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I read this and it it fills me with so much melancholy.

I took biology 101 in college and what I thought would be really interesting turned out to be SO unexpectedly meaningless.

Now years later all I recall is the memorization of phylums and kingdoms on one test and cell structures on another test and sitting in a large auditorium looking at the map and not the territory.

The course was so much about WHAT and never about WHY.

I don't know if I was immature, or if the biology course was a "weed out" course designed to filter out all but the most dedicated, or if biology education is off the rails.

I do know that every subject would benefit from a little storytelling, a little excitement and a good helping of why.

honestly i prefer the boring course, but everyone’s different, so at our school they offered the fun one as a regular credit and the boring one as an AP, and i think that worked out well for everyone
> The course was so much about WHAT and never about WHY.

Biology is pretty notorious for most stuff being arbitrary. There is no model. People who say there's a model, they're talking about something else - sometimes, a literal Platonic ideal of biology, that makes for an appealing pop science course, but not knowledge that like, helps you design experiments or better use drugs or whatever.

From the article:

> It was hard to get through a sentence without having to consult Wikipedia. In immunology in particular the nomenclature is expansive.

This is a common refrain. "Paternal allo-antigens" for example, straight from the literature: people who do immunology research know what that means, they do not get tripped up like this author does.

Programming computers and being good at math does not prepare you at all for understanding this stuff! Watson and Crick were not math savants. They did not have natural gifts.

> Watson and Crick were not math savants. They did not have natural gifts.

They had the 'natural gift' of picking up on the clues hinting that DNA, rather than protein, was central to the mechanism of biological inheritance. It is the natural gift of being able to identify the key features of the forest despite the preponderance of obfuscating trunks and branches. It is the gift of seeing some sort of order behind cirucmstances in which almost all the details are accidental.

Math synthesizes complexity; in biology, you have to analyze what's given.

>They had the 'natural gift' of picking up on the clues hinting that DNA, rather than protein, was central to the mechanism of biological inheritance.

That was Hershey and Chase [0]. Watson and Crick were the first to solve the structure of DNA.

[0] https://en.wikipedia.org/wiki/Hershey%E2%80%93Chase_experime...

Point taken, though that article also says "Hershey and Chase concluded that protein was not likely to be the hereditary genetic material. However, they did not make any conclusions regarding the specific function of DNA as hereditary material, and only said that it must have some undefined role."

Arguably, my general point still holds, though with an expanded cast of characters.

my observations which I think broadly agrees.

-Math/CS: inherently better at abstracting & are "proof" centric.

-Life Sciences: inherently better at observing then reasoning and are "argument" centric.

Coming from the CS side this is not a marriage made in heaven as opinions don't matter by design.

As a Math/CS graduate (I focused on mathy aspects of CS): math cs people struggle at working with real world abstractions. They abstract and simplify, but then tend to convince themselves that simplified model and its conclusions are totally all there is to reality.

And if they accept that model is not super perfect, they completely reject model - to find another simplified model that they convince themselves if flawless.

They struggle with the "this is model with such and flaws we need to keep in mind while interpreting".

I'm also from the mathy aspects of CS. To avoid ticking off a local majority I will simply agree that there are technical practitioners for whom accepting the that life science and data it produces are at best "a system of exceptions" is difficult.

And that this lack of flexibility can create hard times when they attempt to fit biology into a banking app because that is what they learned programming is.

On the converse side life sciences may feel everything is debatable and that having a strong personality should mater as much as an absolute mathematical proof.

Schrödinger published a very interesting treatise (What is Life - http://www.whatislife.ie/downloads/What-is-Life.pdf) which inspired a generation of physicists to study biology. Biology is still mostly at the early observational phase (similar to physics in the early Renaissance period), although slowly more systems-level approaches are being applied to be able to model biology with the same types of tools (namely mathematics) that have been so successful in physics.
> Programming computers and being good at math does not prepare you at all for understanding this stuff!

This is something that lots of people, and especially people in the tech industry, keep forgetting. They go ''well i can calculate partial differential equations, did a course on topology ánd created an api based on open data, how hard can this 'biology' actually be???'' and then it turns out that yes, it is hard.

This isn’t at all like my computer science classes. Biology education must be off the rails.
Only in HN a comment like this is not laughed out of the room.

Biology is packed with useful, relevant models, from the lock and key model for enzymes in one extreme to the Lotka-Volterra (predator-prey) for ecosystems population in the other, there are plenty of models who are A) Theoretically sound. B)Has great quantitative explanatory power.

> Watson and Crick were not math savants. They did not have natural gifts.

You have a very quaint and naive view of biology. Since the work of Maynard-Smith at the very least, has rigorous mathematics taken an important role in biology. Population genetics,neuroscience, systems biology, biochemistry among others are underpinned by lots of math. People working deciphering all the signaling pathways in the cell are working with what is effectively a complicated,messy but fascinating discretely-encoding program.

>Programming computers and being good at math does not prepare you at all for understanding this stuff! Watson and Crick were not math savants. They did not have natural gifts.

Out of all the hn chauvinism I've read over the years this post is a strong contender for the most absurdly delusional. Sorry, being able to program does not make you an ubermensch.

I think there are a few problems that result in this sad state of affairs, and unfortunately they are not constrained to biology (eg 'why isn't mathematics taught with wonder?').

1. Teachers are required to do evaluations, and the way we have settled on doing evaluations is giving students giant, shitty tests. In order to pass these tests, lots of rote memorization is required.

2. Five years of being forced to teach-to-the-test latter, your original wonderment for the material is not going to shine through in period 5 bio.

3. The average teacher is over-worked, over-stressed, and worried about a lot of other baggage that comes along with being a teacher. This last point is true of teachers from public elementary schools all the way to professors at big research institutions (where many lecturers are researchers halfheartedly box-checking a teaching requirement).

4. Teaching - particularly pre-university - is viewed as a relatively low-status career (with a commensurate paycheck), at least in the US. A lot of the people who feel wonderment for these subjects and could teach them well end up being driven away from teaching as a result.

There are teachers who manage to bring joy and wonderment into the classroom, despite all of the problems that lead us here. But we need to address these problems if we want the average bio classroom to be taught with wonder, instead of being 1-hour mind-numbing sessions where you pretend to be studying from your index cards.

I'm somewhat skeptical of this explanation since I went to a private secondary school in Australia where these pressures did not apply, and had the exact same experience with Biology where what we were taught was to memorize taxonomies that made me abandon the subject as early as possible.
One experience doesn’t disprove systemic reasons for the outcomes we’re seeing. Even if hypothetically all teachers were very well paid and the job was regarded as high status, there would be a nonzero chance that some kids still end up with shitty teachers.
I went to public school in Australia, there was a lot of memorization, I can remember my tests were always big on making us label diagrams (here's a kidney match the words with arrows, now do it for the liver, now do it for the heart) etc. But we also did some experimental stuff in Biology. Which at least was memorable to me.

Aside from the ever present dissections I can remember one notable experiment in year 11 involving Agar-Gel plates, we took swabs from various places around our school (Taps in the bathroom, Classroom door handle, AC Vents etc) and incubated the plates and compared what sort of bacteria was found and whereabouts.

Incidentally, for me it wasn't the taxonomies, but rather a teacher who was overly critical of me. He kept insulting my drawings, and since it was India, your parents too join in the "fun". For high school, I switched my stream to computer science almost immediately. It was only in my final years in engineering school (chemical engineering) where I began to get into Machine learning applications for biological processes under a really enthusiastic and encouraging professor (who ended up being a coauthor on a number of papers), that I really began to rekindle an interest in biology.

Funnily, earlier this year, my now-fiancee prepared for and wrote the MCAT, and since I sat along with her during her prep, I decided to give it a shot too, in spite of my relative lack of prep and a full time job on the sidelines. Managed to score a neat 514. Turns out, having a good teacher matters a lot.

If you look at education as a luxury good: I really liked learning economics from an economics Nobel prize winner, math from a Fields medalist, and I'm sure I'm forgetting other luminaries.
Yeah, it's pretty crazy how much I hated biology in high school but how much I love reading medical papers, drug mechanisms of action on wikipedia, watching Chubbyemu or Thought Emporium etc. There's just so much that I would have loved to learn in the field, but the practical starting points were just uninteresting rote memorization I guess so I could never enjoy it or see a practical use case. It seemed like the least interesting science to me, but now I wish I got more out of it.

That or perhaps I can consume an absurd amount of pop-sci garbage.

I would say it's also similar with other subjects, like history, which focus SO MUCH in memorizing dates and names, instead of actually understanding why things were happening.
You cant understand why things happen if you don't know when they happen (the other way around works just fine, which is why quizzes on tv love to ask random dates). You need to know when Caesar crossed the Rubicon in relation to when other events happened to help you understand why he did what he did. If you think he conquered Gaul after becoming dictator your entire narrative changes.

It sucks, but you really do need to know a lot of whens to help you contextualize the why. I've got a BA and MA in history and my first year at university was spend memorizing so many things, which was the absolute worst. But it did really does help a lot once you start doing your own research.

well, hmmm... I think you can tell a good story just by painting a picture of the situation.

(and I think of computer makefiles - you don't need to know times, you just need to know what depended on what, and what things combine to cause something)

I think that this is wrong. It is easier to remember sequence of events in logical order then arbitrary dates. You really dont need to remember exact date of when Caesar crossed the Rubicon in order to understand his motivations. You need context in enough details in order to understand motivations.

> It sucks, but you really do need to know a lot of whens to help you contextualize the why.

I always managed to memorize those dates in high school and elementary school. And then I promptly forgot them after test. I blamed my bad memory, but later when I learn how human memory works, I started to blame the way they taught us. People remember stories and systems well. Our memory works on relationships between facts. Most people sux at remembering unrelated arbitrary numbers.

All that done to me was that I seen history as boring pointless class. Historical characters came across as somewhat inhuman, absurd unrealistical creatures. Their behavior made no sense. Yes, they were actual real people, but the way history was taught made them sound like badly written characters from mediocre fiction.

It was only after I started to read history that was focused more on context, motivations and reasons I both starterd to long-term rememeber times+places and also like it.

When you know the date of an event, you can locate others events that are not in a direct relationship with it. You can then situate the evolution of distant lines of events without needing to memorize too many dependency graphs.
> When you know the date of an event, you can locate others events that are not in a direct relationship with it.

No you cant. Because at that point, you know nothing about the other events you are supposed to locate and have no reason to care.

> You can then situate the evolution of distant lines of events without needing to memorize too many dependency graphs.

I am not even sure what that is supposed to mean in the context of high school history. You drew events you know about into lines or graph and still know nothing about how they relate to each other.

Memorizing if something happened at Nov. 20th or Nov. 21st is not usually that important. We don't have exact dates for ancient history and we can still understand the sequence of events.

Understanding that A happened, which led to B happening later on is what matters. Having a ballpark is good for most things. Or do you still remember the exact dates you memorized on your history classes?

If you only learn dates, of course it makes no sense. Its like memorizing mathematical formulas. They also make absolutely no sense if you never see why you would use them.
But you are a MA in history, which is not true for 99% of the population. For everyone else, knowing the order of the events, and why A led to B, is more than enough.

