Rewriting the Genome
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TR: Right. Now we’re talking about sequencing an individual’s genome.
GC: We might never get a perfect $1,000 diploid genome [the six billion base pairs in a human’s two sets of chromosomes]. The question is, what can we afford and what do we get for it? Think back to the beginning of the computer industry. They didn’t say, “Oh, we’re going to get you a $1,000 supercomputer.” No, they said, “What can people afford? And what can we give them for it?” And what they gave us was the likes of the Apple II computer, and people started writing software for it. Current personal computers cost about the same but deliver more. The same thing may happen with personal genomes.
TR: So what are people likely to spend to know their own genome?
GC: I think what is affordable – and remember, this is a lifetime expense; your personal genome will hopefully last you 80 years or more – is $10,000. If I can save $100 on average a year, it is a no-brainer. That’s the cost of a couple days of missed work, or one diagnostic test that can be put off due to low risk, or avoiding bad choices on a year’s worth of drugs. Then the question is, how much of a person’s genome can we sequence for $10,000? Seven thousand dollars will buy you a million base pairs of DNA [using conventional technology], which is one-6,000th of your diploid genome. Not very much.
Polony sequencing [a method developed by Church and colleagues] is about a hundred times less expensive. So you can sequence about 1 percent of the genome [for $10,000]. That’s not bad. You could focus on likely places you’re going to have problems.We got a factor-of-ten improvement in the last six months, so if we could get another 10 percent improvement in the next year, that would give us 10 percent of the genome. If we could pick 10 percent of the genome for which we have lifestyle, nutritional, or synthetic solutions, that would be a good deliverable for a $10,000 investment. And it will just get better from there.
TR: We jumped from synthesis to sequencing.
GC: I do that all the time. It may sound like a wordplay, but it is actually a very fundamental concept. There is almost no synthesis that doesn’t involve sequencing, and vice versa. And that is why I have really emphasized this connection in my lab. They are very synergistic.
Home page photo credit: Mark Ostow
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