The ENCODE delusion

I can take it no more. I wanted to dig deeper into the good stuff done by the ENCODE consortium, and have been working my way through some of the papers (not an easy thing, either: I have a very high workload this term), but then I saw this declaration from the Electronic Frontier Foundation.

On September 19, the Ninth Circuit is set to hear new arguments in Haskell v. Harris, a case challenging California’s warrantless DNA collection program. Today EFF asked the court to consider ground-breaking new research that confirms for the first time that over 80% of our DNA that was once thought to have no function, actually plays a critical role in controlling how our cells, tissue and organs behave.

I am sympathetic to the cause the EFF is fighting for: they are opposing casual DNA sampling from arrestees as a violation of privacy, and it is. The forensic DNA tests done by police forces, however, do not involve sequencing the DNA, but only look at the arrangement of known variable stretches of repetitive DNA by looking at just the length of fragments cut by site-specific enzymes; they can indicate familial and even to some degree ethnic relationships, but not, as the EFF further claims, “behavioral tendencies and sexual orientation”. Furthermore, the claim that 80% of our genome has critical functional roles is outrageously bad science.

This hurts because I support the legal right to genetic privacy, and the EFF is trying to support it in court with hype and noise; their opposition should be able to easily find swarms of scientists who will demolish that argument, and any scientifically knowledgeable judge should be able to see right through the exaggerations (maybe they’re hoping for an ignorant judge?). That conclusion, that 80% of the genome is critical to function, is simply false, and it’s the notorious dishonest heart of ENCODE’s conclusions.

And then there is this lovely little commercial for ENCODE, narrated by Tim Minchin, and portraying ENCODE as a giant cancer-fighting robot.

Oh, jebus…that was terrible and cringeworthy. Not just the ridiculous exaggerations … the Human Genome Project also claimed that it would provide the answers to all of human disease, as has, to a lesser degree, most every biomedical grant proposal, it seems — but that they invested in some top-notch voice talent and professional animation to promote some fundamentally esoteric science to the general public as a magic bullet…I mean, robot.

Scientists, don’t do this. Do make the effort to communicate your work to the public, but don’t do it by talking down to them and by portraying your work in a way that is fundamentally dishonest and misleading. If you watch that video, ask yourself afterward: if I hadn’t read any of the background on that project, would I have the slightest idea what ENCODE was about from that cartoon? There was no usable information in there at all.

So what is ENCODE, actually? The name stands for Encyclopedia of DNA Elements, and it’s the next step beyond the Human Genome Project. The HGP assembled a raw map of the genome, a stream of As and Gs and Cs and Ts, and dumped it in our lap and told us that now we have to figure out what it means. ENCODE attempts to break down that stream, reading it bit by bit, and identifying what each piece does; this part binds to a histone, for instance, or this chunk is acetylated in kidney cells, or this bit is a switch to turn expression of Gene X off or on. It tries to identify which genes are active or inactive in various cell types. It goes beyond the canonical sequence to look at variation between individuals and cell types. It identifies particular genetic sequences associated with Crohn’s Disease or Multiple Sclerosis or that are modified in specific kinds of cancers.

ENCODE also looks at other species and does evolutionary comparisons. We can identify sequences that show signs of selection within the mammals, for instance, and ENCODE then maps those sequences onto proposed functions.

You know what? This is really cool and important stuff, and I’m genuinely glad it’s being done. It’s going to be incredibly useful information. But there are some unfortunate realities that have to be dealt with.

It’s also drop-dead boring stuff.

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