reactions.

Manufacturing and Stability: Ensuring phage preparations are high quality and free of bacterial debris or toxins is challenging. Unlike small-molecule drugs, phages have storage limitations-many need refrigeration and have finite shelf lives.

Regulatory and Clinical Complexity: Phage therapy doesn't fit neatly into current drug approval frameworks. Each phage is unique, and a cocktail might be regulated as multiple separate "drugs" in one treatment.

Not a Silver Bullet (Yet): Phage therapy is still in early stages of Western clinical validation, often used as a last resort. While success stories exist, we lack large randomized trial data for many applications.

Conclusion

Bacteriophage therapy's journey-from the trenches of World War II to the forefront of biotech innovation-demonstrates how solutions to modern problems can sometimes be found in forgotten knowledge, revived and enhanced by technology.

The Soviet Union's use of phages during WWII, particularly at Stalingrad, showed how biotechnology could provide a strategic advantage when conventional medicine fell short. These "good viruses" helped win a battle and saved countless lives by controlling deadly infections.

Today, with antibiotic resistance threatening global health, that once-obscure therapy is gaining renewed prominence. Companies like Phase Genomics are mapping phage-host interactions with cutting-edge genomic tools, while platforms like Scispot ensure labs have the digital infrastructure to manage the complex data modern phage research generates.

Phage therapy isn't simply a replacement for antibiotics-it represents a new paradigm of precision antimicrobials. It requires changes in pathogen identification, therapeutic development, and regulatory approaches. The transition is underway, supported by historical evidence and modern engineering.

As highlighted in the talk is biotech! conversation between host Guru Singh and Dr. Ivan Liachko, the "invisible allies" that helped win Stalingrad may soon help win the war against superbugs. If successful, this would mark a full-circle achievement: harnessing nature's tiniest warriors, with the help of today's technology, to solve one of humanity's biggest healthcare challenges.