Review of 2023 book: How Life Works: A User’s Guide to the New Biology Philip Ball. ISBN9781529095999
Another metaphor that Ball criticizes is that of a protein with a fixed shape binding to its target being similar to how a key fits into a lock. Many proteins, he points out, have disordered domains — sections whose shape is not fixed, but changes constantly.
I dunno, kinda sounds to me like a good educational metaphor. Yea, not 100% accurate but good enough for high school biology. You need to make some simplifications for the sake of education. Not everyone can care about the complex intricacies of genes and proteins.
Good enough for high school biology. But not when you’re doing influential cancer research. The following is from Subanima’s article on the same subject:
One of the most influential papers in cancer biology published in 2000 was the “Hallmarks of cancer” by Douglas Hanahan and Robert Weinberg. It outlined six of the main capabilities of cancer and laid out a rough program for studying the disease ointo the 21st century. To date, it has over 39,000 citations which, in academia, is officially known as a shitton.
It was so successful that they released a sequel in 2011 which has over 62,000 citations - also known as a metric shitton.
But at the heart of both papers is the machine metaphor and the idea that if we just map out all the functions of proteins in one ginormous map, we’ll just have to run some maths and we’ll know everything we need to know to cure cancer. In 2000 they wrote:
Two decades from now, having fully charted the wiring diagrams of every cellular signalling pathway, it will be possible to lay out the complete ‘integrated circuit of the cell.’
He also notes the same thing you noted, that it’s a good metaphor for high schoolers.
I still feel like he’s nitpicking tbh, wiring diagrams can have devices with variable or probabilistic states and though the maths is very complex it’s theoretically possible to similate and map.
This maybe true, but these states aren’t being represented in the biological diagrams.
Theoretical biologist here. This is an incredibly important book. I just bought it a few minutes ago and so I’m only partway through the beginning, but it’s summarizing everything people from my school of thought (complex adaptive systems theory, multilevel selection models, and so on) have been arguing for two or three decades. It’s a very fast read so far (probably less so if you’re less familiar with the points the author is making), but I really hope that this book has an impact that’s reflective of the timeliness and cohesiveness (as I am reading into what the author is preparing to argue) deserves.
Yeh! Good to see the rusty machine (and self-deprecating) model fading away and being replaced by real appreciation of the true marvels that have emerged over millions of years. (Science’s mechanical models were all so … 18th century!)
(Not so familiar with biology but did enjoy hearing about the tack Lee Cronin’s taken.)
It’s still a rusty machine even if the maths that control it are a bit more complex
Math controls nothing and only models them. It is CRITICALLY important to remember that mathematical models are ONLY models, no matter how closely they match any sampled data.
Everything is math, it’s what controls gravity and cell division and protein folding - there is no god it’s all just math
Of course the model is only a model but the point is you can use the model to predict real world responses, therefore you can test millions of things and do the one which is most likely to work
I think the difference here is between your conception that reality follows a mathematical model while their conception is that mathematical models follow and try to be reflective of reality.
I think their concern is that, if one believes reality follows math, when the model fails to accurately predict something, the person with the model may wonder what’s wrong with reality. If that person believed the model follows reality they would wonder what’s wrong with the model. The latter perspective will yield better results.
It’s the difference between saying “this is how it works” vs “to the best of my knowledge this is how it works.”
That’s ridiculous, if I think that one apple plus one apple is going to result in three apples then I try it and find it’s actually two I’m not going to blame the universe I’m going to know my understanding of arithmetic is flawed.
It’s not the math of the human made model that controls the universe that would be silly. The model is the current best approximation of the actual math that defines the universe.
An accurate model allows you to predict the outcome of events, like we can predict how many apples will be in the bag. With some things it gets very complicated because there’s lots of things and various possible states but we can model that with statistics and calculous and stuff. We can even make a set of all possibile results and use that as a map to tell us if something is possible, how likely it is and what we can do to make it more or less likely - nothing the guy said was controversial, we can map cellar interactions even if that requires using complex multidimensional math (mathematics have had to get used to doing this sort of math a lot recently so I’m sure they’ll manage)
No, you’ve internalized it in the wrong way. The mathematical model comes AFTER the real world. It is not related to the real world what so ever except in correlation. Correlation is not causation. ESPECIALLY with a human-made MODEL.
If the maths actually drove ANYTHING, you wouldn’t be saying, “most likely” to work…
Yes that’s a model, I’m not saying the model magically controls reality but that the underpinning reality is math - the reason you always have two apples in a bag when you start with one and add another is because of math, the human model of that isn’t controlling it but if we want two apples in a bag and we currently only have one then we can use our model to determine how many apples we need to add into the bag.
