Musings of a Cancer Doctor

Wide-ranging views and perspective from George W. Sledge, Jr., MD

Monday, September 17, 2012

On Junk

There is a delightful (delightful in a schadenfreude sort of way) reality cable TV show called Hoarders, which I watch every now and then when I need cheering up. The show’s plot is stereotypical and easily summarized:

1.      We meet the hoarder and see his or her home. The home is usually an unruly and dangerous riot of stuff, covering every square inch of space and piled to the ceiling.

2.      The hoarder is confronted with the reality of his or her situation, with an intervention involving concerned relatives or friends, and a behavioral psychologist (all of whom identify themselves as being specialists in the field: a growth industry, apparently).

3.      The hoarder’s house is de-cluttered, and the hoarder undergoes extensive psychological counseling.

4.      Victory is declared, until the next show.


I said that Hoarders is delightful.  The delight comes, I must admit, from observing someone who is significantly messier than I am, and even more of a pack rat. Sometimes this inability to throw things out is so pathologic that it limits daily functioning, even endangering the hoarder.


We watch the show thinking “I’m not quite that bad yet,” or “Sure I’ve got books piled to the ceiling, but just one room,” or “There but for the grace of God go I.” And, in the back of our heads, while many of us have a lingering concern that Social Services might show up at out own door some day, it’s not today. I can still see the TV, after all.


Most (though not all) of the hoarders are single -- widowers, divorcees, loners ashamed of themselves -- with only the occasional couple.  While there is someone in this world for just about everyone, apparently it’s hard to actually find someone as messy as you who is willing to share his or her space.  Our spouses rein in our worst proclivities, as my wife would no doubt tell you. And, like most males in a long-term relationship, I am required to take out the trash every week, which places limits on how much I can hoard.


Every now and then, usually early in the decluttering process, the hoarder will rebel, stalking angrily around the housecleaners, breaking into fervent or plaintive argument (some real pathos there) with the psychologist or the kids: “That isn’t junk. Don’t throw that away. I need that.”


And what, after all, constitutes junk? Cable TV is filled with other shows devoted to the hidden treasures one find in antique stores and abandoned storage centers. One man’s junk is another’s treasure, or so Antiques Roadshow and Storage Wars assure me. 


The answer given by Hoarders is strictly functional: if you can’t move freely around your house, if you are in danger of being buried by a teetering column, or if the emergency responders can’t bring in the gurney to carry you out after you’ve been crushed, then you are dealing with junk, and it needs to go.


I thought of all this in reading about the recently published ENCODE data.  ENCODE (the Encyclopedia of DNA Elements) is a massive, decade-long international project (442 investigators at 32 institutions) aimed at understanding how our DNA works. Some 30 articles were published simultaneously outlining the project and its findings, with the lead articles (natch!) in Nature. I recommend, for a top-line review of the findings, Elizabeth Pennisi’s article in the September 7 issue of Science.


The headline from ENCODE involved junk DNA.  When the first human genome was decoded in 2001, molecular biologists were confronted with what seemed a cluttered, yet content-empty, landscape. Long stretches of the genome appeared irrelevant to existence: silent, nonfunctional, weighed down with trespasser retroviral DNA and evolutionary leftovers, with only rare protein-coding sequences. In fact, the number of protein-coding genes was not 100,000, as originally thought, but more like 21,000 (20,687 in the latest enumeration). Only about 3% of the human genome appeared active.


The thought arose that most of our DNA is junk.  Our chromosomes, it seemed, were the ultimate hoarders, unwilling or unable to get rid of the useless stuff.  That old behavioral psychologist, Mother Nature, was surprisingly ineffective at eliminating junk DNA. Where was Darwin when you needed him?


ENCODE throws these thoughts overboard. Basically, we mistook ignorance for absence.  The ENCODE investigators calculate that close to 80% of our DNA can be assigned a biological function.  Using the Hoarders definition, our DNA is almost remarkably non-hoardererish. I feel much better about my chromosomes.


While we tend to think of our DNA in terms of protein-coding exons, in fact a huge amount of our genetic code regulates other parts of our genetic code: a large, interactive set of massively parallel feedback loops. A genetic ecosystem, almost a jungle of interacting parts.


The implications for human cancer aren’t all in yet.  Certainly we already have some clues that the regulatory elements will prove important for cancer patients -- microRNAs and their many relatives have been implicated as control elements for many cancers. But ENCODE goes further, suggesting that it is shortsighted for us to focus solely on the exome. Whole new vistas are apparent, almost as if Rhode Island was found to have a back door opening on Texas.


I find this all quite remarkable, and fascinating.  Every time I open up Nature or Science or any of their sister publications, I remember how lucky I am to be living in the heroic age of genomic discovery. Even if, like some old Spaniard sitting on the dock watching the Santa Maria return from the New World in 1492, I am only an observer: it’s just so wonderful.


This isn’t the first time we have recognized our profound ignorance, nor will it be the last.  Remember when we were routinely told how “you only use 10% of your brain?” Well, sure, it’s still true for some people I know, but neuroscientists exploded that myth long ago: we are constantly using almost all of our brain, which explains why 3% of our body mass consumes 20% of our energy. The brain is highly organized, highly cross-linked, filled with redundancies, and it’s all there for a reason.


Other “junk” stories haven’t been told yet. The astrophysicists “dark energy” and “dark matter,” which make up the lion’s share of creation yet are invisible (currently) to human eyes seemingly fall into this category: it’s there (apparently, probably) but we cannot assign form or function to most of the universe. Or at least no function other than gravitational pull.


Does nature like junk, or is junk, as on Hoarders, solely in the eye of the beholder? And where does one draw the boundaries? Even in the ENCODE data what DNA one calls functional is something of a judgment call.


Science aside, I’ve learned, as I grow older, the extent to which our lives are filled with stuff, with things. Material objects are cheaper now than at any point in human history, so we accumulate rather than simplify. I imagine there were relatively fewer hoarders in 10th century England, and the few there were probably had very boring and relatively small junk collections. Hoarding is a very 21st century condition, the pathologic extreme of modern consumer society.


All pack rats I know dread throwing these things away -- you never know when that little knickknack you bought in 1985 might come in handy, might even, MacGyver-like, be lifesaving. And, since time immemorial, it has been the responsibility of our descendants to throw away all that useless stuff once we shuffle off this mortal coil.  I certainly did it for some of my relatives. So it’s not really my problem, right?


Having said that, I see someone standing at my office door, accompanied by several friends with concerned looks on their face, and a trash bin, so I’ll sign off now.