DDP Newsletter July 2011, Volume XXIX, No. 4.
Suppose that we had a readily available, affordable, broad-spectrum, extensively researched, well-tolerated modality that could treat serious disease and also prevent future problems such as cancer, at very low risk, by stimulating the body’s own defenses? Should we want to have these facilities in shopping malls and pharmacies, as vaccines are now?
Not if it’s a demon—like ionizing radiation.
In 1902, low-dose radiation was a popular treatment for infections and cancer, writes Don Luckey (Radiat Prot Management 2004;21(5):21-26). It was used in all types of infectious disease for nearly 50 years, as described in the 1942 book Roentgen Treatment of Infections by JF Kelly and DA Dowell. Studies done at that time are reviewed by LB Berk and PJ Hodes (Yale J Biol Med 1991;64:155-165, http://tinyurl.com/3guff6m), who write that effective antibiotics supplanted radiation, and the current proscription against its use in benign conditions is “no doubt based mainly on [its] well-known tumorigenic effects.”
Since bactericidal doses are in the range of 100,000 roentgens, the therapeutic benefit of low doses (e.g. five treatments of 100 cGy each locally) must have been from indirect effects. Luckey notes that anaerobic bacteria such as those causing gas gangrene die because the oxygen species generated by irradiation disrupt their metabolism. Irradiation also works in tissues with poor blood supply that antibiotics cannot reach.
Luckey states that irradiation stimulates both the cellular and biochemical immune system. It increases the number of circulating lymphocytes, selectively destroying T-repressor cells and increasing the effectiveness of other types of T cells. It also increases the concentration of many enzymes and cytokines.
Cancers are observed of course after high doses of ionizing radiation, especially at high dose-rates. But the concern about low, even negligible doses is wholly dependent on the linear no-threshold (LNT) hypothesis (see Civil Defense Perspectives, May 1994, January 2000, July 2000, May 2004; DDP Newsletter, March 2010).
The disarmament movement’s campaign to stop atmospheric testing of nuclear weapons exploited the LNT hypothesis. But the intellectual foundation was Hermann J. Muller’s Nobel Prize lecture of 1946, citing conclusions later incorporated into what Edward Calabrese calls “the most important publication in the history of risk assessment”: the 1956 report of the Biological Effects of Atomic Radiation (BEAR) Committee of the U.S. National Academy of Sciences (NAS) (Environ Mol Mutagen 2011. doi 10.1002/2m.20662).
Muller won the Nobel Prize for demonstrating that X-rays cause mutations in male fruit fly germ cells. He argued that the dose-response was linear and that there was “no escape from the conclusion that there was no threshold.” He warned the medical community about indiscriminate use of X-rays.
Even at the time of his lecture, however, Muller knew of concerns among his peers about his data, including inadequate reporting of research methods, small sample size, lack of data on quality control parameters, known problems with temperature control, lack of data on lethal clusters, sterility/fecundity, and selection criteria. Moreover the “very low dose” tested was many thousand fold greater than human exposures to background radiation. More seriously, Muller failed to temper his remarks even though he knew about a very large study by Ernst Caspari and Curt Stern, using the lowest dose rate ever tested (2.5 r/day), that supported a threshold interpretation. Calabrese suggests that the lecture was more ideological than scientific (Arch Toxicol 2011. doi 10.1007/s00204-011-0728-8).
Stern never followed up on his commitment to provide more detail, but rather made the “problems” of data contradicting linearity disappear in a 1949 version of a meta-analysis. Calabrese writes that Stern got the LNT model accepted through “multiple manipulations and obfuscations” that reinforced biases within the genetics community. A trans-science concept now known as the precautionary principle acted as an “intellectual virus,” undercutting the integrity of data-driven processes, with a profound effect on policy that persists 60 years later.
As Bobby Scott points out, the deterministic effects of high-dose radiation do have a threshold because a large number of cells need to be killed simultaneously to produce them. These include effects on the central nervous system, gastrointestinal system, and blood-forming system. Scott uses a standard hazard model to show that the likelihood of life-threatening radiation effects on Fukushima recovery workers is very low. He states that the invalid LNT model should not be used for predicting future excess cancers (J Am Phys Surg 2011;16:71-77, www.jpands.org/vol16no3/scott.pdf).
Linearity wipes out the biphasic dose-response curve that applies to nearly everything in nature, for example vitamins. Low doses are beneficial—as by activating repair or immune mechanisms. The ideology of the precautionary principle blinds people to the potential for this effect, called hormesis.
CAN COMPUTED TOMOGRAPHY DETECT AND PREVENT CANCER?
But for the LNT bias, headlines about the National Lung Screening Study (NLST) might read “CT Scans May Protect against Lung Cancer” and cause one to rethink the “Radiation from CT Scans Linked to Cancers, Deaths” article that appeared in USA Today in December 2009. This article quoted studies from the Archives of Internal Medicine stating that CT scans “may contribute to 29,000 new cancers each year, along with 14,500 deaths.” These numbers are derived solely from calculations using dose delivered and the LNT hypothesis. As with global climate change, models supersede data.
The NLST enrolled about 53,000 smokers. Half were screened three times at one-year intervals with “low-dose” (0.15 cSv compared with the more usual 0.8 cSv) spiral CT scan and half with chest radiographs. Subjects were enrolled from August 2002 through April 2004, and data collected on lung cancer diagnosis and death through the end of 2009. In the CT group, a total of 1,060 (645/105 person-years) lung cancers were diagnosed, and in chest x-ray group, 951 (572/105 person-years). Of these, 367 and 525 cancers were found, respectively, in persons who either missed a screening or were diagnosed after the screening period was complete
Patients screened with CT had a 20% lower rate of death from lung cancer than those screened with chest x-rays: 356 (247/105 person-years) vs. 443 (309/105 person-years), P=0.004. It is likely that at the outset, the two groups had about the same number of incipient cancers, but more were uncovered by the CT screening, and in an earlier stage. Of the cancers picked up by the CT scan, 415 were in stage IA or IB, compared with only 160 of those found by the chest x-ray (NEJM 2011;365:395-409). It is assumed that the benefit comes from early detection and treatment.
“Researchers did not consider the possibility that CT-related radiation also stimulated the body’s natural defenses,” writes Dr. Scott. “Doses appear to be in the range that stimulates anticancer immunity and epigenetic pathways to the elimination of pre-cancer cells via apoptosis.” Researchers did, however, worry about long-term radiation-induced cancers and suggest future analysis to detect that.
The CT screening dose is far lower than the dose of whole-body irradiation used by Sakamoto et al. in the successful treatment of cancers: 10-15 cGy twice a week for 5 weeks (see Luckey op cit. and Cuttler and Pollycove, “Can Cancer Be Treated with Low Doses of Radiation, J Am Phys Surg, winter 2003, jpands.org/vol8no4/cuttler.pdf).