`
`Stanley N. Cohen
`
`I joined with a
`Almost‘3‘ years ago,
`group "of scientific colleagues in publicly
`calling attention to possible biohazards
`of certain kinds- of experiments that .
`could be can-ied out with newly devel-
`oped techniques for the propagation of
`genes from diverse sources in bacteria
`(1). Because of the newness and relative
`simplicity of these’ techniques (2), we
`were concerned that experiments in-
`volving certain genetic combinations
`that seemed to us to be hazardous might
`be performed before-adequate consid-
`eration had been given to the potential
`dangers. Contrary to what was believed
`by many observers, our concerns per-
`tained to a few very specific types of
`experiments that could be carried out
`with the new techniques, not to the tech-
`niques themselves.
`Guidelines have long been available to
`protect laboratory workers and the gen-
`eral public against known hazards asso-
`ciated with the handling of certain chem-
`icals, radioisotopes, and pathogenic mi-
`croorganisms; but because of the new-
`ness of recombinant DNA techniques,
`no guidelines were yet available for this
`research. My colleagues and I wanted to
`be sure that these new techniques would
`not be used, for example, for the con-
`struction of streptococci or pneumo-
`cocci resistant to penicillin, or for the
`creation of Escherichia coli capable of
`synthesizing botulinum toxin or diph-
`theria toxin. We asked that these experi-
`ments not be done, and also called for
`deferral of construction of bacterial re-
`combinants containing tumor virus genes
`until
`the implications of such experi-
`ments could be given further consid-
`eration.
`During the past 2 years, much fiction
`has been written about “recombinant
`DNA research.” What began as an act of
`responsibility by scientists, including a
`number of those involved in the devel-
`
`opment of the new techniques, has be-
`
`The author is a molecular geneticist and Professor
`of Medicine at the Stanford University School of
`Medicine. Stanford, Califoniia 94305. This article
`is
`from a statement prepared for a meet-
`ing
`the Committee on Environmental Health of
`1
`.
`tl;e76California Medical Association, 18 November
`654
`
`come the breeding ground for a horde of
`publicists—most poorly informed, some
`well-meaning, some self-serving. In this
`article I attempt to inject some relevant
`facts into the extensive public discussion
`of recombinant DNA research.
`
`Some Basic Information
`
`Recombinant DNA research is not a
`single entity, but rather it is a group of
`techniques that can be used for a wide
`variety of experiments. Much confusion
`has resulted from a lack of understanding
`of this point by many who have written
`about the subject. Recombinant DNA
`techniques, like chemicals on a shelf, are
`neither good nor bad per se. Certain
`experiments that can be done with these
`techniques are likely to be hazardous
`(just as certain experiments done with
`combinations of chemicals taken from
`the shelf will be hazardous), and there is
`universal agreement that such recombi-
`nant DNA experiments should not be
`done. Other experiments in which the
`very same techniques are used—such as
`taking apart a DNA molecule and putting
`segments of it back together again—are
`without conceivable hazard, and anyone
`who has looked into the matter has con-
`cluded that
`these experiments can be
`done without concern.
`-
`Then, there is the area “in between.”
`For many experiments, there is no evi-
`dence of biohazard, but there is also no
`certainty that there is not a hazard. For
`these experiments, guidelines have been
`developed in an attempt to match a level
`of containment with a degree of hypo-
`thetical risk. Perhaps the single point
`that has been most misunderstood in the
`controversy about recombinant DNA re-
`search, is that discussion of ‘ ‘risk” in the
`middle category of experiments relates
`entirely to hypothetical and speculative
`possibilities, not expected consequences
`or even phenomena that seem likely to
`occur on the basis of what is known.
`Unfortunately, much of the speculation
`has been interpreted as fact.
`There is nothing novel about the prin-
`ciple of matching a level of containment
`
`with the level of anticipated hazard; the
`containment procedures used for patho- ‘
`genie bacteria, toxic substances, and ra-
`dioisotopes attempt to do this. However,
`the containment measures used in these
`areas address themselves only to known
`hazards and do not attempt to protect
`against the unknown. If the same prin-
`ciple of protecting only against known or
`expected hazards were followed in re-
`combinant DNA research, there would
`be no containment whatsoever except
`for a very few experiments. In this in-
`stance, we are asking not only that there
`be no evidence of hazard, but that there
`be positive evidence that
`there is no
`hazard. In developing guidelines for re-
`combinant DNA research, we have at-
`tempted to take precautionary steps to
`protect ourselves against hazards that
`are not known to exist——and this unprec-
`edented act of caution is so novel that it
`has been widely misinterpreted as im-
`plying the imminence or at least the likeli-
`hood of danger.
