.. 6 . . -*. a._ . .7 . c -.. i" ^' .. ; ; ICY' - : i c 8 9 10 11 12 :13 14 4 14 17 18 . 15 _' . . -'20 . .21 -. c 22 C. . . -:.. L .: . . .* `# . 23 BILLS H.R. 4759, H.R. AND H.R. 4232 ---a--------- THURSDAY, MARCH 17, 1977 -..- La . -------w.----- * House of Representatives Subcommittee on Health and the . . Environment of the Committet on Interstate and Foreign Commerce Washington, D. C. The eubcommittee met pursuant to notice at 2:00 p.m. in !oom 2123, House Rayburn Office Building, Hon. Paul G. Rogers# !hairman of the subcommittee, presiding. Present: Representatives Rogers, Waxman, Maguire, Ottinqf tnd Carter. Mr. Rogers. The subcommittee will come toTorder. Our Zirst witness is Dr. Donald B, Frederickson, Director, Nationa: kstitutes of Health. We will incorporate in the record, the katemont in its entirety. If you wish`to summarize it or in any other way proceed, .-. EI will certainly appreciate hearing from you any way you would Like to have thctiteitial. (The statement follows:) 3-2 I would like to give an abbreviated ver- which you have suggest&d be incorporated 3-3 STATEMENT OF DR. DONALD B. FRED RICHSON, 4 DIFECTOR, NATIONAL INSTITUTES OF HEALTH, ACCOMPANIED BY: JOSEPH G. PERPICH, M.D., ASSOCIATE DIRECTOR, PROGRAM PLANNING AND EVALUATION, RTCHARD.'BISEBERG, OFFICE OF GENERAL COUNSEL Dr. Fred rickson. t I should say that it is a pleasure for me to appear before the committee today. I have with me, on my left, Dr. Joseph Perpich and on my right, Mr. Richard Riseber of the NIH staff. '. We are ileased to appear before you today to discuss par- ticularly Federal policies concerning Recombinant DNA Research. I would like to specifically tell you about the research ac- tivities of two organizations -- those of the National Xnstitutz of )?ealth and those of the Federal Interagency Committee. As you are well aware, from testimony that you have already heard, the techniques for creatinq recombinant DNA molecules is-a new and powerful tool of science that has generated both I great-hope dnd excitement on the one hand, and many expressions of concern on the other. I These techniques certainly offer promise for better under- standing and improved treatment of human diseases but there may be risks in this new research area as well as anticipated bene- fits. Until the potential risks are better delineated and evalu- .ated in liqht of developing scientific knowledge, the public should expect such research to be conducted under strict con- ditions, insuring safety. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 2s S 3-4 1 This was-the fundamental principle that guided the NIH and 2 the Federal Interagency Committee in their deliberations on 3 recombinant DNA Research. 1 4 I would like to review with the commikee the activities of 3 NIH in developing guidelines to cover this research and devote 6 the rest of my remarks to the activities of the Interagency 7 Committee. 8 As I am sure has already been'covered in testimony before 9 the committee during this hearing, you are aware that the 10 scientists engaged in the use of these techniques were the 11 first to express concern about potential biohazards, a concern 12 which grew and came to a manifestation in July of 1973 at which 13 time a request was made to the National Academy of Sciences .14 to create a committee that might outline restrictions for these . IS types of experiments, and to organize an international confer- 16 .ence to.consider the problem further. .17 The committee also called on the NIH to establish an ad- 18 vfsory committee:to study containment procedures and draft l9 guidelines for the conduct of this research. This was the first : 20 entry of government, in general, and the Federal Government in 21 particular, into the matter relative to the use of recombinant ., 22 DNA techniques. 23 At the conference held in Asilomar in February 1975, tem- _.24 p orary guidelines were issued'calling for a moratorium on some 25 experiments but allowing others to proceed with appropriate I 3-5 biological and physical safeguards, pending issuance of NIH guidelines. In response to the National Academy of Sciences, the NIH Recombinant DNA Molecule Program Advisory Committee, hereafter II the NIH Recombinant Advisory Committee, was established in October 1974 to advise the Secretary of HEW, the Assistant Secretary of Health, and the Director of NIH in accomplishing their tasks. In December 1975, the Committee, after several open meetin' and half a dozen working drafts, recommended proposed guide- II lines to the NIH director for his review and decision. To assist my review of the proposed guidelines, a special meeting of the Advisory Committee to the Director, NIH, was co II vened in February of 1976. Members of the Committee represente 9 10 11 12 13 14 - 1s 16 17 18 19 20 .21 22 23 " 24 25 not only science but such other disciplines as law, ethics, and consumer affairs. Comments received irom committee members and a number of public witnesses represented a wide range of views. Follow-up written comments were also aoficfted. In April, the NIH Re- combinant Advisory Committee considered these comments from tl II February meeting, and a number of changes to the guidelines were made. Concurrently, meetings for information exchange were held with representatives from.other Federal agencies and private s industry as well as with Congressional staffs. Finally, on n- d 7 The provisions were designed to afford protection -- with a 8 wide margin of safety -- to workers and the public and the en- 9 10 ._ 11 12 13 14 ' 1s 16 . i7 18 19 20 21 22 23 -24 25 3-6 June 23, 1976, with the approval of the Secretary of HEW and th Assistant Secretary of Health, the NIH issued guidelines to govern the research it supports on recombinant DNA molecules. The NIH Guidelines established strict conditions for the conduct of this research, prohibiting certain types of experi- ments and requiring special safety conditions for other types. vironment. Two weeks later, on July 7, 1976, the NIH Guidelines -- td- gether with a document indicating the basis of decisions,my decisions, NIH, on principal issues -- were published in the Federal Register for public comment. Over 40,000 copies of the guidelines were widely distri- bu,ted to foreiqn embassies, medical and scientific journals, NIB grantees and contractors, and major professional research societiCs, andata others who requested them. To facilitate implementation of the Guidelines, the NIH, in June, established the Office of Recombinant DNA Activities; to administer and coordinate intramural and extramural activ- ities at the NIH; to review the institutional biohazards committees and.certification statements: and to monitor report and informationconcerning accidents, containment, and safety research innovation. In August, the NIH published a volume containing the 6 7 8 9 10 11 12 '13 14 . 1s 16 17 18 19 20 21 22 23 * 24 25 transcript of the February public hearing guidelines as well as related correspondence received by the Director and the results of relevant data sought prior to the release of guidelines in June. A second volume is planned for publication in late Spring documenting the correspondence that the NIH received on the guidelines, the Environmental Impact Statement, and the Depart mental patent policy. The NIH, in accordance with the National Environmental. Policy Act of 1969, undertook an environment impact assessment to review environmental effects, if any, of research that may conducted under the guidelines. The NIH Guidelines were released prior to the completion o the assessment because they're release provided greater pro- tection fdr .the public and the.environment than the Asilomar Guidelines which they replaced. For example, in a number of instances, the NIH Guidelines require more stringent safety and containment measures, ex- tension of the list of prohibited experiments, and a specific ban on the release of recombinant molecules into the environ- ment. A Draft Environmental Impact Statement was filed and pub- lished in the Federal Register on September 9, 1976, td afford additional public review and'comment. The statement is cur- rently being analyzed and 'comments.received will be responded 1 2 3 -4 5 6 7 8 9 10 11 12 13 14 . 