Darwins
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
The mainstream account of genetics and its demise
The story of modern genetics typically begins with
August Weismanns identification of the
germplasm as the stuff of heredity and the re-discovery of Gregor
Mendels 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 Cricks 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
individuals 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?
Darwins 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.
Darwins 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 Darwins
gemmules.
Liu Yongshen at the Henan Institute of Science and
Technology in Xinxiang, China, described Darwins
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 Darwins Pangenesis must occur before a new
comprehensive genetic theory can be achieved.
Darwins 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 Michurins 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 Michurins 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.
Sopikovs 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.
Whats 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 Darwins gemmules. Consequently, any
change to the DNA and RNA circulating in the
individuals 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 organisms 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
Darwins 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 Darwins theory of Pangenesis
thats 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.
Germany bans
Genetically Modified Corn plantations - What about
Ireland?
The news in April that Germany was joining five other
European Union countries in banning
the cultivation of genetically modified corn met with
mixed reactions. Environmentalists were delighted, while
supporters of GM foods warned it could lead to an exodus
of research efforts from the country.
German Agriculture Minister Ilse Aigner told reporters
she had legitimate reasons to believe that MON 810, a GM
corn produced by the American biotech giant Monsanto,
posed "a danger to the environment," a position
which she said the Environment Ministry also supported.
In taking the step, Aigner is taking advantage of a
clause in EU law which allows individual countries to
impose such bans.
German media commentators have broadly welcomed the
decision, although they say political factors may well
have played a part. Aigner is a member of the
conservative Christian Social Union, the Bavarian sister
party to Chancellor Angela Merkel's Christian Democrats,
and the CSU is keen to tap popular opposition to
genetically modified crops in the heavily agricultural
Alpine region in the run-up to September's German general
election.
The center-left Süddeutsche Zeitung writes:
"The ban is a severe defeat for industry and
research. Agriculture Minister Aigner is being accused of
having taken a purely political decision. There are no
serious studies that prove the corn poses a danger, its
supporters say. But anyone who uses that argument merely
proves that they haven't understood the problem. As long
as the crop's usefulness hasn't been established, there
is no reason to accept the risks involved in farming it.
Aigner had to issue a ban. Anything else would have been
a gigantic open-air experiment with unforeseeable
consequences."
The left-wing Frankfurter Rundschau writes:
"Genetically modified corn is a risk to our
environment, is totally superfluous in farming,
represents industrial agriculture, causes pointless costs
to food production in Germany and can even ruin
beekeepers. All this has been discussed at length. The
fact that this has finally led to an official ban is to
be welcomed."
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