Phages, which are harmless viruses that destroy specific bacteria, are becoming useful tools to protect our food supply.
Every year, one in seven people in America comes down with a foodborne illness, typically caused by a bacterial pathogen, including E.Coli, listeria, salmonella, or campylobacter. That adds up to 48 million people, of which 120,000 are hospitalized and 3000 die, according to the Centers for Disease Control. And the variety of foods that can be contaminated with bacterial pathogens is growing too. In the 20th century, E.Coli and listeria lurked primarily within meat. Now they find their way into lettuce, spinach, and other leafy greens, causing periodic consumer scares and product recalls. Onions are the most recent suspected culprit of a nationwide salmonella outbreak.
Some of these incidents are almost inevitable because of how Mother Nature works, explains Divya Jaroni, associate professor of animal and food sciences at Oklahoma State University. These common foodborne pathogens come from the cattle's intestines when the animals shed them in their manure—and then they get washed into rivers and lakes, especially in heavy rains. When this water is later used to irrigate produce farms, the bugs end up on salad greens. Plus, many small farms do both—herd cattle and grow produce.
"Unfortunately for us, these pathogens are part of the microflora of the cows' intestinal tract," Jaroni says. "Some farmers may have an acre or two of cattle pastures, and an acre of a produce farm nearby, so it's easy for this water to contaminate the crops."
Food producers and packagers fight bacteria by potent chemicals, with chlorine being the go-to disinfectant. Cattle carcasses, for example, are typically washed by chlorine solutions as the animals' intestines are removed. Leafy greens are bathed in water with added chlorine solutions. However, because the same "bath" can be used for multiple veggie batches and chlorine evaporates over time, the later rounds may not kill all of the bacteria, sparing some. The natural and organic producers avoid chlorine, substituting it with lactic acid, a more holistic sanitizer, but even with all these efforts, some pathogens survive, sickening consumers and causing food recalls. As we farm more animals and grow more produce, while also striving to use fewer chemicals and more organic growing methods, it will be harder to control bacteria's spread.
"It took us a long time to convince the FDA phages were safe and efficient alternatives. But we had worked with them to gather all the data they needed, and the FDA was very supportive in the end."
Luckily, bacteria have their own killers. Called bacteriophages, or phages for short, they are viruses that prey on bacteria only. Under the electron microscope, they look like fantasy spaceships, with oblong bodies, spider-like legs and long tails. Much smaller than a bacterium, phages pierce the microbes' cells with their tails, sneak in and begin multiplying inside, eventually bursting the microbes open—and then proceed to infect more of them.
The best part is that these phages are harmless to humans. Moreover, recent research finds that millions of phages dwell on us and in us—in our nose, throat, skin and gut, protecting us from bacterial infections as part of our healthy microbiome. A recent study suggested that we absorb about 30 billion phages into our bodies on a daily basis. Now, ingeniously, they are starting to be deployed as anti-microbial agents in the food industry.
A Maryland-based phage research company called Intralytix is doing just that. Founded by Alexander Sulakvelidze, a microbiologist and epidemiologist who came to the United States from Tbilisi, the capital of Georgia, Intralytix makes and sells five different FDA-approved phage cocktails that work against some of the most notorious food pathogens: ListShield for Listeria, SalmoFresh for Salmonella, ShigaShield for Shigella, another foodborne bug, and EcoShield for E.coli, including the infamous strain that caused the Jack in the Box outbreak in 1993 that killed four children and sickened 732 people across four states. Last year, the FDA granted its approval to yet another Intralytix phage for managing Campylobacter contamination, named CampyShield. "We call it safety by nature," Sulakvelidze says.
Intralytix grows phages inside massive 1500-liter fermenters, feeding them bacterial "fodder."