15 16 -17 18 19 20 21 22 23 3 to in the final Environmental Impact Snatement to be published in late March. In June, shortly before the release of the Guidelines, Stan ford University and the University of California asked NIH to review DHEW policies relating to the patenting of recombinant DNA research inventions! developed.under NIH grants or contracts /' Under current DHEW patent regulations, invention rights to discoveries developed under the Department's research support are normally allocated in either of two ways: One, the Department may enter into an Institutional Patent Agreement with a university or other nonprofit institution that has adequate mechanisms for administering patents on inventions The IPA provides the institution.the first option to own all inventions made in performance of the Department grants or con- 1 tracts, subject t6 a number of conditions deemed necessary to I . protect the public interest. For those institutions that have not entered into a patent agreement with the Department, determination of ownership is deferred until an invention has been made, at which time an in- . stitution may petition the Department`for ownership of the invention. The NIH solicited opinions from a number of different groups in the' scientific community and the public and private sectors concerning those departmental patent policies, with . 25 re+spect to recombinant DNA research inventions. 3-g_; t An analysis of the issues raised by the commentators is 2 under review by the Federal Interagency Committee. 3 I would now like,to devote the remainder of my testimony to 6 7 8 9 10 11 12 13 14 15 16 $7'. 18 19 20 the activities of the Interagency Committee on Recombinant DNA Research. This Committee was created, with the approval of the II President, to address extension of the NIH Guidelines beyond the NIH, to the public and private sectors. The specific mandate of the Interagency Committee is as follows: to review the nature and scope of all recombinant II DNA research conducted in the United States, to determine the applicability of NIH standards to the government of this -.. research nationally; and to recommend mechanisms to ensure that the standards are being complied with. The Committee is advisory to the Secretary of Health, Education and Welfare. It includes representatives of Federal Departments'and Agencies that support and conduct recombinant DNA research, or may do so.in the future, and representatives . * . .- ' of Federal Departments and Agencies that have present or po- tential regulatory activity inthis area. At the Secretary's request, I serve as Chairman of the , ,2t Committee. 22 Two. meetings of the Committee were held in November 1976. The first of the.se, on November 4, was devoted to a review of 23 7 . . . 34 the development of the NIH Guidelines. The Committee alsa're- 25 viewed activities in other countries on the development of 1 quidelines for this research. 2 3 4 5 6 7 8 . 9 . `. to ; 11 12 .: 13 14 - 15 16 :17. ,, 18 19 :,:20 .2t 22 L 23 -24 25 3-10: I will reserve, since you may have questions, Mr. Chairman, a review of those activities abroad which I have reviewed first I hand on a continuing basis, both in numerous countries, includ- ing Britain and Europe and here with conversations with scien- tists and administrators from those countries and from behind the Iron Curtain and'Japan. At the meeting, the Interagency Committee held in November 23, the Federal Research agencies discussed their activities ant! possible roles in the implementation of the NIH guidelines. All research agencies endorsed the Guidelir?es to govern recon- binant DNA research. At present, the NIH,'the National Science Foundation, the Veterans Administration, and the U.S. Department of pgriculture. . At the November 23 meeting, the Federal regulatory agencie . . reported on their regulatory functions. Followinq that review a special Subcommittee was formed to analyze the relevant ,- ' statutory authorities for. the possible'regulatian of recombina . DNA research.' i All regulatory agencies were represented on the Subcom- . mittee, assisted by attorneys from their offices of general counsel. The Subcommittee w&s ch'arged tb determine whether existinq . legislative authority would permit'the regulation of all re- combinant DNA research in the United States, whether or not 4 I 5 9 to 11 12 -13 14 . 15 16 :,t7. ..: 18 19 .20 : 21 '22 .23 ,24 25 federally funded, and would include at least the followiny regulatory requirements. It was the conclusion of this Subcommittee.that..present fawn-oonld permit imposition of some of the above requirements on much recombinant DNA laboratory research, but no single legal authority or combination of authorities currently existed that would clearly reach all research and other uses of re- combinant DNA techniques. Although there is existing authoeity that might be inter- preted broadly to cover most of the research at the present time, it was generally agreed that regulatory actions taken on .-I the basis of any such interpretation would probably be subject to legal challenge. The Subcommittee, in reaching this conclusion, reviewed the following laws that were deemed to warrant detailed con- 'sideration: . The Occupational Safety and Health Act of 1970, Public Law _ 91-596; the Toxic Substances Control A&,-Public Law 94-469; The Hazardous' Materials Transportation Act, Public Law 93-633: . . . and Section 361'of the Public Health Service Act, 42 U.S.C.264 . The full Committee adopted the report of its Subcommittee and agreed that new legislation was required. In considering the'elements for legislation, the committee reviewed federal, state and local,activities bearing on the regulation of recombinant DNA research. Among Congressional I 4 5 6 7 8 9' 10 11 12 I 13 14 . 15 16 .:t7 18 19 .20 -21 22 .23 94 25 3- 12 I proposals reviewed were Senate Bill 621, "The DNA Research Act of 1977", introduced by Senator Dale Bumpers, and the companion measure introduced by Representative Richard L. Ottinqer in the House, H.R. 3591. The Committee also noted the resolution introduced by Representative Ottinger on January 19, 1977, H. Res; 131, re- questing DHEw to regulate recombinant DNA research under Sectio:? 361 of the PHS Act. Hearings held by State and local governments, including State legislatures, were among State and local activities re-' . ! viewed. Recommendations by the New York State Attorney General's Environmental Health Bureau for State regulation, and by the Cambridge, Massachusetts'City Council for city regulation, were also considered: Saveral committee representatives also reported on meetings with other interested parties, which they had held solicitinq views on legislation, to regulate recombinant DNA research. . .- ' Those who were contacted included agricultural scientists, biomedical scientists, environmentalists, labor unions, and ` private industryi. *At my requestr- the Industrial Research Institute and the Pharmaceutical Manufacturers Association are surveying their member firms to.determine the scope of the research efforts in the private sector. The Pharmaceutical Manufacturers Association has adopted I 3-13 9 10 11 12 13 14 15 16 $7 18 19 (20 .gt in 23 24 25 the NIH Guidelines as standards for safe conduct of this re- search. In considering elements of proposed legislation, a number of issues were raised and discussed fully by the Committee. After detailed#deliberations at meetings on March 10 and 14, 1977, the Committee agreed on a set of elements for-proposed legislation. The elements agreed upon and'the various alternatives reviewed by the Committee werWprks&fited:ffl an Interim Report transmitted to HEW Secretary Califano on March 15, 1977. Secretary Califano, in releasing the report on March 16, stated that "legislation in this area would represent an un- usual regulation of actfvities affecting basic science but the . potential hazards posed by recombinant DNA.techniques warrant such a step at this time." . We are not saying that research should be all the more urgent that it shouldi-.proceed under safe guards unless until . a- - we have a better understanding of the risks and benefits posed by use of recombinant DNA techniques without government requ- latfon. The Secretary-added that the Department will begin im- mediately to draft-legislation in-the light of the recommend- ations made by the committee. . . Mr. Chairman, I would like ta*submit for the record, this : "Interim Report of the Federal Interagency Committee on 9 to 11 12 13 14 - 15 16 p 18 19 .20 ,21 52 23 ,.24 25 3-14 ecombinant DNA Research on Suggested Elements on Suggest ,ed Eleme for Legislation,' long with a copy of the Secretary's Secretary' s remark remarks, accompanying its elease. Mr. Rogers. Without objection, objection, we will we will commit that as part the record at this point. int. (COMMITTEE INSERT) 3-15 4 5 6 7 .8 9 10 . 11 12 - 13 14 . 