github.com/CovertLab/WholeCellEcoliRelease is a whole cell simulation model created by Covert Lab and other collaborators.
The project is written in Python, hurray! But according to te README, it seems to be the use a code drop model with on-request access to master, very meh, asked rationale on GitHub discussion, and they confirmed as expected that it is to:Oh well.
- to prevent their publication ideas from being stolen. Who would steal publication ideas with public proof in an issue tracker without crediting original authors?
- to prevent noise from non collaborators. They do only get like 2 issues as year though, people forget that it is legal to ignore other people :-)
The project is a followup to the earlier M. genitalium whole cell model by Covert lab which modelled Mycoplasma genitalium. E. Coli has 8x more genes (500 vs 4k), but it the undisputed bacterial model organism and as such has been studied much more thoroughly. It also reproduces faster than Mycoplasma (20 minutes vs a few hours), which is a huge advantages for validation/exploratory experiments.
The project has a partial dependency on the proprietary optimization software CPLEX which is freeware, for students, not sure what it is used for exactly, from the comment in the
requirements.txt
the dependency is only partial.This project makes Ciro Santilli think of the E. Coli as an optimization problem. Given such external nutrient/temperature condition, which DNA sequence makes the cell grow the fastest? Balancing metabolites feels like designing a Factorio speedrun.
There is one major thing missing thing in the current model: promoters/transcription factor interactions are not modelled due to lack/low quality of experimental data: github.com/CovertLab/WholeCellEcoliRelease/issues/21. They just have a magic direct "transcription factor to gene" relationship, encoded at reconstruction/ecoli/flat/foldChanges.tsv in terms of type "if this is present, such protein is expressed 10x more". Transcription units are not implemented at all it appears.
Everything in this section refers to version 7e4cc9e57de76752df0f4e32eca95fb653ea64e4, the code drop from November 2020, and was tested on Ubuntu 21.04 with a docker install of
docker.pkg.github.com/covertlab/wholecellecolirelease/wcm-full
with image id 502c3e604265, unless otherwise noted.Integrating multiple omics, comes quite close to whole cell simulation.
Never trust an experiment that is not supported by a good theory Updated 2024-12-15 +Created 1970-01-01
Not the usual bullshit you were expecting from the philosophy of Science, right?
Some notable quoters:
- Jacques Monod has the exact quote as presented here: pubmed.ncbi.nlm.nih.gov/22042272/, though presumably it was in French, TODO find the French version
- youtu.be/AYC5lE0b8os?t=41 A Computational Whole-Cell Model Predicts Genotype From Phenotype- Markus Covert by "Calit2ube" (2013), see also: Section "Whole cell simulation"
- the book Genius: Richard Feynman and Modern Physics by James Gleick (1994) mentions a few incidents of this involving Feynman, see e.g. chapter "New Particles, New Language" where he and fellow theorist Hans Bethe immediately spot problems with experimentalists' data in suspicious results
Ron Maimon is a male human theoretical physicist with an all but dissertation started in 1995 at Cornell University[ref][ref].
Ron is mostly known for simultaneously:
- the amazing free online content he has published in online forums such as Stack Overflow and Quora, notably about particle physics, until around 2014 when Ron disappeared from the Internet entirely. Ciro Santilli figures he's hanging out with Ettore Majorana somewhere in the metaverse.
- having either been blocked from or quit every single website he participates in, partly due to his highly combative nature, e.g.:He explicitly defends this combative approach at youtu.be/ObXbKbpkSjQ?t=944 from Video 1. "Ron Maimon interview with Jeff Meverson (2014)":
- Physics Stack Exchange: physics.meta.stackexchange.com/users/4864/ron-maimon
physics.meta.stackexchange.com/questions/976/physics-ses-inability-to-deal-with-users-who-are-highly-persistent-have-kook-b user Marty Green makes one of the best characterizations of Ron's approach to science/collaboration:The thing about Ron Maimon is he definitely comes here to talk about physics. I personally can't get into discussions with him for two reasons: first, he's so single-minded in his own point of view that you can't really communicate with him back and forth; secondly, the structure of this forum is simply not conducive to extended discussions. But he sometimes posts things that are so coherently argued and with such intricate detail that even if I can't understand them myself, I just can't believe he's simply pulling this stuff out of his ass.
