• How much can we learn about human biology from studying a single patient?
  • What findings, using insights gained at the bedside, can help devise scientific questions to study at the lab bench?
  • How might we bring these findings back to the bedside to create medical advancements for other patients with similar disease processes?
The Pathways Consult Service aims to discover new insights into the unifying mechanisms and underlying biology of disease through the close examination of a single patient with unexplained symptoms.

When medical staff at Massachusetts General Hospital encounter patients who have unusual or unexplained symptoms, they can refer them to the Pathways Consult Service. Under the guidance of Dr. Mark Fishman, Chief of Pathways Consult Service and former Chief of Cardiology at Mass General, a team of two or three residents will spend two weeks investigating one of these cases while developing hypotheses regarding the pathophysiology and biological mechanisms underlying the patient’s disorder.

Unlike a standard clinical care rotation in which physicians have limited time to devote to each patient, Pathways Consult Service residents can take a much needed step back and have the time to think deeply about  the pathophysiology of a single patient.

During the consult, the Pathways Consult Service team meets with the patient and their clinical care team, reviews scientific and medical literature, and discusses their hypotheses with a broad variety of experts from around the world and across disciplines. Our expert consultants consistently provide valuable input into the formulation of the team’s hypotheses and investigative plans and contribute a contagious enthusiasm for patient-driven investigation.

To round out the rotation, the residents present the case at a Pathways Consult Service conference where they discuss their hypotheses and potential experiments that could elucidate the pathophysiology of their patient’s unusual phenotype. Bringing together interested residents and senior faculty, the conference acts as a forum to further refine their clinical recommendations and proposed avenues of scientific inquiry.

With connections across the globe, the Pathways Consult Service team seeks to perform the proposed experiments in the weeks and months following the consult. The discoveries from which may lead to new methods of diagnosis, prevention, and treatment of the patient’s pathology.


For over a hundred years, academic medical services have generated new insights into biological pathways underlying disease by applying novel technologies to patients in the clinic. New findings from these applications were often driven by a single patient or a small number of patients who came to the hospital with unusual or unexplained symptoms. For example, in the mid 20th century, the examination of a small number of patients with sickle-cell anemia led to a deeper understanding of oxygen transportation in blood. More recently, the examination of a small group of otherwise healthy people living with HIV has helped researchers gain new insights into viral replication and has led to new therapeutics for fighting viral infection.

Although the link between biological research and clinical medical services has declined over the years, the potential for this approach to both advance our understanding of disease and help patients has only been enhanced by recent developments in technology.

Pathways Consult

During a Pathways consult, a team of residents devote two weeks to investigating the pathophysiology of a single patient’s unexplained symptoms, and propose ways to harness new technologies like next-generation DNA sequencing, induced pluripotent cell culture, and proteomics to discover the underlying mechanisms of disease. We aim to bring these discoveries back to the clinic to help our patients and those whose disorders share similar disease pathways.

The Pathways Consult Service provides an unparalleled educational experience to the residents, promotes cutting-edge scientific research, and has the potential to tangibly improve the health status of patients at Mass General and beyond.