Scientists turn living cells into clocks

Column: This amazing breakthrough rewrites man's ability to play with biology.

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Humans have rejiggered life at the cellular level for quite some time. Designer yeast and bacteria enhance our food and produce such useful products as ethanol and, most recently, artificial vanilla.

But when a joint team from Boston University and the Massachusetts Institute of Technology uses biochemical trickery to give cells computer-like timers, they raise this rejiggering to a higher level.

As Timothy Liu at the Harvard-MIT Division of Health and Computer Sciences explains in the MIT announcement: "Our goal is to build simple design tools that perform some aspect of cellular function."

Translation: this research goes beyond rewriting a cell's DNA to beginning to co-opt basic biochemistry to form tools with which engineers can enhance their control over a living cell's functions. In this case, that means giving cells what amounts to a count-up timer, like those that clock laps in a race, or a count-down timer, like the one on the microwave oven that ticks off the seconds needed to reheat your decaf.

Those interested in the technical details will find them in the May 29 issue of the journal Science. The basic concepts are simple. They are embodied in two different biochemical schemes.

The first is a simple 1-2-3 counter that theoretically could be designed to count up much higher. MIT's announcement explains that the timer "consists of a series of genes, each of which produces a [distinctive] protein." When a cellular event, such as uptake of sugar, is to be counted, the first occurrence stimulates production of one of these proteins. The second occurrence stimulates production of another distinctive protein and so on. It's as though you had a series of markers labeled 1, 2, and 3. You can reset this timer and use it again.

The other type of counter is a series of DNA sequences, each of which includes a gene for a distinctive enzyme. When an event to be counted occurs, this gene activates and writes a distinctive marker into the DNA sequence. This creates a permanent record of the first, second, and third occurrences of the event.

Such a record can aid research. For example, it can show how many times a cell takes in a pollutant within a given time period. It can help time events in embryo development.

It also has a darker side. It can act as a drop dead timer for organisms we don't want to persist in the environment.

BU professor James Collins explains: "There's a lot of concern about engineered organisms – if you put them in the environment, what will happen? [These counters] could serve as a programmed expiration date for engineered organisms." In other words, you've been around for the programmed number of night-day cycles, now drop dead.

That was comforting until I remembered that, in the movie "Jurassic Park," the dinosaurs were not supposed to be able to reproduce. The movie made the point that the biological imperative to survive can overcome human imposed limitations.

It's impossible to foresee all the possible consequences of developing simple tools to help engineers control some aspects of cellular function. But this first step in that development does indeed raise the implications of cellular engineering to a new portentous level.

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