`Much has been made of the fact that,
`even if a particular recombinant DNA
`molecule shows no evidence of being
`hazardous at the present time, we are
`unable to say for certain that it will not
`devastate our planet some years hence.
`Of course this view is correct; similarly,
`we are unable to say for certain that the
`vaccines we are administering to millions
`of children do not contain agents that
`will produce contagious cancer some
`years hence, we are unable to say for
`certain that a virulent virus will not be
`brought to the United States next winter
`by a traveler from abroad, causing a
`nationwide fatal epidemic of a hitherto
`unknown disease—and we are unable to
`say for certain that novel hybrid plants
`being bred around the world will not
`suddenly become weeds that will over-
`come our major food crops and cause
`worldwide famine.
`The statement that potential hazards
`could result from certain experiments
`involving recombinant DNA techniques
`is akin to the statement that a vaccine
`injected today into millions of people
`could lead to infectious cancer in 20
`years, a pandemic caused by a traveler-
`borne virus could devastate the United
`States, or a new plant species could un-
`controllably destroy the world's food
`supply. We have no reason to expect
`that any of these things will happen, but
`we are unable to say for certain that they
`will not happen. Similarly, we are unable
`to guarantee that any of man’s efforts to
`influence the earth's weather, explore
`space, modify crops, or cure disease will
`not carry with them the seeds for the
`ultimate destruction of civilization. Can
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`we in fact point to one major area of
`human activity where one can say for
`certain that there is zero risk? Poten-
`tially, we could respond to such risks by
`taking measures such as prohibiting for-
`eign travel to reduce the hazard of dead-
`ly virus importation and stopping experi-
`mentation with hybrid plants. It is pos-
`sible to develop plausible “scare sce-
`narios" involving virtually any activity
`or process, and these would have as
`much (or as little) basis in fact as most of
`the scenarios
`involving recombinant
`DNA. But we must distinguish fear of
`the unknown from fear that has some
`basis in fact; this appears to be the crux
`of the controversy surrounding recombi-
`nant DNA.
`Unfortunately, the public has been led
`to believe that the biohazards described
`in various scenarios are likely or prob-
`able outcomes of recombinant DNA re-
`search. “If the scientists themselves are
`concerned enough to raise the issue,”
`goes the fiction, “the problem is prob-
`ably much worse than anyone will ad-
`mit.” However, the simple fact is that
`there is no evidence that a bacterium
`carrying any recombinant DNA mole-
`cule poses a hazard beyond the hazard
`that can be anticipated from the known
`properties of the components of the re-
`combinant. And experiments involving
`genes that produce toxic substances or
`pose other known hazards are prohibit-
`ed.
`
`Freedom of Scientific Inquiry
`
`This issue has been raised repeatedly
`during discussions of recombinant DNA
`research. “The time has come,” the crit- ’
`ics charge, “for scientists to abandon
`their long-held belief that they should be
`free to pursue the acquisition of new
`knowledge
`regardless of
`the
`con-
`sequences." The fact is that no one has
`proposed that freedom of inquiry should
`extend to scientific experiments that en-
`danger public safety. Yet, “freedom of
`scientific inquiry” is repeatedly raised as
`a straw-man issue by critics who imply
`that somewhere there are those who ar-
`gue that
`there should be no restraint
`whatsoever on research.
`Instead, the history of this issue is one
`of self-imposed restraint by scientists
`from the very start. The scientific group
`that first raised the question of possible
`hazard in some kinds of recombinant
`DNA experiments included most of the
`scientists involved in the development of
`the techniques—and their concern was
`made public so that other investigators
`who might not have adequately consid-
`18 FEBRUARY I977
`
`ered the possibility of hazard could exer-
`cise appropriate restraint. While most
`scientists would defend their right to free-
`dom of scientific thought and discourse,
`I do not know of anyone who has pro-
`posed that scientists should be free to do
`whatever experiments they choose re-
`gardless of the consequences.
`'
`
`Interference with “Evolutionary
`
`Wisdom”
`Some critics of recombinant DNA re-
`search ask us to believe that the process
`of evolution of plants, animals, and mi-
`crobes has
`remained delicately con-
`trolled for millions of years, and that the
`construction of recombinant DNA mole-
`cules now threatens the master plan of
`evolution. Such thinking, which requires
`a belief that nature is endowed with
`wisdom, intent, and foresight,
`is alien
`to most post-Darwinian biologists (3).