"Evidence" that memorizing dates don't work: no one remembers crap from their history classes.

Edit: > If you think he conquered Gaul after becoming dictator your entire narrative changes.

That's the whole point. You only need to know the order of the events. Do you know the exact date and time when he became officially a dictator?

I also have a theory about history. I think it might be wasted on young people because they lack some maturity and life experience.

I think after you've seen human nature, chaos and conflict, and how people get along, it gets more interesting.

How did people with no fast communication or transportation manage to fashion constitutions or governments that have lasted hundreds of years?

I excelled at AP biology, but college biology was a total drag. Honestly, it's just the teachers, my high school teachers taught with passion in college it was a chore for my professors. At least software has more jobs and better pay, even if it's less fundamentally interesting.
All my high school biology teachers were good. As you point out, there are not as many other good jobs for biology graduates as there are for CS ones.
that's a shame.

I liked the quote in the article:

Imagine a flashy spaceship lands in your backyard. The door opens and you are invited to investigate everything to see what you can learn. The technology is clearly millions of years beyond what we can make.

This is biology.

> I excelled at AP biology, but college biology was a total drag. Honestly, it's just the teachers, my high school teachers taught with passion in college it was a chore for my professors.

An AP biology teacher in high school is teaching a class with disproportionately the most predisposed-to-be-engaged students, and its the central part of their job, in which they are secure and focussed. A lower-division biology professor in a university is probably teaching a class with disproportionately the least predisposed-to-be-engaged students, and if they are a tenured or tenure-track professor at a research university, its also not the core of their job (if they aren't, its a core part of their job -- but one in which they are insecure, are more likely to be adjusting to, and which may be one of several jobs.)

Agree - From personal experience, Biology undergraduate eeducation in the United States and its tendency toward rote learning seems optimized for medical school admissions (MCAT, are you tough enough?, etc) and not for becoming a biologist
I'll tell you something about memorizing phyla, orders, families, genera, and species. If you've never had exposure to any of that, it might seem arbitrary. But now, go out in the woods and try and identify species you see. You can start with birds and mammals because they are the easiest.

As you begin to do so, you can keep a record of them in a spreadsheet or notebook. Look up their biological classifications. All of a sudden the classification system will start to make sense, and help you understand the diversity of the organisms around you.

Biology is one of those subjects where part of the context comes from being outdoors and trying to understand ecological relationships yourself. You don't have to get to the level of a pro biologist, but there is so much you can find out by experiencing nature and trying to understand the basics that anyone can do it.

> As you begin to do so, you can keep a record of them in a spreadsheet or notebook.

This is useful, but probably because you're inverting the order here. You start with the observing and classification and end up using names rather than starting with "learn those names and matches".

Which is why I suspect the obsession of education around the world with biological classification dates to the period where most people lived in the country, not in urban spaces. Us city kids, we didn't get to spend so much time in the woods, to see so many different kinds of plants and animals - and the ones we did, we've already known by their laymen names.

Tangential: it would be helpful if schools explained to kids that all classifications are arbitrary, in biology and otherwise. Their value is in being useful, not correct to some magic metadata tags attached to things.

In context of school biology, I wish we spent more time approaching the classification like: "See that thing in the picture? We classify it as X, because it has $property; subtype Y, because it has $different-property; ... subtype ABC, because initially biologists thought this is different from BCD; now we know it isn't, but the classification remains for now". It would all feel much less boring this way.

There is one important part of taxonomy that is not arbitrary, however. The classification should be hierarchical, reflecting the evolution of the tree of life.
That's absolutely arbitrary too. The tree of life is a lie.

...or at least a very simplified model that breaks down as you move towards simpler and simpler forms of life. That's because horizontal gene transfer is a thing, and when you go all the way back to prokaryotes, there's so much of it going on that any "tree of life" is a statistical picture that's valid only for a select genetic marker that's used to trace dependencies. Pick a different marker, you'll get an entirely different prokaryotic tree of life.

Life ultimately forms a graph

> Which is why I suspect the obsession of education around the world with biological classification dates to the period where most people lived in the country, not in urban spaces.

Honestly, I would be surprised if that "obsession" has been around for nearly all of humanity's existence. If you're a hunter-gatherer (or even just hunt or gather to add variety to your diet and for medicine), being able to classify the biological world in some detail is an essential survival skill.

You people are so dumb trying to blame others for your lack of drive and interest. Study on your own, no one gives a shot if you like it or not all anyone can do is present you with the material. If you choose to ignore it you can't blame them.
This is how nearly every STEM class I've ever taken has been (and really, things like history too). I retained a passing interest in math despite my classes. I was lucky to develop a foundational interest in programming before classes had the chance to ruin it. It's simply par for the course of our education system, at least in the United States.

I wonder how many talented scientists never got started because they were turned off by their first exposure to a subject.

> I wonder how many talented scientists never got started because they were turned off by their first exposure to a subject.

On the positive side, we dont need more scientists. There are too many people trying to be scientists leading to pretty shitty working conditions for PhDs and post docs.

On the negative side, there are too many scientists and professors who should not have been.
That is being caused by exactly the same nonsense that has been happening in high schools. You have to get a high school degree. Why? No one knows. Everyone has a high school degree so you have to get a college degree. Everyone has a college degree so you need to have a masters degree. On and on until the whole thing is a diploma mill and society collapses under the sheer weight of puffed up do nothings grubbing at the controls.
It is not? PhD is not particularly necessary for anything except working in universities and few labs. People who do PhD do it because they want to do science, not because they would thought it is necessary.
In school it seemed the same way to me, it was very superficial and my high school teacher was unable to anwer my "why" questions.

At university it was very different, I finally got my questions answered. Part of that was certainly that it was much more in-depth, but the quality of the teaching and also the textbooks was just much higher. For me there were also maybe a few core things I didn't understand in school that are really crucial to put everything into context. The biggest one maybe being a tiny bit of thermodynamics and understanding what enzymes actually do and what they can't do.

I do suspect that a major problem is trying to cover too much material, which makes the courses too superficial and makes it impossible to actually explain how stuff works, what problems are solved by specific biological systems and why they probably work the way they do.

> The course was so much about WHAT and never about WHY.

WHY is philosophy/metaphysics.

WHAT is science.

I did like biology but at the time couldn't connect it with the impact the field creates in human living.

today I'm obsessed with understanding proteins because predicting protein structure, behaviour, interaction are really hard problems that would unlock huge medical advances if fully solved

>Separate things of different sizes using gels and magnets. (“Gel electrophoresis.”)

Just a minor point, electrophoresis uses electric fields not magnetic fields - hence its name, "electro-" as opposed to "magneto-".

If you want to study biology, study evolution. Darwin. Dawkins. Gould. King. Biology only makes sense in light of evolution, and boy howdy is it beautiful.
Biology doesn't have to make sense, it just is what it is.
Life is a self-sustaining, self-replicating chemical reaction. It obeys the laws of physics. It must somehow preserve the information necessary for its own genesis and regenesis at every generation. It must accumulate the energy needed for its functions from its environment. Makes sense?
Probably an annoying question... do you have an opinion on the mathetical unlikelyhood of evolution happening?
Well, there are documented cases of evolution happening during our lifetimes.

But I would say as a mathematical process, pretty likely once you have the basic ingredients. Richard Dawkins has written some good popular science books like 'Climbing Mount Improbable' that talks about evolution in this light. His 'Selfish Gene' is also an excellent read. It is slightly more technical but definitely understandable without an immense technical background.

How can evolution not happen in a system where you have random mutation and some selection pressure?
Oh, well the 'current' argument is that it's unlikely for a bunch of reasons.

- cambrian explosion of life is seen as unlikely given that changing random genes or dna mutations has such a low success rate in generating new life, that an explosion of life happening all at once seems out of step with the math.

- we don't know how to create life at all. adding up bits and pieces of molecules into cells and onwards can be screwed up at any point in the process and has to start over from square one to succeed. people in the lab can't even get it right and they can write down their progress and adapt unlike nature.

- self-organizing molecules and natural forces guided towards life haven't been seen yet to exist in nature, it has no expressed intent or will to self-organize into life. randomness and infinite time just isn't enough

I don't see the evidence that local minima and maxima changes in body shape, size, ect, act to completely change the species of an animal.

There's a long debate running from the 1980s on this stuff, it's just getting views on youtube more recently and becoming properly structured and scientific arguments instead of just conjecture. The stephen meyer 'intelligent design', david berlinski 'doubting darwin', ect arguments. The hoover institute did a piece a few years ago on youtube.

James Tour has a great series on origin of life that shows in the hard tasks of applying biology we are way off knowing how any of this works. https://youtu.be/zU7Lww-sBPg

The counter arguments to stephen meyer's idea a 'heirarchy of information guides dna changes' seem to be good conjectures and nobody really has the next step in the narrative tied down yet. Some say the cell is the powerhouse of life and sidestep the necessity of explaining dna changes. Some stick to the evolved life like Lee Cronin on the Unbelievable podcast.

Just curious if anyone has a stab in the dark for the next step in the narrative. A heirarchy seems like a red herring to me, cause it just leads back to an energy based universe that produces information, but I'm not qualified enough to have a say.

Ah so you mean the mathematical unlikeliness that evolution brought forth the complexity we see today, not that evolution happens at all. That makes more sense. I think it's hard to come up with solid arguments either way, because we only have a poor understanding of genetics and hence we can only give very rough estimates on the amount of complexity needed, and how much can be introduced in a given unit of time.

I'm not very well versed on that topic, but as for speciation, that happens very easily. For example even relatively short term separation of populations can stop interbreedability, e.g. by changing mating behavior. Once that happens it's just a matter of a few million years of random walks to grow feathers where there has once been fur.

No, I do mean a doubt in evolution over all.

The complexity argument has problems because in the small error bars of dna replication, it's so easy to introduce a sequence that actively hurts the animal, or is useless. Producing a whole new limb or whatever is way more complicated that we'd like it to be.

The discussion overall is part of a larger move by the intellectual/theological groups to bring back language (and psychology elsewhere) back into the old energy and matter world-view.

I agree it's hard to answer, the James Tour video is a nice place to start because he talks about biological engineering problems that his students are covering for him. They make little nano-robots and the like in part of the presentation. It seems inevitable that we won't see an overall answer for thousands of years.

That most mutations are useless is a feature, not a bug. Changes that neither hurt nor benefit are a major stepping stone to adaptions. You can have hair that looks more and more like feathers without hurting its performance as an insulator. You can have a spine with a few more or a couple fewer vertebrae without having a use for a tail or super flexibility. Phenotypic diversity is how populations adapt.
> Producing a whole new limb or whatever is way more complicated that we'd like it to be.

It isn't that much more complicated, though. Because as it turns out, you don't always have to code for that limb from scratch. You just have to flip a switch.

The key phrase here is "evolutionary developmental biology". We've learned that complex life has a lot of Lego-life quality - a lot of DNA codes for signals that enable or disable creation of whole organs at various locations, stages and cadences.

