The new understanding of genes

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
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")

The essence of the above was succinctly summarized by a

world leading expert on this issue, Dr. Craig Venter:
"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."
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: 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

Genetic determinism - the theoretical basis of genetic engineering

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"). 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"

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.

"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."
Dr. J. Craig Venter. Leading Humane Genome expert. Times, Monday
February 12, 2001.
Jaan Suurküla MD
This article was based on materials gratefully obtained from Dr Mae-Wan Ho.

First published in May 1998. Last modified April 12, 2001.

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.

Source: Physicians and Scientists for Responsible Application of Science and

Technology (PSRAST)
www.psrast.org