Does science have enough knowledge about DNA to be able to predict and master the effects of gene transfer?


For a comprehensive non-technical condensate of this document, go to "Incomplete knowledge about DNA"


This article is the theoretical part of a series about the safety of genetic engineering. The other ones are:

  • The Safety of Genetically Engineered Foods.
  • Is there sufficient knowledge about environmental effects to justify release of GE organisms?
  • Summary paper: Is there sufficient scientific knowledge to ensure safe commercial exploitation of genetically engineered foods?


    Contents

    • Summary
    • 1. Is the scientific approach used by molecular biology sufficient to yield exhaustive knowledge of biological systems?
    • 2. Is knowledge of DNA sufficient to enable prediction of all the effects of inserting a foreign gene?
    • 3. Is the doctrine "one gene - one property" valid?

    • SUMMARY

      In genetic engineering of food, DNA code sequences (genes) are artificially inserted into the DNA code sequence of the host. An inserted gene will mostly cause the production of new proteins, in most cases foreign to the host species.

      Knowledge about DNA is incomplete for the following reasons:

      • The research approach ("reductionism") for investigating DNA and its interactions with the cell has yielded a fragmented picture, lacking appropriate means of arriving at an understanding how the parts interact as an integrated whole.
      • In biotechnology, DNA and other molecules involved have been treated as "micro-objects" made up of material particles. Even if the treatment as "objects" has provided relevant information about the DNA coding of proteins, recent research indicate that this is only part of the story. New experimentally findings demonstrate that quantum mechanical phenomena do play an important role in the workings of DNA and its control of cellular processes. This means that DNA is not a "micro-object" that can be taken apart and manipulated mechanically without completely unforeseeable complications. In other words, the theoretical foundation of genetic engineering is demonstratedly seriously incomplete.
      • Science only knows the function of genes constituting less than 2 percent of the DNA in a cell. The investigation of the remaining 98% of DNA has just begun. It may have important influences and interactions with the known genes.
      • The one-gene-one-propety doctrine, which is the very basis of genetic enginering, is outdated. The Human Genome project and other reserach has established beyond any doubt that the effects of a gene are dependent on interaction with its context. There is not enough knowledge to make it possible to predict all the effects of a gene in a foreign context.

      Conclusion

      Due to the very incomplete knowledge about DNA, it is neither possible to reliably predict the influence of a gene transferred to a foreign context nor the effect of any other genetic manipulation. Molecular biology has predicted and verified that unforeseeable metabolic disturbances may occur due to gene transfer. But, in addition to this, it cannot be ruled out that there might occur complications, the nature of which cannot even be predicted because of the incompleteness of knowledge.

      Thus, there is no basis today for excluding that so far unforeseen consequences of gene transfer may add to known risks that may make GE organsims unsuitable or even harmful as food. Already, this ignorance has most probably been the cause of one serious accident, killing 37 people and chronically disabling 1500, see The Showa Denko Tryptophan disaster.

      Furthermore, it cannot be excluded that the abnormality introduced into DNA through gene transfer may make such genes harmful to the environment in ways that cannot be imagined presently.

      From other kinds of interventions there is extensive experience that artificial manipulations of biological systems, in spite of incomplete knowledge, inevitably lead to unpredictable complications some of which may be harmful and difficult to master.

      An important consequence of this is that geneticists and molecular biologists don't have the knowledge and methods required to realistically judge the effects of genetic engineering.

      It is therefore unacceptable and potentially dangerous that geneticists and molecular biologists have an almost exclusively dominant position in the national and international bodies that evaluate the safety of genetic engineering.

      Bottom line

      The knowledge about DNA is much too insufficient and the effects of gene manipulation are too incompletely known for allowing any release into the environment of GMOs and any commercial application of GM-food production.



      "We know far less than one per cent of what will be known about biology, human physiology, and medicine.

      My view of biology is 'We dont know shit.' "

      Dr. J. Craig Venter, Time's Scientist of the year (2000). President of the Celera Corporation. Dr. Venter is recognized as one of the two most important scientists in the worldwide effort to map the human genome.

      Source: "The Genome Warrior", The New Yorker Magazine, June 12, 2000.


