ISIS Report 15/04/09
Epigenetics and Beyond
Darwin’s Pangenesis, the Hidden History of Genetics, &
the Dangers of GMOs
Dr. Mae-Wan Ho
uncovers a fascinating page in the history of genetics expurgated from the mainstream
account that also tells us why genetic modification is so dangerous
A fully referenced
version of this article is posted on ISIS members’ website. Details
here
An electronic version of the full report can be downloaded from the ISIS online
store. Download Now
The mainstream account of genetics and its demise
The story of modern genetics typically begins with August Weismann’s identification
of the ‘germplasm’ as the stuff of heredity and the re-discovery of Gregor
Mendel’s hereditary units, or ‘genes’ controlling the characteristics of organisms,
and the rules of inheritance named after him. Thomas Hunt Morgan mapped the
genes to linear strings on chromosomes. A frantic search for the identity
of the genetic material culminated in the DNA double helix, which neatly explained
all the properties required of a genetic material. DNA replicates faithfully
and is passed on largely unchanged to the next generation; it gives rise to
variations by rare random mutations; it controls the characteristics of organisms
by coding for proteins, and undergoes recombination according to the rules
worked out by Mendel and Morgan.
Francis Crick’s Central Dogma of Molecular Biology - that genetic
information passes one-way from DNA to RNA to protein - became the ruling
paradigm of molecular genetics from the 1950s up to the mid-1970s. It encapsulated
the genetic determinist ideology that led up to it, or rather, projected backwards
from it, to trace out the linear progression of historical advances that serves
to validate the present. This is what I mean by the mainstream account.
But soon after genetic engineering began in the mid-1970s, geneticists
were to find exceptions and violations to every tenet of classical genetics
and the Central Dogma. In direct contradiction to the concept of a relatively static
genome with linear causal chains emanating from genes to the organism and
the environment, they discovered constant cross talk between genes and environment.
Feedback from the environment not only determines which genes are turned on
where, when, by how much and for how long, but marks, moves and changes the
genes themselves. By the early 1980s, ‘the fluid genome’ had emerged to make
genetic determinism obsolete (For more details see [1, 2] (Genetic Engineering Dream or Nightmare,
and Living with the Fluid
Genome, ISIS publications).
In the years following, and especially since the human genome
sequence was announced, the mainstream account became even more untenable
[3] (see Death of the Central Dogma and other
articles in the series, SiS 24).
Evidence of the inextricable entanglement between the organism
and its experience of the environment is forcing us to rethink not only genetics,
but evolution [4, 5] (Epigenetic Inheritance
- What Genes Remember, SiS 41; Development
and Evolution Revisited, ISIS scientific preprint). The phenomenon of
‘epigenetic inheritance’ indicating that experience during a crucial period
of an individual’s life could influence subsequent generations, is nothing
short of the ‘inheritance of acquired characters’, a mechanism of evolution
attributed to Lamarck. Lamarck was the subject of ridicule and derision in
the mainstream account; as opposed to Darwin, whose theory of evolution by
natural selection has remained unquestioningly revered to this day. So, was
Darwin mistaken?
Darwin’s Lamarckian tendencies
As every serious student of evolution knows, Darwin did subscribe to the
inheritance of acquired characters as an important subsidiary mechanism to
natural selection; it was only his followers, the neo-Darwinists who were
vehemently opposed to it [5]. And since the first publication of his Origin
of Species in 1859, Darwin became more and more absorbed in the idea.
In 1868, Darwin put forward the theory of Pangenesis to account
for the inheritance of acquired characters. He suggested that all cells of
an organism shed minute particles, or gemmules, which circulate throughout
the body and are passed on to the nest generation through the germ cells,
thereby transmitting the characteristics of the parents to their offspring.
And if the cells of the parents undergo changes during their life time,
those changes would also be transmitted to the offspring.
Darwin’s cousin Francis Galton designed a series of blood transfusion
experiments on rabbits with different pigments to test the theory of Pangenesis,
or at any rate, to test if gemmules existed; but found no evidence for them,
and the theory was largely abandoned.
Within the past decade, geneticists have discovered substantial amounts of
nucleic acids circulating in the bloodstream which are taken up by cells and
transported to the nucleus, where they could be integrated into the cells’ genome
(see [6, 7] Latest Exposé on the Fluid Genome,
SiS 15; Intercommunication
via Circulating Nucleic Acids, SiS 42)). These nucleic acids appear
suspiciously like Darwin’s gemmules.