15 16 :17 .18 19 30 41 52 23 24 25 Dr. Frederickson. I would like to review very briefly some of the major elements of legislation which were considetied by the committee. The committee determined that, in its view, the Department of Health, Education and Welfare is the appropriate locus in the government for the regulation of use and producti of DNA molecules. In reaching this determination, the committee took into account existing roles of certain.agencies within the HEW,for example,,Tthat of the NIH in developing the guidelines and the Center for Disease Control and Bureau of Biologics of the;Food and Drug Administration in regulating infectious agents and ._ _I other biological products. The dommittee also had before it the petition by the En- . vironmental Defense Fund requesting the HEW to issue regulatio for recombinant DNA research under 361 of the Public Health . Service Act. : The committee reviewed, at great length, the nature and II . .- ' scope of regulations. Consideration was given to regulation-of laboratory-research where hazardous and potentially hazardous substances were 'employed. . There was general committee agreement that present legis- lation .should be restricted; not only to recombinant DNA techniques, allowing for sound administrative and scientific - expertise in developing'safety standards in other area. In this regard, ?lr. Chairman, I-have established a comitt 3-16 4' 5 6 7. a -9 - IO 11 12 13 14 '5. 16 ,17. 18 19 20 .21 52 23 24 25 at NIH Chaired by Richard DeCause (ph), the Director .of the National Institute for Allergy and Infectious.Diseases to stud1 and recommend if necessary, safety standards for other researc) involving actual or potential biohazards. A preliminary report is expected shortly from this commit- tee and I will keep your committee informed of the progress of this NIH review. I .just thought that would be helpful. . . Regulation of just the research aspects of recombinant tee! II niques, DNA techniques , presents a problem because of the diffj culty in determining the border between research and pilot plant production. Therefore, the Interagency Committee has recommended that regulations covering the'production or use of recombinant DNA . molecules, such language would clearly include research activii bit it makes immaterial possible concerns whether a given ac- tivity constitutes research, pilot production or manufacture. The committee.recommends that the Secretary, in consultati . .- - with appropriate regulatory agencies, be allowed to determine the nature of- the activity and. should defer to a national ' I . 'regulatory body'he.determines is better empowered and equipped . to deal with that specific activity. There was general agreement by the committee that regis- tration of projects and`other activities involving the use or production of recombinant DNA molecules was necessary. The committee also recommends the license share of facilities.and 9 10 11 12 13 14 1s 16 ,17 18 19 .20 -21 22 23 24 25 3- 17 that the facility would, under the terms of its license, accept responsibility for the particular activities and the individual:; at the facility.. The committee concluded that licensure of the facility and registration of products would meet the needst:for safety mon- itoring without extension of licensure to the projects them- selves. The committee urges full disclosure to the appropriate regulatory body of all relevant safety and scientific info& mation on the use and production of recombinant DNA molecules; However, the committee recognizes the important worldwide commercial potential of recombinant DNA molecules in medicine, agriculture and other areas, and-in science and technology. It believes that the potential commercial users of recom- binant DNA techniques require that information of a proprietary L. . . nature and patent rights be given an appropriate protection from disclosure by the regulatory agency receiving such infor- *. mation. Because the potential hazards posed by the use of recombin . .-: ant DNA techniques extend's beyond the local to the national an . beyond that to international levels, the committee recommends that a single set of national standards must govern and ac- . ..: cordingly stdte.and lo&l iaws should be preempted to insure national standards and regulations. The committee, however, took into account the activities at state:and local levels on regulation bf recombinant DNA research. It was agreed that if the state passes a law imposing,-qre- quirements identical to that in the Federal statute, then the Secretary may enter into an agreement with the state to .;I 6 t 8 . 9 10 11 12 'Ii 14 utilize its resources to assist the Secretary in caitrying out his duties. A number of other recommendations were made that I can dis cuss further with you, Mr.Chairman, if you have questions.' I would like to emphasize the?,:woirkf of.the'Interagency Committee' and how it hassbeen done in an extraordinarily cooperative and ef fective'fashion. It is most unusual, '1 think, for servants of some 16 to . 20 federal agencies whose territory crisscrosses a difficult 15 and complicated area and yet to achieve gradually through full I . 16 and frank discussion a consensus which was complete on the -17. .I8 19 20 .21 92 23 24 25 3-18 recommendations that I have described before you. . .- - Mr. Rogers. I would-&hare that feeling. That is unusual. Dr. Frederickson. The Department will continue to coopera*:e . . and work with other relevant federal agencies and departments in this' important matteri : In conclusion,.Mr. Chairman,. I think this much is clear. The international, as well'as the national scientific communit is in substantial agreement concerning the potential hazards of recombinant DNA techniques until they are better understood, I It 3-19 I 1 a common set of standards must exist everywhere throughout the 2 -world. 3 Tfreeiah being ,debated now is not that but how is this ' to be accomplished ?'.::Here in this Chamber today we begin to dis-- 'I s cuss how it should be accom@lished within the United States? 4 HW?+T .!y. " matter by no means now confined to only our country ~-~*~~~L~~~~.-rz;f,ltrbr:~~veloped countries of the world, wher w&&m-t and parlimentary committees, committees established -9 II 'by states'in both private and public manner have considered ex- ii I ..~fi:::&zzxA.veYy.~hether this research should go on. I 11 H ' VVuxnerous bodies such as these and the WHO,International 12 Council of Scientific Unions, have determined that this resear ;3 sh*ould proceed but proceed under care and prudence until we 14, have moxe:~kn.&ledge of both its potential and its benefits. t-45 $ Indeed now in .many countries we find a disagreement having . 16 been reached, either the NIH or the guidelines established by jl7 the United Kingdom of Cantida, - i all of which have a common groun , -- ' @.:;$..-$T~ .the Asflomar meeting are being used' for the,spurpose-cjf ' -gradually exu g that commonality of standards for these I activities. -It As.necessary to bear in mind, Mr. Chairman, the changes that is present in all living organ- their inheritative characteristics, also occurs spontaneously in natur'e. They have made possible the never ending process of 9 10 11 12 13 14 15 16 17 18 19 20. -21 22 23 24 2s 3-20 evolution. Research on recumbant DNA holds great promise. It pay become a powerful tool in advancing our knowledge, knowlcdgk which conceivably can be used to further the conquest of dfa- ease. In conclusion, 1 hsve to notk that biomedical research is opening a new era in relationship to society, at least passing from an extended period of relative privacy and autonomy to engagement with some new ethical; legal and social imperatives under increasingly concerned public scrutiny. NIH has responded to this concern by the requirement of formation of review boards to oversee human experimentation, animal care, and now the use of recumbant DNA techniques. Sim- ilar bodies may soon have to be established in many institu- tions to over see other haiardous laboratorpwotk. I think these responsibilities are an inescapable adjustment to the rising demand for public governing of science. I think, however, this need not and should not go beyond what is clearly required for public safety for it is the possibility that we can harm the effectiveness of a creative and responsible scientific apparatus of which this country at the present time is in possession and which has no peer throughout the iorld. Thank you, Mr. Chairman. I will be glad to answer any questions you might have. . Mr. Mgers. Thank you. 'It has been proposed by aome that we effect a ban for a certain period of time. I take it from Y 1 I your testimony you would not share that approach? 2 Dr. Frederickson. I do not share that approach, Mr. Chair- 3 man, for several reasons. I suppose one of them is a practical 4 or prggmatfc view that this research will clearly continue and 5 in many places in the world. 