Recombinant DNA: Fact and Fiction
`
`Stanley N. Cohen
`
`come the breeding ground for a horde of
`Almost· 3 years aso, I joined with a
`groupo( sdentiflc colleagues in publicly publicists-most poorly informed, some
`calling .attention to possible l)iohaz.ards weD-meaning, some self-serving. In this
`of .certain kinds· of experiments that . article l attempt to iriject some relevant
`could be carried out with newly devel-
`facts into the extensive public discussion
`oped techniques for the propagation of of recombinant DNA research.
`genes from divefle sources in bacteria
`(1). Because of the newness and relative
`simplicity of these techniques (2). we Some Buic IDtormation
`were concerned that experiments in(cid:173)
`volving certain genetic combinations
`that seemed to us to.be hazardous might
`be performed before .. adequate consid(cid:173)
`eration had been given to the potential
`dangers. Contrary to wbat was believed
`by many observers, our concerns per(cid:173)
`tained to a few very specific types of
`experiments tbat could be carried out
`with the new techniques, not to the tech(cid:173)
`niques themselves.
`Guidelines have long been available to
`protect laboratory workers and the gen(cid:173)
`eral public against known hazards asso(cid:173)
`ciated with the handling of certain chem(cid:173)
`icals, radioisotopes, and pathogenic mi(cid:173)
`croorganisms; but because of the new(cid:173)
`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(cid:173)
`struction of streptococci or pneumo(cid:173)
`cocci resistant to penicillin, or for the
`creation of EscherichiQ coli capable of
`synthesizing botulinum toxin or diph(cid:173)
`theria toxin. We asked that these experi(cid:173)
`ments not be done, and also called for
`deferral of construction of bacterial re(cid:173)
`combinants containing tumor virus genes
`until the implications of such experi(cid:173)
`ments could be given further consid(cid:173)
`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 ef those involved in the devel(cid:173)
`opment of the new techniques, has be-
`
`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
`~bout 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
`Oust as certain experiments done with
`combinations of chemicals taken from
`the shelf will be hazardous), and there is
`universal agreement that such recombi(cid:173)
`nant DNA experiments sh.ould not be
`done. Other experiments in which the
`very same techniques are used-such as
`taking apan 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(cid:173)
`cluded that these experiments can be
`done without concern.
`Then, there is tbe area "in between."
`For many experiments, there is ~o evi(cid:173)
`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(cid:173)
`thetical risk. Perhaps the single point
`that bas been most misunderstood in the
`controversy about recombinant DNA re(cid:173)
`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 b~sis of what is known.
`Unfortunately, lnudt of the speculation
`has been interpreted as fact.
`There is nothing novel about the prin(cid:173)
`ciple of matching a level of containment
`
`The autbor ia a moleculat aeneticist and Profes.sor
`d Medicillc at tbe Staafoni Uni.vcnily Scbool of
`Medidlle, Stanford, California 9430.5. This article
`is adapted from a atatemenl ~ for a meel·
`iQa of' die COmmittee on EaVli'OillDeDial ~ of
`the CalifOrnia Medical Asaoclalion, 18 November
`1976.
`.
`
`6-54
`
`with the level of anticipated hazard; the
`containment procedures used for patho(cid:173)
`genic bacteria, toxic substances, and ra(cid:173)
`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. [f the same pri~
`ciple of protecting only against known or
`expected hazards were followed in re(cid:173)
`combinant DNA research, there would
`be no containment whatsoever except
`for a very few experiments. In this in(cid:173)
`stance, weare 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(cid:173)
`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(cid:173)
`edented act of caution is so novel that it
`has been widely misinterpreted as im(cid:173)
`plying the imminence or at least the likeli(cid:173)
`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 wJll not
`devastate our planet some years hence.
`Of course this view is correct; similarly,
`we are unable to say for certain that the
`v~ccines weare 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(cid:173)
`come our m~U<>r 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 infectiou.s cancer in 20
`years, a pandemic caused by a traveler(cid:173)
`borne virus could devastate the United
`States, or a new plant species could un(cid:173)
`controllably destroy the world's food
`supply_ We have no reason to expect
`that any of these things wiD 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
`SCIENCE, VOL. I"
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`Sanofi/Regeneron Ex. 1030, pg 911
`
`Merck Ex. 1030, pg 937
`
`

`
`we in fact point to one major area of
`human activity where one can say for
`certain that there is zero risk? Poten(cid:173)
`tially, we could respond to such risks by
`taking measures such as prohibiting for(cid:173)
`eign travel to reduce the hazard of dead(cid:173)
`ly virus importation and stopping experi(cid:173)
`mentation with hybrid plants. It is pos(cid:173)
`sible to develop plausible "scare sce(cid:173)
`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(cid:173)
`nant DNA.
