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A Gulp Of Genetically Modified Bacteria Might Someday Treat A Range Of Illnesses

Mar 8, 2019
Originally published on March 12, 2019 9:33 am

Instead of eating a typical breakfast every day, Jonah Reeder gulps down a special protein shake.

"The nutrients in it like to sit at the bottom, so I usually have to shake it up and get all the nutrients from the protein and everything," says Reeder, 21, of Farmington, Utah, as he shakes a big plastic bottle.

Reeder was born with a rare genetic disorder called phenylketonuria, or PKU. If he eats meat, drinks milk or consumes other common sources of protein, toxic levels of the amino acid phenylalanine could build up in his body and damage his brain.

So Reeder gets his protein from the shake, which is rich in other amino acids, vitamins and proteins that don't contain phenylalanine.

"It's a really healthy drink," Reeder says. "It's basically protein, except without phenylalanine."

But Reeder hopes a new approach for treating diseases could help people like him. The idea is to use bacteria that have been genetically modified to do what Reeder's body can't — get rid of phenylalanine.

"I'm really excited to help out and hopefully find a treatment for PKU," Reeder said recently, as he prepared to volunteer for a study testing the modified bacteria.

The bacteria Reeder is helping test are part of a new field of medical research that has emerged from two realms of biomedical science. One is the study of the human microbiome, the microbes that inhabit our bodies. The other is synthetic biology, a field that looks at genetically engineering living organisms, including bacteria in the human gut.

"It's a new world of being able to use synthetic biology to program microbes to treat diseases, which I believe is the future," says Pamela Silver, a synthetic biologist at Harvard Medical School in Boston.

Scientists hope to genetically modify microbes from the human microbiome to treat a range of diseases, including digestive disorders like ulcerative colitis and inflammatory bowel disease.

"Microbes are something that we as synthetic biologists see as highly engineer-able. We understand how to engineer microbes so it seems like the perfect interface between synthetic biology and health," Silver says.

One company, ActoBio Therapeutics of Ghent, Belgium, has just started using genetically engineered microbes to try to treat Type 1 diabetes. Another one, Oragenics of Tampa, Fla., is testing a modified bacterium to treat mouth sores caused by cancer chemotherapy. And Osel of Mountain View, Calif., hopes engineered microbes could prevent HIV infections.

Reeder is helping test modified E. coli bacteria. While some types of E. coli can cause serious illness, the E. coli type being used in the study is found in the human gut.

"It is a naturally occurring probiotic bacteria," says Caroline Kurtz, a scientist at Synlogic, a Cambridge, Mass., biotech company, which created the modified version of the organism.

"We can enhance its function by introducing genes [or] by changing genes that are there, and design the cells to either produce something or consume something that may be beneficial for a patient," Kurtz says.

Synlogic has also engineered E. coli to rid life-threatening levels of ammonia from the bodies of people with cirrhosis of the liver.

"This is a really exciting new modality that allows us to think about therapies in a new way and really look at diseases in a whole new way: a living medicine that can respond to its environment," Kurtz says.

Preliminary research involving mice and healthy adults published recently in the journal Science Translational Medicine indicates Synlogic's E. coli are safe and may work. So the company is now testing them in patients with cirrhosis and PKU.

Reeder admits he was a little nervous when he first heard about all this.

"When you hear about E. coli you think: sickness, throwing up. So I was a little bit skeptical. I wasn't sure what to think because I was going to be ingesting E. coli," Reeder says.

But the more he learned about it, the more excited Reeder got about trying the engineered microbes.

"I think that's very cool that they found a way to use a natural probiotic that's found in the digestive tract to help the human body," Reeder says.

Reeder spent the weekend in the clinic so doctors could monitor him closely and run tests as he ingested what normally would be dangerous amounts of protein. He then swallowed either the engineered E. coli or a placebo. He wasn't told which.

"It was liquid solution. It tasted kind of like mint taffy. It was pretty sweet," he says.

Reeder thinks he got the engineered microbes.

"I could immediately feel my cognitive abilities falling down after drinking the 20 grams of protein. And then I took the drug and I started feeling a lot better. I obtained more energy and my cognitive abilities got quicker," he says.

"It was really cool to feel that. I could tell it was working. It was pretty cool," Reeder says.

Much more research is needed to know whether genetically engineered microbes are safe and really work. But Synlogic hopes to report results from the cirrhosis and PKU studies later this year.

