<aside> 📐 A few reflections on the use of analytical and empirical models in biology inspired by Eighth Day: http://jck.bio/learning-representations-of-life/
The Eighth Day of Creation is a historical account of early developments in the field of molecular biology. Judson’s central emphasis is on “The Golden Era” of molecular biology, beginning with the Oswald Avery’s discovery of DNA as the molecular basis of heredity and ending with the first glimmers of Fredrick Sanger’s DNA sequencing technology.
Judson shines in his first-person interviews with scientists at the bench and the chalkboard, capturing the mental models early molecular biologists held in their heads as they worked toward the small number of key experiments that were memorialized in textbooks. Too often, the history of science is presented as a straight linear path from one good idea to the next with little murky water in between. Sir Peter Medawar famously lambasted that scientific papers are a form of intellectual fraud because they misrepresent the true history of reasoning that led to a discovery . The pedagogical texts of science might well be critiqued as merely a fraud on a grander scale.
By contrast, Judson spent countless hours with the field’s eminent thinkers, asking them to walk through in detail their sources of confusion, as well as the clarity that came afterward. After a decade in the life sciences, Judson’s interviews were my first exposure to many of the erroneous but dominant models that the classical experiments of molecular biology overturned.
Judson also has a gift for conveying the wonder and excitement early molecular biologist’s felt as they built the discipline. It’s hard to convey the emotions a scientist experiences when the actual, physical work largely consists of moving clear liquid between different tubes, but Judson is able to channel the voices of his subjects to build an adventure story out of these meager settings.
Captured within Judson’s account of the fog of war surrounding these early experiments is the reality that many important discoveries were partly serendipitous. If bacterial conjugation had been attempted in E. coli LM rather than K-12, the field of bacterial genetics may have been set back by a meaningful period. If Nirenberg had used a slightly lower concentration of magnesium in his cell-free translation system, it may have taken significantly longer to crack the amino acid code. Had Gamow been a bit less personable, a bit less eccentric, perhaps many important contributions of the RNA Tie Club would not have emerged for some time longer.
Another of Judson’s strengths is his ability to convey the full personality of many scientists that have been reduced to a single experiment in the collective memory. Oswald Avery was a diligent, persistent, avuncular man as well as the designer of the eponymous experiment. Francois Jacob was a member of the Free French forces, suffering forever-after during his experiments from wounds sustained at Normandy while he searched for the messenger molecule. Monod was a militant Communist, leader of the armed French resistance movement during the second World War, and an important French political figure following his Nobel award.
Eighth Day unfortunately drags a bit in Judson’s presentation of technical details. I admire his commitment to scientific accuracy, but many of the topics presented aren’t quite amenable to his mesoscale summary. They require either a synoptic summary, or a full textbook, but Judson’s presentation of minute details (e.g. specific units of deviation between different iterations of x-ray crystallography experiments) without the conceptual tools to understand them leaves the reader a bit lost. I’d recommend that readers liberally skim portions of the book that present technical details at seemingly the wrong layer of abstraction.
Despite the shortcomings, I heartily enjoyed Eighth Day, and I’m quite shocked that it has never been recommended to me in any portion of my training. It feel out of print for a long period, perhaps explaining why it was never quite incorporated into the canon. I’d eagerly recommend it to any students of molecular and cell biology as a companion to more technical references.
As I read through Eighth Day, I found myself highlighting furiously to record a few key insights shared by molecular biology’s pioneers. I’ve tried to sketch the synoptic versions of these lessons below.
We can reconstruct most of the principals of molecular biology from a surprisingly small number of experimental results. Numinous, abstract questions like “How are traits passed from parent to offspring?” can be answered with fairly simple tools and communicated in scarcely more than a paragraph. The scientific importance of results in a blooming field might be power-law distributed.
We must be careful here to distinguish between scientific impact — the explanatory and predictive power contained in a given result — and utility — the usefulness of a given result for enabling future experiments or technologies.
The majority of experiments scientists perform are required to find the right region of parameter space in which to run the key scientific experiments. These produce utility but not scientific impact per say, but are no less important. If the proper magnesium concentrations had not been known, no one could have crystalized DNA or performed cell-free protein synthesis. Without the right bacterial strains, bacterial genetics wouldn’t have been available to reveal the regulatory genome and unlock the necessity of the messenger.
Perhaps by acknowledging this distinction more explicitly, biologists could make more rapid progress. There is often a hesitation to build useful biological systems or technologies, to optimize essential but “boring” parameters of the experimental setup because the work is considered less valuable. This can lead scientists — myself included! — to perform experiments that try to build a system and use it too, often leading to sub-optimal outcomes on both fronts. We might be better served by identifying the key question we’re trying to answer ahead of time, then spending however long it takes engineering a system to run the right experiment. Our incentive structures need to adapt to reflect this reality, given that is has been true from the foundation of the field!