Biomickwatson's Ridiculous Criticism of ENCODE Critics

Biomickwatson's Ridiculous Criticism of ENCODE Critics

We are not sure why intelligent scientists need to post rather inane commentaries in their blogs to get public attention.

The context here is biomicwatson’s response to the latest Genome Biology and Evolution paper mentioned in our previous commentary. The paper not only challenged ENCODE’s hyped up claim of 80% functionality of human genome, it did so in a way that makes you laugh. These days, you rarely read a funny scientific paper that is not light on its technical correct.

Biomickwatson is upset because we laughed, and he blames the little child, who called out the emperor naked. In his blog, he posted a mock letter from Dan Graur (first author of paper criticizing ENCODE). In fact, the mock letter was written in a funny way and we enjoyed it. However, that is the only positive aspect of his commentary. We also expected him to provide some serious criticism of Dan Graur’s technical discussions, and we did not find anything at all. Not only that, whenever someone pointed out in the comment section he agreed with Dan Graur’s scientific content, Biomickwatson repeated ‘I do not like the tone’, ‘I do not like the tone’ like a parrot. At some point, we started to wonder whether real biomickwatson left town and a computer program took over the blog.

Getting back to Graur paper, we finished reading it and found the scientific argument very solid irrespective of its mocking abstract. In fact, tone of abstract and paper fitted its content perfectly. The question was to whether ENCODE authors pre-determined the percentage of genome they wanted to see as functional (guided by their desire to be on New York Times), and tweaked their definition of ‘functional’ to reach that number. That is what seems to be case, and Dan Graur paper was right in mocking that kind of PR-guided science.

The scariest part is that over 400 scientists signed their names on to ENCODE paper without questioning its overt media-whoring, because to them the grant money ENCODE brought likely justified being sloppy on science. In an earlier era, science took precedence over money. Today ‘getting the grant’ is top priority and science can be adjusted accordingly.

ENCODE decided to inflate the ‘functional content’ of human genome by calling a region functional, whenever it was captured by any of the large-scale experiments (DNA-methylation, CHiP-chip, histone methylation, etc.). Having taken part in several large-scale studies over the last 10 years, we can shed some light on the thinking process that goes behind them.

Step 1. Let us write a huge grant and request for all kinds of large-scale experiments - “sequence all cancer genomes”, “sequence every inch of soil on earth”, etc.

Step 2. Grant is approved. Large-scale data collection begins.

Step 3. We have tons of data. Now we need a ‘high-impact’ paper, or otherwise we will not get the next big grant.

We do not have any problem with steps 1 and 2, but step 3 is where everything gets fast and loose. There are two ways to achieve 3 - through careful science or by using PR. The science-based way requires researchers to dig through the data, find interesting patterns and run small-scale experiments. Even after that, a high-impact publication is not guaranteed. PR approach is to sell the fact that the researchers collected huge amount of data and only needs to invent a punchline. The 80% functionality of human genome is the punchline that got ENCODE to NY Times and potentially secures their next wasteful grant. Whether researchers are still doing science after five or six iterations of above process is a big question.

‘Off camera’, most scientists acknowledge the above process, but they all wimp out, when they have to do the same publicly (as you can see here in Titus Brown’s ‘why I blog’ commentary). After all, who wants to offend 400+ scientists, who would be sitting in his grant committees and reject their grants, because he made legitimate criticism of their research? From that view point, it was rather courageous of Dan Graur and colleagues to point out ENCODE’s ridiculous claims in a paper, and put their names in it.

We can easily answer the question posed by Graur et al. here -

At this point, we must ask ourselves, what is the aim of ENCODE: Is it to identify every possible functional element at the expense of increasing the number of elements that are falsely identified as functional? Or is it to create a list of functional elements that is as free of false positives as possible. If the former, then sensitivity should be favored over selectivity; if the latter then selectivity should be favored over sensitivity. ENCODE chose to bias its results by excessively favoring sensitivity over specificity. In fact, they could have saved millions of dollars and many thousands of research hours by ignoring selectivity altogether, and proclaiming a priori that 100% of the genome is functional. Not one functional element would have been missed by using this procedure.

ENCODE’s aim is to get their next huge grant approved and they need public attention.

We enjoyed Dar Graur’s discussion on why junk DNA was called junk DNA in the first place. The word junk was not used in derogatory sense (such as junk mail) and was more like junk sitting in someone’s garage.

If there was a single succinct take-home message of the ENCODE consortium, it was the battle cry Junk DNA is Dead! Actually a surprisingly large number of scientists have had their knickers in a twist over junk DNA ever since the term was coined by Susumu Ohno (1972). The dislike for the term became more evident following the disappointing finding that protein-coding genes occupy only a minuscule fraction of the human genome.

The paucity of protein-coding genes in the human genome in conjunction with the fact that the lowly nematode Caenorhabditis elegans turned out to have 20,517 protein-coding genes, resulted in a puzzling situation similar to the C-value paradox (Thomas 1971), whereby the number of genes did not sit well with the perceived complexity of the human organism. Thus, junk DNA had to go.

First, we note that Susumu Ohnos original definition of junk DNA referred to a

genomic segment on which selection does not operate (Ohno 1972). The correct usage implies a genomic segment that has no immediate use, but that might occasionally acquire a useful function in the future. This sense of the word is very similar to the colloquial meaning of junk, such as when a person mentions a garage full of junk, in which the implication is that the space is full of useless objects, but that in the future some of them may be useful. Of course, as in the case of the garage full of junk, the vast majority of junk DNA will never acquire a function. This sense of the term junk DNA was used by Franois Jacob in his famous paper Evolution and Tinkering (Jacob 1977): [N]atural selection does not work as an engineer… It works like a tinkerera tinkerer who does not know exactly what he is going to produce but uses whatever he finds around him whether it be pieces of string, fragments of wood, or old cardboards… The tinkerer… manages with odds and ends. What he ultimately produces is generally related to no special project, and it results from a series of contingent events, of all the opportunities he had to enrich his stock with leftovers.

It is accepted that humans are the most complex of all creatures and therefore they should have had the most number of genes. When that did not work out, the complexity was supposed to be reflected by almost 100% of genome being ‘functional’. Interestingly, that struggle to ‘prove’ that human genome is the most complex of all brought ENCODE and creationists arguing for the same thing, as Dan Graur pointed out -

We urge biologists not be afraid of junk DNA. The only people that should be afraid are those claiming that natural processes are insufficient to explain life and that evolutionary theory should be supplemented or supplanted by an intelligent designer (e.g., Dembski 1998; Wells 2004). ENCODEs take-home message that everything has a function implies purpose, and purpose is the only thing that evolution cannot provide.

We request everyone to read and think through Dan Graur’s paper, and then request government to stop funding ENCODE to get back our scientists.



1. PZ Myers posted a good summary of Dan Graur’s paper that we recommend for our readers -

ENCODE gets a public reaming

2. Thanks to @jaredtsimpson for pointing out that the Graur paper was in Genome Biology and Evolution. We made the changes in text.

Written by M. //