Electronic Mail Address:
ely@u.washington.edu
Postal Mail Address:
Radiation Studies, Box 351650
Univ. of Wash., Geophysics
Seattle, WA 98195, USA
(*Independent Study in Medical Science is required for graduation from the UW Medical School.)
The GCR is, for a number of reasons, of vital interest to human society; hence, the occasionally anthropocentric tone of this brief outline. Broadly, the "Radiation Studies" program centers primarily on the several aspects of galactic cosmic radiation (GCR) that influence: (1) solar-terrestrial physics; and especially (2) the geophysical and biophysical characteristics of the environment of importance to mankind. These include both radiation induced physical effects in the earth itself such as specific aspects of weather and climate (i.e., see below Ely predictions re the cirrus hole, the ongoing northern hemisphere floods, etc.), and any biological effects of the background radiation on aging, evolution, human lifespan, neoplastic initiations, etc. (and necessary study of competing aging processes, such as glycation, heavy metal intoxication, etc.). Relevant physics of biological systems, in addition to that of the earth, sun and galaxy must be considered. In recent years, considerable progress has been made (on our work) in life sciences by increasing use of radiation studies technologies such as neutron activation analysis, x-ray fluorescence, inductively coupled plasma mass spectrometers with laser ablaters, etc. As a few examples of secondary work, Ely has proposed theoretical solutions for: E.N. Parker's "solar dynamo dilemma"; and a "grand unification" of solar-terrestrial physics provided via excitation of solar structure.
Thus, as part of the geophysical environment, the GCR may affect numerous important processes (including human aging, weather, climate, solar-system composition gradients,etc.) Our primary research goals are the definitive investigations of these processes, as outlined here. In several areas of this work, theoretical models (developed by Ely) have produced many predictions that were either subsequently substantiated experimentally or offered explanations that were consistent with existing observations not previously understood. As examples, these include: (1) in the life sciences area, as a result of investigating the latitude dependence of longevity and cancer incidence (for GCR effects), we discovered an over-riding effect of sugar intake (the GAA) that we showed was associated with striking results in human cancer patients and in animal studies of cancer and birth defects [and led to our discovery of a strong modulation of glycation (an important aging mechanism)]; (2) in the sun-weather problem, the MCM predicts and explains VUTI and cirrus modulation (and the resulting Hale-cycle cirrus holes), VAI, drought cycles, GCM defect (wrt global warming), LIA, MIA, ongoing northern hemisphere flooding (since 1993), etc.; (3) in solar physics, explanations of the two fundamental solar neutrino problems, "low" intensity and SSC modulation; and (4) in cosmic ray physics, explanations for both Centauro events and the GCR energy range to 10**20 ev (in terms of Witten's high-A quark matter). Problems and progress are summarized in Section 2 for the physical science work, and in Section 3 for the life sciences.
Ely has had theoretical and experimental findings of significance on fundamental questions in several areas including those listed here. As part of the experimental work, he has flown cosmic ray experiments on five satellites and a number of high altitude balloons, discovering four GCR modulations. He has developed theories, strongly supported by experimental findings of ourselves and others, that VUTI (variations in upper troposphere ionization produced by modulations of the GCR) influence other tropospheric processes including lightning, and extremes of weather and climate. In recent years, a major and increasing part of our effort has been spent in tests of the theoretical predictions concerning the role of VUTI in the sun-weather problem and in global change. Much of our present research effort relates to two of our recent exciting discoveries that resulted from his theoretical predictions in the 1970's based on the MCM (Magnetic Coupling Model) that describes the effects of the galactic, solar and terrestrial magnetic fields. These are solar-magnetic-cycle modulations: (1) of cirrus (the discovery of the predicted cirrus modulation (by VUTI), was made possible in 1989 by S.G.Warren's outstanding cloud atlas); and (2) of the coupling GCR circa 1 Gev (in 1991). If Ely's interpretations of these findings prove correct, it will be recognized that these efforts have produced the first credible and self-consistent solutions for: (1) the "Sun-Weather Problem" (considered by many to be a central problem of solar-terrestrial relations); and (2) a fundamental error in the canonical model of global warming that has prevented world unity on the reality of this threat (i.e., to explain the anomalous high latitude cold periods of the 1960's and late 1980's, etc.) He has shown theoretically that: (1) the composition of the sun (and solar system) may have been significantly influenced by the transport of matter as cosmic rays to the contracting proto-solar nebula and by the dynamics of that contraction; and (2) both the deficit of the solar neutrino flux and its anticorrelation with sunspot number may be explained in significant part by a radial Z-gradient and dynamical arguments. He has suggested that the planetary-torque impulses (as elucidated by the work of Jose and Landscheidt) provide a "grand unification" of solar-terrestrial modulations ranging from the sun's core to the earth's surface.