A TL;DR in four minutes by A Capella Science: https://www.youtube.com/watch?v=ydqReeTV_vk.

A nice example that video gives is that snakes have DNA coding for legs, it's just turned off. It can be turned on, and a snake will grow legs.

I don't have a problem with dna coding for legs existing. We don't know how the snake got that sequencing and the music video didnt solve it. It glosses over arbitrary changes in dna sequencing.

James tour's video in my parent post is far more in depth. Good luck.

Yeah, evolution is pretty much a tautology.
On the other hand, one is more likely to rise to success in biology if memorizing countless and ever-increasing mountains of facts is not a taxing chore as you wait to accumulate enough context and experimental expertise see a pattern somewhere and know which assays lend to feasible testing of ideas. Intro biology classes (e.g. cell biology) can in this way often be weeder classes, sadly.
This article rings so true to me. My father is a microbiologist - and now, so is my fiancée. I'm very lucky that I get to learn about genetics through osmosis now, and boy, is it ever fascinating!

I had a dining-table discussion with my dad the other day where the subject of DNA mismatch repair came up. It turns out that, in E. coli, a very simple & widely studied prokaryote, there's a mechanism called DNA mismatch repair which fixes errors which might occur during DNA copying. If an error is detected - a mismatch (e.g. a G paired with a T) - a trio of proteins (MutL, MutS, MutH) spring into action. The original template strand is already methylated - marked with an extra methyl group - at certain points in the genome (usually where there's a C followed by a G). The daughter strand, on the other hand, is usually not methylated yet. So, one of these proteins starts running down the DNA from the mismatch site, looking for a methyl group - up to 1000 base pairs away. When it finds a site with a methyl group on one side but not the other, it nicks (marks) the daughter strand, and another protein complex comes along and chops up everything from the nick to the mismatch site. The DNA polymerase then comes by and resynthesizes the whole strand.

Just three proteins are needed to drive this complex algorithm - a linear search procedure which distinguishes the mother from the daughter strand, a marking procedure which identifies the incision point, and a third to chop up the DNA and prepare it for resynthesis. What's even more bonkers is that E. coli - under stressful situations - will disable certain DNA repair mechanisms to deliberately induce more mutations. And I know that there are thousands more such pathways and complex interactions going on in cells all the time - many of which we simply haven't discovered or probed yet.

I wish that everything in biology could be explained so neatly. Unfortunately, real biology is so incredibly messy. There's just so much we don't know - and so much that we can't neatly slot into an explanation like this. But, I know now that in another life I probably would have been a biologist!

"I'm very lucky that I get to learn about genetics through osmosis..."

I see what you did there.

But...is the genetics knowledge the solute or the solvent, because, well, you know (teaching biology to my homeschooled kid at the moment and we just did a unit on diffusion and osmosis, so please excuse my current state of mind)

I have found that educational osmosis becomes less effective over time as I fill my head with bits of information. I have to exert more pressure learning to cause the information to travel across the barrier into my mind.

This also explains why you start to feel stupid after watching too much television, the osmotic action is working against your self interest.

Next step, start thinking about these systems as tools to be used in making technology. You've stumbled upon a very important thing here. Look up IDT gBlocks. Solid-phase nucleotide synthesis is only 99.9% efficient. This means when you make a 500 nucleotide long synthetic DNA strand, every other one will have an error. How do you clean-out the wrong ones? Well, you make the complementary strand, anneal them together, and pass them through a column with immobilized MutS. Guess what happens? The dsDNA with errors get bound by the enzyme and the perfect duplexes just flow right through. So out the other end is cleaner DNA.

This is how biotechnology works.

>> If an error is detected - a mismatch (e.g. a G paired with a T) - a trio of proteins (MutL, MutS, MutH) spring into action.

One additional thing should be covered in biology teaching -- Not just the process that magically "happens", but how it ends up happening. The said proteins have no free will to just spring into action. I recall being taught during high school about mitosis and meiosis, how this spindle apparatus forms, DNA strands split, etc. How do I connect what happens to the laws of Physics? I understand that I still cannot explain gravity, or why a ball falls to the floor, but biology teaching seems to leave a lot more out, and without saying so.

Ah yes, the recurring obsession hacker news has with biology - except that no startup would pay a biologist a software engineer's wage. Talking about biology is nice. But what's nicer is dismantling the elephant in the room.
Aren’t salaries determined by the market? Just to be clear, this isn’t snark. I’m curious how salaried are determined.
They are determined by the market - mostly - so how much you are paid is going to a function of how replaceable you are, and how much more money the company makes with your position filled or empty, notwithstanding dirty tricks that are somewhat rare.
Salaries are determined by the market, but no one ever mentions how the market determines it... which is usually some combination of scarcity, quality, and, more realistically, how many connections you have, etc. These things give you bargaining power which you can use to negotiate salaries.

(This is all very basic stuff but it's more fleshed out than just saying 'the market determines salary'. The market isn't a magical entity, it is run by human behaviour.)

Yes! The market is the name of the system which sets the salary, but the name has no descriptive power. Just like the opening to the article:

> I should have loved biology but I found it to be a lifeless recitation of names…

"The market" is the name of a place where, once upon a time, you would go to buy things, and perhaps sell some things you made; stable and consistent prices would emerge without any particular rules about how prices for things should be set, or any particular enforcers of the price, but by the dynamics of the supply of the good and the demand for the good.
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it's an oversupply relative to demand:

- lots of washout MDs

- lots of students who wanted to postpone adulthood by getting a PhD (master's are just not respected anymore)

- lots of PhDs who couldn't hack the academic game or got disillusioned by it and are used to low salaries because postdocs exploit the high-stakes attempt to get social cachet of professorships.

- few jobs. Biology is a capital-intensive endeavour, so each dollar of VC can do marginally less.

- it's hard to tell the wheat from the chaff in the labor market (and there's probably a market of lab lemons, too), so a superstar's earning potential is necessarily hamstrung

> Biology is a capital-intensive endeavour

Or, looking at it another way, software is a uniquely capital-light endeavor.

Many people who have been in the industry for a few years have enough savings that they could just quit their job and try whatever crazy idea they have without any external funding. You can't do that in biology, or most other fields for that matter.

Part of the reason software companies pay such high salaries is to make this option less attractive.

Salary is higher in areas where the source of money creation is. The current source by our economic design is currently in the banking credit area. Then the business type, telling the story that appears to be the most interesting for these kind of guys, gets most credit, with this credit, all saleries are paid (so independent from real market or need, just based on a 'market' of imagined future value, if we would sell it would be..remember finance crises, people lost real jobs because money creation stopped). So it is no wonder that health care workers get less and others a lot more. Its not really earned but shared along story telling lines. One fairy tail is "market". Unless the banking investment guy gets sick, once in a while, he has no interest for biology or health care, but he likes big machines and cars. Its hard to imagine how biology is usefull for him, unless just to make a lot more money to buy more cars and penthouses, why not 'invest' in that directly?. Just my little theory :-D
"The market" sucks in situations where bargaining power is unequal, the participants don't have all the information and transaction costs are very high.
it will change, soon.
Even one's with a biologist as a founder? (Also not snark)
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Sure, but luckily there do exist careers somewhere in the middle! Data volumes are becoming much larger and many biotech companies these days are building out extensive software teams to tackle all sorts of challenges.

There's also an entire field of computational biology where you apply (and innovate) on huge datasets using ML/algorithms.

In both types of roles you can remain fairly close to biology while still writing software day to day. Many biotech companies will even compensate at bay area tech salaries.

I remember how some a16z podcast they were talking about this. How for the salary of a decent frontend web developer you could hire the best biologists in the world. So if you had to hire both, the market is determining a salary structure that would almost certainly cause social issues in your startup.
bioinformatics (mixing computation and biology) is a profession that is well paid. I'm have a comp-sci background and I work with computers in academia.

The pay may not be as high as straight engineering but is good enough to cause some grumblings.

I remember reading about bioinformatics as a teenager and thinking it was the best option in the world,a career combining a number of my interests! For a little while I was semi interested in looking at that after HS, but I had a bit of trouble finding out exactly what was involved in day to day work and it wasn't exactly something big in hobbyist circles.

Of course, things didn't work out that way, I never ended up going to college, or ever really thinking about any science again until the last year or two.

No, it does not. It pays better than a lot of scientists in the wet lab, however.

I have to do contract work as a data engineer (which pays about 60% more hourly than my bioinfo job) so I can live a decent life.

Biotech pays people like dumb-fuck children when you account for the amount of education required. Damn, it is interesting, though, which is what keeps me here.

End goal is to have my own company in biotech, which is why I contract to build up a nest egg for eventual entrepreneurial pursuits.

Many people with PhD’s in computational bio/bioinformatics in HCOL areas are bringing in <130k/year. It’s really bad.

Doing biology, as in culturing cells and performing biochemical assays does not come cheap. Software and wetware development are totally different ball games in terms of upfront costs and risk levels. Just building a wetware proof of concept without university resources is non-trivial in terms of the resources it requires. I don't think biology fits at all in the standard startup model.
It only fits the startup model if you know what you’re doing, which is in pretty short supply. You can definitely create a shockingly good lab for ~3000 though.
> It only fits the startup model if you know what you’re doing, which is in pretty short supply. You can definitely create a shockingly good lab for ~3000 though.

Agreed. Biohacking budgets seldom ever go beyond 10k in my experience, I've spent more than that by the time I was 18 on my car and parts. That's not to say that isn't a lot of money, and mostly discretionary, but its entirely do-able.

So much stuff can be bought second hand now, or you can do what some Biohackers did and go dumpster diving at University campuses for broken or old lab equipment--Josiah did that to start the ODIN before going to NASA.

This requires you either to be in school and know the days they do it, usually after the finals in the Spring on my campus, or pay someone to find out. Either way, its doable: I picked up a microscope and a few cracked magnetic stirring hotplates and a random box of misc glassware and metal stands my Junior year when I swore I was going to turn my living room into a wet-lab once I made enough to buy an old BD flow cytometer after graduation.

Those plans were soon dashed when I realized I could just go to the lab of the The Scripps Research Institute after I did my training there my senior year. I think I just ended up giving it all away on Craigslists as a starter 'Lab kit' years later and it was gone pretty fast.

I think this depends a bit on the area. I work in the field of metabolic engineering (i.e. engineering microbes to make new products). When I worked at a biotech company in the Bay Area, I had a pretty decent salary, while still a bit lower than software engineers. Right now, I live in the Netherlands and my guess is that the discrepancy is a big larger here.
Hey I am in my masters of bioinformatics in the Netherlands and was wondering what kinds of salaries you are seeing for metabolic engineering and related fields. In my uni things like salaries rarely get discussed but I think it's quite important.
Are you interested in salary ranges in the US and/or NL?
Mostly the NL since I don't plan on moving to the US.
In the end it's not something particular to biology. It's particular to software engineering in the US. Compare to any other technical field and you'll find that the outlier are US software engineers.
This is why I loved biology before I learned what biology research is really like. What I wanted was to recreate life from scratch, an impossible task with todays technology; the logical sequence of steps behind our biological origins is not hard to see and become enamored with, but I will never get the satisfaction of learning all its secrets.