6 Even $f it were wise, as I think it is not, to attempt a 7 complete moratorium on this research, I see no way in which it 8 could be achieved, with the'positions taken now by many other 9 countries capable of doing the same. 10 I also think, Mr. Chairman, that banning this research or I1 halting it will not answer the very questions that we need to 12 know. We.must have more knowledge in order to proceed and until 13 we get that, we have to prooeed with utmost prudence and 14 caution, and under a rather inhibited pace which the guidelines IS in effect pose upon all of those who are subject to them. 16 Mr. Rogers. I think it would be helpful if you could, 17 for the record, perhaps list for us possible benefits that are 18 I envisioned, that could be developed from this type of research; 19 also a list of possible dangers that you see could develop, al- 20 'so, if you could, for the record, let us have a comparison of 21 the various guidelines that have.been issued or the various 22 regulations that may have been issued in other countries in 23 ' regard to recumbinant DNA kesearch or similar research. 24 If you could point qut in one article for us, or one de- 2s velopment, the difference between our proposed guidelines and II 6 7 8 9 10 I? 12 13 14 15 16 17 18 19 -20 21 22 23 .34 2s 3-22 those of say, England and Canada which would seem to be simila or any others that are significant. Dr. Frederickson. We will be very glad to do that, -ntr. Chairman. Mr. Rogers. Thank you; it would be helpful to the committ Let me just ask this. What was the nature of the Defense De- partment's request for a waiver on certain types of recumbinan DNA research restrictions in time of national emergency? Dr. Frederickson. The Defense Department representatives on the Interagency Committee expressed to the committee a con- cern that it might be necessary to impose some moratorium on exchange of information, or to exempt from the guidelines cer- tain aspects because of national security considerations. I should then tell you, Mr. Chairman, that the committee decided that it did not have the mandate or authority to deter -mine those questions and did not )Lake action.on it. . Mr. Rogers. Should the President be given that authority? Dr. Frederickson. I should think so, that the authority should be at a very high level, perhaps the Cabinet, National Security Council or -- Mr. Rogers. Was the Central Intelligence Fgency invited to participate in the Interagency Committee meeting? Dr. Frederickson. No. Mr. Rogers. Did it participate? Dr. Frederickson. It did not participate. 9 10 11. 12 13 14 15 16 17 18 19 20. 21 22 23 94 2s 3-23 Mr. Rogers. Has there been any interest indicated by the CIA? Dr. Frederickson. There has been no inqtiiry made to the committee or to NIH from the CIA with respect to this matter. Mr. Rogers. I think it would be well for the record,and I would not ask you to document this now, but for the record, would you give us a discussion of the nature of gene transplan- tation; the regulation, but what is actually going on that we know of in the way of experiments in Great Britain, Contindntal Europe and other countries? Are there any countries in which such research is being conducted where they have no guidelines for safety? Dr. Frederickson. I will be-glad to supply that for the II record. I might call to the attention of the committee an' II article in the March 3rd issue of "Nature" in which Mr. Colin II Norman (ph) describes the up to date occurrence of events rela- tive to this. I Mr. Hogers. We will ask staff to acquire that for the II committee. We had a copy, I understand. What about the possf- '. . bility of 0% companies going abroad if we did put on very . strict regulations? Dr. ,Frederickson. I think it is essential for the pro- tdction of all of us on this globe that there be uniformity. : II One finds in the scientific community no question about this II and a great determination to achieve it. 3- 24 4 5 6 7 8 9 10 11 12 '13 14 . 1s 16 17 18 19 20 21 32 23 - 24 25 Of coursecthere-.*would be transmigration of people from one area to another, I would say not only industrialists but scientists in the academic world to other areas if they felt this were possible and that they might conduct research there. I do not imply, however, irresponsibilit$ on the part of either groups because I think, as I emphasized, it was the scientists who raised these questions and it is they who have been extremely responsible in recognizing the dangers and seeking by all means to have a common set of standards. I do hhink that we must attempt to achieve uniformity and conformity throughout the world. I think the way to do that is to have common standards within national jurisdictions whit must not be confusing or pluralistic because by then we can use other devices to get that, create the fabric or the blanke that will go out throughout the whole world, capable of doing this research. Mr, Rogers. Thank you. Dr. Carter? Dr. Carter. Thank you, Mr. Chairman. ;8bwirffar have we gone with -- in implanting genes or nuclei into plant ova-or , cells3or uniting cells in some cases by ddssolving the ecto- derm? Dr. Frederickson. Well, by cell fusion, Dr. Carter; I can supply to you for the records some answers to these ques- tions but I cannot answer'them with any expertise this after- noon. 10 I1 12 13 14 . fs 16 .I7 18 19 20 21 22 23 _ .24 2s 3-25 I There may be some witnesses on your list today who could answer those questions. Dr. Carter. You do not know if this -- whether you have had vegetables formed in this manner? Dr. Frederickson. In'terms of the hybridization of the plants by such techniques? Dr. Carter. Yes, sir. . Dr. Frederickson. They have been going on for many years, Dr. Carter. Dr. Carter. In this method? Dr. Frederickson. They have been going,on by a variety of grit&g. Dr. Carter. I do not mean by grafting, I mean by this method of transplantation of genes? Dr. Frederickson. No, I must defer to witness such as .Dti..Lewis,who may follow me later this afternoon, Dr. Carter, , and have him answer the question. Dr. Carter. What about in bacteria, do we have new strain of bacteria formed by implantation of nuclei in those genes, i . those bacteria? Dr. Frederickson. We have had transformation of bacteria to be created by recombinant DNA techniques in the sense that some new properties have been transposed from one species to another by more or lees.a'replication of the natural process that produces antibiotics resistance in many strains, not by 10 11 12 13 14 - 15 .16 17 18` 19 20 21 22 23 -24 2s 3-26 I nuclei but by single genes, implantation through recombinant DNA techniques. Dr. Carter. We have developed entfrely new strains in some cases, is that not true? Dr. Frederickson. By definition, they are. Dr. Carter. In the case of pseudomonis (ph), particu&a&ly? Dr. Frederickson. I am not certain about pseudomonis. Dr. Carter. I think it was Texaco or Standard Oil that developed that technique, one of them, it is an oil eating. organism. Dr. Frederickson. That is the General Electric Company, Dr. Carter, whiti has been working on that problem. Dr. Carter. I believe we have it. What about animal im- olantation of recombinant genes in animals, how far-:has that gone, Doctor? .Dr:. Frederickson. Genes have been introduced -- foreign genes have been introduced fdto tissue culture from animal cells lines as that kind of recombination has occurred. Dr. Carter. Have ue been able to clone frogs? Dr. Frederickson. No, sir, we have nathbeen able to clone frogs. Dr. Carter. Are you sure of that? Dr. Frederickson. I will certainly have to check on that, Dr. Carter. Dr. Carter. I belfevettihat has been done. I bhlieve they 3-27 I have taken genes from a tadpole, destroyed the nucleus of a cell of a frog and then by implementation of this -- well, a m cell entirely in this case, clone of the frog.-grew. I believe that is being,done at the present time. Doctor, do you think that cloning of humans is possible in the next 15 or 25 years? Dr. Frederickson. I think it highly unlikely, Dr. Carter. Dr. Carter. You see, some people project that this is possible, do they not, some say 15 to 40 years? 10 11 12 13 14 Dr. Frederickson. There are people who have made public utterances to this effect. Dr. Carter. Then in your opinion, we will not have alpha, 1s 16 17 18 19 20 21 i2 23 24 2s beta, delta, gamma man in the foreseeable future, is that II correct? Dr. Frederickson. I thfnk'that the canfusion of recombinal . DNA te,chniques with so-called genetic engineering is a danger01 distortion. Dr. Carter. It is dangerous but y&a do not say if it is possible or not. Dr. Frederickson. I really do not-know, Dr. Carter, nor do I think anybody knows; that is certainly not yet in these things. Dr. Carter. We can define by elimination which gene has what effect, we can do that dt the present time, is that not true? 9 10 11 12 13 14 15 16 . . 