Liu Yongshen at the Henan Institute of Science and Technology
in Xinxiang, China, described Darwin’s theory of Pangenesis in some detail
and reviewed both historical and more recent evidence in support of it, referring
to fascinating findings on blood transfusion that have been expurgated from
the mainstream account. He concluded that [8] “a considerable revision of
views on Darwin’s Pangenesis must occur before a new comprehensive genetic
theory can be achieved.”
Darwin’s Pangenesis and Michurinist genetics
Darwin recognized that cells multiply by division, and preserve their nature,
thus accounting for cell heredity. But it could not explain phenomena such
as the effects of use and disuse (another Lamarckian mechanism of evolution),
the inheritance of acquired characters, graft hybridization (hybrids created
by grafting), which required some means of transferring heritable characteristics.
Other phenomena in need of explanation were variation, development, regeneration,
and reversion (atavism), which required the hereditary influence to change,
and to remain dormant until activated.
Darwin proposed therefore that cells not only grow by means of
cell division, but are also able to throw off minute particles (gemmules)
that self-replicate, move through the body, can vary in response to the environment,
and are capable of dormancy. Furthermore, cells can throw off gemmules throughout
development, and these gemmules can enter the buds and germ cells, and that
is how they can influence the development of the offspring. If the cells of
one part of the body underwent changes as a result of environmental change,
they would throw off modified gemmules that could also be transmitted to the
offspring, and account for the inheritance of acquired characters, and many
other phenomena.
Gemmules released in a stock plant would be transferred into
a graft and become incorporated into the germ cells and meristems (growing
points) of the graft, resulting in heritable changes in the graft and its
progeny. This would account for graft hybridisation, the subject of ‘Michurinist
genetics’ (see below).
Gemmules, like seeds or spores, can be transmitted in a dormant
state, allowing a character to be expressed after several generations. Thus,
reversion is explained as the result of long-dormant gemmules becoming active.
A reserve of gemmules in the tissues could give rise to regeneration of lost
parts, and malformations and monstrosities could be due to gemmules reaching
the wrong destinations in the offspring. The fact that mutilations are not
transmitted by inheritance is explained by the presence of sufficient gemmules
from the previous generations. Characteristics that appeared only at a certain
stage of development were explained as the result of interactions between
the developing cells and gemmules.
Most of all, Darwin saw the theory of Pangenesis providing an
explanation of how variations can arise upon which natural selection could
act. And in that regard, he was closest to Lamarck [5].
Ivan Vladimirovich Michurin.(1855-1935) was a distinguished Russian
geneticist and horticulturist whose work was appreciated and promoted by Lenin.
After his death, Michurin was co-opted by Lysenko for a repressive political
and social campaign and propaganda war under Stalin. Michurin was hailed as
the true follower of Darwin responsible for “productive Soviet Michurinist
Biology”, as opposed to the “fruitless capitalist Weismannist-Morganist-Mendelist
genetics” of Western Europe and the United States [9]. This had done nothing
for Michurin’s true contribution to biology, and at the same time, deepened
the stigma attached to Lamarckism.
Scientifically, Michurin, was true to Darwin, in that
like Darwin, he did believe in the primary role of natural selection while
subscribing to the importance of the environment and Lamarkian inheritance
of acquired characters. Michurin created new fruit plants throughout his life
using graft hybridisation, introducing more than 300 new species. His fruit
garden was admired by Lenin, and he was awarded the Order of Lenin and Order
of the Red Banner of Labour [9].
Interspecific hybridisation by blood transfusion
Francis Galton failed to find any evidence that transfusing blood from white
into silver-grey rabbits and vice versa could change the coat colour
of the offspring, as expected, if the respective gemmules were present in
the blood. But subsequent experiments produced overwhelmingly positive results,
though not reported in the mainstream account of genetics.
Inspired by Michurin’s investigations on graft hybridisation
in plants, Russian biologist P.M. Sopikov began to re-investigate the effect
of blood transfusion in a series of experiments starting in 1950.and well
into the 1970s.
In the first experiment, blood from the Black Australorp roosters
was transfused into White Leghorn hens, which were then mated with White Leghorn
roosters [10]. Injections of 2.5 to 3 ml blood per kg were given twice weekly
for two and a half months before the fertilized eggs were laid. When these
eggs hatched, some of the progeny were found to have several black feathers
in their white plumage.
A similar experiment was carried out with White Leghorn donors
and Black Australorp recipients. White feathers appeared in the otherwise
black plumage of the progeny. There were also other changes. Compared with
the purebred controls, the experimental birds showed an increase in body mass,
larger neck and body size, longer legs and abnormal leg pigmentation. The
egg shell colour of some of the experimental White Leghorn resembled Black
Australorps.
