The recent Ebola outbreak and the subsequent race to find a vaccine and other treatment options has brought the topic of drug development back in the public spotlight. But despite the millions of dollars spent on these efforts and the technological advances in biomedical sciences in the last 20 years or so, the process is still time-consuming and prone to failure. A recent feature story from National Journal (which also appears on The Atlantic's website today) describes the work of several scientists trying to find cures or treatments for some of the most challenging diseases, from infectious diseases, like AIDS and Ebola, to chronic diseases such as Alzheimer’s.
The first disease the article highlights is a rare disorder called progeria, which causes young children to age prematurely. Recent breakthroughs in treatment have come from a team led by Francis Collins, MD, PhD, who is more famous for leading the Human Genome Project and now serves as director for the National Institutes of Health. Collins worked briefly on progeria early in his career and the combination of Collins’s work and genomics made it possible for his team to crack the genetic secret of the rare disease: that it was caused by a single genetic mutation. That finding led to a treatment that extended the lives of patients with progeria by several years. But it also points to some of the overwhelming challenges of chasing down cures and treatments:
The doctors and scientists hunting for new cures and treatments work in a constant state of tension. They operate in a tremendously high-stakes environment, pouring years of their lives into research as the people who inspire them continue to suffer and even die. Drug hunters face failure after failure, almost never followed by success. Decades of work flame out. Promising ideas turn into dead ends. For every 10,000 compounds they explore, scientists wind up with just one drug approved by the Food and Drug Administration. Even when medical science moves as fast as it can—and today, it's moving faster than ever before—it's still an agonizingly slow process.
"As much as we say that failure is part of what we do—if you're not failing, you're probably not doing science that's very interesting—it still hurts," Collins says. "It is frustrating, because you want to come up with the answer. You want to save lives. That's what we all get into this medical research area to try to achieve, and yet the challenges are immense. And we make progress, oftentimes, in very small baby steps, even though what we're hoping for are big leaps."
The research that’s gone into discovering a treatment for Alzheimer’s is also illustrative. In 2012, two different therapies that targeted the disease’s characteristic ameloid plaques failed in human clinical trials. It was a difficult blow to the researchers, but going back to the drawing board revealed another approach:
Although failure is frustrating and expensive, drug hunters say the key to progress is to fail well. A well-designed study that's conducted properly should teach you something, even if the outcome isn't what you wanted. "Some of the greatest insights I've ever had were failures—and some pretty big failures," [Ron DeMattos, a research fellow and group leader at Eli Lilly] says. "We're going to fail thousands of times."
In this case, the lesson was to start earlier. When Lilly's scientists dug a little deeper into their data, they realized that their drug had produced a decent benefit for trial participants who had "mild" Alzheimer's. Every time they cut the data a different way, they remained convinced they were seeing real progress earlier in the disease.
The feature also describes recent work on Ebola and malaria vaccines, and delves into the history of AIDS drug development. One of the challenges, though, is money. Although research funding for the NIH surged in the 1990s, it’s been relatively flat in the past decade and sequestration has eaten into that budget even more. The feature describes the surprising number of variables goes into treatment and how they come together, or don’t.
Previously: Stanford researchers develop a new biosensor chip that could speed drug development, Crowdsourcing cost of drug development, Why drug development is time consuming and expensive (hint: it's hard), Re-engineering the drug-development process to speed medical advances