GAINESVILLE — These fighters wear lab coats, not fatigues, but they help defend the United States against bioterrorism. Several Gainesville area biotechnology companies and 35 University of Florida research programs are working on anti-bioterrorism initiatives. They range from developing smallpox and other vaccines to designing robots that spot chemical agents.

 

Many began their research before 9/11, intensifying their efforts as the potential for war with Iraq grew. Their work recently got a boost from President Bush's Project Bioshield, a $6 billion initiative to quickly develop and stockpile vaccines and treatments against bio-threats.

 

It typically takes scientists three years to turn an idea into an invention, and a few more years to hit the marketplace, said David Day, director of UF's Office of Technology Transfer. However increasing talk of war leaves little time for red tape and commercialization speed bumps. "The government is going to get all sorts of expedited approval processes."

 

 

Two years ago this week, Dr. Jeffrey Hillman and UF professors Martin Handfield and Ann Perogulske-Fox founded Ivigene in Gainesville. They use Vivo Induced Antigen Technology (IVIAT), which identifies bacterial genes that switch on when a disease infects a person.

 

"For the past 100 years or so, we've been studying bacteria as it grows in the laboratory," Hillman said. But a petrie dish is a far cry from a body and it's tough to fool bacteria. "Bacterium are actually very bright. They recognize their environment and when a bacteria is grown in a laboratory, it knows that it doesn't need certain genes to be turned on in order to grow and survive. So it shuts those genes off."

 

Those turned-off genes are the ones scientists want to study. Over the past decade, the top solution was to use animals such as mice. But that presented another problem.

 

"It turned out that mice aren't exactly the same as humans except in certain elements," he said. Plus, certain diseases, such as anthrax, are difficult to handle in a lab.

 

The IVIAT solution involves studying blood from patients who recently suffered various diseases. The blood contains antibodies that a human body generates to defend itself. Scientists can eliminate antibodies that react with proteins the diseased bacteria typically makes when growing in a lab.

 

"What's left," he said, "are antibodies that react with proteins that are made by the pathogen only when it's growing in the human host."

 

Hillman uses those antibodies to probe the bacteria, identifying the gene that gets turned on when the disease infects humans. That gene is what he sells to companies that make vaccines and antibiotics. Hillman focuses on diseases Atlanta's Centers for Disease Control and Prevention targets as bioterror threats. Ivigene can use the same technology to identify gene targets in other bacterial infections, such as tuberculosis and gum disease.

 

One benefit is IVIAT's speed, Hillman said. While other approaches can take years, "We can find all of the targets for an organism in a matter of months. Four, five, six months tops, we can be done with it and have our targets ready for delivery to prospective buyers."

 

Ivigene recently landed licensing deals with Israel's XTL Biopharmaceuticals, with which it's collaborating to develop a gene target for the bacteria that causes pneumonia; and with Miami's Gene Ex, which will develop targets for diagnosing tuberculosis. Thus far, Hillman conducted his research on spec, but Ivigene submitted grant requests for $500,000 from the National Institute of Health and the National Institute of Infectious Diseases to underwrite the cost of further research. The company expects an answer by April.

 

"Of course," Hillman said, "the president is welcome to send me that $6 billion."

 

 

Nanotherapeutics in Alachua is working with Lake Forest, Ill.-based DOR BioPharma (AMEX: DOR), which is developing an inhalant vaccine for anthrax and an oral vaccine for ricin, the second-deadliest poison with no antidote.

Nanotherapeutics focuses on drug delivery systems using nanoparticles and microparticles. When a tiny particle of an organism such as tuberculosis is introduced, "the body thinks it looks like some kind of pathogen floating through the immune system," said Steve Kanzer DOR's vice chairman, who has a South Florida office. The body then launches immune responses. "That's the key to the technology."

 

"Just because you have the bacteria or the protein doesn't mean you can get it into the body and make it work," said Nanotherapeutics co-founder Jim Talton, noting renewed attention on such diseases as smallpox — thought to be a thing of the past until recently. "Those are bacteria or viruses that the world knows how to deal with, but obviously isn't actively looking at or hasn't been over the past couple of decades."

 

To bring vaccines for these and other diseases into the 21st century, scientists increasingly are researching and developing inhalant versions because most available defenses against diseases used in bioterrorism are delivered by injection.

