Public domain biotechnology: biological transistors from Stanford University

Andrew Myers’ Mar. 28, 2013 article for the Stanford School of Medicine’s magazine (Inside Stanford Medicine) profiles some research which stands as a bridge between electronics and biology and could lead to biological computing,

… now a team of Stanford University bioengineers has taken computing beyond mechanics and electronics into the living realm of biology. In a paper published March 28 in Science, the team details a biological transistor made from genetic material — DNA and RNA — in place of gears or electrons. The team calls its biological transistor the “transcriptor.”

“Transcriptors are the key component behind amplifying genetic logic — akin to the transistor and electronics,” said Jerome Bonnet, PhD, a postdoctoral scholar in bioengineering and the paper’s lead author.

Here’s a description of the transcriptor (biological transistor) and biological computers (from the article),

In electronics, a transistor controls the flow of electrons along a circuit. Similarly, in biologics, a transcriptor controls the flow of a specific protein, RNA polymerase, as it travels along a strand of DNA.

“We have repurposed a group of natural proteins, called integrases, to realize digital control over the flow of RNA polymerase along DNA, which in turn allowed us to engineer amplifying genetic logic,” said Endy [Drew Endy, PhD, assistant professor of bioengineering and the paper’s senior author].

Using transcriptors, the team has created what are known in electrical engineering as logic gates that can derive true-false answers to virtually any biochemical question that might be posed within a cell.

They refer to their transcriptor-based logic gates as “Boolean Integrase Logic,” or “BIL gates” for short.

Transcriptor-based gates alone do not constitute a computer, but they are the third and final component of a biological computer that could operate within individual living cells.

The article also offers a description of Boolean logic and the workings of standard computers,

Digital logic is often referred to as “Boolean logic,” after George Boole, the mathematician who proposed the system in 1854. Today, Boolean logic typically takes the form of 1s and 0s within a computer. Answer true, gate open; answer false, gate closed. Open. Closed. On. Off. 1. 0. It’s that basic. But it turns out that with just these simple tools and ways of thinking you can accomplish quite a lot.

“AND” and “OR” are just two of the most basic Boolean logic gates. An “AND” gate, for instance, is “true” when both of its inputs are true — when “a” and “b” are true. An “OR” gate, on the other hand, is true when either or both of its inputs are true.

In a biological setting, the possibilities for logic are as limitless as in electronics, Bonnet explained. “You could test whether a given cell had been exposed to any number of external stimuli — the presence of glucose and caffeine, for instance. BIL gates would allow you to make that determination and to store that information so you could easily identify those which had been exposed and which had not,” he said.

Here’s how they created a transcriptor (from the article),

To create transcriptors and logic gates, the team used carefully calibrated combinations of enzymes — the integrases mentioned earlier — that control the flow of RNA polymerase along strands of DNA. If this were electronics, DNA is the wire and RNA polymerase is the electron.

“The choice of enzymes is important,” Bonnet said. “We have been careful to select enzymes that function in bacteria, fungi, plants and animals, so that bio-computers can be engineered within a variety of organisms.”

On the technical side, the transcriptor achieves a key similarity between the biological transistor and its semiconducting cousin: signal amplification.

Refreshingly the team made this decision (from the article),

To bring the age of the biological computer to a much speedier reality, Endy and his team have contributed all of BIL gates to the public domain so that others can immediately harness and improve upon the tools.

“Most of biotechnology has not yet been imagined, let alone made true. By freely sharing important basic tools everyone can work better together,” Bonnet said.

Here’s a citation and a link to the researchers’ paper in Science,

Amplifying Genetic Logic Gates by Jerome Bonnet, Peter Yin, Monica E. Ortiz, Pakpoom Subsoontorn, and Drew Endy. Science 1232758 Published online 28 March 2013 [DOI:10.1126/science.1232758]

This paper is behind a paywall. As for Myers’ article, it’s well worth reading for its clear explanations and forays into computing history.

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