THE JOHNS HOPKINS UNIVERSITY 
BALTIMORE. MARYLAND 21218 
MERGENTHALER LABORATORY 
FOR BIOLOGY 
November 2k, 1977 
Dr. Donald Fredrickson 
Director, National Institutes of Health 
c/o Office of Recombinant DNA Activities 
National Institute of Allergy and Infectious Diseases 
NIH 
Sethesda, Maryland 2001U 
Dear Dr. Fredrickson, 
As a scientist having worked in microbiology and in bacterial genetics 
for some 25 years, I would like to make some comments on the Prooosed Revised 
Guidelines on Recombinant DNA Research (Federal Register, Vol. U2, No. IS 7 — 
Tues., Sept. 27, 1977, pp. U9596-U9609) and on closely related matters. I 
request that these comments be made available to the Advisory Committee for 
consideration in its deliberations beginning December 15th. 
(1) The Proposed Guidelines should be strengthened with regard to provisions 
for the handling of recombinant DNA molecules once separated from their hosts 
or vectors (Sec. 111-3-5). Most of the recombinant DNA molecules are going to 
be small, circular reolicons that can easily invade, and renlicate in, bacteria 
ubiquitous to the environment. It is utterly absurd to specify PI containment 
for nuclease-protected, small circular molecules while, at the same time, 
carefully clearing "safer" cloning vehicles.' Instead of 3 1 classification, 
DNA molecules free of vectors should be classified at one step in ohysicai 
containment lower than that soecified for the DNA-vector-host comnlex itself. 
AFTER the DNA of interest has been seoarated from the reolicon (AND made 
linear), ONLY THEN should the DNA be allowed a second-steo lower classification, 
but only after clearance with the local 3iohazards Committee. I do not think 
that discussions of recombinant DNA have adequately addressed this point, not 
is either version of the Guidelines truly cognizant of this quaint "loophole". 
(2) All research and oroduction involving biochemically synthesized recombinant 
DNA molecules in the U.S.A. diould be made subject to NIH Guidelines and 
reporting. The Guidelines should be clearly applicable to such research wherever 
conducted and regardless of its ausoices, public or private. I believe strongly 
that new legislation will be required to make this ruling effective, all-inclusive, 
unhindered by minor and obscure prior legislation, non-subject to obstructive 
legal action whether pertinent or not, and clearly understandable and enforceable. 
Laws have indirect value in changing attitudes (and the attitudes of many 
scientists do need changing), as perhaps best seen in recent years in Civil Rights 
legislation. It is not true that "if people are going to break codes of practice 
or codes of honor in this area, they will break the laws" (p. 520, "Recombinant 
Molecules" 1977). Scientists working in the field know that the "code" already 
has been broken a number of times or the rules stretched almost beyond belief. 
The Guidelines need the force of law not only to implement their extension beyond 
NIH-funded research but, also, to encourage strict compliance within a more 
select segment of the scientific community. No "sunset clause" is necessary or 
realistic. Science will not find all the answers "tomorrow"; the new, oroposed 
Guidelines are highly adaptable. 
[Appendix A — 81] 