      1. Is the scientific approach used by molecular biology sufficient to yield exhaustive knowledge of biological systems?


        A. Is the "reductionistic" method sufficient?

        The approach used by molecular biology is called "reductionism". It dominates not only in molecular biology but in most aspects of modern bioscience. It is based on the idea that by analyzing the parts into the minutest detail, it will be possible to deduce the properties of the whole. No doubt, molecular biology has achieved very advanced methods of analyzing the finest parts of living cells. But will this knowledge yield sufficient information to understand the whole? This has been the object of debate for decades.

        Already several decades ago, some scientists pointed out that a key feature of life processess is the great interdependence of the parts. This means that no part, no detail can be fully understood without reference to all other parts. They also pointed out that in such systems, the interactions of the parts leads to the emergence of properties that cannot be deduced from knowledge of the parts. You will find an excellent overview of this issue in the book "The Web of Life" by Fritjof Capra (Harper Collins, London, UK, 1996).

        Excerpt from "The Web of Life"

        ...the key to a comprehensive theory of living systems lies in the synthesis of two approaches that have been in competition since the dawn of scientific thought: the study of pattern (or form, order, quality) and the study of structure (or substance, matter, quantity). The structure approach attempts to understand the properties that make up the object of study, while the pattern approach seeks to understand the relationships between its constituent parts.

        When these two approaches are combined with the central insight of living systems theory — that of the ceaseless flux of matter — it offers a radically new way of conceiving reality, according to Capra. Pattern, structure, and process are three different but inseparable perspectives of the phenomenon of life.

        In effect, this means that to understand any living system, one must answer three questions: what is its structure? What is its pattern of organization? And what is the process of life? In Capra's view, this new approach overcomes two conceptual problems that have plagued science for centuries. First, the interdependence of pattern and structure overcomes the traditional division between the organic and the inorganic, between the living and the nonliving. And second, the interdependence of process and structure overcomes the Cartesian split between mind and matter. Source: "Book review" by Scott London.

        In the last decade, there has been a growing realization in bioscience that the above criticism is justified. For example, the leading science journal "Science Magazine" devoted a whole issue already to this question, see Science, April 04 1999. Its introductory article has the title "Beyond Reductionism". There, the term "complex systems" is applied to designate systems whose properties are not fully explained by an understanding of its parts. Examples of successful applications of a complex system approach are presented including a study of "emergent" properties.


        Addition July 2007

        Recently, as the result of Human Genome research, a new scientific method has appeared, called "Systems Biology". It admits that reductionistic methods are unsuitable for study of Biological systems, and is developing holistic research methods.

        "Biologists, geneticists, and doctors have had limited success in curing complex diseases such as cancer, HIV, and diabetes because traditional biology generally looks at only a few aspects of an organism at a time.

        As scientists have developed the tools and technologies which allow them to delve deeper into the foundations of biological activity — genes and proteins — they have learned that these components almost never work alone. They interact with each other and with other molecules in highly structured but incredibly complex ways..."

        Indeed, understanding this interplay of an organism´s genome and environmental influences from outside the organism (nature and nurture) is crucial to developing a — systems — understanding of an organism that will ultimately transform our understanding of human health and disease.

        The institute for Systems Biology.



        "The world thus appears as a tissue of events in which connections of different kinds alternate or overlap or combine and thereby determine the texture of the whole"

        Werner von Heisenberg, one of the founders of Quantum theory.

        Conclusion regarding scientific methodology

        It is thus very evident that the methodology of genetics and molecular biology, that has been exclusively reductionistic-fragmented, is highly inadequate for obtaining a realistic understanding of the workings of genes.

        This means that geneticists and molecular biologists dont have the knowledge and methods required to correctly judge the effects of genetic engineering.. Yet they have an almost exclusively dominant position in the national and international bodies that evaluate the safety of genetic engineering.


        B. Is it sufficient to treat molecules like DNA as "microobjects"?

        Molecular biological theories treat the DNA and other molecules as "microobjects" thought to follow essentially the same laws as visually perceptible objects. These laws are called the laws of "classical physics". In short, physicists talk about "classical objects" when referring to objects following these laws.

