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Opinion | Phage therapy could arm the world against superbugs
An electron micrograph of bacteriophages attached to a bacterial cell (Photo: Wikpedia)
4 min read . Updated: 28 Oct 2019, 10:23 PM ISTSiddharth Pai
A phage is a kind of virus that can enter a bacterium, multiply, and thus kill its host from within
I have written in this column before about the use of big data techniques to find a new class of antibiotics that can deal with superbugs. Superbugs are bacteria that have become immune to existing antibiotics. The over-prescription of antibiotics and their wide use in poultry, fish, and meat farms means that bacteria have had a chance to mutate and become resistant to many antibiotics. To add to this, we are using old ammunition. The last useful class of antibiotics now in use, fluoroquinolone, was discovered in 1962, about 60 years ago.
Antibiotic cocktails that are used to treat superbugs do exist. They are used sparingly and only as a last resort. The irony here is that whether the patient lives or dies, he or she will not end up being a repeat user. As a result, drug companies pour very little of their resources into the discovery of such drugs, as the economic returns from finding a super class of antibiotics simply do not outweigh the costs. Meanwhile, estimates put the number of deaths because of superbugs at more than one million a year, which is likely to grow to 10 million by 2050. That is one death every three seconds. It's time for action, but if big pharma stays away, this action will lie in the realm of start-ups.
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Many start-ups are using the explosion in big data and computing power to run complicated algorithms that may eventually provide a breakthrough. The use of big data by startups dealing with this problem can broadly be classified into three types. The first lies in the simple but effective mapping of disease patterns within a geography and various sets of people among its population. The second is the use of computational algorithms to presage a scientific molecular level discovery, which is what most new superbug antibiotic development startups are attempting. They use these algorithms in their quest to design a chemistry-based solution that will allow for the isolation of certain proteins in the bacterium, which when disintegrated by a chemical substance, will kill the bacterium. The third technique is to use genomics, which studies how harmful bacteria have changed in response to antibiotic use, and use this new-found knowledge to arrive at changes in genomic sequencing to kill the resistant bacteria.
However, the fight against superbugs can't be won by IT alone. I recently met Dr. Steffanie Strathdee, a chaired professor at the department of medicine at the University of California in San Diego (UCSD). Strathdee is an expert on global health, and apart from her name-endowed professorship at UCSD, is also the associate dean of its department of medicine. Strathdee recounted an intensely personal experience with superbugs, which caused her to start a new line of research. Her husband had been slipping in and out of a coma for two months brought on by a superbug and the doctors had said there was nothing they could do.
Strathdee reached back to her early college training where she had learnt about 'phages' or viruses that attack and kill bacterial cells, a process called 'phage therapy'. Phages were discovered more than 100 years ago by a French-Canadian microbiologist Félix d'Herelle. They were in regular use in the Soviet Union and the Eastern bloc as a treatment protocol. However, the Cold War allowed pharmaceutical purveyors in the West to ignore these therapeutic discoveries for many years. The political climate was conducive, as collaboration of Russia and the Eastern bloc with the West was minimal.
There are trillions of phages on the planet that have evolved over millennia to become the perfect predators of bacteria. The phage latches on to and enters the bacterium, and once that is done, proceeds to take over its machinery and turn it into a kind of phage-manufacturing plant. The newly-minted phages then burst out and the bacterial cell dies. To work, phages have to be matched to the bacterial infection.
Strathdee decided to ask for help, which was forthcoming from labs in Russia, the US Navy, Switzerland and even India, among others, and sourced viruses of eight different strains that were known to be phages of Acinetobacter baumannii, nicknamed Iraqibacter. She then injected billions of these phages into her husband Tom Patterson, another scientist at UCSD.
Patterson recovered as a result of her last-ditch effort. After his case was publicized, people contacted Strathdee from all over the world wanting phage therapy. Strangers had helped her and she felt she had an obligation to help them. Strathdee hasn't always been successful, though, because she was contacted too late in several instances. She says the Food and Drug Administration of the US is now making it easier for people to get phage therapy earlier in the course of their infections.
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Strathdee says that what is needed now are clinical trials to see if this line of therapy works on a broader scale. Strathdee says if she can use this method for one man, then why not for the entire planet? She hopes to create a library of phages or a giant phage bank with specific phage cocktails for many mutations of superbugs. She is on a quest to raise funding to do so.
After Strathdee's success, she and her husband have now written a book, The Perfect Predator. The story is so fascinating that she has already been able to sell its movie rights. She also gives talks on her experience and what she has been doing to regularise phage treatment. She is scheduled to speak at India International Centre, New Delhi, this month, for example.
Siddharth Pai is founder of Siana Capital, a venture fund management company focused on tech and science