The new understanding of genes

Contents


• Summary [EL]
• Genetic determinism - the theoretical basis of genetic engineering
• The new understanding of modern genetics
• Conclusion

Genes are variable, changing their behaviour and even their structure because of influences from other genes or because of influences from the conditions in the cell and the environment. So a gene is not a context-independent carrier of a specific property as was commonly believed when genetic engineering was invented over 30 years ago. Insertion of a gene to a different species may therefore give unpredictable effects.

Summary [EL]

The mindset governing genetic engineering includes important mismatches with reality. The failure to realize this has led to an underestimation of the hazards and difficulties with genetic engineering and to an unrealistic overestimation of its possibilities.

Recent findings about several "single gene" disorders indicate that they are actually caused by different genes or gene patterns resulting in the same diseases. There are actually no simple one to one relationships between genes and traits. In such cases, the attempts at treating "single gene disorders" by replacing one gene are not likely to be successful.

The expression of a gene is the result of a very complex interaction with the whole of the organism and is even influenced by external conditions. The stability of a gene is influenced by the condition of the organism. The genes are actually not well delineated entities as believed formerly. They may change character in response to the state of the organism and the same gene may even give rise to different proteins under different conditions. Therefore one cannot expect to be able to "tailor" the traits of organisms in a predictable way by insertion of "desirable" genes.

Because of the context dependence of a gene it is impossible to predict and master the effects of gene insertion. It may seem that the desired property has been added to the new food plant. But in addition, a number of unexpected other changes may have occurred. There are also other factors that add to the likeliness of unexpected changes . - Including possible appearance of some harmful substance that may be difficult to detect reliably because of the limitations of present safety assessment technologies (see " No safety assessment methods are fully reliable")  [EL].

Genetic determinism - the theoretical basis of genetic engineering [ML]

During the past twenty years, radical changes and advances in the understanding of genes has occurred. In science it is rather the rule than the exception that it takes long time before new insights permeate the whole of the scientific community. This seems also to have been the case in genetic engineering that was born before the new understanding developed.

The old idea we will call "genetic determinism" and it is based on the following basic assumptions:

Assumption 1. Each gene is an independent unit of information. Each gene adds one trait to the build-up and behaviour of the organism. Each gene invariably codes for just one protein molecule (it is by creating different proteins that the genes govern the events in the cell)..

Assumption 2. The information of each gene is expressed straightforwardly without any kind of interaction.

Assumption 3. The genes are stable. They do not change unless mutations occur because of damage such as radioactive irradiation. Therefore the genes are normally passed to the next generation without any changes.

Assumption 4. Genes or sets of genes cannot change in response to the environment.

According to these assumptions of genetic determinism it is meaningful to hunt genes that cause undesirable properties and it is as well meaningful to insert new and desirable genes in an organism in order to "tailor" "better" organisms.

But all these basic assumptions of genetic determinism have been contradicted by recent scientific findings.

The new understanding of modern genetics

Assumption 1 and 2 above are contradicted by massive evidence from genetic and biochemical research showing that no gene works in isolation. It is thus a well proven fact that the same gene may have different effects in different individuals, because the influences of other genes modify how it will express itself.

Assumption 3 and 4 are contradicted by several observations, indicating that genes may change in response to the conditions of the organism and the environmental situation. And these adaptive genetic changes may be passed over to the following generations.

According to the "new genetics", the expression of one single gene into its corresponding protein is the result of a very complex process of feed-back and feed-forward interactions. The expression of a gene is the result of a complicated network of interactions that involves not only the whole cell but the whole organism and even the environment.

The old view ("genetic determinism") was:

Genes (DNA) are stable information carriers determining, by way of RNA (information transmitting molecules), the build up of proteins in a straightforward, one-way fashion. This implies that genes have the same effect independently of surrounding genes and the conditions inside and outside the cell.

The new view ("fluid genome") is:

The expression of each gene is the result of interaction with the totality of the internal and external environment.

Most importantly, the gene in this network of interactions is not stable. There are a number of different mechanisms that are designed to destabilize the genes under certain conditions inside and outside the body. The DNA may mutate and new pieces may be inserted or pieces may be deleted or multiplied many times. Sequences of the genetic code may be rearranged or combined with other sequences. Some genes can jump around between different places in the chromosomes. Some genes can convert other genes to their own DNA sequence. Geneticists have coined the phrases "fluid genome" to describe this behaviour of the totality of the genes, the genome.

