Axial - The Eighth Day of Creation
The Eighth Day of Creation
The Eighth Day of Creation was handed out to me to read on my first day in graduate school. Many of the world’s best life sciences programs do the same. The book is an incredible historical overview of molecular biology - the idea of having multiple ways to proof a biological phenomena (i.e. genetics & biochemistry), the establishment of the Modern Synthesis, and the increasing use of physics and chemistry to study life. This history is incredibly important now to appreciate how much bringing engineering principles (i.e. synthetic biology) will transform biology.
The book is probably the best place to learn about 20th century biology. Essentially, The Eighth Day of Creation is three books in one - mapping out the central dogma:
The discovery of DNA’s structure - “DNA, you know, is Midas' gold. Everybody who touches it goes mad.”
The subsequent study of RNA and the genetic code - “the gene was something in the minds of people as inaccessible as the material of the galaxies.”
Characterizing the structure and functions of proteins - “discovered the second secret of life.”
The Eighth Day of Creation is a foundational book of great experiments in life sciences. Just as important, the book captures the personalities, both good and bad parts, of great inventors in the field and how science actually works. Some parts are absolutely amazing and other parts show the dark side of research.
The first part of the book explores the characterization of DNA and the discovery of its structure. By the 1950s, the nature of DNA was known but its structure was still unclear as well as the encoding method. What is Life? helped guide the theory on these two parts. Three main groups were working on solving DNA’s structure:
Rosalind Franklin and Maurice Wilkins at King’s College in London
Francis Crick and James Watson at the University of Cambridge (Cavendish) - Watson shifted his field of study from ornithology to genetics after reading What is Life?
Linus Pauling at Caltech - the Pauling Lab had published the model for the alpha helix in 1951, which earned him a Nobel Prize; the work was a pioneer in the use of X-ray crystallography and using the information to build molecular model, which became a foundational method to determine the structure of DNA
Just one year after figuring out the structure of the alpha helix, Linus Pauling took a crack at DNA. With very limited electron microscope data he correctly surmised that DNA’s structure must be helical since the images appeared cylindrical. Unfortunately, he didn’t have the best quality images and ended up proposing that DNA is a triple helix. Watson and Crick ended up having access to much better data. Fortunately for them, Franklin was an incredible crystallographer and was able to produce the most clear image of DNA at the time: Photo 51 (image below). What ended up driving Watson and Crick’s success and controversy was their extreme willingness to talk to a lot of people about research and working to put various pieces together to discover DNA’s structure - a double helix.
Photo 51 is the piece of data that ushered in a new era for life sciences. Watson and Crick were building various models of DNA. The breakthrough came when Wilkins showed Photo 51 to Watson in January 1953, this is a controversial event on whether Wilkins was acting ethically in sharing data; however, with a prepared mind Watson immediately went back to Cambridge to London to inform Crick. They immediately figured out that DNA must be a helix since the image is a cross where each arm is a plane of symmetry of the helix viewed from the side. With his expertise in the theory of X-ray crystallography, Crick was able to figure out the distance (~3.4 Ångstroms) and orientation between the bases within DNA by measuring the distance between the dark spots on the image. Watson was able to bring the insight that nucleotide bases matched via hydrogen bonds to maintain the helical structure of DNA. This work progressed rapidly, not withstanding Crick’s conservatism but desire not to be scooped, with the seminal paper on DNA’s structure published a few months later in April 1953.
Ultimately, Franklin did the pioneering work, Crick knew the theory to interpret the work, and Watson had the insight to bring it all together. The book goes into the various personalities and drama during this whole process particularly how Franklin ended up not winning a Nobel Prize alongside Watson and Crick. With fairness, the book examines the motives of Pauling, Watson, Crick, Wilkins, Franklin, and a few others. Common knowledge suggests that Franklin was actively wronged. However, Judson gives her much more agency - not portraying her as naive but giving a more nuanced view. Franklin had been recruited to move to another university in March 1953 and ended up publishing work on the structure of DNA’s A-form (Photo 51 is on the B-form). She began studying RNA and was on track to continue to make important discoveries, but in 1958 she passed away from cancer at the aging of 36. She even stayed with the Crick’s during her treatments. When the Nobel Prize for DNA’s structure was awarded in 1962, she was left out with Wilkins effectively taking her place because the award was not given out posthumously (unless they were previously nominated). Watson published his own version of the story in the book, The Double Helix, giving a sensationalized view of Franklin, which misrepresented her work. Judson does a fantastic job setting the record straight. Various breakthroughs from individuals pieced together led to the discovery of DNA’s structure. Once the encoding method of life was determined, a maelstrom of work was done to characterize the code and learn how to engineer it.
The first third of the book is the most important part. The last two-thirds delves into the study of RNA and proteins up to the mid-1990s. Once the structure of DNA was determined, there was a race to translate the four bases of DNA to the 20 amino acids of proteins. Various theories were put out, mainly by physicists, but the model that aminos acids were encoded by three consecutive bases proved correct - providing the redundancy for an organism to resist mutations given that several base triplets code for the same amino acid. Once, the RNA code was established, work in protein synthesis characterized the mechanism by which RNA was passed through ribosomes - tRNAs (adaptors) were discovered that specifically matched with particular base triplets to bring the appropriate amino acid to the site of synthesis. The final part of the book goes into the use of X-ray crystallography in combination with heavy atom labeling, bringing the story full circle, to determine the structure of proteins. Driven by DNA’s structure, a new era was brought on. Various tools from X-ray crystallography, chromatography to radiolabeling and centrifugation as well as an expansion of model organisms from E. coli and bacteriophages to C. elegans and zebrafishes enabled the mapping of the central dogma and giving us the ability to make new medicines and businesses.
The Eighth Day of Creation is a masterpiece on great experiments in life sciences. Importantly, it shows the power of isolation to make breakthroughs and community to share discoveries and make new ones. The book discusses the re-establishment of Cold Spring Harbor Laboratory, the arguments from the RNA Tie Club, and the competitive nature found within the Biological Laboratories (I used to work on the floor Wally Gilbert was on). By putting a half century’s worth of work in perspective, the characterization of DNA as the genetic material and the flow of information from DNA to proteins created massive levels of value for the world. The next half century has the potential to do so much more.