DNAREF1.ASK doc 4
Donald 8. Fredrickson. "An overview of the role of NIH and other Federal
Agencies in the conduct of research with recombinant dna." in National Academy
of Sciences (U.S.), Research with recombinant DNA/G: an Academy forum, March 7-
9,1977. NLM Call number QU 58 745r 1977. location: dna\dna77\foruns

This forum was organized by Robert R. White with David Hamburg as co-chair.

The invited speakers included: Daniel Koshland, John Abelson, Maxine Singer,
Daniel Callahan, Erwin Chargaff, David Nathans, Alexander Rich, Paul Berg,
Robert L. Sinsheimer, FRancisco Ayala, Sir JOhn Kendrew, Stephan Toulmin,

BRuce Dull, Bernard Davis, Delbert Barth, Anothony Mazzocchi, Irving S.
Johnson, Ruth Hubbard, Raymond Cc. Valentine, Ethan R. Signer, DAvid Baltimore,
gOhnathjan Beckwith, Roger G. Noll and Paul A. Thomas, with a summary by Tracy
M. Sonneborn, and final comments by Donald Kennedy (then FDA Commissioner). The
were many commentators from the floor, including Jeremy Rifkin (with his chorus
of girls decked out in placards "I will not be cloned") and Francis Simring, my
nemesis from the Friends of the Earth.

Professor Bengt Gustaffson of the Karolinska much later told me that he was
there and that when I got up to say what the government was and would do, that
"It was like the Romans".

I did not feel like Hannibal or Pontius at this hearing--yet I left some
impression that we were in control of the situation. Even Mrs. Simring was not
too critical of us:

Francine Simring: I would like to congratulate the NIH and Dr. Fredrickson on
the wonderful job they have done of disseminating materials, transcripts, and
Xeroxs to all interested parties... many nations are looking to the United
States for leadership ...(the IAC listed registration of such research with a
national registry.) However there is a parenthetical opening for indusrtry that
read as follows: "Subject to appropriate safeguards to protect proprietary
interests."...

Fredrickson: Thank you, Mrs. Simring. I'm glad to meet you, even at this
distance, and I hope to close the gap between us...

Later Kennedy commented on the IAC process.

TS > .
(anit ccponks r Sv Vie
Lo nce nN tru Ty

PROBLEMS OF CONTROL AND
REGULATION,

 

AN OVERVIEW OF THE ROLE OF NIH AND OTHER FEDERAL AGENCIES
=IN THE CONDUCT OF RESEARCH WITH RECOMBINANT DNA

Donald s. Fredrickson

Director, National Institutes of Health *

I am very grateful for the opportunity to summarize something about the
government process in this matter which you have been discussing through-
out this Forum.

Covernments in general, and the federal government in particular,
entered the matter of recombinant DNA research several years ago when,

- after Asilomar as you recall, one of the recommendations of the scien-
tists was that the NIH forma committee that might begin to set up
guidelines to establish strict conditions for the conduct of research
that involved the use and production of recombinant DNA molecules.
These guidelines were developed by a recombinant DNA committee, and
after extensive scientific and public review the NIH released them on
June 23, 1976.

The provisions were designed to afford protection with a wide margin
of safety to workers and to the environment. The NIH guidelines were
published in the Federal Register on July 7, 1976, for public commen t.

In September the NIH also filed a draft environmental impact state-
ment on the guidelines for public comment, and the final NIH environ-
Mental impact statement we expect to be published shortly. As many of
you are aware, in August 1976, a volume was published by the NIH that
contains the transcript of a public hearing held on the guidelines as

255
well as all correspondence received by my office on this matter prior
to the release of the guidelines in June. And there will be a Subse~
quent publication of all correspondence and many other related documents
to continue this complete public record of government action in regarg
to recombinant DNA research.

By the time the environmental impact statement had been issued and
the guidelines released, it was already apparent that the internationa}
community of science had come to agreement that recombinant DNA techniques
should be used only with a common set of standards across the world.

The question was how to bring this about. And as matters of this sort
are often settled, first the boundaries of activity were restricted to
those maximum ones in which the law can be operable across a population,
and hence most countries settled down to attempt to enter this secong
phase for themselves before seeking further international comity and
conformity with particular standards.

At the time the NIH guidelines were released there was convened by
the Secretary of Health, Education, and Welfare an Interagency Committee
on Recombinant DNA Research. The committee was formed with the approval
of the President, and at the Secretary's request I have served as
chairman.

Now, this Interagency Committee is composed of representatives of
the federal departments and agencies that do several things. One com-
ponent is made up of those agencies that support or conduct recombinant
DNA research, or may do so in the future. Another group includes the
representatives of all the federal departments and agencies that have
present or possibly potential regulatory authority in this area. And to
these are added a number of other departments, such as the State Depart-
ment, the Department of Justice, and others that have particular interest
in the general aspects of the committee's affairs. There are approxi-
mately twenty-five member agencies that make up this committee.