3.1 Ely is a member of the Division of Biological Physics
of the American Physical Society. One of his principal research interests
relates to what possible role can the background radiation have as a cause
of aging, evolution, neoplastic initiations and the unexplaind sharp truncation
of the human lifespan distribution. For example, especially with respect
to aging and life span, Harman's well established mechanism could act as
a mediator via free radicals produced by cosmic ray muons and neutron decays,
both of which have well known latitude and altitude dependences. To make
progress on these important questions, one must understand the other aging
factors. Glycation is a recognized aging mechanism that is aggravated in
modern society (our own investigation and discovery on this topic is summarized
here) (see also ref. 12, 13 below) . In addition, there are simple reasons
to suspect aging results from chronic exposure to heavy metals at very
low levels which characterize urban life in affluent nations. As a short
example of past research on this topic, in the 1960's, the exact same tissue
levels of Pb found in urban humans were shown to result in accelerated
aging and reduced median life span in animals (31% in male rats!) by a
well known investigator (use of unleaded gasoline now seeks to reduce this
problem). Ely's work on Hg, a common and potent pollutant, resulted in
the development of a model for the phamacology of Hg; its predictions included
that Hg from amalgam could be stored in bone in susceptible individuals
(depending on 3 idiosyncratic factors), and might be a major cause of Alzheimer's
disease and other disorders. Several features of the model have been published
in a national medical news letter. Two papers have been submitted to journals
and others are in process ('95).
3.2 In the beginning. In the 1970's, because of this interest in the mutagenic burden of the penetrating background radiation (secondary cosmic rays at the earth's surface) and its possible role in aging and neoplastic initiations, Ely looked for and found what appeared to be a statistically significant latitude dependence in cancer mortality. The background radiation decreases at low latitudes and cancer deaths appeared to exhibit the same trend [except for some low latitude countries whose high mortalities violated his expectation, until he found (from WHO data) that those countries had high sugar consumption] In 1973, he had already related to Linus Pauling a theoretical reason why the clinical trials of vitamin C against colds and cancer may have failed because of the high blood sugar levels in the affluent nations. He had deduced the theory from two discoveries on leukocytes published by others in '71 and '73. The theory has possible relevance to atherosclerosis, birth defects, cancer and infectious diseases, and is called the "Glucose Ascorbate Antagonism" (GAA).
3.3 The GAA Mechanism. Essentially, this theory says that: (1) certain cell types (such as leukocyte and fetal) normally have intracellular ascorbic acid (AA) levels that are "pumped up" (largely by insulin) circa 50 times higher than serum AA levels in the surrounding blood if the blood glucose (BG) level is in the low range that was normal until the 1900's and is still seen today where the primitive diet prevails; (2) the high AA levels in such cells are necessary to drive the HMP shunt (or pentose pathway) needed for normal functions (including mitosis); (3) "modest" BG elevations (~50%, common after western diet meals) competitively inhibit insulin-mediated active transport of AA into these cells, resulting in low intracellular AA levels, low HMP shunt, and cell dysfunction (i.e., leukocytes don't attack tumors or pathogens, fetal cells divide too slowly, etc.).
3.4 AGC in Humans and Animals. This simple GAA theory gives rise naturally to "Aggressive Glycemic Control" (AGC) as a modality that, properly used, appears to have much value against the disorders named above. In 1978 and 1979, two stage-4 breast cancer patients with large tumor burdens, worsening rapidly ("one month" prognoses) although already on chemotherapy, elected to use AGC and both became tumor free in six months and were still alive in 1992. With partial support (from Fred Hutchinson Cancer Research Center, etc.), Ely and co-workers were able to reproduce this result strikingly in an animal model showing strong glycemic modulation of tumor tolerance (ref. 1, 12). In 1983, an American Cancer Society UW-FHCRC committee (reviewing applications from new investigators) approved AGC as a research topic and urged Ely to pursue it without delay.
