How it's made, when it's not made in the human pancreas: Insulin
February 9, 2014 4:22 AM   Subscribe

In the 1920s, two tons of pig parts were needed to produce eight ounces of purified insulin. In 1982 Humulin, human insulin produced by recombinant DNA, became the first such product approved by the United States Food and Drug Administration. Diabetes Forecast offers a look into modern insulin production.
posted by Rob Rockets (16 comments total) 20 users marked this as a favorite
Four times each day I stick an insulin needle in my stomach to stay on this side of the dirt. If I had been born a hundred years ago, this treatment would not yet have been discovered and I would have died a painful, miserable death at a very young age.

When I was first diagnosed I thought, "Well, that's it. I'm never going to be able to stick myself with a needle, so I might as well eat a gun right now." But you'd be amazed at what you're willing to do stay alive when death becomes a real thing, close enough to touch, and not just some esoteric future concept that we all kind of acknowledge but never really believe.

Diabetes from a failed pancreas, the type that I have, has nothing to do with a lifetime of poor eating and unhealthy choices, it's just the luck of the biological draw. I hope that in another hundred years there's an easier treatment than one of constant syringes, or maybe even a cure, but in the meantime I thank Banting and Macleod for their Nobel Prize winning discovery of insulin.
posted by johnnyace at 5:29 AM on February 9, 2014 [21 favorites]

This is huge. I had a diabetic cat who lived for many additional happy years (~7) with daily Humulin-L injections. We've gone from a time when producing insulin was a laborious, expensive process to one where there's so much insulin we can give it to our pets.

The future is awesome*.

* Individual mileage may vary based on unfair and uneven distribution.
posted by RonButNotStupid at 5:42 AM on February 9, 2014 [7 favorites]

Johnnyace: I have the same type of diabetes and I feel exactly the same way. Thanks for putting it more eloquently than I could.

Diabetes sucks. Needles suck. Death sucks worse.
posted by the_royal_we at 7:29 AM on February 9, 2014

Dr. Fredrick Banter described the early system of preparing insulin in his speech accepting the 1923 Nobel prize. It sounds like a lot of work:

The present method of preparation is as follows. The beef or pork pancreas is finely minced in a large grinder and the minced material is then treated with 5 cc of concentrated sulphuric acid, appropriately diluted, per pound of glands. The mixture is stirred for a period of three or four hours and 95 per cent alcohol is added until the concentration of alcohol is 60 to 70 per cent. Two extractions of the glands are made. The solid material is then partially removed by centrifuging the mixture and the solution is further clarified by filtering through paper. The filtrate is practically neutralized with NaOH. The clear filtrate is concentrated in vacuo to about 1/15 of its original volume. The concentrate is then heated to 50°C which results in the separation of lipoid and other materials, which are removed by filtration. Ammonium sulphate (37 g per 100 cc) is then added to the concentrate and a protein material containing all the insulin floats to the top of the liquid. The precipitate is skimmed off and dissolved in hot acid alcohol. When the precipitate has completely dissolved, 10 volumes of warm alcohol are added. The solution is then neutralized with NaOH and cooled to room temperature, and kept in a refrigerator at 5°C for two days. At the end of this time the dark-coloured supernatant alcohol is decanted off. The alcohol contains practically no potency. The precipitate is dried in vacuo to remove all trace of the alcohol. It is then dissolved in acid water, in which it is readily soluble. The solution is made alkaline with NaOH to pH 7.3 to 7.5. At this alkalinity a dark-coloured precipitate settles out, and is immediately centrifuged off. This precipitate is washed once or twice with alkaline water of pH 9.0 and the washings are added to the main liquid. It is important that this process be carried out fairly quickly as insulin is destroyed in alkaline solution. The acidity is adjusted to pH 5.0 and a white precipitate readily settles out. Tricresol is added to a concentration of 0.3% in order to assist in the iso-electric precipitation and to act as a preservative. After standing one week in the ice chest, the supernatant liquid is decanted off and the resultant liquid is removed by centrifuging. The precipitate is then dissolved in a small quantity of acid water. A second iso-electric precipitation is carried out by adjusting the acidity to a pH of approximately 5.0. After standing overnight the resultant precipitate is removed by centrifuging. The precipitate, which contains the active principle in a comparatively pure form, is dissolved in acid water and the hydrogenion concentration adjusted to pH 2.5. The material is carefully tested to determine the potency and is then diluted to the desired strength of 10, 20, 40, or 80 units per cc. Tricresol is added to secure a concentration of 0.1 per cent. Sufficient sodium chloride is added to make the solution isotonic. The insulin solution is passed through a Mandler filter. After passing through the filter the insulin is retested carefully to determine its potency. There is practically no loss in berkefelding. The tested insulin is poured into sterile glass vials with aseptic precautions and the sterility of the final product thoroughly tested by approved methods.

