Monday, August 10, 2015

Is The World Ready for Digital DNA?

Sixty-year-olds don't often have children, but we are witnessing the birth of a new field of engineering made possible by the marriage of two discoveries that date from the 1950s:  DNA and the integrated circuit.  In a recent article in the San Jose Mercury News, Emily Leproust, CEO of Twist Bioscience, is quoted as saying that her company can manufacture DNA to order, letter by letter.  They do this by using advanced microstructures and computing power made possible by the semiconductor-chip revolution to synthesize DNA based on concepts drawn from the latest biological discoveries.  According to her claims, the possibilities, as the saying goes, are endless:  everything from tailor-made vaccines targeted at the latest flu-virus strain to weirder ideas like nice-smelling bacteria to grow on your skin as a perpetual perfume.  But is this capability really "designing life from scratch," as the headline claims?  And will it really lead to the kinds of radical advances in manufacturing and materials science that its promoters are talking about, without opening the door to some dire consequences as well?

First, we should get straight what companies like Twist Bioscience are really doing.  Say you're a biologist who wants a particular genetic sequence for some reason or other.  In the past, you'd have to find large chunks of what you want lying around and splice them together, sort of like editing a documentary video out of existing footage.  A lot has already been done in this way under the general name of genetic engineering, leading to things like disease-resistant crops, fluorescent fish in bright artificial colors, and so on.  But what Twist Bioscience and similar firms are doing is more like making an animated film, frame by frame.  Each frame (i. e. letter in the genetic sequence) can be whatever you want, and so you can literally get whatever gene you ask for. 

The problem in this novel situation is knowing what to ask for.  And here's where we have to stand back at the designing-life-from-scratch claim and think twice about it. 

 No engineering design is truly de novo—totally original—if for no other reason than the designer has to remain within the constraints of the physics and mathematics of what is possible to design.  If your bridge design ignores the rated strength of the materials used in its construction, it's likely to fall down.  Making DNA that will do a prescribed task in a living cell is a highly constrained problem—constrained by the existing design of the target cell.  Currently, we have adequate (but probably not exhaustive) knowledge of the functions of only a few types of cells—bacteria, mostly—knowledge that is enough to allow us to manipulate their machinery with custom DNA to do things we want.  But we didn't design the cells that the synthetic DNA is going into. 

Most people not handicapped with a Ph. D. can see that there is a Designer behind the unfathomably complex thing that is biological life on this planet.  No human being can claim to have designed an existing cell from scratch.  Clients of Twist Bioscience ordering their customized DNA molecules are like programmers who have laboriously learned an operating system language and are now ready to program a computer they had no hand in designing.  As every coder knows, one little comma in the wrong place can wreck the whole program, and that is why checking and accuracy are so important to DNA synthesis—cells can be as unforgiving as computers when it comes to mistakes.

Fortunately, most mistakes along these lines simply die, or fail to achieve the goal that the designer aimed at.  But along with all the wonderful promises of fantastic new materials comes the downside question:  when and how will the ability to synthesize DNA be used for evil as well as good?

And some answers to that question might not be as simple as the melodramatic picture of some anarchic radical cooking up a kill-everybody-in-sight germ in his secret laboratory.  Take one of the ostensibly good predictions touted by synthetic DNA's promoters:  the ability to make bacteria that would crank out meat and milk without the tedious inconvenience of raising cows or pigs or chickens.

Suppose synthetic milk that is every bit as good as the real thing becomes something you could do in a chemical plant for one-tenth the cost of the way dairy farms do it.  The dairy farmers would immediately find themselves in the position of slide-rule manufacturers when the first cheap electronic calculators hit the market.  Only there are a lot more dairy farmers around the world than there were slide-rule makers.  To a dairy farmer, this so-called advance that the synthetic DNA promoters call a good thing, looks a lot like an evil thing.  Unless some social or governmental factor intervenes, the dairy farmers would simply be out of luck and would have to find some other way to make a living.

This situation reminds me of one of the best classic Ealing comedies of the 1950s:  the Alec Guinness film "The Man In the White Suit."  It was made at a time when postwar industrial Britain was feeling threatened by technological advances.  The story concerned a nerdy chemist played by Guinness who discovered a way to make a type of cloth that never stained, never tore or wore out, and appeared to be capable of lasting forever.  His escapades with unsympathetic managers, union leaders, and other interested parties lead both to some hilarious scenes, and also to a serious point, encapsulated in an encounter he has toward the end of the film with an old, broken-down woman who ekes out a living taking in washing.  Having heard of his invention, she confronts him and asks, "What about me bit of washin', eh?"  What, indeed.

The film avoided a serious answer to this question (spoiler alert!) by giving the cloth a shelf life of only a month or so, and when all existing samples self-destructed, life went back to normal.  But we may not have such an easy out with the products of synthetic DNA.  Throughout history, ways of life have come and gone in response to technological advances, and at this time, it doesn't seem that synthetic DNA is about to plunge us either into a secular Paradise or Hell on earth.  But as its products prove themselves in the marketplace and begin to disrupt older ways of doing things, we may have to decide where designing ends and meddling begins.

Sources:  The article "Designing life from scratch: A fledgling field is about to take off" by Lisa M. Krieger appeared on Aug. 8, 2015 on the San Jose Mercury News website at  I also referred to the Twist Bioscience website at, the Wikipedia articles on recombinant DNA and artificial gene synthesis, and the Internet Movie Database article on "The Man In the White Suit."

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