Reflecting on decades of rich history that led to our modern MG treatments

Every eight weeks, when I sit in an infusion chair, I can’t help but think of the small, patient labor that had to happen before the medication Ultomiris (ravulizumab-cwvz) ever found my veins. Myasthenia gravis (MG) doesn’t care much about history, but I do, and Ultomiris has one worth telling.

The story doesn’t start in a lab dedicated to MG research. It starts in 1882, when a German physician named Paul Strübing first described a strange blood disorder eventually called paroxysmal nocturnal hemoglobinuria. About a decade later, Jules Bordet, a Belgian immunologist, identified something in blood serum that is now known as the complement system, an immune cascade that, left unchecked, can turn against the body itself. In 1920, Bordet won a Nobel Prize for his discovery.

I doubt if either Strübing or Bordet imagined that their work would one day result in a drug that would radically change the lives of many people living with MG. The infusion bag that hangs beside me every eight weeks, making my life worth living, would not exist without these men.

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It took most of the 20th century before their work would eventually result in the development of Soliris (eculizumab). Approved by the U.S. Food and Drug Administration (FDA) in 2007, Soliris was the first drug built to block the complement cascade that Bordet had described, and 10 years later, it became the first new treatment for MG in over 60 years.

However, Soliris had its drawbacks. It requires biweekly infusions (after a weekly loading phase), thus limiting a patient’s lifestyle. So Alexion Pharmaceuticals, which developed Solaris, had its researchers return to the drawing board to make small structural changes to the drug’s chemical structure, resulting in Ultomiris, which the FDA approved for MG in April 2022.

Ultomiris uses the same mechanism as Soliris and has the same target. Its benefit is the frequency of infusions: Ultomiris is infused every eight weeks after the loading phase.

This is not a story of a lightning-bolt discovery. It’s a story of patient refinement, of someone deciding a good thing could be made a little easier to carry.

One female Chinese hamster

So what sent me down this rabbit hole of historical research? I wanted to know something about how Ultomiris is made — its recipe, as I call it. What was the first ingredient? In cake, the first ingredient is flour. Without flour, there is no cake. I learned that scientists called this a building block. Ultomiris, like most modern biologic drugs, isn’t synthesized in a chemical vat. It’s grown, quite literally, inside living cells. And nearly every one of those cells traces back to a single hamster. That is the flour in the recipe.

In 1957, a geneticist named Theodore Puck obtained one female Chinese hamster and extracted cells from its ovary, growing them in a laboratory dish out of nothing more than scientific curiosity about chromosomes. He wasn’t trying to build a drug factory. But those Chinese hamster ovary cells, or CHO cells, turned out to have an extraordinary gift for producing complex proteins that behave like the ones our own bodies make. Every CHO cell used in a bioreactor today is a descendant of that single hamster from 1957, divided and redivided with no additional animals being involved. Today, the echo of that single small and unremarkable day in a Colorado lab is still running through my bloodstream.

I keep coming back to something the prophet Zechariah said to a discouraged people rebuilding a temple out of what looked like nothing much: “For who hath despised the day of small things?” Small things can compound. A single hamster, a young physician’s odd case report, and a Belgian scientist’s obscure serum protein are easy to overlook. Then, decades later, they are changing lives.

George Eliot closed “Middlemarch” with the following words: “For the growing good of the world is partly dependent on unhistoric acts; and that things are not so ill with you and me as they might have been, is half owing to the number who lived faithfully a hidden life, and rest in unvisited tombs.”

The day Puck made the hamster discovery may have seemed as ordinary as any other day. Strübing’s case report might have remained a footnote. But the good that reaches me now, in an infusion chair in Dallas, was half-owing to people who did small, faithful, unhistoric things, and who never knew where they’d lead.

That’s true of medicine. I suspect it’s true of most of what sustains us.

Note: Myasthenia Gravis News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Myasthenia Gravis News or its parent company, Bionews, and are intended to spark discussion about issues pertaining to myasthenia gravis.