        Present knowledge about genes and gene regulation based on "classical object" behavior appears to be very far from being able to explain the extreme complexity and high level of purposeful integration of cellular processes.

        Because of this, already over 30 years ago, physicists and theoretical biologists suggested that key processes in the cell may occur on a quantum physical level. At this level all particles have a wave-particle duality. That is, differently from classical objects, they behave partly as particles and partly as waves. Also constellations of particles (like a gene) have a wave aspect that can mediate interactions at a distance. It has been suggested that this wave aspect may be the basis of the remarkable and incredibly complex integration and coordination of life processes.

        Interestingly, certain analyzes indicate that the wave property is strongly predominant in the essential molecules of life, that is, DNA, RNA and the proteins (See Cochran A. "Quantum Wave Predominance in Proteins", Nanobiology (1993) 2, 31-33).

        Processes in living organisms now considered or suggested to involve quantum-mechanical phenomena include enzyme-substrate interactions, protein synthesis, cell division, cellular communication and information processing. All these phenomena can be affected by a genetic change.

        One reason why quantum physics has been largely left out in Molecular Biology is that its major focus has so far been on DNA coding. This does not require quantum physics. Another reason is that quantum physical theory has so far not provided workable mathematical models for handling the wave mechanics of aggregates of particles.

        Recently, however experimental results have been reported that indicate that some, and perhaps important, aspects of genetic regulation are mediated at a quantum level. Especially the research of Gariaev et al has provided important evidence, see

        This research has generated seeds to entirely new theories about the DNA regulation of cellular processes. This research is just in the very beginning and has already revealed huge "white areas" of ignorance about DNA.

        This lends further support to our opinion that we know far too little to be able to manipulate DNA without the risk of completely unpredictable consequences.

        For more, see "Quantum phenomena in Biology".

        "What really astounds me is the architecture of life. The system is extremely complex. It's like it was designed...There's a huge intelligence there"

        Dr. Gene Myers, Celera Corporation. Architect of the Celera Genomics Human genome map in cooperation with Dr. Craig Venter.

        Source: San Fransisco Chronicle, Feb 19 2001.


        Conclusion regarding quantum mechanical aspects of DNA

        Molecular Biology has largely not considered the quantum mechanical aspect of life processes (as appropriate means have been lacking). Recent experimental research indicates that this aspect must be considered for a full understanding of the extreme complexity and remarkable integration of life processes.

        So already from a basic theoretical standpoint it is apparent that there are very important deficiencies in the methods used to acquire knowledge about DNA and how genes work and interact.

        Therefore it is impossible to master and predict the effects of gene manipulation using the methodology of genetics and molecular biology.

        This adds further strength to our conclusion that genetics and molecular biology cannot provide a reliable and sufficient basis for realistically judging the safety of genetic engineering.

         

      2. Is present knowledge of DNA sufficient to enable prediction of all the effects of inserting a foreign gene?

      Molecular biology has advanced far in describing the structural genes that determine the properties of the bodily parts. These are the simplest part of the genetic system. But knowledge about the important regultory genes that regulate the activity of all the structural genes is incomplete. The codes of these genes are only partially known.

      Altogether, the genes constitute less than 2% of all DNA. The rest, more than 98% of all DNA was long called "Junk DNA" by molecular biologists, as they were unable to ascribe any function to it. Recently it has been found that the it seems that this "Junk" is structured in an orderly way resembling a language. But the meaning of this language is completely unknown. The last few years some experimental observations indicate that the part of DNA that does not consist of genes may have various functions including regulation of the activity of genes. But little is yet known about it. (see also "Junk DNA").

      In any case, this indicates that a very large part of DNA, over 98% may have important, yet to a very large extent unkown functions.

      One more dimension of the "domain of ignorance" about DNA is the histone system. Histones are protein structures that are associated with the DNA string. They were formerly believed to function only as a scaffold making it possible to pack DNA tightly. However, in recent years increasing evidence have appeared indicating that they play an important role in the expression of genes. They may also be involved a/o in DNA repair, replication and recombination.

      The knowledge of these functions of histones is still very incomplete. Recently it has been suggested that they have an own code language that is yet unknown. The authors conclude that understanding the rules and consequences of the histone code will impact on many, if not all, DNA related processes with far reaching implications for human biology and disease. (Brian D Strahl, C.David Allis. "The language of covalent histone modifications." Nature, Vol 403,pp 41-45, 2000).

