Philip J. Regal (c) 1998
University of Minnesota
St. Paul, Minnesota 55108
Scope of this Historical Synopsis
The Earliest Voiced Concerns. Analyses by scholars and scientists of the future impacts of genetic engineering* divided early into the following range of concerns:
2. Biohazard, Biosafety. Some biotech projects could present serious risks to human health and the environment. (Fowle 1987, GAO 1988, Grobstein 1979, Halvorson et al. 1985, House of Representatives 1984, Rogers 1977, Jackson and Stich 1979, Krimsky 1982, 1991, Levin and Strauss 1991, Macdonald 1993, U.S. Congress OTA 1993, Watson and Tooze 1981, Wright 1994, Zilinskas and Zimmerman 1986)
The Limited Scope of the Following Historical Analysis. All these concerns for the future are still very much alive. But the present report will focus on the history of the second of the above five areas that have seriously concerned scholars and scientists -- the biohazard and biosafety concerns. Little will be said here about the issue of food safety because this is an issue that was little appreciated and discussed among independent university scientists or publically until the late 1990s. I deal with the complex scientific and historical issues in a separate essay.
The Engineering Ideal in Biology
The ideal of reducing life completely to human control was promoted most vigorously and thoroughly by Jacques Loeb in the 1920s after he had moved from the University of Chicago to the Rockefeller Institute, during an era when it seemed that technology could and would domesticate the planet.
Then in the 1930s the Rockefeller foundation under physicists Max Mason and Warren Weaver began to recruit chemists and physicists to create the new science of what would be called molecular biology. The expansive Rockefeller program began with the highly idealistic assumption that nearly all human problems could all be solved by genetic and chemical manipulations. (Abir-Am 1987, Kay 1993, Pauly 1987, Regal 1987, 1996)
The agenda for molecular biology and the engineering of life thus was infused with complete optimism from the start, and there was only a positive view of the promise of the new science and of the bio-technologies that it was supposed to produce eventually. Risks and other negative developments were not considered or planned for.
Mason and Weaver had left research in physics in disgust with quantum mechanics and turned to administration. Weaver wrote that they had kept their faith that nature would be found to be simple and sought to infuse this faith into a new Molecular Biology. The faith that they sought to preserve had been motivating physical scientists since at least the 17th century, but it had been seriously shaken philosophers of science by the earliest 20th century (see discussions and references in Regal 1989, 1990b,1996).
Physicists and chemists had long shared a very old and seductive ‘reductionist' and ‘determinist' dream that had extended even to biology. It had been promoted by philosopher/scientists such as Rene Descartes, who argued in his 1637 Discourse on Methods, for example,
Phase I: Early Safety Concerns -- The Germ Warfare, Biohazard Connection
Much of this section has been well-covered in Wright's 1994 history, and Grobstein 1979, 1986.
1960s: Concerns about Germ Warfare. American scientists first began to question in the 1960s whether recombinant DNA technology would always be used safely. At this time the military in the United States began to show an interest in using recombinant techniques to make 'designer weapons' that would transcend the limits of the old biological weapons (E.g. Wright 1994, p.118).
[ Designer weapons designated, for example, diseases that would resist antibiotics, selectively kill one race, etc. To illustrate: the Associated Press reported scientific testimony before the Reconciliation Commission that the white government of South Africa had research programs in place to engineer diseases that would only kill blacks. Just before the presidential election, the United States and Britain tried to convince the government to destroy their stockpiles, but the program was not terminated until Mandela became president (Associated Press 1998). Some scientists estimate that the early use of biological weapons is likely to be against crops and livestock, and that the potential to damage and disrupt is on the scale of nuclear war. Iraq's efforts to develop biological weapons prior to the Gulf War included anticrop weaponry. The U.S. has programs to develop pathogens that it is hoped will specifically kill crops that produce drugs such as cocaine, marijuana, and heroine. "The greatest concern, however, is that the developmnet of a capability to destroy drug crops with plant pathogens will inevitably provide a wealth of knowledge and practical experience that could readily be applied in much more aggressive offensive biological warfare targeting food crops." (Rogers et al. 1999).]
