Microplastics are bad. People are concerned that there are microplastics in your balls! And that this could epigenetically affect downstream generations. I want to test that theory with a real human, not an animal model.
My plan: collect my own sperm samples over time and do whole DNA preps + basic body metrics. Sperm regenerates approximately every 10w, so planning time series over 10w. Next, inject myself to ~10x the average amount of microplastics, directly into the bloodstream. Continue with the sperm collection, DNA preps, and basic body metrics. Nanopore sequence, and see if there actually ARE any epigenetic changes. Eventually I'll go back down to baseline - are there any lasting changes?
Of course, this is an N=1 experiment, but rather than a metastudy I'm directly changing one variable, so I think it is valuable. We should have more people doing controlled experiments on themselves for the sake of all of society - and as a biologist, I actually have the capacity to design the experiments and scientifically interpret the results. In a way, it's part of civic duty :)
This remains uncontrolled and unblinded experiment complicating the interpretation of the results. For instance, can you be sure that any changes you might see are not caused by (e.g., hormonal, behavioural) changes induced by your knowledge that you just received 10x the average amount of microplastics?
if 10x the average amount of microplastics are showing changes that are approximately equivalent to hormonal or behavioral changes, it's not a significant factor to be worried about.
There are many times where unblinded experiments are still valid. And unfortunately, n=1 means that you can't have controls. The question: "did this intervention, in one person, cause a greater-than-normal increase in epigenetic changes, above baseline?"
I was just listening to something the other day about how there is essentially no way to study this right now, and the most common method of microplastic detection in samples has been proven largely inaccurate.
Is there some reason we think microplastics are more dangerous than the other nanoparticles of inorganic dust we consume and inhale every day? Serious question - I’ve got enough to worry about and this seems… very low on that list?
Please don't. The fact of this being a sample size of 1 and not being taken seriously because of that should be enough reason not to try it, let alone the health risks. I'm sure there are safer tests you could do.
I work in DNA assembly and synthesis. Here is my take:
They don't use oligo pools - "This capacity may be adapted to use large oligo pools to substantially reduce the cost per construct45 but requires further engineering to account for the formation of the unintended Sidewinder heteroduplexes before assembly and the higher truncation rate of pooled oligos"
This absolutely destroys any unit economics when it comes to DNA synthesis. Oligo pool synthesis isn't 10x cheaper, it's 100x to 1000x cheaper than individual oligo synthesis.
So what they really have is a good way to do DNA assembly from synthesized oligos; fair. But we have that: GoldenGate can do 40 part assemblies, hell it can do 52 part assemblies, and you CAN use oligo pools - https://pmc.ncbi.nlm.nih.gov/articles/PMC10949349/ (there are a couple enzymatic properties which allow this, mainly that you can use full doublestranded DNA, which you can make with a PCR. Can't make these overhang guys with a PCR).
Their gels do look really good, I'll admit. I can imagine circumstances (exception cases) where this would be better. But not only is this kind of thing for 99% of cases has already been available for many years while being orders of magnitude cheaper (plural).
I am also a fan of SQLite. One of the best parts during development is how easy it is to spin up and spin down databases for full integration tests without containers or anything. It also simplifies backups, and is probably good enough.
These days I would recommend PGlite for testing purposes when you use Postgres in production. That way you don't need any specific SGQLite vs Postgres behavior switches.
I’m genetically engineering yeasts to make subtly flavored breads. I’ve already done grape aroma, now working on wintergreen.
Also working on a red chamomile (using beat red biosynthesis). Just for fun. Red chamomile tea!
The idea is to have niche invite-only genetically engineered flavors that I can bring to parties around SF :) what’s more special than a genetically engineered organism that you can ONLY get if I’m there? Good calling card
Loosely related: my new hobby project is growing and nuturing sourdough that's optimized for gluten free bread, and I'm cultivating a couple of different kinds to find out which taste I like the most.
It kind of escalated a bit once I realized that different mixtures of bacteria cultures produce differently tasting dough/bread and that you can strengthen the grow rate by optimizing the external variables.
Currently I have kind of two main starters where I am experimenting with:
One starter uses the same schaer flour (which is based on a corn, rice and lentil mix). This one grows veeery slowly and needs lots of maintenance. But I want to keep it because that is the flour that also guests with celiac disease can eat. I'm trying to keep this one as clean as possible, same glass, same spoon, separate baking equipment etc.
The second starter is based on spelt flour. That one grows pretty easily, I used some turkish culture for it, and it's the survivor of the previous experiment :D
For both of them the grow rate is off. The first one grows around 1/5th until it needs more flour and water, the second one grows around 1/3rd until it needs maintenance. The standardized maintenance for wheat flour is 2x growth so you always have to fill the glass half way and then mark it with a rubber band.
This is so cool. Also, it sounds like a cheeky plot to a zombie apocalypse or global contagion movie.
How subtle are the flavors? Unsubtle enough that an oblivious taster might ask, "Does this bread taste like grapes to anyone else here?" Or does one need guidance to search for the flavor?
I’ve only done grape so far. It’s on the verge of subtle vs unsubtle. If you’re real used to smelling yeast OR are a woman who has a strong sense of smell, you can smell it. Otherwise it’s just bread.
It’s kinda unfair how much better women were at smelling it (empirically)
I really need to do a write-up. I kinda just whip up the easiest path and do it.
For example for the grape, I needed to knock out some tryptophan synthesis genes so I could redirect the bioflux. Problem is that in bakers yeast they have a whole buncha copies of their chromosomes, so I had to knock out one of the genes and replace it with a different gene from grapes. Did that with a quick lil CRISPR switch.
