An Interview with Professor Brian Goodwin
by Dr. David King

David King is a molecular biologist and editor of GenEthics News.
Professor Brian Goodwin authored How the Leopard Changed Its Spots and is in the Department of Biology at The Open University, Great Britain.

The interview was published in GenEthics News, Issue 11, March/April 1996, pp. 6-8.
David King: What are your criticisms of the prevailing paradigms in biology, particularly Darwinism?
Brian Goodwin: My main criticism of Darwinism is that it fails in its initial objective, which is to explain the origin of species. Now, let me explain exactly what I mean by that. I mean it fails to explain the emergence of organisms, the specific forms during evolution like algae and ferns and flowering plants, corals, starfish, crabs, fish, birds. That sort of spectrum of organism, each of which is distinct from the other. They don't blend with each other, they are distinct from each other. Now the problem is that in order to understand that the kind of distinct structure and form we have to understand how organisms are actually generated, and that means understanding how starting with an egg or a bud, the organism goes through a developmental process and ends up as a particular type of species with a particular morphology (shape and features). So the whole problem then is to try to understand the nature of that process. One of the fundamental issues is whether or not you can get more or less any kind of organism, or whether there are constraints. Darwin turned biology into a historical science, and in Darwinism, species are simply accidents of history, they don't have any inherent nature. They are just 'the way things happened to work out' and there aren't any particular constraints that mean it couldn't have all worked out very differently. An example is the structure of the arm and the wings of birds. There is always only bone at the top of the arm, never two, even though two would be very useful to birds, but it's never evolved. So it looks like this is something that simply cannot happen because there is an intrinsic constraint on that process. Now there is plenty of evidence that that kind of constraint exists through the whole of biology. In other words, the reason why species are distinct is because you have only got certain types of forms that can actually be generated by the developmental process. That really begins to shift the emphasis with respect to how we understand the different species and how they are related to each other.
In order to get a really firm grip on this, we actually need a theory of the whole organism and its transformation. Organisms are organized wholes. That's why they have these constraints. The sort of theory that you need to understand morphogenesis involves understanding the components which organisms are made. You certainly need to know a lot about molecules, but you have to understand how they are put together and what sort of dynamics is involved. Now this is where these new sciences that are called the sciences of complexity come into the picture, where you actually look at the dynamics of complex systems, and see how emergent order arises, in often very unexpected ways. This happens because of what we call the relational order, the relationship between the components. It doesn't matter so much what the components are, what they are made of. The really important thing is the way they interact, and that is what determines the type of order that is going to emerge. Now what I and my colleagues are trying to do is to, in a sense, make a map between the pathways of morphogenesis that are available to species organized in a particular way, like algae or plants or amphibians, and to map that onto taxonomy (classification of species). In other words, it's trying to make sense of what we see in evolution by having a theory of morphogenesis (development of shape and form), and making a map between morphogenesis and taxonomy. So it's turning biology into a rational science rather than a historical science. There is no conflict. Everything that happens has a history, so in a sense all sciences have a historical component, but physics of course also has a very strong rational tradition. The whole point is to try to understand why certain structures are necessary, and this is exactly what we do in physics and the new biology. We are asking why has this particular structure emerged in the biological world and this makes biology much more like physics than the historical science that we got from Darwin.
King:  How does your new model of biology incorporate genetics?
Goodwin:  A major problem is that in contemporary Darwinism, organisms are actually reduced to genes and their products. Darwinism has given us a very good theory of inheritance in terms of a theory of the genes, but what it has done is to sacrifice the whole organism, as a real entity, to this reductionism, genetic reductionism. That means that organisms have disappeared as real entities from biology, and that, I think, this is a fundamental scientific error. There's another aspect of this problem which has to do with the way Darwinists explains embryonic development. They say that there is a genetic program that determines the development of an organism. An organism wants to become a newt, say, or a sea urchin. Because it has particular genes, they say, it undergoes a particular embryonic development and that is sufficient, in other words knowing the genes is sufficient to understand the details of the embryonic development, and the emergence of a species with its characteristic form and behavior. That sounds, on the face of it, plausible because we know that mutations actually cause transformation of morphology. Drosophila can have a mutation that transforms a two winged fly to a four winged fly. Now that is a pretty major transformation, and a single gene can do it. So you might say that's the sort of thing that is involved in evolution. Well, you see, the burden of proof then is on the neo-Darwinists to demonstrate exactly how the genes do this. They use the term genetic programming, and it is a metaphor for what happens in a computer, but if you ask them to use a genetic program to generate an organism, they can't do it, and the reasons are very simple. You need to know more than gene products in order to explain the emergence of shape and form in organisms. You actually need a theory, a theory that involves physics, chemistry, forces and spatial organization. You can have complete details about genes and you are not going to be able to explain how development occurs. So I think that is the fundamental test. When Darwinists say to me 'genes are enough', I say 'Show me.'
King: What are the consequences of Darwinist reductionism?
Goodwin: Let me pick up again this issue of the disappearance of organisms as real entities. Because this really has quite profound consequences. I think that this precipitates a kind of crisis of understanding of living forms. It's an extreme reductionism that makes it impossible for us to understand concepts such as health. Health refers to wholes, the dynamics of whole organisms. We currently experience crises of health, of the environment, of the community. I think they are all related. They are not caused by biology by any means, but biology contributes to these crises by failing to give us adequate conceptual understanding of life and wholes, of ecosystems, of the biosphere, and it's all because of genetic reductionism. That's a pretty heavy charge, but let me just describe some of the consequences of genetic reductionism. Once you've got organisms reduced to genes, then organisms have no inherent natures. Now, in our theory of evolution, species are natural kinds, they are really like the elements, if you like. I don't mean literally, but they have the same conceptual status, gold has a certain nature. We are arguing that, say, a sea urchin of a particular species has a nature. Human beings have a nature. Now, in Darwinism, they don't have a nature, because they're historical individuals, which arise as a result of accidents. All they have done is pass the survival test. The Darwinian theory makes it legitimate to shunt genes around from any one species to any other species: since species don't have 'natures', we can manipulate them in any way and create new organisms that survive in our culture. So this is why you get people saying that there is really no difference between the creation of transgenic organisms, that is moving genes across species boundaries, and creating new combinations of genes by sexual recombination within species. They say that is no different to what is happening in evolution. Well, you know, in my book that's a bit like saying there is no difference between radioactive decay, radioactivity as you find it naturally in Uranium, and using that for nuclear energy. Once you scale something up to a particular level you are into a totally different scene. Now, I think that there are the same problems that arise with respect to creation of transgenics, and the reason is because of the utter unpredictability of the consequences of transferring a gene from one species to another. Genes are defined by context. Genes are not stable bits of information that can be shunted around and express themselves independently of context. Every gene depends upon its context. If you change the context, you change the activity of the gene. There are particular cases where that doesn't appear to happen. You put the human gene into bacteria and you get insulin out, but as you know, there is a recent case in the States where the insulin has actually modified and it's not working properly. And then you have got the problem of genes transferring from one transgenic to a related species, resulting in the problem of ecological meltdown, or ecological change that can be precipitated by the use of transgenic species in agriculture. I'm by no means against biotechnology. I just think that it is something that we have to use with enormous caution in its application. We need stringent safety protocols. Now those are the issues of safety, and they are very serious, because the rhetoric that goes with biotechnology is totally at variance with reality. The biotech companies don't want to face the consequences of this radical unpredictability which comes from the intrinsic complexity of organisms. But there is also this really thorny question of species as natural kinds. And when you transfer genes of one type of organism to another, what are you doing to the nature of the species, the recipient species? Now I think that's a very open question. I don't have a simple answer to this. I just think that it's again, something very serious. It raises ethical issues.
King: How would those ethical questions look in the light of your alternative model of biology?
Goodwin: There is a particular consequence of the idea that species are 'natural kinds' that, I think, is very important for a new type of science in relation to the living realm. It works like this. If you acknowledge that species are natural kinds, so they have natures, then it becomes possible to consider procedures whereby we can understand those natures, that is we go through a process of qualitative evaluation of the conditions under which those natures are being expressed, and cannot be expressed. Let me just clarify that in relation to some specific examples. We know when our domestic animals are distressed and in pain, when they are happy and so on and so forth. In other words we have spontaneous intuitive ways of evaluating the subjective state of domestic animals. Anybody who has an intimate relationship with an animal knows what its subjective states are. Now I say know, they would claim to know, and it seems perfectly legitimate, that claim. But the whole question now is whether we can turn that into a science of subjective states because that would then compliment the science of objectivity which is the mode of contemporary science. In other words what we would be developing is a science of qualities, of qualitative evaluation of other species, and therefore a method of deciding when organisms are being denied the opportunity to express their natures. And this is clearly extremely relevant to the way we treat not just domestic animals and farm animals, but the rest of living nature. And it's that relationship that we need, in order to heal these various crises of the environment and of health and of community, because we've even lost the concept of human nature. Human nature disappears as a concept from neo-Darwinism, and so life become a set of parts, commodities that can be shifted around. But the moment you recover this notion of nature, you are into a different world and you operate in a different way. Now this I think is a pretty urgent development, developing a science of qualities, and it's something we are engaged in at Schumacher College. It has to be done with groups, because you have to try to develop methods of qualitative assessment that are intersubjective, just in the same way that in conventional science the evaluation of what we call reality is dependent upon intersubjective consensus. We come together and carry out these procedures, like experiments and observations and so on, and come to an agreement,about what constitutes reality and what doesn't. And I think we can have a parallel procedure to that in a science of qualities. I think that that would be a fundamental contribution to this issue of how we treat other organisms and at what point a transgenic would be losing its nature.
King: How would the new science affect our social theories?
Goodwin: Well, another consequence of this new view of species and evolution is it does shift the metaphors that are used to understand evolutionary processes. In Darwinism, you know, the metaphors are of competition and conflict and survival, and in Dawkins' writing it becomes embodied in the notion of selfish genes. Well, from the perspective of organisms as complex dynamic systems, with natures and trying to understand the ecosystem from the point of view, what you find is that organisms are interacting with each other in all kinds of different ways. They are as co-operative as they are competitive, and a lot of the time they are simply making a living. In other words, it's not this nature red in tooth and claw, with fierce competition and the survivors coming away with the spoils. In fact, species extinction seems to be as much to do with the lottery which comes from the dynamics of complex systems, as from anything else. The whole metaphor of evolution, instead of being one of competition, conflict and survival, becomes one of creativity and transformation. When you take on that perspective and bring that into society then you say, all right, why don't we use those metaphors in our social system as well. The metaphors of just making a living, just getting by. Not getting profits into double figure percentages. Not survival through serious competition, but making a living and sharing. I'm not being Utopian, I'm not saying we are going to share everything, because there has to be a certain conflict and competition. But instead of making that the predominant mode, we say that's only one of the components of a vibrant creative society. And the sciences of complexity are really taking on this character of illuminating what it means to be creative. This concept of life at the edge of chaos. Now that is a pretty dramatic metaphor, but what it means is that you shouldn't have too much order. You shouldn't have too much chaos. Perhaps you should be at the point where you can move backwards and forwards between the two and actually be creatively responsive to circumstance. Now clearly, that model is very attractive, but when you look at the dynamics of those systems, you find that it is not driven by competition.They have a complex dynamic interaction and it's that which produces creativity. So the whole business about intellectual property rights and competition that we have in our society, people justify them saying they happen in nature. That is not what happens in nature at all. Nature as we read it now is a much more complex, coherent and creative type of process than the one we have in our social and economic system. So we can begin to contemplate the use of different metaphors and different instantiations of these biological metaphors. You always have to be careful with metaphors. You can't say this happens in biology, therefore it should happen in society. You have to examine it on its own merits. But I think that there is a lot to be said for a basic reevaluation of the metaphors we use in describing evolution, economics and social change, that is arising out of the new sciences.
For more information on subscribing to GenEthics News, email David King or write:
P. O. Box 6313
London N16 0DY, Great Britain

Transcending Darwinism in the Spirit of Goethe's Science: A Philosophical Perspective on the Works of Adolf Portmann
by Hjalmar Hegge
University of Oslo, Department of Philosophy
Postboks 1024, Blindern, 0315 Oslo 3, Norway.
About the Author
Republished with permission from Newsletter of the Society for the Evolution of Science (Summer 1996 issue, Vol. 12, No. 2, pp. 1-26) and the author.
 
