S04 E13
22 May 2024/01:50:30

Bookclub: How Life Works by Philip Ball

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:
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 against? And why was there so little innovation in body shapes subsequently?”
  • 🤯 p. 340: “Living organisms are nonequilibrium systems”
  • 🤯🤯 p. 360: “Living organisms can be regarded as entities that attune to (correlate with) their environment by using meaningful information to harvest energy and evade equilibrium. Life can then be considered as a computation that aims to optimize the acquisition, storage, and use of such meaningful information.”
  • p. 363: “The agential system must be out of equilibrium with its environment – in other words, it must be thermodynamically distinct from those surroundings.”
  • p. 375: “Self-replication is, in fact, an especially good mechanism for stabilizing complex systems … Biophysicists Eric Smith and Harold Morowitz have argued that for this reason [??] life is highly likely to arise, purely on thermodynamic grounds, in any environment that has the necessary chemical ingredients along with concentrated reservoirs of energy.”
  • p. 379: “Saving lives doesn’t require much understanding of how life works”
  • p. 385: “Another confounding factor is that the regions (loci) of the genome most commonly linked to disease risk in GWASs (genome-wide association studies) are noncoding: they encode not proteins but probably RNA molecules involved in regulation. For autoimmune diseases this is true of a remarkable 90 percent of all SNPs identified in GWASs, reinforcing the central importance of noncoding RNA in how our bodies work.” (Greg’s work on transposons.)
  • p. 386: “As Topol has said, the root problem is the HGP’s implication – nay, assumption – that our genome sequence is our ‘operating instructions,’ whereas in fact it is just ‘one layer depicting human uniqueness, and does not by itself reveal the depth of the information derived from all of the other layers that include the transcriptome, proteome, epigenome, microbiome, immunome, physiome, anatome, and exposome.’”
  • p. 405: In 2013, cancer scientist Michael Yaffe concluded that looking for cancer-linked genes was not the right strategy, and had been adopted more because scientists had the techniques to pursue it than because they had good reason to think it would work.
  • p. 406: “To develop into tumors is one of the particular hazards of pluripotent stem cells, precisely because they have such fecund versatility.”
  • 🤯 p. 408: “As [David] Smithers put it, ‘Cancer is a disease of organization, not a disease of cells.’”
  • p. 409: “It seems possible that defective epigenetic programming of cells could make [tumor formation] happen – one of the 2014 studies observed that the amount of chemical modification of some genes by DNA methylation was abnormally high.”
  • 🤓 p. 423: “The researchers used [synthetic proteins and synthetic DNA sequences] to alter the root shape of the mouse-ear cress plant Arabidopsis thaliana in a predictable way. Genetic circuits of this kind, they say, might be used to control plants’ response to drought.”
  • 😔 p. 428 Biologist Yoshiki Sasai dies of suicide after a misconduct scandal
  • p. 436: “Xenobots are undoubtedly alive, but one can hardly call them frogs. As with synthetic embryo models made from stem cells, they defy our categories of classification. And that’s precisely because we have tended to think of how life works in the wrong way: as a kind of teleological drive to make the end-forms long familiar to zoologists, rather than as a palette of possibilities arising from the exigencies of the cells themselves.”
  • 🤓 p. 443: “Levin thinks all this is just the start for synthetic morphology… ‘I think that if we knew what we were doing, cells can build basically anything’”
  • p. 446: But a better reason to make the analogy [of linguistics to genetics] is that language is perhaps the only human technology, if we may call it that, which bears any resemblance to the mechanism of life.
  • p. 452: “As theoretical biologist Jeremy Gunawarden has said, ‘We lack an adequate theoretical framework in which both views of component and system are valid on an equal footing.’”
  • p. 456: “The role of natural selection is not to build up these shapes and patterns but to select between them: to cull ones that ‘don’t work’, or not well enough.”
  • p. 458: “The anatomy-generating core system, Gerhart and Kirschner say, is highly conserved in metazoa: it doesn’t change much between different species because that would be disastrous. They write, ‘These DNA regions are effectively excluded from the list of targets at which genetic change could generate viable selectable phenotypic variation. They just cannot be tinkered with.’”
If we got something wrong or missed something, please file a PR! Our next show will likely be on Monday at 5p Pacific Time on our Discord server; stay tuned to our Mastodon feeds for details, or subscribe to this calendar. We'd love to have you join us, as we always love to hear from new speakers!