THE UNIVERSITY OF CHICAGO 
DEPARTMENT OF BIOPHYSICS AND THEORETICAL BIOLOGY 
CUMMINGS LIFE SCIENCE CENTER 
920 EAST S8TH STREET 
CHICAGO • ILLINOIS 60637 
16 August 1978 
Dr. Donald S. Fredrickson 
Office of the Director 
National Institutes of Health 
Bethesda, Md. 20014 
Dear Dr. Frederickson: 
I should like to comment on the proposed revised guidelines for recombinant DNA 
research published in the Federal Register on July 28, 1978. For the record I should 
mention that the majority of my publications over the past 20 years have been on 
viruses that infect plants or bacteria or, more recently, blue-green algae. I was a 
member of the Virology Study Section in the early 1970's and ^ its current chairman, 
tfy- comments follow the contents of the revised guidelines. 
I. Scope of Guidelines . This section is a spectacular improvement over the original 
guidelines. I applaud the language of the statement of purpose and the definition of 
recombinant DNA molecules. The section on prohibited experiments seems reasonable, 
except for I-D-3 which prohibits creation of a plant pathogen with increased virulence. 
There are some experiments involving cloning fragments of the Ti plasmid of Agrobacterium 
tumefaciens that might be interpreted as prohibited under this section but which are, 
to me, both important and safe. As long as the Director has the power to grant exceptions 
from this prohibition, and is willing to use that power, I think we can accept the 
prohibition. 
I support wholeheartedly the decision to exempt all "self-cloning” experiments from 
the guidelines. That should relieve both the institutional committees and the RAC of a 
mountain of unneeded paperwork. 
I also agree with the list of exempted organisms given in Appendix A although I would 
prefer to see it expanded to include all the organisms on the RAC third list, in 
appendix D to the Environmental Impact Statement (p. 33158). Furthermore, I would like 
to see acceptance of the principle that transfer of an R plasmid from an organism to 
E,. coli K12 is a sufficient criterion for addition to the exempted list. 
II. Containment ♦ This section is also vastly improved. Particularly important is the 
clarification of the data to be submitted for certification of biological containment 
level. Of course the procedure will really be improved only if the RAC meets regularly 
and reviews the submitted data in timely fashion. 
III. Containment guidelines for covered experiments . I have read all the new guidelines 
without encountering a single item to complain about. It is particularly important to 
me that the experiments of section III-A-l-b(2) remain no higher than P2+EK1, that the 
recombinant DNA be returnable by transformation to the cell of origin of the cloned 
insert, and that the IBC be empowered to lower containment when the cloned material 
contains no harmful genes. I was also glad to see, in section III-C-2, that the silly 
business about using insect viruses as vectors for other DNA segments was removed. The 
section as written is now appropriate. 
[A-18] 