With programming and computers this is so much closer, because these things are made my humans. Millions of man-years of effort, but still man-made. So, at least with computers I know I can learn how it's all done, and I know the steps needed to make all this technology are also known.

I've been struggling with this same thought recently too, namely because my partner who I love so dearly is struggling with diagnoses that most physicians are just not too informed on yet, let alone the underpaid, overworked public hospital system we're dealing with.

It took us years and years and years, tons of shot gun approaches by doctors with treatments, diagnoses, and medications that treat the symptoms but not the underlying cause til we finally figured out what could possibly be wrong with her!

And that was only after she started working in the health field herself and had physicians and specialists that care about her take into consideration everything about her and run expensive tests.

All this to say, I've been researching others' experiences with what my partner is inflicted with and those who are doing better or have some understanding had to figure a lot of it out on their own with countless medical research and studies they pore over - a lot of these success stories are from physicians inflicted with these diseases themselves!

But, how am i supposed to understand the studies, and papers, and drug mechanism of action sheets?

Do I start at ground 0 and start learning biology? What are some good resources?

And how do I know where to go from there?

All this is really troubling me and i feel so powerless.

I started to reply to one of your other comments before coming to the background one. I was basically going to recommend going the university education route. I have a degree in biochem/molbio, and the topics you are interested was basically the third year of my degree. Not to discourage you (you can do anything if you want to bad enough), but they are pretty complex topics and without the foundational knowledge you are going to be saying "wait, it did what?!" a lot. I know this, because I did have all the foundational knowledge and was frequently saying that.

If you have no background in biology or chemistry, I would email the authors of papers you are interested in. Most of those researchers are starved for attention and would love to break it down for you. Try making friends with one or two of the locals so they can explain more papers to you. Eventually osmosis will do its thing.

hmm thats understandable, ive found im met with that resistance with a LOT of questions i have about a lot of fields that you need an education to understand, yet somehow i manage(d), and will have to for now.

in the immediate time being, do you have any alternative, actionable advice? topics/subjects/key people i can consider or look into that you covered your 3rd year?

not saying i disagree with your comment Nor that i dont want to go the education route, trust me i would love that time and leisure, but right now my brain cant be put at ease until i understand certain things

I'd probably start with basic chemistry and organic chemistry, and cell biology, and probably physiology would help. Once you feel like you have a solid understanding of those, biochemistry, immunology and pharma will be accessible.

I'd start with YouTube and MOOCs. Unfortunately, I don't watch too many videos about this stuff, so I don't have any specific recommendations.

There is also the Manga series, which some people find more accessible as a narrative format: https://nostarch.com/biochem https://nostarch.com/mg_mbiology.htm https://nostarch.com/physiology

Also, keep in mind this field is rapidly moving forward. Crispr was discovered after I graduated, which wasn't that long ago. Try and stick to newer materials where possible.

Beside the links provided in the article,

does anyone have any other articles, books, courses, lectures, youtubers, key people, papers, journals, interesting links/talks/podcasts/quotes they'd like to share to help others on their journy to understand biology better?

Thank you!

In a Nutshell is good (not deep), though you probably already know them
I would recommend the edX Introduction to Biology course [0].

It is a simplified version of the introductory biology course at MIT, that doesn't _focus_ on naming/defining things in biology. Instead, it uses the lenses of genetics and biochemistry to explore how the core machinery of life works, and how we got to our current understanding. That said, there is some amount of memorization that is unavoidable.

[0] https://www.edx.org/course/introduction-to-biology-the-secre...

This is a great article. I had the same realization some years back - this stuff is amazing! Why didn't I get into it when I had a class on it? Of course, it's easy to rail on high school classes for failing to dazzle; maybe it was just my mind not quite being ready or willing to learn. But damn, biology is amazing. How does it all work??!!
I suspect that there is a transition, that happens after high school for some people, where the world goes from a bewildering set of disjointed arbitrary facts that need to be memorized, into comprehensible system that can be understood and behavior predicted (with sufficient effort).

I also suspect that part of this is that software engineers, realizing that they can now purchase things like lab equipment and bacteria cultures, are now free to fund their own learning in their own idiosyncratic way (much like they learned to program), and not worry about burning money on something that doesn't pan out.

Between this, a new confidence that the world is understandable and... debuggable, and the fact they can finance their own experiments, gives a shift in perspective that wasn't available when they were in high school.

"I should have loved biology but I found it to be a lifeless recitation of names"

This is a common complaint when learning many subjects, and many teachers don't explain why the names are needed.

Take music theory, it has an insane amount of vocabulary and concepts to assimilate, but if you watch any of the popular music theory videos on YouTube around these days, you get a glimpse of what mastering those terms looks like.

So, extrapolating to other areas, it seems like school needs to do a much better job of explaining the focus on vocabulary. The language of Algebra, the language of Organic Chemistry, the language of Music Theory, etc, etc ... what superpowers does mastering those languages unlock?

To me, watching someone work who already mastered those languages in action can be very inspiring, even if haven't reached that level of understanding yet.

> what superpowers does mastering those languages unlock?

Maybe think of it this way: it isn't unlocking the superpowers, it's an ultrafilter. If you aren't capable of performing precise and contextualized recall of trivia, then your engagement with the subject is going to be limited to diletanttery. When I was a biochemist, there were several critical instances when recall of some minor thing that I had learned years or even a decade ago, sometimes even an offhanded comment in a journal club, enabled debugging a situation where there wouldn't have been time to "go to the library" much less even know where to start looking.

I know it's fiction, but think about the show House. Would House have been as effective if he didn't have an encyclopedia of knowledge at his fingertips? You have to be able to not just think about things from first principles BUT ALSO literally have indexable fast-access knowledge.

Since you bring up music theory, in jazz, it's one thing to know the theory of what a 2-5-1 pattern is, but if you don't have it in your fingers, you are not going to be able to make good music, imagine a jazz pianist constantly searching the keyboard for the correct notes.

House was effective because the writers made him that way. The real top people in fields are not walking encyclopedias. They have extremely good grasps of core principles, key findings, relationships between ideas, etc.

Specific names and other specifics that don’t fundamentally affect things are not things they clutter their minds with.

Encyclopedic knowledge can be a great tool, no question about it! I think of it as memoization for the brain.

It may well turn out to be that some problem you are attacking could be simplified if you only knew that piece of "trivia", but if you don't know it you need to spend some brainpower re-discovering the thing instead of attacking the main problem.

The way I think about the learning / performance is a bit like an RPG game. Encyclopedic knowledge is just another bar to fill in, with the corresponding trade offs.

If you don't have committed to memory and immediate recall that "aspartic acid" is a negatively charged amino acid, that has dramatically different chemical properties than cysteine, you won't notice something strange is going on when hundreds of amino acids go by your eyes in a BLAST alignment, that you did offhandedly one day:

https://bmcbiochem.biomedcentral.com/articles/10.1186/1471-2...

That's an easy example. Another one: knowing the atomic mass of nickel in a mass spectrogram and explaining a deviation in a MS fragmentation pattern instead of throwing out the data. Another one: Knowing the mechanism of chen-mapp phosphorylation https://www.researchgate.net/publication/7184505_33-Rearrang... and rescuing an otherwise lost synthesis in a group meeting (not published; the downstream results were not otherwise interesting).

Don't discount having raw knowledge at your fingertips.

This is entirely off topic, but the way you phrased your comment makes me think you have experience learning music theory. If so, could you share some resources that you found helpful? I've always wanted to learn music theory (and put it to practice), but besides hiring a teacher I could never get solid recommendations of where to start.
Indeed! There is a vast bibliography but starting with a music-school theory book is often really daunting... so searching for something different I found this series from Michael Hewitt [1], there are 3 books, one for theory, one for harmony and one for composition.

Halfway through reading the first book I decided I needed to get better at inputting music to my computer, so I started to learn Reaper (which is a bit like "the emacs of DAWs" :-).

https://www.hooktheory.com/ is also a great practical resource, focusing on numeral analysis of popular music, and the their composition tool is fantastic!

I have a backburner of other resources that I want to eventually cover but I figured that was as good a starting point as any.

1: https://www.amazon.com/kindle-dbs/entity/author/B001I7U4SM

Not OP, but, I've only ever used online resources -

- https://www.musictheory.net/ is surprisingly good for the basics; their apps are good quality.

- https://www.reddit.com/r/musictheory/ used to have a lot of rabbit holes that were fascinating, but not sure what the community is like now. From a quick look it could still be a useful place to lurk.

- The Youtube channels 12tone, Sideways, 8-Bit Music Theory and Nahre Sol are my go-tos now that I'm no longer in active learning mode. Music Matters, Adam Neely and Signals Music Studio are also good. There are others in the Youtube sphere too but those are the channels I'm most familiar with.

- Music composition videos and classes also tend to be fairly theory-heavy without advertising it overtly.

After 15 years in tech and a life-changing psychedelic trip, I decided to self-learn genetic engineering and share it with the world[1][2] while I look for a meaningful biotech venture to found.

What you can do today from your kitchen or home lab is remarkable. For instance, I taught myself PCR (polymerase chain reaction) and recently published my first genetic sequence at GenBank from fungi that I cultured, extracted, sequenced and aligned. I'm planning to have developed my first GMO yeast in the next 90 days.

If you're interested, I also host the EverymanBio Podcast (YouTube & iTunes) where I talk to folks doing incredible work in the biotech / startup / diybio community.

[1] http://everymanbio.com/

[2] https://www.instagram.com/everymanbio/

[3] https://www.linkedin.com/in/joshuamcginnis/

>life-changing psychedelic trip

Fascinating stuff. Any chance you could expand on this?

I suffer from pretty bad depression and have been battling with it for a while using all available treatments. Someone recommended I try psilocybin mushrooms. I learned how to grow them, grew them and then had my wife help facilitate a safe well-intentioned trip using 7g of dried mushrooms. Happy to answer any questions about it. It was a profound experience. It isn't a cure but it's certainly a tool in my toolbox that has helped reshaped my life in a real and lasting way.
Wonderful to hear it’s had such a positive impact on your life. What part of the experience made you decide to learn about genetic engineering?
By serendipity, I discovered a few YouTubers around that time who were showing how to do synthetic biology and biotech step-by-step on the cheap. After the trip, it dawned on me that perhaps I should put my intellectual abilities to work in this new field as it might bring the connection to life and meaning that I've struggled to find in tech.
Are those youtubers, or their content still around?
Sheesh, 7g is no joke. How “hard” was your trip?
It was difficult and I wouldn't recommend it for newcomers.
Weren't you a (very depressed) newcomer yourself?

Don't take it bad but someone in an already bad mental state taking 2g more than what McKenna considered a god dose is pretty ... irresponsible (?)

