WEBVTT 00:00.540 --> 00:02.040 Hello, everyone. 00:02.040 --> 00:07.400 Thanks to Nina and everyone at Biohack Village for having me. 00:07.400 --> 00:11.700 My name is Anthony DeFranco, and I'm one of the founders of the Open Insulin Project. 00:12.140 --> 00:27.900 And I'd like to tell you a little bit about the general problem that we're addressing and how we're approaching it, and how you all can maybe get involved if you're interested. 00:28.380 --> 00:29.980 So let me begin. 00:32.560 --> 00:45.380 The basic fact is that worldwide 50% of the people who need insulin to survive don't have access to it. 00:47.800 --> 01:29.420 And when we take that figure into account, and also look at the population of people worldwide with diabetes, and some bounds that we have on the death rate that's directly attributed to it, and we also look at the insulin access statistic here, and we put all of the information we have together to get a rough estimate of what the impact of this situation is, 01:29.420 --> 01:34.260 where, you know, fully half of people who need insulin to survive can't get it. 01:35.800 --> 01:50.180 A very rough order of magnitude estimate is that about 20 million people, you know, 10 to 20 million people a year are dying due to lack of access to insulin worldwide. 01:50.520 --> 02:04.960 And to put that in perspective, 12 million people per year was the rate that people were dying due to World War II from all causes, which was the deadliest conflict in history. 02:05.360 --> 02:05.380 So 02:09.940 --> 02:27.240 this situation where half of the people in the world lack access to insulin is really a crisis on a historic level, you know, it's something that it's hard to find anything that compares to this. 02:28.460 --> 02:46.480 However, unlike a war or, you know, a very kind of complex problem like that, the fundamental technical realities of making insulin and getting it to people are fairly simple. 02:46.480 --> 03:00.200 So we're going to look a little bit at why, despite that, there is a problem of this magnitude and how we can try to approach and how we are trying to approach it in the Open Insulin Project. 03:03.840 --> 03:06.540 So that's kind of the worldwide situation. 03:09.360 --> 03:18.380 Here in America, where the many people in the project are based, we know a little bit more. 03:19.180 --> 03:38.460 Now, the worldwide situation is largely due to, you know, supply chain issues and the kind of geopolitics around different countries' access to markets. 03:38.960 --> 03:43.080 So those issues don't really exist within the U.S. 03:43.240 --> 03:44.080 The U.S. 03:44.080 --> 03:48.340 has plenty of infrastructure to get insulin to people. 03:50.560 --> 03:55.420 You know, the technology to produce is well established here. 03:55.620 --> 04:03.620 So it's a little even more puzzling to note that there's still a significant problem in the U.S. 04:05.140 --> 04:08.800 So we want to look a little bit at that. 04:10.200 --> 04:17.540 So here are some figures on just the prevalence of diabetes in the U.S. 04:18.180 --> 04:28.680 You know, almost half of people have either diabetes or a risk of developing it in a fairly short term. 04:29.920 --> 04:39.800 Just diagnosed diabetes alone is a over $300 billion a year cost for everyone. 04:40.180 --> 04:47.080 Having diabetes significantly increases overall health care costs. 04:51.840 --> 05:00.860 And there's a bit more detail on how, you know, diabetes is contributing to the global death rate. 05:00.860 --> 05:19.780 So this is another kind of data point, a little bit more specific about what we were talking about earlier, where, you know, we can actually say that the deaths are directly attributable to diabetes, also quite significant. 05:21.860 --> 05:30.520 So, you know, why is this eminently treatable disease still causing so many deaths? 05:30.520 --> 05:50.620 And why is lack of treatment even in an industrialized, advanced technologically and infrastructurally country like the U.S., you know, why is this disease still causing so much harm and so much clearly preventable death? 05:51.860 --> 06:08.240 Well, one of the factors is that the, you know, supply of insulin, even though it's very easy to empirically speaking, just has a lot of trouble reaching the people who need it. 06:08.720 --> 06:13.740 And the first step in that process is the manufacture of it. 06:13.740 --> 06:25.540 And globally, three manufacturers control almost the entire supply of insulin. 06:25.540 --> 06:28.680 And that is true in the U.S. 06:28.680 --> 06:30.180 as well as true everywhere. 06:31.860 --> 06:43.860 So, you know, already we're seeing that at the very first step in the supply, there is a kind of a restriction that may prove significant. 