VialPackagingLineI can cross “tour an insulin manufacturing facility” off my bucket list.

It was absolutely mind-blowing.

There is a lot of science involved, much of which I am not quite bright enough to understand. But the basic idea is that they start with some E. coli bacteria that is modified to produce insulin as it grows, then it is harvested, the insulin is stripped out, purified, packaged up and delivered to us.

One of the best places I could find that talks about how cells work actually used insulin as an example of biotechnology. From an article at HowStuffWorks.com:

To create insulin inexpensively, the gene that produces human insulin was added to the genes in a normal E. coli bacteria. Once the gene was in place, the normal cellular machinery produced it just like any other enzyme. By culturing large quantities of the modified bacteria and then killing and opening them, the insulin could be extracted, purified and used very inexpensively.

That makes it sound so simple, and I find it ironic that they used the word “inexpensively” more than once. There was nothing inexpensive about what I saw. Maybe it’s a relative term? Comparing it to the process of killing cows and pigs and harvesting insulin from their pancreases? On that note, I had trouble picturing the land we were visiting being a large slaughterhouse no more than thirty years ago.

I also learned that the first insulin made using this method of inserting human genetic instructions into a bacterium at Lilly was made possible through a partnership with Genentech (now owned by Roche).

Big and Small

I couldn’t wrap my brain around the quantities involved, so I’m going to describe it using  very general ideas.

InsulinHexamerImagine growing grass on a field the size of a few football fields. You start with nothing but space. You get the soil and prepare it, plant the proper seeds, then nurture the growing seeds until they’ve grown up into tall stalks of grass. But only a tiny portion of that grass stalk is the part you need. Imagine the entire grass stalk representing 100%, but you only need the 33% piece and 35% piece. The rest is useless to you (but you wouldn’t have those two specific parts without the whole).
Now you harvest each blade of grass and separate the parts you need from the parts you don’t. Then within that 33% piece and 35% piece there are impurities which need to be stripped off and discarded, but that purification process costs you some expensive chemicals and a ton of time.
After a couple of months and three football fields of grass, you end up with a finished batch of product that can fit in your briefcase.
You can run the whole process again, but don’t forget that your soil is only good for a limited number of growths before it too needs to be discarded and replaced.
It’s an incredibly complicated and expensive process. Getting us to appreciate the cost and complexity was surely the main idea behind the tour.
I’m convinced. I appreciate it.

8 Responses to Lilly Diabetes – Making Insulin

  1. StephenS says:

    Scott, thanks for all of the great information in this and your previous post. I’m especially gratified to know that Lilly is giving back to those in need. Glad you were able to go (and then write about it)!

  2. Marie Schadt says:

    Your doing nice work Scott but the companies producing insulin are far from working in the best interest of diabetics. First of all they are letting diabetics inject a fractured chain that has had c-peptide extracted from it. c-peptide was a mystery years ago but they now know it reverses retinopathy, nephropathy, and peripheral nerve damage in early stages. Companies tried to patent the peptide to make even more $$$ but were not allowed because it naturally occurs in the proinsulin chain. C-peptide should be given to the diabetic in equimolar amounts it speeds nerve conduction and rebuilds the broken bridge between cells. Why does the gouvernment allow this horrible manipulation to occur?
    Nature puts c-peptide in insulin!! Educate yourselves diabetics your life depends on it.

    • Thanks, Marie!

      I’d love to read more about the findings on C-peptide. Do you have any sources?

      Bennet (ydmv.net) asked Dr. Kendall about exactly that, and it sounded like he wasn’t convinced it was a beneficial part, but that there was a lot left to study about it. He floated the idea that nature often does things to conserve energy, and perhaps that C-peptide component had more to do with nature growing insulin more efficiently rather than it being an active thing.

      Bennet – did I get that right? Do you remember anything more about what he said?

  3. Scott E says:

    Wow, Scott… thanks for your easy-to-comprehend (yet oh, so difficult to understand) description! I always wondered how they mass-produce this stuff; it’s not like growing just one unit of insulin in a petri dish in a lab!

  4. Thanks Scott. My post on the insulin production topic is in the process of fermenting, i.e. I need to go re-read it. I think you are far more sophisticated in your piece here than I will be. Thanks for that since I compare making insulin to brewing beer.

    C-peptide, as Scott mentioned, was a topic of a side conversation with David Kendall, MD, Medical Affairs, Lilly Diabetes (his card also says, “Distinguished Medical Fellow”), Scott, George and I.

    Before getting into this too deeply it is important for me to point out that I am not a Dr., a biologist, excessively scientifically inclined or even a “Jolly Good Fellow.” I did take a graduate school class in cellular bio, learned enough to make dangerous comments and forgot most of the actual science leaving, just the dangerous part.

    A little basics in case others of Scott’s readers, like me, forgot their science. When humans make insulin our beta cells make a long amino acid chain. That chain gets cut leaving a c-peptide piece and an insulin piece. So like Marie says insulin is a fractured chain, by design or evolution take your pick. Measuring the c-peptide is a marker for insulin production, since the insulin gets used right quick.

    As I recall the conversation with Dr. Kendall (and I could be horribly wrong recalling and that would be my fault not his) when he spoke about c-peptides he noted that there are studies that both suggest that c-peptides do and do not contribute to health. There is not yet conclusive evidence of c-peptide’s role. He said that c-peptide maybe useful or it maybe that evolution has a preference for the conservation of energy. That making the long chain and cutting it may require less energy than making just the insulin. He suggested that there are other hormone production processes that seem to make a number of molecules in one chain and break that long chain into separate useful compounds and residual pieces. It could be that c-peptide is such a residual or it could be that it has medicinal value yet to be confirmed.

    It is noteworthy that the process of growing insulin that Scott outlines above is not the same process that functioning beta cells follow. The zillions of little microorganisms that grow insulin in a factory are not replicating the same amino acid chain beta cells do and then break them down to insulin and c-peptide. They make a specific insulin chain, no c-peptide.

    My view is (in all fairness let me be real clear this is NOT part of what the good Dr. said, see dangerous above.) that the FDA would not allow production and sale of a c-peptide analogue unless it could be shown to be both safe and effective. Those two are what must be shown to market a medication. Until there is conclusive scientific evidence that c-peptide has a medicinal value, “effective” can’t be shown. That is why many researcher are looking at it.

    Thanks for a great post and insightful comment. I hope I have added value to the conversation not just confused it more.

    BD

  5. Zazzy says:

    Fascinating stuff Scott – thanks for posting all this information.

  6. Richard Vaughn says:

    There is a company that has produced an injectable form of c-peptide. Read about it below. It has been shown to be effective in trials with human subjects. I hope it will eventually become available to type 1 diabetics.

    http://asweetlife.org/feature/is-insulin-enough-developing-c-peptide-therapy/

  7. Tavia Vital says:

    Nice post and subsequent comments. I sometimes find it devastating the cost of meds for diabetes. This post helps us understand part of the “why”.
    Did you know that Eli Lily sent a letter in the early days of insulin production apologizing for the increases in pricing? I find that thought touching.

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