This is a very interesting article/video, and well-worth reading to get a sense of how complex proteins are, but I’m not convinced by the principle argument that proteins don’t constitue “machinery”.<p>The core philosophical question is actually interesting: what is a machine?<p>The author suggests a machine is anything with solid parts of that have a specific function, and goes on to argue that the metabolic machinery or cells doesn’t correspond to any of these three criteria. I’m not sure it matters whether the parts are solid, I don’t think multifunctionality disqualifies something from being a machine, and despite the limitations presented, I am not even convinced that it is senseless to decompose a cell into components. On this last point, it bears emphasizing that his criticism bears the analytical method in general, and is not specific to biology. There are edge cases in <i>any</i> decomposition of a whole into parts.<p>So while it’s interesting to see how these philosophical questions are at play in cellular biology, the case remains to be made that “machinery” is a fundamentally bad analogy. Here it also bears emphasizing that confusion between the subject of study and the metaphor is a risk with all metaphors (the map is not the territory), not especially <i>this</i> metaphor.<p>In sum, I wish the author had focused on the philosophical substance of “what even is a machine?”. That’s bound to be a richer investigation.
There's one complaint here that seems valid:<p>> gives us a false sense of confidence in how much we know about the biological world<p>A false sense of confidence could make people vulnerable to bold false claims, which might lead to poor consumer choices and poor policy choices.<p>Beyond that, the approach seems really wrong-headed. Popular science education has a successful approach when you want people to understand the limitations of a model: you hook people with a fun headline of "COOL NEWS, THINGS ARE MUCH WEIRDER THAN YOU THINK!" You teach <i>forward</i> from the oversimplified model.<p>You aren't going to reach many people with a negative, moralizing message that people need to go <i>backwards</i> and give up a model that has given them insight. "Oh, we should never have given you this, you're not smart enough for it, you're going to make a mess."<p>The sad thing is that the information conveyed here is really cool, and it could easily be framed in a fun way! Instead, it's presented in a way that sends the message, "Look, you need to understand how dumb and dangerous it was for you to think you had any insight into this."<p>> It's finally dawning on us that the cell is not a machine<p>I really, really, really don't understand the sense of moralistic fear infusing this whole presentation. Reading the piece and watching the video, I feel like I'm reading and watching a religious sermon on the spiritual dangers of materialism instead of a piece of popular education to help the public have a better-informed understanding of science.
I enjoy when the nice abstract models we work with are given a course-correction, and we are reminded of the profound, gargantuan complexity of the real world.<p>Sometimes, we get lost in our models and start thinking that they <i>are</i> reality, rather than just poor approximations of the real mess that's out there.<p>So, nice article (:<p>For a shorter version, that also gives some of that sense of the real complexity of cells, I like "Cells are very fast and crowded places"[1].<p>One good quote:<p><pre><code> molecules move unimaginably quickly due to thermal motion. A small
molecule such as glucose is cruising around a cell at about 250 miles per
hour, while a large protein molecule is moving at 20 miles per hour. Note
that these are actual speeds inside the cell, not scaled-up speeds. I'm
not talking about driving through a crowded Times Square at 20 miles per
hour; to scale this would be more like driving through Times Square at
20 million miles per hour!
</code></pre>
[1] <a href="http://www.righto.com/2011/07/cells-are-very-fast-and-crowded-places.html" rel="nofollow">http://www.righto.com/2011/07/cells-are-very-fast-and-crowde...</a>
It really depends on how you define a machine.<p>A machine to me is a combination of elements that interact to perform some function.<p>Wether those elements are multifunctional doesn’t matter.<p>Also solid is not a requirement: ropes and pullies, expansion elements, self altering software: etc are all found in human made machines. And they are not solid.<p>I disagree with this video: life is based on molecular machines. It just happens that these machines are really complex and dynamic. But machines nonetheless.
There's some good stuff in this but while I agree with many of his points, I don't agree with his fundamental conclusion. I see several examples of "machines" in biology which satisfy all my requirements. In particular DNA and RNA transcriptase, the ribosome, and motor proteins are all machines. They act with very high fidelity, have a specific and necessary purpose (to the extent that an evolved system can have a well-defined purpose), consume energy to achieve their goals, and eventually break down and make mistakes.<p>The current belief about alphafold is that its confidence is actually a "disorder predictor": when it makes low confidence predictions, it's really that the protein itself doesn't adopt a well-defined structure.<p>But further than this, we actually do protein design and create new proteins that have well-defined functions. FOr example there is a class of proteins known as proteases that "cut proteins" (conceptually like scissors, but physically using enzymatic activity). A well-known protein designer at Genentech took an existing protease and made it more heat-stable (IE, didn't stop working when you raised the temperature). This protein was then sold licensed to laundry manufacturers who added it to their detergent (it does a great job cleaning up protein stains, hence the advertisement "protein gets out protein"). It's literally a machine you put in your machine to make your machine machine better.
