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  •                                 NETFUTURE
                Technology and Human Responsibility for the Future
    Issue #31      Copyright 1996 O'Reilly & Associates       November 5, 1996
                Editor:  Stephen L. Talbott (stevet@netfuture.org)
                         On the Web: http://netfuture.org
         You may redistribute this newsletter for noncommercial purposes.
    *** Editor's note
    *** The trouble with genetic engineering (Stephen L. Talbott)
          Towards a science of the whole organism
    *** About this newsletter

    *** Editor's note

    As those of you who are "long-time" subscribers are aware, I've never done much to promote NETFUTURE to a larger audience. Nevertheless, the newsletter's profile has steadily been rising--a reflection in part of its impressively literate and influential readership. This has me wondering whether I ought to undertake a somewhat more aggressive effort to "carry the newsletter out into the world"--and also to look for possible alliances of mutual benefit, or affiliations, or sponsorships, or--to quote Bob Dole--"whatever." All this, of course, is tied to my own questions about whether and how to continue with the newsletter under my new (and not well supported) circumstances.

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    *** The trouble with genetic engineering

    From Stephen L. Talbott

    Notes concerning the book, Genetics and the Manipulation of Life: The Forgotten Factor of Context, by Craig Holdrege (Hudson, New York: Lindisfarne Press, 1996). Paperback, 190 pages, $14.95.

    [For those of you who insist upon your right to commit the ad hominem fallacy, here is my full disclosure: I was privileged, as a freelance editor, to play an editorial role with the book discussed here. The author, as it happens, is a neighbor and a friend. For those who prefer the argument from authority, I append below some comments from Lynn Margulis, Ruth Hubbard, and others. I have no financial stake in the book's publication.]

    * * * * * * * * * * * * * * * * * * * * * * * *

    First, analyze a thing down to its atoms; then model its behavior computationally. It may be that these two pillars of reductionist science come together most fatefully in genetic engineering: on the one hand, the ever popular quest for genes, and on the other hand the interpretation of the genome as a kind of database and central processing unit, computing the organism's traits. It is, as we will see, a perfect formula for the pursuit of blind power.

    The assumptions here are deeply--and almost mystically--fixed upon our scientific consciousness. They are also frighteningly misguided. But few researchers are able to say clearly why they are misguided. Craig Holdrege not only does so, but pulls it off with a profound simplicity that is stunning. Not that it will ever be easy to change our governing habits of thought. But we can at least begin to recognize the impossible places to which they would lead us.

    Genetic Gender Bending

    The cover of Nature magazine for May, 1991, showed a mouse with testicles clearly visible. This was a "female" mouse, based on normal chromosomal determinants, but male genetic material had been injected at the fertilized-egg stage. The caption on Nature's cover read, "Making a Male Mouse."

    The researchers reported that ninety-three mice were born from the experimental eggs. Of these, only five had taken up the foreign DNA, becoming "transgenic." Two of the five were male according to their chromosomes and "should" have displayed enhanced male characteristics as a result of the foreign DNA, but did not. Two were female; they "should" have become males, but did not. The fifth mouse was displayed on the journal's cover. "This mouse's testicles," Holdrege notes, "were very small and he was sterile. His mating behavior was, however, completely normal male behavior." Holdrege goes on to say:

    It is truly astounding that scientists can bring about such a significant change as sex reversal. But if we do not fix our attention merely on the one successful result (successful, that is, from the researchers' standpoint), many riddles stare back at us. One concerns the fact that four of the five transgenic mice showed no changes at all. The two transgenic female mice "should" have been male. (p. 111)
    Tongue in cheek, he adds:
    A more feministically oriented publication could well have put this interesting result in the foreground with the caption, "female mice resist attempt at male domination." One's universe of concern can determine how one looks at a result. (p. 111)
    Newspaper accounts, of course, virtually never report all the "other" experimental results. In fact, scientific journals typically do not either. But when they do, there's a consistent story to tell. Here are the results of a gene transfer experiment upon cattle:
      2,470  cow eggs were used, of which
    2,297 matured
    1,358 eggs were fertilized (in vitro)
    1,154 eggs were injected with human DNA
    981 survived this procedure
    687 embryos began embryonic development (cleavage)
    129 embryos were transferred into oviducts of cows
    21 cows became pregnant
    19 calves were born
    2 calves were transgenic
    Actually, one of the two calves was only partially transgenic. The foreign DNA was detected in the placenta, but not in the blood or ear tissue. Moreover, "a rearrangement had occurred involving a deletion of part of the [foreign] DNA construct" (p. 112).