`Moreover, there is no evidence that the
`evolutionary process is delicately con-
`trolled by nature. To the contrary, man
`has long ago modified the process of
`evolution, and biological evolution con-
`tinues to be influenced by man. Primitive
`man’s domestication of animals and culti-
`vation of crops provided an “unnatural"
`advantage to certain biological species
`and a consequent perturbation of evolu-
`tion. The later creation by man of hybrid
`plants and animals has resulted in the
`propagation of new genetic combinations
`that are not the products of natural evolu-
`tion. In the microbiological world, the
`use of antimicrobial agents to treat bacte-
`rial infections and the advent of mass
`immunization programs against viral dis-
`ease has made untenable the thesis of
`delicate evolutionary control.
`A recent letter (4) that has been widely
`quoted by critics of recombinant DNA
`research asks, “Have we the right to
`counteract irreversibly the evolutionary
`wisdom of millions of years .
`. .?” It is
`this so-called evolutionary wisdom that
`gave us the gene combinations for bubon-
`ic plague, smallpox, yellow fever,
`ty-
`phoid, polio, diabetes, and cancer. It is
`this wisdom that continues to give us
`uncontrollable diseases such as Lassa
`fever, Marburg virus, and very recently
`the Marburg-related hemorrhagic fever
`virus, which has resulted in nearly 100
`percent mortality in infected individuals
`in Zaire and the Sudan. The acquisition
`and use of all biological and medical
`knowledge constitutes an intentional and
`continuing assault on evolutionary wis-
`dom. Is this the “warfare against na-
`ture” that some critics fear from re-
`combinant DNA?
`
`How About the Benefits?
`
`For all but a very few experiments, the
`risks of recombinant DNA research are
`speculative. Are the benefits equally
`speculative or is there some factual basis
`for expecting that benefits will occur
`from this technique? I believe that the
`anticipation of benefits has a substantial
`basis in fact, and that the benefits fall
`into two principal categories: (i) advance-
`ment of fundamental scientific and medi-
`cal knowledge, and (ii) possible practical
`applications.
`In the short space of 3% years, the use
`of the recombinant DNA technology has
`already been of major importance in the
`advancement of
`fundamental knowl-
`edge. We need to understand the struc-
`ture and function ofgenes, and this meth-
`odology provides a way to isolate large
`quantities of specific segments of DNA
`in pure form. For example, recombinant
`DNA methodology has provided us with
`much information about the structure of
`plasmids that cause antibiotic resistance
`in bacteria, and has given us insights into
`how these elements propagate them-
`selves, how they evolve, and how their
`genes are regulated.
`In the past, our
`inability to isolate specific genetic re-
`gions of the chromosomes of higher orga-
`nisms has limited our understanding of
`the genes of complex cells. Now use of
`recombinant DNA techniques has pro-
`vided knowledge about how genes are
`organized into chromosomes and how
`gene expression is controlled. With such
`knowledge we can begin to learn how
`defects in the structure of such genes
`alter their function.
`On a more practical level, recombi-
`nant DNA techniques potentially permit
`the construction of bacterial strains that
`can produce biologically important sub-
`stances
`such as antibodies and hor-
`mones. Although the full expression of
`higher organism DNA that is necessary
`to accomplish such production has not
`yet been achieved in bacteria, the steps
`that need to be taken to reach this goal
`are defined, and we can reasonably ex-
`pect that the introduction of appropriate
`“start” and “stop” control signals into
`recombinant DNA molecules will enable
`the expression of animal cell genes. On
`an even shorter time scale, we can ex-
`pect recombinant DNA techniques to
`revolutionize the production of antibiot-
`ics, vitamins, and medically and indus-
`trially useful chemicals by eliminating
`the need to grow and process the often
`exotic bacterial and fungal strains cur-
`rently used as sources for such agents.
`We can anticipate the construction of
`modified antimicrobial agents that are
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`not destroyed by the antibiotic in-
`activating enzymes responsible for drug
`resistance in bacteria.
`In the area of vaccine production, we
`can anticipate the construction of specif-
`ic bacterial strains able to produce de-
`sired antigenic products, eliminating the
`present need for
`immunization with
`killed or attenuated specimens of dis-
`ease-causing viruses.
