On a warm spring morning, a teenager named Rachel awakes and gets ready for school. She brushes her teeth, DM’s her best friend about yesterday’s geometry assignment, and quickly swallows two little pills with a glass of water. Although the sixteen-year-old was diagnosed with type 1 diabetes as a young child, today she sits down to a quick breakfast of toast and strawberry jam with orange juice. No blood glucose tests, no counting carbs, no insulin shots or pumps. Rachel goes about her day as if she did not have diabetes, and to all intents and purposes she doesn’t—not as long as she takes the two capsules of probiotics, which have been engineered to release a protein that transforms stem cells in her small intestine into cells capable of secreting insulin.
Sound like something from a Hollywood sci-fi movie? While this scenario is still in the future, John C. March, Biological and Environmental Engineering, doesn’t expect it to stay that way. He is busy bringing it into reality through his research, which focuses on the interaction between microorganisms in the intestinal tract and the cells that line the intestine. In the lab, he and his team have modified common probiotic bacteria into the futuristic diabetes-treating bacteria of Rachel’s story. “They only work on a small number of cells,” says March, “but it’s enough to restore normal levels of blood sugar in diabetic animals tested so far.”
A Futuristic Pill Trumps the Diabetic Shot
The results are extremely promising. For those with type 1 childhood diabetes and late-stage type 2, both of which require insulin injections, March’s findings have the potential to be life transforming. “One of the problems with diabetes is that insulin injection is an imperfect art,” March explains. “It’s hard to get it right, and even though they have some fantastic pumps these days that monitor and deliver insulin, the advantage of our bacteria is that there’s no pump or needle. You would just take the pills each morning, and then your own cells would make the insulin.”
The Language of Cholera
As miraculous as this sounds for the treatment of diabetes, it is just one of the biomedical projects March is currently working on. Another project focuses on designing a harmless bacteria that can communicate with the bacteria that cause cholera. When someone is infected with cholera bacteria, the organisms go straight to the person’s small intestine and colonize it, causing ionic imbalance which results in life-threatening diarrhea and dehydration. While cholera can be treated in modern times with oral rehydration therapy, it is still a massive killer in the developing world, especially of children.
Researchers now know that cholera bacteria communicate with each other using quorum sensing, a type of extra-cellular signal they send to each other. “Originally it was thought that each bacterium was out for itself, trying to divide and thrive,” March says, “but actually, once cholera bacteria reach a certain density, they start to coordinate their behavior through quorum signals, doing things as if they were a multi-cellular organism. That’s how they potentially anticipate that the host is dying and they must detach from the intestinal wall so they can all leave the body with the diarrhea to colonize another host.”
March’s approach would hijack or interfere with that communication by engineering bacteria that would mimic the cholera bacteria’s quorum signal. “When a cholera bacterium entered the intestines, our bacteria would already be there,” he says, “sending the signal that the intestines are already colonized and it is time to leave. So the cholera bacterium would just keep going because it thinks the host is already dying.” As with diabetes, the prevention for cholera could one day be as simple as taking a couple of pills.
Monitoring the Intestinal Environment for Immunity Signals
These therapies are just the tip of what March hopes to achieve with his research into the human intestinal environment and its function as a window on the immune system. He is also working on engineering bacteria that can monitor conditions in the intestine as a way to flag the onset of a disease and perhaps even to treat it automatically. “If you get sick, whatever the illness, your intestinal chemistry changes,” March says. Scientists are still learning how various illnesses specifically change intestinal chemistry, but once that is known, March envisions a situation in which modified bacteria can police our intestinal health. “You can imagine the benefits if we can engineer bacteria that monitor for specific molecules in the gut,” he says, “and when those molecules are in certain patterns, then the bacteria respond, maybe even releasing a therapeutic into the person’s bloodstream.”
Licensing a Technology
March anticipates that his engineered bacteria, if successfully developed and approved by the FDA and other agencies, could revolutionize the treatment of diabetes.
In 2011, a biopharmaceutical company called BioPancreate Inc., was formed after it exclusively licensed March’s novel diabetes technology from Cornell. March continues to collaborate with BioPancreate, which is a wholly owned subsidiary of Cortendo AB, and serves as Chief Scientific Adviser to the company. In 2012, BioPancreate and March obtained a Small Business Technology Transfer Program grant from the National Institutes of Health to continue the proof-of-concept work in animal models. The probiotic that modifies stem cells into pancreatic-like cells for the treatment of diabetes, in particular, has shown positive replicable outcomes in animal models, so the plan is to conduct the additional required tests and then seek FDA authorization to test the engineered bacteria in humans.
March anticipates that his engineered bacteria, if successfully developed and approved by the FDA and other agencies, could revolutionize the treatment of diabetes, but he’s not dwelling on it. He’s already formulating ideas for many more research projects investigating the mysterious world of the small intestine and the organisms that live there. It’s complex work. “You’re trying to do things no one has ever done,” he says, “so you have to keep changing how you come at it and keep trying different approaches. There are some frustrating moments.” He smiles and shrugs: “But that’s what everyone says. It’s just the nature of scientific research.”