Certain viruses, far from causing misery, can be used to fight disease. Scientists are at last pursuing a form of treatment that has been viewed with suspicion for far too long.

 

"The Good Virus

By Tom Ireland

Norton, 389 pages, $30

In 2015, Tom Patterson, a psychiatry professor at the University of California, San Diego, fell ill while on holiday, soon after crawling through a tiny tomb in Egypt's Red Pyramid. His condition deteriorated quickly, and he was transferred first to an intensive-care unit in Frankfurt, Germany, and then to his home hospital in La Jolla, Calif. The underlying cause of his condition: infection with Acinetobacter baumannii -- "the worst bacteria on the planet," according to his doctors. Worse still, the strain was resistant to antibiotics. Mr. Patterson's wife, an accomplished global-health epidemiologist, frantically searched the world for anything that might help. The treatment she landed on was "bacteriophage" -- viruses that attack bacteria. The therapy, amazingly, worked. Mr. Patterson returned from the brink of death and eventually made a full recovery.

In the wake of the Covid pandemic, the idea of a virus being beneficial may seem strange, even implausible. But science journalist Tom Ireland is admirably determined to show us just how potent this disease-fighting approach can be and to persuade us of its importance. As engaging as it is expansive, "The Good Virus" describes the distinctive biology and murky history of bacteriophage (generally shortened to "phage"), a form of life that is remarkably abundant yet obscure enough to have been termed the "dark matter of biology."

Phage viruses are everywhere, from frigid mountain elevations and seawater to plant leaves and, not least, the human body. The body's 30 trillion cells are outnumbered by nearly 40 trillion colonizing bacteria and 10 times as many phage, predominantly in our guts. It is estimated that trillions of types of phage -- most yet undiscovered -- exist in the world, representing the "greatest source of genetic diversity on the planet," Mr. Ireland writes.

Phage are typically less than a 10th the size of a bacterial cell. They come in a range of shapes, but in general they look and act like tiny bulb syringes, with the genetic material (usually DNA, occasionally RNA) coiled tightly within a protein capsule -- the "head" of the virus. The tail, meanwhile, latches onto the target bacterium, enabling the virus to inject its deadly payload. Once inside, the phage DNA hijacks the bacterial machinery to replicate itself and flood the cell with virus particles until the bacterium bursts open, freeing the phage to infect new hosts. Sometimes the infecting DNA opts to lie low, waiting until conditions are right to initiate its lethal attack.

While examples of phage activity have been present throughout history -- phage may account for fabled healing properties of India's Ganges River, for example -- their discovery awaited the turn of the 20th century. This was an era in which, Mr. Ireland writes, "microbe hunting" had become "a glamorous profession that had captured the world's attention." In a South London research institute in the early 1910s, the meticulous English bacteriologist Frederick Twort set out to grow the smallpox virus in petri dishes, hoping it could be "observed and studied like bacteria." He succeeded in growing only contaminating bacteria, but within these colonies he noticed the occasional small clearing, as if something invisible was killing the bacteria. With the outbreak of World War I, Twort lost funding, closed his lab and published his results in 1915, cautiously suggesting that a virus could be the cause of the observed phenomenon. Few took notice.

Twort's unlikely competitor would be Felix d'Herelle, a free-spirited Frenchman who left school at age 16 to travel the world, "spending his well-connected family's money," as Mr. Ireland puts it. At 24, d'Herelle moved to Canada, "where there were so few microbiologists that he simply declared himself one" and set up shop. But soon the urge to travel struck, and he found himself in Mexico, helping the government manage a locust infestation by cultivating bacteria that infected the insects. Later in his career, while studying dysentery, he returned to this playbook, searching for an "ultramicrobe" that might attack the disease-causing bacteria. He found the same glassy spots that Twort had observed and (with noticeably less restraint) announced in 1917 that he had discovered a new form of life, which he called "bacteriophage." D'Herelle went on to use phage to treat five sick boys successfully. But his "wild and abrasive style" (in Mr. Ireland's words) antagonized his peers, who conspired to undermine him.

D'Herelle's discoveries inspired many, including George Eliava, a microbiologist from the Soviet Union's republic of Georgia. In 1936, he would establish the first institute (and still one of the few) devoted to bacteriophage research. Unfortunately for Eliava, he soon ran afoul of the Soviet secret police, who disappeared him in 1937. The institute continued to pursue the development of phage therapy and scored many victories -- phage helped treat soldiers suffering from gangrene, for example. 

But there were also frustrating failures, in part because the phage weren't adequately purified and often because they weren't appropriately matched to the specific strain of infecting bacteria. While the world (including the U.S.) initially "went mad" for phage therapy," Mr. Ireland reports, the results were "inconsistent and unpredictable." Indeed, the "dubious and unreliable nature of commercial American phage products" in the 1930s, we learn, meant that "whether they worked for a particular patient was a complete lottery."

During World War II, the West turned decisively to newly discovered penicillin, sharing the formula for it with the Soviets but not the methods of mass production. Thus the Soviets continued to rely on phage as the therapy of choice for bacterial infections. When a Soviet researcher tried to obtain production rights to penicillin in 1949, he was arrested by government authorities and died under interrogation, all for the crime of nizkopoklonstvo -- adulation of the West.

Western physicians, for their part, embraced clean and well-tested antibiotics and regarded phage, according to Mr. Ireland, as "a relic from medicine's dark and archaic past." But researchers were keen to use phage as a laboratory tool, and it ultimately unlocked a range of important principles of molecular biology -- including the identification of DNA as the underlying genetic material. The study of bacterial resistance to phage would later reveal the presence of distinct DNA sequences, known as Crispr, that help bacteria defend themselves by snipping the DNA of infecting phage. Later research has shown that this molecular editing can be repurposed by scientists for precise genetic engineering.

Once "derided as an idea for cranks and commies," Mr. Ireland writes, phage therapy seems to be enjoying a renaissance. Having been sustained for years by an idiosyncratic global community of true believers, phage-based medicines have now attracted the attention of high-powered biotechnologists and investors. Several teams are trying to synthesize pharmaceutical-grade phage from scratch; others are working to systematize and standardize the process for isolating phage from bacteria and seeking regulatory approval for the entire process. There is certainly a pressing need: The last new class of antibiotics, Mr. Ireland reminds us, was developed decades ago, and the problem of drug-resistant bacteria continues to grow. After years of scientific exile, it may finally be time for therapeutic phage to come in from the cold.

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Dr. Shaywitz is a physician-scientist at Takeda Pharmaceuticals, a lecturer at Harvard and an adjunct fellow at the American Enterprise Institute." [1]

1. REVIEW --- Books: The Enemy of My Enemy --- Certain viruses, far from causing misery, can be used to fight disease. Scientists are at last pursuing a form of treatment that has been viewed with suspicion for far too long. Shaywitz, David A.  Wall Street Journal, Eastern edition; New York, N.Y.. 05 Aug 2023: C.7.