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?"

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 :)

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).

We've even found that with some GoldenGate enzymes, the biology somehow breaks the current models of the physics of ligation by being so efficient - https://www.biorxiv.org/content/10.64898/2026.01.31.702778v1

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’ve been thinking about trying this since my mom is gluten free

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

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.

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

It’s kinda unfair how much better women were at smelling it (empirically)

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

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

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