- physics.meta.stackexchange.com/questions/1376/what-violation-caused-this-suspension user Jerry Schirmer makes another good comment:
The thing that makes me pretty angry about Ron's behaviour is that he does not distinguish between common consensus belief and his own private research - this makes evaluating his claims hard for a third party not familiar with physics.
- Quora: www.quora.com/profile/Ron-Maimon. Ron was very active on Quora, until he was blocked for his views on the Boston Marathon bombing as mentioned at Video 1. "Ron Maimon interview with Jeff Meverson (2014)"
And notably, relevant to cirosantilli.com/china-dictatorship/stack-overflow-mods-refuse-to-clarify-if-anti-ccp-imagery-is-allowed-or-not-2021In order to have this process work [finding of truth] it is extremely important that the tone is hostile, that it is like a court of law, where you have an adversarial relationship with your opponent. Because if you have a friendly relationship with your opponent, then political consensus is preserved.
and he then also mentions that Wolfgang Pauli was a major proponent of this in physics, and so was Galileo.Unfortunately, when you're in a minority, the only way to correct the consensus view is to just shout it, and repeat it, until people go and look and check for themselves. The reason is that it creates an adversarial atmosphere where the people have to pick sides, and they don't like to pick sides, they would rather have everyone be happy. So when you have to pick sides, what do you do? You either butt out, you just leave it alone, you run away. Or you sit and review the evidence until you know which side to pick.
- Physics Stack Exchange: physics.meta.stackexchange.com/users/4864/ron-maimon
Ron seems to share a few philosophies which Ciro greatly agrees with as part of Cirism, which together with his knowledge of physics, make Ciro greatly respect Ron. Such philosophies include:
- he gives great importance to the history of physics and learning from original papers. He appears to know this insanely well, notably emphasizing that there is value in tutorials written by early pioneers of the field, see also Section "How to teach and learn physics". TODO find quote. Ciro Santilli distinctly remembers one specifically taking about this, but can't find it anymore.
- education views, notably emphasising autodidacticism
- www.quora.com/Why-should-high-school-students-learn-physics/answer/Ron-Maimon, highlighted at gmachine1729.livejournal.com/161418.html: "Why should high school students learn physics?" Answer:Yes, please, give it to me baby:
But they should learn it, preferably on their own, because the school doesn't know how to teach physics. Physics is extremely interesting, even the elementary kind. It takes the mathematics you learn in high school and uses it to describe certain natural phenomenon completely, beyond what was imagined possible in the wildest dreams of people like Pythagoras or Archimedes. If you have a computer, Newton's laws plus a tiny code can produce the motion of the planets around the sun, the motion of a free-twirling baton, the motion of colliding billiards, it's very simple.
- www.quora.com/Why-should-high-school-students-learn-physics/answer/Ron-Maimon, highlighted at gmachine1729.livejournal.com/161418.html: "Why should high school students learn physics?" Answer:
- enthusiasm for molecular biology technologies, seen e.g. at: www.quora.com/Why-are-an-abundance-of-physicists-moving-to-theoretical-biology/answer/Ron-Maimon on Quora:Ciro is actually specifically curious about whole cell simulation which he makes reference to.
[biology] is also clearly going to be the major technology of the 21st century, you should have a sugar outlet next to the electrical outlet, and plug in artificial biological technology made out of artificial cells. To plan these requires a complete method of describing biological cells, a precise model of all the processes, so that you can make artificial ones, and it produces a type of precise control on single-molecule chemistry that makes chemists drool.
- effortless effort and the to explain everything he knows online. These can be seen at www.quora.com/How-do-you-control-your-urge-to-access-the-internet-so-you-can-complete-your-assignments "How do you control your urge to access the Internet so you can complete your assignments?":
I don't. I consider the internet the first priority, as it will be viewed by thousands of people, and will have a real impact, while other assignments are lower priority, as they will only have an impact locally.