`Unfortunately, the public has been led
`to believe that the biohazards described
`in various scenarios are likely or prob(cid:173)
`able outcomes of recombinant DNA re(cid:173)
`search. "If the scientists themselves are
`concerned enough to raise the issue,"
`goes the fiction, "the problem is prob(cid:173)
`ably much worse than anyone will ad(cid:173)
`mit." However, the simple fact is that
`there is no evidence that a bacterium
`carrying any recombinant DNA mole(cid:173)
`cule poses a hazard beyond the hazard
`that can be anticipated from the known
`properties of the components of the re(cid:173)
`combinant. And experiments involving
`genes that produce toxic substances or
`pose other known hazards are prohibit(cid:173)
`ed.
`
`Freedom of Scientific Inquiry
`
`This issue has been raised repeatedly
`during discussions of recombinant DNA
`research. "The time has come," the crit(cid:173)
`ics charge, "for scientists to abandon
`their long-held belief that they should be
`free to pursue the acquisition of new
`the con(cid:173)
`regardless of
`knowledge
`sequences." The fact is that no one has
`proposed that freedom of inquiry should
`extend to scientific experiments that en(cid:173)
`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(cid:173)
`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 tm
`
`ered the possibility of hazard could exer(cid:173)
`cise appropriate restraint. While most
`scientists would defend their right to free(cid:173)
`dom of scientific thought and discourse,
`I do not know of anyone who has pro(cid:173)
`posed that scientists should be free to do
`whatever experiments they choose re(cid:173)
`gardless of the consequences.
`
`Interference witb "Evolutionary
`Wisdom"
`
`Some critics of recombinant DNA re(cid:173)
`search ask us to believe that the process
`of evolution of plants, animals, and mi(cid:173)
`crobes has remained delicately con(cid:173)
`trolled for millions of years, and that the
`construction of recombinant DNA mole(cid:173)
`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(cid:173)
`trolled by nature. To the contrary, man
`has long ago modified the process of
`evolution, and biological evolution con(cid:173)
`tinues to be influenced by man. Primitive
`man's domestication of animals and culti(cid:173)
`vation of crops provided an "unnatural"
`advantage to certain biological species
`and a consequent perturbation of evolu(cid:173)
`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(cid:173)
`tion. In the microbiological world, the
`use of antimicrobial agents to treat bacte(cid:173)
`rial infections and the advent of mass
`immunization programs against viral dis(cid:173)
`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(cid:173)
`ic plague, smallpox, yellow fever, ty(cid:173)
`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(cid:173)
`dom. Is this the "warfare against na(cid:173)
`ture" that some critics fear from re(cid:173)
`combinant DNA?
`
`How About tbe 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(cid:173)
`ment of fundamental scientific and medi(cid:173)
`cal knowledge, and (ii) possible practical
`applications.
`In the short space of3~ years, the use
`of the recombinant DNA technology has
`already been of major importance in the
`advancement of fundamental knowl(cid:173)
`edge. We need to understand the struc(cid:173)
`ture and function of genes, and this meth(cid:173)
`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(cid:173)
`selves, how they evolve, and how their
`genes are regulated. In the past, our
`inability to isolate specific genetic re(cid:173)
`gions of the chromosomes of higher orga(cid:173)
`nisms has limited our understanding of
`the genes of complex cells. Now use of
`recombinant DNA techniques has pro(cid:173)
`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(cid:173)
`nant DNA techniques potentially permit
`the construction of bacterial strains that
`can produce biologically important sub(cid:173)
`stances such as antibodies and hor(cid:173)
`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(cid:173)
`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. cart ex(cid:173)
`pect recombinant DNA techniques to
`revolutionize the production of antibiot(cid:173)
`ics, vitamins, and medically and indus(cid:173)
`trially useful chemicals by eliminating
`the need to grow and process the often
`exotic bacterial and fungal strains cur(cid:173)
`rently used as sources for such agents.
`We can anticipate the construction of
`modified antimicrobial agents that are
`
`655
`
`Sanofi/Regeneron Ex. 1 030, pg 912
`
`Merck Ex. 1030, pg 938
`
`

`
`in(cid:173)
`the antibiotic
`not destroyed by
`activating enzymes responsible for drug
`resistance in bacteria.
