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LIFE WITH THE FLUID GENOME
Presentation by Dr. Mae-Wan Ho
National Future of Food Forum
Brook Lodge, Macreddin, Co. Wicklow, Ireland
4 July 2004
LIFE WITH THE FLUID GENOME
A time and a place for gene transfer
These two butterflies, poised so delicately on a flower, are engaged in rampant gene transfer of the natural kind. And they stay like that for hours, quite remarkable considering their short lifespan.
Those butterflies know that there is a proper time and place for gene transfer, and they only do it with soul mates.
(Just to orientate you as to what we are talking about. Here's an organism, a plant, with tissues and cells. Within each cell is a nucleus containing the genome, or all of the plant's genetic material. It is packaged into long thin structures called chromosomes. If you unravel this, you get thin threads called chromatin, and if you strip proteins away from chromatin, you end up with DNA, the genetic material, very, very long double-stranded polymers.)
Life began some 3.8 billion years ago. The geological epochs are marked by origins of major groups, big transitions, radiations and extinctions. There is a time and place for every group and every species to come on the evolutionary stage. The species did not all evolve at once, or all in the same place, so gene transfer was naturally limited by space and time; except at the dawn of life, when the ancestors of the three major life-domains - Archaea, Bacteria and Eukaryotes ‚ were not yet distinct. As a rule, organisms, including bacteria, have many ways to prevent foreign DNA getting into their genomes.
That's important, particularly in view of discoveries that geneticists have been making since the mid 1970s, which turned genetics upside down.
Francis Crick and James Watson, who got the Nobel Prize for working out the structure of the genetic material DNA may be largely right about the structure of DNA, but they are woefully wrong in thinking that genes and genomes are static, and determine the characteristics of organisms in linear, one-way causal chains.
Francis Crick presented this idea as the Central Dogma of molecular biology: genetic information flows strictly one way, from DNA to RNA to protein, and by implication, to the characteristic determined by that protein. This kind of genetic determinism must have been the inspiration for genetic engineering or genetic modification. And if it were really that simple, genetic modification would work just fine.
The scientific myth that launched and sank a thousand companies
And that was the scientific myth that launched a thousand biotech companies. But even as the first biotech companies were set up, genetic engineering, used as a research tool was making momentous discoveries that would overturn every single assumption of the Central Dogma, and eventually sink the industry.
The biotech industry has been retreating and declared a bad investment on Wall Street. The last biotech giant, Syngenta has announced it is departing Britain a few days ago [1], following Monsanto, Dupont and Bayer. The mainstream press, together with the biotech scientists, blame luddites and activists. But the real reason is that they simply got their science wrong, as revealed in my recent book, Living with the Fluid Genome [2].
A more representative picture of genetics is what, in the early 1980s, geneticists were already calling, "the fluid genome". Remarkably, the public has been kept in the dark. This term never reached the textbook, except the one I wrote for the Open University in the late 1980s [3]. Only within the past two years has it become respectable to question the Central Dogma [4].
The term, 'fluid genome' encapsulates very neatly whole swathes of scientific findings that wiped the picture of classical genetics off the map. The genome is not static and constant, nor is it immune to environmental influences; far from it. There is really no holding the genome still, just as there is no holding nature still and looking at it.
Instead, the genome is dynamic and flexible; there is a lot of cross talk between the genome and the environment that not only changes the pattern of gene expression but the very structure of genes and the genome. Most outrageously, Lamarckism, or 'the inheritance of acquired characteristics' - a taboo in classical genetics - is nowhere as evident as in the molecular mechanisms of the fluid genome.
Gabriel Dover and Dick Flavell, two geneticists who played key roles in defining the new genetics, put it succinctly in 1982 [5]:
"The application of new molecular techniques reveals that, beneath the level of the chromosome, the genome is a continuously changing population of sequences. Mobility [genetic material moving around], amplification [certain stretches of DNA being multiplied tens or hundreds of thousand times], deletion, inversion, exchange and conversion of sequences create this unexpected fluidity on both an evolutionary and developmental timescale."
