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The Right Place at the Right Time

December 13, 2022

This year, the Ernest Beutler Prize recognized Dr. John Atkinson of the Washington University School of Medicine in St. Louis, and Dr. Peter Hillmen of the University of Leeds School of Medicine, for their career-long contributions to our understanding of the complement system and its role in human disease, as well as the development of life-changing therapies for patients with complement-mediated disorders. Their careers have been outright exceptional, and their success highlights the fact that while much has changed within medicine in the past five decades, curiosity, collaboration, and gratitude remain strong pillars of academic success.

In 1970, paroxysmal nocturnal hemoglobinuria (PNH), an acquired disorder now known to be caused by loss of expression of CD55 and CD59 from the surface of hematopoietic stem cells, had a grim prognosis. Around half of patients with PNH did not survive long term, and those who did experienced a high symptom burden including extreme fatigue, life-threatening anemia, thrombosis, and evolution to aplastic anemia.1 Subsequent discovery of the molecular mechanisms of PNH and the development of anticomplement therapies, with many more currently in development, translated into an overall survival benefit for these patients similar to that of age-matched controls, with significantly improved quality of life.2

The 2022 Ernest Beutler Lecture was a masterful presentation of hallmarks in the discovery, description, and characterization of the complement elements, their relationship with coagulation, role in disease, and basis for targeted therapeutics. The introduction of anti-C5 therapy (eculizmab) changed the natural history of PNH, offering significant improvement in symptoms, decreased hemolysis, and reduction in red cell transfusion needs. The immediate effects were only the beginning, as reduction of thrombotic risk, safety in pregnancy and normalization of overall survival emerged as meaningful outcomes of treatment. Treatments targeting C5 (eculizumab, ravulizumab), C3 (pegcetacoplan), C5a (avacopan) and C1a (sutimlimab) are now approved, with pegcetacoplan having a significant clinical impact for patients with PNH who continue having hemolysis while on eculizumab due to C3-mediated extravascular hemolysis. A factor D inhibitor (danicopan) and factor B inhibitor (iptacopan) are on their way to the bedside as adjunct treatment in this patient population. From the observation shared by Dr. Atkinson that patients with complement deficiencies, in addition to being susceptible to infection, have a high risk of developing systemic lupus erythematosus, to the thorough characterization of complement proteins, their preferential expression in different cell types, and their role in a broad spectrum of hematologic disorders, it is clear that, as he stated, “complement has made a comeback.”

Dr. Atkinson’s career has been shaped by a series of serendipitous events. Unforeseen circumstances challenged him to take steps in a direction he had neither planned nor imagined. He attended medical school when his dream to become an ornithologist fell apart following the unexpected death of a colleague and mentor. Subsequently, he chose a career in rheumatology “by default” based on the time he spent as a resident and clinical associate at the National Institutes of Health (NIH). His career has been marked by being at the right place at the right time; however, circumstances are only part of the equation, and it was his scientific curiosity and dedication that propelled him toward academic excellence. When asked about his path to success, he highlighted the importance of collaboration, good mentorship, and honest feedback. The relationships he was able to foster with colleagues at NIH and Washington University School of Medicine, were key to advancing his scientific work. Progress does not occur in isolation, and having a multidisciplinary group of clinicians all in the same building enabled him to find inspiration “just a few doors away.” He also emphasized his gratitude toward the individuals who have played important, yet traditionally less visible roles in his professional development, such as postdoctoral fellows, graduate students, and administrative staff.

Professor Hillmen describes himself as an “average medical student” who had not considered a research career. His career in medicine would end up being anything but average. The collaborative work environment between clinicians and scientists at Hammersmith Hospital and the dedicated mentorship of Professor Lucio Luzzatto, were key in building the translational hub that would lead to the description of the molecular basis of PNH and, subsequently, of the first-in-human study of anticomplement therapy. It was the bonds with his patients, many of whom had been under his care for decades with limited treatment options, that drove his desire to continue learning how to translate science into the clinic. And it is the connections with colleagues near and far that continue making the journey a fun and exciting adventure.

Drs. Atkinson and Hillmen inspire us to continue working on our scientific endeavors and remind us not to lose sight of humanity. Cultivating bonds with peers, sharing knowledge and expertise through teaching and mentoring, and chasing our passions remain critical elements of a long and successful career in science and medicine.


  1. Hillmen P, Lewis SM, Bessler M, ET AL. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995;333(19):1253-1258.
  2. Kelly RJ, Hill A, Arnold LM, et al. Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival. Blood. 2011;117(25):6786-6792.

Dr. Perez Botero indicated no relevant conflicts of interest.

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