Biohackers Aim To Make Homebrew Insulin, But Don't Try It Yet

Might people with diabetes someday be able to brew their own insulin for free at home, just as with beer? The answer may be yes, but whether it's a good idea is another question.

Glowing bacteria is part of a project on the open-source laboratory Arcturus BioCloud. Courtesy of Arcturus BioCloud

Glowing bacteria is part of a project on the open-source laboratory Arcturus BioCloud. Courtesy of Arcturus BioCloud

The home-brewed insulin concept is among the latest to emerge from the bio-hacking movement, in which people meet to tinker with biology in inexpensive do-it-yourself laboratories that have popped up in California, New York and a few other places in the United States and Europe.

The field is small so far — around six or seven real biohacker labs, with between five and 40 active members — but interest is growing.

"People wanted to do science outside of classical institutions like universities or big corporations, so we embraced it," says Ryan Bethencourt, an entrepreneur who co-founded San Francisco-based Indie.Bio, which provides seed funding for biotechnology startups. Bethancourt has also worked with several pharmaceutical companies in product development.

Ryan Bethencourt, who is leading the project to biohack insulin, speaks at Indie.Bio Demo Day in San Francisco. Michael O'Donnell/Courtesy of Ryan Bethencourt

Ryan Bethencourt, who is leading the project to biohack insulin, speaks at Indie.Bio Demo Day in San Francisco. Michael O'Donnell/Courtesy of Ryan Bethencourt

Ryan Bethencourt, who is leading the project to biohack insulin, speaks at Indie.Bio Demo Day in San Francisco.

Michael O'Donnell/Courtesy of Ryan Bethencourt

Beyond the creation of a glow-in-the-dark plant, few concrete products have thus far emerged from the biohacking movement. Bethencourt wants to change that.

The insulin idea came from speaking with a friend and fellow biohacker who has Type 1 diabetes and requires costly insulin to stay alive. Even with insurance coverage, a three-month supply can total hundreds of dollars out of pocket. Bethencourt says: "Anthony and I have discussed this for two years. Why is insulin so expensive?"

Indeed, while some of the older insulins are off patent or soon will be, in the United States there are currently no insulin biosimilars — the rough equivalent of "generic" for biological medicines — although one has been approved in Europe. Even with biosimilars, the cost isn't as comparatively low as it is for generic synthetic drugs versus brand names.

About 6 million people in the U.S. use insulin, including all of the 1 to 2 million with Type 1 diabetes and about 15 percent of those with Type 2 diabetes. In poor countries, children still die for lack of it.

"Insulin is the first medicine we're trying this with. It is probably the largest need of any biologic drug I know of," says Bethencourt.

In fact, biohacking it isn't that hard to do: Lab equipment costs have come down considerably in recent years, and the DNA sequences for recombinant human insulin and for the newer analogs are public information.

Bethencourt wants to use a cloud-based automated laboratory platform that would take DNA, insert it into bacteria and make insulin at a far lower cost than the commercial product.

He's planning to crowdfund about $2,000 for the equipment to get it going.

"We'll start by saying it's research only, and make it available to all the biohackers and any researchers who want open-source insulin," Bethencourt says. "Then we have to figure out how to increase the yield and how to purify it. Then people can start using it. They can brew it, like beer."

His ultimate goal is free insulin for everyone who needs it, in the U.S. and globally.

But Dr. Marcus Hompesch, president, CEO and a founder of the Profil Institute for Clinical Research, Inc. in San Diego, says the home-brewing idea is irresponsible and foolhardy. "Manufacturing insulin or any peptide or any biologic for that matter is a very complex affair. If you don't understand what it all entails, you could end up manufacturing something that is downright dangerous for patients."

Making recombinant human insulin is a multistep process, Hompesch explains, and "at any step of the way, things can go wrong .... It's highly regulated." Among the risks, he said, are that a protein sample that is either contaminated or isn't treated properly could trigger an immune response in the recipient that could then cross-react with and neutralize other insulins the patient might be receiving or, in the case of Type 2 diabetes patients, their remaining naturally-produced insulin.

Patients might have to make significant dose changes, which could adversely affect their diabetes control. Hompesch says. More significant immune reactions could happen as well.

Hompesch, who has published extensively on biosimilar insulins, says the discussion of biohacking insulin worries him because it is actually possible. "Practically, it can be done," he says. "The technological hurdle isn't one that couldn't be overcome." Getting it done right is not trivial, he adds. "As a clinician and researcher I wouldn't want to see a large biohacking experiment in patients even started."

But Bethencourt believes the biohacking community, which includes molecular biologists, is capable of addressing the challenges involved with making the protein consistently and safely. "At first, it will not be safe. That's why we have to make it available so other people can develop ways of ensuring that it's safe," he says. "We would get it at least to the same level of safety as current therapeutics. We'd want to use the same technology. We're just trying to make it cheaper."

For now, "The aim for me is more of a statement and concept piece." Bethencourt says. "I want to start a revolution in the way therapeutics are made, starting with insulin."

Miriam E. Tucker is a freelance journalist specializing in medicine and health. You can follow her on Twitter @MiriamETucker.

Stem cell therapies – painfully slow progress or just a bump in the regulatory road?

As many of you know Geron’s promising stem cell therapy (GRNOPC1) for the treatment of debilitating spinal injurie has been put on clinical hold again this month by the FDA due to recent animal data that’s been submitted. This isn’t unusual for the ultra cautious FDA but it does highlight the challenges of a risk adverse regulatory system and developing truly novel therapeutics.