      The presently known parts of DNA have complex, reciprocal interactions. It seems reasonable to assume that interactions, if they occur, between the vast unknown parts of DNA and inserted genes, may likewise be of a reciprocal kind. In any case there is no scientific basis today for exluding the possibility that there are such interactions of significant importance.


      Conclusion regarding knowledge about DNA

      Increasing evidence indicate that the 98% of DNA has an important regulatory function, the nature of which is very little nknown. Moreover the histones surrounding DNA seem also to have important regulatory functions. There exists no knowledge how the insertion of a foreign gene can influence the regulatory function of these elements and how they, in turn, can influence the inserted gene. This is an additional reason why the consequences of gene insertion is unpredictable.

      "These findings demonstrate the fragmentary nature of current knowledge of genome structure and function and regulation of gene expression in general, and the limited understanding of several physiological, ecological, agronomical and toxicological aspects relevant to present-day and planned genetic modifications of crops."

      Visser, A. J. C.; Nijhuis, E. H.; Elsas, J. D. van; Dueck, T. A. "Crops of uncertain nature? Controversies and Knowledge Gaps Concerning Genetically Modified Crops. An Inventory. "Plant Research International (No. 12, 2000) 70 pp. To abstract.

       

      3. Is the doctrine "one gene - one property" valid?

      When genetic engineering was conceived over 30 years ago, it was believed that genes are carriers of single traits - stable units, that govern the activities of the cell unidirectionally and without any influence from the neighbouring genes.

      But this is not the case - Genes are variable, changing their behavior and even their structure because of influences from other genes or because of influences from the conditions in the cell and the environment. So genes are not stable carriers of well defined properties as was believed when genetic engineering was invented. For further details, see "The new understanding of genes" at http://www.psrast.org/newgen.htm.

      Because of this, a foreign gene may have unexpected effects, not appearing in its normal context. There are experimental observations verifying unexpected effects, see http://www.psrast.org/molbeng.htm. Recently, the National Academy of Science in the US has warned that because of this, there may occur unintentional "comopositional changes" including the appearance of unexpected harmful substances, see National Research Council, "Genetically Modified Pest-protected Plants", URL: http://books.nap.edu/books/0309069300/html/63.html#page_top.


      Conclusion regarding the one-gene-one-property doctrine

      This doctrine is outdated. It has been well established that the effects of a gene is dependent on interaction with its context. The insertion of a gene into a foreign context therefore has unpredictable effects that may be of significant importance for the safety of the organisms as food as well as for the stability and functioning of the GMO. For more see "Human Genome research has confirmed the fallacy of the one gene - one property doctrine", footnote 2.

    "Genes exist in networks, interactive networks which have a logic of their own. The technology point of view does not deal with these networks. It simply addresses genes in isolation. But genes do not exist in isolation. And the fact that the industry folks don't deal with these networks is what makes their science incomplete and dangerous."

    Dr. Richard Strohman, Professor Emeritus of Molecular and Cell Biology at University of California, Berkeley. From his article Crisis position.


    General conclusion

    (This is the same text as in the beginning of this document)

    Due to the very incomplete knowledge about DNA, it is neither possible to reliably predict the influence of a gene transferred to a foreign context nor the effect of any other genetic manipulation. Molecular biology has predicted and verified that unforeseeable metabolic disturbances may occur due to gene transfer. But, in addition to this, it cannot be ruled out that there might occur complications, the nature of which cannot even be predicted because of the incompleteness of knowledge.

    Thus, there is no basis today for excluding that so far unforeseen consequences of gene transfer may add to known risks that may make GE organsims unsuitable or even harmful as food. Already, this ignorance has most probably been the cause of one serious accident, killing 37 people and chronically disabling 1500, see The Showa Denko Tryptophan disaster.

    Furthermore, it cannot be excluded that the abnormality introduced into DNA through gene transfer may make such genes harmful to the environment in ways that cannot be imagined presently.

