I recently attended a small dinner hosting Robert Lefkowitz, MD, the winner of the 2012 Nobel Prize in Chemistry for his discovery for G-protein coupled receptors. Throughout the night, the conversation traversed a diverse range of topics — from his adventures in Stockholm, Sweden to his work-life balance — but his remarks on one particular subject stuck with me. It turns out that Dr. Lefkowitz, when interviewing candidates to work in his lab, prefers to work with those who attribute most of their successes to luck and he credits many of his own accomplishments to it as well.
To say that doctors like control would be an understatement — we’re obsessed with it. We like to titrate our drugs carefully for our patients, down to the tenth of a milligram sometimes if we can. In the hospital, every component in blood is compulsively scrutinized that they’re in the correct ranges. The obsession goes beyond the hospital. Patients hoping to enroll in clinical trials can be rejected for the most minor inconsistency. Experiments in the laboratory are repeated ad nauseum until every parameter is just right.
But we’d be fooling ourselves if we thought that we actually had that much control over the direction of medicine. Medicine is intractable and unpredictable, and luck plays a larger role than we’d like.
Recently, researchers at Harvard analyzed the discoveries behind today’s major medications. Take, for example, the hypertensive medication captopril as the researchers cite. It was the first drug of its kind synthesized, and it launched an entire class of hypertensive medications. ACE inhibitors are now considered the first line of treatment in high blood pressure and some 12 percent of the population are taking this class of drugs right now. Though this drug was approved in 1981, the seed for its discovery was planted more than three centuries ago when blood pressure was first measured in a horse in 1733. It was two centuries later, through a convoluted path of discoveries and failures in basic science labs, that scientists finally discovered which culprit molecules in our bodies were responsible was controlling blood pressure.
And the key chemical compound that could reverse their effects and eventually lead the synthesis if ACE inhibitors? It was found in the venom of a snake species indigenous to Brazil.
I can’t speak for the scientists behind these discoveries but surely, the scientists who wanted to find out how pit vipers could so swiftly kill their prey did not anticipate that their discovery would be critical in developing anti-hypertensive drugs two decades later.
History has shown that basic science has fueled scientific discoveries and has done so without the prospect of profits or glory or prizes. These discoveries were steered by curiosity, researchers chasing knowledge for the sake of knowledge. And along the way, serendipity occasionally strikes.
So while the allure of translational medicine is sexy and certainly more profitable, the basic scientists who ask the fundamental questions of human biology equally deserve our attention and funding. It’s a neglected side of medicine that is often overlooked by the public, the media, and even physicians.
I admit that my primary motivation for dedicating a year to research was the hope of making inroads in treating late-stage cancers. And we have made some headway towards this cause. But we have only been able to come this far because we’re lucky enough to stand on the shoulder of those basic science researchers who came before us.
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