
I see so many AI product launches. Is there anyone who is working on non-AI products?
If so what are you working on?
If so what are you working on?
I’ve been working on a synthetic DNA assembly company. Basically, I figured out how to assemble DNA for people at a fraction of what it normally costs, so they give me a sequence, and then I make it in real life for them, then ship it to them.
Most of my customers have been AI protein designers, ironically. Turns out SOMEBODY has to wrangle atoms in the real biological world and that’s me!
After almost a year of work I finally smoothed out all the kinks in the process, so can now go from a design to synthetic DNA in a cell in about a week (not counting oligo pool synthesis time). I can do about 600,000bp per week, which is large enough to synthesize the smallest bacterial genome (each week), tho I only do about 1000bp fragments. I’m also completely bootstrapped and self funded, and only get help from my several opentrons robots
I once met a freelance bespoke industrial adhesive maker. He takes orders from various factories for adhesives with specific properties, then uses his knowledge of chemistry + trial & error to make one that fits the specs provided.
Bespoke synthetic DNA is much cooler though.
A bespoke freelance industrial adhesive maker sounds like such a niche job, that's awesome. I would love to see a hackernews-type post with details of how he thinks about making a specific adhesive.
He was a Russian guy, normally living in Russia. HN post is unlikely, but I would love to see folks of this sort post here.
We both happened to be traveling in the same country one New Year's and got to talking.
Is he a vendor in my Fallout 4 gameplay?
If I ever met you in real life I think you would be the coolest person I've ever met.
Thanks!
That is very cool. I'm curious if you can share some of the things people are using this synthetic DNA for?
I can share a few things! (but definitely not all)
- One is finding different T7 RNA polymerases with unique properties by manipulating the backbone. They can be used for things like in-vitro RNA production for vaccines - Another is synthesizing a phage that has been sequenced for a specific organism, but that the samples are now lost of. So resynthesizing that genome from scratch - A different project (personal one) is building a DNA parts toolkit with standardized DNA parts so you can combine em together like legos. Pretty much nowhere but FreeGenes has open source genetic parts (I used to run that project), and I think open source genetic parts need to be in the world
Do you have in-house protocols or are you using the off the shelf stuff?
I sometimes derive protocols from off-shelf ones, but pretty much everything beyond that is in-house. Most off-shelf protocols work for 1 sample in 1 tube - I had to adapt them to working on 1 plate of 384 tubes (and get those to work with robots). There is a significant amount of robotic code that I use, and a few custom protocols that are from a random obscure scientific paper in 1980s or 1990s
Now this is interesting. I've read about using synthetic DNA for data storage, but other uses surely abound.
I don't suppose you'll need documentation help at some point in the near future...?
Synthetic DNA for data storage seems much higher to degradation (ie, heat, light, or other sources of radiation). Not sure if I would use syn DNA to for anything long term.
The oldest sequenced DNA is 1.6 million years old. In the right conditions, it lasts far longer than pretty much any storage method right now. Plus I also sometimes store things in Bacillus subtilis, which is very hardy https://keonigandall.com/posts/sporenet.html
No, I know pretty much everything I synthesize. Once I don't, I'll just connect some screening software.
can you give a specific instance of a sequence that would be dangerous in a cloning strain and not screenable?
You are asking for a counterexample but I think s/he was asking for what assurances the software can provide. Is it proven to be perfect, bug free in both specification and the physical analysis?
Remember compared to you assume we are all laymen.
It would be interesting for us on the armchairs how such software even works. Is it like (ahem!) antivirus software looking for patterns?
The reasons I ask for a counter example is because the number of “what ifs” are pretty much unlimited and easy to come up with, whereas I have to do a lot more thinking to answer them. It’s asymmetric and gets tiring
Answer is: no, not proven to be perfect. Most source is closed for the software. There is no specification. Never been a red team trying to break it. Unknown if it’s ever stopped any threats. There is no requirement to do it, and it’s all voluntary (though pretty much all synthesis providers do it). Mostly they just hash kmers and translations thereof and scan a pathogens/functional database. So implementable in a simple KV store for the most part. The bigger problem is false positives, and most work is done in de-shittifying the upstream pathogens data.
Here’s a good paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9988571/
Last I checked all the groups charged a lot of money for access, unfortunately, and I’m not really big enough to join a group like the International Gene Synthesis Consortium :(
I appreciate this reply, thanks!
Thank you so much for posting this. It's wonderful to hear how excited you are about it all.