`One practical application of recom-
`binant DNA technology in the area of
`vaccine production is already close to
`being realized. An E. coli plasmid coding
`for an enteric toxin fatal
`to livestock
`has been taken apart, and the toxin
`gene has been separated from the re-
`mainder of the plasmid. The next step
`is to cut away a small segment of the
`toxin-producing gene so that the sub-
`stance produced by the resulting gene in
`E. coli will not have toxic properties but
`will be immunologically active in stimu-
`lating antibody production.
`Other benefits from recombinant DNA
`research in the areas of food and energy
`production are more speculative. How-
`ever, even in these areas there is a scien-
`tific basis for expecting that the benefits
`will someday be realized. The limited
`availability of fertilizers and the potential
`hazards associated with excessive use of
`nitrogen fertilizers now limits the yields
`of grain and other crops, but agricultural
`experts suggest that transplantation of
`the nitrogenase system from the chromo-
`somes of certain bacteria into plants or
`into other bacteria that live symbiotically
`with food crop plants may eliminate the
`need for fertilizers. For many years, sci-
`entists have modified the heredity of
`plants by comparatively primitive tech-
`niques. Now there is a means of doing
`this with greater precision than has been
`possible previously.
`Certain algae are known to produce
`hydrogen from water, using sunlight as
`energy. This process potentially can
`yield a virtually limitless source of pollu-
`tion-free energy iftechnical and biochem-
`ical problems indigenous to the known
`hydrogen-producing organisms can be
`solved. Recombinant DNA techniques
`ofl'er a possible means of solution to
`these problems.
`It is ironic that some of the most vocal
`opposition to recombinant DNA re-
`search has come from those most con-
`cerned about the environment. The abili-
`
`ty to manipulate microbial genes offers
`the promise of more eifective utilization
`of renewable resources for mankind’s
`food and energy needs; the status quo
`ofi'ers the prospect of progressive and
`continuing devastation of the environ-
`ment. Yet, some environmentalists have
`656
`
`been misled into taking what I believe to
`be an antienvironmental position on the
`issue of recombinant DNA.
`
`The NIH Guidelines
`
`Even if hazards are speculative and
`the potential benefits are significant and
`convincing, wouldn’t it still be better to
`carry out
`recombinant DNA experi-
`ments under conditions that provide an
`added measure of safety—just in case
`some of the conjectural hazards prove to
`be real?
`
`This is exactly what is required under
`the NIH (National Institutes of Health)
`guidelines (5) for recombinant DNA re-
`search:
`
`1) These guidelines prohibit experi-
`ments in which there is some scientific
`basis for anticipating that a hazard will
`occur. In addition, they prohibit experi-
`ments in which a hazard, although it
`might be
`entirely
`speculative, was
`judged by NIH to be potentially serious
`enough to warrant prohibition of the ex-
`periment. The types of experiment that
`were the basis of the initial “moratori-
`um" are included in this category; con-
`trary to the statements of some who have
`written about
`recombinant DNA re-
`search, there has in fact been no lifting of
`the original restrictions on such experi-
`ments.
`
`2) The NIH guidelines require that a
`large class of other experiments be car-
`ried out in P4 (high level) containment
`facilities of the type designed for work
`with the most hazardous naturally occur-
`ring microorganisms known to man
`(such as Lassa fever virus, Marburg vi-
`rus, and Zaire hemorrhagic fever virus).
`It is difiicult to imagine more hazardous
`self-propagating biological agents than
`such viruses, some of which lead to near-
`ly 100 percent mortality in infected indi-
`viduals. The P4 containment requires a
`specially built laboratory with airlocks
`and filters, biological safety cabinets,
`clothing changes for personnel, auto-
`claves within the facility, and the like.
`This level of containment is required for
`recombinant DNA experiments
`for
`which there is at present no evidence of
`hazard, but for which it is perceived that
`the hazard might be potentially serious if
`conjectural fears prove to be real. There
`are at present only four or five installa-
`tions in the United States where P4 ex-
`periments could be carried out.
`3) Experiments associated with a still
`lesser degree of hypothetical risk can be
`conducted in P3 containment facilities.
`These are also specially constructed lab-
`oratories
`requiring double door en-
`
`trances, negative air pressure, and spe-
`cial
`air
`filtration devices. Facilities
`where P3 experiments can be perfonned
`are limited in number, but they exist at
`some universities.
`4) Experiments in which the hazard is
`considered unlikely to be serious even if
`it occurs still require laboratory proce-
`dures (P2 containment) that have for
`years been considered suflicient for re-
`search with such pathogenic bacteria as
`Salmonella typhosa, Clostridium bot-
`ulinum, and Cholera vibrio. The NIH
`guidelines require that P2 facilities be
`used for work with bacteria carrying in-
`terspecies recombinant DNA molecules
`that have shown no evidence of being
`hazardous—and even for some recombi-
`nant DNA experiments in which there is
`substantial evidence of lack of hazard.