On the other hand, you get this (from the same speech):

When [a 15-year-old girl] came under my care on August 16th, 1922, the examination showed: patient emaciated; skin dry; slight edema of ankles; hair brittle and thin; abdomen prominent; marked weakness. The patient was brought on a stretcher and weighed forty-five pounds.... Insulin treatment was started immediately....
At present (June 1925) she is in the best of health, and to use her own words "never felt better in all my life". She has grown four inches and weighs 134 pounds.

posted by The Elusive Architeuthis at 7:36 AM on February 9, 2014 [2 favorites]

Diabetes sucks. I was diagnosed Type 1 when I was 37 (16 yrs ago), and have worn a pump for the last 10 years. My opinion, not surprisingly, is that insulin is too expensive for a lot of reasons. One reason is because it's complicated to make. But another reason is because there has been so much consolidation in the diabetes "industry". There is a TON of money to be made off us diabetics. For instance, when I bought my first pump 10 years ago, there were maybe 8 or 10 manufacturers to choose from. When I got my new pump 2 years ago, there were 2. The older suppliers didn't fail - they were bought by the 2 left. And, surprise, the new pumps are more expensive ( and, in my opinion, of lesser quality). Insulin was first synthesized 100 years ago, and there is still no generic insulin. I'm not holding out much hope we'll see any anytime soon.
posted by Benny Andajetz at 7:37 AM on February 9, 2014 [1 favorite]

Oh, and it's not just poor choices or biological luck-of-the-draw. I'm convinced (as is my doc) that my diabetes were precipitated by pancreas damage from two lithotripsies for kidney stones.
posted by Benny Andajetz at 7:44 AM on February 9, 2014

I, too, was majorly bothered by needles before my diagnosis of DM1 as a kid and thought I could never do it, but worked up to six injections a day before getting my first pump. I'm permanently disqualified from giving blood because I was once given beef-based insulin in a hole-in-the-wall rural hospital in the 1980's when they didn't have any Humulin on hand, and (at least my local chapter of) the Red Cross doesn't feel they can rule out any kind of zoonotic infection like mad cow disease.

The 1988 CBC-TV miniseries Glory Enough For All, which dramatizes the work of Banting, Best, and MacLeod in the discovery of insulin at the University of Toronto in the 1920's, is available on youtube. (I loved it as a kid not just because of my personal connection to the subject matter but also my girlhood crush on R.H. Thomson.)
posted by The Underpants Monster at 7:49 AM on February 9, 2014 [2 favorites]

You're not kidding, Benny Andajetz. Some twenty or so years ago, when I had to buy a bottle of insulin outright because my last one was damaged and the insurance wouldn't pay for another week, it was something like forty dollars. The same thing happened a few months ago, and it was $150.
posted by The Underpants Monster at 7:54 AM on February 9, 2014

This is why I will go off on people who post FUD bullshit about transgenic organisms. I like living, thanks.

(And yes, this is much cheaper -- but still prohibitively expensive for those without jobs or insurance. Between the two types of insulin I use, medicating myself runs a bit over $40 a day. I have HRA insurance, where there's $1000 paid for by my employer, then a $3000 deductible, then slightly-little-higher-than-it-could-be copays for the rest of the year. That gap where I'm paying the deductible is unpleasant.)

(I had a jobless acquaintance several years ago who knew he was diabetic and could not afford doctors or meds. There was no preventantive healthcare for him, just expensive, too-late emergency room trips.)

Can we please not characterize type 1 as a disease of bad luck and type 2 as a disease of bad habits, or type 1 as "insulin dependent" and type 2 as "controllable with diet and exercise?"

The actual difference between them is type 1 is an autoimmune disorder that damages the pancreas. Type 2 is everything else (insulin resistance, failure to trigger insulin production in the pancreas, failure of the pancreas, or a combination).

As far "a lifetime of poor eating and unhealthy choices" goes -- I have spent more than half my life fighting type 2. I eat healthier than most people I know. I have friends and inlaws who weigh 2-2.5x what I do and have never had blood sugar issues.

Thanks to one of the meds I started on 20 years ago, my beta cells are almost completely useless. I don't produce enough insulin to counteract anything. That doesn't convert me from type 2 to type 1, it just makes type 2 worse.

If I eat a low-carb diet, exercise for 30-60 minutes per day, and keep checking my blood glucose after every meal to find out whether that half a slice of toast is going to fuck me up or if there was more in that salad dressing than there should have been -- if I work at it and worry about it, AND I inject myself with insulin 5 times a day and take Metformin -- then I can almost control my blood sugar. But I'll still go through periods of watching my blood sugar rise during a 12-hour fast.

Most of the time that is just too much, to be honest. I am not a fighter. I take my meds. I watch what I eat, but more casually. I get some exercise (though not in bad weather or with a cold, and unfortunately that characterizes most of winter) but I don't get fanatic about it. And my A1C numbers suck and every three months my doctor makes concerned faces at me. But I live.
posted by Foosnark at 8:05 AM on February 9, 2014 [16 favorites]

My uncle, diabetic for years just had a radical new surgery where they transplant pancreatic islet cells. Its so new its only an experimental surgery and there isn't even an FDA protocol for it.

Most people need several of these surgeries, but my uncle is already producing insulin and taking far less insulin than he did. This was in mid-January. Another patient in the trial who started the procedure in September no longer has an insulin pump. The down side is anti-rejection drugs for as long as the cells are working.