That is some seriously cool stuff.
https://genomebiology.biomedcentral.com/articles/10.1186/gb-...
Might interest you!
That's how Twist/Agilent do oligo pool synthesis (and Dynegene now). I'm pretty interested in the Genscript / Avery digital method of electrochemical synthesis. Turns out those pools ain't good enough to be used in a biological context, which is where I come in - I can assemble them well into sequence perfect stuff
this is the coolest thing I have ever read. How did you even get into that?
I found a virology textbook at the local Catholic book fair when I was in 6th grade, got hooked, teacher in 7th grade let me order GFP transformation kits to the school that I could do at home, then off to the races from there. I was in this article if you're interested in more deets: https://www.nytimes.com/2018/05/14/science/biohackers-gene-e...
I swear I feel like I'm dreaming this thread.
That's awesome. I also got hit hard by the science bug (pun intended) as a kid, which I can partly attribute to finding a random virology textbook in an academic bookstore dollar bin. I was obsessed with virology at least until college. I ended up majoring in math in college but made it through Ochem II and did some lab internships before committing to that path. Now I'm a ML/software engineer with a healthy interest in biochem.
Incredible! Obviously tons of credit to you individually, but also huge kudos to your teacher for encouraging your curiosity.
Cool! Though it's a bit scary how easy it would be for someone to make something dangerous as mentioned in the nyt article. The 2018 article ends:
>“There are really only two things that could wipe 30 million people off of the planet: a nuclear weapon, or a biological one,” ....
>“Somehow, the U.S. government fears and prepares for the former, but not remotely for the latter. It baffles me.”
I guess we may have seen that kind of thing happen a year later with covid though that would have been government sponsored mucking around rather than DIY if it wasn't natural. Not sure how we stop that happening again?
Personally, I think the threat from the biologics itself is a little overstated. If COVID was released from a lab (I think it was natural), it was most likely due to bad governance and management of the lab. For DIY things - most DNA can be screened. I have had companies offer screening services for about 50k-100k a year. I can't afford that! So hopefully a free service or something near to that comes online.
That's so cool! If I may ask, what is your level of education?
I never went to university or anything, but did work for 4 years at UCI in directed evolution / mitochondrial engineering, then 3 years at Stanford on the FreeGenes project (got invited to work at both). Barely passed high school cause I didn't care about my classes there.
zot zot
How the fuck does one "assemble DNA" lol
Sorry but that's so outside of my understanding it reads like pure science fiction
(I'm sure it's a thing, I'm just a moron)
I use restriction enzymes + ligase to cut DNA, then paste it back together at specific sequences. It's pretty simple honestly! https://www.khanacademy.org/science/ap-biology/gene-expressi...
The key is doing that at an industrial scale, reproducibly, with hundreds to thousands of plasmids at once. Becomes less simple. You encounter bullshit problems with biology, which I guess is valuable because it makes a moat!
After we did DNA extraction in high school we were provided toothpicks to serve the strands onto a microscope plate.
So yeah, at a certain mass...
With nanotechnology.
[dead]
I'm working https://annotate.dev, a tool inspired by the Stripe documentation, to let anyone create step by step code walkthroughs. Here's a sample of a walkthrough you can create: https://annotate.dev/p/hello-world/learn-oauth-2-0-by-buildi...
Would love to hear any feedback thoughts!
This is a great app, especially in this age of AI code generation, I am already using it. Looking forward for features such as light mode and exportability among other things.
This seems like a cool idea but I'd have to see it in action for something I need to learn.
The first thing that jumps to mind is that I want to click on a piece of code and see the explanation for it. It seems that it only goes in the other direction. I could imagine looking at the code and understanding most of it and just wanting to understand part of it.
I could anticipate an issue though - it could be many-to-one from explanation to code. The UI for that would be complicated.
If you’ve not seen it, there’s a vscode extension called CodeTour that does something similar, could be good inspiration (or maybe you already do better!)
It's the first time I've heard of CodeTour, I'm really impressed from what I've seen thus far. Digging a bit deeper now, thanks for sharing!
This is great idea!
I actually have several potential improvement ideas.
1. Put the walkthrough it in a graph, or a minimap to see the whole picture easily? Or in a https://c4model.com/ visualization 2. Why not make clickable code references visually stand out? 3. Make a VScode extension for it
Thanks for taking a look and sharing feedback!
I'm not familiar with the c4 model, I'll need to investigate.
