Open Insulin

Counter Culture Labs in Oakland is a science-oriented community hackerspace, with a focus on biohacking. In one project taking place at the lab, members are engineering yeast to express milk proteins from non-animal sources - next generation of vegan cheeses and milk. Others are busy developing an eco-friendly bacterial sunscreen.

Open Insulin is one of these projects, and its goal is to make it simpler and less expensive to make insulin, starting by investigating some novel ideas for making insulin in e. coli using fewer, easier steps than in common industrial protocols. If successful, the members hope it can be a step towards making generic production more economical, and might also enable more participation in research related to insulin, or production of the medicine at smaller scale, closer to the patients who need it, further reducing costs and giving access to more patients who lack it.

Counter Culture Labs was founded by a group of hackers with diverse backgrounds and interests in the period from 2011 to 2012, with some members coming from Sudo Room, another hackerspace in Oakland that I participated in founding. Many were also involved in Occupy Oakland, and wanted to establish a more permanent organization with the same community spirit and values. Other members came from Biocurious, another biohacking space in Sunnyvale, in the southern end of the Bay Area. I became involved both because I shared the desire to build a community-focused institution, and because I have diabetes type 1 myself, which means I live with the frustration of costly and tedious treatment regimens day in and day out, and I know how much the standard of care for diabetes patients lags behind what recent research suggests might be possible. So, for my own sake, and for the sake of the others with the condition, I sought to take whatever steps I could to close the gap between the research and what is available to patients on the market right now.

About a year ago, some long-standing discussions around making a bioreactor to produce insulin, which had inspired a few previous attempts, turned more concrete when Isaac Yonemoto, another independent researcher of medical treatments, made some suggestions to us about interesting possibilities for innovation and improvement in existing protocols. We started organising regular meetings, and out of those we then organized a successful crowdfunding campaign, which then opened up connections to professionals who work on various aspects of the problem, both the science and engineering around insulin, and the questions of access to medicine. Through this it came to our attention that access to insulin lags far behind the need even now, and even in the most developed countries - costs of insulin are prohibitive even to many people in the US - and all in all, roughly 50% of those in the world who require it have no access to insulin at all, according to the 100 Campaign, a group working on improving access to insulin around the world. There is almost no generic insulin on the American market at the moment - the first one appeared on the market about two weeks after we finished our crowdfunding campaign last year, but it is a long acting type, which is only part of the therapy required by people with diabetes type 1 (about 15-20% of diabetics in USA have type 1; the rest have type 2). And for those who use an insulin pump, short acting insulin is necessary.

The general problem in the first world is that the incentives and interests of producers and patient communities are not aligned.

Right now we’re focused on achieving the first scientific milestones, which is to produce proinsulin, the precursor of the active form of insulin, in e. coli, in our small-scale community lab. Our lab runs mostly on donated and salvaged equipment and reagents and might be comparable in its capabilities to a lab in a less-developed area of the world where there is the least access to insulin. If we succeed, it would show the possibility that small-scale producers in remote areas might be able to make insulin to satisfy local demand, in places where centrally-manufactured supplies can’t reach due to lack of infrastructure - where what roads there are, if any, do not let refrigerated trucks pass to ship needed pharmaceuticals in. Once we have a protocol that embraces everything from production to purification to near the level of purity of pharmaceutical grade insulin, we plan to approach established generics manufacturers with a case for the economic feasibility of serving the unserved market for insulin, and to partner with them to do the rest of the work of achieving sufficient purity of the product and scaling the methods to production. As we proceed with our work, the main batch of patents around the various forms of insulin are expiring, which will further help us make the case for a comprehensive portfolio of treatments to potential generics manufacturers.