The mandate of the Interagency Committee is to review the nature and
scope, particularly of the federal activities, relating to recombinant
DNA research. Second, the committee was directed to determine the extent
to which the NIH guidelines may currently be applied to research in both
the public and the private sectors. It was to recommend, if approrriate,
legislative or executive actions necessary to ensure compliance with the
standards set for this research, and to provide for the full communication
and necessary exchange of information on recombinant DNA research programs
and activities throughout the federal sector.

The Interagency Committee held its first full meeting last November,
and during that month it had a second meeting. The first of those
meetings was held on November 4 and was devoted to a review of the devel-
opment of the NIH guidelines for research involving recombinant DNA mole-
cules. At the same meeting the committee also reviewed in extenso
international activities relative to this same matter. I will not re-
peat that review, because I understand you are to have a report of a
workshop which will summarize it for you in much greater detail than I
can now. But the committee was fully aware of activities relative to
this matter not only in this country but abroad.
257

At the meeting of the committee held on November 23, the federal
research agencies then discussed their activities and possible roles in
the implementation of the NIH guidelines. All of the research agencies
endorsed the NIH guidelines to cover the recombinant DNA research that
they conducted or funded. Three agencies of the federal government are
now supporting research that involves the use of these techniques, the
NIH, the National Science Foundation, and the Department of Agriculture.
The Department of Defense, NASA, and the Energy Research and Development
Administration are not at present conducting such research, but agreed
to use the NIH guidelines to govern future research should they under-
take it.:

In that November 23 meeting the federal regulatory agencies also
reported on their regulatory functions. Following that lengthy review
a special subcommittee was set up to analyze the relevant statutory au-
thorities for the possible regulation of recombinant DNA research. All
regulatory agencies were represented on that subcommittee, and their
representatives were assisted by attorneys from their offices of general
counsel.

The subcommittee was charged to find out whether existing legislative
authority would permit the regulation of all recombinant DNA research in
the United States, whether it was funded by the government or not, and
to seek out whether or not those existing legislative authorities would
include at least the following requirements perceived by the committee
to be important: review of such research before it is undertaken by
an institutional biohazards committee; compliance with physical and
biological standards and prohibitions in the NIH guidelines; registra-
tion of such research in a national registry; and enforcement of the
above requirements through monitoring, inspection, and some sanctions.

It was the conclusion of this subcommittee after extensive review
that present law permits imposition of some of the desired requirements
on much recombinant DNA laboratory research, but no single legal author-
ity or combination of them currently exists that would clearly cover all
research or other uses of recombinant DNA techniques and meet all the
other requirements. The committee examined, first of all, the Occupa-
tional Safety and Health Act, and found that while OSHA has broad
authority it has limited access to many of the laboratories, and it does
not ‘cover self-employed persons. The Environmental Protection Agency
under the Toxic Substances Control Act is directed to contrel chemicals
that may present an unreasonable risk of injury to the health or the
environment. The subcommittee found that probably most recombinant DNA
molecules could come under the definition of chemicals; however, Section
5 of the Toxic Substances Act explicitly exempts registration of chemi-
cal substances used in small quantities for the purposes of scientific
experimentation or analysis. The latter exemption represents the most
serious deficiency in the authorities of that act for the purposes of
regulating the use and production of recombinant DNA molecules.

The Hazardous Materials Transportation Act was also examined. It
gives the Department of Transportation and the Center for Disease Control
in Atlanta considerable authority over interstate shipment of hazardous
258

materials but, indeed, there were many aspects of this act which are
wanting in regard to regulation of recombinant DNA research.

The Environmental Defense Fund, in November of 1976 petitioned the
DHEW to regulate recombinant DNA research under Section 361 of the Publig
Health Service Act, and this petition was filed with the Interagency .
Committee for its consideration. Under this section the authorities are:
restricted to organisms that are communicable and cause human disease. °
To use Section 361 for regulatory authority one would have to assume
that recombinant DNA research may cause human diseases and that these
may be communicable. Further, Section 361 does not apply to plants
or animals or the general environment. It was the conclusion of the
committee that Section 361 lacks the requisite authorities.

The same is true of Section 353 of the Public Health Service Act.

This applies to clinical laboratories, but it is not considered to be
applicable to research laboratories.

Many other authorities, particularly of the EPA and of other agencies
including the Food and Drug Administration, were examined, as were the
powers of the Department of Agriculture, whose authorities were found
applicable solely to nonhuman life and plants.

