By Alan Cocchetto, NCF Medical Director Copyright 2016 – Permission required for reposting

From Fall 2016 Forum

Recently, a patient had mailed us the Spring 2016 copy of Proto, the medical magazine from the Massachusetts General Hospital^[1]. In it was an article about X-rays and the effects of various forms of radiation. Geneticist Hermann Muller was one of the first skeptics of the Atomic Age. In 1927, Muller had made a landmark discovery. He found that exposure to high-energy radiation could induce major chromosomal changes. Thus, the stronger the radiation, the greater the damage. As a result of his scientific discoveries, Muller was awarded the Novel Prize in 1946. His acceptance speech, little more than a year after the bombings at Hiroshima and Nagasaki, ended on a cautionary note about the genetic risks of atomic energy, “a potent source of permanent contamination.” In his later years, Muller continued to raise the alarm about “insidious” damage from nuclear weapons that might not be visible for years. Though his early messages were met with resistance, it wasn’t until later in his life that the world caught up with Muller’s concern about the havoc technology can play on the fragile genome.

As we now know, Muller’s discoveries were right on the money! Recently, we located an important paper by Gridley et. al. that is highly applicable to our research efforts here at the NCF^[2]. As you know, the NCF formally discovered the presence of alpha-radionuclides in their patient cohort. This led to further research that identified severe chromosomal damage in these same patients. This knowledge was of critical importance because alpha-radiation produces high-LET effects. Let us explain further.

Linear energy transfer (LET) is a term used in dosimetiy, the assessment of the radiation dose received by the human body^[3]. lt describes the action of radiation upon matter. It is identical to the retarding force acting on a charged ionizing particle traveling through the matter. lt describes how much energy an ionizing particle transfers to the material transversed per unit distance. By definition, LET is a positive quantity. LET depends on the nature of the radiation as well as on the material traversed.

A high-LET will attenuate the radiation more quickly, generally making shielding more effective and preventing deep penetration. On the other hand, the higher concentration of deposited energy can cause more severe damage to any microscopic structures near the particle track. If a microscopic defect can cause larger-scale failure, as is the case in biological cells, the LET helps explain why radiation damage is sometimes disproportionate to the absorbed dose. Dosimetry attempts to factor in this effect with radiation weighting factors.

This now brings us to the Gridley paper. Since our patient cohort had been identified as having low-levels of high-LET radiation, as measured via specific urinary testing, and since many alpha radionuclides have a long half-life, the disease model became one that is associated with having a radiation source that acts as a chronic or persistent stimulus to the body. One might even classify this as low-level whole body radiation. Gridley’s paper looks at total-body radiation by high-LET particles where she reports on the immunological effects on the body.

Gridley found that the CD19 B-cells were the most sensitive immune cells to radiation whereas the NK-cells were the most resistant. This is important since the NCF had previously reported on research by Dr. Fatih Uckun that had identified statistically significant abnormalities in CD19 B-cells in CFIDS/ME patients^[4]. CD19 B-cells are a measure of humoral immunity and are important for antibody production and regulation. As such, the NCF feels that this is certainly a supportive scientific finding.

In addition, Gridley found that the CD8 cytotoxic T-cells were more sensitive to radiation than the CD4 helper T-cells. This is important since this would create a CD4/CD8 cell ratio that is greater than 2:1 which is what was previously reported in Osler's Web. The NCF has seen very high ratios as directly reported by patients. The CD4/CD8 ratio is a measure of cellular activation associated with the cellular arm of the immune system. The higher the ratio, typically the greater the T-cell activation status. For example, autoimmunity conditions often exceed a 2:1 cell ratio. Again, this too is consistent with the NCF’s previous findings.

This paper further reports that, “Collectively, the data show that lymphoid cells and tissues are markedly affected by high linear energy transfer (LET) radiation at relatively low doses, that some aberrations persist long after exposure, and that different consequences may be induced by various densely ionizing particles. Thus simultaneous exposure to multiple radiation sources could lead to a broader spectrum of immune dysfunction than currently anticipated.”

As if this paper wasn’t good enough, it gets even better. What is CFIDS? Chronic Fatigue Immune Dysfunction Syndrome. At the end of the Gridley paper, the authors conclude that high-LET radiation exposure “may result in chronic immune dysfunction.” Well, folks, to the NCF, this description doesn’t get much better than that!

 

References

1. The trouble with X-rays; Proto Magazine, Massachusetts General Hospital. Spring 2016: 11


2. Total-body irradiation with high-LET particles: acute and chronic effects on the immune system; Gridley DS, Pecaut MJ, Nelson GA; Am J Physio] Regal Integr Comp Physiol. 2002 Mar:,282(3):R677-88.


3. https://en.wikipedia.org/wiki/Linear_energy_transfer


4. Clinical activity of folinic acid in patients with chronic fatigue syndrome; Lundell K, Qazi S, Eddy L, Uckun FM, Arzneimittelforschung. 2006;56(6):399-404.