Photo credit: Living Radiant Photography
Phage preparations are relatively straightforward to make. In nature, phages thrive in any body of water where bacteria live too, including rivers, lakes and bays. "I can dip a bucket into the Chesapeake Bay, and it will be full of all kinds of phages," Sulakvelidze says. "Sewage is another great place to look for specific phages of interest, because it's teeming with all sorts of bacteria—and therefore the viruses that prey on them."
In lab settings, Intralytix grows phages inside massive 1500-liter fermenters, feeding them bacterial "fodder." Once phages multiply enough, they are harvested, dispensed into containers and shipped to food producers who have adopted this disinfecting practice into their preparation process. Typically, it's done by computer-controlled sprayer systems that disperse mist-like phage preparations onto the food.
Unlike chemicals like chlorine or antibiotics, which kill a wide spectrum of bacteria, phages are more specialized, each feeding on specific microbial species. A phage that targets salmonella will not prey on listeria and vice versa. So food producers may sometimes use a combo of different phage preparations. Intralytix is continuously researching and testing new phages. With a contract from the National Institutes of Health, Intralytix is expanding its automated high-throughput robot that tests which phages work best against which bacteria, speeding up the development of the new phage cocktails.
Phages have other "talents." In her recent study, Jaroni found that phages have the ability to destroy bacterial biofilms—colonies of microorganisms that tend to grow on surfaces of the food processing equipment, surrounding themselves with protective coating that even very harsh chemicals can't crack.
"Phages are very clever," Jaroni says. "They produce enzymes that target the biofilms, and once they break through, they can reach the bacteria."
Convincing the FDA that phages were safe to use on food products was no easy feat, Sulakvelidze says. In his home country of Georgia, phages have been used as antimicrobial remedies for over a century, but the FDA was leery of using viruses as food safety agents. "It took us a long time to convince the FDA phages were safe and efficient alternatives," Sulakvelidze says. "But we had worked with them to gather all the data they needed, and the FDA was very supportive in the end."
The agency had granted Intralytix its first approval in 2006, and over the past 10 years, the company's sales increased by over 15-fold. "We currently sell to about 40 companies and are in discussions with several other large food producers," Sulakvelidze says. One indicator that the industry now understands and appreciates the science of phages was that his company was ranked as Top Food Safety Provider in 2021 by Food and Beverage Technology Review, he adds. Notably, phage sprays are kosher, halal and organic-certified.
Intralytix's phage cocktails to safeguard food from bacteria are approved for consumers in addition to food producers, but currently the company sells to food producers only. Selling retail requires different packaging like easy-to-use spray bottles and different marketing that would inform people about phages' antimicrobial qualities. But ultimately, giving people the ability to remove pathogens from their food with probiotic phage sprays is the goal, Sulakvelidze says.
It's not the company's only goal. Now Intralytix is going a step further, investigating phages' probiotic and therapeutic abilities. Because phages are highly specialized in the bacteria they target, they can be used to treat infections caused by specific pathogens while leaving the beneficial species of our microbiome intact. In an ongoing clinical trial with Mount Sinai, Intralytix is now investigating a potential phage treatment against a certain type of E. coli for patients with Crohn's disease, and is about to start another clinical trial for treating bacterial dysentery.
"Now that we have proved that phages are safe and effective against foodborne bacteria," Sulakvelidze says, "we are going to demonstrate their potential in therapeutic applications."
This article was first published by Leaps.org on October 27, 2021.
David and Jen on their wedding day, and Jen undergoing treatment for her rare sarcoma.
It was 15 years ago this month, but I'll never forget those words. When my wife Jen and I asked her oncologist about our plans to start a family, he calmly replied, "Well, I wouldn't do so unless Dave is prepared to be a single father."
About 50 percent of all people with cancer have a rare type, like the one Jen was fighting.
Time stood still. The danger crystalized — we were in a battle for my beautiful bride's life, and the odds were not in our favor.
We felt every emotion expected. Anger, sadness, confusion, frustration, and especially fear. But we made a very intentional choice to take that fear, put it to the side, and do everything we could to live our lives together to the fullest.
