News for hackers. Stuff that matters.
Re:Biohackers take aim at big pharma’s stranglehold on insulin by f6v on Monday June 28, 2021 @01:20PM (#27664645)
As someone who had to create transgenic E.coli in a lab, I admire the effort. It’s hard to get it right, especially when trying to make bacteria produce stuff for you. However, it feels like a huge step backward. Imagine you couldn’t afford to buy a piece of bread. Instead, you need to grow your own grains and build a windmill first. Sounds ridiculous in 2021.
Re:Biohackers take aim at big pharma’s stranglehold on insulin by dnautics on Monday June 28, 2021 @11:34PM (#27671457)
transgenic E coli is easy, not sure what you think is hard.

Insulin, though is possibly one of the most nightmarishly difficult proteins to make. It's kind of astonishing to me that Insulin was both the first protein sequenced and the first pharmaceutically relevant protein synthesized. Mother necessity, I suppose.

Genentech started making separated-chain insulin in E coli, back in the day, and that is emphatically not how it is done today. You get a whole bunch of crap because you need to keep the two chains denatured, and that results in scrambled disulfide bonds. If you try to do it in protein-folding conditions, one of the chains crashes out into plaques structurally similar to alzheimer's plaques.

You could make it as a single-chain protein, and then cleave out the middle section, except that the protease that you would use to cleave it out has another site internally!! And all of the proteases which leave a "clean end" leave a "clean end" in the wrong direction to yield a good insulin molecule.

Industrially, insulin is made (in yeast, not E coli) by going ahead and cleaving at that extra site, and then performing a reverse proteolysis to install a synthetically generated peptide, restoring the molecule. That's also why most insulin variants (e.g. humalog) have mutations in the tail end, that's the part that is "reinstalled". Note how crazy this is. Proteases are usually used to break proteins apart. Although technically all chemical reactions are indeed reversible, to force the chemical reaction in the other direction, you're fighting entropy, to put humpty dumpty back together again.

Honestly OIP's best shot is probably Michael Weiss' one-chain insulin molecule, which should have gone off-patent this year (https://patents.google.com/patent/US8192957B2/en) (15 years, right? IANAL) but for some reason got extended to 2028!!

However, the big danger with insulin analogs is that you really need to test the F out of them because insulin cross-reacts with the IGF-1 pathway and cause cell hypergrowth = cancer. I would also be very careful with home-made stuff because I would need to be convinced that the forumlation whipped up doesn't change the properties in such a way to to increase IGF-1 activation.

I advised Open Insulin on a ton of stuff in the first few months, but they took literally none of my advice on anything, and last I checked their mailing list a few years ago they were still stuck on some stuff I warned them about (e.g. insulin doesn't stain in coomassie blue -- another thing which makes insulin a pain in the ass).

Re:Biohackers take aim at big pharma’s stranglehold on insulin by mkoubaa on Monday June 28, 2021 @02:50PM (#27666037)
I agree with the sentiment but decentralizing and downscaling production is a win for resiliency. This is a good example but others include recycling and power generation have clearer benefits
Re:Biohackers take aim at big pharma’s stranglehold on insulin by dnautics on Monday June 28, 2021 @11:46PM (#27671530)
> decentralizing and downscaling production

I think you are severely underestimating what it takes to produce a protein drug like insulin. Getting the bug to make it is just the first step. Then next step is purifying it. Which takes SO much water, and salts, and specialized equipment (resins, columns, high-pressure apparatus). A decentralized insulin production scheme is going to be VERY ecologically destructive.

Re:Biohackers take aim at big pharma’s stranglehold on insulin by AstralStorm on Wednesday June 30, 2021 @02:34AM (#27685601)
It's not that bad ecologically, but I'm not getting why these people are reinventing the wheel.

Buying out a patent and properly documenting it should be doable.

Re:Biohackers take aim at big pharma’s stranglehold on insulin by jacobwilliamroy on Monday June 28, 2021 @07:25PM (#27669654)
The people plugged into the solar utility co-op on Kaua'i actually end up having a smaller carbon footprint than those generating solar power off the grid.
Re:Biohackers take aim at big pharma’s stranglehold on insulin by f6v on Monday June 28, 2021 @05:11PM (#27668195)
Yes, but what about economies or scale? And the the production is already decentralized. I guess there’s more than one plant in the US.
Re:Biohackers take aim at big pharma’s stranglehold on insulin by shkkmo on Monday June 28, 2021 @05:47PM (#27668625)
Those econmies of scale are simply driving up profits for an oligopoly that uses IP laws and acquisitions to extract maximum value from sick people.

We could revoke the IP and thus force these companies to compete on price... but that hasn't happened. Thus the only solution that is making any progress is circumventing the IP and developing an open process.

