A Defense Department project plans to temporarily alter human genes, and shield people from deadly radiation exposure
In the early morning hours of April 26, 1986, the Chernobyl Nuclear Power Plant in Ukraine exploded, releasing a cloud of toxic fumes and radioactive particles. The fire burned for 10 days, as hundreds of plant staff, firefighters, and emergency responders desperately worked, often without proper safety equipment, to quench the blaze.
Of those, 134 people were eventually diagnosed with acute radiation syndrome, the illness that occurs when a person is exposed to a high dose of radiation across the entire body in a short period of time. Though Chernobyl’s total death toll is still disputed, it has been conclusively documented that 28 first responders died in the three months after the accident from radiation exposure.
In the decades since the Chernobyl disaster, treatment for acute radiation syndrome has remained much the same — supportive care designed to help the body withstand the toxicity of radiation — despite billions of dollars of public investment into medical countermeasures. But an ambitious U.S. government project could change that. The Defense Advanced Research Projects Agency (DARPA), which develops cutting-edge technology for the military, is funding a team of researchers to develop a temporary, reversible radiation countermeasure that uses the gene-editing tool CRISPR. Akin to a vaccine, scientists are trying to produce a genetic medicine that is able to ramp up the body’s natural defenses before and after a person is exposed to radiation.
Researchers will use a modified form of CRISPR that can turn genes on and off without changing the DNA code itself.
CRISPR is a technique that enables scientists to cut, edit, or replace DNA, as if making revisions in a word processing document. But DARPA wanted an intervention that could protect against radiation without making permanent changes to a healthy person’s genome. “We can’t take the risk of permanently modifying the DNA,” DARPA program manager Renee Wegrzyn tells OneZero.
Researchers will instead use a modified form of CRISPR that can turn genes on and off without changing the DNA code itself. These fluctuations are known as gene expression. If DNA is the cell’s instruction manual, gene expression is the way those instructions are interpreted and carried out. At the most basic level, our genes carry instructions to make proteins, and gene expression is the process of those instructions being converted into proteins. Gene expression changes with a cell’s environment, which in turn affects when and how many proteins are made. Some of these proteins are beneficial, while others are harmful. By using CRISPR to tell genes to “stop” or “go,” scientists think they can boost the helpful proteins to protect against radiation while keeping the bad ones at bay.
“This is like giving people a molecular coat of armor,” says Fyodor Urnov, a gene editing pioneer and a professor of molecular and cell biology at the University of California, Berkeley, who is leading the DARPA project along with Jonathan Weissman, a professor of cellular and molecular pharmacology at the University of California, San Francisco. Urnov was a sophomore at Moscow State University during the Chernobyl disaster, and like most Soviet citizens at the time, he was deeply affected by it.
DARPA wants Urnov and Weissman’s team to make a pill or injection that soldiers, first responders, and civilians could take before going into an area with dangerously high radiation levels. Ideally, a similar treatment could also be given after exposure, such as in a nuclear disaster or dirty bomb scenario. In the future, a radiation protection therapy could also be useful for astronauts on long-term missions in space, where they’ll be exposed to cosmic rays and high-speed particles that damage DNA.
But while a handful of biotech companies have recently started clinical trials to use CRISPR in the eye or on cells outside the body, making changes directly inside the body — as Urnov and Weissman aim to do — is trickier because the CRISPR machinery has to reach the right cells, and enough of them, to have an effect. The researchers have received an initial $9.5 million in funding and have four years under the DARPA contract to produce an experimental drug that will be ready to test in human clinical trials.