The program’s methodology is still evolving, but for the first dozen or so patients it worked this way: A primary-care physician sent in a letter describing the case, followed by reams of records documenting the diagnostic dead ends the patient had already confronted. Gahl personally reviewed all the cases and discarded about three-quarters of them, usually because the problem was insufficiently documented, seemed to be psychosomatic or, for some other reason, left Gahl with the impression that the N.I.H. had little new to offer. Then he took the most promising cases to his medical-review board, made up of several dozen clinical investigators from all over the N.I.H. The board reviewed 10 or so cases at each monthly meeting, out of which it accepted just a handful, the ones that seemed most likely to lead to a new insight into a known disease, or, even better, to a diagnosis of a disease never before seen. Then Gahl’s staff arranged to bring in each patient for a week of assessment in Bethesda. There, the patient would meet an array of specialists who did physical exams, took histories and conducted whatever additional tests they needed: ultrasound scans, M.R.I. scans, X-rays, electroencephalograms, maybe a spinal tap or a biopsy of skin or other tissue.
This approach seems in many ways more fruitful than bouncing patients from one specialist to another. Instead get the specialists together for a short period and focus on the patient. But even more tantalizing are the long-term goals:
Gahl’s projected success rate is so low because his aim is so high. His holy grail is a molecular diagnosis: finding not just a description of a new disease but also an understanding of how it works at the level of the gene. With this goal, the Undiagnosed Diseases Program aspires to be a model for how genomic medicine will be done in the 21st century.
The article documents NIH use of a “one-million SNP chip” on these patients and discovering potential molecular targets by combining insertion-deletion analysis with standard practice differential diagnosis. Combined with the recent addition of the National Center for Complementary and Alternative Medicine, NIH seems to be focusing on building clinical expertise in more integrative medicine.