“Knowing about disease is fundamental to asking the right question.”

I recently had the opportunity to speak with Professor Alastair Compston: distinguished physician-scientist, fellow of Jesus College, recipient of a 2016 New Year’s Honours award, and pioneer of alemtuzumab, the current frontline treatment for multiple sclerosis (MS). Over the course of our conversation, he covered a breadth of topics such as advice to aspiring scientists and his views on clinical science. Despite this diversity, I was struck by the themes that seemed to tie together all these ideas, and in many ways his career as a whole: hypotheses, personal relationships, and perseverance.

Professor Compston offered an unusual perspective on technology and contemporary research based on big data: “If you are a clinician scientist, and the focus is on numbers and big data and big numbers, the critical hypothesis needed to understand disease may be lost.” In our conversation, he returned to the view that numbers and technology, while obviously important, are not everything. His approach has prioritised concepts of disease pathogenesis rather than seeing what emerges from big data. This caveat reflects the central role that hypothesis-driven research played in his career and in introducing alemtuzumab as a treatment for MS, the achievement for which he was recognised. MS is a debilitating condition, which manifests as a host of varied, unpredictable symptoms resulting from the deterioration of brain and spinal cord function. Having extensively reviewed and contributed to the MS academic literature, Professor Compston concluded in the late 1980s that the root cause of this heterogeneous disease was the body’s own immune system gone awry.

T-cells are a crucial component of the adaptive immune system, the body’s defence system that ‘adapts’ to best fight off a specific pathogen. T-cells become ‘auto-reactive’ and mistakenly identify parts of the brain and spinal cord as infectious invaders and launch an attack. Most students of medicine and human biology will recognise this hypothesis from lectures and textbooks, but “this was not established dogma at the time.” 25 years ago, Professor Compston followed his hypothesis’s predictions and sought a drug to eliminate auto-reactive T-cells and thereby stop MS’s progress. This search pushed him into turning the Campath-1H antibody, developed here at Cambridge, into a licensed MS therapy.

A sound hypothesis, he argues, was also essential to shepherd this therapy through the many setbacks it faced. A telling example is alemtuzumab’s first clinical trial: an eight-year experiment that found many nasty side effects and few benefits. In spite of this setback, he and his team still believed in their therapy. He realised that he had made the mistake of “treating patients who were too far gone,” late stage patients who had already suffered neurodegeneration from the ravages of autoimmunity in the brain. Professor Compston, then facing even higher resistance and criticism, hypothesised that the T-cells had to be stopped early, before they could inflict irreversible damage on the nervous system. A sound hypothesis, therefore, allowed him to diagnose the flaw in his experiment in a way that masses of data alone would have missed.

Professor Compston believes in the importance of personal relationships as much as in hypothesis, “the power of the advocacy of the individual,” as he put it. Relationships, he says, shaped his career, including those that introduced him to the topic of MS research and brought him to Cambridge, and so allowed him to achieve many of his goals, such as being a founding member of the prestigious Centre for Brain Repair. Personal relationships, “not the force of data,” overcame one of alemtuzumab’s most daunting hurdles: getting a foothold in the business world. “Businesses are easily frightened off,” so alemtuzumab had been bought and sold, though no company chose to develop it as an MS therapy. The breakthrough occurred only when the CEO of ILEX, a San Antonio, Texas-based company, visited Cambridge and met one of Professor Compston’s patients. This patient argued eloquently and persuasively that this therapy had changed her life for the better. This patient and her conviction finally convinced ILEX to back the therapy.

Twenty-five years after crafting a hypothesis, alemtuzumab finally arrived on the market in Europe and in the USA. This brings us to the last of Professor Compston’s themes: perseverance. “There were moments of extreme gloom and moments of considerable excitement.” Only recently has the success of the therapy validated the hypothesis that spawned it in 1988. Congratulations to Professor Compston on a New Year’s Honour more than two decades in the making.