I was depressed, yes. But 7g wasn't my first experience with psilocybin. I was just saying that generally, I would not recommend 7g for newcomers. As for being irresponsible, I don't know man. I grew a Schedule 1 drug and then consumed it on my own terms in a way that affected no one but myself in a positive manner. There were risks involved, but when weighed against how I felt at the time, I took the chance.
Didn't mean to criticize. I've tripped on mushrooms, I get it. It's just ... 7g, holy crap :)
It’s hard to quantify how strong based purely on dose size, but yeah 7g is double what I would consider a strong dose. I did that amount once in high school and I didn’t touch them again for several years haha.
People have wildly different reactions, some of my friends can take 14g+ and be fine, others are barely able to talk after 2g. Plus potency varies wildly between crops and strains.
Also, there are different types of shrooms, saw at least 7 types last in Amsterdam, potency varied significantly. Also, how empty your stomach is makes world of difference. Also, method of consumption - dried vs fresh, raw/cooked, or like me mixing it with raw lemon juice (makes trip shorter but way more intense - 3g trips were full beyond reality with good setting).

Plus individual variation in digestion/enzymes/receptors/god knows what else is most probably also important.

Mm, there's a world of difference between, say, 7g of Cyanescens and the same dry weight of a Cubensis.
In my personal opinion there is a threeshold you have to hit with psylocipin before you can fully let go. 2g would feel emotional worse to me than 7. I take up to 1g semi regularly against my migraines which is just a little below turning super emotional.

Edit:// for reference i am talking about dried golden teachers. There are stronger variants out there.

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this terrifies me, some crazy makes a gene drive super corn pathogen and civilization crashes.
A childhood favorite of mine. It seems infinitely more plausible today than when I read it.
Thanks for the link. Interesting comment there, which somewhat reminds me of the current COVID-19 situation:

"The way the different countries failed to come together in the face of a world-wide catastrophe was plausible. The turn against science... while only briefly touched on, the way the angry masses turned on scientists was believable." by Clackamas in 2008.

It is awesome that you're getting started in this community! Here are just a few very biased recommendations of interesting folks for your podcast:

There are a bunch of different cliches (community bio vs biohacking vs citizen bio vs grinders vs transhumanists are all VERY different), but I'd recommend checking out a few of the conferences. iGEM is going on right now which is super cool, and BioHTP and Biosummit are 2 I always recommend. Since you're into fungi, there are a few cool folks in the DIYbio community you might want to talk to - Rolando Cruz Perez (in Endy Lab right now, off to do amazing fungi things soon! PhD on standardizing fungi growth conditions for distribution of strains) and Phil Ross (Mycoworks CTO, extremely eccentric, very artist, supremely interesting)

If you haven't followed them, David Ishee on Facebook+Twitter and Sebastian Cocioba on Facebook are also real good to follow. I love David's spirit+integrity of hacking and science, and Sebastian radiates an aurora of childlike wonder (specifically in plants) that is inspiring but calming. Might want to also give Josiah Zayner a follow, he is an interesting case of definitely knows-what-he-is-doing but still extremely controversial. He's a generous and kind guy though, and it is extremely respectable what he does.

Gabriel Licinia is another interesting individual in the DIYbio community you might want to reach out to - him and Justin Atkin (the thought emporium on youtube) are some of the few folks who actually do things in the community. Real science and real cool. Gabe is the local angry man who'll always tell ya if something is BS on the DIYbio facebook groups. Those 2 also work with Andreas Stuermer, who is a fantastic DNA designer. Those 3 are quite a superpower.

On the startup side, I'd recommend checking out Ryan Bethencourt's stuff. He is a great guy, transitioned from diy->startup stuff, and often helps others do too. I personally like Elliot Roth's company Spira and what they are doing with cyanobacteria and photosynthetic organisms. The future is cyanobacteria!

On the non-profit side, I really like what the BioBricks Foundation is doing and what the Open Bioeconomy Lab is doing.

Hope some of those things help! Glad your P.olymerase C.rap R.eaction worked - GMO yeast is easier IMO, just follow the culture timings and you'll be fine. Also Sanger is terrible, and Nanopore is awesome. I'd be happy to talk with you too if you'd like - I've been around for a bit, and I love helping other people get started in these communities!

PS: on your website you say you want to "Learn to navigate GenBank". Please be prepared to be disappointed.

if i want to learn more bio not bc i want to hack or edit genes or whatever but because of reasons such as:

understanding autoimmune diseases, the treatments for them, relationship to other issues, medication and their mechanism of actions, and just a whole host of other stuff

basically i want to learn how to help people i know who suffer from multiple autoimmune diseases and the mental health/daily life and fertility struggles associated with them,

where should i go?

thank you!

That's unfortunately much more into the medical field, so I'm not really sure where to start. I only really work with single celled organisms.
Not OP, but thanks for taking the time to share, this is an awesome list.
Hi there - thanks for the thoughtful response and great list of contacts! I'm actually in talks with a few of them already. Rolando Cruz Perez, I didn't know about and will reach out to chat soon. Appreciate your support!
This is a really inspiring comment. I'm an engineering student who's kind of mentally stuck between the worlds of computing and bio. I want to do research in biotech, but I'm having trouble finding the will to do it for some reason.

In a different vein, I've recently started designing a really cheap atomic force microscope, which I plan to open-source, so I think that may be a valuable addition to the bio and nanotech diy community.

> I've recently started designing a really cheap atomic force microscope, which I plan to open-source, so I think that may be a valuable addition to the bio and nanotech diy community.

I hope you do

Thank you, hopefully external validation will push me to actually complete the project.
Planning on using off-the-shelf probes in your AFM? How cheap can you get those nowadays? I remember being worried about crashing them too often with our modest lab budget.
No, I'll be manufacturing them. There are alternative ways of making cantilevers with atomically-sharp tips. Tungsten wire, for instance, can be etched down to less than a few nanometers. And the quartz clocks in almost all electronic devices can be decapped and used as an oscillator.
AFM isn't really used in biology.
But it is used a lot in biophysics!
It is? I mean, that was my PhD, but I don't recall anybody ever using AFM for biology. Huh, apparently now they do.
Yeah lots of single molecule studies (strength of an actin filament, how much force needed to 'unfold' various proteins, etc). And this was 20 years ago when I was in grad school. Haven't kept up with the state of the art today.
interesting. all the people doing that in my day (also 20 years ago) used fluorescent microscopes (Ron Vale) with labelled protein. I can't see how you could unfold a protein using AFM, since it's in vacuum state, although I totally understand how optical tweezers would be fine to do this in solution.
AFMs work in both air and fluid environments.
i asked this elsehwere in the thread, and if you scroll lower you'll see why i want to learn but this is going to sound like a bit of a ramble as im tired and feeling passionate and emotional right now but bear with me...

..if i want to learn more bio not bc i want to hack or edit genes or whatever but because of reasons such as:

understanding autoimmune diseases, the treatments for them, relationship to other issues, medication and their mechanism of actions, and just a whole host of other stuff

basically i want to learn how to help people i know who suffer from multiple autoimmune diseases and the mental health/daily life and fertility struggles associated with them,

where should i go?

thank you!

A good place to start would be to see if there's anything on NCBI Bookshelf, and then search pubmed for recent review articles. And then you can drill down further using their citations.
Go to scholar.google.com, search "autoimmune disease treatment", filter by last five years, use sci-hub to read the paper. Repeat until you learn enough to find your next step forward.
i mean i want to learn about everything before that too, like history, links, diagnoses - to be sure, as well as testing/tracking metrics and the likes,

also reading is the easy part, but what about understanding? when im running into medical terms/and other things im not familiar with or equipped to understand, where do you go? bc i find myself ending down different rabbit holes and my productivty diminishes and my thinking gets scattered

i hope im making sense :)

It can take me weeks if not months to fully comprehend a new paper. One paper will require that I look up a lot of new terms, watch a lot of videos explaining the terms and repeating the process for the cited references. It sounds like you need more structure so I would suggest you take notes, set goals, organize your materials and schedule time for focusing on particular topics, tasks or techniques.
It’s hard to do that when I’m entirely new. Idk where to start or what raw knowledge I possess that combined with biology would achieve the results I want.

I know the end goal though, I want there to be an option, a fix or a painless way to manage autoimmune diseases, things like hormone and metabolic response imbalances -thyroid, androgen, progesterone, insulin - etc they all share a link to deadly lifelong debilitating diseases That make living hell for so many people and I want to take that away for them or at least generations down the line.

I know I’m a rambling scattered mess right now I thank you for being patient

Be aware that on the scale of complexity, the immune system is at the deep end of the pool. Your motives may be admirable, but the chances of you jumping straight in and emerging with the Olympic gold medal are good as zero.

If you want to get into the science of it then I’d suggest you start with general courses in biochem and physiology at the undergrad level and build your way up from there†. Expect to invest a good hard 10-20 years of your life getting up to speed, with no hard guarantees of success at the end of it.

Or, if you just want to help people right now, go get yourself involved in charitable fundraising for an organization that’s already working the problem. Still no guarantees, but at least they’ve got a big head start. Just don’t end up on a list like this, ’kay:

https://sciencebasedmedicine.org/?s=immune+scam

--

† Courses I flunked myself, BTW, but at least I learned just how much I don’t know—an insight I’ve subsequently found both invaluable and frighteningly scarce in tech.

University textbooks. They are written with the goal of building that foundational knowledge.

Scientific papers are great, but they assume a lot of pre-existing knowledge, whereas a textbook is designed to expose you to the concepts without any prior assumptions.

Biologist here. I would start with a textbook called Janeways Immunobiology. It is the textbook that all of us have used to learn immunology and should be accessible for anyone with a high-school understanding of biology. The book already has many explanations of autoimmune diseases, so it should be everything you need.
Seconding this. I would also add that Biochemistry was really the class that first gave me the "I should have loved biology" feeling, so whatever the equivalent Biochem textbook is might be interesting as well.
Add the word "review" to your search queries. Often, single author articles just review history and current state of the art.
Absolutely not. You probably won't understand 10% of what you read. Better: go to your local university library, check out a good medicine/biology textbooks, and read that. Then go read the papers.
Per the article, a deep dive is likely better than a general overview. Also, OP says to repeat until it clicks, which is generally correct.

But the real issue still stands: Bio is hyper complex and it takes a long time to get used to the nomenclature and ideas.

> But the real issue still stands: Bio is hyper complex and it takes a long time to get used to the nomenclature and ideas.

That is exactly the point, which I believe the article author either glossed over or didn't fully appreciate.

I have a B.Sc. in general biology and am about to get my M.Sc. in ecology. I do scientific work at a university and read (ecological) research papers every day. Out of curiosity, I just followed joshuamcginnis' advice and did the Google Scholar search.

I failed to understand the first three items that came up.

The basic principles of biology are usually not actually that complicated, at least when you compare them to particle physics or compiler design or stuff like that. But biology is still hugely, hugely complex, because you simply have so many interacting parts - and yes, you only really understand it when you know about an appreciable fraction of those parts.

That is why they spent the first 1.5 years of our degree simply drilling knowledge into us as fast as we could absorb it. Because it's only once you have a broad overview of how everything works, that you can start to grasp (and reason about) how anything works in detail.

Biology is fascinating. There are millions of cool things to learn and yes, most teachers could probably do a much better job of teaching it. But if you really want to understand it, you just have to put in the effort.