Introduction
There could be at least two reasons for considering Goethe's science of nature important today (1). In the first place, present-day scientists might make explicit reference to Goethe's own science. Secondly, they could themselves apply the methods on which Goethe's science was based. The work of the Swiss biologist and anthropologist Adolf Portmann (1897-1982) both directly refers to Goethe's research and uses the same methods. Thus Portmann brings Goethe's science of nature into a modern context.
Goethe's science is essentially qualitative and teleological in the Aristotelian sense in which processes are understood as a manifestation of "form," which is not to be explained only in causal terms. By emphasizing organic qualities as irreducible to mechanistic and molecular ("reductive") explanation, and by using a teleology of the type employed in explaining the ontogenesis of the human being, Portmann's biology and anthropology are based on the very principles and methods of Goethe's science.
From the viewpoint of the philosophy of science, attention should be drawn to two fundamental aspects of the approaches of Portmann and Goethe as compared with the predominant neo-Darwinian view of the organic sciences. First, there is the relation between phenomena on the macro- and microlevels, a relation that pertains to the status of organic qualities. Secondly, there is the problem of a causal vs. teleological explanation of organic processes of development.
Here both aspects will be discussed as they can be understood in terms of Portmann's morphological research and his investigations into the ontogenesis of mammals and humans. Along the way, however, certain parallels to Goethe's science will be drawn, and explicit remarks by Goethe concerning scientific principles and methods will be included to show the kinship between these two natural scientists. In this connection Portmann's explicit statements about Goethe's science will also be emphasized.
With this as background, it is finally pointed out that the methodological views of Portmann and Goethe involve a fundamental shift in perspective with regard to the phylogenesis of human beings and animals (the theory of evolution), one that radically transcends Darwinism.
Portmann on Goethe
In his essay "Goethes Naturforschung" ["Goethe's Investigationsof Nature"] (1953), Adolf Portmann points out that contemporary concern about Goethe's scientific research "stands in remarkable contrast" to our regard for the science of earlier centuries. This earlier science "usually sinks into the anonymity that characterises our knowledge as to its origin... but things are quite otherwise where Goethe's scientific research is concerned. In our search for knowledge we are repeatedly redirected to it afresh from the most varied quarters." There is consequently every reason to put "the question as to what is so characteristic about this research that... again and again presses us to reconsider and rediscuss it" (2).
What characterizes Goethe's science, according to Portmann? To illustrate this he uses an analogy between a theatrical production and natural phenomena, or "life phenomena." A staged play can be regarded in two essentially different ways. "My desire to know can take me behind the scenes and allow me to make many interesting observations there. I discover how sound and light effects are produced..." and so forth. On the other hand, we know that "what happens behind the scenes.. .requires a quite different angle of view" to become intelligible, namely that "of the spectator before the scene," which we also regard as the "most essential." Only from this viewpoint is "the play's real meaning" revealed (3).
These dissimilar ways of regarding the play illustrate for Portmann the difference between the attitude of the traditional scientist towards objects as observer "behind the scenes" and that of Goethe as observer "before the scene." This is a very pertinent image, upon which Portmann seeks to cast light through a phenomenon "which captured Goethe's attention in particular. It refers to the relation of leaf to flower in higher plants." As an example, Portmann takes Goethe's observation concerning the malformation that occurs when a tulip's petals turn green.
In the modern laboratory this is of course analysed as "a physiological process"--which is to say that one observes what occurs behind the scenes. One demonstrates, for example, that the malformation in question is connected with the lack of a chemical. "But there is another way" to explain the malformation, "by comparative observation" of the formation of flowers in plants--that is, by an approach only from before the scene, in that one studies the interconnections played out before one's eyes. Such a comparison of "forms following one another [Bilderfolge]...reveals a hidden regularity in the transformations, a meaning [Sinn], a 'piece' that is played out through this transformation and which is known as 'the metamorphosis of the leaf'" (4).
As Portmann points out, it is clear that this comparison with a theatrical production is meaningful only if "a 'piece' is in reality played out in nature--that is--if the observable phenomena are integrated into a greater whole in a meaningful way." Stated directly, this is to say that the phenomena given immediately to our senses (forms, colors, and so forth) presentthemselves with a regularity that we can discover only if we concern ourselves with these phenomena as such. In other words, a regularity appears that we cannot trace by shifting to a quite different observational plane--for example, the microscopic or submicroscopic--any more than we have insight into the play's coherence by making observations behind the scenes, however accurate they may be.
Goethe practiced this attitude and method in scientific research consciously and systematically, and also characterised it explicitly when he proclaimed in his Sprьche in Prosa [Prose Aphorisms]: "There is a gentle empirism [zarte Empirie--not conventional "empiricism"] which in the innermost manner identifies itself with the object and thereby becomes the actual theory." Or, as he said in the same connection: "My attention has always been directed exclusively towards objects that surrounded me in the earthly [irdisch] realm and which could be directly perceived through the senses." The way Goethe's attitude and method are illumined through Portmann's analogy of the theatrical production is perhaps most distinctly expressed in the sentence "Seek nothing behind the phenomena, they themselves are the theory" (5).
Here, however, we are also confronted with the first aspect of the philosophy of science mentioned at the start of this essay. It demands our attention, especially when Goethe's (and also Portmann's) scientific method is compared with the view dominant within the organic sciences today. As we suggested, it is a matter of what status to grant to directly observable organic properties or qualities at the macrolevel. As we are aware, the universally predominant tendency has been to "explain" these properties or phenomena precisely by looking "behind" them, above all at the molecular microlevel.
Prior to further presentation of Portmann's and Goethe's views on organic phenomena, we shall therefore attempt to justify them by discussing the relation between research at the macro- and microlevels from the standpoint of the philosophy of science. The relation between the phenomena at these different levels must first be clarified.
Macrolevel Versus Microlevel Phenomena
In the contemporary debate in the philosophy of science, this has been named the "problem of reductionism"--the classical philosophical problem as to whether phenomena at a higher level of organization can be "reduced," in some sense of the word, or "related back to," those at a lower level. In the summary critique in principle of the reductionistic construction that follows, we rely upon discussions of the theory of science by Carl G. Hempel, (6) David Hull (7) and others.
It is not meaningful to "reduce" organic phenomena at the macrolevel (e.g., the forms, colors, behavior of organisms) tomicrophenomena such as genes or their combinations. The latter do not "explain" the former. A description of the properties of phenomena at the macrolevel and a presentation of their coherence (regularities) are not interchangeable with those that apply to phenomena at the microlevel. Organic (biological) properties and their coherence that are specific to the macrolevel are in no respect of secondary status and are thus equally real as those at the microlevel. Thus, of genetic and mutational research in biology we must say, as did the physicist and philosopher Ernst Mach, referring to mechanics in his time, that it "apprehends neither the basis for nor a part of reality, but only an aspect of it" (8).
In discussing the problem of reductionism, Hempel (among others) points out that "the logical situation is the same" as, for example, in the kinetic theory of gases in physics, where it is meaningless to speak of observational phenomena at the macrolevel such as pressure, volume, and temperature as having a secondary status in relation to molecular movements in a gas (9). Indeed, as Hempel asserts: "On the contrary, the theory takes for granted that there are those macroscopic events and uniformities ...." (10).
Faced with this, one has admittedly fallen back upon another though far less pretentious sort of reductionism. One seeks to relate phenomena at different levels through their mere coincidence in time and space (common space/time co-ordinates), based on so-called "extensional definitions" that totally exclude the qualitative content of the phenomena one wishes to reduce. It would lead us astray to go further into this here, and it is also of lesser interest because this form of reduction can no more apply to the levels we are discussing than the one mentioned above (11).
Such reductionism is not even valid between phenomena within the micro-perspective, as, for example, when Hull proves this reductionism inapplicable to the relation between classical Mendelian genetics and molecular genetics (12). Michael Polanyi even shows that neither is there any structural likeness between the so-called chemical genes of molecular genetics and purely chemical processes. The point for him is that the "highly improbable arrangement of particles" in genetic structures represents a form "not shaped by the forces of physics and chemistry. The pattern of information storage can no more be derived from the laws of physics and chemistry when engraved in an RNA molecule than it can be when inscribed on a tape...." (13).
We may summarize this in an analogy: the relation between music and the grooves in a record. Any attempt to derive musical tones and their intervals directly from the grooves would be absurd, as would any attempt to derive organic forms at the macrolevel from genes and their combinations. The latter are far from being the "primary" phenomena--quite the contrary. Just as musical tonesare what create groove configuration, genetic structures at the microlevel must be regarded as determined by organic forms at the macrolevel. "Morphology is the framework," insists Polanyi (14).
This returns us to Goethe's and Portmann's view of organic phenomena, which is fundamentally morphological.
Portmann's and Goethe's Emphasis on Macro-Observables
Here it is obviously not a question of neglecting the actual and significant insights that have been reached in recent decades through research at the micro- and submicroscopic levels. Rather, the question is how the insights thus attained are to be interpreted relative to organic phenomena at the macrolevel, or on the "decimeter-scale," as Portmann calls it. Doubtless it is as he maintains: "that the advances on this [micro- and submicroscopic] research front have led to a forgetful negligence of organic form, that the unconditionally richest area of living phenomena today is banished from the observational field and sensory forms are reduced to sheer 'systematic identificables,'" mere "species terms for the various kinds of plasm" (15).
A pressing need today is therefore to bring organic phenomena on the "decimeter-scale" into the center of research interest, by recognizing that "these higher forms of life set their special research tasks," which, we note, "are complementary to those of plasm research," and do not stand in opposition to them. This is, again, exactly where Portmann is supported by the preceding views in the philosophy of science--that these phenomena (organic forms, colors, shapes, behavior, and so forth) are not to be regarded as reducible but are the fundamental organic phenomena. "With their specific qualities [as] objects of research" (i.e., their phenomenal qualities are "not only a measure of plasmic processes"), they "are themselves the final and decisive element on quite another level of possible manifestation of phenomena [Seinsmтglichkeiten]" (16).
The view that directly observable properties or qualities are a basic area of scientific knowledge also permeates Goethe's attitude towards method. It is the mark of his studies in the organic sciences, as noted in the introduction, and forms the fundament of his theory of color [Farbenlehre], which is the second major area of his scientific research (17). In addition, he has explicitly characterized his attitude and method in a series of essays and in various comments in his Sprьche in Prosa [Prose Aphorisms]. On the one hand, it is expressed in his rejection of the modern scientific tendency to ignore immediate sensory objects in the world; on the other, in his declared faith in our human senses as organs of apprehension.
Goethe maintains: "The human being is sufficiently equipped to fulfill all true needs on earth so long as the senses are trusted and developed in such a way as to be worthy of this trust." Indeed, this made him very cautious about the use of "artificialinstruments" because their one-sided application undermines trust in the senses. It is like someone who habitually directs all attention "behind the scenes" (Portmann's image again) and eventually loses all sense of what is being played onstage. Goethe therefore also claims that "the greatest misfortune of physics is precisely that the experiment has been separated from the person, so to speak, and nature is apprehended only through what is shown by artificial instruments, yes--and one would limit and prove in this manner what nature produces" (18).
Admittedly, he was then speaking of physics, but his viewpoint obviously applies in principle just as much to the organic sciences, where artificial instruments came into use only after his time. This view is consequently in full agreement with that of Portmann quoted above.
Accordingly, it is fully in Goethe's spirit when Portmann sets forth directly observable phenomena on the "decimeter-scale" as the "objects of research," in fact as the "final and decisive element" on a level utterly different from that of microphenomena.
An Epistemological Grounding of Portmann's and Goethe's Standpoint
To place Portmann's and Goethe's view of science in a philosophical perspective, it is important to discuss its epistemology more closely. On the basis of our description of their scientific attitude and method, let us consider Portmann's emphasis on immediately "sensory forms" as the objects of research and Goethe's maxim that the researcher must "trust the senses." In both cases, there is an indisputable emphasis on the empirical character of scientific knowledge, in the strictest sense of the word. This is further stressed in Goethe's assertion that the "highest thing would be to grasp that everything factual is already theory" (19).
This is, nevertheless, only one side of the matter. Though Goethe--followed by Portmann--fundamentally asserts the empirical, there is no question of any "empiricism." On the contrary, the true essence of natural phenomena is not given in immediate sensory observation; it appears only after painstaking research within the observables as a "higher nature within nature" (Goethe) (20). This higher nature (the choice of the term is deliberate) is what appears through human thought in relating to sensory experience. It is the "ideal in the real...the idea in the phenomenon," which, according to Goethe, it is the researcher's task "to seek out" (21).
When Goethe elsewhere strongly advocates sense experience to an extent that could almost be interpreted as "empiricism," he has good reason, namely the wish to distance himself from the sort of theory-construction that has characterized so much modern science. It is precisely because such theoretical constructionhas ignored essential areas of sense experience as the object of scientific research by searching one-sidedly behind the scenes. This has come to expression philosophically chiefly in the theory of so-called primary and secondary sense qualities introduced by Galileo and Descartes, which has strongly characterized scientific thinking up until our time. According to this theory, many sensory properties (e.g., color and sound) simply do not belong to nature, and they are therefore ignored as objects of direct scientific research.
Neither Portmann nor Goethe has explicitly called this theory to account (they were not philosophers), even though their actual research represents a fundamental break with it. Others have done so, however, a main criticism being that the "metaphysical barbarism" upon which this theory rests (to characterize it with the philosopher and historian of science E. A. Burtt) confuses the methodological and the ontological (22). That so-called primary sense characteristics (i.e., mechanical characteristics such as movement and collision) can be described by mathematical methods (i.e., are subject to quantification, measurement) cannot justify their elevation nor be used to deny the real, objective existence in nature of other characteristics (nonquantifiables such as qualities of sound and color) (23).
The basis for regarding quantifiable movements and the like--for example at the molecular level--as "lying behind" and as more fundamental than colors and sounds and other directly observable phenomena is thereby removed. The latter are not considered causally derivable from the former--in fact, there are no "primary" or "secondary" properties/qualities, only phenomena of equal status in respect to both ontology and scientific investigation. Epistemologically, the relation cannot be regarded otherwise because, as objects of observation, there is no difference in real status between movement, extension, or the like, and such properties as color and sound. In going beyond these sensory properties as purely observable objects, one does not, therefore, get at any real underlying causal process but merely at concepts that we form or assume in thinking about phenomena (24).
On this evidence, one must accept immediately sensible colors, forms, and so on as objects of research that are as fundamental as molecular movements are at the microlevel. This is exactly the case in Goethe's theory of color and morphology, as well as in Portmann's work in the organic sciences. Yet investigation of immediately sensible phenomena also demands development of an adequate method, which must be essentially qualitative rather than mainly quantitative. This raises the issue of scientific attitudes, indeed that of ethics.
The method involved here demands more of the researcher as an investigating subject than the more abstract method of theory construction. Goethe points this out in a most apposite way: "Theory is usually the product of the impatient intellect, of thedesire to get rid of the phenomena" (which occurs just when one seeks something "behind them"). On the other hand, a "gentle empirism" [zarte Empirie] directed towards the immediately observable and qualitative aspects of phenomena presumes a "refinement of spiritual capacity." It thus favors persistence in observation and reservation in the construction of quick theories, within a context of "respect for Creation," which Portmann characterizes as Goethe's basic attitude, and one which we have every reason to rediscover today--"to be devout" [Frommsein], as Goethe puts it (25).
Comparison with the Darwinian View and Method
The preceding presentation of Goethe's and Portmann's views and our arguments on behalf of them from the standpoint of the philosophy of science and epistemology provide a basis for distinguishing their view of nature and method from the Darwinian one.
As shown, Portmann and Goethe emphasize immediately observable organic properties on the "decimeter-scale" as a "final and decisive" object of scientific research. Darwinism does not, of course, ignore this aspect of living phenomena; indeed, its historical basis lay precisely in the perception of organic forms, in paleontology. It is nevertheless fundamentally different from Goethe's and Portmann's views.
While Portmann and Goethe start from various qualitative properties and forms as fundamental expressions of an organism or species, Darwinism attends to one aspect of these properties only: their use or function in the "struggle for existence." Darwinism thus excludes from the picture it draws of the organic world the entire manifold of qualities and properties not having such functions, preferring to call them "selectively neutral." In short, they become accidental and without meaning. For Portmann and obviously for Goethe, however, these properties have intrinsic value as the specific forms of expression of an organism or species. "In my view," emphasizes Portmann, "the purely formal structures play a very specific role in the life of animals--they serve the self-representation of the species and must be counted among the highest characteristics of life" (26).
There are thus not one but two categories of organic properties for Portmann: those that serve an organism's "self-preservation" or "self-maintenance" [Selbsterhaltung], which alone are recognized by Darwinism, and those further properties that exhibit an organism's specific type, which is to say its "self-representation" or "self-expression" [Selbstdarstellung]. Typical of the latter are the colors and patterns of organisms that are not perceived in or affected by their natural surroundings or do not otherwise have a "direct life-preserving task, no 'functional role' in the usual sense" (27). Portmann asserts: "In fact we are surrounded by unaddressed phenomena, directed neither at the eye of a sexual partner nor that of anenemy; phenomena whose sole purpose it is to express the phenomenal essence of an animal or plant." Among other examples, "leaves are a case in point," in that "much in the shape and outline of a leaf is not adaptation to the environment but pure self-representation!" (28).
This view accords fully with that of Goethe in The Metamorphosis of Plants, yet with the important difference that Goethe had no Darwinian theory of natural selection with which to contend.
Now, neither does neo-Darwinism explain all organic properties by "natural selection." Genetic changes are also involved, mutations being regarded as the basis of the process of natural selection. However, as indicated earlier, no explanation of forms can arise by reference to the molecular level, any more than musical tones and intervals can be explained with reference to the grooves of a record.
The Empirical Basis of Portmann's Goethean Understanding of Development
Having shown the problems of explaining organic forms in terms of the principle of natural selection, we shall examine Portmann's teleological explanation of organic processes--the second aspect of his research that is of interest in comparison with Goethe's science and methods. Note that this teleology is not simply a preliminary way of understanding of the sort that has a place in Darwinism. We shall see that, for Portmann, the teleological principle is just as fundamental to understanding organic life and development as is the traditional causal explanation, which it supplements in a decisive fashion.
The teleological method as it is used by Portmann does not arise from reflections on the philosophy of science but rather from his empirical research as a zoologist and anthropologist--indeed, it forces itself upon him through the biological facts. Nor is Portmann a philosopher, and it is characteristic that he does not use the philosophical term teleology, which has been debased by its association with goal-orientation to meaning mere "use" or "function." In Goethe's spirit, Portmann is thus critical of a purely "functional" explanation of organisms, calling his own position in certain contexts "critical finalism" [kritischer Finalismus]--which is critical teleology (29).
Birds, mammals, and the early ontogenesis of the human comprise Portmann's central field of research in this connection. He starts by considering the various species' degree of independence at birth: whether they are "nest-dwelling" or "nest-fleeing." The degree of independence of parental care and of further development in protective surroundings varies with remarkable regularity according to the species and their stage of development and, where mammals are concerned, their independence or "nest-fleeing" increases with the degree of development. But what of the human? From the traditional Darwinian evolutionaryview of the human as a well-developed anthropoid, one would expect it to be a very typical "nest-fleeing" species, but this is not so. The human at birth is "helpless" in important respects, typically "nest-dwelling."
Not only that, but in other respects, such as the development of the sense organs, the human is born just as evidently and distinctly "nest-fleeing." The human possesses a special status compared to all other species, in that it is at once both "nest-dwelling" and "nest-fleeing." Its ontogenesis diverges from that of the other species; as Portmann says, "This fact breaks the rule that applies to mammals" (30).
The question then is: how can one explain this peculiar development, since it clearly cannot be taken as an extension of primate development?
Explanation "From Above" vs. Explanation "From Below"
This is where Portmann's anthropological research comes into its own and his teleological perspective gradually emerges. Since human ontogenesis--beginning with the condition at birth--does not seem understandable "from below" (by drawing conclusions from lower stages of development), it becomes doubtful whether it can be understood with regard to previous stages of development at all, even within the sphere of human ontogenesis. This is, however, tantamount to questioning causal explanation as such, since, of course, causality proceeds from an antecedent cause to a consequent effect. Perhaps later stages--or even the form of existence as a whole--must be included to explain development? If so, this would amount to the Aristotelian kind of teleology characterized in our introduction as an understanding of processes as a manifestation of "form." As mentioned there, a teleological explanation of this sort is also found in Goethe, as will be discussed further on.
Starting from the human's quite special condition at birth, Portmann further indicates that, according to the rules of anthropoid development, the human should be born about one year later than is actually the case. Only then does the human reach the developmental stage of "nest-fleeing" in the bodily proportions and motive ability that characterize anthropoids at birth. According to the aforementioned rules for anthropoids, the human exhibits "premature birth" or, as Portmann puts it, "physiological abortion." In other words, the human develops in a postnatal environment during the first year of life, which--had he been a well-developed ape--should have been spent in the womb. Such considerations direct our attention to what occurs in the human's first year of life, or "the extra-uterine first year," as Portmann calls it. This must evidently provide the key to understanding the human's unique birth condition and time, and moreover illuminate all earlier stages, including prenatal, embryonic development. "Early development is also 'human ontogenesis' and not some sort of primate development followingclassificatory schemes for animal stages" (31).
So what, in particular, characterizes the first year of human life? By common agreement, it is the development of erect posture, the basis of language, and action from insight. These abilities are called forth by an extremely intimate social contact with the surrounding environment, which amounts to a social conditioning; these faculties remain incomprehensible when viewed as the mere development of something already present at birth. We know too that these abilities can be called forth in this way only, and not during fetal development. We must look to the special time of birth and unique condition of human infancy as the simultaneous existence of "nest-dwelling" and "nest-fleeing," and seek here also if we wish to understand all states of development as such. All these relationships are necessary to human beings if they are to develop the very abilities that make them human. Development depends, for example, on the human's quite recently and highly evolved sense organs (the "nest-fleeing" aspect). At the same time, the human is not "fully developed" in other respects, but is openly receptive to multifarious influences from the social environment (the "nest-dwelling" aspect). Here Portmann places particular emphasis upon the unique development of the human brain, with its significant size yet "immaturity" at birth, which forms the basis of the human's "openness towards the world" [Weltoffenheit] and distinguishes the human from all other species. "In general, biological work in recent decades has shown most emphatically how large a part of our total course of development is from the first moment directed to the final goal: a creature whose way of life is 'open to the world'" (32).
Explaining Development through "Structure" and "Type"
In Portmann's research into early human ontogenesis as described, a teleological perspective is evident: the explanation of the different developmental stages is to be found in something that appears clearly only later in development. To understand his perspective, however, we must view it within the context of the philosophy of science.
Note carefully that this teleology is not some sort of inverse causal principle whereby "causes" are sought in the future rather than in the past, as certain scientific theorists have misunderstood the concept. Instead of such an absurd "effect from the future," Portmann's research praxis involves apprehending clearly in the later stages of development a whole that also determines that development at each and every stage. Thus an understanding of the earlier stages of development is provided by the later ones, but not by "causing" them. "It [is] a matter of course in morphological research that...interpretation of developmental conditions presumes a thorough acquaintance with the fully-developed Gestalt: from this acquaintance one understands the stages in development" (33).
Thus, viewed ontologically, what actually determines the process of development--its "cause"--is not the finished Gestalt but the underlying holistic structure manifested to a particular degree in the Gestalt. This datum is clearly expressed by Portmann: "The effective factors in the development of the fetus as well as those which direct the mature organism's functions are links--and only links--in a structure [Gefьge]" (34).
In human ontogenesis, this holistic structure is "the human form of existence altogether"; in fact, "ontogenesis is an ordered actualization of the whole form of existence [Daseinsform]" (35). In this lies the fundamental difference from--and transcendence of--the traditional causal view; a transcendence that we have characterized as "teleology," and one that the phenomena themselves demand of the understanding. As Portmann puts it: "Even in the most strictly limiting causal view of development one cannot be blind to the fact that the sequence of causes and effects is directed towards and ordered for a goal that we know," and which thus determines the sequence (36).
It seems clear that the developmental explanation confronting us here is teleology in the sense just defined: an Aristotelian understanding of process as a manifestation of the "form" or "essence" of development. What Portmann characterizes as "structure" or "the whole form of existence" in the case of human ontogenesis is indisputably to be taken in the same sense as "form" or "essence." Just as the latter, as "the essence of what will come about in the process," "commands the process," (37) so does the former determine the "sequence" in a developmental process.
Yet how does this compare with Goethe's understanding and explanation of organic development? Does the kinship between his and Portmann's views and methods, as demonstrated above concerning directly observable phenomena as objects of research, also hold good in this case? The basis of comparison must be Goethe's zoological research, especially his research on vertebrate anatomy. Without a doubt there are similarities.
Thus, when Goethe speaks of the "type" [der Typus] as a key to understanding the development of forms, he clearly means something related to "form" in the above sense, in that it serves to explain the sequence of developmental stages. Such a "type must be set up so as to advance comparative anatomy," holds Goethe. This "type" shares with Portmann's "structure" or "form of existence" a particular physical shape. In Goethe's comparison of the forms of various species, the "type" is the human shape, which is in fact the most recent development of bodily form. To quote Goethe: "In order to further the refinement of a concept of organic essence we must direct our gaze at the human body" (38). With this "type" as his point of departure, Goethe made his famous discovery of the intermaxillary bone in the human jaw.
Both Goethe's "type" and Portmann's "structure" determine the sequence of cause and effect. "The chronological succession of the states of existence of a living entity....does not come to manifestation...through the mechanical-causal determination of the later by the earlier," as was pointed out by Rudolf Steiner in a commentary on Goethe's theory of metamorphosis--but [the chronological succession] is controlled by a higher Principle, belonging above...the states of existence"--which is precisely "the type." "It is inherent in the nature of the whole that a definite state is fixed as the first and another as the last; and the succession of the intervening states is also determined within the idea of the whole" (39).
Thus Goethe's "type" is as little a sensory material quantity as is Portmann's "structure" or the aforementioned Aristotelian "form," even though it expresses itself physically. This is just what Goethe understands by "the ideal in the real....the idea in the phenomenon." The pressing question now is how to mount an epistemological argument for the concepts of "type," "structure," "form," and a teleological explanation of development.
An Epistemological Discussion of "Form" and "Teleology"
Various sorts of conditions apply when a developmental process occurs in nature. First, there is that which triggers the process, usually known as the "cause." Second, there exist the inherent properties of the object of the process, its "nature," "essence," or Aristotelian "form." Third and last, we can see the regularity in the actualization of the inherent properties as directed towards a goal (i.e., it is "teleological," from the Greek telos, meaning goal). With regard to this latter developmental condition, teleology is here spoken of as a manifestation of "form." Characteristically, modern science attends to the first condition only, Aristotle's "efficient cause." This one-side view has also promoted manipulative intervention in natural processes, since it lends itself particularly well to the description of mechanical (technical) relations. Yet the causal explanation is already insufficient in important areas of physics, as Goethe demonstrated in his theory of color. Most remarkable of all is its inadequacy as a means of understanding organic developmental processes, as we have tried to show above with reference to Portmann's discovery that early mammalian and human ontogenesis must be explained in terms of "form" and "goal."
Our present difficulty in transcending the traditional causal viewpoint hinges partly upon a misunderstanding of the concept "teleology," and partly upon philosophical prejudice, as we shall further elucidate.
Laboring under the widespread misconception of Aristotle's philosophy, modern science tends to view teleology in nature as analogous to goal-orientation in human action, where the goal pertains to a conscious intention in a subject and is thereforeseparate from the action itself. Yet this is not so with natural processes, where the goal is not explained in terms of the subject but rather identified with the "form" or "essence." "The essence and the goal are the same," Aristotle asserted, or "that sort of condition or reason that is the goal is actually present: at work in nature's productions and shapes"--i.e., "the shape is the goal-reason" (40). Aristotle here gives a striking image of Portmann's "structure" or "form of existence" and how it functions--also of important aspects of Goethe's type as Herman Siebeck describes it in his book Goethe als Denker: "The idea of a formative and final all-determining type...is already contained in Aristotle's principle of form as ruling matter" (41).
Such a teleology cannot be explained away, as modern analytic philosophy attempts to do, by interpreting it (along with causality) exclusively as a relation concerning "sufficient" and "necessary" conditions. Such formal logical analysis would eliminate teleology as a reality in natural processes and reduce it to causality in relation to the effect (42). First of all, this overlooks "form" (the inherent properties of the developing object) as a condition equally important as what is called "the cause." Second, formal logical analysis abstracts from the real-time sequence of the process, without which there would indeed be no process at all.
A second mode of understanding the concept of teleology is the Kantian. Contrary to the approach just mentioned, Kant assumed teleology to be a reality and even an "inner principle" in nature. Yet he denied the use of such a principle to human understanding [Verstand] in explaining nature. This is because it requires an idea that "moves from the whole to the parts," something that would require an intuitive capacity functioning "quite independently of sense"--a faculty we do not possess. For Kant, our knowledge of nature was thus limited to mechanical causality (43).
Goethe takes issue with just this point in his evaluation of Kant's "critique of the teleological judgement," asserting that he himself has "unceasingly pressed forward to this experience of the archetypal [Urbildliche, Typische]," i.e., precisely the "whole" that Kant denies to human understanding (44). Goethe's morphology and Portmann's research represent, as practical endeavors, an argument against Kant's limitation of the understanding.
Goethe's "type" and Portmann's "structure" or "form of existence"--like Aristotelian "form"--obviously represent an "ideal" entity (an idea or a concept). Why not? The philosophical prejudice that is anchored in nominalism and materialism blocks an understanding of teleology in that it does not recognize ideas or concepts as objectively real. This prejudice also comes out in according the whole a sort of reality in organic processes while putting it beyond human understanding, as Kant certainly does. The idea involved in Goethe's andPortmann's research is not grasped "quite independently of the senses" and thus is not comprehensible only to an "intuitive" faculty of cognition, to use Kant's term. On the contrary, this idea follows upon empirical research, as shown in Portmann. It applies no less to Goethe, in that the idea or "the content of the Type-concept...is arrived at in connection with...the sense world," although it "cannot originate in the sense world as such" (45).
Philosophically speaking, Goethe's and Portmann's position involves a form of idealism, yet one that must be regarded epistemologically as realism. It is not speculative, as was the idealism of Goethe's contemporaries Schelling and Hegel, but rather extremely empirical--Goethe's "gentle empirism" [zarte Empirie]. Nor should it be confused with twentieth-century "vitalism" in the philosophy of nature, which Portmann explicitly rejects. "We cannot get hold of an unknown 'factor' determining the goal but we must recognize the goal-orientation of the developmental process as a fact of maximum importance in living beings" (46)--i.e., it is entirely a matter of an empirically ascertained and nonspeculative relation.
"Form" and "teleology" must therefore be understood from the foregoing epistemological perspective when applied to Portmann and Goethe.
The Transcendence of Darwinism
Above, we have argued epistemologically for Goethe's and Portmann's teleological explanation of organic developmental processes as found in their researches. Since in other respects we have opposed their research to that of the Darwinian approach in organic science, the objection might be made that Darwinism also leaves room for teleological explanation. Such a view is espoused by the researcher Theodosius Dobzhansky, who maintains that "causal explanations do not make it unnecessary to provide teleological explanations where appropriate. Both teleological and causal explanations are called for in such cases" (47).
As indicated earlier, however, this type of teleology does not fundamentally explain organic phenomena, for in the last analysis they are understood only causally in terms of the mechanisms of "natural selection." It is otherwise with Portmann and Goethe, for whom teleological explanation is not only equal to causal explanation but primary, or rather, superior, as a principle of explanation applicable to living organisms and their development. This conclusion clearly follows from Portmann's research on human ontogenesis.
Yet another basic difference pertains. Portmann's and Goethe's teleology applies to all the properties of an organism, not only the "purposive" ones that are "useful in the struggle for existence." We may recall our comments on Portmann's distinction between what he terms "self-preservation" (or "self-maintenance")and "self-representation," which makes it clear that properties such as form and behavior are no less explicable teleologically than those that serve only the "preservation of life." As we have seen, they are indeed more authentic expressions of an organism's "form of existence" as a whole, i.e., its "structure," than are the other properties. But this also means that self-representing forms express the "plan" realized in "development." Consequently, if we want to understand Portmann's and Goethe's teleology, we must free ourselves of the narrow utilitarian view and the one-sided functional model that pervade traditional, Darwinian research.
A New Paradigm for the Theory of Evolution
In the foregoing, we attempted to demonstrate two essential points concerning the difference in method in the organic sciences between the traditional, Darwinian approach and that of Portmann and Goethe. First, we demonstrated the irreducibility of directly observable organic properties and qualities as research objects. Second, we showed that organic and developmental processes are explained by a teleological principle that is neither a functional nor a preliminary explanation but is to be understood rather as a "manifestation of form."
These steps beyond Darwinism involve rejection of its two basic methodological presuppositions: (i) the Neo-Darwinian reduction of organic phenomena to genes and their mutations and (ii) the general Darwinian assumption that organic development is fundamentally intelligible as an inorganic causal relation (the mechanisms of natural selection). In this way, the method of Portmann and Goethe represents no less than a revolution in the organic sciences--a new research paradigm, to use a notion central to the contemporary debate in the philosophy of science (48).
This methodological paradigm, of course, involves a radically new view of the historical development of organic life, of evolution. Rejecting the reductionist theory of mutation, and restricting the significance of the principle of selection and the causal explanation of organic processes means calling into question the dominant neo-Darwinian theory of evolution, for these are precisely the tenets upon which it rests. Though we have concentrated on Portmann's work on ontogenesis, it is clear that in rejecting any explanation of development "from below" and asserting that "the idea of deriving higher from lower leads astray" his view has consequences for phylogenetic development, for evolution (49).
Portmann is extremely critical of peremptory opinions set forth in traditional evolutionary theory, and repeatedly warns that "care and reservation" are necessary in this "uncertain" area. For him, the "magic word 'mutation' deludes us into believing that we know about processes of which no one can have certain knowledge" because "each attempt to attribute to the seedgerm...the capacity to create new types far exceeds the limits of a scientific proposition and is exclusively motivated by the times' unsatisfied need for beliefs. It must be recognized that one of the most active impulses in all biologically oriented thought today has an uncertain basis; the biologically based theory of evolution must be deprived of its rank as a matter-of-course, accepted truth" (50).
Admittedly, Portmann provides no complete alternative theory of phylogenetic development of his own for the same reason that he is critical of the ruling neo-Darwinian theory: we find ourselves on empirically "uncertain" ground. His basic view and method in the organic sciences leaves, however, little doubt that his theory would differ radically from the Darwinian, and would be one whose character is certainly indicated by his views and method as outlined above. To elucidate this relation, we may again look to Goethe, whose views and method are so akin to Portmann's. The kinship between Portmann's "structure" and Goethe's "type" as an ideal "form" realizing itself in the process of development is qualified only in that the former refers to ontogenesis, the latter to phylogenesis--to the natural history of species--and therefore does more to illuminate evolutionary theory.
Goethe's basic view that all species have common origins agrees with Darwinism thus far. But, for Goethe, this origin cannot be one special organic form (e.g., no particular animal form among vertebrates) because "no single one can give the pattern of the whole." The single variants of form can then only be understood "from the general idea of type," which is just such a unitary whole, not at all a material quantity, but an idea (51).
For Goethe, this "type" or ideal "primal organism" is, in Darwinian terms, the "form of common descent" of organic development. "The form of common descent or whatever one calls it is for him [Goethe] always the type itself, as [a sensory-spiritual] idea and it already pertains prior to any definite family of species, which it conditions," asserts Herman Siebeck. The "type" is "a purely apperceptive, typical form manifesting itself in sensory space in a graded sequence...of qualitatively different species" until it reaches its most complete manifestation--in Goethe's words its "highest form of organization"--in the human organism. "The type comes forth more clearly at the higher than the lower level" (52).
Thus we see a striking resemblance between Goethe's concept of "type" as employed in his natural historical studies and Portmann's views on human and mammalian ontogenesis as determined by a "structure," or "form of existence." We should be justified in asserting that Portmann's research into ontogenesis positively prepares the ground for a theory of phylogenesis that transcends Darwinism in Goethe's spirit (53).

Do the Genes Justify the Means?
Pat Cheney
 
The big idea is to isolate the human gene for any given characteristic, and control it for the purposes of therapy. Millions of pounds are being spent on this exploration in the belief that one day we will be masters of our bodies and possibly our souls, if there is a discoverable disposition to violence, deviance, depression and so on. The campaign, for such it seems to be, is as prestigious, as popular to the apologists for 'frontierism', as enthralling, as the exploration of outer space. And I think it is as flawed.
We feel that the search for knowledge is desirable and inevitable. Oppenheimer, one of the scientists responsible for developing the atom bombs which were dropped on Hiroshima and Nagasaki in 1945, when interviewed, himself expressed this view quite forcibly.
We know how to split the atom, how to deforest a country, how to grow more food in the same amount of space, how to get from one place to another without having direct contact with the weather or our fellow travellers. And although we may regret the spin off from these discoveries, we still call it progress. Our curiosity coupled with persistence seems as unavoidable and as natural to us as breathing. Who has not felt inspired by the story of the discovery of the structure of DNA for example: the intense search for truth, the disciplined application of skill, the mind concentrated in the interests of discovery. Because we can, we do, even though we don't understand. And just as the space projects take us to the boundaries of outer exploration, so the genome project heads towards the culmination of our inner explorations.
Why is it then, at this exciting time in our history, that so many of us have doubts and questions? There is, naturally, a strong and fearful feeling response amongst many people to the possible consequences of scientific activity in itself, but I am supposing the unease to be more than that. Could it be the expression of a profound but dim awareness of what we are doing to ourselves as human beings? At the level of reason, the difficulties are seen to be mainly practical. The activity is seen as worthwhile, it's just that we are unable to regulate the ultimate outcome of our interference in nature.
One of the most interesting aspects is the popular misconception of the gene as an autonomous, forming, acting, transmogrifying, singular agent. Geneticists themselves now say that it makes more sense to see a potentiality within a particular context and that this context includes what we call the gene. For example, when mutated, a gene for cell cycle regulation in man produces eye tumours. The identical mutation in mouse, although it produces abnormalities, has not been found to produce eye tumours thus demonstrating that the organism provides the context in which the gene is meaningful. This being so, if we manipulate the isolated gene, how can we be confident that we will not affect any other part of the organism? Do we know the limits of this organism? Are the limits of the human body the body itself or its physical environment, its psychological environment? If we keep our farm animals in cosy sheds, we know that we not only affect them by depriving them of outside air and sunlight, we also deprive the fields of their presence. For the animals the fields are certainly part of the context.
The question of what the gene is, arises with particular force when we consider the question of patenting: are we trying to patent life? We wonder what life is; does such a question have any reality at all. When it comes to manipulation of genes, scientists themselves are already aware that they need to proceed with caution. For example, it is known that one copy of a gene connected with sickle cell anaemia also protects against malaria; the transgenic tomato could in principle transfer antibiotic resistance to gut bacteria; migrating genes from farm animals can transfer the resistance to human beings. And then there are the risks posed by releasing genetically modified organisms into the environment, risks addressed by the 1992 Rio Bio-diversity Convention, the methods for dealing with which depend on a level of brotherly international co-operation, which was it in place, would possibly not have sanctioned such activity in the first instance.
These apparently laudable attempts to do things properly, these applied ethics, are actually false gods.
Biotechnology is big business. The genome project is a multimillion pound investment. Is it intended to save the government money? The screening done for things like cystic fibrosis is thought to be connected to the fact that it is cheaper to abort such children than to maintain them. This is the atmosphere in which what little debate there is takes place. Apart from economic necessity, which motivates governments committed to growth and drug companies seeking profit, there are other factors at work; our fear of death; the view that every illness is bad, and of course, along with all this goes the inevitable whiff of eugenics.
What then is the pursuit of knowledge and what place does science have in that pursuit? Applied science gives us tomatoes in February, vitamin pills and tampons. Scientific endeavour is often presented to us as the apogee of the search for knowledge, yet the science we have often seems more like the expression of a wish to become invulnerable and safe and to have certainty, and appears to have little to do with true knowing. In the Meno, Socrates says that we shall be better braver and more active men if we believe it right to look for what we do not know, than if we think that we cannot discover it and have not a duty to seek it. Human beings can acknowledge the truth of that in many different ways. Is there a way which is not the received way of conventional science? What do we mean by knowledge? A set of facts, something taught, something learnt? Or is it what the individual has discovered for himself by patient application of the trusting intelligence. And can the object of knowledge be anything but what is real and permanent and not the ever changing sense world? Surely we can only begin with the sense world, not make it the object of knowledge.
Scientists say that they will not be influenced by anything subjective. They will look at the objective world 'out there' and draw their conclusions unaffected by feelings or subjectivity. This in itself sounds very commendable and a fine antidote to superstition and sentimentality. But we are tempted to ask whether they are acting in the true spirit of this wish or setting up another orthodoxy; one which denies the existence of the scientist himself and then the whole organism in favour of the part. There is no such thing as reality 'out there', but there are many realities which we ourselves create. We do that because of the way we usually think. And because Creation is generous, we find the concepts we have working in the world, though in a form which is only one part of the whole.
Science as we know it however continues to go round and round in a contracting universe of abstractions, clinging to the idea that the whole of our rich life can be ground in the satanic mills of Bacon, Locke and Newton. The truth was not found, Schoepenhauer says, not because it was unsought but because the intention always was to find again some preconceived opinion or other or at least not to wound some favourite idea. And yet we continually wound ourselves with our way of thinking.
What shall we do with our capacity to explore? We have explored the physical world; we have been to the moon; we are delving into the physical body; we have made a beginning on the human soul. We are searching for the way to live. It is enthralling this exploration, but the uncharted country is not in our bodies nor in our souls but in the spirit, which we have neglected so much. The journey to this place is beset by pitfalls, monsters, false gods; it's the hardest journey anyone ever has to undertake but it is the only one worth going on. It is a prerequisite to any other journey we make. And Socrates meant this when he urged us to find out. He suggests that the truth of all things that are, is always in our soul, all we have to do is remember it and having done that we will naturally act out of it. This seeing and acting is the activity of the spirit - the true heart of our intention - we have only to trust it. Then we shall be living in a world which is exactly the same and yet completely different, the world inside Alice's looking glass. What now looks like the expression of man's highest achievement in the realms of science and technology might then be seen as no more than grubbing around with blinkers on. But as long as we go on thinking that morality is something which we can apply to a given situation and not something which permeates the conduct of our every waking moment, we will continue to reinforce a world divided against itself.
Author's email address: pat.cheney(at)freeuk.com
This article was first published in 'Quaker Monthly' (Vol. 75-8, August 1998, pages 145-8, ISSN 0033-507X) which is edited by Elizabeth Cave and published by Quaker Home Service, Friends House, Euston Road, London NW1 2BJ.
 
What Is the Reality of a Gene?
By Johannes Wirz
At first sight, this question might cause some provocation. Scanning through scientific journals shows that gene based biology is at the centre of most research. How could a science with such a strong commitment and with such obviously impressive capabilities depart from a questionable ground? Don't we all know what genes are? Aren't they the causes for all forms of development, processes and characteristics in the living world? Don't they ensure that people have blue or brown eyes, fair or dark hair etc.?
However, if we take a closer look at modern biology, the question 'What is the reality of the gene' appears justifiable. For instance, we are faced with the intriguing fact that the master gene for eye formation in mouse, the small-eye gene, leads to perfect compound eye formation in eyeless Drosophila, after successful integration of the gene into the fly's genome. We are thus left with the question: What, if not the master gene itself, directs the formation of the specific 'right' eye in the 'right' organism. Can we believe that this specificity is provided by some of the 2,500 or so as yet unidentified genes required for the elaboration of this sense organ?
Even more intriguing are the first and exciting fruits of the various genome projects, the most prominent of which is devoted to the human genome. Some 90,000 genes have been identified, by expressed sequence tags (ESTs), scattered amongst the 23 chromosome pairs in man. A large majority of them have no known function and no remarkable sequence homologies with genes identified in any other organisms, be they bacteria, yeast or mouse. Thus, in contrast to the situation in physics, we are dealing with 'causes', with unknown effects.
Amongst these thousands of genes, a tiny fraction, a mere eight genes, have been found to be expressed in some thirty organs and tissues analysed. This is in strong contrast to the expectation that cell viability is guaranteed by a myriad of 'housekeeping genes' whose expression is thought to be ubiquitous in almost all of some two hundred different cell types. Are the classical concepts of cell biology, from which the ideas of housekeeping genes and their corresponding proteins originates, still correct? When and at what level are all the genes expressed that must provide the proteins for basic metabolic processes and reactions?
The foregoing examples may be sufficient to permit the question as to the reality of the gene. Answers can be given at different levels and show some very important limitations:
1) Genes as structural units: DNA, the chemical basis of genes, can be modified, cleaved and ligated etc. In this sense it is about as interesting as sugars, lipids and other constituents of the cell, - putting it bluntly, relatively boring, or at least, no more interesting than chemical substances in general. However, what is exciting is the fact that it can be reintroduced into living organisms. DNA, as such, has nothing to do with life. It is dead. It is as 'inert' as salt. It does not create life, but it can be integrated into life processes. Results like those I have described demand further investigation and research. Identification of the 2,500 genes required for eye formation, their functions and interactions is a tremendous challenge for generations of molecular biologists. Identification and elaboration of the chromosomal organisation of the 80 - 100,000 genes of the human genome, their functions, regulation in time and space will keep researchers busy for decades. And all the work, all the experimentation, is set to follow the very same scheme: manipulation and engineering, - for we live in the age of 'invasive biology'. At this point these reflections could easily deviate into ethical and moral concerns, but I trust these will be considered later. Suffice it to say here, this first level of reality could be called the 'technical instrumentalisation' of life.
2) Genes as informational units: Genes are carriers of information. From a given sequence of genes, the primary structure of proteins, its amino acid sequence, can be deduced. The flow of information from DNA to RNA to protein can be unequivocally predicted, but is by no means sufficient to draw any conclusion on function. Indeed, any undergraduate could derive the protein primary sequence from a given stretch of DNA, but the genome projects show beyond any doubt that the function of a protein cannot simply be read from its amino acid composition. We are thus left with the problem that either the molecular approach to life does not grasp the entirety of living beings or that there exists occult information in the gene besides that of the genetic code. We either embark on DNA mysticism or acknowledge the limitation of purely genetic explanations of life.
3) Genes as functional units: Let us presume that we have identified a gene and elucidated the function of its product. We have already seen in the example of the eye formation that the function alone is not sufficient to explain its 'meaning' or 'significance' for the organism itself. More importantly, most of us are familiar with the poorly understood situation in animal model systems, where human disease conditions are simulated. Often enough, transgenic animals with the correct genetic changes can be generated, but the expected traits are lacking. One of the most important examples is the retinoblastoma gene. It is essential for cell cycle regulation in man and in its mutated form results in the formation of eye tumours. Mice with the very same genetic change develop a number of abnormalities, but retinoblastomas have not been detected in a single animal. If the gene had first been discovered in mouse it would not have been called the retinoblastoma gene. The genetic condition is necessary, but is obviously not sufficient for the formation of the organismic, phenotypic characteristics.
Another example is the gene for isomerase. Identified in mammals as well as flies and having a strong homology, it catalyses very different functions. In mouse it is involved in the maturation process of cells in the immune system, but in the fly it promotes correct folding of the eye pigment, the opsin protein. The same protein function results in very different phenotypic traits.
This third level of reality of a gene is to provide the functional basis for living beings without determining their organismic meaningfulness.
This list of realities of the gene is far from complete, but it is long enough to make it clear that the gene, in contrast to the objects in our everyday world, is not just a given fact. Rather, it is an entity which depends upon the intentions of scientists. Realities depending on intentions are always of a conceptual nature, they are the synthesis of percept and concept, of matter and mind, of phenomenon and idea.
The three different gene concepts outlined, require different prerequisites or complementation by three different 'worlds'. The gene that is manipulated is dependent on living organisms that are competent to integrate it into their own genome. Life itself is a prerequisite for genetic manipulation and, as such, cannot be explained in molecular terms, it transcends molecular reductionism. Genes are not causes, but conditions for life processes.
Genes provide the information for the primary structure of proteins. But their functions cannot be deduced from the latter; hence, there must be a 'world' of processes where proteins are at its disposal.
And finally, the functions of gene products need to be integrated into the entirety of an organism, by the organism itself. Proteins allow for the expression of phenotypic characters, they are not their causes. It is the mouse that specifies the meaning of a given function, it is the fly that interprets mouse genes in its own context.
We are therefore left with a situation that urgently requires some rethinking as well as a methodological enlargement of science. It is a situation which has resulted from molecular biology itself. We need a biology which unravels the non-molecular essence of life. We have to look for a science that investigates the true nature of organismic processes. And we need a sound scientific approach which is able to investigate the 'flyness' of a fly or the 'mouseness' of a mouse, i.e the essence of living beings.
Molecular biology and genetic engineering uncover the molecular, material basis of life and at the same time they reveal that non-molecular approaches are required in order to understand life processes in depth.
Forshungslaboratorium am Goetheanum, Dornach, Switzerland
 
Hidden Inheritance
Gail Vines
(This article first appeared in New Scientist (28 November 1998, No. 2162, pp. 27-30) and is republished here with permission. It is followed by a response from Jim Cummins which was published in New Scientist 'Letters' section (19/26 December 1998, p. 103).)
 