06:45.200 --> 06:57.340 And as a result, the list prices have risen on a, you know, roughly exponential trajectory. 06:59.500 --> 07:13.500 So this has been part of a pattern of all of the major manufacturers raising their prices at about the same time by about the same increment for decades. 07:13.940 --> 07:23.080 And, you know, this has resulted in the list price becoming unaffordable for many people. 07:25.320 --> 07:30.120 And because of the complexities in the U.S., for instance, you know, the U.S. 07:30.120 --> 07:45.400 kind of has a strange healthcare system where, you know, some aspects of the prices are subsidized in various ways by different parties who negotiate amongst themselves. 07:45.400 --> 07:52.120 You know, there's a very complex system involving insurers and manufacturers and pharmacy benefits managers and pharmacies. 07:52.700 --> 08:00.760 And there's a set of complex and mostly secret agreements among them as to, you know, what people are actually paying. 08:00.760 --> 08:13.220 But anyone who doesn't have insurance, which, you know, is tied to having a job largely in the U.S., you know, they're likely to have to pay that list price and to be unable to afford it. 08:13.660 --> 08:23.540 So this is, you know, implicated in what the problem may be as we come to understand it more. 08:25.760 --> 08:31.560 And then the result of that has been that one in four people with diabetes in the U.S. 08:32.740 --> 08:48.100 have reported rationing their insulin and not taking as much insulin as you need puts you immediately a much greater risk of the complications of diabetes. 08:48.200 --> 08:59.480 In the short term, you can develop diabetic ketoacidosis, which is potentially deadly within hours or days. 09:00.040 --> 09:19.080 And in the longer term, if you're not taking as much insulin as you need, you can develop the longer term complications of diabetes, which are many of which are listed here, you know, blindness, cardiovascular disease, and amputations, for example. 09:22.760 --> 09:39.500 So it's a rather grim situation, but it's kind of difficult to understand why this would be the case since insulin in some form or another has been produced as a medicine for almost a century. 09:39.500 --> 09:50.500 And even the state-of-the-art forms of insulin, you know, the most modern forms that we have are largely off patent. 09:51.340 --> 09:55.780 So why is it that there's still this access crisis? 09:55.780 --> 10:06.520 Why are only, you know, three manufacturers still controlling almost the entire market and able to price the insulin out of reach of many people? 10:08.400 --> 10:22.980 So there have been some investigations into this where people have looked at the price increase patterns and are, you know, finding evidence that there may be collusion. 10:22.980 --> 10:27.480 So some of these cases are still in progress here. 10:27.560 --> 10:42.220 But, you know, the fundamental reality is that, you know, whether or not there is explicit collusion here, there is this pattern of price increases and it has become unaffordable. 10:42.440 --> 10:51.060 And at the technical level, there's really not that much of a challenge to making insulin. 10:51.060 --> 10:57.200 So that's what we're focusing on now in our project is how to make insulin. 11:01.040 --> 11:23.300 So this is part of a broader problem in how health care and the economy around medicine is, you know, thought to what the kind of dominant philosophy and how to manage it is. 11:24.200 --> 12:01.500 There was a kind of economic theory that gained a lot of credibility in policy circles in the mid-20th century that said that, you know, making medicine is kind of different from other economic activities in that subsidies are needed to do all of the research involved and that a monopoly is an expedient form of subsidy. 12:01.500 --> 12:12.920 So that, you know, that would be a sensible policy to tolerate and even encourage monopolies around medicine. 12:13.180 --> 12:19.000 And these claims actually collapse fairly quickly under scrutiny. 12:19.560 --> 12:42.000 You know, most of the R&D involved in making medicines is already done with public money and universities and the companies themselves spend much more of their own budgets on other things like marketing and executive compensation than they do on R&D. 12:42.000 --> 12:50.080 Also, this belief that monopolies are essentially harmless has been, you know, roundly debunked since then. 12:51.340 --> 12:55.420 But nonetheless, that's the system that we've inherited. 12:55.420 --> 13:13.140 So the result of this is that, you know, we've had this complex system of agreements grow up around it, you know, with all those other, you know, parties like pharmacy benefits managers that we'll look a little bit more at later in the presentation. 