These fluid genome processes are not at all haphazard, accidental or meaningless. They occur, under the control of the cell, as adaptive responses to various conditions. For example, plants exposed to herbicides or insects to insecticides are able to respond by mutations that make them resistant to the harmful influence. This has been interpreted as an expression of reverse information flow from the environment to the DNA. Contrary to the old concept, it has been found that starving bacteria and yeast cells have developed what have been called "directed"or "adaptive muations". They responded directly to substances that they are normally unable to metabolize by mutating so that they became able to feed upon this new nutritional source.

The mismatch between reality and the mindset of genetic engineering does not only make genetic engineering unpredictable, it may also be dangerous.

First, the erroneous assumption that each gene just codes for one specific protein has led to unrealistic expectations about the efficacy and reliability of gene transfers. This mistake has repeatedly been disclosed by different kinds of unexpected metabolic changes due to single gene transfers. These changes have resulted in the appearance of unexpected toxins and allergens in transgenic plants and micro-organisms and in very sick and monstrous transgenic animals.

The second mismatch between mindset and reality (the erroneous belief in unidirectional control of gene expression) has led to unrealistic expectations about the usefulness of transgenic plants. The feed-back from the environment may restrict their survival capacity to just the conditions that prevailed where they were developed. This may be the reason why a transgenic maize developed in USA failed completely when planted in the Philippines, why the tomato FlavrSavr, developed in California did not grow well in Florida, and why Monsanto's Bt-cotton crop did not work properly in Texas because it was hotter nor in Australia because it was colder than where it was developed.

The third mismatch between mindset and reality (the belief that genomes are stable and unchanging) has for example lead to an underestimation of the rate and rapidity with which insects develop resistance against built in crop pesticides. For the Bt-toxin produced by transgenic plants, already in the second generation about 70 percent of the insects had become resistant according to a recent study. This is an example of the dynamic fluidity and adaptability of the gene. Only in a stable environment the genes will be fairly stable, while in an environment posing new challenges the genome will rapidly respond with "adaptive instability". In a biotechnology based agriculture, the plants as well as the whole ecology are exposed to many different and unnatural challenges and stresses that invariably will destabilize the genomes of the exposed organisms.

An additional problem is that genomes normally do not accept intrusions by foreign genes. This so called species barrier is mediated by different mechanisms that prevent the insertion or inactivate foreign genes into the genome. This is one of the reasons why most gene insertion attempts fail. It also contributes to the destabilisation of genes that have been successfully inserted. Because of this instability it has turned out to be difficult to create genetically stable transgenic organism strains.

Finally, today we know only the function of about 3 percent of all DNA. The rest is an "unknown territory" (see "Very incomplete knowledge of DNA").  [EL] It seems reasonable to believe that this unknown DNA also has to be taken into account if one wants to understand and predict the total effects of the insertion of a foreign gene. For more about the incompletness of present knowledge about DNA, see "Incomplete knowledge about DNA" [ML]

Conclusion

Genetic engineering is based on a conception of genes as simple codes for determining specific properties. If so, it would be possible to "tailor" new organisms in a predictable way. But this has turned not to be the case. In reality, it has turned out that the expression of a gene is dependent on its interaction with the totality of its environment. As the knowledge about DNA is very incomplete, it is impossible to predict the effects of the insertion of a foreign gene. Unexpected complications may occur in many different ways. This includes unpredictable appearance of harmful substances in GE foods.

Jaan Suurküla MD

This article was based on materials gratefully obtained from Dr Mae-Wan Ho.

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".

Although already more than ten years ago there was important evidence supporing this understanding, 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.

It also 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 outcomes. Therefore it has to be stopped before a major disaster occurs.

To the summary of this article

For an excellent exposition of this issue, se Mae-Wan Ho:s book "Genetic engineering, dreams or nightmares?", 1998. Available from Gateway Books, http://www.gatewaybooks.com  671 Clover Drive Santa rosa, CA 95401, USA, Fax +1-707-566-8005. Paperback - price: $15.95 plus postage )

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