Book Club: The viruses that helped win the Battle of Stalingrad

An extract from Tom Ireland’s The Good Virus: The Mysterious Microbes that Rule Our World, Shape Our Health and Can Save Our Future.

If you’ve just joined us, as a gratifying number of you have, you may not know that on occasion I send you an extract from a book I think you might enjoy. This hasn’t happened in a while – really, my friends need to sort their literary careers out; I’ve got a newsletter to fill – but after a bit of a break, Book Club is back.

Today’s extract comes from the science writer Tom Ireland’s book The Good Virus: The Mysterious Microbes that Rule Our World, Shape Our Health and Can Save Our Future. The good viruses in question are bacteriophages: viruses which have evolved solely to infect and kill bacteria, which influence everything from our gut health to oceanic ecosystems, and of which, despite being the most abundant category of biological entity on the entire planet, hardly anyone has even heard.

The Good Virus is out in paperback now. In this extract, Tom describes how phages were used during one the most pivotal battles of World War II…

In the summer of 1942, as German troops encircled the Russian city of Stalingrad, Nazi commanders began to receive bizarre reports of dead bodies disappearing from German field hospitals. In the middle of the night, Soviet scouts were crossing the front line daringly to steal certain German corpses, before squirrelling them back down into a secret underground laboratory hidden deep beneath the city.

The Germans had been suffering outbreaks of cholera for weeks as they advanced east towards Stalingrad, and the Soviets were desperate to prevent the disease from crossing the front line. Although this nasty bacterial disease had helped further deplete their enemy, it could also spread like wildfire among their soldiers and the civilians crammed into a city under siege. 

So what on Earth were the Soviets doing seeking out potentially infectious German corpses and dragging them into their territory? Professor Zinaida Yermolyeva, from Moscow’s Institute of Experimental Medicine, had been sent by Joseph Stalin to assess the cholera outbreaks on the front and formulate a plan. 

Even with today’s improved sanitation and modern antibiotics, cholera kills over 100,000 people every year. Spread through water contaminated with the tiny tampon-shaped bacteria Vibrio cholerae, if left untreated it causes debilitating cramps, diarrhoea, dehydration and, eventually, shock, coma and death. 

Like other physician-scientists of the era, Yermolyeva had spent her career in a world without effective antibiotics, trying to work out how to kill bacteria like Vibrio cholerae without also killing the people infected with it. In 1942, just one genuine antibiotic substance was known to scientists – penicillin – and scientists were still unable to produce it in large enough quantities to treat patients. Most treatments for bacterial disease at the time were inconsistent, toxic, or useless. 

But one way to treat bacterial disease had shown more promise, especially in treating the diseases of war, and Yermolyeva had become an expert in deploying it under battlefield conditions. It required cultivating a natural and yet invisible enemy of the cholera bacteria, which she could only find on the bodies of those who had cholera or were close to those who had it. And so her morbid plan began. She was going to use viruses to kill the bacteria that were killing soldiers.

                                                                 * * * *

Bacteriophages, known simply as ‘phages’ for short, are viruses that infect and kill bacteria. Essentially harmless to humans, they exist solely to inject their genes into bacterial cells, where they can either lurk indefinitely or replicate themselves madly. In the latter case, they cause their unfortunate host’s metabolism to go haywire, churning out copies of the virus instead of the materials it needs to sustain itself. When the time is right, the new viruses burst the bacteria open like a popped water bomb and spill out to find new hosts in which to repeat the process.

Bacteria have been growing and multiplying on Earth ceaselessly for almost four billion years, since life first emerged on our scorching, primordial rock. Among the most ancient forms of life on the planet, they have evolved into thousands, probably millions of different species, exploiting and colonising virtually every environment possible.

But for as long as all these bacteria have been around, phages have been perfecting the art of infecting and destroying them. For every single one of the immense number of bacterial cells on the planet, there may be as many as 10 phages – perhaps more. Anywhere and everywhere a bacterial strain has evolved to exploit an ecological niche, there will be viruses that have evolved to exploit that bacteria. This makes these seemingly obscure viruses easily the most abundant biological entity on Earth.

Sail out into the middle of the ocean and scoop up a cup of water and it will contain millions, possibly hundreds of millions, of phages. Take some water from a briny marsh or your local stream, a caustic alkaline lake or a scorching hydrothermal vent, and still you’ll find millions of phages in every millilitre. On land, there can be even higher concentrations – billions of phages in a single gram of rich soil. Even a gram of baked desert earth or frozen Arctic peat contains an active community of phages, locked in a never-ending dance with their bacterial hosts.

Of course, these viruses are all over and inside our bodies, too, doing their deadly bacteria-bursting thing millions of times over as you read this. It is often said that there are more bacterial cells in a human body than human cells. Well, there are even more phages: billions and billions of them in our guts in particular. These phages are bursting bacteria open inside you and all around you right now, and in every moment of your life.

And so, when Professor Zinaida Yermolyeva decided, all those years ago, to try to use viruses to kill the bacteria threatening to wipe out the soldiers defending Stalingrad, the problem wasn’t finding one – it was finding the right one.

