Introduction

In June of 2001, a team of gene-transfer researchers led by Matthew During and Michael Kaplitt presented the RAC with a clever new strategy against Parkinson's disease. The second most common neurodegenerative disorder in North America, the cardinal symptoms of Parkinson's disease – tremor, rigidity, and inability to initiate movement – are caused in part by the excessive firing of a structure deep inside the brain called the subthalamic nucleus. The researchers proposed to genetically modify this structure with a gene encoding the inhibitory neurotransmitter, glutamic acid decarboxylase (GAD). With the subthalamic nucleus churning out GAD, the investigators postulated that nearby brain structures would quiet down, and Parkinsonian symptoms would abate.

The protocol required that a surgeon insert a needle through the volunteer's brain and inject small quantities of vector. But you didn't need to be a brain surgeon to recognize the peril. This would be the first administration of AAV vectors to the brains of non-terminal patients, and the investigators could not rule out the possibility that the vector might trigger an autoimmune reaction. Nor, according to members of the RAC, had the investigators decisively established the efficacy of their intervention in non-human primates. Though the RAC never formally advised against initiating the study, controversy trailed the team out of Bethesda. When the study was initiated in 2003, several leading Parkinson's disease researchers denounced it as “a crazy experiment” and “terra incognita.”. Another accused the lead researcher of “raising hopes in people with minimal evidence of benefits.”