- his cheapness as in Ciro Santilli's cheapness as mentioned at youtu.be/ObXbKbpkSjQ?t=2454 from Video 1. "Ron Maimon interview with Jeff Meverson (2014)":Interviewer: there's a question on Quora where you say that you took a vow of poverty when you were very young.Ron: I was ten, I mean, most people would give it up, but I mean I figured I didn't have any need to give it up, so I just kept with it, I mean, I was never was really offered that much more. When we started the startup, I think I was offered 50k, but I said "no, I'll keep it 40k, I took a vow", and then they gave me 40k. And that of sort of set an example, the CEO also took 40k. It was a very good thing because we had very little money, we were a startup, and we were going by seed money.
However he also subscribes to some theories which Ciro Santilli considers conspiracy theories, e.g. his ideas about the Boston Marathon bombing that got him banned from Quora (a ban which Ciro strongly opposes due to freedom of speech concerns!), but the physics might be sound, Ciro Santilli does not know enough physics to judge, but it often feels that what he says makes sense.
chat.stackexchange.com/transcript/message/7104585#7104585 mentions that he was at Cornell University and did all but dissertation, but he mentions that he was still self-taught:This is corroborated e.g. at: web.archive.org/web/20201226171231/http://pages.physics.cornell.edu/~gtoombes/Student_Index.html (original pages.physics.cornell.edu/~gtoombes/Student_Index.html down as of 2023).
Eugene Seidel: On your personal info page you write that you are not a physics Ph.D. but does that mean you were a physics undergrad in college then went to grad school and finished ABD... or are you entirely self taught?Ron Maimon: ABD. I am self- taught though, I only went to school for accreditation. I had a thesis worth of work at the time I left grad-school,Eugene Seidel: ok thanksRon Maimon: I was just kind of sickened by academic stuff that was going on--- large extra dimensions were popular then.Eric Walker: Anyway, thanks Ron -- I'll get back to you with more questions soon, I'm sure.Ron Maimon: Also I was at Cornell, my advisor left for Cincinnatti, and I was not in very good standing there (I was kind of a jerk, as I still am). Some friends wanted to start a biotech company called "Gene Network Sciences", and I joined them.
At youtu.be/ObXbKbpkSjQ?t=2454 from Video 1. "Ron Maimon interview with Jeff Meverson (2014)" he mentions his brother is a professor. At physics.stackexchange.com/questions/32382/could-we-build-a-supercomputer-out-of-wires-and-switches-instead-of-a-microchip confirms that his brother's name is "Gaby Maimon", so this neuroscience professor at the Rockerfeller University is likely him: www.rockefeller.edu/our-scientists/heads-of-laboratories/985-gaby-maimon/. Looks, age, location and research interest match.
Some notable technical posts:
Some notable history posts:
- physics.stackexchange.com/questions/18632/good-book-on-the-history-of-quantum-mechanics/18643#18643 about the history of quantum mechanics give the quadratic explanation
- and closely related for the factor 2: physics.stackexchange.com/questions/27847/why-is-there-a-frac-1-2-in-frac-1-2-mv2/27916#27916
Bibliography:
- gmachine1729.livejournal.com/161418.html Ron Maimon answers about physics and math on Quora (part 1) by Sheng Li (2020) contains a selection of some amazing Ron Maimon posts
- www.reddit.com/r/RonMaimon/ someone made a Reddit for him. Less than 100 users as of 2022, but has potential.
- some Quora threads about him, oh the irony:
- www.quora.com/Is-Ron-Maimon-actually-a-pioneer-or-a-jest
- www.quora.com/Are-Ron-Maimons-answers-on-mathematics-physics-and-computer-science-factually-correct
- www.quora.com/What-do-people-think-of-Ron-Maimons-paper-Computational-Theory-of-Biological-Function-I
- www.quora.com/Who-is-Ron-Maimon/answer/Ron-MaimonAlso in a comment he explains something to a now deleted comment, presumably asking why he dropped out of grad school, and gives a lot more insight:
I'm a physics grad school drop-out working in theoretical biology but I still do physics when I get a chance, but not right now because I am in a middle of a project to understand the properties of a certain virus as completely as possible.