The FDA instituted clinical hold piqued my interest in how things are currently progressing with other stem cell therapies and applications. The NIH provides a useful overview on the current areas of development, as you’d expect the use of stem cells are broad, from Diabetes, to Heart repair through to attempts to restore Neurological function.

Here’s an overview of just some of the promising therapeutic areas published in 2009 in regards to future human stem cell therapies:

  • Induced Pluripotent Stem Cells (i.e. Adult stem cells) Able to Produce Live Mice
  • Cancer-destroying Cells Generated from Human Embryonic Stem Cells
  • Human Corneal Stem Cells Repair Defective Corneas in Mice
  • Induced Pluripotent Stem Cell–Derived Working Heart Muscle Cells

Geron is currently a pioneer in pushing for regulatory approval in the US, however the vast potential of this space to genuinely change medicine as we know it has not escaped most major biotech and pharmaceutical company’s awareness. My bet is that as soon as a feasible path to approval emerges we will be seeing a lot more of these genuinely novel restorative therapies in larger scale clinical testing!

Gene Silencing – our evolving understanding of RNAi and the rapid development of future possible therapies

Back when I was in college studying genetics, messenger RNA (mRNA) and transfer RNA (tRNA) was really the only well understood uses of RNA in our cells. Then in 1998, the classical scientific dogma for the uses of RNA was dramatically altered by Fire, Mello and their colleges when they published their discovery of previously unknown use of RNA… to silence genes (which later resulted in a Nobel Prize)!

Not only was it a fascinating research tool but the newly branded interference RNA (RNAi) was an ancient defence mechanism built into our cells to defend them against viral hijackers, which in turn had incredible therapeutic potential. Fast forward nearly a decade on and we’re now starting to see some of the fruits of the research into this space.

Currently only 10% of RNAi therapies are in clinical development but it’s forecasted that five new Phase II/III RNAi agents (in wet age-related macular degeneration, RSV infection and acute renal failure) will be available on the market by 2012. This is an incredible estimate if you consider that it will then only taken about 14 years to convert a revolutionary basic science discovery into a useful therapeutic. On average it typically takes a biotech/pharma company 8-12 years to develop a standard drug, RNAi’s therapeutic development has moved at breakneck speed!

Augmented vision by 2050? Nope.. it’s here now!

Recently I’ve been debating the idea of laser corrective eye surgery, I like the idea of using technology to modify our bodies and return them to a more functional state but as you may or may not know some forms of Laser eye surgery can be quite invasive.

In classical laser eye surgery, a flap is cut around your eye lens, which is then flipped open and the laser flashes and burns tissue on the cornea to correct imperfections within your eye. This does look very invasive, for those that are a little squeamish you might want to avoid pressing play but it is fascinating how effective the laser is at correcting imperfections. 

 

What’s even more fascinating is that newer forms of laser eye surgery (using customised wavescans of the inside of your eye) may be able to improve your sight more so than conventional glasses or contacts by correcting Higher-order aberrations that can improve night vision, quality of vision and might just be able to improve your vision beyond 20/20. The idea of creating “super vision” with laser eye surgery isn’t new but now it’s a very real prospect with improved all laser eye surgery, the theoretical limit of foveal acuity would be 20/12 for a small pupil and up to 20/5 for a dilated pupil. Super vision anyone?



Curing the Incurable: Using Biomaterials in the Treatment of Central Nervous System Disorders

Discovering a disease-modifying therapy for intractable ailments such as Alzheimer’s, Parkinson’s and Huntington’s diseasehas long been considered the holy grail of central nervous system (CNS) research and drug development.  Symptommanagement is the only therapy currently available for many suffering from these and CNS disorders for which we have not yet found a cure.

 One of the biggest challenges in the development of a successful CNS compound is finding a way to get the drug across the blood-brain barrier (BBB).  If we can get a compound into the brain, we then have to figure out how to get sufficient amounts into the brain without delivering so much drug to the body that systemic toxicity is an issue.  If biomaterials such as lisosomes and polymeric nanoparticles (Nature; September 2009could be used to facilitate efficient transport across the BBB (creating a 1:1 ratio of brain-to-plasma drug levels rather than, say, a 1:10 ratio), we could potentially give less drug and yet see more in the brain.  Dose-limiting toxicity might not be such an obstacle if we could see the desiredpharmacodynamic effect with lower levels of drug circulating in the body.  

 But even disease modification is usually defined as slowing the rate of decline or the rate of progression of symptoms.  What if we could not only change the course of the disease, but what if we could actually restore previous function?  What if further decline was not inevitable?  In addition to serving as drug delivery vehicles, biomaterials can be used to deliver other therapeutic agents (trophic agents and growth factors, e.g.) and even genetically modified cells directly to effected areas. Imagine the possibilities if we could stimulate the regrowth of dopaminergic neurons in Parkinson’s patients while simultaneously protecting the functioning neurons. NsGene has successfully implanted its encapsulated cell biodelivery product (NsG0202) into 6 patients with Alzheimer’s disease.

So many of us are in the race to develop the next blockbuster CNS drug, that we may be missing the mark.  Perhaps the solution is more bio, less tech.  Biomaterials may be the missing piece in the massive efforts being put forth by big pharmato cure the incurable. I say, forget symptom management.  In fact, forget disease modification.  Let’s focus on getting back to baseline. Optimistic?  Naïve?  Maybe.  But if we if we shoot for the stars we just might hit the moon.