> Why not make clickable code references visually stand out
Is the goal here that you want to know that a specific text block annotates a part of the code?
> Make a VScode extension for it
I think I will! I need to noodle a bit on the user experience here
This is awesome!! I can see a major use case for enterprise or government but along with that would come the desire for on-prem. Any chances of that happening?
Thanks for checking it out!
I'd be happy to build and support an on-prem solution, but I'd a need commitment from an enterprise/government org. If that's something you're interested in, shoot me an email at alex@annotate.dev!
This is a really clever idea, and worked great on mobile as well. Is there a way to choose to display the code window underneath the documentation instead of on top?
Thanks for the kind words!
Not currently, can you elaborate why you'd want to the code window at the bottom?
I think I'd also like an option for the code window to be at the bottom. Generally when I'm reading blogs/articles on my phone I put the line of text I'm reading at the top of my screen.
The code being up the top felt like it was in the way of where I was naturally expecting the line I wanted to read was.
Also, I think this is great! Definitely something I'd want for my documentation.
This is great feedback, not something I initially considered. I've add it to my todo list
This is really cool. I wish there was something like that when I learned to code.
That's a cool idea!
Great idea! What did you use for designing the UI?
Thank you for checking it out!
I use Figma to get a proof of concept of how I want things laid out. From there it's more tinkering at the code level.
can this be self-hosted?
Not yet, what use case do you have in mind for self hosting?
I am sure folks at /r/selfhosted would love it.
You know how sometimes the gift you really want is cash or a gift card, but people often prefer to give you physical gifts that you can open and admire?
Imagine a line of faux jewelry that is marked up to real-jewelry prices and that, unbeknownst to the gift giver, comes with a hidden gift card code. So somebody asks you what you'd like for your birthday and you say, "Oh, I'd really like some Lagniappe brand jewelry," and they go out and buy you a $50 necklace that's actually worth only a buck or two, but has a gift card code worth $45 on the underside of the box.
You thank them profusely for the lovely necklace, they feel good for having bought you something besides a gift card, and you feel good that you can put $45 toward a new washing machine.
This is such a first world problem. It's normalized in many 3rd world countries to give and receive cash (red envelopes). Directly not giving money and resorting to gift cards (and roundabout methods like these) just, doesn't make sense to my third world brain is all I'm saying.
Many, meaning, not all. It's obviously a cultural thing. That red envelope idea is ancient.
China and Vietnam that do the red envelope bit would be "second world" countries, incidentally, as they were part of the communist block under that old "three worlds" labeling.
Many countries in the Southeast Asia do it at least.
> China and Vietnam that do the red envelope bit would be "second world" countries, incidentally, as they were part of the communist block under that old "three worlds" labeling.
Although China played both sides & its support is one of the larger factors for why the US won the cold war.
Red Envelopes are more of a formality where you more or less receive as much as you give out. People in Asia still do "first world" presents in Christmas or Birthdays or etc.
>This is such a first world problem.
Indeed it seems that way. It's kind of funny and sad at the same time when people get frustrated over such things.
Okay, and what is your hope by making this comment?
This sounds very useful, but isn't this service going to automatically fail as soon as it starts to be known because you can't market it to the intended audience (the gift-receivers) without marketing at the same time to the adversarial audience (the gift-givers)?
I love the thought! Just a friendly warning - gift cards attract the fraud industry. This could result in a wide array of undesirable effects. Make sure you or someone on your team or someone you can call up and consult with knows the industry of gift card fraud really well. This will be very helpful in early planning and feasibility studies.
We have taken control of your computer. Now go buy 6 necklaces and call us back.
Wouldn't it be simpler to sell $20-30 dollar jewelry for 50$ with explicit promise that this jewelry is very easy to return in exchange for the 50$ gift card? You could add RFC chips to them so people couldn't return counterfeits. Epoxy resin is good at covering chips.
It would solve the problem of littering your house with cheap products, save the buyer the embarrassment of gifting something that looks like 2$ jewelry (it is noticeable when it is that cheap), and it makes easier for people to pretend that they actually want that necklace for the necklace and not for the gift card.
This is so incredibly narcissistic and mercantile. Being a grown up means you understand that you're not owed any gifts and that when somebody makes you a gift it is mainly for their pleasure and something to be grateful for, that they thought of you.
These kind of people who think receiving gifts is some kind of entitlement are the same kind of people who start bringing up their diets when you invite them for dinner. Cold, calculating, reptilian. No human emotion or joy of life.
