
Biohackers Creating Open-Source Insulin - pavornyoh
http://www.popsci.com/these-biohackers-are-making-open-source-insulin
======
replicatorblog
I worked in diabetes for a decade so thought I'd chime in. This is an
admirable project with very low prospects of making a difference in the lives
of people with diabetes. I don't doubt this group will be able to show
"success" in the form of simple clinical results.

I have the highest doubts that they'd have the resources to do the broad-based
clinical trials required to go to market.

Look up "Eroom's Law" which is "Moore's Law" spelled backwards:
[http://www.nature.com/nrd/journal/v11/n3/fig_tab/nrd3681_F1....](http://www.nature.com/nrd/journal/v11/n3/fig_tab/nrd3681_F1.html)

Basically, the increases in pharma regulation means it takes longer and gets
more expensive to create a new drug each year.

This is a cool science project, but the reporting around it is sensational and
not helpful to the millions of people with diabetes who have their cranks
yanked regularly about miracle cures, cost-saving fantasies, etc.

To address some raised in sub-threads:

\+ You can get extraordinarily cheap drugs in India, the rest of the
developing world, and in parts of Europe. The "greedy" drug companies adjust
pricing to what local markets can bear. So instead of letting poor people die
en masse they mark the drugs down and pass the cost onto the developed world.
Fair trade IMO.

\+ The reason there are so few generic insulins is that they are hard to make
consistently enough to please the FDA and European regulators. Companies like
Teva and Perrigo are multi-billion dollar manufacturers of generic drugs who
would love to get get into this game, but as noted, biosimilar drugs,
especially ones as powerful as insulins, are a lot harder to copy than
aspirin.

~~~
EmlynC
This is a really solid response.

I'm a Pharmacologist and I've worked in a number of Biotechs. I have been part
of pricing discussions to value our drugs and your assessment is correct —
price discrimination, as in most industries, is based on what a particular
market can bear. Factors that influence this are the way that healthcare
systems are run (i.e. public healthcare, insurance based), the cost of
compliance and competition. I wouldn't say that the industry subsidises poor
countries via sales in the developed world, it's more a case of it's better to
be paid something rather than be paid nothing. I personally, however, do like
the happy side-effect this has for patients in poor countries.

Increased regulation costs more to comply with and that cost of course is born
by the consumer. The cost of regulatory compliance also varies on the market
you sell to, the US being one of the most expensive. Just as with software or
hardware, the price reflects the cost of production and maintaining the
product.

Notably with biologics (Insulin, any hormone ...) as opposed to small chemical
entity (paracetamol, aspirin etc) is that broadly they are harder to keep in
their stable active form. The are heat sensitive, chemically sensitive and
have a tendency to stick to themselves. This tends to increase the cost of
storage, logistics and compliance. It also means that _if_ you can make a
worthwhile biologic it will generally experience less competition.

~~~
vdaniuk
>happy side-effect this has for patients in poor countries

Sometimes I wonder if some HN comments are being posted from an alternate
universe...

------
snewk
Member of the project here;

Since we have already met our target $ for phase I, we opened up a stretch
goal to fund phase II.

We are in the early stages of establishing the protocols for cutting and
folding the proinsulin into its final, active form, and are looking into
purification methods sufficient for research and potential pharmaceutical use.

Meeting stretch goals will help us purchase the reagents and equipment
necessary to execute these protocols.

~~~
jacquesm
I have a really hard time taking this project serious. Plenty of people in my
surroundings have diabetes so I can see the impact would be huge. If you asked
for a few million then I would find it a lot more believable than the amounts
that are requested in the crowdfunding campaigns.

If someone asked for $25000 to build the next electric car I'd not believe
them either, there is more to making the next electric car in terms of process
and design than being able to buy a battery and some motors.

~~~
codingdave
You seem to be confusing the effort to make a prototype with the effort of
scaling to production. Prototyping has smaller costs.

------
cant_kant
Here is an price from an Indian site "Actrapid Insulin, Neutral 40IU x 1mL
10ml Actrapid VIAL 145.00 "
[http://www.drugsupdate.com/brand/showavailablebrands/830/1](http://www.drugsupdate.com/brand/showavailablebrands/830/1)

That is $2.19 according to xe.com and is a branded version made by Novo
Nordisk. So if you use 40 units a day, it would be less than $7 a month.

Greater regulation, higher wages and higher occupational health and safety
standards keep the price higher in the US.

~~~
dnautics
it's not regulation, occupational health, and safety standards that keep the
price higher. Drugs sold in india have just about as good standards as in the
US. If it's made by Novo Nordisk, it probably comes out of the same plant that
supplies the US supply. Even Indian generics manufacturers get themselves
certified by the FDA because they want the lucrative US market.