`In the area of vaccine production, we
`can anticipate the construction of specif(cid:173)
`ic bacterial strains able to produce de(cid:173)
`sired antigenic products, eliminating the
`present need for immunization with
`killed or attenuated specimens of dis(cid:173)
`ease-causing viruses.
`One practical application of recom(cid:173)
`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(cid:173)
`mainder of the plasmid. The next step
`is to cut away a small segment of the
`toxin-producing gene so that the sub(cid:173)
`stance produced by the resulting gene in
`E. coli will not have toxic properties but
`will be immunologically active in stimu(cid:173)
`lating antibody production.
`Other benefits from recombinant DNA
`research in the areas of food and energy
`production are more speculative. How(cid:173)
`ever, even in these areas there is a scien(cid:173)
`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(cid:173)
`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(cid:173)
`entists have modified the heredity of
`plants by comparatively primitive tech(cid:173)
`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(cid:173)
`tion-free energy if technical and biochem(cid:173)
`ical problems indigenous to the known
`hydrogen-producing organisms can be
`solved. Recombinant DNA techniques
`offer a possible means of solution to
`these problems.
`It is ironic that some of the most vocal
`opposition to recombinant DNA re(cid:173)
`search has come from those most con(cid:173)
`cerned about the environment. The abili(cid:173)
`ty to manipulate microbial genes offers
`the promise of more effective utilization
`of renewable resources for mankind's
`food and energy needs; the status quo
`offers the prospect of progressive and
`continuing devastation of the environ(cid:173)
`ment. Yet, some environmentalists have
`
`6S6
`
`been misled into taking what I believe to
`be an antienvironmental position on the
`issue of recombinant DNA.
`
`The NIH GuideHnes
`
`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(cid:173)
`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(cid:173)
`search:
`I) These guidelines prohibit experi(cid:173)
`ments in which there is some scientific
`basis for anticipating that a hazard will
`occur. In addition, they prohibit experi(cid:173)
`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(cid:173)
`periment. The types of experiment that
`were the basis of the initial "moratori(cid:173)
`um" are included in this category; con(cid:173)
`trary to the statements of some who have
`written about recombinant DNA re(cid:173)
`search, there has in fact been no lifting of
`the original restrictions on such experi(cid:173)
`ments.
`2) The NIH guidelines require that a
`large class of other experiments be car(cid:173)
`ried out in P4 (high level) containment
`facilities of the type designed for work
`with the most hazardous naturally occur(cid:173)
`ring microorganisms known
`to man
`(such as Lassa fever virus, Marburg vi(cid:173)
`rus, and Zaire hemorrhagic fever virus).
`It is difficult to imagine more hazardous
`self-propagating biological agents than
`such viruses, some of which lead to near(cid:173)
`ly IOO percent mortality in infected indi(cid:173)
`viduals. The P4 containment requires a
`specially built laboratory with alrtocks
`and filters, biological safety cabinets,
`clothing changes for personnel, auto(cid:173)
`claves within the facility, and the like.
`This level o( 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(cid:173)
`tions in the United States where P4 ex(cid:173)
`periments could be carried out.
`3) Experiments associated with a still
`lesser degree or hypothetical risk can be
`conducted in P3 containment facilities.
`These are also specially constructed lab(cid:173)
`oratories requiring double door en-
`
`trances, negative air pressure, and spe(cid:173)
`cial air filtration devices. Facilities
`where P3 experiments can be performed
`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(cid:173)
`dures (P2 containment) that have for
`years been considered sufficient for re(cid:173)
`search with such pathogenic bacteria as
`Salmonella typhosa, Clostridium bot(cid:173)
`ulinum, and Cholera vibrio. The NIH
`guidelines require that P2 facilities be
`used for work with bacteria carrying in(cid:173)
`terspecies recombinant DNA molecules
`that have shown no evidence of being
`hazardous-and even for some recombi(cid:173)
`nant DNA experiments in which there is
`substantial evidence of lack of hazard.
`5) The PI (lowest)
`level of con(cid:173)
`tainment can be used only for recombi(cid:173)
`nant DNA molecules that potentially can
`be made by ordinary biological gene ex(cid:173)
`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(cid:173)
`cal pipetting devices or cotton plugged
`pipettes by workers, a pest control pro(cid:173)
`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(cid:173)
`ever, the NIH guidelines for recombi(cid:173)
`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(cid:173)
`combinant DNA molecules.
