Using the tools of synthetic biology, scientists from the J. Craig Venter Institute installed a completely artificial genome inside a host cell without DNA. Like the bolt of lightening that awakened Frankenstein, the new genome invigorated the host cell, which began to grow and reproduce, albeit with a few problems.
The research marks a technical milestone in the synthesis and implantation of artificial DNA. Venter, along with dozens of other companies and researchers in the same field, expects the research will lead to cheaper drugs, vaccines and biofuels in several years.
“This is the first synthetic cell that’s been made,” said Venter. “We call it synthetic because the cell is totally derived from a synthetic chromosome, made with four bottles of chemicals on a chemical synthesizer, starting with information in a computer.”
The research, published today in the journal Science, combines two of Venter’s past achievements.
In 2007 Venter transplanted the genome of one Mycoplasma bacterium into another. Venter and his colleagues also synthesized a trimmed down, artificial version of Mycoplasma’s DNA, a project known as the Minimal Genome Project. Attempts to implant the synthetic DNA all failed, until now.
In the current research Venter and his colleagues, which includes Nobel laureate Hamilton Smith, first synthesized Mycoplasma’s full genome. Then they added hundreds of thousands of additional base pairs to “watermark” the DNA to distinguish it from a natural one.
Venter and his colleagues created a special code, similar to Morse code, to “write” within the DNA itself. Instead of dots and dashes, they used the sequence of four DNA nucleotides, thymine (T), guanine (G), cytosine (C), and adenine (A), as a code for any letter, number or punctuation mark. Using the code, the team included the names of the study co-authors, a website, and even several philosophical quotes, complete with punctuation.
The completed DNA sequence was more than one million base pairs long. The human genome, by comparison, is more than three billion base pairs long.
No machine can turn out a single piece of DNA anywhere close to that long, however. Instead, Venter and his colleagues started with many relatively small pieces of DNA. Then the scientists transferred DNA pieces back and forth between a yeast cell and E. coli bacteria, turning the many short pieces into fewer but longer DNA segments.
Once the synthetic DNA segment reached the desired length the scientists injected it into a Mycoplasma bacterium that had had its own DNA removed earlier. Needless to say, the process of assembling such a lengthy piece of synthetic DNA was complicated.
“I hope the day comes when making genomes is something everyone can do,” said Pamela Silver, a systems biologist at Harvard Medical School.
The new, synthetic DNA “booted up” the bacterium, but not without a few problems; several of the synthesized genes didn’t work properly. And the genes that did work didn’t do anything particularly useful, at least by human standards.
The Mycoplasma bacteria grew and reproduced, but that was about all. Within several years however, Venter, along with dozens of other researchers and companies, hope to create more exciting bacteria that will speed up the production and drive down the costs of biofuels, vaccines and drugs.
Venter has teamed up with a major oil and gas company, and a pharmaceutical company, to help realize these goals.
Venter’s work falls into a nascent field of science known as synthetic biology. Synthetic biology builds on the decades-old field of genetic engineering. Unlike genetic engineering, where scientists introduce a handful of new genes into an organism, synthetic biology aims to reprogram entire organisms, including bacteria and viruses.
The creation and insertion of a synthetic genome more than one million base pairs is a technical landmark, said Frances Arnold, a synthetic biologist at the California Institute of Technology in Pasadena. He says the feat showcases scientists’ ability to precisely manipulate long sections of DNA.
But before consumers see any benefit several significant hurdles have to be solved. One of the biggest problems is that scientists are still searching for the specific genetic code to produce cheap drugs, biofuel and other products.
“We can write anything we want,” said Arnold. “The problem is that we don’t know what to write.”