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Biological Defenses On the Horizon

By Linda D. Kozaryn
American Forces Press Service

WASHINGTON, Feb. 9, 2000, Feb. 9, 2000 – What if your red blood cells could be armed to fight off disease? What if one vaccine could protect you from a host of biological agents? What if you could purify a canteen of water in minutes?

Michael J. Goldblatt says there are no limits to what one can imagine. He should know. As deputy director of the Defense Sciences Office at the Defense Advanced Research Projects Agency, it's his job to encourage people to go beyond what is, to discover what could be.

According to Goldblatt, the Defense Department is leading the field in developing defenses against biological agents. DARPA, specifically, is on the forefront of technological advances that may ultimately save countless lives.

"This is the Defense Department at its best," he said during a recent interview with American Forces Press Service. "We are opening up whole new opportunities that didn't exist before. This is not developing a single vaccine. This is creating new opportunities in biology upon which to develop completely new therapies."

DARPA launched the Biological Warfare Defense Program in 1996. Its goal is to develop technologies to thwart the use of biological warfare agents, including bacterial, viral, bioengineered organisms and toxins, by military opponents and terrorists.

A tremendous mismatch exists between the magnitude of the threat and our ability to defend against biological warfare, according to DARPA officials. Advances in biotechnology now make it possible for adversaries to engineer "super-pathogens" -- disease-causing bacterium, virus or other micro-organisms -- designed to be more deadly and more resistant to antibiotics.

DARPA's efforts are focused on developing broad-spectrum approaches that can be used to defend against current and future threats. "Ultimately," Goldblatt said, "this program is designed to develop a range of protections which are so easy to use and so efficient as to deter anybody from thinking that there's anything to be gained by using these kinds of agents on the battlefield.

"We're making rapid progress, but there's a long way to go from taking some of this stuff from the laboratory to human use," he continued. "The standards required for human use are very rigorous and the FDA and DoD have a lot of provisions to make sure that anything which goes into the body is absolutely safe and efficacious."

Under the DARPA program, DoD provides funds for universities and other organizations to do research and develop new products. "DARPA is a vehicle to select the most imaginative proposals for research from the academic and industrial communities," Goldblatt said. "We will take the high-risk opportunities because they have such big potential payoffs if successful.

"We try to nurture the long-term vision of 'what-ifs,' he stressed. "Who would have imagined you could develop an airplane that could evade radar? Who would have imagined that you'd have an Internet? Both those things came out of imagining what is possible in the future instead of saying, 'how can I improve what exists today?'"

DARPA provides the financial backing for projects that have the opportunity to revolutionize the technical environment, he said. Those projects, he said, capable of causing "the big paradigm shifts where people used to believe one thing and now they've discovered something else is possible."

The DARPA program aims to find better ways to detect and identify biological agents, protect against them and destroy them before they enter the body. In the area of personal protection, DARPA is working to develop gas mask filters that are easier to breathe through than existing filters. "We're trying to develop new technologies to capture both chemical agents and biological agents and yet have an almost unrestricted breathing pattern," Goldblatt said.

The Marine Corps is now field-testing a device that creates safe drinking water from any water source they pick up in the field. The device is about the size of a large fountain pen or mini flashlight and works with just a lithium battery, a common salt tablet and a teaspoon of water. Through some high-tech magic, the water becomes an agent that can purify a canteenful of water.

"This is good for about 140 uses, and then all you have to do is change the tiny battery and put in a new salt tablet," Goldblatt said. "What is most interesting about this is that it not only kills all the normal things chlorine tablets can, but also things that are chlorine resistant."

Researchers are also working on a reverse-osmosis device that makes sea water potable. Water is a big problem everywhere, Goldblatt noted, because disease and nonbattle injuries often incapacitate more people than ballistic injuries.

Since many agents cause nonspecific, flu-like symptoms, DARPA officials are seeking ways to ensure early diagnosis and effective treatment. Officials are working to identify people exposed to a biological agent before they become sick.

"You don't normally get sick instantly," Goldblatt said. "Some people get sick much quicker than others. Still others might not get sick for a long period of time."

