By Duke Medicine News and Communications

DURHAM, N.C. -- The real threat of nuclear and radiation-based "dirty-bomb" terrorist attacks has prompted the National Institute of Allergy and Infectious Diseases (NIAID) to fund a $22.25 million radiologic anti-terrorism center at Duke University Medical Center. The center's immediate tasks are creating a rapid and inexpensive screening test to gauge a person's exposure level and developing new drugs that treat radiation's most toxic effects.

"Significant nuclear material is missing around the world, and these materials could possibly enter the black market where they would be acquired by terrorists," said Nelson Chao, M.D., director of the Duke Adult Bone Marrow Transplant Program. Chao will direct the multi-institution Center for Medical Countermeasures Against Radiation, together with Mark Dewhirst, M.D., and John Chute, M.D. It is one of eight such centers being established nationwide.

"Unfortunately, very few medical products exist to counter the variety of acute and long-term toxicities that can result from nuclear or radiologic attacks, so we must develop a range of different products and medical approaches to protect and treat such a population."

Already underway are experiments to bolster the natural abilities using human growth factor and hematopoietic (blood) stem cells to rescue bone marrow after radiation damage. Bone marrow is the first organ most severely affected by radiation exposure –- it is the factory for blood and immune cells -- so mitigating radiation's effects is essential to preventing bone marrow failure and other life-threatening complications, said Chao.

The Duke team will collaborate with more than a dozen academic medical centers, pharmaceutical companies and federal research laboratories to develop drugs and therapies that reduce radiation injury and to study ways to enhance bone marrow and blood cell proliferation. The discoveries they yield will ultimately play a role in the treatment of patients undergoing stem cell transplants, therapeutic radiation for cancer, and immune recovery among patients with faulty immune systems, he said.

Equally pressing is the need for a quick and simple method to distinguish severely injured patients from the worried individuals following a radiologic attack, said Chao. In the event of a radiation exposure, the immediate surge of patients seeking medical evaluation could easily overwhelm local medical facilities and thereby delay treatment of the sickest patients.

Chao cited the Cesium 137 exposure in Goiania, Brazil, as an example of how quickly a situation can escalate into panic. Approximately 200 people were exposed to the radioactive material, but over 100,000 people turned out to be screened for possible injuries. The ability to properly triage patients with medical needs while simultaneously allaying fears among the population at large is of critical importance for those in the vicinity of an event, he said.

Yet screening patients for radiation exposure currently requires repeated blood collections over a period of several days. By then, severe damage to the blood-and immune systems, as well as the lungs and gastrointestinal tract -– the most sensitive organs -- may have already occurred.

The latest technology being pursued as a rapid test is a laser that measures changes in the luminescence of tooth enamel which follows exposure to gamma radiation. Secondarily, the team is developing a blood test that will pinpoint specific gene changes that accompany varying levels of radiation exposure.

Developing tests that indicate the radiation dose a particular individual received is essential for properly treating exposed patients, said Chao. Injuries could range from obvious burns and external tissue damage to less apparent bone marrow failure accompanied by bleeding, infections and a heightened lifetime risk of cancer.

Bone marrow and stem cell transplants can reconstitute damaged blood and immune systems, yet they require months of treatment and highly specialized medical expertise that isn't widely available, said Chao. Developing quicker and less invasive methods of treating radiation damage will equip community hospitals with the tools necessary to manage large scale radiation exposure within their local population, said Chao.

To make such treatments more widely available, the scientists will analyze and test drugs which are already FDA approved for human use related to other diseases. Novel compounds will later be developed and tested if currently existing drugs fail to demonstrate effectiveness in treating radiation damage.

On the screening front, geneticists will develop genetic "signatures" that depict how specific genes are altered by varying doses of radiation. Scientists will administer high, intermediate and low doses of radiation to mice and to people undergoing cancer treatments. The scientists will analyze blood samples from radiation-exposed individuals to determine the impact of each dose on specific genes.

In other studies, the team will develop and test therapies that: prevent lung damage caused by reactive oxygen species –- damaging byproducts of radiation exposure -- using synthetic compounds already in use for other diseases and to assess the role of innate immune responses in inflammation and radiation-induced lung injury;

• test the capacity of human growth hormone (HGH), already in human use, to accelerate recovery of blood- and immune cells following radiation injury;

• cultivate and expand the population of hematopoietic stem cells by culturing them together with primary endothelial cells, which secrete growth factors essential to stem cell growth;

• stimulate proliferation of human hematopoietic stem cells and enhance the repair of endogenous (native) stem cells by stimulating a key regulatory pathway for blood stem cell formation called the Wnt pathway;

• Assess the efficacy of somatostatin and its analogues in the prevention of gastrointestinal toxicity and contribution of gastrointestinal microbes in radiation induced injury.

For a complete list of centers participating in the project, go to: http://radccore.mc.duke.edu