Remembering Robin Briehl, M.D., Leading Sickle Cell Researcher
One doesn’t need hindsight to know that 2020 was a difficult and disappointing year on many levels. The year concluded on December 31 with the loss of one of Einstein’s long-serving faculty members, Dr. Robin Briehl. He was 92.
Dr. Briehl joined the faculty at Einstein in 1962 as an assistant professor of physiology. Over more than 50 years at the College of Medicine he rose through the ranks, ultimately becoming professor of physiology & biophysics, of biochemistry, and of medicine. His research focused on characterizing the thermodynamics, kinetics, structure, and interactions responsible for the abnormal formation of rigid spicules of hemoglobin (called HbS) in the red cells of people with sickle cell anemia.
Sickle cell anemia is a hereditary disease that occurs when HbS causes increased destruction of red blood cells. It affects many different populations, although its most serious manifestations have been observed in people of African descent. The “pile-up” of abnormally rigid sickle cells in small blood vessels causes great pain and can deprive organs and tissues of oxygen.
“Since the clinical pathology, especially the sickle cell crises, is dependent on the kinetics and other aspects of the physical chemistry of HbS, Robin’s work made many contributions to the understanding of this disease,” noted Dr. Denis Rousseau, professor and chair of physiology & biophysics.
An Exemplary Academic
Among Dr. Briehl’s most significant publications was the first he submitted from Einstein, on the relation of ligand binding and aggregation in lamprey hemoglobin, published in the Journal of Biological Chemistry. “This paper reported cooperativity in the hemoglobin that Nobel laureate Dr. Jacques Monod claimed put him on the path of the Monod-Wyman-Changeux theory of allosteric transitions,” said Dr. Rousseau.
In another important paper, published in the Journal of Clinical Investigation in 1970, Dr. Briehl and his trainee H. Franklin Bunn, reported the hemoglobin-binding site of the physiologically important modifier 2,3 Diphosphoglycerate (DPG). This conclusion was later confirmed by others using X-ray crystallography.
In 1990, Dr. Briehl published another significant paper, this time in Nature, in which he showed that deoxygenated sickle hemoglobin polymerizes into long fibers that distort that decrease the deformability of red blood cells and cause sickle cell crises.
He enjoyed continuous funding throughout his career from the National Institutes of Health and other agencies and foundations. This provided support for a large program that he oversaw between 1997 and 2006. His success in garnering funding led a team of health economists from Columbia to contact him in 2004, to invite his participation in a study they were conducting on the impact of funding. Dr. Rousseau recalled, “They told Robin he would be included in the study because ‘NIH records place you above the 95th percentile of the distribution of extramural NIH grants over the last 25 years.’”
Valued Mentor and Champion of Social Justice
While widely known for his academic acumen, he also was admired for his character. Dr. Frank Ferrone, professor of physics at Drexel University and a leading scientist in the study of sickle cell hemoglobin, shared, “Robin was above all a man of great integrity, whether standing up for the faculty or a political cause, or just the science that he loved. When the double nucleation model for sickle polymerization came out, Robin was seriously skeptical, and was the first to use differential interference contrast microscopy to visualize the events during polymer formation. He intended to demonstrate that his competing model was right, not ours. As soon as he saw the first fibers growing, he said, “Those guys are right,” and he abandoned his model and became a key player in further developing the model he formerly opposed. It was right, now, and that was that!”
Dr. Rousseau added, “Robin loved to teach students and trainees.” Many of his trainees have gone on to leadership positions in the biomedical community.
In 2010, he received the Harlem Dream Award for mentor of the year, bestowed by the Harlem Children Society for mentoring students from under-resourced and underserved communities. Student interns spent summers in his lab learning how to do advanced research on sickle hemoglobin.
He served on a committee at Einstein that would select the speaker for an annual Sam Seifter Lecture, established by Einstein alumnus Dr. Valiere Alcena and held until shortly after Dr. Seifter’s death in 2009. The lecture featured speakers who were leaders in social justice.
Dr. Briehl also penned a letter —A Sacred Commitment—to the editor that appeared in the July 7, 2001 New York Times, decrying a letter published on June 30 from the chief executive officer of the health insurance company Aetna and its tone deafness on health equity. His letter concluded, “The welfare of children and care of the sick are the most sacred commitments of good society. It is a mark of evil when profit and greed infect the practice of medicine.”
Born in Vienna, Austria in 1928, his family eventually came to the United States. He attended high school at the Fieldston School in the Bronx. His pathway to Einstein continued at Swarthmore College, where he majored in physics and mathematics and graduated Phi Beta Kappa. He received his M.D. from Harvard and was then an intern at Montefiore, a resident at Columbia Presbyterian, and a research fellow at Columbia University and at Harvard University. At Harvard, he studied in the lab of Nobel Laureate, George Wald.
While he retired in 2016, he never fully stopped considering possible avenues for alleviating the suffering for those with sickle cell anemia. Dr. Rousseau recalled, “Robin had found residual arterial polymers of sickle hemoglobin, which he hypothesized were pathogenic and a source of seeding polymerization, thereby accelerating the onset of sickle cell crises. He continued to think about ways to decrease the level of arterial polymerization to alleviate the disease, and would frequently come to my office, even though he was in failing health, to discuss his latest ideas.
“He is a sadly missed intellectual force.”
Those wishing to leave a memory of Dr. Briehl may do so by visiting this Remembrance page.
Editor’s Note: Inside Einstein would like to thank Dr. Denis Rousseau for his helpful contributions in the drafting of this in memoriam.
Posted on: Monday, April 12, 2021