[Ken Alibek was the Deputy Chief of Biopreparat in the Soviet Union from 1988 to 1992, before he moved to the United States to work in biodefense. According to him, the USSR biological warfare program was stimulated in 1972/1973 when the possibilities of recombinant DNA for designer weapons were independently realized by Soviet scientists. Military sponsorship in turn gave Soviet molecular biologists support to join at least in some way in the genetic engineering research that was creating so much excitement in the West. The budget for biological weapons research soon quadrupled and included dozens of installations around the USSR, staffed by tens of thousands. Alibek has written that he came to feel that American intelligence agencies did not know about the Soviet programs until 1991, and that the American counterpart programs were insignificant at the time. If this is correct, then the American military interest in biological weapons from the 1960s to the 1990s did not translate into large programs under direct military control as some suspected it would. But military interest in the USSR and China, at the least, did generate rDNA-based biological warfare programs there. (Alibek 1999)]
[Alibek also wrote that, I have encountered an alarming level of ignorance about biological weapons. Some of the best scientists I've met in the West say it isn't possible to alter viruses genetically to make reliable weapons, or to store enough of a given pathogen for strategic purposes, or to deliver it in a way that assures maximum killing power. My knowledge and experience tell me that they are wrong. I have written this book to explain why. (Alibek 1999, p. xi) I had long heard the same naive opinions from leading American biotech advocates when I asked them how they justified to themselves promoting the dramatic proliferation of this technology with its distrubing potential to cause a biological weapons arms race and ultimately perhaps uncountable deaths. My sense is that many of them had talked themselves into sincerely believing that rDNA had no weapons potential, because they felt constantly on the defense and felt a need to protect the image of biotechnology and to protect their own faith in it the benign nature of their community. Their arguments spreat and soon became a misleading 'common wisdom' among American biotechnologists. Thus, it is possible that the differences in self-interest between Soviet and American scientists led to very different consequences in terms of arms development in the two counties.]
Fear of the Public. The American scientists discussed concerns in small meetings that were not attended by the press. The discussions led to broader questions in the late 1960s about the potential misuse of the new technology.
The reactions of those who were to become the leaders of molecular biology set the tone for the future. They argued that risks should not be discussed in public or the public might end the freedoms of the research scientists and cut funding for recombinant DNA research. They argued that so much good would come from the research that it was worth great risks.
1972: Nervous Laboratory Workers. The first genes were spliced in 1971 and recombinant techniques were soon widely used. Many laboratory workers began to wonder if what they were doing was safe. When they would gather at meetings and discuss specific projects, serious questions were raised that could not be answered.
It should be kept in mind, again, that molecular biology grew out of physics and chemistry. These physical scientists who were starting to rearrange the molecules of heredity knew little about living organisms, and some of them were starting to become concerned about the limitations of their discipline. Some of their concerns may have been over-reactions, while others were entirely appropriate.
There were only private meetings about safety in the early 1970s.
1973: Biohazard Controversies Get out of Hand. Discussions at a June 1973 Gordon Conference led the organizers to call for moratorium on some recombinant research and for the U.S. National Academy of Sciences to set up a committee to study questions about the safety of certain laboratory projects.
Concerns over the safety of some genetic engineering projects began to be discussed in publications for the general scientific community.
Wright's research found that leaders of the scientific community then began to express concerns that a 'panic response' would develop.
Leaders of the scientific community, such as the president of the National Academy of Sciences, became troubled over the uncontrolled debate and sought ways to keep the control of molecular biology and its controversies within the scientific community. The result, however, was that, "decisions on whether to slow research were being made by the very people on whom pressures to pursue genetic engineering were the strongest" (Wright 1994, p.137).
Scientists began to talk in 1974 about containment of experiments and about using 'disarmed' laboratory host organisms in order to be doubly safe.
Those in favor of taking the risks began to argue that while the risks could not be exactly predicted,
4. The questions about the safety of specific laboratory projects soon became blurred and the more general, if unlikely, issue emerged regarding the safety of any and all laboratory work with recombinant DNA. There was a focus on highly improbable, but easily dismissed, concerns such as, 'will any arbitrary mixing of DNA across species boundaries be highly dangerous?'
Phase II: 1984 -- The New Deliberate Release Problem
The issue of 'deliberate release' or 'deliberate introduction' was among those issues that faded from view as a result of the Asilomar and RAC focus on contained laboratory experiments and disarmed laboratory organisms.
Thus it came as a surprise to many biologists in 1983-1984 that the technology had advanced greatly and that the genetic engineers were contemplating the 'release' or 'introduction' of ecologically competent genetically engineered organisms (GEOs) into the environment, where it was planned that they would thrive.
It was disturbing that essentially the same types of arguments were being used to argue that ecologically competent GEOs would cause no problems, as had previously been used to argue that ecologically incapacitated laboratory GEOs would not cause problems.