What about some MOOCS? There are plenty that will introduce you to this area.
Can you (or anyone) recommend a good one? Thank you!
> Can you (or anyone) recommend a good one? Thank you!

https://www.coursera.org/learn/biology-everywhere-foundation...

I recommend this as an entry level course series, I actually attended Dr. Peffer's lectures on campus (as a non student) after nearly 10 years after completing my BSc in Cellular and Molecular biology. She holds a post Doc and research position on Campus and really likes Ed-tech and the 'gamification' of Education as a whole; she is what I wished I had when I was doing my undergrad.

When you want to get really into, head over to Josiah Zayner's, The Odin [0], where he takes Bio-hacker methods to Gene Editing and synthetic Biology. He sells kits and has weekly podcasts [1] of his experiments and observations for people to follow along. They did a COVID vaccine trial on themselves, and then moved on to making lab-grown meat, which was actually very cool way to get into the space and the community.

0: https://www.the-odin.com/?

1: https://www.youtube.com/channel/UC-aCKd4djOAf_0BzyUMJ5FA

I'm an electronics/embedded programming guy and I "accidentally" learned biology by listening to a great bunch of podcasts while going to sleep and commuting.

At first you won't get all the terminology, but if you keep listening you'll eventually get it (that's how it worked for me).

The cool thing is that you'll dive right into the state of the art of academic research by the very people who do the research and write the papers. It's geared towards people like you and me: the curious general public.

Since you mentioned autoimmune diseases and medication, I recommend starting with: https://www.microbe.tv/immune/ If you have any particular disease you're interested in I would just do a search on that page and dive right in.

They also have weekly (almost daily now) updates on SARS-CoV2 where they seem to be ahead of the MSM by weeks to months: https://www.microbe.tv/twiv/twiv-683/

They talk with not just virologists and immunologists, but also people in industry who develop vaccines/meds, people who organize clinical trials and PEOPLE LIVE FROM SPACE: https://www.microbe.tv/twiv/twiv-682/

> At first you won't get all the terminology, but if you keep listening you'll eventually get it (that's how it worked for me).

It's kinda like a cooking show. At first, you have no idea what they are doing, but after season three you just know that they don't have enough time to do a proper raspberry vinaigrette before the gong strike.

I love biology yet I could not have described more opposite interests. I have zero interests in producing gmo in my kitchen, but I am definitely hooked on plants interaction and selection in open fields.

Biology is pretty broad a field. Science of the living.

Not to start a holy war, but what is the difference at the end of the day? Isn't one just faster?
There was an instructive novel written by Mary Shelley on that very topic. Recommended reading.
One occurs naturally and thus happens all around us without human interaction. So there's value in understanding how things work without any input from humans.

One is more like studying a natural process while the other is the mechanics of that process.

Yes exactly. The fruit might be the same at the end of the day; red, round, juicy. But there is more that goes into growing fruit than just reaping the end product. There is fertilizers which run off into lakes [1], pesticides and herbicides that get into the soil increasingly making soil less fertile [2], market cornering tactics like seed patenting [3]. I think it is more important to study how to make nature do the work of growing food abundantly with as little side-effects as possible, instead of engineering it to with no caution for side-effects.

[1] https://www.scientificamerican.com/article/fertilizer-runoff...

[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC91132/

[3] https://en.wikipedia.org/wiki/Bowman_v._Monsanto_Co.

Look up mutagenic breeding, the idea breeders are taking a more natural approach is nuts.

I do agree we should invest more heavily in tech like bug resistance to reduce necessary pesticides.

I'd say that one is studying a plant and its interaction with the environment/other organisms whether the other is more interested in the inner works of a fungi. It is a matter os perspective, one is doing ecology and the other one is more weighted to genetics.
When it comes to biology applied to agriculture, I prefer eco systemic research to genetics, as a personal taste but I don’t even think those are mutually exclusive.

Maybe an example is appropriate. Monocrop cultures are efficient short term, easy to control ... but also simplistic and brutal. In this system, gmo can help reduce the nefarious intrants (fertilizers, pesticides ...). This sounds like optimization.

Alternative cultural models, multicrops for instance, are saner but implies many technical and economical issues that still have to be dealt with. This is more like an architectural change.

GMOs are the somewhat intentional introduction of genes from another organism while breeding approaches often involve radiation to expedite random mutations which may have less obvious changes that are not safe.
To be fair, GMOs can just as easily be unsafe; the difference in that regard is that with GMOs there are fewer ways things might go wrong, and they're much more easily enumerated and examined.
The best example of an "unsafe GMO" would be this: https://pubmed.ncbi.nlm.nih.gov/8594427/ (brazil nut proteins were transferred to soybeans; the proteins happened to be ones that cause brazil nut allergy. If this had been rolled out in large scale, probably some fraction of consumers would die).
Nearly everybody in the first world is eating food which has been modified by radiation to expedite mutations for many decades (since the Green Revolution) and I don't think anybody has shown any convincing evidence that the products have been systemically unsafe.
I just want to point out that there is no such thing as genetic engineering. This isn't a nitpick, but an important point that investors and laymen alike can benefit from understanding, particularly in regard to avoid being deceived by exuberant claims of progress by so-called "genetic engineering" startups. The top comment [1] from another HN thread sums it up pretty well. Here's an important excerpt:

...engineering is a tradition built on minimizing variation, while biology is a science founded on understanding a built-in mechanism for generating variation. "Life finds a way"....evolution is always driving against the engineered design

An engineer can design a system that creates 1000 screws with minimal variation. He understands all the effects of the different steel chemical makeups, he understands how to change the pitch and length to his specifications; he understands how to achieve each and every property of that screw, and once created, the screw will not act against its makeup.

A "genetic engineer" is presented with a million million variables. In altering a variable, he may observe some change – maybe some bioluminescence in fungus, some hairlessness in a mouse. But how much also changed that he cannot possibly observe? What other variables were dependent on the altered variable? As it is life, ever in flux, how much more will it change, itself, and its environment?

"Genetic engineering" should rather be called "unprecedented biological experimentation". This is important because "engineering" implies certainty, replicability. Altering some gene isn't engineering. It isn't minimizing variation in a system – it is introducing even more variation into that system. "Genetic engineering" certainly sounds cool and promising. But before you buy into a startup that employs "genetic engineering", don't be so certain; biology is much harder, much more complex, than screws.

[1] Or: Biology is really hard... | https://news.ycombinator.com/item?id=21396311

Your comment makes interesting points but I don't think I agree with the main point.

If engineering is "the application of scientific and mathematical principles to practical ends", the search for practical uses of genetics, could be called, fairly, genetic engineering.

Genetic engineers sound a lot like machine learning engineers— tweaking huge complicated models which can only be understood through observation/experimentation. Often times the training is stochastic and not directly repeatable too.
Any books you would recommend for someone coming from CS background to get a jump start on this topic.
The article has a lot of really good introductory texts in it.
Same pathway as the author!

In high school, biology class meant memorizing modules of the human heart and pricking my finger to find out what my blood type was (I stayed home sick that day). "Loving biology" meant carrying around AP Bio books thicker than an unabridged Webster dictionary. No thanks.

Then later in college, my friend said it would be fun if we both took the genetics class he needed to take for his pre-med reqs. I agreed, and then bombed the class exam after exam.

One day right before Thanksgiving, when all the students are checked out, the profs got up and demoed their research.

They got up and showed us BLAST, the 3 GB human genome, and software tools to search the genome. Most importantly, these 2 professors, masters of the genetics universe as they were, made lots of mistakes while demoing the software. They "oops"ed their way through this and that and said it was ok because the human genome had just recently been sequenced and it was all still new.

"It's a UNIX system! I know this" popped into my head, and I promptly declared myself a biotech entrepreneur. After class I went up to the teachers and told them I would build them better software tools for genetics. Then I wrote every department in school I could find who used digital genomes to build them better tools. Tools for understanding the most important language the universe had ever written.

14 years later, in the wake of that realization is the first hackerspace for biotech BioCurious [1], an open source DNA copy machine OpenPCR [2], and lots of great work with the iGEM [3] and DIYbio [4] communities.

These days the fun continues as I'm engineering the biggest living system out there [5], planet Earth.

[1] BioCurious http://biocurious.org

[2] OpenPCR http://openpcr.org

[3] iGEM http://igem.org

[4] Do-it-yourself Biology http://diybio.org

[5] Mining carbon from the air, AirMiners http://airminers.org & Negative http://gonegative.co

Do you have links to any of the tools you made?
unfortunately, all the tools that exist today are still crappy and misused.
I am an out of work scientist. If you want someone that is happy to chat all things bio, pm me.
If I may ask, what were you working on before? (Just curious, feel free to disregard)
Most recently, protein engineering, before that, medicinal chemistry.
There is no contact info in your profile.
You can to reach me through github.
I started out in computers, spent most my career in biotechnology, and right now spend about half and half in each (for the most part, I run a DNA cloning foundry where I clone new sequences. Need lots of software for that).

If there is one takeaway from working in both fields, I think it is that a lot of computer scientists believe their systems are deep - it is nothing compared to biology.

Biotechnology also has a fundamentally different culture than tech, and so there can be some culture shock between the two. This is improving - I think the author would have loved synthetic biology :)

Given the mutable global state nature of biology, this actually seems like a perfect target to apply machine learning to essentially try trillions of combinations in parallel to uncover ideal states. Once we know the ideal states of cells that eliminate disease and optimize bodily function, we can reverse engineer the precision medicines to “tweak” the chemical balance of cells.
this is my favorite blogger

his 'there's a gold rush on and I'm the shovel' article about his decision to leave programming for writing has always stuck with me

and nothing he's written since then has betrayed that voice (especially the post on 'you're using the wrong dictionary')

I love this article.

Does anyone have suggestions on starting down this path as someone that understands programming but has forgotten all the high school biology I learned?

I love the way I can now learn new programming frameworks. Read small bit by bit projects that build up slowly and teach the important components. Svelte for example. Solving problems and practicing the techniques are the best way for me to memorize things and then apply them to my own projects.

Is there anything similar that could start me down this path?

I'm less interested in videos like the Ninja Nerd. They look great, but it isn't a way of learning that sticks with me.

What are you interested in? Synthetic biology? Bioinformatics? Something else?

Biology is really broad - As an analogy, not sure if you’re interested in how to build a gaming computer or want to learn how make web apps.

I don't know. Which of those is the most fun? I suppose I don't care as much about building something or a career as much as I want to learn something new. Can you suggest a focus for me?
A book I loved when I was first learning is called “Unraveling DNA” from 1988. I remember it reading like a detective novel, as back then the folks writing were mentored by the OG molecular biology folks. It can be yours for only $4 https://www.amazon.com/Unraveling-DNA-Maxim-D-Frank-Kamenets...

“A genetic switch” is another fantastic unraveling of a single virus. If you like diving into like a framework and learning piece by piece how it all works slowly, that is a GREAT book. For a while this was my favorite book.

https://www.amazon.com/Biology-Viruses-Bruce-Phd-Voyles/dp/0... This book started my career. The first chapter, specifically, started my career. It got me hooked, not sure why. You can learn about other WILD things viruses do there too!

