In January 2002, doctors at the Mary Crowley Medical Research Center in Dallas began injecting a genetically modified breed of salmonella into three cancer patients with large, inoperable tumors that had failed to respond to radiation or chemotherapy. For reasons still poorly understood, salmonella proliferates inside malignancies, perhaps because cancerous tumors tend to remain beyond the reach of the immune system. This salmonella was special, though. A Yale University team led by microbiologist David Bermudes inserted an E. coli gene into the bacteria. The gene produced an enzyme that activates a highly noxious, tissue-destroying drug. “The beauty is that neither the enzyme nor the drug that it activates does anything toxic except in places where they end up together,” Bermudes explains. In other words, the system is engineered to be harmless outside a tumor but deadly inside it.
The 2002 pilot trial proved a success, in that the bioengineered salmonella delivered its enzyme payload, produced a modest shrinkage in tumor size, and did no harm to the three patients, but the trial was too small to make any claims of a cure. To move into larger, meaningful trials would require following in Hillman’s footsteps through a battery of federal regulatory review boards. That costs money. Even if the researchers received approval to go ahead, they would need to come up with the many millions of dollars needed to usher any potential cancer treatment through large-scale patient trials.
That investment would most likely come from Vion Pharmaceuticals, the Connecticut biotech firm that currently holds Bermudes’s patent on the tumor-busting salmonella. Vion has no plans to tackle the regulatory process in the near future, however, says Ivan King, Vion’s vice president for research and development. “As a small company, we cannot move many things forward at any one time,” he says. What’s needed, he believes, is interest from a larger pharmaceutical company with much deeper pockets—just the kind of company that has yet to show interest in highly experimental bioengineered bacteria.
Meanwhile, some researchers are focusing on unmodified microbes that could benefit the body. These “probiotics” are sold in grocery and health-food stores, yet few of the numerous available products have been rigorously tested. One of the exceptions is Lactobacillus GG, or “Culturelle,” isolated in the 1980s by Sherwood Gorbach and Barry Goldin of Tufts University. Over the past two decades, Gorbach, Goldin and others have published 250 scientific papers on this strain’s disease-fighting effects. Studies suggest that the bug has an immune-calming effect that may ease some food allergies. But its one clear and proven benefit is to reduce a person’s risk of picking up one of the many nasty intestinal bugs that cause food poisoning, traveler’s diarrhea and antibiotic-induced gastroenteritis, which results when antibiotics kill off a person’s normal intestinal bacteria and a disease-causing invader moves in.
In Europe, where probiotics have long been popular, they have also been used to prevent chronic respiratory and ear infections. In the early 1990s, Swedish ear-nose-and-throat specialist Kristian Roos developed a throat spray containing a medley of throat bacteria that dramatically reduced the recurrence of chronic strep infections. A few years later, Roos developed a similar concoction that protected toddlers and preschoolers who were predisposed to ear infections.
Roos’s probiotics demonstrated their worth in small clinical trials. But they also illustrate the challenge of developing a natural probiotic into a medical therapeutic. A small clinical trial may be enough to put a health claim on a nutritional supplement sold over the counter. But Roos wants to see such cures in the hands of doctors, who would judiciously prescribe them to patients. To do that, he must prove that his probiotics work in the same kind of large, multimillion-dollar trials that have stymied Bermudes’s cancer-fighting GMO.
For that kind of money, Roos admits, investors are right to expect an ironclad patent to protect their investment. But that’s difficult to do with bacteria that occur naturally on and in the human body. “Even though we can patent our particular mixture of organisms, it would be easy for someone else to come along and put together something slightly different from the hundreds of protective strains found in people’s throats,” he explains. Without the assurance of some meaningful patent protection on his product, he has been unable to attract financial investors, and his treatments languish in a storage freezer.
Five amazing, clean technologies that will set us free, in this month's energy-focused issue. Also: how to build a better bomb detector, the robotic toys that are raising your children, a human catapult, the world's smallest arcade, and much more.