These facts were collectively surprising for several reasons.
2. Many scientists who were not inside of the biotech community were unaware that the field was progressing so fast that it would become possible to make ecologically competent GEOs in the foreseeable future. There are in turn several reasons why progress in genetic engineering had become somewhat opaque.
The Demise of Generic Safety Arguments. A variety of theoretical arguments were being used from about 1974-1986 to insist that all releases of GEOs would be safe.
These generic safetly arguments were criticized systematically at a series of scientific symposia, workshops, and in professional publications by Professors Philip Regal of the University of Minnesota, Robert Colwell, then at the University of California, Berkeley, and Richard Lenski, then at the University of California, Irvine (Colwell 1989: Lenski 1993; Regal 1985, 1986, 1988, 1993, 1994; Colwell 1989).
As a result, these generic safety arguments are seldom used anymore in discussions among experts.
However, they are still in circulation among scientists who have not studied the technical issues, and they are still used by biotech public relations persons, and so they should be briefly listed. Criticisms are referenced and summarized (in bold italics) following each model.
4. Genetic engineering can only make an organism less perfect than nature has made it. (But see Lenski 1993, Regal 1985, 1986, 1988, 1994, 1996) This assumes that natural organisms are perfected; again an idea from philosophy and religion (E.g. Natural Theology), and sometimes from mathematical simplifications, not from modern empirical science. Scientists generalize instead that organisms are adequately adapted, not perfectly adapted.
2) Outdated and pedestrian ecological and evolutionary thinking that is rooted in the 'balance of nature' models developed by natural theology in the 16th through 19th centuries.
Phase III: The Continuing Quandary over Regulations
(The following leans heavily on my experiences and my close involvement advising on the scientific aspects of ecological risk assessment throughout the formative period of the 1980s.)
Deregulation Categories? The immediate reaction of many in the biotech industry to the demise of generic safety arguments was to want to get on with their work. 'Just tell us what we can and can not do. Give us two lists -- a yes list and a no list.' The regulators were under pressure to devise categories for introduced GEOs that would not need regulation. But in each attempt the criteria for classification proved to be too simple.
The following are examples of the categories for deregulation that were discussed in the mid-1980s; and some problems with them are listed briefly below each proposal in brackets. Ironically, many are proposed-based categories (in the sense that they do not ask what are the actual biological properties of the GEO product itself, but 'how was it made?' --'from what?') first proposed by those who were also arguing that there was no need to regulate on the basis of process. Some problems with each category are briefly discussed and appear in bold italics following each proposal.
4. Domesticated plants .... Nearly all genetically engineered corn and wheat may be ecologically safe outside of their centers of germ plasm diversity. But 'domesticated' is not a scientific category. Many cultivated species are not so ecologically incapacitated as corn and wheat. Also, some domesticated plants may exchange genetic material with wild relatives that could in some cases create ecological problems secondarily. Moreover, questions about food safety should not be overlooked even if ecological concerns are minimal.
'Case-by-case' Reviews Necessary. It seemed impossible to make comprehensive lists of all possible safe and unsafe GEOs, including lists based strictly on how, from what, the GEO was made. Thus the frustrating conclusion was that GEOs would have to be evaluated on a case-by-case basis. Case-by-case does not necessarily mean that every strain of GEO must be studied extensively, but it does mean that every 'type' of project should be evaluated in terms of its own particularities by experts with a broad understanding of organismal biology and ecology.
Obviously there are no universal rules about how to make case-by-case evaluations for all the possible types of GEOs that might be constructed. And there is no universal definition for what a 'type of project' or 'situation' is or when 'enough' information has been provided.
The devil is in the details. Case-by-case means that the scientific community will have to be assured that each 'situation' has been reviewed by an appropriate mix of qualified experts that has articulated its collective decision with scientifically acceptable reasoning and is prepared to be accountable for its decision.
There has been considerable complaint that the regulatory agencies have not been using scientifically comprehensible criteria in making risk assessments to date (Doyle et al. 1995, GAO 1988, Rissler and Mellon 1993, 1996, PEER 1995, Regal 1994, Wrubel et al. 1992).
This lapse stems in part from the fact that the agencies have been under enormous political pressure to expedite the progress of genetic engineering. As a result they have not adequately staffed themselves with experts from the proper ecological and other scientific disciplines and built the infrastructure to deal with the difficult scientific challenges ahead, let alone with the volume of paperwork expected.