3.5 GAA in Birth Defects. In 1981, Ely had described the obvious theoretical relevance of GAA to birth defects (ref. 2). The causal chain is: hyperglycemia results in low intracellular AA which slows the HMP shunt production of the 5-carbon sugar, ribose; then, since ribose is needed to make copies of DNA, cell division slows. Thus, when high blood sugar occurs in early pregnancy, gross malformations occur (about 60,000 per year in the U.S.!); but if it occurs in late pregnancy when cell division is primarily in the brain, mental retardation or other CNS defect occurs. The theory was kindly received in a lead article by a recognized expert in the field (ref. 3). Motivated by that review and his desire to test the GAA theory in a non-tumor model, Ely et al were again fortunate and, in an animal model, showed that hyperglycemia (high blood sugar) of early pregnancy induced striking reproductive anomalies [mainly fetal resorption in mice (ref. 4)].
3.6 Glycation, Ascorbate and Aging. In the experiments on glycemic modulation of tumor tolerance summarized above, no additional AA was given the animals because mice make their own. However, in mice given supplemental AA (in another experiment), Ely observed a marked depression of glycation of hemoglobin (circa 40%). This dose dependent effect was also found in the GHb (glycated hemoglobin) data of 600 humans on whom we already had both blood chemistries and diet questionnaires including the amounts of supplemental ascorbate habitually taken (at their election). Because glycation has been shown to be an important aging mechanism (by Cerami et al), the implications of these findings are far reaching; they were announced at a meeting (ref. 5), and a paper has been submitted to a major journal.
3.7 No Renal Threshold for DHA (dehydroascorbic). Prior to 1980 Ely had hypothesized that there is no renal threhold for DHA. The simple basis is that, at the stage in evolution when renal thresholds developed, ascorbic acid (AA) was either plentiful in the diet or abundantly synthesized in the liver and there was no pressing reason to conserve this toxic member of the AA-DHA redox pair. Measurements made in the late 1980's by Ely and his collaborators strongly supported the hypothesis. Ely's reasons for thinking that this may have importance in medicine are too conjectural to publicize until some (short) papers now in writing by Ely et al are submitted. However, it appears that multigram daily AA supplementation is mandated for cancer patients on chemotherapy (which otherwise reduces buffy coat AA to scorbutic levels, inducing cellular anergy by depressing the HMP shunt).
3.8 Micromercurialism (MM) and Alzheimer's Disease (AD), etc. During the past decade, Ely has formulated a model of MM with implications for AD and a number of other disorders. Lay versions of various aspects have appeared over the years as special reports in a newsletter published in Seattle (ref. 6). In a self-consistent way, the model incorporates his own observations and theorizing, as well as those from numerous sources in the literature (such as refs. 7, 8 and 9) and provides many predictions such as: (1) in MM, Hg will be stored in bone (supported by ref. 7); (2) Hg may be a principal cause of AD (supported by ref. 9); (3) the uniformity of soft tissue Hg-excretion half-times may be due to the low variation of ascorbate (0.3-0.6 mg%) in non-scorbutic non-supplementing humans if ascorbate is the natural endogenous mobilizer of intracellular bound Hg++ (as suggested by early observations on the medicinal use of Hg) ... if true, enhancement of Hg excretion may be possible (studies are in process); (4) an obvious role for Hg in tubulin defect; (5) in MM, urine Hg will be very low (<10 mcg/d) until amalgams or other sources of Hg intox are removed; etc. The last prediction has been strongly supported experimentally in a 4 year study of 20 subjects; the paper has been submitted to a leading clinical journal (ref. 10). Another paper on three factors that predispose to parenteral intoxication by Hg from amalgams has also been submitted (ref. 11).
Other Hg research projects (Radiation Studies, etc) in process include:
3.8.1. Heavy Metals and Gut Pathology. Using ICP-MS/LA (inductively coupled plasma - mass spectrometer with laser ablator) we have completed a preliminary study of colon biopsy samples from patients with inflammatory bowel disease. As expected, we found significant elevation of Hg on the luminal surface, but, unexpectedly a higher level of another heavy metal. The first draft of the paper is nearly complete. The study was inspired by an observation of Dr William Friend that remission from chronic bowel disease occurred in one of his patients unexpectedly in months following amalgam removal. Ely has conjectured that recovery from monilial overgrowth (reported to occur after amalgam replacement) eliminates the allergenic stimulus for the bowel inflammation (which usually "requires" steroids in therapy which in turn stimulate moniliasis because of C. albicans' receptors for cortisol (a iatrogenic loop)). This indirect effect would also suggest that Friend's observation may be very important.
