Here’s to the Tinkerers

by Guy McKhann, M.D.

July 13, 2016

This is a column from Dana's print publication, Brain in the News.

Today I would like to highlight the work of a French neurosurgeon, Alim-Louis Benabid. Benabid, along with his American colleague Mahlon DeLong at Emory, founded the use of deep brain stimulation to treat Parkinson’s disease. For this work, they shared the Lasker-DeBakey Award for Clinical Medical Research in 2014. For many, the Lasker Awards are the American equivalent of a Nobel Prize. 

As outlined in the article, “Meet the French Neurosurgeon Who Accidentally Invented the ‘Brain Pacemaker,’” Benabid is a most unusual neurosurgeon. First of all, he came from a background in physics, not biology like most neurosurgeons. Secondly, like many inventors, he was a tinkerer. It was not uncommon for Benabid to ask himself, “I wonder what will happen if I do this…” And that is how he came across a unique purpose for deep brain stimulation (DBS). At that time the surgical approach to modifying Parkinson’s disease was to make a lesion in the basal ganglia. When a lesion is made, neurons are permanently damaged and the lesion is irreversible. With DBS, the introduced electric current interrupts the signals in the neuronal systems involving the motor and other signals in this part of the brain. When the current is turned off the neuronal systems return to their previous state.

That is the first part of the equation. The second is the question of where, in the brain, to put the end of the wire that will produce the current. That’s where DeLong and his colleagues come in. First at Hopkins, and then at Emory, DeLong studied the anatomy and physiology of the basal ganglia in normal primates and in primates with a form of experimental Parkinson’s. The experimental Parkinson’s was induced by feeding the animals a poison, MPTP—an analogue of heroin that produces a Parkinson’s-like disease in humans. DeLong’s recordings indicated that in the Parkinson’s-like animals, the neuronal systems were hyperactive. He then placed lesions in various places to see if he could bring that hyperactivity back toward normal and, in turn, relieve the symptoms. He found that the most successful place to lesion was the subthalamic nucleus, a small group of neurons that were a hub for neuronal systems. He discussed this with Benabid, and the subthalamic nucleus became the target of choice for DBS. The rest is history: At least 150,000 patients with Parkinson’s disease have received DBS as therapy.

DBS is now used or being tried for other disorders such as other forms of tremor, dystonia (a condition in which opposing muscles contract simultaneously), depression, and even Alzheimer’s disease. If it does not work in a particular patient, the hardware can be removed and you are back to square one, with the brain intact.

As a neurologist, I have often envied the neurosurgeons because they have direct access to the human brain. Most neurosurgeons don’t take advantage of this. But a few tinkerers do. We need more tinkerers.