Re:Biohackers take aim at big pharma’s stranglehold on insulin by incompatible on Monday June 28, 2021 @10:06PM (#27670850)
It's unclear to me if the lack of competition is due to IP laws. For all I know, they've been coasting with the same production methods for 20+ years (the article mentions that insulin was relatively cheap in 2002). With such large profit margins there wouldn't be much incentive to improve anything.
Re:Biohackers take aim at big pharma’s stranglehold on insulin by shkkmo on Tuesday June 29, 2021 @12:02PM (#27677828)
I don't know the exact details and I could be wrong, but my understanding is:

There is IP around the production process (specifically the genetic strain of e-coli). Because the production process is biological, generics produced with a different process are not automatically approved by the FDA and have to undergo an expensive approval process. Thus the goal here is to devolop a process with open IP and get that process approved.

Re:Biohackers take aim at big pharma’s stranglehold on insulin by erosenbe0 on Monday June 28, 2021 @11:34PM (#27671455)
What IP though? Humalog is off patent. It now appears to be just red-tape or collusiom.
Re:Biohackers take aim at big pharma’s stranglehold on insulin by AstralStorm on Wednesday June 30, 2021 @02:36AM (#27685617)
The problem is that patent system is a joke, and the description is likely broken (or incomplete) enough so that even a bunch of experts will have to experiment with the process to decrypt it.

You really need to buy out trade secrets of this particular brand.

Re:Biohackers take aim at big pharma’s stranglehold on insulin by YHK on Monday June 28, 2021 @07:09PM (#27669513)
There is one plant for each big pharma. Eli lilly is in indianapolis. https://www.industryweek.com/expansion-management/strategic-... Novo Nordisk in Raleigh. https://www.pharmaceutical-technology.com/projects/novonordi...

This is not really decentralized and is really risky, for obvious reason. https://www.ibj.com/articles/eli-lilly-asking-employees-to-w...

Re:Biohackers take aim at big pharma’s stranglehold on insulin by nathanvanfleet on Monday June 28, 2021 @05:19PM (#27668304)
Maybe that's the next big local business idea. Like buying from a local bakery every city can have a local guy growing insulin.
Re:Biohackers take aim at big pharma’s stranglehold on insulin by gentleman11 on Monday June 28, 2021 @01:43PM (#27664961)
My wife bakes bread almost every day and grows her own yeast. She loves it and the bread is fantastic. What is so ridiculous?
Re:Biohackers take aim at big pharma’s stranglehold on insulin by ChefboyOG on Monday June 28, 2021 @01:50PM (#27665091)
There's nothing ridiculous about the fact that your wife enjoys baking bread.

There's a lot that's ridiculous about bread being so expensive that recreating the entire supply chain in your backyard is the only economically viable option for obtaining it.

The metaphor pretty clearly was not about critiquing baking as a hobby.

[dead]
Re:Biohackers take aim at big pharma’s stranglehold on insulin by SketchySeaBeast on Monday June 28, 2021 @02:04PM (#27665295)
Their point was why are people being FORCED to produce a diabetes bio-hack instead of getting insulin. Neither your wife, Amish people, nor home mechanics are forced to make their own bread instead of buying it - they are all choosing to even though bread is cheap and easily available.
Re:Biohackers take aim at big pharma’s stranglehold on insulin by crakenzak on Monday June 28, 2021 @04:31PM (#27667640)
It’s clear from your responses that you seriously can’t handle logical disagreements to your point on online forums and choose to get offended instead.

The replying comment is right, it’s irrational & you’re filled with hubris to think that you could replicate world wide supply chains in your back yard. In no universe does growing yeast == replicating a global supply chain.

Re:Biohackers take aim at big pharma’s stranglehold on insulin by pitched on Monday June 28, 2021 @02:04PM (#27665310)
Growing wheat and grinding it out into flour isn’t something I’ve ever heard anyone take on as a hobby before. Having all that actually cost less (including time) than buying bread would be a huge achievement!
Re:Biohackers take aim at big pharma’s stranglehold on insulin by squeaky-clean on Monday June 28, 2021 @07:05PM (#27669468)
Adam Ragusea actually just did a 2 part video on growing his own bread from scratch in his backyard. Part 2 just came out a few hours ago.

Spoiler :P it definitely took way more time an effort than buying flour from the store and making bread. And the final product was a pretty poor loaf of bread because he couldn't find a way to buy the same type of wheat most farms use and had to settle for "animal feed" quality seeds.

Part 1: https://www.youtube.com/watch?v=HlPm7JtaxE4

Re:Biohackers take aim at big pharma’s stranglehold on insulin by dekhn on Monday June 28, 2021 @05:12PM (#27668212)
I imagine the guy who built his own toaster from scratch probably also contemplating rebuilding the entire pipeline to produce the input to the toast. "Step one: acquire the ore. Step two: smelting iron ore..." http://www.thetoasterproject.org/page2.htm
Re:Biohackers take aim at big pharma’s stranglehold on insulin by ineedasername on Monday June 28, 2021 @05:59PM (#27668759)
At that point we're basically talking about Factorio.
Re:Biohackers take aim at big pharma’s stranglehold on insulin by lotyrin on Monday June 28, 2021 @02:02PM (#27665264)
I'm not sure why you are projecting that, but it's not there.
Re:Biohackers take aim at big pharma’s stranglehold on insulin by jcims on Monday June 28, 2021 @02:35PM (#27665794)
It’s a little more complicated than that. Bread is ingested through a system optimized to absorb nutrients from outside the body.