    From other kinds of interventions there is extensive experience that artificial manipulations of biological systems, in spite of incomplete knowledge, inevitably lead to unpredictable complications some of which may be harmful and difficult to master.

    An important consequence of this is that geneticists and molecular biologists don't have the knowledge and methods required to realistically judge the effects of genetic engineering.

    It is therefore unacceptable and potentially dangerous that geneticists and molecular biologists have an almost exclusively dominant position in the national and international bodies that evaluate the safety of genetic engineering.

    Jaan Suurküla M.D.


    Published in May 1999. Last update: May, 2009


    To the summary of this article.


    Addition July 2007

    In July 2007 a consortium of 35 groups of leading scientists published the conclusion that single genes are not carriers of isolated traits after a four year coordinated research effort. See "Genetech is based on an outdated understanding"

    This definitely confirms the point, stated in the article above, that the one-gene-one-trait concept is wrong.

    Although already more than ten years ago there was important evidence supporing this point, there has been a long period of scientifically ill-founded resistance from scientists sponsored by the biotech companies, see "Dysfunctional science". The conclusion of this authoritative consortium definitely puts an end to this pseudodebate that has confused politicians and postponed and adequate policy for safety assessment of GE foods.

    This underscores our conclusion that gene technology is so unpredictable that its commercial implementation can only be described as seriously irresponsible application of science and technology with unpredictable, potentially dangerous outcomes. Therefore it has to be stopped before a major disaster - a "Chernobyl" occurs - we have most likely already had the "Harrisburg" of genetic engineering, see the Showa Denko Tryptophan disaster.



    Back to: "Is there sufficient scientific knowledge to ensure safe commercial exploitation of genetically engineered foods?"


    Footnote 1.

    This footnote has been moved to a separate page: "Quantum phenomena in Biology"


    Footnote 2. (added 2001-02-14)

    Human Genome research confirms the fallacy of the one gene - one property doctrine

    We are happy to find that the results of the Human Genome project research now strongly support what we have stated about the fallacy of the one gene - one property doctrine which is the very basis of biotechnology. In February 2001, Dr. Craig Venter, world leading expert on Human Genome research said:

    "In everyday language the talk is about a gene for this and a gene for that. We are now finding that that is rarely so. The number of genes that work in that way can almost be counted on your fingers, because we are just not hard-wired in that way."

    "You cannot define the function of genes without defining the influence of the environment. The notion that one gene equals one disease, or that one gene produces one key protein, is flying out of the window."

    Source: Times, Monday February 12, 2001 "Why you can't judge a man by his genes" http://www.thetimes.co.uk/article/0,,2-82213,00.html

    The important connotation of this is that now it can be said with certainty that artificial insertion of genes is unlikely to yield exactly the "desired effect" of the inserted gene. Deviations from the desired effect along with unexpected other effects are likely to be the rule rather than the exception. Such unpredictable effects may include the appearance of harmful substances difficult to detect.

    "Genetic tailoring" of "desirable properties", until now a favorite propaganda slogan of the biotech industry, turns out to be a modern variety of "The Caesar's new clothes". /The Editor


    Richard Strohman, Professor Emeritus of Molecular and Cell Biology at the Berkeley untiversity makes similar conclusions in his article about the present status of the understanding of genetic regulation and the results of the Human Genome Project. See Toward a new paradigm for life - Beyond genetic determinism

    Excerpt:

    If the announcements from the HGP tell us anything, they tell us that we do not now how organisms make themselves. We are still, as many developmental biologists have said, in the dark ages about how organisms regulate their genomes to produce adults.

    It is no more justified to assert that genetic engineering is high-tech science mastering its results. Rather it is groping in the dark - a roulette game with seriously incomplete knowledge of the consequences. This the key reason why PSRAST demands that genetic engineering of every kind should be strictly confined within laboratory walls until science knows enough about DNA to understand what it is doing - which probably will take several decades and might even reach into the next century.

    Back


    "Genetically Engineered Food - Safety Problems"
    Published by PSRAST

    Siteguide   Starting points   Website search   Site Map   Start page   

    News   Introductory articles   Health hazards    Environmental hazards   

    Global issues   Safety issues   Alternatives to GE   FAQ   

    About us   What You can do   Membership   E-mail   How to sponsor us