13:13.460 --> 13:46.420 And, you know, they kind of partition up the market and it's very difficult to do anything outside of one of these kind of proprietary partitions, or to go between them, you know, even to the point that some people who are allergic or don't tolerate one brand of insulin are unable to get it covered by their insurance because the insurance only covers one brand at the preferred tier. 13:46.420 --> 13:52.180 So even when there's clear medical necessity, it still doesn't matter in this system. 13:52.180 --> 14:09.520 So, you know, it's not much of an economy in the end, because it's so thoroughly, you know, shot through with monopolies and monopolistic arrangements. 14:11.940 --> 14:19.040 And we see, you know, the problems that are typically associated with this. 14:20.440 --> 14:46.160 And, you know, one of the most notable is pricing the poor out of the market, but also, you know, you can see that progress that would threaten an existing line of business is discouraged. 14:46.160 --> 14:57.680 And, you know, one example of that was that, you know, an analyst here at Goldman Sachs is asking, is curing patients a sustainable business model? 14:57.680 --> 15:18.800 You know, the answer in an economy where competition is essentially impossible is no, because, you know, the profits are already being maximized by chronically treating things, and so curing them doesn't make any sense if people don't have any alternative. 15:19.200 --> 15:21.920 And so that's kind of the unfortunate result of this. 15:22.960 --> 15:26.960 And this is something that, you know, many have researched this. 15:27.840 --> 15:37.840 One of my favorite theorists of this is Mr. 15:37.840 --> 15:39.200 Schmitz at Minneapolis Fed. 15:39.200 --> 15:47.460 So, you know, he has looked at how monopolies actually do cause the harms that we've discussed. 15:47.600 --> 16:04.820 And in the case of medicine, the harms aren't just economic, they are directly related to you know, lost lives and, you know, really tragic and tragically avoidable health consequences for people. 16:07.100 --> 16:21.440 So one of the things that is noted in general that we've seen in insulin is, in the case of insulin in particular, is that, you know, we have 16:25.100 --> 16:40.900 seen people, you know, turning to crowdfunding because the cost of insulin when they lose health insurance or health coverage of some sort is, you know, more than many people make in a month . 16:40.900 --> 16:43.440 It could be many thousands of dollars a month. 16:43.820 --> 16:54.720 So this is really a quite egregious example of how, you know, people get priced out of the market fairly quickly. 16:54.760 --> 17:14.240 And, you know, it's not just a subtle effect, it is a really, you know, a very large difference in prices that people have to bear to the point where, you know, it'll be exceed everything else that they're paying for in life by quite a bit. 17:16.940 --> 17:33.100 So just to make that a little bit more concrete, the cost of manufacture of insulin is about $5 per vial, but the list prices have risen to the point where they're around $300 to $600 per vial in some cases. 17:35.860 --> 17:44.060 And, you know, these conditions have persisted for decades, and they've only gotten worse. 17:44.060 --> 17:47.940 There hasn't been any successful pushback against them yet. 17:49.440 --> 17:59.280 So what we are trying to do is kind of invert everything that we've observed in our project. 17:59.540 --> 18:22.100 So instead of relying on proprietary development and mechanisms of monopoly, we are sharing everything that we develop in a commons, and we are looking to produce insulin in low overhead distributed networks of small scale manufacturing sites. 18:23.060 --> 19:04.800 And instead of having this really strong conflict of interest between the producers who are motivated by profits and to deliver profits to investors, instead we're looking to have the people who use the insulin actually be directly involved in the governance of the organizations that are making the insulin so that they'll be able to make decisions as to how everything is managed in the interests of themselves and each other and the people using the insulin. 19:04.800 --> 19:13.600 And a helpful side effect of this will hopefully be that we'll be able to be a lot more nimble and 19:17.340 --> 19:45.220 actually make a lot more improvements and not be incentivized to keep old things around just because they're already profitable and actually move things forward and hopefully make progress And in part, we're inspired by other successes in the diabetes community. 