Provided all this goes well, we might then pursue another idea, closer to our original hope of a bioreactor that produces insulin, and a kind of ‘holy grail’ goal in the DIY bio world, which is a desktop biofactory, an analog of desktop 3D printers, but for proteins and biologics, which we might develop to first execute one of our protocols to produce insulin, but which we might also design with more flexibility in mind. This would consist of a bioreactor portion that could grow a culture of e. coli or yeast, and then extract and purify a product from it - very roughly speaking, the union of a fermenter with an FPLC, a piece of equipment that purifies proteins. If that is possible, supply of insulin could be placed very close to the demand of the diabetics around the world in a simple, economical package, and reliance on distribution infrastructure would be minimized. It would also reduce the need to have skilled technicians with years of lab experience to execute these protocols by hand.

Ultimately, I hope that opening up the tools for research to more people can help to bring research on cures to patients, and not just treatments. Let me mention a few of the more promising ideas that have had some success in research settings. One approach is to implant functioning pancreatic cells from a donor and protect them from immune attack by various means - hard to scale if you need a constant supply of donors,but it might be possible to grow cultures of the cells in vitro to address this. Another approach is to get the immune system to cease its attack on pancreatic cells, and promote the regrowth of the body’s own insulin-producing cells, either in the pancreas, or in another tissue via gene therapy - a simpler approach to apply once it is developed. Some of the ideas use very inexpensive supplies such as adjuvants, the materials in vaccines that provoke an immune response - and there has been some success using adjuvants alone, or with carefully chosen additions, to get the bodies of diabetic patients to reduce or cease their autoimmune attacks. Other concepts address the metabolic changes behind type 2 diabetes. Several drugs between the research and commercial worlds of medicine can act directly on the metabolic control mechanisms of the body, changing its pattern of energy use and other aspects of metabolism back from the pathological state of metabolic syndrome and type 2 diabetes to the normal, healthy base state. Some of them are small organic molecules, easier to make than proteins such as insulin, but due in part to reasons of cost and incumbency, are not mainstream treatments yet.

At the most general level, what we seek to prove is that if an order of magnitude more people get involved in research and development of science and technology, medicine can progress much faster, and might no longer be held back by institutional constraints and perverse incentives in the economics of the institutions. Right now, we’re a group about half a dozen people working regularly on the project, with a few dozen more people in touch every now and then to help out, and a hundred or two in the extended community, ready to answer a question or call for help. Every week or two, someone new comes to the group, who just learned about the project via the media or our regular meetups, and wants to help. Some are complete beginners and end up taking our introductory classes to biohacking, some already have experience but got tired of the limits of the institutions where they worked, or have relatives with diabetes and want to contribute to progress. Though we’re building up a broader community of participation in research slowly, we hope our efforts can plant many seeds out of which future innovations will grow.

Meanwhile, we are looking to broaden a circle of people who can advise us, experienced scientists and engineers who can help us troubleshoot issues that inevitably come up when investigating the unknown, but we also hope to inspire other groups to work independently in a broader community of innovation. We would like to set up a network of both institutional and DIY researchers living all around the world who have different approaches and ways of making insulin as well as tackling other diabetes and health related issues. Beyond producing drugs, participants might research questions of access to medicine, investigate what patient communities need the most, look at academic publications to identify the most promising research that is not making it out to serve patients, or help establish the effort to build the desktop biofactory. Part of our goal is to prove it’s possible and worthwhile for people outside institutions to take the initiative on these questions, and inspire others to take the lead in their own efforts and bring about the broader changes we seek.

Do you have any projects in health, medicine, or biohacking that you’d like to work on, but lack people, knowledge, or resources to make it happen? Are you working on a diabetes-related solution? Or do you feel like a network of care biohackers is something you’d like to get involved with? Leave a comment and let us know.

277% funded!?

Congrats for your work! The money quote for me is:

what we seek to prove is that if an order of magnitude more people get involved in research and development of science and technology, medicine can progress much faster, and might no longer be held back by institutional constraints and perverse incentives in the economics of the institutions.