These changes became more marked in each successive generation
of treatment. In the third generation, the birds had white plumage, or white
with black feathers, light-grey to grey, or became black like the donors.
Blood from Chuvash geese injected in White Leghorn and Khaki
Campbell ducks as recipients, or blood from Bronze turkey injected into White
Leghorn recipients, all resulted in abnormal characters in the progeny. The
blood transfusion itself was found to increase viability, productivity, reproductive
efficiency and body mass of recipients and their progeny, eliminating the
adverse effects of inbreeding and facilitating hybridization between species,
exactly as in the case of graft hybridisation in plants.
The Leningard White and Leningard Black breeds were created by
blood transfusion between White Leghorns and Black Australorps over three
generations, followed by interbreeding and selection. A heavy type of Leningard
White fowl with males weighing 4-5 kg and females 3.3-3.5 kg was created in
the same way.
Sopikov’s findings were confirmed by many Soviet researchers.
Reports of the success achieved by Soviet biologists reached geneticists in
other countries. Similar experiments were conducted in France, Switzerland
and elsewhere with comparable results. For example, blood from guinea fowl
injected into a strain of Rhode Island Red chickens gave progeny in the first
and second generations with extensive changes in the quantity and distribution
of melanin pigment in the plumage [11]. The transmission of modifications
continued to the seventh generation after a single series of injections of
guinea fowl blood. However, some investigators failed to induce heritable
changes in chickens by blood transfusion. Among 50 reports on blood transfusion
collected by Liu [8], 45 showed positive results and only five had negative
results.
So why did Galton fail to find such effects in his experiments?
Liu suggested blood group incompatibilities, or else the volume of blood transfused
may have been insufficient. Bird red blood cells are nucleated whereas mammalian
red blood cells are not, which would reduce the amount of transforming DNA
present.
DNA induced heritable transformations
As is well known in the mainstream history of genetics, Avery, Macleod and
McCarty were the first to describe transformation of bacteria by foreign DNA
in 1944 [12], thus providing the first proof that DNA was the genetic material,
and not protein, as was then widely believed.
What’s missing from the mainstream account is that subsequently,
a successful induction of heritable changes in the Pekin duck was demonstrated
using DNA from the Khaki-Campbell duck. Moreover, the treatment of recipient
ducks with erythrocyte DNA not only induced hybridization in the progeny,
but also affected the recipient parents [13]. The majority of the treated
birds and their offspring developed a range of characters (pigmentation of
beak, feather morphology, head shape, body conformation and size) that apparently
resembled the donor breed. Heritable modifications of morphological characters
in ducks as a result of DNA and RNA injection from other breeds of ducks were
also report by other workers [14].
In 1995, Japanese researchers reported that a single intravenous
injection into pregnant mice of a plasmid (replicating piece of DNA outside
the genome in cells) genetically modified to express a foreign gene in a complex
with lipopolymine was sufficient to transfer the gene into the embryos [15].
A few years later, researchers in Germany [16] demonstrated that viral or
bacterial plasmid DNA fed to mice during pregnancy could be detected in cells
of the foetuses and the newborn.
Within the past decade, geneticists have discovered substantial amounts of
DNA and RNA circulating in the bloodstream and fluid surrounding cells [7].
The circulating DNA binds to receptors on the surface of living cells and is
taken up and transported to the nucleus and incorporated into the genome. The
ease with which nucleic acids are taken up by living cells, widely exploited
in experiments in ‘gene therapy’, highlights the potential hazards of the huge
amounts and diversity of genetically modified nucleic acids released into the
environment and into our food chain [17] (Slipping through the regulatory
net, ISIS/TWN publication).
Environment-induced changes to DNA and RNA transmitted through germ cells
The numerous experiments in birds, like those in bacteria, showed that donor
DNA injected into and circulating in the bloodstream of recipients could indeed
transform the recipient and its offspring, behaving rather like Darwin’s gemmules.
Consequently, any change to the DNA and RNA circulating in the individual’s
blood stream would also be expected to transform the individual and its offspring.
We now know that environmentally induced changes to both DNA
and RNA are part of normal development, especially prominent in the central
nervous system and the immune system, where a great deal of research has been
done [18] (see Rewriting the Genetic
Text in Human Brain Development, SiS 41). One major mechanism is
RNA editing induced by specific environments that systematically alters the
genetic messages transcribed from the genome by changing its base sequence,
thus creating new proteins, new RNA species that regulate the expression of
whole sets of genes. Genomic DNA of cells can be rewritten by reverse transcription
from the RNA altered as the result of specific experiences of the environment.
