SynBio3: DNA computers and storage in the future? (v1.0)

Computer users face frequent upgrades that make older models obsolete and eventually unusable. The same goes for data storage which degrades over time. By contrast, computers using synthesized DNA for storage and processing could in theory offer a stable super-compact system that would last for millions of years. Intriguing idea? 

Famed physicist Richard Feynman is known as the father of DNA computing. In his lecture in 1959 "There is plenty of room at the bottom", he said "This fact - that an enormous amount of information can be carried in an exceedingly small space - is of course well known to the biologists, and resolves the mystery which existed before we understood all this clearly, of how it could be that, in the tiniest cell, all of the information for the organization of a complex creature such as ourselves can be stored.". These thoughts were ignored for decades but now lays the cornerstone of both DNA computing and nano technology. 

In 1994 Prof Leonard Max Adleman demonstrated for the first-time using DNA for computing to solve a math problem (The travelling salesman problem). This was an early proof of concept. While the demonstration by Adleman showed the possibility of DNA-based computers, the DNA design was trivial because as the number of nodes in a graph grows, the number of DNA components required in Adleman's implementation would grow exponentially. 

In 2012 Prof George Church (who has cofounded about 50 biotech companies) led a team that encoded 70 billion html copies of his 304-page book in DNA. That’s 1,000 times more data than the previous record. Using next-generation sequencing technology, Church’s team successfully stored the text, images and formatting of the book onto "standalone DNA" obtained from commercial DNA microchips. This was achieved by assigning the four DNA nucleobases the values of the 1s and 0s in the existing html binary code – the adenine and cytosine nucleobases represented 0, while guanine and thymine stood in for 1. The density at which the data was stored is truly impressive, coming in at 5.5 petabits (one million gigabits) per cubic millimeter. At that rate, according to research partner Sriram Kosuri, the entire amount of digital data created worldwide in one year could theoretically be stored on just four grams of DNA. 

For the problem of data storage media, this approach has potentially huge benefits in terms of density and compactness and energy consumption and cost and will last for an extremely long time intact (hundreds of thousands or even millions of years). Can synthesized DNA storage solve our ever-expanding needs for long term data storage or act as a backup or archival or catalog media? The data is accessed by DNA sequencing (see reading DNA in previous essay). There are even startup companies like Catalog Technologies today that offer to store data in synthesized DNA. In 2022 Catalog Technologies made a historic breakthrough in DNA computation by demonstrating the ability to search data stored in DNA in a massively parallel and scalable manner with resource usage almost independent of the data size.

In 2013, scientists built transcriptors which is a DNA version of a transistor. When we think of computers, we often envision electronic circuits and silicon-based transistors. However, bioengineers have pushed the boundaries by creating a biological transistor made from genetic material—specifically DNA and RNA—instead of traditional mechanical gears or electrons. This remarkable invention is aptly named the "transcriptor". “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.

Here’s how it works:

1. Biological Transistors:

   • In electronics, a transistor controls the flow of electrons along a circuit. Similarly, in biology, a transcriptor controls the flow of a specific protein called RNA polymerase as it travels along a strand of DNA.
   • The team of Stanford University bioengineers repurposed natural proteins (called integrases) to achieve digital control over RNA polymerase’s movement along DNA. This allows them to engineer amplifying genetic logic.

2. Logic Gates in Living Cells:

   • Using these transcriptors, the team has created what are essentially logic gates within living cells.
   • These logic gates, known as Boolean Integrase Logic (BIL gates), can derive true-false answers to virtually any biochemical question posed within a cell. 

 

This is still very early days for this technology. One of the challenges of DNA computing is its speed. While DNA as a substrate is biologically compatible i.e. it can be used at places where silicon technology cannot (even within a cell), its computation speed is still very slow. There are multiple methods today for building a computing device based on DNA, each with its own advantages and disadvantages. Most of these build the basic logic gates (AND, OR, NOT) associated with digital logic from a DNA basis. It will be fascinating to monitor how this technology advances and what real world practical applications it finds!!