17 18 19 20 21 $2 23 L 24 25 3-28 Dr. Frederickson. That is very true. Dr. Carter. It is a long process but by'process of elimin- ation, we could determine which gene has certain effects? Dr. Frederickson. I think eventually over a long period of time. Dr. Carter. That is being done now, Doctor? Dr. Frederickson. Yes. Dr. Carter. All right, sir. Now should a researcher who uses recombinant genes be licensedyif he is engaged in this work? Dr. Frederickson. It was the view of the committee which considered this at great length that facilities should be licensed and that those who used?:them should be subject to registration of the project, but not licensing of individuals. Dr. Carter. Not licensure of the individuals, I see. The laboratory,'65 course, should be one of: four types, I believe you said; is that correct? Dr. Frederickson. Yes, in terms of physical containment. Dr. Carter. What about the projects? When they attempt a project, should they be registered with some agency to determil just what they are going to do, if they are going to clone bacteria-or attempt to do so or attempt to implant genes and vegetable 0.8 whatever? Should this project be licensed or should it be registered and approved before it can be done? 6 7 8 9 10 11 12 13 14 * 15 16 17 18 19 20 21 22 23 I 24 25 3-29 Dr. Frederickson. On the current implementation of the NIH I guidelines, all of our projects are first approved by study sections and registered. Dr. Carter. Under the NIH guidelines, but what if some independent laboratory wants to do this? Dr. Frederickson. I think that is the whole purpose of the legislation that we are::dfscussing, to extend that same registration requirement. Dr. Carter. At this present time, there -are.20 rules or regulations concerning them are there? Dr. Frederickson. At the present time, there are no rules, that cover,prfvate. Dr. Carter. Now, sir, the Class I, 2-B, l-B, 2-B, B-3 and B-4, would you tell me what experiments could be done in each one? Dr. Frederickson. That is an extensive -answer, Dr. C8rter. We can supply you -- Dr. Carter. As briefly as possible, would you include it for the reoord? Dr. Frederickson. If we could insert that for the record, we could do 30. Mr. Rogers. Without objection, it will be received for the record. Dr. Carter. Do you think that would take quite a long time, that you could not give us any rough idea of what 6 7 8 9 10 11 12 13 14 . 15 16 17 18 19 20 21 22 23 - 24 25 ~ 3- 30 I experiments should be done in each one of these? Dr. Frederick&on. We will get the guidelines out. We can briefly summarize it for you, if you like, but it will not take us long to'provide. the material for-the record. It is a por- tion of the guidelines. Dr. Carter. You do not foresee any brave newworld in the immediate future then, is that correcti Dr ,Fredetickson. Nt,, I donot. Dr. Carter. Thank you, sir. Mr, Rogers. Mr. Ottinger? 6r. Ottfnger. No. Mr. Rogers. Mr. Waxman? Mr. Waxman. Dr. Frederickson, I was interested, in glanc- ing at your testimony regarding other countries that are'&n- valved in recombinant DNA research. You mentioned a number of western countries that were- foll&wing the guidelines set up by the United Kingdom. To your knowledge, what guidelines are being followed in -- by the E&stern European Bloc countries, including the Soviet. Union? Dr. Frederickson. The Soviet Union has a committee of the Academy of Sciences which is still developing guidelines for conduct or use of these techniques. We have disaussed 0 with the Chairman of that committee, its general direction and it is considering an amalgamation of both the United States and 3-31 the UK guidelines but it has not published those or made them 7 available to us at the present time. Mr. Waxman. Do you feel that there will be full coop- 9 10 11 12 13 14 15 16 17 18 19 20 .2? i2 23 24 25 eration internationally including the.Soviet Union Eastern Bloc countries in working out guidelines of the -- will cross nation 1 boundaries? Dr. Frederickson. My opinion is that will occur. That arises because of the excellent exchange and demonstration of intere9t on the part of the Eastern European countries and the International Council for Scientific Union meetings in which there is an opportunity for western and eastern people to -- scientists to exchange views. Mr. Waxman. How advanced is the recombinant research in other countries, particularly eastern bloc countries? Dr; Frederickson. I would say, as,-a matter, that it is not as advanced in eastern bloc countries as it is in the Western World at the present time. Mr. Waxman. In the international scientific community, is there a full exchange of information about the projects that are undertaken and how advanced they are so that there is some learriing from each other. Dr. Frederickson. There is what I would have to characterize .as quite full.exchange. We, are certainly learnfnq , from each other and the connections between the European eco- nomic community countries and the United States is excellent, , 1 2 3 4 5 6 7 8 each of the 16 member countries of the European Science Foun- dation. 9 -There they are sharing their views on what de&:f+&ons 10 11 12 13 14 16 17 18 19 20 21 .6 L . . / 23 6 " 24 !. -, cd 25 3-32 both at the administrative and scientific level in regard to this. We just had our own NIH representative and liaison to the meeting of the European Science Foundation last week of the genetic Manipulation Advisory Groups, the so-called G-mags, a new word for the acronym for the future, which operate now in _ they are making, what projects they have reviewed and other common problems relative to conforming to a common set of stan- dards. . Mr. Waxman. fs there a risk of contamination from abroe given your knowledge of the research projects that are now beir undertaken? Dr. Frederickson, I think that we cannot say there is no risk of contamination. There is a hypothetical, speculative risk to recombinant DWA research which is the very basis for the'matter being here discussed. . * I know of no experimentation goipg onr however, which . proposes any serious or even topical hazard to us at the present time. -- Mr. Maxman. You mentioned that the interagenqy level or the NIB guidelines w&r& adopted and the CIA was not involv- i ed? 10 11 12 13 14 - 1s 16 17 18 19 20 21 i2 23 c 24 25 I 3-33 Dr. Frederickson. It was not, sir. Mr. Waxman. Do you know whether the CIA is involved in research with DNA recombinant combinations and experimentation? Dr. Frederickson. We have no knowledge, Mr.Waxxnan, whether they might or:might not be so involved. Mr. Waxman. You are under the Secretary of HEW? Dr. Frederickson. Yes. Mr. Wanman. At the Cabinet level. Do you-know whether II there has been any discussion of exchange of ffiformation about DNA recombinant research? Dr. Frederickson. I am not aware whether that has occurred or not. Mr. Waxman. We heard testimony yesterday indicating that the Department of Agriculture has not yet adopted the NIH guidelines. Have you attempted to get other federal department to comply and why are they resisting compliance? Dr. Frederickson. The Department of Agriculture has formally adopted the NIH guidelines and so have all federal agencies that are conducting or say they-may ever conduct recombinant DNA research.. .I . . That includes the Department of Defense which is not conducting such experiments at the present time. Mr. Ottinger. Will the gentleman yield? Mr. Waxman. Will be @leased to. Mr. Ottinger. Does that include all grants, all agent ies 10 11 12 .13 14 - 1s 16 17 18 19 so because they conduct no research or support no such research 20 21 22 23 34 25 3-34 which make grants for such research or contracts for such re- search? Dr. Frederickson. Yes, it does, Mr. Ottinger. Mr. Ottinger. Thank you. Mr. Waxman. How about the National Security Agency, are they in adherence to the NIH guidelines? Dr. Frederickson. They were not represented on the committee: we have no communication from the National Security Agency. ~ Mr. Waxman. Do you know whether they are involved in DNA recombinant research? Dr. Frederickson. No, I do not. Mr. Waxman. How about.the Arms Control Disarmament Agency? Dr. Frederickson. They are represented on the Inter- Agency Committee. Mr. Waxman. They have subscribed to the NIH guidelines Dr. Frederickson. I think they have formally not done Mr. Waxman, but they are on the committee and represented. Mr. Waxman. I would be pleased to yield to Mr. Carter. . Dr. Carter. There are, I believe, just three federal ;agen&.es or groups in-this National Science Foundation, Vet- erans Administration and U.S. Depaitment of Agrikdture are now ding some experimentation, is that correct? 