Biohackers Creating Open-Source Insulin
popsci.com
popsci.com
I have the highest doubts that they'd have the resources to do the broad-based clinical trials required to go to market.
Look up "Eroom's Law" which is "Moore's Law" spelled backwards: http://www.nature.com/nrd/journal/v11/n3/fig_tab/nrd3681_F1....
Basically, the increases in pharma regulation means it takes longer and gets more expensive to create a new drug each year.
This is a cool science project, but the reporting around it is sensational and not helpful to the millions of people with diabetes who have their cranks yanked regularly about miracle cures, cost-saving fantasies, etc.
To address some raised in sub-threads:
+ You can get extraordinarily cheap drugs in India, the rest of the developing world, and in parts of Europe. The "greedy" drug companies adjust pricing to what local markets can bear. So instead of letting poor people die en masse they mark the drugs down and pass the cost onto the developed world. Fair trade IMO.
+ The reason there are so few generic insulins is that they are hard to make consistently enough to please the FDA and European regulators. Companies like Teva and Perrigo are multi-billion dollar manufacturers of generic drugs who would love to get get into this game, but as noted, biosimilar drugs, especially ones as powerful as insulins, are a lot harder to copy than aspirin.
I'm a Pharmacologist and I've worked in a number of Biotechs. I have been part of pricing discussions to value our drugs and your assessment is correct — price discrimination, as in most industries, is based on what a particular market can bear. Factors that influence this are the way that healthcare systems are run (i.e. public healthcare, insurance based), the cost of compliance and competition. I wouldn't say that the industry subsidises poor countries via sales in the developed world, it's more a case of it's better to be paid something rather than be paid nothing. I personally, however, do like the happy side-effect this has for patients in poor countries.
Increased regulation costs more to comply with and that cost of course is born by the consumer. The cost of regulatory compliance also varies on the market you sell to, the US being one of the most expensive. Just as with software or hardware, the price reflects the cost of production and maintaining the product.
Notably with biologics (Insulin, any hormone ...) as opposed to small chemical entity (paracetamol, aspirin etc) is that broadly they are harder to keep in their stable active form. The are heat sensitive, chemically sensitive and have a tendency to stick to themselves. This tends to increase the cost of storage, logistics and compliance. It also means that if you can make a worthwhile biologic it will generally experience less competition.
Sometimes I wonder if some HN comments are being posted from an alternate universe...
Did I understand it correctly? Why is it so?
That said, I understand why the laws have been shaped the way they have.
Every big pharma/biotech I've worked for has always pushed the FDA to make exceptions to the rules. They certainly aren't push for more of them.
As a Type 1 Diabetic, this cracked me up. I regularly get sent articles and have conversations with friends about "research on such-and-such cure for Diabetes!" Ten-to-fifteen years, right? Add it to the pile. Call me when something's on the market.
> cost
Typically for most drugs it really just means they extract less profits from developing countries (slim margins), not that they sell for a loss, while making lots of money with large margins in developed countries.
Since we have already met our target $ for phase I, we opened up a stretch goal to fund phase II.
We are in the early stages of establishing the protocols for cutting and folding the proinsulin into its final, active form, and are looking into purification methods sufficient for research and potential pharmaceutical use.
Meeting stretch goals will help us purchase the reagents and equipment necessary to execute these protocols.
If someone asked for $25000 to build the next electric car I'd not believe them either, there is more to making the next electric car in terms of process and design than being able to buy a battery and some motors.
That is $2.19 according to xe.com and is a branded version made by Novo Nordisk. So if you use 40 units a day, it would be less than $7 a month.
Greater regulation, higher wages and higher occupational health and safety standards keep the price higher in the US.
once these disulfide linkages are created, this insulin precursor undergoes a multi step enzymatic cleavage which cuts off some bits and makes biologically active insulin.
There are many ways to create insulin synthetically, and some of them lead to product contaminated with misfolded proteins. Misfolded proteins may have no effect, but sometimes they can activate the IGF-1 signal pathway which has been associated with cancer. There is also a chance of an autoimmmune reaction to the misfolded insulin, which would also be very bad.
