16 August 2012Harvard University researchers converted a 53 000-word book into DNA and then read the DNA-encoded book using gene-sequencing technology, the researchers report this week in Science. The project is by far the largest demonstration of digital information storage in DNA and the densest consolidation of data in any medium, the authors say.

There is a clear need for improved long-term storage of massively large data, says George Church, a geneticist at Harvards Wyss Institute and one of the leaders of the research. There is data that we are throwing away or dont collect because we cant afford to store it, such as video surveillance of public spaces and large research projects, he says. Someday that wont be necessary. The question is, What will get us there first: electronic or molecular memory?

DNA offers advantages over electronic storage, but whether it will ever make sense practically or economically is unclear. DNA can store more digital information per cubic millimeter than flash memory or even cutting-edge experimental memories such as quantum holography. Data stored in DNA is also recoverable for millennia (consider the 7000-year-old DNA archaeologists have extracted from human remains). And given DNAs biological importance, we can safely assume its going to remain a readable standard for a long time. If you look at the size per bit of stored memory as DNA, its unlikely that well ever get better than that, says Joseph Jacobson, a synthetic biologist at MIT who was not involved in the project.

But making and reading DNA isnt yet practical. Synthesizing and sequencing DNA is expensive, although the cost for both of these technologies has been dropping at a rate of five- and twelvefold per year, respectively. Whats more, unlike electronic bits, most DNA data cannot be changed once its written. And with todays technology, information in DNA usually has to be accessed as a whole, not in parts. (There is no way to make random-access DNA memory.)

Church and his colleagues set out to demonstrate a simple way to densely store data in DNA. They converted an html draft of a book comprising 53 426 words, 11 JPG images, and one JavaScript program into a 5.27 megabit set of zeros and ones. Using software they wrote, zeros were assigned the letter A or C for the DNA bases adenine and cytosine, and ones were assigned the letter G or T for DNA bases guanine and thymine. A lowercase f from the book, for example, was represented in binary as 01100110 and encoded in DNA as ATGAATTC.

Synthesizing that string of bits would yield a stretch of DNA that was 5.27 million bases long. Such long stretches of DNA are particularly expensive to work with, so Church and his colleagues split the DNA sequence into short chunks that were each 96 bases long. Each chunk included a 19-bit bar code, or address, to show where that chunk belonged in the whole of the book. The DNA was synthesized, inkjet-printed on a glass DNA microchip, and then cleaved off and dried to form a 50-nanogram clump smaller than a speck of pollen.

To convert the DNA back to a book, Church and his colleagues read out the bases using commercially available sequencing technology. They then arranged the sequence, decoded it back to zeros and ones, and converted those back to an HTML book. The researchers were able to complete the project with errors in only 10 bits out of 5.27 millionon par with the raw error rate of other storage media, says Sriram Kosuri, a staff scientist at the Wyss Institute who also worked on the project.

The tome that got the honor of becoming the worlds first biological book is the forthcoming Regenesis: How Synthetic Biology Will Reinvent Nature and Ourselves. The book, coauthored by Church, will be published in more conventional forms this fall.

Similar approaches have been demonstrated before, but on a smaller scale. In 2001, Carter Bancroft and his colleagues at the Mount Sinai School of Medicine encoded in DNA the opening lines of Charles Dickenss A Tale of Two Cities. A 2010 project from the J. Craig Venter Institute encoded a 7920-bit watermark in a bacterium genome sequence. Churchs paper, however, takes us from a few bits to many megabits, says Jacobson. If you have a big enough quantitative advance, at some point theres a qualitative shift, and Id say thats the case here.

But another researcher who studies the intersection of biology and technology and asked to remain anonymous calls Churchs paper a silly vanity project with little value. Its like showing you could painstakingly use an abacus to solve a Hamiltonian path problem that would take the average computer a microsecond, he says. Other than maybe military intelligence, finding real-world applications for DNA storage technology under no conceivable set of circumstances is even remotely likely, he says.

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Reading and Writing a Book With DNA