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Responses to the ENCODE Project: When Scientists Have to Deal with Beetles in Boxes

How is the word “function” like a beetle in a box? No, this isn’t a twist on the Mad Hatter’s “Why is a raven like a writing desk?”

As I’ve covered in a previous blog, the ENCODE Project released some astounding results of their multi-year study last September, claiming that approximately 80% of the human genome is functional. Following this, numerous statements were made that hailed the death of “junk DNA”. In response, the findings have received a heavy backlash from many scientists who disagree with the interpretations of the results and have since tried to, shall we say, reanimate junk DNA from beyond the grave. And as far as potential paradigmatic shifts are concerned, from my vantage point it seems they’ve been fairly successfully quashed (to my own chagrin).

One of junk DNA’s more outspoken proponents, Dan Graur, an evolutionary molecular biologist working at the University of Houston, has published a notable rebuttal in the journal, Genome Biology and Evolution. In it, he argues that the grandest flaw within the consortium project methodology was its selected definition of the term “function”. ENCODE opted to define it by three primary variables in which a DNA sequence was considered “functional” if it:

1) produces an RNA transcript 2) binds a protein 3) is methylated.

Graur, in contrast, argues that functionality should be defined by sequence conservation according to population genetics, which he says gives a better indication of function over evolutionary time. From his definition, this would indicate that only approximately 10% of the human genome is functional.

Who is correct?

Language is an exceptionally complex, cultural, and personal thing. It’s a symbolic abstraction which we use to communicate ideas to one another. And yet language is so embedded in our ways of life that it can take on a feeling of concretion, like it’s as real as the cells we use it to describe. To understand precisely why scientists are arguing so fervently with one another over “function” and why this is providing such a challenge to the communication of biological concepts, we can glean some help from the great linguistic philosopher, Ludwig Wittgenstein.

To give us some clarity through metaphor, Wittgenstein would place a small box before each of us. In each box, respectively, is something each of us would term a “beetle”. We examine the “beetles” in our own boxes and then we talk of our “beetles” with one another. But each person, regardless of the term, may have something entirely different in his box. One may have a beetle, another a spider, another a piece of string, and another perhaps nothing at all. The point which is made is that the definition of a “beetle” is unique to each individual, a “private language” as philosophy calls it. Meanwhile, the means to communicate our concept of beetle, the word “beetle” itself, is part of a common language. But the common language, at best, is a broader schema which can communicate general concepts but breaks down when one attempts to derive a precise universal definition for an idea.

The same problems we have in attempting to define “love” or “pain” scientists are currently having in defining the word “function” and even “junk DNA”. While there may be some overlap, obviously not everybody can agree. ENCODE has one definition of functional, Graur another. Neither is necessarily wrong. Although that’s not to say that one definition may not be more useful than another under different circumstances of investigation.

What is simultaneously interesting and frustrating is that scientists are spending a hell of a lot of energy  vehemently arguing over who is wrong, when the problem is primarily one of language, not of science. And it’s a worthy passtime for Philosophers of Science to study, but is it really a good allocation of time for scientists? It seems to me that arguing in circles over words doesn’t get us very far in understanding the implications of the ENCODE studies, neither their flaws nor their relevance.

Let’s face it, everybody probably has a slightly different definition of “function”. I know mine would match neither of the above. And in this instance I think it would be useful for scientists to acknowledge those inherent differences. Treating the term “functional” as a concrete identifiable entity will only lead to further confusions, raised tempers, and bruised egos. Look at the debacle so far.

#humangenome #linguisticphilosophy #privatelanguagearguments #aboutgenes #genetics #junkDNA #elephantintheroom #PhilosophicalInvestigations #beetleinabox #logicalpositivism #DNAtopology #privatelanguageargument #Wittgenstein #language #complexity #DanGraur #function #ordinarylanguagephilosophy #evolution #DNA #LudwigWittgenstein #ENCODE #RNA #DNAmethylation #DNAsequence #functional #humanDNA


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