We focused first on Jen's health and learned everything we could about MFH Sarcoma. I was with her every step of the way — for hundreds of medical appointments, six intense surgeries, and twenty different types of chemotherapy. During such a challenging time, our choice to reject fear allowed us to live our best lives. Our careers blossomed, we enjoyed several international vacations, and Jen inspired thousands of fellow patients through her blog and speeches.
When we researched treatment options we learned that Jen was not alone. About 50 percent of all people with cancer have a rare type, like the one Jen was fighting. However, rare cancers don't get the funding they desperately need so effective treatment options are hard to find. The lack of funding felt unfair — and urgent. We didn't worry about everything that can go wrong when starting a new venture. Instead, we jumped in head first and convinced a small group of friends and family to ride stationary bikes with us to raise money for rare cancer research.
Jen Goodman Linn, riding a stationary bike for Cycle for Survival.
(Courtesy David Linn)
From those humble beginnings, Cycle for Survival grew steadily. After starting from scratch, Jen and I ran Cycle for Survival on our own for two years. We quickly realized that if we wanted to help as many people as possible, we needed the best partners. In 2009, we agreed that Memorial Sloan Kettering Cancer Center would take over the ownership of Cycle for Survival and Equinox officially became the Founding Partner. Flash forward to today, and Cycle for Survival has raised more than $220 million! I'm proud that 100% of every donation, yes every penny, goes directly into life-saving rare cancer research within six months of the annual indoor cycling events, which now take place in 17 cities nationwide.
While Cycle for Survival's trajectory was heading straight up, Jen's health struggle was devastatingly swinging up and down. With her incredible spirit and tenacity, Jen would beat the cancer through chemo and surgery, but then it would frustratingly come back again and again. After going into remission six times, it returned with such a vengeance in 2011 that even the world's leading doctors were forced to say, "I'm sorry, there's nothing more we can do."
Those were the most difficult words I've ever heard, by far. I hope no other family has to hear these crushing words.
When Jen died soon after, I didn't know what would happen to me, to my life, and to Cycle for Survival. I do remember making two very important choices at the time. First, I chose to get out of bed and put one foot in front of the other. It wasn't easy. Tears, pain, and grief would hit at any hour of the day or night. I did have a great support network of family and friends who kept me moving forward. One friend in particular changed the route of her morning runs so that I would join her and start getting back to exercising.
My second key choice was to stay involved with Cycle for Survival. At times, it was an excruciatingly difficult decision because I felt the depth of my loss each and every time I stepped into one of the events. However, it was also rewarding and energizing because I could see firsthand how many people it was helping, even though it was too late for Jen.
I began to travel across the country with the Cycle for Survival staff. My hope was to spread the word about rare cancers; along the way I met a lot of wonderful people who shared their stories with me. What I soon realized is that each of us faces obstacles in our lives. For me, it was losing the person who I wanted to spend my life with. For others, it might be challenges with their kids or in their professional lives. The common theme is that we don't have control over the fact that we have to face these challenges. But the biggest lesson I've learned is that we very much do have a choice in how we react.
I made the choice to do everything I can to help rare cancer patients and their families and it has been transformative and healing for me. The small group who rode in the first Cycle for Survival event has grown into a powerful movement of nearly 40,000 riders making a real difference. If Jen were diagnosed today, there are new treatments available– including genomic sequencing, targeted therapies, and immunotherapies – that could help her. Those weren't even options a short time ago. That's the result of funding research.
A recent Cycle for Survival event shows the passion and power of the community.
(Courtesy David Linn)
I also want to share one more choice I made. Remember that friend who changed the route of her morning runs so I could start exercising after Jen died? Well, over the years friendship grew into love, and we're now building a home together and can't wait to see what the future holds for us.
So with all that in mind I ask – when you face those inevitable challenges in your life, how will you choose to react? Remember that even in the midst of hopelessness, you can find choices. Those will be the decisions that define and guide you.