53268 
Federal Register / Vol. 53, No. 251 / Friday. December 30. 1988 / Notices 
Crobatein C. and Flower M.: 1984. "Gene 
therapy: proceed with caution". Hastings 
Center Report. 14(2). 13-17. 
Kevles D.J.: 198S. In the Name of Evgenies. 
Alfred A. Knopf. New York. 
Ludmerer K.M.: 1972. Genetics and American 
Society. The Johns Hopkins University 
Press. Baltimore. 
Manipulating life: ethical issues in genetic 
engineering. 1982. Church and Society. 
World Council of Churches. Geneva. 
Mercola K.E. and Cline M.J.: 1960. "The 
potentials of inserting new genetic 
information". New England Journal of 
Medicine 303. 1297-1300. 
Miller H.I.: 1983. "Gene therapy: not to be 
feared or over-regulated". Bio/Technology. 
June. 382. 
Motulsky AG.: 1983, “Impact of genetic 
manipulation on society and medicine". 
Science 219. 135-140. 
National Commission for the Protection of 
Human Subjects of Biomedical and 
Behavioral Research: 1978. The Belmont 
Report. Ethical principles and guidelines 
for tbe protection of human subjects in 
research. U.S. Government Printing Office. 
Washington. DC DHEW publication no. 
JOS) 78-0012. 
Nelson J.R.: 1984. "From genesis to genetics: a 
theological-ethical exercise", in Human 
Life — .4 Biblical Perspective for Bioethics. 
Fortress Press. Philadelphia, pp. 155-173. 
Parliamentary Assemply of the Council of 
Europe. 33rd Ordinary Session. 
Recommendation 934 (On genetic 
engineering). 1982. 
Pope John Paul II: 1982. Statement to the 
Pontifical Academy of Sciences (10/23/82). 
"Biological research and human dignity". 
Origins 12. 342-343. 
Pope John Paul 11: 1983. Statement to the 
World Medical Association (10/29/83). 
“The ethics of genetic manipulation". 
Origins 13. 385-389. 
President's Commission for the Study of 
Ethical Problems in Medicine and 
Biomedical and Behavioral Research: 1982. 
Splicing Life. U.S. Government Printing 
Office. Washington. DC 
Rifkin ]- 1983. Algcny. Viking Press. New 
York. pp. 14. 23. 228. 231-234. 
Shinn R.L: 1978. “Gene therapy: ethical 
issues", in W.T. Reich (ed.) Encyclopedia 
of Bioethics. Free Press. Macmillan. New 
York, pp 521-527 
U.S. Congress: 1982. Human Genetic 
Engineering. Hearings Before the 
Subcommittee on Investigations and 
Oversight of the Committee on Science and 
Technology. U.S. Government Printing 
Office. Washington. DC pp. 2301-2346. 
U.S. Congress: 1984. Human Gene Therapy — 
A Background Paper. Office of Technology 
Assessment. U.S. Government Printing 
Office. Washington. DC p. 47. 
Wade N.. 1982a. "Whether to make perfect 
humans". New York Times. July 22. p. A22. 
Wade N.: 1982b. "The rules for reshaping 
life". New York Times. December 29. p. 
A 28. 
Walters L: 1988. 'The ethics of human gene 
therapy". Nature 320. 225-227. 
Williams D.A. and Orkin S.H.: 1988. "Somatic 
gene therapy: current status and future 
prospects". Journal of Clinical 
Investigation 77. 1053-1056. 
Williamson R-: 1982. "Gene therapy". Nature 
298. 415-118. 
VII. Proposed Amendment of Section-I- 
ll — Definition of Recombinant DNA 
Molecules 
Section 1-B of the NIH Guidelines 
currently reads as follows: 
"1-B— Definition of Recombinant DNA 
Molecules 
"In the context of these Guidelines, 
recombinant DNA molecules are defined 
as either (i] molecules which are 
constructed outside living cells by 
joining natural or synthetic DNA 
segments to DNA molecules that can 
replicate in a living cell, or (ii) DNA 
molecules that result from the 
replication of those described in (i) 
above. 
"Synthetic DNA segments likely to 
yield a potentially harmful 
polynucleotide or polypeptide (e.g.. a 
toxin or a pharmacologically active 
agent) shall be considered as equivalent 
to their natural DNA counterpart. If the 
synthetic DNA segment is not expressed 
in vivo as a biologically active 
polynucleotide or polypeptide product it 
is exempt from the Guidelines." 