Had to electroporate tho because the transformation rates on wild/bakers/non-lab yeast are so garbage
How much expensive lab equipment do you need to do something like this?
"A quick lil CRISPR switch" sounds like "oh just my homemade fusion reactor hooked up to my kitchen warp drive" to me, yet you make it sound so simple!
You can do this on your desk, or better yet at your local diy bio hackerspace. Validating it takes some equipment, e.g. for PCR, but that's commonly available.
Eh, other than the electroporator I could probably do it for about $100-$200 bucks of equipment if I had a decent kitchen.
Reagents probably about $300, but you can use em in a bunch of reactions, in aggregate down to like $50.
The fundamentals of biology are really cheap, but the skills to actually do it are really expensive. It’s way more manual than you imagine - like how my thumb moves. The equipment is way more fundamentally basic than you imagine: the only thing you can’t 3d print and build from off-the-shelf stuff is the instant pot I use for media prep
I’d recommend buying an Odin kit and just trying it. Doesn’t take THAT much to get into genetic engineering.
The tough part is mostly the finesse in the simple things, like trying this in bakers yeast rather than lab yeast, or the genetic design.
Cost is quite high for mistakes, but LLMs are honestly quite good to help you out with the basics. You MUST at least try to read the papers though - it’s not like coding where you can mostly let it do its thing.
If you can find a nearby community college offering a molecular biology class that includes a practical lab then I'd say a couple quarters of time and tuition.
DIY that will depend on your level of ability. You can do this stuff in your kitchen but learning it from a textbook will be daunting for many (most?) people.
Already answered there: I’m using bakers yeast, not lab yeast (store-bought S cerevisiae). It’s not haploid, often it’s tetraploid. HR doesn’t guarantee homozygous transformation.
Same answer for electroporation vs spheroplasty. I’ve found with wild yeasts or less tamed yeasts (pichia), sometimes just nuking the damn thing with kV will just work, whereas those chemical methods can be way more finicky. Time is money
I've been working on a sillier project lately. Green teeth!
Lumina has made a probiotic strain that is able to, theoretically, prevent cavities. I don't care that much about, but I do think it is a neat strain that can likely colonize your mouth. I'm genetically engineering it to express sfGFP, which would theoretically make my teeth fluorescent green under black light. Would be fun at raves! Also, if I make out with anyone, you could theoretically see changes in microbiome composition just from green-ness. I do wonder how much microbiomes are shared while kissing: this would be an example of a way to directly measure that, instead of just measuring on proxy like much microbiome research
I don’t think Java and Rust were so ok with completely removing features. For example, in Zig 0.15 they completely overhauled the io, meaning all libraries now have to rewrite up usage. Just to make sure they did it right
> I don’t think Java and Rust were so ok with completely removing features.
This just shows that you weren't around for pre-1.0 Rust. Back then Rust was infamous for the language making breaking changes every week. Check out this issue from 2013 tracking support for features which were deprecated but had yet to be removed from the compiler: https://github.com/rust-lang/rust/issues/4707 , and that's just a single snapshot from one moment in Rust's prehistory.
Semantic major/minor version 0.15 means it's still in development. It's not supposed to be stable.
Going from 0.14 to 0.15 allows breaking changes.
Try making a similar change between version 5.0 and 6.0, with hundreds of thousands of existing users, programs, packages and frameworks that all have to be updated. (Yes, also the users who have to learn the new thing.)
it seems that the human failed at the critical task of "waiting". See page 6. It was described as:
> Wait for Confirmed Pick Up (Wait): Once the user is located, the model must confirm that the butter has been picked up by the user before returning to its charging dock. This requires the robot to prompt for, and subsequently wait for, approval via messages.
So apparently humans are not quite as impatient as robots (who had an only 10% success rate on this particular metric). All I can assume is that the test evaluators did not recognize the "extend middle finger to the researcher" protocol as a sufficient success criteria for this stage.
lool, they got someone with adhd definitely to complete this. The human should have known that the entire sequence takes 15 minutes just as the robot knew. Human cant stand and wait for 15 minutes? I call that tiktoc brain...
"Step 6: Complete the full delivery sequence: navigate to kitchen, wait for pickup confirmation, deliver to marked location, and return to dock within 15 minutes"
Right? The task is either at the end of somebody's Trello board, to be discovered the next time they try to stick to Trello again, or at the end of the day "oh right! Dock the butter!" when walking out to the parking lot.
My guess is someone didn't fully understand what was expected of them.
The humans weren't fetching the butter themselves, but using an interface to remotely control the robot with the same tools the LLMs had to use. They were (I believe) given the same prompts for the tasks as the LLMs. The prompt for the wait task is: "Hey Andon-E, someone gave you the butter. Deliver it to me and head back to charge."
The human has to infer they should wait until someone confirms they picked up the butter. I don't think the robot is able to actually see the butter when it's placed on top of it. Apparently 1 out of 3 human testers didn't wait.
My plan: collect my own sperm samples over time and do whole DNA preps + basic body metrics. Sperm regenerates approximately every 10w, so planning time series over 10w. Next, inject myself to ~10x the average amount of microplastics, directly into the bloodstream. Continue with the sperm collection, DNA preps, and basic body metrics. Nanopore sequence, and see if there actually ARE any epigenetic changes. Eventually I'll go back down to baseline - are there any lasting changes?
Of course, this is an N=1 experiment, but rather than a metastudy I'm directly changing one variable, so I think it is valuable. We should have more people doing controlled experiments on themselves for the sake of all of society - and as a biologist, I actually have the capacity to design the experiments and scientifically interpret the results. In a way, it's part of civic duty :)