More recently, James Shapiro [6] referred to the same processes as the "natural genetic engineering" that the organism has to do to survive. But this natural genetic engineering has all the appearance of being quite precise, and to be regulated by the organism as a whole. Genetic modification in the lab, by contrast, is crude, unreliable and unpredictable. The industry is failing because its products are no good: unreliable, unstable as well as dangerous.
ENDNOTES
Genetic modification is breaking all the rules of evolution. Genetically modified organisms are unnatural, not just because they have been produced in the laboratory, but because many of them can only be made in the laboratory, quite unlike what nature has produced in the course of billions of years of evolution. It is short-circuiting the evolutionary process.
Above all, what makes genetic engineering worse is that it is targeting the very mechanisms of 'natural genetic engineering' that coordinate the expression of genes and change the genome in non-random ways during development and in response to the ecological environment, which is what the fluid genome is about.
There is a dance of life going on in the organism with all parts intercommunicating and perfectly coordinated. Imagine the genes playing musical chairs in the genome, and along comes the rogue piece of genetically modified DNA that does not know the score, shouting non-stop at the top of its voice with a powerful amplifier, and has a tendency to run amok besides. That's the extent of the mayhem caused.
How to live with the fluid genome
The fluid genome is telling us that we have been completely misguided in our health and environmental policies. Genetic engineering would not work and is dangerous besides.
Genes, unlike diamonds are not forever. The responsiveness of genes and genomes to the environment makes clear that the only way to keep them constant and healthy is to have a balanced ecology. On the other hand, it is definitely futile to think that we can go on ruining our ecosystem and still keep healthy if we have 'good' genes.
We have a national health crisis in the UK, as indeed in most industrialized countries: environmental pollution from industrial wastes and agrochemicals, together with the junk food industry, are creating rising epidemics of cancers, allergies, obesity and related disorders such as diabetes, heart disease and many other nameless chronic illnesses. Having squandered tens of millions of public money creating GM crops that we don't need and not at all safe, our governments can think of nothing better to do than to keep on supporting GM crops even after the industry is deserting it. And having poured hundred of millions into sequencing the human genome, they are setting up DNA Biobanks of entire populations, to find out which genes make different individuals susceptible to which disease; another exercise in futility, and you don't have to be a geneticist to know that.
Even allowing for the fluid genome, our genes won't change within a generation to make vast numbers of people suddenly 'susceptible' to all kinds of diseases. Rather than addressing the problems at source: which is to end environmental pollution and shift over comprehensively to sustainable organic agriculture, they are promising us pie-in-the-sky individually customised drugs that are really palliatives at best, and more often than not, poisonous pills.
Sydney Brenner, who shared the 2002 Nobel Prize in physiology and medicine jointly with John Sulston and Robert Horvitz, for discoveries concerning "genetic regulation of organ development and programmed cell death", had been a critic of the Human Genome Project to sequence the entire human genome when it was proposed.
He told the BBC in September 2003 that more money should be invested in health education than in designing genetically tailored drugs [7]. He does not think personalised medicine and drugs from genomics are the answer.
This and other articles I am going to mention are all in this most exciting Science in Society magazine that you can't live without; in order to get critically informed to challenge and influence cutting edge science, to reclaim science for the public good.
New evidence is emerging that toxic agents in the environment can scramble genome sequences, and that those scrambled sequences may be linked to a range of chronic illnesses such Gulf War Syndrome, chronic fatigue syndrome, autoimmune diseases and leukaemia. All that is featured in the "Health and the fluid genome" series, Science in Society 19 [8].
Recent research also reveals that the mother's diet can change the whole pattern of gene expression in her unborn child, affecting its long-term health prospects. This early nutrition in the womb can indeed affect people's susceptibility to chronic diseases much later on in life, diseases such as cancer, stroke, diabetes, schizophrenia, and manic depression [9]. Moreover, these effects can persist through successive generations.
On the other hand, appropriate dietary supplements are also able to reverse some of these damaging effects by changing the genes themselves. For example, female mice, given dietary supplements sometime before they became pregnant, turned a large proportion of the offspring, which would have been obese mice into lean and healthy mice. That is to say, given half the chance, the fluid genome can even mend itself, if we stop insulting it with bad air, bad water and bad food. This article is found in Science in Society 20.
The organic revolution in science
The fluid genome is just one aspect of the organic revolution in western science that has been happening ever since the beginning of the last century, but which has been temporarily eclipsed by the mechanistic biology of the Central Dogma. The contrast is striking: the mechanical way is a linear chain of command and control, the organic way is intercommunication and participation at all levels.
As a special treat, I am going to offer you a new vision of the healthy organism: in which electric and electromagnetic energies of all kinds enable the tissues and cells and all the molecules in the body to intercommunicate and coordinate their activities. When intercommunication and coordination are perfect, we get to a state of coherence or wholeness. The living organism is so coherent that it looks like a dynamic liquid crystal display, because all its molecules are dancing coherently together. I call this the rainbow worm, which gave the title to a book I have written on the subject [10].
I have referred to this dance of life as 'quantum jazz', where every single player, however small, is improvising freely from moment to moment, and yet keeping in beat and in sync with the whole. This thoroughly organic view of life is reinforced by the recent quantum revolution that you can read about in the "Quantum world coming" series in the current issue of Science in Society [11].
These colour images of organisms are not just pretty to look at. I am showing you another one here. The brightness of the colours is proportional to the coherence or vitality of the organism; and the same physical basis can allow us to assess food quality, as described in the "Good food" series of Science in Society 21 [12].
This organic approach to understanding organisms also explains why sustainable systems are like organisms, and depends on the ability to store a lot of vital energy in diverse activities, ranging over many different space and time scales, another riveting article in Science in Society 21 [13].
You have no idea how exciting life can be. To live with the fluid genome is to leave behind the mechanistic culture of death and destruction for a thoroughly organic one that regenerates life and creativity.
That is why a group of scientists have got together to launch an Independent Science Panel to produce this must-read ISP report [14], a dossier of damning evidence against GM crops, and in favour of non-GM sustainable agriculture.
Ethiopia has been doing just that: reviving traditional composting together with tree-planting and other measures over the past 6 years, has led to increased yields and turned eroded land back into productive greenery [15]. Thanks to the imagination and energy of Tewolde Egziabher and Sue Edwards of the Institute of Sustainable Development in Addis Ababa.
And the butterflies are still at it!
1. "Syngenta to move its labs to US", John Mason, Food and Rural Affairs Correspondent
Financial Times, June 30 2004 http://news.ft.com/servlet/ContentServer?
2. See Ho MW. Living with the Fluid Genome, ISIS and TWN, London & Penang, 2003, for sources and references.
3. Ho MW, Goodwin, BC et al. Genetics S298, A Second Level Course, The Open University, Milton Keynes, 1987.
4. Mattick JS. Challenging the dogma: the hidden layer of non-protein-coding RNAs in complex organisms. BioEssays 2003, 25, 930-9.
5. Dover G and Flavell D. Genome Evolution, Oxford University Press, Oxford, 1982, backcover.
6. Shapiro J. Genome organization, natural genetic engineering and adaptive mutation. Trends Genet. 1997, 13, 98-104.
7. "Nobel Geneticist spurns gene drugs & biobanks" by Sam Burcher, Science in Society 2003, 41.
8. Ho MW and Hooper M. Health and the fluid genome series, Science in Society 2003, 19, 22-37.
9. Ho WM. Diet trumping genes. Science in Society 2003, 20, 38-39.
10. Ho MW. The Rainbow and The Worm, The Physics of Organisms, World Scientific, Singapore, 1993, 2nd ed. 1998; reprinted, 1999, 2001, 2003.
11. Ho MW. Quantum world coming series, Science in Society 2004, 22, 4-13.
12. Ho MW. Good food series, Science in Society 2004, 21, 12-20.
13. Ho MW. Energy, productivity and biodiversity. Science in Society 2001, 21, 48-49.
14. Ho MW, Lim LC et al. The Case for a GM-Free Sustainable World, ISP Report, TWN & ISIS, 2003.
15. Edwards S. Greening Ethiopia for self-sufficiency series, Science in Society 23 (to appear).
