Researchers aim to engineer cells that they can control
Using bacteria and genes, Boston-area researchers have built living versions of a basic component of digital circuits - in essence, cells that can count.
Bacteria with crude math skills may seem a novelty, but the research was motivated by one of the major concerns about engineered organisms: the fear that they could escape scientists' control, with unknown repercussions. The genetic networks they built could provide a way to keep tabs on - and control of - the reproduction of such cells that might otherwise get out of hand.
"There's growing worry as we engineer these organisms and put them in the body or the environment. What do you do once you have them out there?" said James Collins, an author of the paper and professor of biomedical engineering at Boston University. "Wouldn't it be interesting if you could engineer a circuit that you could program into a microbe such that after some number of cell divisions or days, the organism was programmed with a natural expiration date?"
Scientists and engineers from BU, Harvard Medical School, and MIT - who reported on their work last week in the journal Science - designed two kinds of circuits in the bacteria E. coli. One counted things that happened on a short time scale, over minutes, and another counted events over many hours.
For now, the two simple gene circuits count to two or three, and glow once they have hit their target. When researchers decide on a use for such a counter, the gene network could be built to count much higher, and could count a variety of substances.
Researchers are beginning to think about possible applications that range from environmental sensors to medicine.
If a cell counts pulses of an environmental toxin, for example, it could be programmed to glow a certain color as an alert that pulses of some toxin had been released into the environment.
A medical therapy that involved giving a patient cells could potentially be made safer if the cells were programmed to self-destruct if it divided too many times, as cancer cells do.
An engineered organism used to clean up toxic waste, or that inadvertently spread in the environment, could have a counter linked to a light sensor, causing the cell to kill itself automatically after a set number of days.
"It's extremely important to develop technology that allows us to put small amounts of computation inside of living cells," said Tom Knight, a senior research scientist at MIT who was not involved in the research. "Conventional computers are not able to sense or to change the chemical environment very well at all . . . But living cells are inherently very good at both detecting and influencing the chemical world, and having small amounts of computation allows us to take control over those systems."
In the first circuit the researchers developed, a pulse of sugar triggered production of a protein that was in charge of a second gene. If a second pulse of sugar was added, the chain of events continued, resulting in production of a second protein from the second gene. When the set number had been reached, the cells were designed to produce a final protein that made them glow.
In a second circuit, adding sugar caused an enzyme to snip out a chunk of DNA, flip it around, and prime another gene for the same process. A second pulse of sugar triggered another gene to be snipped out and flipped. When the cell had counted up to a preassigned number, it glowed.
"One of the next challenges is taking some of these model circuits and moving them into real applications," said Christina Smolke, assistant professor of bioengineering at Stanford University not involved in the research.
"I think this represents a very important step and a significant one in building the first example of a complex biological processing system that the field has been talking about for awhile."
Carolyn Y. Johnson can be reached at cjohnson@globe.com. 