A decade-long effort in artificial biology has culminated in the creation of artificial bacteria that cannot survive outside of the environment for which they are designed. If picked up by industry, this advancement could ensure that potentially dangerous artificial bacteria do not get into the environment.
Researchers from Yale and Harvard published papers simultaneously in the journal Nature detailing how each team was able to encode into bacteria a dependence on synthetic amino acids — the building blocks necessary to create proteins — that do not occur in nature. If an artificial bacterium were to escape into the environment, it would starve and die. The papers were published in Nature on Jan. 20.
“One of the longstanding problems [in safety] that really has remained unsolved is a robust solution to biocontainment to artificial environments,” said Farren Isaacs, co-lead author of the Yale paper and professor at the Yale School of Medicine. The recent advance, he added, is an answer to that question.
The researchers used a strain of bacteria whose genetic code they had previously re-written, said Jesse Rinehart, professor at the School of Medicine and co-senior author of the Yale paper. From there, they did genome-wide recoding, so that the new bacteria would be dependent on artificial amino acids to survive, he added.
This research comes after a 10-year period in which Yale and Harvard researchers worked together to modify the entire genomes of E. coli bacteria — the first time scientists have performed genome-wide modifications.
“We had to develop massively parallel genome technologies that would allow us do genome modification across hundred of sites in the genome of E. coli,” Isaacs said.
According to Marc Lajoie, a postdoctoral researcher at Harvard and co-lead author of the Harvard study, the escape and survival rates achieved with this new artificial organism — less than one in 1 trillion — are sufficiently small that one should not expect a single bacteria in a one-liter sample to escape into the environment.
Isaacs explained that since the development of recombination DNA technologies in the 1970s, a scientific advance that allowed industry to created artificially modified organisms, there has been a need for biocontainmentto ensure that the use of those organisms is safe.
Among the challenges the researchers faced was trying to design modifications to the cells that would not kill those cells. Dan Mandell, a postdoctoral researcher at Harvard and co-lead author of the Harvard paper, was primarily responsible for designing proteins that took advantage of artificial amino acids in a way that would be non-lethal, but were necessary to its normal functioning. In order to do this, he had to use both experimental and computational trials to narrow down the list of potential proteins to modify.
The researchers also had to make sure that if a cell were to escape, it would not be able to use any molecules in its environment to replace the functioning of their now deficient proteins, Lajoie said.
“We are always expecting surprises and challenges, but what surprised me was how how quickly we were able to apply these challenges and how quickly they worked,” Rinehart said. “[As] an experienced scientist, things take a lot of work and it usually takes much longer than you’d expect. We were really surprised at how quickly we were able to introduce these ideas and innovations.”
Isaacs said he hoped that artificial organisms will allow for advances in medicine, materials and nanotechnology.
“I think we are at the early stages of the biotech century, similar to the impact of chemistry and then physics had in the 20th century,” he said. “I anticipate that biology and biotechnology will have a similar impact on a societal technological and economic perspective this century.”
Artificial E. coli are used to produce human proteins like insulin and clotting factors.