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
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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
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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
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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.
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