Many medical researchers think that the only route to progress is through basic research, and even then, progress may only consist of incrementally longer life or modest reductions in side-effects. For instance Dr. Paul Marks, who was influential in Nixon’s war on cancer, believed Nixon should only fund basic science, by which he meant cell genetics, and that such research would probably not cure cancer, but only help us to better manage it. Some medical researchers (e.g. Prasad and Cifu 2015; Raza 2019) have criticized this approach as “reductionism.” Others (e.g., Devita and Devita-Raeburn 2015; Prasad and Cifu 2015; Raza 2019) support a pluralistic approach–any method that yields major advances, especially cures, is okay.
Those who advocate basic science seek mechanisms of disease, and when they think they have found one, they seek a chemical that will interfere or block that mechanism. The article quoted below tells the illuminating story of scientists who identified inflammation as a major mechanism of atherosclerosis and found a drug (ziltivekimab) that interferes with that mechanism. They then tested it using the “gold standard”: a large-scale, double-blind randomized controlled trial (RCT). But to their “shock” they found that cardiovascular death rates were not lower for those taking the drug than for those taking a placebo.
The ultimate goal is cures. Finding a mechanism, and a chemical that blocks it, can be one path to a cure. But that path sometimes leads to a dead end. So we should allow researchers to follow other paths as well.
(p. D4) Novo Nordisk stunned the cardiology world last week when it announced that a large study it was running on an experimental drug for heart disease had failed. The drug, widely expected to be a blockbuster, was no better than a placebo.
The drug, ziltivekimab, reduces inflammation, which is generally thought to be a cause of atherosclerosis. Stopping that inflammation was hoped to be a way to save lives.
Now the drug’s failure is raising a troubling question. Is inflammation really a cause or is it just a marker of atherosclerosis, the way gray hair is a marker of aging?
Cardiologists had mixed reactions to the news. Dr. Sanjay Kaul, a cardiologist at Cedars Sinai, quoted Thomas Huxley on X: “The great tragedy of science — the slaying of a beautiful hypothesis by an ugly fact.”
Dr. David Maron of Stanford, who is president of the American Society for Preventive Cardiology, said the result “comes as a surprise and a big disappointment.”
But he added, something could have been wrong with the study: Perhaps it just wasn’t the right drug to target heart disease inflammation, or maybe patients in the trial were too sick to be helped by anti-inflammatory medications. There is too much evidence, he said, from pathology studies of plaques in arteries, animal studies, epidemiology and other clinical trials, to toss out the inflammation hypothesis.
“Inflammation is more than a marker of disease, it is a cause of the disease,” Dr. Maron said.
The Novo Nordisk study, called Zeus, involved more than 6,300 patients with heart disease or advanced kidney disease. They also had high levels in their blood of a marker of inflammation known as C reactive protein, or CRP. And they had high levels of interleukin-6, or il-6, a chemical that causes inflammation.
The drug did what it was supposed to do. It made il-6 levels plunge. CRP levels fell in concert.
With those signals indicating that inflammation was controlled, it seemed only logical that heart disease complications and cardiovascular death rates would drop, too. But that didn’t happen.
“I think we’re all in a state of shock,” said Dr. Martha Gulati of Houston Methodist, past president of the American Society for Preventive Cardiology.
For the full story, see:
(Note: the online version of the article has the date Aug. 6, 2026, and has the title “A Promising Heart Drug Fails, Challenging a Long-Held Theory of Disease.”)