Imagine aliens from Outer Space announcing that they had engineered lasting alterations into the human race. The changes are going to make our children, and our children's children, smaller, weaker and easier to control. But grassroots resistance is fierce, and soon technicians are working round the clock to screen millions upon millions of human genomes in an effort to weed out anyone whose genes show signs of alien tinkering.
A mystery swiftly unfolds. The human genes appear to be untouched, yet downsized babies are born in ever- increasing numbers. Then, just when it looks like our number's up, the aliens take pity and decide to reveal their biotechnical knowhow. "There's more to heredity than DNA," an alien boffin begins...
Back in the real world, molecular biologists now sequencing DNA as part of the multimillion-dollar human genome project will finish the job in a few years. Yet masters of the genome we won't be. A spate of mysterious observations made by Earthling scientists suggest that those alien boffins are right -- that there is a lot more to heredity than DNA.
Just as cells inherit genes, they also inherit a set of instructions that tell the genes when to become active, in which tissue and to what extent. This much is uncontroversial. Without this "epigenetic" instruction manual, multicellular organisms would be impossible. Every cell, whether it's a liver cell or a skin cell, inherits exactly the same set of genes, and it is the manual, which has different instructions for different cell types, that allows the cell to develop its distinctive identity.
Established theory has it that the instruction manual is wiped clean during the formation of sperm and egg cells, ensuring that all genes are equally available, until the embryo starts to develop specific tissues. But outlandish evidence now suggests that changes in the epigenetic instruction manual can sometimes be passed from parent to offspring. These findings have even inspired some biologists to suggest that changes in the manual passed down through the generations could provide a way for populations of animals to quickly adapt to their environment, creating a fast-track supplement to the more sedate Darwinian selection.
Speculation aside, one thing is certain. "Bizarre things are going on that we are just beginning to get a handle on," says Marcus Pembrey, a clinical geneticist at the Institute of Child Health in London. Consider the pregnant Dutch women who starved during the famine of the Second World War. Not unexpectedly, they had small babies. Far more surprisingly, those babies went on to have small babies, even though the postwar generation was well fed and no genes had been tinkered with.
Then there are the perplexing findings in mice and rats. Give just one generation of male rats a drug called alloxan, which decreases the body's sensitivity to the hormone insulin, and their offspring and their offspring's offspring become progressively more prone to diabetes. Expose mice to high doses of morphine and the damage to the nervous system persists in their descendants. And one injection of the thyroid hormone thyroxine into a newborn rodent permanently depresses levels of both that hormone and thyroid stimulating hormone -- and levels remain low in the next generation, too.
Many of these observations are decades old and have long been relegated to the scrap heap of unexplained and inconvenient findings. They trouble geneticists, because they seem to fly in the face of classical genetics, even smacking of Lamarckian inheritance, the discredited notion that animals actively acquire characteristics and pass them on to their offspring-by Lamarck's reckoning, body builders would beget muscle-bound babies.
In fact, the way mammals are built should stop a parent's environment having any direct impact on its offspring's genes. The sperm and eggs are packed away in ovaries and testes from very early in development. While other cells become specialised, turning genes on and off to create the different tissues of the body, these "germ" cells remain quietly sequestered, shielded from the environment, until called upon to pass their still pristine genes on to the next generation.
So it's not surprising that scientists have tried to explain away the disturbing aftermath of the Dutch famine and the results of the mice and rat experiments with more conventional reasoning. Did the first generation of small babies suffer some strange hormonal imbalance which, when they reached adulthood, affected the growth of their infants in the womb? Or in the case of the rodent experiments -- which passed down the male line, too -- were the experiments just plain suspect? No firm conclusions were ever reached, but doubts lingered.
"It has become difficult for people to think of heredity as involving non-genetic material," says Steven Rose, a biologist at Britain's Open University in Milton Keynes. The research has continued, he says, but epigenetic research "remains semi-underground. You're not supposed to talk about it". That, however, could be about to change. Last year, Wolf Reik, a molecular biologist at the Babraham Institute outside Cambridge, and his colleagues at the Free University in Berlin, stumbled upon the best evidence yet that epigenetic changes can pass from one generation of mammals to the next.
Reik's main interest is in an epigenetic phenomenon called "imprinting". Genes exist in pairs, one from the mother, one from the father. And whereas most genes in animals such as mice and humans behave in exactly the same way regardless of which parent they come from, imprinted genes are different. In some cases, an imprinted gene is activated only if it is inherited from the father; in other cases, only if it comes from the mother. No one knows quite how this process works, but clearly some sort of "mark" must persist through the generations to tell the offspring's cells which genes to re-imprint.
While much about imprinted genes remains a mystery, initial studies suggest that they often help to regulate the growth of the fetus, and that they are marked for shutdown by small, molecular clusters called methyl groups ("Where did you get your brains?" New Scientist, 3 May 1997, p 34). The methyl groups both block transcription-the first step in gene activation-and, by binding certain proteins, help to fold the DNA into tight, inaccessible coils. Other control mechanisms, still poorly understood, are also at work. But however they work, the existence of imprinted genes demonstrates that, each generation, not all genes are wiped totally clean of their epigenetic marks.
Last year, Reik and his colleagues found clues to the identity of genes that potentially, at least, carry epigenetic information with them as they move from parents to offspring. First, the researchers discovered that some genes become methylated if you move the nucleus from a just-fertilised mouse embryo into the egg of a mouse of a different strain that had had its nucleus removed, and then put the newly manufactured embryo into the womb of another mouse and let it develop normally. The resulting mouse pups were also noticeably smaller.
By measuring the amount of protein in the livers, brains and hearts of these mice, Reik was able to show that two genes had been shut down: a gene for a liver protein called major urinary protein (MUP) and a gene for a protein made in the cells lining the nose, called olfactory marker protein (OMP). Although the DNA sequence of each gene remained unchanged, they had been methylated.
But the real bombshell was yet to come. MUP proteins are usually secreted in mouse urine and, along with pheromones, are signalling chemicals vital to normal sexual behaviour in mice. OMP, on the other hand, is part of the olfactory system that allows mice to recognise pheromones. Not surprisingly, when the smaller mice grew up they were slow to mate. When they did mate eventually, Reik and his colleagues Irmgard Roemer, Wendy Dean and Joachim Klose were amazed to discover that not only were the offspring smaller than usual, but that the MUP and OMP genes were again methylated and switched off. The epigenetic changes had passed down from one generation to the next.
Once you accept that epigenetic inheritance occurs, it's far easier to envisage how drugs, hormones and starvation could have created the bizarre transgenerational effects in rodents and perhaps even in humans, says Reik: the chemicals and the diet may have triggered the heritable methylation of certain genes. At first, however, "we tried very hard to disbelieve our results", says Reik. But as they checked and double-checked their data, and studied the literature, things just fell into place.
It turned out that there had been a smattering of earlier reports of mice inheriting epigenetic changes. Ten years ago, Christine Pourcel at the Pasteur Institute in Paris discovered that when a gene from a virus was inserted into mice it became methylated and silenced, and that the modification was passed on to the offspring. And in 1990, Azim Surani and his team at the Wellcome Trust and Cancer Research Campaign Institute of Cancer and Developmental Biology in Cambridge found other cases of epigenetic inheritance when genes were shifted from viruses into mice. Those earlier transgenic experiments were generally deemed too artificial to be of any consequence in the natural world.
Not so Reik's mice, it seems. "It's lovely work," says Lawrence Hurst, an evolutionary geneticist at the University of Bath. Transferring a nucleus from one mouse egg to another is undoubtedly an unnatural thing to do, but as Reik points out, the procedure could mimic changes that happen naturally. In of development, the activity of genes is in tremendous flux, being turned up and down as methyl groups and proteins are added and removed. Similarly, as the nucleus is moved from one egg to another in Reik's experiment, it experiences differences in temperature and concentrations of various chemicals, all of which could permanently change the methylation of certain genes.
Curiously, cloned lambs and calves created by nuclear transfer -- a technique similar to the one used to create Reik's undersized mice -- may be up to twice as large as normal. No one knows what causes the phenomenon, whether genes are "inappropriately" methylated or whether the oversized offspring, if bred, would pass the trait on. "But our observations raise the question of whether or not such manipulations could actually have a long-term impact by being transmitted to future generations," says Reik.
And if physical manipulations of embryos is all it takes to trigger inappropriate methylation of some genes, then that may be a good reason to worry about what happens to human sperm, eggs and embryos during high-tech fertility treatments. All three are routinely squirted through pipettes, swirled around in lab dishes, or frozen during procedures such as in vitro fertilisation or genetic testing of embryos. What's more, there have been some reports -- albeit controversial -- that babies born following IVF are smaller than normal (see "Shots in the dark for infertility", New Scientist, 27 November 1993, p 13).
Reik's mice also highlight another potentially worrying issue. Hurst, and developmental biologists such as Martin Johnson of the University of Cambridge, argue that in an effort to sell the genome sequencing projects to the public and the funding agencies, molecular biologists have created the misleading impression that genes alone run the show. The constant emphasis on the power of genes, he says, has created "a 20th-century form of fatalistic predestination", in which people believe they are the product of their genes, nothing more, nothing less. Even geneticists, he says, have lost sight of the huge range of environmental factors that can change a gene's activity, ranging from an adult's diet to certain high-tech fertility treatments. For those reasons, some geneticists are calling for a new definition of the gene, based on not only its DNA sequence, but also its epigenetic instruction manual -- the degree of methylation, for example.
But can epigenetic alterations, heritable or otherwise, really be worth the fuss? Yes, according to Eva Jablonka, an evolutionary biologist at Tel-Aviv University. In her book with Marion Lamb, Epigenetic Inheritance and Evolution, The Lamarckian Dimension, she points out that the idea that the effect of the environment on one generation's epigenetic instruction manual can be passed to the next is old hat to students of simpler organisms like bacteria, yeast, plants, and even fruit flies. For example, in yeast, the epigenetic silencing of one of two genes produces changes in sex that are inherited. And just a few months ago, Renato Pare of the Centre for Molecular Biology in Heidelberg, Germany, reported a striking example of epigenetic inheritance in laboratory fruit flies (Cell, vol 93, p 505). The activity -- but not the sequence -- of a key gene was changed in embryos that went through a brief heat shock, activating another gene that caused the flies to have red eyes, a trait they passed on to their offspring.
Jablonka theorises that epigenetic inheritance in lower organisms at the very least play a key role in evolution by providing an additional source of variation on which selective pressures can act. Although epigenetic changes may be as random as mutations in the DNA sequence, they could also be adaptive, triggered by environmental changes to enable simple organisms to respond quickly to a fluctuating environment. For example, if one source of bacterial food is in short supply, heritable epigenetic modifications could help populations of bacteria to switch to another food source. Jablonka also points out that epigenetic inheritance is not at odds with classic inheritance via the genes. Instead, it would be a complementary inheritance system, with Darwin's natural selection acting on both the modified gene and on the genes that control epigenetic modifications.
Meanwhile, Pembrey, provocatively calling himself a "neo-Lamarckian", is prepared to stick his neck out even further, and suggest an adaptive role for epigenetic inheritance in higher organisms such as humans. He speculates that the inheritance of epigenetic factors which control a few select genes may have enabled human populations to regulate the growth of individuals according to food availability. Food shortages could generate physiological responses in adults, say, a change in hormone levels, that influence the activity of key growth genes. This could then be passed on to their offspring by varying the genes' methylation.
In the short term, such an adaptive mechanism could, for example, ensure that the baby's head is not too big for the mother's birth canal. In the longer term, if the offspring also passed those epigenetic changes on to their offspring, it would result in generations of progressively smaller people, until a period of plenty created the epigenetic changes that reversed the trend. The two generations of small babies that followed the Dutch famine could be explained by just such epigenetic adaptation, says Pembrey Perhaps, he says, the giants of Patagonia (literally "the place of big feet") reported by Ferdinand Magellan in the 16th century and countless later European travellers, really did exist.
"What we can see now is the tip of the iceberg," says Marilyn Monk, a molecular embryologist and geneticist and a colleague of Pembrey's at the Institute of Child Health in London. She predicts that many more examples of epigenetic inheritance in mammals will come to light once geneticists develop ways to monitor methylation across the entire genome during an embryo's development. What's more, she says, the much- cherished notion that sperm and egg genes are totally sheltered in the ovaries and testes starts to look shaky when you examine it more closely: in humans, the primordial cells that generate eggs and sperm are busy dividing up until the 15th week of development.
Not everyone is prepared to take such radical positions as those of Lamb and Pembrey. John Maynard Smith, an evolutionary biologist at the University of Sussex, remains sceptical. He points out that even if epigenetic modifications occur naturally in mammals and are passed down the generations, there is still no reason to suspect that they are any more "adaptive" than random gene mutations that are passed on to offspring. Reik, too, cautions against overinterpreting his results. "Whether any such epimutations have any adaptive significance remains to be established," he says. No one has yet shown that inherited epigenetic changes occur naturally in mammals, and even if they did they may still be rare, random and inconsequential events -- even downright dangerous.
Whatever the final verdict on the significance of epigenetic changes, one thing is already clear, says Hurst: "Epigenetics matters." As the human genome project rushes to completion, the really interesting insights are going to come not from the sequences, he predicts, but "from working out how genes are controlled".
Epigenetic Inheritance and Evolution, The Lamarckian Dimension by Eva Jablonka and Marion Lamb (Oxford University Press, 1995)
Genomic Imprinting, edited by Wolf Reik and Azim Surani (Oxford University Press, 1997)
"Epigenetic programming of differential gene expression in development and evolution" by Marilyn Monk, Developmental Genetics, vol 17, p 188 (1995)
"Epigenetic inheritance in the mouse" by Irmgard Roemer and others, Current Biology, vol 7, p 277 (1997)
"Imprinting and transgenerational modulation of gene expression: human growth as a model" by Marcus Pembrey, Acta Genet Med Gemmellol, vol 45, p111 (1996)
"Transgenerational effects of drugs and hormone treatment in mammals: a review of observations and ideas" by J. Campbell and P Perkins, Progress in Brain Research, vol 73, p 535 (1988)
From the Letters page, New Scientist, 19/26 December 1998, p. 103
Not by genes alone
Gail Vines's nice article on epigenetic effects ("Hidden inheritance", 28 November, p 26) rightly points to imprinted genes as the main players -- although it would be interesting to look at marsupials, where imprinting supposedly doesn't occur.
However, there may be other non-genetic factors. For example, a sperm contributes a structure known as the centriole to the fertilised egg, and this is now known to be the template for the first cleavage spindle in most mammals (mice are an exception). In addition, calcium oscillations responsible for activating the oocyte are triggered by an extranuclear factor or factors from a sperm's perinuclear region.
Sperm also carry mitochondria that are normally destroyed but they may occasionally evade this process -- possibly by fusing with an egg's mitochondria. There are a number of other components such as a unique alpha-tubulin protein and elements of the tail that could contribute to axis formation and factors such as nucleo-cytoplasmic ratios in the early embryo.
As human-assisted reproductive technologies are becoming increasingly intrusive -- for example, attempts to rescue bad eggs by cytoplasmic transfer -- it is imperative that we come to grips with the biology of what's going on. Small babies may foreshadow much nastier anomalies, and we now have boys being born with the Y chromosome deletions that caused infertility in their fathers.
We urgently need research in appropriate animal models, particularly primates. Mice are not especially relevant to human embryogenesis.
Jim Cummins
Anatomy, Division of Veterinary and Biomedical Sciences, Murdoch University, Western Australia 6150
 

Manipulating consciousness with advertising strategies e.g. 'biotech' instead of 'genetic engineering'
Ingeborg Woitsch
Translation of an article which appeared in Das Goetheanum - Wochenschrift für Anthroposophie (No. 30, 26 July 1998, pp 441-443)
 
The majority of people at present are against manipulating life. This arises from an assortment of motives: an inner sense; religious conviction; direct personal concern or from the prospect of unpredictable consequences. This strong rejection of genetic engineering (GE), especially with foods, has prompted the European genetic engineering industry to engage the globally active public relations agency, Burson-Marsteller (B-M). This American advertising company is expected to use its resources to bring about public acceptance of genetically modified foods and support for genetic engineering in Europe. B-M's advertising strategy was first used in the preparations for the 'First European Bioindustry Congress' in Amsterdam in 1997, organised by EuropaBio,1 the umbrella organisation of the European genetic engineering industry to which belong, amongst others, Bayer, Hoechst, Monsanto, Hoffmann-La Roche and the food producers Nestlé, Unilever and Danone.
Burson-Marsteller's recent activities unfolded in the background of the Swiss referendum campaign on the genetic security initiative, which on 7 June 1998 was rejected by a majority of 66.6%. For example, here the 'Genetic Protection Initiative' was renamed the 'Genetic Prohibition Initiative' by its opponent organisations such as Gensuisse and Interpharma in consultation with B-M. In fact a large part of Swiss biomedical research would have been affected by the Initiative's proposals. They wanted to ban the production, acquisition and transfer of transgenic animals. Patents would no longer be permitted on genetically modified (GM) plants and animals and their components. All releases of GM plants would have been forbidden. But the scare kept within limits. Christophe Lambs, spokesman for Ares Serrono, the Swiss biotech company, said 'We'll most probably move our laboratories into France, a few kilometres beyond the Swiss border.' And the loss of patenting would have been relatively insignificant for the transnational companies because EU patent rights are assigned at the European Patent Office in Munich. It is estimated that the Genetic Protection Initiative had 5 million Swiss francs at its disposal as against the 35 million, which the chemical and food industry could invest on its lavish publicity for achieving a 'victory for gene research on cancer, Alzheimer's and BSE'.
Presentation replaces reality
There is an awesome logic in that genetic engineering's advance in laying hold of the physical basis of life calls for a few millions worth of know- how for manipulating the basis of consciousness. 'Perceptions are real' says B-M's motto on its home page on the Internet. 2 But these 'perceptions' are intended to divert attention from reality. Here the 'presentation of reality' is supposed to correspond with reality. Following this line, to be truthful it should really say 'presentations are real'. We are dealing with an attempt at constructing reality through emotion provoking language. 'Perceptions are real. They color what we see ... what we believe ... how we behave. They can be managed ... to motivate behavior ... to create positive business results.' It is all a matter, so we are told, of how one looks at a thing.
A B-M internal strategy document that reached the public via Greenpeace, 3 lists four principles as to how the public's attitude to GM foods should be manipulated in favour of the GE lobby:
Stay off the killing fields: Any contentious issues (killing fields) to do with the industry should be avoided. So called 'risk discussions' for instance on ecological or health dangers of GE should not be entered into.
Create positive perceptions: The positive and beneficial characteristics of GM products should be put to the media, e.g. ecological advantages or the creation of jobs. Discussion should centre on the benefits of the product, not the technology itself. 'Producing positive perception' of course depends on appropriate use of the language. Thus the following GE vocabulary is recommended: instead of 'cloning', 'propagating identical offspring'; instead of 'genetically manipulated', 'genetically modified'; instead of 'genetic engineering', 'biotechnology'. Following this linguistic strategy 'harvests are secured with care for the environment' by genetic engineering, 'cultivable areas are extended' and 'unfavourable localities are made useful'. It is better to call experts 'specialists', and corporations sound friendlier as 'enterprises'.
Fight fire with fire: This means that the actual battle is conducted at the emotional level. Critics of GE should be discredited by showing that their rejection of it can be traced to the purely emotional level, for instance to fear. Instead, positive feelings like hope, care and optimism should be evoked in connection with GE. To achieve this powerful symbols will be used because they speak not to logic but to people's feelings.
Create service-based media relations: B-M is developing the following strategy for its customer EuropaBio: 'EuropaBio must turn itself into the best and most reliable source of biotechnology/bioindustries inspiration and information -- the first-stop help-desk where they get not industry propaganda but practical editor-pleasing, deadline-beating connect to interesting stories and personalities -- even adversarial -- relevant to their readerships.' Through such a media service the press should be supplied with purposeful information, above all 'good stories, stories - not issues'. Neither trade nor industry should publish their own statements on GE but let them all pass through the media service. This amounts to a monopoly of information.
Examples of Burson Marsteller projects
BSE
Burson Marsteller has worked for several years in Germany on the BSE issue. It got the contract from the English Meat and Livestock Commission (MLC). The MLC was founded by the British government and had the task during the BSE crisis of 'optimising' the marketing of British meat products. This aim was pursued for specialist groups and consumers under B-M's guidance with the help of market information and scientific publications.
East Timor, Indonesia
At the end of 1991 B-M was hired by the Indonesian government. The firm was supposed to avert the damage to President Suharto's image which threatened his foreign politics after his army carried out the massacre in Dili. Indonesia occupied East Timor in 1975. Amnesty International announced: 'since the invasion about 200,000 inhabitants of East Timor, a third of the original population, have been killed, disappeared or fallen victim to torture...' At the end of 1996, B-M was engaged once again by the government as the leaders of the East Timor opposition, Jose Ramos-Horta and Bishop Carlos Belo, got the Nobel Peace Prize and the Suharto regime was criticised worldwide for the crimes in East Timor.
Bhopal, India
Following an accident at the production plant of the chemical company Union Carbide in 1984 about 2,000 people died and 200,000 were injured. After the catastrophe the Union Carbide leadership got together with representatives of B-M to work out a plan for the ensuing PR strategy.
GE soya, Europe
The export by Monsanto of GM soya was heatedly debated by the European public in autumn 1996. Advised by B-M, Monsanto thereafter set up in Germany and other European countries a 'Soya Information Bureau', which has since become their 'Biotechnology Information Bureau'.
B-M is part of the American advertising company Young & Rubicam, the third biggest in this sector in the USA. Within the organisation, B-M specialises in worldwide 'crisis communication for industry and politics'. B-M is active in over 30 countries and has become known for its aggressive media strategies with politically explosive issues. Whether it is industry or politics, B-M offers appropriate image management advice as a complete PR package with comprehensive strategies and forward planning to its customers amongst whom are authoritarian regimes, chemicals transnationals and British beef exporters.
Disguising the realties by manipulating word usage is of course aimed primarily at the young, the future consumer. The comic strip A little trip through biotechnology financed by Swiss state funds, Nestlé, Monsanto, Roche and Novartis, and distributed free around schools, depicts a little Biotech-Hero extolling the research of the future with carefully picked words.
It is a massive undertaking involving subtly- working, but in the last analysis, primitive means of deception. But with consistent cultivation of one's senses through both devoted responsibility for the word and the power of clear thinking it can be disarmed wherever it is encountered.
1. European Association for Bioindustries (EuropaBio) with its headquarters in Brussels.
2. http://www.bm.com
3. Information: Genetic Engineering Campaign, Greenpeace e.V., D-22745 Hamburg, Germany. Tel. +49 40 30618 386.
 