    Holdrege reviews many other sorts of experiment. He also points out how sadly empty-handed researchers have been in relation to the promises of human benefit from genetic discoveries. The problem is that the simplistic notion that "genes cause traits" inevitably dissolves into a sea of complexities upon further investigation. One case among the ones Holdrege describes involves the "cystic fibrosis gene," discovered in 1989:

    As often happens, euphoria greeted the discovery of the alleged cause of the disease. Since then the picture has become more and more complex. The "healthy" gene does not just mutate (change) in one place, but 350 different mutations have been found. These are partially correlated with different symptoms. Some healthy individuals, for example, can have mutations that are identical to those usually found in people with cystic fibrosis. If one considered merely their genes, then, as the researcher Barbara Handlelin states, "they should have cystic fibrosis, but they clearly don't." (p. 85)
    Regarding the diverse results of the animal experiments, Holdrege notes that "we do not control what occurs in the organism." While the surgical and analytical procedures are precise and well defined, "once the threshold between laboratory procedure and organism is breached, everything becomes opaque. The life of the organism takes over, exhibiting a certain autonomy despite all manipulation." He concludes: "Even if the effects of our actions penetrate into the organism, our understanding does not."

    However, there is a reason why the researcher tends not to worry about all the "other" results. The one transgenic mouse or calf--if it turns out fertile--enables him to produce and maintain a line of genetically altered organisms. In other words, there is effective power given to him in that one successful result, even if the achievement stands against a background of mysterious failures. This is as good an example as any of the tendency within science to exchange understanding for power--a devil's bargain if ever there was one.

    The Expression of Heredity

    Holdrege's own concern is to understand. What are we ignoring, he wonders, in that vast, "opaque background of success"? Nothing less than the living organism in all its wholeness and resilience. What the non- reduced organism teaches us about heredity is a remarkable story of plastic potential expressing itself fluidly within particular environments. But at the same time one can say it is limitation--the organism's specific identity--that expresses itself, for there are bounds to its variability. It preserves its own, recognizable nature amid all the freedom of expression.

    Heredity, then, is not something fixed and mechanical; it can only be understood in this living play of plasticity and limitation as the organism realizes its unique existence.

    No thing is inherited....The openness of the plant to its surroundings precludes fixity. The plant could not develop and, in developing, relate to the specific conditions of its surroundings if it were fixed and rigidly determined. The capacity to develop out of an undetermined state lies at the basis of heredity.
    Holdrege tries to open our eyes to this capacity, beginning with the dandelion. Not the dandelion in the laboratory, however, but the dandelion between the cracks of the sidewalk in front of your house, the dandelion competing with the grass in your yard, and the dandelion in the woods. (How many geneticists today would present their readers with drawings of carefully preserved leaves from such environments!) These plants are remarkably different in leaf shape and overall growth pattern, yet they are all recognizably dandelions. A species unity shines through all the extraordinary variety.

    (Our recognition of this unity, incidentally, is not a recognition of something material in the usual sense of the word. No individual leaf form or arrangement of leaves is exactly like any of the others. What we recognize as the reality of the dandelion is qualitative and immaterial, living between the "data" given as sense perceptions.)

    What the dandelion "is," in other words, can only be seen throughout the range of its diverse responses to different environments--and also throughout its entire life cycle from seed to leafy plant to flowering plant to seed again. A lazy thinking would identify dandelions statically and abstractly by counting pistils, stamens, leaf lobes, (and chromosomes). It requires a more muscular and qualitative inner effort to grasp in a revelatory way the "dandelion character"; but when we have done so, we can forever afterward "recognize the nature of the species plastically expressing itself in every plant characteristic" and in every environment (p. 48).

