He’s Gleaning the Design Rules of Life to Re-Create It

With the current technology, you can make transgenic organisms by editing. But you do not really have complete freedom of expression. That’s because you are relying on natural templates to tinker with.

What’s your approach to writing the first draft of the synthetic yeast genome?

The way to write the genome is piece by piece. You take an existing book chapter; you rewrite the first paragraph, and then you put that into the cell. Now the yeast becomes your proofreader. The yeast will start reading your rewritten first paragraph and say, “Does this make sense?” If it doesn’t make sense, the yeast will complain. It’ll become sick, or it will become unviable.

You do that paragraph by paragraph, and eventually you end up with a new chapter.

Imagine that yeast has 16 chapters, which are its 16 chromosomes. So each of us [on the team], we take one chapter, and we write paragraph by paragraph. This is a bottom-up approach to rewriting the genome.

How are you coming up with the design blueprint of the new synthetic genome?

We don’t use Scramble to write the genome. But we use Scramble to devise new genomes.

If you see the yeast genome as a deck of cards, where each card is a gene, this Scramble system allows you to shuffle the order of the cards, to invert some cards, to throw away some cards, to duplicate some cards. The genome reshuffling technology Scramble gives you an opportunity to systematically sample all combinations possible. So instead of making one genome, you’re effectively making billions of genomes at the same time.