`5) The P1
`(lowest)
`level of con-
`tainment can be used only for recombi-
`nant DNA molecules that potentially can
`be made by ordinary biological gene ex-
`change in bacteria. Conformity to even
`this lowest level of containment in the
`laboratory requires decontamination of
`work surfaces daily and after spills of
`biological materials, the use of mechani-
`cal pipetting devices or cotton plugged
`pipettes by workers, a pest control pro-
`gram, and decontamination of liquid-and
`solid waste leaving the laboratory.
`In other areas of actual or potential
`biological hazard, physical containment
`is all that microbiologists have had to
`rely upon; if the Lassa fever virus were
`to be released inadvertently from a P4
`facility, there would be no further barrier
`to prevent the propagation of this virus
`which is known to be deadly and for
`which no specific therapy exists. How-
`ever, the NIH guidelines for recombi-
`nant DNA research have provided for an
`additional level of safety for workers and
`the public: This is a system of biological
`containment that is designed to reduce
`by many orders of magnitude the chance
`of propagation outside the laboratory of
`microorganisms used as hosts for re-
`combinant DNA molecules.
`An inevitable consequence of these
`containment procedures is
`that
`they
`have made it diflicult for the public to
`appreciate that most of the hazards un-
`der discussion are conjectural. Because
`in the past, governmental agencies have
`often been slow to respond to clear and
`definite dangers in other areas of tech-
`nology, it has been inconceivable to sci-
`entists working in other fields and to the
`public at
`large that an extensive and
`costly federal machinery would have
`been established to provide protection in
`this area of research unless severe haz-
`ards were known to exist. The fact that
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`recombinant DNA research has prompt-
`ed international meetings, extensive cov-
`erage in the news media, and govem-
`mental intervention at the federal level
`has been perceived by the public as
`prima facie evidence that this research
`must be more dangerous than all the rest.
`The scientific community's response has
`been to establish increasingly elaborate
`procedures to police itself—but
`these
`very acts of scientific caution and respon-
`sibility have only served to perpetuate
`and strengthen the general belief that the
`hazards under discussion must be clear-
`cut and imminent in order for such steps
`to be necessary.
`It is worth pointing out that despite
`predictions of imminent disaster from
`recombinant DNA experiments, the fact
`remains that during the past 3% years,
`-many billions of bacteria containing a
`wide variety of recombinant DNA mole-
`cules have been grown and propagated in
`the United States and abroad , incorporat-
`ing DNA from viruses, protozoa,
`in-
`sects, sea urchins, frogs, yeast, mam-
`mals, and unrelated bacterial species in-
`to E.
`coli, without hazardous con-
`sequences so far as I am aware. And the
`majority of these experiments were car-
`ried out prior to the strict containment
`procedures specified in the current feder-
`al guidelines.
`.
`Despite the experience thus far, it will
`always be valid to argue that recombi-
`nant DNA molecules that seem safe
`today may prove hazardous tomorrow.
`One can no more prove the safety of a
`particular genetic combination under all
`
`imaginable circumstances than one can
`prove that currently administered vac-
`cines do not contain an undetected self-
`propagating agent capable of producing
`cancer in the future, or that a hybrid
`plant created today will not lead to disas-
`trous consequences some years hence.
`No matter what evidence is collected to
`document the safety of a new therapeutic
`agent, a vaccine, a process, or a particu-
`lar kind of recombinant DNA molecule,
`one can always conjure up the possibility
`of future hazards that cannot be dis-
`proved. When one deals with conjecture,
`the number of possible hazards is unlimit-
`ed; the experiments that can be done to
`establish the absence of hazard are finite
`in number.
`Those who argue that we should not
`use recombinant DNA techniques until
`or unless we are absolutely certain ‘that
`there is zero risk fail to recognize that no
`one will ever be able to guarantee total
`freedom from risk in any significant hu-
`man activity. All that we can reasonably
`expect is a mechanism for dealing re-
`sponsibly with hazards that are known to
`exist or which appear likely on the basis
`of information that is known. Beyond
`this, we can and should exercise caution
`in any activity that carries us into pre-
`viously uncharted territory, whether it is
`recombinant DNA research, creation of
`a new drug or vaccine, or bringing a
`spaceship back to Earth from the moon.