 

"The government realizes the logistical difficulties of immunizing our population in any type of meaningful timeframe … if we have to line everybody up with a doctor who's available and give them a shot," Kanzer said.

 

Inhalant vaccines may prove particularly critical by building defenses in patients' mucosal immune systems, which involve mucous linings in the nose, lungs and intestines.

 

"Most of the threats out there are coming in the form of aerosolized or airborne pathogens," Kanzer said. The mucosal system is the body's first line of defense against most diseases, secreting natural antibodies to create protection. Inhalant vaccines stimulate immunity better than oral or injected versions.

 

Like IVIAT, Nanotherapeutics' and DOR's technologies promise quick turnarounds on products. Federal legislation passed last year minimized phase three clinical trial requirements, which involve human testing and make up the bulk of costs associated with bringing a product to commercialization. Those trials likely would cost DOR $200,000. Once it shows a product's safety in a limited number of humans, it can develop a drug for "well under $50 million," Kanzer said. "Then it's a question of, 'How many doses do you want to buy?'"

 

Bush's initial order calls for 250 million doses of smallpox vaccine, 25 million doses for anthrax. The going rate — $20 a dose. With funding, Kanzer said, DOR can have an approved ricin vaccine on the market within a year. Gen. Alexander Haig, who joined the company's board of directors last month, helps the cause. He served as former President Reagan's secretary of state and as secretary of defense under Presidents Nixon and Ford.

 

Having Haig on board "assists us with working through the government system, which is not very well defined in the areas of biodefense," Kanzer said, noting the Department of Homeland Security is barely under way. "It helps us with cutting through the bureaucracy so we can deliver a product to the population."

 

Inhalant and oral vaccines and drugs also could save the medical industry and patients millions when it comes to intravenous delivery, Talton said. Today, a patient may stay in a hospital for days receiving drugs through IVs.

 

"Sending them home so they could take [the medication] in a capsule is a major advantage in outpatient therapy," Talton said. "It's a major cost saving for the economy as well as less invasive to the patient."

 

Like Ivigene, the technology can be applied to treatments for more common diseases. Nanotherapeutics and DOR BioPharma have pending grants for oral vaccines for influenza and tuberculosis.

 

"We'll be in position to be the delivery vehicle for the vaccines of the 21st century," Kanzer said. "That's multibillions of dollars. It's a great boost in the arm for the vaccine business."

 

 

UF researchers logged thousands of hours of bioterror research since well before 9/11. But few knew until Ian Phillips, then UF's associate vice president for research and graduate programs, created an online network for sharing information.

 

 

"After 9/11, I realized we needed to be aware of research going on that would be anti-bioterrorism," said Phillips, who recently left UF for the vice president post at Tampa's University of South Florida. After launching rgp.ufl.edu/fyi/pub/registry.html, he was surprised to find 35 research projects well underway.

 

"The people are in all different places and didn't know about each other," Phillips said. They do now. "Groups have started to get together, collaborating not only within the university, but with others, including the University of South Florida, Duke and Emory."

 

Research projects fall into four categories: detection, diagnosis, detoxification and dissemination. Subjects include safeguarding food supplies from deliberate contamination, destroying anthrax stockpiles, and designing a uniform electronic data program for disseminating information about mass casualty and battlefield situations as well as disease epidemics to health care providers nationwide.

 

UF's machine intelligence lab is researching using autonomous robots to detect presence of certain biological agents and operate in contaminated areas. "We build hundreds of different kinds of robots," Assistant Director Eric Schwartz said. "Flying, crawling, walking." A robot equipped with a chemical sensor could survey an area by land, air or water, sniffing for harmful chemical agents. Actual development needs funding, Schwartz said.

 

Phillips' work involves creating an anthrax toxin inhibitor.

 

"The anthrax bacteria are normally treated with an antibiotic which kills the bacteria," he said. "But if the bacteria releases a toxin, then the result is fatal."

Many of UF's bioterrorism research projects originated with different goals. Researchers tailored existing data and techniques to the bioterror initiative. Phillips' anthrax toxin research began as a cardiovascular disease protection project and might well be applied to cancer.

 

"The great thing about scientists is they have techniques that can be applied to different problems," he said. "It's always impressed me that every time there's a national emergency, if you go to a university, there's always somebody working on some obscure subject that becomes useful."