You might call it the smallest movie ever made.
This week, a team of scientists report that they have successfully embedded a short film into the DNA of living bacteria cells.
The mini-movie, really a GIF, is a five-frame animation of a galloping thoroughbred mare named Annie G. The iconic images were taken by the pioneering photographer Eadweard Muybridge in the late 1800s for his photo series titled Human and Animal Locomotion.
“The horse was one of the first examples of a moving image and very recognizable,” said Seth Shipman, a postdoctoral fellow in genetics at Harvard Medical School who led the work. “We liked that about it, but we didn’t spend a ton of time thinking about it. We weren’t sure how the research would go.”
Scientists had already shown that a great deal of information can be encoded and stored in synthesized DNA. For example, Shipman’s boss, George Church, a molecular chemist and engineer at Harvard, once converted an entire book into a strand of genetic code.
“DNA has a lot of properties that are good for archival storage,” Shipman said. “It’s much more stable than silicon memory if you wanted to hold something for thousands of years.”
In the new study, published Wednesday in the journal Nature, Shipman wanted to see if bacterial DNA could be used to record the order in which new information was added to its genome.
“Last year we reported some success encoding a handful of sequences and getting some time information back from it,” he said. “But this time we decided to encode real information rather than arbitrary sequences.”
Coding five frames of a movie seemed like a perfect place to start.
The researchers began the work by breaking each frame of the film into a grid of 36 pixels by 26 pixels. Next they developed a way to code the color of each pixel using the nucleotides A, C, T and G, which are the building blocks of DNA. They also included a code that indicated where in the frame each pixel belonged. They did not encode the order of the frames, however.
“That was important to us,” Shipman said. “We wanted to see if when the bacterial DNA captures the new information, it captures it in order.”
In the end, each frame consisted of 104 DNA sequences that the team inserted into a population of bacteria cells using a process called electroporation. Basically, they zapped the cells with electricity, which caused pores in their membrane to open, allowing the synthesized DNA to pass into them.
Once the DNA pieces were in the cells, the researchers relied on the gene editing system known as CRISPR to grab the free-floating pixel codes and insert them into the bacteria’s genome.
Using this process, Shipman and his colleagues “uploaded” their movie into the bacteria’s DNA one frame each day.
After the entire movie had been inserted into the genome, the authors boiled the cells to extract the DNA and then sequenced the regions where they thought the encoded movie frames would be. After running the extracted sequences through a computer program, the team found they were able to play back their movie with 90% accuracy.
It turns out that the first information introduced to the bacteria DNA is captured downstream, compared with information introduced later, Shipman said.
He added that when the group uploaded the movie backward and then extracted it, they were able to watch the horse run in reverse.
The team also learned that tacking on a whole bunch of nucleotides to a strand of DNA does not appear to hurt a cell.
“If there was a fitness cost, you would imagine the information would be lost over time, but it doesn’t seem to cost the cell anything to have it,” he said.
Encoding a short movie into cellular DNA is a neat trick, but Shipman said the work only represents a stepping stone toward his ultimate goal — building tiny biological recorders that can capture and store what is going on in a cell or in its environment.
For example, Shipman is interested in learning what causes developing brain cells, which all look the same, to mature into one type of neuron or another.
“There are certain places we can’t go that a cell can go,” Shipman said. “The brain is locked away inside the skull, and these changes happen rapidly and all at the same time.”
Eventually he hopes to create a way for individual cells to record the molecular steps that tell them what type of neuron to become. He noted that other researchers in Church’s lab are building sensors that could collect that information.
What this work shows is that the genome would be able to store the details of a cell’s changing chemical environment, as well as a record of the order in which those changes occur.
“Getting back information we already knew is great,” he said. “But we eventually want to get back information we didn’t know.”