On the experimentation side, try a transformation kit https://www.the-odin.com/colorbacteria/ it’s $30, and at least you’d be able to tell friends and family you’ve genetically modified life before. That is a nice intro into synthetic biology. This is how I got started.

On the bioinformatics side, miniPCR has some nice kits to go barcode environmental strains. I personally hate doing PCR and don’t care about barcoding, so I’m biased here. I’m much more of a synthetic biologist, so bioinformatics study is only relevant to me in context of the things above.

I’d probably buy some books + the transformation kit and then see what interests you from there. There are a couple things that are 1 step away from transformation kit plus some learning, which is why I recommend that path.

Idk biochemistry? Cell, molecular, structural bio? Genetic engineering?

These are all so abstract to me but I wanna head down a path to better understand autoimmune diseases, research being done, viable options...

Idk but how can I leverage modern day understanding and tech to have an end goal of creating a biologic that makes it so people don’t have to live with their body fighting themselves everyday or give a mother at risk of miscarriages another chance?

It’s all such a big messy abstract sound storm in my mind and I wish I could focus it more to ask the right question but unfortunately I can not

Big problem with the field of biology, like Peter Thiel says, is it's the science field people go into to avoid math.
I was thinking similar thing while reading through the article. The school system does the selection of mindsets and sets the stage for whole discipline. The approach for intro classes seems to be absorbing textbook material, and not curious mind doing investigation. It may change later on, but the filtering of students is already done by that time.

I wouldn't say that biologists avoid math without some data to support that. Just that schooling system is doing huge disservice to biology field by ignoring scientific method in early education stages.

I have microbiology and electrical engineering degrees. Started a PhD (microbiology and immunology) and washed out with a masters to go into the dot com boom.

There is so much potential for biology to be engineering, but the reality is you can spend your whole life studying one tiny aspect of something esoteric. You can spend your whole life trying to find one amazing cure (or not).

Biology is great if you are interested in learning how the world works, but not so great if you love to create new things.

Even with medicine you are essentially a mechanic for humans instead of cars and the technology improves a lot slower.

I considered doing bioinformatics, but there was essentially no way to make money because grad students were doing everything for 12K/year.

One great thing about biology is that it is easy to understand because everything makes sense and "works" like you think it should. Human created systems often times dont make sense at all.

Synthetic biology is pretty good for creating things. Agree with other points tho
> One great thing about biology is that it is easy to understand because everything makes sense and "works" like you think it should. Human created systems often times dont make sense at all.

Interesting. I tend to view it as the opposite.

Someone else’s system might not be created using the abstractions I would have chosen but with enough head scratching you can generally at least surmise causality. And with computer systems, you can test and re-run until there’s a grain of certainty.

With biology there’s so many independent moving pieces that it feels, to me, like our explanations of molecular and cellular processes are almost certainly lacking an encompassing view. And using them to explain macro biological phenomenon borders astrology. Sure our, experiments tell us something but we interpret results as rules while neglecting the wider context. I don’t want to project onto others but I don’t think my brain is equipped to understand the emergent processes at that scope of nested, interdependent, hierarchies. If you thought object-oriented programming was bad!...

> One great thing about biology is that it is easy to understand because everything makes sense and "works" like you think it should. Human created systems often times dont make sense at all.

That's probably because people choose to test only the most obvious hypotheses. There s an amazing amount of data but it s mostly at the level of "describing the clouds". there seems to be a need for theoretical breakthroughs

Reminds me of The Vital Question by Nick Lane. I highly recommend this book. I had that same sensation reading it: "Man, why was high school biology so boring when it could have been like this?!"

It's about the role of energy in the emergence of life (pre-biotic -> single-cell -> multicellular -> animals). You'll see some chemical names, but it also tells interesting human stories too.

Perhaps more interesting than learning that "every cell in my body has the same DNA" is learning that they don't. Many mutations aren't repaired and the result is "mosaicism" which turns out to be more common than was once thought, particularly for neurons since they are so long-lived:

Scientists Surprised to Find No Two Neurons Are Genetically Alike https://www.scientificamerican.com/article/scientists-surpri...

Inspiring. His message doesn't apply only to biology. Several subjects in schools are teached in an uninteresting manner that doesn't captivate the students, and so they don't learn, and so they rather hate school. Memorization of the wrong type of things for the sake of tests should end. We should focus more on what sticks with people.
Science, and biology in particular, was one of the few subjects I actually did enjoy growing up. I could occasionally be found reading some random books related to the subject.

Of course, one of the things that ultimately lead to me doing software, was that it was something I could do "real" work in my own home without a ton of extremely expensive equipment not available to the general public, and immerse myself in it, which is more than I can say for most of the things that have captured my interest.

Before reading the article I started writing a comment about how during a 1st year genetics class at university I was amazed at the software and hardware (for lack of better terms) involved in DNA replication are mind blowing. Now I see the author makes the comparison to a Lisp program.

Also wanted to mention the differentiation of cells in an embryo (how the f*ck can that even work ... not in a lab, but our own bodies?!) - it's explained really well in "The Gene" (hormonal gradients in the embryonic fluid). Author also mentions this.

Natural selection ... is our DNA some kind of cosmic RAM memory that stores all this information over millions of years?

The other day I went to get my hearing checked and the doc explained to me how sound is captured by the ear drum and transferred to the brain through a few bones and along hairs & nerves. It's basic high school stuff but if you take a step back and think about how this mechanism makes us perceive the beauty of our favorite sounds (music, hearing our children laugh), how complex it must actually be and that this ... "evolved", out of a cosmic chemical soup, it's just incomprehensible.

Biology, genes, brains are nothing short of amazing. I'm not a religious person but if something points to the existence of a god then you'll find it in biology.

This isn't just biology, it's school. The only time you're taught processes and methods, it's when they're busywork, and you're wasting a year memorising how to do something nobody does any more because we have computers and calculators. What you're being taught is to squash your individuality, demand and follow orders, and to seek your worth only in the approval of your betters.

But most of all, you're being kept out of the house so that both your parents can go back to jobs they don't like.

You made me exhale in amusement at this comment, because it is true to a degree.

Do you think most people don't actually mind this kind of education? I'm asking because I'm baffled this is the way education seems to work in most places and has done for ages . I also assume that something would eventually change if enough people disagreed.

Or might it be because that is still how we think about the employer-employee relationship and the latter's duties - follow orders and ignore your individuality?

I think that comment just reflects the current thinking that you can have something without putting any effort.
I think this comment reflects the current thinking that the amount of effort is intrinsically tied to attained value.
I certainly wasn't saying that, nor do I think it. I don't see what it has do to with the topic at all.
Education is actually changing all the time. There are some efforts to improve it in general, improve it for selected groups (disabled) and periodical efforts to dismantle and destroy its public form entirely.
Computers and calculators will not help you if you have no idea what you are doing.
Not all schools are like that. Vote with your (children's) feet.
Probably not the same education system, but there are many things I no longer do explicitly that are nevertheless important for understanding the concept.

Off the top of my head, for just mathematics:

- Long division

- Calculate limits

- Curve sketching

These aren't things I do by hand any more. But if I hadn't learned how to do them, I wouldn't be able to apply them to more advanced problems.

From my extremely limited exposure to US education methods, I would concur that some algorithms are practiced in an excessive manner. But that does not mean that they are useless, even if computers can help you often enough.

Maybe you can name a thing or two that you consider "busywork [that] nobody does any more because we have computers and calculators"?

(I will note though that biology courses always stood out to me in exactly the way that is lamented in this thread - almost entirely memorizing arbitrary things.)

I would say the times tables is a good example, once you know the mechanics of multiplying 2 numbers you don't need to redundantly memorize the exact values of tables of numbers. The mechanics and how to solve for it are the important pieces to learn. Further I think it actually does more harm as it hinders the child's ability to look at numbers as placeholders and variables when they get into higher level maths. Spending so many years on the basics of mathematics could be speed up if we ensured that children fundamentally understood the mechanics and principles and then moved on to more interesting math like algebra and geometry. Where you can see more real world applications by applying them to easily solve those word problems that we all hated as children. We really don't do a good job of teaching children how to think most of it is teaching them how to memorize. It's the whole concept of cramming for a test, memorize it just long enough to get past this test, then let it fall out of your brain.

I don't even know where to start with english and literature, I just muscled thru those but man that was like death to me, just not my interest at all. It's very evident in my writing that I was not very attentive in those classes. Thank goodness for spellcheck and a very pedantic highschool friend that did not mind proofreading and shaking his head at me, after each paragraph.

You don't need to memorize the times tables once you understand multiplication, but having fluency in being able to do that makes subsequent mathematics much easier (for example, I'm not sure how you could learn algebra without having a fluent ability to do arithmetic).
The times table seems like a perfect example to me of a GREAT thing to memorize. It's only 36 facts (2 through 9 times each other, knowing that ab==ba), and from then on you don't have to do repeated addition.
I hated school as well, but I think most things we studied have a purpose. Even limits are "useless," but mind-bending enough to possibly help you develop.

What I personally didn't like was reciting mathematical rules; Being able to apply them should be good enough.

Long division perhaps does teach you how to follow a complex algorithm by hand, but it's not at all necessary for the math curriculum at any stage from K-12 up to university.

It's somewhat out of fashion because a good sense of number is just as useful for dividing by hand, and more useful for understanding what's going on (plus, you do now always have a calculator in your pocket).

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Agreed 100%, I have a troubled kid in school right now, who is off the charts smart but the only thing he will apply himself to is Advanced Math, Auto Shop and his Culinary program. If it's not hands on or mechanical he just has no interest in rote memorization. School needs to fundamentally change especially for adolescent males, it just stacks the decks against the high functioning learn by doing types. I often wonder how many great minds we have lost to being store clerk (no looking down on them, its just a waste of a mind if you have it)
I think student-led education is a useful model: where students have a say in what they find important and in their own education. (This applies for all children, not only for adolescent boys)

The curriculum has too much influence from adults whose goals (sometimes openly stated!) are for a compliant labour force with a reduced training cost on particular work-focussed skills.

That's at the expense of (for example:) relationship and mental health education, creative arts, critical thinking skills, financial education, talent development, practical entrepreneurship, and the idea that children can have and create value in their own right.

As such, this is regularly a complete mismatch to what's going to be useful to kids when and as they grow up, and kids often know it: even while they don't have the political power to make change.

It boggles my mind how broken the model of rote memorization to pass written tests is. School should teach you the fundamentals of how to acquire knowledge and then get out of your way. Reading, writing, speaking, logic, geometry, mathematics, and programming along with a whirlwind tour of all the good and bad ideas throughout history then pack it up. Instead we have a public babysitting service that pretends to add value when it’s probably no better than dropping your kid off at a library for the day (whether they choose to stay and read or not).
I suspect teachers are the bottleneck. They hardly have any useful skills (except keeping children in line), so they can only teach memorization which is easy to teach/grade.
Your suspicion is incorrect.

Twenty years ago, my wife came out of graduate school where they learned about differentiated instruction and inquiry based instruction.

