What follows is an imagined “dinner party conversation” about atypical hemolytic uremic syndrome (aHUS) among aHUS pioneers—Professor Conrad von Gasser, Professor Tim Goodship, Dr. Lenny Bell. With the author also attending.
e.Last night, I had the extraordinary privilege of imagining a dinner party unlike any other—a gathering of aHUS pioneers whose ground breaking work has shaped our understanding of this rare and complex disease.
Picture this: a warm dining room, the clink of wine glasses, and the aroma of roasted lamb wafting through the air. At the table sat Professor Conrad von Gasser, the Swiss pediatrician who first named hemolytic uremic syndrome (HUS) in 1955; Professor Tim Goodship, a nephologist whose research illuminated the complement system’s role in aHUS; Dr. Lenny Bell, a visionary behind the development of eculizumab, the game-changing complement inhibitor; and myself, a tireless patient advocate representing the aHUS community’s voice ( hey I am writing this!)*.
What unfolded was a conversation as rich as the meal itself—part history lesson, part scientific debate, and wholly inspiring.
The evening began with Professor Conrad von Gasser, his Swiss accent as charming as ever, raising a glass.
“To the syndromes—plural, mind you—that I stumbled upon all those years ago,” he said with a twinkle in his eye. Back in ’55, I had seen those poor children in Zurich Kinderspital —Susi , Carmen , Barbara , Ruth and Walter —with their hemolytic anemia, thrombocytopenia, and kidney failure. I scribbled ‘Hämolytisch-urämisches Syndrom’ on a death certificate and thought, ‘This is something!.’ Little did I know it would spark all this!”
Professor Tim Goodship chuckled, swirling his wine. “Conrad, you gave it a name, but it took decades to untangle the quandaries that followed . When my team in Newcastle started digging into the genetics in the ’90s, we had families in Devon with far too many aHUS cases—way beyond chance. That’s when we found the factor H mutations in ’98. It was like finding the key to a lock we didn’t even know existed. The complement system, overactive and unchecked, was wreaking havoc on their microvasculature.
I , ever the voice of the patient, leaned forward and agreed saying . “Tim, that discovery changed everything for us. I’ve met so many families through the aHUS Alliance in the past who’d been told it was just bad luck—recurrent episodes, dialysis, lost kidneys. When you pinned it to complement dysregulation, it gave us a target. But it wasn’t until Lenny here brought eculizumab to the table and coupled it to your complement connection had that patients began to have real hope.”
Dr. Lenny Bell grinned, cutting into his lamb. “Thanks, Len. You know, back at Alexion, we were betting big on complement inhibition. The idea was simple but bold . Eventually knowing aHUS is driven by an overactive complement system—especially the alternative pathway—we thought why not block it? Eculizumab binds C5, stops the complement cascade, and suddenly those clots in the kidneys don’t form. The trials in the late 2000s were a revelation—patients who’d been tethered to plasma exchange and acute kidney failure were stabilizing. It wasn’t a cure, but it was a lifeline.”
Conrad tilted his head, intrigued. “So, my syndromes split into two—typical HUS from those nasty E. coli toxins, and this atypical beast you’ve tamed with genetics and drugs. But tell me, Tim, how did you know it was factor H?
Tim leaned back, his tone turning professorial. “It was the families, Conrad. In Devon, we mapped their pedigrees and saw inheritance patterns. Then using DNA ( you may recall Watson and Crick’s work in your day) , with my wife Judith’s lab, we sequenced the genes. Factor H regulates the alternative pathway, and when it’s mutated it cannot work , the complement system attacks endothelial cells unchecked. Later on , mutations were found in C3, membrane cofactor protein, and more. Hundreds. It’s not just one gene—it’s a whole orchestra of dysregulation, often needing a trigger like infection or pregnancy to strike.
I nodded vigorously. “That’s the bit that gets me—triggers. I’ve heard stories of aHUS hitting after a flu, a birth, even a vaccine. It’s like the mutation’s a loaded gun, and life pulls the trigger. Lenny, does eculizumab stop it every time?
Lenny sighed, his optimism tempered. “Not always, Len. It’s brilliant for genetic complement-mediated aHUS—about 60-70% of cases or some whose genetic cause has not been traced yet. But some patients, maybe 10%, have non-complement drivers like DGKE mutations, and eculizumab doesn’t touch those. Plus, it’s a lifelong commitment—infusions every two weeks, cost through the roof. There is also ravulizumab now, longer-lasting, but access is still a battle.
Conrad raised an eyebrow. “Cost? In my day, we worried about diagnosis, not wallets. I rang that cowbell in the wards. In 1983 – Bernard Kaplan did it for me in Hannover—to celebrate the first HUS symposium. Now you’re ringing bells for treatment. I digress. What’s next?
Tim jumped in. “Personalized medicine, Conrad. Refining genetic profiling to predict who’ll respond to eculizumab or need something else. The KDIGO conferences like the one I led in 2015 pushed for that. And there’s research into oral complement inhibitors, less invasive than infusions.
I added, “And patients want a voice in it. We need faster diagnosis too—too many still wait weeks while their kidneys fail.
Lenny nodded. “ Diagnosis can be a bottleneck. Blood tests for anemia, platelets, and kidney function are quick, but ruling out STEC-HUS or TTP etc takes time. Genetic panels can sometimes take months. We need point-of-care complement assays—something to say ‘aHUS’ on day one.”
As the dessert—Swiss chocolate mousse, naturally—arrived, Conrad leaned forward, eyes bright. “So, my little syndrome has grown up—split, mapped, medicated. I’m proud, but curious: will you ever cure it?
Tim smiled wryly. “Cure’s a big word. Gene therapy’s on the horizon—fix the mutations, not just the symptoms. But for now, we manage it, and that’s a victory”.
I raised my glass. “To managing—and to all of you. Conrad named it, Tim explained it, Lenny treated it, and I’ll keep shouting about it. Here’s to aHUS pioneers, past and present.
We clinked glasses, the room buzzing with the weight of history and the promise of tomorrow. If only such a night could happen—four voices, one mission, united over lamb and chocolate, plotting the next chapter for aHUS.
This blog blends factual milestones in the public domain like von Gasser’s 1955 naming, Goodship’s factor H discovery in 1998, and Bell’s role in eculizumab’s development (reflecting Alexion’s real-world impact)—with Woodward’s advocacy. It’s a tribute to their legacies, structured by Grok and conceived / specified/ corrected/ altered by the author together as a warm, human exchange with no financial gain.
Article No. 720
