Sunday, July 17, 2011

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.


  1. "TFIIS may play a role in pausing and transcription termination that is similar to the role of NusA in bacteria."

    "...identifies a switch that allows RNA polymerase to shift gears from neutral into drive and start transcribing."

    It looks like your earlier idea was confirmed by the later study that actually identified the "switch" involved.

  2. I would love to read Eighth Day of Creation but it costs $30, new and used. Why is it still so high?

  3. That's right, we are now firmly into an era where professors who lecture don't know the history themselves.

    Almost ten years ago I discovered, to my dismay, that a graduate student in the lab didn't know what Hershey–Chase experiment was (nor, for that matter, Meselson-Stahl). Turns out, it wasn't part of his biochemistry. Since then, I ask the same question of most other students. 100% failure so far. N is probably around 7.

    Not knowing names is not really a problem. Problem is, most students/postdocs don't have an appreciation of how smart and inventive some of their predecessors were. The prevailing feeling seems to be "things were too easy and crude back then with their phages and E.coli". Not co-incidentally, this attitude is coupled with the approach to science as a series of tasks to be accomplished. I've come to hate the word "protocol" because most of the time it is part of the "I need a project and a series of protocols to apply to it; then, if I do it faithfully and carefully, my scientific task will be successfully accomplished".

  4. Encode keeps ignoring the history ( as well and is denying new data contradicting their conclusions. Their critics respond:

  5. And why is "cell biology" in courses and departments and textbooks always eukaryotic cell biology. Bacteria have cells too!!

  6. @Mark Pallen,

    It's even worse than you imagine. These "eukaryotic cell biology" courses are almost always about mammalian cells and, maybe, yeast cells. Plants and protists also have cells!

    Many introductory biochemistry courses are taught from the perspective of fuel metabolism and relevance to medicine. What this means is that we are graduating students who are completely unaware of the fundamental principles of biochemistry that apply to all species.

    We've talked about this problem before. For example, when transcription is taught properly, based on all the fundamental concepts discovered in bacteria, students will appreciate how RNA polymerase binds to DNA. They will understand non-specific binding and why spurious transcription is an expected property.

    If they are not taught properly they may grow up to become scientists who are completely ignorant of these fundamental concepts. These researchers may discover that most of the mammalian genome is transcribed at one time or another. Because they haven't been taught proper molecular biology, they may jump to a ridiculous conclusion. They may interpret this to mean that most of the genome has a function.

    Whose fault is this? It's OUR fault (university professors)! Unfortunately, I can't even convince my colleagues that there's a problem so there's little chance that we can fix it.

  7. I think the problem with leaving out the history is not terribly unique to biochemistry, though I certainly noticed eventually. I don't think it is even really a problem about knowing stuff. The bigger impact is that without the history, as Larry pointed out science is largely reduced to technological puzzle solving. History and biography are important for conveying all of those other parts about being a scientist to the next generation, at least as much as getting the concepts right.

  8. It's even worse in my field. Most synthetic biologists I know come from an engineering background, so not only are they ignorant of most of the older research in biology, they're proud of it.

  9. I use this book in my courses. I agree, it should be required material for any self-respecting molecular biologist (and derivatives).

  10. What this means is that we are graduating students who are completely unaware of the fundamental principles of biochemistry that apply to all species.

    Well... principles of biochemistry that were hoped to apply to all species, especially to medically relevant species like humans. I wouldn't begrudge the people that actually validate these "universal principles" their moment in the sun for finally establishing human biology relevance.

  11. I'm shocked to hear that these things are no longer taught. It seems to me the primary reason for teaching them isnt even the history, its the logic and elegance of the experiments which should inspire future generations. So much in mol bio seems to be massive data collection without a shred of creativity...but then again I'm old (48)

  12. "The Eighth Day of Creation" is one of my favorite books, both because Horace Freeland Judson was a brilliant author, and because I had some direct experience with the subject of the book, first as an undergraduate biology student from 1962 to 1966 and later as a graduate student working at first on gene regulation in bacteriophage lambda.

    I have read the book twice and for many years recommended it to students in my lectures on "gene technology", saying that it should be considered as the preface to the stuff I would tell them about. I'm not sure that any of them actually read it, but if they were ever to look again at the course notes I distributed, there would be a page with a picture of the book cover and in large print at the top, "Read this book!"

