Greetings from hibernation nation. I did say I’d come out if something really big happened. Guess what? One of my current scientific obsessions was Big News today! No, don’t go away – it’s not the microbiome. It’s my other obsession: junk DNA. I’ve written about it before, here and here and here.

In a stunning “no doh?” development, a vast international array of researchers has discovered that the 99% of the human genome that was considered “useless junk” isn’t junk after all.

Here’s the story: when the human genome was decoded somewhere around the turn of the present century we were able to identify all the genes responsible for encoding the proteins in our bodies. The gene for insulin causes a cell to manufacture insulin, etcetera. This is Very Important because proteins are what make us function. Enzymes? hormones? Antibodies? All proteins. Without proteins life wouldn’t exist. Even slime molds  and politicians are made of proteins.

This exciting news was jumped upon like candy out of a pinata. Now we know all the genes! Now we can pinpoint which genes cause disease! Now we have Drug Targets! The End of Disease is just around the corner! A whole new industry was born as people rushed off to get their genomes sequenced at great expense, eager to see what diseases lay in wait for them down the road and how they could try and outwit their “genetic destiny.”

There was just one glitch. It turns out that only about 1% of our DNA is actually involved in encoding proteins. The other 99% was a total mystery. Nobody could figure out what it did. For lack of a better alternative, or perhaps just wanting to wrap things up and retire, scientists concluded in a colossal fit of hubris that all this DNA was probably just nonfunctional filler.

As so often happens in science, what we thought was the Holy Grail –  decoding the human genome will end all disease!  – turned out to be more like a plastic sippy cup. Pinpointing genes involved in disease turned into a massive game of whack-a-mole; most diseases like cancer involve complicated interactions between many genes. We knew all the genes but we still couldn’t figure the puzzle out. Drug development stalled.

In 2003, a vast international project code-named ENCODE started to look at the other 99%. (One journalist cleverly called it the “occupy” movement of genetics.) The results of that research are now starting to emerge; Nature has a batch of (open access!) papers and a whole web page out this week if you’re interested in reading esoteric biological gobbledygook.

If, like me, you’re not, here’s what the newspapers are saying: the majority of what we thought was “junk” DNA is in fact an enormous network of switches. This seemingly random assemblage of nucleotides is responsible for turning the coding genes – the 1% –  on and off, and, to take the electrical metaphor even further, dimming and brightening their level of expression.

To make things even more interesting, scientists also realized that the three-dimensional structure of DNA was important. The 10 feet of DNA in each of our cells is endlessly coiled up upon itself into a vanishingly tiny volume; as one scientist described it (in a mastery of mixed metaphor) “It is like opening a wiring closet and seeing a hairball of wires.”

When stretched out into a long line of C,G,A and Ts, (which is how geneticists “look” at the genome in order to decode it), the switch bits are often far removed from the coding bits. Back in hairball formation, however, they’re right next door. Things were starting to make more sense.

They also discovered that “transcription factors” were racing around the hairball like rambunctious children, flipping and dimming the switches in response to environmental cues. This, I think, (remember, I’m no biologist) is what’s known as “epigenetics” – when factors external to a particular organism cause changes in genetic expression.

This would explain some mysteries – for example, why in twins who have exactly the same genetic material, one twin will develop disease and the other won’t. Something in the environment of the unlucky twin has caused a naughty transcription factor to flip a switch.

Predictably, the press and the scientists are once again in pinata mode. Personalized Medicine and the End of Disease are Just Around the Corner! Targeting individual genes was a wash, but now we can design drugs to target the switches!

If you can ignore all the drug development hype, however, I still think the news is good. Number one, the scientists are being humble; they admit there is much they do not understand, such as the 30,000 genes that encode RNA strands, whose role in the cell is still a mystery. There’s not really much talk about Holy Grails any more. (They’re leaving that to the Higgs chasers). Number two, it’s not all about drugs. Here’s one sentence (out of a 2-page article) in the New York Times version of the story:

[The findings] can also help explain how the environment can affect disease risk.”

That’s, in a nutshell, what I find really interesting here. Not finding the switches and then figuring out how to circumvent them pharmaceutically. That’s like being in a dark room, having someone come and turn on the lights, but then immediately someone comes and turns the lights off again. Chances are, if it’s an important room, there’s more than one switch and we’re back to whack-a-mole. (See, I can mix metaphors too!)

Seems to me if an autoimmune disease switch is flipped, there’s probably a good reason for it. Maybe if we don’t put the cell in a bad place to begin with, the disease-causing switch won’t be flipped in the first place? Just saying.

I hope that’s what the researchers will study. But I doubt it. Number one, a lot of research money flows from pharma and they don’t make money if people get healthier. Number two, it’s way easier to study individual switches in the lab than it is to untangle the hairball of what’s going on in the environment and how it might be affecting the transcription factors. Scientists need to publish papers. They’re going to go after the switches, trust me.

Google “encode news” if you’re interested; there’s lots of press.

Image: http://www.westpawdesign.com/catalog/cats/best-cat-toys/catnip-cat-toys/hair-ball

(PS – why would someone sell a hairball cat toy? Do we really want them playing with hairballs? Ick.)