||David J. Brenner
The idea of a terrorist attack with a "dirty bomb" a conventional explosive filled with radioactive material is a chilling scenario for any city. Apart from the initial damage from the explosion, the bomb could cause additional injury and death among those exposed to the radiation and most certainly panic in those who think they've been exposed. Hundreds of thousands of people would demand testing and treatment, but in such a situation, would hospitals be able to quickly determine who needs life-saving treatment and who can be reassured and sent home?
To prepare for a dirty bomb incident, the City of New York Department of Health has been looking for high throughput radiation biodosimeters screening devices that estimate how much radiation a person has received but has so far not found any system that can handle more than a few cases per day.
This problem will be tackled by David J. Brenner, Ph.D., professor of radiation oncology, who is the principal investigator of a new multi-institute consortium that will develop high throughput biodosimetry devices to process tens of thousands of samples per day.
The $25 million, five-year grant from the National Institute of Allergy and Infectious Diseases includes Columbia, the lead institution; Harvard's School of Public Health; Arizona State University's Biodesign Institute; the National Cancer Institute; University of Pittsburgh Medical Center; Translational Genomics Research Institute; Sionex Corporation; Charles University in Prague; and New York's Department of Health and Mental Hygiene.
To imagine the chaos a dirty bomb attack would create, one can look to a 1987 incident in Goiânia, Brazil, a city with about the same population as Manhattan. There, residents searching for scrap metal opened an abandoned canister of radioactive cesium, dispersing radiation. About 130,000 people inundated the city's screening centers; only 20 needed treatment.
"Even though it wasn't a terrorist attack, the Goiânia incident shows what public health or emergency room departments can expect if a dirty bomb went off in Manhattan or a major city," says Dr. Brenner.
To reduce a major bottleneck that might ensue when drawing blood from thousands of people, Dr. Brenner's consortium will develop minimally invasive high throughput biodosimeters that can work with blood from a finger stick, saliva, sweat, or other rapidly attainable samples. A perfect biodosimeter that can measure the complete range of possible doses at any time after exposure is probably impossible, so the consortium will develop three complementary devices.
The first device will use an assay that dates to the 1950s. After radiation exposure, pieces of damaged chromosomes, micronuclei, appear in the nucleus of the exposed cells and can be tested for DNA breaks. Advances in robotics and automated image analysis of cells will increase the capacity of this assay to 30,000 samples a day per machine, based on blood from a fingerstick.
A second approach will be based on the fact that ionizing radiation produces a characteristic "signature" of changes in gene expression. The biodosimetry device will be a small cassette containing a self-contained DNA biochip. Blood from a fingerstick will be injected into the cassette, and a same-day dose estimate will result.
The third project uses the fact that ionizing radiation produces characteristic alterations in the spectrum of metabolites in sweat, urine, or sputum. If successful, this would be the quickest and simplest biodosimeter.
"The three biodosimetry devices each have a different characteristic in terms of product development," says Dr. Brenner. "Each has challenges but we expect to eventually be able to determine the best way to test large numbers of people to reassure the 99 percent who won't need treatment and quickly identify the very small number who will."
Other Columbia researchers are: Eric Hall, Sally Amundson, Charles Geard, Gary Johnson and Gerhard Randers-Pehrson (Center for Radiological Research at P&S); Marianthi Markatou, Stephen Morse and Frederica Perera (Mailman); Lawrence Yao (Department of Mechanical Engineering); James Rothman (Judith P. Sulzberger Columbia Genome Centers, and Department of Physiology and Cellular Biophysics); and John Zimmerman (Department of Biomedical Informatics and SDOS).