Thus, in the course of an organism’s life, its complement of circulating nucleic
acids will be changing according to its unique experiences. These changes
are constantly communicated to other cells of the body via the circulatory
system. They may also be passed on to the germ cells to influence the next
generation. The circulating nucleic acids may pass through the placenta to
the cells of the embryos [15, 16]. There is also evidence that sperm cells
may be particularly adapt at taking up circulating nucleic acids and transferring
them to the egg during fertilization [19, 20] (Epigenetic
Inheritance through Sperm Cells, the Lamarckian Dimension in Evolution,
SiS 42).
Horizontal gene transfer denied and dismissed by proponents of GMOs
What are the implications of these findings now that Darwin’s theory of Pangenesis
has been restored to its rightful place in the history of genetics?
In the 1990s, a few colleagues and I found ourselves fighting a lonely battle
warning regulators and the scientific community about the dangers of horizontal
gene transfer from the rampant creation of GMOs and GM constructs [17 19] (Gene
Technology and Gene Ecology of Infectious Diseases, ISIS Scientific Publication).
A major hazard inherent to GM is indeed enhanced horizontal gene
transfer and recombination. There are many reasons for suspecting that is
the case (see [20] (Horizontal Gene Transfer
from GMOs Does Happen, SiS 38), of which I shall mention only two.
First genetic modification involves making artificial synthetic combinations
of nucleic acid sequences that had never existed in billions of years of evolution;
these recombinant sequences are highly mosaic, with similarities to a wide
range of species including pathogenic bacteria and viruses; hence they are
more likely to take part in horizontal gene transfer and recombination. Second,
GM constructs are designed to invade genomes with recombinogenic ends; this
makes them inherently unstable and more likely to move again once integrated,
and there is evidence both for transgenic instability [21] (Transgenic Lines Unstable
hence Illegal and Ineligible for Protection, SiS 38), and horizontal
transfer of transgenic DNA [20].
Horizontal gene transfer and recombination not only create new
disease-causing bacteria and viruses, but also spread antibiotic resistance
marker genes in transgenic DNA, making infections untreatable. Integration
of foreign DNA into cells can disrupt genes, cause cancer, and reactivate
dormant viruses that are in all genomes.
These potential hazards take on new significance in the
light of the DNA and RNA found circulating in the bloodstream and extracellular
fluids of both healthy and diseased individuals, and the ease with which they
are taken up into cells [7, 17]. Genetic modification is indeed more dangerous
than the intentional creation of biological agents simply because its hazards
are underestimated by practitioners and regulators alike [22] (No Biosecurity without
Biosafety, SiS 26). It must be strictly confined and contained
in laboratories. There is no need and no case for continuing to release GMOs
into the environment.
It is not only Darwin’s theory of Pangenesis that’s in need of
rehabilitation in the bicentenary of his birth. The entire history of genetics
and its continuity with epigenetics need to be truthfully retold, to put an
end to the abuses and misuses of the subject that endanger society.
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There are 4 comments on this article so far. Add your comment
| Sharon Medway Comment left 5th May 2009 14:02:00
There is too much money at stake here. These companies want world domination through food. It is not some conspiracy theory - it is a fact. They are even producing plants that "commit suicide" after one generation so that they can make profits continuously. Aside from the genetic problems which cannot even be traced because of the amount of the GE/GM organisms out there. This should scare the hell out of people and they do not even know they are eating it. Thank you for your bravery and dedication to this issue. | Louis Krut Comment left 15th April 2009 21:09:11
Dr. Wang Ho:
Thank you (again) for keeping at us. In our age, in which the giant corporations rule the world, it is difficult to overcome their influence. Our only weapon is knowledge, and your mission to keep us informed provides the best chance we have of surviving in a form we would recognise. We might not be the best there could be, but we are the best we know. We cannot know what alternative(s) might be generated and that should frighten us enough to stop our mad charge into areas best left unexplored. It is an old lesson, but one we have not yet learnt. | Rory Short Comment left 15th April 2009 21:09:09
It is a great relief to hear that genetic science has caught up with my gut feeling that genetic engineering is a dangerous activity especially when the GMO's are released into the environment. | Bridget HamelSmith Comment left 20th April 2009 17:05:12
This is deeply disturbing to me that those giant corporations continue to do as they please in interfering with our food crops for their 'misguided gain' - It is so true that great technological knowledge in the hands of the 'unwise'is a very dangerous situation! It seems clear to me with very little scientific understanding, that this is the reason why we now have so many more auto-immune diseases and growth of cancer in younger people. A fascinating subject but in my mind one that should not be played around with. |
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