                                                                 * * * *

Today, in a few scattered pockets of the former Soviet Union, swigging a tiny vial of yellowish liquid, thick with trillions of phages, is just as common as taking an antibiotic pill. In parts of Georgia and Russia, you can buy packets of phages over the counter to help treat stomach bugs, infected cuts or spots. In Tbilisi, the capital of Georgia, and in the Polish city of Wroclaw, clinics offer more intense ‘phage therapy’ – concentrated viruses washed straight into infected wounds or, for severe infections, injected intravenously.

Since the break-up of the USSR in the 1990s, an increasing number of patients from all over the world, with bacterial infections that Western medicine just can’t treat, have taken the long and expensive trip to these strange and often outdated clinics. Bacteria that have evolved resistance to our most important antibiotics are becoming increasingly widespread and, for millions of people, infections that were once easy to treat are now unstoppable.

Phages were first discovered around 1917 and were first used medically just a couple of years later, in 1919, almost 25 years before the first true antibiotic drug, penicillin, became widely available to doctors. For a few decades in the early 20th century, the world went mad for phages, and phage therapy was everywhere – from chemists’ shops in Britain to Brazilian public hospitals. Large European and American pharmaceutical companies mass-produced mixtures of different phages for the treatment of an assortment of bacterial diseases, and the viruses were brewed in industrial-sized copper vats by the Soviets during World War II to try to keep troops free from gangrene, cholera, dysentery and other nasty diseases of war.

But there’s a catch. You can’t use just any old phage to treat any old bacterial disease. Certain phages only infect certain bacteria, and most are extraordinarily specific in which bacteria they target. Some will only infect just one or perhaps two very similar species of bacteria, and most are even choosier, infecting only a specific strain of a specific species. For doctors in the early 20th century, this made phages extremely difficult to work with: if a phage they had was active against the strain of bacteria causing the disease, the results could be spectacular – patients brought back from the brink of death, up and walking and rid of their bacterial invaders completely within days. But if the phages weren’t an exact match, it was completely useless.

Yermolyeva, looking for phages that could keep the people of Stalingrad safe from the cholera spreading on the German side of the front line, needed to find phages that could infect and kill the exact strain of Vibrio cholerae bacteria causing the local outbreaks. The best place to find these viruses was in and around the deadly bacteria itself. And the best place to find the deadly bacteria was on the bodies of people who were dying from it.

Working with the corpses in her underground lair, she soon isolated the strain of Vibrio cholerae bacteria causing the disease, and then the phages living alongside it. She tested which ones could kill the bacteria most effectively, and using only rudimentary equipment, isolated them, concentrated them and purified them. The phages in their natural state had clearly not helped the dead soldiers on which they were found – but Yermolyeva aimed to create a concentrated mix of the most powerful viruses that together might be able to overpower a nascent cholera infection before it took hold. Soon she had made enough anti-cholera phage mixture to ensure 50,000 preventative doses were given out to soldiers and civilians in the city every day with their daily bread rations.

Ahead of what would become a pivotal battle of World War II and the defeat of the German Army, Yermolyeva is said to have received a call from none other than the commander-in-chief of the Soviet Union, Joseph Stalin. “Is it safe to keep more than a million people at Stalingrad? Can the cholera epidemic interfere with the military plans?” he asked. Yermolyeva replied that she was winning on her front – no cholera outbreaks had broken out within the city. Now it was the Red Army’s turn to win on theirs.

In the coming years, western scientists would develop manufacturing processes that allowed the production of ever larger quantities of their new “miracle antibiotic”, penicillin. These convenient, cheap and very effective tablets spelled the end for the more laborious and unpredictable phage-based medicines – in the west at least. By the 1950s, phage therapy was hardly used, and by the 1970s, with dozens of even more effective antibiotics coming onto the market, it had been virtually forgotten about. 

But in the Soviet Union, where modern antibiotics were harder to come by, the use of phage therapy persisted. Unbeknown to the western world, by the late 1970s, the USSR’s main phage production operation in Tbilisi had become vast. The institute employed a staggering 800 people to churn out thousands of litres of phage medicines in giant metal vats that operated twenty-four hours a day. 

Of course, by then, Cold War relations between east and west had deteriorated to the point that collaborating or even communicating with western scientists was a crime in the Soviet Union. And the first warning signs that bacteria were becoming resistant to many different types of western antibiotics were just starting to appear. A global antimicrobial resistance crisis was brewing, and the group of people who knew how best to fight it just happened to be working in one of the most secretive places in the world.

Want to find out more? You’ll have to buy the book: it’s available in paperback, eBook and audiobook from Amazon, Blackwell’s, Bookshop.org, and Foyles now. 

When not writing books that are picked as the New York Times editor’s choice, described by Forbes as “One of the best books of any genre I’ve read in 2023”, and so forth, Tom Ireland is the editor of The Biologist. He and I go way back – *way* back; when first we worked on the same news desk, Lehman Brothers was still a going concern – so I’ve almost forgiven him my jealousy regarding the tide of compliments that have greeted The Good Virus. It’s terrific, and you should buy it right now.

And if you have a book you’d like to promote to the readers of the Newsletter of (Not Quite) Everything, why not hit reply and tell me about it now…?