The same is true of more complex systems, if we can accurately model the cellar interactions then we can derive solutions in the same way
That’s the thing: It’s NOT math. Math is an expression of relationships. The underpinning of reality IS NOT math. Ever. Math is a simplification. Always.
Maybe finish the book before you decide?
If you’re familiar with the subject, you can tell exactly where the author is going to go with it. I’ve been working on and teaching this material for about 20 years, and I’ve applied it against quite a diverse number of areas.
I’m not learning anything new from the book, but simply reading a well-assembled argument as to why it should become a dominant paradigm.
Lol you’re saying with a chapter you don’t even need to read the rest of it? And you’re a scientist?
Yes, because I know this material well enough that I could have written this book, and have written multiple papers on closely related topics as well as taught courses on this material.
I’m sorry if that seems weird but it’s what happens when you become an expert in a field, especially one as narrow as theoretical biology. I knew exactly where he was going with his argument.
It’s like when you have a twin and you can finish each other’s sandwiches.
What’s weird is claiming the book is “incredibly important” but also, the author’s thoughts on the subject are so obvious that you do not need to finish the book.
Let’s say you were an expert in epidemiological modeling, and you and a modestly sized group of your fellow researchers had been working on an approach that demonstrated what should have been done in 2020, and what a shitshow it would be if it wasn’t done. Then, of course, it wasn’t done. Then one of your fellow travelers wrote a book saying what should have been done. You know the work - you’d contributed to it yourself - but you think other people should know about it.
Would you consider that book “very important?”
IDK, I only read the first line of your comment
Or, you know, they’re commenting based on what they know, which is most than most of us in this thread, and they’re doing it now while the conversation is happening instead of waiting until they’ve finished the book, because by then everyone will have moved on.
What a dishonest bs. It’s not the scientists who communicate these dumbed down “theories”, it’s journalists and trivial science books and shows.
Makes me loose all respect for the author.
At the university where I studied professors were constantly talking about what we don’t know. Formulated every theory extremely carefully, there was no “it is like that”. What kind of scientists is he talking about?
Yeah, I graduated with my BS in zoology over 20yrs ago and my professors wouldn’t have talked about genetics as a blueprint even back then. My focus was evolutionary biology and the one sentence in the article on the topic made me cringe. I would guess that people who focused in molecular bio probably cringed through the rest of it.
Craig Venter, the infamous head of the Human Genome Project and who created the first “synthetic” cell, has been saying this stuff for years. It’s remarkable how ahead of the times he is, perhaps because he’s not beholden to an academic institution.
He claims that a “tree of life” is fallacious, that there is no junk DNA, and that the bare minimum genes necessary for a living cell still can’t be determined even after decades of research.
I hope that the authors of the new Extended Evolutionary Synthesis will admit the deficiency of outdated assumptions and reject dogmatic approaches to the theory, as implied by the author of the book reviewed in this article.
How could there be no junk DNA? There are plenty of inserted regions of repeating codons, between regions that are read (outside of replication). DNA replicators are very simple machines, they copy until they’re told to stop, I agree that any junk DNA in the human genome has been there for a very long time, but it’s not difficult to find single cell organisms that have introduced previously non-self DNA in their genome. If that DNA isn’t used besides replication then it’s junk is it not?
Also telomeres are pretty synonymous with junk DNA, until they aren’t, or is every shortening of the telomere removing information vital to a cells function?
So I think I can make the claim that I am an expert in this, at least compared to 95%+ of biological researchers. My research foci include epigenetic and emergent interactions like the ones discussed in the article, and although I am not going to back this up by identifying myself, please believe me when I say I’ve written some papers on the topic.
The concept of junk DNA is perhaps the problem here. Obviously there are large swaths of our genome that do not encode anything or have instructions for proteins. However, dismissing all non-coding DNA as “junk” is a critical error.
Your telomeres are a great example. They don’t contain vital information so much as they serve a specific function-- providing a buffer region to be consumed during replication in place of DNA that does contain vital information. Your cells would work less well without telomeres, so calling them junk is inaccurate.
Other examples of important non-coding regions are enhancer and promoter regions. Papers describing the philosophical developments of stochasticity in cellular function note how enhancers are vital for increasing the likelihood of transcription by making it more likely that specific proteins floating in the cellular matrix interact with each other. Promoter regions are something most biologists understand already, so I won’t describe them here (apologies for anyone who needs to go read about them elsewhere!). Some regions also inform the 3D structure of the genome, creating topological associated domains (TADs) that bring regions of interest closer together.