Transgenic Transgression of Species integrity and Species Boundaries
Mae-Wan Ho
Biology Department, Open University, Walton Hall, Milton Keynes, MK7 6AA, U.K.
tel: 44-1908-653113 fax: 44-1908-654167
Beatrix Tappeser
Oeko-Institute e. V., Institute of Applied Ecology, P.O. Box 6226, D-79038, Freiburg, Germany
fax: 49-761-475437
 
Summary
Biodiversity and species integrity are inextricably linked. Transgenic technology transgresses both species integrity and species boundaries, leading to unexpected, systemic effects on the physiology of the transgenic organisms produced as well as the balanced ecological relationships on which biodiversity depends. Allergenic and toxic products have arisen in transgenic organisms and recent evidence suggests that transgenic resistance to pests and diseases may be associated with increased allergenity. Vectors for multiplying and transferring genes are chimaeric recombinations of parts of different genetic parasites so as to increase their host range, thus allowing them to transgress species barriers. They are now also designed to overcome endogenous cellular mechanisms which help to maintain species integrity. The vectors, carrying transgenes and antibiotic resistance marker genes, form potentially infectious units for further transgressions of species barriers by horizontal gene transfer, i.e., by infection.
Recent evidence also suggests that vectors carrying transgenes may spread horizontally via microorganisms, animals and human beings in an uncontrolled and uncontrollable manner. The teeming microbial populations in the terrestrial and aquatic environments serving as a horizontal gene transfer highway and reservoir, facilitating the multiplication, recombination of vectors and infection of all plant and animals species.
Vector-mediated horizontal gene transfer and recombination have been shown to be responsible for the rapid evolution of multiple antibiotic resistance and for the emergence of new and old pathogens. Horizontal gene transfer can effectively create new LMOs across national boundaries. It is a runaway process that cannot be regulated. This makes it paramount to control what is released in the first place. We shall discuss the implications of the findings for biosafety risk assessment and the biosafety protocol.
Biodiversity and species integrity
Biosafety cannot be considered apart from the biodiversity that we are concerned to protect, nor from the human beings who have actively maintained and generated biodiversity past and present, in the course of making their livelihood. Thus, socioeconomic impacts cannot be excluded from biosafety considerations.
What is biodiversity? It is a dynamically balanced ecology of multiple, interdependent, interconnected species that are nevertheless autonomous and distinct. Each species is a complex developmental system that has evolved in concert with its ecological environment while maintaining its integrity for tens, if not hundreds of millions of years.
This intimate interrelationship between organism and environment is particularly high-lighted by the rapid advances in genetics within the past 20 years, as recombinant DNA technology offers powerful investigative tools. The relevant findings have been extensively reviewed beginning more than 10 years ago (Dover and Flavell, 1982; Pollard, 1984, 1988; Ho, 1987, 1996a, Rennie, 1993, Jablonka and Lamb, 1995) and have been incorporated into our Open University Genetics Course (Ho et al, 1987). They show that genes function in an extremely complex network, such that ultimately, the expression of each gene depends on that of every other. That is why an organism will tend to change in nonlinear, unpredictable ways, even when a single gene is introduced. Furthermore, the genome itself is dynamic and fluid, and engages in feedback interrelationships with the cellular and ecological environment, so that changes can propagate from the environment to give repeatable alterations in the genome (reviewed in Pollard, 1988; Ho, 1987; 1996). Conversely, as demonstrated in current transgenic experiments, introducing a single exotic gene into an organism can impact on the ecological environment. Holmes and Ingham (1994) showed that a common soil bacterium, Klebsiella planticola, engineered to produce ethanol from crop waste, drastically inhibited the growth of wheat seedlings. Similarly, the release of transgenic plants with the Bt insecticide led to the rapid evolution of Bt resistance among major insect pests (Hama et al, 1992; Commandeur and Komen, 1992).
The logical conclusion from all of the findings is that heredity does not reside solely in the constancy of DNA in the genome, but in the complex network of intercommunications extending from the socioecological environment to the genes. It is this complex, entangled network that is responsible, both for the integrity of species and for the maintenance of ecological biodiversity. Unfortunately, current practices of gene biotechnology and biosafety risk assessment are still (mis)guided by the mindset of the old reductionist paradigm in which genes are seen to be stable units, separable from each other and from the environment (see Ho, 1995).
Species integrity and biodiversity are inextricably linked, and that is why current transgenic technology poses such a threat to biodiversity. By its very nature, transgenic technology transgresses species integrity and species boundaries. This is associated with the use of genetic parasites or vectors for multiplying and transferring genes, which are designed to overcome species barriers as well as the cellular defence mechanisms that protect the organism against the invasion of foreign DNA. Let us consider transgenic technology in more detail.
What is transgenic technology?
Transgenic technology bypasses conventional breeding by using artificially constructed parasitic genetic elements as vectors to multiply copies of genes, and in many cases, to carry and smuggle genes into cells which would normally exclude them. (Parasites, by definition, require the host cell's biosynthetic machinery for replication.) Once inside cells, these vectors slot themselves into the host genome. In this way, transgenic organisms are made carrying the desired transgenes. The insertion of foreign genes into the host genome has long been known to have many harmful and fatal effects including cancer (Wahl et al, 1984; see also relevant entries in Kendrew, 1994); and this is borne out by the low success rate of creating desired transgenic organisms. Typically, a large number of cells, eggs or embryos have to be injected or infected with the vector to obtain a few organisms that successfully express the transgene(s).
The most common vectors used in gene biotechnology are a mosaic recombination of natural genetic parasites from different sources, including viruses causing cancers and other diseases in animals and plants, with their pathogenic functions 'crippled', and tagged with one or more antibiotic resistance 'marker' genes, so that cells transformed with the vector can be selected. For example, the vector most widely used in plant genetic engineering is derived from a tumour-inducing plasmid carried by the bacterium Agrobacterium tumefaciens. In animals, vectors are constructed from retroviruses causing cancers and other diseases. Unlike natural parasitic genetic elements which have varying degrees of host specificity, vectors used in genetic engineering are designed to overcome species barriers, and can therefore infect a wide range of species. Thus, a vector currently used in fish has a framework from the Moloney murine leukemic virus, which causes leukemia in mice, but can infect all mammalian cells. It has bits from the Rous Sarcoma virus, causing sarcomas in chickens, and from the vesicular stomatitis virus, causing oral lesions in cattle, horses, pigs and humans (Lin et al, 1994). Genetic engineering is also known as recombinant DNA or rDNA technology, as it uses enzymes to cut and join, and therefore recombine genetic material from different sources. Box 1 summarizes why rDNA technology differs radically from conventional breeding methods.
--------------------------------------------------------------------------------
Box 1. rDNA Technology Differs Radically from Conventional Breeding Techniques
1. rDNA technology recombines genetic material in the laboratory between species that have very little probability of exchanging genes otherwise.
2. While conventional breeding methods shuffle different forms (alleles) of the same genes, rDNA technology enables completely new (exotic) genes to be introduced with unpredictable effects on the physiology and biochemistry of the transgenic organism.
3. Gene multiplications and a high proportion of gene transfers are mediated by vectors which have three undesirable characteristics:
a. Many are derived from disease causing viruses, plasmids and mobile genetic elements - parasitic DNA that have the ability to invade cells and insert themselves into the cell's genome causing genetic damages.
b. They are designed to breakdown species barriers so that they can shuttle genes between a wide range of species. Their wide host range means that they can infect many animals and plants, and in the process pick up genes from viruses of all these species to create new pathogens.
c. They carry genes for antibiotic resistance, which will exacerbate a major public health problem.
--------------------------------------------------------------------------------
The vectors used for transferring genes play the key role in transgressing species integrity and species barriers. We shall deal with each in turn.
Transgressing species integrity results in unpredictable physiological effects
Transgenic vectors themselves can cause severe immune reaction. Direct health hazard from the adenovirus vector, used in attempted gene therapy for Parkinson's disease, Alzheimer's disease and Cystic Fibrosis, has been reported (Coghlan, 1996). It caused such severe immune reaction that one patient almost died. Rats receiving injections of the virus directly into the brain and then into the foot 2 months later developed severe inflammation in the brain. These findings have to be seen in the light that not a single successful gene therapy has been documented. Some geneticists are now looking into even more aggressive gene transfer vectors: the latest one constructed from a disabled AIDS virus (J. Cohen, 1996), even though it has been pointed out that the disabled virus could recombine into a virulent form and cause AIDS.
It is not easy to transfer genes naturally between species, because there are endogenous cellular mechanisms that excise or inactivate foreign genes (Doerfler 1991, 1992). These are also responsible for the instability of transferred genes in transgenic organisms, which is posing a problem for the technology (Finnegan and McElroy, 1994). Vectors are now increasingly engineered to overcome these cellular defence mechanisms (Höfle, 1994), thus further undermine the ability of the species' developmental system to resist invasion by exotic genes carried on such transgenic vectors.
One area of major concern is the allergenicity of transgenic foods, which has become a concrete issue since the discovery of a brazil-nut allergen in a transgenic soybean (Nordlee et al, 1996). Most identified allergens are water-soluble and acid-resistant. Some, such as those derived from soya, peanut and milk, are very heat-stable, and are not degraded during cooking, while fruit-derived allergenic proteins are heat-labile (Lemke and Taylor, 1994). There are also indications that allergenicity in plants is connected to proteins involved in defence against pests and diseases. Thus, transgenic plants engineered for resistance to diseases and pests will have a higher allergenic potential than the unmodified plants (see Franck and Keller, 1995).
Another instructive case is the transgenic yeast engineered for increased glycolytic activity with multiple copies of one of its own genes, which resulted in the accumulation of a metabolite at highly mutagenic levels (Inose and Kousaku, 1995). Thus, even increasing the expression of non-exotic genes can have unpredictable toxic effects. This should serve as a warning against applying the 'familiarity principle' in risk assessment. We simply do not understand the principles of physiological regulation to enable us to categorize, a priori, those genetic modifications that will pose a risk and those that do not. It is a strong argument for the case by case approach.
Current risk assessment of transgenic foods is limited to the characterization of the introduced gene(s) and gene product(s) and known toxins. That is clearly inadequate in view of the nonlinear changes that can arise within the highly interconnected genetic network, which can only be revealed by characterizing the overall profile of expressed proteins and metabolites. Clear labelling of transgenic food products is also an integral part of biosafety so that consumers can avoid known allergens.
Transgressing species barriers
Unintended transboundary movements of LMOs, as everyone knows, can occur by cross-pollination between transgenic crop-plants and its wild relatives (see Meister and Mayer, 1994). Field trials have shown that cross-hybridization has occurred between transgenic Brassica napa and its wild relatives: B. campestris (Jorgensen and Anderson, 1994; Mikkelsen et al, 1996), Hirschfeldia incana (Eber et al, 1994; Darmency 1994) and Raphanus raphanistrum (Eber et al, 1994). Rissler and Mellon (1993) have predicted those problems arising from the introduction of exotic species, whether genetically engineered or not.
A much more insidious, uncontrollable way for the transgenes (and associated marker genes) to spread, which is peculiar to LMOs, is by horizontal gene transfer, i.e., by infection. This process recognizes no species barriers, and is inherent to many current transgenic technologies. It is, to a large extent, why transgenic organisms are different from those obtained by conventional breeding methods.
The vectors for gene transfer are the means whereby the original species barriers are transgressed. They have the potential to infect and transgress further species boundaries in the process of horizontal gene transfer.
Horizontal gene transfer links the whole biosphere
Horizontal gene transfer is the transfer of gene by infection, between species that do not interbreed. It has been known to occur among bacteria and viruses for at least 20 years. There are three different ways for genes to be transferred. Conjugation, the mating process, requires cell to cell contact. Transduction is transfer with the help of viruses, while transformation is the direct uptake of DNA by the bacteria. As mentioned earlier, there are three kinds of genetic parasites - viruses, plasmics and mobile genetic elements. Mosaic recombinations of all classes are made and currently used by genetic engineers to multiply genes or to transfer genes. Viruses are probably the most infectious as they do not require cell to cell contact for infection and can persist in the environment indefinitely. Plasmids and mobile genetic elements are generally exchanged by cell to cell contact during conjugation or when one cell ingests (or phagocytoses) another.
It must be stressed that horizontal gene transfer has mostly been documented with specially designed plasmids in studies carried out in microcosms (Mazodier and Davies, 1991), but the spread of antibiotic resistance markers throughout bacterial communities (see later) shows that it can happen without intentional intervention. The observed correlation between the presence of antibiotics and enhanced gene transfer activities led to the speculation that low concentrations of antibiotics act like pheromones to enhance gene transfer (Davies, 1994). That has particular implications for the secondary mobility of transgenes carried in association with antibiotic resistance marker genes, as the profligate use of antibiotics is allowed to continue.
Like all other species, bacteria possess different 'restriction systeme' which degrade or silence foreign DNA. However, stressful conditions appear to reduce the effectiveness of these systems and to encourage recombination. Starving bacteria are also more competent in taking up isolated DNA. Transgenic plasmids, as mentioned earlier, are designed to overcome these restriction systems as well as to cross species barriers. So they are potentially much more effective in horizontal gene transfer, despite the 'crippling'.
For a long time, it was supposed that horizontal gene transfers did not involve higher organisms, and certainly not organisms like ourselves, because there are genetic barriers between species and genetic parasites are species-specific.
Within the past two to three years, however, the full scope of horizontal gene transfer is slowly coming to light. A search of the isi database conducted under "horizontal gene transfer" came up with 75 references published in mainstream journals between 1993 and 1996, all but 2 giving direct or indirect evidence of horizontal gene transfers. Transfers occur between very different bacteria, between fungi, between bacteria and protozoa, between bacteria and higher plants and animals, between fungi and plants, between insects ... in short, as Stephenson and Warnes (1996) remark, "The threat of horizontal gene transfer from recombinant organisms to indigenous ones is ... very real and mechanisms exist whereby, at least theoretically, any genetically engineered trait can be transferred to any prokaryotic organism and many eukaryotic ones."
The current state of our understanding is presented in Fig. 1 (not shown), where the arrows indicate transfers for which direct or circumstantial evidence already exists. If you follow those arrows, you will realize how a gene transferred to any species in a vector can reach every other species on earth, the microbial/viral pool providing the main genetic thoroughfare and reservoir. Earlier this year, a mobile genetic element, called mariner, first discovered in Drosophila, was found to have jumped into the genomes of primates including humans, where it causes a neurological wasting disease (P. Cohen, 1996). Geneticists suspect the Drosophila gene might have got into a virus which infected the primates.
Although horizontal gene transfers have occurred in our evolutionary past, they were relatively rare events among multicellular plants and animals (and some geneticists have disputed the involvement of horizontal gene transfer in favour of convergent evolution). However, the scope of horizontal gene transfer may have, or will be, increased because the vectors constructed for genetic engineering are chimaeras of many different vectors designed to transgress species integrity and species barriers, and therefore capable of infect many species. In the process, these vectors will recombine with a wide range of natural pathogens. That they have been 'crippled' should not lull us into a false sense of security, because it is well-known that they can be helped by other viruses and mobile genetic elements to jump in and out of genomes. Otherwise, it would have been impossible to construct any transgenic organisms at all.
Vectors mediate horizontal transfer of antibiotic resistance genes
Among the 75 references on horizontal gene transfer are documentations for the rapid spread of antibiotic resistance genes carried on plasmids among bacterial populations (Heaton and Handwerger, 1995; Coffey et al, 1995; Kell et al, 1993; Amabilecuevas and Chicurel, 1993; Bootsma et al, 1996). Multiple antibiotic resistance has spread among pathogens worldwide, and reported to be endemic in many U.K. hospitals. The rapid spread of antibiotic resistance is the result of the indiscriminate use of antibiotics which predates genetic engineering. However, using antibiotic resistance markers in transgenic vectors will exasperate the situation. The transgenic tomatoes currently marketed here and the U.S. both carry genes for kanamycin resistance. Kanamycin is used to treat tuberculosis, which is coming back all over the world, and the TB bacteria are already resistant to many antibiotics (see New Scientist, May 4 issue, 1996). One of the two out of 75 references which reported 'negative' for horizontal gene transfer is a review produced by the staff of Calgene, assuring us that the kanamycin resistance gene used in the Calgene transgenic tomato is safe (Redenbaugh et al, 1994). That study was based, not on empirical data, but on theoretical considerations.
Vectors mediate genetic recombination to generate new pathogens
As pathogens become antibiotic resistant they also exchange and recombine virulence genes by horizontal gene transfer, thereby generating new virulent strains of bacteria and mycoplasm. This has been shown for Vibrio cholerae involved in the new pandemic cholera outbreak in India (Reidl and Mekalanos, 1995; Prager et al, 1995; Bik et al, 1995), Streptococcus (Upton et al, 1996; Kapur et al, 1995; Whatmore et al, 1994, 1995; Schnitzler et al, 1995), involved in the world-wide increase in frequency of severe infections including the epidemic in Tayside Scotland in 1993, and Mycoplasma-genitalium (Reddy et al, 1995), implicated in urethritis, pneumonia, arthritis, and AIDS progression. Many unrelated bacterial pathogens, causing diseases from bubonic plague to tree blight, are now found to share an entire set of genes for invading host cells, which have almost certainly spread by horizontal gene transfer (Barinaga, 1996). Public health is approaching a major crisis everywhere in developed as well as developing countries, as, within the past twenty-five years, at least 30 new infectious diseases have appeared together with the re-emergence of old ones.
The dangers of generating pathogens by vector mobilization and recombination are real. Over a period of ten years, 6 scientists working with the genetic engineering of cancer-related oncogenes at the Pasteur Institutes in France have contracted cancer (reported in New Scientist, June 18 issue, 1987, p. 29).
The natural microbial populations form a major thoroughfare and reservoir for horizontal gene transfer
Horizontal gene transfers have been directly demonstrated between bacteria in the marine environment (Frischer et al, 1994), in the freshwater environment (Ripp et al, 1994) and in the soil (Neilson et al, 1994). It is significant that in all the experiments, horizontal gene transfers were mediated by special hybrid plasmid vectors, of the sort used in transgenic technology.
An obvious route for the vectors containing transgenes in transgenic higher plants and animals as well as microorganisms to spread is via the teeming microbial populations in the soil, where transgenic plants are grown, and in aquatic environments, where transgenic fish and shellfish are currently being developed for marketing. Aquatic environments are known to contain some 108 or more virus particles per millilitre, all capable of transferring genes, of helping endogenous 'crippled' vectors move and recombining with them to generate new viruses. Microbial populations in all environments form large reservoirs supporting the multiplication of the vectors, enabling them to spread to all other species. There will also be opportunity for the genetic elements to recombine with other viruses and bacteria to generate new genetic elements and pathogenic strains of bacteria and viruses, which will, at the same time, be antibiotic resistant.
This route cannot be ignored, as transfers of transgenes and marker genes have been experimentally demonstrated: from transgenic potato to a bacterial pathogen (Schluter et al, 1995), and between transgenic plants and soil fungi (Hoffman et al, 1994). We do not know the precise frequencies for such horizontal gene transfer, as very few studies have been carried out. Similarly, there is very limited published data on the degree of stability of integrated vectors carrying trangenes and antibiotic resistance marker genes. As mentioned earlier, transgenes are often inactivated or 'silenced' by cellular mechanisms that prevent expression of foreign DNA (Finnegan and McElroy, 1994). A substantial degree of transgene instability has been reported for transgenic livestock (Colman,1996) and transgenic plants (see Lee et al, 1995), which includes non-expression of integrated genes as well as loss of integrated genes. This severely compromises the commercial viability of transgenic technology, but raises the important question of how the integrated genes are lost.
Viral resistance transgenes can generate live viruses by recombination
A major class of transgenic plants are now engineered for resistance to viral diseases by incorporating the gene for the virus' coat protein. Viruses are notoriously rapid in their mutation rate. They play a large role in horizontal gene transfer between bacteria (Reidl and Mekalanos, 1995; Ripp et al, 1994) and also exchange genes among themselves thus increasing their host range (Sandmeier, 1994). Molecular geneticists have expressed concerns that transgenic crops engineered to be resistant to viral diseases with genes for viral coat proteins might generate new diseases by several known processes. The first, transcapsidation - has been detected by Creamer and Falk (1990). It involves the DNA/RNA of one virus being wrapped up in the coat protein of another so that viral genes can get into cells which otherwise exclude them. The second, recombination, has been demonstrated in an experiment in which Nicotiana benthamiana plants expressing a segment of a cowpea chlorotic mottle virus (CCMV) gene was inoculated with a mutant CCMV missing that gene (Green and Allison, 1994). The infectious virus was indeed regenerated by recombination. A third possibility is that the transgenic coat protein can help defective viruses multiply by complementation (Osbourn et al, 1990). As plant cells are frequently infected with several viruses, recombination events will occur and new and virulent strains may be generated. Thus, the transboundary movement of the transgene will be disguised by recombination, and can only be traced with the appropriate molecular probes.
In view of the documented occurrence of transcapsidation and recombination, it is important that trial releases should include monitoring for the emergence of new viruses that may pose new threats to crop plants.
Vectors resist breakdown in the gut and can infect mammalian cells
One question which has not yet been addressed in biosafety regulations is the extent to which vector DNA can resist breakdown in the gut and infect the cells of higher organisms. In a study to test for the ability of bacterial viruses and plasmids to infect mammalian cells, it was found that plasmids of E. coli, carrying the complete poliovirus, can be transferred to cultured mammalian cells and the polioviruses recovered from the cells, even though no eukaryotic signals for reading the genes are contained in the plasmid (Heitman and Lopes-Pila, 1993). In the same paper, the authors review experimental observations made since the 1970s that the lambda phage of bacteria, and the baculovirus, supposedly specific for insect cells, are also efficiently taken up by mammalian cells; and in the case of the baculovirus, transported to the cell nucleus. Similarly, E. coli plasmids carrying the complete Simian virus (SV40) genome were also taken up simply by exposing the cell culture to a bacterial suspension. These mammalian cells accept foreign DNA parasites so well because they phagocytose bacteria and viral particles directly. Transgenic medaka and mummichog fish have even been constructed by injecting fish embryos with a bacteriophage fX174 vector carrying an oncogene, which is integrated into the fish chromosome (Winn et al, 1995). The unintended infectivity of transgenic vectors is yet another area that needs urgent investigation.
It has long been assumed that our gut is full of enzymes which can digest DNA. However, genes carried by vectors may be especially resistant to enzyme action, and much more infectious than ordinary bits of DNA. In a study designed to test the survival of viral DNA in the gut, mice were fed DNA from a bacterial virus, and large fragments were found to survive passage through the gut and to enter the bloodstream (Schubbert et al, 1994). Again, more studies of this kind are needed particularly as transgenic foods are already being marketed. Within the gut, vectors carrying antibiotic resistance may also be taken up by the gut bacteria, which would then serve as a mobile reservoir of antibiotic resistance genes for pathogenic bacteria. Horizontal gene transfer between gut bacteria has already been demonstrated in mice and chickens (Doucet-Populaire, 1992; Guillot and Boucard, 1992).
Genes carried by vectors can persist indefinitely in the environment
This subject has been extensively reviewed by Jäger and Tappeser (1996) who showed that genes carried by vectors can survive indefinitely in the environment, in dormant bacteria, or as naked DNA adsorbed to solid particles, where they are efficiently taken up by microbes. In a recent study in Eastern Germany, streptothricin was administered to pigs beginning in 1982. By 1983, plasmids encoding streptothricin resistance was found in the pig gut bacteria. This has spread to the gut bacteria of farm workers and their family members by 1984, and to the general public and pathological strains of bacteria the following year. The antibiotic was withdrawn in 1990. Yet the prevalence of the resistance plasmid has remained high when monitored in 1993 (Tschäpe, 1994), confirming the ability of microbial populations to serve as stable reservoirs for replication, recombination and horizontal gene transfer, in the absence of selective pressure. In a direct test of persistence of streptomycin-resistance, Schrag and Perrot (1996) cultured many independent lines of a streptomycin-resistant mutant of E. coli in the absence of the antibiotic. They found that all retained the resistance after 180 generations. Furthermore, they have also in the mean time, accumulated compensatory mutations in other parts of the genome that increased their competitive ability relative to the wild-type.
Bacteria and viruses can indeed, apparently disappear as they go dormant, and then reappear in a more competitive form. This has been documented for a laboratory strain of E. coli K12, which when introduced into the sewage, went dormant and undetectable for 12 days before reappearing, having acquired a new plasmid for multidrug resistance that enabled it to compete with the naturally occurring bacteria (Tschäpe, 1994). Dormant forms of bacteria and viruses can survive indefinitely as biofilms in the body and in the environment (Costerton et al, 1994; Lewis and Gattie, 1991), when they can accumulate new mutations to come back with a vengeance.
The hazards of transgenic technologies are summarized in Box 2, and the routes for transboundary movements of transgenes and marker genes via vector-mediated horizontal gene transfer in Box 3.
--------------------------------------------------------------------------------
Box 2. Hazards of Transgenic Technologies
1. Toxic or allergenic effects due to transgene products or products from interactions with host genes.
2. Spread of transgenes to related weed species, creating superweeds (e.g. herbicide resistance).
3. Accelerating the evolution of biopesticide resistance in insect pests.
4. Adverse immune reactions caused by gene transfer vectors.
5. Vector - mediated horizontal gene transfer to unrelated species via bacteria and viruses, with the potential of creating many other weed species.
6. Potential for vector-mediated horizontal gene transfer and recombination to create new pathogenic bacteria and viruses.
7. Vector recombination to generate new virulent strains of viruses, especially in transgenic plants engineered for viral resistance with viral genes.
8. Potential for vector mediated spread of antibiotic resistance to bacteria in the environment, exacerbating an existing public health problem.
9. Vector-mediated spread of antibiotic resistance to gut bacteria and to pathogens.
10. Potential of vector-mediated infection of cells after ingestion of transgenic foods, to regenerate disease viruses or insert itself into the cell's genome.
11. The vectors carrying the transgene, unlike chemical pollution, can be perpetuated and amplified given the right environmental conditions. Once let loose, they are impossible to control or recall.
--------------------------------------------------------------------------------
Box 3. Routes for Uncontrollable Transboundary Movements of LMOs Via Vector-mediated Horizontal Gene Transfer
1. Ingestion by insects, and infection via insects, of other plants and animals.
2. Ingestion by birds, and dispersal of seeds and DNA in bird droppings.
3. Release of LMOs in laboratory effluents to the general environment, and further transport by wind and water.
4. Release of vectors carrying transgene and marker genes from dead transgenic organisms, solid wastes and cells and transfer to soil bacteria and fungi where they form a long-term reservoir for replication, recombination and infecting other non LMO crops.
5. Release of vectors carrying transgene and marker genes from dead transgenic organisms, solid wastes and cells in aquatic environments and uptake by microorganisms which form a long term aquatic reservoir for replication and recombination, and also a system for long-distance dispersal.
6. Ingestion by human beings and animals, carried and deposited in sewage system or faeces in other countries.
7. Ingestion by human beings and animals, and infection of gut bacteria, creating mobile long-term enteric reservoirs for replication, recombination and dispersal of vectors.
8. Ingestion by human beings and animals, and potential infection of gut cells, which form temporary storage depots for vectors (as gut cells turnover).
9. Ingestion by human beings and animals, and passage into the bloodstream to other cells, which can form further storage depots for vectors.
--------------------------------------------------------------------------------
Conclusion
According to the 1996 WHO report (see Mihill, 1996), old and new infectious diseases are coming back worldwide within the past twenty-five years, claiming the lives of 50000 men, women and children every day. Antibiotic resistance of the pathogens is identified as a major contributing factor. There is sufficient evidence that horizontal gene transfer is responsible for the emergence of both old and new pathogens, and for the evolution of multiple antibiotic resistance. We certainly do not need any more releases of transgenic organisms that would provide yet more vehicles for horizontal gene transfer. There are obvious gaps in the information required for proper risk assessment which are simply not addressed by the regulating bodies. Despite that, we know that the transboundary movement of transgene and marker genes by horizontal gene transfer cannot be controlled if current transgenic practices are allowed to continue.
Horizontal gene transfer, especially when mediated by transgenic vectors, respects neither species nor national boundaries. As Salyers and Shoemaker (1994) state, "It is probably impossible to eliminate all [horizontal] transfer capacity from a genetically engineered strain that is going to be released into the environment." This makes it paramount to control what is being released in the first place. Once transgenic organisms are released, by intent or by accident, neither they, nor the transgenes can be recalled. That is why adequate monitoring procedures must be put in place which includes tracking horizontal gene transfers at and around the site of release. Deliberate releases, as well as tolerated releases from contained uses, may indeed have unintended transboundary effects, and that must be included for consideration in the biosafety protocol.
Nature is interconnected in such a way that each and every species maintains its own integrity, and that may be the essence of biodiversity. Biodiversity may simply be a state of coherence for the ecological system akin to that which exists for an organism as a whole (see Ho, 1993, 1996b). Gene biotechnology can only be safely practised, if at all, by safe-guarding the coherence of nature's biodiversity.
 