Wait, hang on, not wanting to be served poison for dinner is a cold calculating reptilian thing to do? What else do these reptilians do? Run the government?
What these reptilians do is only think about themselves.
If you're invited for dinner it doesn't mean that somebody owes you a meal. It means somebody wanted to make a nice gesture towards you and get to know you more intimately, perhaps to discuss important things.
You eat something before you go, because it's not about the food. You can ask about the ingredients when you are at the table.
So people with allergies shouldn't tell the people who will be preparing food for them about their allergies before the food is served?
Exactly. Because being invited for dinner is not about stuffing your belly for free, it is a social meeting with more important matters. So if you have an allergy or a diet, you can mention that when you're seated. The host can make something that suits you, and if they aren't able, you can just have the drinks. That's why you eat before going out to dinner, so you don't have to worry about your belly. And it is also very convenient in case if the cooking is just bad.
I've noticed that these kind of social rules and politeness has been increasingly lost in people, and it is because of widespread narcissism. It's "me, me, me". The result is that people don't invite each other to dinners or other social gatherings, and everybody is worse off because of that.
> So if you have an allergy or a diet, you can mention that when you're seated. The host can make something that suits you, and if they aren't able, you can just have the drinks.
If I invited someone over for dinner and went through the effort to prepare a nice meal for them, and they waited until they were seated at the table to tell me that the food I've just put on their plate is something they can't eat or they will go into anaphylaxis, I would be pretty ticked off. "Oh, don't worry, I ate ahead of time" would make me feel even more ticked off, because I wouldn't have gone through the effort and expense of preparing a nice meal just to have a bunch of uneaten food sitting on the table while we have a social meeting.
The purpose of giving the host a heads up about food allergies is to avoid the host putting effort into preparing a meal that the guest can't eat. How is it a better outcome for the guest to remain unfed, food to go to waste, and the host to have this information sprung on them at the last moment?
You're saying that this kind of gentle heads up is an indication of narcissism, but I think it's exactly the opposite. It's a way of helping to ensure that things go according to plan.
> I would be pretty ticked off.
Then the problem is with you. Like I've repeated, it is not about the food, it's about the company. You're thinking about your effort and your expenses, but inviting somebody for dinner is a nice gesture. What if you burnt the food by mistake while stressing about in the kitchen? Should the guest have a right to be mad because they're not getting their delicious meal? Of course not (and I hope I didn't need to state this). So why should you be ticked off if somebody does not eat at a dinner? Exception if you are only two people, and it's really about the food. But then I'd expect you to combine things ahead.
> "Oh, don't worry, I ate ahead of time"
That's not something you tell and not something you ask.
> How is it a better outcome for the guest to remain unfed, food to go to waste, and the host to have this information sprung on them at the last moment?
Because it's not about the food. You eat the leftovers for lunch the next day. You have something at home that you can make the guests if they're really hungry and can't eat the main meal.
If you're invited for dinner it's not about you or your aching belly. It is about having a more intimate meeting with other people. So don't bother them about your diet unless they ask, and don't go on an empty belly. The guests are not there to get "fed", inviting somebody for dinner is an excuse to have a nice time in a relaxed environment with people you like or want to know better.
Goes both ways actually.
I cannot count the times someone felt the need to bend over backwards to accommodate me because of something I didn’t want to do/eat/drink/whatever when I‘d been perfectly fine without any special treatment and moving on with whatever we were doing.
well, the secret will come out at the moment they google up that lagniappe jewelry.
Awesome! Makes me think of this song: https://youtu.be/4s0KidJf5FQ?si=H56SCAivnsU6jy6W
Isn't it super likely the gift buyer will realize what's up when making the purchase?
There would have to be two websites or something.
> There would have to be two websites
Yes. That... doesn't sound like a very hard technical challenge?
ding ding ding
Plausible deniability can often short-circuit bullshit rituals. White lies are social lubricant. Come on, this isn't very advanced grass-touching here. I don't know if it will work, but I like the idea and admire the attempt.
'advanced grass-touching' never change hn lol
Is it? It just seems wasteful and unnecessery. Even gifts cards are pretty stupid for anyone that has access to a credit card. It’s strictly worse than having the actual cash for all but the unbanked (including kids).
Agreed... my first thought was "wow, this would create a lot of unnecessary waste going into a landfill."
I mean... this is kinda... fraud... I guess not in the legal sense. Gift fraud. Christmas fraud!