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

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

• 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).

  Recently there has been a growing realization in bioscience that the above criticism is justified. Therefore, the leading science journal "Science Magazine" recently devoted a whole issue 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.

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  Addition July 2007

  Recently, as the result of Human Genom 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.

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  "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.

  
  

• 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

  • "The DNA-wave Biocomputer" (an MS Word document) and
  • "Crisis in Life Sciences. The Wave Genetics Response".

  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 contention 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 of section 1

  From being a dogma that few bioscientists dared to question, an acceptance is growing that reductionism, the philosophical basis underpinning the methodological approach of Molecular Biology, cannot yield an exhaustive understanding of life processes. There is an abundant and advanced knowledge of the parts. But there are no appropriate means of achieving a full understanding how these parts interact.

  In addition, 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 needs to be included for a full understanding of the extreme complexity and remarkable integration of life processes.

  So already from a basic theoretical standpoint it appears that there are important deficiencies in the methods used to acquire knowledge about DNA. Without exhaustive knowledge, it is impossible to master and predict the effects of gene manipulations.

   

• 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 are represent less than 5 % of all DNA. The rest, more than 95 percent 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 have been made indicating 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 95% 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

Knowledge of DNA is very incomplete. Because of this, it is impossible to predict all the effects of the artificial insertion of a foreign gene.

"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 20 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

The one gene - one property doctrine is outdated. The effects of a gene is dependent on interaction with its context. The insertion of a gene a into a foreign context has unpredictable effects that may be of significant importance a/o for the safety of the organisms as food. Recently Human Genome research has confirmed the fallacy of the one gene - one property doctrine, see footnote 2.

General conclusion

Due to the very incomplete knowledge about DNA, it is neither possible to fully 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 incompletetness of knowledge.

Thus, there is no basis today for excluding that so far unforeseen consequences of gene transfer may make GE organsims unsuitable or even harmful as food in the long run. And 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.

Jaan Suurküla M.D.

Published in May 1999. Last update: July, 2007

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.

Also other points, especially concerning the nature of "Junk DNA" and the quantum nature of DNA has been confirmed beyond any doubt.

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 occurs.

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:

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.

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:

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.