The National Wildlife Federation has 
submitted a request that the NIH 
Guidelines "be expanded to encompass 
research involving organisms 
engineered by techniques other than 
recombinant DNA.'* 
The letter proposing this change is as 
follows: 
The NWF requests that the National 
Institutes of Health (NIH) Recombinant DNA 
Advisory Committee (RAC) recommend to 
the NTH Director that the Guidelines for 
Research Involving Recombinant DNA 
Molecules ("Guidelines") be expanded to 
encompass research involving organisms 
engineered by techniques other than 
recombinant DNA. 
Expanding the scope of the Guidelines is 
necessary because recent advances in 
science have added to the list of techniques 
capable of producing genetically novel 
organisms. A growing number of such 
organisms are not subject to the current 
Guidelines, which provide oversight only of 
those organisms formed by narrowly definpd 
recombinant DNA techniques. Like 
recombinant DNA these new techniques will 
produce organisms that may pose human 
health and environmental risks. 
We readily acknowledge the difficulty of 
defining the scope of NIH guidelines in an era 
of rapid technological change. Although there 
may be other approaches, to begin the 
discussion, we propose that Section l-B of the 
NIH Guidelines. Definition of Recombinant 
DNA Molecules, be replaced by a new 
section bringing within the scope of the 
guidelines all organisms into which foreign 
DNA has been stably integrated, regardless 
of technique. We do not propose particular 
language because we believe that tho precise 
contours of the Guidelines would benefit 
from thorough discussion by the RAC. 
Background 
The Guidelines were developed in 1978 to 
provide standards of safety in research with 
recombinant DNA techniques. The purpose of 
the Guidelines was to protect researchers 
and the public from potential hazards to 
human health and the environment posed by 
genetically novel organisms. 1 
The central concern of the Nil I was the 
genetic novelty of the organisms created by 
recombinant DNA techniques. As the NIH 
stated in its 1977 Environmental Impact 
Statement on the Guidelines (2). "Jcjoncem 
over the potential for hazard in organisms 
containing recombined DNA develops from 
the central idea that such recombinants will 
be unique types of organisms, not normally 
arising in nature, and that their properties 
will therefore be unknown and 
unpredictable." 
As there was only one technique capable 
of providing transgenic organisms in 1970. the 
Guidelines are written to cover only that 
technique. Current Guidelines (3) apply only 
to recombinant DNA molecules, which they 
define as either (i) molecules which 
arc constructed outside living cells by joining 
natural or synthetic DNA segments to DNA 
molecules that can replicate in a living cell, 
or (ii) DNA molecules that result from the 
replication of those described in (i) above." 
This definition captured most genetically 
novel organisms for review because the 
recombinant DNA technique depends on 
joining the foreign DNA to be transferred to 
vector DNA outside of living cells. 
The New Transgenic Techniques 
Since that time, scientists have developed 
other gene transfer techniques (e.g.. 
electroporation, microprojectilc techniques, 
microinjection, chemical poration. cell fusion) 
that can produce genetically novel organisms 
but will not necessarily involve "a joining of 
natural or synthetic segments to DNA 
molecules" outside living cells. References 4- 
13 provide a sample of techniques currently 
capable of producing so-called transgenic 
organisms — those with DNA from dissimilar 
parent organisms. 
The key to these new transgenic techniques 
is that they are not dependent upon vectors 
to transfer the foreign DNA. Although these 
techniques are not yet well understood, it is 
known that small pieces of foreign DNA 
introduced into a cell without vectors can 
become incorporated into ihe chromosomes 
and be expressed. 
As a result of these advances, transgenic 
organisms may be produced by a number of 
techniques, including, but not limited to 
recombinant DNA. Transgenic techniques 
that do not require "recombinant DNA" 
procedures produce organisms that can be 
1 The 197ft "th-cisloo of the Director. NIH. to 
Release Guidelines for Research oo Recombinant 
DNA Molecules" (1. p 279(v»| declared that "(l|h«- 
object of these guidelines is to ensure that 
experimental DN A recopibixalion will have no HI 
effects on ibose engaged in the *voA. on the genmil 
public, or nn the environment”. 
Recombinant DNA Research, Volume 13 
[329] 