The education field is well aware of how to teach better. However, there are obstacles to the implementation.

1. Resources. Inquiry based education (where the children drive the study) requires a different student to teacher ratio than 30:1.

2. Inertia. You need a systemic change otherwise those fresh new teachers with their fancy up to date pedagogy run into #1 and principals, teachers, and students who are not ready for it.

3. Parents. Parents are also not ready for it. You have parents who want to be certain their child is prepared and ranked.

> It boggles my mind how broken the model of rote memorization to pass written tests is. School should teach you the fundamentals of how to acquire knowledge and then get out of your way.

That's utopian and a rather unrealistic, incomplete view. Education is also about imparting a fundamental shared body of knowledge as well, and it also has to deal with a very wide diversity of ability and motivation. Your proposal is pretty lacking in specifics, but what you have in mind seems to be something that's optimized to work very well with an idealized student, which would only be a small fraction of all students, and would likely do worse on average when considering all students.

> Reading, writing, speaking, logic, geometry, mathematics, and programming along with a whirlwind tour of all the good and bad ideas throughout history then pack it up.

That's a weird list. You include programming but not civics?

It’s not particularly utopian, I’m proposing reducing the number of subjects and the duration of public education which should allow for a larger share of the current educational resources to be spent on each student. This is to enable those resources to be spent preparing the student to solve problems themselves. I limited the list to a minimum of topics necessary to consume, produce, synthesize and communicate ideas and information. Programming is in there because I consider it as necessary as literacy and numeracy since it allows you to reify some of your cognition in the same way that writing notes or performing a calculation does. Civics doesn’t belong in that list because it’s not a fundamental skill, it’s not even taught in many countries. A student who has been taught to read comprehensively, communicate clearly and think critically should have no trouble acquiring that knowledge.
> It’s not particularly utopian....A student who has been taught to read comprehensively, communicate clearly and think critically should have no trouble acquiring that knowledge.

That sounds pretty utopian. Firstly, I don't think you can reasonably assume any mass educational program will reliably produce students like that, so any program that assumes that will likely fail a large proportion of its students in pretty significant ways. Secondly, your exclusive focus what you define to be "fundamental skills" and exclusion of anything that you deem "not fundamental" seems more of a personal bias than a well-founded educational program. There certainly exist bright and highly-motivated students (perhaps you were one of them) who would build on that foundation and complete their education like you assume they would, but I'd judge they're a minority. Thirdly, there's a social aspect to education that your focus on skills misses. Things like civics need to be part of the curriculum, because even if a student would have no trouble learning the subject independently, there's no guarantee they would actually choose to do so. However, the American system of government (unlike some other systems) can't function without widespread civic knowledge and engagement.

> Agreed 100%, I have a troubled kid in school right now, who is off the charts smart but the only thing he will apply himself to is Advanced Math, Auto Shop and his Culinary program. If it's not hands on or mechanical he just has no interest in rote memorization. School needs to fundamentally change especially for adolescent males, it just stacks the decks against the high functioning learn by doing types. I often wonder how many great minds we have lost to being store clerk (no looking down on them, its just a waste of a mind if you have it)

Huh... this sounds exactly like me growing up, except I took to Biology and did rather poor in Math until I taught myself Bio-centric Calculus in University and realized I actually did understand the concepts and could apply them to my desired ends.

I'd start by considering that his formal education should only account for 20% of his actual learning, and use that as a standard which allows him t pursuit other avenues (independent research and projects) outside of his schooling. Which can include College or University level courses, I personally started skipping HS altogether except for exam dates and attending University level Philosphy and Biology courses by Junior year. This wasn't without controversy despite having a cumulative 3.5 GPA.

One of the things I always told myself was that I'd buy my child, boy or girl, a non-running car of their choice as an extra circular activity by age 12 in order to have them explore their curiosity, hone their research skills, learn how to apply knowledge to an actual tangible medium and interact with other people who also identify with the same car culture and give them a 'tribe' of sorts which for males is very critical, especially at that age.

Furthermore, and this is difficult due to COVID to do in person, but I would encourage you both to watch conferences that are related to those fields and maybe take some entry and then advance classes together on Coursera or Udemy, Khan Academy and all the ED-tech platforms.

CU Boulder has a really cool entry level Biology series right now, I attended one of the instructors courses on campus for a few weeks and as person who did their under grad in Bio and then worked in a diagnostics labs for several years I wish I had that kind of instructor in my early formative years--I've only had 2 good teachers, both chemists, my whole Life in ~18 years of formal education.

In fact many of us who went through the Academia based Biology track and then turned Biohackers often wished we hadn't done it all, as it stunted our initial curiosity and sense of wonder that is essential in making luminaries and vast advancements in Science in exchange for complying to the rote learning method that yields 'good grades.'

Anyhow, I'm glad that you have made this observation in your child's life, I struggled with it a lot with my parents, but ultimately I can tell you that despite the unorthodox methods and leaving my Industry, I achieved a great deal in all of the other Industries I focused on (Biology/Automotive/Culinary-Agriculture and too a smaller degree Fintech) and was able to accomplish a lot from the wide skill-set I had developed through my years of hands-on learning. My parents are very proud of my achievements and are probably more interested in the awards I've gained as a 'polymath' in those fields than I am at this point.

My only wish being that I had something more than online friends on Newsgroups and Forums (some who I'd meet in real Life) for support to help guide me through the journey, so I hope you take a hands on approach in your son's life.

I agree with you, I augment their education and he excels when we work on Robotics, programming, Welding, fabrication and he has a love for math because very early on as I was teaching him these things, I was constantly showing him how to solve the problems at a more fundamental level with math. He learned math as a means to cut thru the red tape and as proofs, he learned the real world value of it very early on.
> School needs to fundamentally change especially for adolescent males, it just stacks the decks against the high functioning learn by doing types.

The point of school is to teach discipline and grit - the subjects in and of themselves are merely incidental. Do you really think that these "great minds" - the kids who can't sit through a lecture and half-ass everything off of natural talent alone - would be doing great things if it weren't for the evil school system getting in the way?

"Smart but lazy" is probably the most insufferable combination of character traits. Nothing else even comes close.

(See also: "The Bipolar Lisp Programmer" - http://www.marktarver.com/bipolar.html)

The problem is it is not "smart but lazy" it is a value proposition and some kids don't see the value, even if they are smart enough. The reality is many smart kids today know that even higher education, unless specifically focused is a waste of resources. The smart ones generally leave the uni for a business venture before they even complete postsecondary.

Further grade inflation and the continuing of lowering standards means that the ones that know how to game the system, can skate in general ed, pull out 2, 4.0 GPA years at community, where they get some choice in their direction, save money and then usually gain admittance into a decent school. As I said, it's not lazy it's a value proposition and in many ways the ones that don't totally wash out, don't see the value in applying their faculties to the endeavor of educating themselves the way the State proscribes.

Boot camp is for discipline and grit, compulsory education is well compulsory and you don't get a choice in how you learn, not everyone learns the same, and not everyone is lazy for seeing the emperor has no clothes. Many successful tech Founders/CEO's would meet your definition of "Smart but Lazy" but some smart people do just wash out. Maybe it's just like burnout that is so prevalent in the tech industry, yet they hit it early.

For example my youngest son can look at a fairly complex algebraic equation, and within a few seconds he can tell you the answer by calculating it in his head. It's some nearly savant level stuff, one time I asked him how does he do that and he said the equations are a painters pallet, each part has a color, he takes the color and paints a picture in his mind and that picture is the answer. I think you can imagine sitting him down to force him to learn algebra the way most of us do it, is painful to say the least. Not only can he arrive at the answer faster than us, he has to actively suppress the way he learns to learn a process he will never use in reality. He does not see the point, he already has the answer. He is not being lazy, his mind just uses the creative half to solve logic, its pretty messed up, but it works for him, so you can imagine his frustration when he has to show his work because we "The Education System" want him to think and solve the problem the same way we do. The value proposition for him is not there. My older son is the exact opposite, once he learned the mechanics of solving equations and how to apply them to real world problems like fabrication, fuel maps, etc. etc. he was hooked but he is the one that struggles in other areas, because he sees the value proposition of focusing on what he is interested in and sees subjects such as English and Literature as a complete waste of his time. I sympathize with him, because I hated those two subject as well.

Thanks for sharing that precious perspective. Good luck with/for your kids :-)
Thanks for the well wishes I think they will do fine, it's just a struggle with traditional education. I help them learn the way they learn, my oldest daughter ended up an Architect she never really struggled. My Youngest daughter is well on her way in Marine Biology, my oldest boy (14) has started to venture out into classic car restoration and fabrication of custom parts and my youngest son is still to young to have a path, but he really likes robotics and programming. I work with him a lot of projects that he is interested in. They will land on their feet, just wanted to add to the conversation that there are very bright people, not getting the education they could if we ventured to understand a better way.

I come from a family that is generally above average intelligence (not claiming that for myself, just making a basic observation about my family to make the following point). In the not too distant past, my family was fairly well know in Florida for being involved in organized crime. To the extent that they got the nickname the "Mullet Mafia" because they did most of their crime under the guise of legitimate fishing and maritime operations. Some of them were pure geniuses in the way they operated their criminal cartel and only one of them did hard time (the smart ones, are not the ones that get caught). This is where the smart kids can potentially wash out to, without guidance and that is my concern. This is why I see it as a value proposition. The smarter a person is, the higher the propensity to surf the gaps.

> The point of school is to teach discipline and grit

Have you heard of neoliberal magical voluntarism?

> you're being kept out of the house so that both your parents can go back to jobs they don't like.

I was left home alone from, like, 4 years old? I definitely preferred that to going to school.

It depends on the curriculum and the teachers.

Some teachers can get super excited about sharing the amazing stuff that's the results of their field. Sure, there's a bit of jargon and memorization to be able to discuss the problem. You can't be amazed by the results of concentration gradients, gene expression on the formation of proteins if you think concentration means something about your eyebrows, gradients are a function of WordArt, gene was a guy who played Willy Wonka, expressions are things your face does, and protein is a number on your dad's whey powder.

If you can make students excited about using, testing, and comprehending the awesome information about their world that are just behind a minor speed bump of some jargon you need to cross, most will hurdle those difficulties as if it was effortless. The standardized tests that check whether they know the jargon will be just a wasted day that they don't get to learn more about the subject!

If, instead, you set the end goal as passing the standardized test that checks whether they know the jargon or not, they'll begrudgingly do the minimum required to not get in too much trouble. The tragedy is that kids who don't even know the bare minimum jargon are often unprepared to function as independent adults, and so the rational, fair, game-theoretic optimum outcome demands resources need to be allocated to help those more than they need to be allocated to help those who are already functional.

Also, there's the tragedy that teachers who pour their hearts into their students aren't adequately valued by society - we pay lawyers and administrators huge sums of money as if what they do is more important than what my 9th grade bio teacher did while using his weekends to crawl through the mud on bog walks to learn about sphagnum mosses and carnivorous plants with some kids he met for an hour a day for 8 months, while barely keeping his family out of poverty.