Wednesday evenings the hackers and biologists of Counter Culture Labs, a North Oakland “anarchist collective,” meet to work on a project aiming to create an open-source protocol for manufacturing a more accessible and affordable version of insulin, made by recombinant DNA, also known as genetic engineering.
From day jobs at such powerhouse facilities as UC San Francisco, Amgen Inc., and Lawrence Livermore National Laboratories, they come to work on the project called Open Insulin. The project aims to accelerate development of a generic version of the lifesaving medicine while showing that citizen scientists and biohackers can contribute an alternative to methods now used by the for-profit pharmaceutical business model, says the group’s 33-year-old co-founder Anthony Di Franco of Berkeley.
Di Franco, a Yale-educated software developer, spends his days alternating between working with Wikipedia on open access, and in building financial technology for the startup Credibles, a prepaid food business funding enterprise. Open Insulin is a quest that merges both his scientific goals and personal health interests.
The team chose insulin because it is a complex molecule to synthesize. By setting the bar high they intend to show that community labs can produce quality research on issues of serious public health concern. In genetically-engineered medicines, a product is manufactured by inserting genes into cell cultures that then act as tiny factories.
Insulin is used to treat some forms of diabetes, a metabolic disease in which the body has difficulty turning sugar into energy. According to the Centers for Disease Control and Prevention (CDC) there are different forms of diabetes. In Type 1, comprising around 5 percent of cases, the pancreas fails to produce enough insulin. In Type 2 a person’s cells are unable to efficiently utilize insulin to uptake sugar. (Gestational diabetes, a third kind, is a temporary interference between normal pregnancy hormones and insulin.) When insulin can’t properly do its work, chronic high blood sugar can lead to serious long-term health complications including blindness, heart disease and amputation.
In the U.S., the number of people diagnosed with diabetes rose to 22 million in 2014 from 5.5 million in 1980. An additional 7 million with the disease are undiagnosed and untreated, according to the most recent CDC data. For those undergoing treatment, around 6 percent require insulin. The U.S. incurs $245 billion per year in diabetes-related costs, according to the CDC.
In November, National Diabetes Month, Di Franco’s group launched an initial funding goal of $6,000 on experiment.com, a crowd funding website for scientific projects. They raised over $16,000—or more than two-and-a-half-times that goal—by the December 4 closing date. The initial funds will allow the purchase of new equipment, reagents and the contracting of external facilities. The additional funds will support a second version of the insulin molecule.
Counter Culture Labs is housed at Omni Commons, a 20,000 square-foot warehouse in North Oakland. The sprawling complex was originally built in the 1930s to house a collective of Italian immigrants who specialized in materials recycling. The building holds a special connection for Di Franco. “They used to have a bocce ball court here,” he said. “It reminded me of my childhood, because that’s what all the old men would do, play bocce in the backyard.”
Omni Collective, “an anarchist collective of anarchist collectives” was formed from partial remains of Occupy, widespread demonstrations that sprang from dissatisfaction with economic inequity and the political status quo. The group moved into the building in early 2014. Di Franco said the group aims to allow autonomous participants to come together to work on art, science and other projects fostering a sense of communal responsibility for the members and the larger public. The Commons also houses other social interest groups such as a chapter of Food Not Bombs, the social issue film collective Liberated Lens, and Timeless Infinite Light, a small publisher focused on poetry and critical theory, among others.
“I think the focus on having as much community autonomy as possible and coming together with the love of radical open-mindedness and tinkering is a very powerful combination,” he said.
The insulin project is set up as a series of milestones with the goal of developing a simple and less expensive insulin production protocol than those now in use. Their hope is that open source technology will make it more attractive for a pharmaceutical company to take the technology to scale. Di Franco’s group is focusing on open-source methods, rather than a leap into manufacturing and sales. He said the process of Food and Drug Administration approval—needed for any product destined for human consumption—is “another order of magnitude from what we are trying to accomplish right now.”
By starting with development of an open protocol, the group hopes to avoid one of the barriers to production. Developing a form of the drug for medical use requires passing regulatory hurdles and massive capital investment. However, companies are wary of sinking money into research and development for a generic product that may not have the profit potential of proprietary formulations.
Di Franco acknowledged the difficulties. “It’s going to be a gradual process that unfolds over a number of years,” he said. “It’s not going to be all that flashy. It’s going to be keeping our heads down into a lot of hard work for a long time.”