In summary, the Interagency Committee concluded that no single
authority or combination of authorities currently exists that could
clearly reach all recombinant DNA research in a manner that the commit-
tee deemed was appropriate. It was agreed that regulatory actions could =
be taken under existing authorities, but that they would be in consider-
able jeopardy of legal challenge. -

The full committee then adopted the report of the subcommittee, agree-
ing with its conclusion about existing authority. It then turned its
attention to examining possible new legislation. In considering elements
for new legislation the committee reviewed federal, state, and local
actions and activities that bear on the regulation of DNA research. In
addition to activities in municipalities such as Cambridge, it received
a report from the New York State Attorney General's Environmental Health
Bureau for State Regulation, which made certain recommendations for
regulation in New York State. The committee was aware of the hearings in
the California legislature, and it also was able to examine legislation
now submitted to the Congress, specifically Senate Bill 621, the DNA
Research Act of 1977, introduced by Senator Dale Bumpers, and the com-
panion measure introduced into the House by Mr. Ottinger.

The committee also had available to it comments elicited by its
various members from a number of persons whose opinions were sought
concerning questions relative to legislation. These sources included
agricultural scientists, biomedical scientists, environmentalists, and
leaders from labor unions and private industry. In the light of this
background the committee has been considering in its most recent meetings
what should be the elements of new legislation that might cover the
regulation of the use and production of recombinant DNA molecules. It
has had to consider issues of definition, the question of registration
of all activities, and the question of whether licensure might be an
effective part of a regulatory process, and it has dealt strongly with
259

aspects of interagency cooperation. It also has had to deal with the
difference or the distinction between research and commercial use of
recombinant DNA products, particularly because many commercial aspects
are clearly covered by existing legislation or authority invested in the
Environmental Protection Agency and the Food and Drug Administration.

It has also had to contend with the fact that the NIH is not a regulatory
agency and that it has no intention of becoming one, and that it would be
inappropriate for NIH to assume inspection and enforcement authorities
when it has participated in standards setting.

The Interagency Committee meets again tomorrow. We expect and hope
that it may produce an interim report dealing with some recommendations
with respect to legislation within a week. Then the committee will turn
to other agenda relative to this problem, and at some point will probably
self-destruct when it has carried out fully the terms of its mandate.

In brief, there is a strong and active focus within the executive
branch to formulate recommendations to help set federal standards, which
I think to be very much needed, with regard to the regulation of the
use and production of recombinant DNA molecules. The task has not been
simple. The committee has recognized its responsibility to protect fully
the public interest. It recognizes that recombinant DNA activities can
pose some threat to workers, to the general population, to the environment,
and also to a creative and responsible scientific apparatus. Thus, the
task of recommending appropriate, effective, and reasonable legislation
for regulation of this activity is a matter of very grave concern.

DISCUSSION

NORTON ZINDER, Rockefeller University: I would like to support, and I
am surprised that I am going to do so, the idea of having legislation,
federal legislation, with regard to recombinant DNA research. The
proliferation of local option with different guidelines in different
states and different cities can only lead to a situation of chaos,
confusion, and ultimately to hypocrisy amongst the scientists involved.
I strongly plead that the government move ahead on this as rapidly as
possible.

FREDRICKSON: Thank you, Dr. Zinder.

AL PLUMMER, retired civil engineer: I am neither for nor against rapid

research in recombinant DNA. I am here to learn what the facts are

so as a private citizen I can choose sides when it becomes appropriate.
I have listened to 85 percent of the discussion, and so far I have not
been able to identify who in the federal government is responsible for
bringing together in one comprehensive document all the history, facts,
alternative pathways, along with calculations, as best they can be
made, of benefits and costs and the environmental impacts of this
260

problem. In other words, who is doing the planning that will point
out where we are going so that we as private citizens can make inte]~
ligent decisions? Is there a group planning what kind of a program
would be appropriate for the nation as a whole? I understand you
are dealing with regulation and setting standards, and that is fine,
but it doesn't really attack the problem of where we are going with
this. Is it good? Is it bad? What are the problems? Can you tell
me who is going to come up with a document?

FREDRICKSON: Yes, Mr. Plummer. First of all, several documents have al~
ready been issued which may be helpful to you. I referred to two of
them. One is the NIH preparation of the history relative to its
guidelines. The second is the environmental impact statement issued
relative to its guidelines. The Interagency Committee now contains
all the elements of the federal supporters and conductors of this
research, and probably they are responsible for at least 90 percent
of the research that is doubtless going on at the present time in this
country. They will be reporting to the Secretary of Health, Educa-
tion, and Welfare, in whose office now, as this matter ascends higher
up in the Department, will be the next focus for disseminating and
developing some of the considerations that you represent. A third
focus will open up next week when the Congress of the United States
will, I think, have the first of a number of hearings on this whole
matter of recombinant DNA research. I believe that there are several
committee hearings that are scheduled or are about to be, which will
deal not only with the matter of legislation, but also the general
aspects of the recombinant DNA research. Finally, we have been this
week, and I expect to return to, the Appropriations Committee in the
House, and the Senate next week, where we have also been answering a
number of questions of the kind that you have posed.

