Section of the structure of human insulin, which is stored as a zinc complex in specialized cells of the pancreas. Image: bernd schroder, based on data from the protein data bank
In the labyrinth of hopping – forays through a biotope – part 2
In 2015, there were 415 million people worldwide with diabetes – and the number is rising. Those without access to insulin suffer the complications that can lead to blindness, cardiovascular disease, amputations, nerve and kidney damage, and ultimately death.
Today, insulin therapy enables patients to manage the disease and limit the adverse effects of elevated blood glucose levels. The first insulin preparations were obtained from the pancreas of cattle and pigs and are similar to human insulin. Today, insulin is produced biotechnologically – it is the first drug produced by genetic engineering.
But there is a problem: although insulin has been on the market as a drug since 1923, no generic counterpart is yet available despite the rough demand, especially in the poorer parts of the world. The substance is also expensive in the usa. Of the 21 million diabetes patients in the u.S. Today, six million take insulin. The associated monthly out-of-pocket costs for uninsured patients range from $120 to $400.
The investment costs for a new drug are now beyond the one billion us dollar mark. These costs serve as a justification for the often obscene prices of new drugs, which are initially beyond the reach of many patients. After the patent expires, generic competition makes them significantly cheaper – a rule that does not apply to the first wonder drug of the 20th century. The following seems to be applicable at the beginning of the 21st century: insulin.
One difficulty faced by generic pharmaceutical companies: in contrast to other pharmaceutically important molecules, insulins as biopharmaceuticals are significantly more complicated in design and more difficult to copy, and the approval procedures are considered to be complex. In addition, research into improvements to designer insulins is complicated by the complex nature of current standard protocols for insulin synthesis. In addition, pharmaceutical companies patent minor changes to earlier insulins and at the same time remove these earlier versions from the market, instead of making them available cheaply to those for whom the modern preparations are unaffordable.
The insulin price tag represents only a portion of the total cost of diagnosed diabetes in the u.S., which was estimated at $245 billion in 2012.
Openaps and open insulin
Unequal access to medical care has motivated biohackers to explore what can be done with their tools to help those affected, often in the form of self-help.
So under openaps, tech-savvy families of diabetics are taking matters into their own hands and making their own homemade insulin pumps that can automatically dose the right amount of the hormone in response to blood sugar levels. The family members build these devices on their own, calibrate and develop them, develop the software. Artificial pancreas devices have been in development for decades, but only improvements in sensor technology for real-time glucose monitoring have brought them to market. The us food and drug administration (fda) has made the approval of such devices a top priority. But the relatives of diabetics do not want to wait any longer. By the end of january 2017, the openaps platform already had more than 200 known users of various exports worldwide. Openaps is not a commercial product and is not regulated by the fda.
In turn, a team of biohackers from oakland’s counter culture labs in california is developing an open-source protocol to produce insulin easily and economically – via genetic modification of e. Coli bacteria. The work will serve as the basis for generic production of the drug and further research into improved versions of insulin.
Bander model of the protein structure of insulin glargine (trade name lantus from sanofi). Like other delaying insulins, it is absorbed more slowly and evenly by the body after injection; a single daily dose is sufficient. By 2015, patent protection had expired in most countries. Image: bernd schroder, based on data from protein data bank
The biohackers at counter culture labs want to help the generic pharmaceutical companies with their research in this way. You know that the project is difficult. And in the event of success, an even greater challenge awaits: the approval for production granted by the fda.
The approval process and monitoring of biosimilars, which mimic biopharmaceuticals, are more complex than those of traditional generics. In 2016, the fda approved basaglar, the first insulin biosimilar in the usa, developed by lilly and boehringer ingelheim as a biosimilar of insulin glargine and approved in europe as abasaglar since 2014. It remains to be seen whether the product will actually be offered to diabetes patients as a low-cost alternative. Observers do not expect price reductions of 80-90%, but at least 30% are expected.
With their project, the enthusiasts also want to show that they are capable of high-level scientific work with a minimal budget and without being connected to one of the world’s top laboratories.