Progress towards complementarity in genetics
Johannes Wirz
Forschungslaboratorium am Goetheanum, Hьgelweg 59, CH-4143 Switzerland
Abstract
The appearance of adaptive mutations in bacteria raises basic questions about the genetic theory of spontaneous mutation and hence the concept of the generation of biological variation. Adaptive mutations were observed in bacteria exposed to selective conditions during the stationery phase of growth in the absence of DNA replication. Both anabolic and catabolic traits were affected. None of the classical explanations, which depend on errors and irregularities during the replication process, is able to account for these mutations. Various observations suggest new mechanisms for the generation of genetic variation. The theory of adaptive mutations paves the way for the introduction of complementarity in modern genetics.
Theories of adaptive mutations elaborated before the era of molecular genetics argue strongly for holistic approaches to life and heredity. They make a revision of the current concepts of reductionist biology necessary. A synthesis is presented that considers the function of spontaneous as well as adaptive mutations in the development and evolution of organisms. Both forms of mutations reflect the fundamental quality inherent among all living beings; i.e. self-relation and world-relation.
Introduction
According to modern theories of heredity and evolution the tremendous variation amongst living organisms comes about in two ways, namely through spontaneous mutation and through chance hybridisation during sexual reproduction. An overwhelming number of publications provides evidence for chance variation. Because of this chance variation and DNA molecular replication (doubling) processes, which produce changes in the genetic make-up, spontaneous mutations pass undisputed as the driving force of variation and thus speciation. According to this view, in a second step, choice or selection determined by the environmental conditions sees to it that only the most fitting forms survive, thus limiting the variation which arises.
In spite of the many confirmations of the theory based on spontaneous mutation this article aims to outline and provide support for another possible theory, one in which the environmental conditions do not merely select, but direct and bring about variation. This is not intended to cast doubt on the reality of spontaneous or chance mutation, but rather to challenge its claim to absolute and exclusive validity.
The current situation in modern genetics is like that which prevailed in physics at the beginning of the 20th century. Just as at that time wave and particle theories of light were shown to be complementary views, it will be demonstrated that the present theory of chance evolution of organisms must be enlarged to include a complementary one, namely directed evolution. The theory of spontaneous mutation is placed beside that of adaptive or selection-induced mutation. Which of the two types of genetic change is realised depends on the physiological circumstances and the environmental conditions. These two types of change require different concepts for describing the relation of organism and environment and are dependent upon different molecular processes. Whether complementarity in genetics will have paradigmatic consequences for the overall understanding of living nature or whether, like complementarity in physics, it remains without effect on a wider public, remains to be seen.
There has been no shortage of attempts to develop concepts of variation other than that of spontaneous mutation. The best known goes back to Lamarck1. His was the first attempt in a modern scientific approach to evolutionary theory to explain how organismic variety arises. Lamarck's idea of inheritance of acquired characteristics, as discussed in more detail by Lefиvre2, formed an important though not central support for the theory. Whether it is justified to treat 'inheritance of acquired characteristics' and 'adaptive mutations' as synonymous is discussed in more detail below. Both Darwin3 and Haeckel4 embedded the inheritance of acquired characters. Because of this, Haeckel's biogenetic law was largely rejected (c.f. De Beer5).
As controversial as adaptive mutation is amongst modern biologists, as certain does its underlying evolutionary principle render service to convinced Darwinists (e.g. Mayr6) as an explanation for cultural evolution. Cultural advance is unthinkable without the passing on of acquired characteristics. Experiences are received inwardly and as capabilities are passed on to others (descendants). This principle is essential to the evolution of human communities. If one asks which quality is fruitful for this kind of evolution, the answer has to be cooperation. But the same question posed of Darwinian evolutionary theory gives competition as its answer. The demonstration of adaptive mutations in modern genetics is a contribution to a new understanding of nature. At the same time it leads to a humanising of natural science in that in this kind of genetic change the central human evolutionary principle finds expression in organic nature.
Spontaneous mutations
To understand the discoveries which have led to the concept of adaptive mutations, it is necessary first to be clear about the premises which gave rise to the theory of spontaneous mutation. This also means dealing with molecular interpretations.
Although genetic research was initially confined to plants and animals, bacteria soon played a significant part in answering the questions which arose. Procedures for producing pure cultures of totally different strains as well as for characterising toxin or viral resistance genes were a precondition for genetic experimentation. The other precondition comes from the bacteria themselves. Short generation times and large cell numbers made experiments possible which with other organisms would have lasted years and taken up a vast amount of space. In addition, as bacteria, having only one chromosome, are haploid, genetic changes usually show up phenotypically immediately after they have occurred.
Despite these advantages interpreting genetic changes proved to be difficult because the results were not reproducible. Whilst it is true that the phenomenon of bacterial virus resistance could be observed on repetition, the number of resistant cells in each replicate experiment exhibited wide variations.
Luria and Delbrьck7, from studies for which they later received a Nobel prize, suspected that it was just this observed variability which might explain how virus resistance comes about in bacteria. They neatly hypothesised that if resistance is acquired by contact with the virus the number of resistant bacterial cells should be proportional to the total number of cells used in the experiment, provided that the probability of cells becoming resistant is the same for all cells. A series of identical parallel experiments would thus allow one to expect a Poisson frequency distribution of resistant cells. But if the mutations occur spontaneously in bacterial cultures before contact with the virus, then the number of resistant cells should be independent of the total number of cells used in the experiment - provided that the mutation event is very rare - and would simply depend on the time elapsed between the appearance of the mutation and contact with the virus. If the mutation occurs long before virus contact, the number of resistant cells will be large. If it occurs only a short time before contact, the number will be correspondingly small. The frequency distribution of resistant cells from parallel experiments is clonally determined. All resistant cells come from one and the same parent cell. Testing the variance or fluctuation can thus allow a conclusion to be drawn as to the kind of mutation which has arisen.
In their experiments Luria and Delbrьck inoculated between ten and twenty tubes containing nutrient broth with 50 to 500 cells of a virus sensitive strain. After a few hours incubation the cell densities rose to about 109 cells/ml. 0.1 ml of each liquid culture was spread on petri dishes containing culture medium treated with a large number of bacterial viruses (ca. 1014). After overnight incubation, resistant cells formed colonies visible to the naked eye. Almost all the bacteria plated-out (ca. 108) were destroyed (lysed) by the virus and died.
In accordance with expectations, the results were unequivocal. The fluctuation in the number of resistant cells in the cultures tested in parallel was very great. In one experimental series there were petri dishes with no colonies and some with more than 500. The distribution of resistant cells clearly showed itself to be clonal. The mutation event most probably must have arisen before virus contact had taken place and must therefore be spontaneous or 'chance'. The virus simply selected the resistant cells.
This result was in total agreement with the hypotheses of Darwinian evolution. The resulting excitement was so great that Delbrьcks warning at a conference in 1947 not to generalise from his discovery went unheard (see Stahl8). After the presentation of a paper by Ryan et al.9, in which it is shown how the number of genetic changes in a metabolic mutant increased in a matter of days, he said 'In the case of mutations of bacteria ... to phage resistance ... the phage does not cause themutations. In your case of mutations permitting the mutants to utilize succinate... as a sole carbon and energy source ... it is an obvious question to ask whether this particular medium had an influence on the mutation rate.... One should keep in mind the possible occurrence of specifically induced adaptive mutations'.
Another milestone in the development of a theory of spontaneous mutation was reached when Lederberg and Lederberg, using their replica-plating method, managed to isolate from a virus-sensitive bacterial strain cells which were resistant to the virus without having come into contact with it10. This showed that resistance mutations arise spontaneously, that is without contact with the selecting agent.
The discovery of the double-helical structure of DNA by Watson and Crick11 and the biochemical investigations of the replication events in the material of inheritance (c.f. Alberts et al.12) made possible an explanation of spontaneous mutation. In principle perfect replication of the material of inheritance is guaranteed by the physico-chemical conditions of its molecular structures. A host of proteins participate in this synthesis and minimise the errors which arise during replication. Such errors can manifest as mutations and are interpreted as the reason why evolution happens at all. It is also clear that the faithfulness of replication of DNA is directly proportional to the size of the genome (the quantity of the substance of inheritance) (c.f. Maynard Smith13). The smaller the genome the higher the mutation rate. Put another way, a text with thousands of words can be transcribed many times without distorting the meaning when one wrong word is substituted in every ten thousand. If errors were to occur with the same frequency in a text with a hundred thousand words, ten words would be altered at each transcription. With frequent transcription, distortion of the meaning could not be ruled out. To avoid unacceptable changes, the transcription accuracy would have to be increased.
If during replication of the material of inheritance the mutation rate is too high it could have catastrophic consequences for the organism concerned. But if DNA replication were absolutely perfect, undirected 'chance' evolution of living organisms would be rendered impossible. Spontaneous mutations are an essential component or instrument of the evolution of all living beings on earth. Such mutations are not determined by environmental conditions but arise mainly through replication of the material of inheritance.
Adaptive mutations: the concept clarified
In order to deal properly with adaptive mutations it is necessary first to clarify a misunderstanding and a conceptual confusion. Equating the concepts 'inheritance of acquired characteristics' and 'adaptive mutations' is often criticised (c.f. Lenski et al.14). The first explicitly emphasises the fact that characteristics must first be formed before they can be passed on. But the second concept implies that known mutations are seen to revert to the wild type. After a reversion event the cells concerned exhibit characteristics that were shown by their ancestors prior to the mutation. Reversions provide modern genetics with a tool that allows phenotype and genotype to be kept equally in view. I will use the two expressions 'inheritance of acquired characteristics' and 'adaptive mutations' synonymously, because in both cases it is true to say that there must be an effect on the material of inheritance directed from the environment and the living organism. Furthermore, new characteristics that must be inherited can manifest only through modification of already existing heritable material.
Another difficulty concerns the view that the theory of adaptive mutations is 'Lamarckian' (c.f. Marx15, Symonds16, Mayr6 ). There are several objections to this. As already mentioned Darwin and Haeckel include the inheritance of acquired characteristics in their theories, although they have both expressly countered Lamarck's teleological evolutionary theory. The term 'adaptive mutations' expresses the fact that the constraints of life and the environmental conditions not only work selectively on preformed characteristics, but also can determinenew ones. Such characteristics can be described as 'goal-directed' without, like Lamarck, presupposing an evolutionary goal. Even Darwin3 coined an expression for this: 'Effects of habit and the use or disuse of parts'.
Early supporters of the theory of adaptive mutations
Since Mendel, adaptive mutations became a topic of increasing interest and was described in reputable journals. One of the most outspoken representatives of the theory was Kammerer. On one of his trips to the USA he was even heralded by the newspapers as the 'new Darwin' (Koestler18). In many publications and using a wide variety of animals he sought to demonstrate the existence of the inheritance of acquired characteristics (c.f. Kammerer19,20). He described them for the midwife toad Alytes obstetricans. By raising the temperature of its surroundings the animal can be made to depart from its usual behaviour of reproducing in water. Under the new conditions the male forms 'nuptial pads'. These thumb-like structures occur on the forelimbs of many amphibians that reproduce under water. It is thought that they help the males get a better hold during copulation. After copulation on land, the male carries the strands of spawn containing the fertilised eggs around with him wrapped round the hind leg until the larvae hatch. Under the new conditions the spawn remains in water. The tadpoles which have undergone their embryonic development in water exhibit external gills similar to the larvae of other toads and frogs.
Both nuptial pads and external gills can be regarded as an expression of an adaptation to the new conditions. Both features also appear in subsequent generations even when the animals are returned to normal living conditions. They appear to be genetically fixed.
More convincing were the experiments with the sea squirt (ascidian), Ciona intestinalis. Kammerer described them as providing the most significant evidence for adaptive mutations. After repeated amputation of the terminal tubes which are used for feeding and excretion, these organs grow extremely long. Specimens with long tubes give rise to long-tubed offspring thus giving rise to the supposition that inheritance of acquired characteristics is involved. To exclude the possibility of prior chance mutation causing the long tubes, Kammerer removed the gonads. After regeneration of these organs long-tubed specimens once again developed out of the newly formed germ cells. Thus it seemed that clear evidence for acquired characteristics had been obtained.
Kammerer's experiments are clearly described and from their methodical structure withstand critical appraisal today. Nevertheless alternative explanations such as cytoplasmic or maternal effects that could bring about developmental modifications without changing the DNA would nowadays have to be excluded. In view of the tragic circumstances of Kammerer's death, which is interpreted as admission of his scientific fraud, Koestler18 emphasised the need for a repeat of these experiments.
In Russia, Mitschurin (see Sankjewitsch21), using the most varied cultivars investigated the questions of environmental influence on seeds and rootstock on fruit. He too observed environmental influences which were genetically fixed. But his work fell into disrepute and oblivion probably through the political polemic from and surrounding Lysenko and his unsuccessful wheat vernalization experiments.
Waddington22 and Piaget23 reported theoretical considerations, suggestions and descriptions regarding experiments on adaptive mutations which will be discussed below. At the level of molecular genetics, the phenomenon of adaptive mutations has been reported for flax (Marx15, Cullis24).
Adaptive mutations since 1988
The publication of evidence for adaptive mutations by Cairns et al.25 brought about a change. The standing of both the author, as former director of the respected Cold Spring Harbour Laboratory, together with that of the journal Nature in which the work was published, left littledoubt as to the scientific quality of the work and sparked-off discussion and controversy which has lasted to this day. Many 'main stream' geneticists felt obliged to take positions and carry out further experiments. Since then there have been a considerable number of publications describing adaptive mutations for various microorganisms and cellular anabolic and catabolic processes. Furthermore some authors tend to the view that this form of inheritance also plays a part in tumour formation (for reviews see Foster 26,27).
Cairns' group investigated the frequency of reversion of a well known and genetically characterised metabolic mutant lac in E.coli. Cells with this mutation can no longer use lactose and are dependent for their growth on glucose or another sugar in the growth medium. The reversion of the mutation to lac+ can easily be demonstrated by plating out the cells onto a medium containing lactose and a colour indicator. Revertant cells form red colonies.
In an experimental design based on that of Luria and Delbrьck7, analysis of the frequency distribution of sixty cultures prepared in parallel showed that spontaneous reversions must have taken place before selection. However, others appeared to have occurred adaptively only after contact with lactose the selecting agent. Further observations showed that the number of reversions increased when the petri dishes containing lac- bacteria were incubated for several more days. Obviously in the course of time more revertants were generated. Control experiments showed that reversions only occurred when the growth medium contained lactose. If this sugar was missing, or only sprayed on the bacteria after one or more days, the number of lac+ colonies remained unchanged with longer incubation. Finally, it was shown that with mutations such as valR, which are not selectable, no reversions occurred. Increase in the reversion rate only resulted when it was 'useful' for the multiplication and growth of bacteria. They were without doubt adaptive, or, as Cairns' group put it, directed.
The results stood in contradiction to the theory of spontaneous mutations. The reversions occurred only during selection and in appropriate environmental conditions. Lactose had to be present. The medium appeared to 'entice' out the reversions. Particularly noteworthy is the fact that they only took place during the stationary phase when DNA replication errors cannot occur. None of these observations were new. In 1961 Ryan's group had already published work suggesting mutation events without replication (Ryan et al.9 and Symonds28), but this received little attention amongst geneticists. The Cairns' group managed only to publish once more in their entirety the most important observations evidencing non-spontaneous mutations.
The Cairns work is also noteworthy for another reason. Since 1943 bacterial genetics has concerned itself with cells in the exponential growth phase and investigated many phenomena which determine the life and death of bacteria. But adaptive mutations occur only when cells are not dividing and even then only when the genetic change is choosing between growth/division or rest. For this reason it is possible to speculate as to the significance of adaptive mutations for natural conditions. From the still young science of the genetics of the stationary phase, there are reports, which suggest that adaptive mutations occur also under natural conditions (Kolter29).
Hall's work
Adaptive mutation research was greatly extended in variety and scale by Hall, a microbiologist based in Rochester (USA). Working intensively with the conceptual problems of the new theory, he investigated several organisms and catabolic processes as part of his interest in reversions of point mutations (substitution of individual base pairs) and deletions. The conclusions he drew from this were uncertain and provisional. Where observed changes were at first adaptive (Hall30), they later were explained as spontaneous (Hall31,32), or occasionally in the following paradoxical way 'Spontaneous point mutations that occur moreoften when advantageous than when neutral' (Hall31). These he called 'selection induced mutations' in a later publication (Hall33), and he ultimately reached the conclusion that there is indeed a phenomenon of adaptive mutation, but there is no explanation for it (Hall34).
Hall's initial work was on the double mutation in the bgl operon in E.coli (Hall30). This operon codes for the necessary enzymes for the catabolism of glucosides. The individual reversion rates experimentally determined for the two mutants is 4x10-8 and <2x10-12 per cell division. Assuming that the two mutations are independent from one another, in bacterial strains with both mutations the reversion rate, given by the product of the two individual reversion rates, is 8x10-20. Such an event would never be observable under experimental conditions because at least 8x1020 cells would need testing, thus requiring at least 100,000 litres of liquid culture. Bacteria incubated for two to three weeks in petri dishes formed colonies of revertant cells able to catabolize glucosides. The reversion rate of was 2x10-8, far higher than expected. Here too reversion managed to take place in the stationary phase and only when glucosides were present in the medium.
Further work investigated point mutation behaviour in the tryptophan operon in E.coli (Hall31,33,35). Once again the reversion rate was far higher than was expected on the basis of spontaneous mutation and appeared under conditions of selection. The author also demonstrated that reversion was independent of DNA replication and increased according to the length of time cells were in contact with the selective substrate. Control experiments ruled out the possibility that cryptic growth of cells or retarded division of preexisting revertants determined the reversions. Experiments with baker's yeast Saccharomyces cerevisiae (Hall36) showed that adaptive mutations can also be demonstrated for eukaryotes.
Objections and attempts at a molecular explanation
Critical and partially justified objections to the idea of the existence of adaptive mutations were not slow in appearing. Several experiments were repeated with more stringent controls. The mobilisation of the bacterial virus Mu which the Cairns group25 observed and interpreted as a directed mutation proved to be a spontaneous mutation (Mittler and Lenski37). The high reversion rate which Hall30 had observed with double mutants was explicable in terms of the growth of intermediary genotypes (Mittler and Lenski). Finally it was shown that the difference in reversion rates between two independent mutations (Cairns et al.25) could be ascribed to known physiological processes (MacPhee39).
The criticism had the result that in subsequent work the necessary control experiments were carried out. Thus in his investigation of the reversion of mutations in the tryptophan operon Hall34,35,36 was able to rule out that adaptive effects were arising through intermediary growth or death of cells. Both possibilities would have given a deceptive nominal increase in the mutation rate thus allowing spontaneous mutations to appear as adaptive events (Mittler & Lenski40). The criticism as to the reality of adaptive mutations eventually led to their experimentally verified acceptance.
Still unsolved was the question of how adaptive mutations could occur. The search for an explanation based on the underlying molecular processes was linked to the hope that phenomena which would not fit in could nevertheless eventually be interpreted 'classically'. The lynch pin in the structure of modern genetics is still its central dogma which states that 'information' flows only from the material of inheritance to the protein (DNA>RNA>protein). This underpins the idea that heritable changes are never determined by protein. The phenotype has no influence on the genotype. Since the discovery of retroviruses, whose viral RNA chromosome after successful infection is transcribed into DNA, the dogma is only partly valid. Adaptive mutations now threaten to overthrow it completely.
To explain adaptive mutations, various working hypotheses were formulated (summarised in Koch41) which, under selective conditions and with known molecular mechanisms would have allowed a raised mutation rate to be assumed. The postulates of three most important hypotheses are stated here.
Hypermutability: The basic mutation rate in bacteria under stress conditions is significantly raised (Symonds42, Hall31) and that amongst many chance mutations some also occur which are selected.
Increase in the mutation rate through reverse transcription (Stahl43): In cells in the stationary phase there are always transcription processes going on, i.e. DNA is transcribed to RNA. It is known that in these processes the transcription accuracy is relatively small and thus the mutation rate is increased. RNA molecules arising in this way which enable the synthesis of a protein necessary for growth can, after being changed to DNA, replace the original chromosomal sequences.
Slow repair (Stahl43): Under stationary phase conditions small pieces of DNA are broken down and resynthesised. The repair mechanisms which normally replace wrongly inserted nucleotides are not active.
All hypotheses were experimentally tested and had to be rejected. With hypermutability the frequency of the adaptive reversions in the trp operon signified a mutation rate of 0.04 per base pair (Hall32). Thus on average every 25th base pair would have to be substituted. Such a high rate would without doubt have been lethal for the bacteria. Hall investigated the relevant gene locus by sequencing to determine whether, in the neighbourhood of the necessary reversion, other substitutions had taken place. But he was without success. Such a 'directed' localised increase in the mutation rate would however have only postponed the crisis of finding an explanation.
The second hypothesis also had to be rejected (Hall31) because with some bacterial strains which exhibit adaptive mutations no reverse transcriptase activity has so far been demonstrated.
The slow repair hypothesis failed because as well as the expected selective mutations, independent mutation events in other genes would also have had to occur (Hall32). In no case could these be detected.
That the molecular basis of adaptive mutations is of a non-classical kind was revealed by a series of unexpected results, which, however, in retrospect an unprejudiced observer would hardly wonder at. Adaptive mutations always appear in the bacterial stationary phase. DNA turnover is minimal. Mutation events are time dependent. But spontaneous mutations occur by maximal DNA turnover in the phase of exponential growth and are dependent on replication.
A first indication of the difference at the molecular level in the occurrence of the two types of mutation was given by the analysis of the spectrum of reversions under selective (adaptive) and non-selective (spontaneous) conditions (Hall44). Thirteen strains with different mutations in the same gene (lac) were used to compare reversion rates during exponential growth with those during the stationary phase. The rates were as much distinguished by the two culture conditions as by the individual strains. Base pair substitutions, insertions and deletions are dependent on the physiological state of cells and the type of change in the environment.
Unlike spontaneous mutations, adaptive mutations are dependent upon various components of the recombination system (RecA, RecBCD, Harris et al.45). Under normal conditions, this system mediates homologous recombination between chromosomes and enables insertions and deletions of DNA sequences in the bacterial chromosome. If the proteins of the RecBCD system are lacking, adaptive mutations no longer take place. These findings have been described as progress towards the understanding of genetic intelligence (Thaler46).
Another piece in the jigsaw was the discovery that not only the recombination system but also intercellular DNA transduction, the transfer of genetic material during bacterial conjugation (a kind of primitive sexual pairing), participates in the appearance of adaptivemutations.
Conjugation proved significant is several ways: for bacterial strains which had the selective gene on the chromosome rather than on the transduction plasmid, the reversion rate was 25 to 50 times smaller (Radicella et al.47, Galatski & Roth48). Removal of the conjugation apparatus with detergents or additional mutations in the enzymes of the transfer function reduced the adaptive mutation rate to the same extent.
According to Shapiro49, these results have far reaching consequences for evolutionary theory, although he also holds that they make the hypothesis of 'directed mutation' superfluous. The transfer of the transduction plasmid is dependent on DNA replication, which is why mutations associated with chromosomal replication can occur by 'chance'. Even so the results show that the rate of meaningful mutations can be significantly increased by selection and that by transduction, which can be regarded as a primitive form of intercellular communication, meaningful mutations can be passed on. Recombination and plasmid transfer are cellular functions which allow an active reaction to its environmental conditions. A significant component of genetic variation is without doubt no longer attributable solely to chance events in the replication of the material of inheritance, but can only be understood by considering the relationships between living organism and the world in which it lives.
Non-molecular concepts of adaptive mutation
I hope to have shown in the foregoing that modern genetics has reached a turning point. But true insight as to the significance of adaptive mutations cannot be gained through describing molecular processes. This is because, by reducing the phenomena to molecular processes, the fundamental and qualitative differences between spontaneous and adaptive forms of inheritance are overlooked. The description gets lost in detailing DNA-protein interactions. But the differences lie in the possibility of manifesting in the most varied of ways relationships and interconnections between organism and environment and of making these available to the next generation. They are of course dependent on molecular processes, but they are not determined by them. Thus molecular genetics points to the necessity of looking beyond its current paradigm for alternative concepts and approaches to organisms and their inheritance. Paradoxically this leads first to the rediscovery of theoretical foundations which have been forgotten. I shall illustrate this with reference to the work of three individuals.
I turn first to a pamphlet essay by Steiner50. In it the 'inheritance of acquired characteristics' is seen as a consequence of Haeckel's biogenetic law. Steiner emphasises that without this law a monist evolutionary theory has no validity. The essay is in essence against the last vestiges of vitalism and the preformation theory associated with Weismann.
Monistic evolutionary theory signified a big challenge to understand 'being' and 'appearance', requiring one to grasp the organic as a process which takes place as much from top downwards (from idea to world of the senses) as from bottom upwards. In this process both aspects - the ideal in the type at work in the organism and the real as its appearance in the world of the senses - undergo changes and metamorphoses in reciprocal interdependence.
These ideas are substantially developed in an earlier essay by Steiner51 in which the relationship of the Goethean idea of type (archetype) to the organism which actually manifests is clarified and discussed. It is the essence of all living organisms that they respond inwardly to the experiences they undergo in their development and thus eventually pass them on to their offspring.
Waddington22 offered a further theoretical principle. According to him there are two distinct possibilities for genetic variation. One concerns isolated features which are altered accidentally. Industrial melanism in the peppered moth Biston betularia is a textbook example of this and for modern evolutionary biology provides irrefutable evidence for theoccurrence of spontaneous mutation. The other possibility for genetic variation concerns features which are embedded in the totality of the organism and its environment. Waddington's example for this is the forequarters of the gibbon and pangolin (scaly ant-eater): the gibbon's forelimbs point in their slenderness, length and exceptional mobility to activities such as climbing and hanging, whereas the form of forelimbs of the scaly ant eater exhibit rigidity, shortness and compactness of bone formation which are easily comprehensible in terms of a digging function. Both animals reproduce in their entire bodily make up the specific orientation of their different activities and modes of behaviour. The logical construction of the entire form is unmistakable. According to Waddington it is extremely unlikely that the extremities have come about by a large number of accidental individual changes. It seems more plausible that they were formed through the specific behaviour of the animal in its respective habitat during the course of the evolution of the species.
Waddington used Drosophila experiments to develop the concept of organismic totality and adaptive reaction to specific qualities in the surroundings. He described short term physiological changes that had become genetically fixed 'genetic assimilation'. Such changes as take place over a long period, he described as 'evolutionary adaptation'.
Piaget23, the Swiss developmental psychologist, provides a third fundamental consideration. The idea of adaptive mutations was a logical outcome of his investigations into cognitive processes and their biological basis. It is an undoubted fact that the human being gains knowledge by constantly taking in experiences and as a result of this process is able to pass on faculties. According to Piaget the act of cognition is only possible through (subjective) receptivity and (objective) external stimulus. It produces a relationship between object and subject. Thoughts are contoured by percepts and determine our intentions. Intentionality fixes what is extracted from the sense perceptible world and determines the framework of elements of observation. As zoologist, I look primarily at animals and through an interest in morphology further restrict observations to their form.
Both aspects, thinking and perceiving, reciprocally determine and alter one another. Because cognitive processes have and must have a biological basis, this in turn must have a functional structure like the cognitive process itself. Organic regulatory processes follow the same laws as those of cognition: they undergo adaptive change and development, not only physiologically but also genetically. Piaget's morphological investigations of the water snail (Lymnaea stagnalis L.) in a wide range of habitats appeared to confirm the hypothesis of adaptive mutation.
The discussion of these three authors provides more than a foundation for a theory of adaptive mutation. All three overcome the materialistic tendency in the modern view of heredity. With Steiner, the overcoming is quite explicit. Development and heredity can only be grasped through a combination of sensory and supersensible processes. All living organisms are an expression and result of ideal-material processes. The unity of matter and spirit is the basis of Steiner's monist evolutionary theory.
With Waddington the overthrow of the materialistic view of heredity is reflected in the idea of organismic wholeness, which is not to be thought of as solely material. Relationships and interactions with the environment belong just as much to the organism as to its organs, cells and molecules. The basis of his evolutionary theory is unified life of organism and surroundings.
Finally, Piaget postulates unity of cognitive and living processes. As psychologist he did not doubt the former, nor as biologist the latter. One could describe his theory of development as a monism of the soul, keeping consciousness and body together.
Complementary genetics and enlivening of the concept of heredity
To quote Steiner: 'the essence of monism is the idea that all occurrences in the world, from the simplest mechanical ones to thehighest human intellectual creations, evolve themselves naturally in the same sense, and that everything which is required for the explanation of appearances, must be sought within that same world.' In relation to adaptive mutation, this view means, as we have seen, that genetic changes must be understood as an expression of an interrelationship between living organism and its habitat. Steiner, Waddington and Piaget have shown approaches to such an understanding. Bockemьhl's work on groundsel Senecio vulgaris provides striking examples of such an understanding.
Spontaneous mutations also have a part to play in a monist evolutionary theory. They show that genetic changes can also occur in the relation of the organism to itself. They are complementary to adaptive mutations. The polarity of world relation and self relation and its overcoming through the organism itself are hallmarks of the living. I have attempted to elaborate this in studies on developmental processes in amphibians. Similar polarities have come to light in other studies (Pankow et al., Schad, Suchantke). Spontaneous and adaptive mutations are not causes of the variation in form and function, but results of a variety of organic processes. These thoughts will be extended in a further article. Furthermore, I shall report on experiments investigating the existence of adaptive mutations in Drosophila.
   
Reductionism and Organicism in Science
by Henk Verhoog
 
Faculteit der Wiskunde en Natuurwetenschappen
Instituut voor Evolutionaire en Ecologische Wetenschappen
Rijks Universiteit Leiden
Kaiserstraat 63
Postbus 9516 2300 RA Leiden, Netherlands
NOTE FROM TRANSLATOR: The following text is a translation by Dr. David Heaf of Chapter 2 of "Genmanipulation an Pflanze, Tier und Mensch - Grundlagen zur Urteilsbildung" published by Verlag Freies Geistesleben, Stuttgart (1994, ISBN 3-7725-1449-9, pp 11-22) which is an edited translation from the Dutch original entitled "Zit er toekomst in ons DNA?" published by Werkgroep Genenmanipulatie en Oordeelsvormung, Louis Bolk Instituut, Hoofdstraat 24, 3972 LA Driebergen, Holland (1993, ISBN 90 74021 12 3).
 