They are very excited!
posted by Ironmouth at 8:53 AM on February 9, 2014 [6 favorites]

My sister died of Type 1 diabetes when she was 27, in 1977. It hit her when she was 12, along with grand mal epilepsy, and the horrific course of her disease was basically due to the interaction between her seizures and the diabetes. She was never well after the age of 12 and when she died she was blind, in kidney failure, had suffered two major heart attacks and a stroke, and had finger and foot amputations.

But - here's what I want to say: In 1977, they didn't even have home blood glucose monitoring! She had to check her urine for sugar spillage and then adjust her insulin accordingly; of course, by the time it showed up in her urine, she was way, way past the time she should have had a shot.

She took so many shots her skin, in her abdomen and her thighs, was impenetrable. She found a little spring-loaded thingy that she'd set her loaded syringe into and then line it up and pull the trigger and it would shoot the needle through the dense tissue - it was powerful, and it hurt, but she was pleased to have it because it made her life much easier.

She had to weigh all her food - every single thing that went into her mouth - in grams. And adjust her insulin accordingly - except that that never worked, of course, because her pancreas would pump out a whole bunch of insulin on Monday afternoon and then nothing more until Thursday in the middle of the night - there was no pattern, no way to control anything, yet all they did was chew on her about her "noncompliance" - to this day, I detest that word because it was used so unfairly on my sister.

The doctor switched her insulins around and around, trying to get a handle on it - and I do remember that at some time she used pork insulin - for several years, I think, though maybe not entirely by itself.

If she were alive today, she'd have a blood glucose monitor! She'd be gobsmacked. And she'd have an insulin pump - good Lord, an insulin pump! She'd still be sick - very, very sick - but so many horrid memories that I have of what she went through would be just bad dreams. My mother took her to Children's Hospital in LA, to Phoenix (we lived in Tucson), to Houston, and finally to Stanford, where she was helped, at last - the other places were worthless.

She had no medical insurance and no way of getting any. She was eligible for aid through the State of Arizona, but there was no coverage for any of those other places, obviously. Stanford treated her as an inpatient for six weeks and as an outpatient for even longer - and they wrote off the bill. My mother was working as a real estate agent and a bookkeeper to try to pay the bills, but Stanford refused to take the money. Children's, the hospital in Houston and that in Phoenix, had no problems dunning her mercilessly for payment - this was in the days when bill collectors had no real regulations or restrictions on what they could do to harass someone.

I wish they'd get diabetes pinned down and a solid, reliable treatment definitized because I can tell you from personal experience that a child with Type 1 diabetes is no better off than a child with cancer. It's a horrid disease that chews a person up by bits and pieces.

Good luck to you who have diabetes - every day brings good stuff closer for you. It won't be long now before islet cell transplants or stem cells will be used to make the pancreas do its job and you'll be so much better off.
posted by aryma at 10:50 PM on February 9, 2014 [1 favorite]

I'm pretty sure there were four pumps two years ago... animas, medtronic, omnipod, acucheck. Now there's t-slim & asante snap too. It sounds like t-slim has the hardware to integrate with the dexcom cgms as soon as they clear it with the fda. I personally think they're getting better and better. Although I wouldn't have bothered switching from syringes if it weren't for cgms.
posted by BrotherCaine at 1:18 AM on February 10, 2014

Logged in to second Foosnark's comment: "Can we please not characterize type 1 as a disease of bad luck and type 2 as a disease of bad habits".

AMEN. I just want to punch people sometimes... I have 2 grandparents who had type 2 diabetes yet out of my 4 siblings I'm the only one who got it. The others are also heavy and have been at various times more or less disciplined with regards to exercise, yet they are fine.

It's nice for you type 1's who don't get told your disease is your own fault. I not only apparently gave myself mine, but my continued need for medication is because I am a lazy fatty (everybody has a relative or friend who "beat it with diet and exercise").
posted by diane47 at 12:11 PM on February 10, 2014 [2 favorites]

As a type I I often get asked if it'll go away if I diet and exercise. I explain that my body doesn't produce insulin and that even for type ii diabetics weight is often not the cause.
posted by BrotherCaine at 1:37 PM on February 10, 2014

It's nice for you type 1's who don't get told your disease is your own fault.

Oh, we get it, too, although not as often. There's no shortage of ignorance out there.
posted by The Underpants Monster at 2:37 PM on February 10, 2014

It's nice for you type 1's who don't get told your disease is your own fault.

Oh, we get it, too, although not as often.

I suspect the idea that type 2 is self-inflicted comes largely from type 1 diabetics trying to explain that type 1 is not self-inflicted. It does for me, at least. After way too many conversations with people confused that I’m diabetic despite being really thin, I eventually settled on a quick way to end that conversation: “there are 2 types of diabetes, you’re thinking of the other type.” After reading this thread, I’ll experiment again with other ways to end that conversation.

But I’m not going to explain the full complexity of diabetes to everyone who notices my pump. There’s something wrong with asking people with noticeable differences to explain their differences. It’s like a sort of conformity tax, and I’m a conscientious objector.
posted by scottreynen at 12:25 AM on February 11, 2014 [1 favorite]

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