Insulin must make it into the bloodstream intact, typically through injection. It’s also incredibly potent, a unit of insulin dried to crystalline form weighs less than 40 micrograms, so it much be administered in a sterile carrier fluid.

Lastly the penalty for overdosing is generally called insulin shock or diabetic hypoglycemia, and ‘it is rare but possible for diabetic hypoglycemia to result in brain damage or death. Indeed, an estimated 2–4% of deaths of people with type 1 diabetes mellitus have been attributed to hypoglycemia.‘ [1]

That’s with pharmaceutical insulin, not DIY.

1 - https://en.wikipedia.org/wiki/Diabetic_hypoglycemia

Re:Biohackers take aim at big pharma’s stranglehold on insulin by AstralStorm on Wednesday June 30, 2021 @02:40AM (#27685635)
On the other hand, glucose blood levels are reasonably easily measurable and being slightly on the high side is fine, but the precision pumps (or microfluidics) to do this dosing automatically and accurately are still expensive.
Re:Biohackers take aim at big pharma’s stranglehold on insulin by margalabargala on Monday June 28, 2021 @02:01PM (#27665251)
Growing enough viable yeast to bake 10 loaves of bread is orders of magnitude simpler than growing, harvesting, threshing, and milling enough grain to bake 10 loaves of bread.
Re:Biohackers take aim at big pharma’s stranglehold on insulin by rootusrootus on Monday June 28, 2021 @03:54PM (#27667004)
It can as simple as doing nothing. You can start your own sourdough at home completely from scratch, and do nothing but wait for the yeast to show up.
Re:Biohackers take aim at big pharma’s stranglehold on insulin by dekhn on Monday June 28, 2021 @05:15PM (#27668248)
most times the results will be contaminated by bacteria. The knowledge of what was actually going on when you do this was only gained in the past 250 years or so (before that, yeast was known as godisgreat).

In addition to doing it the way you described (put out flour and water in a bowl and wait for it to bubble and smell nice), you can also buy a $100 microscope, collect wild yeast, clean the bactiera off, and grow mass cultures. Sometimes it pays to work at the last step of the industrial, scientific and agricultural revolutions.

Re:Biohackers take aim at big pharma’s stranglehold on insulin by ipsum2 on Monday June 28, 2021 @03:52PM (#27666979)
The parent mentioned growing their own grain, which is substantially more difficult (planting, harvesting, milling) than growing your own yeast.
Re:Biohackers take aim at big pharma’s stranglehold on insulin by dekhn on Monday June 28, 2021 @05:16PM (#27668268)
Let's go back to before real agriculture. 10K years ago People harvested wild grain, processed it, managed to make yeast starter, and produce an edible bread that sustained humanity until we learned how to domesticate it and build the infrastructure to study it until we know how all this works at the molecular level. But they managed to do it without any science or technology.
Re:Biohackers take aim at big pharma’s stranglehold on insulin by ineedasername on Monday June 28, 2021 @06:15PM (#27668951)
10k years ago they had actually already domesticated crops and weren't reliant (at least not in many places) on finding wild grain.

Regardless, it was all still done with science: Observation followed by trial and error informed by those observations. Maybe not the scientific method formalized by Francis Bacon, but it's still there in the outlines.

Re:Biohackers take aim at big pharma’s stranglehold on insulin by dekhn on Monday June 28, 2021 @07:34PM (#27669723)
OK, 12K years not ten. I wouldn't call that science- while observation and trial and error necessary, they aren't sufficient. What was done to turn teosinte into maize was more of... a large scale, long-term, unintentional engineering experiment.
Re:Biohackers take aim at big pharma’s stranglehold on insulin by ineedasername on Monday June 28, 2021 @08:58PM (#27670369)
I'm not sure you can have engineering without some at least rudimentary approximation of a scientific method. Maybe that's a nitpick though.

Either way, I don't see a fundamental aspect of the scientific method missing from an observation -> trial -> results loop. I also don't see crop cultivation as unintentional, although I'm not clear what you meant by that. What wasn't intentional? Deciding to experiment with planting seeds would have been a deliberate choice. Probably based on some observation that where wild grains were gathered together and and little things fell off of them, sometimes the same type of plant would grow. Followed by the idea that putting those things in different places might produce the same effect. Etc.

I don't think you get from wild gathering in a nomadic lifestyle to settled agriculture without observing, coming up with ideas about what you observed, testing those ideas, and checking the results. That is. A scientific process.

Toesinte turning into maize would may have simply been a blind generations long domestication process, but not that spark of insight and experimentation that led to stationary agricultural societies.