    Holdrege also talks about animal heredity, where the plasticity is not so much a plasticity of form, as in plants, but a plasticity of behavior. And he talks about human plasticity, which operates at a higher level yet. But even at the solid, physical level of the bones, the human form is surprisingly fluid and adaptable. Astronauts living in orbit lose bone mass. The bones in the racket arm of a tennis player are thicker than those in the other arm. The thigh bones of long-time soccer players are thicker than those of non-athletes.

    Similarly with bone contours. Holdrege shows an x-ray image of the remarkably bowed legs possessed by an 18-month-old boy. If subject to nothing more than mechanical stresses, the legs would only have flared more extremely as he put increasing weight upon them. But at five years of age in the course of normal development, this boy's legs grew as straight and strong as could be. "This indicates that not merely an accommodation to stresses is occurring, but in a certain sense stresses are being overcome by the tendency toward uprightness" (p. 146).

    In other words, we cannot understand the shape of the leg bones simply as the result of a specification for "leg bone shape" in some genetic database. Among many other factors, those bones are "specified" by the distinctive human urge toward uprightness. Our usual way of thinking is to say that the upright human posture is determined by the given shape of our bones. This is broadly true, but there is also a nearly opposite truth: the child feels compelled to stand up before he has suitable instruments for doing so. Only then can his limbs become fit instruments for walking and running. In other words, within the given hereditary potential, walking and running is what produces limbs that can walk and run.

    In cases of disease we learn what happens when the upright posture is not assumed:

    The shaft of the tibia (shinbone) of a child up to about two years old has a circular form in cross section, whereas that of an adult is triangular. If the muscles of the lower leg are paralyzed at a young age, the circular form persists--"a sign that the functional demands determine the three- edged form" [quoting Benninghof and Goerttler].
    As Holdrege puts it when discussing the development of bones in the feet: "The feet we walk on when we are seven are not the ones we inherited" (p. 142).

    Mendel's Selective Vision

    It is this full-fleshed reality of the organism expressing itself in a dance of plasticity and limitation that has been willfully excluded from the modern science of genetics. Holdrege traces the act of exclusion in the pioneering work of Gregor Mendel, who founded genetics during the second half of the nineteenth century. Mendel said, in effect, "I will ignore everything having to do with plasticity, focusing solely on limitation." Here's how he stated it in his famous article of 1866:
    Some of the traits listed do not permit a definite and sharp separation, since the difference rests on a "more or less" which is often difficult to define. Such traits were not usable for individual experiments; these had to be limited to characteristics which stand out clearly and decisively in the plants. (p. 54)
    So Mendel set about looking for traits that lent themselves, without undue blurring of categories, to a binary yes or no. He found such traits in the occurrence of violet or white flowers, yellow or green seeds, round or angular seeds. And even here he narrowed his focus further by refusing to concern himself with the variation in color and shape that still occurred in flower and seed. The critical thing was to be able to classify a flower as white or not, so that the plant could be entered without ambiguity as a digit in a column of the experimental ledger.

    In other words, by ignoring all inexactness, Mendel found a way to construct a science of (relatively) exact prediction for a handful of traits.

    Holdrege allows generously for the abstract and mathematical results made possible by Mendel's method, however narrow their scope. What he asks of geneticists in turn is that they make allowance for the near entirety of the organism's life excluded by the method. It is, after all, this entirety that constitutes the "opaque background" of the genetic engineer's experiments. The organism that asserts its identity by, for example, fashioning its bones in accordance with the entire pattern of its life, is also the organism that responds in its own distinctive way to the constraint--the specificity and limitation--represented by foreign genetic material. To ignore this power of response in favor of imagined computations by atom-genes is to cut oneself off from most of the organism's reality.

    Given such a blindness to the organism as a whole, it is no wonder that ethical questions become acute--and are largely trampled upon--within the genetic sciences. While I have not chosen to discuss the ethical questions here, Holdrege deals with them in a powerful manner.

    The Limitations of Analysis

    Finally, it is worth following in some detail Holdrege's diagnosis of the error through which we view the organism as little more than a host for a microscopic set of genetic computing engines, with all the rest relegated to the opaque background.