Even the sequences with less obvious non-coding functions often have some emergent effect on cellular function. Transcription occurs in nonsense regions despite no mRNA being created; instead, tiny, transient non-coding RNAs (ncRNAs) are produced. Because RNA can have functional and catalytic properties like proteins, these small RNAs “do jobs” while they exist. The kinds of things they do before being degraded are less defined than the mechanistic models of proteins, but as we understand more stochastic models, we are beginning to understand how they work.
One last type of DNA that we used to consider junk: binding sites for transcription factors, nucleosome remodelers, and other DNA binding proteins. Proteins are getting stuck to DNA all the time, and then doing things while they’re stuck there. Sometimes even just being a place where a nucleosome with a epigenetic flag can camp out and direct other cellular processes is enough to invalidate calling that region “junk”.
Anyway I’m done giving my spiel but the take home message here is that all DNA causes stochastic effects and almost all of it (likely all and we haven’t figured it out yet) serves some function in-context. Calling all DNA that doesn’t encode for a protein “junk” is outdated-- if anything, the protein encoding regions are the boring parts.
Thank you for taking the time to respond, I respect your knowledge and agree with you for the most part. From an evolutionary perspective there’s very little pressure to cull genetic material that does not have a purpose, genome replication is already taking place and takes very little overall energy/time.
There may not be as much useless DNA in the system as previously thought, but not every codon pair has a use. There are undoubtedly identical transcription codes being suppressed in one section of DNA that are active in other regions, and it may have been useful to have that extra region available if pressures ever applied that caused that region to be reactivated, but if mutation occurred and caused that region to no longer have the original blueprint it was coding for, it could theoretically create actual evolutionary pressure to eliminate/suppress that section of the genome, it could be suppressed/inactive harmful DNA, not junk but also not beneficial.
My biggest hang-up on the whole “every codon has a purpose” argument is that it blatantly ignores the evidence occurring so much more frequently at “lower” life forms. Eukaryotic single cell organisms swap DNA rather readily, it’s a much higher risk/reward mechanism of evolution, a lot of that DNA, if it turns out to be beneficial, will be ancillary to the actual genes with benefit. Plants have genomes that vary in length from generation up generation, often times much larger than required, maybe it’s because they chill in the sun all day and are more susceptible to genetic mutation, but just because there’s extra targets for codon swapping, doesn’t mean that DNA is set there with purpose. It just exists. It may have been beneficial at one point, but it’s only there because it isn’t detrimental enough to have selection pressure repercussions. If pressures were high enough they every codon mattered, (or if it were designed intelligently so that every codon mattered) a lot of genomes (I’m not to nervous to claim I believe all genomes) would be shorter due to junk culling, it’s just such a small factor in the schema that it isn’t ever selected against.
I would encourage you to read the linked Science paper and Dan Nichol’s paper, Is the Cell Really a Machine?
You feel that if a codon isn’t meant for something, if it doesn’t have a purpose– then it is junk. This is a mindset that is reflective of the machine model of the cell. We used to expect that each protein was bespoke for a function, each transcript necessary.
The whole paradigm shift at hand is this model falls flat, even for coding regions. I think you’re actually very spot in here with the prokaryotic DNA or the plant genomes (love me some violets for their weird genomes). Some parts of a genome will rapidly change and appear to serve no real purpose, but the next bite is the important one: even if it seems like there isn’t a purpose, like a top-down prescription for functionality, those regions are still doing something while they are present.
For example, some long non-coding regions affect the likelihood that a person will develop Parkinson’s disease, or in the case of plants with various polyploidies, the relative expression of their genes won’t necessarily change, but the absolute expression may.
Basically, you aren’t wrong that these regions dont have a purpose, because no genes have a purpose. The cell isn’t a machine.
The cell isn’t a machine.
What do you mean by this? I feel like you think the meaning is obvious after everything you’ve said, but it’s not.
Even if we accept that everything you said is true, all it means is that the cell is a very, very complex machine. More complex than current models account for. It’s just chemistry, after all. The chemicals behave in predictable fashion or else life wouldn’t be possible at all. Molecules moving around, transforming, causing other molecules to transform, etc, etc, to turn food into shit and babies. You can always use the word “machine” to describe that, no matter how complex it is. Just like the word “algorithm” can be used to describe the function of code no matter how complex it is, whether it’s a simple path finding algorithm, or the newest machine learning one.
But I probably shouldn’t use the word “function” because that implies purpose, and, as you say, no part of the chemistry of life has purpose. I hope you can detect my snark. That’s a pretty lame argument that’s philosophical at best. The purpose of the machinations of the cell is to maintain life and reproduce. No mater how many times you say it, your words won’t change the fact that that is the purpose of the chemistry of life.
You’ve twisted around the word “purpose” in your head until it has no useful meaning. Nonsense. A molecule can many overlapping, hard to discern purposes. That does not mean it doesn’t have a purpose.
