Cellular computers: 'Genetic circuit' biological transistor enables computing within living cells

Mar 28, 2013

When Charles Babbage prototyped the first computing machine in the 19th century, he imagined using mechanical gears and latches to control information. ENIAC, the first modern computer developed in the 1940s, used vacuum tubes and electricity. Today, computers use transistors made from highly engineered semiconducting materials to carry out their logical operations.

And now a team of Stanford University bioengineers has taken computing beyond mechanics and electronics into the living realm of biology. In a paper to be 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 and the paper's lead author.

The creation of the transcriptor allows engineers to compute inside living cells to record, for instance, when cells have been exposed to certain external stimuli or environmental factors, or even to turn on and off as needed.

"Biological computers can be used to study and reprogram living systems, monitor environments and improve cellular therapeutics," said Drew Endy, PhD, assistant professor of bioengineering and the paper's senior author.

The biological computer

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.

Using transcriptors, the team has created what are known in electrical engineering as 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.

Despite their outward differences, all modern computers, from ENIAC to Apple, share three basic functions: storing, transmitting and performing on information.

Last year, Endy and his team made news in delivering the other two core components of a fully functional genetic computer. The first was a type of rewritable digital data storage within DNA. They also developed a mechanism for transmitting genetic information from cell to cell, a sort of biological Internet.

It all adds up to creating a computer inside a living cell.

Boole's gold

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 —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.

By the same token, you could tell the cell to start or stop reproducing if certain factors were present. And, by coupling BIL gates with the team's biological Internet, it is possible to communicate genetic information from cell to cell to orchestrate the behavior of a group of cells.

"The potential applications are limited only by the imagination of the researcher," said co-author Monica Ortiz, a PhD candidate in bioengineering who demonstrated autonomous cell-to-cell communication of DNA encoding various BIL gates.

Building a transcriptor

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 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.

With transcriptors, a very small change in the expression of an integrase can create a very large change in the expression of any two other genes.

To understand the importance of amplification, consider that the transistor was first conceived as a way to replace expensive, inefficient and unreliable in the amplification of telephone signals for transcontinental phone calls. Electrical signals traveling along wires get weaker the farther they travel, but if you put an amplifier every so often along the way, you can relay the signal across a great distance. The same would hold in biological systems as signals get transmitted among a group of cells.

"It is a concept similar to transistor radios," said Pakpoom Subsoontorn, a PhD candidate in bioengineering and co-author of the study who developed theoretical models to predict the behavior of BIL gates. "Relatively weak radio waves traveling through the air can get amplified into sound."

Public-domain biotechnology

To bring the age of the 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.

Explore further: Earliest stages of ear development involve a localized signaling cascade

More information: "Amplifying Genetic Logic Gates," by J. Bonnet et al., Science, 2013.

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User comments : 8

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kochevnik
1 / 5 (1) Mar 28, 2013
The transcriptor is another liberal atheist joke like evolution. Everyone knows god made man perfect. It is impossible to improve god's design
Whydening Gyre
2 / 5 (4) Mar 29, 2013
Was that sarcasm, ko? Cuz it sounded too stupid to be anything else...
Lurker2358
3 / 5 (2) Mar 29, 2013
The transcriptor is another liberal atheist joke like evolution. Everyone knows god made man perfect. It is impossible to improve god's design


The Bible does not claim man is God's highest possible creation, nor even his highest existing creation.

Hebrews 2:7
Thou madest him a little lower than the angels; thou crownedst him with glory and honour, and didst set him over the works of thy hands:

Lower than the angels means there are created beings more intelligent, and certainly more "perfect" than us in the sense of "life" or "fitness".

Anyway, bio computers would need to be contained in an ohterwise sterile container. You would not want something which functions by hacking up DNA to be in your body or to be accessible to ordinary viruses and such, because it would clearly be carcinogenic.

Though I do recognize the potential for certain forms of parallel processing could be enormous IF you could make a self-replicating bio computer which can network itself, as they want...
Lurker2358
3 / 5 (2) Mar 29, 2013
What they are dealing with here is still "Digital" logic, although not quite like classical computers.

Neural nets, such as our brains, do something which DNA can't do directly, and that is analog thoughts. Even though the carriers are electrical and "digital" in the sense of the molecules which pass between neurons, the signal is analog because it is "broadcast" through multiple synapses which work in a "fuzzy" environment, and in some cases can change their own functions or add new functions on the fly. This is what allows humans brains to adapt to all new skill sets, such as typing or driving an automobile, even though those skills did not exist and were not needed throughout 99.9% of all biological history.

A DNA computer would have a hard time doing that trick directly, because what he's doing is essentially the same as a boolean computer, except it works in base 4 instead of base 2. While they may do good chemical sensory functions, I don't expect them to replace electronics...
CQT
3 / 5 (2) Apr 01, 2013
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. Article's author.

There is only one single life form that displays the ability to pose questions.
You need more than one data point to obtain statistical meaning.
I simply assert no other form of life poses questions.
I further assert whatever "?" means, the meaning is man made.

kochevnik
3 / 5 (2) Apr 02, 2013
Was that sarcasm, ko? Cuz it sounded too stupid to be anything else...
Actually I was hoping to finally get a '5' vote from user 'lite'
Whydening Gyre
3 / 5 (2) Apr 02, 2013
Well, I got the usual 1. I'd prob'ly be disappointed if I got anything else - that would mean he might have read the article and even the comment...
Accidental TemporalGhost2_0
3 / 5 (2) Apr 06, 2013
Quote:Lurker2358;Neural nets in digital systems by their nature (1's&0"s) might simulate "whole brain behavior," through ELIZA brute force, if its "fast enough". In neuromorphology there is no real separate HW&SW. Since "thinking, etc" appears to cause morphological change thats innate in the process. As far as neuron-to-neuron "chatter," it seems it's not the proximity that determines which neuron is signaled to, but morphological topology thats the most "similar". Perhaps thats part of neurological robustness, (as in a more forgiving) nature.

Even on a social scale humans feel less threatened by people they perceive are "like them". Maybe an asynchronous soliton or fractal moves from one geo-spacial area to another? Regarding DNA, I agree with you. It's depressing to see us try to emulate digital functions in DNA, but we have to start somewhere. I really think we have to emulate the biology of the brain which is constantly physically changing, to get real thought not a "simulatio

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