So looking at your crowdfunding, people not only support, but actually fund scientific research in a crowdfunding campaign. And more so, research that is traditionally funded big time by big companies. I hope your time is also funded, as I’ve seen on the Counter Culture Labs site that it is volunteer led?

How long do you expect it to take from producing the proinsulin to getting at serious talks with manufacturers? Do you need more certifications or proofs of validity of sorts…or would they deal with this once they want to play ball?

Crowdfunding and R&D / commercialization work

We did have a fairly successful crowdfunding campaign, but it was not nearly enough to compensate anyone in the project for their time. The funds raised so far (about $15k) are just providing a small financial floor under us to cover the reagents we need to reach our first milestone and we will need to seek more funding after that to continue the work.

It will be a matter of a few years before we might expect to have demonstrated enough success in the work to get the attention of generics manufacturers, and in addition to the science/engineering work on the protocol we will need to get financials together concerning the economics of manufacture at scale, and perhaps results of tests relevant to regulatory compliance. Orders of magnitude more money and resources will be involved. We are only taking the first steps toward bootstrapping to that level right now. But in doing so we have gotten the attention of larger organizations with more resources who might be able to help us in taking these next steps.

I hope OPENandChange application can help

I would love to see this collective bid help you figure out manufacturing at scale. For the MacArthur foundation call  on which I’m hoping we’ll work together, if we can spin the story to evidence the less experimental part of your work and a solid plan for reshaping markets it would be great. They’re looking for durable solutions more than innovation, or so the briefing says. Either way, you win already just by being so daring.

Also, not sure if this is valid in your case, but it’s possible that fame comes earlier than success - so getting attention by being in the right places and company can help your mission.Hang in there :-)

Network of contributors

Thank you for sharing this interesting background info! I’ve been following the project from a distance for a while.

I was wondering: which steps have you taken to involve people abroad or to build a network of contributors for working on this project in different locations? I’m sure there are lots of interested parties globally. The biohackerspace in Ghent, Belgium where I’m involved surely would be.

Thanks for following Winnie!

We’ve been occupied enough with holding the lab work together that we haven’t gotten around to tackling the aspect of establishing partnerships with any sustained effort. Though perhaps a half-dozen potential collaborators with serious interest have reached out, we’re still at the point of initial discussions.

I’d love to discuss more about your hacker space in Ghent to see how you can get involved!

Let’s Skype

Great! Let’s talk on Skype if you’re up for that @dfko . I read @trythis  is also interested in joining the discussion. You can find me under my name on Skype (or Twitter) and we can find a moment to call via there.

pinged you on skype.

on the account with the image

What a wonderful idea…

Wow, @WinniePoncelet and @dfko ! This is a wonderful vision: biohacking spaces all over the world collaborating on a difficult process like producing insulin.

In the software world, we see this a lot. Turns out much software work is “packetizable”: the whole is much more valuable than the sum of its parts, but a single part still has some value, and it can be built in relative independence from the other parts. Think Wikipedia: it is so great because it spans human knowledge, but I can work on my entry about, say, the Duchy of Modena with no need to coordinate with you guys as you edit the kin selection entry.

@dfko , is making open insulin that kind of work? Can it be broken down into pieces that Winnie could take and work on?

A resilience argument

This is great work, @dfko . Congratulations, really. I remember hearing from @LucasG that the Canary Islands, where he lives, are home to 7,000 diabetes patients. The islands have no capacity for insulin production: these patients fly insulin in from Germany. This is relevant to Lucas because he is the man standing watch in case of pandemics: if pandemic flu hits, flights are cancelled and, once local stocks of insulin are exhausted, diabetes patients start to die.

Lucas even considered talking to local crystal meth manufacturers: shady types, but the only people on the islands with any organic chemistry manufacturing capacity (he decided against it, turns out their skill is insufficient to make insulin after all). A system of insulin production that is lighter on logistics and more reliant on local production is more robust to external shocks – an additional advantage to your idea.

