Sunday, October 03, 2021

RNA Is The Embodied Information That Sets Causal Boundary Conditions

axial  |  Schrödinger won the Nobel Prize in Physics in 1933 and was exiled from his native home Austria after the nation was annexed by Nazi Germany. He moved to Ireland after he was invited to set up the Dublin Institute of Advanced Studies. This follows the past history of Ireland acting as a storehouse of knowledge during the Dark Ages. After decades of work, biology was becoming more formalized around the 1940s. Better tools were emerging to perturb various organisms and samples and the increasing number of discoveries was building out the framework of life. With the rediscovery of Mendel’s work on genetics, scientists probably most importantly Thomas Hunt Morgan and his work on fruit flies (Drosophila) set up the rules of heredity - genes located on chromosomes with each cell containing a set of chromosomes. In 1927, a seminal discovery was made that irradiation by X-rays of fruits flies can induce mutations. Just the medium was not known where Schrödinger was thinking through his ideas on biology. At the same type, organic chemistry was improving and various macromolecules in the cell such as enzymes were being identified along with the various types of bonds made. For Schrödinger, there were no tools to characterized these macromolecules (i.e. proteins, nucleic acids) such as X-ray crystallography. Really the only tool useful at the time was centrifugation. At the time, many people expected proteins to be the store and transmitter of genetic information. Luckily, Oswald Avery published an incredible paper in 1944 that found DNA as probably the store instead of proteins.

With this knowledge base Schrödinger took a beginner’s mind to biology. In some ways his naivety was incredibly useful. Instead of being anchored to some widely-accepted premise that proteins transmitted genetic information (although he had a hunch some protein was responsible), the book thought from first principles and identified a few key concepts in biology that were not appreciated but became very important. Thankfully Schrödinger was curious - he enjoyed writing poetry and reading philosophy so jumped into biology somewhat fearlessly. At the beginning of the book, he sets the main question as:

“How can the events in space and time which take place within the spatial boundary of a living organism be accounted for by physics and chemistry?”

Information

In the first chapter, Schrödinger argues that because organisms have orderly behavior they must follow the laws of physics. Because physics relies on statistics, life was follow the same rules. He then argues that because biological properties have some level of permanence the material that stores this information then must be stable. This material must have the ability to change from one stable state to another (i.e. mutations). Classical physics is not very useful here, but for Schrödinger his expertise in quantum mechanics helped determine that these stable states must be held together through covalent bonds (a quantum phenomena) within a macromolecule. In the early chapters, the book argues that the gene must be a stable macromolecule.

Through discussion around the stability of the gene, the book makes its most important breakthrough - an analogy between a gene and an aperiodic crystal (DNA is aperiodic but Schrödinger amazingly didn’t know that at the time): “the germ of a solid.” Simply, a periodic crystal can store a small amount of information with an infinite number of atoms and an aperiodic crystal has the ability to store a near infinite amount of information in a small number of atoms. The latter was more in line with what the current data suggested what a gene was. Max Delbrück had similar ideas along with J.B.S. Haldane, but the book was the first to connect this idea to heredity. But readers at the time and maybe even still overextended this framework to believe that genetic code contains all of the information to build an organism. This isn’t true, development requires an environment with some level of randomness.

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