Unraveling the Intricacies of Prions and Protein Functions

The long-awaited Oxide and Friends bookclub! Bryan and Adam were joined by special guest--and real life biologist--Greg Cost to discuss Philip Ball's terrific book, How Life Works: A User’s Guide to the New Biology. Spoiler: Alan Turing makes a very expected appearance!

In addition to Bryan Cantrill and Adam Leventhal, we were joined by special guest Greg Cost.

Some of the topics we hit on, in the order that we hit them:

• The Turing pattern
• RNA as a precursor to DNA
• Xenopus frog
• Xenobots
• Anton computer

Bryan's reading notes

Central themes

• Power and limitations of metaphor – especially mechanical ones
• The fundamental, diametrical opposition between life and machines. (Nature does not use simulations!)
• Rejecting the neo-Darwinian paradigm

Passages of note:

• p. 91: “of the common SNPs seen in human populations, fully 62 percent are associated with height” … “the most common genomic associations for complex traits like this are in the noncoding regions” What is cognition? p. 137: “Life is, as biologist Michael Levin Jeremy Gunawardenaand philosopher Daniel Dennet have argued, ‘cognition all the way down’” AlphaFold2 p. 148 “AlphaFold does not so much solve the infamously difficult protein-folding problem as sidestep it. The algorithm makes no predictions about how a polypeptide chain folds, but simply predicts the end result based on the sequence.”
• p. 156: allostery refers to how a
• 🤯 p. 160: “The popular view that science is the process of studying what the world is like needs to be given an important qualification: science tends to be the study of what we can study.”
• p. 166: “The misfolding pathology of PrPs (prion proteins) is the price paid for the benefits of disorder. … Disordered proteins can increase the complexity and versatility of our regulatory networks, but at the cost of increased risk of toxic aggregates formed from misfolded proteins.”
• p. 181: “The [training] analogy is far from perfect, not least because proteins don’t need to be ‘trained’ to acquire their roles.” Ball himself loves to use computing a metaphor, even when it is inapt or imperfect!
• p. 189: “What you’re really looking at here is a diagram not of a molecular event but of a failed paradigm.”
• p. 201: Clifford Brangwynne: “Many of the textbooks and even our language conveys this kind of factory-floor image of what goes on inside the cell. But the reality is that the computational logic underlying life is much more soft, wet and stochastic than anyone appreciates.” To which I would add: the information machine is MUCH more deterministic than anyone appreciates!
• p. 205: “Because the binding of BMPs to BMP receptors can be altered by other molecules, the BMP pathway can interact with other pathways to create crosstalk between cells during development.” Mike Olson’s observation of everything working through side-effect. 🤯 p. 212: “It seems likely that metazoans have evolved this evolvability. One of the odd features of transcription factors that bind to DNA is that, in eukaryotes, the base sequences that they recognize are often surprisingly short – perhaps six or so base pairs long. … But there’s no reason the selectivity has to be this approximate; in prokaryotes the binding sites are longer and therefore more specific. It seems that eukaryotes have, so to speak, chosen this sloppiness – probably because it allows new regulatory pathways to develop.”
• p 217: “While causal emergence seems to be a general design principle for life, it is rarely evident in our own technologies.” Disagree with: “...maybe the better computers of the future will be more causally emergent.” We can’t even get asynchronous systems working!
• 🤯 p. 222: “Is there, after all, really such an obvious advantage to being multicellular? If so, we don’t know what it is.” … “If [evolutionary biologist Michael] Lynch is right, the implication is humbling: we are here not because the multicellular lifestyle of metazoans like us is superior or even advantageous, but because chance mutations created possibilities for new regulatory and multicellular behaviors that natural selection merely found no reason to eliminate.”
• p. 226: “If we want to understand the mechanisms behind some key evolutionary shifts – for example, the emergence of complex body shapes and lifestyles in the Cambrian explosion, the emergence of nervous systems and of new modes of cognition, and the divergence of mammals and other vertebrates – genomes are the wrong place to look.”
• p. 245: “The switching of cell states often happens gradually rather than by abrupt switching at a sharply defined fork in the landscape.”
• p. 248: “One of the most useful pieces of advice I heard from Nature’s biology editor many years ago was that the answer in biology is always ‘yes’”
• p. 258: “Such leveraging of noise, the researchers suggested, might represent ‘a central and unifying principle underlying the properties of stem and progenitor cells that are central to the evolution of metazoan life.’ Noisiness helps to keep all the cell-fate options open.”
• p. 263: “In short, says biologist Dennis Bray, the cells circuitry (if that is even a good metaphor at all) ‘is a long way from a silicon chip or any circuit a human would design.’ The more we learn about living systems, Bray writes, ‘the more we realize how idiosyncratic and discontinuous they are’ relative to computers.”
• p. 267: “Planarians challenge our notions of what life can be.”
• p. 276: “Lewis Wolpert is said to have once claimed, ‘It is not birth, marriage, or death, but gastrulation which is truly the most important time in your life.’”
• p. 291: “The heart drives and shapes its own formation, bootstrapping itself into existence by virtue of its very function.”
• p. 293: “If there’s a central feature of how life works, it is surely in this ability to create outcomes that are neither arbitrary nor wholly prescribed.”
• p. 295: “The plasticity of form shown by living organisms might be not only a good way but the only way of making entities as complex as us”, but goes onto to liken us to universal computation
• p. 296: “But what really is ‘normal’? … There are many types of benign skin growths; I’ve had a lipoma on my upper arm throughout my adult life.”
• 🤔 p. 297: “Conjoined twins like the Hensels are the result of an incomplete separation.” I think this is wrong? Certainly, it is odds with Mutants by by Armand Marie Leroi.
• 😡 p. 309: “Once a relatively obscure figure, Turing is now widely hailed as a visionary genius, thanks in part to the 2014 biopic The Imitation Game and the decision to feature him on the British fifty-pound note.” WTAF
• p. 326: “The positioning of our organs on the correct side is controlled by stirring!” Mutants goes into this as well
• p. 331: “Hsp90 acts as a kind of ‘capacitor for morphological evolution,’ storing up variation of form that might be released in times of stress”
• p. 333: “It seems that the exploration of shape in the early Cambrian was excessively profligate: some of the body plans found in the fossil record of that time soon vanished. How could they have been selected for, only then to be so rapidly selected a...