19:45.960 --> 20:15.240 So although we're the first effort I know of to make insulin itself open source, for about 10 years now, people have been working on artificial pancreas systems, which is essentially a software algorithm that controls an insulin pump to determine the timing and the amount of the dose of insulin automatically, 20:15.240 --> 20:19.380 usually based on feedback from a continuous glucose monitor. 20:19.760 --> 20:38.120 And this is something that was already possible with technology from the 80s, but the manufacturers just never seemed to be able to bring it to market for whatever reason. 20:38.300 --> 21:08.740 But once the technology to do this became more widespread, you know, once embedded computers became cheaper and easier to work with, and knowledge of software and how to write these kinds of algorithms became more widespread, individual diabetics and small groups were able to just pick up this work and bring it to completion within the space of a few years. 21:08.740 --> 21:25.460 For almost a decade, there have been DIY artificial pancreas systems that, you know, many people have been relying on and trusting with their own lives and the lives of their children, and, you know, they're working very well. 21:25.900 --> 21:31.240 And this was done without any, you know, large R&D budgets or institutional overhead. 21:31.460 --> 21:38.140 It was just people collaborating in these horizontal networks to solve their own problems and each other's problems. 21:38.720 --> 21:52.840 So we're working on enabling this for the insulin itself so that we can kind of complete the open source economy for treating diabetes. 21:53.840 --> 22:07.680 And it turns out that the same trends that made the DIY artificial pancreas systems possible are also going to help us. 22:08.940 --> 22:28.080 The, you know, more pervasive and cheap computing technology is going to play some role in letting us automate different aspects of the production and purification, and it also just makes it easier for us to collaborate with each other. 22:28.740 --> 22:34.880 And so we're seeing signs that we can reproduce this kind of success. 22:36.020 --> 22:51.520 And, you know, the result of that will be ideally to move this activity from these, you know, proprietary fiefdoms and into the commons. 22:51.520 --> 22:55.800 And this is something that is good for people. 22:55.960 --> 23:06.040 It's very good for business as well, you know, judging by how it's gone with, you know, open source software businesses. 23:06.680 --> 23:26.660 But, you know, major difference is that it actually respects and promotes competition and innovation instead of sabotaging it and, you know, trying to go on needlessly suffering and dying for no reason. 23:28.120 --> 23:30.080 So that's our goal. 23:31.640 --> 23:45.540 And we're working on developing both the technology and the organizational forms that are associated with this to, you know, create a comprehensive alternative for the status quo. 23:45.540 --> 24:07.220 And we're trying to prioritize the people who currently lack insulin and need it most in how we develop things so that we can most directly address the most urgent problems that people in society have. 24:09.120 --> 24:19.920 So this is a closer look at the existing supply chain just so that we can contrast it with what we're setting up. 24:19.920 --> 24:34.420 So I mentioned earlier that there are, you know, these multiple middlemen who operate in these complex networks in between the manufacturer and the consumer. 24:34.420 --> 24:46.300 And so I won't even really try to go through this in any detail, but you can see that there are, you know, quite a few complex patterns of interrelationship among them. 24:46.300 --> 24:55.120 And most of these are done in secret, so there's no transparency into how this works in any detail. 24:56.800 --> 25:15.660 And, you know, it involves kickbacks being passed up and down the chain and, you know, all kinds of things that just are in themselves a great challenge to making any sense of things. 25:15.660 --> 25:41.160 And so when the system produces the nonsensical result of, you know, denying people insulin that they need to survive that costs very little to make, you know, this is kind of how that is able to grow and that kind of problem can grow and sustain itself in this environment of artificial complexity. 25:41.160 --> 25:51.220 So we're going to address that by making things as simple and as direct as possible. 25:51.220 --> 26:04.940 So right now we're working in our community labs to develop the microbes and the technology, and then we're going to publish the information associated with them. 26:05.300 --> 26:26.340 And then using that public information about how the technology works, we're looking at setting up a system of cooperatives where the insulin users can participate directly in the ownership and the governance of those organizations. 