The Familiarity Pitfall
It is commonly agreed that 'familiarity' with the parent organism of the GEO or the GEO itself should be a key consideration in risk assessment.
The pitfall is that 'familiarity' means different things to different people. One can be familiar with an organism in terms of its taxonomy, molecular structure, agronomic features, marketing characteristics, and so on. None of these forms of familiarity are will be key to making sound biosafety evaluations. That is, there are many forms of scientific expertise that may be quite inappropriate for making sound safety evaluations. An ecologically oriented plant systematists may have a familiarity with the parent of a GEO that is valuable in one case, and a traditional economic botanist in another case. And in some cases the familiarity of agronomists or geneticists with the parent plant may be of only tertiary value.
Moreover, names do not necessarily mean what they might seem. For example, many scientists call themselves microbial ecologists because they study interactions of two or more species, as in fermentation processes. But they may not be familiar with modern concepts of the dynamics of natural communities. A tradional economic botanist should know a great deal about the systematics, biogeography, and ecology of crop plants and their relatives. But other economic botanists will not be familar with this sort of information and they will be much too specialized to be valuable resources for risk evaluations.
It is often said naively that a GEO will be safe if the parent is familiar, and or that various previous engineerings of the parent 'did not cause problems.' Yet it is not enough to have grown a GEO or its parent under simple conditions, even for years, to be able to predict how it may interact in nature.
The type of familiarity that would be a valid aspect of risk assessment would be familiarity with those particular characteristics of the parent and the GEO that could influence its ecological future and its effects on health, as suggested in Table 1.
Often, "The Principle of Familiarity" is used to suggest that since something is known about the unmodified, parent, organism or about closely related organisms, the GEO will behave in the same manner. The Principle of Familiarity comes from the chemical industry, where, if the structure and activity of a chemical is known, then closely related chemicals, with nearly the same chemical structures, will likely behave the same way. This often, but not always, works for chemicals. But it rarely works for organisms.
Simple inorganic chemical reactions always occur in the same manner in a constant environment. But organisms adapt and change with amazing regularity. Mutation, recombination, genetic drift, and natural selection are always at work in reproducing populations. Add to this the fact that genetic engineering has an implicit uncertainty regarding where transgenes insert, how many transgenes will insert, how much mutation they will cause, how errors produced by the transgenes will be corrected or buffered by the host, and it is highly doubtful when this Principle of Familiarity could ever be applied to GEOs.
Further, if engineered organisms are different enough from all other organisms to be patentable, then it follows logically that parent and GEO are not similar enough to use the Principle of Familiarity. The Precautionary Principle may make more sense: 'First do no harm," or 'If you don't know how something works, don't use it.'
The criterion of 'familiarity' may sound superficially reasonable, but it must be defined and the definition must be spelled out or it can only mislead.
The False Sense of Security Trap
Scientists began to express concerns over the the future of genetic engineering some 30 ago, even before the most simple gene splicing had become possible. There has been a common progression among persons who begin to study genetic engineering safety issues, and this progression can result in a false sense of security.
4. They conclude that genetic engineering is 'not as dangerous as people think.'
6. They are easily convinced that risk assessment is only a political necessity to keep an ignorant public calm. They become wary of taking concerns too seriously. Or if they do have concerns they become wary of showing them too publically.
10. They may not have heard about the problems or potential problems that have happened. Or, if they hear that problems were averted in such cases as the Brazil nut allergenicity that was passed on to soybeans, or the Klebsiella bacteria that was found to kill plants, they assume that the fact that the projects were stopped means that 'the system was working.'
11. Humanity's interest in the development of safe technology is compromised.
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* The terms GEO and transgenic used here closely follow traditional definitions such as those endorsed by the American Chemical Society and other scientific organizations. For example:
Genetic engineering: (... "The formation of new combinations of heritable material by the isolation of nucleic acid molecules, produced by whatever means outside the cell, into any virus, bacterial bacterial plasmid or other vector system so as to allow their incorporation into a host organism in which they do not naturally occur, but in which they are capable of continued propagation." (P. 110. Quoting the 1978 Genetic Manipulation Regulations.)
Transgenic animal: "An animal whose genetic composition has been altered to include selected genes from other animals or species by methods other than those used in traditional animal breeding." (p.238) [The use of ‘transgenic' to include hosts altered with artificial genes, or organelles, for example, is looser than this definition, but is unmistakably in the same spirit.]