Recombinant DNA Advisory Committee - 09/14-15/92 
embodying their concerns, and suggested that the resolution should be submitted for 
consideration at the next RAC meeting. The resolution recommends that the NIH 
establish uniform standards for the payment of medically related costs for injuries arising 
out of non-therapeutic biomedical research. Dr. Walters said that he supported Dr. 
Zallen's proposal. 
Dr. Leventhal suggested that Data Management reporting should also be included as an 
agenda item for the next RAC meeting. 
VI. PRESENTATION: RADIATION AND MUTATION RATES IN HUMAN 
POPULATIONS/DR. NEEL 
Dr. Wivel explained that the HGTS formed a working group to discuss germ line gene 
therapy issues. These discussions resulted in a proposal to invite a series of experts to 
speak on issues that are relevant to the area of germ line gene therapy. While germ line 
gene therapy cannot be considered an imminent procedure, it is not premature to begin 
to discuss these issues in the event that this type of therapy becomes a reality. Since the 
RAC voted to merge the subcommittee with the parent committee, it is appropriate that 
these presentations be made to the RAC. He presented the first in this series of expert 
speakers, Dr. James Neel, a population geneticist from the University of Michigan. 
Presentation--Dr. Neel 
Dr. Neel noted that a relevant issue for the discussion of germ line therapy is an analysis 
of spontaneous and induced genetic mutations. Spontaneous mutation data reveals the 
frequency of DNA mutations in the absence of external factors, whereas induced 
mutation data reveals the magnitude of the response to known perturbing factors. 
Conclusions can be drawn regarding the homeostatic properties of the genome. Despite 
considerable research, there is a significant amount of information that needs to be 
obtained about the frequency of human germ line mutation rates. 
Functional genes have a mutation rate between 1 to 2 x 10' 5 per gene per generation. 
With 50,000 functional genes, a newly fertilized egg has two to four point mutations in 
these functional genes. At the DNA level, the frequency of spontaneous mutation for 
nucleotides is 1 to 2 x 10 -8 per generation. With 3 x 10 9 nucleotides in the haploid 
genome, this corresponds to 30 to 60 mutations per gamete and 60 to 120 per zygote. 
Many of these mutations occur in DNA with little functional consequence, but the 
remainder will occur in DNA whose integrity must be maintained. 
Purines and pyrimidines are constantly being displaced from the DNA. Purines are 
displaced at the rate of 3 x 10' 11 per second, suggesting remarkable stability for any 
specific site. Mammals lose approximately 10,000 purines from their DNA every 20 
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