Phage therapy – a case of science fiction preceding fact

Phages were trialled as antimicrobial treatments in the 1920s against plague and cholera

An illustration of bacteriophages with their distinctive capsid head. The bacteriophage inspired a very early scientist-hero novel, Arrowsmith by Sinclair Lewis, published in 1925

An illustration of bacteriophages with their distinctive capsid head. The bacteriophage inspired a very early scientist-hero novel, Arrowsmith by Sinclair Lewis, published in 1925

 

We are all rather tired of the latest news on our current viral nemesis. But did you know that even bacteria can be infected by viruses? And that these viruses have been considered useful to treat disease?

Bacteriophages look a little like spiders wearing ring pops: a kind of jewel-shaped head on legs. Rather than injecting venom, they inject their genetic material into a bacterium which then replicates the phages. The build-up of phages bursts the cell before infecting the next bacterium, very like how a virus works in a human cell.

The bacteriophage inspired a very early scientist-hero novel, Arrowsmith by Sinclair Lewis, published in 1925. In the book, Martin Arrowsmith is a determined scientist who sees promise and possibility in the growing science of bacteriology. “It was a portentous hour,” Lewis wrote, “He was going to specialise in bacteriology; he was going to discover enchanting new germs.”

The fictional Arrowsmith becomes one of the discoverers of phages and later uses them to cure plague on a fictional Caribbean island (although only after dithering over scientific principles and allowing many people to die from it).

Pulitzer Prize

The book won a Pulitzer Prize, leading me to believe that readers 100 years ago had a lot more patience than I do. If you want to try your hand at reading it you can find it on Archive.org. Or you can just listen to Race for the Prize by the Flaming Lips a few times instead which gives the same kind of narrative in a much shorter format.

As historian William Summers has pointed out, Lewis owed a lot of his understanding of germs, phages and the scientific laboratory to a collaboration with the scientist Paul de Kruif. De Kruif essentially provided a scientific education for the author, one that was particularly focused on what he saw as exciting (as yet unproven) developments.

The science of phages was only in its infancy when Lewis was writing his book. Antibiotics did not exist and phages were seen as a potentially promising therapy for bacterial diseases. The hope was that they could kill bacteria in the human body in the same way that they did in the body.

One of the most striking aspects of the phage therapy trials in India in the late 1920s is their contrast with clinical trials

Phages, depending on who you ask, had been discovered either by British scientist Frederick Twort in 1915 or French scientist Felix d’Herelle in 1917. Twort observed the effects of bacteriophages on his bacterial cultures, grown on petri dishes. Plaques, or areas of dead bacteria appeared. When he took a sample from these plaques and added it to another plate of bacteria he could transfer the killing effect.

He assumed that an enzyme or other chemical was killing the bacteria by “lysing” or bursting the cell wall. D’Herelle, by contrast, saw the same effect but ascribed it to an organism that he called the bacteriophage.

Experimentation in India

During the 1920s, phages were isolated from bacterial cultures and trialled as antimicrobial treatments against plague and cholera. D’Herelle was at the forefront of this research which involved experimentation in India and Egypt, both places with a significant European colonial presence alongside endemic cholera and plague.

Summers has suggested that in the case of phage therapy, science fiction directly preceded fact: Arrowsmith treated people on the fictional island with phage in a way that was later practised in India. In 1927, a year after Lewis had politely declined the Pulitzer Prize for Arrowsmith, D’Herelle was dosing Indian cholera victims with a phage preparation. The idea was that the phages would infect and kill off the cholera bacillus which the patient’s body was not able to kill fast enough.

Haphazard

One of the most striking aspects of the phage therapy trials in India in the late 1920s is their contrast with clinical trials. Rather than rigorous controls, safety measures and huge numbers, the phage trials were a little haphazard. Most trials dealt in hundreds of patients rather than thousands. Sometimes patients were given phages as treatment and sometimes as prevention.

Perhaps the largest scale trials were those where phages were put into drinking wells serving thousands of people. In all cases it appears that the phages had some effect, reducing mortality from cholera. However, the trials failed to satisfy even the lower standards of rigour of the age. Phages never managed to overtake vaccination and sanitation as the primary tools of cholera management.

Dr Juliana Adelman is an associate professor of history at Dublin City University – @AdelmanJuliana

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