The major question facing all biologists at some time or other is the question of the secrets of life. People try to escape it by saying that all questions as to life's meaning or what it actually is cannot be answered by science. Science should only concern itself with the phenomena of life. Questions as to what something means or is are metaphysical and go beyond the realm of scientifically observable physical phenomena. If you ask philosophers for an answer to the question of life, it is soon apparent that since the breakthrough of natural scientific thinking in the life sciences, metaphysics or natural philosophy have been increasingly thrust into the background. If such subjects make any contribution, it is at most an attempt to bring about a synthesis of the results of scientific research, rather than any independent method for studying Nature.
However, as a result of the world environmental crisis, there has already been a drastic change in interest in natural philosophy. In books on environmental philosophy and ethics one frequently comes across suggestions that the concept of Nature underlying science is partly responsible for the present crisis in our relationship with Nature. In genetic engineering too, problems are not caused by faulty methods, but by a particular mind set. Put another way, science is not neutral when it comes to natural philosophy, but is itself based on metaphysical foundations having a lot to do with materialism and reductionism. These foundations are revealed as soon as scientists claim to be able to say something about reality, for instance when it is said that the secret of life is to be found in DNA. The history of biology is characterised by opposites - mechanism v. vitalism, reductionism v. organicism - opposites which exist to this day.
Reductionist thinking means investigating living phenomena by 'objectifying' them (I shall come back to this later) and separating them into their component aspects and processes for analysis. This happens above all in the laboratory where it is the researcher who creates and varies the conditions under which the phenomenon is to be investigated. Under laboratory conditions living processes are reproducible, controllable and predictable. The 'objectivity' of scientific facts is a result of this.
We can venture that, within certain limits, 'facts' are constructed in the laboratory. Some philosophers even speak of a 'secondary Nature' arising. If we accept that all knowledge is the result of observation and thinking, we can say of the reductionist tendency that abstract, model-based thinking plays an increasing part at the expense of observation. For instance, in modern physics, direct perception plays an almost insignificant part. This process of bstraction is supported to a significant degree by mathematics.
Organicism
Organicism takes an opposite course. The tendency to analyse is controlled and attention is directed to the wholeness of organisms and living processes and to the place or function of structures and functions in the wider context, for instance in morphology or the theory of form, in ethology or behavioural science and in ecology or the science of living communities. The object of research is usually Nature as she appears to us by direct experience. Nature as 'given' is investigated in her own right. Here, in contrast with the reductionist's approach, direct observation plays a more important part in relation to thinking. Closely related with the concept 'organic' are those of 'holistic' and 'phenomenological'. In the genetic engineering debate it is sometimes suggested that the reductionism-organicism contrast is no longer relevant (1). Nevertheless, there are countless examples to the contrary. For example, the contrast becomes most marked in the arguments between biotechnologists and ecologists over the risks connected with releasing genetically modified organisms into the environment. Furthermore, features of the value systems of both approaches are also to be found in the debate about combining DNA from various plants and animals (2). The supporters take a strongly anthropocentric position by laying emphasis on possible uses for mankind. Highest value is accorded to the freedom of research and progress of science. The right to manipulate life processes is regarded as self-evident, especially if the results are useful to Man. In contrast, opponents of genetic engineering, as well as feeling a moral responsibility for their fellow human beings and future generations, lay great emphasis on their responsibility for life on earth. Of significance here is the holistic world view which is critical of the kind of science that tinkers with life. Such a view also argues for a 'science of phenomena' in the sense of organicism.
Ernst Mayr says in his book The growth of biological thought that when looking for a solution to a problem in modern biology, a historical approach is sometimes more helpful than a logical one, especially when the development of a theme is traced over time (3). We argue that this is also true for a better understanding of inheritance and genetic manipulation. The ahistoric attitude of current science veils the fact that then as now decisions have been taken which have far reaching consequences for the world we share with one another and with other kingdoms of Nature. What we at any particular time regard as scientific, is itself one of these decisions.
Nowadays thinking about the phenomena of life is dominated by reductionism. In social practice, the reductionist tendency is closely linked to the existing power structure which is glad to make use of the obvious possibility of controlling Nature. As reductionism has the upper hand, many alternative ways of looking at things (mostly organic) are excluded. 'Hard' scientists thus disqualify the alternative views as 'unscientific', as obstacles on the way to what they regard as true insight.
Nevertheless, if reductionism is not to be regarded as the only way to truth, society can no longer place exclusive reliance on it when it comes to taking important decisions such as those concerning the development and application of genetic engineering. To develop a more complete picture and opinion of the problem of genetic engineering, non-reductionist views are at least as important as those of reductionism. The former were in earlier times frequently described as 'Reading in the book of Nature'. The anthroposophical approach also falls into this category.
The Book of Nature
In a now famous article on the origins of the modern environmental crisis, Lynn White concludes that the 'desecration of Nature' must be seen as primarily caused by Judeo-Christian thought (4). For ancient cultures, even in the early stages of Greek civilisation, Nature was the 'theatre of the Gods'. The Gods were active in Nature and everything observed in Nature was seen as the result of their work. In western Christian tradition, Nature is much more regarded as the result of God's Creation. God stands above nature (transcendent), and Man, as steward of the earth, is accountable to God. More recently, many people no longer hold valid the 'God hypothesis' for explaining Nature. Man is completely self-sufficient.
Critics of Lynn White have shown that there is rarely a directly demonstrable connection between ideas of Nature and what is done in practice and that even in Christianity there is a greater variety of ideas of Nature than White claims. For instance, in the Middle Ages, Nature was described as a book. The Apostle Paul spoke of the three revelations of God: To the Jews God was revealed through the commandments and through the prophets; to Christians through the Bible to heathens through the Creation of the world (5). After Paul, we come to Augustine who spoke of God's authorship of two books, the Bible and the book of Nature.
Raimund Sabundus (6) opposed the idea that god was revealed to the heathen only in the book of Nature. The book of Nature has been a gift to mankind since the Creation. Every creature is a letter in the book written by the hand of God. Only when Man could no longer read the book of Nature did God give him the Bible. Sabundus sees this as a loss to man and shows how man can again learn how to read the book of Nature.
The idea of Nature as a book, in addition to indicating that God is the 'Author', contains two other important elements. Firstly, what is observed (letters, natural phenomena) must have a deeper significance. This is clear in the 'doctrine of signatures' of people such as Paracelsus and Jacob Böhme (7). Signatures, for instance the perceptible symptoms of a disease, are the visible signs, which one must learn to interpret as an expression of something deeper. According to Böhme it is a matter of getting to know the essence of the thing through its signature. This is possible if one 'looks into the heart of things'.
Secondly, Man must have the possibility to get to know the deeper significance of what is referred to. Mankind is capable of this because a deep relationship exists between Man and Nature. Both are created by God. What happens in Nature concerns mankind itself. It gives mankind's existence a meaning. One can also say that Man can be regarded as the microcosm in which Nature as macrocosm is reflected. 'Reading' involves empathising and feeling at one with Nature. That is to say it requires an attitude of sympathy (8). Sabundus says that people can again read the book of Nature by distilling out the Divine Wisdom inscribed in the bodily form of God's creatures and recreate them in the human soul through imagination. This can be achieved by comparing one creature with another. This comes very close to what Goethe later developed as his comparative method, based on exact sensorial imagination. From such a combination 'the real significance leaps out'.
Reading in the book of Nature is based on the idea that Nature, as God's Creation, is a harmonious, self-regulating and purposeful totality before which Man is mindful of respect. In the later Middle Ages, a different picture of nature gained predominance which can be described as the model of 'fallen Nature' (9), as the mirror of the Fall of Man through original sin. This makes Nature into something negative. We talk of natural forces which must be ordered and controlled by mankind (human intellect). This strong emphasis on letting the human intellect guide our intervention in Nature is characteristic of all founders of modern science.
 
Galileo and Mathematical Symbols
Konrad von Megenburg's The book of Nature, which reached six editions after its first appearance in 1350, was described by Bohler (10) as a phenomenological work in the Aristotelian tradition of an organic conception of Nature. Along with investigators such as Vesalius and Harvey it was above all Galileo, Descartes and Bacon who fathered modern science. In the 16th century people paid little heed to the Aristotelian tradition. Paracelsus, one of its last representatives, drew attention to the crucial difference between a printed book with abstract, lifeless letters and the book of Nature with its living script. As a contrast to Paracelsus, Galileo, at the threshold of modern natural science, said that the book of Nature should be read as if it were written with abstract, lifeless characters.
Following Cusanus, Galileo conceived God the Creator as a technologist, who had written the book of Nature in mathematical symbols. The letters became triangles, circles and other geometrical figures. This freed reading in the book of Nature from direct observation and the experiences which go with direct observation. In order to read it thus, people have inwardly to distance themselves from Nature and become 'onlookers'. They become a perceiving and thinking subject confronting Nature as a material object. Such 'objectifying' Nature is characteristic of the scientific revolution which took place throughout the 16th and 17th centuries.
This objectifying is recognisable for example in Descartes' famous distinction between Res cogitans and Res extensa, between subject and object. The world of the human subject, equated with thinking, is confronted with the world of extension, as if two mutually exclusive worlds are involved. According to Descartes (and Bacon), using concepts that depended on the human subject, such as consciousness, purposefulness and freedom, to describe the world of extension was not allowed.
The world of material objects was seen as determined and functioning according to mechanistic principles. From Aristotle's 'four causes', which explain why everything is as it is, only causa efficiens and causa materialis were allowed. Causa formalis and causa finalis (purpose) were eradicated. Descartes' methodological maxim that every problem should be analyzed into its greatest number of parts fitted well a view of Nature as a material world of extension, or a machine.
Bacon, especially, campaigned against the 'speculative thinking' of the Middle Ages. Although he is described as the father of empiricism, he was suspicious of direct perception by the senses. This had to be replaced with observation by means of precise instruments.
This is partly connected with the distinction between primary and secondary qualities that arose around about this time. Primary qualities are objective properties of the world of extension that can be measured and expressed mathematically. Galileo held that only what is measurable is valid. Primary qualities stand in contrast to 'subjective' secondary qualities like the visible colours. This view holds that colours are not properties of the reality of the physical world but arise only indirectly through the senses and nervous system.
In short it can be said that the picture of Nature, and with it Man's place in Nature, radically changed in the Middle Ages. The picture we have of Nature is always only a reflection of a particular relationship we have with Nature. 'Objectifying' Nature thus goes hand in hand with the 'subjectifying' or individualisation of the human being. In a Nature no longer seen to be ruled by Gods, Man can develop in freedom, feeling himself to be the creator of his own thinking.
We turn to the sense perceptible world to restrict speculative thinking. Human perception is strongly directed to its surroundings and thinking has to get its bearings from what is perceived. However, in science, perception is increasingly mediated by instruments and is influenced by the conditions of scientific experimentation.
At the same time it can be said that there is a growing tendency to thinking abstractly and in terms of models. This involves purely intellectual thinking on the one hand and, guided by this head-thinking, ever increasing experimental manipulation on the other. An interplay arises between thinking and doing (willing) which almost totally excludes feeling (the heart). This development shows just as much in the separation of art and science as in the separation of science and religion (and thus ethics). What was at the height of Greek culture seen as a close threefold relationship - Truth, Beauty and Goodness - now becomes fragmented.
The transition to a mechanistic approach to looking at Nature was initially directed at lifeless Nature. Even so, Descartes also turned his attention to animals and Man. For Descartes' dualistic thinking, an animal has no soul. For him it is an automaton. The human body too is extended in space, thus giving rise to an unbridgeable rift between soul (spirit) and body. This shift in thinking is illustrated by comparing Fludd's (11) cosmic physiology with Boerhaave's (12) mechanistic model inspired by Newton a century later.
The activity of the soul is confined in Boerhaave's thinking to the head. The weaknesses of mechanistic models applied to the phenomena of life led at the close of the 18th century to a flowering of vitalist and organicist currents in thinking.
 
Goethe's Organicism
Reading in the book of Nature, as practised by Goethe around 1800, is a paradigm for a holistic approach to biology (13). Goethe like no other was conscious of the fact that each part belongs to a whole and that the whole belongs to the parts. The zoologist Portmann (14) tried to portray the difference between the mechanistic and organic approaches using a theatrical metaphor. Behind the stage there is the assemblage of machinery. Portmann compares this with the 'realm of biotechnology' now dominating biology and serving to control Nature. On the stage itself, a certain 'meaning' is conveyed by words and gestures. It was this 'meaning' that Goethe sought to discover by paying attention to Nature's directly observable phenomena.
Goethe's method is described as 'phenomenological' (15). This means that he started with the phenomena observable by the senses, remained true to the phenomena throughout his method of research and ended up with the 'primal phenomenon' or 'archetype'. Natural phenomena show themselves in many ways. A phenomenon must first be observed and described from all available angles so that a concrete idea of it can arise.
As Goethe's approach is built upon immediate perception of natural phenomena it is thoroughly 'empirical'. Goethe never looked for the physico-chemical causes. Rather was he interested in the various conditions under which a phenomenon manifests. Therefore, the 'primal phenomenon' can be interpreted as the 'law' governing the appearance of a phenomenon under the various conditions given.
Goethe experimented, not so as to test prior hypotheses, but to extend our range of experience and to discover its inner relationships and pattern. He sought the 'inner necessary connections' as an expression of the phenomenon itself. We can discover the pattern by developing a living experience of the 'language of form' or the 'gesture' of a developing plant or a series of related plants or animals. The investigator must be prepared to let the other 'speak for itself'. The stage is sooner or later reached when living concepts, revealed not only in the phenomenon but also in thought, are experienced as if actually seen with the eyes.
Goethe's approach features full confidence in sense perception as well as intuitive ideas that are produced through interrelations of percepts. Goethe wanted 'to understand natural objects through ourselves', since according to him a hidden relationship exists between Man and Nature. In Nature, 'something expresses itself' which the human being can 'read' inwardly, when perceiving and thinking has been schooled in a certain way. The sort of thinking to be developed here can be designated in various ways. 'Objective thinking' and 'intuitive thinking' are terms that Goethe used. An English phenomenologist who followed Goethe's method used the terms 'sensuous thinking, pictorial thinking and imaginative reason' (16).
Goethe brought new life to the medieval idea of reading in the book of Nature. The real being of a living organism did not, according to him, reveal itself to direct sense perception. Matter cannot exist without spirit and spirit cannot exist without matter. In this connection Goethe was speaking of the omnipresence of God. Man cannot reach the Divine through his intellect, but rather through his reason. The Godhead works in living Nature, in what is becoming, not in what has already become fixed (not in what has already come into existence and rigidified). Intellect applies itself to the fixed, to the dead. Thus we can also apply knowledge developed with the intellect to technology. With these kinds of ideas, Goethe was a man of his time. A number of contemporary investigators - Ritter, Steffens, Oken, Carus - had similar ideas. In contrast to modern science, where schooling oneself has no place, they were convinced that knowledge of Nature and self-knowledge must go hand in hand. They criticised the one sidedness of the mechanistic ideals of modern science and tried to rebuild the lost unity of Man and Nature (17).
 
19th Century Reductionism
In his book on the history of physiology Rothschuh (18) summarised the 19th century breakthrough of experimental- reductionism in biology in the following way: "The physiology of the Romantics was totally self-consistent. They pursued an ideal understanding of Nature which was satisfied with characterising the place of an individual phenomenon within the framework of a comprehensive concept. The principles of analogy and polarity were used to order the things of the world. But the new physiology which arose in the middle of the 19th century sought order among the manifestations of life through their causal interconnections. Since cause-effect relationships can only be tested in narrowly defined parts of Nature, physiology was increasingly dependent on the causal-analytical experiment. Their results gave rise to something totally alien to the romantic physiologists, namely taking hold of living processes. Indeed it allowed these processes to be manipulated as has already been learnt for physical and chemical processes and was at the time just beginning to be exploited in the development of techniques for the manufacture of machines and useful materials."
This 19th century development in biology can be seen as the breakthrough of the kind of causal-analytical reductionist thinking described at the beginning of this chapter. The ideal of experimental research in the laboratory spread to all fields of biology. In 1865 Claude Bernard stated the principles of this trend (19). According to him, the experimental method has the task of guiding ideas. In the experimental situation reproducible results can be achieved whose reliability can be enhanced by instrumentation. The investigator must confine himself to reducible relationships between the observed phenomena. Conditions under which a phenomenon occurs can be controlled in the laboratory, thus enabling measurement and prediction. Bernard described the laboratory as the 'shrine' of biomedical science.
Interest in the approach of natural philosophy dwindled. People were more interested in exact information about details and this led to the splitting up of biology into a multitude of disciplines. The unity of all things living was no longer sought in the realm of ideas but in matter. The discovery of the cell as a structural and functional biological unit was an important step in this development. The discovery of cell organelles led ultimately to the discovery of genes and DNA
I should like to close this historical section with some observations of M. and D. Gersch (20) on the history of the concept of the biological object. They describe the radical change from the descriptive to the experimental-analytical approach in biology. This change was only possible after the idea of a living organism being an indivisible unit was abandoned. With the introduction of the experimental method, living organisms increasingly became the 'material' of research.
Gersch and Gersch describe this process as one of 'de-individualising'. It manifests in two forms. Firstly, the personal connection between the investigator and the object of research disappears. Secondly, the author loses sight of the uniqueness and the individual significance of the object. Through the process of reduction, the general applicability of statements about the object and the possibilities for its manipulation increase. What is here meant is particularly evident in the developments of research in genetics. To molecular biologists, the genetic code as the 'basis of life' is universal in that it is essentially similar in all living things. Obvious differences between phenomena at higher levels of organisation disappear from sight at the molecular biological level or are no longer traceable to differences in biochemistry. In contrast to this, in the tradition of organicism there is a hierarchy of levels of organisation. Each level has its own principles which are not derivable from a lower one.
 
Perspectives from Natural Philosophy and Ethics
Ethics is based on the 'Good' in the context of human deeds. We have seen that after the scientific revolution the question of the 'True' has been separated from that of the Good. From the beginning of this new era science claims to deliver certain knowledge about Nature, in the sense that the knowledge gained is in accord with reality as it exists independently of Man. For this, knowledge must be 'value-free'; objective knowledge also means value-free knowledge. It is interesting to note that the more value-free a science is in the methodological sense, the more it can be used to control Nature, which itself can never be value-free. That the scientific method could be used to wield power over nature was noticed by Descartes, Bacon and Galileo, though they linked it with the belief that this power would be used to reduce human suffering and to increase the prosperity of mankind.
Although, through the application of the reductionist method, the power that Man has over Nature has steadily increased, nothing is gained from the value-free knowledge that this method yields in the way of guidance as to the use of this power. Because of the separation of ethics and knowledge, scientists in their training experience little of ethics. Questions about ethics in connection with research are rarely asked. Whilst scientific knowledge grows ever more important as a factor determining culture, the foundations of world views which are expected to yield ethical guidelines are increasingly undermined by materialistic scientific thinking. As western pluralistic societies now lack an obligatory faith, science, because of its universality, tends to fill this vacuum. Science thus manifests increasingly overtly as a world view. It even pursues a sort of witch hunt with everything it considers 'pseudo science' or 'quackery' (alternative agriculture, alternative medicine).
Logically speaking, science can neither confirm nor deny the existence of a spiritual world. However, this does not mean that the scientific method is ethically neutral. Science is more than just an uncommitted way of looking at the world. We have already seen that the reductionist approach manipulates Nature and thus in a certain sense itself produces the conditions under which its knowledge is true. This means that the greater the scope for reductionist scientific thinking in society, the greater is the extent to which the materialistic world view establishes and realises itself.
Gradually, therefore, Nature, which once was the cosmos that encircled and permeated us, is slowly but surely being replaced by a man-made Nature. This process is already so far advanced that many experience it as the 'death of primal Nature' (21). That things could have gone so far, is partly attributable to Nature, now objectified in the reductionist sense, having a value no longer for its own sake but for the use mankind can make of it. This corresponds to the model of 'fallen Nature' that invites manipulation and control.
In biology, Nature's worth in its own right is recognised more easily by the organic approach. Goethe even went so far as to speak of the 'rights of Nature'. (About his relationship with Schiller he said: 'He preached the Gospel of freedom, I did not want the rights of Nature restricted.'). Goethe repeatedly emphasised that each being exists in its own right and not as a useful tool for mankind.
In the animal and environmental ethics that has arisen in the last two decades this instrumental view of Nature is blamed for the plunder of animal and plant resources. People now argue for a biocentric approach whereby Nature retains it own worth (22).
It is hardly a coincidence that those people who plead for a different attitude to animals and plants refer to disciplines like ethology and ecology, with their stronger orientation towards the organic approach. This is understandable because the organic approach is directed at studying and comprehending Nature for her own sake and the relationship between Man and Nature is thus not destroyed.
 
Ethical Questions
From the foregoing it follows that genetic engineering is ultimately the result of applying to living beings the reductionist approach. With it, the apprehension of truth is more and more displaced from a correspondence with reality to what can be achieved in the laboratory (If it works, it's true). In the molecular biological view, the qualitative differences between living and non-living Nature, between plant, animal and Man disappear. Reproductive processes become increasingly 'unnatural' with increasing domestication, in the sense that it is no longer 'left to Nature', but more and more guided and regulated by human intervention.
When the concept 'unnatural' is used in an evaluative sense this can best be understood from an organic point of view. The trouble biotechnologists take to emphasise the 'naturalness' of gene manipulation is very conspicuous. For instance, they regard DNA itself (instead of the whole organism or species) as the 'natural unit' of life (23), or describe biotechnology itself as 'natural' (24). Metaphors which belong to the organic approach are misused to describe the control of fallen Nature. In molecular biological thinking, individuals are only vehicles for the transport of genes. Living organisms have become information carriers determined by a code which can be deciphered and altered at will. It was Rifkin (25) who among others criticised the tendency for the idea of a living organism as a separately identifiable unity based on our pre-scientific experience to be increasingly abandoned in favour of justifying the manipulation of 'living material'.
The ever more pressing basic ethical question which this poses is whether genetic engineering, especially its creation of transgenic organisms, whereby species boundaries are violated, is not in contradiction to the individual worth and integrity of the plants and animals involved. Individual worth and integrity of living organisms is in a certain way connected directly with their qualitative properties, with being a whole and being part of wider living communities. When it comes to risk assessment, it is regarded by and large as a technical problem rather than an ethical one. Recourse to the ethical approach is only made, when, starting from the assumption that genetic manipulation as such is 'ethically neutral', ethics only becomes important if the consequences are harmful and must be balanced against the advantages. These kinds of arguments are enhanced by the molecular biological way of looking at the phenomena of life. At this level, the investigator has long since ceased to be at one with his object of study.
That certain risks are connected with genetic engineering, is nowadays acknowledged by all involved. The isolated gene and the genetic construct produced in the laboratory are reintroduced into a living organism which is then released into the environment. From the point of view of organicism this is not possible without risks. What might happen at higher levels of organisms is to a large extent unpredictable, just as one cannot predict the properties of water when one only knows those of hydrogen and oxygen (emergent properties).
The attitude of supporters of genetic engineering can at best be characterised as a 'Yes, if' attitude: Genetic engineering should be allowed if the risks are negligible. In order to minimise risks, organisms are modified in such a way that they will not survive in the environment (disabled bacteria). The attitude of the opponents is 'No', or 'Not unless': No genetic engineering unless what it is used for is essential for mankind's continued existence and there is no other way of achieving this goal (26).
Resistance to the violation of species boundaries also exists within the scientific community itself, especially amongst biologists and others with an organicist ideology. To many Christians, who hold a static view of the species boundaries, the violation of species boundaries is an insuperable obstacle. In discussions about the permissibility of genetic engineering, arguments which seem to go against the neo-Darwinian theory of evolution are not usually taken seriously. Here it is clear that the influence of science has become so great that ideas which are at odds with it are not allowed to have part in the public debate. But science is a world view which must be treated just like any other world view. Here we are touching on the fundamental question of the freedom of cultural life. In this connection, the philosopher Feyerabend (27) argued for a separation of state and science to make way for a real pluralism in cultural life. At the moment, most of the advisory committees of the state are dominated by the ideology of modern natural science. Therefore, under the veil of objectivity, only biased advice is given.
 
Freedom and Determination
In the foregoing, I have shown that Man has won through science a high degree of freedom with respect to Nature. Much has become technically feasible which would not have been so without this development. This greatly extended the options available. The seed of free thinking has quickened through the scientific approach to Nature. With scientific thinking come limitations, especially those which have led to the materialist-reductionist way of dealing with Nature.
This shows up nowhere more clearly than in genetics where one frequently hears mention of 'genetic determinism'. Living phenomena are not only reduced to the molecular biological level, but also people think that these phenomena are directed from that level (DNA as 'program' or 'blueprint'). Although the method associated with this approach has been fundamentally challenged (28), people still feel compelled to look for genetic factors which the approach implies to be 'responsible' for deviations from normality. When these are discovered intervention at this level follows as a matter of course. The consequences of this thinking are especially noticeable when it comes to the human being.
If the dualistic scientific model is applied to human beings as the objects of investigation they become separated into 'biological life' and 'personal life'. Human biological life, like other living processes, is investigated as a material mechanism thereby increasing our ability to manipulate it technically. Ethics and law have to oversee that such manipulation is not against the will of the experimental subject or the patient. Science has already increased the options open to us - one need only think of the pill, in vitro fertilisation, prenatal screening and abortion if there is likely subsequent handicap of the unborn. The future may offer genetic manipulation.
At first glance and from a materialistic point of view, everything seems to be in order. But there are a number of issues that can be raised. Firstly, self-fulfilling scientific thinking would explain, on a merely scientific basis, an increasing number of aspects of what it is to be human. This is seen to be valid not only for biological life, divorced as it is from the body as experienced, a process comparable with estrangement from Nature, but also for personal life, in that human consciousness is seen as an 'appendage' of the body.
Some psychologists of the behaviourist school have given particularly clear expression to this: Human freedom and individual responsibility are illusions they say. Everything is explained by environmental influences. Reductionist explanations by geneticists are essentially the same, only it is the genes that determine. If we say Down's syndrome is genetically determined and we can identify the genes responsible, then it seems reasonable to try to intervene at the level of the genes in order to correct the disorder, or we undertake to prevent any attempt to give birth to a child with a disorder of that sort.
Put another way: With the extension of reductionism to man, the idea of freedom, which was the point of departure, becomes an ever greater illusion. In order to really make a 'free' decision, all knowledge relevant to Man must be taken into consideration, rather than just allowing the natural scientific picture of man and the world to take the lead. For this, it is necessary to have complete freedom of thought in cultural life (29). At present we are under an illusion about freedom. A trend can be observed in society of normative judgement criteria being borrowed from the natural scientific picture of Man. One can think of several examples such as the choice of a morally relevant understanding of the concept 'species', of brain death as the biological criterion of 'death', and of the matter of course by which genetically disordered embryos are aborted - in all these cases a conceivable spiritual dimension of reality, in which phenomena such as health and illness appear in a totally different light, is completely denied. Nowadays it is almost the norm that a woman who brings a Down's syndrome child into the world is looked at askance: 'You should have prevented that'.
In the social context too, the freedom of the individual to reach a well considered decision continues to decrease through the dominance of a materialistic world view. If the idea we have of Man that gives us the standard by which to reach an opinion about tinkering with life is only formed by science, we end up in a vicious circle from which it is difficult to escape.
Summary
In this chapter, developments in the field of biotechnology are evaluated in a historical context. The history of biology can be described as an ongoing struggle between the reductionist and organicist (holistic) approaches to understanding Nature. In the medieval conception of reading in the book of Nature, Nature is seen as an organism, as the body of Mother Earth, a harmonious self-regulating whole, to be treated with respect. In the 16th century this concept of Nature was replaced by the concept of 'fallen Nature'. Nature was then seen as disorderly and chaotic. In this view the 'blind' forces of nature have to be conquered with the help of human intelligence. Man was no longer seen as an essential part of God-created Nature. Nature was objectified and materialised in the scientific revolution of the 16th and 17th centuries. In a Nature which is no longer ruled by a Divine Being, Man became free to manipulate Nature and use her as an instrument for his own purposes. Experimental natural science provided the means to this end.
Goethe and other scientists at the turn of the 18th century tried to breathe new life into reading in the book of Nature. His phenomenological method was however forgotten with the breakthrough of the experimental and reductionist approaches in biology in the 19th century. The laboratory became the shrine of the biomedical sciences. Nature as directly experienced by the senses was replaced by laboratory Nature. In the laboratory, facts are no longer facts because they correspond with reality but because they are controllable and reproducible. Biotechnology is the natural outcome of this approach to living Nature.
At the moment the reductionist approach dominates the life sciences. As a consequence holistic and phenomenological approaches get less funding. This leads to a self-fulfilling process. Scientific facts are constructed in the laboratory and implemented in society through technology. A second manmade Nature is increasingly replacing Nature as given and scientific results are considered true 'if they work'. More and more is it realised that the instrumental approach of science and technology must be subordinated to other, higher values. It is through the neglected holistic approach, among others, that we can find these values. This implies that the results of reductionist thinking should not dominate social and political decision-making about biotechnology. The increasing influence of reductionist and materialistic thinking threatens to undermine our ideals of individual responsibility and freedom. It also obstructs our making well-founded decisions about the genetic manipulation of living organisms. 