3.8.2. Hg Conc in AD Cadaver Skull Temporal Bone Fragments (0.01 to 300 ppm). Using both ICP-MS/LA and XRF (x-ray fluorescence) to span this 30,000:1 range, Bloch (ref.7) below, Ely and a 3rd collaborator planned (and have been ready since early 1994) to measure Hg bone storage in AD fragments (from a 4th investigator) for comparison to bone Hg in living dentists (ref. 7), and in non-AD cadavers with no occupational exposure. Unexplained problems of the AD pathologist delay us.
3.8.3. Skull Hg in non-AD Cadavers. Ely and UW autopsy personnel still plan to use XRF for noninvasive measurement of Hg concentration in skull temporal bone of cadavers for comparison with medical histories (as an extension of the work on living dentists reported in ref.7 below).
3.8.4. Jerome Hg Vapor Analyzer. Ely has measured Hg flux from amalgams in circa 200 people to date with this excellent instrument. The results are in close accord with the values published by the Swedish chemist Jaro Pleva for the "low Cu" amalgams (10-20 mcg/cm2d). The less common "high Cu" amalgams are easy to detect by their much higher release rates. The Jerome is an invaluable diagnostic aid.
3.9. Coenzyme Q10. Ref 14 gives a Web page to update physicians and others on the remarkable potential reported in recent years for this molecule in all diseases and to assess the demand for a Q10 blood test at UW Medical Center. (Ely, Santisteban and Warner had planned a study in 1987 to measure the effects of Q10 on thymic involution in young and very old mice). In Ref 15, Ely et al report a startling unexpected complete stroke recovery that was observed (serendipidously) incidental to routine investigation of the many benefits (claimed in the literature) for supplementation of Q10. For us and anyone familiar with the record of Q10 in animal model (gerbil, dog and rat) studies of stroke, the recovery was immediately plausible as it unfolded in two weeks in spite of the vegetative prognosis forseen by the very experienced stroke unit specialists. It is unlikely that they or any one else has ever seen a stroke patient pretreated for 28 days with 400 mg of Q10/day (it may be that only accidental trauma could have induced a stroke after such pretreatment).
References
1. Santisteban, G.A., Ely, J.T.A. et al, Glycemic modulation of tumor tolerance in a mouse model of breast cancer. Biochem Biophys Res Commun 132(3): 1174-1179, 1985. (Animal study results strongly consistent with tumor-free recovery by two terminal human breast cancer patients using Ely's Aggressive Glycemic Control, approved by UW-ACS committee for research study).
2. Ely, J.T.A. Hyperglycemia and major congenital anomalies. N Engl J Med 305(14): 833, 1981 (An Ely theory explaining the role of high blood sugar in birth defects).
3. Cousins, L. Congenital anomalies among infants of diabetic mothers: Etiology, prevention, prenatal diagnosis. Am J Obstet Gynecol 147(3): 333-338, 1983 (This well known author gave Ely's theory a favorable review).
4. Hamel, E.E., Santisteban, G.A., Ely, J.T.A., et al. Hyperglycemia and reproductive defects in non-diabetic gravidas: A mouse model test of a new theory. Life Sciences 39(16): 1425-1428, 1986 (Animal study strongly supports Ely's reproductive anomaly theory). Hamel, now an MD, was an ISMS student supervised by Ely for Med School.
5. Ely, J.T.A., Warner, G.A., et al. Protein glycation: Ascorbate antagonism. Bull. Amer. Phys. Soc. (Div. Biological Physics) 33(3): 296, 1988 [Abstract of the report of the discoveries that ascorbate opposes glycation (a principal aging mechanism) in animals and humans]. Denham Harman told Ely this was an important discovery.
6. Ely, J.T.A. Various aspects of a theoretical model of "micromercurialism" (MM), the intoxication resulting (in susceptible people, ref. 11 below) from chronic exposure to Hg at very low levels (as are readily shown to emanate from dental amalgams), have appeared in Well Mind Association Newsletter issues including June 1993 and January, April and June '94. Also in these issues, evidence is cited suggesting strongly that MM is a prodromal state thru which people pass undiagnosed to many serious disorders including AD (ref.9, etc; manuscripts on the model are in process for submission to major journals).
7. Bloch, P., Shapiro, I.M. An x-ray fluorescence technique to measure the mercury burden of dentists, in vivo. Med. Physics 8: 308-311, 1981 (The impressive discovery that bone Hg storage reaches 300 ppm in the skulls of living dentists as is predicted by the MM model (ref. 6 above)). Bloch was one of Ely collabs in plan to xrf Hg in AD skulls in 1993.