`Today, as in the past, there are those
`who would like to think that there is
`
`freedom from risk in the status quo.
`However, humanity continues to be buf-
`
`feted by ancient and new diseases, and
`by malnutrition and pollution; recombi-
`nant DNA techniques ofl‘er a reasonable
`expectation for a partial solution to some
`of these problems. Thus, we must ask
`whether we can afford to allow pre-
`occupation with and conjecture about
`hazards that are not known to exist, to
`limit our ability to deal with hazards that
`do exist. Is there in fact greater risk in
`proceeding judiciously, or in not pro-
`ceeding at all? We must ask whether
`there is any rational basis for predicting
`the dire consequences of recombinant
`DNA research portrayed in the scenarios
`proposed by some. We must then exam-
`ine the “benefit" side of the picture and
`weigh the already realized benefits and
`the reasonable expectation of additional
`benefits, against the vague fear of the
`unknown that has in my opinion been the
`focal point of this controversy.
`lleferencesantlliotes
`
`. P. Berg D. Baltimore, H. W. Boyer, S. N.
`Cohen, it. w. Davis, D. s. Hogness, D. Na-
`thans, R. Roblin, J. D. Watson, S. Weissman, N.
`D. Zinder, Proc. Natl. Acad. Sci. U.S.A. 71,
`2593 (1974).
`, H. W. Boyer, R.
`2. S. N. Cohen, A. C. Y. C
`3); S. N. Cohen,
`B. Helling, ibid. 70, 3240 (1
`Sci. Am. 233 (No. 7), 24 (I975).
`3. Ifwe accept the view that any natural barriers to
`the propagation of enetic material derived from
`unrelated species 0 not owe their existence to
`the intent of nature, we can reason that evolu-
`tion has created and maintained such barriers
`
`in nature.
`her-more, we must conclude that
`because ofirttrnities for genetic mixing occur
`limitations to
`ne exchange have evolved be-
`cause the
`' ng of genes from diverse orga-
`nisms is biol
`'cslly undesirable—not in a moral
`or theol
`sense as some observers would
`’
`have us°gelieve—but to those organisms in-
`.
`.
`. crence
`,
`.
`4 ‘r'z°1i:fi'rga1r S ‘
`192 938 (1976)
`5. 3Reg. 41076) (9 September 1976), pp. 38426-
`
`IIIWS AND COHHINT
`
`Brazil’s Nuclear Program: Carter’s
`
`" Nonproliferation Policy Backfires
`
`Brasilia. The Carter Administration’s
`attempt to convince West Germany to
`renege on its controversial agreement
`with Brazil for supplying nuclear tech-
`nology has created a major furor here.
`Vice President Mondale’s discussion of
`the matter with West German oflicials on
`his first foreign mission, before any con-
`sultation with Brazil, has fanned an ear-
`lier but muted concern into a nationwide
`outpouring of resentment at what is seen
`as U.S. interference with Brazil’s efforts
`to become a major world power. The
`18 FEBRUARY 1977
`
`alfair seems likely to further damage
`U.S-Brazilian relations, which were al-
`ready deteriorating, and to accelerate a
`discernible tilt toward Europe and Japan
`as the favored partners for cooperative
`development projects and trade deals.
`The resentment expressed here is not
`confined to government ofiicials but
`comes from many disparate elements of
`Brazilian society and seems to have had
`the effect of strengthening political sup-
`port for President Ernesto Geisel and his
`authoritarian military regime. Spokes-
`
`men for the opposition party, the Brazil-
`ian Democratic Movement (MDB), have
`publicly condemned the U.S. moves and
`defended the West German agreement.
`In December a leading MDB figure, Sen-
`ator Paulo Brossard of Rio Grande do
`Sul, said in response to then President-
`elect Carter’s call for cancellation of the
`agreement that while he respected Car-
`ter’s position, "it is not possible to ac-
`cept
`it without protesting the inter-
`ference in matters that are the exclusive
`competence of my country and its own
`interests." The tone of the rhetoric has
`become harsher in recent weeks. There
`has been heavy press coverage in Brazil
`of the Mondale trip, and editorial opinion
`has been overwhelmingly anti-Ameri-
`can. Even university scientists who had
`been openly critical of the nuclear deal
`on technical grounds have closed ranks
`behind the government.
`Ironically, President Carter’s
`657
`
`un-
`
`Sanofi/Regeneron Ex. 1030, pg 914
`
`Mylan Ex. 1030, pg 914