Genetically encoded memory could track cell division inside the body

By Alexandra Witze

Web edition: May 21, 2012
Print edition: June 30, 2012; Vol.181 #13 (p. 14)

They aren’t yet competition for Intel, but bioengineers have created a one-bit “memory” made of DNA that can record, erase and rewrite data within living cells.

One day, doctors might be able to insert such devices into a cancer patient to tally how many times a cell divides and flag when to shut the cancer down. Or researchers might track exactly what happens inside cells as they age.

The work is a step forward in synthetic biology, a new field in which scientists create tools to control life’s basics from the cell on up.

“We can write and erase DNA in a living cell,” says Jerome Bonnet, a bioengineer at Stanford University. “Now we can bring logic and computation inside a cell itself.”

Bonnet and his colleagues, led by Stanford’s Drew Endy, describe the feat in a paper published online May 21 in the Proceedings of the National Academy of Sciences.

Scientists have long dreamed of putting tiny computers inside the body to monitor and perhaps even control what’s going on. But nobody has yet made a silicon-based computer chip small enough to embark on a fantastic computing voyage inside a cell.

So researchers are turning instead to biological tools, such as enzymes and DNA. Some biologists have devised DNA switches that can be turned on and off within a cell. And in 2009, bioengineers reported making a genetic “counter” that could tally the number of times a particular event, like a cell dividing, took place (SN: 6/20/09, p. 5).

But these previous efforts made systems that could write a piece of information only once. Truly useful digital data storage allows the information to be erased and rewritten over and over again, like burning new information onto a CD with each pass. “What we didn’t have is some kind of logic that also has memory,” says Pakpoom Subsoontorn, a graduate student on the team.

The researchers chose DNA as the stuff of memory and used enzymes called recombinases as the tools to flip it on and off. Those enzymes came from bacteriophages, which are viruses that infect bacteria. These viruses use one enzyme to integrate into the genome of the bacterium they’re infecting.

In the experiment, the enzyme traveled to a particular place on the sequence of DNA that contains genetic information and flipped a small section so that it read backward. Sending a second signal then flipped the sequence back to its original state. The flipped and unflipped versions thus represent the “0” and “1” states of a computer bit, says Bonnet.

Working in the bacterium Escherichia coli, the team also tweaked the DNA so that it would fluoresce in different colors depending on the orientation of the strand in question. By watching the cells’ glow change between red and  green and then back again, the scientists could tell when the DNA strand had been flipped.

So far, Endy’s team has just one bit of memory. Next they hope to scale up to eight bits, or a byte — a goal that could take many more years, Bonnet says. The scientists are also working on speeding up the flips; it currently takes about an hour to invert a DNA segment.

But the team has gotten the flips to hold for more than 100 generations within a living cell, a laboratory first. “This was an important proof of concept that it was doable,” says Bonnet. “Now we want to build a more complex system, something other people can use.”

Though interesting, it’s not yet clear whether DNA-based memory will ever replace silicon-based memory for certain applications, says Roger Brent, a researcher at the Fred Hutchinson Cancer Research Center and director of the Center for Biological Futures in Seattle. “It will need to prove itself in the marketplace of ideas.”