Hello World, I'm Synthia

In 1674, the son of basket-maker Philips Teunisz Leeuwenhoeck and Margriete Jacobsdr van den Berch used a microscope to study Selenemonad, motile crescent-shaped bacteria. For Antonie Philips van Leeuwenhoek the discovery of the Selenemonad was more about the power of microscopy than the biological implications of the bacterium. Three years later, he would go on to discover spermatozoa, but for Leeuwenhoeck, trouble with the church and other scientists eclipsed one of the most vital careers in biology.

Nearly 346 years later the bacterium was cast, once again, into the spotlight. This bacterium, known rather blandly as JCVI-sync1.0 (Synthia to those who read newspapers and watch TV), was creating waves around the world for one simple reason… it had no ancestors.

JCVI is an abbreviation of the J Craig Venter Institute, a pioneer in synthetic biology. Earlier this month Venter and his team at Synthetic Genomics, a part of JCVI, created the first ‘synthetic life form’, what they didn’t do — although elements in the media would have you believe that they did — is create a whole new life form.

The life form, Mycoplasma mycoides, existed long before Venter was a glint in a randy genome’s eye. In this case, however, the bacterium was not itself…literally. It had its original genome removed and replaced with a lab-created genome. The result was a life form, which for all intents and purposes was created in a lab. But the bacterium retained the structure engineered by nature, it followed all of her biological processes and never once threatened to rise up and kill its maker. Mary Shelley will have to wait a while.

Were Venter and his team playing god? Did they go boldly, where only foolish men have been before? To answer that one must first understand the man behind the project.

James Shreeve, author of The Genome War, wrote of Venter: “A 100 yards away you see a man strolling in the shallows. He is bald, bearded, and buck-naked. He stoops every once in a while to pick up a shell or examine something in the sand. His pate is sunburned, and his beard makes him look younger and more relaxed, not that I ever saw him looking tense, even when the genome race got ugly, and his enemies were closing in.”

The genome race Shreeve talks about is one of the most exciting smackdowns of modern science. It pitted the government-funded Human Genome Project (HGP) against the private firm Celera Genomics in a race to be the first to sequence the human genome.

At the helm of HGP was Francis Collins. Supported by the governments of the US, UK, Japan, France, Germany, China, India, Canada and New Zealand, it had formidable resources… and when it began in 1990 it had one hell of a headstart.

Venter, in the mean time, frustrated by the lack of funding forthcoming from government circles decided to go financially rogue and approached biotech company Perkin-Elmer (later Applera). He cast, they bit and in 1998, Celera Genomics joined the race for the human genome.

Eight years behind in the race, Venter decided that what was needed was a short-cut, or as he would so infamously put it, “a shotgun method”. In the eight years since HGP began, a large portion of the human genome had already been sequenced and was in the public domain at GenBank. That was just the ammo required for Venter’s “shotgun”.

When the HGP was founded, the entire undertaking was to take 15 years; that means that by 2005, the genome should have been sequenced. But no one counted on Venter and Celera jumping into the fray and mixing it up with the government-backed big boys. The gloves were off and it was full steam ahead.
On April 3, 2003, a full two years ahead of schedule it was announced that an “essentially complete genome” had been sequenced. But who had got there first, HGP or Celera? The answer would go down more as a political masterclass than a scientific one. On June 2006, US President Bill Clinton and British Prime Minister Tony Blair announced, at a joint press conference, that both the HGP and Celera Genomics would be credited with the sequencing. Of course, what he didn’t mention was that HGP had spent over $3 billion while Celera had spent roughly around $300 million.

Venter then fell out with Celera, and promptly boarded his sloop, Sorcerer II, and sailed the world’s oceans with the aim of genetically documenting every living thing on the planet. Needless to say, that project is as yet unfinished. In October 2006, Venter founded the J Craig Venter Institute (JCVI).

While all this was happening, Venter and his team were mixing the colours for his 2010 living masterpiece, Synthia. In 2003, the team synthesised the genome of a virus phi-X174. The genome itself was sequenced back in 1974. When the genome was inserted into a cell, the cell began to reproduce new viruses. It was a breakthrough, albeit not a pioneering one. A similar thing had been done on the polio virus in 2002.

What they also found was that within a few cell-generations all traces of the original cell were lost, as though its ancestors had never existed. Venter and his team then moved on to a bacterium, Mycoplasma genitalium. They planned to get rid of the cell’s original genome and replace it with a synthetic one. But M genitalium was a bit of a laggard when it came to growing, so they switched to its cousin, the far more virile Mycoplasma mycoides. The result was Synthia.
But what does Synthia mean to you and me? Is she going to break out of her sterile prison and invade her human host wiping us off the face of the Earth?
Jim Thomas, a research programme manager at Action Group on Erosion, Technology and Concentration (ETC) calls the creation of Synthia a “quintessential Pandora’s box moment — like the splitting of the atom or the cloning of Dolly the sheep”.

“Synthetic biology is a high-risk profit-driven field, building organisms out of parts that are still poorly understood,” he says.

But for those who worked with Venter on the project, like Radha Krishnakumar, Synthia will allow the scientific community “to better
under-stand the workings of a cell, and thus potentially harness more effectively what nature has to offer”.

Krishnakumar, who worked with Dan Gibson to assemble Synthia’s synthetic genome, believes that although this technology is in its basic stages, it will eventually help scientists to harness beneficial features from micro-organisms that are otherwise intractable, “thus allowing us to create cells that have pathways built in to make bio-fuels, antimicrobial compounds and vaccines”.

And fuel is Synthia’s maiden name. In July 2009, oil giant ExxonMobil announced that it had launched a $600 million collaborative effort with Venter’s Synthetic Genomics to research and develop next-generation biofuels.

But in order to do that Synthia will have to grow up substantially; from 1µm to about 70µm, which is the size of a single algae cell. It is in algae where the biofuel conundrum could be solved. Rather than using microbes to make biofuel through the process of fermentation, synthetic, hence controlled algae could use atmospheric carbon dioxide to produce petrol or diesel.

In his Descent Of Man, Charles Darwin writes: “It has often and confidently been asserted, that man’s origin can never be known: Ignorance more frequently begets confidence than does knowledge: it is those who know little, not those who know much, who so positively assert that this or that problem will never be solved by science.”

Synthia may be giving ethicists sleepless nights and may well have Hollywood screenwriters burning the midnight oil, but if the end does justify the means then maybe Venter and his rogue methods could find acceptance in the annals of history, and science will be the better for it.