Horace Judson (1931 - 2011)

Horace Freeland Judson died on May 6, 2011. He is best known as the author of The Eighth Day of Creation first published in 1979 and later re-published in an expanded edition in 1996. This is a "must-read" book for all students of biochemistry and molecular biology.

Mark Ptashne has published an obituary in PLoS Biology [Horace Judson (1931 - 2011)]. Ptashne raises an issue that should be of concern to all biological scientists; namely, the fact that modern molecular biologists seem to be completely unaware of the history of their field and of all the fundamental work done with bacteria and bacteriophage. This was a problem that Judson tried hard to rectify before it was too late but it's beginning to look like he was not successful.

Here's Ptashne's take on it.

The Eighth Day, first published in 1979, is a gift that keeps on giving. It is not the completeness of his history, nor even the vivid prose that imparts its lasting effect. Rather, Judson had the drive and wit to probe until he understood not just who did what, and with what quirks of personality, but why they did it, and how they did it. At each stage he reveals what was at stake, what the crucial alternatives were, and how the problems were solved (or not, as the case may be). Who cares about this past, you might ask, we scientists being neither artists nor composers?

Could it be that—for scientists as well as composers and artists—the past can be a source of inspiration, and that we ignore it at our peril? Consider the question of how states of gene expression are conveyed from mother to daughters as cells divide. Are instructions passed along by regulatory proteins present in the cytoplasm (so-called “cytoplasmic determinants”), or is the information somehow built into, or attached to, the DNA and transferred along with it? Experiments performed by Francois Jacob and Jacques Monod and their colleagues at the Institut Pasteur in the 1960s distinguish between the models, strikingly supporting the first of these possibilities. These experiments (including the famous “zygotic induction” and “PaJaMa” experiments—see Judson's book) were, of course, performed with bacteria.

I recently spoke with an editor of a major journal that regularly publishes sensational papers on the question as it applies to higher organisms, and learned that s/he, like many of the journal's authors, had never heard of these bacterial experiments! You realize, reading Judson's book, that the challenge is to engage the thought processes of these French scientists, ponder their approaches and results, and design experiments of comparable power and clarity to confirm or refute their conclusions in a different setting. Without that engagement, the new answers are apt to be (and in my opinion usually are) baloney.

Shortly after I read this obituary I was browsing Biology News Net and came across this remarkable opening statement in a press release from Stowers Institute for Medical Research in Kansas City, Missouri, USA.

Look up “transcription”—the copying of a gene’s DNA into RNA intermediaries—in any old molecular biology text book, and it all seems very simple: RNA polymerase II, the enzyme that catalyzes the reaction, assembles at the start site and starts motoring down the strand, cranking out the RNA ribbon used to construct proteins. But researchers now know that RNA polymerase II often stalls on DNA strands where it was once assumed to just barrel down.

A report from the Conaway lab at the Stowers Institute for Medical Research in the July 8, 2011, edition of the journal Cell identifies a switch that allows RNA polymerase to shift gears from neutral into drive and start transcribing. This work sheds light on a process fundamental to all plant or animal cells and suggests how transcriptional anomalies could give rise to tumors.

This is a very misleading statement. Back in 1989 I wrote an extensive section on "RNA Polymerase Pauses While Transcribing Some Sequences" in my first textbook. I described the effects of sequence and secondary structure on the rate of elongation and explained how a protein component of the the transcription complex (NusA) promotes pausing in order to enhance transcription termination. The idea that rates of elongation were NOT constant was an important part of most molecular biology textbooks.

But this was in bacteria (E. coli), where most of these fundamental discoveries were first made. The press release refers specifically to eukaryotic RNA polymerase II. In the second edition of my textbook (1994) I talked about RNA polymerase II elongation factors (eukaryotes) and specifically mentioned that "TFIIS may play a role in pausing and transcription termination that is similar to the role of NusA in bacteria." The point is that older molecular biology textbooks were well aware of the fact that even the eukaryotic transcription elongation complexes did not move at a constant rate. The press release is quite incorrect.

The actual paper is not about transcription elongation but transcription initiation and how various factors assist in the transfer from the initiation complex to the elongation complex. All this was known for transcription in E. coli back in the 1970s. The old molecular biology textbooks explain abortive initiation and how RNA polymerase can stall at initiation sites until sigma factors are replaced by elongation factors. None of that is new in spite of what the press release implies.

How does this happen? I think it's because modern researchers are completely unaware of the history of their field. That's partly because the work on bacteria and bacteriophage—where the basic concepts were often discovered—is no longer taught in biochemistry and molecular biology courses. This leads to the false idea, as expressed in the press release, that all new discoveries in eukaryotes are truly new concepts that nobody ever thought of before.

The solution to this problem is to make all students read The Eighth Day of Creation.

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