PLUMMER: Well, my basic statement is that it is fragmented and it isn't
pulled together in such a way that we can quietly analyze it and come
to conclusions. As a result I see in this meeting that the opponents
and proponents are polarizing and that will lead to emotional situa-
tions, and it will get more and more difficult to resolve unless we
get the facts all laid out.

DAVID 0. KRASSIK, Engineering and Applied Science, UCLA: I am interested
in learning more about how one has established the adequacy of the
current NIH guidelines. My background is not biology or biochemistry,
and I have been listening to try to keep the words vector, phage, and
so forth apart in my mind.

I did go to the containment workshop last night and there tried to
find out whether there exist documents that would give details on
the efficacy of physical containment and biological containment, but
I was told no. I must confess, I was a little surprised at what
seemed to be the relative ineffectiveness of Pl to P3 containment,
assuming that there is a risk, and I have to rely on my medical and
biological colleagues to tell me that.
261

With regard to the biological containment, again, one hears numbers
of large factors, but again, there are uncertainties. So as I lis-
tened I found in my own mind no way of knowing as a result of these
few days how the guidelines were arrived at, how the kinds of questions
raised by Dr. Sinsheimer here at the Forum yesterday and previously
have been dealt with or are being dealt with in deciding that these
guidelines are adequate, that they are not too strict or not strict
enough. ‘

FREDRICKSON: Have you had opportunity to read the NIH guidelines, their
appendixes, and all of the comments relative to them?

KRASSIK: Yes, I have, but with my limited background I could only
digest part of it.

PREDRICKSON: If you will give us your name at the NIH one of the documents
that will be very helpful to you is the revised or final environmental
impact draft statement, which has addressed in detail comments of the
kind and questions of the kind that you have raised. The development
of both the guidelines in their final form and the environmental
impact statement have involved an exchange of correspondence and a
full attention to a wide range of public comment, each of which has
been addressed in the revised document.

FRANCINE SIMRING, Friends of the Earth: I would like to congratulate the
NIH and Dr. Fredrickson on the wonderful job they have done of dissemi-
nating materials, transcripts, and Xeroxes to all interested parties.
And in the interest of expanding the accuracy, I want to make three
short additions to what was said by Dr. Fredrickson.

You mentioned, I believe, that all correspondence was included in
the yellow volume of August. I believe we would have to make that
"some" correspondence in the interest of accuracy.

You mentioned that the nations settled down by themselves to do
their guidelines. A few did, but for the most part in the correspon-
dence that I read, many nations wrote to state they are looking to the
United States for leadership, and will follow the U.s. guidelines when
they are published. In the light of this afternoon's press conference,
I think that is particularly important.

The last point that I would like to make is that Dr. Fredrickson
mentioned that the Interagency Committee listed registration of such
research with a national registry. However, there is a parenthetical
opening for industry that reads as follows: "Subject to appropriate
safeguards to protect proprietary interests," which means that they
might not have to register their projects.

FREDRICKSON: Thank you, Mrs. Simring. I am glad to meet you even at this
distance, and I hope to close the gap between us.
indeed, the volume that I referred to does refer only to correspon-
dence relative to the guidelines. Many of the subsequent letters we
262

have received will have a broader base because More action has
occurred since that time. There will be another issuance. I know
that some of your correspondence will also appear there.

With respect to extension of the U.S. guidelines, it is true that
there are other countries that are using them, as well as the United
Kingdom guidelines. You will hear more about that, I am sure, in the
final description.

With respect to the matter of registration and the issue of proprie-
tary information, this is certainly one matter which the Interagency
Committee is discussing and will grapple with completely, you can be
sure.

AUDIENCE: Dr. Fredrickson, like many people I am beginning to share a

Mania against federal intrusion into so Many aspects, and I think it
is rare and unique for the American scientific community to actually
invite a federal incursion. Yet, with so Many recent experiences,
occupational safety and health and what have you, it has been proven
that the federal government is probably the least adept. I am happy
to see that you are working with the Hill on legislation, but you
just mentioned that the NIH doesn't have or want enforcement author-
ity regarding this work. Who would the legislation give it to? HEw?
Federal bureaucrats? Who is going to monitor it? I assume that there
will be legislation, but I hate to see an element of control removed
from the scientific community, and I wonder who they will award it to.

FREDRICKSON: I am not sure to whom it will be awarded either. But you

can be sure that this is a matter which the committee is now actively
considering and will deal with in its report.