Was that a breakthrough? How do we know for sure?
“Medical Breakthrough” gets 1.9 million Google hits. We crave breakthroughs; they are the food of press coverage. The urge to call every step in the right direction a breakthrough is strong, if only because it increases excitement – and the prospect of raising badly needed funds.
Honestly defined, a breakthrough is a new result that greatly alters the view of what is true. It is an insight that is productive.
We look for breakthroughs in our work at Cerco Medical, where we develop an islet encapsulation system designed to be a functional cure for diabetes. We are lucky that our goal can be easily measured in real time: if the blood sugar is normal, the device is working. (This is not true for most disease therapies; a pill to prevent heart attacks must be used in many people for a long time to prove it works.) Everybody wants clinical results, or at least results in diabetic animals. Right now, we can’t satisfy that want.
We have already proven the Islet Sheet can do what it must do: keep islets alive and happy, and remain intact in small and large animals. But in reviving a dormant project we decided to take this opportunity to make the thin sheet as good as possible. Over the past year we have carefully reviewed all aspects of how we make the thin Islet Sheet. We have compared sources for our main ingredient: alginate from kelp. This remarkable polymer gels under mild conditions that do not threaten the viability of cells like islets. If you have been to the Monterey Bay Aquarium, and looked at the enormous kelp tank with its forty-foot tall Macrocystis pyrifera kelp, you are looking at a marine algae that is mostly alginate. We harvest kelp from the waters off San Diego and purify it to make a material best suited for sheet fabrication. We’ve proven that our own alginate is better than any we could buy.
In the second half of the year we found that the sheets were not as stable in animals as we’d hoped. We puzzled over this for a while. Was the alginate defective? Was there something odd about the strain of rat we selected to test sheet stability? Were the sutures destabilizing the sheet somehow? Finally we turned to an unlikely factor: the reinforcing paper.
Like rebar in concrete, we reinforce the alginate sheet to prevent it from tearing, and to provide strong suture points. (Without the reenforcing fibers the sutures would pull out and the sheet crumple and fail.) It appeared that the reinforcing fibers were providing a failure plane for the alginate. The mere presence of the fibers was making the thin alginate sheet flake apart.
We set about to solve this recently. Of the proposed ways to fix it, the most promising was to make the fibers sticky, or at least sticky to alginate. This involved modifying the fibers so that the fiber surface looks like alginate and thus chemically participates in the gel. (The titanium oxide on the surface of an artificial hip looks like bone to bone cells; thus the hip becomes firmly attached to surrounding bone).
While I was traveling, Randy send me an e-mail with a picture of the fibers, modified to be sticky; they were visibly blue. (Cerco’s chemists used a blue dye to show that the fibers were properly modified. See the image below.) We were ready to try the improved sheet in animals to look again at stability.
Blue Dye Fibers
We’ve just now looked at the first improved sheets implanted into rats at Jon Lakey’s lab at UC Irvine. They look as good as we hoped they would. They are clearly more stable, and it seems like that will be stable enough.
Is this a breakthrough? It feels like a hint of a breakthrough. But it is only one point in time.
Medical invention mostly is incremental, a process marked by steady improvements. We are making the Islet Sheet better every month. We yearn to cure some animals and some people. But we would ultimately lose more time if we failed to learn all we can with the simple models we use now. We’d only have to backtrack later. The trick is to leap to the next landing, and move fast, but to somehow know just the right length for each leap.
So, when we show the Islet Sheet works, then and only then will we know we’ve just had a breakthrough. A real one.