Life from Scratch

Not read it. Write it. Synthesize a complete human genome—all three billion base pairs—from scratch. Build the source code of a human being the way a programmer writes software: nucleotide by nucleotide, codon by codon, chromosome by chromosome.

They called it the Genome Project-Write, a conscious callback to the Human Genome Project, which spent thirteen years and $2.7 billion to read the genome. That project finished in 2003. The scientists who launched GP-Write thought we were ready for the next step: if we can read it, can we write it?

The question sounds straightforward. It is not.

Reading a genome is like decoding an existing book. Writing one is like composing it. And the human genome isn't a neat program—it's three billion years of accumulated edits, evolutionary patches, redundant code, and regulatory instructions we still don't fully understand. We have genes whose function we know, vast stretches we initially called "junk DNA" (we were wrong about that), and regulatory networks so complex that single nucleotide changes can cascade into entirely different organisms.

The GP-Write consortium wasn't naive about this. The stated goal wasn't to build a human being—it was to build the capacity to write large-scale genomes as a research tool. Synthesize chromosomes to test hypotheses about what sections do. Engineer disease-resistant cell lines. Develop organisms that could produce medicines. The genome-from-scratch ambition was partly symbolic: a declaration that we'd moved from reading biology to writing it.

What makes this genuinely strange is the time scale problem.

Evolution wrote the human genome across approximately 3.8 billion years of trial-and-error. Every base pair is there because organisms without it died before reproducing. The genome is, in a sense, a four-billion-year compressed archive of survival strategies—encoding everything from how to make a heart valve to how to respond to stress to why humans are inexplicably bad at synthesizing certain vitamins.

We proposed to understand it well enough to write it in a decade.

There's a flavor of cosmic comedy here worth sitting with. Not the arrogance of it, exactly—scientific ambition isn't arrogance, it's just optimism with equipment. But the gap between "we can sequence a genome" and "we can write one that works" is the gap between being able to read Ulysses and being able to write it. Except Ulysses wasn't written by four billion years of death.

The honest answer, a decade on from GP-Write's launch, is that we've made extraordinary progress in the components—synthetic chromosomes in yeast, minimal bacterial genomes, increasingly sophisticated gene-writing tools—while the full ambition remains genuinely, appropriately hard.

Which is exactly where you'd want to be.

Science is most interesting at the edge where ambition outruns current capacity, but just barely. That gap is where the strange things happen. GP-Write put a flag in that territory in 2016. The terrain is still being mapped.

The universe's source code is being reverse-engineered. Nobody knows yet if it's truly writable. The three billion years of trial-and-error are unimpressed either way.

i · sources

• The Genome Project-Write — Science, 2016-06-02