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You can't rewrite the human body like a computer program

Posted on 8 Feb 2013 at 09:46

Dick Pountain says hopes the human genome could be reprogrammed to eliminate disease are unfounded

Last night I watched the latest addition to the dismal genre of populist TV science programmes (I exclude Horizon, which at least attempts to be serious).

A not very funny Irish comedian/game-show host and a young journalist with a striking Bollywood coiffure were baiting the distinguished scientist, Sir John Sulston, because the human genome project hasn’t yet delivered cures for cancer and the common cold, despite spending so much of "our taxpayers' money".

Sir John grinned weakly and bore it, even admitting that scientists sometimes play on the ignorance of politicians to obtain funding, but his main rebuttal was that the way genes work is far more complicated than either the public or even geneticists understand. This "backlash" thinking arises because we have perhaps imagined the genome as a cookbook, where all you have to do is read off a recipe and bake it.

Anyone who has written computer programs in anger will know that self-modifying programs are best avoided

Our bodies contain several separate but co-operating information processing systems – the nervous (including the brain), immune, muscular, metabolic and skeletal systems, plus the DNA itself – which form a complex heterogeneous network, talking to each other via nerves, hormones and other chemical signals. Recently the ENCODE (ENCyclopedia Of DNA Elements) project has highlighted just how complex: the sequence of base pairs in DNA encodes only a small fraction of the information required to run our bodies, and the huge stretches of what used to be called "junk DNA" are actually switches that modify the "runtime" course of the computations.

We’re built mostly of proteins, and protein-based enzymes control almost all of our cellular chemistry. Genes are templates from which these proteins are fabricated, and although every cell in your body contains a full copy of your genome, most of its genes are turned off. Otherwise, every cell would be churning out every possible protein all the time and you’d be a large (and very short-lived) sticky blob. Selectively turning genes on and off controls the activities of individual cells, which in turn determines how our bodies grow, survive and act in the world.

The decade-long ENCODE project (funded by the National Human Genome Research Institute) has identified the regions of the human genome where such controls operate, and in September 2012 it published 30 seminal papers that assign functions to 80% of the genome. Since this is a PC site, I won’t dwell on the details, beyond saying that control is exerted mostly through big proteins called histones sticking to DNA sequences to mask them from being expressed, or by methyl groups being added as stoppers to certain bases. (The journal Nature has a brilliant interactive widget if you want to know more). The result is that genetics became orders of magnitude more complex, which makes our impatience with the rate of medical spin-offs tragically misplaced.

We might once have pictured the genome as a computer program, which "executed" its genes to build our bodies and make us do stuff. Now we know it’s more like a database of blueprints for computer components, rather than program instructions. So where are the executables? Well, they’re proteins operating within particular cellular environments.

Those proteins are still made by DNA, and where and when they’re made depends on all those gene switches that ENCODE describes. Some of these instructions in turn control the way the DNA is transcribed, so it’s a dynamic, recursive, self-modifying program whose behaviour is generated on the fly rather than recorded in the DNA sequence (which is mostly static data, except occasionally when a mutation occurs or a virus inserts its own code).

Anyone who has written computer programs in anger will know that self-modifying programs are best avoided. Sure, when you’re a cocky newbie it feels clever to write self-modifying code, but it soon becomes impossible to debug or understand. Microsoft once flirted with self-modifying code for selecting different hardware options in early versions of Windows, but options are now set by reading in external config files.

So how does nature manage the dynamic, self-modifying computation system that’s a living organism? The answer is through 3.5 billion years of evolution, rather than studying algorithms. Snipping and inserting genes to cure a disease isn’t like editing program code – we’ve already seen one genetic medicine project halted because it gave the test subjects leukaemia.

Author: Dick Pountain