After Medical School at Vanderbilt, David trained in Internal Medicine in the Osler Service at Johns Hopkins where he was Assistant Chief of Service before returning to Vanderbilt to train in Clinical Pharmacology under the mentorship of John A. Oates, focusing on autonomic pharmacology. Since early in his career David decided to apply this training to develop novel therapies for the treatment of autonomic disorders. His contributions to the fields of Clinical Pharmacology and autonomic neurosciences are numerous and seminal. David has 330 peer reviewed original publication in high impact journals (including 13 in the N Engl J Med) and almost 200 additional review articles and books. He has had uninterrupted NIH funding for over 30 years, including a Program Project Grant now in its 20th year (PO1 HL056693) and a multicenter Rare Disease Clinical Research Consortium (U54 N065736) that has been just renewed. He has trained dozens of clinical pharmacologists, many of them now in leadership positions in academia and industry. I will attempt to summarize his main scientific contributions.
David has discovered two new diseases, an accomplishment very few can match. Based on clinical and biochemical observations, David recognized individuals with a congenital absence of norepinephrine, and characterized dopamine-beta-hydroxylase deficiency, initially reported in the New England Journal of Medicine in 1986, one of his thirteen publications in that journal, and later described its genetic basis (Am J Hum Genet 2002). He then discovered a pharmacological cure for this disorder, by administering droxidopa (called then DOPS). Droxidopa is converted in the body to norepinephrine through dopa-decarboxylase, thus bypassing the congenital enzymatic defect (Lancet 1987). This is a premier example of the application of Clinical Pharmacology principles to the therapy of human disease. Droxidopa was later developed as a treatment of more common forms of orthostatic hypotension and has recently been approved by the FDA for that indication.
His second disease discovery was that of norepinephrine reuptake deficiency (N Engl J Med 2000), a genetic defect in the norepinephrine transporter producing orthostatic tachycardia due to synaptic accumulation of the neurotransmitter. Later on, he repurposed norepinephrine transporter blockers for the treatment of orthostatic hypotension (Hypertension 2007 and 2014).
Another example of his therapeutic creativity is his recognition that bolus ingestion of 500 ml water elicits a pressor response in autonomic failure patients, with increases in blood pressure of 40-50 mm Hg (Lancet 1999). We normally do not think of water as a pharmacological agent, but in these patients it is as potent as commonly used pressor agents. He has extended this research to human and animal models to show that the pressor effects of water are due to sympathetic activation (Circulation 2000) elicited by hypoosmolar stimuli activating transient receptor potential vanilloid (TRPV) 4 receptors at the level of the portal circulation (Hypertension 2010). Thus, his research unmasked a heretofore unrecognized autonomic reflex with unique pathways that we did not realized were important for cardiovascular regulation.
David has also used Clinical Pharmacology as a research tool to understand underlying physiology and pathology of cardiovascular regulation. One of his earlier works as a trainee was the characterization of the cardiovascular effects of caffeine (N Engl J Med 1978) and the recognition of the development of tolerance to its effects (J Clin Invest 1981). He then applied this knowledge to use caffeine as a treatment of the postprandial hypotension seen in patients with autonomic failure (N Eng J Med 1985).
There are numerous other examples of David’s contribution to hypertension. He has 42 publications in Hypertension, the flagship journal of the Council. His research is characterized by its innovation and creativity and the use of rare autonomic disorders to improve our understanding of cardiovascular regulation. He has mentored many individuals who are now in leadership positions, ensuring his legacy.
The detailed description on Dr. David Robertson’s achievements is provided by Italo Biaggioni, M.D. from Vanderbilt University.