The Start-up That Translates the ABCs of DNA

Genome Compiler is not your typical Tel Aviv start-up: It aims to exploit genes to make our kids' lives greener, cleaner and better. Glowing fish instead of nightlights, anyone?

In a perfectly usual Tel Aviv apartment near ritzy Rothschild Boulevard, the Israeli team behind Genome Compiler is busy writing code. One might think it's just another Internet or phone-app start-up, like the dozens clustered in the neighborhood. But Genome Compiler is anything but just another start-up.

Founded last year by 34-year-old biochemist Omri Amirav-Drory, Genome Compiler aims to develop software for writing genetic sequences. A creepy cobwebby castle might have been a more appropriate backdrop for this company, for all its cutting-edge aspirations.

"I want to plan living beings," says Amirav-Drory. A Frankensteinian fantasy? Not at all.

How could it be done? By harnessing biology to wean the world of its dependence on non-renewable resources, he explains. "We are entirely dependent on coal, oil and natural gas, and the situation isn't sustainable," he says. "Living things can use renewable energy sources like sugar, sunlight and carbon dioxide, and they are also flexible enough to create almost everything that we produce using fuel. Also, living things can grow in order to meet global challenges."

Of DNA, that greeny helix

Terrific progress has been made in decoding and writing DNA sequences, those complex molecules that carry the genes to life. ("Writing" a DNA sequence means, simply, manufacturing one, which is easier said than done.)

The first, primitive generation of genetic engineering involved people selected plants or animals (or each other) and reproducing them selectively. A farmer who liked white sheep would mate two of them rather than the black one with the white one, for instance, thereby encouraging the proliferation of white sheep. That phase of genetic engineering has gone on since the dawn of time.

The second generation began in the 1970s, when scientists learned how to take DNA from one creature and splice it into the DNA of another. Again, easier said than done – the methodology was crude in the extreme and at no point in the process could the engineers be certain they'd managed to implant the genes, certainly not in the right places – not until the genes expressed themselves. There was also extreme danger that while the genes might have been taken up, the process caused other damage.

Now humanity is in the third generation of genetic engineering, which is synthetic biology: creating DNA molecules from scratch, not taking them from plants or animals.

Genome Compiler is at the forefront of this work. It is writing software that it hopes will code for new biological structures that don't exist in nature, based on pre-defined characteristics.

A bacteria spelled with 1 million letters

The most important research breakthrough in the field occurred in 2002, when scientists managed to write genetic code for a living organism for the first time.

It was the humble polio virus, which has a very small genetic code with 7,500 nucleotide bases. (DNA is made of nucleotides, which are basic – not acidic – molecules that are represented by the letters A, G, T and C).

After eight years the American biologist Craig Venter synthetically recreated the entire genome of the bacteria Mycoplasma mycoides, whose length is about 1 million letters. He then transplanted the entire thing into a different bacterium.

Reading about Venter's success, Amirav-Drory had a Eureka moment. "When I read the article by Venter everything connected for me," he says. "I finally got it that genomes are files, and they can be opened and closed, programmed and printed. I started looking for software that would allow me to program genomes, but I couldn't find it. So I decided to develop it myself."

Insulin and spice and everything nice

Genome Compiler is hardly the first company of its kind. Since the 1970s, several businesses have gotten into synthetic biology, and even marked some successes.

In 1978, the American company Genentech whipped up organic insulin producers by Iifting the genetic sequence responsible for creating the stuff and transplanting it into bacterial genomes.

Today, Genentech employs about 11,000 people. It was acquired in 2009 by the Swiss chemicals giant F. Hoffmann-La Roche, based on an estimated market value of $46.8 billion.

Venter, meanwhile, is today the head of Synthetic Genomics, a company trying to bring synthetic genetic code transplantation to the energy and chemical markets. And he has competition: Companies like LS9 and Amyris are also scrambling to unravel the helix and beat him to the punch.

Even in the specific niche of Genome Compiler, the market is crowded. Companies such as Synbiota, Life Technologies and DNA 2.0 are also eager to develop interfaces that will make it easier to program and produce genetic sequences. When it comes to the mysteries of life, there are no shortage of sleuths.

Under the light of the tree

Even in the most cutting-edge laboratories, money talks, and Amirav-Drory's effort has been given a boost by the sliding cost of reading and writing genomes.

Reading human DNA, a process that in the 1990s could have cost a scientist a cool $3 billion, today requires only $1,000, Amirav-Drory explains. Writing a single letter of DNA, he says, once cost $1.50 but now will cost maybe a quarter. The price is expected to further shrink by half in just a few years. Basic supply and demand, then, means that global databases are now literally swimming with genetic information.

But after reading and writing comes translation, and it is here, Amirav-Drory says, the scientists continue to be stymied.

"Genetic programmers still write in the biological counterpart to ones and zeros," Amirav-Drory says. In the black void between biological code and evolved human expression, he says, lies the rub.

"Just like programmers don't write code in binary, but instead use a software developing tool, people in the field of biology need a simpler way to create DNA so that we can synthesize it," he says. "Computers understand only ones and zeros, but we don't write software by entering ones and zeros. Instead, we use software writing tools to locate mistakes and to compile programs that are ready to run."

What bioloigsts need is a genome compiler to take that code and build it into executable genes/genomes. Genome compiler, as its name suggests, is ready to step up to this plate by helping biologists design, debug and compile their code.

"When I was doing my doctorate, I used pen and paper," says Amirav-Drory. "I wrote sequences with the letters A,T, G and C. My professor has notebooks full of letters. Our challenge with the software is to transform the process into something as simple as possible, and to assist in 3-D imaging [of DNA]."

Amirav-Drory grew up in the small community of Talmei Menashe in central Israel. During his mandatory army service he served in a technological unit in the Intelligence Corps and after his release he completed an honors track undergraduate degree in biology at Tel Aviv University. He then did his doctorate in biochemistry there as well. In 2007, Amirav-Drory received a Fulbright Fellowship to Stanford University to do his post-doctorate. It was in Palo Alto that he developed the beta version of Genome Compiler's software.

When he came back to Israel, he sought out co-founders and turned his project into a full-fledged company.

The initial investment in Genome Compilers, roughly $500,000, came from private investors. Last January, they got an additional $2 million boost from the American company AutoDesk, which develops the software for the computer-aided design and drafting program AutoCAD. They now have 10 full-time employees.

And they continue to think big.

"We want to make it possible … to take the genetic component that lets fireflies glow and splice it into a tree," Amirav-Drory says, explaining a radical crowd-funded project in the works that places light-emitting bacteria into organic matter. "Eventually, we will be able to create a glowing tree. Why shouldn't trees replace streetlamps?"