    Finally, the talent for good scientific writing has been passed down to another generation in the Judson family-- see the texts by H.F.'s daughter Olivia Judson.


  13. Anonymous said...
    I'm shocked to hear that these things are no longer taught. It seems to me the primary reason for teaching them isnt even the history, its the logic and elegance of the experiments which should inspire future generations. So much in mol bio seems to be massive data collection without a shred of creativity...but then again I'm old (48)

    Gasp! Are you me? You stole both the lines I use when defending my insistence that students read this book, and my age! Is this the twilight zone? The Matrix? Is there a spoon?

  14. I am at a small liberal arts college. On my campus, biology gets the "molecular biology" content. The course is all about the latest papers without critically thinking about what it means. Biochemistry is taught in the Chemistry department. Before I got there, polymerases were only taught in any depth by the Biology department. I now go into detail on structure/function & kinetics but regulation I still have to leave the molecular biology course. I am also the only one that discusses molecular evolution. At first the students dislike it but come around when they realize it really helps to understand biological macromolecules and the pathways we are covering.

    Wish I could get the biology department to do the same. Still haven't won them over on the sequence hypothesis distinction from the central dogma.

  15. But students are being taught to think for themselves. Right?

  16. Is the 1996 edition a great improvement on the 1979 edition? I ask only because I can get the 1979 edition for about $5 whereas the 1996 edition is $30. Does the 96 version add decent detail on the intervening years or is it only a new preface and end chapter as many updates seem to be?

  17. Negative Entropy said...

    "Gasp! Are you me?"

    Hmmm...I see you post at 4pm when I'm usually at work so unless there is some sort of Tyler Durden thing going on I doubt it.

    I have to admit I've never read EDOC though its been on my LONGLIST for years. I'm sure Judson does a great job of 'humanizing' the story as most good science writers do but I would think to really understand the nuts and bolt of the experiments ( which is what you'd want for a college course), you'd have to go to the primary literature

  18. I'll obviously need to add ECOC to my list; my go-to book for similar reasons has long been PATOOMB (Phage and the Origins of Molecular Biology).

  19. Horace Judson's masterpiece remains in a class of its own, no matter its vintage. Four of Judson's essays are well worth the read - even though they appear poorly known. They can be downloaded here:

  20. An e-book edition, or pdf, of the Eighth Day of Creation (ideally the updated 1996 edition) does not appear to exist, a deplorable gap in knowledge availability that needs to change....

    So To quote and endorse this plea:

    "Although I really agree with Larry Moran’s concluding sentence “The solution to this problem is to make all students read The Eighth Day of Creation” I think that the chances are remote without good modern publishers helping the process along. Do something useful today, go to the Amazon webpage of Eighth Day of Creation and click on the link (usually just under the picture) to request a Kindle version from the publisher."

  21. Some more gems in the shape of eulogies to Horace Judson - I append some quotes from both superb commentaries:
    including this observation of note attributed to Judson :

    "Terry and I were in Horace’s workshops together. All I can add to Terry’s elegant, intelligent essay here is Horace’s rule for a good sentence: it has an arrow running through it, it’s ordered beginning to end, every word is in the right place. Try that for even a paragraph and you’ll break a sweat."

    This tribute also includes useful insights into the ingredients of powerful prose...

    see the appended Comments to this euology, especially the story about training under live fire in telephonic interviews.

    And then there is Judson's pithy take on the place of popular science writing:

    "Writing about music is not the same as composing it or performing it—and in just that trivial way writing about science, talking about science, explaining science, is not science. But is the pleasure taken in science by the non-scientist therefore illegitimate? Listening to music with an instructed ear and the aid of a score is certainly a musical activity—and in just that self-evident way, along a continuum from dummy to savant there is a point p at which reading about science with an instructed mind and with reference to original research becomes a scientific activity."
    "...It’s a coda by the pioneer himself, and it remains a worthy meditation for anyone in our line of work
    “I like a florid line,” Horace once told me....Fine and witty rage, master of language, mordant stylist—yes, also Horace."
    he was distinctly Huxleyian - not least in his attention to dress and indeed all matters of style. He was indeed, “the last living Edwardian."

    And another tribute:
    "Whereas too many academics are selfish, aspergeric and nasty behind their smiling and convivial personas, Horace was the other way around...."