We are exploring a few different methods for our insulin production specifically with this concern in mind.
Insulin, on the other hand, is a free floating small molecule not anchored to a cell. Misfolded insulin is not 'infectious' like PrPsc.
The biological role of prions is still not well known, but one reason prion diseases are such a big deal is that prions are resistant to normal biological protein degredation. They are hard buggers to get rid of. Unlike insulin, which has a specific protease enzyme which breaks it down.
Insulin-like Growth Factors (IGF) have been implicated in some cancers. As the name suggests, these enzymes are very similar to Insulin -- so every time someone tweaks insulin there's concern that they might end up triggering whatever (as yet poorly understood) metabolic pathway connects IGFs to cancer.
That will barely get you a kitchen, not a laboratory that will produce something that will pass FDA approval after you spend a very large multiple of that on tests.
As far as FDA trials go, it is something currently outside the scope of this campaign. This is from the crowdfunding page:
"
$6,000 is needed to initiate Phase I of the project. In Phase I, the team will insert an optimized DNA sequence for insulin into E. coli bacteria, induce the bacteria to express insulin precursors, and verify that human proinsulin has been produced.
If we raise more than the minimum required for Phase I, we will proceed to establish the protocols for cutting and folding the proinsulin into its final, active insulin form, and develop purification methods sufficient for research and potential pharmaceutical use.
All protocols we develop and discoveries generated by our research will be freely available in the public domain. We will also be proactively investigating strategies to protect the open status of our work.
"
It's pretty staggering how inexpensive experimenting with DNA can be. Recent advances in DNA synthesis are outpacing Moore's Law. Creating genetic constructs for insulin is also cheaper because insulin itself is a relatively simple protein.
And fortunately there are also a ton of extremely qualified people on the team who seem to love working for free.
EDIT: you shouldnt need to use facebook. you can sign up for experiment .com with just an email addy.
If it's the latter, why start with such a hard molecule; isn't there a lower-hanging fruit?
If it's the former, it would seem grounded in the assumption that biosimilar insulin unavailability in the Western markets is due to the lack of a royalty-free production method. I'm not sure that is the case (and please, correct me along the way). Biosimilars face a more rigorous/expensive approval process than generics (as they should), they're more expensive to produce under GxP conditions, and they're more expensive to store/transport/etc—the upfront costs are higher, the production costs are higher, and the logistical costs are higher. A small portion of NRE costs in the beginning would seem to be a drop in the bucket compared to the rest. Are you planning to address the rest of the lifecycle? Also, there would seem to be a lot of handwaving over the folding problem… do you have direct plans to address it?
I don't intend for this to come across harshly—I'm genuinely curious and hope this comes across constructively.
That is an unfortunate naming choice. Phase + Roman numbers have a well defined meaning in drugs development (clinical trial phases). I saw you refer to phases elsewhere in the comments and misunderstood what you meant.
1. the final phase of the election campaign: stage, period, chapter, episode, part, step, point, time, juncture.
Pick one, and run with it :-)
“I don't think the major hurdle is that the companies don't know how to make insulin, because that part is reasonably straightforward,” he says. “The real hurdles are getting the drug approved by the FDA (and since insulin is a biologic drug, it requires a lot more original data than an application for a small-molecule generic would), and then upfront manufacturing costs (because making a biologic drug is different, so it requires different equipment).” "
I don't know if that might qualify as very expensive but one can get one month worth of insulin for $50.
http://theperfectd.com/2014/10/23/type1-diabetes-no-insuranc...
This seems to be a small-scale expression and optimization, and I'd guess that this is not the expensive part of developing a generic insulin. Large-scale manufacturing and making sure you're producing the correct molecule reliable, and then demonstrating that to the FDA are probably orders of magnitude more expensive.
Is there a hand on the doomsday clock for biological engineering?
"A lot of biohackers (even PhD level biohackers ensconced in academia) are basically script kiddies – cut and paste these bits of DNA and cross your fingers and hope the result you expect pops out."
