ISIS Report 2nd May 2002
Latest Exposé on the Fluid Genome*
Circulating DNA Converts Genomes?
Russian scientists suggest that circulating DNA from dead cells are taken in by living cells in order to replace mutated genes with good copies. What are the implications for the safety of transgenic DNA? Dr. Mae-Wan Horeports.
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Geneticists have recently made a surprising discovery. Substantial amounts of degraded genomic DNA are present in the in blood plasma and fluids surrounding cells, coming from cells in the body that have died. This circulating DNA binds to receptors on the surface of living cells and is
taken up and transported to the cell nucleus.
Now, a group of scientists in Russia from the Novosibirsk Institute of Bioorganic Chemistry and the Institute of Cytology and Genetics, Russian Academy of Sciences, Siberia, have taken this finding further, and reported the results in the Academy’s biochemical journal, translated into
English.
They suggest that, within the nucleus of the cell, homologous recombination of genomic DNA with these fragments takes place. Homologous recombination is the exchange of parts between DNA sequences that are very similar or nearly identical. They suggest that this process can correct
mutations as well as induce genetic changes, with the external DNA fragments serving as reference. This would ensure that all the cells in the body have the same genome.
So, provided the reference DNA itself does not contain harmful mutations, it would be useful for eliminating mutations from the cells, thus keeping the body healthy.
Cancer is a multi-factorial genetic disease and numerous genetic changes, both mutational and inherited, are thought to be responsible. If malignant cells are offered genomic DNA from a healthy subject as external reference, couldn’t the reverse transformation of malignant to normal
cells take place?
The researchers tested the idea in three cultured human cell lines derived from. breast cancer cells, ovarian carcinoma cells, and leukemic cells. These were treated either with chromatin (complex of DNA and protein) from human sperm of healthy subjects, digested with enzymes to obtain
fragments 200 to 3000 bp; or else with genomic DNA isolated from sperm cells with a commercial reagent kit.
They did find changes in expression of some proteins associated with cancer, scrambling of the cell genome due to the DNA introduced, as well as changes in the behaviour of the cells.
The DNA therapy caused no toxic effects or changes in cell protein expression for the first week. After two weeks, however, the cells noticeably changed. On the 15th to 16 day, the number of cells decreased, to as little as half that of the control without DNA, and a proportion of the cells
were dead. These changes were irreversible even if no further DNA preparations were added. Cell growth was further inhibited and stopped even upon treatment with purified DNA instead of chromatin. After transferring the cells to a fresh plate, the cells attached to plastic and remained alive for a
month, though they did not form a complete monolayer and their number decreased constantly. So, both malignant cell death and arrest of cell division were observed.
There is no doubt that the DNA had affected the cells, but it is not clear whether the effects can be regarded as a ‘cure’ of the cancer, or whether they had anything to do with the DNA being taken up by the cells.
In the early 1950s, British biomedical researcher Peter Medawar and his team reported that mice tolerant to a foreign graft could be obtained by prenatal injection of donor blood lymphocytes into recipient mice before giving them the graft. The question as to why antigenic challenge can be
either tolerated or immunogenic (provoking an immune reaction) is still up in the air.
Another phenomenon that remains unexplained is the inheritance of acquired tolerance, as reported by immunologists Gorczinsky and Steele in the 1980s. This meant that the state of immunological tolerance, once acquired by the body, could be passed on to the offspring, not just by a female,
but by the male as well. That is because, as Gorczinsky and Steele claimed, some change in the DNA is involved. This aroused so much controversy that Nature’s then Editor, John Maddox declared Steele’s book should be ‘burnt’ for proposing the Lamarckian heresy. And
Medawar and others published articles in the journal refuting their work.
Lamarck, and not Darwin, was the first to propose the theory of evolution in the early 1800s. Unfortunately, Lamarck was ridiculed by Darwin’s followers - neo-Darwinians - for believing in the inheritance of acquired characters, which, to this day, is attributed to Lamarck. In reality,
Darwin himself was also a ‘Lamarckian’. Furthermore, all the findings in genetics since the mid-1970s has vindicated Lamarck’s major thesis that there was much more feedback between the environment and the genome than hitherto supposed.
So, could it be that immunological tolerance was linked to the genomic DNA injected with the lymphocytes that converted genes in the graft-recipient’s cells?
The Russian researchers carried out another experiment. DNA from mice prone to develop tumours, were injected into another strain that was resistant to tumour cells from the first strain. After the injection, 30 to 50% of the resistant mice developed tumours at the site of injection, whereas
none of the control, non-injected, mice developed any tumours. In other words, the resistant mice had become tolerant to the tumour cells.
No DNA data were provided, which would have made the results more convincing. If they are right, it would suggest that horizontal transfer of genetic material is a normal physiological process between cell communities, which include the organism’s own DNA as well as introduced, foreign
DNA. This has significant implications for the safety of transgenic DNA in food or taken in as vaccines, as some of us have warned.
Three years ago, another research group had reported that DNA from dead cells is scavenged by living cells, and that integrated viral sequences may be preferentially incorporated into genomes, with potentially harmful effects including cancer. In our report "Reusable DNA alert" (ISIS News 3, December 1999 ), we warned against using viral sequences in transgenic constructs, such as the cauliflower mosaic viral promoter. The promoter is now found to have widely contaminated landraces of maize in Mexico ("Worst ever contamination of Mexican landraces", ISIS report 28 April 2002). The safety of this viral promoter in food must now be seriously addressed by experiments
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