Tom Ireland is a science journalist who has been researching and writing about phages for the last three years. He edits The Biologist magazine and is a regular contributor to BBC Science Focus.
Below, Tom shares five key insights from his new book, The Good Virus: The Untold Story of Phages. Listen to the audio version—read by Tom himself—in the Next Big Idea App.
1. Phages are nature’s antibiotics.
Phages are viruses that have evolved to infect and kill bacteria. For almost four billion years, these viruses have been evolving. Everywhere there are bacteria, these viruses are not far away, infecting them, replicating inside them, and bursting open from the inside out.
Phages can be used to kill the bacteria that cause infectious diseases in humans. Amazingly, they were first used to treat bacterial infections over a hundred years ago, in 1919, almost two decades before the world’s first antibiotic drug, penicillin, was widely available. In fact, in the 1920s and 30s, they were a hugely popular way of treating bacterial disease, all over the world. But this was before the strict regulations and clinical trials that we have now for proving that medical formulas are safe and effective. Scientists also didn’t understand these viruses very well. If you got the right phage for infecting the bacteria causing the disease, the results could be spectacular. But if you used the wrong phage, they were completely useless.
With such inconsistent results, phages got a bad reputation. When antibiotic drugs came along, doctors in most countries found them far more consistent and convenient. Over the course of the 20th century, much of the world abandoned the idea of using phages, and then virtually forgot all about it.
But as we’ve become increasingly dependent on chemical antibiotics, bacteria have developed resistance to these drugs. The crisis of antibiotic resistance is starting to hit hard, with millions of people dying every year from infections that our best antibiotics can’t treat. If we don’t adopt new approaches, we face a return to the time before antibiotics—when even minor ailments, like food poisoning or surgical wounds, could cause life-threatening complications.
Using phages to treat infections is once again being taken seriously. Phages are still challenging to use as medicines. We’re talking about things that self-replicate and evolve inside the body. This has made them hard to test in clinical trials and to regulate. There’s also the problem of having to find the right phage for every patient’s particular infection—this is not an off-the-shelf solution. But we now finally have the technology and the will to drag this hundred-year-old idea into the 21st century.
2. We have a lot to learn from Soviet and post-Soviet medicine.
There are some places in the world that never stopped using phages to treat infections. One of those places is Georgia, the former Soviet country at the southern tip of Russia. Here, doctors prescribe phages for all manner of ailments. In pharmacies, you can get solutions of concentrated phages to swig, or phage-infused creams to rub on wounds or spots.
Throughout the 20th century, scientists and doctors in places like Georgia, and other former Soviet countries like Russia and Poland, kept refining the use of phages as medicines. Drugs like penicillin were often hard to get in the Soviet Union and so they poured their efforts into producing thousands of litres of phage-based medicines every year.
“When doctors in the West do try to use phages, it is often as a last resort.”
But because of the Cold War and the complete blockade of information between East and West, we in the West knew nothing about it. Even when the USSR collapsed and the Iron Curtain came down, Western scientists mostly derided the idea as backward. But with bacteria increasingly becoming resistant to every antibiotic in our arsenal, more and more people are traveling to Georgia to be treated with phages.
When doctors in the West do try to use phages, it is often as a last resort. As well as regulatory challenges, there are just very few people in the Western world who know how to administer this strange type of treatment. Meanwhile, decades’ worth of experience and records from Soviet countries lie unused and unseen.
3. Phages helped defeat the Nazis in World War II.
In the summer of 1942, as German troops encircled the Russian city of Stalingrad, Nazi commanders began receiving bizarre reports of dead bodies disappearing from German field hospitals. In the dead of night, Soviet scouts were daringly crossing the front line to steal certain German corpses, before squirreling them back into a secret underground laboratory hidden deep beneath the city.
The Germans had been suffering outbreaks of cholera for weeks as they had 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 the soldiers and civilians crammed into a city under siege. So, a woman called Professor Zina-ida Yermol-yeva, 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.