Determining who was sufficiently exposed to become sick is another concern. The terrorist Sarin gas attack in Tokyo's subway is a good example of this problem, he said. Some people died. Some were ill. About 20,000 people reported to hospitals because they feared they'd been exposed.

"Yet, very few of those were ever actually seriously exposed or exposed at all, but people have an understandable desire for preventive treatment, which is appropriate. The question in any case of mass exposure is who has been exposed and who has not," he said.

People are sick long before clinical symptoms crop up -- a fever, muscle cramps, whatever, he noted. "So," he asked, "can you build detectors sensitive enough to determine who is coming down with an illness before they actually get sick?"

DARPA officials are looking at a nitric oxide detector similar to Breathalyzer devices that measure alcohol levels in a person's breath. "People who are infected have much higher levels of nitric oxide than people who are not, and that's true long before they show any other symptoms," Goldblatt said.

The next step is the real challenge, he said, and the one DARPA thinks is a very real opportunity: to diagnose and inhibit an illness early enough to prevent its physical symptoms from developing.

DARPA officials are working to develop additional medical countermeasures. An effort is under way, for example, to enhance the body's natural defenses. Researchers are just now beginning to discover how to manipulate and accelerate the body's natural immune system, Goldblatt said.

"We can make vaccines much more efficient by getting the body to respond in ways it hasn't been able to before," he explained. "For instance, specific kinds of cells in the body take up a vaccine and convert it into an immune response. We're learning how to get these cells to come to the point of injection. Therefore, you could create a more potent vaccine with just a fraction of the dose you previously used."

In another area, officials are seeking ways to combat a plethora of agents rather than tackling each individually.

"The body basically has only a couple ways it can respond. We're trying to see what common mechanisms all these agents induce," Goldblatt said. "By finding the common mechanisms of those responses, we feel we can achieve broad success.

One of the reasons the program has become so popular in the biotechnology and the pharmaceutical communities, Goldblatt said, is that by elucidating these common responses, DARPA also sheds light on a wide range of more common problems -- everything from toxic shock syndrome to food poisoning.

"All these illnesses ultimately cause the same kind of physiological reaction. If you can identify a common factor, then you can identify common solutions," he said.

Already, Goldblatt noted, the program has paid dividends. "The last time a new class of antibiotics was actually discovered was in 1976," he said. "This program has identified some real opportunities for whole new families of antibiotics."

Biological organisms' resistance to antibiotics is becoming a problem worldwide, he said. Tuberculosis, for example, is resurging globally because the germs are becoming resistant to traditional antibiotics.

"There is less risk for most pharmaceutical companies in trying to find variations of existing drugs than in trying to identify a fundamental biological mechanism that would allow the creation of a whole new class of antibiotics," he said.

"The problem is too daunting. Frankly, it's very difficult for large organizations to take on those kinds of challenges," he said. "Small entrepreneurial groups, people with a passion, a tolerance for high-risk, and a commitment to solve a problem, can be much more effective and much more efficient than whole cascades of large organizations."

DoD is investing in "a tremendous amount of novel opportunities to develop new drugs to combat specific threats," Goldblatt said. "It's very hard sometimes to get the commercial sector to invest the tens of millions, sometimes hundreds of millions of dollars, necessary to take a product through approval process and years of research when the target market may be small," Goldblatt said.

Civilian society will benefit from the military-sponsored efforts as well. "As more and more people in the medical community find out about the program, they're just absolutely dumbfounded," he said. "This is very exciting stuff. It opens up possibilities that didn't exist five years ago."

Pharmaceutical companies are starting to take notice, he said. "People are seeing the potential for this program to have much wider application, and therefore, are vying to have the opportunity to extend this for a whole host of other kinds of normal, everyday, civilian applications."

Overall, Goldblatt concluded, DARPA is interested in new ideas. "We use the research communities' imagination to dream up solutions to help individual war fighters," he said. "We also spend a lot of time talking to service members about their needs. They're our customers."

Goldblatt said he'd be happy to receive service members' suggestions via e-mail: mgoldblatt@darpa.mil.

For more information on DARPA programs their Internet web site at www.darpa.mil.

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