~~~
melling
Now if we could only convince India to move upmarket and develop new drugs
instead of simply making generics. India would be richer and their population
of 1.3 billion people would greatly benefit, as would little countries like
the United States.

------
mdup
I remember reading in another HN thread about insulins (too lazy to search it
right now) that plenty of prototype insulins have been developed, but most of
them could cause nasty diseases, notably cancer. Hence only a low number of
well-tested commercial insulins have been pushed to the market. Does someone
knowledgeable have more info about those "good" vs. "bad" insulins?

~~~
snewk
biologically produced insulin starts as a monomeric protein (meaning it only
consists of one string of amino acids) called preproinsulin. this amino acid
chain must interact with itself to form stabilizing interactions and disulfide
bonds.

once these disulfide linkages are created, this insulin precursor undergoes a
multi step enzymatic cleavage which cuts off some bits and makes biologically
active insulin.

There are many ways to create insulin synthetically, and some of them lead to
product contaminated with misfolded proteins. Misfolded proteins may have no
effect, but sometimes they can activate the IGF-1 signal pathway which has
been associated with cancer. There is also a chance of an autoimmmune reaction
to the misfolded insulin, which would also be very bad.

We are exploring a few different methods for our insulin production
specifically with this concern in mind.

~~~
ff7c11
Misfolded proteins also cause Alzheimer's disease. They are the number one
reason why cannibalism is bad. If you eat a human brain with misfolded human
proteins (prions) it can cause your proteins to misfold. I think.

~~~
snewk
Yes, misfolded prion proteins(PrPsc) can 'infect' other correctly folded prion
proteins(PrPc). Prions are glycoproteins found on the surface of cells, and
they affect cell signaling from the exterior of a cell to the interior.

Insulin, on the other hand, is a free floating small molecule not anchored to
a cell. Misfolded insulin is not 'infectious' like PrPsc.

The biological role of prions is still not well known, but one reason prion
diseases are such a big deal is that prions are resistant to normal biological
protein degredation. They are hard buggers to get rid of. Unlike insulin,
which has a specific protease enzyme which breaks it down.

------
jacquesm
That's on first glance a really nice project and goal but _$12K_ to create a
generic insulin is not going to cut it.

That will barely get you a kitchen, not a laboratory that will produce
something that will pass FDA approval after you spend a very large multiple of
that on tests.

~~~
snewk
There are already multiple lab spaces online with many active members
participating in this project.

As far as FDA trials go, it is something currently outside the scope of this
campaign. This is from the crowdfunding page:

"

$6,000 is needed to initiate Phase I of the project. In Phase I, the team will
insert an optimized DNA sequence for insulin into E. coli bacteria, induce the
bacteria to express insulin precursors, and verify that human proinsulin has
been produced.

If we raise more than the minimum required for Phase I, we will proceed to
establish the protocols for cutting and folding the proinsulin into its final,
active insulin form, and develop purification methods sufficient for research
and potential pharmaceutical use.

All protocols we develop and discoveries generated by our research will be
freely available in the public domain. We will also be proactively
investigating strategies to protect the open status of our work.

"

~~~
pygy_
_> In Phase I, the team will insert an optimized DNA sequence for insulin into
E. coli bacteria_

That is an unfortunate naming choice. Phase + Roman numbers have a well
defined meaning in drugs development (clinical trial phases). I saw you refer
to phases elsewhere in the comments and misunderstood what you meant.

~~~
snewk
good point. The project is referring to its own phase 1, 2, etc independently
from "FDA phase x clinical trials"

~~~
pygy_
From my computer's thesaurus:

1\. _the final_ phase _of the election campaign_ : stage, period, chapter,
episode, part, step, point, time, juncture.

Pick one, and run with it :-)

~~~
snewk
thanks, pygy. we changed our terminology to 'stage'

------
cant_kant
"Kevin Riggs, an instructor in medicine at Johns Hopkins University who co-
authored an article about generic insulin earlier this year, doesn't think
that Open Insulin will be enough to bring a generic insulin drug to the
market:

“I don't think the major hurdle is that the companies don't know how to make
insulin, because that part is reasonably straightforward,” he says. “The real
hurdles are getting the drug approved by the FDA (and since insulin is a
biologic drug, it requires a lot more original data than an application for a
small-molecule generic would), and then upfront manufacturing costs (because
making a biologic drug is different, so it requires different equipment).” "

------
kgwgk
> Since there are no generic versions available in the United States, insulin
> is very expensive

I don't know if that might qualify as very expensive but one can get one month
worth of insulin for $50.