This is exactly the kind of scenario that motivates our work! To get there it seems we may need to move beyond a manual protocol to automating the production at a small scale though - as you mention, even professional underground organic chemists need a broader base of skill to express and purify proteins.

What about ethics?

@Noemi, @Alberto at the first glance it looks cool, but am i the only one that  get some associations to dystopia SF (e.g. the ^biohacker^ in minorityreport)?

If I understand correctly we are talking about genetic manipulation to create an alternative to already fully disclosed, but patented medicine. Skipping clinical trials phases 1…4 to eventually offer this experimental product to the poor and  3world countries? Personally I’m not sure if this is an ethically acceptable approach. How can you be confident that your homebrew dna is safe when evidence based  research has to spend years and millions? Isn’t it like giving guns to children? @dfko Why can’t you just get proper NIH funding?

Can be paralysing…

It’s a valid point, @Rune . Honestly I am really scared by the ethical implications of research, any research. They can be paralysing. Of course, if your tools are lasercutters rather bioreactors, and your goal is design rather than human health, the ethics become less scary.

In practice, though, insulin is insulin. There are ways to test whether a chemical is, indeed insulin, or something else. And if it is, you are good: the same molecule should work in the same way, no matter its production process. Also, GMOs per se are not illegal in the U.S. Their attitude is very different from that of Europe.

That’s not quite the plan we’ve got planned for the project. We share your concern for questions of safety and ethics so we are only trying to accomplish a proof of concept right now.

The goal is first to make normal human insulin using methods broadly similar to those used already, but keeping the information needed to do so open, avoiding proprietary restrictions on the work, and trying to take opportunities to keep things as simple, inexpensive, and easy to reproduce as possible. If we succeed on any of those points, we would then hope that an existing generics manufacturer might be interested in taking up the work to bring a generic version to market, and we would try to partner with one to do the necessary work to ensure purity and safety. The general regulatory rubric this would fall under is the biosimilar regime, which is mid-way between the rigor required in vetting an entirely new drug and that required of a copy of an old one made with strictly chemical means. This was the plan we outlined in our original crowdfunding pitch and remains our current thinking.

We’d welcome funding from the NIH or another large funding organization if they’d have us but, among many other reasons to be skeptical about such a  prospect, I doubt there would be enough that’s novel about our work to qualify it as fundable science.

Testing a new way of funding biotech research is, for me, already a giant undertaking worth doing. Lots of perverse effects in biotech are a direct result of how research is structured, especially financially. Huge R&D capital requirements and high risks involved all along the process from idea to lab scale to factory scale to market. The time to market can easily be over 10 years, which adds to the complexity. (Sorry for the extremely short summary, a long analysis could fill a few books).

This is, in my eyes, the most feasible and direct impact you can have with a project like Open Insulin. More background reading and stories from the news today: The Shkreli story has been all over the web for a while now and shows exactly the perversities that are going on. And the real problem is summed up in a quote I read from Shkreli himself, which basically said what he did was common practise. And he’s right.

The obvious societal and ethical implications of having eg. insulin more accessible makes it worth pursuing as well… The insulin is a long way off being useful as a medicine and I’ve read most of the team is aware of this. The potential of open medicine is there in the long term however. It will need some serious conversation on ethical, medical, legal and other consequences. Luckily, the biohacker community has strong ethics and is open to have the conversation they are starting. It’s one worth having in my eyes.

Anyway, how about that Skype call @dfko ? I’ve messaged the OI account on Twitter, but no reply.

Can we join?

@dfko , @WinniePoncelet , I would be interested in being in the call too. I have nothing to contribute, I am just curious. Maybe @Amelia too?

Next year

I’ll be offline until the end of December, looking forward to have a call after that.

Roger that

Enjoy your offline time!

The state of California just announced a $100 million project where the state will make its own insulin and sell it at or near cost and undercut the drug companies.

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That’s wonderful. They should hire @dfko… wait, maybe they already did!