1 2 3 4 S 6 7 8 9 10 11 12 13 14 ' 1s 16 .17. 18 19 20 21 22 23 r 24 25 3-35 Dr. Frederickson. Yes, they are doing it or supporting it. Dr. Carter. I yield. Mr. Waxman. I thank you very much for your testimony and your answers to these questions have been very helpful. Mr. Rogers. Mr. Maguire? Mr. Maguire. Thank you, Mr. Chairman. Dr. Fredericksoh, you have indicated that the committee decided not to attempt to address the question of other research involving biohazards, that is other research than recombinant DNA. I understand that there are techniques for cell hybrid- ization, bacterial transormation and transduction and plasmic engineering, among others. Was 'it your feeling that those did not pose the same kind of hazards or that you simply could not deal with more than one thing at a time? What was the rationale for not broadening it? Dr. Frederickson. The committee clearly recognizes as do we at NIH individually that there are other hazards, other techniques for genetic recombination which we do think need evaluation. For purposes of making that analysis, we have estab- lished at NIH a committee on other aspects of genetic recom- bination and laboratory safety which has: had several meetings. It now has three subcommittees, one on cell fusion, another on mutogenesis and another on recombination experiments other thar. 6 7 8 9 10 _ 11 12 13 14 . 1s 16 -17 18 19 20 21 $2 23 c 24 2s 3- 36 I recombinant DNA techniques as defined by the NIH guidelines. ThiWcommfttee is examining and attempting to develop recon- mendations to the NIH with respect to possible need for other guidelines to govern this type of research. Mr. kagufre. I am looking now, not at your statement, but -the iaterim report of the committee which I assume you also have a,copy of. I will be referring to various pages of that. Dr. Frederickson. Yes, I do. Mr.- &tguire.On page 17 , you indicate that the Secretary, inconsultation with appropriate regulatory agencies, should be allowed to determine the nature of the activity and should defer to a regulatory body he determines is better empowered an3 equipped to deal with it. .I take it that you have fallen short of saying that he should be required to defer to.that regulatory body? Do I . read.that correctly and are you reserving then to him the right not to defer if he should choose not to, if he felt, for example, q:,lack of confidence in what some other regulatory body might do.in:a given instance? .>' Dr. Frederickson. The choice of verb form there.is de- liberate and one that the.committee debated and considered at : great length. It felt that it was necessary to embody in one person the first discretionary r&ponsibiXity that someone would have to make that determination. . . . However, it recognized that there are already at least 10 il 12 li 14 . 1s 16 17 18 19 20 21 22 23 c 24 2s 337 two other regulatory agencies, EPA for example and FDA in the commercial area and that these authorities, when clearly ap- plicable to a given activity, might very well mean that those agencies should be the one to take over regulation of that activity. Mr. Maguire. But the discretion should remain with the Secretary? Dr. Frederickson. We felt that the discretion had to be placed within the Secretary. ; I just wanted to clarify the Secretary should have Mr. Maguire. I agree with that that. On page 18, you indicate that the authority to exempt certain classes of projects from this requirement, namely the registration requirement. In view of the fact that you are simply asking for regis- tration other than licensure or prior approval or what have you, I am finding it difficult to envisage what classes of projects might require or need the benefit of that exemption. I am wondering why that exemption is there if all we are asking for is simply registration. It would seem simple enough to register. Dai; Prede&fcksodYz-*You ar&blsa+referfing, II?beli.eve, Mr. Maguire, to the suggested elements of legislation which also appear on page 12? Mr.Maguire. I am really reading from page 18, although there may be some -- 6 ? 8 9 there was no unreasonable risk. Dr. Frederfckson. No, Mr. Maguire. I think that I have I ijust referred you to page 12 and the other element relevant to registration is the third paragraph on page 13. Let me clarify 10 the intent, what the committee had in mind here. 11 It is envisioned that as more knowledge is acquired, it 12 13 14 - 15 16 'will be possible to determine with a high degree of accuracy ~that certain kinds of experiments may no longer pose any hazarc and that then it will be possfble.with appropriate justificatic /for the Secretary to place an exemption on those but it is not 17 18 19 ,meant to exempt commercial or other activities. Mr,Maguire. Then the reference to page 12 was not a correct reference, We are talking about -- Dr. Frederickson. Page 13.is the reference with respect : ~ to registration. ~ Mr..Maguire. On page 13 though, you see I am worried about loopholes. I am wondering, registration would seem to bc such a simple matter, r .am'justwondering why we just cannot 20 21 22 23 -24 25 3-38 Dr. Frederickson. That is an extension or comments on the nore specific element; that is on page 12 in the second paragra if I might call your attention to it there. Mr. Maguire. I see. Then let us deal -- 1,see. In other words, if there were a specific commercial purpose or where simply ask anybody concerned`in any way with this to register and why we would want to'introduce an exemption which could be 3-39~. . 1 exploited either by peo$le seeking exemptions or people who are 2 granting them, in a way that might be consistent with the public, 3 interest. 4 I am not saying that would happen: I am saying why permit 5 that exemption, particularly when I think we would agree there 6 might be some difficulty, in some cases, in defining the test 7 for unreasonable risk. 8 Dr. Frederickson. I understand that. The committee, too, 9 was concerned about loopholes and sought to create none and to 10 avoid all, however, it was a major aspect of our consideration 11 and it remains a great concern that it is certain that our 12 knowledge of the meaning of these techniques, their potential 13 for either benefit or harm, must-vastly increase in the new 14 few years. 15 It is very probable, it seems to me, that some experiments 16 between now; placed.;ander sanctions or regulation, may prove 17 to be completely harmless or have either no benefit or any 18 I hazard so that there will be a change in these standards. 19 I think that is one of the extraordinary problems we face 20 here in this'kind of regulationsiith which we are dealing, a 21 field in which.knowledge is going to advance rapidly, where 22 resynthesis will indicate that we will have to be able to 23 change a view which cannot be fixed in an inflexible fashion. 24 Mr. Maguire. Then you feel the exemption is important? 25 Dr. Frederickson. Yes. I 6 7 8 9 10 11 12 13 14 . 15 16 17 18 19 20 21 22 23 r 24 25 3-40 Mr. Maguire. What about those that you choose not to exempt, why would you not ask for the right to approve projects before they commence or is it your feeling that would be equi- valent to licensure and you are trying to avoid licensure? Why, if you are going to insist on registration for those that you do not exempt, why would you not also insist on projec f approval? Dr. Frederickson. I think that the ability to examine in extraordinary detail each use of a recombinant DNA technique ., maybe-.an- impossible regulatory task, that is to require prior approval 6f every small. change in protocol or utilization of these techniques. Indeed, these are not single experiments which have a long time scale necessarify. The matter of using recombinant DNA techniques is comparable in many ways outside of its uncertain- . -ties with regard to hazard and benefit, to the use of an extra- ordinary number of techniques that are used in experimentation. We felt this would impose an intolerable burden on any regulatory group if it had to approve each change in the project. It`must know, however, the nature of the general activities and that by proximal determination, the NIH guide- lines which are very explicit in regard to how each individual project shall be carried out, that they should be followed be- cause we do have codified in those guidelines an explicit set of directions which far exceeds that of the other existing 3-41 ' guidelines that have been referred to today. 