The period from 1950 to 1960 was called “the golden age of antibiotic discovery”, as half the antibiotics we use today were discovered during that time. The researchers found the new drugs by testing the soil for microorganisms that produced compounds deadly to other pathogens. But that well essentially ran dry in the late 1960s, and bacteria acquired mutations that made them resistant to once-effective antibiotics.
Enter the iChip, a device developed by Northeastern's Slava Epstein that could help us return to those glory days.
On Tuesday night, Epstein, Distinguished Professor of Biology, will give a talk after the screening of the short documentary The History of Resistance about his contribution to the search for beneficial microorganisms in places as close to home as his own backyard and, perhaps one day, as far away as the planet Mars. The film traces the development of antibiotics from the discovery of penicillin in 1928 to Epstein's current research with the iChip.
The iChip allows researchers to tap untold numbers of microorganisms that won't grow under artificial laboratory conditions. For example, 99 percent of soil-based microorganisms will not grow there. The iChip isolates and grows individual microorganisms in their natural habitat, each in its own little chamber.
“The applications for the iChip are growing,” says Epstein. “One version works best on land, another in aquatic environments, a third in the human body, and a fourth in hostile or abrasive environments.” He serves as a consultant on current iChip projects that include searching in China for new microorganisms in mangroves to harness new metabolites and in Chile for microorganisms that can produce compounds to help plants survive drought.
The original iChip, above, isolates and grows individual microorganisms in their native soil, each in its own little chamber. Photo courtesy of Slava Epstein
“Slava is an unmade thinker,” he says Kenneth W. Henderson, dean of the College of Sciences, who will host the event. “The development of the iChip has transformed our ability to grow previously uncultivable microbes. Breaking this bottleneck has the potential to save countless lives through the development of antibiotics and other pharmaceuticals.”
In 2003 Epstein et Kim Lewis, University Distinguished Professor of Biology, co-founded the Cambridge, Mass.-based biotech company Novobiotic Pharmaceuticals to accelerate antibiotic discovery using the iChip. In 2015, they and their colleagues discovered teixobactin, a new antibiotic that kills pathogens without dealing with resistance. Two additional lead compounds are now in the pipeline: a promising cancer agent called Novo10 and one that targets Mycobacterium tuberculosiswhich causes tuberculosis.
“Worlds Without Imagination”
For Epstein, the iChip is just the beginning. It recently received a grant from the National Science Foundation to develop the first stage of an extensive technology platform called Gulliver, which would find, sort, grow and analyze autonomous microbial species living everywhere from the ocean floor to, perhaps one day, Mars. and distant moons.
“All existing technologies that cultivate microorganisms share one element—they require a microbiologist,” says Epstein. “One has to take the sample—whether from the gut, or from the soil, or from a marine environment—extract the cells and then grow and manipulate them to learn about the properties of the organism. With Gulliver, no microbiologist is required. All these steps happen on site, in the microorganism's natural environment, providing a real result.”
The development of the iChip … has the potential to save countless lives through the development of antibiotics and other pharmaceuticals.
Kenneth W. Henderson
Dean, College of Science
Gulliver will be a simple box with wall decals. Nanometer-sized pores will decorate the walls. A hole, the “entry pore,” will be larger, with a diameter close to the size of a bacterium, about a micron. A researcher will drop the box at the desired location, say under the sea. The microorganism will travel through the entry pore into the membrane, blocking the entry pore as it simultaneously begins to divide and multiply, forming a chain of progeny that soon fills the box. Natural nutrients and growth factors will diffuse from the environment into the box, making the conditions inside the same as outside.
Epstein expects to complete a prototype of the box by the end of 2017. Further work on the project will include building nanosensors into the walls of the box that can measure parameters of microbial growth. Epstein and his team eventually hope to drop about 1 million boxes, all connected together by microfluidic tunnels with valves, to the ocean floor. Each box will contain substances that will be tested against micro-organisms. The sensors will be relayed to Epstein's iPhone, whose boxes show microbial growth.
But that's not all, says Epstein. Let's imagine, for example, that 100,000 of these boxes have microbial growth and you want to know which of the microorganisms can convert cellulose into biofuel. “Using my iPhone, I open the valves and release cellulose into those 100,000 boxes,” says Epstein. “If the microorganism in one of those 100,000 can break down cellulose into, say, ethanol, the ethanol sensor will transmit that information to me.”
In Jonathan Swift's book, Gulliver, you will remember, travels to Lilliput, Brobdinnag and beyond. Why give his name to the technology platform? “It will travel to worlds unimaginable,” says Epstein.
The screening of his film The History of Resistance and Slava Epstein's talk will take place on Tuesday at 6 p.m. at the Interdisciplinary Science and Engineering Complex Auditorium, 805 Columbus Ave., Boston. A reception follows.