Same is true of Neuro phds: "scan brains in fmri/eeg that i have no idea how it works from a physics perspective", run this matlab script here, use this proprietary software there, calculate "connectivity|power|correlation" - "does this look good for my paper? yes, shiny grant coming right up! Will it move the field forward? Not anymore than the thousand other papers out there but the university pr office is on it!" (in no particular order).
I say this because if all this was more out in the open (methods, software, caveats on every level on a git repo) and more available to people in other fields/expertise to look at and source materials and parts, a lot could be moved forward in general from what I'm observing going on in academia now along the lines of:
"As I worked on insulin in grad school, I risked my job as a lowly postdoc, chiming in and pointedly telling him (in front of the program manager) why it wouldn’t work. Some of my coworkers speculated that I might not show up the next day, but I survived to tell the tale."
I see some well intentioned people fumbling around, being derided in private by academics (who play the same human status games in different ways) who are still willing to talk with such people (because $$$, and maybe because some other academic they "collaborate" with is talking with them), who are pretty smart in their field (who are finding alternative funding sources!) who I secretly hope burn a fire under the ass of what goes now, so I won't write it all off.
I could probably whip it up myself, but I'm already stretched thin doing two biology projects that aren't paying me anything - and in fact are costing me (my nonprofit and a startup) and I make barely enough on some part-time contract coding work that I am really lucky to have landed through roommate-nepotism.
As to why I'm not really that excited about helping the Open Insulin Project any further: I've become kind of wary about prevailing attitudes in the tech-to-bio transition field that basically takes an exploitative attitude following the Postdocapalypse... There's this investor class expectation that they can hire frustrated grad students and postdocs for cheap. I think this is true, but they better watch out, in 99% of cases they are going to get what they are paying for.
I've decided to quit impostor syndrome and accept that I am kind of a biochemistry badass (I redesigned an enzyme and made it 4x better on my first shot based on first principles), and that if anyone wants my expertise they have to pay $$ for it. The other week an ALS advocate showed me a drug candidate structure and I correctly identified the mechanism of action without knowing much about the target. I've never been terribly excited about bringing the marginal cost of scientific labor closer to zero, and the OIP is basically that.
But good luck to them.
I think the work you do is pretty awesome (at least from reading your posts here and on your blog) and can understand that you are stretched, but I can see that you also want to move the field forward (and not in the "lets shit some papers out and maximize for 'impact factor'" way).
>"As to why I'm not really that excited about helping the Open Insulin Project any further: I've become kind of wary about prevailing attitudes in the tech-to-bio transition field that basically takes an exploitative attitude following the Postdocapalypse... There's this investor class expectation that they can hire frustrated grad students and postdocs for cheap. I think this is true, but they better watch out, in 99% of cases they are going to get what they are paying for."
I can see where you are coming from about the whole Postdocapalypse economics… I see it heating up as well with mindfulness being the current carrying agent in moving the neural tech forward (some neuro phd i was talking to on twitter said this to when I was mocking the "run matlab on cluster for months mentality" and saying it could be done way faster (hours) and cheaper: "Sounds a little bit more complicated than just reporting what you did in a paper.", so yeah, the investors who fund people like that are going to get exactly what they are paying for), but I'm going to help people milk it for what its worth just to help foster something that can compete with the abomination that academia has metastasized into that masquerades such games as science.
> "…I've never been terribly excited about bringing the marginal cost of scientific labor closer to zero, and the OIP is basically that."
Yeah I can understand that, but I also think the way that resources are allocated as a society are in for a major shake up (esp with the whole crowdfunding bonanza across so many industries, and have people who worked for the UN and a gov agency in Turkey contact me about the software I wrote to track it on social media), which I think is why people aren't terribly excited on top of the personal stress all the uncertainty brings which I'm familiar with being a drop out who's in the neck of it up here in the boston area (and happen to be the only one it seems to have open-sourced a spacial beamformer in c++ for real time neural feedback for eeg that can be adapted for dual eeg/fmri). I do think though, because you aren't necessarily confining yourself to what things have to be (as defined by the status quo), you'll probably end up doing way more than you think you are capable of now.
