Sunday, 4 September 2011

It's not The Central Dogma, my dear Watson

Long before James Watson was stirring up controversy for making comments that could be construed as sexist, racist and pro-eugenics, he was creating problems of another kind. Problems that are still haunting molecular biologists to this day. Problems with The Central Dogma of Molecular Biology.

The "Central Dogma" is something that gets attacked on a regular basis. Attacks come both from scientists and Creationists. The former are trying to sex up their science a little in order to catch the eye of an editor from a "high impact" journal, or science news site. The latter get hung up on the term "dogma", under the mis-guided belief that overturning one cherished idea of contemporary biology somehow invalidates the rest, including evolution.

So, what is The Central Dogma [ominous timpani drum roll]? And why/how does it get attacked so much?

I must confess that I didn't really understand the fuss until I read an old post about it on Larry Moran's blog, Sandwalk. Why do people keep refuting/attacking an idea that is so obviously wrong? Furthermore, why is there still "The Central Dogma" if it is obviously wrong and gets refuted every couple of years? To be frank, I didn't concern myself too much with it because I am much more interested in ideas and mechanisms than the names given to those ideas and mechanisms. Now that I know what the problem is, however, I realise that I have a responsibility to help do something about it - at the very least to make sure that I teach my students the right thing.

The answer, it turns out, is disturbingly simple. When "The Central Dogma" gets refuted every few years, they aren't refuting The Central Dogma. At least, they are not refuting it as originally defined by genius and polymath, Francis Crick. Instead, they are refuting a badly redefined version his once student, James Watson. (I may be a bit harsh on James Watson but it seems very clear to me who the real brains behind the operation was.) Meanwhile, the original "proper" Central Dogma still hangs around because it has never been refuted.

Crick's original is defined thus:

"The Central Dogma. This states that once “information” has passed into protein it cannot get out again. In more detail, the transfer of information from nucleic acid to nucleic acid, or from nucleic acid to protein may be possible, but transfer from protein to protein, or from protein to nucleic acid is impossible. Information means here the precise determination of sequence, either of bases in the nucleic acid or of amino acid residues in the protein."

Crick, F.H.C. (1958) On protein synthesis. Symp. Soc. Exp. Biol. XII:138-163 quoted in Judson, H.F. The Eight Day of Creation, Expanded Edition (1979, 1996) p. 332. (quoted on Sandwalk blog.)

Note that it is explicitly sequence information that cannot get out again. In other words, a protein sequence is never reverse-engineered into the nucleotide sequence that encoded it. In a nutshell, there is no reverse translation. Now, that doesn't seem like a big deal to us now, precisely because it has not been disproven in over sixty years, but it was not such a trivial statement at the time.

The Watson version, which sadly gets repeated in lots of biochemistry textbooks (and I may have even repeated myself in the past), is just the sequential flow of genetic information during transcription and translation, e.g. DNA → RNA → protein, published in his 1965 book [Watson, J.D. (1965) The Molecular Biology of the Gene. W.A. Benjamin. Inc. New York]. This is the version that keeps getting "refuted" by reverse transcription, epigenetic etc. This model is not wrong - it does happen - but it is certainly not the only flow of information. Nucleotides and proteins both pass information to both nucleotides and proteins. But this is old news and certainly does not challenge any of the core principles of modern molecular biology or evolutionary theory. To pretend otherwise, is just dishonest. (Or ignorant.)

Larry Moran ends his blog post by appealing to all teachers of biochemistry and molecular biology to explicitly adopt the "correct" Crick version. After all, (a) he defined it first, and (b) his is right as a universal principle. I am inclined to agree and will be sure to point out the difference to my students in future. And if you come across authors claiming to have refuted "The Central Dogma", ask them: have you really?!

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