1. NAS Committee on Gene Editing
Carrie D. Wolinetz, PhD
Associate Director for Science Policy
National Institutes of Health

2. Three simultaneous conversations
Gene editing for germline modification
Gene editing for human gene therapy
Gene drives (but that’s a different committee’s problem….)

3. Germline modification
April 29, 2015: “NIH will not fund any use of gene-editing technologies in human embryos.” –Francis Collins
“The NIH will not at present entertain proposals for germline alterations…” – Guidelines, Appendix M

4. Gene editing and the Guidelines
NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules
Covered:
Basic research involving recombinant vectors/plasmids and/or expression of gene editing components (e.g., generation of transgenic organisms).
Human gene transfer involving vectors/plasmids or expression of gene editing components

5. But….
Use of gene editing technology without a vector could fall outside the Guidelines under the basic research exemption

6. IOM report of the RAC, 2013
“The IOM committee finds that the major concerns about recombinant DNA from 40 years ago do not raise the same level of concern today, as hundreds of gene therapy clinical trials have evaluated the technique’s safety and effectiveness.”
“Exceptional cases that would warrant RAC review would be those that otherwise could not be adequately reviewed by other regulatory and oversight processes such as IRBs, IBCs, and FDA and that meet one or more of the following criteria:
The protocol uses a new vector, genetic material, or delivery methodology which represents a first-in-human experience, thus presenting an unknown risk.
The protocol relies on preclinical safety data that were obtained using a new preclinical model system of unknown and unconfirmed value.
The proposed vector, gene construct, or method of delivery is associated with possible toxicities that are not widely known which may render it difficult for local and federal regulatory bodies to rigorously evaluate the protocol.”

7. Oct 2015 – FR proposal RAC reform
Registration and review of human gene editing research under proposed amendments
Protocols will continued to be registered with OSP
RAC review will be initiated if an oversight body determines that a protocol would significantly benefit from RAC review, and one or more of certain criteria are met (i.e., use of new vector, genetic material, or delivery, relies on preclinical safety data of unknown value, associated with toxicities that are not widely known). If the NIH agrees that the criteria are satisfied, the NIH Director will convene the RAC for public review and in-depth discussion of the protocol.

8. IOM on emerging technologies
“Therefore, the IOM committee recommends that the NIH Director consider exploring the necessity of oversight of applications of other emerging areas of science in human clinical intervention in addition to gene transfer.”

9. Thinking deep thoughts..
What about the Guidelines?
Overlap with rules/regs of today
State of the science
IBCs, Public convening power of the RAC
If Asilomar was held today, what would an oversight system look like?