2 Mr. Maguire. Thank you, Mr. Chairman. I have additional 3 questions if we can come back. 4 Mr. Rogeas. If we could get them answered in the record, 5 would that be satisfactory? You could submit them and they 6 will -- 7- Mr. Maguire. I would like to ask some additional ques- 8 tions rather than submit them for the record because I think 9 they are important for this discussion, Mr. Chairman. 10 ' Mr. Rogers. I want everyone to but we do have nine ad- 11 dftional witnesses to finish this afternoon, if possible. 12 Mr. Maguire. May I submit some of them for answering in 13 14 . 15 16 t7 t8 19 20 2'1 22 the record and ask one or two more, ?+?r. Chairman? Mr.Rogers. Sure. Mr. Maguire. Would youllike for me to do that now? Mr. Rogers. If you could do that rapidly, it would help us. ' Mr. Maguire. You said you did not want to license indi- viduals in answer to Dr. Carter, why not register individuals? . Dr. Frederickson. We think we shou$d. Mr. Maguire. That was not clear. Dr.'Frederickson. I am sorry; we did not clarify that, w I 23 should know who they are. I 24 Mr. Magufre. On page 18, midway down the page, there is 25 a very interesting sentence which says, "There was concern 9 10 with respect to that matter or @hat ought to be a minimum position in relation to the public interest. It looks as if there were a lot of people here who were 11 saying in effect, let us do all of this but let us not punish 12 13 anybody if they get out of line. I found this a very troublin wording on that point. I wonder if you could comment on that? 14 15 16 Dr. Ereder,ickson. I would be glad to. There are two reasons why the committee took this position. One, it felt tha . it would be extremely difficult that the qualifer's serious 17 18 19 and willful, are not to easy to deal with in.many. situations. Second, it felt that given that, that an infraction of the rules by a single investigator, that might penalize an 20 21 22 23 c 24 25 I 3-42 xpressed unattributed that revocation was a very punitive IQ easure but it was agreed that the Secretary may wish to consfde it for serious violations of the standards." While I would emphatically agree that the Secretary ought to be able to consider sanctions in the event that things are seriously wrongr I just wondered why it was necessary in this I document to back into what I would assume was a minimum positio ! 1 entire institution would indeed in many instances be punitive and certainly very serious. It did not want to exclude the fact-that there might be -circumstances that would &early warrant that action but it did not want to go on record as indicating that this would be an extreme action in regard to an institution or whole facility' 6 .7 8 9 to 11 12 13 14 1s t6 17 18 19 20 21 $2 23 -24 25 or could be and that it often may very difficult to determine what was willfulor not. Mr. Maguire. From the public's point of view, willfulness is less important than the fact about what is happening if there are serious violations,c:it would seem to me we do not have to make a lot of apologies to anyone to revoke. I would hope we would not get ourselves into an apologetic framework from out outside on that po$ht. Dr. Frederickson. Yes, the committee did not intend to be apologetic but it felt that the Secretary here should have discretion. It may be a very difficult problem. Mr. Maguire. At one point in this document you talk about giving the Secretary the authority to enjoin use for production,! . on page 20; at anoCh&lpo&tit%.page 13, you talk about giving him authority to sue to enjoin use or production. . Those, I think, are very different matters. One requires that he go to court first before he can enjoin and the other I says that he can simply enjointwhich is it you are suggesting and why? * Dr. Frederickson. I think that what happened here is there may have been some general language that could imply the remedies that he might seek to bring action. I would like to answer that question for the record, however, after studying its appearance here and irk what places. Mr. Magfiire. You cannot tell the committee right at this t 6 7 8 9 to 11 12 -13 14 15 16 .t7 18 19 20 21 22 23 c 24 25 3-44 moment which,-of those two you intend? If you cannot, submit it forthe. rdcord'i:-but I think -- Dr. Frederickson. I am advised by my counsel that we intended to sue in court but I should like to reserve for a clarification. Mr. Maguire. If that is the case, I should also like to ask you to review that point and see if you might want to take another position on it. Thank you, Mr. Chairman. Mr. Rogers. Mr. Ottinger? Mr. Ottinger. Thank you, Mr. Chairman. I think thisris' one of the most concerning issues that we have had raised con- cerning our obligations to public health and safety in the Congress, perhaps ever since we had to deal with the splitting of the atom. I wonder what makes you so confident that the risks that have been outlined for us by some very responsible and well' qualified scientists in the course of this hearing are not going to actually happen? Why is there any great rush to promote this research in view of the tremendous risk that seem to be attendant. I am seriously contemplating legislation which would call for a moratorium and get the international scientific community to- gether and see if we cannot come to better consensus on this before we expose society to this kind of risk. In view of the experiences such as were had at Ft. Detric 6 7 8 9 10 It 12 13 14 . 1s 16 17 18. 19 20 21 22 23 -24 25 3-45 as has been described to us as happened at other research laboratories, and in view of the dangers and the cost to societt_p thbt have been caused by our rushing headlong into other scientific developments throughout the country, I wonder if we would be much wiser to say well, let us stop, let us take a look both at the dangers involved in this research and in the degree of controls and let us have thosexontrols if we are to go ahead with this in place before we have to encounter a catastrophy of the kind that is predicted, is at least-possible through recombinant DNA research. Dr. Frederickson. My view of the problem, and of the current. state of regulation and of the activities of the govern- ment and public sector, my views are derived from an extra- ordinary exposure and experienceain the last three years or the last two years, derived from my position as Director of NIH and responsible for listening to all of the scientific and public-testimony, to which I have been exposed and a&attempt to determine from listening to all of the arguments that I can, whether I think this work ought to proceed. I have come to the conclusion that this set of guidelines and the actions taken are very conservative indeed. I have not been exposed to any argumentation outside the arguments that were posed in the course of the development of the guide- lines at Asilcmar and atmy oQn scientific advisory committee which have represented any increment of scientific informatio:1 1 2 3 4 5 6 7 8 9 10 said they should not go forward at all. . 11 Dr. Fredericksan. Yes. I have been briefed on the hear- 12 -13 14 . 15 16 .nobody that has said that the-.gufdelines that were adopted 17 18 19 20 21 22 23 r 24 25 3-46 that indicated these guidelines might not be as conservative and as prudent as possible. Mr.' Ottinger; I Have you followed our hearings or have you had somebody follow our hearings? Dr. Frederickson. Yes, I have. Mr. Ottinger. Because we have had a whole parade of scientific and some public witnesses who have said, including an imminent scientist at MIT, that is working in this kind of biological research, as a matter of fact, two of them: it was ing testimony here. It represents attitudes and opinions from a variety of people that I have heard from extensively over this entire period of review. Mr. Ottinger. You told me just then that you had heard were not adequate. Dr. Frederickson. No, that is not what I said, sir. What I said was that I heard many opinions, concerns and anxieties that'they were not adequate but I have not heard, in the course of this, substantial scientific arguments that allowed one to conclude that was a correct view or that they altered my opinions about the guidelines, once revised. These guidelines, when I received them, had been extensiv ly revised and strengthened since the time they were handed to 9 10 11 12 13 14 . 15 16 17 18 19 20 .21. 22 23 . 