Environment as Data versus "Being": Is Goetheanism possible in the West?
William Brinton
 
Woods End Research Laboratory, Mt. Vernon, MAINE, USA
*based on a presentation at the Conference: Goethean Science in Holistic Perspective,
Teachers College, Columbia University, New York, May 20-22, 1999
Introduction
For many scientists who work in the environmental field, it is increasingly problematic to imagine a way of knowing nature that is different from modern science's mode of data capture and "factual" interpretation. Environmental engineers say that "... if you can't measure it, you can't manage it". Knowing nature's parts and successfully managing nature are seen as inseparable necessities of modern living.
Modern science grows out of the conceptual modus operandi to investigate each part of nature singly until we achieve a complete understanding of all the underlying mechanisms. In a sense, we have not changed the original formulation of Rene Descartes (1596-1650) who elaborated the view that the universe is a "gigantic clock-mechanism". This has led logically to the surprising conclusion by some thinkers that essentially we know the world and universe nearly completely, and any new additions to knowledge will be diminishingly small (Horgan, 1996).
This author's view is that a new orientation to nature, consisting of a comprehensively holistic in contrast to a reductionistic approach, may provide not only interesting, but also very necessary new dimensions in the modern understanding of the world. A holistic approach could become an important tool for seeing and acquiring a deeper grasp of natural processes where other approaches are showing signs of failure. Thus, a new approach may also be very useful. In a contextual sense, a holistic approach corresponds to new social trends making their appearance now and which reflect a desire for nurturing and healing the world, in contrast to the out-dated motifs of control and competition implicit in modern society's forms.
Post Western Science: A Crack in the Wall or a Flaw in the Crack?
Countless western ecologists and environmental scientists today are truly concerned about the role and influence of technology - and business - on their fields. A post-green-revolution view has emerged and holds that there are significant sociological dimensions to modern environmental problems that cannot be ignored (Brown, 1998; Lovins & Lovins, 2000). Many scientists place western "self-oriented" epistemology on a collision course with nature, and argue for a non- anthropocentric nature view - a transpersonal view - in order to achieve survivable harmony (Fox, 1995).
A dilemma arises when examining closely the precepts of any one of many alternative approaches to science and nature. Most do not appear to contain a view of nature that is essentially different from scientific reductionism. From this, it may be questioned whether these alternatives will be able to cause an appreciable shift in the current direction. Even more difficult, ecological perspectives within the sciences often only strengthen reductionistic directions, since they provide important details about relationships, which in turn help "fine tune" the existing mechanical models.
Sachs has provided an example of the dilemma by characterizing the mixing of alternative approaches with existing reductionistic modalities to form the abstract concept "environment". Arising out of this abstraction of nature is an emerging ecological bureaucracy, called by Sachs "eco-cracy", which is obviously needed in order to maintain the complex new view of the environment (Sachs, 1992). It is a question whether or not this form of intensification of our understanding of nature can be sustained. Goetheanistic science of nature if it does anything represents a path that is distinctly different than just taking details of the world and arranging them " holistically".
The crux of developing a Goetheanistic approach (and the author finds the expression "Goetheanistic" to be potentially misleading as well) lies in recognizing that a dimension of mind is involved in constructing any view of the universe. To a large extent, alternative movements from ecology to biological farming do not deal with the mind and cognitive component of their approach. Indeed, many do not know there is a choice at all. The focus of many modern western alternatives particularly within medicine and agriculture is on re-arranging the parts already explained reductionistically, and success is imminent (IFOAM, 1998). On a crude level, organic farming may be seen similar to reductionism in that it uses current scientific approaches to replace man-made chemicals with "natural" ones. This is not a fundamentally new direction and it permits alternatives to be launched from within the ranks of science that compete for "natural" technologies, such as genetic engineering.
There is no doubt that much good can be done simply by more scientific study of nature and re-examining the results of mechanical sciences. Models to reduce chemical loading of the environment or to enhance bio-degradation, are some examples. Errors and incorrect theories are constantly being revealed within science itself. In this sense, modern science does contain a partial self-corrective element within it. Thus, ecological farming has with ordinary science made huge advances in general understanding of soil and plant communities – contributions that have been widely accepted even within conventional farming. However, by overlooking the cognitive element implicit in how we know the world, we may essentially handicap ourselves to deal with the bigger problems we face. We become forced – by definition – to remain within the same reductionistic flow. In this way, many well conceived efforts to progress beyond conventional science may be fundamentally – and technically – flawed.
A prerequisite to developing a holistic, Goetheanistic approach that alters the course and direction of science is to discretely address the cognitive aspect of seeing nature. This can be done at a number of levels. The challenge of the modern age at the start of the millennium is simply that in order to effect the needed change we must be far more comprehensive than we are initially prepared for or capable of being. The hermeneutic question is: how can we begin if we cannot clearly see the new, previously hidden start point?
Science and Society: The Industrial, Secular Era
Many if not most of the truly significant developments within the sciences have had a corresponding social component, which may in fact have preceeded the science itself. The recognition of this phenomena goes back to Thomas Kuhn's basic work (Kuhn, 1962). Yet, this fact is continually overlooked in examining modern scientific developments.
We can begin to grasp the root causes of the dilemma in how we know the world mechanistically by recognizing how closely science and modern industrial society have developed together. By appreciating more specifically the deep sociological dimensions of science we may begin to overcome our failure to grasp the cognitive dimension of seeing the world.
It must be said at the outset that scientists are mostly unprepared to see themselves as "socially embedded", still less cognitively constrained. It is a chicken and egg phenomena. Much worse, science has been presented to society as a form of absolute knowing. Thus, significant internal resistance may exist if we shift emphasis to a cognitive element, where we recognize a world of groundless being with no "outside" to turn to in order to derive "fundamental scientific findings".
It is instructive to look back 160 years to Victorian England, and view the emergence of modern, industrial society simultaneous with modern biological science. By the end of the 19th century, the captivating and important concern of western society as a whole was mechanisation and industrialisation, which in turn shaped the new sciences (Ada, 1989; Marx, 1964). It is forever problematic to state which condition came first. Clearly, the concept of western dominance arises in close concert with the paradigm of control and exploitation of nature, which arose out of sciences preoccupation with the details. With the steam engine and the train arriving in society, near complete human fascination was invested in building a manufacturing society. Whether you read the American pioneer Thomas Jefferson, or Scottish political economist Adam Smith or Charles Darwin, the direction is the same. The basic principles of the accumulation of capital, the division of labor and the improvement of mechanisation, were all being simultaneously enunciated.
Probably no shift in scientific innovation and social causes has been more significant than that produced by Darwin. It is evident from all that is known of his life that he drew significant elements of his theory of nature's division of labor from non-scientific sources, including the emerging economic theories, especially those of Thomas Malthus (Desmond & Moore, 1992). Malthus was an economist for the East India Tea Company – perhaps the largest corporation in the world at the time – and it was he, and not Darwin, who first clearly formulated the basic premise of survival of the fittest: "as population rises and the food supply diminishes, struggle and starvation are the result".
The need to secularize trade in order for the new manufacturers to grow in their own right concerned Darwin's peers every day. What is less well appreciated – due to its sensitive social nature – is Darwin's extreme interest with familial inbreeding and its apparent negative effects (Desmond & Moore, 1992). He developed these concerns concurrent to his investigation of evolution. Within his own family, marrying within the family – Darwin married his first cousin – was very common. Darwin seems to have been greatly preoccupied with his children's condition. The early death of his favorite daughter for inexplicable causes and the apparent slow learning abilities of several of his children caused him extraordinary grief. These apparent physical hereditary factors were powerful antecedents for Darwin's developing a new view of "natural selection". It was only Gregor Mendel who glimpsed the actual hereditary links. Not surprisingly, one of Darwin's sons chaired the first London Congress on eugenics sponsored by the Galton Society: its facile objective, among others, was to examine the brains of rich to determine if they were larger than those of the poor "less fit" classes. It is therefore surprising to recognize that this new evolutionary science also triggered the eugenics movement.
Darwin's extraordinary struggle with class and socials issues extended deep into his writings and extensive personal notes. We know from the record that Darwin deliberately withheld publishing his views regarding evolution by at least two decades. He felt that by prematurely publishing the struggle-for-existence, the lower working classes would seize upon it as a rationale for an uprising in the very turbulent and unstable 1840's and 50's (Desmond & Moore, 1992).
It is ironic that Darwin's views go very much to the upper, privileged class even while challenging religious authority. He held that by accumulating capital we "rise above lower races" (Adas, 1989). In notes Darwin made during his five years of ocean travel in the Beagle we find numerous references to European society as a "pinnacle" system compared to other societies which are described as "lesser" or "savage" in nature. Darwin described the South American natives he encountered as "barbarians haunted by the grossest superstitions... their mouths frothed with excitement, their expression wild.... and mistrustful" (Darwin, 1871). He adds – and unmistakably he is talking of the European – "Man may be excused for feeling some pride at having risen... to the very summit of the organic scale". Today, such viewpoints could easily be characterized as distorted and racist, and certainly would be political suicide for a naturalist. At the time it was consistent with the emerging worldviews of dominant European society. Ironically, Karl Marx presented a shrewd commentary on Darwinism when he said "he [Darwin] recognizes in beasts and plants his English society" (Marx & Engels, 1863).
Looked at another way, Darwin's theory was so important and influential because it re-focused virtually all the social issues of the time, particularly the turbulent forces democratising business and secularizing science, while at the same time protecting privilege, {delete hyphen} or in other words, "class struggle converted to natural science" (Marx and Engels, 1863). A similar modern critique of anthropomorphisms dominating E.O. Wilson's biology is seen in the work of Deborah Gordon (Gordon, 1999). At this early time of social upheaval in England, we find naturalists and worker class peoples struggling together to limit the enormously powerful Anglican, Christian church. Darwin was keenly aware of this social context, and he carefully picked his friends and collaborators. In 1838 he wrote: "I need only show that one species passes in to another, and the whole edifice [of society] totters and falls". This is no ordinary scientist who wishes to reveal new facts – he is keenly aware of his views triggering an entire social shift.
The powerful influence this new scientific "survivability" thinking exerted within the emerging competitive, industrial Euro-American-centered world must not be underestimated. Going further, there are very unsettling aspects to these new, popular 19th century views. It is not just that they present the "sociologically embedded scientist" (Gould, 1997). They also reveal typical racist elements of European white culture tied to the new popular view of dominating nature by industry. Closely linked to Darwin was Galton who established the London Galton Society, the first overtly eugenic society in the western world. This extension of Darwinistic natural science was taken up in America at the turn of the century, and by 1910 the first full government eugenics agency, the Eugenicist Records Office (ERO) had been established in New York with the goal of "... uplifting the country by improving the blood of the nation" (Davenport Papers, 1910; Perkins 1934). From prominent industrialists like Averill Harriman and banker T.H. Morgan and the Rockerfellers, to inventors like Alexander Graham Bell and natural scientist Luther Burbank, we see broad acceptance of the Darwinian notion that "the environment is the architect of heredity" (Burbank, 1907) whichin its most extreme form led to the eugenic holocaust of Europe.
This thought may be expressed differently by stating that the current era of science bears within it logically the legacy of a dehumanizing, industrializing worldview. One cannot separate the two and say "here are the objective observations of nature " and "here are the developments of secular industry". They are linked together, each supporting the other. Darwin's singular act is that he secularized and industrialized human cognition of nature. It is not surprising that this new view had the power to break the Church domination. Today, we are challenged to ask if it is possible at all to develop a holistic ecology or a culturally supportive society from such a starting point or even perhaps by using any of its building blocks.
Science and Society: The Genetic Engineering Era
The huge sweeping reforms that grew out of Newtonian physics and Darwinian industrialisation altered the way we perceive nature and continue in their modern effects. It is easy today to grasp that we see the world in a manner similar to how we mechanize the world: virtually all the theories and models that we work from are now mechanical in nature. This reform of the human experience of the world that started nearly 400 years ago is being deepened by means of the emerging electronic-genetic era.
The frontier sciences in bio-tech and electronic biological interfaces may be the equivalent to the manufacturing obsession 150 years ago. Humans are "reinventing" nature as a bio-genetic network, a complex web of basic genetic building blocks that can be manipulated at will. At the same time we are building a web of computer units linked around the world. At every turn in modern business and science we see heightened fascination with natural phenomena as "networks" or "decentralized units" and we are witnessing unprecedented use of Darwinian metaphors. As one writer has spoken: "The 21st Century will be more like the 16th than like the 20th, with biology standing in for the discovery and exploration of the New World." (Gruber, 1998).
Here, unfortunately, is where the blurring of boundaries so common to modern times becomes problematic. It is difficult to distinguish a productive from a fallacious or dangerous direction. In a crude sense, Darwinian natural science prompted a world eugenics movement. While the darker aspects of this application of modern science have been stopped, bio-technology is raising again significant ethical questions that are similar. It is important to recognize that the same logical, positivistic and de-humanizing impulse implicit in modern western science is simply expressing itself in new territory. Without a holistic dimension to the understanding heredity as co-joining of the environment and the part, for example, these eugenic problems will continue to arise.
Thus, we have enhanced reductionism with its ever-present Darwinian eugenics foundation, balancing against a new emergent wholism, with a strong social ethical dimension. The "middle ground" is growing, and represents an amorphous mixing of all views, chiefly apparent in the internet, bio-tech communities. This in turn is influencing the views and practice of science itself.
Suddenly it is fashionable that so-called "natural laws" in nature are seen as "potentialities". Darwinian survival of-the-fittest and genetic determinism are slipping from their high status as iron laws. We are examining the notion that natural reproduction means organisms pass on genes as well as the environment in which the genes were imbedded (undoubtedly one of the most truly holistic notions that has come out of biology). Thus, as we continue to investigate nature, we find directional signs pointing everywhere. "Nature rejoices in illusion", said Goethe. Here, instead of finding the ultimate groundwork of nature, our modern reductionism is at best able to relativise everything and "network" is a good metaphor for it. "There is no understanding possible anymore", lament two writers, because now "everything stands between" (Taylor & Suarinen, 1994).
Closely tied to the current era's massive production of piecemeal data about Nature is the information technology age itself - computers being central to it. This information technology gives us the opportunity for the first time ever to truly gather all the data produced by an atomistic world view. Indeed, Descartes who expounded the entire world to be mechanical has been in a sense waiting all the while until such a moment would arise when we would be actually capable of physically storing the detail of the cosmic mechanism.
If one considers the historicity of science itself (Bortoft, 1995) one cannot overlook the problems encountered for early thinkers when introducing an atomistic world view in the absence of the requisite mechanisms to do something with it, since clearly the human mind unaided is not capable of it. From this point of view, genetic science thus becomes an invention of the computer era - we are mapping the human genome not because we understand the territory, but because we can finally comprehensively capture the billions of pieces of data produced. Genetic science today by definition is an extension of mechanical reductionism.
Descartes, Newton, Darwin - and for that matter all of them - certainly had no concept of data storage. At that time, the most advanced people had been reading from movable typed books for only about 150 years, and only in specific regions of Europe. Indeed, I imagine that Descartes postulation of the mechanical universe might not have been made or so fully acted upon prior Johann Gutenberg's press - which after all, began the process of atomization in so far as it reduced the word to units of inserted letters. Darwin expressed great frustration at the limits of humans cataloging all the details about nature. What these early revolutionists could not do, we can begin to do now: replace the experiential world around us with a computer retrievable, mechanical copy of that world in all its details. It is this copy from which successive generations are likely to draw much of their explanation if not experience of the world.
A careful assessment needs to be made of the new direction being taken. Preceding generations of industrial reductionists concerned themselves with implanting the machine in the garden, an expression coined by historian Leo Marx (Marx, 1964). It seems apparent that present and future generations will focus on "the garden in the machine", an expression from bio-tech spokesperson Claus Emmeche (Emmeche, 1994). Tired of anthropomorphizing the world we will alter the course and attempt to "naturalize" the machine newly created. This is somewhat similar to how Ludwig Bertallanffy characterized the trend in modern science "... human forms of cognition... are modified and eliminated and... replaced by constructs increasingly abstract, general and unvisualizable...". (Bertallanffy, 1967). Only it goes further than this, and becomes a very active type of involvement with intrinsic mechanical seeing, called by many a "virtualisation" of the world.
Is it possible that we may be glimpsing the beginning of the information-atomistic age? Everywhere we turn, modern persons are incorporating mechanical concepts into deeper layers of nature and human investigation. The essential thrust of advanced science and bio-technology is not to find alternatives but to accommodate the underlying and build upon the atomistic world view, allied with new nature metaphors. To complete this thought, and with apologies to Wes Jackson, it is apparent that the essential intent of our age is "becoming native to this machine" (see Jackson, 1994) – in other words, a complete uniting of human with machine forms of perception. To become wholists, to invest one iota of human purpose into Goetheanism, must we not become new pioneers, strangers to our country and to our age?
Observing Nature as the "Open Sceptic"
This paper critiques modern science as an enterprise that is fundamentally flawed if our concern is to develop a new, qualitative understanding of nature. Where that is not our concern, we need not question science. That so many good workers wish to develop alternatives but only by tinkering with the existing structures is deeply problematic. Realistically, for most, there is no other way.
A good way to formulate a new beginning in any kind of enterprise is to become aware of the obstacles to it. One way to go about this is to notice that Goetheanism lights up as we become aware of what we do not see with traditional scientific approaches. Traditional science contains predictable blind spots. These invisible zones can become hindrances quickly- depending on the investigation. It may appear surprising if not incomprehensible to many that in this modern data- rich era we have extraordinary observational handicaps. Goetheanistic environmental working must attempt to bring awareness of this to the forefront.
To develop a new field means to establish a conceptual framework for it. Yet, this requires considerable "bootstraps", since by definition the concepts needed do not yet exist. A space needs to be opened up, and we need to become accustomed to that space. This requires patience and new skills not previously used. When new concepts come into play, we begin to discover slowly a world not previously seen. It is a comprehensive world overlying the detailed world science perceives.
It is also true that alertness is a key to participatory observation. This is a quality of openness. Ranged in front of it and all around, are the obstacles. As one step, we must learn to mistrust data — not all of it all at once, but some of it selectively, by practice. Spencer Brown points out, that modern science has produced its great advances by "selective blindness" (Brown, 1997). If this is true, then a new Goetheanistic science will achieve its goals by a different process of wide-eyed non-selective participation. Refraining from accepting carte blanche modern "scientific consensus" is a good starting point.
There is nothing more powerful and less liked in modern science than to presume your idea to be faulty from which you first launched an investigation. Yet, many scientists and educators are prepared to do just this. It is in fact a key to discovery. Overthrowing customary views helps open us to new concepts which themselves permit a new seeing. Thus, Goetheanisms embodies healthy scepticism.
Concepts lead to "Seeing New": The Case of the Riparian-Buffer
Goetheanism in a sense may be simpler than we are lead to believe: it is the art of being-in-what-is-seen. Said differently: the Goetheanist starts by recognizing that the investigator is a cognizing and seeing entity. Failure to grasp this at the outset lead Goethe to caution: "Nature surrounds us with her dance... we live in her midst and know it not". Becoming conscious of our participatory awareness we find "data" co-mingled with the end result (concept), but never alone initially, as naive empiricism would have it. This is no cause to become a reactionary scientist; rather, it emancipates the human to more fully realise his or her potentiality as an observer.
 
Figure 1. Riparian Buffer, healthy state of clean water with plant boundary zone.  This awakening is most poignantly realized when we take scenes from a natural landscape, and ask: what do we observe? In the case of Figure 1, we see what most see: a quaint rural-agricultural scene. But the loss of what is now recognized to be a "riparian buffer phenomena" (Figure 2) has caused us to see the same scene, but more richly (Isaacson, 1999).
Figure 2. Riparian Bufffer, disorganised state, polluted water missing boundary zone.
 
The riparian water-plant border phenomen is expressed in nature's unique activity at boundaries with yield special environmental functions, not "seen" by just looking at the separate parts, water and plant. In figure 1, there is an active presence—the harmony of clean water and exisiting plant borders— that we do not see until the loss of it is grasped in the second (Fig 2): the water becomes polluted because the riparian phenomena (bordering trees and shrubs) are no longer present in the same relationship. Instead of seeing "clean water" in the first picture we learn to see it more actively as "cleansed water". Then, the polluted water in the second scene we grasp now as "water which has lost context". A useful excercise that helps here is to attempt to imagine water without any boundary – does it even exist? A wholeness emerges in contrasting the scenes that teaches us to re-see water united with its boundary condition. Once seen in this light, we cannot "un-see" the new concept. The recognition of riparian phenomen is one way that we are led to grasp that water is clean actively as opposed to clean passively. We debunk the environmentalist's concept "clean water", a fact seen as existing by itself. Thus, in this exercise an entirely new thrust in given "to the concept "environmental contamination".
While studying riparian phenomena is instructive and interesting, we need to go beyond this. Within the new environmentalism that must arise, a fundamental lesson is to make the observer aware of the simultaneous conceptual activity that illuminates the nature scene. Deborah Gordon's work observing ant colonies illuminates this to a high degree (Gordon, 1999). On several levels, simple exercises can be developed to prompt the active participation in the student, which yields deeper insights. These exercises use nature as a starting point, and examine how concepts illuminate or conceal the observed landscape.
This new approach is not data oriented; yet it does not reject data. Indeed, data may be indispensable to it. Thus, despite our critique of modern science, a holistic approach does not set itself up as opposition per se. Looked at more broadly in its social context, this new approach is harmonious with modern impulses seen in young people who are clearly trying to discover the whole as distinct from the parts, while society punishes them by providing more and more parts.
In this sense, it must be said that Goetheanism is most powerful when it is at work, and no better place than in nature herself. In the enriching relationship nature-to-human, the cognitive human world gains ground and substance acquires meaning, together. It is a shame that we accept so much less.
 
References
Adas, W. (1989) Machines as the Measure of Men. Cornell Press New York
Bertalanffy, L. (1967) Robots, Men and Minds. Brazillier Press, New York
Bortoft, H. (1997) The Wholeness of Nature. Lindisfarne Press New York
Brown, S. (1997) Laws of Form. Bohmeier Verlag, Luebeck, Germany
Brown, L (1998) State of the World 1998. Worldwatch Institute, Washington. DC
Burbank, L. (1907) The Training of the Human Plant. Century Company, New York
Davenport, C.B. (1910) The Daveport Papers. American Philosophical Library.
Desmond, A & J. Moore (1994) The Life of a Tormented Evolutionsist. Norton Publishers, New York
Emmeche, K. (1994) The Garden in the Machine. Princeton Univ Press, New Jersey
Fox, L. (1995) Towards a Transpersonal Ecology. SUNY Press, New York
Gordon, D. (1999) Ants at Work. Free Press. New York
Gruber, S. (1998) Hack the Gene, Map the Gene. Wired magazine, October 1997. San Francisco, California
Horgan, J. (1996) The End of Science. Addison Wesley Press, New York
Huxley, T.H. (1869) Volume 1, Nov. 4, 1869, pp 9-11.
IFOAM (1998) International Conference on Organic Markets. Christchurch, Oxford England
Isaacson, K. (1999) Riparian Corridors. USDA-NRCS Spring Newsletter
Jackson, W. (1994) Becoming Native to the Place. Counterpoint Press, Washington DC
Lovins, A.B. and L.H. Lovins (2000) A Tale of Two Botanies. Wired magazine, April 2000, 247. San Francisco, California.
Markl, H. (1997) Der Spiegel. Vol 3, Jan 20 1997
Marx, L. (1964) The Machine in the Garden. Oxford Univ. Press
Perkins, H.F. (1934) A Decade of Progress in Eugenics. William&Wilkins, Baltimore Maryland
Sachs, W. (1992) The Development Dictionary. Zed Books, London New York
Taylor, H. & S. Suarinen (1994). In Terra Nova: Nature and Culture. MIT Press
Wilson, E.O. (1996) Biodiversity. Harvard Press
William Brinton, Ph.D. is director of Woods End Research Laboratory in Maine USA. and co- director of Agar- und Umwelt-Consult, GmbH, Bonn Germany
Author's address:
Woods End Research Laboratory, PO Box 297 - Rome Road, Mt Vernon, MAINE 04352, USA


Progress towards complementarity in genetics
Johannes Wirz
Forschungslaboratorium am Goetheanum, Hügelweg 59, CH-4143 Switzerland
Abstract
The appearance of adaptive mutations in bacteria raises basic questions about the genetic theory of spontaneous mutation and hence the concept of the generation of biological variation. Adaptive mutations were observed in bacteria exposed to selective conditions during the stationary phase of growth in the absence of DNA replication. Both anabolic and catabolic traits were affected. None of the classical explanations, which depend on errors and irregularities during the replication process, is able to account for these mutations. Various observations suggest new mechanisms for the generation of genetic variation. The theory of adaptive mutations paves the way for the introduction of complementarity in modern genetics.
Theories of adaptive mutations elaborated before the era of molecular genetics argue strongly for holistic approaches to life and heredity. They make a revision of the current concepts of reductionist biology necessary. A synthesis is presented that considers the function of spontaneous as well as adaptive mutations in the development and evolution of organisms. Both forms of mutations reflect the fundamental quality inherent among all living beings; i.e. self-relation and world-relation.
Introduction
According to modern theories of heredity and evolution the tremendous variation amongst living organisms comes about in two ways, namely through spontaneous mutation and through chance hybridisation during sexual reproduction. An overwhelming number of publications provides evidence for chance variation. Because of this chance variation and DNA molecular replication (doubling) processes, which produce changes in the genetic make-up, spontaneous mutations pass undisputed as the driving force of variation and thus speciation. According to this view, in a second step, choice or selection determined by the environmental conditions sees to it that only the most fitting forms survive, thus limiting the variation which arises.
In spite of the many confirmations of the theory based on spontaneous mutation this article aims to outline and provide support for another possible theory, one in which the environmental conditions do not merely select, but direct and bring about variation. This is not intended to cast doubt on the reality of spontaneous or chance mutation, but rather to challenge its claim to absolute and exclusive validity.
The current situation in modern genetics is like that which prevailed in physics at the beginning of the 20th century. Just as at that time wave and particle theories of light were shown to be complementary views, it will be demonstrated that the present theory of chance evolution of organisms must be enlarged to include a complementary one, namely directed evolution. The theory of spontaneous mutation is placed beside that of adaptive or selection-induced mutation. Which of the two types of genetic change is realised depends on the physiological circumstances and the environmental conditions. These two types of change require different concepts for describing the relation of organism and environment and are dependent upon different molecular processes. Whether complementarity in genetics will have paradigmatic consequences for the overall understanding of living nature or whether, like complementarity in physics, it remains without effect on a wider public, remains to be seen.
There has been no shortage of attempts to develop concepts of variation other than that of spontaneous mutation. The best known goes back to Lamarck1. His was the first attempt in a modern scientific approach to evolutionary theory to explain how organismic variety arises. Lamarck's idea of inheritance of acquired characteristics, as discussed in more detail by Lefèvre2, formed an important though not central support for the theory. Whether it is justified to treat 'inheritance of acquired characteristics' and 'adaptive mutations' as synonymous is discussed in more detail below. Both Darwin3 and Haeckel4 embedded the inheritance of acquired characters. Because of this, Haeckel's biogenetic law was largely rejected (c.f. De Beer5).
As controversial as adaptive mutation is amongst modern biologists, as certain does its underlying evolutionary principle render service to convinced Darwinists (e.g. Mayr6) as an explanation for cultural evolution. Cultural advance is unthinkable without the passing on of acquired characteristics. Experiences are received inwardly and as capabilities are passed on to others (descendants). This principle is essential to the evolution of human communities. If one asks which quality is fruitful for this kind of evolution, the answer has to be cooperation. But the same question posed of Darwinian evolutionary theory gives competition as its answer. The demonstration of adaptive mutations in modern genetics is a contribution to a new understanding of nature. At the same time it leads to a humanising of natural science in that in this kind of genetic change the central human evolutionary principle finds expression in organic nature.
Spontaneous mutations
To understand the discoveries which have led to the concept of adaptive mutations, it is necessary first to be clear about the premises which gave rise to the theory of spontaneous mutation. This also means dealing with molecular interpretations.
Although genetic research was initially confined to plants and animals, bacteria soon played a significant part in answering the questions which arose. Procedures for producing pure cultures of totally different strains as well as for characterising toxin or viral resistance genes were a precondition for genetic experimentation. The other precondition comes from the bacteria themselves. Short generation times and large cell numbers made experiments possible which with other organisms would have lasted years and taken up a vast amount of space. In addition, as bacteria, having only one chromosome, are haploid, genetic changes usually show up phenotypically immediately after they have occurred.
Despite these advantages interpreting genetic changes proved to be difficult because the results were not reproducible. Whilst it is true that the phenomenon of bacterial virus resistance could be observed on repetition, the number of resistant cells in each replicate experiment exhibited wide variations.
Luria and Delbrück7, from studies for which they later received a Nobel prize, suspected that it was just this observed variability which might explain how virus resistance comes about in bacteria. They neatly hypothesised that if resistance is acquired by contact with the virus the number of resistant bacterial cells should be proportional to the total number of cells used in the experiment, provided that the probability of cells becoming resistant is the same for all cells. A series of identical parallel experiments would thus allow one to expect a Poisson frequency distribution of resistant cells. But if the mutations occur spontaneously in bacterial cultures before contact with the virus, then the number of resistant cells should be independent of the total number of cells used in the experiment - provided that the mutation event is very rare - and would simply depend on the time elapsed between the appearance of the mutation and contact with the virus. If the mutation occurs long before virus contact, the number of resistant cells will be large. If it occurs only a short time before contact, the number will be correspondingly small. The frequency distribution of resistant cells from parallel experiments is clonally determined. All resistant cells come from one and the same parent cell. Testing the variance or fluctuation can thus allow a conclusion to be drawn as to the kind of mutation which has arisen.
In their experiments Luria and Delbrück inoculated between ten and twenty tubes containing nutrient broth with 50 to 500 cells of a virus sensitive strain. After a few hours incubation the cell densities rose to about 109 cells/ml. 0.1 ml of each liquid culture was spread on petri dishes containing culture medium treated with a large number of bacterial viruses (ca. 1014). After overnight incubation, resistant cells formed colonies visible to the naked eye. Almost all the bacteria plated-out (ca. 108) were destroyed (lysed) by the virus and died.
In accordance with expectations, the results were unequivocal. The fluctuation in the number of resistant cells in the cultures tested in parallel was very great. In one experimental series there were petri dishes with no colonies and some with more than 500. The distribution of resistant cells clearly showed itself to be clonal. The mutation event most probably must have arisen before virus contact had taken place and must therefore be spontaneous or 'chance'. The virus simply selected the resistant cells.
This result was in total agreement with the hypotheses of Darwinian evolution. The resulting excitement was so great that Delbrücks warning at a conference in 1947 not to generalise from his discovery went unheard (see Stahl8). After the presentation of a paper by Ryan et al.9, in which it is shown how the number of genetic changes in a metabolic mutant increased in a matter of days, he said 'In the case of mutations of bacteria ... to phage resistance ... the phage does not cause themutations. In your case of mutations permitting the mutants to utilize succinate... as a sole carbon and energy source ... it is an obvious question to ask whether this particular medium had an influence on the mutation rate.... One should keep in mind the possible occurrence of specifically induced adaptive mutations'.
Another milestone in the development of a theory of spontaneous mutation was reached when Lederberg and Lederberg, using their replica-plating method, managed to isolate from a virus-sensitive bacterial strain cells which were resistant to the virus without having come into contact with it10. This showed that resistance mutations arise spontaneously, that is without contact with the selecting agent.
The discovery of the double-helical structure of DNA by Watson and Crick11 and the biochemical investigations of the replication events in the material of inheritance (c.f. Alberts et al.12) made possible an explanation of spontaneous mutation. In principle perfect replication of the material of inheritance is guaranteed by the physico-chemical conditions of its molecular structures. A host of proteins participate in this synthesis and minimise the errors which arise during replication. Such errors can manifest as mutations and are interpreted as the reason why evolution happens at all. It is also clear that the faithfulness of replication of DNA is directly proportional to the size of the genome (the quantity of the substance of inheritance) (c.f. Maynard Smith13). The smaller the genome the higher the mutation rate. Put another way, a text with thousands of words can be transcribed many times without distorting the meaning when one wrong word is substituted in every ten thousand. If errors were to occur with the same frequency in a text with a hundred thousand words, ten words would be altered at each transcription. With frequent transcription, distortion of the meaning could not be ruled out. To avoid unacceptable changes, the transcription accuracy would have to be increased.
If during replication of the material of inheritance the mutation rate is too high it could have catastrophic consequences for the organism concerned. But if DNA replication were absolutely perfect, undirected 'chance' evolution of living organisms would be rendered impossible. Spontaneous mutations are an essential component or instrument of the evolution of all living beings on earth. Such mutations are not determined by environmental conditions but arise mainly through replication of the material of inheritance.
Adaptive mutations: the concept clarified
In order to deal properly with adaptive mutations it is necessary first to clarify a misunderstanding and a conceptual confusion. Equating the concepts 'inheritance of acquired characteristics' and 'adaptive mutations' is often criticised (c.f. Lenski et al.14). The first explicitly emphasises the fact that characteristics must first be formed before they can be passed on. But the second concept implies that known mutations are seen to revert to the wild type. After a reversion event the cells concerned exhibit characteristics that were shown by their ancestors prior to the mutation. Reversions provide modern genetics with a tool that allows phenotype and genotype to be kept equally in view. I will use the two expressions 'inheritance of acquired characteristics' and 'adaptive mutations' synonymously, because in both cases it is true to say that there must be an effect on the material of inheritance directed from the environment and the living organism. Furthermore, new characteristics that must be inherited can manifest only through modification of already existing heritable material.
Another difficulty concerns the view that the theory of adaptive mutations is 'Lamarckian' (c.f. Marx15, Symonds16, Mayr6 ). There are several objections to this. As already mentioned Darwin and Haeckel include the inheritance of acquired characteristics in their theories, although they have both expressly countered Lamarck's teleological evolutionary theory. The term 'adaptive mutations' expresses the fact that the constraints of life and the environmental conditions not only work selectively on preformed characteristics, but also can determinenew ones. Such characteristics can be described as 'goal-directed' without, like Lamarck, presupposing an evolutionary goal. Even Darwin3 coined an expression for this: 'Effects of habit and the use or disuse of parts'.
Early supporters of the theory of adaptive mutations
Since Mendel, adaptive mutations became a topic of increasing interest and was described in reputable journals. One of the most outspoken representatives of the theory was Kammerer. On one of his trips to the USA he was even heralded by the newspapers as the 'new Darwin' (Koestler18). In many publications and using a wide variety of animals he sought to demonstrate the existence of the inheritance of acquired characteristics (c.f. Kammerer19,20). He described them for the midwife toad Alytes obstetricans. By raising the temperature of its surroundings the animal can be made to depart from its usual behaviour of reproducing in water. Under the new conditions the male forms 'nuptial pads'. These thumb-like structures occur on the forelimbs of many amphibians that reproduce under water. It is thought that they help the males get a better hold during copulation. After copulation on land, the male carries the strands of spawn containing the fertilised eggs around with him wrapped round the hind leg until the larvae hatch. Under the new conditions the spawn remains in water. The tadpoles which have undergone their embryonic development in water exhibit external gills similar to the larvae of other toads and frogs.
Both nuptial pads and external gills can be regarded as an expression of an adaptation to the new conditions. Both features also appear in subsequent generations even when the animals are returned to normal living conditions. They appear to be genetically fixed.
More convincing were the experiments with the sea squirt (ascidian), Ciona intestinalis. Kammerer described them as providing the most significant evidence for adaptive mutations. After repeated amputation of the terminal tubes which are used for feeding and excretion, these organs grow extremely long. Specimens with long tubes give rise to long-tubed offspring thus giving rise to the supposition that inheritance of acquired characteristics is involved. To exclude the possibility of prior chance mutation causing the long tubes, Kammerer removed the gonads. After regeneration of these organs long-tubed specimens once again developed out of the newly formed germ cells. Thus it seemed that clear evidence for acquired characteristics had been obtained.
Kammerer's experiments are clearly described and from their methodical structure withstand critical appraisal today. Nevertheless alternative explanations such as cytoplasmic or maternal effects that could bring about developmental modifications without changing the DNA would nowadays have to be excluded. In view of the tragic circumstances of Kammerer's death, which is interpreted as admission of his scientific fraud, Koestler18 emphasised the need for a repeat of these experiments.
In Russia, Mitschurin (see Sankjewitsch21), using the most varied cultivars investigated the questions of environmental influence on seeds and rootstock on fruit. He too observed environmental influences which were genetically fixed. But his work fell into disrepute and oblivion probably through the political polemic from and surrounding Lysenko and his unsuccessful wheat vernalization experiments.
Waddington22 and Piaget23 reported theoretical considerations, suggestions and descriptions regarding experiments on adaptive mutations which will be discussed below. At the level of molecular genetics, the phenomenon of adaptive mutations has been reported for flax (Marx15, Cullis24).
Adaptive mutations since 1988
The publication of evidence for adaptive mutations by Cairns et al.25 brought about a change. The standing of both the author, as former director of the respected Cold Spring Harbour Laboratory, together with that of the journal Nature in which the work was published, left littledoubt as to the scientific quality of the work and sparked-off discussion and controversy which has lasted to this day. Many 'main stream' geneticists felt obliged to take positions and carry out further experiments. Since then there have been a considerable number of publications describing adaptive mutations for various microorganisms and cellular anabolic and catabolic processes. Furthermore some authors tend to the view that this form of inheritance also plays a part in tumour formation (for reviews see Foster26,27).
Cairns' group investigated the frequency of reversion of a well known and genetically characterised metabolic mutant lac in E.coli. Cells with this mutation can no longer use lactose and are dependent for their growth on glucose or another sugar in the growth medium. The reversion of the mutation to lac+ can easily be demonstrated by plating out the cells onto a medium containing lactose and a colour indicator. Revertant cells form red colonies.
In an experimental design based on that of Luria and Delbrück7, analysis of the frequency distribution of sixty cultures prepared in parallel showed that spontaneous reversions must have taken place before selection. However, others appeared to have occurred adaptively only after contact with lactose the selecting agent. Further observations showed that the number of reversions increased when the petri dishes containing lac- bacteria were incubated for several more days. Obviously in the course of time more revertants were generated. Control experiments showed that reversions only occurred when the growth medium contained lactose. If this sugar was missing, or only sprayed on the bacteria after one or more days, the number of lac+ colonies remained unchanged with longer incubation. Finally, it was shown that with mutations such as valR, which are not selectable, no reversions occurred. Increase in the reversion rate only resulted when it was 'useful' for the multiplication and growth of bacteria. They were without doubt adaptive, or, as Cairns' group put it, directed.
The results stood in contradiction to the theory of spontaneous mutations. The reversions occurred only during selection and in appropriate environmental conditions. Lactose had to be present. The medium appeared to 'entice' out the reversions. Particularly noteworthy is the fact that they only took place during the stationary phase when DNA replication errors cannot occur. None of these observations were new. In 1961 Ryan's group had already published work suggesting mutation events without replication (Ryan et al.9 and Symonds28), but this received little attention amongst geneticists. The Cairns' group managed only to publish once more in their entirety the most important observations evidencing non-spontaneous mutations.
The Cairns work is also noteworthy for another reason. Since 1943 bacterial genetics has concerned itself with cells in the exponential growth phase and investigated many phenomena which determine the life and death of bacteria. But adaptive mutations occur only when cells are not dividing and even then only when the genetic change is choosing between growth/division or rest. For this reason it is possible to speculate as to the significance of adaptive mutations for natural conditions. From the still young science of the genetics of the stationary phase, there are reports which suggest that adaptive mutations occur also under natural conditions (Kolter29).