It's a complicated boring story.I dropped out mainly to do biology with friends at a startup, because I figured out how you're supposed to do theory in biology, but also I truly believe it was next to impossible for me to get a degree without selling out, and I would rather be shot than write a paper with an idea I don't believe.My grad school phase was a disaster. I first worked for Eric Siggia, but I got away because he had me do something boring and safe, I figured I have only a limited number of years before I turn 30 and my brain rots, and I wasn't going to sell out and do second-rate stuff. I found a young guy at the department doing interesting things (Siggia was also doing interesting things, like RNA interactions, he just wouldn't assign any of them to ME), this was Philip Argyres, and got him to take me. Argyres wanted me to work on large-extra dimensions (this was 1998), but I made it clear to him that I would rather be boiled in oil. I worked a little bit on a crappy experimental setup that didn't work at all, because I didn't know enough about electromagnetic screening nor about how to set up experiment. But EVERYONE LOVED IT! This is also how I knew it was shit. Good work is when everyone hates it. But I learned Lifschitz's ideas for quantum electrodynamics in media from this project.Me and every competent young person in high-energy physics knew large extra dimensions was a fraud on the day it came out, and I had no intention of doing anything except killing the theory. Once Wikipedia appeared, I did my best to kill it by exposing it's charlatanry on the page for large extra dimension. That was in 2005 (after getting fired from the company), and from this point onward large-extra-dimensions lost steam. But I can't tell how much of this was my doing.Argyres liked N=2 theory, and we did something minor in N=2 SUSY models around 2000, but I was bogged down here, because I was trying to do Nicolai map for these, and it ALMOST worked for years, but it never quite worked. But I knew from the moduli interpretation and Seiberg-Witten solution that it must work. If I live long enough, I'll figure it out, I am still sure it isn't hard. But this was the link to statistical stochastic models, the work I was doing with Jennifer Schwarz, and I wanted to link up the two bodies of work (they naturally do through Nicolai map).But I had my own discovery, the first real discovery I made, in 1999, this thing that I called the mass-charge inequality, what Vafa and Motl called "the weakest-force principle" when they discovered it in 2006. It was swampland, and Vafa hadn't yet begun swampland. My advisor didn't believe my result was correct, because he saw me say many stupid things before this. So he wouldn't write it or develop it with me (but I had read about Veltman telling 'tHooft he couldn't publish the beta-function, I knew Argyres was wrong about this)Anyway, Argyres left for Cincinnatti in 2000, and I joined the company then. I was in the company until january 2005. Then they fired me, which was ok, by then it was a miserable hell-hole full of business types.I discovered Wikipedia, and started killing large extra dimensions. I wanted to finish my thesis, and some people agreed to help me do this, but I had told myself "no thesis until you get the Nicolai map sorted out" and I never did. I worked with Chris Henley a little bit, who wanted me to do some stuff for him, and I discovered an interesting model for high-Tc, but Henley said it was out of fasion, and nobody would care, even though I knew it was the key to the phenomenon (still unpublished, but soon).This was 2008-2009, and I became obsessed with cold fusion, so Henley dropped me, as I had clearly gone crazy. I developed the theory of cold fusion during the last weeks of working for Henley. Then I dropped out for good.Honestly, by the time I was gone, I realized that the internet would make a degree counterproductive, because I knew I had better internet writing skills than any of the old people, I was a Usenet person. Online, the degrees and accreditation were actually a hinderance. So by this point, I secretly preferred not to have a PhD, because I knew I was good at physics, and I could attack from the outside and win. It's not too hard if you know the technical material.The only problem is that I was unemployed and isolated in Ithaca for about 7 years after having gone through my first productive phase. But I developed the cold-fusion ideas in this period, I learned a lot of mathematics, and I developed a ton of biology ideas that are mostly unpublished, but will be published soon. It astonished people that I could have no degree and be unemployed and have such a sky-high ego. The reason is that I could evaluate my own stuff, and I liked it!
Backlinks:
- 2022: twitter.com/johncarlosbaez/status/1556085484937310209 by John Baez. This page was one of the top Google hits for "Ron Maimon" at the time.
Studies biology from a more global point of view, if putting all little pieces of an organism make up the final biological function.
Some key activities:
Ciro Santilli started taking some notes at: github.com/cirosantilli/awesome-whole-cell-simulation. but they are going to be all migrated here.
It is interesting to note how one talks about single cell analysis, in contrast to whole cell simulation: experimentally it is hard to analyse a single cell. But theoretically, it is hard to simulate a single cell. This mismatch is perhaps the ultimate frontier of molecular biology.