Before any of these experimental treatments could be used routinely, they would have to be reviewed and approved by the Food and Drug Administration. That's a process that could take years.

Copyright 2019 NPR. To see more, visit https://www.npr.org.

STEVE INSKEEP, HOST:

It may be time to update what we know about bacteria. Needless to say, an infection by the wrong kind of bacteria can make you ill. We also learn about good bacteria, which play a healthy role in our digestive systems. Now think of genetically engineered bacteria. Scientists believe they can send these bacteria through your body to treat medical problems. Here's NPR health correspondent Rob Stein.

ROB STEIN, BYLINE: Jonah Reeder is starting his day at his home in Farmington, Utah. But instead of eating a normal breakfast, Reeder, who's 21, is getting ready to gulp down a special protein shake.

JONAH REEDER: The nutrients in it like to sit at the bottom, so I usually have to shake it up.

STEIN: This isn't just any protein shake. Reeder was born with a rare genetic disorder known as phenylketonuria, or PKU. If he eats meat, drinks milk or consumes most other common proteins, toxic levels of a chemical called phenylalanine builds up in his body and could damage his brain.

REEDER: So it doesn't have phenylalanine, which my body can't have. So it's basically protein, except without phenylalanine, you know.

STEIN: Later this morning, Reeder is checking into a clinic in Salt Lake City. He's volunteering for a study testing an experimental treatment for his disease. The treatment's a genetically modified bacteria, modified to essentially do what Reeder's body can't - get rid of phenylalanine.

REEDER: I'm excited. I'm really excited to help out and hopefully find a treatment for PKU.

STEIN: And so...

REEDER: Bye, Mom.

UNIDENTIFIED PERSON: Bye.

STEIN: Reeder heads off to the clinic in Salt Lake City to start the study. The bacteria Reeder is helping test is a form of E. coli. Some types of E. coli make people really sick. But Caroline Kurtz, a scientist at a company called Synlogic, says this E. coli lives in our guts.

CAROLINE KURTZ: It is a naturally occurring probiotic bacteria. But we can enhance its function by introducing genes, by changing genes that are there and design the cells to either produce something or consume something that may be beneficial for a patient.

STEIN: Like chew up phenylalanine - Synlogic has also engineered E. coli to fight other diseases - for example, to get rid of life-threatening levels of ammonia that build up in the bodies of people with cirrhosis of the liver.

KURTZ: This is a living medicine that can respond to its environment.

STEIN: Synlogic's modified microbes are part of a whole new field of medical research that emerged from two of the hottest realms of biomedical science - our microbiomes, the friendly microbes that inhabit our bodies, and synthetic biology, the power to genetically engineer all kinds of life, including bacteria in our guts. Pam Silver is a synthetic biologist at Harvard.

PAM SILVER: It's an exciting new world of being able to use synthetic biology to program microbes to treat diseases, which, I believe, is the future.

STEIN: Scientists hope to genetically modify our microbes to treat a long list of diseases; things like ulcerative colitis and inflammatory bowel disease.

SILVER: Microbes are something that we, as synthetic biologists, see as highly engineerable. We understand how to engineer microbes well, so it seems like the perfect interface between a synthetic biology and health.

STEIN: One company is already testing genetically modified microbes to heal mouth sores from cancer chemotherapy. Another just started trying to treat Type 1 diabetes. For his part, Reeder admits he was a little nervous at first.

REEDER: When you hear about E. coli, you think sickness, like throwing up. So I was a little bit skeptical. I wasn't sure what to think because I was going to be ingesting E. coli.

STEIN: But the more he learned, the more excited Reeder got about trying some of these engineered microbes.

REEDER: I think that's very cool that they found a way to use sort of a natural probiotic that's found in the digestive tract to help the human body, you know?

STEIN: Reeder doesn't know if he ended up getting the genetically modified microbes or placebo, but he thinks he got the microbes.

REEDER: I could immediately feel my cognitive abilities slowing down after drinking the 20 grams of protein. And then I took the drug, and I started feeling a lot better. I obtained more energy, and my cognitive abilities got quicker. It was really cool to feel that. I could tell it was working. It was pretty cool.

STEIN: Now, a lot more research is needed to know whether genetically engineered microbes are safe and might really work. But Synlogic hopes to report results from the cirrhosis and PKU studies later this year. Rob Stein, NPR News. Transcript provided by NPR, Copyright NPR.