This is really cool!<p>I just think that the definition of “machine” is too restrictive. To me a machine is a very broad word and no matter how complex we find our bodies to be, it’s still ok to think of them as machines. That doesn’t mean it’s ok to oversimplify how they work or to presume we know everything about them.
Reading this on mobile, I feel really lost about what the article is trying to say. The problem is all the sources are in between the essay-bits. I would prefer it if the author just used footnotes like Wikipedia when citing a claim and stuck all the sources on at the end.
> I like when humans finally caught up to this advanced biological process and had to compare it to machines that humans created that led to this discovery just to understand it.<p>The solar system is like a clock. Cells are like machines. Brains are like computer networks.<p>It's interesting to realize how regularly we map our discoveries about the physical world to the technologies of the day, "just to understand it," and also interesting to be reminded of the limitations of such analogies.<p>The best and most literal parallel I can think of is <i>DNA is like code</i>. Yet I find it interesting, almost uncanny, that we discovered that right around the same time we started developing prgoramming languages.
I have been wondering if a better representation of a cell would actually be a large centralised message “queue”, which represents the state of the cell somehow (one entry for each metabolite molecule, or for each proteoform).<p>The enzymes/proteins would then sample this queue, and return the message, process the message, or add new state to the queue. So this is essentially a large decentralised message processing mechanism, and what you would expect is that over time the state of the queue would shift, representing a shift in the state of the cell.
My TL;DR take on this: thinking of proteins like rigid little single-purpose parts might fall short of the mark. Proteins are kind of wiggly, and nature can easily multi-purpose a given molecule.<p>Backed up with lots of references. Good read.
I wonder how this relates to the "mystical realm" - the yogic concept that a certain "life-force" (prana / chi) exists that coordinates, at a higher level, the behavior of cells.
I couldn't figure out if the author is trying to make a point about the definition of machine, or if they're trying to make a point that the animations are misleading. Because they say the animations are misleading, but then they go into a discussion about what makes a machine a machine.<p>> the animations are misleading.<p>Ok, why are the animations misleading? Are they representing a process that does not occur?<p>> Let's go from the start. Why isn't the cell run by molecular machines like the animations suggest? Well, first we need to come up with some criteria to distinguish machines from non-machines.<p>Wait, what? No, we don't first need to define what we mean by machine. I just want to know why the animation is misleading as an approximate model. Does the animation represent the interactions occurring in the cell or not?<p>> I also know that many machines have bendy parts, and that some machines have multi-functional parts.<p>Ok, further digging into what people think about when they talk about a machine. I still just want to know if the thing in the video is misleading, as accused.<p>> the structure of proteins isn't hard and rigid like we see in the animations. They're actually more like "dense liquids" that constantly jiggle around inside the cell.<p>But do they do what is shown in the video? Maybe just in a less rigid manner? It's just a model! In the ted talk there's another video of some process and you can see it's all liquid. Can we focus on the animation and why it's misleading?<p>> This is already strike one for the machine metaphor because, if my bike jiggled this much I wouldn't be able to go very far.<p>Well yeah, it wouldn't work very well as a bicycle, but a jiggly machine wouldn't be a bicycle, it would be something else. Doesn't mean it's not a machine. And we're still not talking about the accusation of misleading videos.<p>> Proteins almost never have one shape, they have a bunch of different configurations that they shift between.<p>But for the model in the video, for that particular protein shape, does it represent the interactions that are occurring? Does the Helicase process the DNA strands? Does the DNA wrap around Histones?<p>> It is finally dawning on us that the cell is not a machine.<p>No, there was an accusation made that was not backed up aside from an elaborate side argument about whether the cell is machine-like. Obviously the animations don't completely represent reality. They're just models after all. Simplified for presentation and communication of a particular concept. I still don't know if the interactions in the animation are false or not. Or if the author is really calling them misleading because they're more rigid than in real life, and they don't represent the full complexity of every possible protein type.