24 25 3-47 me by the?Recombinant DNA Committee. In the cotirsecof that, 1 benefitted greatly by reading testimony and talking personally, listening to the statements of a variety of people, many of whom had legitimate concerns. I sent these back to the committee and I came to a final decision on each element, each criticism, each point of sub- stantive nature that was raised about those guidelines so f have attempted to examine them a< great length. Mr. Ottinger. Give us some odds as roughly as you can, because I guess that really is the calculation that we have to make, what are the odds on their being developed, some strain that would be damaging to either human beings or the plant life on which human beings depend?. * Dr. Frederickson. I cannot give you accurate odds: I can on$y give you some yes' and some explanation which is . . spelled out further in the environmental impact statement which we have developed. My own opinion is that the odds are very small indeed. Mr. Ottinger. What range are we talking about: are we * talking about one in 1,000, one in 100,000, one in l,OOO,OOO, one in ~e~ooo,ooo3 Dr. Frederickson. I would have to say, giving you my own personal opintan, derived from the sources I have describe to you that they might be one in l,QOO$OOO~;~~'.. Mr. Ottinger. What kind of odds do you,?pat on their bein 1 2 3 4 5 6 7 .8 9 10 11 12 13 14 . 15 16 17 18 I 19 20 2t 22 23 * 24 25 4 2 3-48 major, beneficial breakthroughs derived from this experimen- tation? Dr. Frederickson. Again, that is a qualified statement a to what is major or beneficial but the odds are already one to one or one because the use of these techniques in the developm of pure gene material to a degree of purity that cannot'be achieved bv any other known technique has already been exploit ed and used. Mrr Ottinger. The kinds of things we have been hearing a possibilities on the beneficial side range from I suppose the most spectacular, the possibility of cancer cure, to the possi bility of using this technology to clean up oil spills, cure diabetes. . In terms of the actual applied benefits that could be achieved, are those speculative benefits or are those things that you can see as likely to happen within the next three, five, ten years? Dr. Frederickson. I think a number of the benefits that have been mentioned for the use of these techniques are * &so highly speculative, although I think it is extremely likely, the probability is very high they will allow us to advance knowledge of the nature of genes but-much more, par- ticularly their control, the control of their expression in organisms and that fundamental knowledge will prove someday tc be extremely valuable. 6 7 8 9 10 11 12 13 14 1s 16 .17 18 19 : 20 21 22 23 .a 25 3- 49 I think it has a potential for developing eventually some knowledge which will be practical and perhaps very useful. Mr. Ottinger. On what do your base your one in a million guess on the risk side? Is it on the kind of logic given to us by Dr. Davis from Harvard of an extremely small lfkelihood that the recombinant can survive in the environment in view of the basic genetic nature of survival of the fittest? Is it that you think these guidelines are so strong that nothing is going to get out? Dr; Frederickson. Certainly all of us realize that the strongest guidelines in the world can be -- if human error occurs. I would base that opinion on several points. One, actually these guidelines are very stringent, too restriotive in the view of many scientists. They clearly are retarding the utilization of these techniques and I think that is the appropriate intent at the present time. Not only do they retard the use of the techniques in certain ways, but they actually prohibit a number of experiments. Those experiments, as best one can judge, might be the most potentially harmful derivatives of this kind of activity. Furthermore, the containment that is used to scale down, based on rationale which is developed in-the guidelines in such ways that all and a&l the guidelines do provide through their attempts to contain all of these molecules in satisfactory, either physically or by so-called biological containment, that 1 9 10 11 1.2 13 14 . 15 16 li 18 Bumpers and I put through, you have indicated that you were I 19 against licensure, I take it. I 20 21 22 23 -24 25 3-50 they must reduce tremendously the risk of an organism that is a recombinant product actually getting out and into the environ- ment in the first instance and surviving, should it escape in the second instance. Mr. Ottinger. I do not quiet understand. I would like to get a little clearer in my own mind. Are you saying that the risk is in fact great, but the guidelines will prevent it I getting out into the environment or are mu,..saying that the risk itself is not great and the risk not being great, combine I with the guidelines give -- m,, Frederickson. My personal belief is that the risk is ~ not-very great but that I do not know that for sure, and to I allow the possibility that I and others are wrong, I think the I . guidelines are, in a sense, an overkill and I think a delibera e and appropriate overkill in this situation. Mr. Ottinger. Let me ask a specific question; I know we do have time constraints. Under the legislation which Senator 1,have not seen the interagency agreement. Where do you come out with respect to the patent and liability provisions of 6ur legislation7 Dr. Frederickson. You will note that in the report of the committee, which is on page i3,-- Mr. Ottinger. I oniy have your testimony before me, sir. 6 7 8 9 10 11 12 13 14 ' 15 16 .l7 18 19 . 20 21 i2 23 * 24 25 3-51 Dr. Frederickson. I.am sorryIS this is the report of the Interagency Committee, page 18, Mr. Ottinger. Mr. Ottinger. I have a copy before me now,;lwhere yoti:-.reft to disclosure of information on page pages 14 and 18, basicall! the line of thought of the committe ran like this. It feels that there is potential commercial use of recombinant DNA technfques and it felt that appropriate measures should be taken to protect the nature of proprietaryffnformation but it was very clear in making, in attempting to indicate that it felt that the public safety must eventually override, of course, the protection of any proprietary information that it describes in certain language. It would hope that this could come about. Do you provide for disclosure to some select group of people I everything which is of a proprietary nature? Dr. Frederickson. We think that all relevant to safety and scientific information must be provided to the regulatory group. Mr. Ottinger. But not to the public at large? Dr. Frederickson. No, except under certain provisions, .- ._ if there is an overriding need for the public to know on an issue of safety, then the committee clbarly has its own record as indicating the Secretary must indicate that and discuss it, :- . .- how he might take such stepsin informing the submitter and giving the submitter some administrative or judicial right to . 9 10 11 12 13 14 IS 18 1.7 !8 19 20 21 22 23 24 25 3-52. contestthat. Mr. Ottinger. Do you reserve to yourselves the decision asl-,to what is proprietary? Dr. Frederickson. No, not in the sense that the Secretar (can first make a determination that he may want to reveal some thltng which the submitter thinks is proprietary but I think ultimately we recognize that this .micjht 'have.to be settled in the courts. Mr. Ottinger. Where do you come out on liability? We call for absolute liability without fault on the theory that if there was that kind of liability, then there would be much greater care exercised by private groups engaged:fn this re- search. Dr. Frederickson, On page 20, Mr. Ottinger, the committe discusses its views and it considers -- it is unlike the:.: question of'civil liability. The committee believed that actions or damages should be left to state and local. law. It was concerned that the inclusions of standards for 'strict liability as proposed in the measure submitted by Senator Bumpers and yourself could place a very severe con- straint on the ability qf institutions to obtain liability insurance. It felt,. after lengthy discussion with a number of in- stitutions, that it was very possible they might have to ter- minate all of their research activities unless some national 1 2 3 4 5 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 353 I legislation were passed to fndemnify them against this possi- bility. Mr. Ottinger. One last question which you may submit for the record. I would like to know what efforts -- you can answer this -L are there any efforts at the present time by the United States as to trying to get international agreement: are there negotiations going on for an international agreement to adopt guidelines simiElar to those which you have put forward? Dr. Frederickson. Yes, there are informal activities at the level of scientific organizations and the federal govern-' ment in this direction. The committee knows in