"Doing something useful always feels good." In the aftermath of 9/11, Adrian Ponce's basic research into spore chemistry opened the way to the development of a novel technology for detecting anthrax.

Sounding the Alarm for Anthrax
By Michael Rogers

Over the past couple of years, Adrian Ponce, PhD ’00, has been fascinated by the chemistry of spores: primitive life forms whose molecules are so robust that they can lie dormant for hundreds of thousands of years in extreme environments only to spring back to an active life when conditions improve. But he admits that even his mother didn’t show much interest in his work until October 2001, when the anthrax attacks left five people dead.

In the months since those incidents introduced the American public to bioterrorism, Ponce has used his knowledge of chemistry to develop the prototype of a device that can detect airborne bacterial spores, including anthrax spores. Caltech has already patented the device, a company has licensed the technology so that it can manufacture anthrax detectors, and Ponce, who shares a tiny office in a nondescript building at JPL, has suddenly found a new purpose to his work.

“This research poses some interesting scientific questions to be answered,” says Ponce, who is also a visiting associate in chemistry at the Institute. “But doing something useful always feels good, and I’ll feel like I’ve contributed something useful once it prevents someone from getting sick.”

Ponce’s introduction to chemical sensors began when he was an undergraduate at Michigan State University in the early 1990s. He was working for Daniel Nocera, PhD ’84, then a professor of chemistry at Michigan State and now the W. M. Keck Professor of Energy at MIT. Nocera focuses on the basic mechanisms of energy conversion in biology and chemistry. Ponce helped Nocera develop supramolecular detection schemes for finding long-chain hydrocarbons and other pollutants that might be located at Superfund sites.

At Caltech, Nocera had been a graduate student in a research group led by Harry Gray, Caltech’s Beckman Professor of Chemistry. After Ponce graduated from Michigan State in 1993, he followed Nocera’s example and went to the Institute to join Gray’s group.

As a graduate student, Ponce focused on electron transfer in proteins. The year he got his doctorate, he was hired for a postdoctoral position in chemistry at JPL and a year later he became a senior member of JPL’s technical staff.

JPL hired Ponce to study how to use vibrational spectroscopy to detect life on Mars. While thinking about biology on the Red Planet, Ponce crossed paths with spores. If you’re going to find extraterrestrial life, he figured, it might well be in the form of spores, since they’re robust enough to survive under a variety of extreme conditions. And if you’re looking for bacterial spores, it helps to know that within the cores of bacterial spores are high concentrations of a molecule called dipicolinic acid, or DPA.

For all known life forms, DPA is unique to bacterial spores and is not found in mold or fungal spores, so its presence can be used to sound an alarm for bacterial spores. When the spores are exposed to microwave radiation, they release DPA, causing a chemical reaction that triggers intense green luminescence when viewed under ultraviolet light.

Ponce was busy investigating the chemistry and detection of spores for space applications when the first anthrax cases appeared in October 2001. The disease was spread in the form of spores, which became toxic once they were inhaled and began germinating inside victims’ lungs. Ponce immediately realized that the work he was doing for JPL could be applied to build an anthrax-spore detection device.

Ponce says that while methods for detecting anthrax were already in use, they were cumbersome, partly because they required trained technicians to take samples from a site for analysis in a lab—a costly procedure that also delays detection. Furthermore, pollutants could easily contaminate the samples, leading to inaccurate results. Ponce’s own research led him to think in terms of an automated device that he figured he could build. Ideally, it would continuously monitor for bacterial spores in the air, providing a warning system like a smoke alarm.

With a $30,000 grant from NASA and help from a Baylor University undergraduate named Elizabeth Lester, who participated in Caltech’s Minority Undergraduate Research Fellowships (MURF) Program, Ponce set out to build an anthrax detector last summer.

The machine that he and Lester built involves three components: an aerosol capture device to haul in the anthrax spores, a microwave beam to release the DPA from the spores, and a luminescence spectrometer with a fiber-optic probe that detects the DPA. Over three weeks of testing, in which they used harmless Bacillus subtilis spores to simulate anthrax, Ponce and Lester were able to get the device to detect the DPA within 15 minutes of the release of spores.

Ponce talks about two worst-case scenarios in which he predicts that the device will operate effectively. In the first case, a letter containing anthrax is opened, releasing a puff of anthrax powder into the air. Ponce’s device should record the contamination within 15 minutes so that the location can be sealed off immediately and persons in the area sent for treatment. The second case would be one in which a low concentration of anthrax powder slowly spreads through an enclosed area. In this scenario, the device could take up to a few hours to sound the alarm, depending upon spore concentration, but it would still be half the time it would take for exposed people to accumulate a lethal dose (about 10,000 spores). Since anthrax is only lethal if left untreated for several days, there would still be plenty of time to seal the area and treat victims.

Timing is the key to treating anthrax, since it usually takes a few days for symptoms to show up. “If you can take antibiotics before the symptoms show up, it’s a safe bet that you will survive,” says Ponce.

One downside to Ponce’s detector is that it is susceptible to false positives, since a bacterial spore that doesn’t cause anthrax could trigger the alarm. But Ponce maintains that the cost
involved in shutting down a facility for the time it takes first-responders to determine whether or not the detected spores are harmful is a small price to pay compared to the illnesses and deaths that could result from an attack that goes undetected for days.

“Since we’re monitoring changes in spore concentration, I can’t imagine many cases of false positives, other than those that are deliberate hoaxes, and one would want to know about those anyway,” Ponce says. “The fact that this was developed over a summer with an undergraduate demonstrates that this is simple and robust technology.”

Asked to identify the biggest challenge of the project, Ponce says that there really weren’t any, since he had already done the basic research into spore chemistry. He says that it was just a matter of marrying the science to off-the-shelf technology—coupling detection with an aerosol-collecting device. So why hadn’t anyone thought of such a device before? Ponce figures that his chemistry background combined with the related work he was doing at JPL provided the serendipitous spark.

Ponce hopes to have a second, more sensitive prototype ready this August. It will incorporate aerosol-sampling equipment from Universal Detection Technology, the Beverly Hills company that licensed Ponce’s idea and is also funding the second prototype. Jacques Tizabi, the firm’s CEO, says that a commercial anthrax detector could be available sometime later this year. “It will probably cost around $50,000, so the first customers will likely be large commercial operations, such as hotels, convention centers, and airports,” he said. “In a few years, we should be able to get the cost down.”

Although the cost clearly makes it impractical for residential use, Ponce points out that automated monitoring of aerosolized bacterial spores would also be helpful in mail-sorting facilities, office buildings, sports arenas, and other public locations. Besides anthrax, the detector could also monitor for other spore-forming organisms, such as those that cause tetanus, botulism, and gas gangrene, which could prove helpful in food preparation facilities and hospitals.

Not to forget JPL, which initiated Ponce’s anthrax adventure in the first place, the detector also has applications for space research. It could be used to quantify the concentration of bacterial spores in spacecraft assembly facilities, thus avoiding or at least reducing the possibility of contaminating other planets with microbes from Earth. Ponce is also seeking funding for an experiment to build an instrument that would search for spores in the martian polar ice cap or permafrost. For the moment, though, he’s feeling pretty good about the thought that his biodetector could be used to save lives on Earth.

“Like other government agencies, JPL has a responsibility to contribute to the homeland defense,” he says. “It’s nice to work on something that has a strong chance of making a useful contribution to society. In research, there’s always a balance between fundamental work and work that has practical applications. I like to do a little of both, and this allows me to do that.”

 

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