8. Stortebecker, P., Mercury Poisoning from Dental Amalgam, 1985, Bio-Probe, Inc., P.O. Box 580160, Orlando, FL 32858 (This noted neurologist and pathologist gives excellent coverage and much insight on many aspects of MM; p.72, 116 re Bloch).
9. Thompson CM, Markesbery WR, Ehmann WD, Mao YX, Vance DE. Regional brain trace-element studies in Alzheimer's disease. NeuroToxicology 9: 1-7, 1988 (Another milestone discovery that Hg in the nucleus basalis of Meynert (a heavily lesioned region) of circa 80% of the AD cadaver brains, averaged 400% of the age-matched control brains). As Ely predicted on Jim French radio show in mid '80's.
10. Ely, J.T.A. et al. Urine Hg in micromercurialism: A bimodal distribution and its diagnostic implications [In essence, this paper supports the hypothesis that the diagnoses for many (possibly most) MM patients are missed due to a state called "retention toxicity" that causes their Hg excretion to be extremely low until some months after their amalgams are removed. If the AD (Alzheimer's Disease) cadaver results (ref. 9 above) are correct, the continuous flow of circa 400,000 people per year into the US AD population of 4 million may be greatly reduced in the future by improved MM diagnosis.] Although all Hg-free dentists and a well-known researcher from the AD cadaver group have urged I publish this ms, dental journals have rejected it without one valid criticism. It has been submitted to a non-dental journal, 98.8.
11. Ely, J.T.A. Risk factors for parenteral intoxication from dental amalgam. [This paper shows that, although most amalgam wearers escape significant parenteral Hg intox, three idiosyncratic risk factors exist such that a person with all three can theoretically receive over 400,000 times the parenteral dose absorbed by another person with the identical amalgam geometry but none of the three factors; circa 5% of the amalgam wearing population is estimated at high risk. This manuscript is being revised for a major toxicology journal 98.9.]
12. Ely. Glycemic Modulation of Tumor Tolerance. J Orthomolecular Med 11(1): 23-34, 1996. [Discussion of GAA and AGC in cancer in animals and humans.]
13. Ely. Unrecognized Pandemic Subclinical Diabetes of the Affluent
Nations: Causes, Cost and Prevention. J Orthomolecular Med 11(2): 95-99,
1996. [Details the literature support for (and presents) the argument
that B6 (with B9, B12, etc), Mg, Cr and coenzyme Q10 (taken properly) will
prevent nearly all of the vascular disease and diabetes that cause
over 50% of the M&M in developed nations. Shows the simple (in principle)
path to high quality and low cost health care by bringing new discoveries
rapidly to clinical attention, instead of lying buried 50 yrs.]
14. http://faculty.washington.edu/~ely/
Update and clinicians' electronic questionnaire to estimate demand
for blood test as asked of Ely by Clin Chem.]
15. Author: Ely JTA, Fudenberg HH, Bliznakov EG, Branch JD.
Title: Hemorrhagic Stroke in Human Pretreated with Coenzyme Q10: Exceptional
Recovery as Seen in Animal Models.
Source: Journal of Orthomolecular Medicine. 13(2): 105-09, 1998
Abstract: Minimizing neurologic injury from stroke is still the
elusive goal of large scale controlled clinical trials of new synthetic
agents whose efficacy is dependent upon prompt post-insult administration.
In 26 years of animal model stroke studies, one substance that afforded
a markedly higher degree of protection than all others tested was a normal
endogenous molecule, coenzyme Q10 (Q10). Because of increasing worldwide
use of Q10, we are able serendipidously to report on possibly the first
observation of a human recovering almost completely from an unexpected
cerebral hemorrhage following four weeks of pretreatment with Q10 at a
pharmacologic dose commonly employed for a wide variety of disorders. Clearly,
clinical studies are needed to confirm the significance of our observed
result. These would be facilitated by the safety and efficacy of
Q10 already proven in nine large scale international trials in cardiomyopathy,
etc., and its apparent benefits in numerous disorders, including AIDS and
possibly aging itself. However, the confirmation should be done in
trials specifically designed for stroke because of detection difficulty
arising from the anticipated protection. If confirmed, this result
does not diminish the urgent need for development of synthetic stroke agents,
but may facilitate their realization by decreasing the protective functions
needed from the agents.