17170 
Federal Register / Vol. 47, No. 77 / Wednesday, April 21, 1982 / Notices 
with pathogens has had an 
extraordinary safety record for decades. 
The reason there was so much interest 
in control of recombinant DNA is that 
recombinant DNA technology became 
available in the 1970s, in an era of 
regulation. He cited procedures for 
research involving human subjects, 
which changed drastically in the early 
1970s. He said he supports these 
constraints as they protect the public, as 
well as individual subjects, and they 
facilitate communication between the 
public and clinical investigators. He said 
being responsive to the public is very 
important and if a significant segment of 
the public is still concerned about 
recombinant DNA, this committee 
should be sensitive to that concern. He 
said that he would like to see something 
like the December 4, 1981, proposal 
ultimately adopted, but not immediately. 
Dr. Ahmed said he wished to quote 
and highlight several points from the 
letter from the Public and Scientific 
Affairs Board of the American Society 
for Microbiology. He quoted from that 
letter that, “Our concern is for the fact 
that only sparse information is available 
for other host-vectors. With less 
characterized systems, new 
combinations may result in organisms 
with potentially increased pathogenicity 
than either the donor or the recipient.” 
Dr. Ahmed further quoted, "We are not 
only concerned with the paucity of 
information but also with the lack of 
mechanisms for its dissemination. Many 
woricers using modem genetic 
technology are not versed in pathogenic 
microbiology and cannot be assumed to 
have proper training or access to up-to- 
date information.” 
Dr. Martin said he believed as a 
scientist that recombinant DNA should 
not be singled out for special oversight. 
However, this position must be viewed 
within the historical contest. He said 
that the State legislators and County 
supervisors with whom he had spoken 
are not primarily interested in the 
scientific basis for relaxation or 
eliminataion of the Guidelines, but 
rather in public opinion. RAC must be 
careful not to excite a public reaction 
that could result in greater bureaucratic 
and regulatory problems from local 
jurisdictions. 
Dr. Saginor said he would like to 
propose an amendment to the December 
7, 1981. proposal, should it pass, that a 
working group be formed to further 
refine, simplify and reorganize that 
proposal, and that this group report to 
the R.^C at a future meeting. 
A discussion was held of the proper 
parliamentary procedure for the 
Committee to use to proceed. Mr. 
Thornton suggested that the Committee 
might vote now on Dr. Nightingale's 
motion to substitute the December 7 
proposal for the December 4 proposal. 
This would result in the Committee 
choosing which "vehicle” it wished 
initially to adopt. Following this, RAC 
members could propose amendments to 
“perfect” the vehicle chosen, before the 
final vote on it. 
Dr. Baltimore “called the question.” 
By a vote of nineteen in favor, two 
opposed, and no abstentions, the RAC 
agreed to limit further debate and to 
vote on the motion to substitute the 
December 7, 1981, proposal for the 
December 4, 1981, proposal as the 
vehicle to be used for further 
amendments. Dr. Baltimore said that 
although, following this vote, any aspect 
of the winning proposal would be open 
for further amendments, he felt the vote 
should be viewed as a decision about 
whether “to go in the voluntary or 
mandatory direction.” Dr. Nightingale 
reminded the RAC that her motion 
included the commitment to work 
towards future simplification of the 
Guidelines. By a vote of sixteen in favor, 
five opposed, and no abstentions, the 
RAC adopted the substitute motion, thus 
choosing the Gottesman proposal as the 
vehicle to be placed before the 
Committee, open to further amendments. 
Mr. Thornton recognized Dr. Susan 
Wright. Dr. Wright focused her 
comments on large-scale applications as 
she thought that while many other 
issues are being addressed, the RAC 
was not adequately addressing that 
issue. She said the primary focus of RAC 
has been on the hazards of research, not 
the hazards of industrial processes. She 
said that one cannot dismiss change of 
scale with regard to accidental release 
of recombinant organisms. She felt the 
data base on industrial hazards is very 
poor. She said she had heard some 
industrialists in other countries were 
considering using open fermentation 
tanks. If there is no oversight, 
companies will use whatever 
fermentation process they think is in 
their best interest. There are 
irresponsible companies willing to cut 
comers and take risks to try to gain a 
competitive advantage over responsible 
companies. Furthermore, there are no 
risk assessment experiments with 
organisms making insulin, interferon, 
etc. She said the committee ia assuming 
that whatever product is being made 
will be harmless. 
Dr. Wright said the RAC 
recommendation at the previous meeting 
to exempt from NIH review, certain 
large-scale experiments utilizing E. coli 
K-12, Saccharomyces cerevisiae and 
Bacillus subtiHs host-vector systems 
was an error which produced a major 
gap in oversight. She urged the RAC to 
reconsider and re-evaluate its oversight 
over large-scale work. 
Dr. Irving Johnson of Eli Lilly and 
Company said that industry has 
produced hundreds of gallons of the 
causative agents of polio, diphtheria, 
whooping cough, etc., with no great 
hazard to workers or to the 
environment, and in fact with great 
benefit to the population. Dr. Johnson 
said the only open vats he is aware of 
are in the beer brewing industry. Most 
industrial fermentations are generally 
highly contained to protect against 
contamination. Inocula are introduced 
into the growth tank through a rigid 
stainless steel structure. The connection 
does not leak and is steam sterilized. 
Dr. Wright said she was not making a 
categorical statement about hazards, but 
rather about the data base. In her 
opinion, the data are extremely poor 
and incomplete, and assumptions that 
problems will be uncomplicated or easy 
to deal with are premature. These new 
technologies should remain under RAC 
review until a better data base develops. 
Dr. Mason said that many industrial 
issues, though of concern, are beyond 
the scope of the RAC. Local, State or 
Federal authorities that make on-site 
inspections may wish to evaluate these 
issues, but RAC should not. Dr. Ahmed 
felt a distinction should be drawn 
between organisms concentration and 
total amount in industrial processes. 
Dr. Gottesman said that the December 
7, 1981, proposal still requires that non- 
exempt large-scale procedures be 
reviewed by the local IBC before the 
project begins, and PI-LS containment 
would still apply. It extends to all large- 
scale experiments the conditions 
approved by RAC at the previous 
meeting for certain large-scale 
experiments. 
Dr. Bems questioned the language of 
Section I-B, Definition of Recombinant 
DNA Molecules, in the December 7, 
1981, proposal. The relevant text of 
Section I-B reads as follows: 
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 
polynucleotide or polypeptide product, it is 
exempt from the Guidelines. 
Dr. Gottesman pointed out that this is 
a reformulation of text which appears as 
Section III-E of the current (July 1, 1981) 
Guidelines. Dr. Bems suggested the real 
issue is whether the synthetic fragment 
would produce a biologically active 
product; he proposed to amend the 
[ 404 ] 
