Phoenix Rising - Cort Johnson's Column
...Presenting complex chronic fatigue syndrome (ME/CFS) research in a way we can all understand.
Thursday, April 26th, 2012:
Unstable At the Core? NCF Funds Cutting-Edge ME/CFS Gene Study
Dr. Ronald Glaser - Chronic Fatigue Syndrome and the Pathophysiology of EBV Infection
by Cort Johnson
In a year of intriguing studies this is one of the more intriguing. Stress has been something of a keynote in CFS research lately and researchers now regularly employ different kinds of stress tests to provoke abnormalities in patients. But does this unusual response to stress make its way all into the DNA of our cells? The National CFIDS Foundation in collaboration with the Nancy Taylor Foundation is betting $133,000 that it does…
It looks like it might be a good bet. Dr. Henry Heng has been evolving a uique theory of ‘genomic instability’ for over a decade. The theory proposes that random hits to the genome over time powered by cellular stress can derange chromosomes enough to cause complex disorders such as cancer.
Genomic instability or the inability to duplicate the cells genome properly when cells replicate has been shown to contribute to a large variety of disorders including retinoblastoma, Ataxia telangiectasia, Xedorerma pigmentosum, Nijmegen Break syndrome, Werner syndrome, colon cancer, breast cancer, among many others. Cells that become damaged in this way can exhibit chromosomal dysfunction.
Gulf War Syndrome Research Opens Up New Ground - A Discovery Channel project finding that five Gulf War Vets exhibited rates of chromosomal damage similar to those found in people with birth defects and cancer prompted the DOD to fund a $900,000 study. (Study results have not been published).
Uranium was believed to be the culprit in the Gulf War Vet findings but high rates of cellular stressors, such as oxidative stress, have been found in chronic fatigue syndrome. Viruses, vaccination, environmental stresses (radiation) are known to be able to cause genomic instability but Heng believes all kinds of cellular stressors can cause genomic instability (ie ‘pulverized chromosomes’) in right (wrong) person. Replace the word ‘war’ in the below quote with another stressful situation ‘ infection’ and you might have a nice theory of ME/CFS.
We propose that under the extreme environment of war, some individuals’ genomes will become increasingly unstable, and war-induced genetic instability will lead to diverse disease traits that can be characterized as GWI..Dr Henry Heng”
Chromosome ‘pulverization’ refers to a process in which part of a chromosome winds up getting broken apart and then pieced onto the tops of other chromosomes. Pulverization was previously thought due to such stressors as vaccination, defective genes or ‘environmental stresses’ (such as toxins, radiation, etc.) but Heng’s evidence suggests that ordinary cellular stresses can as well.
"Our data suggest that cell death is a highly complex process, and multiple forms of cell death result from a simple response to overwhelming stress(es).." - Dr. Henry Heng
ME/CFS Link – Heat shock proteins ability to protect chromosomes may play a key role in the fragmentation process. Heat shock proteins help keep chromosomes intact as they become amplified during mitosis; without their protection pieces of chromosomes become detached from each other during this process.
Heng has linked the reduction of a specific heat shock protein called HSP90 to increased chromosome fragmentation. HSP’s have been studied in ME/CFS. Two French studies (Jammes, 2011/James 2009) found reduced levels of other HSP’s after stress (aerobic exercise) in ME/CFS and a 2007 Canadian study found reduced levels of HSP 90 after exercise.
Paradigm Changing – Heng’s genomic theory of cancer evolution, published in 2009, is potentially paradigm changing. Heng does not believe that the standard method of targeting specific genes that trigger cancers will tell the tale in cancer and other complex disorders because the cellular damage comes from more or less random hits that disable what he calls ‘genomic networks’.
‘Stress’ Again – Cellular stress plays a big role in this theory. Heng believes it causes the genome to start shifting about – patching pieces of chromosomes onto each other – in order to form an optimal response to it. One of the potential results of all this shifting is the formation of cells that shoot out of control; ie become cancerous, which then starts a new search stabiilty….. Heng’s finding indicating that genomic diversity increases rapidly during cancer suggests an almost herauclean effort by the genome to get it under control.
Because the networks are disabled in some cases by one set of genes and sometimes by other sets, following specific genes is not effective. The key, Heng believes, is in identifying patterns of genome-wide instability…
"A growing body of evidence suggests that no distinguishable pattern can be discerned from single gene studies. Instead, it appears that finding a general mechanism will require us looking to the system as a whole – the genome.” - Dr. Henry Heng
Dr. Heng will be looking at the genome of chronic fatigue syndrome patients to see if their genomes have become ‘unstable’; ie, if in their efforts to fit the stresses they’ve encountered their cells have patched together a new genome. Heng’s theory is a variation at the genomic level on the idea that ME/CFS is a protective state.
Conclusion – Heng’s theory is new, the Gulf War Illness study award came just a month ago, and uranium radiation was the suggested stressor there…but it is intriguing and, in its own way, it’s similar to other efforts looking at system stability, not at the gene expression level this time, but at the genome level.
"…the true challenge is to understand the system behavior (stability or instability)…" - Dr. Henry Heng
If Heng finds genomic instability the next step might be to find what is triggering the genome to undergo such drastic changes; changes that are dramatic enough to be disabling to the patient, but may reflect an attempt at adaptation at some level.
The number of cutting-edge studies in ME/CFS belies the poor funding the disorder gets…From the CAA’s KnowledgeBase, Biovista and epigenetics studies to the high tech CFI Lipkin-Hornig and the BSRI CAA/CDC pathogen studies to the Light/Broderick gene expression studies, ME/CFS researchers are taking advantage of the latest technology and the Heng study is another example of that. Heng is no fly-by-night researcher; with over 130 publications to his name he’s has got quite a track record. It’ll be fascinating to see what he comes up with.
Read more at Phoenix Rising