Back then, just one genuine antibiotic substance was known to scientists: penicillin. And they were still unable to produce it in large enough quantities to treat patients. With this limitation, Yermolyeva had become an expert in phage therapy.
The whole planet is teeming with bacteria and phages. When Yermolyeva was sent to use viruses to keep the people of Stalingrad safe from the cholera spreading on the German side of the front line, the problem wasn’t finding them—it was finding the right one.
“The best place to find the deadly bacteria was on the bodies of people who were dying from it.”
She 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. 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 cholera bacteria causing the disease, and then the viruses 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. Soon she had made enough anti-cholera phage cocktail 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, Yermol-yeva is said to have received a call from Stalin himself. “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 within the city. Now it was the Red Army’s turn to win on theirs.
4. Phages are fundamentally important to life on Earth.
For a long time, scientists thought that the number of viruses in the environment was fairly insignificant. Virologists tended to study human environments, not wild ones.
It was only in the 1990s that a group of virologists took some samples of clean water from the open ocean and looked for viruses there. They found that in a few milliliters of water, scooped from a random point in the open ocean, existed millions of viruses—most of them phages. If there were millions of viruses in a few milliliters, then how many were there in the whole world? The number would be astronomical. Other groups started taking samples of water from bays, lakes, rivers, marches, and briny swamps. Everywhere they looked, millions and sometimes hundreds of millions of phages sat in every drop.
Rather suddenly, and surprisingly recently, we have come to realize that the number of viruses in the environment is not insignificant at all. Phages are easily the most abundant biological entity on Earth. Life on this planet simmers in a soup of bacterial viruses and always has. Despite individual viruses being sub-microscopic, the world’s phages are estimated to hold roughly 200 megatons of carbon at any one time. That’s fifty times the amount of carbon emitted by human activities across the entire U.S. each year. All our models of how nutrients are cycled through ecosystems have had to be rewritten.
“Phages are easily the most abundant biological entity on Earth.”
The discoveries about viral abundance kept coming. Virologists then began exploring the number of phages on dry land. Concentrations were even higher in soil, with up to a billion phages in a gram of particularly rich soils. Even a teaspoon of earth from a baked desert, or ice locked into glaciers for thousands of years, can contain an active community of thousands or millions of phages. When a group of researchers installed collection devices on a concrete platform almost 3km above sea level in the Sierra Nevada mountains, in Spain, they found hundreds of millions and sometimes billions of viruses were simply falling from the sky every day, perhaps blown high into the air from sea spray or dust and transported around the world on global air currents. These studies have changed our understanding of our planet.
The well-established idea that microbes drive ecosystems on Earth has rather suddenly been reappraised: microbes may well rule the world, but secretly, viruses rule the microbes. The more we look at these phages, the more stunning insights about their importance are revealed.
The crazy thing is, we know hardly anything about any of these viruses. They are known as the dark matter of biology and represent the greatest untapped pool of genes on Earth that could tell us many things about how life on Earth works and where it came from.
5. Phages are the future.
With the antibiotic crisis becoming more acute and deadly, and investment in new antibiotics stalling, radical new approaches are needed. Several exciting technologies are emerging to make phages easier to use in medicine, from cocktails of genetically engineered phages to man-made phages designed and synthesized at the patients’ bedside. In the developing world, where antibiotic resistance is likely to hit hardest, naturally occurring phages found in the environment could offer an extremely cost-effective source for killing bacteria.
These hyper-abundant and adaptable little viruses could make many impacts, from delivering drugs to tumor cells in the body to helping change the microbial make-up of ecosystems. They are sophisticated, self-replicating little nanomachines that are all around us, waiting to be used for good. It’s thought that over 99 percent of the phages in the world are unknown to science—so there’s lots more to discover.
To listen to the audio version read by author Tom Ireland, download the Next Big Idea App today:
