extract from Chapter 20
The nature of Viruses
The more I have learnt about the cells that make us, and all the life on our planet, the more I have been amazed by the skills they display. It has transformed my understanding of biology and entranced me. I now cannot learn enough about cells and their creations.
The works of some great woman of biology have inspired me, particularly Barbara McClintock. She was one of the first to describe the intelligence of the cell, a concept she developed after studying plant cells! Her view was at first highly disputed among scientists. But, after being practically ignored and belittled most of her life, she was in her old age awarded a Nobel Prize in 1983 for discovering the transposon - from which the retrovirus may have evolved. It was her work that made me ask: if she is right in saying cells make carefully considered responses to their environment, then what are cells doing when they make the viruses that we link to diseases?
In her Nobel Lecture of 8th December 1983 she boldly spoke of cells as intelligent, as sophisticated in their responses to the environment and as making ‘wise decisions.' She explained ‘a genome may reorganize itself when faced with a difficulty for which it is unprepared.' She gave an example: ‘cells are able to sense the presence in their nuclei of ruptured ends of chromosomes, and then activate a mechanism that will bring together and then unite these ends, one with another, a particularly revealing example of the sensitivity of cells to all that is going on within them. They make wise decisions and act upon them.'
McClintock continued: ‘Cells must be prepared to respond to many sources of stress. Mishaps that affect the operation of a cell must be occurring continuously. Sensing these and instigating repair systems are essential. ... It is becoming increasingly apparent that we know little of the potentials of a genome. Nevertheless, much evidence tells us that it must be vast.'
She predicted: ‘In the future attention undoubtedly will be centred on the genome, and with greater appreciation of its significance as a highly sensitive organ of the cell, monitoring genomic activities and correcting common errors, sensing the unusual and unexpected events, and responding to them, often by restructuring the genome. We know about the components of genomes ... [but] we know nothing, about how the cell senses danger and instigates responses to it that often are truly remarkable.'
This was far from the mechanistic view found in many virological studies in which the cell is described as the passive invaded victim of the cunning hijacking germ. It made me think - might the production of viruses sometimes not be due to ‘infections?' Could virus production be sometimes a natural part of a cell's ‘wise' response to the environment?
....... and I went on to say....
‘Cross-species’ help between cells is vital and common. In 2007 the cells of invertebrates were found to accept genes from bacterial cells when repairing ‘damaged genes.’ Dr. Werren and colleagues reported in Science there was ‘widespread transfer of bacterial genes into the genome of numerous invertebrates.’ As most cells within us are bacterial, this points to considerable cooperation happening within us. No talk here of a race between selfish cells or germs as fiercely independent individuals – or of a need to kill this bacteria. Rather the more female vision of cellular survival, evolution and growth, through compromise, symbiosis and cooperation.
Another biologist who inspired me is Dr Mae-Wan Ho, the founder of the Institute of Science in Society (ISIS), at the UK’s Open University. She took the ideas of Barbara McClintock and ran with them. What emerges from her work is a picture of cells as centres of dynamic fields of energy, as fluid crystals, electric, magnetic, coherent and quantum. In one of her papers she shares the vision that drives her. ‘I see all nature developing and evolving, with every organism participating, constantly creating and recreating itself anew.’ From her I learnt that cells have many ways of communicating, that little is static in nature and that life itself is woven into the fabric of the universe.
Then there is the work of a man – of Professor James A. Shapiro, who teaches in the States but was formerly at the Institut Pasteur. His work reveals our cells use massive amounts of information with seemingly great computational skills, having in their DNA a massive ‘read-write’ memory. His ideas helped me to better understand the role ‘viruses’ might play in the cellular world. To continue his metaphor, I now see viruses, exosomes, retroviruses, functioning as the natural flash memory sticks used by cells to share encoded information with each other.
Shapiro wrote: ‘The expectation of its pioneers was that molecular biology would confirm the reductionist, mechanical view of life. However, the actual studies of heredity, cell biology and multicellular development has been to reveal a realm of sensitivity, communication, computation and indescribable complexity.’ He also said: ‘The conceptual changes in biology (since the work of McClintock was recognized) are comparable in magnitude to the transition from classical physics to relativistic and quantum physics.’
An editorial in the Journal of Cell Science similarly said of cells: ‘their behaviour such as solid-state channelling of substrates, error-checking, proof-reading, regulation and adaptiveness … imply an ‘intelligence.’
Shapiro stated that cells are capable of ‘Boolean calculations’ during a 2007 lecture in the UK. The intelligence we often credit solely to our brains exists at the cellular level in all parts of our bodies. He said of bacterial cells; ‘they display astonishing versatility in managing the biosphere’s geochemical and thermodynamic transformations: processes more complex than the largest human-engineered systems. This mastery over the biosphere indicates that we have a great deal to learn about chemistry, physics and evolution from our small, but very intelligent, prokaryotic relatives.’ He added: ‘there can be no doubt that bacteria received evolutionary benefits by having mobile DNA in their genomes and systems for transferring DNA from cell to cell.’
Cells carry out this transfer by making the particles that we have called viruses. By using a base of four (the four nucleotides) to encode information into the RNA and DNA of viruses, rather than the base of two used by computers, our cells have achieved the ability to process and pack an incredible amount of information into extremely small spaces – making it possible ‘viruses’ that can economically transport much information between cells. It has been pointed out that: ‘the bases are spaced every 0.35 nm [billionths of a metre] along the DNA molecule, giving DNA a data density of over one-half million gigabits per square centimetre.’ However, the transported information is not just stored in the genetic acid. It is also encoded into proteins of viruses, as we will see.
Cells do not only communicate by means of exosomes or viruses; they also do so by movement, electric currents, chemical emissions (smells), photons and magnetic fields. They can send light signals to each other to make near instantaneous communications. The water within the cell is also used. Rich in salts, it preserves information, and, as it flows within the cell, it generates the electric current needed for the signals sent through the nerves.
Protein molecules take on specialised functions through the information that cells encode into their folds. For example, cells can produce the specialist p53 protein when exposed to radiation or to other causes of DNA damage. In 2007 this protein was found to vibrate when it detects DNA damage. Other molecules apparently vibrate to help regulate genes, almost as if they are talking. P53 molecules play an important role in regulating the production of exosomes and retroviruses - and thus also help to move information between cells.
I mentioned how McClintock discovered that ‘cells are able to sense the presence in their nuclei of ruptured ends of chromosomes' and repair these. Is this why some retroviruses reportedly have powerful anti-tumor effects, as mentioned in the last chapter? Likewise it is reported of the particles called ‘retroelements' (including the retrotransposon) that: ‘Unusually high activity or unexpected appearance of retroelements within cells is often found in connection with stress events.' It seems these particles are also produced when the cellular DNA is inadequately ‘methylated' and thus not properly protected from toxins.
Professor James A. Shapiro noted; ‘molecular analysis has confirmed the generality of Barbara McClintock's revolutionary discoveries of internal systems for genome repair and genome restructurin.'8 I would add that such repair systems do not stop at the borders of a cell in multicellular organisms - they extend to the whole of the organism. Cells produce clouds of ‘hundreds of' defensive vesicles whenever they are challenged, ‘in response to danger signals.' It is further reported that these viruses or particles help activate our T-cells by merging with them - and this of course could be easily mistaken for HIV infection.
We need an information genetic highway that weaves our cells together, and we have it - the world of retroviruses, viruses, exosomes, microvesicles, mRNA, microRNAs - all carrying information encoded by our cells.
But - I must not leave out the bacteria. These are cells, thus entirely unlike viruses. The use of the term ‘germ' for both has confused things. A bacterium is a cell with a more independent style of life that nevertheless lives communally with and communicates with other bacteria. It can make toxins to kill pathogens, change its DNA, and make viruses that travel to other bacteria. It can use the enzyme RT to change the proteins making up its ‘skin' to make it harder for it to be recognised by enemies. It can take on specialisations to serve the collective good of its colony. Shapiro has produced excellent pictures of beautifully constructed bacterial colonies.
There are extremely small bacteria called ‘mycoplasmas,' that are true parasites capable of living inside cells without harming them. Like jellyfish each is covered in a thin pliable membrane. Thus they can change shapes dramatically and be hard to recognize in the microscope. They are our smallest life form but still have a genome over 50 times bigger than the typical virus at half a million to 1.2 million base pairs. They are nevertheless so small that they have contaminated many a scientific experiment and been mistaken for viruses, although unlike viruses they are truly alive and can reproduce. Montagnier in 1990 suggested that they might be a co-factor in causing AIDS since he found them in one third of blood samples from AIDS patients. A sneeze can spread them and they are suspected to cause a mild pneumonia.
Surprisingly it is said that there are in us some ten times more bacterial cells than there are of ‘human cells'. Thus there must be a great deal of inter-species communication if we are to smoothly function.
Bacteria sometimes take on the role of scavengers. They may multiply within us when cells die during a severe illness. As soon as they have completed this scavenging work, the bacterial numbers will naturally decline.
However, when human cells are severely diseased, bacterial cells may multiply out of control and produce toxic by-products, as in severe TB. Bacteria are intelligent cells that might well prefer to cooperate, but it seems they can put their own survival first when necessary. They also will bond with other bacterial cells to form self-protective ‘biofilms' that are often hazardous to us. The NIH states that ‘80% of chronic infections are biofilm related' (and thus not viral).
Boston Review: Is Darwin in the Details? A Debate http://www.bostonreview.net/br22.1/shapiro.html
G. Borisy; ‘Beyond cell toons.' Editorial. Journal of Cell Science, Vol. 113, Issue 5.
J. A. Shapiro; Stud. Hist. Phil. Biol. & Biomed. Sci. 38 (2007) 807-819
Tiana G et al. ‘Oscillations and temporal signalling in cells' Phys Biol 4 (2007) R1-R17
The Regulation of Exosome Secretion: a Novel Function of the p53 Protein
Xin Yu1, Sandra L. Harris1 and Arnold J. Levine Cancer Research 66, 4795-4801, May 1, 2006.
Hansen and Heslop-Harrison. 2004. Adv.Bot.Res. 41: 165-193. Page 14 of 34.
(Dahal et al., 2000; Lockhart et al., 2000; Mhiri et al., 1997
Carolina Obregon et al. Exovesicles from Human Activated Dendritic Cells Fuse with Resting Dendritic Cells, Allowing Them to Present Alloantigens 2006 American Society for Investigative Pathology
Mycoplasmas: Sophisticated, Reemerging, and Burdened by Their Notoriety by Joel Baseman and Joseph Tully http://www.cdc.gov/ncidod/eid/vol3no1/baseman.htm
Monroe D (2007) Looking for Chinks in the Armor of Bacterial Biofilms. PLoS Biol 5(11): e307 doi:10.1371/journal.pbio.0050307 Published: November 13, 2007
Medical Microbiology Fall 2000. Tritz Professor/Chairman Department Microbiology & Immunology http://www.kcom.edu/faculty/chamberlain/Website/Lects/MECHANIS.HTM
Burcher, Sam. Selenium conquers AIDS? Institute of Science in Society. http://www.i-sis.org.uk/AidsandSelenium.php
Melinda A. Beck Antioxidants and Viral Infections: Host Immune Response and Viral Pathogenicity. Departments of Pediatrics and Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. April 27 2000 or 1999 issue of the FASEB Journal, a scientific journal published by the Federation of American Societies for Experimental Biology.
Fabio Farinati et al. Oxidative DNA damage in circulating leukocytes occurse as an early event in chronic HCV infection. Free Radical Biology and Medicine, December 1999. Pages 1284-1291.
J. Exp. Med. vol. 13, no. 4, pp. 397-411 (April, 1911).
Boycott AE. The transition form life to death; the nature of filterable viruses. Proc. Royal Soc. Med. 1928;22:55-69.
Sloane-Kettering Institute for Cancer Research, Progress Report XV, Viruses and Cancer. January 1963
Nucleic Acids Res. 1977 August; 4(8): 2713-2723.
Nucleic Acids Res. 1977 August; 4(8): 2713-2723.
J. A. Shapiro; Stud. Hist. Phil. Biol. & Biomed. Sci. 38 (2007) 807–819