Hall's work
Adaptive mutation research was greatly extended in variety and scale by Hall, a microbiologist based in Rochester (USA). Working intensively with the conceptual problems of the new theory, he investigated several organisms and catabolic processes as part of his interest in reversions of point mutations (substitution of individual base pairs) and deletions. The conclusions he drew from this were uncertain and provisional. Where observed changes were at first adaptive (Hall30), they later were explained as spontaneous (Hall31,32), or occasionally in the following paradoxical way 'Spontaneous point mutations that occur moreoften when advantageous than when neutral' (Hall31). These he called 'selection induced mutations' in a later publication (Hall33), and he ultimately reached the conclusion that there is indeed a phenomenon of adaptive mutation, but there is no explanation for it (Hall34).
Hall's initial work was on the double mutation in the bgl operon in E.coli (Hall30). This operon codes for the necessary enzymes for the catabolism of glucosides. The individual reversion rates experimentally determined for the two mutants is 4x10-8 and <2x10-12 per cell division. Assuming that the two mutations are independent from one another, in bacterial strains with both mutations the reversion rate, given by the product of the two individual reversion rates, is 8x10-20. Such an event would never be observable under experimental conditions because at least 8x1020 cells would need testing, thus requiring at least 100,000 litres of liquid culture. Bacteria incubated for two to three weeks in petri dishes formed colonies of revertant cells able to catabolize glucosides. The reversion rate of was 2x10-8, far higher than expected. Here too reversion managed to take place in the stationary phase and only when glucosides were present in the medium.
Further work investigated point mutation behaviour in the tryptophan operon in E.coli (Hall31,33,35). Once again the reversion rate was far higher than was expected on the basis of spontaneous mutation and appeared under conditions of selection. The author also demonstrated that reversion was independent of DNA replication and increased according to the length of time cells were in contact with the selective substrate. Control experiments ruled out the possibility that cryptic growth of cells or retarded division of preexisting revertants determined the reversions. Experiments with baker's yeast Saccharomyces cerevisiae (Hall36) showed that adaptive mutations can also be demonstrated for eukaryotes.
Objections and attempts at a molecular explanation
Critical and partially justified objections to the idea of the existence of adaptive mutations were not slow in appearing. Several experiments were repeated with more stringent controls. The mobilisation of the bacterial virus Mu which the Cairns group25 observed and interpreted as a directed mutation proved to be a spontaneous mutation (Mittler and Lenski37). The high reversion rate which Hall30 had observed with double mutants was explicable in terms of the growth of intermediary genotypes (Mittler and Lenski38). Finally it was shown that the difference in reversion rates between two independent mutations (Cairns et al.25) could be ascribed to known physiological processes (MacPhee39).
The criticism had the result that in subsequent work the necessary control experiments were carried out. Thus in his investigation of the reversion of mutations in the tryptophan operon Hall34,35,36 was able to rule out that adaptive effects were arising through intermediary growth or death of cells. Both possibilities would have given a deceptive nominal increase in the mutation rate thus allowing spontaneous mutations to appear as adaptive events (Mittler & Lenski40). The criticism as to the reality of adaptive mutations eventually led to their experimentally verified acceptance.
Still unsolved was the question of how adaptive mutations could occur. The search for an explanation based on the underlying molecular processes was linked to the hope that phenomena which would not fit in could nevertheless eventually be interpreted 'classically'. The lynch pin in the structure of modern genetics is still its central dogma which states that 'information' flows only from the material of inheritance to the protein (DNA>RNA>protein). This underpins the idea that heritable changes are never determined by protein. The phenotype has no influence on the genotype. Since the discovery of retroviruses, whose viral RNA chromosome after successful infection is transcribed into DNA, the dogma is only partly valid. Adaptive mutations now threaten to overthrow it completely.
To explain adaptive mutations, various working hypotheses were formulated (summarised in Koch41) which, under selective conditions and with known molecular mechanisms would have allowed a raised mutation rate to be assumed. The postulates of three most important hypotheses are stated here.
Hypermutability: The basic mutation rate in bacteria under stress conditions is significantly raised (Symonds42, Hall31) and that amongst many chance mutations some also occur which are selected.
Increase in the mutation rate through reverse transcription (Stahl43): In cells in the stationary phase there are always transcription processes going on, i.e. DNA is transcribed to RNA. It is known that in these processes the transcription accuracy is relatively small and thus the mutation rate is increased. RNA molecules arising in this way which enable the synthesis of a protein necessary for growth can, after being changed to DNA, replace the original chromosomal sequences.
Slow repair (Stahl43): Under stationary phase conditions small pieces of DNA are broken down and resynthesised. The repair mechanisms which normally replace wrongly inserted nucleotides are not active.
All hypotheses were experimentally tested and had to be rejected. With hypermutability the frequency of the adaptive reversions in the trp operon signified a mutation rate of 0.04 per base pair (Hall32). Thus on average every 25th base pair would have to be substituted. Such a high rate would without doubt have been lethal for the bacteria. Hall investigated the relevant gene locus by sequencing to determine whether, in the neighbourhood of the necessary reversion, other substitutions had taken place. But he was without success. Such a 'directed' localised increase in the mutation rate would however have only postponed the crisis of finding an explanation.
The second hypothesis also had to be rejected (Hall31) because with some bacterial strains which exhibit adaptive mutations no reverse transcriptase activity has so far been demonstrated.
The slow repair hypothesis failed because as well as the expected selective mutations, independent mutation events in other genes would also have had to occur (Hall32). In no case could these be detected.
That the molecular basis of adaptive mutations is of a non-classical kind was revealed by a series of unexpected results, which, however, in retrospect an unprejudiced observer would hardly wonder at. Adaptive mutations always appear in the bacterial stationary phase. DNA turnover is minimal. Mutation events are time dependent. But spontaneous mutations occur by maximal DNA turnover in the phase of exponential growth and are dependent on replication.
A first indication of the difference at the molecular level in the occurrence of the two types of mutation was given by the analysis of the spectrum of reversions under selective (adaptive) and non-selective (spontaneous) conditions (Hall44). Thirteen strains with different mutations in the same gene (lac) were used to compare reversion rates during exponential growth with those during the stationary phase. The rates were as much distinguished by the two culture conditions as by the individual strains. Base pair substitutions, insertions and deletions are dependent on the physiological state of cells and the type of change in the environment.
Unlike spontaneous mutations, adaptive mutations are dependent upon various components of the recombination system (RecA, RecBCD, Harris et al.45). Under normal conditions, this system mediates homologous recombination between chromosomes and enables insertions and deletions of DNA sequences in the bacterial chromosome. If the proteins of the RecBCD system are lacking, adaptive mutations no longer take place. These findings have been described as progress towards the understanding of genetic intelligence (Thaler46).
Another piece in the jigsaw was the discovery that not only the recombination system but also intercellular DNA transduction, the transfer of genetic material during bacterial conjugation (a kind of primitive sexual pairing), participates in the appearance of adaptivemutations.
Conjugation proved significant is several ways: for bacterial strains which had the selective gene on the chromosome rather than on the transduction plasmid, the reversion rate was 25 to 50 times smaller (Radicella et al.47, Galatski & Roth48). Removal of the conjugation apparatus with detergents or additional mutations in the enzymes of the transfer function reduced the adaptive mutation rate to the same extent.
According to Shapiro49, these results have far reaching consequences for evolutionary theory, although he also holds that they make the hypothesis of 'directed mutation' superfluous. The transfer of the transduction plasmid is dependent on DNA replication, which is why mutations associated with chromosomal replication can occur by 'chance'. Even so the results show that the rate of meaningful mutations can be significantly increased by selection and that by transduction, which can be regarded as a primitive form of intercellular communication, meaningful mutations can be passed on. Recombination and plasmid transfer are cellular functions which allow an active reaction to its environmental conditions. A significant component of genetic variation is without doubt no longer attributable solely to chance events in the replication of the material of inheritance, but can only be understood by considering the relationships between living organism and the world in which it lives.
Non-molecular concepts of adaptive mutation
I hope to have shown in the foregoing that modern genetics has reached a turning point. But true insight as to the significance of adaptive mutations cannot be gained through describing molecular processes. This is because, by reducing the phenomena to molecular processes, the fundamental and qualitative differences between spontaneous and adaptive forms of inheritance are overlooked. The description gets lost in detailing DNA-protein interactions. But the differences lie in the possibility of manifesting in the most varied of ways relationships and interconnections between organism and environment and of making these available to the next generation. They are of course dependent on molecular processes, but they are not determined by them. Thus molecular genetics points to the necessity of looking beyond its current paradigm for alternative concepts and approaches to organisms and their inheritance. Paradoxically this leads first to the rediscovery of theoretical foundations which have been forgotten. I shall illustrate this with reference to the work of three individuals.
I turn first to a pamphlet essay by Steiner50. In it the 'inheritance of acquired characteristics' is seen as a consequence of Haeckel's biogenetic law. Steiner emphasises that without this law a monist evolutionary theory has no validity. The essay is in essence against the last vestiges of vitalism and the preformation theory associated with Weismann.
Monistic evolutionary theory signified a big challenge to understand 'being' and 'appearance', requiring one to grasp the organic as a process which takes place as much from top downwards (from idea to world of the senses) as from bottom upwards. In this process both aspects - the ideal in the type at work in the organism and the real as its appearance in the world of the senses - undergo changes and metamorphoses in reciprocal interdependence.
These ideas are substantially developed in an earlier essay by Steiner51 in which the relationship of the Goethean idea of type (archetype) to the organism which actually manifests is clarified and discussed. It is the essence of all living organisms that they respond inwardly to the experiences they undergo in their development and thus eventually pass them on to their offspring.
Waddington22 offered a further theoretical principle. According to him there are two distinct possibilities for genetic variation. One concerns isolated features which are altered accidentally. Industrial melanism in the peppered moth Biston betularia is a textbook example of this and for modern evolutionary biology provides irrefutable evidence for theoccurrence of spontaneous mutation. The other possibility for genetic variation concerns features which are embedded in the totality of the organism and its environment. Waddington's example for this is the forequarters of the gibbon and pangolin (scaly ant-eater): the gibbon's forelimbs point in their slenderness, length and exceptional mobility to activities such as climbing and hanging, whereas the form of forelimbs of the scaly ant eater exhibit rigidity, shortness and compactness of bone formation which are easily comprehensible in terms of a digging function. Both animals reproduce in their entire bodily make up the specific orientation of their different activities and modes of behaviour. The logical construction of the entire form is unmistakable. According to Waddington it is extremely unlikely that the extremities have come about by a large number of accidental individual changes. It seems more plausible that they were formed through the specific behaviour of the animal in its respective habitat during the course of the evolution of the species.
Waddington used Drosophila experiments to develop the concept of organismic totality and adaptive reaction to specific qualities in the surroundings. He described short term physiological changes that had become genetically fixed 'genetic assimilation'. Such changes as take place over a long period, he described as 'evolutionary adaptation'.
Piaget23, the Swiss developmental psychologist, provides a third fundamental consideration. The idea of adaptive mutations was a logical outcome of his investigations into cognitive processes and their biological basis. It is an undoubted fact that the human being gains knowledge by constantly taking in experiences and as a result of this process is able to pass on faculties. According to Piaget the act of cognition is only possible through (subjective) receptivity and (objective) external stimulus. It produces a relationship between object and subject. Thoughts are contoured by percepts and determine our intentions. Intentionality fixes what is extracted from the sense perceptible world and determines the framework of elements of observation. As zoologist, I look primarily at animals and through an interest in morphology further restrict observations to their form.
Both aspects, thinking and perceiving, reciprocally determine and alter one another. Because cognitive processes have and must have a biological basis, this in turn must have a functional structure like the cognitive process itself. Organic regulatory processes follow the same laws as those of cognition: they undergo adaptive change and development, not only physiologically but also genetically. Piaget's morphological investigations of the water snail (Lymnaea stagnalis L.) in a wide range of habitats appeared to confirm the hypothesis of adaptive mutation.
The discussion of these three authors provides more than a foundation for a theory of adaptive mutation. All three overcome the materialistic tendency in the modern view of heredity. With Steiner, the overcoming is quite explicit. Development and heredity can only be grasped through a combination of sensory and supersensible processes. All living organisms are an expression and result of ideal-material processes. The unity of matter and spirit is the basis of Steiner's monist evolutionary theory.
With Waddington the overthrow of the materialistic view of heredity is reflected in the idea of organismic wholeness, which is not to be thought of as solely material. Relationships and interactions with the environment belong just as much to the organism as to its organs, cells and molecules. The basis of his evolutionary theory is unified life of organism and surroundings.
Finally, Piaget postulates unity of cognitive and living processes. As psychologist he did not doubt the former, nor as biologist the latter. One could describe his theory of development as a monism of the soul, keeping consciousness and body together.
Complementary genetics and enlivening of the concept of heredity
To quote Steiner50: 'the essence of monism is the idea that all occurrences in the world, from the simplest mechanical ones to thehighest human intellectual creations, evolve themselves naturally in the same sense, and that everything which is required for the explanation of appearances, must be sought within that same world.' In relation to adaptive mutation, this view means, as we have seen, that genetic changes must be understood as an expression of an interrelationship between living organism and its habitat. Steiner, Waddington and Piaget have shown approaches to such an understanding. Bockemühl's work on groundsel Senecio vulgaris provides striking examples of such an understanding52.
Spontaneous mutations also have a part to play in a monist evolutionary theory. They show that genetic changes can also occur in the relation of the organism to itself. They are complementary to adaptive mutations. The polarity of world relation and self relation and its overcoming through the organism itself are hallmarks of the living. I have attempted to elaborate this in studies on developmental processes in amphibians53. Similar polarities have come to light in other studies (Pankow et al.54, Schad55, Suchantke56,57). Spontaneous and adaptive mutations are not causes of the variation in form and function, but results of a variety of organic processes. These thoughts will be extended in a further article. Furthermore, I shall report on experiments investigating the existence of adaptive mutations in Drosophila.

Acknowledgement
I thank all my colleagues in the Goetheanum Research Institute and especially Wilfried Gabriel for our many fruitful conversations and Norbert Pfennig for drawing my attention to the work of Piaget. I thank Hans Christian Zehntner, Jochen Bockemühl and Wilfried Gabriel for their critical comments on the manuscript and Birgit Althaler for the stylistic improvements. I gratefully acknowledge support over many years' work from the Rudolf Steiner-Fonds für wissenschaftliche Forschung.

References
1    Lamarck, J. B. (1809): Philosophie zoologique. Paris.
2    Lefèvre, W. (1984): Die Entstehung der biologischen Evolutionslehre. Frankfurt, Berlin.
3    Darwin, C. (1859): The Origin of the Species
4    Haeckel, E. (1866) Prinzipien der generelle Morphologie der Organismen., Berlin
5    DeBeer, G. (1958): Embryos and Ancestors. Oxford.
6    Mayr, E. (1984): Die Entwicklung der biologischen Gedankenwelt. Berlin, Heidelber, New York, Tokyo.
7    Luria, S.E. and Delbrück, M. (1943): Mutations of bacteria from virus sensitivity to virus resistance. Genetics, 28, 491.
8    Stahl, F. W. (1990): If it smells like a unicorn. Nature 346, 791.
9    Ryan, F., Nakada, D. and Schneider, M. (1961): Is DNA Replication a Necessary Condition for Spontaneous Mutation? Z. Vererbungsl. 92, 38.
10    Lederberg, J. and Lederberg, E. (1952): Replica plating and indirect selection of bacterial mutants. J. Bacteriol. 63, 399.
11    Watson, J.D. and Crick, F.H.C. (1953): Molecular structure of nucleic acids: A structure for deoxyribose nucleic acid. Nature 171, 737.
12    Alberts, B., Bray, D., Lewis, J., Raff, M., Roberts, K. and Watson, J.D. (1989): Molecular Biology of the Cell. New York.
13    Maynard Smith, J. (1989): Evolutionary Genetics. Oxford, New York, Tokyo.
14    Lenski, R. E., Slatkin, M. and Ayala, F.J (1989): Mutation andselection in bacterial populations: Alternatives to the hypothesis of directed mutation. Proc. Natl. Acad. Sci. USA 86, 2775.
15    Marx, J. L. (1984): Instability in Plants and the Ghost of Lamarck. Science, 224, 1415.
16    Symonds, N.D. (1991): A fitter theory of evolution? New Scientist 21, 30.
17    Mayr, E. (1994): War Darwin ein Lamarckist? Natw. Rdsch. 47. Jhrg. Heft 6, 240.
18    Koestler, A. (1971): The Case of the Midwife Toad. New York.
19    Kammerer, P. (1923): Breeding experiments on the inheritance of acquired characters. Nature 111, 637.
20    Kammerer, P. (1924): Neuvererbung oder Vererbung erworbener Eigenschaften. Stuttgart-Heilbronn.
21    Sankjewitsch, E. (1950): Die Arbeitsmethoden der Mitschurinschen Pflanzenzüchtung. Stuttgart.
22    Waddington, C.H. (1959): The Evolution of an Evolutionist.
23    Piaget, J. (1974): Biologie and Erkenntnis. Über die Beziehungen zwischen oganischen Regulationen und kognitiven Prozessen. Frankfurt a.M.
24    Cullis, C.A. (1988) Control of variation in higher plants. In: Evolutionary Processes and Metaphors; Mae-Wan Ho and Sydney W. Fox, Chichester.
25    Cairns, J., Overbaugh, J. and Miller, S. (1988): The origin of mutants. Nature 335, 142.
26    Foster, P. L. (1992): Directed Mutation: Between Unicorns and Goats. J. Bacteriol. 174, 1711.
27    Foster, P. L. (1993): Adaptive Mutation: The Uses of Adversity. Annu. Rev. Microbiol. 47, 467
28    Symonds, N.D. (1993): Francis Ryan and the Origins of Directed Mutagenesis. Mutation Res. 285, 9.
29    Kolter, R. (1992): Life and Death in Stationary Phase. ASM News 58, 75.
30    Hall, B. G. (1988): Adaptive Evolution That Requires Multiple Spontaneous Mutations. I. Mutations Involving an Insertion Sequence. Genetics, 120, 887.
31    Hall, B. G. (1990): Spontaneous Point Mutations That Occur More Often When Advantageous Than When Neutral. Genetics 126, 5.
32    Hall, B. G. (1991a): Is the Occurrence of Some Spontaneous Mutations Directed by Environmental Challenges? The New Biologist, 3, 729.
33    Hall, B. G. (1991b): Increased Rates of Advantageous Mutations in Response to Environmental Challenges. ASM News 57, 82.
34    Hall, B. G. (1991d): Adaptive evolution that requires multiple spontaneous mutations: Mutations involving base substitutions. Proc. Natl. Acad. Sci. USA 88, 5882.
35    Hall, B. G. (1993): The Role of Single-Mutant Intermediates in the Generation of trpAB Double Revertants during Prolonged Selection. J. Bacteriol. 175, 6411.
36    Hall, B. G. (1992): Selection-induced mutations occur in yeast. Proc. Natl. Acad. Sci. USA 89, 4300.
37    Mittler, J. E. and Lenski, R. E. (1990): New data on excisions of MU from E. coli MCS2 cast doubt on directed mutation hypothesis. Nature 344, 173
38    Mittler, J. E. and Lenski, R. E. (1992): Experimental evidence for an alternative to directed mutation in the bgl operon. Nature 356, 446.
39    MacPhee, D. G. (1993): Directed mutation: paradigm postponed. Mutation Res. 285, 109.
40    Mittler, R.E. and Lenski, R. E. (1993): The Directed Mutation Controversy and Neo-Darwinism. Science 259, 188.
41    Koch, A. L. (1993): Genetic Response of Microbes to Extreme Challenges. J. theor. Biol. 160, 1.
42    Symonds, N.D. (1989): Evoltuion: Anticipatory Mutagenesis? Nature 337, 119.
43    Stahl, F. W. (1988): A unicorn in the garden. Nature 335, 112.
44    Hall, B. G. (1991c): Spectrum of mutations that occur under selectiveand non-selective conditions in E. coli. Genetica 84, 73.
45    Harris, R.S., Longerich, S. and Rosenberg, S.M. (1994): Recombination in Adaptive Mutation. Science 264, 258
46    Thaler, D.S. (1994): The Evolution of Genetic Intelligence. Science 264, 224.
47    Radicella, J.R., Park, P.U. and Fox, M.S. (1995): Adaptive Mutation in Escherichia coli: A Role for Conjugation. Science 268, s. 418
48    Galitski, T. and Roth, J.R. (1995): Evidence that F Plasmid Transfer Replication Underlies Apparent Adaptive Mutation. Science 268, 421
49    Shapiro, J.S. (1995): Adaptive Mutation: Who's Really in the Garden? Science 268, s. 373
50    Steiner, R. (1900): Haeckel und seine Gegner. In: Methodische Grundlagen der Anthroposophie, GA 30, Dornach 1989.
51    Steiner, R. (1891): Über den Gewinn unserer Anschauungen von Goethes naturwissenschaftlichen Arbeiten durch die Publikationen des Goethe-Archivs. In: Methodische Grundlagen der Anthroposophie, GA30, Dornach 1989.
52    Bockemühl, J. (1980) Eine neue Sicht der Vererbungserscheinungen. In: Lebenszusammenhänge erkennen, erleben, gestalten. Published by the author. Dornach, 2nd Ed. 1986.
53    Wirz, J. (1990): Schritte zu einem neuen Ansatz in der Entwicklungsbiologie. Elemente der Naturwissenschaft. 53(2), 3.
54    Pankow, W. et al. (1991) The significance of Mycorrhozas for Protective Ecosystems. Experientia 47, 391.
55    Schad, W. (1983) Zur Biologie der Gestalt der mitteleuropäischen buchenverwandten und ahornartigen Bäumen. In: Goetheanistische Naturwissenschaft, Bd. 2. Stuttgart.
56    Suchantke, A. (1974) Biotoptracht und Mimikry bei afrikanischen Tagfaltern. Elemente der Naturwissenschaft, 21, 1
57    Suchantke, A. (1976) Biotoptracht bei südamerikanischen Schmetterlingen. Elemente der Naturwissenschaft, 21, 1