26:26.340 --> 26:56.580 And we may also be partnering with hospitals and local pharmacies that already do work that is similar in some technical aspects to this, and they already have, you know, people who would need the insulin, they have relationships with them, and we may also be looking at collaborating with local and state governments. 26:56.620 --> 27:10.020 And, you know, aside from these fairly small and simple low overhead organizations, it's going to be as direct to the users as possible. 27:12.140 --> 27:18.360 So a closer look at some of the technical work that we're doing. 27:19.720 --> 27:30.440 And this is, you know, this is just a general look at how protein production purification works and how this applies to insulin. 27:30.440 --> 27:39.160 So right now we've designed some genetic modifications to some microbes. 27:39.580 --> 27:53.860 We have actually three systems we're working on now, this is two of them, but we have two yeast-based systems for producing insulin glycogene, which is a long -acting insulin, and one E. 27:53.860 --> 27:58.840 coli-based for producing LISPR, which is a rapid-acting insulin. 27:59.100 --> 28:05.060 And so we have ongoing work with the microbe engineering. 28:06.180 --> 28:16.120 Some of it has produced some small yields already, but we're working on getting the production to be reliable in the practical level. 28:16.660 --> 28:33.380 And then once the microbes are engineered, we're going to focus on a small-scale purification system, initially using proprietary equipment, but we're also working on making open-source equipment for that. 28:33.440 --> 28:42.220 And we've also started to look at the 28:45.760 --> 28:53.280 verification and quality assurance questions of making that product suitable for use as a medicine . 28:54.300 --> 29:03.940 And so once we've got all of these aspects in place, we've got all the technical problems for making insulin in a small-scale setting solved. 29:05.420 --> 29:13.720 So here's a look at a kind of demonstration version of a bioreactor. 29:13.720 --> 29:27.520 So it is essentially just a bit of plumbing, and aside from having to keep it sterile, there isn't anything terribly technically complex about it. 29:27.520 --> 29:40.460 You're going to have some, you know, some pumps and some valves and temperature sensors, pH sensors, and that sort of thing. 29:40.460 --> 29:53.720 And then for the purification, you're going to have, you know, perhaps a column, which is a, you know, just a tube with certain ports filled with 29:57.140 --> 30:12.840 some materials that may be a little bit costly, but for the most part, this is something that, you know, you can, as these people have for this demonstration unit, they fit everything you need to do it onto a tabletop. 30:12.860 --> 30:17.320 So, you know, we can work in a similar envelope. 30:18.820 --> 30:30.620 You know, the corner of a room could be enough to produce insulin for you know, a small city if we are, you know, running at a reasonable efficiency. 30:32.300 --> 30:43.400 And as a result, we can bring the cost of insulin back down to what the cost of production already is. 30:43.780 --> 30:54.780 So our own projections for what our cost of production be are in line with what they are for the large-scale production that dominates right now. 30:55.320 --> 31:07.900 So based on our preliminary model, we could be providing this to people for seven dollars a vial, which is, you know, very close to the three to five dollars a vial that it's usually produced for. 31:07.900 --> 31:22.760 So, you know, we're seeing that there isn't really any economy of scale here and that, for the limited supply that we see right now. 31:25.440 --> 31:35.840 So as I mentioned, we are still working on the microbe engineering, but we have started to work on the open hardware as well. 31:35.840 --> 31:53.640 So we're making progress on the technical aspects of this process and we're looking forward to reaching some of the milestones on that fairly soon. 31:53.780 --> 32:14.960 And we've, you know, begun working not just on the open hardware but also on some of the regulatory and organizational research to make that hypothetical system of cooperatively organized production a reality. 