WIRED, January 24, 2008
Yesterday the news broke, and it broke big: genome pioneer Craig Venter and his team of scientists at his eponymous institute had created a microbe’s genome from scratch. Massive stories ran in newspapers and magazines, tingling with the sense that we were on the edge of a revolution. Time’s piece was accompanied by a foreboding picture of Venter in a forest, wearing a dark coat and scarf, his beard giving his scowl a particularly dire look. The picture matched the story’s ominous mood: “He has gone beyond merely sequencing a genome and has designed and built one. In other words, he may have created life,” the article intoned.
The Economist promised that when Venter is done, he will “have erased one of the last mythic distinctions in science–that between living and non-living matter.”
I get the impression I am supposed to be tingling, my heart racing with exaltation or terror or…something. And yet I feel like I have a lesion in my amygdala, unable to respond to the threat of an electric shock. In some ways, this is actually old news. And in other ways, it’s news that hasn’t yet been written, and won’t be for decades.
Let me make it clear that I am impressed with the new work from the J. Craig Venter Institute. As a technical tour-de-force, it really speaks for itself. It is very hard to synthesize big chunks of DNA–especially if you want them to match a desired sequence with perfect accuracy. In the past, scientists have synthesized the tiny genomes of viruses, and larger segments from the genomes of microbes. The newly synthesized genome–a copy of the genome of Mycobacteria genitalium–comes in at over half a million base pairs.
Venter’s team ordered up parts of its genome from commercial DNA sequencers and then figured out how to piece them together. When they resequenced the genome, they found that it matched their original specs. Their plan is to then insert one of these artificial genomes into a DNA-free cell and see if it lives. The next step will then be to slim down Mycobacteria’s genome to the bare minimum–perhaps just under 400 genes–and boot up a cell with it. At that point, the scientists will have brought to life an organism that never before existed.
But what does it really signify to do this? What does it teach us about life that we didn’t know before? There was indeed a time when scientists believed there was something fundamentally different about living matter and non-living matter.
It’s called the Middle Ages.
The scientific revolution helped open our eyes to the fact that living things are made of the same stuff as non-living things. By the early 1800s, it was possible for scientists to synthesize an organic molecule (urea). In the twentieth century, quantum physicists wondered if life defied the laws of physics that governed the rest of the universe. But molecular biology made clear that it didn’t.
So, ultimately, putting together a synthetic organism would simply confirm what scientists have known for a long time. The challenge to the project is not conceptual, but technical. And if you actually read the paper in which Venter’s team report the latest step in their project, it is supremely, fiendishly technical. They have a lot more tedium to survive before they create new life. And once they figure out how to build a viable genome and get it safely into a host cell, and if the two can cooperate nicely, what else would you expect but for life to emerge?
There is a lot we don’t understand about life, of course, but Venter’s project isn’t going to answer all the questions. We are a long way from playing God. The scientists didn’t assemble the fragments of DNA by themselves, nor did they program robots to do so. Instead, they injected the fragments into E. coli, and let the bacteria do the job themselves. Eventually, it turned out that E. coli could only build up a quarter of the genome. The scientists don’t quite know why. So they injected those big chunks of Mycoplasma DNA into yeast. Lo and behold, the yeast were able to finish up the job for the scientists. They don’t quite know how the yeast did their own biochemical magic either. I would assume that God would have this kind of stuff figured out.
When and if Venter’s team does create a viable synthetic life form, our ignorance will still remain profound. Out of 382 genes that the scientists have identified as potentially essential, 110 of them are absolute mysteries. Scientists have almost no idea what they’re for. There’s nothing unusually mysterious about Mycoplasma’s genes–other species have genomes loaded with genes of unknown functions. Scientists have gotten very good at manipulating genes–at copying them or using them to make biotechnology products like insulin–but they still know relatively little about how genes work together in living things.
Creating a new living thing will just mean creating a new set of mysteries. To solve them, scientists will have to plod away with a vast number of experiments. Only then will they get a deeper understanding of life. If we’re lucky, we’ll be alive to read the headlines. Then, maybe, the tingle will kick in.
Copyright 2008 WIRED Magazine. Reprinted with permission.