A Radiation Ameliorating Factor: A Reappraisal.



Probably the most damaging finding of the Chernobyl disaster was the revelation of the lack of any therapy for the treatment of a populace subjected to a radiation injury. Bone marrow transplants, a specialized surgical procedure, is deficient because it demands a skilled surgical team operating in sterile, well equipped facilities; a situation which probably will not exist under crisis conditions. In addition, there is the requirement for donor typing, followed by marrow fractionation to hopefully minimize the associated life-threatening auto-immune reactions. Immediacy of treatment is essential for a patient's survival and recovery.
This is a summary of some of the procedures used to isolate the Radiation Ameliorating Factor (SRAF), a protein, with the potential for treating victims of excessive radiation exposure. Jacobson and coworkers, Argonne National Laboratory, established that spleen-shielded mice subjected to 1000 r total body irradiation exhibited a 77% survival in contrast to the 1% survival for controls. Ellinger and colleagues at the Naval Medical Research Institute (NRMI) demonstrated that both homologous and heterologous cell-free spleen extracts increased the survival rate of male guinea pigs subjected to 650 r radiation from 32% to 67%. Katz and Ellinger then developed an alcohol fractionation process for the isolation of a spleen factor. F-4, which at 5 mg/kg level conferred a protective effect equivalent to 200 mg freezed-dried spleen extract. Physiochemical studies: quantitative membrane dialysis, gel chromatography, solubility profiles in ammonium sulfate and ethanol, biuret analysis, spectral and also Acrylamide gel electrophoretic studies provided evidence that SRAF is either a protein or a high-affinity protein-SRAF complex. On the basis of cytological studies it is proposed that SRAF acts by stimulating the body's defense mechanisms by the regeneration of the splenic, hematopietic and lymphatic tissues, with the concomitant activation of the immune systems. Double-blind studies with several proteins and with heat-treated SRAF demonstrated no radiation-sparing activity.
The following factors indicate why SRAF is suited for inexpensive large-scale therapeutic use:


[1] Intramuscular injections can be administered by paramedic personnel

[2] The possibility of deleterious immune reactions are minimal because:
[a] The body's immune system is suppressed by radiation.
[b] The estimated dosage, based on small animal studies, would be 2-4 mg/kg body weight.

[3] SRAF can be stored at freezer temperature for at least a year with no loss of activity.

[4] Alcohol fractionation a low-cost process is environmentally clean - solvent recovery.

[5] Since heterologous SRAF is effective for therapeutic purpose - source material is readily available
     [Similar to insulin]

[6] Immediate treatment is essential for survival - injection can be initiated by paramedics.
(1) Jacobson, C.O Cancer Research 12,315 (1952)
(2) Katz S. and Ellinger, F. Nature 197,397 (1963)