32:14.960 --> 32:43.070 So, that's going to involve some outside-of-the-box thinking and we're, you know, getting into looking at a lot of interesting precedents like ideas from personalized medicine and other forms of cooperative medicine and health care and state-level frameworks for things like direct public offerings, 32:43.070 --> 33:09.570 you know, financial mechanisms, and so it's really taking us on both a deep and a broad look at a lot of very promising alternative ways of doing things that we hope will apply not just to insulin but to perhaps medicine in general and business in general in the near future as well. 33:11.530 --> 33:28.610 So here's a closer look at the bioreactor design that we have just recently completed the first look at. 33:28.610 --> 33:46.110 So, as you can see, the bioreactor, when we break it down to the specifics, as I was saying before, it's kind of some pumps and some sensors and, you know, an air pump and some heating pads 33:49.430 --> 33:59.790 and this is a design that was based on one that another fellow in the community, Sebastian Kosioba, was working on. 33:59.790 --> 34:07.510 So he was kind enough to show us around his design and we have a group of interns that's working on this right now. 34:07.530 --> 34:24.010 So this was made by Paige Hanoka and it took her just a couple of weeks to come up with this and the bill of materials for this comes out to $115.80. 34:24.010 --> 34:39.350 So this would have a capacity of a few liters and a capacity of a few liters if you run it fairly close to continuously that can supply insulin for a few thousand people. 34:39.390 --> 34:49.070 So, you know, this is still leaving out the purification and the QA aspects but, you know, those don't add an order of magnitude more cost to this. 34:49.070 --> 34:55.010 So you can see that the, you know, capital requirements for doing this are negligible. 34:57.670 --> 35:12.630 So we've talked a bit about how we're looking to organize the production ultimately but we are also organizing the R&D work that we're doing right now in a similar way. 35:12.630 --> 35:18.070 So we're a fairly horizontal open source oriented 35:21.510 --> 35:22.450 organization. 35:22.450 --> 35:28.750 We're taking cues from other open source foundations that are stewards of different kinds of technology. 35:28.830 --> 35:52.630 So we have groups working on the wet lab R&D, the hardware supporting software for our organization, developing the business plans, doing the legal and policy research, and doing communications with our supporters and touching on fundraising as well. 35:54.050 --> 36:05.270 And here a few folks from the team, you know, we are a loosely organized network of volunteers so people kind of come in and out. 36:05.270 --> 36:12.050 We weren't able to list everyone but here are a few of the more regularly involved folks. 36:13.830 --> 36:25.950 You know, Jan is our chief scientist working on the microbe stuff and David and Max are also working on that here in our Oakland lab. 36:26.870 --> 36:34.930 Alex Hay recently developed an open source glucometer which we have a blog post up on our blog about which is very interesting. 36:35.530 --> 36:40.770 Nicole has been helping us with the legal work that we're doing. 36:40.970 --> 36:43.830 Yifei has helped with software. 36:44.410 --> 36:49.310 Louise is working on communications and fundraising with the interns. 36:49.690 --> 37:00.190 Jessica is also working on the microbe engineering in the wet lab and with an intern group as well. 37:00.190 --> 37:22.390 Remy has helped us with some collaborations and Kadi is actually one of our international collaborators in Senegal who is getting her lab set up now to join us and perhaps help us look at some new possibilities involving plant-based production. 37:22.390 --> 37:26.110 So, very interesting potential there. 37:28.010 --> 37:34.410 Within our group, we are fairly horizontal as I said. 37:34.410 --> 37:49.790 So, you know, we kind of go on the open source credo of, you know, loose consensus and working protocols we could say and just take on tasks on our initiative. 37:49.910 --> 37:58.730 For the most part, so we've had to collaborate remotely. 37:58.730 --> 38:02.830 So, you know, we're doing things in online meetings, which anyone is welcome to join. 38:04.170 --> 38:10.370 And, you know, if anyone is interested in that, you can go to our website, openinsulin.org. 38:11.210 --> 38:16.910 And we have some posts up there that will give you some contact information and information about the meetings. 38:18.210 --> 38:31.490 So, you know, with that, I'd be happy to hear from any of you if you're interested in learning more about what we're doing or, you know, helping with any aspect of this. 38:32.090 --> 38:40.210 And the more the merrier and the more people are helping out, the faster we're going to be able to solve this very urgent problem. 38:40.210 --> 38:44.150 So, it would be a pleasure to hear from you. 38:44.150 --> 38:47.450 And, again, thank you for having me here. 38:47.450 --> 38:51.870 And thanks to Nina and the Valhack Village folks.