The World Health Organization declared that smallpox had been eradicated in 1979, but the possibility that variola, the virus that causes this deadly illness, could surface in the form of a bioweapon engineered in a lab has worried military and public health planners ever since. A weaponized version immune to existing vaccine stockpiles could put billions of people at risk. In the event of an attack, scientists would have precious hours to develop and mass-produce an antidote. Conventional methods, which rely on inactivated viruses bred in animal cell cultures, would take months to scale up — far too long to be an effective response to a surprise attack.
But thanks to the latest science, researchers now have new tools in their arsenal. One of them involves DNA vaccines, in which scientists use bits of genetic material to raise an alarm and flag a pathogen to the human immune system. The process of making them is quick enough that scientists could potentially cook up a vaccine in time to inoculate the troops. Scientists have even developed a “gene gun” to painlessly shoot DNA vaccines into the troops.
This speed is made possible by rapid genetic sequencing technology, which gives scientists a way of analyzing the genetic makeup — DNA or RNA — of a virus for telltale sequences that the human immune system can use to identify it and neutralize it. It’s like pinning a bull’s-eye on the virus.
These sequences usually code for the surface proteins that form a protective shell on viruses; smallpox is known for its particularly robust protein shell. Soldiers would get vaccines with these snippets of genetic material, and after a few days, voila — their immune systems would learn to attack the surface proteins of the new virus.
Top and above: “I asked myself, ‘What kind of stupid enzyme trick can I use on a DNA sample that would copy it?’,” says John Nelson, a molecular biologist working at GE Global Research (second from the right in blue lab coat). Top and above images credit: GE Global Research.
A key step in this scenario remains, however: going from small samples of these sequences to volumes large enough to supply the manufacturing of what could potentially be hundreds of thousands of doses — or even billions, if civilian populations were under threat. At the moment, researchers produce the DNA in bacterial cultures, which takes weeks to months of valuable time. This January, the Department of Defense (DOD) awarded GE’s Global Research Center in Niskayuna, New York, a $4.7 million grant to help demonstrate a quicker method.
In particular, the DOD is interested in GE’s expertise in “amplifying” DNA — increasing the amount of DNA in a sample synthetically so that scientists can run a multitude of tests on that one sample. John Nelson, a GE molecular biologist working at the labs, developed a key technique for DNA amplification back in the late 1990s. At the time, he and other biologists were working on the Human Genome Project, looking for a way around the cumbersome process of growing cells in a bacterial culture and breaking them open to spill their genetic payload for DNA sequencing. This process required the biologists to isolate the specific bits of DNA they were interested in from the rest of the bacterial guts before they could sequence them.
Nelson’s radical thought was, instead of growing cells for the sake of copying one specific strip of DNA, why not take the process used to copy the DNA inside the cells and take it out into a test tube? “I asked myself, ‘What kind of stupid enzyme trick can I use on a DNA sample that would copy it?’” he said.
After much trial, error and tinkering with enzymes, one day Nelson finally got a yield of DNA so dense that it was no longer a liquid, but more like Silly Putty — his method had produced “so much DNA,” he recalls, “I couldn’t even pipette it.”
For Nelson, it was one of his first professional eureka experiences. “As a scientist,” he says, “you live for these moments.”
Nelson got a patent for this genetic “printing press” technique — so called because using it to copy DNA is nearly as easy and prolific as hitting control-P on the computer keyboard. He’s since seen it used in a myriad of projects within GE and with GE customers.
In the DOD project, GE will help show that rapidly manufacturing vast quantities of DNA for a protective vaccine is feasible. His team will measure the quality of the DNA produced by GE’s printing press method against DNA made the old-fashioned way, over many weeks, using conventional means to purify the DNA from bacteria. “The purpose of the grant is to demonstrate to the DOD that my synthetic DNA is just as good as, or better than, theirs,” Nelson says. “But also that I can make it in a day.”