Circulating DNA Converts Genomes?

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ISIS Report 2nd May 2002

Latest Exposé on the Fluid Genome*

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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.

If you wish to see the complete document

(http://www.i-sis.org.uk/full/leofgFull.php) with references, please

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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 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, 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 http://www.i-sis.org.uk/isisnews/i-sisnews3.php#reusable), 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

http://www.i-sis.org.uk/contamination.php). The safety of this viral

promoter in food must now be seriously addressed by experiments

If you wish to see the complete document

(http://www.i-sis.org.uk/full/leofgFull.php) with references, please

consider becoming a member or friend of ISIS. Full details here

(http://www.i-sis.org.uk/membership.php)