`An inevitable consequence of these
`containment procedures is that they
`have made it difficult for the public to
`appreciate that most of the hazards un(cid:173)
`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(cid:173)
`nology, it has been inconceivable to sci(cid:173)
`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(cid:173)
`ards were known to exist. The fact that
`SCIENCE, VOL. 195
`
`Sanofi/Regeneron Ex. 1 030, pg 913
`
`Merck Ex. 1030, pg 939
`
`

`
`recombinant DNA research has prompt(cid:173)
`ed international meetings, extensive cov(cid:173)
`erage in the news media, and govern(cid:173)
`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(cid:173)
`sibility have only served to perpetuate
`and strengthen the general belief that the
`hazards under discussion must be clear(cid:173)
`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(cid:173)
`cules have been grown and propagated in
`the United States and abroad, incorporat(cid:173)
`ing DNA from viruses, protozoa, in(cid:173)
`sects, sea urchins, frogs, yeast, mam(cid:173)
`mals, and unrelated bacterial species in(cid:173)
`to E. coli, without hazardous con(cid:173)
`sequences so far as I am aware. And the
`majority of these experiments were car(cid:173)
`ried out prior to the strict containment
`procedure!! specified in the current feder(cid:173)
`al guidelines.
`Despite the experience thus far, it will
`always be valid to argue that recombi(cid:173)
`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(cid:173)
`cines do not contain an undetected self(cid:173)
`propagating agent capable of producing
`cancer in the future, or that a hybrid
`plant created today will not lead to disas(cid:173)
`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(cid:173)
`lar kind of recombinant DNA molecule,
`one can always conjure up the possibility
`of future hazards that cannot be dis(cid:173)
`proved. When one deals with conjecture,
`the number of possible hazards is unlimit(cid:173)
`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(cid:173)
`man activity. All that we can reasonably
`expect is a mechanism for dealing re(cid:173)
`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(cid:173)
`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(cid:173)
`nant DNA techniques offer a reasonable
`expectation for a partial solution to some
`of these problems. Thus, we must ask
`whether we can afford to allow pre(cid:173)
`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(cid:173)
`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(cid:173)
`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.
`
`~-Notes
`I. P. BelllL.. D. Baltirn.ore, H. W. Boyer, S. N.
`Cohen, K. W. DaVIs, D. S. Hojpless, D. Na(cid:173)
`thans, R. Roblin, J. D. Watson, S. Weissman, N.
`D. Zinder, Proc. Nat/. A.cad. Sci. U.S.A. 71,
`2j93 (1974).
`2. S. N. C~he~, ~·C. Y. Chana, H. W. Boyer, R.
`B. HeUIJI8, rbid. 70, 3240 (1!»3); S. N. Cohen,
`Sci. A.m. l33 (No. 7), 24 (1975).
`3. If we accept the view that any natural barrien to
`the propaption of genetic material derived from
`unrelated species do not owe their existence to
`the intent of nature, we can reason that evolu(cid:173)
`tion has created and maintained such barriers
`because OJIPOrtunities for genetic mixi1111 occur
`in nature. Furthennore, we must conclude that
`limitations to gene exchange have evolved be·
`cause the mixillll or genes from divene orsa·
`nisms is biologicaUy undesirable-not in a moral
`or theological sense as some observen would
`have us believe-but to those OI"JIIIIlisms in(cid:173)
`volved.
`4. E. Cbargatf, ScieiiCe l9Z. 938 (1976).
`$. Fed. Reg. 4i(l76) (9 September 1976), pp. 38426-
`38483.
`
`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(cid:173)
`nology has created a mlijor furor here.
`Vice President Mondale's discussion of
`the matter with West German officials on
`his first foreign mission, before any con(cid:173)
`sultation with Brazil, has fanned an ear(cid:173)
`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
`
`affair seems likely to further damage
`U.S.-Brazilian relations, which were al(cid:173)
`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 officials but
`comes from many disparate elements of
`Brazilian society and seems to have had
`the effect of strengthening political sup(cid:173)
`port for President Ernesto Geisel and his
`authoritarian military regime. Spokes-
`
`18 FEBRUARY l'Tn
`
`men for the opposition party, the Brazil(cid:173)
`ian Democratic Movement (MD B), have
`publicly condemned the U.S. moves and
`defended the West German agreement.
`In December a leading MDB figure, Sen(cid:173)
`ator Paulo Brossard of Rio Grande do
`Sui, said in response to then President(cid:173)
`elect Carter's call for cancellation of the
`agreement that while he respected Car(cid:173)
`ter's position, "it is not possible to ac(cid:173)
`cept it without protesting the inter(cid:173)
`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(cid:173)
`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 un-
`
`657
`
`Sanofi/Regeneron Ex. 1 030, pg 914
`
`Merck Ex. 1030, pg 940