Di Franco said the scientists have visionary, longer-term goals, such as allowing the creation of biologic products from a desktop fabricator. Envisioning a machine that holds the basic components of the product, called reagents, and programmed with blueprints for various compounds, Di Franco says he believes the technology is now at a similar point in bioengineering that personal computers were at in the 1970s.
Although this type of desktop bio printing technology is still 20 years away, Di Franco said he thinks citizen scientists will be a driving force behind its development. “That’s one of the Holy Grail, long-term visions among biohackers and DIY biologists,” he said. “There is nothing in the laws of physics that says you can’t do something like that.”
Di Franco’s personal interest in the project began in 2005 as he was preparing his senior thesis in computer science at Yale. Di Franco lost 70 pounds over the course of a couple months. He said he ignored the symptoms and was eventually drinking two to three gallons of water per day as his body fought to maintain balance under his undiagnosed Type 1 diabetes. When he finally went to the university’s health clinic he said his “blood sugar was off the charts.”
Di Franco said that insulin plays a crucial role in signaling the body to take sugar out of the blood and coordinate its use throughout the body. “It’s regulating this really fundamental aspect of your metabolism, playing a central role in moving the energy in your body around and dealing with it in the right way. And if you’re unable to produce insulin at all, as in the case of Type 1 diabetes, you are a essentially starving from the inside out,” he said.
Six or seven times a day, when Di Franco injects his medication, he is reminded of the demands of managing diabetes and the strengths and weaknesses of current treatments. He said his treatment options are basically the same as they were ten years ago and that options are even fewer for those in developing countries.
In the U.S. six million people require insulin—at a cost to the uninsured of between $120 and $400 per month, according to a March 2015 article by Drs. Jeremy Greene and Kevin Riggs. The article, published in the New England Journal of Medicine, analyzed the historic reasons there is no generic insulin available.
When the University of Toronto first identified insulin in 1921 the school attempted to secure open access to the discovery. The university patented their methods in the hopes that, once published, it would mean that “anyone would be free to prepare the extract, but no one could secure a profitable monopoly,” according to Greene and Riggs.
Bringing the technology to scale proved a challenge and in 1923 the school began teaming up with the pharmaceutical industry to begin large-scale production. With this came a series of innovations in manufacturing, composition and efficacy. Until the late 1970s, insulin was extracted from animal sources. Then, with the advent of genetic engineering, scientist became able to reprogram bacteria and yeast to mass-produce a copy of human insulin for medical use.
Genetic engineering companies and their lobbyists have argued exact generic copies of human molecules like insulin are too complicated to replicate as done with generic drugs made from chemicals in the test tube. This set up a different and more complicated regulatory pathway at the FDA for approving so-called “bio-similars” (or the generic version of biotech drugs) and this has had the effect of slowing the emergence of low-priced copies.
Each subsequent innovation spurred a new patent protection and each patent protection extended exclusive rights to production. As these new products entered the market, older —and potentially cheaper—versions were discontinued. This ‘evergreening’ of patents meant that a low-cost generic never arose, leaving many unable to afford the drug, according to the article by Greene and Riggs.
The Biotechnology Industry Organization (BIO) didn’t respond to requests for comment about the Open Insulin project.
Andrew Powaleny, a spokesperson on science and regulatory advocacy issues for the industry group Pharmaceutical Research and Manufacturers of America (PhRMA), said that, while he couldn’t comment specifically on the reasons for a lack of a generic insulin, his members were committed to “continuing to look for new treatment methods to diabetes.”
As of 2014, pharmaceutical companies had 180 different medications in development for diabetes and related diseases, Powaleny said. “On average, it takes more than 10 years for just one medicine to make its way through the entire (research and development) process. And the average cost to develop just one medicine has risen to $2.6 billion. Despite these risks and challenges, America’s biopharmaceutical companies are tireless in their pursuit of discovering new innovative medicines to improve the lives of patients,” he said.
Still, a low-cost generic insulin remains unavailable, so people in poor rural villages around the world may lack access to such critical medicines, Di Franco said, adding these are the people his group’s project aims to help.
“It doesn’t have that much to do with me in the end because I can afford good state-of-the-art treatments,” Di Franco said, but added, “There’s still a big gap between who needs insulin and who can afford it.”