Scientists speak out
Editorial: Venter: The implications of our synthetic cell
MAKE a genome - check. Transplant it into an emptied cell to create the world's first synthetic life form - check. Frenzied media coverage accusing the researchers concerned of "playing God" - check.
Craig Venter and his teams at the J. Craig Venter Institute in Rockville, Maryland, and San Diego, California, have shown themselves to be technical wizards by synthesising a genome from code contained on a computer, and using it to start a cell line of the resulting synthetic organism (see "How the synthetic bacterium was made"). If demonstration was needed that there is no such thing as the "mystery of life", they have provided it in stunning style. The new life form they have made is derived from information, pure and simple.
Other synthetic biology researchers, while impressed by Venter's technical achievement, are restrained about its implications, both practical and philosophical. They were already well aware that there is no magical Wizard of Oz behind life's curtain, and they feel the first fruits of synthetic biology - organisms designed to make clean fuels and cheap pharmaceuticals, for example - are more likely to come through less ambitious approaches.
"It's cool and has taken a lot of effort," says Alistair Elfick at the University of Edinburgh, UK. "But it doesn't take us that much further scientifically." He and many other researchers in the field say they are unlikely to synthesise whole bacterial genomes themselves.
It's cool and has taken a lot of effort, but it doesn't take us that much further scientifically
"This is a marvellous advance, but it doesn't immediately open up or enable new studies for the broad community," says James Collins of Boston University, who notes that Venter's team spent about $40 million to create the synthetic cell. "We don't have that kind of money in academic research."
The costs of making long stretches of DNA - currently about $1 per letter - will almost certainly fall. But even if synthetic genomes become dramatically cheaper to make, there is still the question of how to write one. "We have a long way to go to really develop sufficient understanding to build an operational genome from scratch," Collins says.
Genomes are too much of a black box for deliberate and predictable tinkering, says Gos Micklem at the University of Cambridge. "It's like trying to build a car engine when you don't understand what the individual parts do."
Even if biologists learn how to write novel genomes fluently, they face another huge hurdle: getting the enormous molecules to "boot up" in a foreign cell. Venter's genome was modelled on that of a mycobacterium, and was implanted into the cytoplasm of a closely related species. It remains to be seen whether these vessels will accept the genome of drug-making Escherichia coli or, more difficult still, a biofuel-producing alga. "It will be very challenging to jump between very different species," Collins says.
These criticisms may be unfair to Venter and his team, as their stated goal was to synthesise a bacterial genome that existed as data and implant it into a cell. As Venter is fond of saying: "This is the first self-replicating species that we've had on the planet whose parent is a computer."
More than anything, the guarded reception from Venter's peers demonstrates how far synthetic biology has come via other routes. In recent years, it has yielded the once costly anti-malarial drug artemisinin, a valuable polymer, and even biofuels. "Those didn't involve millions of genetic changes, those involved a dozen," says George Church at Harvard Medical School in Boston.
The chemical company DuPont has spent the better part of a decade and hundreds of millions of dollars identifying about 20 genetic changes that enable E. coli to produce a polymer called 1,3-propanediol. Church and his team have come up with a way of introducing multiple genetic changes into bacteria more quickly and cheaply, called multiplex automated genome engineering or MAGE.
Church is now working on improving the technique. "It's an order of magnitude less expensive to do partial genomes than to do the whole ones, and there are really amazing things that can be done," he says.
For now the preferred approach - and one that is acknowledged by Venter - is to create a "toolbox" of genetic components or "BioBricks" that act in a predictable way, ready for assembly into combinations with whatever properties are desired. These genes or circuits of genes are kept ready and available for assembly into bio-devices that actually have a function.
The Massachusetts Institute of Technology keeps a registry of 2500 BioBricks. Many of these have come from students competing in an annual event called the International Genetically Engineered Machine competition, or iGEM, but according to Richard Kitney at Imperial College London, only about 10 per cent work properly.
So Kitney, in collaboration with the University of California, Berkeley, and Stanford University in California, is creating a professional BioBrick registry. "There are now about 300 parts that are fully understood and characterised," he says. "You can use them to make professionally engineered biological devices."
In contrast to Venter's latest achievement, which demonstrates a proof of principle but has no immediate practical use, everyone involved in BioBrick projects is using biological tools to try and solve practical problems, Kitney says. "All of us are focused on applications... producing devices and systems that spawn new industries."
Kitney and his colleagues have made a biological sensor which detects a protein from bacteria that cause urinary tract infections. The device has three BioBrick components: a detector; an amplifier that increases the signal; and an indicator. The three components form a bio-device which is then placed into E. coli.
Going one step further, the team is developing a version that doesn't need an E. coli cell. Instead, the three genes are added to a broth and produce a response equivalent to that of a live cell. "We're working on a new version that detects the superbug MRSA, with a red fluorescent protein," Kitney says.
Elfick and his colleagues are tinkering with six enzymes that together can break down cellulose, the normally indigestible polymer in waste plant matter, with the aim of turning plant waste into biofuel.
Venter has the same goals. He just envisions a different way of achieving them, and perhaps it is this ambition that sets him apart from his peers. "There's zero doubt in my mind that being able to control the whole thing from scratch is orders of magnitude more powerful than changing a genome," Venter says. "The unknown is how long it will take us."
