Book contents
- Frontmatter
- Contents
- Acknowledgments
- List of abbreviations
- 1 Introduction: gene transfer lost in translation
- 2 What is gene transfer?
- 3 Safety, values, and legitimacy: the protean nature of risk in translational trials
- 4 Taming uncertainty: risk and gene-transfer clinical research
- 5 Succor or suckers? Benefit, risk, and the therapeutic misconception
- 6 Looking backward: a model of value for translational trials
- 7 The chasm: the ethics of initiating first-in-human clinical trials
- 8 Tropic of cancers: gene transfer in resource-poor settings
- 9 Great Expectations and Hard Times: expectation management in gene transfer
- 10 Something in the sight adjusts itself: conclusions
- Epilogue
- Index
7 - The chasm: the ethics of initiating first-in-human clinical trials
Published online by Cambridge University Press: 28 January 2010
- Frontmatter
- Contents
- Acknowledgments
- List of abbreviations
- 1 Introduction: gene transfer lost in translation
- 2 What is gene transfer?
- 3 Safety, values, and legitimacy: the protean nature of risk in translational trials
- 4 Taming uncertainty: risk and gene-transfer clinical research
- 5 Succor or suckers? Benefit, risk, and the therapeutic misconception
- 6 Looking backward: a model of value for translational trials
- 7 The chasm: the ethics of initiating first-in-human clinical trials
- 8 Tropic of cancers: gene transfer in resource-poor settings
- 9 Great Expectations and Hard Times: expectation management in gene transfer
- 10 Something in the sight adjusts itself: conclusions
- Epilogue
- Index
Summary
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.”
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- Chapter
- Information
- Gene Transfer and the Ethics of First-in-Human ResearchLost in Translation, pp. 110 - 131Publisher: Cambridge University PressPrint publication year: 2009