that detailed the bizarre story of heroin users in the Bay Area who,
overnight, became PD sufferers.
Dr. DeLong stayed at Johns Hopkins following his neurology residency,
forming his own lab to continue his exploration into the basic anatomy and
function of the basal ganglia. The news of MPTP-afflicted patients
inspired DeLong to see if he could create an animal model for PD. His
hunch was that PD’s damage was far more complicated than theorists had
proposed. To decipher the cause and cure of the disease would demand
great imagination, and because DeLong “was very good at putting things
in their perspective and thinking conceptually,”^24 he was the right man to
crack the complex code of the black box in the deep part of the brain.
DeLong’s earliest work on the lab animals with artificially created PD
turned the world of brain research upside down. While most of us
associate a tremulous hand with PD, the other major symptoms are
stiffness of limbs, slowing of movement, the loss of facial expression, and
the slurring of speech. All told, most of the symptoms imply an inhibition,
or “dumbing down,” of the nerve transmissions from the motor cortex to
the muscles; therefore, scientists had concluded that, conceptually, PD
could be summarized as a slowing of nerve transmissions among the
neurons that control and coordinate movement. Instead, Mahon DeLong
recalls, “There were skeptics, but on Day One we saw that the activity
patterns and firing rates were quite altered, and that the output from the
basal ganglia was increased rather than decreased.”^25
DeLong and his colleagues realized that the Gordian knot of the basal
ganglia was the key in understanding movement disorders. As experiments
progressed, a Rube Goldberg contraption was revealed, where neural
circuitry between the cortex of the brain and the elements of the basal
ganglia came into focus. The breakthrough observation was that some of
the neural pathways triggered an inhibitory signal to other nests of cells,
so that increased firing along an “inhibitory” conduit would result in
decreased signaling along the next stopover.
This is a critical concept in physiology and medicine: there are
functional elements in our DNA, in our cells, between glands and organs,
and along nerve pathways, where an increase in the signaling molecule or
nerve transmission results in a decrease in a corresponding effect. A
classic example is the tumor suppression gene, p53. When active, the
“anti-oncogene” p53 helps repair DNA defects and stabilizes cellular