    He tells how, in the spring of 1992, a yeast chromosome became the first to have its complete DNA sequence mapped out. One hundred forty-eight new genes were added to the thirty-four already identified. But when is a gene a gene? That is, were these genes correlated with traits, or were they just "meaningless" pieces of DNA?

    One finds this out by disturbing the genes ("gene disruption") and then looking for observable consequences. When the researchers did this with fifty-five of the newly identified genes, they discerned effects in just fourteen cases. (Further experimentation will presumably increase that number.) The researchers concluded that "our understanding of yeast physiology and cell biology is lagging behind our molecular genetic analysis." But Holdrege suggests a different way to view this whole process of gene disruption and observation:

    We gain a knowledge of genes--as opposed to a mere assertion of their material existence--only through knowledge of the organism as a whole. The more knowledge we have of the organism as a whole, the more information we have. This information is not in the genes; it is in the conceptual thread that weaves together the various details into a meaningful whole. (p. 80. Emphasis in original.)
    For example, these same researchers found a yeast gene that was homologous in structure to a "nitrogen-fixing" gene in certain bacteria. Yeast, however, do not fix nitrogen, so this particular gene must be understood differently in the two organisms. The organisms, that is, provide different contexts, and these prove critical to the functioning of the gene. "The primary genetic information alone gives no information about a gene's significance in the organism" (p. 80).

    The root problem here is the attempt to turn the gene into a mechanically conceived efficient cause. But it is impossible to build up a picture of the organism by trying to move from the part to the whole in a causal fashion. The parts, after all (as we are given them by the reigning science) result from ceaseless analysis, during which we consciously exclude everything qualitative. The mathematically sketched atom, shorn of all qualities, is the paradigmatic "part."

    But we cannot get back to the living organism of our actual experience by piling qualityless atom upon qualityless atom. Somewhere along the line we have to re-introduce the qualities we so strenuously ignored on the downward path of analysis. And since these qualities have no recognized place in the science of genetics--Mendel, remember, wanted only yesses or noes, not the luxuriant, adaptable, plastic fullness of the plant--they are typically introduced illicitly, via such loaded terms as "information." In other words, after all of our (quite literally) life- destroying analysis, we get the organism back by "projecting a whole process of knowledge into a substance" (p. 89).

    It would be far better not to play illicit games, but instead to figure out where qualities belong in science to begin with--and to keep them in view throughout all our analyses. This will doubtless prove difficult, given the tremendous, one-sided energies driving science today. But Holdrege's book provides welcome evidence of newer, fresher energies bent upon creating a science of the whole organism.

    * * * * * * * * * * * * * * * * * * * * * * * *

    From the book jacket:

    Lynn Margulis, co-developer of the Gaia hypothesis and Distinguished University Professor at University of Massachusetts, remarked that "this essay by Craig Holdrege is for all of us who want to understand the biological revolution of the late 20th century....This knowledgeable explanation is the single most accessible source not only of information...but of knowledge and wisdom."

    Wes Jackson of The Land Institute and author of New Roots for Agriculture: "Reading Craig Holdrege, I am tempted to shout that this may be the most essential new book of our time."

    David Suzuki, co-author of Genethics: "In our search for universal truths disconnected in time and space, we lose all sense of the context that made the problem interesting in the first place. All budding geneticists, indeed, all biologists, ought to read this important book."

    Ruth Hubbard, Professor Emerita of Biology, Harvard University, and co-author of Exploding the Gene Myth: In this readable book Holdrege provides a lovely exposition of living organisms not as objects but as process....[He] offers an antidote to the current mechanistic thinking about genes as causes of health, disease, and behaviors. But the special contribution of this book is that it details, simply, and with fascinating examples, how scientists' ways of conceptualizing organisms and manipulating them and their parts are at the heart of the formulations they offer about how organisms and their molecules function. The reader can thus observe how scientific observations and their interpretations fuse in the creation of systems of scientific explanation."

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    Steve Talbott :: NetFuture #31 :: November 5, 1996

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