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True scientific advancement happens when researchers refuse to accept 'no' as an answer. When immunotherapy was dismissed for lung cancer, pioneers investigated why it worked in melanoma but not other cancers. This mindset—questioning failures and studying successes—is key to turning scientific impossibilities into standard treatments.
For years, the KRAS oncogene was considered a key cancer driver but impossible to target with drugs. Through resilient investigation, scientists recently developed effective therapies against it, proving that even long-held beliefs about 'undruggable' targets can be overturned with persistence.
True scientific progress comes from being proven wrong. When an experiment falsifies a prediction, it definitively rules out a potential model of reality, thereby advancing knowledge. This mindset encourages researchers to embrace incorrect hypotheses as learning opportunities rather than failures, getting them closer to understanding the world.
Progress in drug development often hides inside failures. A therapy that fails in one clinical trial can provide critical scientific learnings. One company leveraged insights from a failed study to redesign a subsequent trial, which was successful and led to the drug's approval.
The most valuable lessons in clinical trial design come from understanding what went wrong. By analyzing the protocols of failed studies, researchers can identify hidden biases, flawed methodologies, and uncontrolled variables, learning precisely what to avoid in their own work.
The strength of scientific progress comes from 'individual humility'—the constant process of questioning assumptions and actively searching for errors. This embrace of being wrong, or doubting one's own work, is not a weakness but a superpower that leads to breakthroughs.
Dr. Radvanyi emphasizes that foundational discoveries in immunotherapy arose from basic immunology and serendipitous observations, like his own unexpected T-cell proliferation with an anti-CTLA-4 antibody. This highlights the risk of over-prioritizing translational research at the expense of fundamental, curiosity-driven science.
Reflecting on his PhD, Terry Rosen emphasizes that experiments that fail are often the most telling. Instead of discarding negative results, scientists should analyze them deeply. Understanding *why* something didn't work provides critical insights that are essential for iteration and eventual success.
CZI set an audacious goal to cure all disease. When scientists deemed it impossible, CZI's follow-up question, "Why not?" revealed the true bottleneck wasn't funding individual projects, but a systemic lack of shared tools, which then became their core focus.
Solving truly hard problems requires a form of 'arrogance'—an unwavering belief that a solution is possible, even after months or years of failure. This 'can-do' spirit acts as an accelerator, providing the persistence needed to push through challenges where most would give up.
Biomarkers provide value beyond predicting patient response. Their core function is to answer 'why' a treatment succeeded or failed. This explanatory power informs sequential therapy decisions and provides crucial scientific insights that advance the entire medical field, not just the individual patient's case.