[http://theperfectd.com/2014/10/23/type1-diabetes-no-
insuranc...](http://theperfectd.com/2014/10/23/type1-diabetes-no-insurance-
how-little-can-you-pay/)

------
protonpopsicle
I have type 1. In an emergency situation, when demand outweighs supply for
life-saving drugs, I would think it useful that there be recipes available
online for ambitious DIYers. I think about this from time-to-time since since
reading Alas, Babylon in which the diabetic characters are the first to die
(maybe I'm too paranoid).

~~~
refurb
If the situation is an emergency, would you really have time to make a drug
yourself? Even the simplest drug takes a long time to make.

------
fabian2k
My impression is that the production of biological drugs (as opposed to small
molecules) is simply more expensive on a large scale. There isn't as much
potential to save costs as with small molecule generic drugs.

This seems to be a small-scale expression and optimization, and I'd guess that
this is not the expensive part of developing a generic insulin. Large-scale
manufacturing and making sure you're producing the correct molecule reliable,
and then demonstrating that to the FDA are probably orders of magnitude more
expensive.

------
mentos
> “Every year it gets so much easier and cheaper to do genetic engineering.”

Is there a hand on the doomsday clock for biological engineering?

------
ff7c11
Not going to happen. "Biohacking" is 100% hype. 0% science. On insulin
specifically: [http://blog.indysci.org/insulin-is-hard-but-not-
impossible/](http://blog.indysci.org/insulin-is-hard-but-not-impossible/)

~~~
dnautics
well this is fun.

1) wrote that blog post

and

2) gave the open insulin guys the design they're using. I am a little bit
dismayed that credit for the design is somewhat buried in the public facing
materials, but whatever.

and

3) agree that it's mostly hype - both this project and 'biohacking' in
general. I run a nonprofit that is working on an patent-free cancer drug.
Raised 60k and I'm doing ok, about to launch into production phase pre- animal
model study. I would hesitate to call myself a biohacker - I have a PhD in
chemistry and two postdocs in biochemistry and molecular biology, so I'm not
coming from the CS/IT side - although I do currently code for a living.

but

4) think that whatever, the project could be interesting.

As it is, the way insulin is manufactured is pretty terrible, it could be way
cheaper, and it's with that in mind that I designed the scheme the way that I
designed it.

~~~
januswandering
Hey Issac. Sorry that we didn't make your design contributions clear enough in
our promotional material. I was wondering if you might be willing to either
write up a lab note for experiment.com or an article for our publication so we
can point to it and do a better job of giving you credit.

------
eveningcoffee
_United States, insulin is very expensive—that cost was_ likely _a large
proportion of the $176 billion in medical expenditures incurred by diabetes
patients in 2012 alone._

Well, the report itself says:

 _prescription medications to treat complications of diabetes (18%)_

So this is up to $31.68 billion in 2012. I will assume for simplification that
all of it goes for insulin.

There are about 20 million patients in US (according to
[http://www.diabetes.org/diabetes-
basics/statistics/](http://www.diabetes.org/diabetes-basics/statistics/)). So
this puts us into $100-150 in a month range for the insulin.

~~~
cperciva
I'm not sure which report you're looking at, but "prescription medications to
treat complications of diabetes" means things like painkillers for neuropathy,
antibiotics for infections, et cetera. Insulin falls under "antidiabetic
agents", which treat diabetes itself, not the complications.

But most of the 20 million diabetics in the US are type 2 and do not require
insulin; it's only Type 1s and the most severe cases Type 2s who take insulin.

~~~
mikeyouse
The CDC keeps pretty good stats, as of 2011, there were about 6 million
diabetics taking insulin;

[http://www.cdc.gov/diabetes/statistics/meduse/fig1.htm](http://www.cdc.gov/diabetes/statistics/meduse/fig1.htm)

------
kevindeasis
[https://experiment.com/projects/open-
insulin](https://experiment.com/projects/open-insulin)

------
refurb
I'll have to admit it's a pretty cool project, but if you want to create a
cheap source of insulin, you're really just creating a generics company.

And the reason why there isn't any generic insulin is because each new insulin
is "next generation" and people would rather pay more for the added benefit
than use the old stuff.

------
unknown_apostle
I don't understand this. So just one question: if it's that simple, why hasn't
the market done it yet?

~~~
TeMPOraL
Because there's no(t enough) profit in it? Markets don't always create the
stuff we need, even if they're not full of safety regulations because stuff
that's being made is dangerous.

------
ZLeviathan
guys, please tweet or share this news to your friends.

------
ZLeviathan
truly remarkable only if it's real...