And after spearheading several bio-hacking-type calls within DARPA, and seemingly being groomed to take Arati Prabhukar's position, she seems to have suddenly disappeared from her position at DARPA altogether in the past few months.
DARPA is doing the same pretty much with some stuff going on at MIT in neuroimaging… so i hear… :P
And there's a lab in Wisconsin that's sucking up 10's million of dollars from private foundations of which a co pi of that lab visited ours to tell us about their soon to be created public outreach arm… on top of the questionable custom eeg head cap for dual/eeg frmi thats close to a million who knows nothing about e&m, who I confronted directly about that while getting the backing from the senior research scientist (who is on a visa…) in my lab whose phd is in soft condensed matter physics who worked on SQUIDs at yale, who is now conveniently "volunteering" most of the time doing mobile apps for some company attached to our lab who wrote most of the code for the system people saw Anderson Cooper hooked up too on CNN not too long ago… but you'll never hear about him over others trying to capture 100% of what they think is the only opportunity now.
#WhatAFuckingJokeThingsAre and this is why things are due for a shake up lol
Trying to pretend otherwise is ignoring all the technologies becoming available on a ramen budget.
When your quality of life, or even the remaining duration of it, is largely in the hands of a few executives at a single company, it's generally a good move to do whatever is necessary to reduce your dependence on them, before they realize that they can bleed you dry--along with those like you--with a few keystrokes in their inventory system.
It is inevitable that people made desperate by medical circumstance will do dangerous things with biology on a shockingly low budget.
For instance, did you know that some people are doing at-home fecal transplants using thrift-store blenders and over-the-counter enema kits?
How long do you think it will be before someone tries converting cells in their intestinal lining into beta cells, or implanting an artificial pancreas made from their own cells? It is very likely that any successes will be unknown, while the first person to inadvertently kill himself while attempting to cure his own diseases with garage-scale biotech will be criticized and demonized worldwide. And that will be the spark falling on dry tinder, as people realize that the cost of biohacking is now low enough to be within reach of ordinary people.
1) wrote that blog post
and
2) gave the open insulin guys the design they're using. I am a little bit dismayed that credit for the design is somewhat buried in the public facing materials, but whatever.
and
3) agree that it's mostly hype - both this project and 'biohacking' in general. I run a nonprofit that is working on an patent-free cancer drug. Raised 60k and I'm doing ok, about to launch into production phase pre- animal model study. I would hesitate to call myself a biohacker - I have a PhD in chemistry and two postdocs in biochemistry and molecular biology, so I'm not coming from the CS/IT side - although I do currently code for a living.
but
4) think that whatever, the project could be interesting.
As it is, the way insulin is manufactured is pretty terrible, it could be way cheaper, and it's with that in mind that I designed the scheme the way that I designed it.
Well, the report itself says:
prescription medications to treat complications of diabetes (18%)
So this is up to $31.68 billion in 2012. I will assume for simplification that all of it goes for insulin.
There are about 20 million patients in US (according to http://www.diabetes.org/diabetes-basics/statistics/). So this puts us into $100-150 in a month range for the insulin.
But most of the 20 million diabetics in the US are type 2 and do not require insulin; it's only Type 1s and the most severe cases Type 2s who take insulin.
I'm a type 1 diabetic (for ~30 years) and take Apidra (short acting) and Lantus (long acting) daily. I use about 5 vials of each per 3 months. I "think" the cost of each vial, if I was paying sticker price, would be about $250.00.
So... 2 * 5 * 250 / 3 = $833 / month
As it turns out, there's several mitigating factors:
1. I have insurance, so I pay much less than that
2. For those without insurance, the insulin creator has programs to help such people pay for the insurance (discounts for some, max out-of-pocket for others)
And the reason why there isn't any generic insulin is because each new insulin is "next generation" and people would rather pay more for the added benefit than use the old stuff.